Search results for "mutation."

Outcome of patients with CML treated with dasatinib or nilotinib after failure of second prior TKIs.

2010

Abstract Abstract 2294 Background. The TKIs Nilotinib and Dasatinib offer additional therapeutic options for patients with CML who are resistant or intolerant to Imatinib. These agents, active against the majority of Imatinib resistant BCR-ABL mutated clones, have a different pattern of kinase target selectivity, pharmacokinetics parameters, cell uptake, efflux properties and adverse events profiles. Preliminary results suggest that some patients may respond to a second TKI used as third line therapy, but little is known about the long term benefit of such an approach.Aim of this collaborative Italian study was to verify the response (rate and duration) and the clinical outcome in patients …

KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.

2009

Background: Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling. Objective/Methods: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data. Results/conclusions: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be consi…

Targeted next generation sequencing of breast implant-associated anaplastic large cell lymphoma reveals mutations in JAK/STAT signalling pathway gene…

2016

Deregulation of the EGFR/PI3K/PTEN/Akt/mTORC1 pathway in breast cancer: possibilities for therapeutic intervention

2014

// Nicole M. Davis 1 , Melissa Sokolosky 1 , Kristin Stadelman 1 , Stephen L. Abrams 1 , Massimo Libra 2 , Saverio Candido 2 , Ferdinando Nicoletti 2 , Jerry Polesel 3 , Roberta Maestro 4 , Antonino D’Assoro 5 , Lyudmyla Drobot 6 , Dariusz Rakus 7 , Agnieszka Gizak 7 , Piotr Laidler 8 , Joanna Dulinska-Litewka 8 , Joerg Basecke 9 , Sanja Mijatovic 10 , Danijela Maksimovic-Ivanic 10 , Giuseppe Montalto 11,12 , Melchiorre Cervello 12 , Timothy L. Fitzgerald 13 , Zoya N. Demidenko 14 , Alberto M. Martelli 15 , Lucio Cocco 15 , Linda S. Steelman 1 and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University Greenville, NC 27858 USA 2 …

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

2006

Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified ac…

The transcriptional activator rfiA is quorum-sensing regulated by cotranscription with the luxI homolog pcol and is essential for plant virulence in …

2009

The gram-negative phytopathogen Pseudomonas corrugata has an acyl-homoserine lactone (AHL) quorum-sensing (QS) system called PcoI/PcoR that is involved in virulence on tomato. This work identifies, downstream of pcol, a gene designated rfiA, which we demonstrate is directly linked to QS by cotranscription with pcol. The deduced RfiA protein contains a DNA-binding domain characteristic of the LuxR family but lacks the autoinducer-binding terminus characteristic of the QS LuxR-family proteins. We also identified, downstream of rfiA, an operon designated pcoABC, encoding for the three components of a tripartite resistance nodulation-cell-division (RND) transporter system. The expression of pco…

Helicobacter pylori and Epstein–Barr Virus Co-Infection in Gastric Disease: What Is the Correlation with p53 Mutation, Genes Methylation and Microsat…

2023

Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein–Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with and without gastric diseases. The patients were stratified into four groups. Significant methylation status differences among CDH1, DAPK, COX2, hMLH1 and CDKN2A were observed for coinfected (Hp-EBV group) patients; particularly, a significant presence of COX2 (p = 0.0179) was observed. For microsatellite instability, minor stability was described in the Hp-HBV group (69.23…

STUDY OF SMALL MOLECULES IN THE FIGHT AGAINST NONSENSE AND SPLICING MUTATIONS THAT CAUSE CYSTIC FIBROSIS.

2023

Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis

2011

Heat shock proteins (HSPs) are necessary for cancer cell survival. We identified a mutant of HSP110 (HSP110ΔE9) in colorectal cancer showing microsatellite instability (MSI CRC), generated from an aberrantly spliced mRNA and lacking the HSP110 substrate-binding domain. This mutant was expressed at variable levels in almost all MSI CRC cell lines and primary tumors tested. HSP110ΔE9 impaired both the normal cellular localization of HSP110 and its interaction with other HSPs, thus abrogating the chaperone activity and antiapoptotic function of HSP110 in a dominant-negative manner. HSP110ΔE9 overexpression caused the sensitization of cells to anticancer agents such as oxaliplatin and 5-fluorou…

Molecular analysis of a human liver mitochondrial ornithine transcarbamylase deficiency.

1990

The liver of a young girl which had been successfully transplanted was investigated at the ornithine transcarbamylase (OTC, EC 2.1.3.3) gene expression level. Northern blot hybridization using a human OTC cDNA probe showed a greater than 80% decrease in specific OTC mRNA although having the same molecular size as a normal control. OTC polypeptide was simultaneously synthesized with a normal molecular size but at a low level (20%) as shown by immunoblotting. The OTC enzyme from the deficient liver exhibited very little catalytic activity (7.2% as compared to the normal subject). These results may support several explanations of this disease such as mutation of the OTC gene promoter leading t…