PARPi focus the spotlight on replication fork protection in cancer

Nature Cell Biology 19, 1309 (2017). doi:10.1038/ncb3638 Author: Katharina Schlacher PARP inhibitors (PARPi) kill BRCA1/2-mutated cancers, which become resistant when DNA repair functions are restored. Now, MUS81 nuclease inhibition due to EZH2 downregulation is found to restore DNA replication fork protection but not repair, leading to PARPi-resistance in mutant BRCA2 cells and patients. This challenges the DNA repair dominance in synthetic lethality.
Source: Nature Cell Biology - Category: Cytology Authors: Tags: News and Views Source Type: research

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The most common occult malignancy in gynecologic surgery is uterine cancer. Unintentional spillage of cells can occur during morcellation and subtotal hysterectomy performed with supportive repair. While available screening for endometrial cancer may reduce the risk of occult malignancy, it is not cost effective in the asymptomatic patient. One diagnostic method that has not been explored for the uterine body, but has shown promise in cervical, breast, prostate, and skin cancer is bioimpedance analysis.
Source: American Journal of Obstetrics and Gynecology - Category: OBGYN Authors: Tags: Non-Oral Poster Source Type: research
SummaryPurpose To elucidate the radiosensitizing effect and underlying mechanism of a new kind of DNA methyltransferase (DNMT) inhibitor with biological availability.Methods A novel non-nucleoside compound, designated as MA-17, was recently derived from a phthalimido alkanamide structure. DNMT expressions were confirmed in cultured human lung cancer (A549) and normal astrocyte (NHA) cells, radiosensitivity was measured using clonogenic assay, and assays of cell cycle alteration, apoptosis, DNA damage repair, and differential gene expression were undertaken.Results MA-17 significantly radiosensitized A549 cells with a mean ...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
(Helmholtz Zentrum M ü nchen - German Research Center for Environmental Health) The use of stem cells to repair organs is one of the foremost goals of modern regenerative medicine. Scientists at Helmholtz Zentrum M ü nchen and Ludwig Maximilian University of Munich (LMU) have discovered that the protein Akna plays a key role in this process. It controls, for example, the behavior of neural stem cells via a mechanism that may also be involved in the formation of metastases. The study was published in the renowned journal 'Nature'.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
by Jingming Wang, Bryan Chan, Michael Tong, YiTing Paung, Ukhyun Jo, Dwight Martin, Markus Seeliger, John Haley, Hyungjin Kim The Fanconi Anemia (FA) pathway is a multi-step DNA repair process at stalled replication forks in response to DNA interstrand cross-links (ICLs). Pathological mutation of key FA genes leads to the inherited disorder FA, characterized by progressive bone marrow failure and cancer predisposition. T he study of FA is of great importance not only to children suffering from FA but also as a model to study cancer pathogenesis in light of genome instability among the general population. FANCD2 monoubiqui...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
ConclusionsSeveral immunohistochemical markers might be helpful in predicting the response to conservative treatment of endometrial hyperplasia and early endometrial cancer on pre ‐treatment and follow‐up specimens. Further studies are needed to confirm their usefulness and possibly integrate them in a predictive immunohistochemical panel.This article is protected by copyright. All rights reserved.
Source: Acta Obstetricia et Gynecologica Scandinavica - Category: OBGYN Authors: Tags: Systematic review Source Type: research
In this study, we revisited this claim by independently evaluating the proposed marker haplotype using 2 different patient cohorts recruited in different research settings. Meta-analysis of these new postmastectomy cohorts and the original cohort confirmed significant association of the CACNG2 haplotype with PMP. In addition, we tested whether the same markers would predict chronic postsurgical pain in men who underwent surgery for inguinal hernia repair, and whether there is significant genetic association with cutaneous thermal sensitivity in postmastectomy and postherniotomy patients. We found that the biomarker is sele...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
ConclusionThis study reveals the key role of HSP90 in the mechanism of tumor radio-sensitization by MN-OA.General significancePresent work provides a deeper understanding about the mechanism of MN-OA-induced tumor radiosensitization, highlighting the role of HSP90 protein. In addition to diagnostic and magnetic hyperthermia abilities, present remarkable radiosensitizing activity of MN-OA would further excite the clinicians to test its anti-cancer potential.Graphical abstract
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research
Publication date: 19 February 2019Source: Cell Reports, Volume 26, Issue 8Author(s): Deeksha Munnur, Joanna Somers, George Skalka, Ria Weston, Rebekah Jukes-Jones, Mohammed Bhogadia, Cyril Dominguez, Kelvin Cain, Ivan Ahel, Michal MalewiczSummaryAlthough poly-ADP-ribosylation (PARylation) of DNA repair factors had been well documented, its role in the repair of DNA double-strand breaks (DSBs) is poorly understood. NR4A nuclear orphan receptors were previously linked to DSB repair; however, their function in the process remains elusive. Classically, NR4As function as transcription factors using a specialized tandem zinc-fin...
Source: Cell Reports - Category: Cytology Source Type: research
Some of the voices of the past can appear entirely contemporary, because they saw further and with greater clarity than most of their peers. John W. Campbell, editor of Astounding Science-Fiction Magazine, died of heart disease at age 61 in 1971. In 1949 he wrote an editorial on the future of medicine, aging, and longevity that wouldn't seem out of place today. He anticipated what we presently call actuarial escape velocity, or longevity escape velocity, the idea that gains in life span through progress in medical technology allow greater time to benefit from further gains - and eventually, we are repaired more rapidly tha...
Source: Fight Aging! - Category: Research Authors: Tags: Healthy Life Extension Community Source Type: blogs
Introduction: Endometrial cancer (EC) is one of the mostly widespread gynaecological tumours worldwide. Loss of DNA mismatch repair (MMR) is a frequent event in ECs, leading to an easily recognizable molecular phenotype known as microsatellite instability (MSI). Though in colorectal cancers MSI appears to be of prognostic significance, the relationship between MSI and outcome and other clinicopathologic variables in EC has not been firmly established.
Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology - Category: OBGYN Authors: Tags: Session 25 – Oncology Source Type: research
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