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Observational Study to Evaluate the Use of Targeted Therapies in Metastatic Colorectal Cancer

ABSTRACT: The purpose of this study is to evaluate, in terms of overall survival, the benefit of monoclonal antibodies in the start time of the diagnosis of advanced disease or administer a deferred basis after progression to treatment with chemotherapy alone. Initially expected target population was 1950 patients (pts), in 2015 protocol was ammended to 1028 patients, because the size was sufficient to evaluate the superiority of the use of monoclonal antibodies the start time of the diagnosis against deferred use, with HR of 0.8, power of 90% and an alpha of 0.05. Finally in July 2018, recruitment was completed with a total of 1104 patients enrolled.

DISEASE(S): Metastatic Colon Cancer,Colonic Neoplasms

PROVIDER: 2175524 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Pharmacogenomics of HIV Therapy - Atazanavir Bilirubin-related Side Effects

Project description:This is an evaluation of genetic associations with atazanavir (ATV) discontinuation for bilirubin-related causes within 12 months of treatment. Patients were treated at an HIV primary care clinic in Nashville TN from 1998 to 2012. A previously known SNP in UGT1A1 (rs887829) was used to define metabolizer genotypes (extensive, intermediate, slow metabolizer). Over 500,000 SNPs from genome-wide genotyping were used to define MDS (Multidimensional Scaling) coordinates to account for population stratification. Patients were defined as cases if they discontinued ATV for bilirubin-related causes within 12 months of treatment, otherwise they were defined as controls if they did not stop treatment. Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of black, 21.4% of Hispanic, and 8.6% of white patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 (95% C.I.: 1.7 to 31.5; p = 0.007). Among 152 white patients the HR was 14.4 (95% CI: 2.6 to 78.7; p = 0.002), but among 153 black patients the HR was 0.8 (95% C.I. 0.05 to 12.7; p = 0.87).

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Transcriptional profiling reveals differential changes in the respective expression of oxytocin and CART mRNA levels in the nucleus accumbens and dorsal striatum of compulsive methamphetamine taking rats (nucleus accumbens)

Project description:Methamphetamine addiction is mimicked in rats that self-administer the drug and accelerate their intake when given long access to it. Self-administration (SA) models do not include adverse consequences that are necessary to reach a diagnosis of addiction in humans. Here, we studied transcriptional consequences of methamphetamine SA and repeated foot-shocks in rat brain.

2017-09-26 | GSE95569 | GEO

Transcriptional profiling reveals differential changes in the expression of oxytocin and CARTpt mRNAs in the nucleus accumbens and dorsal striatum of rats (striatum)

2017-09-26 | GSE95570 | GEO

Sequencing the anti-MUC1 hybridoma antibody 139H2

Project description:Mucin 1 (MUC1) is a transmembrane mucin expressed at the apical surface of epithelial cells at different mucosal surfaces including breast and intestine. The MUC1 extracellular domain contains a variable number of tandem repeats (VNTR) of 20 amino acids, which are heavily O-linked glycosylated. Monoclonal antibodies against the MUC1 VNTR can be powerful tools because of their multiplicity of binding and possible applications in the diagnosis and treatment of MUC1-expressing cancers. One such antibody is the hybridoma mouse monoclonal 139H2 which is also widely used as a research tool to study non-cancer MUC1. Here we report direct mass spectrometry-based sequencing of hybridoma-derived 139H2 IgG, which enabled reverse engineering of a recombinant 139H2.

2024-03-18 | PXD043489 | Pride

Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation (RNA-seq data set)

Project description:Mutations in the nucleophosmin 1 (NPM1) gene are considered founder mutations in the pathogenesis of acute myeloid leukemia (AML). To further characterize the genetic composition of NPM1 mutated (NPM1mut) AML, we assess mutation status of five recurrently mutated oncogenes (FLT3, DNMT3A, IDH1, IDH2, NRAS) in 129 paired NPM1mut samples obtained at diagnosis and relapse. We find a substantial shift in the genetic pattern from diagnosis to relapse including NPM1mut loss (n=11). To gain further insight into these NPM1mut loss cases, we perform whole exome sequencing (WES) and RNA-Seq. At the time of relapse, NPM1mut loss patients (pts) feature distinct mutational patterns that shared almost no somatic mutation with the corresponding diagnosis sample and impact different signaling pathways including loss of characteristic NPM1mut associated gene expression patterns. In contrast, profiles of pts with persistent NPM1mut at relapse are reflected by a high overlap of mutations between diagnosis and relapse. Thus, our findings confirm that relapse often originates from persistent leukemic clones, though NPM1mut loss cases suggest a second “de novo” or treatment-associated AML (tAML) as alternative cause of “relapse" in a subgroup of cases.

2019-05-14 | GSE128603 | GEO

Clonal evolution patterns in acute myeloid leukemia with NPM1 mutation (Affymetrix SNP data set)

2019-05-14 | GSE128602 | GEO

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2017-12-23 | GSE108433 | GEO

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Sumana2018 - Mathematical modeling of cancer-immune system, considering the role of antibodies.

Project description:Mathematical modeling of cancer-immune system, considering the role of antibodies. Ghosh S1, Banerjee S2. Author information 1 Department of Mathematics, Indian Institute of Technology Roorkee, Roorkee, Uttaranchal, 247667, India. 2 Department of Mathematics, Indian Institute of Technology Roorkee, Roorkee, Uttaranchal, 247667, India. sandofma@iitr.ac.in. Abstract A mathematical model for the quantitative analysis of cancer-immune interaction, considering the role of antibodies has been proposed in this paper. The model is based on the clinical evidence, which states that antibodies can directly kill cancerous cells (Ivano et al. in J Clin Investig 119(8):2143-2159, 2009). The existence of transcritical bifurcation, which has been proved using Sotomayor theorem, provides strong biological implications. Through numerical simulations, it has been illustrated that under certain therapy (like monoclonal antibody therapy), which is capable of altering the parameters of the system, cancer-free state can be obtained. KEYWORDS: Antibodies; B cells; Cancer cells; Global stability; Plasma cells; Transcritical bifurcation

2024-09-02 | BIOMD0000000885 | BioModels

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