Search results for "RCC"
showing 10 items of 42 documents
Targeting components of the alternative NHEJ pathway sensitizes KRAS mutant leukemic cells to chemotherapy.
2014
Abstract Activating KRAS mutations are detected in a substantial number of hematologic malignancies. In a murine T-cell acute lymphoblastic leukemia (T-ALL) model, we previously showed that expression of oncogenic Kras induced a premalignant state accompanied with an arrest in T-cell differentiation and acquisition of somatic Notch1 mutations. These findings prompted us to investigate whether the expression of oncogenic KRAS directly affects DNA damage repair. Applying divergent, but complementary, genetic approaches, we demonstrate that the expression of KRAS mutants is associated with increased expression of DNA ligase 3α, poly(ADP-ribose) polymerase 1 (PARP1), and X-ray repair cross-comp…
Thermo-mechanical analyses and ways of optimization of the helium cooled DEMO First Wall under RCC-MRx rules
2017
Abstract The EUROfusion Consortium develops a design of a fusion power demonstrator plant (DEMO) in the framework of the European “Horizon 2020” innovation and research program. One of the key components in the fusion reactor is the Breeding Blanket (BB) surrounding the plasma, ensuring tritium self-sufficiency, heat removal for conversion into electricity, and neutron shielding. Among the 4 candidates for the DEMO BB, 2 of them use helium as coolant (HCPB, HCLL), and another one (DCLL) uses helium to cool down the First Wall (FW) only. Due to uncertainties regarding the plasma Heat Flux (HF) load the DEMO BB integrated FW will have to cope with, a set of sensitive thermal and stress analys…
Excision repair cross-complementation group 1 protein overexpression as a predictor of poor survival for high-grade serous ovarian adenocarcinoma.
2010
Abstract Objective The excision repair cross-complementation group 1 (ERCC1) expression is a predictor of survival after surgical treatment for several malignancies. Its overexpression has been reported as a marker of platinum resistance in lung cancer. However, the relevance of ERCC1 expression in ovarian cancer (OC) is the subject of controversy, both as a predictive parameter for platinum resistance and because of its association with poor prognosis. Therefore, we performed a retrospective study investigating ERCC1 expression and its correlation with patients' survival in OC. Methods We analyzed the ERCC1 protein expression using four different ERCC1 antibodies (clone 8F1) with different…
Poly(ADP-ribosyl)ation accelerates DNA repair in a pathway dependent on Cockayne syndrome B protein
2003
Activation of poly(ADP-ribose)polymerases 1 and 2 (PARP-1 and PARP-2) is one of the earliest responses of mammalian cells to DNA damage by numerous genotoxic agents. We have analysed the influence of PARP inhibition, either achieved by over-expression of the DNA binding domain of PARP-1 or by treatment with 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone, on the repair of single-strand breaks (SSB), pyrimidine dimers and oxidative base modifications sensitive to Fpg protein (mostly 8-hydroxyguanine) in mammalian cells at very low, non-cytotoxic levels of DNA damage. The data show that the repair rates of all three types of DNA damage are significantly lower in PARP-inhibited c…
Ontoloģijas shēma topoloģiskas un ģeometriskas informācijas apstrādei
2022
Bakalaura darbā “Ontoloģijas shēma topoloģiskas un ģeometriskas informācijas apstrādei” ir aprakstīti galvenie jēdzieni, kas saistās ar izvēlēto pētījuma tēmu, veikta izveide topoloģiskas un ģeometriskas informācijas ontoloģijai, kā arī veikta izveidotās ontoloģijas validācija. Ontoloģijas ir viens no mūsdienīgākajiem datu glabāšanas veidiem. Ontoloģijas tiek izmantotas daudz dažādās nozarēs, piemēram, medicīnā un datorikā. tomēr, lai ontoloģijas būtu noderīgas arī, piemēram, ģeogrāfisko informāciju sistēmās, ir nepieciešams definēt ģeogrāfiskas, ģeometriskas un topoloģiskas attiecības. Šī darba mērķis ir aprakstīt un atrast veidus, kā izveidot ontoloģiju, kurā būtu iekļautas toploģiskas un…
Molecular modes of action of cantharidin in tumor cells
2005
Cancer chemotherapy is often limited by patient's toxicity and tumor drug resistance indicating that new drug development and modification of existing drugs is critical for improving the therapeutic response. Traditional Chinese medicine is a rich source of potential anticancer agents. In particular, cantharidin (CAN), the active principle ingredient from the blister beetle, Mylabris, has anti-tumor activity, but the cytotoxic mechanism is unknown. In leukemia cells, cantharidin induces apoptosis by a p53-dependent mechanism. Cantharidin causes both DNA single- and double-strand breaks. Colony-forming assays with knockout and transfectant cells lines showed that DNA polymerase beta, but not…
Hypoxia and Human Genome Stability: Downregulation of BRCA2 Expression in Breast Cancer Cell Lines
2013
Previously, it has been reported that hypoxia causes increased mutagenesis and alteration in DNA repair mechanisms. In 2005, an interesting study showed that hypoxia-induced decreases in BRCA1 expression and the consequent suppression of homologous recombination may lead to genetic instability. However, nothing is yet known about the involvement of BRCA2 in hypoxic conditions in breast cancer. Initially, a cell proliferation assay allowed us to hypothesize that hypoxia could negatively regulate the breast cancer cell growth in short term in vitro studies. Subsequently, we analyzed gene expression in breast cancer cell lines exposed to hypoxic condition by microarray analysis. Interestingly,…
Further improvements in the structural analysis of DEMO Divertor Cassette body and design assessment according to RCC-MRx
2019
Abstract This paper presents the enhancements related to the structural analyses of DEMO Divertor in the framework of the EUROfusion Power Plant Physics & Technology (PPPT) program. This activity started two years ago and its preliminary results were published in previous papers. It has been divided in some areas defined by the similarity of the matters they contain: the structural analysis, of utmost importance, has been preceded by a preliminary phase, like the geometry definition or the thermal and the electric-magnetic analysis for loads evaluation; then the structural analysis has been finally confirmed with further evaluations related to excessive deformation or plastic instability. T…
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…
Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series.
2011
Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. H…