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Clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy

ABSTRACT: This study was conducted to identify transcriptional profiles predictive of a clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE14208 | GEO | 2011/06/01

SECONDARY ACCESSION(S): PRJNA114459

REPOSITORIES: GEO

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Clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy

Project description:This study was conducted to identify transcriptional profiles predictive of a clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy. Endoscopic biopsy samples were collected from CF-treated metastatic gastric cancer patients prior to therapy and following the development of resistance to therapy.

2011-06-01 | E-GEOD-14208 | biostudies-arrayexpress

Gastric cancer: cancer vs. normal, chemoresistance signature that correlates with time to progression of disease

Project description:microRNA profiling of gastric cancer vs. normal, pre-/-post CF (cisplatin/fluorouracil) chemotherapy. Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray. In order to identify an miRNA signature for chemotherapy resistance, we correlated miRNA expression levels with the time to progression (TTP) after CF. 90 pre-treatment gastric cancer samples, 34 healthy volunteers, 8 post-treatment samples.

2011-12-16 | E-GEOD-30070 | biostudies-arrayexpress

The genes associated with the response to S-1,cisplatin and docetaxel combination chemotherapy (DCS therapy) for metastatic gastric cancer:

2014-08-31 | GSE31811 | GEO

The genes associated with the response to S-1,cisplatin and docetaxel combination chemotherapy (DCS therapy) for metastatic gastric cancer:

Project description:Despite the effort in defining the molecular mechanisms for the drug resistance, predictors of response to chemotherapy have yet to be developed in gastric cancer. With microarray of whole human genes, we determined 29 genes associated with the response to cisplatin and docetaxel combination chemotherapy for metastatic gastric cancer. We obtained Fresh-frozen samples of tumor tissue and background gastric mucosa tissue from 19 patients with gastric cancer by endoscopic biopsy before DCS therapy. Total RNA was extracted from individual microdissected populations of cancer cells and background mucosa cells using RNAeasy mini kits and amplified with a random primer, WT-Ovation FFPE RNA Amplification System V2; NuGEN, Cincinnati, Ohio) according to the manufacturer’s protocols. The amplified fragmented RNA was hybridized on a Whole Human Genome Oligo Microarray Chip (Agilent Technologies) containing 44,000 cDNA clones.

2014-08-31 | E-GEOD-31811 | biostudies-arrayexpress

Gastric cancer: cancer vs. normal, chemoresistance signature that correlates with time to progression of disease

2011-12-16 | GSE30070 | GEO

A gene expression signature of acquired chemoresistance to cisplatin and fluorouracil combination chemotherapy in gastric cancer patients.

Project description:BackgroundWe initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives.Methodology/principal findingsA prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF) combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre- and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P<0.01) separated the 101 pretreatment patient samples into two groups with significantly different times to progression (2.5 vs. 4.7 months). This 633-gene signature included the upregulation of AKT1, EIF4B, and RPS6 (mTOR pathway), DNA repair and drug metabolism genes, and was enriched for genes overexpressed in embryonic stem cell signatures. A 72-gene acquired resistance signature (a subset of the 633 gene signature also identified in ES cell-related gene sets) was an independent predictor for time to progression (adjusted P = 0.011) and survival (adjusted P = 0.034) of these 101 patients.Conclusion/significanceThis signature may offer new insights into identifying new targets and therapies required to overcome the acquired resistance of gastric cancer to CF.

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A pilot study of cisplatin, irinotecan, leucovorin and 5-fluorouracil (PILF) combination chemotherapy for advanced gastric cancer.

Project description:PurposeIrinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study.Materials and methodsChemotherapy-naive AGC patients received irinotecan 150 mg/m(2) on day 1, and leucovorin 200 mg/m(2) and a 22-h infusion of FU 1000 mg/m(2) on days 1 and 2. Cisplatin 30 mg/m(2) was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity.ResultsOf the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response.ConclusionThis novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.

| S-EPMC2741674 | biostudies-literature

Combination chemotherapy with epirubicin, docetaxel and cisplatin (EDP) in metastatic or recurrent, unresectable gastric cancer.

Project description:Based on single agent activities and the additive or synergistic effects of three individual drugs in gastric cancer, we performed a phase II study of a new regimen combining epirubicin, docetaxel and cisplatin (EDP) for unresectable gastric cancer. The patients with histologically confirmed metastatic or recurrent, unresectable gastric cancer and no history of palliative chemotherapy were eligible for this trial. In total, 40 mg m(-2) epirubicin (reduced to 30 mg m(-2) due to high incidence of febrile neutropaenia; 75%) intravenously (i.v.) over 30 min, followed by 60 mg m(-2) docetaxel i.v. over 1 h, then 75 mg m(-2) cisplatin i.v. over 1 h was administered every 3 weeks. Between January 2002 and February 2003, 30 patients (epirubicin 40 mg m(-2), eight; 30 mg m(-2), 22) were enrolled. The median age was 52 years (range, 33-68). The patients received a median of four cycles (range, 1-8). One patient (3%) achieved a complete response, 13 (43%) showed partial responses, 13 (43%) had stable diseases and three (10%) progressed. The overall response rate was 47% (95% CI, 28-66%), and the median duration of response was 5.0 months (95% CI, 3.0-7.0). The median time to progression was 4.1 months (95% CI, 2.4-5.9), and the median overall survival was 11.0 months (95% CI, 9.5-12.4). Grade 4 neutropaenia were observed in 41%, and febrile neutropaenia in 32%, out of the patients receiving 30 mg m(-2) of epirubicin. Grade 3 nonhaematological toxicities included nausea, vomiting, anorexia and peripheral neuropathy. In conclusion, EDP is active in gastric cancer, with a manageable and predictable toxicity profile.

| S-EPMC2364756 | biostudies-other

Enhanced phosphorylation of c-Jun by cisplatin treatment as a potential predictive biomarker for cisplatin response in combination with patient-derived tumor organoids.

Project description:Despite recent advancement in sequencing technologies and large-scale drug screenings with hundreds of cell lines, the predictive accuracy of mutation-based biomarkers is still insufficient to guide cancer therapy. Therefore, novel types of diagnostic methods with alternative biomarkers are highly appreciated. To develop the novel methods, we hypothesized that sensitivity-specific changes in phosphorylations of signaling molecules could be useful as predictive biomarkers. Here, we aimed to develop predictive methods for cisplatin with a combination of such type of biomarker(s) and patient-derived tumor organoids (PDOs). We found that cisplatin sensitive cell lines or PDOs showed enhanced phosphorylation of c-Jun (p-c-Jun) within 24 h in response to cisplatin treatment. We also compared responses to cisplatin in 6 PDOs with therapeutic effect of neoadjuvant chemotherapy (docetaxel/cisplatin/5-fluorouracil) in 6 matched patients. Mechanistically, the c-Jun induction was partly related to TNF signaling induced by cisplatin. Thus, our data implicates the feasibility of enhanced p-c-Jun by cisplatin treatment as a predictive biomarker for the efficacy.

2023-06-01 | GSE186142 | GEO

Expression data from human endoscopic biopsy samples

Project description:This SuperSeries is composed of the following subset Series: GSE14208: Clinical response of metastatic gastric cancer patients to cisplatin and fluorouracil (CF) combination chemotherapy GSE14209: Dysregulated genes associated with acquired resistance Refer to individual Series

2011-06-01 | E-GEOD-14210 | biostudies-arrayexpress

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