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)

Weakly immunogenic, but highly malignant, rat MADB106 breast cancer cells were retrovirally transduced with the membrane form of macrophage colony-stimulating factor (mM-CSF). The cloned mM-CSF-transfected MADB106 cells physically conjugated with macrophages, but were not killed by the macrophages in 48-h cytotoxicity assays. Macrophages killed the mM-CSF-expressing tumors in the presence of noncytotoxic doses of either taxol or taxol plus cisplatin. This indicated that macrophages bind to the mM-CSF expressed on the tumor cells, but for successful macrophage cytotoxicity to occur against mM-CSF-transduced tumor cells other factors must be present. The mM-CSF-transfected tumor cells were rejected when inoculated subcutaneously into normal rats. Cloned MADB106 tumor cells which expressed high amount of mM-CSF were rejected, while tumor cells that displayed lower levels of mM-CSF grew in 60% of the inoculated rats. The mM-CSF-transfected tumors that grew were smaller and had a greater amount of necrosis, compared to the viral vector tumors. Rats that spontaneously rejected the mM-CSF-transfected MADB106 cells showed rechallenge resistance to unmodified parental MADB106 and R3230Ac breast cancers, but not to the F98 glioma. These observations suggest that breast cancer-specific immunity was induced by the inoculation of mM-CSF-expressing MADB106 tumor cells.
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PMID:Membrane macrophage colony-stimulating factor on MADB106 breast cancer cells does not activate cytotoxic macrophages but immunizes rats against breast cancer. 1123 78

Many different tumor cell types (breast, ovarian, glioma, liver and colon) were retrovirally transduced with the human macrophage colony stimulating factor (M-CSF) gene (either the membrane associated form [mM-CSF] or the secreted form [sM-CSF]). These cells were tested for their ability to display increased amounts of mM-CSF in response to dexamethasone. M-CSF-transfected tumor cells expressed additional mM-CSF in response to 18-72 h incubations with 3-15 microg/ml dexamethasone, while non-transfected parental cells were unaffected by this treatment. Increased mM-CSF protein expression on the M-CSF transduced cells was observed by flow cytometry and Western blotting using M-CSF specific antibodies. Northern blot analysis revealed an increase in the mM-CSF specific transcripts within the dexamethasone-treated mM-CSF transduced cells, but this was not seen within the non-transfected tumor cells that were treated with dexamethasone. ICAM-1 expression was unaffected by dexamethasone treatment, indicating that this response is mM-CSF specific. All trans-retinal and 1,25-dihydroxy vitamin D3 compounds that have been reported to induce M-CSF expression failed to increase mM-CSF. When dexamethasone-treated mM-CSF transfected clones were used as target cells for macrophage-mediated cytotoxicity assays, an increased killing with the dexamethasone-treated cells was seen. The macrophage-mediated cytotoxicity of these mM-CSF expressing tumor cells was blocked with excess recombinant M-CSF by saturating M-CSF receptors on the macrophage that is required for this form of tumor cell killing. This work suggests the possibility that dexamethasone may prove useful for vaccination purposes using mM-CSF retrovirally transfected tumor cells.
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PMID:Dexamethasone increases the expression of membrane macrophage colony stimulating factor from retrovirally transduced tumor cells expressing macrophage colony stimulating factor. 1135 85

Congenital midline nasal masses are rare anomalies that occur in about one in 20,000-40,000 live births. The most common are dermoid/epidermoid tumors, nasal cerebral heterotopias (nasal gliomas), and nasal encephaloceles; some have an actual or potential central nervous system connection. Nasal gliomas are CNS masses of neurogenic origin which have lost their intracranial connections and present as an obvious external or intranasal mass at birth without associated surgical symptoms. Careful evaluation is required to confirm the diagnosis and appropriate management. The interpretation of CT and MR images can be difficult but is useful in differentiating nasal gliomas from other congenital nasal masses. The presence of a fibrous stalk may be associated with cranial defects and CSF leak. Excisional biopsy allows histopathologic diagnosis and is the definitive treatment. They are benign lesions, and recurrences are rare, so conservative cosmetic surgical techniques should be chosen for gliomas where there is no proven intracranial extension. The authors report an illustrative nasal glioma case in a one-year-old male infant with extranasal and intranasal components, and discuss the therapeutic options.
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PMID:Midline nasal mass in infancy: a nasal glioma case report. 1171 71

Polyamine synthesis inhibitors, such as a-difluoromethylornithine (DFMO), inhibit tumor cell growth in vitro and in vivo. However, upon cessation of treatment, tumor growth resumes. We hypothesized that incorporation of radioactive polyamines might kill the growth-arrested cells. This hypothesis was previously tested in rat 9L brain tumor cells in which DFMO increased both the uptake and the retention of [3H] putrescine. In these rat cells, DFMO-induced retention of high-specific-activity [3H] putrescine for 20 days resulted in several logs killing. In the present studies all of the 5 different human glioma cell lines tested with DFMO treatment also showed enhanced uptake of exogenous [3H] putrescine, reduced cell counts and enhanced killing of colony forming cells (CSF). Extending the time of DFMO treatment of cells that had taken up high-specific-activity (80 Ci/mmol) [3H] putrescine further increased the killing. A 10-day extension resulted in a 10,000-fold reduction in cumulative cell growth. A 5-day extension resulted in a 2-3 log decrease in numbers of surviving CFC. These data further support the hypothesis and suggest that DFMO-induced cell cycle arrest enhances cellular retention of [3H] putrescine, increasing the effective internal radiation dose enough to cause proliferative death. In a clinical setting, the short (approximately 1 microm) path-length of the tritium beta particle should limit effects to the tumor cells and spare adjacent normal cells. These results support the concept that treatment with the combination of polyamine inhibitors and radioactive polyamines might be a useful adjunct to current therapies for glioblastoma multiforme.
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PMID:The effect of DFMO induced uptake of [3H] putrescine on human glioma cells. 1181 4

Diffuse astrocytic gliomas extensively infiltrate brain tissue and contain numerous microglial cells, but it is unknown whether these two characteristic features are pathogenetically related. We therefore studied the effects of murine microglial cells on motility of GL261 mouse glioma cells using Boyden chamber assays. In the presence of microglia, glioma cell migration occurred earlier, and after 48 h it was threefold higher as compared to incubations without microglia. This effect was mediated by substances released from microglia, because similar effects were observed by microglia-conditioned medium, and it was specific to microglia, because oligodendroglia and endothelial cells only weakly stimulated glioma cell migration. Microglia activating substances (GM-CSF, LPS) led to a further increase of motility. These data support the notion that microglia accumulation in diffuse glial tumors does not merely represent a nonspecific reaction to tissue injury, but reflects participation of these cells in supporting and promoting the invasive phenotype of astrocytoma cells.
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PMID:Microglia promote glioma migration. 1190 54

The combined therapeutic effect of cytokine-producing cancer cell vaccines and local radiotherapy was studied in a mouse glioma 261 (GI261) brain tumor model. Brain tumor-bearing mice were treated with cytokine (IL -4, IL-6, IL-7, GM-CSF, TNF-alpha, LIF, LT) producing vaccines made by in vitro transduction of GI261 cells with the corresponding adenoviral vectors. Vaccines producing either IL-4 or GM-CSF cured 20-40% of mice. The antitumor effect strongly depended on the secreted cytokine level. Vaccination therapy induced specific activation of cytotoxic T lymphocytes measured by cell-mediated cytotoxicity assay. Brain tumors were heavily infiltrated by CD4+ lymphocytes after treatment with IL-4- or GM-CSF-secreting cells. GM-CSF vaccination induced moderate CD8+ infiltration, as well. Depleting either CD4+ or CD8+ lymphocyte subsets abolished the anticancer effect of GM-CSF-expressing cells. Strong synergism was observed by combining cytokine vaccination (GM-CSF, IL-4, IL-12) with local tumor irradiation: about 80-100% of the glioma-bearing mice was cured. The high efficiency of combined treatment was maintained even under suboptimal conditions when neither of the modalities cured any of the mice alone. This suggests that vaccination therapy might open a new potential in the clinical treatment of high-grade gliomas when applied as adjuvant to existing treatment modalities.
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PMID:Local tumor irradiation augments the antitumor effect of cytokine-producing autologous cancer cell vaccines in a murine glioma model. 1191 44

The injection of irradiated tumor cells genetically engineered to express the granolocyte macrophage-colony stimulating factor (GM-CSF) is reported as stimulating antitumoral immunity in several animal models. We used the 9L gliosarcoma rat model to investigate the potency of this strategy in relation to the central nervous system. After in vitro transduction experiments to generate 9L murine cells producing GM-CSF (9LmGM-CSF cells), we found that with the exception of one rat subcutaneously (s.c.) grafted with 108 9LmGM-CSF cells, syngenic rats s.c. injected (dorsal route) with 106-108 viable 9LmGM-CSF cells did not develop s.c. 9L gliosarcomas, while rats s.c. grafted with the same number of naive 9L cells died between 25 and 45 days postgraft. Intracerebral stereotactic injections of 4.104 naive 9L (without s.c. 9LmGM-CSF treatment) killed all the rats within 18-24 days, while s.c. grafting with 108 9LmGM-CSF cells wholly prevented the development of 9L brain gliosarcomas. These results outline the feasibility of the GM-CSF gene transfer approach in glioma (or at least gliosarcoma) gene therapy and could therefore serve as a basis for the development of an adjuvant treatment of glioblastomas using GM-CSF-producing tumor cell vaccines.
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PMID:Granulocyte macrophage-colony stimulating factor gene transfer to induce a protective anti-tumoral immune response against the 9L rat gliosarcoma model. 1195 7

Cloned T9 glioma cells (T9-C2) expressing the membrane form of macrophage colony stimulating factor (mM-CSF) inoculated subcutaneously into rats do not grow and glioma-specific immunity is stimulated. Immunotherapy experiments showed that intracranial T9 tumors present for one to four days could be successfully eradicated by peripheral vaccination with T9-C2 cells. CD4+ and CD8+ T splenocytes from immunized rats, when restimulated in vitro with T9 cells, produced interleukin-2 and -4. Protective immunity against intracranial T9 gliomas could only be adoptively transferred into naive rats by the CD4+ splenocytes obtained from T9-C2 immunized rats. Rats immunized by the T9-C2 tumor cells also resisted two different syngeneic gliomas (RT2 and F98) but allowed a syngeneic NUTU-19 ovarian cancer to grow. Such cross-protective immunity against unrelated gliomas suggests that mM-CSF transfected tumor cells have immunotherapeutic potential for use as an allogeneic tumor vaccine.
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PMID:T9 glioma cells expressing membrane-macrophage colony stimulating factor produce CD4+ T cell-associated protective immunity against T9 intracranial gliomas and systemic immunity against different syngeneic gliomas. 1214 31

Cloned T9-C2 glioma cells transfected with membrane macrophage colony-stimulating factor (mM-CSF) never formed subcutaneous tumors when implanted into Fischer rats, whereas control T9 cells did. The T9-C2 cells were completely killed within 1 day through a mechanism that resembled paraptosis. Vacuolization of the T9-C2 cell's mitochondria and endoplasmic reticulum started within 4 hours after implantation. By 24 hours, the dead tumor cells were swollen and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL)-positive. Bcl2-transduced T9-C2 cells failed to form tumors in rats. Both T9 and T9-C2 cells produced cytokine-induced neutrophil chemoattractant that recruited the granulocytes into the tumor injection sites, where they interacted with the tumor cells. Freshly isolated macrophages killed the T9-C2 cells in vitro by a mechanism independent of phagocytosis. Nude athymic rats treated with antiasialo GM1 antibody formed T9-C2 tumors, whereas rats treated with a natural killer cell (NK)-specific antibody failed to form tumors. When treated with antipolymorphonuclear leukocyte (anti-PMN) and antimacrophage antibodies, 80% of nude rats formed tumors, whereas only 40% of the rats developed a tumor when a single antibody was used. This suggests that both PMNs and macrophages are involved in the killing of T9-C2 tumor cells. Immunocompetent rats that rejected the living T9-C2 cells were immune to the intracranial rechallenge with T9 cells. No vaccinating effect occurred if the T9-C2 cells were freeze-thawed, x-irradiated, or treated with mitomycin-C prior to injection. Optimal tumor immunization using mM-CSF-transduced T9 cells requires viable tumor cells. In this study optimal tumor immunization occurred when a strong inflammatory response at the injection of the tumor cells was induced.
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PMID:Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a "paraptosis"-induced pathway that promotes systemic immunity against intracranial T9 gliomas. 1214 20

Oncolytic herpes simplex virus type 1 (HSV-1) vectors are emerging as an effective and powerful therapeutic approach for cancer. Replication-competent HSV-1 vectors with mutations in genes that affect viral replication, neuropathogenicity, and immune evasiveness have been developed and tested for their safety and efficacy in a variety of mouse models. Evidence to-date following administration into the brain attests to their safety, an important observation in light of the neuropathogenicity of the virus. Phase I clinical traits of three vectors, G207, 1716, and NV1020, are either ongoing or completed, with no adverse events attributed to the virus. These and other HSV-1 vectors are effective against a myriad of solid tumors in mice, including glioma, melanoma, breast, prostate, colon, ovarian, and pancreatic cancer. Enhancement of activity was observed when HSV-1 vectors were used in combination with traditional therapies such as radiotherapy and chemotherapy, providing an attractive strategy to pursue in the clinic. Oncolytic HSV-1 vectors expressing "suicide" genes (thymidine kinase, cytosine deaminase, rat cytochrome P450) or immunostimulatory genes (IL-12, GM-CSF, etc.) have been constructed to maximize tumor destruction through multimodal therapeutic mechanisms. Further advances in virus delivery and tumor specificity should improve the likelihood for successful translation to the clinic.
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PMID:Oncolytic herpes simplex virus vectors for cancer virotherapy. 1252 36


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