PREMIUM, Observational Study
Ontology highlight
ABSTRACT:
DISEASE(S): First Line Wt Kras Mcrc
PROVIDER: 2137393 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:The Treatment Choices, Duration and Outcomes in Patients with Ras Wild Type (RAS WT) Metastatic Colorectal Cancer (mCRC). Retrospective, Multi-Center, Real-World Data Analysis
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Project description:Primary objectives: The primary objective of first line treatment is:- Evaluation of efficacy (in terms of PFS) of ongoing FOLFIRI + Cetuximab as first line treatment in wild type (WT) K-ras metastatic colorectal cancer patients.
the primary objective of second line treatment is:- evaluation of efficacy (in terms of PFS) of ongoing cetuximab as second line tretment in combination with chemotherapy after progerssion of first line treatment with FOLFIRI plus cetuximab in wild type (WT) K-ras metastatic colorectal cancer patients.
Primary endpoints: The primary objective of first line treatment is:- Evaluation of efficacy (in terms of PFS) of ongoing FOLFIRI + Cetuximab as first line treatment in wild type (WT) K-ras metastatic colorectal cancer patients.
the primary objective of second line treatment is:- evaluation of efficacy (in terms of PFS) of ongoing cetuximab as second line tretment in combination with chemotherapy after progerssion of first line treatment with FOLFIRI plus cetuximab in wild type (WT) K-ras metastatic colorectal cancer patients
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Project description:Previously, we have demonstrated that wild type N-ras (wt N-ras) harbors an anti-malignant effect against mutated Ras and in tumors without Ras mutations. To investigate the molecular bases of this anti-malignant activity, we have studied the potency of this anti-malignant effect in a model system against SV40 T. We show that wild-type N-ras (wt N-ras) counteracts the effects of SV40T in NIH3T3 cells as seen by a decrease in proliferation, anchorage independence and changes in migration). We also show that wt N-ras also elicits the same anti-malignant effects in some human tumor cell lines (HT1080 and MDA-MB-231). Through mRNA and microRNA (miRNAs) expression profiling we have identified genes and miRNAs modulated by wt N-ras potentially responsible for the anti-malignant effect. wt N-ras appears to mediate its anti-malignant effect by downregulating some of the targets of the TGFb pathway and decorin, which are able to reverse the inhibition of migration induced by wt N-ras. Our experiments show that the molecules that mediate the anti-malignant effect appear to be different than those modulated by transforming N-ras. The components of the pathways modulated by wt N-ras mediating its anti-malignant effects are potential targets for therapeutic intervention in cancer. We report that the N-ras proto-oncogene has anti-malignant effects and that it does so by modulating different genes than its oncogenic counterpart, which indicates that it should be activating different pathways. Gene expression profiles from 3T3 cells transformed by SV40 (SV5) and cells expressing both SV40T and wt N-ras (SV5-NN clones) were compared using genome wide mRNA expression profiling by Affymetrix genechip arrays (Mouse 430 2.0) and key targets were validated by real time RT-PCR.
2011-04-19 | E-GEOD-28678 | biostudies-arrayexpress
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Project description:Previously, we have demonstrated that wild type N-ras (wt N-ras) harbors an anti-malignant effect against mutated Ras and in tumors without Ras mutations. To investigate the molecular bases of this anti-malignant activity, we have studied the potency of this anti-malignant effect in a model system against SV40 T. We show that wild-type N-ras (wt N-ras) counteracts the effects of SV40T in NIH3T3 cells as seen by a decrease in proliferation, anchorage independence and changes in migration). We also show that wt N-ras also elicits the same anti-malignant effects in some human tumor cell lines (HT1080 and MDA-MB-231). Through mRNA and microRNA (miRNAs) expression profiling we have identified genes and miRNAs modulated by wt N-ras potentially responsible for the anti-malignant effect. wt N-ras appears to mediate its anti-malignant effect by downregulating some of the targets of the TGFb pathway and decorin, which are able to reverse the inhibition of migration induced by wt N-ras. Our experiments show that the molecules that mediate the anti-malignant effect appear to be different than those modulated by transforming N-ras. The components of the pathways modulated by wt N-ras mediating its anti-malignant effects are potential targets for therapeutic intervention in cancer. We report that the N-ras proto-oncogene has anti-malignant effects and that it does so by modulating different genes than its oncogenic counterpart, which indicates that it should be activating different pathways.
2011-04-19 | GSE28678 | GEO
Project description:The AVAglio and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy/temozolomide. To establish whether certain patient subgroups derived OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy assessed for each patient subgroup. A multivariate analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with Proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the Proneural subtype biomarker and treatment arm (P = .023). The group of patients with Mesenchymal and Proneural tumors derived a PFS benefit from bevacizumab, compared with placebo; however, this translated to an OS benefit in the Proneural subset only. Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type Proneural glioblastoma may derive OS benefit from first-line bevacizumab treatment. The predictive value of the Proneural subtype observed in AVAglio should be validated in an independent dataset.
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