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Epigenetic regulation of TP53 is involved in prostate cancer radioresistance and DNA damage response signaling

Signal Transduction and Targeted Therapy 2023年第11期8卷 5404-5416页

作者： Catarina Macedo-Silva Vera Miranda-Gonçalves nuno Tiago tavares Daniela Barros-Silva Joana Lencart João Lobo Ângelo Oliveira Margareta PCorreia Lucia Altucci Carmen Jerónimo Cancer Biology&Epigenetics Group Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Precision Medicine University of Campania“Luigi Vanvitelli”80138NaplesItaly Department of Pathology and Molecular Immunology ICBAS-School of Medicine&Biomedical SciencesUniversity of PortoR.Jorge de Viterbo Ferreira 2284050-313PortoPortugal Medical Physics Radiobiology and Radiation Protection Group-Research Center of IPO Porto(CI-IPOP)/CI-IPOP@RISE(Health Research Network)Portuguese Oncology Institute of Porto(IPO-Porto)/Porto Comprehensive Cancer Center Raquel Seruca(Porto.CCC)R.Dr.António Bernardino de Almeida4200-072PortoPortugal Department of Medical Physics Portuguese Oncology Institute of Porto4200-072PortoPortugal Department of Pathology Portuguese Oncology Institute of PortoPortoPortugal Department of Radiation Oncology Portuguese Oncology Institute of PortoPortoPortugal BIOGEM Molecular Biology and Genetics Research Institute83100AvellinoItaly IEOS Institute of Endocrinology and Oncology80100NaplesItaly

External beam radiotherapy(RT)is a leading first-line therapy for prostate cancer(PCa),and,in recent years,significant advances have been ***,RT resistance can arise and result in long-term recurrence or disease progression in the worst-case ***,making crucial the discovery of new targets for PCa ***,we generated a radioresistant PCa cell line,and found p53 to be highly expressed in radioresistant PCa cells,as well as in PCa patients with recurrent/disease progression submitted to *** dissection revealed that RT could promote p53 expression via epigenetic ***,a decrease of H3K27me3 occupancy at TP53 gene promoter,due to increased KDM6B activity,was observed in radioresistant PCa ***,p53 is essential for efficient DNA damage signaling response and cell recovery upon stress induction by prolonged fractionated ***,KDM6B inhibition by GSK-J4 significantly decreased p53 expression,consequently attenuating the radioresistant phenotype of PCa cells and hampering in vivo 3D tumor ***,this work contributes to improve the understanding of p53 as a mediator of signaling transduction in DNA damage repair,as well as the impact of epigenetic targeting for PCa radiosensitization.

关键词： TP53 damage cancer

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Chlorophyll-a Fluorescence in Ecology： Theoretical Considerations and Examples around Marine Macroalgae

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Journal of Environmental Science and Engineering(A) 2013年第10期2卷 606-616页

作者： Vinicius Peruzzi de Oliveira nuno tavares Martins Yocie Yoneshigue-Valentin Alex Enrich-Prast Biogeochemistry Laboratory Department of Ecology Biology Institute Federal University of Rio de Janeiro Rio de Janeiro 21941-902. Brazil Macroalgae Laboratory Department of Botany Biology Institute Federal University of Rio de Janeiro Rio de Janeiro 21941-902 Brazil

Over the last decades, the usage of PAM （pulse amplitude modulated） fluorometers for assessment of chlorophyll-a fluorescence variations became widely applied on marine macroalgae physiology and ecophysiology researches. Due to the increased use of these methods, a large number of studies, mainly relating to macroalgae ecology and physiology were worldwide reported. In this context, it was also created a mismatch of concepts about fluorescence of the chlorophyll-a and its application. Under this background, this study compile and summarize the state of the art knowledge regarding to the chlorophyll fluorescence, contextualizing the use of the PAM method with the main factors regulating photosynthesis （light, temperature, salinity nitrogen and phosphorus） in marine macroalgae. Moreover, this study also references the most used terms and shows some examples found in literature about the applicability of fluorescence parameters. The herein findings and the discussed examples, helps to emphasize the importance of fluorescence usage, that highlights the understanding of photosynthetic responses in macroalgal physiology and ecology.

关键词： Fluorometry PAM quenching analysis stress.

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Impact of Drug-Drug Interaction between CDK4/6 Inhibitors and Proton Pump Inhibitors on Survival Outcomes in the Treatment of Metastatic Breast Cancer—Real World Data from a Portuguese Center

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Journal of Cancer Therapy 2022年第5期13卷 266-274页

作者： Joana Reis Inês Costa Mariana Costa Ana Valente Catarina Almeida Marta Freitas Cláudia Caeiro Catarina Fernandes nuno tavares Miguel Barbosa Centro Hospitalar SÃ O JOÃ O E.P.E. Porto Portugal

Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world dat

关键词： Drug Interaction Survival Impact Advanced Breast Cancer CDK4/6 Inhibitors Proton Pump Inhibitors

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