Randomized phase II study of dose schedule of TS-1 for resected Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Stage Iii Colorectal Cancer
PROVIDER: 2628537 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: UFT/LV as postoperative adjuvant chemotherapy for the stage II colorectal cancer is tested as follows: one patient group for 28 days with 7 days rest (everyday medication) and another patient group for 5days with 2days rest (5-days on/2-days, Saturday and Sunday, off). Both medications are conducted for 25weeks as 5 courses (1 course=5weeks, 35days) from the date of the start of the therapy. After the treatment, both patient groups are simply observed without any more therapy, unless any recurrent lesions or any other cancer lesions are observed in them.
The surgery alone group is simply observed without therapy, unless any recurrent lesions or any other cancer lesions (synchronous cancers or multiple colorectal cancers) are observed in them.
Primary outcome(s): Disease-free survival
Study Design: Parallel Randomized
| 2623196 | ecrin-mdr-crc
Project description:Interventions: UFT/LV as postoperative adjuvant chemotherapy for the stage II colorectal cancer is tested as follows: one patient group for 28 days with 7 days rest (everyday medication) and another patient group for 5days with 2days rest (5-days on/2-days, Saturday and Sunday, off). Both medications are conducted for 25weeks as 5 courses (1 course=5weeks, 35days) from the date of the start of the therapy. After the treatment, both patient groups are simply observed without any more therapy, unless any recurrent lesions or any other cancer lesions are observed in them.
The surgery alone group is simply observed without therapy, unless any recurrent lesions or any other cancer lesions (synchronous cancers or multiple colorectal cancers) are observed in them.
Primary outcome(s): Disease-free survival
Study Design: randomized controlled trial, open(masking not used), active control, parallel assignment, treatment purpose
| 2614017 | ecrin-mdr-crc
Project description:miR-28-5p is downregulated in some tumor tissues in which it has been demonstrated to have a tumor suppressor (TS) activity. Here, we demonstrate that miR-28-5p acts as a TS in prostate cancer (PCa) cells affecting cell proliferation/survival as well as migration and invasion. Using the miRNA pull out assay and next generation sequencing we collected the complete repertoire of miR-28-5p targets obtaining a data set (miR-28-5p targetome) of 191 mRNAs. Filtering the targetome with TargetScan 7, PITA and RNA22 we found that the 61% of the transcripts had miR-28-5p binding sites. To assign a functional value to the captured transcripts, we grouped the miR-28-5p targets into gene families with annotated function and showed that six transcripts belong to the transcription factor category. Among them we selected SREBF2, a gene with increasing importance in PCa. We validated miR-28-5p/SREBF2 interaction demonstrating that SREBF2 inhibition affects almost all the tumor processes affected by the miR-28-5p re-expression, suggesting that SREBF2 is an important mediator of miR-28-5p TS activity. Our findings support the identification of the targetome of cancer-related miRNAs as a tool to discover genes and pathways fundamental for tumor development and potential new targets for anti-tumor therapy.
2020-02-06 | GSE143589 | GEO
Project description:We charted the transcription start sites (TSSs) landscape globally to determine the expressed isoform of each gene and validate the precence of transposable element-derived transcript. Cryptic promoters within transposable elements (TEs) are transcriptionally reactivated in tumors to create novel TE-gene chimeric transcripts, which can produce immunogenic antigens. We performed the most comprehensive screen to date for these TE exaptation events in 33 TCGA tumortypes,675 cancer cell lines, and 11,686 GTEx adult tissue transcriptomes and identified 201,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Resultant whole lysate and HLA-pull down mass spectrometry data confirmed that TS-TEAs are presented on cancer cell surfaces. In addition, we highlight the tumor-specific membrane proteins transcribed from TE promoters that can expose novel epitopes on the extracellular surface of cancer cells. Here, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that can be therapeutically exploited through immunotherapy approaches.
2023-01-20 | GSE201021 | GEO
Project description:Background: In both Turner syndrome (TS) and Klinefelter syndrome (KS) copy number aberrations of the X chromosome lead to various developmental symptoms. To date there has not been a comprehensive and directly comparative analysis of TS vs. KS regarding the changes on the molecular level Methods: We analyzed gene expression patterns with RNA-Seq and DNA methylation patterns with the CpGiant assay in lymphocytes, and chromatin conformation with in situ Hi-C in lymphoblastoid cell lines, from TS and KS patients together with their same gender controls. Results: In TS, differentially expressed escape genes were downregulated but differentially expressed inactive genes were upregulated. In KS, differentially expressed escape genes were upregulated while inactive genes appeared unchanged. Interestingly, 81 differentially expressed genes (DEGs) were associated with both TS and KS, and uniformly displayed expression changes into opposite directions. DEGs on the X chromosome and the autosomes were coexpressed in both TS and KS, indicating that there are molecular ripple effects of the changes in X chromosome dosage that extend to autosomes. Four potentially candidate genes (RPS4X, SEPT6, NKRF and CX0rf57) for KS were identified on Xq. Broad hypomethylation of the X chromosome is observed in TS whereas hypermethylation of chromosome X is present in KS. Only promoters of inactive genes were differentially methylated in both TS and KS while escape genes remained unchanged. The intrachromosomal contact map of the X chromosome in TS was partitioned into two superdomains and exhibited the structure of an active X chromosome. Conclusions: Components of the molecular basis of TS and KS were identified on the levels of the transcriptome and the epigenome, with candidate central genes on Xp for TS and on Xq for KS. The discovery of shared DEGs indicates the existence of common molecular mechanisms for gene regulation in TS and KS that are transmitting the gene dosage changes to the transcriptome.
2020-02-28 | GSE126712 | GEO
Project description:Expression profiling of tumor samples obtained during CA209-038 (ClinicalTrials.gov Identifier: NCT01621490). The purpose of this study is to evaluate pharmacodynamic changes of nivolumab and nivolumab in combination with ipilimumab treatment on the biomarkers measured in the peripheral blood and tumor tissues of subjects with advanced melanoma (unresectable or advanced). Samples are rumor core needle biopsies obtained at trial enrolment (i.e. Screen) and/or at Cycle 1 Day 29 (i.e.Week 4) from Subjects With Advanced Melanoma (Unresectable or Metastatic) treated with nivolumab (BMS-936558,MDX-1106) 3 mg/kg solution intravenously every 2 weeks on Bristol-Myers Squibb clinical trial protocol CA209-038 Part 1 . Cohort 2 patients have progressed on anti-CTLA4 (ipilimumab) monoclonal antibody therapy. Values are from an interim lock of the trial data in July 2014. Best overall response (BOR) was defined using RECIST 1.1 criteria: tumor assessments between date of first dose and the date of first objectively documented progression, or the date of non-missing subsequent anti-cancer therapy (whichever occurs first) were used to derive BOR. MPCT is Maximum reduction in tumor size (index lesions only) up to first progression, and is the value typically shown on a waterfall plot.
2022-01-01 | E-MTAB-4030 | biostudies-arrayexpress
Project description:While it has been clearly established that well positioned H2A.Z-containing nucleosomes flank the nucleosome depleted region (NDR) at the transcriptional start site (TSS) of active mammalian genes 1,2, how this chromatin-based information is transmitted through the cell cycle is unknown. We show here that in trophoblast stem (TS) cells, the level of H2A.Z at promoters decreases during S phase coinciding with homotypic (H2A.Z/H2A.Z) nucleosomes flanking the TSS becoming heterotypic (H2A.Z/H2A). Surprisingly, these nucleosomes remain heterotypic at M phase. At the TSS, we identify an unstable heterotypic H2A.Z-containing nucleosome in G1 which, strikingly, is lost following DNA replication. These dynamic changes in H2A.Z at the TSS mirror a global expansion of the NDR at S and M which, unexpectedly, is unrelated to transcriptional activity. Coincident with the loss of H2A.Z at promoters, it is targeted to the centromere when mitosis begins. We surveyed whole genome expression using microarrays, in combination with H2A.Z ChIP-Seq (Illumina) data, to study the H2A.Z distribution on promoters of coding genes in different stages of the cell cycle in Trophoblast Stem (TS) cells. These data are published in Nekrasov et al., H2AZ inheritance during the cell cycle and it's impact on promoter organization and dynamics, Nature Structural and Molecular Biology (in press: accepted for publication on 24 Sep 2012). Mouse Trophoblast stem (TS) cells were grown in cell culture medium. By adding specific drugs cells were arrested at particular stages of the cell cycle: G1; S and M. Total RNA was extracted from TS cells arrested at G1; S and M stages of cell cycle using TRizol (Invitrogen) extraction protocol and purified further the by RNAeasy Extraction Kit (Qiagen). RNA quality was assesed on Bioanalyzer total RNA chip. RNA samples were reverse transcribed and resulted cDNA samples were subjected to DNA microarray analysis (in triplicate) using the GeneChip Mouse Gene 1.0 ST Array (Affymetrix). Robust Multichip Average (RMA) correction and probe set summaries were obtained using Affymetrix Power Tools software annotation (Affymetrix) based on the mm9 mouse genome. Unless otherwise stated, all subsequent expression analyses (see Supplementary Methods) were performed in the R statistical computing environment (version 2.11.1).
2012-11-23 | E-GEOD-41370 | biostudies-arrayexpress
Project description:Typical rodent toxicology experiments are performed at human thermoneutral temperatures (thermostandard; TS = 20 – 24° C). Reports have indicated that investigation of metabolic endpoints at mouse thermoneutral temperatures (TNM = 28 – 30° C) improves translation to humans when they are not chronically cold-stressed. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to dose-dependently induce metabolic disease in mice at including liver steatosis, steatohepatitis, and periportal fibrosis. To test whether dose-dependent hepatotoxicity caused by TCDD is altered by housing temperature we gavaged male C57BL/6 mice every 4 days for 28 days with TCDD (0.03 – 30 µg/kg) or sesame oil vehicle at TS and TNM. Mice held at TNM exhibited less marked relative liver weight gain and histopathology with milder steatosis, immune cell infiltration, hepatocellular hypertrophy, and an absence of biliary hyperplasia compared to mice held at Ts. Mice housed in both temperature conditions had a similar dose-dependent decrease in total cholesterol, but mice at TS had more elevated serum ALT and decreased glucose and triglycerides at 30 µg/kg TCDD. Mice at TNM had fewer differentially expressed genes (DEGs) than TS, although most of the DEGs at TNM were shared with the DEGs at TS. Benchmark Dose (BMD) analysis performed on the DEGs revealed largely similar trends, however, the most induced DEGs, which constituted some of the AhR-battery genes (e.g. Cyp1a1), exhibited lower BMDs at TNM. Moreover, at 30 µg/kg TCDD both sets of mice had increased pro-inflammatory cytokines. The only cytokine which was clearly different between the two sets of mice irrespective of dose was VEGF-A. Overall, mice held at TNM showed reduced severity at equivalent doses to mice held at TS.
2023-09-18 | GSE203300 | GEO
Project description:Purpose: Selecting muscle-invasive bladder cancer patients for adjuvant therapy is currently based on clinical variables with limited power. We hypothesized that genomic-based signatures can outperform clinical models to identify patients at higher risk. Method:Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. A cohort comprised of 225 patients with organ-confined, muscle-invasive (pT2N0M0),extravesical (pT3-4aN0M0), and node-positive (pTanyN1-3M0) UCB who underwent radicalcystectomy at the University of Southern California between 1998 and 2004 was used. Each patient had aminimum two-year follow-up post-cystectomy unless they recurred prior to that date. Patients receiving neoadjuvant chemotherapy, and those with clinical evidence of lymphadenopathy or distant metastasis at diagnosis were excluded.
2014-10-27 | E-GEOD-57933 | biostudies-arrayexpress
Project description:Starting Treatment with Agonist Replacement Therapy (START)
| PRJNA324306 | ENA