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)

N2-Isobutyryl-2'-deoxyguanosine-N7-cyanoborane derivatives were observed to be potent antineoplastic agents and to be active against a number of human tissue culture tumor cells, e.g. Tmolt3 leukemia, HeLa-S3 uterine carcinoma. Selective agents were active against colon adenocarcinoma, osteosarcoma and glioma growth. These agents preferentially inhibited both DNA and RNA synthesis of L1210 cells. De novo synthesis of purines was significantly inhibited at the regulatory sites of PRPP amido transferase and IMP dehydrogenase. Other sites of inhibition were thymidylate synthetase, OMP decarboxylase and thymidine kinases. The agents also significantly reduced deoxyribonucleotide levels and caused DNA strand scission.
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PMID:The synthesis and anti-neoplastic activity of N2-isobutyryl-2'-deoxyguanosine-N7-cyanoborane derivatives. 149 12

A series of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes and cyanoboranes were synthesized. These compounds have potent hypolipidemic effects, antineoplastic and antiinflammatory activities in rodents. Furthermore, they demonstrated potent cyctotoxicity against standard human tissue culture lines. The compounds which afforded the best hypolipidemic activity, i.e. greater than 40% reduction of serum cholesterol and triglyceride levels, were diphenyl-(4-methylphenyl)-phosphine borane and triphenylphosphine carboxyborane. Other derivatives demonstrated more potent antineoplastic activity against the Ehrlich ascites carcinoma growth including triphenylphosphine cyanoborane, 2-amino-4-methyl-pyridine cyanoborane and 2-amino-pyridine cyanoborane. Most of the derivatives showed good activity against murine L1210 lymphoid leukemia, Tmolt3 human leukemia, uterine HeLaS cells, and human glioma cell growth. Select compounds were active against colon adenocarcinoma, KB nasopharynx, lung bronchogenic and osteosarcoma cell growth. Tricyclohexyl- and triphenylphosphine boranes and the carboxy derivatives of the latter borane demonstrated good antiinflammatory activity.
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PMID:Relationship of hypolipidemic and antineoplastic activities of tricyclohexyl- and triphenylphosphine boranes, carboxyboranes, cyanoboranes, and related derivatives. 152 68

Benzohydroxamic acids proved to be potent cytotoxic agents suppressing the growth of a number of murine and human cell lines grown in tissue culture, e.g. leukemia, colon, uterine and glioma. Selected compounds demonstrated activity against the growth KB nasopharynx, bronchogenic lung, osteosarcoma and skin cancer. In vivo activity against Ehrlich ascites carcinoma growth was shown with certain compounds. In L1210 cells compound 2 inhibited DNA synthesis significantly within 60 min. the site of action of the agent appears to involve the purine de novo synthesis pathway at PRPP amido transferase and IMP dehydrogenase. Dihydrofolate reductase and nucleoside kinase activities were inhibited by the agent. The levels of d(NTP)s in L1210 cells were reduced after drug treatment. The drug did not appear to affect the DNA template directly causing any damage which might alter transcription and replication nor was there any inhibition of HeLa topoisomerase activity by the drug. Thus the drug appears to be a metabolic inhibitor of nucleoside metabolism.
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PMID:The antineoplastic and cytotoxicity of benzohydroxamic acids and related derivatives in murine and human tumor cells. 152 9

Sulfhydryl boron hydride (BSH) (10B enriched) is presently used for boron neutron capture therapy of malignant gliomas. BSH must be close to the target cells to be effective in the inactivation of cell proliferation because of the short range of the reaction products (5-9 microns). Clinical experience indicates that BSH is taken up in gliomas but it is not known to which structures it binds at the cellular level. In vitro tests on monolayer cultured cells have indicated that BSH does not bind, or only shows very weak binding, to single isolated cells. It is possible that BSH accumulates in tumor regions due to the special conditions in poorly vascularized tumor tissue, such as low pO2, low extracellular pH, metabolic gradients, and degenerative changes. To test this we incubated three types of multicellular tumor spheroids with BSH for different times and analyzed both penetration and binding. The spatial distribution of 10B in sections of the spheroids was analyzed by neutron capture autoradiography. We found extensive accumulation of 10B in the central regions of both glioma and colon carcinoma spheroids. The accumulation closely followed the pattern of the degenerative changes which were characterized by massive necrosis in the central regions of the colon carcinoma spheroids and by a continuously increasing frequency of pyknotic nuclei as a function of depth in the glioma spheroids. The accumulation of 10B in the prostatic carcinoma spheroids was much lower. The penetration assay, based on freeze-drying and vapor fixation, showed that BSH penetrated easily since 10B equilibrated within 5-15 min in the studied spheroids. Thus, the low accumulation in the prostatic carcinoma spheroids was not due to penetration difficulties. The results of the present study on cellular spheroids and the results from previous studies on transplanted tumors support the observation that BSH penetrates easily into the degenerative tumor areas and that 10B, for some tumor types, might accumulate in these regions as a result of the BSH administration.
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PMID:Accumulation of 10B in the central degenerative areas of human glioma and colon carcinoma spheroids after sulfhydryl boron hydride administration. 154 Sep 68

Mouse myeloma cells were fused with spleen cells from mice that had been immunized with a human ependymoma derived cell line, KMS II. Hybridomas producing monoclonal antibodies (MAbs) were screened and cloned. Specificity of the antibody was determined by enzyme-linked immunosorbent assay (ELISA) and/or indirect immunofluorescence assay. One of the MAbs, designated Ep-C4 (subclass = IgG1), reacted with two cell lines derived from ependymoma but did not react with 17 cell lines derived from other types of brain tumor nor with 4 neuroblastoma cell lines or 19 cell lines derived from carcinoma, hematopoietic tumors and amnion. Indirect immunofluorescence and immuno-electron microscopy studies revealed that the antigen recognized by MAb Ep-C4 was located on cell surface membrane. The membrane antigen of KMS II cells, immunoprecipitated by MAb Ep-C4, was a protein of 81,000 dalton. The reactivity of MAb Ep-C4 was further examined using immunofluorescence and/or immunoperoxidase methods and frozen sections and short-term cultures of various types of brain tumors. No cross-reactivity with normal adult or fetal brain tissues was detected by absorption assay and immunoperoxidase staining. Our results suggest that the antigen defined by MAb Ep-C4 is specific for ependymoma cells, and different from the antigens of glioma cells or other neuroectodermal-derived cells previously described.
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PMID:Monoclonal antibody against ependymoma-derived cell line. 154 75

We have studied the cellular immune response that accompanies primary and metastatic brain cancers induced experimentally in rats by inoculation of RG-2 glioma and Walker 256 (W256) carcinoma cells, respectively. The inflammatory cell infiltrates were characterized with lectin histochemistry to visualize microglial cells and macrophages and with immunohistochemistry, using a panel of monoclonal antibodies, to detect major histocompatibility complex (MHC), lymphocytic, and macrophage antigens. The metastatic tumor was composed of a loose stroma with multiple, often large, necrotic areas, whereas the RG-2 glioma was composed of a dense collection of tumor cells showing only rare necrotic foci. Both tumor types were heavily infiltrated with microglia and/or macrophages, and these were positive for MHC Class II (Ia) antigens. Expression of MHC Class I antigens was absent from RG-2 glioma cells, but it was present in W256 metastatic carcinoma cells. The metastatic tumor was also characterized by a much heavier infiltrate of lymphocytes, as shown by the presence of cells positive for CD4, CD8, and leukocyte common antigens. These lymphocytic markers were absent from reactive microglia in the W256 carcinoma, whereas they were present in the RG-2 glioma. Polymorphonuclear leukocytes were seen only in the metastatic tumor. Our study delineates differences between the inflammatory cell infiltrates found in metastatic brain tumors and those found in primary brain tumors. The differences in cell composition and immunophenotype may indicate a more effective antitumor response in the metastatic tumor that could account for the observed tissue destruction.
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PMID:Inflammatory cell infiltrates vary in experimental primary and metastatic brain tumors. 161 93

2,3-Dihydrophthalazine-1,4-dione derivatives demonstrated potent cytotoxicity against the growth of murine leukemia cells and human single cell suspension, i.e. Tmolt3 leukemia and HeLa-S3, as well as colon adenocarcinoma and KB nasopharynx. However, only select compounds demonstrated activity against bronchogenic lung, osteosarcoma and glioma growth. 2,3-Dihydrophthalazine-1,4-dione was active in vivo against L1210 leukemia, Lewis lung and Ehrlich ascites carcinoma growth. In L1210 cells the agents inhibited both DNA and RNA synthesis, and a few of the compounds were capable of inhibiting protein synthesis at 3 times their ED50 values. When 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione were examined for their mode of action in the L1210 lymphoid leukemia cells, the sites of inhibition by the agents appear to be the de novo purine pathway at the enzymes IMP dehydrogenase and PRPP amido transferase. IMP dehydrogenase activity was inhibited at least 45% by 45 min at 100 microM concentration of drugs whereas the remaining enzymes that were affected by the drugs were not inhibited as early. Secondary sites were dihydrofolate reductase and thymidylate synthetase. The d(NTP) levels were also reduced specifically dATP and dCTP levels.
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PMID:The anti-neoplastic activity of 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione in human and murine tumor cells. 162 17

We have examined the distribution of antigens detected by MB1, MB2 and MB3 on non-hematopoietic normal human tissues and various types of benign and malignant tumors. MB1 and MB2 reacted with various organs, such as the epithelium of various glands, smooth muscle cells, vascular endothelial cells, and peripheral nerve tissue. The distributions of these two antibodies were essentially identical. Reactivity with MB3 was confined to the ductal epithelium of salivary glands, the pancreas, and sweat glands, and the cortex of the adrenal gland. Immunoblotting analysis demonstrated that MB1 and MB2 reacted with a few bands of an extract of myometrial cytoskeletal fraction and salivary gland cytosol fraction, whereas MB3 failed to show any bands on these materials. The reactivities of MB1 and MB2 with various neoplasms were similar to those in normal organs, with slight variations of staining pattern and preponderance in well differentiated tumors. Exceptionally, carcinoid tumor and small round cell tumors, such as small cell carcinoma or neuroblastoma, were not reactive with MB1 and MB2. MB3 reacted with several cases of well differentiated benign and malignant epithelial tumors in various organs, and exceptional cases of malignant schwannoma and glioma. These results indicate that the antigens detected by MB1 and MB2 are distributed broadly on non-hematopoietic normal organs, whereas those detected by MB3 are confined to exceptional cases of epithelial and non-epithelial tumors. Thus, although the use of MB1, MB2 and MB3 is of little value for differential diagnosis of various tumors, these three antibodies may be useful for determining of the origin of some tumor types.
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PMID:Distribution of antigens detected with MB1, MB2 and MB3 on non-hematopoietic human organs and various tumors. 163 36

Proliferating cell nuclear antigen (PCNA) is a 36-kDa DNA polymerase-delta auxiliary protein which accumulates in the nucleus during S phase of the cell cycle. Immunohistochemical labeling indices (LI) of PCNA and Ki-67 were compared using an avidin-biotin complex method on frozen sections of 27 nervous system tumors. 3 normal cerebral cortices, and 3 peripheral nerves. In glial tumors, PCNA and Ki-67 LI increased with increasing tumor grade (Daumas-Duport system). In 5 low-grade glial tumors, PCNA and Ki-67 LI were less than or equal to 1%, except for one optic nerve glioma (Ki-67 LI = 6%). In 7 grade 3 astrocytomas and 1 mixed glioma, PCNA LI were less than or equal to 1-1.5%, while Ki-67 LI were 2%-10%. In 7 grade 4 astrocytomas and 1 metastatic carcinoma, PCNA LI ranged from 6%-15% while Ki-67 LI ranged from 17%-30%. In 5 of 6 schwannomas, focally high PCNA LI (4%-65%) were noted, despite low LI with Ki-67 (less than or equal to 1.6%). Scattered normal schwann cell nuclei also stained with PCNA, but normal cerebral cortex did not.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Proliferating cell nuclear antigen and Ki-67 immunohistochemistry in brain tumors: a comparative study. 167 78

Malignant gliomas are difficult to treat systemically because of exclusion of many chemotherapeutic agents by the blood brain barrier. Furthermore, as opposed to other neoplasms, malignant gliomas recur locally, at the site of original presentation. These tumors are remarkably vascular and hence may be more dependent on angiogenesis for continued growth than other tumors. The inhibition of tumor angiogenesis can control tumor growth by preventing the exponential vascular growth phase. We report the inhibition of the growth of the 9L glioma by the localized, controlled release of known angiogenesis inhibitors administered in a biodegradable polyanhydride polymer matrix. In the presence of heparin and cortisone and of cortisone alone there was a 4.5- and 2.3-fold reduction, respectively, in the growth of the 9L glioma. We compared these results to the inhibition of tumor neovascularization in the rabbit cornea by the localized delivery of the same agents. In the rabbit cornea model, the local release of heparin and cortisone and of cortisone alone resulted in a 2.5- and 2.0-fold reduction, respectively, in the angiogenesis response evoked by the VX2 carcinoma. This study introduces two new potential therapeutic modalities for the treatment of malignant gliomas: the use of the combination of heparin and cortisone as antineoplastic agents and the use of polymeric carriers for the local delivery of such agents in the central nervous system.
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PMID:Growth inhibition of the 9L glioma using polymers to release heparin and cortisone acetate. 170 49


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