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

A survey of 56 normal and neoplastic tissues has shown that plasminogen activators were released by cultured human cells in several molecular weights and their susceptibility to inhibition by antibodies to the normal urinary enzyme, urokinase. Melanoma cells characteristically secreted plasminogen activators which were immunochemically distinct from urokinase and which migrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a prominent, closely spaced doublet with an apparent molecular weight of approximately 70,000 and a minor molecular weight component of approximately 60,000. Enzymes with similar characteristics have been observed in serum-free harvest fluids collected from other neoplastic tissue (a breast carcinoma, a glioblastoma, a malignant teratoma, a uterine sarcoma, and a carcinoma of the renal pelvis) and from normal tissue (8-week embryo fibroblasts, normal esophageal fibroblasts, and one culture of normal adult bladder epithelium). Plasminogen activators released by cells derived from most normal adult tissues, or from a 26-week-old embryo, and from other tumors of ectodermal or mesenchymal origin were inhibited by anti-urokinase antibody and showed a closely spaced doublet with a molecular weight of 60,000 as the most abundant molecular species with no evidence of the enzyme with a molecular weight of 70,000.
 ...
PMID:Molecular species of plasminogen activators secreted by normal and neoplastic human cells. 719 17

O6-methylguanine-DNA methyltransferase (MGMT) gene promoter hypermethylation is observed in a number of solid tumors and is correlated with the silencing of MGMT expression. In glioblastoma patients treated with the alkylating agent temozolomide, MGMT gene methylation status was shown to have predictive value in terms of prolonged overall survival. Recently, temozolomide has demonstrated promising activity in the treatment of soft tissue sarcomas, including those of the uterus. The tissue specimens involving tumor samples and normal uterine fragments were obtained from nine patients with smooth muscle uterine sarcoma, 11 with stromal uterine sarcoma and 17 with mixed uterine tumors. MGMT gene promoter methylation was analyzed by combined bisulfite restriction analysis (COBRA) while its expression levels were assessed using the real-time reverse transcription polymerase chain reaction (qRT-PCR). MGMT promoter methylation was observed in 27% of all tumor samples analyzed. When stratified by the disease type, 55.5% (5/9) of smooth muscle sarcomas, 23.5% (4/17) of mixed uterine tumor tissues and 9% (1/11) of stromal sarcomas showed MGMT methylation. The MGMT promoter methylation was associated with lower levels of gene expression in tumors when compared with those with an unmethylated promoter (P=0.0232) or normal tissues (P=0.0141). To conclude, MGMT promoter methylation and downregulation of gene expression is observed in a fraction of carcinosarcomas and non-epithelial malignant tumors of corpus uteri. The assessment of MGMT promoter methylation status may potentially identify patients who would benefit from temozolomide treatment.
 ...
PMID:The promoter methylation and expression of the O6-methylguanine-DNA methyltransferase gene in uterine sarcoma and carcinosarcoma. 2297 54

A new alkaloid, belonging to the pretazettine group of Amaryllidaceae alkaloids, was isolated from dried bulbs of Narcissus jonquilla quail and named jonquailine. Its structure, including the absolute configuration, was elucidated using various NMR, ECD and ESI MS techniques. Initial biological evaluation revealed significant antiproliferative effects against glioblastoma, melanoma, uterine sarcoma and non-small-cell lung cancer cells displaying various forms of drug resistance, including resistance to apoptosis and multi-drug resistance. Jonquailine was also found to synergize with paclitaxel in its antiproliferative action against drug-resistant lung cancer cells. The results obtained compared with literature data also showed that the hydroxylation at C-8 is an important feature for the anticancer activity but this seems unaffected by the stereochemistry or the acetalization of the lactol.
 ...
PMID:Jonquailine, a new pretazettine-type alkaloid isolated from Narcissus jonquilla quail, with activity against drug-resistant cancer. 2559 89

Isoxanthohumol (2) and its 4'-O-monoacylated (3) and 7,4'-O-diacetylated (4) derivatives were synthesized and evaluated in vitro for their cytotoxic activity against several cancer cell lines of various origins: MCF-7 (breast), A549 (lung), MESSA (uterine sarcoma), LoVo (colon), drug-resistant human cancer cells (MESSA/DX and LoVo/DX), glioblastoma (U-118 MG), and also towards the non-cancerous cell line MCF-10A (normal breast cells). An antiproliferative assay indicates that 7,4'-di-O-acylisoxanthohumol (4) has similar cytotoxicity to its precursor, isoxanthohumol (2), against selected cell lines (A549, MES-SA, MES-SA/5DX, and U-118 MG). Compound 4 was only slightly more cytotoxic to lung, colon, breast (cancerous and normal) and uterine sarcoma (drug sensitive and drug resistant) cell lines compared to its monoacylated derivative (3). Both acylated isoxanthohumols showed preferential activity against tumor cells (MCF-7) and low cytotoxicity to normal cells (MCF-10A), which suggests selectivity of the acylated isoxanthohumols towards cancer cells. Additionally, the activity of the acylated isoxanthohumols was higher than for 2. To the best of our knowledge this is the first report on bioactivity of monoacylated isoxanthohumol (3) and its ester derivatives as antiproliferative compounds in drug resistant cell cultures. Acylation of 2 decreased the antioxidant activity determined by the DPPH method in the order isoxanthohumol (2) >4'-O-acetylisoxanthohumol (3) >7,4'-di-O-acetylisoxanthohumol (4).
 ...
PMID:Synthesis and biological evaluation of 4'-O-acetyl-isoxanthohumol and its analogues as antioxidant and antiproliferative agents. 2880 57