Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Gliomas”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2004

C6 glioma cells retrovirally engineered to express IL-18 and Fas exert FasL-dependent cytotoxicity against glioma formation.

The decreased antitumor immune response significantly contributes to the progression of glioma. To evaluate whether the antitumor immunity is restored by stable co-expression of IL-18 and Fas receptor, we retrovirally introduced these two genes into rat C6 glioma cells. We found that IL-18-transduced glioma cells secreted IL-18 and induced PBMC IFN-gamma production in vitro. We also found that Fas-transduced glioma cells were susceptible to Fas-mediated apoptosis. In vivo, we found that IL-18 expression and Fas expression synergistically inhibited C6 cell tumorigenesis with the glioma cells being subcutaneously injected in rat flank. Furthermore, we found that co-expression of IL-18 and Fas also produced a marked survival advantage with the rats being intracerebrally implanted with the glioma cells. Finally, we demonstrated that FasL-dependent PBMC cytotoxicity participated in the anti-glioma immunity induced by IL-18 and Fas expression. Taken together, these findings demonstrate that increasing IL-18 production in tumor microenvironment and prompting functional Fas receptor expression of tumor cells could enhance FasL-dependent cytotoxic antitumor immunity.

Animals↗
PubMed2006

Related to testes-specific, vespid, and pathogenesis protein-1 (RTVP-1) is overexpressed in gliomas and regulates the growth, survival, and invasion of glioma cells.

In this study, we examined the expression and functions of related to testes-specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was expressed in high levels in glioblastomas, whereas its expression in low-grade astrocytomas and normal brains was very low. Transfection of glioma cells with small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the cell lines examined and induced cell apoptosis in some of them. Overexpression of RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage-independent growth of the cells. In addition, overexpression of RTVP-1 rendered glioma cells more resistant to the apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand and serum deprivation. To delineate the molecular mechanisms involved in the survival effects of RTVP-1, we examined the expression and phosphorylation of various apoptosis-related proteins. We found that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase and increased the expression of Bcl2 and that the protective effect of RTVP-1 was partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion of glioma cells as was evident by their enhanced migration through Matrigel and by their increased invasion in a spheroid confrontation assay. The increased invasive potential of the RTVP-1 overexpressors was also shown by the increased activity of matrix metalloproteinase 2 in these cells. Our results suggest that the expression of RTVP-1 is correlated with the degree of malignancy of astrocytic tumors and that RTVP-1 is involved in the regulation of the growth, survival, and invasion of glioma cells. Collectively, these findings suggest that RTVP-1 is a potential therapeutic target in gliomas.

Amino Acid Sequence↗
PubMed1989

Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low-grade glioma.

A retrospective analysis is presented of factors affecting the length of survival of 285 consecutive adults with newly diagnosed biopsy-proven supratentorial anaplastic glioma (188 cases of glioblastoma multiforme, 76 of anaplastic astrocytoma, 11 of anaplastic mixed glioma, and 10 of anaplastic oligodendroglioma) treated at a regional cancer center from July, 1982, through December, 1987. The approach to initial therapy included maximum feasible resection and radiotherapy. The median survival time for all patients was 35 weeks. Multivariate analysis demonstrated that age, duration of symptoms, preirradiation performance status, tumor histology, accessibility to resection, extent of resection, radiotherapy, and prior low-grade glioma were significant independent variables influencing survival. The prognostic importance of age, duration of symptoms, performance status, and tumor histology are already recognized, but three "new" findings are reported. First, patients with anaplastic oligodendroglioma had the longest median survival time (278 weeks). Second, corrected for accessibility and all other variables, patients with gross total resection lived longer than those with partial resection, and patients with any degree of resection lived longer than those who underwent only a biopsy procedure. Third, patients with anaplastic glioma in whom there was a prior history of low-grade glioma lived significantly longer after the diagnosis of anaplastic glioma than did patients in whom the anaplastic glioma apparently arose de novo.

Adult↗
PubMed2002

Expression of lymphocyte-specific chemokines in human malignant glioma: Essential role of LARC in cellular immunity of malignant glioma.

Lymphocytes are frequently observed in human malignant glioma, the mechanism(s) underlying their appearance is not fully understood. To clarify tumor immunity in malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern blot, immunoblot and immunohistochemistry, and examined the correlation with the infiltration of various subsets of lymphocytes. For the 8 chemokines examined (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1alpha), expression of LARC was clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally, expression of TARC and SCM-1alpha was detectable in the majority of glioma cell lines. However, the expression level of most chemokines was low, so that Northern blot analysis could not demonstrate their expression with the exception of LARC in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by phorbol myristate ester in U87 MG cells. The production of LARC protein was demonstrated in 4 of 8 glioblastoma tissues by immunoblotting, and 9 of 33 samples (27.3%) by immunohistochemistry. Interestingly, the positivity of LARC staining was significantly correlated with the infiltration of CD8-, CD4-, and CD45R0-positive cells (p<0.001). Although the constitutive expression level of LARC is low, certain stimulations could strongly induce its expression, and play a crucial role in the tumor immunity of human malignant glioma.

Blotting, Northern↗
PubMedDate not supplied

Action and efficacy of p-[131I]iodo-L-phenylalanine on primary human glioma cell cultures and rats with C6-gliomas.

BACKGROUND: Recently we demonstrated high selectivity and long retention of p-[123I]iodo-L-phenylalanine (IPA-123) for diagnostic purposes in gliomas. Here we describe the potency of the iodine-131-labelled analogue p-[131I]iodo-L-phenylalanine (IPA-131) for experimental treatment of gliomas. MATERIALS AND METHODS: Two human glioma cell cultures and 15/20 rats with C6-gliomas were exposed to IPA-131. RESULTS: After 24-h-exposure the cell number of the glioma cell cultures was reduced by 77% and 79%, respectively. Four out of five untreated rats died 8-24 days after implantation and had verifiable tumours. Seven animals died despite therapy, while 8 were soon healthier, gained body weight and were sacrificed 81 days after implantation, at which time survival of the treated animals was significantly prolonged (p < 0.05). At autopsy, instead of tumours there were substance defects, surrounded by pre-existing parenchyma infiltrated by probable tumour cells that were not discernible from reactive astrocytes, lymphocytes, monocytes and multinuclear giant cells. CONCLUSION: IPA-131 has promising activity against human glioma cells in vitro and experimental gliomas in vivo.

Animals↗
PubMedDate not supplied

Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro.

Interleukin 10 (IL-10) is a cytokine with a broad spectrum of immunosuppressive activity, but itoffs role in the oncogenesis of solid tumors is still unclear. In previous experiments we have shown that IL-10 specific mRNA is produced within glial tumors in vivo. The aim of the present study was to investigate the expression of the IL-10 protein in vivo and to identify the cells producing IL-10 within the tumor tissue. Expression levels significantly increased with malignancy of the gliomas. 87.5% of grade III and IV, but only 4% of grade II tumors expressed high levels of mRNA. Elevation of IL-10 serum levels was found in 11% of low grade and in 63.6% of high grade glioma patients. In situ hybridization analysis with combined immunohistochemistry revealed that: a) IL-10 is not produced by infiltrating B- or T- lymphocytes, b) both microglia and astroglia contributed to IL-10 expression in malignant gliomas in vivo. These data suggested the functional role of IL-10 in glioma progression. Therefore, the effects of IL-10 on proliferation and migration of glioma cells were determined in vitro. Two human glioma cell lines were grown as monolayer as well as spheroids in the presence of different concentrations of IL-10. IL-10 increased cell proliferation significantly in both culture systems with a dose optimum of 25 ng/ml. Glioma cell motility was enhanced with 25 ng/ml as the optimal dose. Adding the IL-10 specific antibody reversed both effects. We conclude from our data that IL-10 is involved in the progression of glial tumors, especially in the enhancement of tumor cell proliferation and migration which promotes infiltration of the surrounding tissue.

Brain↗
PubMed1998

Disparity in expression of protein kinase C alpha in human glioma versus glioma-derived primary cell lines: therapeutic implications.

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcinogenesis and cellular growth regulation. Recent studies have suggested that the PKC isoform alpha may be a critical target for antiglioma therapy in humans (G. H. Baltuch et al., Can. J. Neurol. Sci., 22: 264-271, 1995). We studied the expression and subcellular distribution of the PKC alpha isoform in human high- and low-grade gliomas and also in glioma-derived cell lines with immunoblot analyses. Cell lines derived from high-grade gliomas expressed higher levels of PKC alpha than did cell lines derived from low-grade gliomas. In glioblastoma-derived cell lines, PKC alpha was mainly expressed in the soluble (cytosolic) fraction, indicating an inactive state of the enzyme. When analyzed in freshly frozen samples from human gliomas, the expression of PKC alpha was at similar levels in high- and low-grade tumors and was also similar to the levels in normal brain tissue controls. The PKC partial antagonist bryostatin 1, currently undergoing Phase II testing in patients with malignant gliomas, was capable of specifically down-regulating PKC alpha in vitro in glioblastoma-derived cell lines. However, this was not associated with significant growth inhibition. We conclude that the observed overexpression of PKC alpha in glioblastoma-derived cell lines may be an artifact of in vitro growth. Furthermore, we conclude that expression of PKC alpha in glioma-derived cell lines is not essential for cellular growth in vitro because down-regulation of PKC alpha following treatment with bryostatin 1 was not associated with growth inhibition.

Antineoplastic Agents↗
PubMed1995

Products of cells from gliomas: IX. Evidence that two fundamentally different mechanisms change extracellular matrix expression by gliomas.

Four human astrocytic gliomas of high grade of malignancy were each evaluated in tissue and in vitro for percentages of cells expressing glial fibrillary acidic protein (GFAP), collagen type IV, laminin and fibronectin assessed by immunofluorescence with counterstaining of nuclear DNA. Percentages of cells with reticulin and cells binding fluorescein-labeled Ulex europaeus agglutinin were also assessed. In tissue, each extracellular matrix (ECM) component was associated with cells in the walls of abnormal proliferations of glioma vessels, and all four tumors had the same staining pattern. Two strikingly different patterns of conversion of gene product expression emerged during in vitro cultivation. (1). In the most common pattern, percentages of all six markers consistently shifted toward the exact phenotype of mesenchymal cells in abnormal vascular proliferations: increased reticulin, collagen type IV, laminin and fibronectin; markedly decreased glial marker GFAP and absent endothelial marker Ulex europaeus agglutinin. The simplest explanation of this constellation of changes coordinated toward expression of vascular ECM markers is that primary glioma cell cultures are overgrown by mesenchymal cells from the abnormal vascular proliferations of the original glioma. These cell cultures were tested for in situ hybridization (ISH) signals of chromosomes 7 and 10. Cells from one glioma had diploid signals. Cells from the other glioma had aneuploid signals indicating they were neoplastic; however, their signals reflected different numerical chromosomal aberrations than those common to neoplastic glia. (2). The second pattern was different. Cells with ISH chromosomal signals of neoplastic glia retained GFAP, and gained collagen type IV. Their laminin and fibronectin diminished, but persisted among a lower percentage of cells. Cloning and double immunofluorescence confirmed the presence of individual cells with glial and mesenchymal markers. A cell expressing GFAP in addition to either fibronectin, reticulin or collagen type IV is not a known constituent of glioblastoma tissue. This provides evidence of a second mechanism of conversion of gene expression in gliomas.

Astrocytoma↗
PubMed2004

Depression in patients with high-grade glioma: results of the Glioma Outcomes Project.

OBJECTIVE: To study the incidence of depression among patients undergoing surgery for high-grade glioma, document factors associated with the presence of depression, and examine the relationship between depression and patient outcome. METHODS: Physician and patient reports of depression were analyzed immediately postoperatively and again 3 and 6 months after surgery for high-grade glioma. Physician-reported depression was defined according to the Diagnostic and Statistical Manual of Mental Disorders, ed 4. Patient self-assessment of depression was based on responses to questions contained in two validated functional status surveys. Concordance of physician- and patient-reported depression was examined, along with the extent of use of pharmacological treatment for depression. Additional outcomes examined included quality of life, survival, patient satisfaction, and posttreatment complications. RESULTS: Data from 598 patients were analyzed. In the early postoperative period, physicians reported depression in 15% of patients, whereas 93% of patients reported symptoms consistent with depression. The incidence of patient self-reported depression remained similar at 3- and 6-month follow-up, whereas physician reported depression increased from 15% in the early postoperative period to 22% at both 3- and 6-month follow-up. Concordance between physician recognition of depression and treatment of depression was low initially (33%) and increased at 3 and 6 months (51 and 60%, respectively). As compared with patients who were not depressed, survival was shorter and complications were more common among depressed patients. CONCLUSION: Symptoms of depression were common immediately after surgery for glioma, and they increased throughout the 6-month period after surgery. These findings support the hypothesis that clinically important depression is a common complication in patients with high-grade glioma. Concordance between physician recognition of depression and self-reports of depression by patients was low. Concordance between physician recognition of depression and initiation of pharmacological antidepressant therapy was fair in the early postoperative period and improved somewhat over the subsequent 6-month period; however, within the 6-month period after surgery for glioma, antidepressant therapy was provided for only 60% of patients in whom the physician recognized depressive symptoms and in only 15% of patients who self-reported symptoms of depression. Findings from this observational study suggest the need for a controlled trial that is designed to test the hypothesis that more attention to the identification of postoperative depression and aggressive treatment of depressive symptoms can improve the quality of life and survival of patients after surgery for high-grade glioma.

Adolescent↗
PubMed2003

Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project.

OBJECT: The Glioma Outcomes Project represents a contemporary analysis of the management of malignant (Grade III and Grade IV/GBM) gliomas in North America. This observational database was used to evaluate the influence of resection, as opposed to biopsy, on patient outcome as measured by the length of survival. Attempts were made to reduce the impact of selection bias by repeating the data analysis after omitting patients with major negative prognostic factors. METHODS: Outcome data from 788 patients accrued from multiple sites over a 4-year period (1997-2001) were analyzed with the primary outcome measure being length of survival. Of these, 565 patients with recent diagnoses formed the basis of the present analysis. Patients were systematically followed up until death or up to 24 months after enrollment in the study, and survival data were correlated with the histopathological grade and location of the tumor, the extent of surgery, the patient's performance status, and demographic factors. The median length of survival was 40.9 weeks for patients with recently diagnosed GBMs. The true median length of survival for patients with Grade III gliomas was not reached, although there was a 58% survival rate at 104 weeks. In multivariate analysis, resection rather than biopsy (p < 0.0001), age 60 years or younger (p < 0.0001), and a Karnofsky Performance Scale (KPS) score of 70 or greater (p = 0.0004) were associated with a prolonged survival time for patients with Grade III or IV gliomas. The prognostic value of resection compared with biopsy was maintained (p < 0.0001), even after eliminating patients considered to be "poor risk" (those with age > 60 years, KPS score < 70, or presence of multifocal tumors), who may have been overrepresented in the biopsy group. Survival "tails" at 24 months were 58% for Grade III gliomas and 11% for GBMs. CONCLUSIONS: These data provide Class II evidence to support tumor grade, patient's age, and patient's functional status as prognostic factors for survival in individuals with recently diagnosed malignant gliomas. Resection (compared with biopsy) is also a strong prognostic factor; however, no quantitative attempt was made to assess the true extent of the resection.

Adult↗
PubMed2003

Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945.

BACKGROUND: The objectives of the current study were to determine the outcome of children who were treated with chemotherapy and radiotherapy on the Children's Cancer Group (CCG) high-grade glioma protocol (CCG-945) who were diagnosed with low-grade gliomas on post hoc central pathologic review and to identify clinical and biologic features associated with prognosis. METHODS: Between 1985 and 1991, 250 children with institutionally classified high-grade gliomas were enrolled on CCG-945. Patients older than 24 months with intracranial lesions were assigned randomly to receive either lomustine, vincristine, and prednisone (control regimen) or the 8-drugs-in-1-day regimen (experimental regimen); younger patients and those with primary spinal cord tumors were assigned nonrandomly to the experimental regimen. Central independent review by 5 neuropathologists led to a reclassification of low-grade glioma in 70 patients, who were the focus of the current study. RESULTS: The study involved 42 males and 28 females (median age, 7.7 years) with a median follow-up of 10.4 years. At 5 years, the progression-free survival (PFS) rate was 63% +/- 6%, and the overall survival (OS) rate was 79% +/- 5%, compared with a PFS rate of 19% +/- 3% (P < 0.0001) and an OS rate of 22% +/- 3% (P < 0.0001) in the remainder of the cohort. Significantly poorer 5-year PFS was seen in children younger than 24 months, those with fibrillary astrocytoma, and those with posterior fossa tumors. Patients demonstrated a modest improvement in PFS but no improvement in OS compared with children with low-grade gliomas who were treated with contemporary chemotherapy-alone approaches. CONCLUSIONS: The current report calls attention to the importance of central pathologic review in large multiinstitutional trials of children with gliomas and suggests that aggressive front-line combined chemoradiotherapy does not confer a survival advantage in this highly selected population of patients.

Adolescent↗
PubMed1983

Electron-microscopic visualization of binding of antibodies from sera of glioma patients on cultured glioma cells.

Several human cell lines (normal and neoplastic glia, cerebral metastases from adenocarcinoma, fibroblasts) were incubated with sera from patients with well and poorly differentiated glioma and with sera from healthy donors and then stained with PAP complex to define and localize the antibody reaction with cell surface antigens by means of electron microscopy. The sera of glioma patients proved to contain antibodies which bound the tumor-associated antigenic determinants on the cell membranes of gliomas and of cerebral metastases from adenocarcinoma in tissue cultures. Further, absorption testing of the reactive sera on normal brain, well-differentiated astrocytoma and cultured glioblastoma cells, together with cross-reactivity experiments suggests that at least two antigens or groups of antigens are expressed on the glioma cell surface: one shared by well and poorly differentiated glioma cells and the other by poorly differentiated glioma cells and the cells of cerebral metastases from adenocarcinoma.

Antibodies↗
PubMed2001

Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells.

Several reports of clinical trials of immunotherapy using dendritic cells have been published to date. In this study, we investigated the safety and clinical response of immunotherapy with fusions of dendritic and glioma cells for the treatment of patients with malignant glioma. Eight patients with malignant glioma, ranging in age from 4 to 63 years old, participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells of dendritic and glioma cells were prepared with polyethylene glycol, and the fusion efficiency ranged from 9.2 to 35.3% (mean, 21.9%). All patients received the fusion cells every three weeks for a minimum of 3, and a maximum of 7, immunizations. Fusion cells were injected intradermally, close to a cervical lymph node. The percentage of CD16- and CD56-positive cells in peripheral blood lymphocytes slightly increased after immunization in 4 out of 5 cases investigated. Peripheral blood mononuclear cells were incubated with irradiated autologous glioma or U87MG cells and supernatants were harvested. In 6 cases analyzed, the concentration of interferon-gamma in the supernatant increased after immunization. Clinical results showed that there were no serious adverse effects and two partial responses. Although the results of the phase I clinical trial of fusion cells indicated that this treatment safely induced immune responses. we were unable to establish a statistically significant treatment-associated response rate, due to the limited sample population. Therefore, further evaluation of the role of adjuvant cytokines is necessary.

Adult↗
PubMed1986

Lymphokine activated killer (LAK) cell-mediated lysis of murine glioma: trypsin-chymotrypsin-sensitive glioma protein is responsible for tumor-selective recognition by LAK cells.

The killing of Fischer rat 9L glioma in vitro by lymphokine-activated killer (LAK) cells was studied. LAK cells generated by culturing Fischer spleen cells with recombinant interleukin 2 markedly lysed glioma cells but did not kill syngeneic normal brain tissue in a chromium release microcytotoxicity assay. Susceptibility of glioma to lysis by LAK cells was markedly diminished by pretreating the glioma cells with trypsin or chymotrypsin but was unaffected by pretreatment with neuraminidase, glycosidases, or sodium periodate. These results suggest that LAK cell killing of glioma is probably tumor-selective and that a crucial cell surface determinant on glioma cells responsible for its tumor-selective lysis by LAK is a protein sensitive to trypsin and chymotrypsin.

Animals↗
PubMed2003

In vitro growth suppression of human glioma cells by a 16-mer oligopeptide: a potential new treatment modality for malignant glioma.

Fibroblast growth factor-2 (FGF-2) is involved as an autocrine growth factor in the autonomous proliferation of glioma cells. To develop a new strategy for treating patients with glioma, we studied the effect on human glioma cells of a 16-mer oligopeptide with conformational similarity to the putative receptor-binding domain of FGF-2. A synthesized oligonucleotide was assessed its receptor-binding activity by BIAcore instrument. Its biological effect on glioma cell lines was examined in vitro by MTT assay. The peptide suppressed the in vitro growth of human glioma cells U87MG, T98G and U251MG cells, but not of A431 cells whose growth is not dependent on FGF-2. Apoptotic bodies were noted after 24-h incubation in the presence of the peptide; Ac-YVAD-CHO, a caspase-3 inhibitor, suppressed apoptosis. Furthermore, we examined the modulation of the cytotoxic effect of anticancer drugs by the oligopeptide. The addition of this oligopeptide to the chemotherapeutic agents CDDP, ACNU and VP16 had additive effects in vitro. These results suggest that the pathway of the FGF-2 autocrine loop through the FGF receptor plays an important role in the proliferation of glioma cells. New drugs targeting this loop may be highly effective in treating FGF-2-dependent tumors. Our results suggest that its addition to the therapeutic arsenal may lead to improved treatment regimens for patients with FGF-2-dependent tumors.

Antineoplastic Agents↗
PubMed2000

Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions.

Herpes simplex virus thymidine kinase (HSV-tk) gene transfer and ganciclovir (GCV) administration have been suggested for the treatment of malignant gliomas. To understand tissue responses and possible ways to improve the treatment effect, we studied tumor growth, tissue reactions, and survival time after HSV-tk/GCV treatment in a syngeneic BT4C rat glioma model by mixing various ratios of stably transfected HSV-tk-expressing BT4C-tk glioma cells with wild-type BT4C glioma cells (percentage of BT4C-tk cells: 0%, 1%, 10%, 30%, 50%, and 100%), followed by injection into BDIX rat brains (n = 79). With the exception of some animals with end-stage tumors, very little astroglia or microglia reactivity was detected in the wild-type tumors as analyzed by immunocytochemistry using glial fibrillary acid protein (GFAP)-, vimentin-, human histocompatibility leukocyte antigen-DR-, OX-42-, and CD68-specific monoclonal antibodies. After 14 days of GCV treatment, tumors induced with > or = 10% BT4C-tk cells showed a significant reduction in tumor size (P < .05) and prolonged survival time (P < .01). Astrogliosis, as indicated by a strong GFAP and vimentin immunoreactivity, was seen in the tumor scar area. GFAP and vimentin reactivity was already present after the GCV treatment in tumors induced with 1% BT4C-tk cells. Much less human histocompatibility leukocyte antigen-DR-positive microglia was seen in the treated animals, indicating low microglia reactivity and immunoactivation against the tumor. However, GCV-treated tumors were positive for apoptosis, indicating that apoptosis is an important mechanism for cell death in the BT4C-tk glioma model. Our results suggest that > or = 10% transfection efficiency is required for a successful reduction in BT4C glioma tumor size with HSV-tk/GCV treatment in vivo. Tissue reactions after 14 days of GCV treatment are characterized by astrogliosis and apoptosis, whereas microglia response and immunoactivation of the brain cells appear to play a minor role. Stimulation of the microglia response by gene transfer or other means might improve the efficacy of the HSV-tk/GCV treatment in vivo.

Animals↗
PubMedDate not supplied

Vaccination of glioma patients with fusions of dendritic and glioma cells and recombinant human interleukin 12.

Despite aggressive treatment, the median survival of patients with high-grade malignant astrocytoma is about 1 year. The authors investigated the safety and clinical response to immunotherapy using fusions of dendritic and glioma cells combined with recombinant human interleukin 12 (rhIL-12) for the treatment of malignant glioma. Fifteen patients with malignant glioma participated in this study. Dendritic cells were generated from peripheral blood. Cultured autologous glioma cells were established from surgical specimens in each case. Fusion cells were prepared from dendritic and glioma cells using polyethylene glycol. All patients received fusion cells intradermally on day 1. rhIL-12 was injected subcutaneously at the same site on days 3 and 7. Response to the treatment was evaluated by clinical observations and radiologic findings. No serious adverse effects were observed. In four patients, magnetic resonance imaging showed a greater than 50% reduction in tumor size. One patient had a mixed response. These results show that administration of fusion cells and rhIL-12 safely induces clinical antitumor effects in some patients with malignant glioma.

Adult↗
PubMed1987

Distribution of type VI collagen in human gliomas: comparison with fibronectin and glioma-mesenchymal matrix glycoprotein.

The distribution of type VI collagen was examined immunohistochemically in normal tissues and in 24 human gliomas and six medulloblastomas. Its localization in the neoplasms was compared with that of fibronectin and glioma-mesenchymal extracellular matrix (GMEM) glycoprotein. In normal non-neural tissues type VI collagen was demonstrated in the interstitial connective tissue and in some basement membranes. In normal brain it was localized to the vasculature, leptomeninges, and pial-glial membrane. In neoplasms type VI collagen and fibronectin codistributed in the vasculature and stromal connective tissue. The GMEM glycoprotein, as identified by monoclonal antibody (MAb) 81C6, and a related glioma-mesenchymal matrix antigen identified by MAb 2A6, were expressed not only in the tumor vasculature and connective tissue, but also within the tumor parenchyma in association with glioma cells. The staining intensity was variable in 20 malignant gliomas and weak to absent in two pilocytic astrocytomas and six medulloblastomas. An oligodendroglioma and ependymoma both expressed the 2A6 epitope, but staining with MAb 81C6 was weak to absent. The antigens identified by MAb 81C6 and MAb 2A6 represent the only recognized extracellular matrix components, other than proteoglycans, that are associated with glioma cells in vivo. As prominent constituents of the pericellular matrix, they may be involved in recognized matrix functions such as the modulation of cell adhesion and migration.

Animals↗