97e59a9d-975d-4a6c-bbe6-419a6aeb3f62 - samples
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ABSTRACT:
PROVIDER: EGAD00001009834 | EGA |
REPOSITORIES: EGA
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Project description:Transcriptome sequencing of 97 matched TNBC breast cancer metastasis samples obtained from 50 unique patients assayed at two timepoints: at baseline (directly after patient randomization), and post-induction treatment or control waiting period. The included raw transcriptome sequencing data (fastq-format) were generated using Illumina HiSeq2500 instruments.
| EGAD00001004858 | EGA
Project description:The Phase 3 1L urothelial carcinoma (IMvigor130) trial revealed more favorable effects on overall survival with atezolizumab combined with gemcitabine and cisplatin (GemCis) than with atezolizumab combined with gemcitabine and carboplatin (GemCarbo). This study investigates the immunomodulatory effects of cisplatin vs carboplatin as a potential explanation for these clinical observations. GemCis compared with GemCarbo ± atezolizumab induced transcriptional changes in circulating immune cells, including upregulation of antigen presentation and T-cell activation programs. In vitro experiments demonstrated that cisplatin, compared with carboplatin, exerted direct immunomodulatory effects on cancer cells, promoting dendritic cell activation and antigen-specific T cell killing. These results underscore the key role of immune modulation in cisplatin's efficacy in urothelial carcinoma and highlight the potential importance of specific chemotherapy backbones for immune checkpoint blockade combination therapies.
2023-11-02 | GSE235066 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological breast cancer subtype but published data on trials specific for ILC are so far lacking. Translational research revealed that a subset of ILCs may be immune-related and more sensitive to DNA-damaging agents such as platinum. In murine ILC models, synergy between immune checkpoint blockade and platinum has been observed. Here, we tested this concept in the phase II, GELATO-trial (NCT03147040), in which patients with metastatic ILC were treated with weekly carboplatin (AUC 1.5) as immune induction treatment for 12 weeks and atezolizumab (PD-L1 blockade; every three weeks) from the third week onwards until disease progression. Four out of 23 evaluable patients had a partial response (17%, 95%CI 5-39%) and two patients had stable disease for at least 24 weeks, resulting in a clinical benefit rate of 26% (95%CI 10-48%). Out of these six patients, four patients had triple-negative ILC (TN-ILC). In serial biopsies of metastatic lesions, we observed higher CD8 T-cell infiltration, expression of immune checkpoints, and exhausted T cells upon carboplatin/PD-L1 blockade. This is the first report of a clinical trial specifically for ILC and we demonstrate promising anti-tumor activity of atezolizumab with carboplatin as immune induction, in particular for TN-ILC. While activity of carboplatin/PD-L1 blockade in classical ER+ ILC was limited, our translational data yield important insights for the design of highly needed clinical trials in ILC.
| EGAS00001006902 | EGA
Project description:DNA copy number profiles can identify patients with a defect in BRCA1 or BRCA2. We previously showed that patients with a BRCA1 like profile benefit from intensified alkylating chemotherapy (IA, 4 cycles 5-fluorouracyl (5FU), epirubicin, cyclophosphamide (C) + 1 cycle carboplatin, thiotepa and cyclophosphamide with autologous stem cell transplantation (ASCT)). Presumably, this is because of the defect in error free homologous recombination DNA repair. Here we present an independent study IA chemotherapy (2 cycles induction, followed by ifosfamide, 12 g/m2; carboplatin, 900 mg/m2; and epirubicin, 180 mg/m2 with ASCT) versus anthracyclin-C (AC) or C-methothrexate-5FU (CMF) regimens in high risk breast cancer.
2014-12-22 | GSE50407 | GEO
Project description:In chronic lymphocytic leukemia, measurable residual disease (MRD) depth following fixed-duration treatment is associated with progression-free survival (PFS). Often, MRD is reported as a static parameter, but successive MRD measurements may more accurately capture MRD dynamics and reveal valuable prognostic information. We used our recently developed IGHV leader-based NGS assay to measure MRD at four timepoints in 60 patients treated in the HOVON-139/GIVE trial, in which previously untreated patients received one year induction treatment with obinutuzumab and venetoclax, followed by randomization to consolidation treatment with venetoclax or MRD-conditional consolidation. Induction treatment resulted in MRD undetectability (<10-5) in 93% of assessed patients, with 85% and 74% of patients retaining MRD undetectability at six and twelve months after randomization. Uniquely, we measured MRD at a very early timepoint, during the fourth week of venetoclax ramp-up after obinutuzumab pre-induction. Here, MRD levels showed large interindividual variation, and, importantly, were associated with the probability of achieving MRD undetectability after induction treatment, MRD conversion after randomization and PFS. Additionally, the IGHV leader-based NGS assay allows characterization of the healthy background IGHV repertoire. Of note, venetoclax consolidation treatment, compared to no consolidation treatment, significantly impaired polyclonal IGHV repertoire reconstitution after induction treatment with venetoclax and obinituzumab.
2024-03-01 | GSE225043 | GEO
Project description:DNA copy number profiles can identify patients with a defect in BRCA1 or BRCA2. We previously showed that patients with a BRCA1 like profile benefit from intensified alkylating chemotherapy (IA, 4 cycles 5-fluorouracyl (5FU), epirubicin, cyclophosphamide (C) + 1 cycle carboplatin, thiotepa and cyclophosphamide with autologous stem cell transplantation (ASCT)). Presumably, this is because of the defect in error free homologous recombination DNA repair. Here we present an independent study IA chemotherapy (2 cycles induction, followed by ifosfamide, 12 g/m2; carboplatin, 900 mg/m2; and epirubicin, 180 mg/m2 with ASCT) versus anthracyclin-C (AC) or C-methothrexate-5FU (CMF) regimens in high risk breast cancer. DNA isolated from untreated resection specimens of 117 patients was labeled using Enzo labeling kit for array CGH and hybridized to a custom 135k Nimblegen platform.
2014-12-22 | E-GEOD-50407 | biostudies-arrayexpress
Project description:To investigate effects of standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy on T cell immunity, we surveyed changes in the peripheral T cell receptor repertoire. We performed bulk TCR sequencing of peripheral blood before chemotherapy (baseline), after 3 cycles (C3) and after 6 cycles (C6).
2022-06-22 | GSE206339 | GEO
Project description:All patients with suspected ovarian cancer (Raised CA 125 and a complex pelvic mass in a perimenopausal woman) were radiologically staged using CT scan and a chest x-ray. Patients with evidence of intra-abdominal metastasis and/or malignant pleural effusion were approached for entry to the study. Tissue biopsy was obtained either under radiological control (core needle biopsy) or via laparoscopic surgery (punch biopsy). Patients with histologicaly confirmed epithelial ovarian cancer were randomized to receive either three cycles of carboplatin (AUC 7) or paclitaxel (175 mg/m2). Patients with suspected ovarian cancer had a biopsy obtained before and after 3 cycles of either Carboplatin or Paclitaxel. Samples were immediately frozen for RNA extraction.
2009-04-09 | E-GEOD-15622 | biostudies-arrayexpress
Project description:A randomized, open-label, multicenter, phase II trial (NCT00455533) enrolled previously untreated women with histologically-confirmed primary invasive breast adenocarcinoma (T2–3, N0–3, M0, tumor size ≥2.0 cm), regardless of hormone receptor or HER2 expression status. Patients received sequential neoadjuvant therapy starting with 4 cycles of AC (doxorubicin 60 mg/m2 intravenously and cyclophosphamide 600 mg/m2 intravenously) given every 3 weeks, followed by 1:1 randomization to either ixabepilone (40 mg/m2 3-hour infusion) every 3 weeks for 4 cycles, or paclitaxel (80 mg/m2 1-hour infusion) weekly for 12 weeks. Fresh tumor biopsies at screening were a mandatory prerequisite for study entry for biomarker analyses. Gene expression profiling was performed by Affymetrix GeneChip to determine if pre-specified gene models could distinguish between the clinical activity of two microtubule stabilizing agents, ixabepilone and paclitaxel. Three core needle tumor tissue biopsies were obtained from all subjects before neoadjuvant therapy with AC and immediately combined in RNAlater® solution for subsequent RNA extraction, cRNA labeling and gene expression profiling. Pre-specified gene models were tested for their capacity to distinguish pathologic complete response rates between the AC followed by ixabepilone versus the AC followed by paclitaxel treatment regimens. All samples were collected prior to treatment. All subject received cyclophosphamide/doxorubicin (AC) prior to randomization to either Ixabepilone or Paclitaxel.
2013-01-01 | E-GEOD-41998 | biostudies-arrayexpress
Project description:A phase I trial of a SRC kinase Inhibitor, dasatinib, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Background: We conducted a phase I study of dasatinib, an oral SRC tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in advanced and recurrent epithelial ovarian cancer (EOC). Methods: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included toxicity, response rate (RR), pharmacokinetics and pharmacodynamics. Based on the 3+3 design, cohorts of 3-6 pts received paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks with escalating doses of dasatinib (100, 120, 150 mg daily), followed by an 8 patient expansion cohort. Results: Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 yrs (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. There were 3-6 pts in each cohort, and 8 in the expansion cohort. Pharmacokinetics were observed over the first 2 cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia. Other toxicities in all cycles included neutropenia (95% grade 3-4), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 45% (complete responses, 3/18(17%); partial responses, 5/18(28%)) and 56% (10/18) had stable disease. The PFS6-month actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. Conclusions: Due to the high incidence of myelosuppression with subsequent cycles the recommended phase II dose is 150 mg daily of dasatinib in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity in advanced EOC. Global profiles of expression were characterized using unsupervised clustering methods and gene- and pathway-analyses of differential expression.
2012-04-11 | E-GEOD-37180 | biostudies-arrayexpress