Search results for " Repair"

Induction of DNA Repair Genes in Mammalian Cells in Response to Genotoxic Stress

2006

Genotoxic agents provoke the activation of receptor-triggered pathways and DNA damage-related functions. Here we review data on immediate-early cellular responses and transcriptional activation of DNA repair genes following exposure of mammalian cells to genotoxic stress. Functional consequences of induction of DNA repair genes are also briefly discussed.

P678Elevated levels of 2-arachidonoylglycerol promote atherogenesis and hamper endothelial repair in murine models

2017

Zebrafish Fins as a Model System for Skeletal Human Studies

2007

Recent studies on the morphogenesis of the fins ofDanio rerio(zebrafish) during development and regeneration suggest that a number of inductive signals involved in the process are similar to some of those that affect bone and cartilage differentiation in mammals and humans. Akimenko et al. (2002) has shown that bone morphogenetic protein-2b (BMP2b) is involved in the induction of dermal bone differentiation during fin regeneration. Many other groups have also shown that molecules from the transforming growth factor-beta superfamily (TGFβ), including BMP2, are effective in promoting chondrogenesis and osteogenesisin vivoin higher vertebrates, including humans. In the present study, we review…

Immunoscore in Mismatch Repair-Proficient and -Deficient Colon Cancer

2017

Abstract The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8. Lymphocytes were then digitally calculated to categorize IS from grade …

The Abdominal Compartment Syndrome (ACS) after Abdominal Aortic Aneurysm (AAA) open repair

2009

Objective: The abdominal compartment syndrome (ACS) is a ‘condition in which increased tissue pressure in a confined anatomic space, causes decreased blood flow leading to ischaemia and dysfunction and leading to permanent impairment of function’. Methods: Between June 2007 and June 2008 we treated surgically 23 cases of AAA (14 in election and nine in emergency), with indirect intra- abdominal pressure (IAP) monitoring (intra-vescical catheter). Mean age was 68 (64–84) years, 19 males and 4 females. Mean transverse diameter was 6.2 cm (5.5–9.0). Preoperative diagnostic procedure was ultrasound and tomography when possible. All patients were managed in hypotensive hemostasis (restricting fl…

In the literature: April 2020

2020

Deficient DNA mismatch repair (dMMR) may be caused by germline or somatic mutations in mismatch repair genes ( MLH1 , MSH2 , MSH3 , MSH6 and PMS2 ) or through epigenetic silencing of MLH1 .1 dMMR induces a hypermutator phenotype, also known as microsatellite instability (MSI). Next-generation sequencing identifies MSI in 12 cancer types. The highest prevalence is seen in endometrial cancer (31.4%), followed by colorectal cancer (19.7%) and gastric cancer (GC, 19.1%). MSI was related to better prognosis for colorectal cancer and GC . Moreover, the dMMR/MSI hypermutator phenotype is thought to produce large numbers of immunogenic neoantigens that can be recognised by immune cells, leading to …

Phosphorylation of mismatch repair proteins MSH2 and MSH6 affecting MutSα mismatch-binding activity

2002

Mismatch repair (MMR) is involved in the removal of mispaired bases from DNA and thus plays an important role in the maintenance of genomic stability and the prevention of mutations and cancer. Moreover, MMR triggers genotoxicity and apoptosis upon processing of DNA lesions such as O6-methylguanine. Whereas the enzymology of MMR has been elucidated in great detail, only limited data are available concerning its regulation. Here we show that the major mismatch-binding proteins MSH2 and MSH6, forming the MutSalpha complex, are phosphorylated in vitro by protein kinase C and casein kinase II, but not by protein kinase A. Phosphorylation of MSH2 and MSH6 was also found within the cell, with MSH…

Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs

2017

Background Mismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the deve…

WRN protects against topo I but not topo II inhibitors by preventing DNA break formation

2008

The Werner syndrome helicase/3′-exonuclease (WRN) is a major component of the DNA repair and replication machinery. To analyze whether WRN is involved in the repair of topoisomerase-induced DNA damage we utilized U2-OS cells, in which WRN is stably down-regulated (wrn-kd), and the corresponding wild-type cells (wrn-wt). We show that cells not expressing WRN are hypersensitive to the toxic effect of the topoisomerase I inhibitor topotecan, but not to the topoisomerase II inhibitor etoposide. This was shown by mass survival assays, colony formation and induction of apoptosis. Upon topotecan treatment WRN deficient cells showed enhanced DNA replication inhibition and S-phase arrest, whereas af…

Targeting DNA double strand break repair with hyperthermia and DNA-PKcs inhibition to enhance the effect of radiation treatment

2016

// Bregje van Oorschot 1 , Giovanna Granata 1 , Simone Di Franco 2 , Rosemarie ten Cate 1 , Hans M. Rodermond 1 , Matilde Todaro 3 , Jan Paul Medema 1 , Nicolaas A.P. Franken 1 1 Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine, Department of Radiation Oncology, Academic Medical Center, Cancer Genomics Center, Amsterdam, The Netherlands 2 Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy 3 Biomedical Department of Internal and Specialistic Medicine (DIBIMIS), University of Palermo, Palermo, Italy Correspondence to: Nicol…