Search results for "Repair"

2019

From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)…

DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis

2011

DNA damaging agents are potent inducers of cell death triggered by apoptosis. Since these agents induce a plethora of different DNA lesions, it is firstly important to identify the specific lesions responsible for initiating apoptosis before the apoptotic executing pathways can be elucidated. Here, we describe specific DNA lesions that have been identified as apoptosis triggers, their repair and the signaling provoked by them. We discuss methylating agents such as temozolomide, ionizing radiation and cisplatin, all of them are important in cancer therapy. We show that the potentially lethal events for the cell are O(6)-methylguanine adducts that are converted by mismatch repair into DNA dou…

Checkpoint adaptation in repair-deficient cells drives aneuploidy and resistance to genotoxic agents

2018

AbstractHuman cancers frequently harbour mutations in DNA repair genes, rendering the use of DNA damaging agents as an effective therapeutic intervention. As therapy-resistant cells often arise, it is important to better understand the molecular pathways that drive resistance in order to facilitate the eventual targeting of such processes. We employ repair-defective diploid yeast as a model to demonstrate that, in response to genotoxic challenges, nearly all cells eventually undergo checkpoint adaptation, resulting in the generation of aneuploid cells with whole chromosome losses that have acquired resistance to the initial genotoxic challenge. We demonstrate that adaptation inhibition, eit…

DNA repair in defence against genotoxin-induced apoptosis

2006

DNA repair systems

2006

Improvement of baculovirus as protein expression vector and as biopesticide by CRISPR/Cas9 editing

2019

The clustered regularly interspaced short palindromic repeats (CRISPR) system?associated Cas9 endonuclease is a molecular tool that enables specific sequence editing with high efficiency. In this study, we have explored the use of CRISPR/Cas9 system for the engineering of baculovirus. We have shown that the delivering of Cas9-single guide RNA ribonucleoprotein (RNP) complex with or without DNA repair template into Sf21 insect cells through lipofection might be efficient to produce knockouts as well as knock-ins into the baculovirus. To evaluate potential application of our CRISPR/Cas9 method to improve baculovirus as protein expression vector and as biopesticide, we attempted to knockout se…

Nuclear expression of apurinic/apyrimidinic endonuclease increases with progression of ovarian carcinomas.

2003

Apurinic/apyrimidinic endonuclease (APE alias Ref-1) is a key enzyme in the base excision repair pathway. Besides its function in DNA repair, APE serves to maintain several transcription factors in an active reduced state such as c-Fos, c-Jun, NF-kappaB, p53 and HIF-1alpha, all of which have been shown to play a role in tumorigenesis. Because of the importance of APE in maintaining genomic stability and gene regulation, we examined whether APE expression is associated with survival and histopathological parameters of patients with ovarian cancer.Tissue sections of primary epithelial ovarian carcinomas from 141 patients were immunostained using a monoclonal antibody directed against APE.Nucl…

Survival in extreme dryness and DNA-single-strand breaks.

1992

A wide variety of organisms (the so-called "anhydrobiotes') is able to survive long periods of time in a state of utmost dehydration and can thus survive in extremely dry environments including artificially imposed or space vacuum. Known strategies of survival include the accumulation of certain polyols, especially disaccharides, which help prevent damage to membranes and proteins. Here we report that DNA in vacuum-dried spores is damaged to a very substantial degree by processes leading to DNA strand breaks. Most of these lesions are obviously repaired during germination, but extensive damage to DNA and enzymes after long exposure times (months to years) finally diminish the chances of sur…

Composite Scaffolds with a Hydrohyapatite Spatial Gradient for Osteochondral Defect Repair

2018

Osteochondral defects derived by traumatic injury or aging related disease are often associated with severe joint pain and progressive loss of joint functions for millions of people worldwide and represent a major challenge for the orthopedic community. Tissue engineering offers new therapeutic approach to repair the osteochondral defects, through the production of scaffolds manufactured to mimic their complex architecture, which consists of cartilage and bone layers. Composite scaffolds based on a PLLA polymeric matrix containing hydroxyapatite (HA) as a filler were prepared through a modified thermally induced phase separation (TIPS) protocol. A suspension was prepared by adding sieved HA…

Endovascular Aneurysm Repair

2002

Background — The purpose of the present study was to systematically analyze the histopathologic organization processes in excluded aneurysms after endovascular stenting and to develop a noninvasive monitoring method for these processes using MRI. Methods and Results — In 36 mongrel dogs, autologous aortic aneurysms were created. Endovascular treatment was performed using covered stents. Follow-up was after 1 week, 6 weeks, and 6 months. MRI was performed with T 2 -weighted turbo-spin-echo sequences and T 1 -weighted spin-echo sequences and was repeated after contrast bolus with gadolinium. Histopathologic findings were correlated to signal intensities (SIs) of MRI images. SIs of distinct a…