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PROVIDER: PRJNA263824 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan
| PRJNA263167 | ENA
Project description:In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
2014-10-06 | GSE62080 | GEO
Project description:Background: The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumor efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study. Methods: Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: We enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2-11.8) months (vs. 6 months in historical control, p=0.018). The median overall survival was 16.5 (90% CI 9.8-17.5) months. Sixty-seven percent of patients experienced grade 3 or higher treatment-related adverse events. The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhea, nausea, and vomiting). Conclusions: Irinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard of care therapy is warranted.
2024-08-26 | GSE275628 | GEO
Project description:To measure global gene expression in primary advanced colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy Samples from primary advanced colorectal cancer patients were collected. The effects of chemotherapy were evaluated, and patients were divided into an experimental group and a control group.
2015-12-31 | GSE69657 | GEO
Project description:In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting. All tissue samples were maintained at −180°C (liquid nitrogen) until RNA extraction and were weighed before homogenization. Tissue samples were then disrupted directly into a lysis buffer using Mixer Mill MM 300 (Qiagen, Valencia, CA). Total RNA was isolated from tissue lysates using the RNeasy Mini Kit (Qiagen), and additional DNAse digestion was performed on all samples during the extraction process (RNase-Free DNase Set Protocol for DNase treatment on RNeasy Mini Spin Columns; Qiagen). After each extraction, a small fraction of the total RNA preparation was taken to determine the quality of the sample and the yield of total RNA. Controls analyses were performed by UV spectroscopy and analysis of total RNA profile using the Agilent RNA 6000 Nano LabChip Kit with the Agilent 2100 Bioanalyser (Agilent Technologies, Palo Alto, CA) to determine RNA purity, quantity, and integrity.
2014-10-06 | E-GEOD-62080 | biostudies-arrayexpress
Project description:Irinotecan, an analogue of camptothecin, is frequently used in combination with various anticancer drugs or as a single agent in treatment of colorectal cancer. But drug resistance of tumor is still a major obstacle to overcome for the success of cancer treatment. In this study, We established chronic irinotecan resistant cell line for new marker to increase the sensitivity to irinotecan and investigated gene expression profiles of the irinotecan-resistant colorectal cancer cell line.
2014-07-18 | GSE59501 | GEO
Project description:Irinotecan, an analogue of camptothecin, is frequently used in combination with various anticancer drugs or as a single agent in treatment of colorectal cancer. But drug resistance of tumor is still a major obstacle to overcome for the success of cancer treatment. In this study, We established chronic irinotecan resistant cell line for new marker to increase the sensitivity to irinotecan and investigated gene expression profiles of the irinotecan-resistant colorectal cancer cell line. To create stable CRC cell line chronically resistant to Irinotecan, LoVo cell was exposed to an initial Irinotecan concentration of 0.1 M-NM-<mol/L in RPMI 1640 supplemented with 10% FBS. When the growth of the cultured cells reaches at 80% confluency, cells were passaged twice at same drug concentration to ensure adaptation and then concentration of Irinotecan was sequentially increased in the same manner to 8 M-NM-<mol/L and then we investigated the gene expressions between parental colorectal cancer cell line, LoVo and Irinotecan resistant LoVo cell lines
2014-07-18 | E-GEOD-59501 | biostudies-arrayexpress
Project description:To measure global gene expression in primary advanced colorectal cancer patients who have undergone fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy Samples from primary advanced colorectal cancer patients were collected. The effects of chemotherapy were evaluated, and patients were divided into an experimental group and a control group. All patients underwent standard FOLFOX4 regimen chemotherapy in four cycles after signing the chemotherapy agreement; subsequently, they were evaluated in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST).Each samplewas collected immediately following resection. Each sample was divided in half: one half was fixed in formalin and embedded in paraffin; the other half floated in ice-cold phosphate-buffered saline and was stored in liquid nitrogen until total RNA extraction. CEL files available for only 16/30 samples. Remaining CEL files have been lost.
2015-12-31 | E-GEOD-69657 | biostudies-arrayexpress
Project description:Advanced colorectal cancer (CRC) is an unresolved clinical problem. Epigenetic drugs belonging to the group of histone deacetylase inhibitors (HDACi) may combat CRC in rationally designed treatment schedules. Unfortunately, there is sparse evidence on molecular mechanisms and markers that determine cellular sensitivity to HDACi. Irinotecan is widely used to treat CRC and causes replication stress (RS) and DNA damage as topoisomerase-I inhibitor. We applied irinotecan and the class I HDACi entinostat (MS-275) to isogenic p53-positive and -negative CRC cells. Combinations of irinotecan and MS-275 evoke mitochondrial damage, caspase-mediated apoptosis, and RS-associated DNA damage synergistically and p53-dependently. Targeted mass spectrometry and immunoblot show that irinotecan induces phosphorylation, acetylation, and accumulation of p53 and its target genes. Addition of MS-275 augments the irinotecan-induced acetylation of C-terminal lysine residues of p53 but decreases its phosphorylation and p53 target gene induction. Furthermore, MS-275 increases the amount of acetylated p53 at mitochondria and dysregulates the expression of pro- and anti-apoptotic BCL2 proteins in irinotecan-treated cells. Regarding DNA repair, we see that MS-275 represses the homologous recombination (HR) filament protein RAD51, which limits DNA damage and pro-apoptotic effects of irinotecan. These data suggest that key class I HDAC-dependent functions of p53 in cells with RS are linked to mitochondrial damage and a breakdown of HR. Most importantly, combinations of irinotecan plus MS-275 also kill short-term primary CRC cell cultures and organoids from CRC patients but spare organoids of adjacent matched normal tissue. Thus, irinotecan/HDACi treatment is a promising new approach for the therapy of p53-proficient tumors with clinically tractable inhibitors.
2022-02-15 | PXD019999 | Pride
Project description:MicroRNA signature predict chemotherapy response in patients with advanced colorectal cancer
| PRJNA210969 | ENA