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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This study involved patients from the North-East Indian population, where the numbers of reported cases are increasing rapidly and alarmingly. Oxidative stress, based on 8-OH-dG levels, was found to be significantly higher in gallbladder anomalies (cholelithiasis [CL] and cholecystitis [CS]) and GBC at the plasma and DNA level, and was associated with GBC severity. The expressions of key BER pathway genes were downregulated in gallbladder anomalies and GBC compared to controls, and in GBC compared to both non-neoplastic controls and gallbladder anomalies. Expression of XRCC1 and hOGG1 was significantly associated with both...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research
Publication date: Available online 23 May 2019Source: CellAuthor(s): Ninib Baryawno, Dariusz Przybylski, Monika S. Kowalczyk, Youmna Kfoury, Nicolas Severe, Karin Gustafsson, Konstantinos D. Kokkaliaris, Francois Mercier, Marcin Tabaka, Matan Hofree, Danielle Dionne, Ani Papazian, Dongjun Lee, Orr Ashenberg, Ayshwarya Subramanian, Eeshit Dhaval Vaishnav, Orit Rozenblatt-Rosen, Aviv Regev, David T. ScaddenSummaryStroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis, and repair. Studies of the bone marrow stroma have defined individual populations in th...
Source: Cell - Category: Cytology Source Type: research
Conclusion MethodologyUmbilical cord samples were collected after delivery of full-term, healthy babies with written consent from both parents. All 3 generations (newborn, parents and grandparents) were screened for genetic mutations, infections, cancers and other inherited diseases. Samples were transferred to a certified Good Manufacturing Practice laboratory for processing. Subjects were infused with either low dose (LD, 65 million cells) or high dose (HD, 130 million cells) of CLV-100 followed up for 6 months. We measured cytokines level using ELISA including the acute phase reactant high-sensitivity C-reactive protein...
Source: Cytotherapy - Category: Cytology Source Type: research
This study aimed to deliver a total dose of 25 Gy in blood bags at different dose rates using a blood specific irradiator and a linear accelerator in order to monitor the concentration of extracellular potassium as a function of the dose rate for 28 days, which is the expiration time of the irradiated bag. Blood was collected from 10 volunteers of the Biobank of Clinics Hospital of Federal University of Parana, Brazil. The volume of each concentrated blood bag was divided into three parts: one for inspection sample and the other two irradiated at different dose rates (135 cGy/min, 456 cGy/min, 545 cGy/min - linear ...
Source: Radiation Physics and Chemistry - Category: Physics Source Type: research
Publication date: Available online 23 May 2019Source: Molecular Aspects of MedicineAuthor(s): Judith E. Grolleman, Marcos Díaz-Gay, Sebastià Franch-Expósito, Sergi Castellví-Bel, Richarda M. de VoerAbstractThe somatic mutation spectrum imprinted in the genome of a tumor represents the mutational processes that have been active in that tumor. Large sequencing efforts in various cancer types have resulted in the identification of multiple mutational signatures, of which several have been linked to specific biological mechanisms. Several pan-cancer mutational signatures have been identified, while ...
Source: Molecular Aspects of Medicine - Category: Molecular Biology Source Type: research
ConclusionsIncisional hernia subsequent to colonic cancer resection was associated with reduced QOL several years after surgery and should be considered taken into account when evaluating the long-term outcome of colonic cancer resection.
Source: Hernia - Category: Sports Medicine Source Type: research
Reactive oxygen species (ROS) are cellular by-products produced from metabolism and also anticancer agents, such as ionizing irradiation and chemotherapy drugs. The ROS H2O2 has high rates of production in cancer cells because of their rapid proliferation. ROS oxidize DNA, protein, and lipids, causing oxidative stress in cancer cells and making them vulnerable to other stresses. Therefore, cancer cell survival relies on maintaining ROS-induced stress at tolerable levels. Hepatocyte growth factor receptor (c-MET) is a receptor tyrosine kinase overexpressed in malignant cancer types, including breast cancer. Full-length c-ME...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
In Chinese high ‐grade serous ovarian carcinoma (HGSOC) patients, we observed 10.2% of mutated genes in theRas/Raf pathway, all co ‐occurring withTP53 mutations in the same tumor, which was unrecognized previously. Our results show that in HGSOC patients, there may be an unrecognized co ‐occurrence ofTP53 mutations with mutations inRas/Raf pathway. AbstractHigh ‐grade serous ovarian carcinoma (HGSOC) is a major form of ovarian epithelial tumor that is often diagnosed only at an advanced stage when it is already highly aggressive. We performed comprehensive genomic profiling using an analytically validated clinical ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Haruhiko Sugimura DNA Polymerase Theta (POLQ) is a DNA polymerase involved in error-prone translesion DNA synthesis (TLS) and error-prone repair of DNA double-strand breaks (DSBs). In the present study, we examined whether abnormal POLQ expression may be involved in the pathogenesis of lung adenocarcinoma (LAC). First, we found overexpression of POLQ at both the mRNA and protein levels in LAC, using data from the Cancer Genome Atlas (TCGA) database and by immunohistochemical analysis of our LAC series. POLQ overexpression was associated with an advanced pathologic stage and an increased total number of somatic mutati...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Messersmith WA Abstract In the last year, several impactful updates have been added to the NCCN Guidelines for Colorectal Cancer (CRC) for the management of metastatic disease, including additional options for BRAF-mutated advanced CRC and the inclusion of combination immunotherapy (PD-1 and CTLA-4) for deficient mismatch repair/microsatellite instability (MSI)-high advanced CRC. According to Dr. Wells A. Messersmith, targeted therapies (ie, VEGFR, EGFR, multitargeted tyrosine kinase inhibitors) play an important role in CRC management, but none of them have been successful in the adjuvant setting (althoug...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
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