Expression data from human pancreatic cells PANC-1 infected with oncolytic vaccinia virus GLV-1h153
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE48121 | GEO | 2013/06/20
SECONDARY ACCESSION(S): PRJNA208954
REPOSITORIES: GEO
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Project description:Pancreatic cancer is a fatal disease associated with resistance to conventional therapies. GLV-1h153 is an oncolytic virus which has shown promise for the targeted treatment of cancer, and is engineered to carry the human sodium iodide symporter (hNIS) for the imaging of viral replication within tumors via enhanced uptake of several radionuclide probes. We used microarrays to determine changes in gene expression patterns over time associated with infection and susceptibility of pancreatic cancer cells to GLV-1h153. Understanding into the molecular mechanisms associated with PANC-1 sensitivity to GLV-1h153 may enable identification of cancers resistant to viral therapy, avoid undesirable side effects associated with the need for higher doses of viral treatment, and development of safer and more efficacious oncolytic virotherapies. PANC-1 cells were infected with GLV-1h153. Zero (T0), 6 (T6) and 24 (T24) hours after infection, 3 samples of each time point were harvested and gene expression patterns assessed using HG-U133A cDNA microarray chips as compared to uninfected control (T0).
2013-06-20 | E-GEOD-48121 | biostudies-arrayexpress
Project description:Previously we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-green fluorescent protein (RUC-GFP) fusion, b-galactosidase, and b-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase, TK), and A56R (encoding hemagglutinin, HA) loci of the viral genome, respectively. Intravenous (i.v.) injections of GLV-1h68 (1 Ã 107 pfu/mouse) into nude mice with established (500 mm3) subcutaneous (s.c.) GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity and oncolytic efficacy. GLV-1h68 demonstrated an enhanced tumor targeting specificity and much reduced toxicity compared to its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers. Objective: To determine the gene expression changes induced by GLV-1h68 vaccinia virus injection in mouse carrying human breast cancer implant and leading to tumor eradication. Methods: Gene expression was analyzed using oligonucleotide microarrays. Responsiveness to vaccina virus injection was assessed by toxicity and survival study, gene expression anaysis and tumor volume change. Result: The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. Conclusion: Our findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers. Experiment Overall Design: tumor tissues 3 and 6 weeks post virus injection
2008-06-16 | E-GEOD-8513 | biostudies-arrayexpress
Project description:Previously we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-green fluorescent protein (RUC-GFP) fusion, b-galactosidase, and b-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase, TK), and A56R (encoding hemagglutinin, HA) loci of the viral genome, respectively. Intravenous (i.v.) injections of GLV-1h68 (1 × 107 pfu/mouse) into nude mice with established (500 mm3) subcutaneous (s.c.) GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity and oncolytic efficacy. GLV-1h68 demonstrated an enhanced tumor targeting specificity and much reduced toxicity compared to its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers. Objective: To determine the gene expression changes induced by GLV-1h68 vaccinia virus injection in mouse carrying human breast cancer implant and leading to tumor eradication. Methods: Gene expression was analyzed using oligonucleotide microarrays. Responsiveness to vaccina virus injection was assessed by toxicity and survival study, gene expression anaysis and tumor volume change. Result: The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. Conclusion: Our findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers. Keywords: Responsiveness to vaccina virus injection
2007-12-26 | GSE8513 | GEO
Project description:Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. This therapy relies on efficient replication of virus in tumor cells in vivo with minimal or no replication in normal tissues. We recently described GLV-1h68 as a modified Vaccinia Virus (VACV) construct with exclusive in vivo tropism for tumor cells in experimental animal models. Moreover, we had previously observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro during the first 20 hours following infection and the in vivo ability to colonize and eliminate the corresponding tumor implant. Thus, we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines, extensively characterized and used for the assessment of novel therapeutic modalities. All cell lines were cultured and infected in identical conditions. Pre-infection transcriptional profiling was obtained to search for correlates of permissivity to viral infection. Selected cell lines were also tested for permissivity to another VACV and a vesicular stomatitis virus (VSV) strain. We observed that permissivity to VACV infection during the first 20 hours is quite heterogeneous among cell lines but highly reproducible within each cell line. The tissue of origin of each cell line does not influence permissivity to infection with the exception of B cell derivation. Permissivity correlates between two VACV constructs and between them and VSV suggesting a common permissive phenotype. No clear transcriptional pattern predictive of permissivity to infection could be identified though weak associations were observed that suggest a multifactorial control of viral replication. This study adds to the current characterization of the NCI-60 panel to guide the design and interpretation of experimental models testing oncolytic therapies. Seventy-four microarray samples were obtained from 8 renal cancer cell lines (786-0, A498, ACHN, CAKI-I, RXF-393, SN12C, TK-10, UO-31); 12 melanoma cell lines (888-MEL, 1858-MEL, 1936-MEL, 397, A375-MEL, LOX IMVI, M14, SK-MEL-2, SK-MEL-5, SK-MEL-28, UACC 62, UACC 257 ); 11 lung cancer cell lines (A549 p7, A549 p107, EKVX, HOP-62, HOP-92, NCI-H23, NCI-H226, NCI-H322M, NCI-H460, NCI-H522, NCI-H1299); 13 colon cancer cell lines (HCT-15, HCT-116, HT-29 p155, HT-29 p9, KM-12, SW-620, Colo 205, HCC 2998, NCI-ADR-RES, OVCAR 3 p7, OVCAR 3 p42, OVCAR 5, SK-OV-3); 3 ovarian cancer cell lines (OVCAR 4, OVCAR 8, IGROV); 1 cervical cancer cell line (Siha); 6 brain cancer cell lines (SNB 19, SF 295, SF 298, SNB 75, U251, SF 539); 7 breast cancer cell lines (BT-549, GI101A, HS-578T, MCF 7, MDA-MB-231 p41, MDA-MB-435, MDA-MB-231 p6); 7 hematopoietic cancer cell lines (CCFR-CEM, HL-60, K-562, MOLT-4, RPMI 8226, SR, T-47D); 3 prostatic cancer cell lines (Du-145, PC 3 p7, PC 3 p35); 1 hepatic cancer cell lines (Huh 7.5.1); and 2 pancreatic cancer cell lines (MIA PACA 2, Panc 1). Two technical repeats were performed (cell lines Siha and SNB-19). Reference T-RNA was obtained from 6 normal donor PBMCs.
2012-03-24 | E-GEOD-28472 | biostudies-arrayexpress
Project description:Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. This therapy relies on efficient replication of virus in tumor cells in vivo with minimal or no replication in normal tissues. We recently described GLV-1h68 as a modified Vaccinia Virus (VACV) construct with exclusive in vivo tropism for tumor cells in experimental animal models. Moreover, we had previously observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro during the first 20 hours following infection and the in vivo ability to colonize and eliminate the corresponding tumor implant. Thus, we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines, extensively characterized and used for the assessment of novel therapeutic modalities. All cell lines were cultured and infected in identical conditions. Pre-infection transcriptional profiling was obtained to search for correlates of permissivity to viral infection. Selected cell lines were also tested for permissivity to another VACV and a vesicular stomatitis virus (VSV) strain. We observed that permissivity to VACV infection during the first 20 hours is quite heterogeneous among cell lines but highly reproducible within each cell line. The tissue of origin of each cell line does not influence permissivity to infection with the exception of B cell derivation. Permissivity correlates between two VACV constructs and between them and VSV suggesting a common permissive phenotype. No clear transcriptional pattern predictive of permissivity to infection could be identified though weak associations were observed that suggest a multifactorial control of viral replication. This study adds to the current characterization of the NCI-60 panel to guide the design and interpretation of experimental models testing oncolytic therapies.
2012-03-24 | GSE28472 | GEO
Project description:Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. A better understanding of the mechanisms of NIS regulation in breast cancer may lead to strategies for increasing cell surface NIS and radioactive iodide uptake (RAIU) in breast cancer. The MCF-7 cell line is the only human breast cancer cell line with inducible endogenous NIS expression. Kogai et al. [2000] first reported that trans-retinoic acid (tRA) induces NIS mRNA expression in MCF-7 cells and it was later reported that a combination treatment of tRA and hydrocortisone (tRA/H) further increases tRA-induced NIS expression/function in MCF-7 cells (Kogai et al., 2005; Dohan et al., 2006). In this study, we used gene expression profiling to identify genes that correlate with NIS expression in MCF-7 cells such that mechanisms underlying NIS modulation may be elucidated.
2011-09-16 | GSE32161 | GEO
Project description:Na+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. A better understanding of the mechanisms of NIS regulation in breast cancer may lead to strategies for increasing cell surface NIS and radioactive iodide uptake (RAIU) in breast cancer. The MCF-7 cell line is the only human breast cancer cell line with inducible endogenous NIS expression. Kogai et al. [2000] first reported that trans-retinoic acid (tRA) induces NIS mRNA expression in MCF-7 cells and it was later reported that a combination treatment of tRA and hydrocortisone (tRA/H) further increases tRA-induced NIS expression/function in MCF-7 cells (Kogai et al., 2005; Dohan et al., 2006). In this study, we used gene expression profiling to identify genes that correlate with NIS expression in MCF-7 cells such that mechanisms underlying NIS modulation may be elucidated. MCF-7 cells were treated with DMSO vehicle, tRA (1µM), or tRA(1µM)/H(1µM) for 12 hours and total RNA was extracted. There are two replicates for each treatment group.
2011-09-15 | E-GEOD-32161 | biostudies-arrayexpress
Project description:Regional delivery of oncolytic viruses has been shown to promote immune responses. Malignant pleural effusions comprise an immunosuppressive microenvironment, and the ability of oncolytic viruses to generate immune responses following regional delivery in patients with malignant pleural effusions is unknown. We conducted a phase I clinical trial that studied the intrapleural administration of oncolytic vaccinia virus to establish the safety and feasibility in patients with malignant pleural effusion due to malignant pleural mesothelioma or metastatic disease. In patients with malignant pleural mesothelioma, by correlative analysis of pre- and post-treatment tumor biopsies, we provide insight into tumor-specific viral uptake and associated immune responses.
2023-01-27 | GSE223395 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) has been characterized as immune suppressed. Oncolytic viruses can increase tumor antigenicity via immunogenic cell death (ICD). In this study, tumor-targeting and cytokine-armed vaccinia viruses (vvDD, vvDD-IL2, vvDD-IL15) were used to infect carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments we tested the cytotoxic response and the activation of human natural killer-(NK-)cells during the oncolytic process.
2024-09-20 | PXD048276 | Pride
Project description:Expression data from human pancreatic cells PANC-1 infected with oncolytic vaccinia virus GLV-1h153
| PRJNA208954 | ENA