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)

Human glioblastoma cells secrete a peptide, termed glioblastoma-derived T cell suppressor factor (G-TsF), which has suppressive effects on interleukin-2-dependent T cell growth. As shown here, complementary DNA for G-TsF reveals that G-TsF shares 71% amino acid homology with transforming growth factor-beta (TGF-beta). In analogy to TGF-beta it is apparently synthesized as the carboxy-terminal end of a precursor polypeptide which undergoes proteolytic cleavage to yield the 112 amino-acid-long mature form of G-TsF. Comparison of the amino-terminal sequence of G-TsF with that of porcine TGF-beta 2 and bovine cartilage-inducing factor B shows complete homology, which indicates that we have cloned the human analogue of these factors. It is tempting to consider a role for G-TsF in tumor growth where it may enhance tumor cell proliferation in an autocrine way and/or reduce immunosurveillance of tumor development.
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PMID:Complementary DNA for human glioblastoma-derived T cell suppressor factor, a novel member of the transforming growth factor-beta gene family. 332 13

Five different lipid conjugates of 1-beta-D-arabinofuranosylcytosine (ARA-C) were tested in comparison with ARA-C, the ether lipid ET-18-OCH3 (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) and their equimolar mixtures. The compounds were tested in vitro for cytotoxicity in the trypan blue dye exclusion test with cells from six different leukemias, one glioblastoma and two bronchogenic carcinomas of human origin. The compounds were given in vivo to assess their therapeutic activity against 3-Lewis lung carcinoma (3-LL) of syngeneic C57Bl6 mice. Although some of the conjugates have shown cytotoxic activity in vitro against the cell samples tested, they have not revealed higher cytotoxicity than ET-18-OCH3, ARA-C or their equimolar mixtures. In these experiments, ARA-CDP-D,L-MBA was the conjugates significantly inhibited tumor growth and also increased survival of C57Bl6 mice with intraperitoneally (ip) implanted 3-LL. In these experiments, ARA-CDP-D,L-PTBA, ARA-CDP-D,L-PBA, ARA-CDP-L-dipalmitin and ARA-CDP-D,L-PCA were more active than either the parent compounds ARA-C and ET-18-OCH3 alone or their equimolar mixtures. Furthermore, when the conjugates were injected as adjuvant chemotherapy shortly after the surgical removal of the primary 3-LL, they inhibited the metastasis of 3-LL to the lungs of the animals, demonstrated by an increase of the survival time and the number of surviving animals. The mode of action of these new antineoplastic compounds still is speculative.
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PMID:Antineoplastic activity of conjugates of lipids and 1-beta-D-arabinofuranosylcytosine. 344 89

16 different free amino acids were determined in cerebrospinal fluid and plasma of each 5 patients with glioblastomas, meningiomas, and low grade gliomas as well as in 21 patients with lumbar disk herniations (control group). The values from the control group were in good accordance with those previously observed in normal adults of 5 studies of the literature. Significant changes were seen only in 6 of 16 amino acids. Absolute values of free CSF amino acids showed significant lower levels of valine, leucine and asparagine in the 3 subgroups whereas serine remained constantly high. The greatest changes were observed in glioblastoma and meningioma patients. Relative values gave similar results. No significant changes were found in CSF-plasma free amino acid relations. The authors conclude that changes of free CSF amino acids are due to a non-specific reaction of the brain itself to tumor growth. The different histology of the tumor does not give specific results. Determination of free CSF amino acids may help in early diagnosis of brain tumor recurrence after operation and to watch the effect of chemotherapy and radiation on brain tumor growth.
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PMID:[Cerebrospinal fluid and plasma aminograms in patients with primary and secondary tumors of the CNS]. 361 Mar 11

The energy metabolism of living tumors in rats and hamsters were investigated by obtaining in vivo 31P-NMR spectra, and the effects of chemotherapy on tumors were evaluated by observing the changes of these spectra. Tumor cells of rat glioma, human glioblastoma and human neuroblastoma were inoculated subcutaneously in the lumbar region of the animals. After the tumor grew to over 1.5 cm in diameter, in vivo 31P-NMR spectrum data was obtained selectively from the tumor with a TMR-32 spectrometer (Oxford Research Systems, U.K.). Several peaks (ATP, inorganic phosphate (Pi), phosphodiesters and phosphomonoesters (PME) were observed in the tumors. The heights of these peaks varied widely corresponding to the tumor growth. However, the spectrum pattern of each tumor in an active stage was found to be essentially the same regardless of histological type or tumor origin. The phosphocreatine (PCr) peak was small, ATP and PME peaks were large and tissue pH calculated from the chemical shift of Pi was low in each tumor group. After intravenous injection of a large dose of a chemotherapeutic agent, ATP peaks decreased and the Pi peak increased gradually, resulting in a dominant Pi peak pattern after several hours in all groups. With lower drug doses, spectrum changes were temporarily seen in the tumors. These findings indicated that drugs with a high dose have a selective and a direct action on the energy metabolism of tumor tissues. In vivo 31P-NMR spectra measurement is very valuable not only to investigate the energy metabolism in tumor tissue but also to evaluate the effects of chemotherapy on the tumor.
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PMID:Observations of energy metabolism in neuroectodermal tumors using in vivo 31P-NMR. 403 75

Twenty-five neonatal beagles were used for this study. Gliosarcoma was injected into the cerebral hemisphere of 7 neonatal beagles (Group I). These animals were then treated by boron neutron capture therapy. The response of the tumor to therapy was evaluated by serial CT scans and 3 times magnification of cerebral angiography. The animals were sacrificed at varying post-therapy periods for histological study. Fifteen neonatal beagles implanted gliosarcoma without therapy (Group II) and 3 normal controls without tumor (Group III) were subjected to the same follow-up studies. (Results) (1) Neonatal beagles with implanted tumor showed moderate degree of ventricular dilatation within a short period. The finding of communicating hydrocephalus was interpreted as initial growth of tumor. (2) Animals after therapy had variable cavitation in the hemisphere that had contained calcium deposit on CT. Moderate dilatation of the lateral ventricle was present without any significant midline shift and there was an area of porencephaly extending out from the right lateral ventricle on CT (Fig. 1, Case 2). Cerebral angiography demonstrated hydrocephalus with an avascular region in the right cerebral hemisphere, compatible with the previously described porencephalic cyst (Fig. 2, Case 2). (3) Three cases out of 7 showed neurological symptoms after tumor implantation (Cases 3, 5 and 6). Carotid angiography showed large temporal lobe tumor with some tumor stain and also some involvement of the right frontal lobe after therapy (Fig. 7, Case 3). In postmortem examination, there was tumor seen coating the right lateral ventricle as well as the left temporal horn. The right cerebral hemisphere was slightly smaller than the left. The left lateral ventricle was remarkably enlarged (Fig. 9). (4) Four out of 7 treated animals with injected gliosarcoma showed no evidence of tumor at postmortem examination. CT demonstrated moderate dilatation of the lateral ventricle without any significant midline shift, an area of porencephaly and definite decrease in size of the right cerebral hemisphere and calvarium (Fig. 4). (5) Fifteen neonatal beagles implanted gliosarcoma without therapy (Group II) developed symptomatic and died within two weeks. (6) Control animals showed no ventricular dilatation or other abnormalities. (7) Microscopic examinations showed no similarities between implanted gliosarcoma and human glioblastoma. (Conclusion) Serial CT scans and magnification cerebral angiography in this experimental model appear extremely helpful in following the effects of therapy and important tool for the evaluation of a tumor growth or regression.
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PMID:[Neuroradiological Evaluation of an experimentally implanted tumor into cerebral hemisphere of neonatal beagles (author's transl)]. 709 78

In primary malignant brain tumors increased vascularity and marked edema strongly suggest a possible role of the vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). This was confirmed by earlier in situ hybridization studies, by analysis of the expression of the mitogen in different subsets of glioblastoma cells, and by the fact that the VEGF/VPF receptor flt-1 (fms-like tyrosine kinase) is up-regulated in tumor cells in vivo. To assess and quantify the expression of the VEGF/VPF gene and of the receptor gene, 26 surgical specimens of brain tumor tissue from 24 patients were analyzed. In most malignant gliomas, the expression level of the VEGF/VPF gene is elevated and can be increased up to 20- to 50-fold in comparison with low-grade tumors. Using polymerase chain reaction-based amplification, it could be shown that the messenger RNAs of three different VEGF/VPF forms are synthesized in tumor tissue samples. Northern blot studies revealed that in some samples a significant expression of the gene coding for placenta growth factor, a growth factor closely related to VEGF/VPF, was observed. In addition, using a radioreceptor assay it was possible to detect high VEGF/VPF-like activity in the cyst fluids of brain tumors, indicating the accumulation of the mitogen and permeability factor in brain tumor cysts. Further investigations revealed that astrocytoma and glioblastoma cells in culture express the VEGF/VPF gene and secrete the VEGF/VPF protein, whereas gene expression of the two known VEGF/VPF receptors, kinase insert domain-containing receptor and flt-1, could not be detected. These data support previous reports, which stated that VEGF/VPF acts as a paracrine growth and permeability factor in brain tumors and may contribute to tumor growth by initiating tumor angiogenesis.
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PMID:Detection and quantification of vascular endothelial growth factor/vascular permeability factor in brain tumor tissue and cyst fluid: the key to angiogenesis? 752 59

The effectiveness of in vivo suppression of neovascularization and growth of malignant glial tumors by in situ administration of an antibody directed against basic fibroblast growth factor (bFGF), a strong mitogen for cells of mesodermal origin, was tested. One hundred fifty congenitally athymic nude rats (han rnu/rnu) were implanted intracerebrally with U-87MG tumor cells, known constitutive producers of bFGF. The animals were randomly assigned to six groups of 25 animals each. Animals were treated by in situ application of saline (Group F), control antibody (Group D), or polyclonal anti-bFGF antibody (Group B). In additional groups a putative effect on tumor growth caused by the treatment application device itself (between growth control Groups A and E), and the effect of heat-inactivated tumor cells (negative control Group C) were tested. After 3 weeks of treatment, tumor progression and degree of neovascularization were morphometrically recorded. In the untreated Groups A and E massive tumor growth was recorded, consisting of 19.9% +/- 0.4% and 27.1% +/- 0.5%, respectively, of the total brain cross-sectional area. In Group C, no tumor growth occurred. In control Groups D and F tumor progression consisted of 18.6% +/- 0.4% and 18.5% +/- 0.4%, respectively, of the total brain cross-sectional area; whereas in the anti-bFGF treated Group B, significantly smaller tumor masses measuring 7.2% +/- 0.1% were recorded. New blood vessels were located both peritumorally and intratumorally and defined as numerical density and area fraction (number/area and area/area). Significantly more new blood vessels were found in Groups A, D, E, and F, ranging from 41,380/mm2 +/- 464/mm2 to 53,442/mm2 +/- 150/mm2 peritumorally and 51,846/mm2 +/- 495/mm2 to 64,660/mm2 +/- 183/mm2 intratumorally than in the anti-bFGF treated Group B, which numbered 8220/mm2 +/- 225/mm2 peritumorally and 16,554/mm2 +/- 236/mm2 intratumorally. The authors conclude that treatment with anti-bFGF antibody is effective in inhibiting tumor-induced angiogenesis and correlated tumor progression. However, owing to the character of the experimental system used, one cannot exclude the possibility that application of the specific anti-bFGF antibody also counteracts device-induced neovascularization. The authors suggest that combined surgical excision and adjuvant immunotherapy of tumors such as glioblastoma and other malignant brain tumors that express bFGF might prevent tumor recurrence.
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PMID:In vivo inhibition of angiogenesis and growth of the human U-87 malignant glial tumor by treatment with an antibody against basic fibroblast growth factor. 753 64

Expression levels of the immunostimulatory 90K antigen in mammary carcinoma, glioblastoma, and other tumor-derived cell lines inversely correlate with their tumorigenicity in athymic mice. Engineered enhancement of 90K expression results in significant (> 80%) tumor growth inhibition, not by direct action on the tumor cell, but by stimulation of the residual cell-mediated immune defense of the nude mouse. Enhanced 90K level effects are both localized and systemic and involve induction of ICAM-1 and VCAM-1 in the tumor endothelium. The findings presented suggest a role for 90K as a molecular alarm signal for the body's cellular defense against pathogens, which in a subset of tumors is suppressed to allow cancer progression.
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PMID:Suppression of tumor growth in vivo by local and systemic 90K level increase. 754 66

Interferons (IFNs) are a natural body defense with powerful effects on tumor growth, including gliomas. The direct effects of IFN-gamma on (1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU)-induced deoxyribonucleic acid (DNA) damage and cytotoxicity were investigated in two human glioblastoma cell lines, A-172 and T98G, using a single cell microgel electrophoresis technique and a microculture tetrazolium assay. The results demonstrated a synergistic effect of IFN-gamma with ACNU on intracellular damage in both cell lines. 10 micrograms/ml ACNU induced a cell inhibition rate of 23.9% in A-172 cells, and almost no effect on T98G cells. 1000 U/ml IFN-gamma and 10 micrograms/ml ACNU caused a significant increase in cell inhibition, 51.2% for A-172 and 72.3% for T98G cells. DNA damage in individual A-172 and T98G cells exposed to ACNU was enhanced significantly by IFN-gamma (p < 0.001). The findings suggest a direct effect of IFN-gamma on ACNU-induced cell damage in human glioma, in addition to its effect on immunomodulation.
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PMID:Effect of interferon-gamma on ACNU-induced DNA damage and cytotoxicity in human glioblastoma cells. 768 31

We evaluated the usefulness of an in vitro tumor organ culture system using a specialized collagen gel matrix derived from pig skin as a chemosensitivity test for human brain tumors. Two xenograft tumors derived from human glioblastoma and medulloblastoma were examined with this system and the results were compared with data obtained from a nude mouse assay. Xenograft tumors exhibited in vivo-like three-dimensional growth on the collagen gel matrix and had increasing incorporation of tritiated (3H)thymidine for 2 weeks. Drug sensitivity, as measured by this assay at therapeutic peak plasma concentrations of anticancer drugs, corresponded with that measured with the nude mouse assay. Chemosensitivity of 16 surgical specimens of malignant brain tumors were also examined successfully by this collagen gel matrix (CGM) assay. When the highest inhibition rate in dose-inhibition curve was equal to or greater than 50%, the tumor was regarded to be sensitive to the agent. The efficacy rates in CGM assay for 16 lesions were 25.0% (4/16) for ACNU, 67.8% (11/16) for adriamycin, 31.3% (5/16) for cisplatin, and 67.8% (11/16) for etoposide. The CGM assay has advantages as a chemosensitivity test because of its simple procedure, rapidity, high rate of evaluable tumor growth, and in vivo-like three dimensional tumor growth. Our results indicate that the CGM assay is feasible to test the chemosensitivity of malignant brain tumors.
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PMID:In vitro chemosensitivity test of human brain tumors using a three-dimensional organ culture with a collagen gel matrix. 769 17


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