IGR_Michels_PARP
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: justine guegan
PROVIDER: E-MTAB-1353 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Here, we used an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens. Only the fragmented proteins elicited effective multi-specific T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased significantly upon anti-PD-1 therapy, and correlated with patients’ survival and decreased PD-1 expression.
2020-05-27 | PXD016997 | Pride
Project description:From a tumoral line IGR-Heu; resulting from a biopsy of the primitive tumour of a patient reached of a bronchial cancer not with small cells (NSCLC); we established; by successive co-cultures of this line with the autologous CTL (clone T H161); a resistant line to the cytotoxic lysis induced by H161 (IGR-HeuR8 line). This resistant line was then cloned by limiting dilutions and a resistant clone was obtained (tumoral clone IGR-HeuR8). The goal of this study is to define profiles of genetic expression of the tumoral resistance to the CTL after phenotypical and functional study of the resistant clone IGR-HeuR8.
2006-01-23 | E-TABM-71 | biostudies-arrayexpress
Project description:We had previously demonstrated the role of CD103 integrin on lung tumor-infiltrating lymphocyte (TIL) clones in promoting specific TCR-mediated epithelial tumor cell cytotoxicity. However, the contribution of CD103 on intratumoral T-cell distribution and functions, and the prognosis significance of TIL subpopulations in non-small cell lung carcinoma (NSCLC) have thus far not been systematically addressed. Here we investigate the transcriptomic profil of these cell population, using PBMC cells as control.
2015-06-29 | E-MTAB-3266 | biostudies-arrayexpress
Project description:Lung cancer is the leading cause of cancer-related deaths and its treatment is based in chemotherapy using platinum containing compounds, mainly cisplatin (CDDP). Many patients show resistance to CDDP leading to treatment failure. To understand the mechanisms involved in CDDP resistance in lung cancer, we used CDDP-sensitive (A549) and –resistant (A549/CDDP) cells to identify newly synthesized proteins in response to CDDP treatment using BONCAT technique. In addition the steady-state proteome of A549 and A549/CDDP cells was also evaluated. It was identified 70 and 69 proteins upregulated by CDDP in A549 and A549/CDDP cells, respectively. The set of proteins upregulated by CDDP in both cells are associated to GO terms related to proteostasis, telomere maintenance cell, RNA processing, cytoskeleton and response to oxidative stress. Interestingly, the profile of biological processes enriched in A549 cells after CDDP treatment is very similar to those identified in the steady-state proteome of A549/CDDP cells, suggesting their positive selection in CDDP-resistant cells development. Therefore, this study of proteomic response to CDDP is relevant to the identification of potential protein targets to development of therapeutic strategies to block drug resistance pathways.
2023-03-10 | PXD021779 | Pride
Project description:Radiotherapy has a critical role in the treatment of small cell lung cancer (SCLC). Effectiveness of radiation in SCLC remains limited as resistance results from defects in apoptosis. In the current study, we investigated whether using a Bcl-2/Bcl-XL inhibitor S44563 can enhance radiosensitivity of SCLC cells in vitro and in vivo. In vitro studies confirmed that S44563 induce apoptosis in SCLC cells by inducing hallmarks of apoptosis (cleaved caspase-3, sub-G1 fraction induction and induction of the mitochondrial caspase activation pathway). S44563 markedly enhanced sensitivity of H146 cells and H69 cells to radiation in clonogenic assay. In addition, the combination S44563 and cisplatin-based chemo-radiation showed a dramatic tumor growth delay and increased overall survival in mouse xenograft models. In vitro experiments demonstrated a greater induction of apoptosis (sub-G1 fraction and cleaved caspase-3) with the combination as well as in vivo caspase-3 immunostaining. This positive interaction between S44563 and radiation was greater when S44563 was given after the completion of the radiation, which may be explained by the radiation-induced over expression of anti-apoptotic proteins (Bcl-2 and Bcl-XL) through the NF-?B pathway activation. Taken together, these data underline the critical role of sequence administration of targeted therapies with conventional therapies. SCLC cells which survive to IR highly rely on the induction of anti apoptotic proteins in part through NF- ?B activation for their survival yielding to the concept of 'contextual oncogene addiction' to the Bcl-2/Bcl-XL pathway providing rational for targeting survival pathways to potentiate IR. For transcriptome analysis, 106 cells were seeded in T25 flasks, allowed to growth for 24 h, and then left untreated or treated with 2 Gy radiation. After 24 hours, cells were harvested, lysed for the extraction of RNA, and processed to analyze gene expression.The design of this study consists to 6 hybridizations in dual color with Agilent Human Genome 4x44K (design 014850). The reference is always the untreated condition.
2013-02-01 | E-MTAB-966 | biostudies-arrayexpress
Project description:This experiment is designed to screen miRNAs that are deregulated during chemoresistance-associated metastasis of lung cancer cells. Chemoresistant metastatic in vivo tumor model of A549-luc-Vector cells was established after four rounds of cisplatin (CDDP) treatments compared to corresponding control solvent treatments. Upon examining profiles of miRNA expression differential between tumor-derived cultured cells from the Ctrl-4th and CDDP-4th treatments, most markedly upregulated and downregulated miRNAs in chemoresistant, metastatic A549-luc-CDDP-4th cells were identified. In order to establish a chemoresistant in vivo tumor model, after inoculation of A549-luc-Vector cells, cisplatin (CDDP) or control solvent was intraperitoneally (i.p.) injected six rounds in a two-week period and cells were isolated from corresponding resultant tumors, cultured and re-transplanted into syngeneic mice to receive the next round of treatment. In our experimental model, human lung cancer xenografts developed chemoresistance in the third round of CDDP treatment (CDDP-3rd) and chemoresistance-associated metastases following the fourth round of treatment. Tumor-derived cultured cells from Ctrl-4th and CDDP (cisplatin)-4th treatment were subjected to miRNA array (Agilent-031181 human miRNA (8*60k) V16.0) analysis, with two biological replications for each treatment.
2015-04-10 | E-GEOD-67727 | biostudies-arrayexpress
Project description:Goal of the experiment Recurrence is a frequent phenomenon in intracranial childhood ependymomas. To understand this process, we investigated whether the gene expression profiling of matched ependymomas at diagnosis and at relapse could reveal key molecular events involved in tumor progression. To gain new insight in this process and identify pathways associated with recurrence, we compared the gene expression profiles of local recurrences with the corresponding initial tumors. Brief description We analyzed 17 tumor samples at diagnosis and a total of 27 paired recurrences. Recurrences analyzed occurred after surgery only in 12 cases, surgery plus chemotherapy only in 9 cases and any treatment plus radiotherapy in 6 cases. We compared the level of gene expression for each tumor at recurrence relative to its expression at diagnosis using Agilent 44K dual color gene expression microarrays.
2010-12-31 | E-TABM-873 | biostudies-arrayexpress
Project description:VHL is a tumor suppressor gene involved in the oxygen-sensing pathway whose germline mutations predispose to distinct phenotypes. Heterozygous mutations predispose to von Hippel-Lindau disease characterized by the development of multiple tumors (including hemangioblastomas, renal cell carcinomas and pheochromocytomas)1-3. More recently, a specific VHL-R200W mutation was shown to be responsible for Chuvash Polycythemia in homozygous carriers whereas heterozygous individuals have no clinical manifestation4. We report here a family carrying, on the same allele, VHL mutations characteristics of the two types of disease (a Chuvash polycythemia-R200W mutation and a von Hippel-Lindau disease-R161Q mutation). Genotyping, modeling analysis and functional studies, including transcriptomic profile of the distinct mutants validated for the first time on direct HIF target genes, show a gradual capacity of the VHL mutants to regulate the hypoxia responsive pathway that correlate with the severity of the developed phenotype. Our study provide original results that illuminate genotype/phenotype correlations in von Hippel-Lindau disease.
2013-09-03 | E-MTAB-1269 | biostudies-arrayexpress
Project description:Background: Although histology is the corner stone for decision analysis in bladder cancer, it still needs refinement and new tools to better identify tumours with the highest risk of progression or recurrence. Objective: We designed a prospective study to evaluate whether microarray analysis could find a molecular signature for pathologic staging and/or grading. Design, setting and participants: Prospective multicentric study conducted from September 2007 to May 2008 (108 bladder tumours (45 pTa, 35 pT1 and 28> pT1)). Microarray analysis was performed with Agilent Technologies Human Whole Genome 4 x 44K oligonucleotide microarrays and used a method of dual color type versus a reference consists of a pool of tumours. From the lists of genes provided by the BrB Class Comparison analyses, we validated the microarray results of 38 selected differentially expressed genes by RT-QPCR in another bladder tumour cohort (n = 95). Results: The cluster M-^Ssuperficial vs invasive stageM-^T properly classified 92.9% of invasive stages and 66.3% of superficial stages. Among the superficial tumours, the cluster analysis showed that pT1b tumours were closer to invasive stages than pT1a tumours. We also found molecular differences between low and high-grade superficial tumours. However these differences were less caricatural than the one observed for staging.Conclusions: We confirm that the histopathological classification into subgroups pTa, pT1a and pT1b may have a translation in a M-^Smolecular signatureM-^T with a continuous progression of deregulation (overexpression or repression of these genes) from superficial (pTa) to more invasive (pT1a then b stage).
2013-08-13 | E-MTAB-993 | biostudies-arrayexpress
Project description:Non-small cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) responds to EGFR tyrosine kinase inhibitors such as erlotinib. However, secondary somatic EGFR mutations (e.g. T790M) confer resistance to erlotinib. BMS-690514, a novel panHER/VEGFR inhibitor described here, exerted antiproliferative and pro-apoptotic effects on NSCLC cell lines, with prominent efficacy on H1975 cells expressing the T790M mutation. In this model, BMS-690514 induced a G1 cell cycle arrest, as well as ultrastructural hallmarks of apoptosis, mitochondrial release of cytochrome c, and activation of caspases involved in the intrinsic (e.g. caspase -2, -3, -7 and -9), but not in the extrinsic (e.g. caspase-8) pathway. Caspase inhibition conferred partial protection against BMS-690514 cytotoxicity, pointing to the involvement of both caspase-dependent and -independent effector mechanisms. Transcriptome analyses revealed the upregulation of pro-apoptotic (e.g. Bim, Puma) and cell cycle inhibitory (e.g. p27Kip1, p57Kip2) factors, as well as the downregulation of anti-apoptotic (e.g. Mcl1), heat shock (e.g. HSP40, HSP70, HSP90) and cell cycle promoting (e.g. cyclins B1, D1 and D3, CDK1, MCM family proteins, PCNA) proteins. BMS-690514-induced death of H1975 cells was modified in a unique fashion by a panel of siRNAs targeting apoptosis modulators. Downregulation of components of the NF-kappaB survival pathway (e.g. p65, Nemo/IKK, TAB2) sensitized cells to BMS-690514, whereas knockdown of pro-apoptotic factors (e.g. Puma, Bax, Bak, caspase-2, etc) and DNA damage-related proteins (e.g. ERCC1, hTERT) exerted cytoprotective effects. BMS-690514 is a new pan-HER/VEGFR inhibitor that may become an alternative to erlotinib for the treatment of NSCLC.
2007-07-24 | E-TABM-239 | biostudies-arrayexpress