Search results for "P21"
showing 10 items of 131 documents
Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial
2015
KRAS mutation has been reported as a marker of radio-resistance in rectal cancer and unfavourable outcome in both colon and rectal cancer. This study suggests that a single-nucleotide polymorphism of the KRAS gene (LCS-6 variant) may predict response to neoadjuvant treatment and mitigate the poor prognosis associated with KRAS mutation in locally advanced rectal cancer.
Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients
2015
// Bruno Vincenzi 1 , Chiara Cremolini 2 , Andrea Sartore-Bianchi 3 , Antonio Russo 4 , Francesco Mannavola 5 , Giuseppe Perrone 6 , Francesco Pantano 1 , Fotios Loupakis 2 , Daniele Rossini 2 , Elena Ongaro 7 , Erica Bonazzina 3 , Emanuela Dell’Aquila 1 , Marco Imperatori 1 , Alice Zoccoli 1 , Giuseppe Bronte 4 , Giovanna De Maglio 7 , Gabriella Fontanini 8 , Clara Natoli 9 , Alfredo Falcone 2 , Daniele Santini 1 , Andrea Onetti-Muda 6 , Salvatore Siena 3 , Giuseppe Tonini 1 and Giuseppe Aprile 7 1 Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy 2 Azienda Ospedaliero-Universitaria Pisana, Istituto Toscano Tumori, Pisa, Italy 3 Niguarda Cancer Center, Osped…
Mutations in the RAS-MAPK, PI(3)K (phosphatidylinositol-3-OH kinase) signaling network correlate with poor survival in a population-based series of c…
2008
The RAS-MAPK, PI (3)K signaling pathways form a network that play a central role in tumorigenesis. The BRAF, KRAS and PI3KCA genes code 3 partners of this network and have been found to be activated by mutation in colorectal cancer; these mutations lead to unrestricted cell growth. We evaluated the clinicopathological features and the prognosis of patients with activated-network colon cancers in a population-based study. A total of 586 colon adenocarcinomas were evaluated using sequencing for mutations of KRAS and PI3KCA, and allelic discrimination for mutation of BRAF. Clinicopathological characteristics were correlated to the risk of bearing a mutation of the network using logistic regres…
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
2018
Abstract There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 ca…
Further Delineation of Duplications of ARX Locus Detected in Male Patients with Varying Degrees of Intellectual Disability
2022
The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, paediatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telencephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants …
Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma
2013
Background Tumor models are critical for our understanding of cancer and the development of cancer therapeutics. Here, we present an integrated map of the genome, transcriptome and immunome of an epithelial mouse tumor, the CT26 colon carcinoma cell line. Results We found that Kras is homozygously mutated at p.G12D, Apc and Tp53 are not mutated, and Cdkn2a is homozygously deleted. Proliferation and stem-cell markers, including Top2a, Birc5 (Survivin), Cldn6 and Mki67, are highly expressed while differentiation and top-crypt markers Muc2, Ms4a8a (MS4A8B) and Epcam are not. Myc, Trp53 (tp53), Mdm2, Hif1a, and Nras are highly expressed while Egfr and Flt1 are not. MHC class I but not MHC class…
Subcellular distribution of ras in human and murine fibroblasts.
1996
Abstract Ras proteins play a significant role in signal transduction in response to growth factors and in cell transformation. To be active, ras has to be translocated to the cell membrane. Since subcellular distribution has been mainly studied in vector-transformed cells which highly express ras proteins, and it has been difficult to detect ras in cells expressing the protein at physiological levels, we studied subcellular distribution in human and murine fibroblasts. Here we show for the first time that a significant amount of ras is associated with the membrane skeleton and the cytoskeleton.
Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases.
2008
Abstract The CpG island methylator phenotype (CIMP) is a distinct phenotype in colorectal cancer, associated with specific clinical, pathologic, and molecular features. However, most of the studies stratified methylation according to two subgroups (CIMP-High versus No-CIMP/CIMP-Low). In our study, we defined three different subgroups of methylation (No-CIMP, CIMP-Low, and CIMP-High) and evaluated the prognostic significance of methylation status on a population-based series of sporadic colon cancers. A total of 582 colon adenocarcinomas were evaluated using methylation-specific PCR for 5 markers (hMLH1, P16, MINT1, MINT2, and MINT31). No-CIMP status was defined as no methylated locus, CIMP-…
Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations
2018
Background: The present study investigated the efficacy and safety of nivolumab in pre-treated patients with advanced NSCLC harbouring KRAS mutations. Methods: Clinical data and KRAS mutational status were analysed in patients treated with nivolumab within the Italian Expanded Access Program. Objective response rate, progression-free survival and overall survival were evaluated. Patients were monitored for adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: Among 530 patients evaluated for KRAS mutations, 206 (39%) were positive while 324 (61%) were KRAS wild-type mutations. KRAS status did not influence nivolumab efficacy in terms of …