Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A pilot clinical trial on radiotherapy of glioblastoma with and without hyperbaric oxygen was performed at the Columbia-Presbyterian Medical Center. Eighty previously untreated patients with histologically proved glioblastoma were evaluated; 38 were irradiated under hyperbaric oxygen and 42 (controls) in atmospheric air. The survival rates were calculated according to the actuarial analysis method. At the end of 18 months, the survival rate appeared considerably higher in the oxygen group (28%) than in the controls (10%). At the end of 36 months, no patients in the control group survived, whereas 2 patients in the oxygen group were alive beyond 45 and 48 months, respectively. The median survival time was 38 weeks for those treated under oxygen and 31 weeks for the air control group. Owing to the small population samples and the pilot nature of this study, the difference in survival rates between the two groups was not statistically significant. The toxicity of hyperbaric oxygen was well tolerated by most patients, and the quality of survival in the hyperbaric oxygen group was equal to or slightly better than that of the control group. This pilot clinical study paved the way for further controlled clinical trials of hyperbaric oxygen and oxygen-mimicking drugs, including the electron-affinic compounds that could have differentially sensitized the hypoxic tumor cells.
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PMID:Hyperbaric oxygen and radiation therapy in the management of glioblastoma. 20 35

Inefficient vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue. Examples include the compensatory development of collateral blood vessels in ischaemic tissues that are otherwise quiescent for angiogenesis and angiogenesis associated with the healing of hypoxic wounds. But the presumptive hypoxia-induced angiogenic factors that mediate this feedback response have not been identified. Here we show that vascular endothelial growth factor (VEGF; also known as vascular permeability factor) probably functions as a hypoxia-inducible angiogenic factor. VEGF messenger RNA levels are dramatically increased within a few hours of exposing different cell cultures to hypoxia and return to background when normal oxygen supply is resumed. In situ analysis of tumour specimens undergoing neovascularization show that the production of VEGF is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions) and the clustering of capillaries alongside VEGF-producing cells.
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PMID:Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. 127 31

For the past several years immunologists have been fascinated by a series of experiments showing that transforming growth factor beta (TGF beta) suppresses T- and B-lymphocyte growth as well as IgM and IgG production by B cells. Moreover, while exerting chemotactic activity on monocytes and inducing expression of interleukin-1 and interleukin-6 by these cells, TGF beta interferes with bacterially induced tumor necrosis factor alpha production, oxygen radical formation and the adhesiveness of granulocytes to endothelial cells. These mechanisms may provide the basis for the effect of TGF beta to prevent the microvascular changes associated with brain edema formation in bacterial meningitis. Given the potential of lymphocytes as well as macrophages to produce TGF beta 1, this cytokine may exert negative feedback signals on the immune response, provided the cytokine is processed from its latent form to the bioactive homodimer. Potent effects of TGF beta have been observed in experimental animals including the inhibition of the generation of virus-specific cytotoxic T cells and antiviral antibodies as well as the diminution of cellular infiltrates with decreased major histocompatibility complex class-II expression and CD8+ T cells in the tissue of virally infected animals. TGF beta may also be of importance in tumor immunology. By the production of bioactive TGF beta as detected in glioblastoma and acute T-cell leukemia, tumor cells may induce an immunodeficiency state and escape immune surveillance. In inflammation, monitoring of TGF beta in the tissue will bring light on the immune regulation in acute and chronic inflammatory diseases.
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PMID:Modulation of the immune response by transforming growth factor beta. 148 57

Nitric oxide (NO) is a newly identified, multifunctional biological mediator. However, it also has deleterious effects on biological materials. For instance, nucleic acids, proteins, and some prosthetic groups of enzymes can be modified by NO or its reaction products with other reactive oxygen species. Endogenous nitrosamine formation through the reaction of NO or its oxidized products with amines might be involved in carcinogenesis. These deleterious effects of NO are often associated with inflammatory processes both in experimental animals and human. We analyzed the molecular mechanism of control of expression of the inducible nitric oxide synthase (NOS) gene in mouse cells by cloning its putative promoter region. This promoter responded to various cytokines and endotoxin similarly to the endogenous NOS gene in mouse cells. No appreciable induction of NOS was observed in human peripheral blood cells, but induction was detected in a human glioblastoma cell line A-172. Therefore, the human inducible NOS cDNA was cloned from A-172 cells and its cDNA-deduced amino acid sequence found to have about 80% similarity to those of both mouse and rat inducible NOSs. The effects of various cytokines on the induction of the gene were somewhat different from those observed in mouse cells, but the mouse promoter responded to these cytokines similarly to the endogenous NOS gene in human cells, indicating functional similarity of cis-elements of the genes encoding both human and mouse inducible NOS. Structural analysis of the human inducible NOS gene by Southern blot analysis revealed putative genetic restriction fragment length polymorphism in intron 5.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Implication of nitric oxide synthase in carcinogenesis: analysis of the human inducible nitric oxide synthase gene. 758 89

We measured kinetic rate constants and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with meningioma. Ten patients including one recurrent case, two males and eight females aged from 44 to 71 years with a mean age of 54 years old, were studied prior to surgical interventions. Histological diagnosis was as follows: seven cases of meningothelial type, two cases of angiomatous type and one fibrous type. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter in comparison with eight cases with malignant gliomas (five cases of malignant astrocytoma and three cases of glioblastoma, aged from 14 to 70 years with a mean age of 41 years old). Hemocirculation of the tumor was exceedingly higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Low rOEF implicated an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl) suggested rather aerobic glycolysis as compared with malignant gliomas. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three compartment model of 18F-fluorodeoxyglucose (FDG). Tumor k1 and k2 values markedly increased in all examined cases, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Kinetic analysis of glucose metabolism in meningiomas--comparison with malignant gliomas]. 760 82

Antioxidants and reactive oxygen species are considered to play an important role in experimental in vivo carcinogenesis studies. We attempted in this study to evaluate the repercussions on the antioxidant and lipid peroxide status of the growth of human malignant tumors xenografted into athymic mice. We selected three tumor models: two urothelial carcinomas (bladder tumors stage 3) and one brain tumor (glioblastoma stage 4). All these tumors exhibited a fast growth pattern when xenografted into athymic mice. Tumoral tissue was implanted subcutaneously. After growth establishment each tumor size was measured at regular intervals: every 2 d for bladder tumor and twice a week for glioblastoma. The period of observation was 3 wk for bladder tumors and 5 wk for glioblastoma. At the end of the observation period, all mice were sacrificed; tumoral tissue was taken and blood collected. Superoxide dismutase activity (SOD), glutathione peroxidase activity (GSH-Px), zinc (Zn), selenium (Se), and thiobarbituric acid reactive substances (TBARS) were measured in blood. TBARS alone were measured into tumoral tissue. A modification of the antioxidant blood status was observed in mice xenografted with bladder tumors with decrease in Se status and GSH-Px activities, and increase in TBARS. Such an effect was absent in mice xenografted with glioblastoma. It would appear that an oxygen-mediated stress exists in the animal bearing an implanted tumor compared with the control group, and that tumoral tissue itself is able to induce an oxidative stress into its host. All this leads to a disturbance of the antioxidant defense system.
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PMID:Antioxidant status and lipid peroxidation in athymic mice xenografted with two types of human tumors. 777 35

5,8,11,14-eicosatetraynoic acid (ETYA), an isomorphic competitive analogue of arachidonic acid, spontaneously generates a chemiluminescence signal detected with a liquid scintillation spectrometer operated at ambient temperature in the out-of-coincidence mode. The intensity of the signal was 10- or more-fold above background, required oxygen for its generation, was inhibited by antioxidants, and approximately doubled in D2O. Arachidonic acid, which contains 4-alkene rather than alkyne bonds did no more than double the chemiluminescent signal above background. When examined at 37 degrees C in a Berthold AutoLumat 958 luminometer, DBA (lucigenin) was required to detect a signal above background. Catalase or peroxidase, and to a lesser extent mannitol or histidine but not superoxide dismutase, strongly diminished the signal intensity. These observations provide a baseline for interpreting the functional and electron microscopic changes produced by ETYA in PC3 prostate and A172 glioblastoma cell lines, consistent with a contribution from oxidative stress associated with free radicals, and the absence of these morphological changes in U937 monoblastoid cells.
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PMID:Spontaneous chemiluminescence of ETYA (5,8,11,14-eicosatetraynoic acid) is inhibited by catalase or peroxidase. 784 95

Human solid tumors (prostate carcinomas PC-3 and DU-145, breast carcinoma MX-1, cervical carcinoma ME-180, small cell lung carcinoma SW2, and glioblastoma T98G) were grown as xenografts in nude mice. Using the Eppendorf pO2 histograph microelectrode system, the oxygen profiles of the tumors were determined while the animals breathed air or carbogen (95% O2/5% CO2), and after administration of the perfluorochemical emulsion Oxygent-CA (8 ml/kg) under air breathing and carbogen breathing conditions. Under normal air breathing with or without Oxygent-CA administration the mean oxygen tensions were between 4.9 and 9.3 mmHg and each tumor had severely hypoxic regions where the pO2 was less than 5 mmHg. The severely hypoxic regions comprised 41-71% of the oxygen tension measurements under normal air breathing conditions. Carbogen breathing alone increased the mean oxygen tensions to 10.9-23.9 mmHg. Administration of Oxygent-CA and carbogen breathing increased the mean oxygen tensions over the levels of carbogen breathing alone to varying degrees. The highest mean oxygen tensions were 40.8 mmHg in the T98G glioblastoma and 24.5 mmHg in the ME-180 cervical carcinoma. Investigation of the use of Oxygent-CA/carbogen to increase the oxygenation of clinical tumors is warranted.
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PMID:Oxygenation of human tumor xenografts in nude mice by a perfluorochemical emulsion and carbogen breathing. 784 46

There is evidence that pentoxifylline may be both a radioprotector of normal tissue and a radiosensitizer of tumor cells. This article reviews this evidence and then describes our own laboratory study to determine whether pentoxifylline is a radiosensitizer of human glioblastoma cells in vitro. Human glioblastoma multiforme cells (SNB19 cell line) were irradiated in vitro with and without pentoxifylline. Regression of the log ratios (quotient of surviving colonies) revealed greater tumor cell kill in the PTX group, and the difference increased as the radiation dose increased (p < 0.01 at the 750 and 1000 cGY doses). Before the hypothesis that PTX is a radiosensitizer of hypoxic tumor cells can be confirmed or denied, it must be determined if the agent also has a separate mechanism of tumoricidal activity. Whereas in vivo models allow the well-documented rheologic, immunologic and oxygen-related effects of PTX to be active simultaneously, the in vitro model described herein excludes the effects of such systemic actions and focuses on mechanisms at the cellular or subcellular level. These data suggest there exists such a mechanism of tumoricidal activity of PTX that has not been previously identified.
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PMID:The in vitro radiosensitization of human glioblastoma with pentoxifylline. 821 23

Several studies have shown a decrease in blood perfusion and oxygen partial pressure (pO2), and an increase in interstitial fluid pressure (IFP) with increasing tumor size. However, it is not evident if the elevated IFP is a key parameter responsible for the poor perfusion and oxygenation of solid tumors. To this end, IFP and pO2 were measured in nine human tumor xenografts in immunodeficient mice at a fixed tumor size (approximately 250 mm3). IFP and pO2 were also measured as a function of tumor volume in one human colon adenocarcinoma (LS174T) and in one human glioblastoma (HGL-9). In LS174T tumors IFP did not vary with size (P < .07); however, median pO2 decreased from approximately 35 mm Hg in 100-mm3 tumors to approximately 15 mm Hg in tumors of approximately 500 mm3 (P < 0.001). In HGL-9 tumors an inverse correlation between IFP and pO2 was found; IFP increased (P < 0.001) and pO2 decreased (P < 0.001) with increasing tumor size. At a fixed tumor size of 250 mm3 no correlation was found between mean IFP and median pO2 (P < 0.5) or between the mean IFP and the hypoxic fraction (pO2 < 2.5 mm Hg) (P < 0.7) in the nine tumors studied. The absence of a general relationship between IFP and pO2 could result in part from differences in vascular resistance between tumors. For example, a high geometric resistance to blood flow on the arterial side will lead to a low IFP and blood flow, whereas an elevation of the venous resistance will reduce blood flow and increase IFP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lack of general correlation between interstitial fluid pressure and oxygen partial pressure in solid tumors. 853 98


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