| Czubatka-Bieńkowska A, Sarnik J and Poplawski T (2023), "Biological properties of (1–4)-thio disaccharides", Carbohydrate Research. Vol. 533 Elsevier Ltd. |
| Abstract: Thio sugars are carbohydrate derivatives in which one or more oxygen atoms have been replaced with sulfur. Thio sugars are effective inhibitors of glycosylases, have considerable therapeutic potential, and are used as drugs in the treatment of diabetes and infectious diseases. The development of this branch of carbohydrate chemistry would not be possible without the development of novel methods for its synthesis and the analysis of their biochemical properties. In this Review Article, we summarize our findings on the biological properties of a collection of thio sugars and their derivatives synthesized by the Witczak and Bielski team using their original methods based on the Michael addition of sugar thiols to levoglucosenone. © 2023 |
BibTeX:
@article{Czubatka-Bieńkowska2023,
author = {Czubatka-Bieńkowska, A. and Sarnik, J. and Poplawski, T.},
title = {Biological properties of (1–4)-thio disaccharides},
journal = {Carbohydrate Research},
publisher = {Elsevier Ltd},
year = {2023},
volume = {533},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85170705900&doi=10.1016%2fj.carres.2023.108934&partnerID=40&md5=e477c108ff7d1b4a60a6234089475b87},
doi = {10.1016/j.carres.2023.108934}
}
|
| Wieckowska M, Szelenberger R, Niemcewicz M, Harmata P, Poplawski T and Bijak M (2023), "Ochratoxin A—The Current Knowledge Concerning Hepatotoxicity, Mode of Action and Possible Prevention", Molecules. Vol. 28(18) Multidisciplinary Digital Publishing Institute (MDPI). |
| Abstract: Ochratoxin A (OTA) is considered as the most toxic of the other ochratoxins synthesized by various fungal species belonging to the Aspergillus and Penicillium families. OTA commonly contaminates food and beverages, resulting in animal and human health issues. The toxicity of OTA is known to cause liver damage and is still being researched. However, current findings do not provide clear insights into the toxin mechanism of action. The current studies focusing on the use of potentially protective compounds against the effects of the toxin are insufficient as they are mainly conducted on animals. Further research is required to fill the existing gaps in both fields (namely the exact OTA molecular mechanism and the prevention of its toxicity in the human liver). This review article is a summary of the so far obtained results of studies focusing on the OTA hepatotoxicity, its mode of action, and the known approaches of liver cells protection, which may be the base for expanding other research in near future. © 2023 by the authors. |
BibTeX:
@article{Więckowska2023,
author = {Wieckowska, M. and Szelenberger, R. and Niemcewicz, M. and Harmata, P. and Poplawski, T. and Bijak, M.},
title = {Ochratoxin A—The Current Knowledge Concerning Hepatotoxicity, Mode of Action and Possible Prevention},
journal = {Molecules},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
year = {2023},
volume = {28},
number = {18},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85172787139&doi=10.3390%2fmolecules28186617&partnerID=40&md5=be7406b2524b04a139cc806c14ec65d7},
doi = {10.3390/molecules28186617}
}
|
| Budlewski T, Sarnik J, Galita G, Dragan G, Brzezińska O, Popławska M, Popławski T and Makowska J (2023), "SNP in PTPN22, PADI4, and STAT4 but Not TRAF1 and CD40 Increase the Risk of Rheumatoid Arthritis in Polish Population", International Journal of Molecular Sciences. Vol. 24(8) Multidisciplinary Digital Publishing Institute (MDPI). |
| Abstract: Single nucleotide polymorphisms in non-HLA genes are involved in the development of rheumatoid arthritis (RA). SNPS in genes: PADI4 (rs2240340), STAT4 (rs7574865), CD40 (rs4810485), PTPN22 (rs2476601), and TRAF1 (rs3761847) have been described as risk factors for the development of autoimmune diseases, including RA. This study aimed to assess the prevalence of polymorphisms of these genes in the Polish population of patients with rheumatoid arthritis as compared to healthy controls. 324 subjects were included in the study: 153 healthy subjects and 181 patients from the Department of Rheumatology, Medical University of Lodz who fulfilled the criteria of rheumatoid arthritis diagnosis. Genotypes were determined by Taqman SNP Genotyping Assay. rs2476601 (G/A, OR = 2.16, CI = 1.27–3.66; A/A, OR = 10.35, CI = 1.27–84.21), rs2240340 (C/T, OR = 4.35, CI = 2.55–7.42; T/T, OR = 2.80, CI = 1.43–4.10) and rs7574865 (G/T, OR = 1.97, CI = 1.21–3.21; T/T, OR = 3.33, CI = 1.01–11.02) were associated with RA in the Polish population. Rs4810485 was also associated with RA, however after Bonferroni’s correction was statistically insignificant. We also found an association between minor alleles of rs2476601, rs2240340, and rs7574865 and RA (OR = 2.32, CI = 1.47–3.66; OR = 2.335, CI = 1.64–3.31; OR = 1.88, CI = 1.27–2.79, respectively). Multilocus analysis revealed an association between CGGGT and rare (below 0.02 frequency) haplotypes (OR = 12.28, CI = 2.65–56.91; OR = 3.23, CI = 1.63–6.39). In the Polish population, polymorphisms of the PADI4, PTPN22, and STAT4 genes have been detected, which are also known risk factors for RA in various other populations. © 2023 by the authors. |
BibTeX:
@article{Budlewski2023,
author = {Budlewski, T. and Sarnik, J. and Galita, G. and Dragan, G. and Brzezińska, O. and Popławska, M. and Popławski, T. and Makowska, J.},
title = {SNP in PTPN22, PADI4, and STAT4 but Not TRAF1 and CD40 Increase the Risk of Rheumatoid Arthritis in Polish Population},
journal = {International Journal of Molecular Sciences},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
year = {2023},
volume = {24},
number = {8},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85158043886&doi=10.3390%2fijms24087586&partnerID=40&md5=c308c7675865f545a90f653043fcf203},
doi = {10.3390/ijms24087586}
}
|
| Chojnacki C, Poplawski T, Blonska A, Konrad P, Chojnacki J and Blasiak J (2023), "The Usefulness of the Low-FODMAP Diet with Limited Tryptophan Intake in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome", Nutrients. Vol. 15(8) MDPI. |
| Abstract: (1) Background: A low-FODMAP diet is often recommended in the treatment of irritable bowel syndrome, but it does not improve abdominal symptoms in all patients, and an alternative diet is desirable. The purpose of this study was to evaluate the efficacy of a low-FODMAP diet with a concomitant reduction in tryptophan (TRP) intake in irritable bowel syndrome with diarrhea predominance (IBS-D) in relation to its metabolism via the serotonin and kynurenine pathways. (2) Methods: 40 healthy people (Group I, Controls) and 80 patients with IBS-D were included in the study. IBS-D patients were randomly divided into two groups of 40 each (Groups IIA and IIB). In Group IIA, the low-FODMAP diet was recommended, while in Group IIB, the same diet was recommended but with limited TRP intake for 8 weeks. The TRP intake was analyzed with the use of the nutritional calculator. Abdominal complaints were assessed using the Gastrointestinal Symptom Rating Scale (GSRS-IBS), and psychological status was simultaneously determined using two scales: the Hamilton Anxiety Scale (HAM-A) and the Hamilton Depression Scale (HAM-D). TRP and its metabolites: 5-hydoxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were measured in urine using liquid chromatography tandem mass spectrometry (LC-MS/MS). (3) Results: The consumption of TRP per mg/kg/b.w./24 h has decreased in Group IIA from 20.9 ± 2.39 to 17.45 ± 2.41 (16.5%) and in Group IIB from 21.3 ± 2.33 to 14.32 (34.4%). Significantly greater improvement was found after nutritional treatment in patients in Group IIB as compared to Group IIA (GSRS score: 38.1% vs. 49.8%; HAM-A: 38.7% vs. 49.9%; HAM-D: 13.8% vs. 35.0%; p < 0.01). Reducing TRP intake showed a negative correlation with the degree of improvement in the GSRS score. (4) Conclusions: Lowering the TRP content in a low-FODMAP diet may be useful in treating IBS-D. © 2023 by the authors. |
BibTeX:
@article{Chojnacki2023,
author = {Chojnacki, C. and Poplawski, T. and Blonska, A. and Konrad, P. and Chojnacki, J. and Blasiak, J.},
title = {The Usefulness of the Low-FODMAP Diet with Limited Tryptophan Intake in the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome},
journal = {Nutrients},
publisher = {MDPI},
year = {2023},
volume = {15},
number = {8},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85156158754&doi=10.3390%2fnu15081837&partnerID=40&md5=8b4371ff86eeb2dd7ee89e507f26774a},
doi = {10.3390/nu15081837}
}
|
| Chojnacki C, Gąsiorowska A, Popławski T, Błońska A, Konrad P, Zajdler R, Chojnacki J and Blasiak J (2023), "Reduced Intake of Dietary Tryptophan Improves Beneficial Action of Budesonide in Patients with Lymphocytic Colitis and Mood Disorders", Nutrients. Vol. 15(7) MDPI. |
| Abstract: Lymphocytic colitis (LC) is a gastrointestinal (GI) tract disease with poorly known pathogenesis, but some environmental and lifestyle factors, including certain dietary components, may play a role. Tryptophan is an essential amino acid, which plays important structural and functional roles as a component of many proteins. It is important in the development and maintenance of the body, in which it is metabolized in two main pathways: kynurenine (KYN) and serotonin. In this work, we explored the effect of reducing of TRP in the diet of patients with LC with mood disorders. We enrolled 40 LC patients who had a normal diet, 40 LC patients with the 8-week diet with TRP content reduced by 25% and 40 controls. All LC patients received budesonide at 9 mg per day, and the severity of their GI symptoms was evaluated by the Gastrointestinal Symptoms Rating Scale. Mood disorders were evaluated by the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D). The concentration of TRP and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA), in urine were determined. Budesonide improved the GI and mental states of LC patients, and the diet with reduced TRP content further amended these symptoms. Dietary intervention decreased the concentration of 5-HIAA by about 50% (3.4 vs. 6.3) and QA by about 45% (3.97 vs. 7.20). These changes were correlated with a significant improvement in the profitable action of budesonide on gastrointestinal and mental health of LC patients as they displayed significantly lower GSRS, HAM-A and HAM-B scores after than before the intervention—10.5 vs. 32, 11.0 vs. 21 and 12 vs. 18, respectively. In conclusion, a reduction in TRP intake in diet may improve GI and mental symptoms in LC patients treated with budesonide and these changes may be mediated by the products of TRP metabolism. © 2023 by the authors. |
BibTeX:
@article{Chojnacki2023,
author = {Chojnacki, C. and Gąsiorowska, A. and Popławski, T. and Błońska, A. and Konrad, P. and Zajdler, R. and Chojnacki, J. and Blasiak, J.},
title = {Reduced Intake of Dietary Tryptophan Improves Beneficial Action of Budesonide in Patients with Lymphocytic Colitis and Mood Disorders},
journal = {Nutrients},
publisher = {MDPI},
year = {2023},
volume = {15},
number = {7},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152687407&doi=10.3390%2fnu15071674&partnerID=40&md5=b93e7a0543201b9188b9c5deece04ac4},
doi = {10.3390/nu15071674}
}
|
| Chojnacki C, Blonska A, Konrad P, Chojnacki M, Podogrocki M and Poplawski T (2023), "Changes in Tryptophan Metabolism on Serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome", Nutrients. Vol. 15(5) Multidisciplinary Digital Publishing Institute (MDPI). |
| Abstract: (1) Background: L-tryptophan is a substrate for the synthesis of many biological compounds through the serotonin and kynurenine pathways. These compounds have a significant influence on gastrointestinal functions and mental processes. The aim of the study was to evaluate the urinary excretion of selected tryptophan metabolites in patients with constipation-predominant and diarrhoea-predominant irritable bowel syndrome (IBS-C and IBS-D, respectively), related to somatic and mental symptoms. (2) Methods: 120 people were included in the study and three groups were distinguished, with 40 individuals each, including healthy subjects (controls), patients with IBS-C and patients with IBS-D. The Gastrointestinal Symptoms Rating Scale (GSRS-IBS) was used to assess the severity of abdominal symptoms. The Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D) were used to evaluate the mental state of patients. Using liquid chromatography tandem mass spectrometry (LC-MS/MS), L-tryptophan and the following metabolites in urine, related to the creatinine level, were measured: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA). (3) Results: In both groups of patients with IBS, changes in tryptophan metabolism were found as compared to the control group. We observed an increase in the activity of the serotonin pathway and a positive correlation between the 5-HIAA level and the GSRS score (p < 0.01) and HAM-A score (p < 0.001) in IBS-D patients. The IBS-C group was characterized by a higher concentration of kynurenines (KYN, QA) in urine. Moreover, the QA (p < 0.001) and KYNA (p < 0.05) levels were correlated with the HAM-D score among IBS-C patients. (4) Conclusions: Various changes in the tryptophan metabolism pathway can determine the differences in the clinical picture of irritable bowel syndrome. These results should be included in the nutritional and pharmacological treatment of this syndrome. © 2023 by the authors. |
BibTeX:
@article{Chojnacki2023,
author = {Chojnacki, C. and Blonska, A. and Konrad, P. and Chojnacki, M. and Podogrocki, M. and Poplawski, T.},
title = {Changes in Tryptophan Metabolism on Serotonin and Kynurenine Pathways in Patients with Irritable Bowel Syndrome},
journal = {Nutrients},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
year = {2023},
volume = {15},
number = {5},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149720823&doi=10.3390%2fnu15051262&partnerID=40&md5=8834a94a982811b4b399e74e366f63c5},
doi = {10.3390/nu15051262}
}
|
| Galita G, Sarnik J, Brzezinska O, Budlewski T, Dragan G, Poplawska M, Majsterek I, Poplawski T and Makowska J (2023), "Polymorphisms in DNA Repair Genes and Association with Rheumatoid Arthritis in a Pilot Study on a Central European Population", International Journal of Molecular Sciences. Vol. 24(4) MDPI. |
| Abstract: Rheumatoid arthritis (RA) is a chronic, multifactorial autoimmune disease characterized by chronic arthritis, a tendency to develop joint deformities, and involvement of extra-articular tissues. The risk of malignant neoplasms among patients with RA is the subject of ongoing research due to the autoimmune pathogenesis that underlies RA, the common etiology of rheumatic disease and malignancies, and the use of immunomodulatory therapy, which can alter immune system function and thus increase the risk of malignant neoplasms. This risk can also be increased by impaired DNA repair efficiency in individuals with RA, as reported in our recent study. Impaired DNA repair may reflect the variability in the genes that encode DNA repair proteins. The aim of our study was to evaluate the genetic variation in RA within the genes of the DNA damage repair system through base excision repair (BER), nucleotide excision repair (NER), and the double strand break repair system by homologous recombination (HR) and non-homologous end joining (NHEJ). We genotyped a total of 28 polymorphisms in 19 genes encoding DNA repair-related proteins in 100 age- and sex-matched RA patients and healthy subjects from Central Europe (Poland). Polymorphism genotypes were determined using the Taq-man SNP Genotyping Assay. We found an association between the RA occurrence and rs25487/XRCC1, rs7180135/RAD51, rs1801321/RAD51, rs963917/RAD51B, rs963918/RAD51B, rs2735383/NBS1, rs132774/XRCC6, rs207906/XRCC5, and rs861539/XRCC3 polymorphisms. Our results suggest that polymorphisms of DNA damage repair genes may play a role in RA pathogenesis and may be considered as potential markers of RA. © 2023 by the authors. |
BibTeX:
@article{Galita2023,
author = {Galita, G. and Sarnik, J. and Brzezinska, O. and Budlewski, T. and Dragan, G. and Poplawska, M. and Majsterek, I. and Poplawski, T. and Makowska, J.S.},
title = {Polymorphisms in DNA Repair Genes and Association with Rheumatoid Arthritis in a Pilot Study on a Central European Population},
journal = {International Journal of Molecular Sciences},
publisher = {MDPI},
year = {2023},
volume = {24},
number = {4},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149023445&doi=10.3390%2fijms24043804&partnerID=40&md5=e59d2e6b31282bba03ccfd30d8da66ee},
doi = {10.3390/ijms24043804}
}
|
| Chojnacki C, Gąsiorowska A, Popławski T, Konrad P, Chojnacki M, Fila M and Blasiak J (2023), "Beneficial Effect of Increased Tryptophan Intake on Its Metabolism and Mental State of the Elderly", Nutrients. Vol. 15(4) MDPI. |
| Abstract: The elderly often suffer from sleep disorders and depression, which contribute to mood disorders. In our previous work, we showed that elderly individuals with mood disorders had a lower intake of TRP and recommended a TRP-based dietary intervention to improve the mental state of such individuals. In this work, we assessed the impact of a TRP-rich diet on the mental state of, and TRP metabolism in, elderly individuals with mood disorders. Forty elderly individuals with depression and sleep disorders and an equal number of elderly subjects without mood disorders were enrolled in this study. TRP intake was evaluated with the nutrition calculator. Patients with mood disorders had a lower TRP intake than their normal counterparts and received a TRP-rich diet with TRP content of 25 mg per kilogram of the body per day for 12 weeks. The mental state was assessed before and after this dietary intervention with the Hamilton Depression Rating Scale (HAM-D) and the Insomnia Severity Index (ISI). At those times, urinary levels of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. After TRP-based dietary intervention, the score of ISI and HAM-D decreased by more than half. A correlation analysis reveals that TRP, 5-HIAA, and KYNA might have anti-depressive action, while KYN and QA—pro-depressive. The levels of TRP, 5-HIAA, and KYNA in urine of mood disorder patients increased, while the levels of KYN and QA decreased. In conclusion, dietary consumption of adequate amount of tryptophan has a beneficial effect on mental health of the elderly with mood disorders and improves metabolism of this amino acid. Therefore, a TRP-enriched diet may be considered as a component of the treatment of elderly individuals with mood disorders. © 2023 by the authors. |
BibTeX:
@article{Chojnacki2023,
author = {Chojnacki, C. and Gąsiorowska, A. and Popławski, T. and Konrad, P. and Chojnacki, M. and Fila, M. and Blasiak, J.},
title = {Beneficial Effect of Increased Tryptophan Intake on Its Metabolism and Mental State of the Elderly},
journal = {Nutrients},
publisher = {MDPI},
year = {2023},
volume = {15},
number = {4},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85148864546&doi=10.3390%2fnu15040847&partnerID=40&md5=104c2f10782ee69cd2be22b8f385cb46},
doi = {10.3390/nu15040847}
}
|
| Chojnacki C, Medrek-Socha M, Blonska A, Zajdel R, Chojnacki J and Poplawski T (2022), "A Reduced Tryptophan Diet in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Improves Their Abdominal Symptoms and Their Quality of Life through Reduction of Serotonin Levels and Its Urinary Metabolites", International Journal of Molecular Sciences. Vol. 23(23) MDPI. |
| Abstract: (1). An essential component of any treatment for patients with irritable bowel syndrome (IBS) is an adequate diet. Currently, a low FODMAP diet is recommended as a first-line therapy, but it does not relieve abdominal discomfort in all patients, and alternative nutritional treatment is required. The purpose of this study was to evaluate the effect of a tryptophan-lowering diet (TRP) on abdominal and mental symptoms in patients with irritable bowel syndrome with predominant diarrhea (IBS-D). (2). The study included 40 patients with IBS-D, and 40 healthy subjects served as a baseline for IBS-D patients, after excluding comorbidities. The TRP intake was calculated using the nutritional calculator. The severity of abdominal symptoms was assessed using the gastrointestinal symptom rating scale (GSRS-IBS). Mental state was assessed using the Hamilton anxiety rating scale (HAM-A), the Hamilton depression rating scale (HAM-D), and the insomnia severity index (ISI). The serum levels of serotonin and melatonin and the urinary excretion of their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 6-sulfatoxymelatonin (aMT6) were determined by the ELISA method. The severity of symptoms and laboratory data were analyzed before and after a 12 week diet with tryptophan restricted to a daily dose 10 mg per kilogram body weight. (3). Compared to the control group, patients with IBS-D had a higher serum level of serotonin (198.2 ± 38.1 vs. 142.3 ± 36.4 ng/mL; p < 0.001) but a similar level of melatonin (8.6 ± 1.1 vs. 9.4 ± 3.0 pg/mL; p > 0.05). The urinary excretion of 5-HIAA was also higher in patients with IBS-D patients (7.7 ± 1.5 vs. 6.0 ± 1.7 mg/24 h; p < 0.001). After nutritional treatment, both the serum serotonin level and the urinary 5-HIAA excretion significantly decreased (p < 0.001). The severity of the abdominal symptoms and anxiety also decreased, while the HAM-D score and the ISI score remained unchanged (4). Lowering the dietary intake of tryptophan may reduce abdominal complaints and does not alter the mental state of IBS-D patients. © 2022 by the authors. |
BibTeX:
@article{Chojnacki2022,
author = {Chojnacki, C. and Medrek-Socha, M. and Blonska, A. and Zajdel, R. and Chojnacki, J. and Poplawski, T.},
title = {A Reduced Tryptophan Diet in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Improves Their Abdominal Symptoms and Their Quality of Life through Reduction of Serotonin Levels and Its Urinary Metabolites},
journal = {International Journal of Molecular Sciences},
publisher = {MDPI},
year = {2022},
volume = {23},
number = {23},
note = {cited By 2},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143699849&doi=10.3390%2fijms232315314&partnerID=40&md5=e315031623cd36f662d2cfdd54a777f5},
doi = {10.3390/ijms232315314}
}
|
| Chojnacki C, Popławski T, Konrad P, Fila M, Błasiak J and Chojnacki J (2022), "Antimicrobial treatment improves tryptophan metabolism and mood of patients with small intestinal bacterial overgrowth", Nutrition and Metabolism. Vol. 19(1) BioMed Central Ltd. |
| Abstract: Background: Optimal composition of intestinal bacteria is an essential condition for good health. Excessive growth of these bacteria can cause various ailments. The aim of this study was to assess the mental state and gastrointestinal complaints of patients with small intestinal bacterial overgrowth (SIBO) in relation to tryptophan metabolism and rifaximin treatment. Methods: 120 subjects, aged 23–61 years, were enrolled in the study, and divided into 3 groups, 40 individuals each: healthy subjects (Controls), patients with SIBO and chronic diarrhea (SIBO-D), and with chronic constipation (SIBO-C). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The mental state of patients was assessed using the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D). L-tryptophan (TRP) and its metabolites: 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), xanthurenic acid (XA) and quinolinic acid (QA) were measured in urine by liquid-chromatography-tandem mass spectrometry and related to creatinine level. Patients with SIBO were recommended to take rifaximin for 10 days at daily dose 1200 mg, and this cycle was repeated in subsequent two months. Results: Mild and moderate anxiety, as well as mild depression were diagnosed in all SIBO patients. Changes in TRP metabolism were also observed in these patients. Specifically, an increase in the activity of the serotonin pathway of TRP metabolism in the group SIBO-D was observed. The SIBO-C patients showed an increase in the concentration of KYN, XA and QA. 5-HIAA/TRP and KYN/TRP ratios significantly decreased in group SIBO-D, and KYN and QA levels decreased in group SIBO-C after treatment with rifaximin. The levels of anxiety and depression decreased in both groups. Conclusion: Rifaximin treatment of SIBO patients ameliorated their mood disorders and gastrointestinal aliments underlined by changes in tryptophan metabolism. Trial registration Retrospectively registered (if applicable). © 2022, The Author(s). |
BibTeX:
@article{Chojnacki2022,
author = {Chojnacki, C. and Popławski, T. and Konrad, P. and Fila, M. and Błasiak, J. and Chojnacki, J.},
title = {Antimicrobial treatment improves tryptophan metabolism and mood of patients with small intestinal bacterial overgrowth},
journal = {Nutrition and Metabolism},
publisher = {BioMed Central Ltd},
year = {2022},
volume = {19},
number = {1},
note = {cited By 2},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85139215942&doi=10.1186%2fs12986-022-00700-5&partnerID=40&md5=1430a9b1217554c24a8ccb71a30048ca},
doi = {10.1186/s12986-022-00700-5}
}
|
| Kowalczyk M, Kowalczyk E, Gogolewska M, Skrzypek M, Talarowska M, Majsterek I, Poplawski T, Kwiatkowski P and Sienkiewicz M (2022), "Association of polymorphic variants in GEMIN genes with the risk of depression in a Polish population", PeerJ. Vol. 10 PeerJ Inc.. |
| Abstract: Background. The role ofmiRNAin depression is widely described by many researchers. miRNA is a final product of many genes involved in its formation (maturation). One of the final steps in the formation of miRNAs is the formation of the RISC complex, called the RNA-induced silencing complex, which includes, among others, GEMIN proteins. Single-nucleotide polymorphisms (SNPs) may lead to disturbance of miRNA biogenesis and function. The objective of our research was to assess the relationship between the appearance of depression and single nucleotide polymorphisms in the GEMIN3 (rs197388) and GEMIN4 (rs7813; rs3744741) genes. Our research provides new knowledge on the genetic factors that influence the risk of depression. They can be used as an element of diagnostics helpful in identifying people at increased risk, as well as indicating people not at risk of depression. Methods. A total of 218 participants were examined, including individuals with depressive disorders (n D 102; study group) and healthy people (n D 116, control group). All the patients in the study group and the people in the control group were non-related native Caucasian Poles from central Poland. Blood was collected from study and control groups in order to assess the SNPs of GEMIN genes. Results. An analysis of the results obtained showed that in patient population, the risk of depression is almost doubled by polymorphic variants of the genes: rs197388/GEMIN3 genotype A/A in the recessive model and rs3744741/GEMIN4 genotype T/T, codominant and recessive model. The dual role of rs7813/GEMIN4 is noteworthy, where the G/A genotype in the codominant and over dominant model protects against depression. © 2022 Kowalczyk et al. |
BibTeX:
@article{Kowalczyk2022,
author = {Kowalczyk, M. and Kowalczyk, E. and Gogolewska, M. and Skrzypek, M. and Talarowska, M. and Majsterek, I. and Poplawski, T. and Kwiatkowski, P. and Sienkiewicz, M.},
title = {Association of polymorphic variants in GEMIN genes with the risk of depression in a Polish population},
journal = {PeerJ},
publisher = {PeerJ Inc.},
year = {2022},
volume = {10},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85141996806&doi=10.7717%2fpeerj.14317&partnerID=40&md5=dbc637f0acd77ce007be7d5d4a3aeca5},
doi = {10.7717/peerj.14317}
}
|
| Kowalczyk M, Kowalczyk E, Galita G, Majsterek I, Talarowska M, Popławski T, Kwiatkowski P, Lichota A and Sienkiewicz M (2022), "Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population", International Journal of Molecular Sciences. Vol. 23(18) MDPI. |
| Abstract: Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system. Single-nucleotide polymorphisms (SNPs) of AGO genes can lead to deregulation of the processes in which AGO proteins are involved. The contribution of different SNPs in depression has been extensively studied. However, there are hardly any studies on the contribution of AGO genes. The aim of our research was to assess the relationship between the occurrence of depression and the presence of SNPs in genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) in a Polish population. One hundred and one subjects in the study group were diagnosed with recurrent depressive disorder by a psychiatrist. The control group comprised 117 healthy subjects. Study participants performed the HDRS (Hamilton Depression Scale) test to confirm or exclude depression and assess severity. The frequency of polymorphic variants of genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) was determined using TaqMan SNP genotyping assays and the TaqMan universal PCR master mix, no AmpErase UNG. The rs4961280/AGO2 polymorphism was associated with a decrease in depression occurrence in the codominant (OR = 0.51, p = 0.034), dominant (OR = 0.49, p = 0.01), and overdominant (OR = 0.58, p = 0.049) models. Based on the obtained results, we found that the studied patients demonstrated a lower risk of depression with the presence of the polymorphic variant of the rs4961280/AGO2 gene—genotype C/A and C/A-A/A. © 2022 by the authors. |
BibTeX:
@article{Kowalczyk2022,
author = {Kowalczyk, M. and Kowalczyk, E. and Galita, G. and Majsterek, I. and Talarowska, M. and Popławski, T. and Kwiatkowski, P. and Lichota, A. and Sienkiewicz, M.},
title = {Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population},
journal = {International Journal of Molecular Sciences},
publisher = {MDPI},
year = {2022},
volume = {23},
number = {18},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85138354119&doi=10.3390%2fijms231810586&partnerID=40&md5=cd8cca4bb478a1c93c0b8635af9a051e},
doi = {10.3390/ijms231810586}
}
|
| Chojnacki C, Konrad P, Blonska A, Medrek-Socha M, Przybylowska-Sygut K, Chojnacki J and Poplawski T (2022), "Altered Tryptophan Metabolism on the Kynurenine Pathway in Depressive Patients with Small Intestinal Bacterial Overgrowth", Nutrients. Vol. 14(15) MDPI. |
| Abstract: The causes of depression are diverse and are still not fully understood. Recently, an increasing role is attributed to nutritional and inflammatory factors. The aim of this study was to evaluate selected metabolites of the tryptophan kynurenine pathway in depressive patients with small intestinal bacterial overgrowth (SIBO). The study involved 40 healthy people (controls) and 40 patients with predominant small intestinal bacterial overgrowth (SIBO-D). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The severity of symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS–IBS) and the Hamilton Depression Rating Scale (HAM-D). The concentration of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) in urine was determined using an LC–MS/MS method, before and after cyclic treatment with an antibiotic drug, rifaximin, for three months. The number of intraepithelial lymphocytes (IELs) in the duodenum and small intestinal mucosa, fecal calprotectin (FC) and serum level of C-reactive protein (CRP) were also determined. In patients with SIBO, a higher level of KYN and QA were found as compared to the control group. These two groups also differed in KYN/TRP (higher in SIBO) and KYNA/KYN ratios (lower in SIBO). A positive correlation was found between HAM-D and the number of IELs and the level of FC. Treatment with rifaximin improves the kynurenic pathway, as well as abdominal and mental complaints. Therefore, small intestinal bacterial overgrowth can be a cause of abdominal symptoms, but also mental disorders. © 2022 by the authors. |
BibTeX:
@article{Chojnacki2022,
author = {Chojnacki, C. and Konrad, P. and Blonska, A. and Medrek-Socha, M. and Przybylowska-Sygut, K. and Chojnacki, J. and Poplawski, T.},
title = {Altered Tryptophan Metabolism on the Kynurenine Pathway in Depressive Patients with Small Intestinal Bacterial Overgrowth},
journal = {Nutrients},
publisher = {MDPI},
year = {2022},
volume = {14},
number = {15},
note = {cited By 6},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85136531858&doi=10.3390%2fnu14153217&partnerID=40&md5=f99409203f03c1b11e4742b69e60ffe8},
doi = {10.3390/nu14153217}
}
|
| Sakowski S, Waldmajer J, Majsterek I and Poplawski T (2022), "DNA Computing: Concepts for Medical Applications", Applied Sciences (Switzerland). Vol. 12(14) MDPI. |
| Abstract: The branch of informatics that deals with construction and operation of computers built of DNA, is one of the research directions which investigates issues related to the use of DNA as hardware and software. This concept assumes the use of DNA computers due to their biological origin mainly for intelligent, personalized and targeted diagnostics frequently related to therapy. Important elements of this concept are (1) the retrieval of unique DNA sequences using machine learning methods and, based on the results of this process, (2) the construction/design of smart diagnostic biochip projects. The authors of this paper propose a new concept of designing diagnostic biochips, the key elements of which are machine-learning methods and the concept of biomolecular queue automata. This approach enables the scheduling of computational tasks at the molecular level by sequential events of cutting and ligating DNA molecules. We also summarize current challenges and perspectives of biomolecular computer application and machine-learning approaches using DNA sequence data mining. © 2022 by the authors. |
BibTeX:
@article{Sakowski2022,
author = {Sakowski, S. and Waldmajer, J. and Majsterek, I. and Poplawski, T.},
title = {DNA Computing: Concepts for Medical Applications},
journal = {Applied Sciences (Switzerland)},
publisher = {MDPI},
year = {2022},
volume = {12},
number = {14},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85137351014&doi=10.3390%2fapp12146928&partnerID=40&md5=7901ec7a7f5d409b7126508ee3b3c5d0},
doi = {10.3390/app12146928}
}
|
| Czubak-Prowizor K, Macieja A, Poplawski T and Zbikowska H (2022), "Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin", PLoS ONE. Vol. 17(7 July) Public Library of Science. |
| Abstract: Perioperative blood transfusion in colorectal and some other cancer patients has been linked to the increased risk for recurrence, but a causal mechanism remains unclear. During the preparation and storage of packed red blood cells (PRBCs) bio-active substances accumulate in the acellular fraction (supernatant). Viability, proliferation, reactive oxygen species (ROS) levels, and DNA damage of colon (LoVo) and breast (MCF7) adenocarcinoma cells and non-tumorigenic MCF-10A cell line were determined in response to the supernatants of fresh and long-stored (day 42) PRBCs, leukoreduced (LR) or non-leukoreduced (NLR). The effect of supernatants on the cytotoxicity of cisplatin (cisPt) towards the cells was also examined. Supernatants, especially from a day 1 PRBCs, both LR and NLR, reduced the viability and inhibited proliferation of tumor cells (LoVo, MCF7), accompanying by the excessive ROS production, but these were not the case in MCF-10A. Moreover, supernatants had no effect on the cytotoxicity of cisPt against LoVo and MCF7 cells, while caused increased drug resistance in MCF-10A cells. The findings suggest the acellular fraction of PRBCs does not exhibit any pro-proliferative activity in the cancer cell lines studied. However, these are pioneering issues and require further research. © 2022 Czubak-Prowizor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
BibTeX:
@article{Czubak-Prowizor2022,
author = {Czubak-Prowizor, K. and Macieja, A. and Poplawski, T. and Zbikowska, H.M.},
title = {Responses of human colon and breast adenocarcinoma cell lines (LoVo, MCF7) and non-tumorigenic mammary epithelial cells (MCF-10A) to the acellular fraction of packed red blood cells in the presence and absence of cisplatin},
journal = {PLoS ONE},
publisher = {Public Library of Science},
year = {2022},
volume = {17},
number = {7 July},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85133728684&doi=10.1371%2fjournal.pone.0271193&partnerID=40&md5=69fc19b328aecaf67e1eaa61549807ff},
doi = {10.1371/journal.pone.0271193}
}
|
| Czubak-Prowizor K, Macieja A, Poplawski T and Zbikowska H (2022), "Packed Red Blood Cell Supernatants Do Not Promote Growth or Cisplatin Resistance of Myeloid Leukemia K-562 Cells", Journal of Blood Medicine. Vol. 13, pp. 121-131. Dove Medical Press Ltd. |
| Abstract: Background: A decreased immune surveillance as a consequence of packed red blood cell (PRBC) transfusions has been linked to cancer recurrence and progression, but a causal mechanism remains unclear. During processing and storage of PRBC, numerous bioactive substances accumulate in the acellular fraction (supernatant) of PRBC. Aim: The study aimed to determine whether the supernatant of leukocyte-reduced (LR) and non-leukocyte-reduced (NLR) long-stored PRBC can modulate the survival and proliferation of myeloid leukemia K-562 cells, and the influence of cisplatin (cisPt) on these processes. Methods: Viability, proliferation, DNA damage, intracellular reactive oxygen species (ROS), caspase-3/7 and caspase-9 levels were determined in response to the LR or NLR, fresh (day 1) and long-stored (day 42) PRBCs. Results: The supernatants of fresh (day 1) and stored (day 42) PRBC, in the absence and presence of cisPt, promoted apoptosis of K-562 cells via the increased production of reactive oxygen species (ROS) and increased level of DNA damage, which was manifested by the viability reduction and inhibition of K-562 cell proliferation. No significant influence of the pre-storage leukocyte-filtration and storage time of PRBC units on their anti-proliferative effect was demonstrated. Conclusion: The findings may suggest that the PRBC acellular fraction does not affect chronic myeloid leukemia (CML) progression. However, these issues are pioneering and require further study. © 2022 Czubak-Prowizor et al. |
BibTeX:
@article{Czubak-Prowizor2022121,
author = {Czubak-Prowizor, K. and Macieja, A. and Poplawski, T. and Zbikowska, H.M.},
title = {Packed Red Blood Cell Supernatants Do Not Promote Growth or Cisplatin Resistance of Myeloid Leukemia K-562 Cells},
journal = {Journal of Blood Medicine},
publisher = {Dove Medical Press Ltd},
year = {2022},
volume = {13},
pages = {121-131},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126761775&doi=10.2147%2fJBM.S349965&partnerID=40&md5=c01a9f39b7d625ee0141635f48ff8cd9},
doi = {10.2147/JBM.S349965}
}
|
| Cieslak A, Galita G, Mik M, Dziki L, Dziki A, Sokolowski I, Poplawski T and Majsterek I (2021), "Association of GEMIN4 gene polymorphisms with the risk of colorectal cancer in the Polish population", Polski Przeglad Chirurgiczny/ Polish Journal of Surgery. Vol. 93, pp. 40-45. Index Copernicus International. |
| Abstract: Aim: Gem-associated protein 4 (GEMIN4), a member of the GEMIN gene family, is a key compound of the regulating factors responsible for miRNA biogenesis. Genetic variability within this gene can alter the risk for development of colorectal cancer (CRC) as was shown for other genes involved in miRNA biogenesis. Therefore, presented study was intended to identify genetic variants of three single nucleotide polymorphisms (SNPs) in the GEMIN4 gene (rs1062923, rs2740348 and rs910925) and their relationship with CRC. Methods: The study comprised 203 patients and 179 age and sex matched controls. Genotyping of GEMIN4 gene variants was done using Taqman® assay. The association of GEMIN4 variants with CRC was done by odds ratio analysis. Haplotype analysis was done to see the combined effect of studied variants on CRC. Results: Patients carrying all variant genotypes for GEMIN4 rs1062923 (odds ratio [OR]= 0.205; 95% confidence interval [CI] = 0.1034-0.4065 for CC variant and [OR] = 0.1436; [CI] = 0.0869-0.2373 for CT variant, respectively) and GEMIN4 rs2740348 (odds ratio [OR] = 0.4498; 95% confidence interval [CI] = 0.2342-0.8637 for CC variant and [OR] = 0.3986; [CI] = 0.2043-0.7776 for CG variant, respectively) showed significant association in lower occurrence of cancer, whereas in case of GEMIN4 G/C rs910925 variant genotype, no significance correlation was found. Conclusion: Our study gives a substantive support for the association between the GEMIN4 gene variants/miRNA biogenesis and CRC risk. © 2021 Index Copernicus International. All rights reserved. |
BibTeX:
@article{Cieslak202140,
author = {Cieslak, A. and Galita, G. and Mik, M. and Dziki, L. and Dziki, A. and Sokolowski, I. and Poplawski, T. and Majsterek, I.},
title = {Association of GEMIN4 gene polymorphisms with the risk of colorectal cancer in the Polish population},
journal = {Polski Przeglad Chirurgiczny/ Polish Journal of Surgery},
publisher = {Index Copernicus International},
year = {2021},
volume = {93},
pages = {40-45},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85125902844&doi=10.5604%2f01.3001.0015.5164&partnerID=40&md5=daadff0aaaf23e5e4e5fc2bc97b8611a},
doi = {10.5604/01.3001.0015.5164}
}
|
| Sarnik J, Popławski T and Tokarz P (2021), "BET proteins as attractive targets for cancer therapeutics", International Journal of Molecular Sciences. Vol. 22(20) MDPI. |
| Abstract: Transcriptional dysregulation is a hallmark of cancer and can be an essential driver of cancer initiation and progression. Loss of transcriptional control can cause cancer cells to become dependent on certain regulators of gene expression. Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that regulate the expression of multiple genes involved in carcinogenesis. BET inhibitors (BETis) disrupt BET protein binding to acetylated lysine residues of chromatin and suppress the transcription of various genes, including oncogenic transcription factors. Phase I and II clinical trials demonstrated BETis’ potential as anticancer drugs against solid tumours and haematological malignancies; however, their clinical success was limited as monotherapies. Emerging treatment-associated toxicities, drug resistance and a lack of predictive biomarkers limited BE-Tis’ clinical progress. The preclinical evaluation demonstrated that BETis synergised with different classes of compounds, including DNA repair inhibitors, thus supporting further clinical development of BETis. The combination of BET and PARP inhibitors triggered synthetic lethality in cells with proficient homologous recombination. Mechanistic studies revealed that BETis targeted multiple essential homologous recombination pathway proteins, including RAD51, BRCA1 and CtIP. The exact mechanism of BETis’ anticancer action remains poorly understood; nevertheless, these agents provide a novel approach to epigenome and transcriptome anticancer therapy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
BibTeX:
@article{Sarnik2021,
author = {Sarnik, J. and Popławski, T. and Tokarz, P.},
title = {BET proteins as attractive targets for cancer therapeutics},
journal = {International Journal of Molecular Sciences},
publisher = {MDPI},
year = {2021},
volume = {22},
number = {20},
note = {cited By 22},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85116995129&doi=10.3390%2fijms222011102&partnerID=40&md5=23afcaedc188df955ad8643b5b1508fd},
doi = {10.3390/ijms222011102}
}
|
| Chojnacki C, Poplawski T, Konrad P, Fila M, Chojnacki J and Blasiak J (2021), "Serotonin pathway of tryptophan metabolism in small intestinal bacterial overgrowth—a pilot study with patients diagnosed with lactulose hydrogen breath test and treated with rifaximin", Journal of Clinical Medicine. Vol. 10(10) MDPI. |
| Abstract: Small intestinal bacterial overgrowth (SIBO) is a condition associated with diverse clinical conditions and there is no gold standard in its diagnosis and treatment. Tryptophan (Trp) metabolism may be involved in etiology of gastrointestinal diseases and is regulated by intestinal microbiota. In our study we investigated aspects of the serotonin (5-HT) pathway of Trp metabolism in three groups of individuals based on the hydrogen concentration in the lactulose hydrogen breath test (LHBT): controls (<20 ppm) and SIBO patients (≥20 ppm), with diarrhea (SIBO-D) or constipation (SIBO-C). The SIBO-D patients showed an increased serum concentration of 5-HT and small intestinal mucosa mRNA expression of tryptophan hydroxylase 1 (TPH-1), a rate-limiting enzyme in 5-HT biosynthesis. Urinary 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of 5-HT, was higher in both group of SIBO patients than controls. A positive correlation between 5-HIAA and LHBT was observed. A two-week treatment with rifaximin decreased hydrogen in LHBT and 5-HIAA concentration in SIBO patients. In conclusion, the serotonin pathway of Trp metabolism may play a role in the pathogenesis of hydrogen-positive SIBO and it may influence the diversification of SIBO into variants with diarrhea or constipation. As urinary 5-HIAA concentration correlates with LHBT, TPH-1 expression in colonic mucosa and TH-5 in serum of SIBO patients, it can be considered as a non-invasive marker of this condition. © 2021 by the authors. |
BibTeX:
@article{Chojnacki2021,
author = {Chojnacki, C. and Poplawski, T. and Konrad, P. and Fila, M. and Chojnacki, J. and Blasiak, J.},
title = {Serotonin pathway of tryptophan metabolism in small intestinal bacterial overgrowth—a pilot study with patients diagnosed with lactulose hydrogen breath test and treated with rifaximin},
journal = {Journal of Clinical Medicine},
publisher = {MDPI},
year = {2021},
volume = {10},
number = {10},
note = {cited By 2},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113191825&doi=10.3390%2fjcm10102065&partnerID=40&md5=e93f664f078eb5b66565774d524d4d7a},
doi = {10.3390/jcm10102065}
}
|
| Chojnacki C, Popławski T, Gasiorowska A, Chojnacki J and Blasiak J (2021), "Serotonin in the pathogenesis of lymphocytic colitis", Journal of Clinical Medicine. Vol. 10(2), pp. 1-10. MDPI. |
| Abstract: Lymphocytic colitis (LC) is a chronic inflammatory disease associated with watery diarrhea, abdominal pain, and colonic intraepithelial lymphocytosis. Serotonin (5-hydroxytryptamine, 5-HT) is reported to increase in certain colon diseases; however, little is known regarding its metabolism in LC. In the present work, the level of 5-HT in serum and the number of enteroendocrine cells (EECs) as well as the expression of the 5-HT rate-limiting enzyme tryptophan hydroxylase 1 (TPH1) in colonic biopsies and urine 5-hydroxyindoeoacetic acid (5-HIAA) were determined in 36 LC patients that were treated with budesonide and 32 healthy controls. The 5-HT serum and 5-HIAA urine levels were measured using ELISA, the EEC number was determined immunohistochemically, and the colonic TPH1 mRNA expression was determined using RT-PCR. The levels of 5-HT and 5-HIAA and the number of EECs were higher in LC patients than in the controls, and positive correlations were observed between the 5-HT and 5-HIAA levels, 5-HT and EEC number, TPH1 mRNA and EEC number, as well as the severity of disease symptoms and 5-HIAA. Budesonide decreased the levels of 5-HT, 5-HIAA, and TPH1 expression and the number of EECs to values that did not differ from those for controls. In conclusion, the serotonin metabolism may be important for LC pathogenesis, and the urinary level of 5-HIAA may be considered as a non-invasive marker of this disease activity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. |
BibTeX:
@article{Chojnacki20211,
author = {Chojnacki, C. and Popławski, T. and Gasiorowska, A. and Chojnacki, J. and Blasiak, J.},
title = {Serotonin in the pathogenesis of lymphocytic colitis},
journal = {Journal of Clinical Medicine},
publisher = {MDPI},
year = {2021},
volume = {10},
number = {2},
pages = {1-10},
note = {cited By 6},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85108826444&doi=10.3390%2fjcm10020285&partnerID=40&md5=0b26c355a14191648362c396035eb19b},
doi = {10.3390/jcm10020285}
}
|
| Kopa P, Macieja A, Pastwa E, Majsterek I and Poplawski T (2021), "DNA double-strand breaks repair inhibitors potentiates the combined effect of VP-16 and CDDP in human colorectal adenocarcinoma (LoVo) cells", Molecular Biology Reports. Vol. 48(1), pp. 709-720. Springer Science and Business Media B.V.. |
| Abstract: I. Background: A combination of etoposide (VP-16) and cisplatin (CDDP) is the standard treatment for certain colon cancers. These drugs promote the death of cancer cells via direct and indirect induction of the most lethal DNA lesions – DNA double-stand breaks. However, cancer cells can reverse the DNA damaging effect of anticancer drugs by triggering DNA repair processes. In eukaryotic cells, the main DNA repair pathway responsible for DNA double-stand breaks repair is non-homologous end-joining (NHEJ). Inhibitors of DNA repair are of special interest in cancer research as they could break the cellular resistance to DNA-damaging agents and increase the efficiency of standard cancer treatments. In this study, we investigated the effect of two NHEJ inhibitors, SCR7 and NU7441, on the cytotoxic mechanism of VP-16/CDDP in a LoVo human colorectal adenocarcinoma cell line. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding, whereas NU7441 is a highly potent and selective DNA-PK inhibitor. II. Methods and Results: Both inhibitors synergistically increased the cytotoxicity of CDDP and VP-16 when combined, but the effect of SCR7 was more pronounced. SCR7 and NU7441 also significantly increased VP-16; CDDP induced DNA double-stand breaks level and delayed drug-induced DSB repair, as seen on the comet assay and measured using H2AX foci. We also observed changes in cell cycle distribution and enhanced apoptosis ratio in colorectal adenocarcinoma cells treated with DNA repair inhibitors and VP-16/CDDP. III. Conclusions: Our data support the hypothesis that NHEJ inhibitors could be used in conjunction with standard therapy to provide effective clinical improvement and allow reduction in drug doses. © 2021, The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature. |
BibTeX:
@article{Kopa2021709,
author = {Kopa, P. and Macieja, A. and Pastwa, E. and Majsterek, I. and Poplawski, T.},
title = {DNA double-strand breaks repair inhibitors potentiates the combined effect of VP-16 and CDDP in human colorectal adenocarcinoma (LoVo) cells},
journal = {Molecular Biology Reports},
publisher = {Springer Science and Business Media B.V.},
year = {2021},
volume = {48},
number = {1},
pages = {709-720},
note = {cited By 2},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098701115&doi=10.1007%2fs11033-020-06124-9&partnerID=40&md5=b71c7d80e61391a925d54422c10a5411},
doi = {10.1007/s11033-020-06124-9}
}
|
| Witczak Z, Bielski R and Poplawski T (2021), "Functionalized CARB Pharmacophore (FCP) approach to thio and unsaturated carbohydrate scaffolds with potential anticancer activity", Carbohydrate Chemistry. Vol. 44, pp. 130-150. Royal Society of Chemistry. |
| Abstract: This brief review discusses some new developments in the functionalized carb pharmacophore (FCP) concept introduced by us in 2014. While the examples concentrate mainly on biological data of selected newly designed carbohydrate molecules, the chemical syntheses are also included. This review also summarizes new developments in the stereoselective synthesis of 1,4-S-thiodisaccharides and 4-S-thiosaccharides, from levoglucosenone (LG) and a preliminary evaluation of their biological activity. New methodologies utilizing a saturated analog of levoglucosenone, dihydrolevoglucosenone (DHLG), in the synthesis of derivative enones bearing heterocyclic and aromatic moieties at the exocyclic position are also discussed. All exocyclic enones were prepared in good yields by straightforward direct aldol condensation of heterocyclic and aromatic aldehydes with dihydrolevoglucosenone under base conditions. When o-hydroxybenzaldehydes were used as substrates, the original condensation was followed by cyclization forming the domino product, a carbohydrate-fused chromanone system. Additionally, when o-hydroxyacetophenones were used, the base catalysed condensation furnished spiro-chromanones in excellent yield. The stereoselectivities of all reactions are discussed and plausible reaction mechanisms are proposed for the formation of chromanone and spiro-chromanone. © The Royal Society of Chemistry 2021. |
BibTeX:
@article{Witczak2021130,
author = {Witczak, Z.J. and Bielski, R. and Poplawski, T.},
title = {Functionalized CARB Pharmacophore (FCP) approach to thio and unsaturated carbohydrate scaffolds with potential anticancer activity},
journal = {Carbohydrate Chemistry},
publisher = {Royal Society of Chemistry},
year = {2021},
volume = {44},
pages = {130-150},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85094162673&doi=10.1039%2f9781788013864-00130&partnerID=40&md5=dd8e289d13b264d043646e1d72cac77a},
doi = {10.1039/9781788013864-00130}
}
|
| Morawska K, Popławski T, Ciesielski W and Smarzewska S (2020), "Interactions of lamotrigine with single- and double-stranded DNA under physiological conditions", Bioelectrochemistry. Vol. 136 Elsevier B.V.. |
| Abstract: This study presents evaluation of the possible mechanisms of interaction between the antiepileptic drug lamotrigine (LMT) and single- and double-stranded DNA (ssDNA and dsDNA, respectively). These interactions were studied in phosphate-buffered saline (PBS) at physiological pH 7.4 by cyclic voltammetry (CV) and square wave voltammetry (SWV) using a glassy carbon electrode (GCE) in a bulk incubated solution. The addition of both types of DNA to LMT solution decreased peak currents and led to a negative shift in peak potentials, thus indicating the dominance of electrostatic interactions. UV–Vis absorption spectroscopy was also used to assess the interaction between ds/ssDNA and LMT. The data obtained from spectroscopic analysis confirmed that electrostatic interaction is the predominant interaction between LMT and both types of DNA. The calculated binding constants for LMT-dsDNA and LMT-ssDNA complexes as determined by SWV were 6.46 × 105 and 1.81 × 106, respectively, while the values obtained from UV–Vis spectroscopy were 6.93 × 105 and 1.19 × 106, respectively. The obtained results indicated a higher affinity of LMT for ssDNA than for dsDNA. © 2020 Elsevier B.V. |
BibTeX:
@article{Morawska2020,
author = {Morawska, K. and Popławski, T. and Ciesielski, W. and Smarzewska, S.},
title = {Interactions of lamotrigine with single- and double-stranded DNA under physiological conditions},
journal = {Bioelectrochemistry},
publisher = {Elsevier B.V.},
year = {2020},
volume = {136},
note = {cited By 8},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089340434&doi=10.1016%2fj.bioelechem.2020.107630&partnerID=40&md5=cd1327d06f25e2ecc14e70d3b23f1059},
doi = {10.1016/j.bioelechem.2020.107630}
}
|
| Chojnacki C, Popławski T, Chojnacki J, Fila M, Konrad P and Blasiak J (2020), "Tryptophan intake and metabolism in older adults with mood disorders", Nutrients. Vol. 12(10), pp. 1-11. MDPI AG. |
| Abstract: The role of serotonin in the pathogenesis of depression is well-documented, while the involvement of other tryptophan (TRP) metabolites generated in the kynurenine pathway is less known. The aim of this study was to assess the intake and metabolism of TRP in elderly patients with mood disorders. Ninety subjects in three groups, 30 subjects each, were enrolled in this study: controls (healthy young adults, group I) and elderly individuals without (group II) or with (group III) symptoms of mild and moderate depression, as assessed by the Hamilton Depression Rating Scale (HAM-D) and further referred to as mood disorders. The average TRP intake was evaluated with the nutrition calculator. Urinary levels of TRP, 5-hydroxyindoleacetic acid (5-HIAA), L-kynurenine (KYN), kynurenic acid (KynA), xanthurenic acid (XA), and quinolinic acid (QA) were determined by liquid chromatography with tandem mass spectrometry and related to creatinine level. The average daily intake of TRP was significantly lower in group III than the remaining two groups, but group III was also characterized by higher urinary levels of KYN, KynA, XA, and QA as compared with younger adult individuals and elderly patients without mood disorders. Therefore, mild and moderate depression in the elderly may be associated with a lower intake of TRP and changes in its kynurenine metabolic pathway, which suggests a potential dietary TRP-based intervention in this group of patients. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. |
BibTeX:
@article{Chojnacki20201,
author = {Chojnacki, C. and Popławski, T. and Chojnacki, J. and Fila, M. and Konrad, P. and Blasiak, J.},
title = {Tryptophan intake and metabolism in older adults with mood disorders},
journal = {Nutrients},
publisher = {MDPI AG},
year = {2020},
volume = {12},
number = {10},
pages = {1-11},
note = {cited By 21},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092705167&doi=10.3390%2fnu12103183&partnerID=40&md5=ba4c9266bb827d011702725c341c035b},
doi = {10.3390/nu12103183}
}
|
| Szejk-Arendt M, Czubak-Prowizor K, Macieja A, Poplawski T, Olejnik A, Pawlaczyk-Graja I, Gancarz R and Zbikowska H (2020), "Polyphenolic-polysaccharide conjugates from medicinal plants of Rosaceae/Asteraceae family protect human lymphocytes but not myeloid leukemia K562 cells against radiation-induced death", International Journal of Biological Macromolecules. Vol. 156, pp. 1445-1454. Elsevier B.V.. |
| Abstract: The aim of the study was to investigate whether the polyphenolic-polysaccharide conjugates (PPCs), isolated from flowers of Sanguisorba officinalis L. and Erigeron canadensis L., and from leaves of Fragaria vesca L. and Rubus plicatus Whe. Et N. E., can protect human peripheral blood mononuclear cells (PBMCs) against gamma-irradiation damage while maintaining the radiosensitivity of the myeloid leukemia K562 cell line. PPCs isolated from the four plant sources are water-soluble macromolecules (14–50 kDa) that were previously chemically and structurally characterized. Cells were incubated with PPCs (25 μg/ml, 1 h) prior exposure to 15 Gy gamma-irradiation, non-irradiated appropriate samples served as controls. It was found that the PPCs were able to increase the post-radiation viability of PBMCs by inhibiting apoptosis, while they did not protect the leukemic cells against radiation-induced apoptotic death. The PPCs offered an efficient protection of PBMCs through scavenging of intracellular ROS and decreasing DNA damage, while they provided no reduction of the oxidative stress and DNA damage in K562 cells. Our findings strongly suggest that the PPCs, especially these isolated from S. officinalis and E. canadensis, can selectively protect normal lymphocytes against radiation injury, therefore they meet the criteria of radioprotectors for potential use in radiotherapy. © 2019 Elsevier B.V. |
BibTeX:
@article{Szejk-Arendt20201445,
author = {Szejk-Arendt, M. and Czubak-Prowizor, K. and Macieja, A. and Poplawski, T. and Olejnik, A.K. and Pawlaczyk-Graja, I. and Gancarz, R. and Zbikowska, H.M.},
title = {Polyphenolic-polysaccharide conjugates from medicinal plants of Rosaceae/Asteraceae family protect human lymphocytes but not myeloid leukemia K562 cells against radiation-induced death},
journal = {International Journal of Biological Macromolecules},
publisher = {Elsevier B.V.},
year = {2020},
volume = {156},
pages = {1445-1454},
note = {cited By 11},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086135347&doi=10.1016%2fj.ijbiomac.2019.11.186&partnerID=40&md5=fe6ee053e5414da9e4611206ea97f658},
doi = {10.1016/j.ijbiomac.2019.11.186}
}
|
| Galita G, Brzezińska O, Gulbas I, Sarnik J, Poplawska M, Makowska J and Poplawski T (2020), "Increased sensitivity of PBMCs isolated from patients with rheumatoid arthritis to DNA damaging agents is connected with inefficient DNA repair", Journal of Clinical Medicine. Vol. 9(4) MDPI. |
| Abstract: Rheumatoid arthritis (RA) is a systemic, inflammatory disease of the joints and surrounding tissues. RA manifests itself with severe joint pain, articular inflammation, and oxidative stress. RA is associated with certain types of cancer. We have assumed that RA patients’ increased susceptibility to cancer may be linked with genomic instability induced by impaired DNA repair and sensitivity to DNA damaging agents. The aim of this work was to analyze the sensitivity of peripheral blood mononuclear cells (PBMCs) isolated from RA patients to DNA damaging agents: tert-butyl hydroperoxide (TBH), bleomycin, ultraviolet (UV) radiation, and methyl methanesulfonate (MMS) and calculate the repair efficiency. TBH induce oxidative DNA lesions repaired mainly by base excision repair (BER). Bleomycin induced mainly DNA double-strand breaks repaired by non-homologous end joining (NHEJ) and homologous recombination repair (HRR). We included 20 rheumatoid arthritis patients and 20 healthy controls and used an alkaline version of the comet assay with modification to measure sensitivity to DNA damaging agents and DNA repair efficiency. We found an increased number of DNA breaks and alkali-labile sites in the RA patients compared to those in the controls. Exposure to DNA damaging agents evoked the same increased damage in both groups, but we observed statistically higher PMBC sensitivity to TBH, MMS, bleomycin as well as UV. Examination of the repair kinetics of both groups revealed that the DNA lesions induced by TBH and bleomycin were more efficiently repaired in the controls than in the patients. These data suggest impaired DNA repair in RA patients, which may accelerate PBMC aging and/or lead to higher cancer incidence among RA patients. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. |
BibTeX:
@article{Galita2020,
author = {Galita, G. and Brzezińska, O. and Gulbas, I. and Sarnik, J. and Poplawska, M. and Makowska, J. and Poplawski, T.},
title = {Increased sensitivity of PBMCs isolated from patients with rheumatoid arthritis to DNA damaging agents is connected with inefficient DNA repair},
journal = {Journal of Clinical Medicine},
publisher = {MDPI},
year = {2020},
volume = {9},
number = {4},
note = {cited By 9},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85107266286&doi=10.3390%2fjcm9040988&partnerID=40&md5=12f2e5ccf3cb584209a6f4927271d4e5},
doi = {10.3390/jcm9040988}
}
|
| Sarnik J, Gajek A, Toma M, Pawelczyk J, Rykowski S, Olejniczak A, Sliwinski T, Bielski R, Witczak Z and Poplawski T (2020), "(1–4)-Thiodisaccharides as anticancer agents. Part 5. Evaluation of anticancer activity and investigation of mechanism of action", Bioorganic and Medicinal Chemistry Letters. Vol. 30(4) Elsevier Ltd. |
| Abstract: (1–4)-Thiodisaccharides, thiosugars with the 1–4-thio bridge, were recently shown to induce oxidative stress, as well as, apoptosis in cancer cells in the low micromolar range; however, the detailed mechanism of their anticancer action still remains unknown. In order to clarify the mechanism of (1–4)- thiodisaccharides action, we performed a series of tests including cytotoxic, clonogenic and apoptosis assays using an in vitro glioma cancer model with one ATCC cell line U87 and two novel glioma cell lines derived from cancer patients – H6PX and H7PX. We also evaluated the ability of (1–4)-thiodisaccharides to interfere with protein folding and synthesis processes, as well as, the thioredoxin system. (1–4)-thiodisaccharides induced glioma cell death, which were found to be accompanied with endoplasmic reticulum stress, inhibition of global protein synthesis, reduced overall cellular thiol level and thioredoxin reductase activity. We also performed a RT-PCR and Elisa analysis of (1–4)-thiodisaccharides-treated glioma cells to identify any changes within the pathway affected by (1–4)-thiodisaccharides. We observed a significant increase of expression in key markers of endoplasmic reticulum stress and pro-apoptotic protein, FASLG. We proposed that (1–4)-thiodisaccharides react with cellular thiols and disturb any cellular thiol-depended processes like thioredoxin system or protein folding. © 2019 Elsevier Ltd |
BibTeX:
@article{Sarnik2020,
author = {Sarnik, J. and Gajek, A. and Toma, M. and Pawelczyk, J. and Rykowski, S. and Olejniczak, A. and Sliwinski, T. and Bielski, R. and Witczak, Z.J. and Poplawski, T.},
title = {(1–4)-Thiodisaccharides as anticancer agents. Part 5. Evaluation of anticancer activity and investigation of mechanism of action},
journal = {Bioorganic and Medicinal Chemistry Letters},
publisher = {Elsevier Ltd},
year = {2020},
volume = {30},
number = {4},
note = {cited By 10},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077171942&doi=10.1016%2fj.bmcl.2019.126904&partnerID=40&md5=41c328272b4539c146e8782f69311413},
doi = {10.1016/j.bmcl.2019.126904}
}
|
| Chojnacki C, Poplawski T, Blasiak J, Fila M, Konrad P and Chojnacki J (2020), "Altered dopamine signalling in chronic epigastric pain syndrome", Journal of Physiology and Pharmacology. Vol. 71(6) Polish Physiological Society. |
| Abstract: Chronic epigastric pain syndrome (CEPS) is an important diagnostic problem, especially in patients without macroscopic and microscopic changes in gastric mucosa. The cause of this ailment is unclear. The aim of this study was the assessment of coexistence between symptoms of this syndrome and secretion level of dopamine (DA), as well as the efficacy of peripheral and central D2 receptors antagonist. Sixty depressive patients with CEPS occurring independently of the diet and with no Helicobacter pylori infection and 30 healthy subjects were enrolled in this study. Plasma DA and urinary homovanilic acid (HVA) concentration were measured by ELISA, and the mRNA expression of dopa decarboxylase (DDC) in gastric mucosa was evaluated by RT-PCR in 30 patients with CEPS and 30 controls. Severity of epigastric pain before and after 12 weeks 2 × 50 mg itopride or sulpiride treatment was evaluated using the modified 10-point Visual Analogue Scale. Higher average levels of plasma DA and urinary HVA levels in CEPS patients than controls 129.5 ± 22.0 versus 109.1 ± 18.4 pg/ml (p < 0.001) and 6.82 ± 1.55 versus 5.39 ± 1.04 mg/24 h, respectively were obtained. Moreover, the expression of DDC in gastric mucosa of CEPS patients was higher than in healthy subjects (p < 0.01). Sulpiride subsided epigastric pain in 73.3%, but itopride reduced it only in 6.6% of CEPS patients. We concluded that altered dopamine signalling may affect locally-and-centrally mediated chronic epigastric pain. © 2020, Polish Physiological Society. All rights reserved. |
BibTeX:
@article{Chojnacki2020,
author = {Chojnacki, C. and Poplawski, T. and Blasiak, J. and Fila, M. and Konrad, P. and Chojnacki, J.},
title = {Altered dopamine signalling in chronic epigastric pain syndrome},
journal = {Journal of Physiology and Pharmacology},
publisher = {Polish Physiological Society},
year = {2020},
volume = {71},
number = {6},
note = {cited By 3},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85103144259&doi=10.26402%2fjpp.2020.6.05&partnerID=40&md5=63f2ea9f42a17af011f7ba2703bc2b72},
doi = {10.26402/jpp.2020.6.05}
}
|
| Kopa P, Macieja A, Gulbas I, Pastwa E and Poplawski T (2020), "Inhibition of DNA-PK potentiates the synergistic effect of NK314 and etoposide combination on human glioblastoma cells", Molecular Biology Reports. Vol. 47(1), pp. 67-76. Springer. |
| Abstract: Etoposide (VP-16) is the topoisomerase 2 (Top2) inhibitor used for treating of glioma patients however at high dose with serious side effects. It induces DNA double-strand breaks (DSBs). These DNA lesions are repaired by non-homologous DNA end joining (NHEJ) mediated by DNA-dependent protein kinase (DNA-PK). One possible approach to decrease the toxicity of etoposide is to reduce the dose while maintaining the anticancer potential. It could be achieved through combined therapy with other anticancer drugs. We have assumed that this objective can be obtained by (1) a parallel topo2 α inhibition and (2) sensitization of cancer cells to DSBs. In this work we investigated the effect of two Top2 inhibitors NK314 and VP-16 in glioma cell lines (MO59 K and MO59 J) sensitized by DNA-PK inhibitor, NU7441. Cytotoxic effect of VP-16, NK314 alone and in combination on human glioblastoma cell lines, was assessed by a colorimetric assay. Genotoxic effect of anticancer drugs in combination with NU7441 was assessed by comet assay. Cell cycle distribution and apoptosis were analysed by flow cytometry. Compared with VP-16 or NK314 alone, the combined treatment significantly inhibited cell proliferation. Combination treatment was associated with a strong accumulation of DSBs, modulated cell cycle phases distribution and apoptotic cell death. NU7441 potentiated these effects and additionally postponed DNA repair. Our findings suggest that NK314 could overcome resistance of MO59 cells to VP-16 and NU7441 could serve as sensitizer to VP-16/NK314 combined treatment. The combined tripartite approach of chemotherapy could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the anticancer effect to treat human glioma cells. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than mono therapy or dual therapy to treat and increase the survival of the glioblastoma patients. © 2019, The Author(s). |
BibTeX:
@article{Kopa202067,
author = {Kopa, P. and Macieja, A. and Gulbas, I. and Pastwa, E. and Poplawski, T.},
title = {Inhibition of DNA-PK potentiates the synergistic effect of NK314 and etoposide combination on human glioblastoma cells},
journal = {Molecular Biology Reports},
publisher = {Springer},
year = {2020},
volume = {47},
number = {1},
pages = {67-76},
note = {cited By 9},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073992959&doi=10.1007%2fs11033-019-05105-x&partnerID=40&md5=d131962149ac518d203299a1416af795},
doi = {10.1007/s11033-019-05105-x}
}
|
| Macieja A, Kopa P, Galita G, Pastwa E, Majsterek I and Poplawski T (2019), "Comparison of the effect of three different topoisomerase II inhibitors combined with cisplatin in human glioblastoma cells sensitized with double strand break repair inhibitors", Molecular Biology Reports. Vol. 46(4), pp. 3625-3636. Springer Netherlands. |
| Abstract: Topoisomerase II (Topo2) inhibitors in combination with cisplatin represent a common treatment modality used for glioma patients. The main mechanism of their action involves induction of DNA double-strand breaks (DSBs). DSBs are repaired via the homology-dependent DNA repair (HRR) and non-homologous end-joining (NHEJ). Inhibition of the NHEJ or HRR pathway sensitizes cancer cells to the treatment. In this work, we investigated the effect of three Topo2 inhibitors—etoposide, NK314, or HU-331 in combination with cisplatin in the U-87 human glioblastoma cell line. Etoposide as well as NK314 inhibited Topo2 activity by stabilizing Topo2-DNA cleavable complexes whereas HU-331 inhibited the ATPase activity of Topo2 using a noncompetitive mechanism. To increase the effectiveness of the treatment, we combined cisplatin and Topo2 inhibitor treatment with DSB repair inhibitors (DRIs). The cells were sensitized with NHEJ inhibitor, NU7441, or the novel HRR inhibitor, YU238259, prior to drug treatment. All of the investigated Topo2 inhibitors in combination with cisplatin efficiently killed the U-87 cells. The most cytotoxic effect was observed for the cisplatin + HU331 treatment scheme and this effect was significantly increased when a DRI pretreatment was used; however, we did not observed DSBs. Therefore, the molecular mechanism of cytotoxicity caused by the cisplatin + HU331 treatment scheme is yet to be evaluated. We observed a concentration-dependent change in DSB levels and accumulation at the G2/M checkpoint and S-phase in glioma cells incubated with NK314/cisplatin and etoposide/cisplatin. In conclusion, in combination with cisplatin, HU331 is the most potent Topo2 inhibitor of human glioblastoma cells. © 2019, The Author(s). |
BibTeX:
@article{Macieja20193625,
author = {Macieja, A. and Kopa, P. and Galita, G. and Pastwa, E. and Majsterek, I. and Poplawski, T.},
title = {Comparison of the effect of three different topoisomerase II inhibitors combined with cisplatin in human glioblastoma cells sensitized with double strand break repair inhibitors},
journal = {Molecular Biology Reports},
publisher = {Springer Netherlands},
year = {2019},
volume = {46},
number = {4},
pages = {3625-3636},
note = {cited By 16},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064946755&doi=10.1007%2fs11033-019-04605-0&partnerID=40&md5=dba35ab47c82f036c64749f8b366aa95},
doi = {10.1007/s11033-019-04605-0}
}
|
| Poplawski T (2019), "DNA damage response as a pharmacological target for cancer and infectious diseases", Current Medicinal Chemistry. Vol. 26(8), pp. 1423-1424. Bentham Science Publishers. |
BibTeX:
@article{Poplawski20191423,
author = {Poplawski, T.},
title = {DNA damage response as a pharmacological target for cancer and infectious diseases},
journal = {Current Medicinal Chemistry},
publisher = {Bentham Science Publishers},
year = {2019},
volume = {26},
number = {8},
pages = {1423-1424},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068135860&doi=10.2174%2f092986732608190516092613&partnerID=40&md5=d52033662390b5adecf449dddb717c7a},
doi = {10.2174/092986732608190516092613}
}
|
| Poplawski T, Pytel D, Dziadek J and Majsterek I (2019), "Interplay between Redox Signaling, Oxidative Stress, and Unfolded Protein Response (UPR) in Pathogenesis of Human Diseases", Oxidative Medicine and Cellular Longevity. Vol. 2019 Hindawi Limited. |
BibTeX:
@article{Poplawski2019,
author = {Poplawski, T. and Pytel, D. and Dziadek, J. and Majsterek, I.},
title = {Interplay between Redox Signaling, Oxidative Stress, and Unfolded Protein Response (UPR) in Pathogenesis of Human Diseases},
journal = {Oxidative Medicine and Cellular Longevity},
publisher = {Hindawi Limited},
year = {2019},
volume = {2019},
note = {cited By 12},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066879119&doi=10.1155%2f2019%2f6949347&partnerID=40&md5=a979009df733d8d8fa8257c9833652ff},
doi = {10.1155/2019/6949347}
}
|
| Rozpedek W, Pytel D, Poplawski T, Walczak A, Gradzik K, Wawrzynkiewicz A, Wojtczak R, Mucha B, Diehl J and Majsterek I (2019), "Inhibition of the PERK-dependent unfolded protein response signaling pathway involved in the pathogenesis of Alzheimer’s disease", Current Alzheimer Research. Vol. 16(3), pp. 209-218. Bentham Science Publishers B.V.. |
| Abstract: Objectives: There is a body of evidence that neurodegenerative disease entities are directly correlated with the perturbations on the molecular level. Hence, the ER stress-mediated Unfolded Protein Response (UPR) is activated resulting in PERK-dependent phosphorylation of the Eukaryotic initiation factor 2 (eIF2α). Thus, the levels of ATF4 and CHOP proteins are significantly increased, which subsequently switches the pro-adaptive branch of the UPR into the pro-apoptotic directly leading to neuronal loss and initiation of the neurodegenerative process. The aim of the presented study was the evaluation of the biological activity of highly specific, small-molecule inhibitors of the PERKdependent UPR signaling pathway. Methods: The study was conducted on rat astrocytic DI TNC1 cell line. The level of p-eIF2α was measured by Western blot technique, the cytotoxicity of the investigated compound was assessed by the MTT assay and using the FITC-conjugated Annexin V (Annexin V-FITC) to indicate apoptosis and propidium iodide (PI) to indicate necrosis. The effect of tested compound on cell cycle progression was measured by flow cytometry, where the PI-labelled nuclei were analysed for DNA content. Results: As a result one of the investigated compound LDN-0060609 triggers a significant inhibition of the eIF2α phosphorylation in DI TNC1 cell line. Moreover, we showed that compound LDN-0060609 is non-cytotoxic and has no effect on cell cycle progression. Conclusion: In conclusion, LDN-0060609 may constitute a novel, targeted treatment approach against neurodegenerative diseases, including Alzheimer’s disease (AD), where pathogenesis and progression are closely associated with the overactivation of the PERK-dependent UPR signaling pathway. © 2019 Bentham Science Publishers. |
BibTeX:
@article{Rozpędek2019209,
author = {Rozpedek, W. and Pytel, D. and Poplawski, T. and Walczak, A. and Gradzik, K. and Wawrzynkiewicz, A. and Wojtczak, R. and Mucha, B. and Diehl, J.A. and Majsterek, I.},
title = {Inhibition of the PERK-dependent unfolded protein response signaling pathway involved in the pathogenesis of Alzheimer’s disease},
journal = {Current Alzheimer Research},
publisher = {Bentham Science Publishers B.V.},
year = {2019},
volume = {16},
number = {3},
pages = {209-218},
note = {cited By 17},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064239261&doi=10.2174%2f1567205016666190228121157&partnerID=40&md5=4c225960d3e93887d56742160f98b7d9},
doi = {10.2174/1567205016666190228121157}
}
|
| Chojnacki C, Poplawski T, Blonska A, Blasiak J, Romanowski M and Chojnacki J (2019), "Expression of tryptophan hydroxylase in gastric mucosa in symptomatic and asymptomatic Helicobacter pylori infection", Archives of Medical Science. Vol. 15(2), pp. 416-423. Termedia Publishing House Ltd.. |
| Abstract: Introduction: Helicobacter pylori infection induces clinical symptoms in 15–20% of subjects, and the reason for this variation is still not clear. The aim of the present study is to evaluate the expression of tryptophan hydroxylase (TpH-1) in gastric mucosa of patients with symptomatic and asymptomatic H. pylori infection in relation to the intensity of bacterial colonization and severity of dyspeptic symptoms. Material and methods: Ninety subjects (aged 35–49 years) were enrolled in the study and separated into 3 groups of 30 subjects each. Group I – healthy volunteers without H. pylori infection, group II – subjects with asymptomatic H. pylori infection, group III – H. pylori-infected patients with dyspeptic symptoms, mainly fasting and nocturnal epigastric pain. To diagnose H. pylori infection the urea breath test (UBT-13C) and histological analysis were performed. The level of mRNA expression of tryptophan hydroxylase (TpH-1) was estimated in gastric mucosa with RT-PCR. Results: The expression of this enzyme in antral mucosa was 2.69 ±0.97 in group I, 2.28 ±0.69 in group II (p > 0.05) and 4.40 ±1.64 in group III (p < 0.001). The levels of expression of TpH-1 in gastric body mucosa were 2.16 ±0.70, 1.57 ±0.52 (p > 0.05) and 3.40 ±1.51 (p < 0.001), respectively. In group III a positive correlation was found between intensity of H. pylori colonization and TpH-1 expression as well as between TpH-1 expression and severity of dyspeptic symptoms. Conclusions: Increased expression of TpH-1 in gastric mucosa plays a role in pathogenesis of chronic dyspepsia. Copyright © 2018 Termedia & Banach. |
BibTeX:
@article{Chojnacki2019416,
author = {Chojnacki, C. and Poplawski, T. and Blonska, A. and Blasiak, J. and Romanowski, M. and Chojnacki, J.},
title = {Expression of tryptophan hydroxylase in gastric mucosa in symptomatic and asymptomatic Helicobacter pylori infection},
journal = {Archives of Medical Science},
publisher = {Termedia Publishing House Ltd.},
year = {2019},
volume = {15},
number = {2},
pages = {416-423},
note = {cited By 3},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062729975&doi=10.5114%2faoms.2018.76928&partnerID=40&md5=a9bcbb3b6551af75afc03089fafc6712},
doi = {10.5114/aoms.2018.76928}
}
|
| Kopa P, Macieja A, Galita G, Witczak Z and Poplawski T (2019), "DNA double strand breaks repair inhibitors: Relevance as potential new anticancer therapeutics", Current Medicinal Chemistry. Vol. 26(8), pp. 1483-1493. Bentham Science Publishers. |
| Abstract: DNA double-strand breaks are considered one of the most lethal forms of DNA damage. Many effective anticancer therapeutic approaches used chemical and physical methods to generate DNA double-strand breaks in the cancer cells. They include: IR and drugs which mimetic its action, topoisomerase poisons, some alkylating agents or drugs which affected DNA replication process. On the other hand, cancer cells are mostly characterized by highly effective systems of DNA damage repair. There are two main DNA repair pathways used to fix double-strand breaks: NHEJ and HRR. Their activity leads to a decreased effect of chemotherapy. Targeting directly or indirectly the DNA double-strand breaks response by inhibitors seems to be an exciting option for anticancer therapy and is a part of novel trends that arise after the clinical success of PARP inhibitors. These trends will provide great opportunities for the development of DNA repair inhibitors as new potential anticancer drugs. The main objective of this article is to address these new promising advances. © 2019 Bentham Science Publishers. |
BibTeX:
@article{Kopa20191483,
author = {Kopa, P. and Macieja, A. and Galita, G. and Witczak, Z.J. and Poplawski, T.},
title = {DNA double strand breaks repair inhibitors: Relevance as potential new anticancer therapeutics},
journal = {Current Medicinal Chemistry},
publisher = {Bentham Science Publishers},
year = {2019},
volume = {26},
number = {8},
pages = {1483-1493},
note = {cited By 11},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059886297&doi=10.2174%2f0929867325666180214113154&partnerID=40&md5=7b989d04c4ab95e3b8aa57ad635d2764},
doi = {10.2174/0929867325666180214113154}
}
|
| Morawska K, Popławski T, Ciesielski W and Smarzewska S (2018), "Electrochemical and spectroscopic studies of the interaction of antiviral drug Tenofovir with single and double stranded DNA", Bioelectrochemistry. Vol. 123, pp. 227-232. Elsevier B.V.. |
| Abstract: In the present study, the electrochemical behavior of the antiviral drug tenofovir (tnf) on a boron-doped diamond electrode (BDDE) has been studied using square-wave voltammetry (SWV). The experimental conditions such as the supporting electrolyte composition and the SWV parameters were optimized. Under the optimized conditions, a simple and sensitive SWV procedure for tnf determination was developed in the concentration range of 5.0 × 10−6 to 1.0 × 10−4 mol L−1. The calculated limit of detection and limit of quantification were equal to 5.6 × 10−7 and 1.9 × 10−6 mol L−1, respectively. The biological significance of the developed method was demonstrated by a quantitative analysis of the pharmaceutical formulations Viread and Tenofovir disoproxil Teva. Moreover, both voltammetric and spectroscopic techniques were used to study the interaction between tnf and DNA. Changes in the electrochemical and spectroscopic behavior of tnf in the presence of DNA were used to calculate the binding constants of the formed complexes. The estimated values of Gibbs free energy revealed that the formation of the drug–DNA complexes was a spontaneous and favorable process. Moreover, for free and bound tenofovir, kinetic parameters such as heterogeneous rate constant, electron transfer coefficient, and diffusion coefficient were determined. © 2018 |
BibTeX:
@article{Morawska2018227,
author = {Morawska, K. and Popławski, T. and Ciesielski, W. and Smarzewska, S.},
title = {Electrochemical and spectroscopic studies of the interaction of antiviral drug Tenofovir with single and double stranded DNA},
journal = {Bioelectrochemistry},
publisher = {Elsevier B.V.},
year = {2018},
volume = {123},
pages = {227-232},
note = {cited By 32},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85048569834&doi=10.1016%2fj.bioelechem.2018.06.002&partnerID=40&md5=2f8f69f1d56f59138da42d90e6d7dc17},
doi = {10.1016/j.bioelechem.2018.06.002}
}
|
| Chojnacki C, Blasiak J, Fichna J, Chojnacki J and Poplawski T (2018), "Evaluation of melatonin secretion and metabolism exponents in patients with ulcerative and lymphocytic colitis", Molecules. Vol. 23(2) MDPI AG. |
| Abstract: Inflammatory bowel diseases, particularly ulcerative colitis (UC) and lymphocytic colitis (LC), affect many people. The role of melatonin in the pathogenesis of UC is precisely determined, whereas in LC it remains unknown. The aim of this study was to compare the expression of the melatonin-synthesizing enzymes tryptophan hydroxylase (TPH1), arylalkylamine-N-acetyltransferase (AANAT), and N-acetylserotonin methyltransferase (ASMT) in the colonic mucosa and urinary excretion of 6-sulfatoxymelatonin in patients with ulcerative and lymphocytic colitis. The study included 30 healthy subjects (group C), 30 patients with severe ulcerative colitis (group UC), and 30 patients with lymphocytic colitis (group LC). The diagnosis was based on endoscopic, histological, and laboratory examinations. Biopsy specimens were collected from right, transverse, and left parts of the colon. The levels of mRNA expression, TPH1, AANAT, and ASMT were estimated in the colonic mucosa with RT-PCR. The urine concentration of aMT6s was determined by the photometric method. The expression of TPH1, AANAT, and ASMT in colonic mucosa in UC and LC patients was significantly higher than in healthy subjects. Significant differences were found in the urinary aMT6s excretion: group C—13.4 ± 4.8 µg/24 h, group UC—7.8 ± 2.6 µg/24 h (p < 0.01), group LC—19.2 ± 6.1 µg/24 h (p < 0.01). Moreover, a negative correlation was found between fecal calprotectin and MT6s—in patients with UC − r = −0.888 and with LC − r = −0.658. These results indicate that patients with UC and those with LC may display high levels of melatonin-synthesizing enzymes in their colonic mucosa, which could possibly be related to increased melatonin synthesis as an adaptive antioxidant activity. © 2018 by the authors. |
BibTeX:
@article{Chojnacki2018,
author = {Chojnacki, C. and Blasiak, J. and Fichna, J. and Chojnacki, J. and Poplawski, T.},
title = {Evaluation of melatonin secretion and metabolism exponents in patients with ulcerative and lymphocytic colitis},
journal = {Molecules},
publisher = {MDPI AG},
year = {2018},
volume = {23},
number = {2},
note = {cited By 10},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041133898&doi=10.3390%2fmolecules23020272&partnerID=40&md5=b1115b71b5de25d5d1745854a8cf5286},
doi = {10.3390/molecules23020272}
}
|
| Guziejewski D, Morawska K, Popławski T, Metelka R, Ciesielski W and Smarzewska S (2018), "Lactofen – Electrochemical Sensing and Interaction with dsDNA", Electroanalysis. Vol. 30(1), pp. 94-100. Wiley-VCH Verlag. |
| Abstract: The electrochemical reduction of lactofen (LCT) at the glassy carbon (GCE) and silver amalgam film electrode (AMFE) is investigatedin detail by the means of square wave voltammetry (SWV), square wave stripping voltammetry (SWSV) and cyclic voltammetry. The influence of various factors such as supporting electrolyte composition and SW parameters were studied. The AMFE electrode showed an excellent electrochemical activity toward the electro-reduction of LCT, leading to a significant improvement in sensitivity as compared to the glassy carbon electrode.The SWSV detection limits for GCE and AMFE were 285.0 nM and 2.0 nM, respectively. The applicability of the developed voltammetric method for analysis of tap water and river water is illustrated with spiked samples analysis. Moreover, as lactofen is highly toxic to fish and other aquatic organisms, its interaction with dsDNA isolated from salmon sperm was tested. The intercalative mode of LCT binding to dsDNA was estimated. The heterogeneous rate constants were calculated for the free LCT and the LCT-dsDNA complex. Moreover, LCT-dsDNA complex binding ratio and equilibrium constant were determined. The decrease in the SWV peak current of LCT in the presence of dsDNA was used for the determination of dsDNA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
BibTeX:
@article{Guziejewski201894,
author = {Guziejewski, D. and Morawska, K. and Popławski, T. and Metelka, R. and Ciesielski, W. and Smarzewska, S.},
title = {Lactofen – Electrochemical Sensing and Interaction with dsDNA},
journal = {Electroanalysis},
publisher = {Wiley-VCH Verlag},
year = {2018},
volume = {30},
number = {1},
pages = {94-100},
note = {cited By 8},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033452147&doi=10.1002%2felan.201700472&partnerID=40&md5=f1440ced2f6377fb1855137698a1a370},
doi = {10.1002/elan.201700472}
}
|
| Sakowski S, Krasinski T, Waldmajer J, Sarnik J, Blasiak J and Poplawski T (2017), "Biomolecular computers with multiple restriction enzymes", Genetics and Molecular Biology. Vol. 40(4), pp. 860-870. Brazilian Journal of Genetics. |
| Abstract: The development of conventional, silicon-based computers has several limitations, including some related to the Heisenberg uncertainty principle and the von Neumann “bottleneck”. Biomolecular computers based on DNA and proteins are largely free of these disadvantages and, along with quantum computers, are reasonable alternatives to their conventional counterparts in some applications. The idea of a DNA computer proposed by Ehud Shapiro’s group at the Weizmann Institute of Science was developed using one restriction enzyme as hardware and DNA fragments (the transition molecules) as software and input/output signals. This computer represented a two-state two-symbol finite automaton that was subsequently extended by using two restriction enzymes. In this paper, we propose the idea of a multistate biomolecular computer with multiple commercially available restriction enzymes as hardware. Additionally, an algorithmic method for the construction of transition molecules in the DNA computer based on the use of multiple restriction enzymes is presented. We use this method to construct multistate, biomolecular, nondeterministic finite automata with four commercially available restriction enzymes as hardware. We also describe an experimental applicaton of this theoretical model to a biomolecular finite automaton made of four endonucleases. © 2017, Sociedade Brasileira de Genética. Printed in Brazil. |
BibTeX:
@article{Sakowski2017860,
author = {Sakowski, S. and Krasinski, T. and Waldmajer, J. and Sarnik, J. and Blasiak, J. and Poplawski, T.},
title = {Biomolecular computers with multiple restriction enzymes},
journal = {Genetics and Molecular Biology},
publisher = {Brazilian Journal of Genetics},
year = {2017},
volume = {40},
number = {4},
pages = {860-870},
note = {cited By 5},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85035745351&doi=10.1590%2f1678-4685-gmb-2016-0132&partnerID=40&md5=a3b4f1556e1f3d1b942d74514ef967ff},
doi = {10.1590/1678-4685-gmb-2016-0132}
}
|
| Sakowski S, Krasiński T, Sarnik J, Blasiak J, Waldmajer J and Poplawski T (2017), "A detailed experimental study of a DNA computer with two endonucleases", Zeitschrift fur Naturforschung - Section C Journal of Biosciences. Vol. 72(7-8), pp. 303-313. Walter de Gruyter GmbH. |
| Abstract: Great advances in biotechnology have allowed the construction of a computer from DNA. One of the proposed solutions is a biomolecular finite automaton, a simple two-state DNA computer without memory, which was presented by Ehud Shapiro's group at the Weizmann Institute of Science. The main problem with this computer, in which biomolecules carry out logical operations, is its complexity-increasing the number of states of biomolecular automata. In this study, we constructed (in laboratory conditions) a six-state DNA computer that uses two endonucleases (e.g. AcuI and BbvI) and a ligase. We have presented a detailed experimental verification of its feasibility. We described the effect of the number of states, the length of input data, and the nondeterminism on the computing process. We also tested different automata (with three, four, and six states) running on various accepted input words of different lengths such as ab, aab, aaab, ababa, and of an unaccepted word ba. Moreover, this article presents the reaction optimization and the methods of eliminating certain biochemical problems occurring in the implementation of a biomolecular DNA automaton based on two endonucleases. © 2017 Walter de Gruyter GmbH, Berlin/Boston. |
BibTeX:
@article{Sakowski2017303,
author = {Sakowski, S. and Krasiński, T. and Sarnik, J. and Blasiak, J. and Waldmajer, J. and Poplawski, T.},
title = {A detailed experimental study of a DNA computer with two endonucleases},
journal = {Zeitschrift fur Naturforschung - Section C Journal of Biosciences},
publisher = {Walter de Gruyter GmbH},
year = {2017},
volume = {72},
number = {7-8},
pages = {303-313},
note = {cited By 3},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85026753400&doi=10.1515%2fznc-2016-0137&partnerID=40&md5=9b7c8f20702faf1b30324364bb967365},
doi = {10.1515/znc-2016-0137}
}
|
| Szejk M, Poplawski T, Czubatka-Bienkowska A, Olejnik A, Pawlaczyk-Graja I, Gancarz R and Zbikowska H (2017), "A comparative study on the radioprotective potential of the polyphenolic glycoconjugates from medicinal plants of Rosaceae and Asteraceae families versus their aglycones", Journal of Photochemistry and Photobiology B: Biology. Vol. 171, pp. 50-57. Elsevier B.V.. |
| Abstract: Radioprotective potential of the polyphenolic glycoconjugates, isolated from flowers of Sanguisorba officinalis L. (So) and Erigeron canadensis L. (Ec), and from leaves of Fragaria vesca L. (Fv) and Rubus plicatus Whe. Et N. E. (Rp) as well as their aglycones (SoA, EcA, FvA and RpA, respectively), against γ-radiation-induced lipid peroxidation in human plasma and DNA damage in lymphocytes, were investigated in vitro. These properties were assessed by measuring the concentration of thiobarbituric acid reactive substances (TBARS) and using the alkaline comet assay, and were compared to the protective effects of rutin (R) and quercetin (Q). Cytotoxicity of the glycoconjugates/aglycones towards L929 mouse fibroblasts and human lymphocytes were also measured. Plant products from S. officinalis, similar to Q, were able to reduce the most radiation-induced lipid peroxidation as well as DNA damage and extent of oxidative damage to the DNA basis. Contrary to the pure flavonoids, where Q was shown to be significantly more effective than its glycoside R, the results did not show more benefit with application of SoA/EcA over So/Ec in terms of lipid peroxidation inhibition. Moreover, glycoconjugates Ec and So showed much higher capacity in protecting lymphocytes against radiation-induced genotoxicity which may suggest that between the polyphenolic and polysaccharide parts exist some synergistic effects. There were no significant differences between Fv versus FvA or Rp versus RpA in terms of the provided radioprotection. Summarizing, plant glycoconjugates isolated by the multi-step method offered sufficient radioprotection. In addition, they possess many advantages, compared to the synthetic polyphenolic compounds or the plant extracts, such as water-solubility and minor toxicity. © 2017 Elsevier B.V. |
BibTeX:
@article{Szejk201750,
author = {Szejk, M. and Poplawski, T. and Czubatka-Bienkowska, A. and Olejnik, A.K. and Pawlaczyk-Graja, I. and Gancarz, R. and Zbikowska, H.M.},
title = {A comparative study on the radioprotective potential of the polyphenolic glycoconjugates from medicinal plants of Rosaceae and Asteraceae families versus their aglycones},
journal = {Journal of Photochemistry and Photobiology B: Biology},
publisher = {Elsevier B.V.},
year = {2017},
volume = {171},
pages = {50-57},
note = {cited By 10},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018429624&doi=10.1016%2fj.jphotobiol.2017.04.027&partnerID=40&md5=cc088b1155ee3efbb333443c09f87a86},
doi = {10.1016/j.jphotobiol.2017.04.027}
}
|
| Korycka-Machala M, Brzostek A, Dziadek B, Kawka M, Poplawski T, Wtczak Z and DziadeK J (2017), "Evaluation of the mycobactericidal effect of thio-functionalized carbohydrate derivatives", Molecules. Vol. 22(5) MDPI AG. |
| Abstract: Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 ≤ 50 μM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential. © 2017 by the author. |
BibTeX:
@article{Korycka-Machala2017,
author = {Korycka-Machala, M. and Brzostek, A. and Dziadek, B. and Kawka, M. and Poplawski, T. and Wtczak, Z.J. and DziadeK, J.},
title = {Evaluation of the mycobactericidal effect of thio-functionalized carbohydrate derivatives},
journal = {Molecules},
publisher = {MDPI AG},
year = {2017},
volume = {22},
number = {5},
note = {cited By 12},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020185129&doi=10.3390%2fmolecules22050812&partnerID=40&md5=401eda8bfbd56e946a55578829714154},
doi = {10.3390/molecules22050812}
}
|
| Czubatka-Bienkowska A, Sarnik J, Macieja A, Galita G, Witczak Z and Poplawski T (2017), "Thio-functionalized carbohydrate thiosemicarbazones and evaluation of their anticancer activity", Bioorganic and Medicinal Chemistry Letters. Vol. 27(12), pp. 2713-2720. Elsevier Ltd. |
| Abstract: Thiosemicarbazides and their analogs have shown potential medical applications as antiviral, antibacterial and anticancer drugs. We designed, synthesized and evaluated in vitro anticancer activity against ovarian (A2780), cervix (HeLa), colon (LoVo), breast (MCF-7) and brain (MO59J) human cancer cell lines of seven novel compounds –S-glycosylated thiosemicarbazones. We assessed the cyto- and genotoxic properties of all novel compounds using a variety of methods including comet assay, XTT assay, various fluorescent assays and toxicology PathwayFinder expression array. We tried to evaluate their possible mechanism of action with particular attention to induction of DNA damage and repair, apoptosis, oxidative stress analysis and cellular response in terms of changes in gene expression. The most sensitive cell line was human ovarian cancer. The results revealed that the major activity against A2780 cancer cell line displayed by our compounds is induction of DNA damage. This effect is not associated with apoptosis or oxidative stress induction and the resulting damage will not lead to cell cycle arrest. We also observed up-expression of heat shock related genes and NQO1 gene in response to our compounds. The second effect seems to be specific to glycosylated S-bond compounds as we observed it earlier. Upregulation of heat shock protein encoding genes suggest that our compounds induce stressful conditions. The nature of this phenomena (heat shock, pH shift or hypoxia) needs further study. © 2017 Elsevier Ltd |
BibTeX:
@article{Czubatka-Bieńkowska20172713,
author = {Czubatka-Bienkowska, A. and Sarnik, J. and Macieja, A. and Galita, G. and Witczak, Z.J. and Poplawski, T.},
title = {Thio-functionalized carbohydrate thiosemicarbazones and evaluation of their anticancer activity},
journal = {Bioorganic and Medicinal Chemistry Letters},
publisher = {Elsevier Ltd},
year = {2017},
volume = {27},
number = {12},
pages = {2713-2720},
note = {cited By 16},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018876208&doi=10.1016%2fj.bmcl.2017.04.051&partnerID=40&md5=b9b533d18f5caffb1f08e3779440d0a5},
doi = {10.1016/j.bmcl.2017.04.051}
}
|
| Sarnik J, Czubatka-Bienkowska A, Macieja A, Bielski R, Witczak Z and Poplawski T (2017), "The induction of oxidative stress in cervix carcinoma cells by levoglucosenone derived 4-S-salicyl derivative and (1–4)-S-thio-disaccharides. Part 4", Bioorganic and Medicinal Chemistry Letters. Vol. 27(5), pp. 1215-1219. Elsevier Ltd. |
| Abstract: (1–4)-S-thiodisaccharides were shown to kill various cancer cell lines, including cervix, lung, mammary-gland and colon by unknown mechanisms. Here we identified two actions of levoglucosenone derived (1–4)-S-thiodisaccharides against cervix cancer cells: induction of oxidative stress and DNA damage. In consequence, (1–4)-S-thiodisaccharides lowered the cellular GSH level and changed the expression profile of genes encoding key proteins involved with oxidative stress response. We also observed that (1–4)-S-thiodisaccharides induced DNA damage and interfered with the thioredoxin (Trx) system. Both actions, as induced by FPC6, were stronger when dihedral angles of sulfur bridge were set to 110°, 100° and 109°, clearly indicating differences when compared to FPC8. These findings demonstrate that the 1–4-thio bridge of disaccharide is a powerful anticancer pharmacophore, and its potential use needs further studies. © 2017 Elsevier Ltd |
BibTeX:
@article{Sarnik20171215,
author = {Sarnik, J. and Czubatka-Bienkowska, A. and Macieja, A. and Bielski, R. and Witczak, Z.J. and Poplawski, T.},
title = {The induction of oxidative stress in cervix carcinoma cells by levoglucosenone derived 4-S-salicyl derivative and (1–4)-S-thio-disaccharides. Part 4},
journal = {Bioorganic and Medicinal Chemistry Letters},
publisher = {Elsevier Ltd},
year = {2017},
volume = {27},
number = {5},
pages = {1215-1219},
note = {cited By 7},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85011599321&doi=10.1016%2fj.bmcl.2017.01.064&partnerID=40&md5=9732783ef2ed32c688d5e81a41da724b},
doi = {10.1016/j.bmcl.2017.01.064}
}
|
| Czubatka-Bienkowska A, Macieja A, Sarnik J, Witczak Z and Poplawski T (2017), "The oxidative induction of DNA lesions in cancer cells by 5-thio-D-glucose and 6-thio-D-fructopyranose and their genotoxic effects. Part 3", Bioorganic and Medicinal Chemistry Letters. Vol. 27(5), pp. 1210-1214. Elsevier Ltd. |
| Abstract: Thio-sugars have been described as potent inhibitors of cancer cell growth but the detailed mechanism of action remains unknown. Herein we investigated the mechanism of their anticancer action in the HeLa cell line. We investigated two thio-sugars: 5-thio-D-glucose (FCP1) and 6-thio-β-D-fructopyranose (FCP2). We have observed that FCP1 as well as FCP2 clearly induced oxidative DNA lesions in cancer cells and increased the level of cellular ROS. A spin trap and antioxidants have decreased the level of DNA lesions induced by FCPs. FCPs also induced significant changes in the oxidative-stress gene expression. Therefore, we assume that ROS generation is correlated with the increased NOX5 expression by FCPs. Higher cyto- and genotoxicity of FCPs for HeLa cells in a low glucose environment suggested their role in the glucose metabolism. The data indicates that thio-sugars may become drug alternatives for the cancer treatment but such undertaking needs further studies. © 2017 Elsevier Ltd |
BibTeX:
@article{Czubatka-Bienkowska20171210,
author = {Czubatka-Bienkowska, A. and Macieja, A. and Sarnik, J. and Witczak, Z.J. and Poplawski, T.},
title = {The oxidative induction of DNA lesions in cancer cells by 5-thio-D-glucose and 6-thio-D-fructopyranose and their genotoxic effects. Part 3},
journal = {Bioorganic and Medicinal Chemistry Letters},
publisher = {Elsevier Ltd},
year = {2017},
volume = {27},
number = {5},
pages = {1210-1214},
note = {cited By 7},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85009770672&doi=10.1016%2fj.bmcl.2017.01.011&partnerID=40&md5=abc6c46309615981e8b6fb3eab4a57a1},
doi = {10.1016/j.bmcl.2017.01.011}
}
|
| Szejk M, Poplawski T, Sarnik J, Pawlaczyk-Graja I, Czechowski F, Olejnik A, Gancarz R and Zbikowska H (2017), "Polyphenolic glycoconjugates from medical plants of Rosaceae/Asteraceae family protect human lymphocytes against γ-radiation-induced damage", International Journal of Biological Macromolecules. Vol. 94, pp. 585-593. Elsevier B.V.. |
| Abstract: Radioprotective effects of the water-soluble polyphenolic glycoconjugates, isolated from flowers of Sanguisorba officinalis L.(SO) and Erigeron canadensis L.(EC), and from leaves of Fragaria vesca L. (FV) and Rubus plicatus Whe. Et N. E. (RP), against γ-radiation-induced toxicity in human peripheral blood lymphocytes were investigated. Cell treatment with glycoconjugates (1, 5 and 25 μg/mL) prior exposure to 10/15 Gy radiation resulted in concentration-dependent reduction of DNA damage including oxidative DNA lesions (comet assay), substantial inhibition of lipid peroxidation (TBARS) and restoration of superoxide dismutase and S-glutathione transferase activities. Glycoconjugates isolated from SO and EC ensured better protection versus these from RP and FV, with the SO product potential comparable to that of the reference quercetin. Strong antioxidant/radioprotective activity of the SO and EC glycoconjugates could be attributed to high abundance of syringol-type and ferulic acid units in their matrices, respectively. Moreover, polyphenolic glycoconjugates (25 μg/mL), including RP and FV products, significantly decreased DNA damage when applied post-radiation suggesting their modulating effects on DNA repair pathways. Preliminary data on the glycoconjugate phenolic structural units, based on GLC/MS of the products of pyrolysis and in situ methylation, in relation to application of plant products as potential radioprotectors is promising and deserves further investigation. © 2016 Elsevier B.V. |
BibTeX:
@article{Szejk2017585,
author = {Szejk, M. and Poplawski, T. and Sarnik, J. and Pawlaczyk-Graja, I. and Czechowski, F. and Olejnik, A.K. and Gancarz, R. and Zbikowska, H.M.},
title = {Polyphenolic glycoconjugates from medical plants of Rosaceae/Asteraceae family protect human lymphocytes against γ-radiation-induced damage},
journal = {International Journal of Biological Macromolecules},
publisher = {Elsevier B.V.},
year = {2017},
volume = {94},
pages = {585-593},
note = {cited By 12},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84994226428&doi=10.1016%2fj.ijbiomac.2016.10.053&partnerID=40&md5=c2b9a5c0148d2b3572ca31db85cab105},
doi = {10.1016/j.ijbiomac.2016.10.053}
}
|
| Sarnik J, Czubatka-Bieńkowska A, Dziadek J, Witczak Z and Popławski T (2016), "Thiosugars used as drugs [Polish]", Postepy biochemii. Vol. 62(4), pp. 526-534. |
| Abstract: Thiosugars are carbohydrate analogs in which one or few of the oxygen atoms were replaced by sulfur. The sulfur atom which is present in the furan and pyran structures, changes biological properties of carbohydrates, as compared to their oxygen analogs. Among others, thiosugars are effective inhibitors of various cellular and enzymatic pathways and also have great therapeutic potential. They are used as a drugs in diabetes and infectious diseases treatment. Recent evidence suggests that these compounds may have therapeutic properties and be also used in the treatment of some pathological conditions, including cancer diseases. This research are aimed towards the development and improvement of the current methods of synthesis of new thiosugars through stabilization of sulfur bonds and in vitro and in vivo analysis of their potential therapeutic properties. In this work the summary of the latest reports about thiosugars and their application in the medicine is presented for the first time in the Polish language literature. Tiocukry są analogami węglowodanów, w których jeden lub kilka atomów tlenu zostały zastąpione siarką. Atom siarki obecny w strukturze furanu lub piranu zmienia właściwości biologiczne węglowodanów, w porównaniu z ich zwierającymi atom tlenu odpowiednikami. Tiocukry są między innymi efektywnymi inhibitorami różnych komórkowych szlaków enzymatycznych i mają duży potencjał terapeutyczny, są wykorzystywane jako leki w leczeniu cukrzycy oraz chorób infekcyjnych. Ostatnio prowadzone są również badania sugerujące wykorzystanie tiocukrów jako leków w innych stanach patologicznych człowieka w tym do leczenia nowotworów. Badania te zmierzają w kierunku opracowania metod syntezy nowych tiocukrów, udoskonalenia obecnych poprzez stabilizację wiązań siarkowych oraz analizy in vitro i in vivo ich potencjalnych właściwości terapeutycznych. Najnowsze badania podsumowane w tej pracy są pierwszymi i jedynymi doniesieniami na temat tiocukrów i ich zastosowania w medycynie jakie dotąd ukazały się w polskiej literaturze naukowej. |
BibTeX:
@article{Sarnik2016526,
author = {Sarnik, J. and Czubatka-Bieńkowska, A. and Dziadek, J. and Witczak, Z.J. and Popławski, T.},
title = {Thiosugars used as drugs [Polish]},
journal = {Postepy biochemii},
year = {2016},
volume = {62},
number = {4},
pages = {526-534},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85038641498&partnerID=40&md5=0c2841b3610c6e3163a6114c66cc2a86}
}
|
| Poplawski T, Sobczuk A, Sarnik J, Pawlowska E and Blasiak J (2015), "Polymorphism of DNA mismatch repair genes in endometrial cancer", Experimental Oncology. Vol. 37(1), pp. 44-47. Morion LLC. |
| Abstract: Endometrial cancer (EC) is the second most common malignancy associated with hereditary non-polyposis colorectal cancer (HNPCC) family. The development of HNPCC is associated with defects in DNA mismatch repair (MMR) pathway resulting in microsatellite instability (MSI). MSI is present in a greater number of EC than can be accounted for by inherited MMR mutations, therefore alternative mechanisms may underline defective MMR in EC, including polymorphic variation. Aim: We checked the association between EC occurrence and two polymorphisms of MMR genes: a 1032G>A (rs4987188) transition in the hMSH2 gene resulting in a Gly22Asp substitution and a -93G>A (rs1800734) transition in the promoter of the hMLH1 gene. Material and methods: These polymorphisms were genotyped in DNA from peripheral blood lymphocytes of 100 EC patients and 100 age-matched women by restriction fragment length polymorphism PCR. Results: A positive association (OR 4.18; 95% CI 2.23-7.84) was found for the G/A genotype of the -93G>A polymorphism of the hMLH1 gene and EC occurrence. On the other hand, the A allele of this polymorphism was associated with decreased EC occurrence. The Gly/Gly genotype slightly increased the effect of the -93G>A-G/A genotype (OR 4.52; CI 2.41-8.49). Our results suggest that the -93G>A polymorphism of the hMLH1 gene singly and in combination with the Gly322Asp polymorphism of the hMSH2 gene may increase the risk of EC. Copyright © Experimental Oncology, 2015. |
BibTeX:
@article{Poplawski201544,
author = {Poplawski, T. and Sobczuk, A. and Sarnik, J. and Pawlowska, E. and Blasiak, J.},
title = {Polymorphism of DNA mismatch repair genes in endometrial cancer},
journal = {Experimental Oncology},
publisher = {Morion LLC},
year = {2015},
volume = {37},
number = {1},
pages = {44-47},
note = {cited By 6},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84927657300&doi=10.31768%2f2312-8852.2015.37%281%29%3a44-47&partnerID=40&md5=05bc4218ec72ddc78a5c860963f8a213},
doi = {10.31768/2312-8852.2015.37(1):44-47}
}
|
| Czubatka A, Sarnik J, Lucent D, Blasiak J, Witczak Z and Poplawski T (2015), "A novel carbohydrate derived compound FCP5 causes DNA strand breaks and oxidative modifications of DNA bases in cancer cells", Chemico-Biological Interactions. Vol. 227, pp. 77-88. Elsevier Ireland Ltd. |
| Abstract: 1,5-Anhydro-6-deoxy-methane-sulfamido-D-glucitol (FCP5) is a functionalized carbohydrate containing functional groups that render it potentially therapeutically useful. According to our concept of 'functional carb-pharmacophores' (FCPs) incorporation of the methanesulfonamido pharmacophore to 1,5 glucitol could create a therapeutically useful compound. Our previous studies revealed that FCP5 was cytotoxic to cancer cells. Therefore, in this work we assessed the cytotoxic mechanisms of FCP5 in four cancer cell lines - HeLa, LoVo, A549 and MCF-7, with particular focus on DNA damage and repair. A broad spectrum of methods, including comet assay with modifications, DNA repair enzyme assay, plasmid relaxation assay, and DNA fragmentation assay, were used. We also checked the potential for FCP5 to induce apoptosis. The results show that FCP5 can induce DNA strand breaks as well as oxidative modifications of DNA bases. DNA lesions induced by FCP5 were not entirely repaired in HeLa cells and DNA repair kinetics differs from other cell lines. Results from molecular docking and plasmid relaxation assay suggest that FCP5 binds to the major groove of DNA with a preference for adenosine-thymine base pair sequences and directly induces DNA strand breaks. Thus, FCP5 may represent a novel lead for the design of new major groove-binding compounds. The results also confirmed the validity of functional carb-pharmacophores as a new source of innovative drugs. © 2014 Elsevier Ireland Ltd. All rights reserved. |
BibTeX:
@article{Czubatka201577,
author = {Czubatka, A. and Sarnik, J. and Lucent, D. and Blasiak, J. and Witczak, Z.J. and Poplawski, T.},
title = {A novel carbohydrate derived compound FCP5 causes DNA strand breaks and oxidative modifications of DNA bases in cancer cells},
journal = {Chemico-Biological Interactions},
publisher = {Elsevier Ireland Ltd},
year = {2015},
volume = {227},
pages = {77-88},
note = {cited By 12},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84921327792&doi=10.1016%2fj.cbi.2014.12.023&partnerID=40&md5=e3a1dc294d627e0aad6222cc2e963318},
doi = {10.1016/j.cbi.2014.12.023}
}
|
| Witczak Z, Sarnik J, Czubatka A, Forma E and Poplawski T (2014), "Thio-sugar motif of functional CARB-pharmacophore for antineoplastic activity. Part 2", Bioorganic and Medicinal Chemistry Letters. Vol. 24(24), pp. 5606-5611. Elsevier Ltd. |
| Abstract: Diverse functionalized representatives of (1-4)-S-thiodisaccharides, 6-9 were synthesized and assessed for cytotoxicity and apoptosis against human cancer cell lines (A549, LoVo, MCF-7 and HeLa). The FCP 6 was more active against MCF-7 cells (i.e., an estrogen-dependent breast cancer line), whereas other (1-4)-S-thiodisaccharides showed strongest activity against A549 cells (i.e., a lung adenocarcinoma line). We propose to use a concept of functional 'CARB-pharmacophores' when evaluating a potential for the compounds' general antineoplastic activity. Future studies will determine the reasons for cell-type specificity of these compounds. The thio-sugar motif appears to be a promising lead for future developments. ©. |
BibTeX:
@article{Witczak20145606,
author = {Witczak, Z.J. and Sarnik, J. and Czubatka, A. and Forma, E. and Poplawski, T.},
title = {Thio-sugar motif of functional CARB-pharmacophore for antineoplastic activity. Part 2},
journal = {Bioorganic and Medicinal Chemistry Letters},
publisher = {Elsevier Ltd},
year = {2014},
volume = {24},
number = {24},
pages = {5606-5611},
note = {cited By 24},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84911920917&doi=10.1016%2fj.bmcl.2014.10.095&partnerID=40&md5=c039263f40679b1c12963a85cced6a56},
doi = {10.1016/j.bmcl.2014.10.095}
}
|
| Witczak Z, Poplawski T, Czubatka A, Sarnik J, Tokarz P, Vanwert A and Bielski R (2014), "A potential CARB-pharmacophore for antineoplastic activity: Part 1", Bioorganic and Medicinal Chemistry Letters. Vol. 24(7), pp. 1752-1757. Elsevier Ltd. |
| Abstract: Diverse functionalized representatives of various classes of sugars, such as thio-, anhydro-, and sulfamido-sugars and myo-inositol oxide, were synthesized and assessed for cytotoxicity against human cancer cell lines (A549, LoVo, MCF-7 and HeLa). The inositol oxide (4) was more active against MCF-7 cells (i.e., an estrogen-dependent breast cancer line), whereas all 3 sulfur-containing compounds showed strongest activity against A549 cells (i.e., a lung adenocarcinoma line). We propose to use a concept of functional 'CARB-pharmacophores' when evaluating a potential for the compounds' general antineoplastic activity. Future studies will determine the reasons for cell-type specificity of these compounds. The thio-sugar motif appears to be a promising lead for future developments. © 2014 Elsevier Ltd. All rights reserved. |
BibTeX:
@article{Witczak20141752,
author = {Witczak, Z.J. and Poplawski, T. and Czubatka, A. and Sarnik, J. and Tokarz, P. and Vanwert, A.L. and Bielski, R.},
title = {A potential CARB-pharmacophore for antineoplastic activity: Part 1},
journal = {Bioorganic and Medicinal Chemistry Letters},
publisher = {Elsevier Ltd},
year = {2014},
volume = {24},
number = {7},
pages = {1752-1757},
note = {cited By 21},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897413915&doi=10.1016%2fj.bmcl.2014.02.036&partnerID=40&md5=3f255088139913df481218f41d018aa4},
doi = {10.1016/j.bmcl.2014.02.036}
}
|
| Pastwa E, Poplawski T, Lewandowska U, Somiari S, Blasiak J and Somiari R (2014), "Wortmannin potentiates the combined effect of etoposide and cisplatin in human glioma cells", International Journal of Biochemistry and Cell Biology. Vol. 53, pp. 423-431. Elsevier Ltd. |
| Abstract: The combination of etoposide and cisplatin represents a common modality for treating of glioma patients. These drugs directly and indirectly produce the most lethal DNA double-stand breaks (DSB), which are mainly repaired by non-homologous DNA end joining (NHEJ). Drugs that can specifically inhibit the kinase activity of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), the major component of NHEJ, are of special interest in cancer research. These small molecule inhibitors can effectively enhance the efficacy of current cancer treatments that generate DNA damage. In this study, we investigated the effect of DNA-PKcs inhibitor, wortmannin, on the cytotoxic mechanism of etoposide and cisplatin in MO59K and MO59J human glioblastoma cell lines. These cell lines are proficient and deficient in DNA-PKcs, respectively. Wortmannin synergistically increased the cytotoxicity of cisplatin and etoposide, when combined, in NHEJ-proficient MO59K cells. Surprisingly, wortmannin sensitizing effect was also observed in DNA-PKcs-deficient MO59J cells. These data suggest that wortmannin sensitization to etoposide and cisplatin in human glioma cells is mediated by inhibition of not only DNA-PKcs activity but other enzymes from PI3-K family, e.g. ATM and ATR. A concentration-dependent increase in etoposide and cisplatin-induced DSB levels was potentiated by inhibitor in both cell lines. Moreover, drug-induced accumulation in the G2/M checkpoint and S-phase was increased by wortmannin. Wortmannin significantly inhibited drug-induced DSB repair in MO59 cells and this effect was more pronounced in MO59J cells. We conclude that the mechanism of wortmannin potentiation of etoposide and cisplatin cytotoxicity involves DSBs induction, DSBs repair inhibition, G2/M checkpoint arrest and inhibition of not only DNA-PKcs activity. © 2014 Published by Elsevier Ltd. |
BibTeX:
@article{Pastwa2014423,
author = {Pastwa, E. and Poplawski, T. and Lewandowska, U. and Somiari, S.B. and Blasiak, J. and Somiari, R.I.},
title = {Wortmannin potentiates the combined effect of etoposide and cisplatin in human glioma cells},
journal = {International Journal of Biochemistry and Cell Biology},
publisher = {Elsevier Ltd},
year = {2014},
volume = {53},
pages = {423-431},
note = {cited By 23},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84903842213&doi=10.1016%2fj.biocel.2014.06.007&partnerID=40&md5=2167e1af55c1bfe9f2973001f98d4349},
doi = {10.1016/j.biocel.2014.06.007}
}
|
| Krasinski T, Sakowski S, Waldmajer J and Poplawski T (2013), "Arithmetical analysis of biomolecular finite automaton", Fundamenta Informaticae. Vol. 128(4), pp. 463-474. |
| Abstract: In the paper we present a theoretical analysis of extension of the finite automaton built on DNA (introduced by the Shapiro team) to an arbitrary number of states and symbols. In the implementation we use a new idea of several restriction enzymes instead of one. We give arithmetical conditions for the existence of such extensions in terms of ingredients used in the implementation. |
BibTeX:
@article{Krasiński2013463,
author = {Krasinski, T. and Sakowski, S. and Waldmajer, J. and Poplawski, T.},
title = {Arithmetical analysis of biomolecular finite automaton},
journal = {Fundamenta Informaticae},
year = {2013},
volume = {128},
number = {4},
pages = {463-474},
note = {cited By 6},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84887983953&doi=10.3233%2fFI-2013-953&partnerID=40&md5=29b0c15f6a5dda3861a5e2991ba63285},
doi = {10.3233/FI-2013-953}
}
|
| Chojnacki C, Popławski T, Blasiak J, Chojnacki J, Reiter R and Klupinska G (2013), "Expression of melatonin synthesizing enzymes in Helicobacter pylori infected gastric mucosa", BioMed Research International. Vol. 2013 |
| Abstract: Helicobacter pylori colonization of gastric mucosa causes pain of unknown etiology in about 15-20% of infected subjects. The aim of the present work was to determine the level of expression of enzymes involved in the synthesis of melatonin in gastric mucosa of asymptomatic and symptomatic H. pylori infected patients. To diagnose H. pylori infection, histological analysis and the urea breath test (UBT C13) were performed. The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AA-NAT) and acetylserotonin methyltransferase (ASMT) were estimated in gastric mucosa with RT-PCR. The level of AA-NAT expression and AMST was decreased in H. pylori infected patients and was increased after H. pylori eradication. We conclude that decreased expression of melatonin synthesizing enzymes, AA-NAT and ASMT, in patients with symptomatic H. pylori infection returns to normal level after H. pylori eradication. © 2013 Cezary Chojnacki et al. |
BibTeX:
@article{Chojnacki2013,
author = {Chojnacki, C. and Popławski, T. and Blasiak, J. and Chojnacki, J. and Reiter, R.J. and Klupinska, G.},
title = {Expression of melatonin synthesizing enzymes in Helicobacter pylori infected gastric mucosa},
journal = {BioMed Research International},
year = {2013},
volume = {2013},
note = {cited By 15},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84880915147&doi=10.1155%2f2013%2f845032&partnerID=40&md5=5f539275e924bd789c52d0e4ff82a307},
doi = {10.1155/2013/845032}
}
|
| Poplawski T, Chojnacki C, Czubatka A, Klupinska G, Chojnacki J and Blasiak J (2013), "Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells", Molecular Biology Reports. Vol. 40(8), pp. 5205-5212. |
| Abstract: Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. This bacterium may induce cancer transformation and change the susceptibility of gastric mucosa cells to various exogenous dietary irritants. The aim of the study was to evaluate the influence of H. pylori infection on the reaction of the stomach cells to a genotoxic effect of heterocyclic amines (HCAs). These well-known mutagens are formed during cooking of protein-rich foods, primarily meat. Taking into account that persons consuming a mixed-western diet are exposed to these compound nearly an entire lifetime and more than half of human population is infected with H. pylori, it is important to assess the combined effect of H. pylori infection and HCAs in the context of DNA damage in gastric mucosa cells, which is a prerequisite to cancer transformation. We employed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) because these substances are present in a great amount in cooked and fried meat. Using alkaline comet assay, we showed that the extent of the DNA damage induced by HCAs was significantly higher in H. pylori infected gastric mucosa cells than in non-infected counterparts. We did not observed any difference in the efficiency of repair of DNA lesions induced by HCAs in both type of cells. Vitamin C reduced the genotoxic effects of HCAs in H. pylori infected and non-infected gastric mucosa cells. Melatonin more effectively decreased DNA damage caused by HCAs in H. pylori infected gastric mucosa cells as compared with control. Our results suggest that H. pylori infection may influence the susceptibility of gastric mucosa cells to HCAs and dietary antioxidative substances, including vitamin C and melatonin may inhibit the genotoxic effects of HCAs on gastric mucosa cells and may reduce the risk of carcinogenesis caused by food borne mutagens and H. pylori infection. © 2013 The Author(s). |
BibTeX:
@article{Poplawski20135205,
author = {Poplawski, T. and Chojnacki, C. and Czubatka, A. and Klupinska, G. and Chojnacki, J. and Blasiak, J.},
title = {Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells},
journal = {Molecular Biology Reports},
year = {2013},
volume = {40},
number = {8},
pages = {5205-5212},
note = {cited By 17},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84881171343&doi=10.1007%2fs11033-013-2622-3&partnerID=40&md5=d4463d461b465fb3d75ffb70d75d8636},
doi = {10.1007/s11033-013-2622-3}
}
|
| Chojnacki C, Poplawski T, Blasiak J, Chojnacki J and Klupinska G (2013), "Does melatonin homeostasis play a role in Continuous Epigastric Pain Syndrome?", International Journal of Molecular Sciences. Vol. 14(6), pp. 12550-12562. MDPI AG. |
| Abstract: Two clinical forms of functional dyspepsia (FD) are listed in the Rome III criteria: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), differing in the recurrence of ailments depending on the diet. Continuous EPS (CEPS) is observed in some EPS patients, also at night, but its cause is still unknown. We showed previously that melatonin (MEL) homeostasis may be associated with FD. In the present work we evaluated selected components of melatonin homeostasis in patients with CEPS. The study included 30 patients with CEPS, 21 women and nine men, aged 21-49 years and 30 control subjects (EPS excluded); organic and mental diseases, as well as Helicobacter pylori infection, were excluded in both groups. The average severity of abdominal pain in the last three months was estimated in a 10-point scale (Visual Analog Scale). The levels of mRNA expression of arylalkylamine-N-acetyltransferase (AANAT) and hydroxyindole-O-methyltransferase (HIOMT), the main components of MEL homeostasis, were determined in gastric mucosa with real time PCR. The fasting serum level of MEL (at 09:00 a.m.) and circadian urine excretion of 6-sulfatoxymelatonin (6-HMS) were determined with ELISA. AANAT expression in antral mucosa of control subjects was 1.76 ± 0.41, in the gastric body 1.35 ± 0.38, and in the dyspeptic group 1.42 ± 0.38 (p < 0.05) and 0.92 ± 0.55 (p < 0.05), respectively. HIOMT expression in the control was 2.05 ± 0.70 in the antrum and 1.57 ± 0.69 in the body and in the CEPS group, it was: 1.51 ± 0.57 (p < 0.05) and 0.74 ± 0.31 (p < 0.001), respectively. MEL concentration (pg/mL) was 9.41 ± 3.09 in the control group and 5.62 ± 1.34 (p < 0.01) in the CEPS group. Urinary 6-HMS excretion (μg/24 h) was 11.40 ± 4.46 in the controls and 7.68 ± 2.88 (p < 0.05) in the CEPS. Moreover, a negative correlation was found between the tested parameters and severity of epigastric pain. These results indicate that patients with CEPS may display low level of AANAT and HIOMT expression in gastric mucosa, resulting in decreased MEL synthesis. © 2013 by the authors; licensee MDPI, Basel, Switzerland. |
BibTeX:
@article{Chojnacki201312550,
author = {Chojnacki, C. and Poplawski, T. and Blasiak, J. and Chojnacki, J. and Klupinska, G.},
title = {Does melatonin homeostasis play a role in Continuous Epigastric Pain Syndrome?},
journal = {International Journal of Molecular Sciences},
publisher = {MDPI AG},
year = {2013},
volume = {14},
number = {6},
pages = {12550-12562},
note = {cited By 4},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84879135787&doi=10.3390%2fijms140612550&partnerID=40&md5=a0fad587c861f926baa4302ffbe8816d},
doi = {10.3390/ijms140612550}
}
|
| Krasinski T, Sakowski S and Poplawski T (2012), "Autonomous push-down automaton built on DNA*", Informatica (Slovenia). Vol. 36(3), pp. 263-276. |
| Abstract: In the paper we introduce a biomolecular implementation of the push-down automaton (one of the theoretical models of computing devices with unbounded memory) using DNA molecules. The idea of this improved implementation was inspired by Cavaliere et al. (2005). Povzetek: Predstavljen je avtonomni avtomat na osnovi DNK po vzoru Cavaliereja. |
BibTeX:
@article{Krasinski2012263,
author = {Krasinski, T. and Sakowski, S. and Poplawski, T.},
title = {Autonomous push-down automaton built on DNA*},
journal = {Informatica (Slovenia)},
year = {2012},
volume = {36},
number = {3},
pages = {263-276},
note = {cited By 15},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84867734449&partnerID=40&md5=f31291ffa5a0def8c9a7c44e61e07226}
}
|
| Sobczuk A, Poplawski T and Blasiak J (2012), "Polymorphisms of DNA repair genes in endometrial cancer", Pathology and Oncology Research. Vol. 18(4), pp. 1015-1020. |
| Abstract: Endometrial cancer belongs to the commonest malignancy in females. Its development may be associated with the high exposure of endometrium to exo- and endogenous estrogens. Estrogens produce DNA bulky adducts and oxidative base damages which are removed in nucleotide excision repair (NER) and base excision repair (BER) pathways. The reaction of endometrial cells to DNA damage may be crucial for their susceptibility to cancer transformation. This reaction is executed mainly by DNA repair, which can be modulated by the variability in the genes encoding DNA repair proteins. In this report we genotyped 4 polymorphisms of 3 DNA repair genes in 94 endometrial cancer patients and 114 age-matched cancer-free women using RFLP-PCR. The following polymorphisms were studied: p.Arg194Trp, p.Arg399Gln of the XRCC1 gene, p.Ser326Cys of the hOGG1 gene and p.Lys751Gln of the ERCC2 gene. We found an association between the ERCC2 751Gln variant and endometrial cancer occurrence (OR 3.95; 95 % CI 1.88-8.31). Gene-gene interaction between the ERCC2 751Gln and XRCC1 194Trp variants also increased the risk of endometrial cancer (OR 4.41; 95 % CI 2.01-9.67). The risk in the carriers of the ERCC2 751Gln variant was increased by a positive cancer history in first degree relatives (OR 4.97; 95 % CI 1.98-12.48). The risk of endometrial cancer was not alter by polymorphism p.Ser326Cys of the hOGG1 gene. The 751 Lys/Gln polymorphism of the ERCC2 gene may be linkedwith endometrial cancer occurrence and its effect can be potentiated by variants of the XRCC1 gene or first degree relatives positive cancer history. © Arányi Lajos Foundation 2012. |
BibTeX:
@article{Sobczuk20121015,
author = {Sobczuk, A. and Poplawski, T. and Blasiak, J.},
title = {Polymorphisms of DNA repair genes in endometrial cancer},
journal = {Pathology and Oncology Research},
year = {2012},
volume = {18},
number = {4},
pages = {1015-1020},
note = {cited By 22},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84868503632&doi=10.1007%2fs12253-012-9537-5&partnerID=40&md5=ac8a8557054a385ed50cfafc35a1f733},
doi = {10.1007/s12253-012-9537-5}
}
|
| Blasiak J, Synowiec E, Tarnawska J, Czarny P, Poplawski T and Reiter R (2012), "Dental methacrylates may exert genotoxic effects via the oxidative induction of DNA double strand breaks and the inhibition of their repair", Molecular Biology Reports. Vol. 39(7), pp. 7487-7496. |
| Abstract: Methacrylate monomers used in dentistry have been shown to induce DNA double strand breaks (DSBs), one of the most serious DNA damage. In the present work we show that a model dental adhesive consisting of 45% 2-hydroxyethyl methacrylate (HEMA) and 55% bisphenol A-diglycidyl dimethacrylate (Bis-GMA) at concentrations up to 0.25 mM Bis-GMA induced oxidative DNA in cultured primary human gingival fibroblasts (HGFs) as evaluated by the comet assay and probed with human 8-hydroxyguanine DNA-glycosylase 1. HEMA/Bis-GMA induced DSBs in HGFs as assessed by the neutral comet assay and phosphorylation of the H2AX histone and sodium ascorbate or melatonin (5-methoxy-N-acetyltryp-tamine) both at 50 μM reduced the DSBs, they also inhibited apoptosis induced by HEMA/Bis-GMA. The adhesive slowed the kinetics of the repair of DNA damage induced by hydrogen peroxide in HGFs, while sodium ascorbate or melatonin improved the efficacy of H2O2-induced damage in the presence of the methacrylates. The adhesive induced a rise in the G2/M cell population, accompanied by a reduction in the S cell population and an increase in G0/G1 cell population. Sodium ascorbate or melatonin elevated the S population and reduced the G2/M population. In conclusion, HEMA/Bis-GMA induce DSBs through, at least in part, oxidative mechanisms, and these compounds may interfere with DSBs repair. Vitamin C or melatonin may reduce the detrimental effects induced by methacrylates applied in dentistry. © 2012 Springer Science+Business Media B.V. |
BibTeX:
@article{Blasiak20127487,
author = {Blasiak, J. and Synowiec, E. and Tarnawska, J. and Czarny, P. and Poplawski, T. and Reiter, R.J.},
title = {Dental methacrylates may exert genotoxic effects via the oxidative induction of DNA double strand breaks and the inhibition of their repair},
journal = {Molecular Biology Reports},
year = {2012},
volume = {39},
number = {7},
pages = {7487-7496},
note = {cited By 39},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864289579&doi=10.1007%2fs11033-012-1582-3&partnerID=40&md5=83099ed37c27989246e47d68dc2a61d8},
doi = {10.1007/s11033-012-1582-3}
}
|
| Szczepanska J, Poplawski T, Synowiec E, Pawlowska E, Chojnacki C, Chojnacki J and Blasiak J (2012), "2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation", Molecular Biology Reports. Vol. 39(2), pp. 1561-1574. |
| Abstract: HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the c-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action. © 2011 Springer Science+Business Media B.V. |
BibTeX:
@article{Szczepanska20121561,
author = {Szczepanska, J. and Poplawski, T. and Synowiec, E. and Pawlowska, E. and Chojnacki, C.J. and Chojnacki, J. and Blasiak, J.},
title = {2-Hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation},
journal = {Molecular Biology Reports},
year = {2012},
volume = {39},
number = {2},
pages = {1561-1574},
note = {cited By 40},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84860341149&doi=10.1007%2fs11033-011-0895-y&partnerID=40&md5=f51fe948e866fe2b32e7f11f0e3dd3c2},
doi = {10.1007/s11033-011-0895-y}
}
|
| Wisniewska-Jarosinska M, Poplawski T, Chojnacki C, Pawlowska E, Krupa R, Szczepanska J and Blasiak J (2011), "Independent and combined cytotoxicity and genotoxicity of triethylene glycol dimethacrylate and urethane dimethacrylate", Molecular Biology Reports. Vol. 38(7), pp. 4603-4611. |
| Abstract: Dental composite materials contain polymers of methacrylates, which, due to mechanical abrasion and enzymatic action of saliva, may release their monomers into oral cavity and the pulp. Moreover, polymerization is always incomplete and leaves usually considerable fraction of free monomers. Mechanisms of the genotoxicity of methacrylate monomers have been rarely explored. As the polymerization of a monomer is catalyzed by a co-monomer, their combined action should be considered. In the present work, we investigated cytotoxic and genotoxic effects of urethane dimethacrylate (UDMA), often used as a monomer, at 1 mM, and triethylene glycol dimethacrylate (TEGDMA), a typical co-monomer, at 5 mM singly and in combination. Experiments were conducted on Chinese hamster ovary cells. Cell viability, apoptosis and cell cycle were assessed by flow cytometry, whereas DNA damage was evaluated by plasmid conformation test and comet assay. Both compounds decreased the viability of the cells, but did not induce strand breaks in an isolated plasmid DNA. However, both substances, either singly or in combination, damaged DNA in CHO cells as evaluated by comet assay. Both compounds induced apoptosis, but a combined action of them led to a decrease in the number of apoptotic cells. The combined action of UDMA and TEGDMA in the disturbance of cell cycle was lesser compared to the action of each compound individually. Individually, though UDMA and TEGDMA may induce cytotoxic and genotoxic, however, a combination of both does not produce a significant increase in these effects. © 2010 The Author(s). |
BibTeX:
@article{Wisniewska-Jarosinska20114603,
author = {Wisniewska-Jarosinska, M. and Poplawski, T. and Chojnacki, C.J. and Pawlowska, E. and Krupa, R. and Szczepanska, J. and Blasiak, J.},
title = {Independent and combined cytotoxicity and genotoxicity of triethylene glycol dimethacrylate and urethane dimethacrylate},
journal = {Molecular Biology Reports},
year = {2011},
volume = {38},
number = {7},
pages = {4603-4611},
note = {cited By 50},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80052442008&doi=10.1007%2fs11033-010-0593-1&partnerID=40&md5=bd65383c55dcc669d058033028f06f79},
doi = {10.1007/s11033-010-0593-1}
}
|
| Blasiak J, Krasinski T, Poplawski T and Sakowski S (2011), "[DNA computing] [Polish]", Postepy biochemii. Vol. 57(1), pp. 13-23. |
| Abstract: Biocomputers can be an alternative for traditional "silicon-based" computers, which continuous development may be limited due to further miniaturization (imposed by the Heisenberg Uncertainty Principle) and increasing the amount of information between the central processing unit and the main memory (von Neuman bottleneck). The idea of DNA computing came true for the first time in 1994, when Adleman solved the Hamiltonian Path Problem using short DNA oligomers and DNA ligase. In the early 2000s a series of biocomputer models was presented with a seminal work of Shapiro and his colleguas who presented molecular 2 state finite automaton, in which the restriction enzyme, FokI, constituted hardware and short DNA oligomers were software as well as input/output signals. DNA molecules provided also energy for this machine. DNA computing can be exploited in many applications, from study on the gene expression pattern to diagnosis and therapy of cancer. The idea of DNA computing is still in progress in research both in vitro and in vivo and at least promising results of these research allow to have a hope for a breakthrough in the computer science. |
BibTeX:
@article{Błasiak201113,
author = {Blasiak, J. and Krasinski, T. and Poplawski, T. and Sakowski, S.},
title = {[DNA computing] [Polish]},
journal = {Postepy biochemii},
year = {2011},
volume = {57},
number = {1},
pages = {13-23},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80052615952&partnerID=40&md5=894d904d635f7e669092307bee1ba728}
}
|
| Krupa R, Sobczuk A, Popławski T, Wozniak K and Blasiak J (2011), "DNA damage and repair in endometrial cancer in correlation with the hOGG1 and RAD51 genes polymorphism", Molecular Biology Reports. Vol. 38(2), pp. 1163-1170. |
| Abstract: The cellular reaction to the DNA-damaging agents may modulate individual's cancer susceptibility. This reaction is mainly determined by the efficacy of DNA repair, which in turn, may be influenced by the variability of DNA repair genes, expressed by their polymorphism. The hOGG1 gene encodes a glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair. Both proteins can be involved in the repair of DNA lesions, which are known to contribute to endometrial cancer. In the present work we determined the extent of basal DNA damage and the efficacy of removal of DNA damage induced by hydrogen peroxide and N-methyl-N′-nitro N-nitrosoguanidyne (MNNG) in peripheral blood lymphocytes of 30 endometrial cancer patients and 30 individuals without cancer. The results from DNA damage and repair study were correlated with the genotypes of two common polymorphisms of the hOGG1 and RAD51 genes: a G>C transversion at 1245 position of the hOGG1 gene producing a Ser → Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G>C substitution at 135 position of the RAD51 gene (the 135G>C polymorphism). DNA damage and repair were evaluated by alkaline single cell gel electrophoresis and genotypes were determined by restriction fragment length polymorphism PCR. We observed a strong association between endometrial cancer and the C/C genotype of the 135G>C polymorphism of the RAD51 gene. Moreover, there was a strong correlation between that genotype and endometrial cancer occurrence in subjects with a high level of basal DNA damage. We did not observe any correlation between the Ser326Cys polymorphism of the hOGG1 gene and endometrial cancer. Our result suggest that the 135G>C polymorphism of the RAD51 gene may be linked to endometrial cancer and can be considered as an additional marker of this disease. © 2010 The Author(s). |
BibTeX:
@article{Krupa20111163,
author = {Krupa, R. and Sobczuk, A. and Popławski, T. and Wozniak, K. and Blasiak, J.},
title = {DNA damage and repair in endometrial cancer in correlation with the hOGG1 and RAD51 genes polymorphism},
journal = {Molecular Biology Reports},
year = {2011},
volume = {38},
number = {2},
pages = {1163-1170},
note = {cited By 41},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79951580991&doi=10.1007%2fs11033-010-0214-z&partnerID=40&md5=3d7d25e6f7ac3c4d201e791bb10141c2},
doi = {10.1007/s11033-010-0214-z}
}
|
| Slupianek A, Poplawski T, Jozwiakowski S, Cramer K, Pytel D, Stoczynska E, Nowicki M, Blasiak J and Skorski T (2011), "BCR/ABL stimulates WRN to promote survival and genomic instability", Cancer Research. Vol. 71(3), pp. 842-851. |
| Abstract: BCR/ABL-transformed chronic myeloid leukemia (CML) cells accumulate numerous DNA double-strand breaks (DSB) induced by reactive oxygen species (ROS) and genotoxic agents. To repair these lesions BCR/ABL stimulate unfaithful DSB repair pathways, homologous recombination repair (HRR), nonhomologous end-joining (NHEJ), and single-strand annealing (SSA). Here, we show that BCR/ABL enhances the expression and increase nuclear localization of WRN (mutated in Werner syndrome), which is required for processing DSB ends during the repair. Other fusion tyrosine kinases (FTK), such as TEL/ABL, TEL/JAK2, TEL/PDGFβR, and NPM/ ALK also elevate WRN. BCR/ABL induces WRN mRNA and protein expression in part by c-MYC-mediated activation of transcription and Bcl-xL-dependent inhibition of caspase-dependent cleavage, respectively. WRN is in complex with BCR/ABL resulting in WRN tyrosine phosphorylation and stimulation of its helicase and exonuclease activities. Activated WRN protects BCR/ABL-positive cells from the lethal effect of oxidative and genotoxic stresses, which causes DSBs. In addition, WRN promotes unfaithful recombination-dependent repair mechanisms HRR and SSA, and enhances the loss of DNA bases during NHEJ in leukemia cells. In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability. ©2010 AACR. |
BibTeX:
@article{Slupianek2011842,
author = {Slupianek, A. and Poplawski, T. and Jozwiakowski, S.K. and Cramer, K. and Pytel, D. and Stoczynska, E. and Nowicki, M.O. and Blasiak, J. and Skorski, T.},
title = {BCR/ABL stimulates WRN to promote survival and genomic instability},
journal = {Cancer Research},
year = {2011},
volume = {71},
number = {3},
pages = {842-851},
note = {cited By 47},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79551530347&doi=10.1158%2f0008-5472.CAN-10-1066&partnerID=40&md5=0f28ad5c242bb753a141d0bf803ae52a},
doi = {10.1158/0008-5472.CAN-10-1066}
}
|
| Chojnacki C, Poplawski T, Klupinska G, Blasiak J, Chojnacki J and Reiter R (2011), "Secretion of melatonin and 6-sulfatoxymelatonin urinary excretion in functional dyspepsia", World Journal of Gastroenterology. Vol. 17(21), pp. 2646-2651. Baishideng Publishing Group Co. |
| Abstract: Aim: To evaluate blood concentration of melatonin and urinary excretion of its metabolite, 6-sulfatoxymelatonin (6-OHMS), in functional dyspepsia (FD). Methods: Ninety individuals were enrolled in the study: 30 in each study group: patients with postprandial distress syndrome (PDS), epigastric pain syndrome (EPS), and controls. Blood samples were drawn at 02:00 and 09:00 h and 24-h urine collection was performed. Serum melatonin and urinary 6-OHMS concentrations were measured by enzyme-linked immunosorbent assay. Results: Serum melatonin concentration at night and in the morning was significantly (P < 0.001) higher in PDS patients [at 02:00 h-93.3 pg/mL, quartile range (QR): 79.8-116.2; at 09.00 h-14.3 pg/mL, QR: 7.06-19.0] than in EPS (57.2 pg/mL, QR: 42.6-73.1; 8.1 pg/mL, QR: 4.1-9.3) and control patients (57.7 pg/mL, QR: 51.2-62.5; 8.1 pg/mL, QR: 5.4-10.3). A similar relationship was observed for urinary 6-OHMS excretion. Patients with severe PDS symptoms had a higher melatonin concentration than these with moderate syndromes, whereas patients with severe EPS had a lower urinary 6-OHMS excretion than patients with moderate symptoms. Conclusion: Evaluation of melatonin serum concentrations and 24-h urinary 6-OHMS excretion are useful methods for differential diagnosis of various clinical forms of FD. © 2011 Baishideng. |
BibTeX:
@article{Chojnacki20112646,
author = {Chojnacki, C. and Poplawski, T. and Klupinska, G. and Blasiak, J. and Chojnacki, J. and Reiter, R.J.},
title = {Secretion of melatonin and 6-sulfatoxymelatonin urinary excretion in functional dyspepsia},
journal = {World Journal of Gastroenterology},
publisher = {Baishideng Publishing Group Co},
year = {2011},
volume = {17},
number = {21},
pages = {2646-2651},
note = {cited By 14},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79958049202&doi=10.3748%2fwjg.v17.i21.2646&partnerID=40&md5=788f439e67f803ce6c5edfa7a1fdeffc},
doi = {10.3748/wjg.v17.i21.2646}
}
|
| Pawlowska E, Janik-Papis K, Poplawski T, Blasiak J and Szczepanska J (2010), "Mutations in the PAX9 gene in sporadic oligodontia", Orthodontics and Craniofacial Research. Vol. 13(3), pp. 142-152. |
| Abstract: Authors: Pawlowska E, Janik-Papis K, Poplawski T, Blasiak J, Szczepanska J. Objectives: Oligodontia, a congenital lack of six or more teeth, is often associated with mutations in the PAX9 gene; therefore, we searched for mutations in this gene. Design: In the present work, we sequenced fragments of the PAX9 gene in individuals with sporadic oligodontia. Next, we genotyped some mutations we found in patients with oligodontia and individuals without tooth agenesis. Setting and Sample Population: DNA sequencing was performed in the material isolated from peripheral blood lymphocytes of six unrelated patients with sporadic, non-syndromic oligodontia. These patients were selected based upon explorative cluster analysis. Genotyping was performed in 38 patients with oligodontia and 100 control individuals. Material and Methods: Direct sequencing and restriction fragment length polymorphism PCR were employed. Results: We detected two homozygotic substitutions, IVS2-109G>C and IVS2-54A>G, in intron 2 in three patients. Another homozygotic substitution in intron 2, IVS2-41A>G, was revealed in two patients. Two patients had an IVS3+40G>A homozygotic change in intron 3 and 4 patients displayed a 717C>T transition in exon 4 (silent mutation). One patient had a heterozygotic 718G>C transversion, resulting in a missense Ala240Pro substitution. We detected also several other intronic substitutions. Further genotyping of the IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations suggested that they can display polymorphic changes. Conclusion: The IVS2-54A>G, IVS2-109G>C, and IVS2-41A>G mutations of the PAX9 gene may represent polymorphism associated with sporadic oligodontia. © 2010 John Wiley & Sons A/S. |
BibTeX:
@article{Pawlowska2010142,
author = {Pawlowska, E. and Janik-Papis, K. and Poplawski, T. and Blasiak, J. and Szczepanska, J.},
title = {Mutations in the PAX9 gene in sporadic oligodontia},
journal = {Orthodontics and Craniofacial Research},
year = {2010},
volume = {13},
number = {3},
pages = {142-152},
note = {cited By 24},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77955135928&doi=10.1111%2fj.1601-6343.2010.01488.x&partnerID=40&md5=ed052293b18992407f074cb906e9a5ea},
doi = {10.1111/j.1601-6343.2010.01488.x}
}
|
| Poplawski T and Blasiak J (2010), "BCR/ABL downregulates DNA-PKCS-dependent and upregulates backup non-homologous end joining in leukemic cells", Molecular Biology Reports. Vol. 37(5), pp. 2309-2315. |
| Abstract: Non-homologous end joining (NHEJ) and homologous recombination repair (HRR) are the main mechanisms involved in the processing of DNA double strand breaks (DSBs) in humans. We showed previously that the oncogenic tyrosine kinase BCR/ABL stimulated DSBs repair by HRR. To evaluate the role of BCR/ABL in DSBs repair by NHEJ we examined the ability of leukemic BCR/ABL-expressing cell line BV173 to repair DNA damage induced by two DNA topoisomerase II inhibitors: etoposide and sobuzoxane. DNA lesions induced by sobuzoxane are repaired by a NHEJ pathway which is dependent on the catalytic subunit of protein kinase dependent on DNA (DNA-PKCS; D-NHEJ), whereas damage evoked by etoposide are repaired by two distinct NHEJ pathways, dependent on or independent of DNA-PKCS (backup NHEJ, B-NHEJ). Cells incubated with STI571, a highly specific inhibitor of BCR/ABL, displayed resistance to these agents associated with an accelerated kinetics of DSBs repair, as measured by the neutral comet assay and pulsed field gel electrophoresis. However, in a functional NHEJ assay, cells preincubated with STI571 repaired DSBs induced by a restriction enzyme with a lower efficacy than without the preincubation and addition of wortmannin, a specific inhibitor of DNA-PKCS, did not change efficacy of the NHEJ reaction. We suggest that BCR/ABL switch on B-NHEJ which is more error-prone then D-NHEJ and in such manner contribute to the increase of the genomic instability of leukemic cells. © 2009 Springer Science+Business Media B.V. |
BibTeX:
@article{Poplawski20102309,
author = {Poplawski, T. and Blasiak, J.},
title = {BCR/ABL downregulates DNA-PKCS-dependent and upregulates backup non-homologous end joining in leukemic cells},
journal = {Molecular Biology Reports},
year = {2010},
volume = {37},
number = {5},
pages = {2309-2315},
note = {cited By 11},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77955658191&doi=10.1007%2fs11033-009-9730-0&partnerID=40&md5=d26ed0c1c2ce9e05aec93be8be927915},
doi = {10.1007/s11033-009-9730-0}
}
|
| Poplawski T, Loba K, Pawlowska E, Szczepanska J and Blasiak J (2010), "Genotoxicity of urethane dimethacrylate, a tooth restoration component", Toxicology in Vitro. Vol. 24(3), pp. 854-862. |
| Abstract: Urethane dimethacrylate (UDMA) is used in dental restorative materials in its polymeric form. However, the process of polymerization is usually incomplete and the monomers of UDMA can diffuse into the oral cavity and the pulp, reaching millimolar concentrations. In the present work we showed that UDMA at 0.1 and 1.0 mM decreased the viability of and induced DNA damage in lymphocytes in a concentration dependent manner, but it did not affect a plasmid DNA in vitro. UDMA at 1 mM induced apoptosis in lymphocytes. The lymphocytes exposed to UDMA were able to repair their DNA within 60 min. Analysis with DNA repair enzymes Endo III and Fpg showed that UDMA induced mainly oxidative DNA lesions. Vitamin C and chitosan decreased genotoxic effect of UDMA. Our results show that monomers of UDMA may exert pronounced cyto- and genotoxic effects in human lymphocytes and chitosan can be considered as a protection against such effects. © 2009 Elsevier Ltd. All rights reserved. |
BibTeX:
@article{Poplawski2010854,
author = {Poplawski, T. and Loba, K. and Pawlowska, E. and Szczepanska, J. and Blasiak, J.},
title = {Genotoxicity of urethane dimethacrylate, a tooth restoration component},
journal = {Toxicology in Vitro},
year = {2010},
volume = {24},
number = {3},
pages = {854-862},
note = {cited By 26},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77649182948&doi=10.1016%2fj.tiv.2009.12.004&partnerID=40&md5=024986e38d6b554a6d41123ac3e14c6c},
doi = {10.1016/j.tiv.2009.12.004}
}
|
| Pawlowska E, Poplawski T, Ksiazek D, Szczepanska J and Blasiak J (2010), "Genotoxicity and cytotoxicity of 2-hydroxyethyl methacrylate", Mutation Research - Genetic Toxicology and Environmental Mutagenesis. Vol. 696(2), pp. 122-129. |
| Abstract: Resin-based methacrylate materials are widely used in restorative dentistry. They are viscous substances that are converted into solid material via polymerization. This process, however, may be incomplete, leading to the release of monomers into the oral cavity and the pulp, which can be reached through the dentin micro-channels. This opens the opportunity for the monomers to reach the bloodstream. Monomers can reach concentrations in the millimolar range, high enough to cause cellular damage, so it is justified to study their potential toxic effects. In the present work we investigated the cytotoxicity and genotoxicity of 2-hydroxyethyl methacrylate (HEMA) in human peripheral blood lymphocytes and A549 lung-tumour cells. HEMA at concentrations up to 10 mM neither affected the viability of the cells nor interacted with isolated plasmid DNA during a 1 h exposure. However, HEMA induced concentration-dependent DNA damage in lymphocytes, as assessed by alkaline and pH 12.1 versions of the comet assay. HEMA did not cause double-strand breaks, as assessed by the neutral version of the comet assay and pulsed-field gel electrophoresis. The use of DNA repair enzymes, spin traps and vitamin C produced results suggesting that HEMA induced oxidative modifications to DNA bases. DNA damage caused by HEMA at 10 mM was removed within 120 min. HEMA induced apoptosis in a concentration-dependent manner and caused cell-cycle delay at the G0/G1-checkpoint. Methylglycol chitosan displayed a protective effect against the DNA-damaging action of HEMA. The results obtained in this study suggest that HEMA induces adverse biological effects, mainly via reactive oxygen species, which can lead to DNA damage, apoptosis and cell-cycle delay. Chitosan and its derivatives can be considered as additional components of dental restoration to decrease the harmful potency of HEMA. © 2010 Elsevier B.V. All rights reserved. |
BibTeX:
@article{Pawlowska2010122,
author = {Pawlowska, E. and Poplawski, T. and Ksiazek, D. and Szczepanska, J. and Blasiak, J.},
title = {Genotoxicity and cytotoxicity of 2-hydroxyethyl methacrylate},
journal = {Mutation Research - Genetic Toxicology and Environmental Mutagenesis},
year = {2010},
volume = {696},
number = {2},
pages = {122-129},
note = {cited By 62},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77249112686&doi=10.1016%2fj.mrgentox.2009.12.019&partnerID=40&md5=613a34df40328e5681de5fd32306494c},
doi = {10.1016/j.mrgentox.2009.12.019}
}
|
| Poplawski T, Pastwa E and Blasiak J (2010), "Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures", Genetics and Molecular Biology. Vol. 33(2), pp. 368-373. Brazilian Journal of Genetics. |
| Abstract: DNA double-strand breaks (DSBs) are a serious threat to the cell, for if not or miss-repaired, they can lead to chromosomal aberration, mutation and cancer. DSBs in human cells are repaired via non-homologous DNA end joining (NHEJ) and homologous recombination repair pathways. In the former process, the structure of DNA termini plays an important role, as does the genetic constitution of the cells, through being different in normal and pathological cells. In order to investigate the dependence of NHEJ on DSB structure in normal and cancer cells, we used linearized plasmids with various, complementary or non-complementary, single-stranded or blunt DNA termini, as well as whole-cell extract isolated from normal human lymphocytes, chronic myeloid leukemia K562 cells and lung cancer A549 cells. We observed a pronounced variability in the efficacy of NHEJ reaction depending on the type of ends. Plasmids with complementary and blunt termini were more efficiently repaired than the substrate with 3' protruding single-strand ends. The hierarchy of the effectiveness of NHEJ was on average, from the most effective to the least, A549/ normal lymphocytes/ K562. Our results suggest that the genetic constitution of the cells together with the substrate terminal structure may contribute to the efficacy of the NHEJ reaction. This should be taken into account on considering its applicability in cancer chemo- or radiotherapy by pharmacologically modulating NHEJ cellular responses. © 2010, Sociedade Brasileira de Genética. |
BibTeX:
@article{Poplawski2010368,
author = {Poplawski, T. and Pastwa, E. and Blasiak, J.},
title = {Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures},
journal = {Genetics and Molecular Biology},
publisher = {Brazilian Journal of Genetics},
year = {2010},
volume = {33},
number = {2},
pages = {368-373},
note = {cited By 10},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77954367668&doi=10.1590%2fS1415-47572010005000018&partnerID=40&md5=834c0cc769ba2e58011839a641e8f3ac},
doi = {10.1590/S1415-47572010005000018}
}
|
| Blasiak J, Wozniak K, Szaflik J, Zaras M, Sklodowska A, Janik-Papis K, Poplawski T and Szaflik J (2009), "DNA damage/repair and polymorphism of the hOGG1 gene in lymphocytes of AMD patients", Journal of Biomedicine and Biotechnology. Vol. 2009 |
| Abstract: Oxidative stress is thought to play a role in the pathogenesis of age-related macular degeneration (AMD). We determined the extent of oxidative DNA damage and the kinetics of its removal as well as the genotypes of the Ser326Cys polymorphism of the hOGG1 gene in lymphocytes of 30 wet AMD patients and 30 controls. Oxidative DNA damage induced by hydrogen peroxide and its repair were evaluated by the comet assay and DNA repair enzymes. We observed a higher extent of endogenous oxidative DNA damage and a lower efficacy of its repair in AMD patients as compared with the controls. We did not find any correlation between the extent of DNA damage and efficacy of DNA repair with genotypes of the Ser326Cys polymorphism. The results obtained suggest that oxidative DNA damage and inefficient DNA repair can be associated with AMD and the variability of the hOOG1 gene may not contribute to this association. Copyright © 2009 KatarzynaWozniak et al. |
BibTeX:
@article{Blasiak2009,
author = {Blasiak, J. and Wozniak, K. and Szaflik, J.P. and Zaras, M. and Sklodowska, A. and Janik-Papis, K. and Poplawski, T.R. and Szaflik, J.},
title = {DNA damage/repair and polymorphism of the hOGG1 gene in lymphocytes of AMD patients},
journal = {Journal of Biomedicine and Biotechnology},
year = {2009},
volume = {2009},
note = {cited By 23},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-71149088272&doi=10.1155%2f2009%2f827562&partnerID=40&md5=85eea16cf56e6dd0c68ad988dc61d3c3},
doi = {10.1155/2009/827562}
}
|
| Klupinska G, Popławski T, Smigielski J, Blasiak J and Chojnacki J (2009), "The effect of melatonin on oxidative DNA damage in gastric mucosa cells of patients with functional dyspepsia [Wpływ melatoniny na oksydacyjne uszkodzenia DNA w komórkach błony śluzowej żoładka u osób z dyspepsja czynnościowa]", Polski Merkuriusz Lekarski. Vol. 26(155), pp. 366-369. |
| Abstract: The oxidative damage of DNA expresses severe cell lesion. The excess of oxygen free radicals is one of the causes of this type of disorders. Such a situation could occur in the ciurse of H. pylon infection. Melatonin is a natural and very active antioxidant compound. The aim of study was to establish weather an administration of melatonin decreases oxidative DNA damage in gastric mucosa cells. Material and methods. The study comprised 80 subjects, divided into two groups: group I (n=30) - patients with functional dyspepsia, H. pylori positive (+), with Epigastric Pain Syndrome, with H. pylori infection; group II (n=30) - patients H. pylori negative (-) with the same form of functional dyspepsia. The control group (O) comprised 20 subjects, aged 21 - 60 years. Results. In healthy subjects, non-infected with H. pylori the level of oxidative DNA damage in gastric mucosa cells was 6,95 ± 2,98. In both study groups the percentage of oxidative DNA damage was respectively: 12,12 ± 5,48% and 13,62 ± 4,58% (p<0,001). The differences in the results obtained in both study groups, that is H. pylori (+) and H. pylori (-) were similar (p>0,05). In group of patients with functional dyspepsia and H. pylori infection the level of oxidative DNA damage in gastrocytes was 12,12 ± 5,48%, and after 3 months administration of melatonin it decreased to the value 10,55 ± 0,63% (p<0,001). In patients with functional dyspepsia, without H. pylori infection the decrease of the level of oxidative DNA damages after melatonin administration was statistically significant and it was respectively: 13,62 ± 4,58% (p<0,001). Conclusions. In functional dyspepsia, especially with coexisting H. pylori infection the oxidative DNA damage in gastric mucosa cells is observed. The melatonin administration changes the above mentioned oxidative DNA damage significantly. |
BibTeX:
@article{Klupińska2009366,
author = {Klupinska, G. and Popławski, T. and Smigielski, J. and Blasiak, J. and Chojnacki, J.},
title = {The effect of melatonin on oxidative DNA damage in gastric mucosa cells of patients with functional dyspepsia [Wpływ melatoniny na oksydacyjne uszkodzenia DNA w komórkach błony śluzowej żoładka u osób z dyspepsja czynnościowa]},
journal = {Polski Merkuriusz Lekarski},
year = {2009},
volume = {26},
number = {155},
pages = {366-369},
note = {cited By 8},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-67949094437&partnerID=40&md5=0cdd02a1ebe07894e974d6d74ffeeecf}
}
|
| Poplawski T, Pawlowska E, Wisniewska-Jarosinska M, Ksiazek D, Wozniak K, Szczepanska J and Blasiak J (2009), "Cytotoxicity and genotoxicity of glycidyl methacrylate", Chemico-Biological Interactions. Vol. 180(1), pp. 69-78. |
| Abstract: Methacrylates are used in the polymer form as composite restorative materials in dentistry. However, the polymers can release monomers and co-monomers into the oral cavity and pulp, from where they can migrate into the bloodstream reaching virtually all organs. The local concentration of the released monomers can be in the millimolar range, high enough to induce adverse biological effects. Genotoxicity of methacrylate monomers is of a special significance due to potential serious phenotypic consequences, including cancer, and long latency period. In the present work, we investigated cytotoxicity and genotoxicity of glycidyl methacrylate (GMA) in the human peripheral blood lymphocytes and the CCR-CM human cancer cells. GMA at concentrations up to 5 mM evoked a concentration-dependent decrease in the viability of the lymphocytes up to about 80%, as assessed by flow cytometry. This agent did not induce strand breaks in the isolated plasmid DNA, but evoked concentration-dependent DNA damage in the human lymphocytes evaluated by the alkaline and neutral comet assay. This damage included oxidative modifications to the DNA bases, as checked by DNA repair enzymes Endo III and Fpg as well as single and double DNA strand breaks. The lymphocytes exposed to GMA at 2.5 μM were able to remove about 90% of damage to their DNA in 120 min. The ability of GMA to induce DNA double-strand breaks was confirmed by pulsed field gel electrophoresis. The drug evoked apoptosis and induced an increase in the G2/M cell population, accompanied by a decrease in the S cell population and an increase in G0/G1 cell population. Due to broad spectrum of GMA genotoxicity, including DNA double-strand breaks, and a potential long-lasting exposure to this compound, its use should be accompanied by precautions, reducing the chance of its release into blood stream and the possibility to induce adverse biological effects. © 2009 Elsevier Ireland Ltd. All rights reserved. |
BibTeX:
@article{Poplawski200969,
author = {Poplawski, T. and Pawlowska, E. and Wisniewska-Jarosinska, M. and Ksiazek, D. and Wozniak, K. and Szczepanska, J. and Blasiak, J.},
title = {Cytotoxicity and genotoxicity of glycidyl methacrylate},
journal = {Chemico-Biological Interactions},
year = {2009},
volume = {180},
number = {1},
pages = {69-78},
note = {cited By 44},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-67349085767&doi=10.1016%2fj.cbi.2009.02.001&partnerID=40&md5=88ac90943a05189ae7feccc08d4ddfb0},
doi = {10.1016/j.cbi.2009.02.001}
}
|
| Poplawski T, Stoczynska E and Blasiak J (2009), "Non-homologous DNA end joining--new proteins, new functions, new mechanisms [Polish]", Postepy biochemii. Vol. 55(1), pp. 36-45. |
| Abstract: Humans use primarily nonhomologous end joining (NHEJ) to repair DNA double strand breaks (DSBs), which are the most serious DNA damage, resulting in cell death if non-repaired or missrepaired. NHEJ directly joins together DNA ends resulted from DSBs. This pathway plays a key role in the development of vertebrate immune system through its involvement in the V(D)J recombination. Classical NHEJ in vertebrates involves a heterodimer of Ku proteins, the catalytic subunits of DNA-dependent protein kinase (DNA-PKCS), Artemis, Cernunnos-XLF and XRCC4/ligase DNA IV complex. This classical pathway may be assisted by DNA polymerases mu and lambda. Last 2 years brought new information on the mechanisms, proteins and functions of this DNA repair pathway. In 2006 Cernunnos-XLF was discovered, a protein playing a key role in NHEJ. Some alternative NHEJ pathways were also identified, lacking some of the main proteins of classical NHEJ, but involving other factors, including BRCA1, 53BP1, hPNK, WRN or MDC1. The results obtained so far suggest that not all key components and basic mechanisms of NHEJ have been identified. Future aspects of NHEJ research should include the determination of its role in cancer, aging, immune system development and basic nuclear metabolism. |
BibTeX:
@article{Popławski200936,
author = {Poplawski, T. and Stoczynska, E. and Blasiak, J.},
title = {Non-homologous DNA end joining--new proteins, new functions, new mechanisms [Polish]},
journal = {Postepy biochemii},
year = {2009},
volume = {55},
number = {1},
pages = {36-45},
note = {cited By 7},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-67649234480&partnerID=40&md5=f0adadf975ae24d4cc7e59b8915b1096}
}
|
| Pytel D, Sliwinski T, Poplawski T, Ferriola D and Majsterek I (2009), "Tyrosine kinase blockers: New hope for successful cancer therapy", Anti-Cancer Agents in Medicinal Chemistry. Vol. 9(1), pp. 66-76. Bentham Science Publishers B.V.. |
| Abstract: Tyrosine kinases (TKs) are attractive targets for cancer therapy, as quite often their abnormal signaling has been linked with tumor development and growth. Constitutive activated TKs stimulate multiple signaling pathways responsible for DNA repair, apoptosis, and cell proliferation. During the last few years, thorough analysis of the mechanism underlying tyrosine kinase's activity led to novel cancer therapy using TKs blockers. These drugs are remarkably effective in the treatment of various human tumors including head and neck, gastric, prostate and breast cancer and leukemias. The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia. The introduction of STI571 for the treatment of leukemia in clinical oncology has had a dramatic impact on how this disease is currently managed. Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase. The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava). Herein, we discuss the chemistry, biological activity and clinical potential of new drugs with tyrosine kinase blockers for cancer treatment. © 2009 Bentham Science Publishers Ltd. |
BibTeX:
@article{Pytel200966,
author = {Pytel, D. and Sliwinski, T. and Poplawski, T. and Ferriola, D. and Majsterek, I.},
title = {Tyrosine kinase blockers: New hope for successful cancer therapy},
journal = {Anti-Cancer Agents in Medicinal Chemistry},
publisher = {Bentham Science Publishers B.V.},
year = {2009},
volume = {9},
number = {1},
pages = {66-76},
note = {cited By 111},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-61749085561&doi=10.2174%2f187152009787047752&partnerID=40&md5=6fe49cbe3be88be3cc43f61492925e2d},
doi = {10.2174/187152009787047752}
}
|
| Poplawski T, Wisniewska-Jarosinska M, Jeske T, Socha K, Klupinska G, Blasiak J and Chojnacki J (2008), "An association between the XRCC1 gene polymorphisms and a family history of gastric cancer", Gastroenterologia Polska. Vol. 15(4), pp. 225-228. |
| Abstract: Introduction: XRCC1 is a component of human DNA repair multi-subunits protein complex contained also DNA polymerase β, DNA ligase I, and PARP (poly(ADP-ribose) polymerase) involved in DNA base excision repair and single-strand break repair. Single nucleotide polymorphisms of the XRCC1 gene have been shown to cause a reduction in the repair activity of its product. The development of gastric cancer may be associated with multiple genetic factors but currently, there is no solid evidence that gastric cancer has hereditary character, in case part of breast or colorectal cancers. Aim of study: The aim of this study was to test the hypothesis of an association between the XRCC1 gene polymorphisms and a family history of gastric cancer. Material and methods: We performed a case-control study to test the association between two polymorphisms in the XRCC1 gene: a C→T transition producing an Arg → Trp substitution at codon 194 (the Arg194Trp polymorphism) and a G → A transition resulting in an Arg → Gly change at codon 399 (the Arg399Gly polymorphism) and a family history of gastric cancer. Genotypes were determined in DNA of peripheral blood lymphocytes from 152 patients with a positive family gastric cancer history including first degree relatives and from 368 healthy individuals with no such family history in the interview polymorphic variants were studied by restriction fragment length polymerase chain reaction (RFLP-PCR) analysis. Results: Gln/Gln variant of the Arg399Gln polymorphism of the XRCC1 gene was more common in patients with a family history of gastric cancer (odds ratio 2.04; 95% confidence interval 1.27-3.29). Conclusions: These data suggest that the XRCC1 399Gln allele may be considered as a marker for gastric cancer, but there is a need to check its possible coupling with effects other genetic factors. Copyright © 2008 Cornetis. |
BibTeX:
@article{Popławski2008225,
author = {Poplawski, T. and Wisniewska-Jarosinska, M. and Jeske, T. and Socha, K. and Klupinska, G. and Blasiak, J. and Chojnacki, J.},
title = {An association between the XRCC1 gene polymorphisms and a family history of gastric cancer},
journal = {Gastroenterologia Polska},
year = {2008},
volume = {15},
number = {4},
pages = {225-228},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-70449578851&partnerID=40&md5=37b6d2eecc802c022bcdc37a5c442e05}
}
|
| Poplawski T, Tomaszewska K, Galicki M, Morawiec Z and Blasiak J (2008), "Promoter methylation of cancer-related genes in gastric carcinoma", Experimental Oncology. Vol. 30(2), pp. 112-116. |
| Abstract: Genetic changes associated with gastric cancer are not completely known, but epigenetic mechanisms involved in this disease seem to play an important role in its pathophysiology. One of these mechanisms, an aberrant methylation in the promoter regions of genes involved in cancer induction and promotion, may be of particular importance in gastric cancer. Aim: To analyze the methylation status of eight genes: Apaf-1, Casp8, CDH1, MDR1, GSTP1, BRCA1, hMLH1, Fas in gastric cancer patients. Methods: The methylation pattern of the genes was assessed by methylation specific restriction enzyme PCR (MSRE-PCR) in gastric tumors taken during surgery of 27 patients and compared with the methylation pattern in material obtained from biopsy in 25 individuals without cancer and pre-cancerous lesions. Results: We observed a promoter hypermethylation in the Casp8, hMLH1, CDH1 and MDR1 in gastric cancer patients as compared with the controls. Additionally, we investigated the relationship between promoter hypermethylation and age, gender, smoking and gastric cancer family history. The hypermethylation of the hMLH1 gene occurred more frequently in female than in men, and the hypermethylation of the CDH1 gene was observed preferentially in smoking than in non-smoking individuals. Conclusion: The data obtained indicate that changes in DXA methylation may contribute to gastric carcinogenesis. Copyright © Experimental Oncology, 2008. |
BibTeX:
@article{Poplawski2008112,
author = {Poplawski, T. and Tomaszewska, K. and Galicki, M. and Morawiec, Z. and Blasiak, J.},
title = {Promoter methylation of cancer-related genes in gastric carcinoma},
journal = {Experimental Oncology},
year = {2008},
volume = {30},
number = {2},
pages = {112-116},
note = {cited By 35},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-46749128980&partnerID=40&md5=a6f21f4a9f27244ef8ab67d4a72e0686}
}
|
| Stoklosa T, Poplawski T, Koptyra M, Nieborowska-Skorska M, Basak G, Slupianek A, Rayevskaya M, Seferynska I, Herrera L, Blasiak J and Skorski T (2008), "BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutations", Cancer Research. Vol. 68(8), pp. 2576-2580. |
| Abstract: BCR/ABL kinase-positive chronic myelogenous leukemia (CML) cells display genomic instability leading to point mutations in various genes including bcr/abl and p53, eventually causing resistance to imatinib and malignant progression of the disease. Mismatch repair (MMR) is responsible for detecting misincorporated nucleotides, resulting in excision repair before point mutations occur and/or induction of apoptosis to avoid propagation of cells carrying excessive DNA lesions. To assess MMR activity in CML, we used an in vivo assay using the plasmid substrate containing enhanced green fluorescent protein (EGFP) gene corrupted by T:G mismatch in the start codon; therefore, MMR restores EGFP expression. The efficacy of MMR was reduced ∼2-fold in BCR/ABL-positive cell lines and CD34+ CML cells compared with normal counterparts. MMR was also challenged by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG), which generates O6-methylguanine and O4-methylthymine recognized by MMR system. Impaired MMR activity in leukemia cells was associated with better survival, accumulation of p53 but not of p73, and lack of activation of caspase 3 after MNNG treatment. In contrast, parental cells displayed accumulation of p53, p73, and activation of caspase 3, resulting in cell death. Ouabain-resistance test detecting mutations in the Na +/K+ ATPase was used to investigate the effect of BCR/ABL kinase-mediated inhibition of MMR on mutagenesis. BCR/ABL-positive cells surviving the treatment with MNNG displayed ∼ 15-fold higher mutation frequency than parental counterparts and predominantly G:C→A:T and A:T→G:C mutator phenotype typical for MNNG-induced unrepaired lesions. In conclusion, these results suggest that BCR/ABL kinase abrogates MMR activity to inhibit apoptosis and induce mutator phenotype. ©2008 American Association for Cancer Research. |
BibTeX:
@article{Stoklosa20082576,
author = {Stoklosa, T. and Poplawski, T. and Koptyra, M. and Nieborowska-Skorska, M. and Basak, G. and Slupianek, A. and Rayevskaya, M. and Seferynska, I. and Herrera, L. and Blasiak, J. and Skorski, T.},
title = {BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutations},
journal = {Cancer Research},
year = {2008},
volume = {68},
number = {8},
pages = {2576-2580},
note = {cited By 81},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-42349116637&doi=10.1158%2f0008-5472.CAN-07-6858&partnerID=40&md5=f3cddfd4f8eb393aa7a91db70c6d8c21},
doi = {10.1158/0008-5472.CAN-07-6858}
}
|
| Klupinska G, Harasiuk A, Poplawski T, Chojnacki C, Blasiak J and Chojnacki J (2007), "Nocturnal secretion of melatonin in patients with functional dyspepsia", Gastroenterologia Polska. Vol. 14(2), pp. 103-106. |
| Abstract: Introduction: It has been suggested that disturbances of circadian and seasonal rhythmicity in the release of melatonin (MLT) may be among the causes of recurrence of peptic ulcers. Similar seasonal regularity is observed in clinical pictures of functional dyspepsia (FD). However, there are no reports on possible role of MLT in pathogenesis of dyspepsia. Aim of study: The aim of the study was to investigate nocturnal secretion in subjects in different subgroups of FD. Material and methods: The investigations were carried out in 53 patients, aged 20-54 years. According to the results of clinical and enodoscopic examinations and Rome III Criteria - epigastric pain syndrome (EPS) was diagnosed in 28 patients and postprandial distress syndrome (PDS) in 25 patients. 25 healthy persons, aged 25-45 years, constituted the control group (K). Blood samples were taken from each subject at 10.00 p.m., 2.00 a.m. and 6.00 a.m. Melatonin concentration was measured with ELISA method (enzyme linked immunosorbent assay). Results: The average concentration of MLT in healthy subjects was 34.7±8.1 pg/ml, in patients with EPS - 40.4±9.1 pg/ml (p>0.05) and with PDS - 60.1±0.2 pg/ml (p<0.05). Conclusions: 1. Nocturnal secretion of MLT in patients with different subgroups of FD is varied. 2. Diversity of MLT secretion may be the cause of different dyspeptic symptoms. Copyright © 2007 Cornetis. |
BibTeX:
@article{Klupińska2007103,
author = {Klupinska, G. and Harasiuk, A. and Poplawski, T. and Chojnacki, C. and Blasiak, J. and Chojnacki, J.},
title = {Nocturnal secretion of melatonin in patients with functional dyspepsia},
journal = {Gastroenterologia Polska},
year = {2007},
volume = {14},
number = {2},
pages = {103-106},
note = {cited By 3},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-34247517239&partnerID=40&md5=78bc1a6229771f99e3b6d46a3fcdb70c}
}
|
| Klupinska G, Poplawski T, Drzewoski J, Harasiuk A, Reiter R, Blasiak J and Chojnacki J (2007), "Therapeutic effect of melatonin in patients with functional dyspepsia", Journal of Clinical Gastroenterology. Vol. 41(3), pp. 270-274. |
| Abstract: BACKGROUND AND GOAL: Melatonin may inhibit reactive oxygen species-related pathogenesis in the alimentary tract by neutralizing free radicals. In the present study we assessed the potential protective action of melatonin in ulcerlike dyspepsia. STUDY: Sixty patients aged 19 to 39 years with the diagnosis of functional dyspepsia according to the Rome Criteria II and no Helicobacter pylori infection were involved in the study. Melatonin, at a dose of 5 mg (n=30), or placebo (n=30) were taken in the evening for a period of 12 weeks. At this time, patients were on an equivalent diet and were only to take an alkaline drug in case of the abdominal pain. RESULTS: After 12 weeks, the dyspeptic symptoms completely subsided in 17 patients in the melatonin-treatment group (56.6%). In other 9 individuals (30.0%) a partial improvement in health was achieved, especially in the frequency and intensity of nocturnal pain. After placebo, the majority of patients (93.3%) did not experience any improvement in symptoms. Multivariate analysis indicated that melatonin (odds ratio 95.86, 95% confidence interval 3.72-2469.37, P<0.01) correlated independently with significantly improved patients health. H. pylori past infection decreased positive effect of melatonin in ulcerlike dyspepsia. CONCLUSIONS: Melatonin can be considered as an auxiliary drug in the treatment of ulcerlike dyspepsia. © 2007 Lippincott Williams & Wilkins, Inc. |
BibTeX:
@article{Klupińska2007270,
author = {Klupinska, G. and Poplawski, T. and Drzewoski, J. and Harasiuk, A. and Reiter, R.J. and Blasiak, J. and Chojnacki, J.},
title = {Therapeutic effect of melatonin in patients with functional dyspepsia},
journal = {Journal of Clinical Gastroenterology},
year = {2007},
volume = {41},
number = {3},
pages = {270-274},
note = {cited By 42},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33847371219&doi=10.1097%2fMCG.0b013e318031457a&partnerID=40&md5=46f8b1580bfb9c3eb072a3892335ead7},
doi = {10.1097/MCG.0b013e318031457a}
}
|
| Poplawski T, Arabski M, Kozirowska D, Blasinska-Morawiec M, Morawiec Z, Morawiec-Bajda A, Klupińska G, Jeziorski A, Chojnacki J and Blasiak J (2006), "DNA damage and repair in gastric cancer-A correlation with the hOGG1 and RAD51 genes polymorphisms", Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. Vol. 601(1-2), pp. 83-91. |
| Abstract: The cell's susceptibility to mutagens and its ability to repair DNA lesions are important for cancer induction, promotion and progression. Both the mutagens' sensitivity and the efficacy of DNA repair may be affected by variation in several genes, including DNA repair genes. The hOGG1 gene encodes glycosylase of base excision repair and RAD51 specifies a key protein in homologues recombination repair. Both can be involved in the repair of oxidative DNA lesions, which can contribute to stomach cancer. In the present work we determined the level of basal and oxidative DNA damage and the kinetics of removal of DNA damage induced by hydrogen peroxide in peripheral blood lymphocytes of 30 gastric cancer patients and 30 healthy individuals. The metrics from DNA damage and repair study were correlated with the genotypes of common polymorphisms of the hOGG1 and RAD51 genes: a G → C transversion at 1245 position of the hOGG1 gene producing a Ser → Cys substitution at the codon 326 (the Ser326Cys polymorphism) and a G → C substitution at position 135 (5′-untranslated region) of the RAD51 gene (the G135C polymorphism). DNA damage and repair were evaluated by alkaline single cell gel electrophoresis (comet assay) assisted by DNA repair enzymes: endonuclease III (Nth) and formamidopyrimidine-DNA glycosylase (Fpg), preferentially recognizing oxidized DNA bases. The genotypes of the polymorphism were determined by restriction fragment length polymorphism PCR. We observed a strong association between gastric cancer occurrence, impaired DNA repair in human lymphocytes and the G/C genotype of the G135C polymorphism of the RAD51 gene. Moreover, there was a strong correlation between that genotype and stomach cancer occurrence in subjects with high level of oxidatively damaged DNA. We did not observe any correlation between the Ser1245Cys polymorphism of the hOGG1 gene and gastric cancer, including subjects with impaired DNA repair and/or high levels of endogenous oxidative DNA lesions. Therefore, our result suggest that the G135C polymorphism of the RAD51 gene may be linked with gastric cancer by the modulation of the cellular response to oxidative stress and this polymorphism may be a useful additional marker in this disease along with the genetic or/and environmental indicators of oxidative stress. © 2006 Elsevier B.V. All rights reserved. |
BibTeX:
@article{Poplawski200683,
author = {Poplawski, T. and Arabski, M. and Kozirowska, D. and Blasinska-Morawiec, M. and Morawiec, Z. and Morawiec-Bajda, A. and Klupińska, G. and Jeziorski, A. and Chojnacki, J. and Blasiak, J.},
title = {DNA damage and repair in gastric cancer-A correlation with the hOGG1 and RAD51 genes polymorphisms},
journal = {Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis},
year = {2006},
volume = {601},
number = {1-2},
pages = {83-91},
note = {cited By 61},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33749526460&doi=10.1016%2fj.mrfmmm.2006.06.002&partnerID=40&md5=9451d5f1c66667db20c013c7a00fefd0},
doi = {10.1016/j.mrfmmm.2006.06.002}
}
|
| Majsterek I, Sliwinski T, Poplawski T, Pytel D, Kowalski M, Slupianek A, Skorski T and Blasiak J (2006), "Imatinib mesylate (STI571) abrogates the resistance to doxorubicin in human K562 chronic myeloid leukemia cells by inhibition of BCR/ABL kinase-mediated DNA repair", Mutation Research - Genetic Toxicology and Environmental Mutagenesis. Vol. 603(1), pp. 74-82. |
| Abstract: Imatinib mesylate (STI571), a specific inhibitor of BCR/ABL tyrosine kinase, exhibits potent antileukemic effects in the treatment of chronic myelogenous leukemia (CML). However, the precise mechanism by which inhibition of BCR/ABL activity results in pharmacological responses remains unknown. BCR/ABL-positive human K562 CML cells resistant to doxorubicin (K562DoxR) and their sensitive counterparts (K562DoxS) were used to determine the mechanism by which the STI571 inhibitor may overcome drug resistance. K562 wild type cells and CCRF-CEM lymphoblastic leukemia cells without BCR/ABL were used as controls. The STI571 specificity was examined by use of murine pro-B lymphoid Baf3 cells with or without BCR/ABL kinase expression. We examined kinetics of DNA repair after cell treatment with doxorubicin in the presence or absence of STI571 by the alkaline comet assay. The MTT assay was used to estimate resistance against doxorubicin and Western blot analysis with Crk-L antibody was performed to evaluate BCR/ABL kinase inhibition by STI571. We provide evidence that treatment of CML-derived BCR/ABL-expressing leukemia K562 cells with STI571 results in the inhibition of DNA repair and abrogation of the resistance of these cells to doxorubicin. We found that doxorubicin-resistant K562DoxR cells exhibited accelerated kinetics of DNA repair compared with doxorubicin-sensitive K562DoxS cells. Inhibition of BCR/ABL kinase in K562DoxR cells with 1 μM STI571 decreased the kinetics of DNA repair and abrogated drug resistance. The results suggest that STI571-mediated inhibition of BCR/ABL kinase activity can affect the effectiveness of the DNA-repair pathways, which in turn may enhance drug sensitivity of leukemia cells. © 2005 Elsevier B.V. All rights reserved. |
BibTeX:
@article{Majsterek200674,
author = {Majsterek, I. and Sliwinski, T. and Poplawski, T. and Pytel, D. and Kowalski, M. and Slupianek, A. and Skorski, T. and Blasiak, J.},
title = {Imatinib mesylate (STI571) abrogates the resistance to doxorubicin in human K562 chronic myeloid leukemia cells by inhibition of BCR/ABL kinase-mediated DNA repair},
journal = {Mutation Research - Genetic Toxicology and Environmental Mutagenesis},
year = {2006},
volume = {603},
number = {1},
pages = {74-82},
note = {cited By 19},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33644835864&doi=10.1016%2fj.mrgentox.2005.10.010&partnerID=40&md5=04ad1286c5b5a8d3ddf03068e29d9933},
doi = {10.1016/j.mrgentox.2005.10.010}
}
|
| Poplawski T and Blasiak J (2006), "DNA homologous recombination repair in mammalian cells [Polish]", Postepy biochemii. Vol. 52(2), pp. 180-193. |
| Abstract: DNA double-strand breaks (DSBs) are the most serious DNA damage. Due to a great variety of factors causing DSBs, the efficacy of their repair is crucial for the cell's functioning and prevents DNA fragmentation, chromosomal translocation and deletion. In mammalian cells DSBs can be repaired by non-homologous end joining (NHEJ), homologous recombination (HRR) and single strand annealing (SSA). HRR can be divided into the first and second phase. The first phase is initiated by sensor proteins belonging to the MRN complex, that activate the ATM protein which target HRR proteins to obtain the second response phase--repair. HRR is precise because it utilizes a non-damaged homologous DNA fragment as a template. The key players of HRR in mammalian cells are MRN, RPA, Rad51 and its paralogs, Rad52 and Rad54. |
BibTeX:
@article{Popławski2006180,
author = {Poplawski, T. and Blasiak, J.},
title = {DNA homologous recombination repair in mammalian cells [Polish]},
journal = {Postepy biochemii},
year = {2006},
volume = {52},
number = {2},
pages = {180-193},
note = {cited By 7},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-39049187054&partnerID=40&md5=9bd0bec530716005bf6ae17fc3dd5254}
}
|
| Poplawski T, Zadrozny M, Kolacinska A, Rykala J, Morawiec Z and Blasiak J (2005), "Polymorphisms of the DNA mismatch repair gene HMSH2 in breast cancer occurence and progression", Breast Cancer Research and Treatment. Vol. 94(3), pp. 199-204. |
| Abstract: The response of the cell to DNA damage and its ability to maintain genomic stability by DNA repair are crucial in preventing cancer initiation and progression. Therefore, polymorphism of DNA repair genes may affect the process of carcinogenesis. The importance of genetic variability of the components of mismatch repair (MMR) genes is well documented in colorectal cancer, but little is known about its role in breast cancer. hMSH2 is one of the crucial proteins of MMR. We performed a case-control study to test the association between two polymorphisms in the hMSH2 gene: an A → G transition at 127 position producing an Asn → Ser substitution at codon 127 (the Asn127Ser polymorphism) and a G → A transition at 1032 position resulting in a Gly → Asp change at codon 322 (the Gly322Asp polymorphism) and breast cancer risk and cancer progression. Genotypes were determined in DNA from peripheral blood lymphocytes of 150 breast cancer patients and 150 age-matched women (controls) by restriction fragment length polymorphism and allele-specific PCR. We did not observe any correlation between studied polymorphisms and breast cancer progression evaluated by node-metastasis, tumor size and Bloom-Richardson grading. A strong association between breast cancer occurrence and the Gly/Gly phenotype of the Gly322Asp polymorphism (odds ratio 8.39; 95% confidence interval 1.44-48.8) was found. Therefore, MMR may play a role in the breast carcinogenesis and the Gly322Asp polymorphism of the hMSH2 gene may be considered as a potential marker in breast cancer. © Springer 2005. |
BibTeX:
@article{Poplawski2005199,
author = {Poplawski, T. and Zadrozny, M. and Kolacinska, A. and Rykala, J. and Morawiec, Z. and Blasiak, J.},
title = {Polymorphisms of the DNA mismatch repair gene HMSH2 in breast cancer occurence and progression},
journal = {Breast Cancer Research and Treatment},
year = {2005},
volume = {94},
number = {3},
pages = {199-204},
note = {cited By 27},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-27944445872&doi=10.1007%2fs10549-005-4793-7&partnerID=40&md5=7306071bc6e8913cd71ec4aa6d73b610},
doi = {10.1007/s10549-005-4793-7}
}
|
| Czechowska A, Poplawski T, Drzewoski J and Blasiak J (2005), "Imatinib (STI571) induces DNA damage in BCR/ABL-expressing leukemic cells but not in normal lymphocytes", Chemico-Biological Interactions. Vol. 152(2-3), pp. 139-150. Elsevier Ireland Ltd. |
| Abstract: Imatinib (STI571) is a 2-phenylaminopyrimidine derivative used mostly in the treatment of chronic myeloid leukaemia. It targets the BCR/ABL oncogenic tyrosine kinase, inhibiting its activity. Using the alkaline comet assay we showed that STI571 at concentrations ranging from 0.2 to 2 μM induced DNA damage in human leukemic K562 and BV173 cells expressing the BCR/ABL oncogene, whereas it had no effect in normal human lymphocytes and leukemic CCRF-CEM cells without the expression of BCR/ABL. Imatinib did not induce DNA strand breaks in the direct interaction with DNA as examined by the circular plasmid relaxation assay. Because the extent of DNA damage observed in the neutral and pH 12.1 versions of the comet assay was much lesser than in the alkaline version, we concluded that the drug induced DNA alkali-labile sites rather than strand breaks. K562 cells were unable to repair H2O2-induced DNA damage during a 120-min incubation, if they had been preincubated with STI571, whereas normal lymphocytes did so within 60 min. Pre-treatment of K562 cells with Vitamins A, C and E reduced the extent of DNA damage evoked by STI571. Similar results brought experiments with the nitrone spin traps POBN and PBN, suggesting that free radicals may be involved in the formation of DNA lesions induced by STI571 in K562 cells. These cells exposed to imatinib and treated with endonuclease III, formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, the enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes. Therefore, the mechanism of the anti-leukemic action of STI571 may involve not only the inhibition of BCR/ABL, but also DNA damage in the cells expressing this fusion protein. DNA damage induced by STI571 may follow from oxidative and alkylative base modifications. © 2005 Elsevier Ireland Ltd. All rights reserved. |
BibTeX:
@article{Czechowska2005139,
author = {Czechowska, A. and Poplawski, T. and Drzewoski, J. and Blasiak, J.},
title = {Imatinib (STI571) induces DNA damage in BCR/ABL-expressing leukemic cells but not in normal lymphocytes},
journal = {Chemico-Biological Interactions},
publisher = {Elsevier Ireland Ltd},
year = {2005},
volume = {152},
number = {2-3},
pages = {139-150},
note = {cited By 26},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-17144426933&doi=10.1016%2fj.cbi.2005.03.002&partnerID=40&md5=d2f7bcc9d946ce420b1023d49e962477},
doi = {10.1016/j.cbi.2005.03.002}
}
|
| Arabski M, Kazmierczak P, Wisniewska-Jarosinska M, Poplawski T, Klupinska G, Chojnacki J, Drzewoski J and Blasiak J (2005), "Interaction of amoxicillin with DNA in human lymphocytes and H. pylori-infected and non-infected gastric mucosa cells", Chemico-Biological Interactions. Vol. 152(1), pp. 13-24. Elsevier Ireland Ltd. |
| Abstract: Amoxicillin is a penicillin derivative belonging to a group of β-lactam antibiotics used in Helicobacter pylori eradication. Clinical application of amoxicillin is underlined by its antibacterial activity, but little is known about its interaction with DNA of human cells. Using the alkaline comet assay we investigated the genotoxicity of amoxicillin in human peripheral blood lymphocytes as well as in H. pylori-infected and non-infected human gastric mucosa cells. To assess the role of reactive oxygen species in the genotoxicity of amoxicillin we employed a set of antioxidant and free radical scavengers, including Vitamins C and E, melatonin and the nitrone spin trap N-tert-butyl-α-phenyl-nitrone (PBN). Amoxicillin-induced DNA damage was completely repaired after 60 min. The vitamins, melatonin and the spin trap decreased the extent of the damage. The cells exposed to amoxicillin and treated with endonuclease III and 3-methyladenine-DNA glycosylase II, the enzymes recognizing oxidized bases displayed greater extent of DNA damage than those not treated with these enzymes. H. pylori non-infected gastric mucosa cells exposed to hydrogen peroxide repaired their DNA in a 60 min incubation, but the infected cells were not able to do so. The action of DNA repair enzymes, the vitamins, melatonin and PBN indicated that amoxicillin-induced oxidative DNA damage. The drug did not induce DNA strand breaks in isolated pUC19 plasmid DNA. Our results suggest that amoxicillin can induce DNA damage in human lymphocytes and gastric mucosa cells and this effect may follow from the production of reactive oxygen species. Cellular activation of the drug is needed to induce DNA damage. Free radical scavengers and antioxidants may be used to assist H. pylori eradication with amoxicillin to protect DNA of the host cells. Our results suggest also that H. pylori infection may alter gastric mucosa cells response to DNA-damaging agents and in this way contribute to initiation/promotion of cancer transformation of these cells induced by external or internal carcinogens. © 2005 Published by Elsevier Ireland Ltd. |
BibTeX:
@article{Arabski200513,
author = {Arabski, M. and Kazmierczak, P. and Wisniewska-Jarosinska, M. and Poplawski, T. and Klupinska, G. and Chojnacki, J. and Drzewoski, J. and Blasiak, J.},
title = {Interaction of amoxicillin with DNA in human lymphocytes and H. pylori-infected and non-infected gastric mucosa cells},
journal = {Chemico-Biological Interactions},
publisher = {Elsevier Ireland Ltd},
year = {2005},
volume = {152},
number = {1},
pages = {13-24},
note = {cited By 30},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-17644415374&doi=10.1016%2fj.cbi.2005.01.004&partnerID=40&md5=218e711dbdcfe430cfc2faede14b2dc2},
doi = {10.1016/j.cbi.2005.01.004}
}
|
| Poplawski T and Blasiak J (2005), "Non-homologous DNA end joining [Polish]", Postepy biochemii. Vol. 51(3), pp. 328-338. |
| Abstract: DNA double strand breaks (DSB) are the most serious form of DNA damage. Repair of DSBs is important to prevent chromosomal fragmentation, translocations and deletions. Non-homologous end joining (NHEJ) is one of three major pathways for the repair of DSBs in human cells. In this process two DNA ends are joined directly, usually with no sequence homology, although in the case of same polarity of the single stranded overhangs in DSBs, regions of microhomology are utilized. NHEJ is typically imprecise, a characteristic that is useful for immune diversification in lymphocytes in V(D)J recombination. The main components of the NHEJ system in eukaryotes are the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku proteins, XRCC4, DNA ligase IV, and Artemis. This review focuses on the mechanisms an dregulation of DSB repair by NHEJ in mammalian cells. |
BibTeX:
@article{Popławski2005328,
author = {Poplawski, T. and Blasiak, J.},
title = {Non-homologous DNA end joining [Polish]},
journal = {Postepy biochemii},
year = {2005},
volume = {51},
number = {3},
pages = {328-338},
note = {cited By 1},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-33645727747&partnerID=40&md5=ba0d8070891fdab2b30e63fe470bc563}
}
|
| Pastwa E, Poplawski T, Czechowska A, Malinowski M and Blasiak J (2005), "Non-homologous DNA end joining repair in normal and leukemic cells depends on the substrate ends", Zeitschrift fur Naturforschung - Section C Journal of Biosciences. Vol. 60(5-6), pp. 493-500. Verlag der Zeitschrift fur Naturforschung. |
| Abstract: Double-strand breaks (DSBs) are the most serious DNA damage which, if unrepaired or misrepaired, may lead to cell death, genomic instability or cancer transformation. In human cells they can be repaired mainly by non-homologous DNA end joining (NHEJ). The efficacy of NHEJ pathway was examined in normal human lymphocytes and K562 myeloid leukemic cells expressing the BCR/ABL oncogenic tyrosine kinase activity and lacking p53 tumor suppressor protein. In our studies we employed a simple and rapid in vitro DSB end joining assay based on fluorescent detection of repair products. Normal and cancer cells were able to repair DNA damage caused by restriction endonucleases, but the efficiency of the end joining was dependent on the type of cells and the structure of DNA ends. K562 cells displayed decreased NHEJ activity in comparison to normal cells for 5′ complementary DNA overhang. For blunt-ended DNA there was no significant difference in end joining activity. Both kinds of cells were found about 10-fold more efficient for joining DNA substrates with compatible 5′ overhangs than those with blunt ends. Our recent findings have shown that stimulation of DNA repair could be involved in the drug resistance of BCR/ABL-positive cells in anticancer therapy. For the first time the role of STI571 was investigated, a specific inhibitor of BCR/ABL oncogenic protein approved for leukemia treatment in the NHEJ pathway. Surprisingly, STI571 did not change the response of BCR/ABL-positive K562 cells in terms of NHEJ for both complementary and blunt ends. Our results suggest that the various responses of the cells to DNA damage via NHEJ can be correlated with the differences in the genetic constitution of human normal and cancer cells. However, the role of NHEJ in anticancer drug resistance in BCR/ABL-positive cells is questionable. © 2005 Verlag der Zeitschrift für Naturforschung. |
BibTeX:
@article{Pastwa2005493,
author = {Pastwa, E. and Poplawski, T. and Czechowska, A. and Malinowski, M. and Blasiak, J.},
title = {Non-homologous DNA end joining repair in normal and leukemic cells depends on the substrate ends},
journal = {Zeitschrift fur Naturforschung - Section C Journal of Biosciences},
publisher = {Verlag der Zeitschrift fur Naturforschung},
year = {2005},
volume = {60},
number = {5-6},
pages = {493-500},
note = {cited By 10},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-22144452193&doi=10.1515%2fznc-2005-5-619&partnerID=40&md5=d1f8244f824497cd28bb36c2fab685bc},
doi = {10.1515/znc-2005-5-619}
}
|
| Dziadek B, Dziadek J, Poplawski T and Goscicka T (2004), "Two murine homologues of human MCP-1 chemokine are differently expressed during intracellular infection with Listeria strains", Central-European Journal of Immunology. Vol. 29(1), pp. 23-28. Termedia Publishing House Ltd.. |
| Abstract: The murine cells express two homologues of human MCP-1 β-chemokine, which plays a crucial protective role in the early phase of immunological response against intracellular pathogens. We have found that the expression of mRNA for murine MCP-1/JE and MCP-5 CC-chemokines is upregulated in peritoneal exudate cells during Listeria infection. The MCP-5 mRNA expression was observed exclusively in the early stage of infection with both pathogenic and nonpathogenic Listeria strains. The upregulation of MCP-1/JE mRNA production depended on strain pathogenicity and increased gradually during four hours postinfection. |
BibTeX:
@article{Dziadek200423,
author = {Dziadek, B. and Dziadek, J. and Poplawski, T. and Goscicka, T.},
title = {Two murine homologues of human MCP-1 chemokine are differently expressed during intracellular infection with Listeria strains},
journal = {Central-European Journal of Immunology},
publisher = {Termedia Publishing House Ltd.},
year = {2004},
volume = {29},
number = {1},
pages = {23-28},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-20444499438&partnerID=40&md5=775fa66ae7b429d8a9a07cffbb7832cb}
}
|
| Poplawski T and Blasiak J (2003), "Mismatch repair [Polish]", Postepy biochemii. Vol. 49(3), pp. 126-135. |
BibTeX:
@article{Popławski2003126,
author = {Poplawski, T. and Blasiak, J.},
title = {Mismatch repair [Polish]},
journal = {Postepy biochemii},
year = {2003},
volume = {49},
number = {3},
pages = {126-135},
note = {cited By 0},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-2442639185&partnerID=40&md5=a284370c5a064e5ef72855a41f45fa6b}
}
|
