Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxol, a microtubule-stabilizing agent, has been shown to have antineoplastic activity against various tumors. In addition, it has been shown that taxol resembles bacterial lipopolysaccharide in its ability to activate macrophages. Recently we have shown that lipopolysaccharide induces the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) in murine B-cell lines. In light of the similarity of taxol and lipopolysaccharide in their effects on macrophages, we tested whether taxol could also induce the expression of GM-CSF in B-cell lines. In the present study we used the murine B-lymphoma cell line M12.4.1. In unstimulated cells, no GM-CSF mRNA was detected, whereas in taxol-stimulated stimulated cells at a concentration of 30 microM, GM-CSF mRNA was induced 4-8 h after stimulation. This induction of GM-CSF mRNA was down-regulated by 10 ng/ml of interleukin 4. Actinomycin D chase experiments revealed that interleukin 4 did not affect the half-life of the taxol-induced GM-CSF cytoplasmic mRNA, nor did it alter GM-CSF gene transcription. Polymerase chain reaction analysis of nuclear RNA, utilizing probes specific for sequences in the first intron of GM-CSF, indicated that taxol enhances accumulation of nuclear precursor RNA and that interleukin 4 decreases this accumulation. The present study shows a novel activity of taxol in inducing the release of the hematopoietic growth factor GM-CSF from B-cells. Since GM-CSF is known to recruit macrophages and enhance their cytotoxicity against tumor cells, our observations suggest that part of the known antitumor activity of taxol may be due to synergistic effects of GM-CSF activity together with direct cytotoxic actions through microtubule stabilization.
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PMID:Taxol induces the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor in murine B-cells by stabilization of granulocyte-macrophage colony-stimulating factor nuclear RNA. 791 12

A dose-finding study was performed in 27 ovarian cancer patients to define the maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with a fixed dose of carboplatin. The median age of the patients was 55 years (age range, 30 to 74 years), the median performance status was 0 (range, 0 to 2), and the sizes of tumors residual to first surgery were identified as > or = 1 cm (14 patients) or less than 1 cm (13 patients). All patients received carboplatin at a fixed dose of 300 mg/m2 over 1 hour. Paclitaxel was administered as a 3-hour infusion at five dose levels, starting at 150 mg/m2 and increasing in 25 mg/m2 increments to 250 mg/m2. In the absence of toxicity, courses were repeated every 4 weeks for a total of six cycles. Mild emesis, general alopecia, and moderate myalgias occurred. Hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients, respectively. Moderate peripheral neuropathy was experienced by 30% of patients. Grade 3 and 4 neutropenia lasted less than 7 days; no patients required hospitalization for sepsis or febrile neutropenia, and no supportive treatment with granulocyte/granulocyte-macrophage colony-stimulating factor was needed. Twenty-one patients were evaluable for response. Overall response rate (complete response+partial response) was 81%, and responses were observed at all paclitaxel dose levels. The maximum tolerated dose was not achieved. In conclusion, with a fixed dose (300 mg/m2) of carboplatin, paclitaxel can be administered by 3-hour infusion at 250 mg/m2 with manageable toxicity and no supportive care is needed.
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PMID:Pilot study with fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. 855 81

A dose-finding study involving 27 untreated patients with ovarian cancer was performed to define the maximum tolerated dose of a 3-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combined with a fixed dose of carboplatin. The median age of the study patients was 55 years (age range, 30 to 74 years), the median Eastern Cooperative Oncology Group performance status was 0 (range, 0 to 2), and residual tumor to first surgery was > or = 1 cm in 14 patients and less than 1 cm in 13 patients. All patients received carboplatin at a fixed dose of 300 mg/m2 over 1 hour. Paclitaxel was administered at five dose levels starting at 150 mg/m2 and increasing in 25-mg/m2 increments to 250 mg/m2. In the absence of toxicity, courses were repeated every 4 weeks for a total of six cycles. World Health Organization grade 1 hypersensitivity and cardiotoxicity were observed in 7.4% and 14.8% of patients, respectively. Moderate peripheral neuropathy was experienced by 29.6% of patients. Grades 3 and 4 neutropenia lasted less than 7 days; no patient required hospitalization for sepsis or febrile neutropenia, and no supportive treatment with granulocyte or granulocyte-macrophage colony-stimulating factor was needed. The maximum tolerated paclitaxel dose was not achieved.
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PMID:A phase I trial with fixed-dose carboplatin and escalating doses of paclitaxel in advanced ovarian cancer. 904 31