Search results for "DNA Repair"
showing 10 items of 295 documents
Long-time expression of DNA repair enzymes MGMT and APE in human peripheral blood mononuclear cells.
2001
The DNA repair enzymes O6-methylguanine-DNA methyltransferase (MGMT) and apurinic/apyrimidinic endonuclease (APE, also known as Ref-1) play an important role in cellular defense against the mutagenic and carcinogenic effects of DNA-damaging agents. Cells with low enzyme activity are more sensitive to induced DNA damage and may confer a higher carcinogenic risk to the individuals in question. To study the level of variability of MGMT and APE expression in human, we analyzed in a long-time study MGMT and APE expression in peripheral blood mononuclear cells (PBMC) from healthy individuals. The data revealed high inter- and intraindividual variability of MGMT but not of APE. For MGMT, the inter…
Ribonucleotide Reductase Messenger RNA Expression and Survival in Gemcitabine/Cisplatin-Treated Advanced Non-Small Cell Lung Cancer Patients
2004
Abstract Purpose: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity. Experimental Design: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcit…
Chemoradiotherapy of Newly Diagnosed Glioblastoma With Intensified Temozolomide
2009
Purpose To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma. Patients and Methods A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m 2 (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m 2 ), maintenance TMZ starting at 150 mg/m 2 using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily). Results The median follow-up interval was 21.7 months. Grade 4 hematologic toxicit…
NOA-05 phase 2 trial of procarbazine and lomustine therapy in gliomatosis cerebri.
2011
The NOA-05 multicenter trial was performed to analyze the efficacy of primary chemotherapy with procarbazine and lomustine (PC) in patients with gliomatosis cerebri (GC) and to define clinical, imaging, and molecular factors influencing outcome.Thirty-five patients with previously untreated GC were treated with up to six 56-day courses of 110mg/m(2) lomustine on day 1 and 60mg/m(2) procarbazine on days 8 to 21. The primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause, or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy.The failure-free survival rate at 8 months was 50.3…
Activity of O 6 -methylguanine DNA methyltransferase in mononuclear blood cells of formaldehyde-exposed medical students
1999
A recent study reported that exposure of student embalmers in Cincinnati to high concentrations of formaldehyde (2 mg/m3) reduced the activity of the DNA repair protein O6-methylguanine DNA methyltransferase (MGMT). Reduction in a DNA repair enzyme may strongly increase the cancer risk not only with respect to the repair-enzyme causing agent but with respect to all carcinogens causing lesions subject to repair by the enzyme in question. Thus, we examined whether formaldehyde exposure of 57 medical students during their anatomy course at two different Universities in Germany influenced MGMT activity in mononuclear blood cells. Mean formaldehyde exposure of 41 students was 0.2 +/- 0.05 mg/m3 …
Activity and safety of temozolomide in advanced adrenocortical carcinoma patients
2019
Objective Temozolomide has shown a significant anti-proliferative activity on adrenocortical cancer (ACC) cells in vitro. Design On the basis of these results the drug was prescribed as second/third line in advanced metastatic ACC patients in four referral centers in Italy. Methods We retrospectively collected anagraphic, clinical and pathological data of patients with advanced ACC with disease progression to standard chemotherapy plus mitotane who were treated with temozolomide at the dose of 200 mg/m2/die given for 5 consecutive days every 28 days. The primary endpoint was the disease control rate, defined as objective response or disease stabilization after 3 months. Secondary endpoints…
Repair of oxidatively generated DNA damage in Cockayne syndrome
2013
Defects in the repair of endogenously (especially oxidatively) generated DNA modifications and the resulting genetic instability can potentially explain the clinical symptoms of Cockayne syndrome (CS), a hereditary disease characterized by developmental defects and neurological degeneration. In this review, we describe the evidence for the involvement of CSA and CSB proteins, which are mutated in most of the CS patients, in the repair and processing of DNA damage induced by reactive oxygen species and the implications for the induction of cell death and mutations. Taken together, the data demonstrate that CSA and CSB, in addition to their established role in transcription-coupled nucleotide…
Change in expression of MGMT during maturation of human monocytes into dendritic cells.
2005
Dendritic cells (DCs) maturated from monocytes play an important role in the immune system, not only in defense against conventional infections but also in cancer rejection. Because of the central role of DCs in tumor host defense it is highly important that DCs as well as the progenitor cell population are protected during cancer therapy. Since most anticancer drugs target DNA, the DNA repair capacity is most importance for the response of DCs and their precursor cells. Here, we studied the expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) in monocytes obtained from peripheral blood of healthy donors and DCs maturated from monocytes (moDCs). We show that MG…
Transgenic systems in studies on genotoxicity of alkylating agents: critical lesions, thresholds and defense mechanisms
1998
Abstract Transgenic systems, both cell lines and mice with gain or loss of function, are being used in order to modulate the expression of DNA repair proteins, thus allowing to assess their contribution to the defense against genotoxic mutagens and carcinogens. In this review, questions have been addressed concerning the use of transgenic systems in elucidating critical primary DNA lesions, their conversion into genotoxic endpoints, low-dose effects, and the relative contribution of individual cellular functions in defense. It has been shown that the repair protein alkyltransferase (MGMT) is decisive for protection against methylating and chloroethylating compounds. Protection pertains also…
Assessment of mechanisms driving non-linear dose-response relationships in genotoxicity testing.
2014
In genetic toxicology, risk assessment has traditionally adopted linear dose-responses for any compound that causes genotoxic effects. Increasing evidence of non-linear dose-responses, however, suggests potential cellular tolerance to low levels of many genotoxicants with diverse modes of action. Such putative non-linear dose-responses need to be substantiated by strong mechanistic data that identifies the mechanisms responsible for the tolerance to low doses. This can be achieved by experimental demonstration of cytoprotective mechanisms and by providing experimental support for the existence of tolerance mechanisms against low dose effects. By highlighting key experiments into low dose me…