Search results for "CLC"
showing 10 items of 160 documents
A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy
2011
Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM.One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P5.0 10(-7)), and two of them, rs10927875 and rs2234962, were replicated in ind…
Prognostic factors and outcomes of patients with hepatocellular carcinoma in non-cirrhotic liver
2012
To report the outcome of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver depending on the mode of primary treatment and to define clinicopathological factors influencing patients' prognosis.A retrospective analysis of an unselected cohort of 105 patients was performed. Overall survival (OS) was estimated by the Kaplan-Meier method and potentially prognostic factors were analyzed in Cox regression models.OS of the whole cohort at 1, 3, and 5 years was 66%, 47%, and 29%, respectively. Tobacco consumption, ECOG0, macroscopic vascular invasion, continuous tumor diameter, and treatment other than resection were predictors of decreased OS in the whole cohort. Resection was per…
Lungscape: Resected Non–Small-Cell Lung Cancer Outcome by Clinical and Pathological Parameters
2014
INTRODUCTION: The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC).MATERIALS AND METHODS: A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue.RESULTS: Fifteen centers contributed 2449 cases. The 5-yea…
Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the f…
2021
Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems wit…
Oral versus intravenous vinorelbine: clinical safety profile
2005
The availability of chemotherapeutic drugs administrable by oral route represents a step forward in the management of cancer patients. Among oral agents, vinorelbine is particularly interesting for its pharmacological characteristics and clinical efficacy. Oral vinorelbine is rapidly absorbed (1.5-3 hours) with an elimination half-life of approximately 40 hours. It shows a low level of binding to plasma proteins (13%), is highly bound to platelets (78%) and has a hepatic metabolism and an absolute bioavailability of 40% with a moderate and similar interpatient variability for the two forms. Food has no influence on the pharmacokinetic profile of oral vinorelbine even if nausea/vomiting is l…
p38α and NF-κB regulate antioxidant defense in the liver through an age-dependent mechanism
2017
p38α MAPK is a sensor of oxidative stress. The aim of this work was to assess the role of p38α in the regulation of the antioxidant defense in the liver with aging. Livers ofyoung and old wild type (WT) and p38α liver-specific knock out (KO) mice were used to determine glutathione redox status by mass spectrometry; malondialdehyde (MDA) levels by HPLC; mRNA expression of glutamate cysteine ligase (Gclc), Sod1, Sod2 and catalase by RT-PCR and nuclear levels of NF-κB subunit p65 by western-blotting. Chromatin immunoprecipitation (ChIP) assay of p65 was performed. Young KO liver exhibited increased in GSSG/GSH ratio and MDA levels when are compared with young WT mice. However, old KO mice had …
Efficacy of BET Bromodomain Inhibition in Kras-Mutant Non–Small Cell Lung Cancer
2013
Abstract Purpose: Amplification of MYC is one of the most common genetic alterations in lung cancer, contributing to a myriad of phenotypes associated with growth, invasion, and drug resistance. Murine genetics has established both the centrality of somatic alterations of Kras in lung cancer, as well as the dependency of mutant Kras tumors on MYC function. Unfortunately, drug-like small-molecule inhibitors of KRAS and MYC have yet to be realized. The recent discovery, in hematologic malignancies, that bromodomain and extra-terminal (BET) bromodomain inhibition impairs MYC expression and MYC transcriptional function established the rationale of targeting KRAS-driven non–small cell lung cance…
EML4-ALK translocation identification in RNA exosomal cargo (ExoALK) in NSCLC patients: A novel role for liquid biopsy
2019
Abstract: The introduction of druggable targets has significantly improved the outcomes of non-small cell lung cancer patients (NSCLC). EML4-ALK translocation represents 4-6% of the druggable alterations in NSCLC. With the approval of Crizotinib, first discovered drug for the EML4-ALK translocation, on first line treatment for patients with detected mutation meant a complete change on the treatment landscape. The current standard method for EML4-ALK identification is immunohistochemistry or FISH in a tumor biopsy. However, a big number of NSCLC patients have not tissue available for analysis and others are not suitable fir biopsy due to their physical condition or the location of the tumor.…
Phase 0/1 of Positron Emission Tomography (PET) imaging agent [18F]-ODS2004436 as a marker of EGFR mutation in patients with non-small cell lung canc…
2018
e24184Background: Multiple EGFR tyrosine kinase inhibitors (TKIs) are approved for treatment of NSCLC harboring EGFR activating mutations or secondary TKIs resistant mutation. We evaluate a new PET...
Soluble biomarker signature to predict outcome of patients with non-small-cell lung cancer (NSCLC) treated with anti-PD1/PDL1 monoclonal antibodies.
2019
e20685 Background: Immunotherapy with anti-PD1/PDL1 monoclonal antibodies has become the second line standard treatment for most patients diagnosed of advanced Non-Small-Cell lung cancer (NSCLC). The aim of this study is to assess the utility of circulating biomarkers such as sPDL1, sPDL2, sCD137, sIDO, sTIM3, sCD28, sCD27, sCTLA4, sHVEM, sLAG3, sCD80 and sGITR for predicting efficacy of immunotherapy with anti-PD1/PDL1 therapies. Methods: Blood samples were collected before treatment from 50 NSCLC patients who received anti PD1/PDL1 therapies (second line). Plasma biomarkers´ levels were measured by Multiplex bead-based assays. Continuous variables were categorized using the median as a c…