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)

We have cultured peripheral blood lymphocytes (PBL) from glioblastoma patients in recombinant interleukin-2 (IL-2) containing medium for a period of 5 days. The cytotoxicity of these cells was tested on 51Cr-labelled autologous dissociated glioblastoma cells which had not been cultured. Significant cytotoxicity against glioma cells was observed in seven out of nine cases. IL-2 activated PBL from normal donors were equally cytotoxic against these glioma cells. Autologous lymphocytes activated by phytohaemagglutinin were also lysed in most cases, and the erythroleukemia cell line K562 was highly susceptible to the cytotoxic capability of the IL-2 activated PBL. In cold target inhibition experiments, K562 inhibited the cytotoxicity against both autologous and allogenic glioma cells, and glioma cells inhibited the cytotoxicity against K562. Following immunomagnetic separation, the IL-2 activated cells demonstrated cytotoxicity against glioma cells, K562 cells, and PHA blasts in both the CD8+ and the CD8- subsets.
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PMID:Human interleukin-2 activated cytotoxic cells kill autologous glioma cells in vitro. 326 Sep 42

Genetically engineered tumor cells secreting immunostimulatory molecules could facilitate the obtention of a vaccination against tumor antigens. To test this approach, we transfected genes encoding for rat and mouse IL-2 into PROb cells. These cells originate from a dimethylhydrazine induced colon carcinoma of BD IX rats. We observed an inhibition of the in vivo tumor growth directly proportional to the IL-2 secretion. An immunohistochemical analysis revealed that the tumors were infiltrated by leucocytes expressing the IL-2 receptor, suggesting their activation within the tumor. A strong delay of tumor growth was observed in rats challenged with PROb cells after a previous rejection of IL-2 secreting cells. Yet two rats out of six were completely protected. This protection is specific since rejection of PROb-IL-2 does not confer protection towards the syngeneic glioma A15A5. In addition, we could show by depletion experiments that NK/LAK, CD8, and CD4 lymphocytes were involved in the rejection of cells secreting large amounts of IL-2. Macrophages appear to be involved in the rejection process too, but also in the induction of an immune memory. Vaccination experiments using irradiated PROb IL-2 cells were performed. Only a partial protection towards a challenge with parental PROb cells could be obtained, also depending on the amount of secreted IL-2: the best protection being obtained after vaccination with cells synthesizing a small amount of IL-2. However, this protection was not superior to that obtained by coinjection of irradiated PROb cells and BCG.
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PMID:[Vaccination with genetically modified IL-2 secreting cells in a rat model of colonic carcinoma]. 869 24

Malignant brain neoplasms present great therapeutic challenges due to their extremely aggressive behavior and relative isolation by the blood-brain and blood-tumor barriers. Endothelial cells may be versatile platforms for delivering genes to solid tumors by virtue of their location at blood-tissue interfaces and their proliferation in response to endothelial mitogens produced by tumors. Immortalized rat brain endothelial cells that express the E. coli lacZ reporter gene and the gene for murine interleukin-2 (RBEZ-IL2) were co-inoculated with 9L glioma cells to Fisher rats to examine the effects of endothelial cell-based cytokine delivery on glioma growth in vivo. 9L glioma growth was not affected by the implantation of control RBEZ cells. The growth of subcutaneous and intracranial 9L gliomas was significantly inhibited by RBEZ-IL2 cells (P < 0.005 and P < 0.01, respectively) when compared to control transfected RBEZ cells. Rats receiving intracranial 9L glioma cells with RBEZ-IL2 cells showed increased survival (P < 0.001). Histologic and immunohistologic analysis showed enhanced activation of microglia/macrophages and CD8-positive T lymphocytes and/or natural killer cells within brain at sites of 9L inoculation with RBEZ-IL2 cells. This report establishes that immortalized endothelial cells can be used for cytokine gene delivery and to activate anti-tumor host responses to experimental gliomas within the central nervous system.
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PMID:Endothelial cell-based cytokine gene delivery inhibits 9L glioma growth in vivo. 888 66

The C6-2B is a well-characterized glioma cell line used extensively in the study of malignant glial biology. While the C6-2B cell line has traditionally been thought of as a homogenous cell line, the in vitro phenotype of the C6-2B cell line can vary considerably depending on the culture technique used and the stratum on which the cells are grown. Thus, we asked whether the in vitro phenotype of the C6-2B cell line was significantly different than the in vivo phenotype of the cell line once it was engrafted into the striatum of nude rats. Under culture conditions used in our laboratory, 100% of the C6 cells were found to express p75, the low-affinity nerve growth factor (NGF) receptor, and Major Histocompatability Class I (MHC Class I), while only 10-15% demonstrated vimentin reactivity. Immunohistochemistry was consistently negative for GFAP, trkA (the high-affinity receptor for NGF), CD4, CD8, and a macrophage specific marker (Ox-41). Once engrafted into the striatum of nude rats, the cells remained 100% p75 and MHC Class I positive, and again, only 15% of the cells demonstrated vimentin reactivity. The grafted cells retained this characteristic for 28 days in vivo. Although an immunoincompetent host was selected to minimize the effects an inflammatory response would have on the graft, a transient inflammatory response was detected. During the first week of engraftment, numerous MHC class II cells, some of which were macrophages, were seen infiltrating the graft. However, by 4 weeks postengraftment, no inflammatory cells were appreciated in the graft and surprisingly little reactive gliosis was seen in the penumbra of the tumor mass. Thus, the limited number of in vitro phenotypic characteristics we examined in the C6-2B cell line remained constant once the cells were engrafted into the striatum of athymic nude rats.
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PMID:Engraftment of C6-2B cells into the striatum of ACI nude rats as a tool for comparison of the in vitro and in vivo phenotype of a glioma cell line. 917 Nov 64

The production of alloreactive cytotoxic T-lymphocytes (CTL) for therapy of recurrent brain tumours was performed in the CELLMAX artificial capillary system composed of cell-culture modules containing cellulose acetate or cuprammonium rayon hollow fibres. Lymphocytes, obtained from the brain-tumour patient to be used for sensitization, were stimulated with OKT3 (anti-CD3) and interleukin-2 (IL-2) and inoculated into the extracapillary space of artificial capillary modules. For allogeneic CTL production, the expanded patient lymphocytes were harvested, irradiated and placed into a second artificial capillary system with allogeneic lymphocytes from a healthy donor. In a one-way mixed lymphocyte reaction, CTL developed in the presence of low-concentration IL-2 (60 i.u. of IL-2/ml). In 18-21 days the cell preparation usually displayed a predominantly CD3+, CD8+ phenotype, which consorted with the dual-labelled CD8/CD11a markers used to identify CTL. Chromium (Cr)-release assays demonstrated lysis of patient tumour in relation to allogeneic glioma; the response observed in cold-target-inhibition assays confirmed lysis of the relevant tumour by the CTL.
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PMID:Artificial-capillary-system development of human alloreactive cytotoxic T-lymphocytes that lyse brain tumours. 919 73

For a single-dose toxicity assessment, five patients with recurrent malignant glioma (ages 29-46 years) were treated with intracavitary alloreactive cytotoxic T lymphocytes (CTL) and interleukin-2 (IL-2). The trial tested the hypothesis that alloreactive CTL, sensitized to the major histocompatibility complex (MHC) proteins of the patient, offer selective, targeted killing of glioma cells that express MHC. Patient lymphocytes, which also express MHC, were irradiated and placed into CellMax artificial capillary systems with lymphocytes from MHC-disparate donors and CTL developed over a 2- to 3-week period with a low concentration of IL-2. The CTL largely expressed CD3 and CD11a/CD8 markers and lysed targets displaying patient MHC. CTL were implanted into the tumor bed at surgery and a catheter was used for subsequent infusions. Patients received one to five treatment cycles every other month; one cycle generally consisted of two or three CTL infusates administered within a 1- to 2-week period. Different unrelated donors were used for each cycle. Treatment was well tolerated; transient toxicity at grades 1-3 was recorded by NCI Common Toxicity Scale criteria. Two glioblastoma patients have died; one from tumor recurrence locally and the other from recurrence at a site distant from the treatment. Two of the five patients completed five cycles; one anaplastic oligodendroglioma patient shows no evidence of tumor 30 months from the start of immune therapy and an anaplastic astrocytoma patient shows stable disease 28 months after initiation of therapy. One anaplastic oligodendroglioma patient, who dropped the protocol during her second treatment cycle, has no evidence of tumor 28 months after recurrence.
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PMID:Treatment of recurrent glioma with intracavitary alloreactive cytotoxic T lymphocytes and interleukin-2. 939 Jan 98

A crucial question in the study of tumor neuro-immunology concerns the capacity of the central nervous system to initiate and execute an immune response. In a 100% fatal rat malignant glioma model, genetically modified tumors secreting INF-gamma intracerebrally generate an immune response resulting in a substantial increase in survival time, tumor rejection and specific systemic immunity. Tumors modified to secrete IL-2 alone do not change the biologic behavior of transfected gliomas. INF-gamma induces elevated expression of major-histocompatibility-complex-class-I and -class-II molecules in microglia throughout the brain and invokes enhanced tumor infiltration by CD4, CD8 and NK cells. These findings demonstrate successful immunization against a central-nervous-system tumor by direct priming in the brain with a live growth-competent tumor vaccine.
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PMID:Priming in the brain, an immunologically privileged organ, elicits anti-tumor immunity. 946 18

A cancer treatment is described in which i.m. injection of plasmid DNA (pDNA) encoding murine interferon alpha (mIFN-alpha) leads to potent antitumor effects on primary and metastatic tumors in mice. Mice bearing s.c. B16F10 melanoma, Cloudman melanoma, or glioma 261 tumors were injected i.m. with mIFN-alpha pDNA. In all three tumor models, a significant reduction in tumor volume and enhancement of survival was found after IFN pDNA therapy. The mIFN-alpha pDNA could be injected as infrequently as once every other week and still produce a significant antitumor effect, and, in a metastatic tumor model, the therapy markedly reduced the number of lung tumor metastases. Depletion of immune cell subsets indicated that CD8(+) T cells were required for the antitumor response. These studies demonstrate that primary and metastatic tumors can be treated systemically by i.m. injection of a plasmid encoding a cytokine gene.
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PMID:A gene therapy for cancer using intramuscular injection of plasmid DNA encoding interferon alpha. 999 62

Recent physiological and anatomical studies have demonstrated that a major fraction of brain interstitial and cerebrospinal fluid drains into cervical lymph nodes (CLN) in a number of experimental animals. To investigate the role of CLN in brain tumour immunity, temporal profiles of MHC class II molecule expression and T lymphocyte subsets in brain tumours, CLN and other lymphoid tissues were analysed by immunocytochemistry. A total of 64 Wistar rats weighing 250 g were used. Two weeks after the transplantation of C6 glioma cells (10(6) cells/1 microl) into a rat brain, expression of MHC class II molecules was induced in the brain and all systemic lymphoid tissues examined. However, the subsequent appearance of CD4 or CD8 positive cells was strictly confined to CLN, and coincided with the infiltration of such cells into the brain tumour 2 weeks after transplantation. In the group of animals in which cervical lymphadenectomy was followed by intracerebral transplantation of C6 glioma cells, infiltration of CD4 or CD8 positive cells into the brain tumour was delayed until 3 weeks after the transplantation, and the production of such cells was by the spleen. These results suggest that CLN act as regional lymph nodes in brain tumour immunity.
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PMID:Cervical lymph nodes play the role of regional lymph nodes in brain tumour immunity in rats. 1021 99

In order to determine the mechanism of tumour destruction by tumour-infiltrating lymphocytes (TIL), we examined the ability of both CD4+ and CD8+ effector TIL, and TIL clones, to manifest granzyme-mediated and Fas-mediated destruction of tumour targets. In many in vitro studies TIL have been shown to manifest anti-tumour reactivity, yet many tumours escape immunological destruction. To investigate the role of Fas expression and the concomitant sensitivity to the inducibility of apoptotic death, we derived TIL from four melanomas and one glioma. The glioma, and all but one of the melanomas, expressed Fas, but Fas-mediated apoptosis could only be detected if the targets were treated with cyclohexamide. The melanomas and the glioma all expressed detectable cytoplasmic Bcl-2 protein, known to exert anti-apoptotic activity. Lysis of tumours by CD8-enriched cultures and CD8+ clones was Ca2+-dependent and could not be modified by an anti-Fas MoAb. In CD4-enriched cultures or CD4+ clones with cytotoxic potential against tumour cells, cytotoxicity was also Ca2+-dependent. As Ca2+-dependent cytotoxicity is usually the result of secretion of perforin/granzyme-B, we investigated the presence of perforin in cytotoxic CD4+ clones and demonstrated the presence of granular deposits of this enzyme in some of the CD4+ clones. Although an anti-Fas MoAb did not block the lysis of melanoma targets by CD4+ clones, the examination of Fas-dependent targets demonstrated that these clones also had the potential to kill by the Fas/Fas ligand system. These data suggest that the predominant mechanism in tumour killing by TIL appears to be perforin-granzyme-dependent, and that the solid tumour cell lines we studied are less susceptible to Fas-mediated apoptosis. As non-apoptotic pathways may enhance tumour immunogenicity, exploitation of the perforin-granzyme-dependent cytotoxic T lymphocyte (CTL) pathways may be important for achieving successful anti-tumour responses.
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PMID:Studies of the mechanism of cytolysis by tumour-infiltrating lymphocytes. 1036 Dec 24


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