The Experts below are selected from a list of 198 Experts worldwide ranked by ideXlab platform
Kyaw Zin Thein - One of the best experts on this subject based on the ideXlab platform.
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A systematic review and meta- analysis of randomized controlled trials to evaluate the risk of hematological toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors.
Journal of Clinical Oncology, 2018Co-Authors: Anita Sultan, Sriman Swarup, Yin Mon Myat, Htay Htay Aung, Kalpana Panigrahi, Kyaw Zin TheinAbstract:217Background: Poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors have shown to benefit in DNA repair-deficient tumors by enhancing synthetic lethality in cancer cells and are currently...
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Risk of gastrointestinal and hepatic toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase inhibitors: A meta-analysis of seven phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Anita Sultan, Sriman Swarup, Yin Mon Myat, Khaing Khaing Htwe, Aung Myo Hein, Tsujung Yang, Kyaw Zin TheinAbstract:219Background: Inhibition of poly Adenosine Diphosphate Ribose polymerase (PARP) enzymes terminates an alternative DNA repair pathway, resulting in synthetic lethality in homologous recombination deficient tumors. Many PARP inhibitors have shown to improve survival in many solid tumors with noteworthy safety concerns. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018. Phase III RCTs that mention GI toxicities and elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ov...
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Discontinuation of poly(Adenosine Diphosphate-Ribose) polymerase inhibitors due to adverse events in patients with recurrent ovarian cancer: A meta-analysis of three phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Kyaw Zin Thein, Anita Sultan, Sriman Swarup, Yin Mon Myat, Catherine Jones, Fred Hardwicke, Sanjay AwasthiAbstract:118Background: Ovarian cancer is the fifth leading cause of cancer-related death among women. Poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in patients with recurrent ovarian cancer. Yet, there are notable adverse events which led to treatment discontinuation, interruption, or dose reduction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of PARP inhibitors discontinuation due to adverse events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs which employed PARP inhibitors maintenance in ovarian cancer and mentioned treatment interruption, dose reduction and treatment discontinuation due to adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase III RCTs with a total...
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Risk of health-related quality-of-life events and pulmonary toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase inhibitors: A meta-analysis of seven phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Sriman Swarup, Anita Sultan, Yin Mon Myat, Kalpana Panigrahi, Rachana Yendala, Nyein Htwe Yu, Kyaw Zin TheinAbstract:213Background: Poly Adenosine Diphosphate Ribose polymerase (PARP) enzymes aide in the repair of DNA damage. PARP inhibitors showed synthetic lethality in cancer cells and were utilized in many solid tumors with notable toxicities. Fatigue and pain are the major determinants of health-related quality of life (HRQOL) in cancer patients undergoing chemotherapy. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of HRQOL events and pulmonary toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs that mention HRQOL events and pulmonary toxicities as adverse effects were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ovarian, and gastric cancer were eligible. Studies compared olaparib or niraparib or ru...
Anita Sultan - One of the best experts on this subject based on the ideXlab platform.
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A systematic review and meta- analysis of randomized controlled trials to evaluate the risk of hematological toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors.
Journal of Clinical Oncology, 2018Co-Authors: Anita Sultan, Sriman Swarup, Yin Mon Myat, Htay Htay Aung, Kalpana Panigrahi, Kyaw Zin TheinAbstract:217Background: Poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors have shown to benefit in DNA repair-deficient tumors by enhancing synthetic lethality in cancer cells and are currently...
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Risk of gastrointestinal and hepatic toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase inhibitors: A meta-analysis of seven phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Anita Sultan, Sriman Swarup, Yin Mon Myat, Khaing Khaing Htwe, Aung Myo Hein, Tsujung Yang, Kyaw Zin TheinAbstract:219Background: Inhibition of poly Adenosine Diphosphate Ribose polymerase (PARP) enzymes terminates an alternative DNA repair pathway, resulting in synthetic lethality in homologous recombination deficient tumors. Many PARP inhibitors have shown to improve survival in many solid tumors with noteworthy safety concerns. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018. Phase III RCTs that mention GI toxicities and elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ov...
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Discontinuation of poly(Adenosine Diphosphate-Ribose) polymerase inhibitors due to adverse events in patients with recurrent ovarian cancer: A meta-analysis of three phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Kyaw Zin Thein, Anita Sultan, Sriman Swarup, Yin Mon Myat, Catherine Jones, Fred Hardwicke, Sanjay AwasthiAbstract:118Background: Ovarian cancer is the fifth leading cause of cancer-related death among women. Poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in patients with recurrent ovarian cancer. Yet, there are notable adverse events which led to treatment discontinuation, interruption, or dose reduction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of PARP inhibitors discontinuation due to adverse events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs which employed PARP inhibitors maintenance in ovarian cancer and mentioned treatment interruption, dose reduction and treatment discontinuation due to adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase III RCTs with a total...
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Risk of health-related quality-of-life events and pulmonary toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase inhibitors: A meta-analysis of seven phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Sriman Swarup, Anita Sultan, Yin Mon Myat, Kalpana Panigrahi, Rachana Yendala, Nyein Htwe Yu, Kyaw Zin TheinAbstract:213Background: Poly Adenosine Diphosphate Ribose polymerase (PARP) enzymes aide in the repair of DNA damage. PARP inhibitors showed synthetic lethality in cancer cells and were utilized in many solid tumors with notable toxicities. Fatigue and pain are the major determinants of health-related quality of life (HRQOL) in cancer patients undergoing chemotherapy. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of HRQOL events and pulmonary toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs that mention HRQOL events and pulmonary toxicities as adverse effects were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ovarian, and gastric cancer were eligible. Studies compared olaparib or niraparib or ru...
Jun Zheng - One of the best experts on this subject based on the ideXlab platform.
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overactivation of poly Adenosine phosphate Ribose polymerase 1 and molecular events in neuronal injury after deep hypothermic circulatory arrest study in a rabbit model
The Journal of Thoracic and Cardiovascular Surgery, 2007Co-Authors: Yue Tang, Cun Long, Liangxin Tian, Zhengyi Feng, Jun ZhengAbstract:Objective Although deep hypothermic circulatory arrest has been known to induce neuronal injury, the molecular mechanism of this damage has not been identified. We studied the key molecular mediators through cellular energy failure, excitotoxicity, and overactivation of poly(Adenosine Diphosphate–Ribose) polymerase 1 in brain tissues of a rabbit model of deep hypothermic circulatory arrest similar to clinical settings. Methods We established 2 models of cardiopulmonary bypass (n = 15) and deep hypothermic circulatory arrest (n = 15) associated with cerebral microdialysis in rabbits. Deep hypothermic circulatory arrest lasted for 60 minutes. The measurements of glucose, lactate, pyruvate, and glutamate collected by means of microdialysis were quantified by using a microdialysis analyzer and high-performance liquid chromatography. The overactivation of poly(Adenosine Diphosphate–Ribose) polymerase 1 was assessed by detecting immunostaining of poly(Adenosine Diphosphate–Ribose). Histologic studies were used to identify neuronal morphologic changes and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end-labeling staining and poly(Adenosine Diphosphate–Ribose) polymerase 1 Western blotting were used to identify apoptotic cells and early apoptotic signals. Results Deep hypothermic circulatory arrest significantly increased the lactate/pyruvate and lactate/glucose ratios and the glutamate value, whereas cardiopulmonary bypass did not ( P P P Conclusions This study demonstrated that deep hypothermic circulatory arrest results in an overactivation of poly(Adenosine Diphosphate–Ribose) polymerase 1, and that there were molecular events consisting of cellular energy failure, excitotoxicity, overactivation of poly(Adenosine Diphosphate–Ribose) polymerase 1, and necrosis and/or apoptosis in neuronal injury.
Jonathan A. Ledermann - One of the best experts on this subject based on the ideXlab platform.
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The status of poly(Adenosine Diphosphate-Ribose) polymerase (PARP) inhibitors in ovarian cancer, part 2: extending the scope beyond olaparib and BRCA1/2 mutations.
Clinical advances in hematology & oncology, 2016Co-Authors: Rowan E. Miller, Jonathan A. LedermannAbstract:Poly(Adenosine Diphosphate-Ribose) polymerase (PARP) inhibitors have shown clinical activity in epithelial ovarian cancer, leading both the US Food and Drug Administration (FDA) and the European Medicines Agency to approve olaparib for tumors characterized by BRCA1 and BRCA2 mutations. However, it is becoming increasingly evident that tumors that share molecular features with BRCA-mutant tumors-a concept known as BRCAness-also may exhibit defective homologous recombination DNA repair, and therefore will respond to PARP inhibition. A number of strategies have been proposed to identify BRCAness, including identifying defects in other genes that modulate homologous recombination and characterizing the mutational and transcriptional signatures of BRCAness. In addition to olaparib, a number of other PARP inhibitors are in clinical development. This article reviews the development of PARP inhibitors other than olaparib, and discusses the evidence for PARP inhibitors beyond BRCA1/2-mutant ovarian cancer.
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The status of poly(Adenosine Diphosphate-Ribose) polymerase (PARP) inhibitors in ovarian cancer, part 1: olaparib.
Clinical advances in hematology & oncology, 2016Co-Authors: Rowan E. Miller, Jonathan A. LedermannAbstract:Poly(Adenosine Diphosphate-Ribose) polymerase (PARP) inhibitors have shown promising clinical activity in epithelial ovarian cancer. Following the observation in vitro that PARP inhibition is synthetically lethal in tumors with BRCA mutations, PARP inhibition has become the first genotype-directed therapy for BRCA1- and BRCA2-associated ovarian cancer. However, it is becoming clear that PARP inhibition also may have clinical utility in cancers associated with defects or aberrations in DNA repair that are unrelated to BRCA mutations. Deficient DNA repair mechanisms are present in approximately 30% to 50% of high-grade serous ovarian cancers, the most common histologic subtype. Olaparib is the best-studied PARP inhibitor to date, and a number of phase 3 trials with this agent are underway. This article reviews the development of olaparib for ovarian cancer and discusses the current evidence for its use, ongoing studies, future research directions, and the challenges ahead.
Sriman Swarup - One of the best experts on this subject based on the ideXlab platform.
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A systematic review and meta- analysis of randomized controlled trials to evaluate the risk of hematological toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors.
Journal of Clinical Oncology, 2018Co-Authors: Anita Sultan, Sriman Swarup, Yin Mon Myat, Htay Htay Aung, Kalpana Panigrahi, Kyaw Zin TheinAbstract:217Background: Poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors have shown to benefit in DNA repair-deficient tumors by enhancing synthetic lethality in cancer cells and are currently...
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Risk of gastrointestinal and hepatic toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase inhibitors: A meta-analysis of seven phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Anita Sultan, Sriman Swarup, Yin Mon Myat, Khaing Khaing Htwe, Aung Myo Hein, Tsujung Yang, Kyaw Zin TheinAbstract:219Background: Inhibition of poly Adenosine Diphosphate Ribose polymerase (PARP) enzymes terminates an alternative DNA repair pathway, resulting in synthetic lethality in homologous recombination deficient tumors. Many PARP inhibitors have shown to improve survival in many solid tumors with noteworthy safety concerns. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of gastrointestinal (GI) and hepatic toxicities. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018. Phase III RCTs that mention GI toxicities and elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ov...
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Discontinuation of poly(Adenosine Diphosphate-Ribose) polymerase inhibitors due to adverse events in patients with recurrent ovarian cancer: A meta-analysis of three phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Kyaw Zin Thein, Anita Sultan, Sriman Swarup, Yin Mon Myat, Catherine Jones, Fred Hardwicke, Sanjay AwasthiAbstract:118Background: Ovarian cancer is the fifth leading cause of cancer-related death among women. Poly Adenosine Diphosphate Ribose polymerase (PARP) inhibitors maintenance has shown to improve survival in patients with recurrent ovarian cancer. Yet, there are notable adverse events which led to treatment discontinuation, interruption, or dose reduction. We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of PARP inhibitors discontinuation due to adverse events. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs which employed PARP inhibitors maintenance in ovarian cancer and mentioned treatment interruption, dose reduction and treatment discontinuation due to adverse events were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: Three phase III RCTs with a total...
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Risk of health-related quality-of-life events and pulmonary toxicities in patients with cancer treated with poly Adenosine Diphosphate Ribose polymerase inhibitors: A meta-analysis of seven phase III trials.
Journal of Clinical Oncology, 2018Co-Authors: Sriman Swarup, Anita Sultan, Yin Mon Myat, Kalpana Panigrahi, Rachana Yendala, Nyein Htwe Yu, Kyaw Zin TheinAbstract:213Background: Poly Adenosine Diphosphate Ribose polymerase (PARP) enzymes aide in the repair of DNA damage. PARP inhibitors showed synthetic lethality in cancer cells and were utilized in many solid tumors with notable toxicities. Fatigue and pain are the major determinants of health-related quality of life (HRQOL) in cancer patients undergoing chemotherapy. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of HRQOL events and pulmonary toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through June 2018 were queried. Phase III RCTs that mention HRQOL events and pulmonary toxicities as adverse effects were included. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Random effects model was applied. Results: 3188 patients from 7 phase III RCTs with breast, ovarian, and gastric cancer were eligible. Studies compared olaparib or niraparib or ru...
