Repair of DNA damage induced by the novel nucleoside analogue CNDAG through homologous recombination

ConclusionCNDAG-induced double-strand breaks are repaired mainly through homologous recombination.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research

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Conclusions: The expression of ERCC1 and NF- κ B give a worse prognosis for relapse, and only ERCC1 had an influence on the overall survival of TGCT patients treated with platinum-based chemotherapy. These may represent markers that predict poor clinical outcome and response to cisplatin.
Source: International Braz J Urol - Category: Urology & Nephrology Source Type: research
AbstractGenetic complexity and DNA damage repair defects are common in different cancer types and can induce tumor-specific vulnerabilities. Poly(ADP-ribose) polymerase (PARP) inhibitors exploit defects in the DNA repair pathway through synthetic lethality and have emerged as promising anticancer therapies, especially in tumors harboring deleterious germline or somatic breast cancer susceptibility gene (BRCA) mutations. However, the utility of PARP inhibitors could be expanded beyond germlineBRCA1/2 mutated cancers by causing DNA damage with cytotoxic agents in the presence of a DNA repair inhibitor. US Food and Drug Admin...
Source: Drugs in R&D - Category: Drugs & Pharmacology Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsIt appears that CSCs play a major role in the underlying mechanisms of oncogenesis and development of relapse in EOC. Part of promising future plans would be to not only use them as therapeutic targets, but also extent their value on a preventative level through engineering mechanisms and prevention of EOC in its origin.
Source: Archives of Gynecology and Obstetrics - Category: OBGYN Source Type: research
Cells become senescent in response to a variety of circumstances. The vast majority are cases of replicative senescence, somatic cells reaching the Hayflick limit. Cell damage and toxic environments also produce senescence, and senescent cells are also created as a part of the wound healing process. A senescent cell ceases replication and begins to secrete inflammatory and pro-growth signals, altering the nearby extracellular matrix and behavior of surrounding cells - even encouraging them to become senescent as well. Near all senescent cells last a short time only, as they self-destruct or are removed by the immune...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Conclusion: Although PD-L1 expression is associated with prolonged survival, it was not identified as an independent prognostic marker. Microsatellite status did not influence long-term survival. PMID: 32191146 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
We examined the expression of proposed effectors in homologous recombination (HR: RAD51, ATM, FANCD2), error-prone non-homologous end-joining (NHEJ: 53BP1), and base excision repair pathways (BER: PAR and PARP1) in a cohort of sequential OC samples obtained at diagnosis, after neoadjuvant chemotherapy (NACT), and/or at relapse from a total of 147 patients. Immunohistochemical (IHC) expression was quantified using the H-score (0–300), where H ≤ 10 defined negativity. Before NACT, a significant number of cases lacked the expression of some effectors: 60%, 60%, and 24% were PAR-, FANCD2-, or RAD51-negative, w...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
e;n Z Abstract Germinal or somatic mutations of the BRCA genes may serve as therapeutic targets. Deficient functioning of the BRCA genes render the cancer vulnerable to such therapeutic interventions as chemotherapy with DNA-targeted agents and PARP inhibitors targeting DNA repair capacity. Although BRCA mutations may be detected in a large variety of cancers, the mentioned specific therapies are efficient in the so called BRCA-associated cancers only including ovarian, breast, pancreatic, prostate cancers and the rare uterine sarcomas. While in ovarian and prostate carcinomas both germinal and somatic, in breast ...
Source: Magyar Onkologia - Category: Cancer & Oncology Authors: Tags: Magy Onkol Source Type: research
SummaryThe recent  exciting findings on the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor (PARPi) maintenance therapy in the first-line and later lines of treatment in ovarian cancer are illustrated. Unprecedented advantages have been shown in first-line therapy not only in BRCA-mutated cancer s, but also in tumor exhibiting a homologous recombination repair deficiency (HRD) unrelated to BRCA aberrations. The advantages of PARP maintenance therapy in around 50% of HR-proficient high-grade ovarian cancers are far less clear and, even though of statistical significance, the clinical benefi t ...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
ad CJ Abstract In response to DNA damage, cell cycle checkpoints produce cell cycle arrest to repair and maintain genomic integrity. Due to the high rates of replication and genetic abnormalities, cancer cells are dependent on replication stress response (RSR) and inhibitors of this pathway are being studied as an anticancer approach. In this direction, we investigated the inhibition of CHK1 and WEE1, key components of RSR, using Polypurine Reverse Hoogsteen hairpins (PPRHs) as gene silencing tool. PPRHs designed against WEE1 or CHK1 reduced the viability of different cancer cell lines and showed an increase of ap...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
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