Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal models of leptomeningeal metastasis (LM) should give insight into pathophysiological mechanisms and allow to evaluate new treatments including their neurotoxicity. Syngeneic models use tumor cells of mouse, rat, rabbit or guinea pig origin. Allogeneic models usually rely on human tumor cells injected into nude mice or rats. A review of the literature revealed 2 (4) different glioma, 3 medulloblastoma, 3 (3) carcinoma, 3 (1) melanoma, 1 rhabdomyosarcoma, 2 (8) leukemia and 2 (2) non-Hodgkin's lymphoma allogeneic (syngeneic) models of LM. These models have been used to study the evolution of LM and to evaluate systemic or intrathecal chemotherapy, intrathecal immunotherapy (interleukin-2, interferon-beta, uncoupled, toxin- or radionuclide-conjugated antibodies), and recently gene therapeutic approaches. On the whole, pathophysiological, therapeutic and neurotoxic findings have been well transferable to the clinical situation. Therefore, it seems rational to preclinically test new treatments in an appropriate animal model of LM before using them in patients.
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PMID:Animal models of leptomeningeal metastasis. 969 72

Intracellular production of human interferon-beta (HuIFN-beta) was enhanced in three glioma cell lines (U251-MG, U251-SP, and U251-NN) using modified superinduction with cationic liposomes containing polyinosilic:polycytidilic acid (polyI:polyC), initially given with cycloheximide, to decrease the toxicity due to polyI:polyC. Modified superinduction had a significantly (p < 0.02-0.0001) greater inhibitory effect on all three glioma cell lines, and less toxicity than superinduction. A pilot trial in experimental gliomas implanted into nude mice was also performed. Superinduction including intratumoral injection of cationic liposomes containing polyI:polyC resulted in growth inhibition of U251-NN tumors and eradication of U251-SP tumors. Weight gain in mice was not inhibited by modified superinduction. Cationic liposomes decreased drug toxicity, and may help to target tumor cells in the modified superinduction of endogenous HuIFN-beta production.
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PMID:Growth inhibition of experimental glioma by human interferon-beta superinduced by cationic liposomes entrapping polyinosilic:polycytidilic acid. 978 Jun 44

In the present study, the synergistic effect of mild hyperthermia in combination with gene expression of interferon-beta (IFN-beta) was examined in vitro in the human glioma cell line U87MG. The cells transiently expressed the IFN-beta gene under the control of the mouse mammary tumor virus promoter and were then subjected to temperature elevation (41 degrees C for 1 h). In terms of the cell killing effect, the optimum scheme was obtained by transfection for 4 days before hyperthermia, i.e. rate in the time course of IFN-beta gene expression. The relative specific growth rate decreased to 32% compared with the control while it was only 40% under the hyperthermic conditions. These observations suggest that IFNbeta expression was able to enhance the sensitivity of transfected glioma cells to mild hyperthermia.
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PMID:Synergism between mild hyperthermia and interferon-beta gene expression. 1039 72

Cationic liposomes containing the human interferon-beta (IFN-beta) gene induce marked growth inhibition in human glioma cells. In vivo experiments using an human glioma implanted into the brains of nude mice have demonstrated a definite growth-inhibitory effect, achieving complete tumor regression with multiple intratumoral injections of the gene. However, nude mouse studies are inadequate to evaluate antitumor effects fully, especially those related to activation of the host immune response. This article aimed to investigate antitumor effects and immune response activation by murine IFN-beta gene transfer in syngeneic mice. In vitro experiments demonstrated a stronger growth-inhibitory effect of liposomes containing the murine IFN-beta gene on a GL261 mouse glioma cell line than exogenously added murine IFN-beta. In in vivo experiments, intratumoral administration of liposomes containing the murine IFN-beta gene resulted in a 16-fold reduction in the mean volume of residual gliomas in the brains of C57BL/6 mice and massive infiltration of cytotoxic T lymphocytes (CTL) within the residual tumor, while few CTL were infiltrated in controls including murine IFN-beta, empty liposomes, naked plasmid expressing murine IFN-beta, and liposomes containing beta-galactosidase gene. In addition, 40% of mice treated with liposomes containing the murine IFN-beta gene were completely cured. These findings indicated that activation of cellular immunity participates in antitumor effects in vivo together with direct effects of the IFN-beta gene.
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PMID:Antitumor effect and cellular immunity activation by murine interferon-beta gene transfer against intracerebral glioma in mouse. 1049 Jul 73

Combined treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy was assessed in patients with malignant glioma who had not received previous cytotoxic drug therapy. Forty-three patients up to 75 years old with histopathologically confirmed malignant glioma were studied. All patients had tumors measurable by neuroimaging, a Karnofsky performance score exceeding 40, and an expected survival exceeding 2 months. A response rate of 49% (21/45) was observed, including 6 complete remissions (14%) and 15 partial remissions (35%). Of the 43 patients who completed initial therapy, 19 were given sequential maintenance therapy. Survival time was much longer with than without maintenance therapy. Toxic side effects were moderate and did not substantially affect patients' general condition. We concluded that this combination therapy had a pronounced effect on untreated malignant glioma, particularly in patients whose initial therapy was followed up with maintenance therapy.
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PMID:Initial and maintenance combination treatment with interferon-beta, MCNU (Ranimustine), and radiotherapy for patients with previously untreated malignant glioma. 1113 87

We constructed an adeno-associated virus (AAV) vector containing the human interferon-beta (HuIFN-b ) gene (AAV-IFN-beta) and investigated its antitumor effect against human glioma cells (U251-SP) inoculated into the brain of nude mice. Prior to this, we examined human glioma cells transduced with AAV-IFN-beta using video-enhanced contrast differential interference contrast (VEC-DIC) microscopy. Infection of AAV-IFN-beta induced apoptosis and secondary necrosis in human glioma cells. In in vivo experiments, we confirmed production of HuIFN-beta and induction of heat-shock protein (HSP) in glioma cells transduced with AAV-IFN-beta. Growth of the experimental gliomas was completely inhibited by six injections of AAV-IFN-beta, starting 7 days after transplantation of glioma cells. In addition, the survival of mice treated with AAV-IFN-beta was remarkably prolonged. These results indicate that AAV-IFN-beta induces apoptosis of glioma cells and has a strong antitumor effect in this experimental glioma model.
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PMID:Antitumor effect of an adeno-associated virus vector containing the human interferon-beta gene on experimental intracranial human glioma. 1185 87

Hypoxic cells play a key role in the radioresistance of malignant glioma. Interferon-beta, ACNU as nimustine hydrochloride and radiotherapy (IAR) is a common therapy for malignant glioma in Japan. Since hyperbaric oxygenation (HBO) increases oxygen pressure in glioma tissue, we applied a modified IAR therapy, radiotherapy after HBO combined with interferon-beta and ACNU (HBO/IAR therapy), for supratentorial malignant gliomas. Daily radiation therapy was completed within 15 min after HBO. We assessed HBO/IAR with respect to toxicity, response rates and the time of tumor progression (TTP). We also examined the incidence of responses by some prognostic factors before HBO/IAR, namely, age, Karnofsky performance scale (KPS), histological type, tumor size, tumor site and operation type. Of 39 patients who participated in this study, 35 underwent a complete schedule of HBO/IAR therapy in which toxicity was permissible. Thirty patients (76.9%) either maintained or increased KPS during HBO/IAR with a mean duration of 68 +/- 14 days. The response rates (CR + PR%) for glioblastoma, anaplastic astrocytoma and overall were 50%, 30% and 43%, respectively. The incidence of therapeutic responses among all prognostic factors before HBO/IAR did not significantly differ. Median TTP for patients with glioblastoma, patients with anaplastic astrocytoma, and overall were 38, 56 and 43 weeks, respectively. The present study suggested that HBO/IAR therapy could be applied to especially patients with poor prognostic factors, because of its short treatment period, its permissible toxicity and identical response to patients with good prognostic factors.
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PMID:A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas. 1262 55

T cell subset, natural killer (NK) cell activity and tumor necrosis factor alpha (TNF-alpha) productivity of lymphocytes in the peripheral blood were investigated in order to study host-immunity before and after administration of Juzentaiho-to (TJ-48) with or without Interferon-beta (INF-beta) for 29 patients with brain tumors (15 cases of gliomas and 14 cases of non-glial tumors). "A" group was given TJ-48 (7.5 g/day, p.o.) with INF-beta 300 million IU/1-2 weeks after initial treatment, and "B" group was treated by only TJ-48. % values of helper T cells (CD4+, CD45RA-), cytotoxic T cells (CD8+, 11b-), suppressor T cells (CD8+ +. 11b+) and NK activity were calculated with two color flowcytometry before and at 1 month, 2 months and 3 months after the administration of TJ-48. TNF-alpha productivity of lymphocytes was examined by the ELISA method at the same time. Suppressor T cells decreased significantly after 2 months following administration of JT-48 in 16 of 17 cases in both A and B group. After administration of TJ-48, helper T cells tended to increase slightly, but cytotoxic T cells and NK activity did not change. TNF-alpha productivity was measured in 8 cases of gliomas and increased to levels higher than they were before administration of TJ-48 in all of the cases which were examined more than 2 months after treatment. Adjuvant therapy with TJ-48 in both A and B group improved the host-immunity of the patients with brain tumors. It was concluded that it was useful as an assistant treatment for brain tumors.
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PMID:[Improvement of host-immunity by adjuvant therapy with juzen-taiho-to for patients with brain tumors]. 1270 21

Interferon-beta (IFN-beta) has been used as an antitumor drug against human glioma, melanoma and medulloblastoma since the 1980s. Recently, we developed a new gene therapy using the IFN-beta gene against malignant gliomas and then began clinical trials in 2000. Since stimulation of immune system was one mechanism of antitumor effect induced by IFN-beta gene therapy, we hypothesized that combination of IFN-beta gene therapy with immunotherapy might increase its effectiveness. In the present study, we tested whether combination therapy with IFN-beta gene therapy and immunotherapy using tumor cell lysate-pulsed dendritic cells (DCs) would increase the efficacy of IFN-beta gene therapy. In an experimental mouse intracranial glioma (GL261), which cannot be cured by either IFN-beta gene therapy or DC immunotherapy alone, IFN-beta gene therapy following DC immunotherapy resulted in a significant prolongation in survival of the mice. Moreover, when this combination was performed twice, 50% of treated mice survived longer than 100 days. Considering these results, this combination therapy may be one promising candidate for glioma therapy in the near future.
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PMID:Vaccination with tumor cell lysate-pulsed dendritic cells augments the effect of IFN-beta gene therapy for malignant glioma in an experimental mouse intracranial glioma. 1525 50

Interferon-beta gene therapy for cancer is the first such protocol developed in Japan. Here we describe the development process of our interferon-beta gene therapy from basic research to clinical application. Interestingly, the biological and biochemical characteristics of interferon-beta gene therapy through transfer of the interferon-beta gene into tumor cells by means of cationic liposomes differed from those of conventional interferon-beta protein therapy. Interferon-beta gene transfer could induce apoptosis in interferon-beta protein-resistant tumor cells, such as glioma, melanoma, and renal cell carcinoma. Induction of apoptosis was related to the level of intracellular mRNA of interferon-beta, prolongation of the phosphorylation time of molecules in the interferon-beta signal transduction pathway, such as JAK1, Trk2, and STAT1, and activation of DNase gamma. In our preclinical study we developed lyophilized cationic liposomes containing interferon-beta gene (gene drug) for clinical use and confirmed their safety. Thereafter, we performed a pilot clinical trial in patients with malignant glioma and confirmed the safety and effectiveness of this interferon-beta gene therapy. In this review we also comment on the status of gene therapy regulation in Japan. Interferon-beta gene therapy is expected to become widely available for clinical use in cancer patients, and this new strategy might be extended to molecular targeting therapy, or used in combination with cell therapy or other therapies.
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PMID:Interferon-beta gene therapy for cancer: basic research to clinical application. 1554 2


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