Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Taxol is a new cytotoxic agent which arrests cell division in the G2 and the M phases, due to its unique property of inhibiting microtubule function by stabilization. In contrast to other microtubule antagonists except griseofulvin, taxol did not inhibit monocyte phagocytosis. It is suggested that lack of interference with the function of mature leukocytes may reduce the immunosuppression induced by a cytotoxic agent.
Med Oncol Tumor Pharmacother 1988
PMID:A cytostatic drug (taxol) which does not inhibit monocyte phagocytosis. 290 Sep 16

For several reasons, including its demonstrated activity in ovarian cancer, large size, hepatic metabolism, and lack of vesicant properties, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an interesting agent to consider for intraperitoneal administration in the management of ovarian cancer. Two phase I trials have confirmed a major pharmacokinetic advantage (> or = 1,000-fold) for peritoneal cavity exposure compared with the systemic compartment following intraperitoneal delivery of paclitaxel. A Gynecologic Oncology Group phase II trial of second-line intraperitoneal paclitaxel in ovarian cancer patients is currently in progress to determine whether the high concentrations and prolonged duration of exposure to paclitaxel of the surface of the peritoneal cavity can be translated into increased tumor cell kill and objective responses in this clinical setting. Future development of this novel therapeutic strategy will depend on the results of this important clinical trial.
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PMID:Intraperitoneal paclitaxel in the management of ovarian cancer. 748 68

The anticancer drug, taxol, blocks cell division by stabilizing microtubules. However, taxol has distinct cell-cycle-independent effects. For example, taxol and bacterial LPS induce strikingly similar responses in murine macrophages. Here we report that taxol, like LPS, provides a "second" signal for murine macrophage activation to tumoricidal activity. Tumoricidal activity was determined by the release of 51Cr from prelabeled P815 mastocytoma target cells. Taxol or LPS alone weakly induced C3H/OuJ (Lpsn) murine macrophages to kill P815 mastocytoma cells, and tumoricidal activity was not induced by the classic "priming" signal, IFN-gamma. However, combinations of taxol or LPS with IFN-gamma synergized to activate macrophages to lyse tumor cells. Taxol activation of macrophages required an intact LPS signaling pathway, as taxol did not induce IFN-gamma-treated C3H/HeJ (Lpsd) macrophages to lyse target cells. In normal (Lpsn) murine macrophages, IFN-gamma, LPS, or taxol alone induced low or moderate levels of nitric oxide synthase gene expression and nitric oxide secretion. However, this gene and cytostatic metabolite were induced synergistically by combinations of taxol or LPS with IFN-gamma. Secretion of nitric oxide correlated with tumor cell killing, and taxol-activated macrophages failed to kill tumor targets in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. The data illustrate the potential for taxol to activate macrophage mediated-antitumor mechanisms in addition to its better characterized role as an anti-mitotic agent.
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PMID:Taxol provides a second signal for murine macrophage tumoricidal activity. 750 36

A cooperative, phase II single-arm trial was conducted at two large tertiary referral cancer centers to evaluate the antineoplastic activity and toxicities of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced esophageal cancer. The drug was given at a dose of 250 mg/m2 as a 24-hour continuous infusion. Repeat courses were given at 21-day intervals. De-escalation was based primarily on myelosuppression. All patients received recombinant human granulocyte colony-stimulating factor to minimize the risk of neutropenic fever. The primary goal of the study was tumor response. In the trial, which is ongoing, 42 patients have been assessed to date. Adenocarcinoma was the predominant histology in 30 patients, while epidermoid cancer was seen in 13 patients. Paclitaxel was identified as an active agent. Thirty percent of patients with adenocarcinoma and 25% of the smaller group with epidermoid carcinoma have had partial remissions. Complete remissions have not been seen to date. The median duration of response was 9 weeks. The major toxicity was myelosuppression; 11 patients required admission for neutropenic fever on 13 different occasions. Paclitaxel is an active drug in the treatment of esophageal cancer. Currently, there does not appear to be a difference in response on the basis of histologic subtype. Further studies with paclitaxel in combination with other drugs (eg, cisplatin and 5-fluorouracil), on different treatment schedules, and as part of multimodality therapy are indicated.
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PMID:A phase II trial of paclitaxel (Taxol) in advanced esophageal cancer: preliminary report. 752 58

Lung cancer cell lines are between seven and 1,000 times more sensitive to paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) when exposed for 120 hours (5 days) compared with 3-hour exposure. A phase I study of 4-day infusion of paclitaxel plus bolus cisplatin for patients with lung cancer has defined the recommended phase II dose. In this study, paclitaxel infused at 30 mg/m2/d for 4 days followed by a cisplatin bolus of 80 mg/m2 after infusion completion was associated with acceptable hematologic toxicity. Nine of the 16 patients with non-small cell lung cancer treated with at least two cycles of this regimen attained an objective tumor response (one complete response and eight partial responses; overall response rate, 56%). The recommended phase II dose of a 4-day infusion of paclitaxel plus bolus cisplatin followed by the administration of granulocyte colony-stimulating factor has not yet been determined.
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PMID:Four-day paclitaxel infusion with cisplatin for patients with lung cancer. 754 27

Taxol is a novel cytostatic agent which inhibits the depolymerisation of microtubulin. The stabilization of this important substance leads to cellular arrest and consecutively apoptosis. Accordingly, taxol is capable to influence neoplastic growth in several malignancies. At present the following standard regimen is recommended: 175 mg/m2 taxol in a 3-hour i. v. infusion following corticosteroid + diphenhydramine + cimetidine premedication. Its antitumour activity has been proved especially in advanced ovarian and breast cancer. Encouraging results have been reported in various bronchial, testicular malignancies, lymphomas and leukemias. Clinical investigations in several other malignancies are ongoing.
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PMID:[Use of taxol in the management of malignant tumors]. 756 29

In this study we evaluated the antitumor efficacy of taxol in four solid tumor models derived from wap-ras line 69 transgenic mice. Taxol inhibited the growth of spontaneous salivary and mammary gland adenocarcinomas in wap-ras mice. In nude mice it was also effective against solid tumors caused by WR21 cells derived from a wap-ras salivary gland tumor. Taxol was not able to prevent tumor emergence in wap-ras/F mice, a subline of the wap-ras strain in which all males develop palpable mammary gland tumors between 1.5 and 3.0 months of age. Our data indicate the range of results that can be expected when this panel of related transgenic tumor models is used to study the antitumor effects of taxol and other therapeutic drugs that act by affecting tubulin polymerization. These models of ras-mediated neoplasia should prove useful for testing anticancer compounds with taxol-like mechanisms of action.
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PMID:Strategy for developing transgenic assays for screening antineoplastic drugs that affect tubulin polymerization. 760 14

Three metabolites of the cytotoxic drug paclitaxel (Taxol) were isolated and purified from the feces of cancer patients receiving the agent as an intravenous infusion. The procedures involved sample homogenization in water followed by liquid-liquid extraction with diethyl ether and high-performance liquid chromatography (HPLC). Approximately 1-3.5 mg of each metabolite was obtained from 100 g of feces. As judged from the chromatographic traces of analytical HPLC with ultraviolet (UV) detection at 227 nm, the purity of each compound was > 97%. On-line photodiode-array detection demonstrated that the UV spectrum of the isolated compounds closely resembles that of the parent drug. Mass spectrometry provided evidence that these metabolites are mono- and dihydroxy-substituted derivatives, namely, 6 alpha-hydroxypaclitaxel, 3'-p-hydroxypaclitaxel, and 6 alpha, 3'-p-dihydroxypaclitaxel. The two 6 alpha-hydroxy-substituted metabolites were shown to have lost their cytotoxicity in in vitro clonogenic assays using the A2780 human ovarian carcinoma and the CC531 rat colon-carcinoma tumor cell lines. In addition, the metabolites showed reduced myelotoxic effects as compared with paclitaxel in an in vitro hemopoietic progenitor toxicity assay. Our procedure for the isolation and purification of paclitaxel metabolites in milligram quantities should be useful for testing the biological activities of these compounds and for the preparation of calibration standards essential for pharmacokinetics studies.
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PMID:Isolation, purification, and biological activity of mono- and dihydroxylated paclitaxel metabolites from human feces. 762 49

Taxol is the prototype of a class of antineoplastic drugs that target microtubules. It enhances tubulin-monomer polymerization and stabilizes tubulin polymers, increasing the fraction of cells in the G2 or M phase of the cell cycle. We report that treatment of HL-60 and U937 myeloid cell lines with 1-10 microM taxol induces DNA fragmentation and the appearance of morphological features consistent with the process of apoptosis. Taxol-induced apoptosis is inhibited neither by cycloheximide nor by actinomycin D and therefore appears to be independent of new protein synthesis. Taxol causes arrest in the G2 phase of the cell cycle and affects cell viability but does not induce DNA fragmentation in the K562 erythromyeloid cell line. Protein-synthesis inhibitors, colcemid, ionomycin, and starvation, known to trigger apoptosis, proved ineffective as well. These results suggest that the antineoplastic effect of taxol is mediated in susceptible cell lines by induction of the apoptotic machinery and that K562 partial resistance may depend upon the intrinsic inability of these tumor cells to undergo apoptosis.
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PMID:Taxol cytotoxicity on human leukemia cell lines is a function of their susceptibility to programmed cell death. 763 80

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an attractive agent to combine with radiation for non-small cell lung cancer. We have been conducting clinical trials of weekly paclitaxel and concurrent radiation therapy. In a phase I study in non-small cell lung cancer, we determined the maximum tolerated dose of paclitaxel to be 60 mg/m2/wk with radiation. Patients received paclitaxel 60 mg/m2/wk as a 3-hour infusion for 6 weeks with radiation to the primary tumor and regional lymph nodes (40 Gy) followed by a boost to the tumor (20 Gy). From March 1994 to February 1995, 33 patients have been entered by the Clinical Oncology Group of Rhode Island. The overall response rate (complete plus partial responses) of 25 evaluable patients as of March 1995 was 84%, with a confidence interval of 68 to 96. The major toxicity was esophagitis. Twenty percent of patients had grade 4 esophagitis. Only 8% of patients had grade 3 neutropenia. Combined-modality therapy with paclitaxel and radiation is a promising treatment for locally advanced non-small cell lung cancer with a high response rate and acceptable toxicity.
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PMID:Preliminary analysis of a phase II study of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer. 764 29


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