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)

Thiram-tetramethylthiuram disulphide--a chelator of heavy metals, inhibited DNA synthesis and induced apoptosis in cultured bovine capillary endothelial cells. Bovine capillary endothelial cells were 10-60-fold more sensitive to thiram than other cell types. These effects were prevented by addition of antioxidants, indicating involvement of reactive oxygen species. Exogenously added Cu2+ impeded specifically and almost completely the inhibitory effect of thiram for bovine capillary endothelial cells. Moreover, thiram had markedly inhibited human recombinant Cu/Zn superoxide dismutase enzymatic activity (85%) in vitro. Moreover, PC12-SOD cells with elevated Cu/Zn superoxide dismutase were less sensitive to thiram treatment than control cells. These data indicate that the effects of thiram are mediated by inhibition of Cu/Zn superoxide dismutase activity. Oral administration of thiram (13-30 microg mouse(-1)), inhibited angiogenesis in CD1 nude mice. Tumour development is known to largely depend on angiogenesis. We found that oral administration of thiram (30 microg) to mice caused significant inhibition of C6 glioma tumour development (60%) and marked reduction (by 3-5-fold) in metastatic growth of Lewis lung carcinoma. The data establish thiram as a potential inhibitor of angiogenesis and raise the possibility for its use as therapy in pathologies in which neovascularisation is involved, including neoplasia.
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PMID:Thiram inhibits angiogenesis and slows the development of experimental tumours in mice. 1187 43

Highly migratory neuroectodermal cells share a common embryonic origin with cells of the central nervous system (CNS). They include enteric, parasympathetic, sympathoadrenal, and sensory neurons of the peripheral nervous system, Schwann cells, melanocytes, endocrine cells, and cells forming connective tissue of the face and neck. Because of their common embryologic origin, these cells and the tumors that derive from them can share genetic and antigenic phenotypes with gliomas, tumors derived from CNS glia. We recently discovered that chlorotoxin (ClTx), a 4-kD peptide purified from Leiurus quinquestriatus scorpion, is a highly specific marker for glioma cells in biopsy tissues (Soroceanu et al. Cancer Res 58:4871-4879, 1998) that can target tumors in animal models. We report on the specificity of ClTx as a marker for tumors of neuroectodermal origin that include peripheral neuroectodermal tumors (PNET) and gliomas. Specifically, we histochemically stained frozen and paraffin tissue sections of human biopsy tissues from 262 patients with a synthetically manufactured and biologically active ClTx bearing an N-terminal biotin. The vast majority (74 of 79) of primary human brain tumors investigated showed abundant binding of ClTx with greater than 90% ClTx-positive cells in each section. By comparison, 32 biopsies of uninvolved brain used for comparison were largely ClTx-negative, with only a few isolated reactive astrocytes showing some ClTx binding. However, as with gliomas, the vast majority of PNETs examined showed specific ClTx binding (31 of 34). These include medulloblastomas (4 of 4), neuroblastomas (6 of 7), ganglioneuromas (4 of 4), melanomas (7 of 7), adrenal pheochromocytomas (5 of 6), primitive PNET (1), small cell lung carcinoma (2 of 3), and Ewing's sarcoma (2 of 2). Under identical staining conditions, normal tissues from brain, skin, kidney, and lung were consistently negative for ClTx. These results suggest that chlorotoxin is a reliable and specific histopathological marker for tumors of neuroectodermal origin and that chlorotoxin derivatives with cytolytic activity may have therapeutic potential for these cancers.
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PMID:Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. 1211 67

p53 interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function involving cell cycle control, gene regulation, cell differentiation, apoptosis and tumor suppression. To identify these proteins, we used the yeast two-hybrid system and screened a HeLa cDNA library. Six positive colonies were isolated from 1.5x10(6) transformants. The cDNA sequence of each positive colony was determined. Two novel cDNA fragments (p53BP1 and p53BP2) were cloned. These two cDNA fragments code for the same protein composed of 158 amino acids, which shows high similarity to the ubiquitin-conjugating enzyme (UBC9) of H. sapiens as well as to E2s from other organisms, such as UBC (76 %) of C. elegans, HUS5(66 %) of S. pombe, UBC(66 %) of A. thaliana and UBC9(56 %) of S. cerevisiae. A cDNA fragment from p53BP1 was used to probe a Northern blot containing poly(A)(+) RNA from various human tissues and various cell lines. At high stringency this probe hybridized to a single mRNA of approximately 1.2 kb that was expressed in heart, brain, placenta, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood leukocyte, human cervical carcinoma cell (HeLa), human mammary carcinoma cell (MCF-7), human lymphoma cell (Jurkatt) and human teratocarcinoma cell (PA-I). It is not expressed in brain, lung, human lung carcinoma cell, human heptocellular carcinoma cell (HepG2) and human glioma cell(U251MG).
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PMID:A Novel cDNA Encoding Ubiquitin-conjugating Enzyme of Homo sapiens. 1217 72

Some cancers, particularly malignant melanomas and carcinomas of the breast and lung, metastasize to the central nervous system (CNS) in advanced stages. In order to develop into clinically manifest metastases, hematogenously disseminated tumor cells must respond to trophic factors within the CNS microenvironment. We have previously identified a nuclearfactor, com1, expressed in human breast carcinoma cells upon formation of experimental metastatic tumors in the CNS. In the present study distinct com1 mRNA expression was detected in cerebral metastases from patients with lung carcinomas, whereas the expression level was generally much lower in glioblastomas (primary brain tumors). In tissue specimens from normal brain and lung, as well as in glioma and lung carcinoma cell lines, com1 expression was barely detectable. One potential mechanism involved in the induction of com1 expression was indicated in the metastatic MCF7/LCC2 breast carcinoma cells. Significant increases in the level of com1 mRNA were observed upon activation of receptor tyrosine kinase signaling, which is known to operate during metastatic tumor cell proliferation within the CNS. The observations in this study strengthen the assumption that com1 may be involved in the tumor cell response to regulatory signals upon metastasis formation.
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PMID:Clinical and cell line specific expression profiles of a human gene identified in experimental central nervous system metastases. 1217 69

Soluble form of intercellular adhesion molecules (sICAM) are increased in serum of many inflammatory diseases and tumours: the expression of such molecules is regulated by cytokines. In the present paper serum levels of interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R) and sICAM-1 were evaluated in patients with glioma compared with different tumours (lung and kidney carcinoma) in order to investigate the compromise of the immune system in these malignancies and to understand the host defence mechanisms. 14 cases of astrocytomas (WHO grade II, III), 20 cases of glioblastomas (GBL, WHO grade IV), 5 cases of lung carcinoma and 6 cases of kidney carcinoma were studied; the results were compared with 15 healthy controls. IL-2, sIL-2R, sICAM-1 concentrations were assessed by an enzyme-linked immunosorbent assay (ELISA) technique. The results were analyzed by Student's t test. Our findings showed that serum levels of IL-2 and sIL-2R were increased in all cancer patients; on the contrary, sICAM-1 serum levels were not significantly increased in GBL and astrocytoma patients. The increased values of IL-2 and sIL-2R are in agreement with a depression of the immune reactivity in patients with glioblastoma and astrocytoma, as reported in literature. On the contrary the levels of sICAM-1 are unchanged in astrocytic tumours while patients with kidney carcinoma presented the higher levels and an unfavourable prognosis.
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PMID:Evaluation of serum levels of cytokines and intercellular adhesion molecule-1 (ICAM-1) in astrocytic tumours. 1289 44

Despite advancements in therapeutic regimens, the prognosis remains poor for patients with malignant gliomas. Specificity has been an elusive goal for current modalities, but immunotherapy has emerged as a potential means of designing more tumor-specific treatments. Dendritic cells (DC) are the specialized antigen presenting cells of the immune system and have served now as a platform for therapeutic immunizations against such cancers as lymphoma, multiple myeloma, melanoma, prostate cancer, renal cell carcinoma, non-small cell lung carcinoma, colon cancer, and even malignant gliomas. DC-based immunizations offer a number of advantages over traditional immunotherapeutic approaches to brain tumors, approaches that have proved promising despite concerns over central nervous system immune privilege and glioma-mediated immunosuppression. The future success of clinical trials will depend on the optimization and standardizing of procedures for DC generation, loading, and administration.
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PMID:The history, evolution, and clinical use of dendritic cell-based immunization strategies in the therapy of brain tumors. 1295 97

An immunoconjugate of doxorubicin (adriamycin) and a tumor-specific monoclonal antibody, BR96-DOX (now SGN-15) targets chemotherapy to cells that express the LewisY antigen. This immunoconjugate is internalized into lysosomes in antigen-expressing cells, with release of free doxorubicin after hydrolysis of the acid-labile linker. We review our studies using BR96-DOX in a human small-cell lung carcinoma intracerebral xenograft model in nude rats. We have found that the immunoconjugate is effective against intracerebral tumors when delivery is enhanced with osmotic disruption of the blood-brain barrier (BBB). Enhanced delivery of BR96-DOX with BBB opening can work together with radiotherapy to increase antitumor efficacy, which is maximally effective if immunoconjugate is administered prior to radiotherapy. In heterogeneous brain tumors, enhanced delivery of BR96-DOX significantly reduced tumor volumes, but local release of doxorubicin by targeting antigen expressing cells shows modest cytotoxicity against adjacent non-expressor cells. Although BR96-DOX is not effective against glioma cells tested, it does provide a model for drug-immunoconjugate therapy of gliomas. Our studies in a rat brain tumor model point out the importance of optimized delivery, antigenic heterogeneity, and bystander effect for brain tumor therapy. We review additional studies of drug-mAb immunoconjugates pertinent to the treatment of gliomas.
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PMID:BR96-DOX immunoconjugate targeting of chemotherapy in brain tumor models. 1464 85

Exposure to environmental radiation and the application of new clinical modalities, such as radioimmunotherapy, have heightened the need to understand cellular responses to low dose and low-dose rate ionizing radiation. Many tumor cell lines have been observed to exhibit a hypersensitivity to radiation doses <50 cGy, which manifests as a significant deviation from the clonogenic survival response predicted by a linear-quadratic fit to higher doses. However, the underlying processes for this phenomenon remain unclear. Using a gel microdrop/flow cytometry assay to monitor single cell proliferation at early times postirradiation, we examined the response of human A549 lung carcinoma, T98G glioma, and MCF7 breast carcinoma cell lines exposed to gamma radiation doses from 0 to 200 cGy delivered at 0.18 and 22 cGy/min. The A549 and T98G cells, but not MCF7 cells, showed the marked hypersensitivity at doses <50 cGy. To further characterize the low-dose hypersensitivity, we examined the influence of low-dose radiation on cell cycle status and apoptosis by assays for active caspase-3 and phosphatidylserine translocation (Annexin V binding). We observed that caspase-3 activation and Annexin V binding mirrored the proliferation curves for the cell lines. Furthermore, the low-dose hypersensitivity and Annexin V binding to irradiated A549 and T98G cells were eliminated by treating the cells with pifithrin, an inhibitor of p53. When p53-inactive cell lines (2800T skin fibroblasts and HCT116 colorectal carcinoma cells) were examined for similar patterns, we found that there was no hyperradiosensitivity and apoptosis was not detectable by Annexin V or caspase-3 assays. Our data therefore suggest that low-dose hypersensitivity is associated with p53-dependent apoptosis.
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PMID:Low-dose radiation hypersensitivity is associated with p53-dependent apoptosis. 1549 30

The crude methanolic extracts of six species of Hypericum growing in southern Brazil (Hypericum caprifoliatum Cham. & Schlecht., H. carinatum Griseb., H. connatum Lam., H. myrianthum Cham. & Schlecht., H. polyanthemum Klotzsch ex Reichardt and H. ternum A. St. Hil.) were screened for their antiproliferative activity against two cell lines (HT-29 human colon carcinoma cells and H-460 non-small cell lung carcinoma). The most active crude extracts were those from H. caprifoliatum, H. myrianthum and, to a lesser extent, from H. connatum. All plants were submitted to fractionation with solvents in increasing polarity and re-assayed for the two cell lines used previously, as well as U-373 human malignant glioma cells. The most active fractions were the hexane fractions obtained from H. caprifoliatum, H. myrianthum and H. ternum.
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PMID:Screening for antiproliferative activity of six southern Brazilian species of Hypericum. 1569 17

N-Phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas were found to be a novel class of potent inhibitors for the vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase through synthetic modifications of a lead compound and structure-activity relationship studies. A representative compound 6ab, termed Ki8751, inhibited VEGFR-2 phosphorylation at an IC(50) value of 0.90 nM, and also inhibited the PDGFR family members such as PDGFRalpha and c-Kit at 67 nM and 40 nM, respectively. However, 6ab did not have any inhibitory activity against other kinases such as EGFR, HGFR, InsulinR and others even at 10000 nM. 6ab suppressed the growth of the VEGF-stimulated human umbilical vein endothelial cell (HUVEC) on a nanomolar level. 6ab showed significant antitumor activity against five human tumor xenografts such as GL07 (glioma), St-4 (stomach carcinoma), LC6 (lung carcinoma), DLD-1 (colon carcinoma) and A375 (melanoma) in nude mice and also showed complete tumor growth inhibition with the LC-6 xenograft in nude rats following oral administration once a day for 14 days at 5 mg/kg without any body weight loss.
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PMID:Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas. 1574 79


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