Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection

Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Mu-Yan Cai, Connor E. Dunn, Wenxu Chen, Bose S. Kochupurakkal, Huy Nguyen, Lisa A. Moreau, Geoffrey I. Shapiro, Kalindi Parmar, David Kozono, Alan D. D’AndreaSummaryCells deficient in ataxia telangiectasia mutated (ATM) are hypersensitive to ionizing radiation and other anti-cancer agents that induce double-strand DNA breaks. ATM inhibitors may therefore sensitize cancer cells to these agents. Some cancers may also have underlying genetic defects predisposing them to an ATM inhibitor monotherapy response. We have conducted a genome-wide CRISPR screen to identify genetic vulnerabilities that sensitize lung cancer cells to ATM inhibitors. Knockout of genes in the Fanconi anemia (FA)/BRCA pathway results in hypersensitivity to the ATM inhibitor M3541. Knockdown of either an FA gene or of ATM results in reduced double-strand break end resection, enhanced non-homologous end joining (NHEJ) repair, and decreased homologous recombination repair. Knockout of both the FA/BRCA pathway and ATM strongly inhibits end resection and generates toxic levels of NHEJ, thereby elucidating a mechanism of cellular death by synthetic lethality. ATM inhibitors may therefore be useful for the treatment of tumors with a defective FA/BRCA pathway.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

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Authors: Zhou S, Wei J, Wang Y, Liu X Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. Despite clinical advances, the survival rate of patients with HCC remains low, as most patients are diagnosed with HCC when they are already at the advanced stage. Certain circular RNAs (circRNAs) are closely associated with the development of liver cancer. In the present study, a circRNA array was performed to screen differentially expressed circRNAs in HCC tissues. The further analysis focused on the newly identified circRNA_101237, the host gene of which, cyclin-dependent kin...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Li L, Zheng Y, Zheng Q, Jiang J Abstract The present study aimed to investigate the antiproliferative effect of embryonic stem cell-conditioned medium (ESC-CM) on the mouse liver cancer Hepa1-6 cells in vitro. Furthermore, in order to elucidate the underlying molecular mechanism, the microRNAs (miRNAs) in ESC-CM associated with the inhibition of Hepa1-6 proliferation were identified. Following the co-culture of ESC-CM and Hepa1-6 in Transwell chambers, the proliferation, cell cycle, apoptosis and associated protein expression were determined in Hepal-6 cells. Moreover, miRNA array analysis was employed to ...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Authors: Dolkhani S, Najafpour A, Mohammadi R Abstract Purpose: The improvement of techniques using conduits that connects the ends of damaged nerves and guides the growth of nerve fibers between the stumps, including adoption of natural or synthetic materials still is a challenge in peripheral nerve repair. The aim of the present novel study was to fabricate and transplant chitosan-selenium biodegradable nanocomposite conduit on transected sciatic nerve in rat model.Methods: In NORMAL group, the left sciatic nerve was exposed through a gluteal muscle incision and after careful hemostasis skin was closed. In TRANSE...
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
Bacteria in some tumors may hinder cancer treatments. (read more)
Source: Environmental Factor - NIEHS Newsletter - Category: Environmental Health Source Type: news
Publication date: Available online 31 March 2020Source: Actas Urológicas Españolas (English Edition)Author(s): D. Nieblas-Toscano, A.J. Arenas-Bonilla, J.F. Flores-Martín, F. Gutiérrez-Tejero, C. Velarde-Muñoz, C.I. Ramos-Alaminos, M.C. Salas-Moreno, R. Galisteo-Moya, J. Moreno-Jiménez
Source: Actas Urologicas Espanolas - Category: Urology & Nephrology Source Type: research
This report provides an in-depth look at public drug program spending in Canada, using the Canadian Institute for Health Information's (CIHI) National Prescription Drug Utilization Information System. Public drug program spending does not include spending on drugs dispensed in hospitals or on those funded through cancer agencies and other special programs. Public drug program spending increased by 6.8% in 2018, compared to an increase of 5.3% in 2017. The growth in 2018 was largely because of the introduction of Ontario Health Insurance Plan+ (OHIP+), which extended drug coverage to all Ontario residents age 24 years or y...
Source: Healthcare Quarterly - Category: International Medicine & Public Health Source Type: research
This article analyzes data on 28 indicators prioritized over these years and demonstrates that 25 have shown sustained improvement over time. The performance management approach, lessons learned and gaps in knowledge are described to inform future research and practice.
Source: Healthcare Quarterly - Category: International Medicine & Public Health Source Type: research
Publication date: Available online 31 March 2020Source: Preventive MedicineAuthor(s): Dean Connolly, Xan Hughes, Alison Berner
Source: Preventive Medicine - Category: International Medicine & Public Health Source Type: research
This study assessed the utility and safety of robot-assisted ISR by comparing groups of patients who underwent low anterior resection (LAR) with or without ISR and ISR extent.MethodsThis study enrolled 897 patients who underwent curative LAR between 2010 and 2017. Patients were divided into those who did (ISR+) and did not (ISR −) undergo ISR, with the former group subdivided by ISR extent (partial, subtotal, and total). Tumor recurrence and survival were compared in the two groups by one-to-one nearest neighbor matching (218 patients each).ResultsRobot-assisted ISR was performed via an entirely transabdominal approa...
Source: Surgical Endoscopy - Category: Surgery Source Type: research
ConclusionsIntracorporeal anastomosis using linear staplers reduced anastomotic bleeding and stenosis compared to extracorporeal anastomosis after LTG. Future research will be required to determine the ideal method for intracorporeal anastomosis in LTG.
Source: Surgical Endoscopy - Category: Surgery Source Type: research
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