Synthetic lethality in malignant pleural mesothelioma with PARP1 inhibition

AbstractMalignant pleural mesotheliomas (MPM) are most often surgically unresectable, and they respond poorly to current chemotherapy and radiation therapy. Between 23 and 64% of malignant pleural mesothelioma have somatic inactivating mutations in the BAP1 gene. BAP1 is a homologous recombination (HR) DNA repair component found in the BRCA1/BARD1 complex. Similar to BRCA1/2 deficient cancers, mutation in the BAP1 gene leads to a deficient HR pathway and increases the reliance on other DNA repair pathways. We hypothesized that BAP1-mutant MPM would require PARP1 for survival, similar to the BRCA1/2 mutant breast and ovarian cancers. Therefore, we used the clinical PARP1 inhibitors niraparib and olaparib to assess whether they could induce synthetic lethality in MPM. Surprisingly, we found that all MPM cell lines examined, regardless of BAP1 status, were addicted to PARP1-mediated DNA repair for survival. We found that niraparib and olaparib exposure markedly decreased clonal survival in multiple MPM cell lines, with and without BAP1 mutations. This clonal cell death may be due to the extensive replication fork collapse and genomic instability that PARP1 inhibition induces in MPM cells. The requirement of MPM cells for PARP1 suggests that they may generally arise from defects in HR DNA repair. More importantly, these data demonstrate that the PARP1 inhibitors could be effective in the treatment of MPM, for which little effective therapy exists.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research

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CONCLUSIONS: Simultaneous CRC and CRLM resections seem to be safe when patients are carefully selected, also considering the risk of recurrence concerning oncologic outcomes. The pre-planning of simultaneous resection is mandatory to plan trocar positioning, procedure sequencing, and patient position. PMID: 32490901 [PubMed - in process]
Source: Acta Cirurgica Brasileira - Category: Surgery Authors: Tags: Acta Cir Bras Source Type: research
Abstract PURPOSE: To evaluate the in vivo response of photobiomodulation therapy associated with norbixin-based poly(hydroxybutyrate) membrane (PHB) in tenotomized calcaneal tendon. METHODS: Thirty rats were randomly allocated to six groups (n=5 each): LED groups (L1, L2 and L3) and membrane + LED groups (ML1, ML2 and ML3). The right calcaneal tendons of all animals were sectioned transversely and were irradiated with LED daily, one hour after surgery every 24 hours, until the day of euthanasia. At the end of the experiments the tendons were removed for histological analysis. RESULTS: The histological an...
Source: Acta Cirurgica Brasileira - Category: Surgery Authors: Tags: Acta Cir Bras Source Type: research
Authors: Ordak M, Nasierowski T, Pawlik K, Muszynska E, Bujalska-Zadrozny M Abstract Objectives: The purpose of this research was to investigate the effectiveness of the methadone programme in a group of patients taking mephedrone with heroin.Methods: The research involved 230 people who took part in the methadone programme between 2010 and 2019: 101 people on a mephedrone binge and taking heroin and 129 people addicted to heroin.Results: Number of re-hospitalisations was higher in a group of patients on a mephedrone binge taking heroin in comparison to heroin dependent patients (91.9 vs 79.8%, p 
Source: International Journal of Psychiatry in Clinical Practice - Category: Psychiatry Tags: Int J Psychiatry Clin Pract Source Type: research
Publication date: Available online 3 June 2020Source: Carbohydrate PolymersAuthor(s): Ben Newland, Carmine Varricchio, Yvonne Körner, Franziska Hoppe, Christian Taplan, Heike Newland, Dimitri Eigel, Giusy Tornillo, Dagmar Pette, Andrea Brancale, Petra B. Welzel, F. Philipp Seib, Carsten Werner
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
Publication date: Available online 3 June 2020Source: Carbohydrate PolymersAuthor(s): Zhuodong Chai, Chao Teng, Lei Yang, Lianjie Ren, Zhongyue Yuan, Siyuan Xu, Manman Cheng, Yanmei Wang, Zhen Yan, Chao Qin, Xiaopeng Han, Lifang Yin
Source: Carbohydrate Polymers - Category: Biomedical Science Source Type: research
CONCLUSION: a Navigation Program was developed adapted to the Brazilian reality, and attributions of the navigators were created. PMID: 32491120 [PubMed - in process]
Source: Revista Latino-Americana de Enfermagem - Category: Nursing Authors: Tags: Rev Lat Am Enfermagem Source Type: research
Publication date: Available online 3 June 2020Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Houhe Liu, Yusi Quan, Xinlin Jiang, Xiaotian Zhao, Yi Zhou, Jijun Fu, Lingran Du, Xiaoya Zhao, Jing Zhao, Lu Liang, Di Yi, Yugang Huang, Guodong Ye
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research
Publication date: Available online 3 June 2020Source: Sensors and Actuators B: ChemicalAuthor(s): Hui-Min Wang, Ai-Jun Wang, Pei-Xin Yuan, Jiu-Ju Feng
Source: Sensors and Actuators B: Chemical - Category: Chemistry Source Type: research
Chem. Commun., 2020, Accepted Manuscript DOI: 10.1039/D0CC03589K, CommunicationLongbing Ling, Haizhou Yu, Muhammad Ismail, Yan-Ping Zhu, Yuan Du, Junhui Qi An amphiphilic dimeric-podophyllotoxin (PODO) phospholipid was synthesized to assemble into liposomes as a combination of prodrug and nanocarriers. Results have demonstrated cell membrane-like delivery system possessed an improved cellular uptake... The content of this RSS Feed (c) The Royal Society of Chemistry
Source: RSC - Chem. Commun. latest articles - Category: Chemistry Authors: Source Type: research
Authors: Cheng J, Yang A, Cheng S, Feng L, Wu X, Lu X, Zu M, Cui J, Yu H, Zou L Abstract BACKGROUND MicroRNAs (miRNAs) are attracting substantial interest as promising noninvasive biomarkers for gastric cancer (GC). Our study aimed to identify circulating miRNAs that are potential noninvasive markers for precancerous lesions and early gastric cancers (EGCs). MATERIAL AND METHODS Plasma specimens were obtained from 58 gastritis subjects, 54 patients with precancerous lesions, and 38 EGC patients for study. RESULTS Significant differences in the plasma expression levels of miR-19a-3p, miR-22-3p, miR-146a-5p, and miR-483-5p (all P
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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