Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokine gene therapy for the induction of potent immune responses against central nervous system tumors has proven to have significant potential. However, this strategy needs improvement in the process of antigen presentation and/or insufficient recruitment of immunocompetent cells to achieve successful eradication of established brain tumors. We investigated the therapeutic potential of induced systemic immunity in peripheral tissues combined with interleukin-2 (IL-2) production in the vicinity of brain tumors to treat established brain tumors. Sequential magnetic resonance image monitoring showed that the combinatory therapy consisting of intracerebral (i.c.) transplantation of IL-2-producing rat gliosarcoma 9L (9L/IL-2) cells and s.c. vaccination using irradiated 9L or 9L/IL-2 cells could cure 9L-bearing rats, whereas either the i.c. injection of 9L/IL-2 cells or the s.c. vaccination produced little or marginal antitumor effects, respectively. Xenogeneic murine neuroblastoma cells secreting IL-2 could substitute for 9L/IL-2 cells, producing significant antitumor effects in the vaccinated rats. Tumor-specific cytotoxic activity was induced in the vaccinated rats but not fully in the rats treated only with i.c. injection of 9L/IL-2 cells. Immunohistochemical analysis revealed that a number of CD4(+) and CD8(+) T cells infiltrated into the brain tumors which were treated with the combinatory therapy. The level of cell infiltration was similar to that found in s.c. 9L/IL-2 tumors which were subsequently rejected. In contrast, the brain tumors treated with either i.c. transplantation of 9L/IL-2 cells or the s.c. vaccination showed only moderate infiltration of T cells. The combinatory strategy, i.c. grafting of IL-2-producing cells, and s.c. immunization of irradiated whole tumor cell vaccine, is, thus, effective for recruiting activated T cells into the brain tumor site and could be a potential therapy for brain tumors.
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PMID:Induction of immunity in peripheral tissues combined with intracerebral transplantation of interleukin-2-producing cells eliminates established brain tumors. 1175 97

Effective induction of systemic antitumor immunity is a crucial step for success of immune gene therapy for intracerebral gliomas. We examined in this study the ability to induce glioma-specific cytotoxic T lymphocytes (CTL) by subcutaneous (s.c.) immunization of irradiated whole-tumor cell vaccine with or without artificial cytokine production, and also examined in vivo efficacy of the induced CTL against a rat brain tumor model with 9L gliosarcoma cells. Murine neuroblastoma C1300 cells transduced with the interleukin-2 (IL-2), IL-4 or granulocyte-macrophage colony-stimulating factor (GM-CSF) gene (C1300/IL-2, C1300/IL-4 or C1300/GM-CSF) were used as cytokine-producers. Glioma-specific CTL activity was equivalently induced in the rats vaccinated s.c. with irradiated 9L, irradiated IL-2-producing 9L cells or the mixed population of irradiated 9L and C1300/IL-2 cells, while the activity was relatively lower in the rats vaccinated with irradiated 9L cells mixed with either C1300/IL-4 or C1300/GM-CSF cells. In the rats immunized s.c. with irradiated 9L cells, intracerebral (i.c.) 9L tumors implanted together with either C1300/IL-2 or C1300/IL-4 were completely rejected. Pre-established brain tumor also could be eliminated by the s.c. immunization of irradiated 9L cells and i.c. transplantation of IL-2-producers. These results suggest that glioma-specific CTLs could be effectively induced by s.c. immunization of irradiated wild-type tumor cells without artificial cytokine production.
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PMID:Glioma-specific cytotoxic T cells can be effectively induced by subcutaneous vaccination of irradiated wild-type tumor cells without artificial cytokine production. 1285 99

Our group has recently developed 1-(t)butyl carbamoyl, 7-methyl-indole-3-ethyl isothiocyanate (NB7M), a novel indole ethyl isothiocyanate analog. We now describe its selective cytotoxicity in both central nervous system (CNS) and neuroblastoma (NB) cancer cells. In an effort to understand its mechanism of action we examined the effects of NB7M on apoptosis, cell cycle arrest, and pro-survival/mitogen-activated protein kinase (MAPK) signaling in neuroblastoma cells. NB7M proved highly cytotoxic to NB cell lines (SMS-KCNR, SK-N- SH, SH-SY5Y, IMR-32) with IC(50) values ranging from 1.0-2.0 microM, whereas lung fibroblasts were less affected (IC(50) > or =10 microM). In the NCI 60 cell screen 1-dose assay, NB7M (10 microM) reduced the growth (-89 to -27 % growth) of CNS cancer cell lines SF-268, SF-295, SNB-75 (glioblastoma), SF-539 (gliosarcoma), and U251 (astroglioma) while SNB-19 glioblastoma cells were relatively resistant (19% growth). Hoechst staining of SMS-KCNR cells treated with NB7M (3 microM) for 24 hrs exhibited significant chromatin condensation and DNA fragmentation, whereas Annexin-v/7AAD staining revealed that the majority of cells accumulated in the early-apoptotic and late-apoptotic/necrotic stages. NB7M treatment of SMS-KCNR and SH-SY5Y cells also led to the cleavage of procaspases-3, and PARP-1 while causing activation of pro-apoptotic MAPKs and down-regulation of pro-survival factors AKT and PI-3K. Furthermore, NB7M treatment caused S-phase arrest in SMSKCNR and G1-phase arrest in SH-SY5Y cells. NB7M is active against CNS cancers and NB.
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PMID:Induction of cytotoxicity, apoptosis and cell cycle arrest by 1-t-butyl carbamoyl, 7-methyl-indole-3-ethyl isothiocyanate (NB7M) in nervous system cancer cells. 1992 Aug 94