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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 x 10(7) UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 x 10(5) cells/cm2. The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 microM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm3) were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm3 by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.
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PMID:Characterization and development of UCI 107, a primary human ovarian carcinoma cell line. 767 98

Although the antineoplastic efficacy of Taxol against a variety of tumors has been established, it has only recently been used for malignant brain tumors. We evaluated in vitro chemosensitivity of glioblastoma to Taxol and the affect of Taxol on glioblastoma cell locomotion. The clonogenic assay was used to evaluate the chemosensitivity of five human glioblastomas and the C6 rat glioma. Cells exposed to Taxol (0-250 nM) were suspended in agar in capillary tubes. Following incubation, colonies were counted to determine percent survival. All six cell lines demonstrated sensitivity to Taxol (LD50 1 nM to > 250 nM). However, even at concentrations exceeding those achievable clinically, all cell lines had surviving cells, indicating a saturation threshold for Taxol cytotoxicity. Cell locomotion was evaluated using the radial dish assay to determine the rate of egress of cells from a region of high cell density to the periphery. Increasing Taxol concentration caused increased locomotion in all six cell lines (p < 0.0001). Although Taxol has significant cytocidal impact, it increases in vitro locomotion of glioblastoma cells. These findings suggest that the clinical use of Taxol for glioblastoma may slow the growth of bulk disease, but may also lead to increased tumor invasion.
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PMID:In vitro assessment of Taxol for human glioblastoma: chemosensitivity and cellular locomotion. 779 75

Taxol is a promising agent for use in ovarian cancer and other malignancies. One problem associated with taxol is its low aqueous solubility, requiring Cremophor EL (polyethoxylated castor oil) and ethanol as excipients (Diluent 12); these agents cause serious adverse effects. Liposomes containing taxol and phospholipid (in a 1:33 mole ratio, respectively) were prepared from phosphatidylglycerol and phosphatidylcholine in a 1:9 mole ratio. Antitumor effect was evaluated against Colon-26, a taxol-resistant murine tumor. Given as 1, 4, or 9 injections, free taxol given i.v. in Diluent 12 was ineffective at delaying tumor growth at doses < or = 30 mg/kg per injection (the maximum tolerated dose). In contrast, taxol-liposomes were well tolerated at doses greater than or equal to the maximum tolerated dose of free taxol and showed significant tumor growth inhibition at 10-45 mg/kg per injection.
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PMID:Antitumor effect of taxol-containing liposomes in a taxol-resistant murine tumor model. 790 97

Taxol is a novel antitumor alkaloid that has shown clinical activity against several tumors, including ovarian and breast carcinoma and melanoma. To evaluate taxol's potential as a therapy for malignant brain tumors, we measured the sensitivity of four human (U87, U373, H80, and D324) and two rat (9L, F98) brain-tumor cell lines to taxol. The cells were exposed to taxol in vitro using a clonogenic assay. Log cell kill (LD90) occurred at concentrations of 42 (9L), 25 (F98), 19 (H80), 7.2 (U373), 9.1 (U87), and 3.9 nM (D324) when cells were continuously exposed to taxol for 6-8 days. The human cell lines were uniformly more sensitive to taxol than were the rat lines. The duration of exposure had a significant effect on taxol's cytotoxicity. When cells were exposed to taxol for 1 h the LD90 increased to 890 nM for the 9L rat line and 280 nM for the human U373 line. On the basis of these results, we conclude that taxol has significant potency in vitro against malignant brain tumors and that the activity occurs at concentrations of taxol that have previously been shown to be effective for several tumors against which the drug is currently being evaluated clinically.
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PMID:Cytotoxicity of taxol in vitro against human and rat malignant brain tumors. 790 92

The activity of Taxol and Taxotere was evaluated on three established cell lines and 19 primary cultures of human ovarian cancers and compared with that of cisplatin and doxorubicin. The cytotoxic activity of the different drugs was assessed with a clonogenic assay in cell lines and with a proliferative assay (based on [3H]thymidine [3H-dT] incorporation of cells grown in double-layer agarose for four days) in primary tumor cultures. The two assays run in parallel on the OVCA432 cell line provided similar ranking of activity for all the drugs. Taxotere was more cytotoxic than Taxol in two cell lines and showed the same degree of activity in one cell line. Moreover, the two drugs were more cytotoxic than cisplatin and doxorubicin in all cell lines. In primary cultures both Taxol and Taxotere were less active than cisplatin and doxorubicin. An activity by at least one of these two compounds was seen in 9 of 19 cases. Taxol was more frequently active than Taxotere and generally more potent. A direct relationship was observed between the proliferative activity of the tumor cell population and response to Taxol and/or Taxotere. In fact, cell lines that were highly sensitive to Taxol and Taxotere displayed 3H-dT labeling index (LI) values much higher than those observed in primary cultures (39% to 45% versus 0.2% to 12.6%). Again, primary cultures sensitive to Taxol and/or Taxotere were characterized by a median 3H-dT LI value about three times higher than that observed in resistant cultures (8.0% versus 2.6%).
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PMID:In vitro cytotoxic activity of Taxol and Taxotere on primary cultures and established cell lines of human ovarian cancer. 790 83

In this study the antimicrotubular agents taxol, taxotere, and vinblastine were compared for their ability to inhibit the clonal growth of human bladder tumor cell lines using a soft-agar clonogenic assay. The stability of taxol and taxotere was evaluated by high-performance liquid chromatography over a range of pH in human urine. Both taxol and taxotere were shown to maximally inhibit the clonal growth of human bladder cell lines within 1 h of drug incubation. The most active agent in the panel of tumor lines was taxotere, with 6 of 12 lines being sensitive to the agent at 0.01 microM and all cell lines being sensitive at 0.1 microM. Taxol was active in 1 of 12 lines at 0.01 microM and in 11 of 12 at 0.1 microM. Only 2 of 12 cell lines were sensitive to vinblastine over the 0.01- to 0.1-microM dose range. Taxol and taxotere were found to be stable in human urine for 4 h over a pH range of 5-7. At least 85% of both drugs were present during this period of drug incubation. Our findings suggest that both taxol and taxotere may be clinically useful agents for systemic and intravesical use in bladder cancer.
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PMID:Taxol and taxotere in bladder cancer: in vitro activity and urine stability. 790 52

Taxol is a novel antitumor agent with demonstrated efficacy against ovarian, breast, and non-small cell lung cancers in Phase II clinical trials, but which has been shown not to cross the blood-brain barrier. To adapt taxol as a therapy for brain tumors, we have incorporated it into a biodegradable polyanhydride matrix for intracranial implantation and evaluated this formulation in a rat model of malignant glioma. Fischer 344 rats bearing intracranial 9L glioma tumors were treated with 10 mg poly[bis(p-carboxyphenoxy)propane-sebacic acid] (20:80) copolymer discs, containing 20-40% taxol by weight, 5 days after tumor implantation. The taxol-loaded polymers doubled (38 days, 40% taxol loading, P < 0.02) to tripled (61.5 days, 20% taxol loading, P < 0.001) the median survival of rats bearing tumor relative to control rats (19.5 days). Drug loadings of 20-40% taxol by weight released intact taxol for up to 1000 h in vitro. In rats followed up to 30 days postimplant, the polymer maintained a taxol concentration of 75-125 ng taxol/mg brain tissue (100-150 microM taxol) within a 1-3-mm radius of the disc. At points more distant from the disc (up to 8 mm away, the size limit of the rat brain), the polymer maintained a taxol concentration of greater than 4 ng taxol/mg brain tissue (5 microM). We conclude that taxol shows promise as a therapy for malignant glioma when delivered interstitially from a biodegradable polymer.
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PMID:Interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma. 790 20

Taxol, dissolved in cremophor/ethanol (50/50), followed by further dilution with saline, was successfully administered intravenously (IV) to mice bearing subcutaneously (SC) implanted murine Madison 109 lung carcinoma (M109), M5076 sarcoma, or seven different human tumor xenografts, including A431 vulva; A2780 ovarian; LX-1, H2981, and L2987 lung; and RCA and HCT-116 colon carcinomas. Taxol was active in all these distal site tumor models except the M5076 sarcoma. Schedule dependency and dose-response evaluations involving Taxol were studied in the SC M109 model. Taxol was given IV, and all treatments were of 7 days' duration. Each schedule was evaluated using several dose levels designed to incorporate the likely optimal (and maximum tolerated) dose(s). On the best schedule, daily injections for 7 days, Taxol exhibited a flat dose response; that is, good activity was obtained at Taxol dose levels that were only a fraction of its maximum tolerated dose. This profile provided an advantageous opportunity to evaluate Taxol-based combination chemotherapy. In a format in which Taxol was given every day on days 1 through 5, IV, and other drugs were given on days 1 and 5 (IV or intraperitoneally, IP) versus SC M109, dose titrations of each agent were evaluated singularly and in various Taxol-based combinations. The combination of Taxol plus cisplatin yielded a delay in tumor growth (17.8 days) that was minimally superior (P < .05) to the best delays caused by either drug alone (e.g., 13.5 days for Taxol); there was no enhancement of lifespan beyond that obtained using Taxol alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Taxol-based combination chemotherapy and other in vivo preclinical antitumor studies. 791 29

The purpose of this study was to estimate the potential usefulness of currently available chemosensitizers (CS) for clinical reversal of P-glycoprotein-mediated Taxol resistance. The 8226/DOX6 human myeloma cells were used to evaluate CS effects in serum-rich medium by means of the human tumor cloning assay. The 8226/DOX6 cells express low levels of P-glycoprotein as typically found in clinical cancer specimens and are approximately 40-fold resistant to Taxol when continuously exposed to the drug in serum-rich medium. The CS were used at maximum tolerated plasma levels (Cmax) and at the concentrations achieved in human plasma by oral administration (Coral). Of nine CS tested, cyclosporine A (CSA), verapamil (VER), quinidine (QD), and quinine (Q) were able to overcome Taxol resistance. QD and Q were effective at Coral, whereas CSA and VER required Cmax to significantly enhance Taxol cytotoxicity. The most potent agent was CSA, which increased sensitivity to Taxol by 8-, 12-, and 18-fold when used at concentrations of 1.0, 2.0, and 4.0 microM, respectively. At 5.0 microM, CSA was capable of fully normalizing Taxol sensitivity. On the basis of these data, infusional CSA might prove useful for clinical reversal of P-glycoprotein-associated Taxol resistance. It remains to be seen, however, whether the CSA concentrations needed to reverse Taxol resistance effectively can be safely achieved in human plasma when CSA is coadministered with Taxol.
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PMID:In vitro evaluation of chemosensitizers for clinical reversal of P-glycoprotein-associated Taxol resistance. 791 31

Taxol is a complex diterpenoid natural product under investigation for therapy of colon, ovarian, lung, and breast cancer, as well as for melanoma and lymphoma. One problem associated with the administration of Taxol is its low solubility; the formulation used clinically contains polyethoxylated castor oil (Cremophor EL) and ethanol as excipients. Cremophor EL is implicated in hypersensitivity reactions observed on infusion of Taxol. To eliminate the Cremophor EL vehicle and possibly improve the antitumor efficacy of Taxol, a systematic approach was taken to formulate Taxol in phospholipid suspensions (liposomes). Prototype formulations were developed that have sufficient chemical and physical stability to test the hypothesis that liposomes can alter the pharmacology of Taxol, in addition to providing a biologically compatible carrier in which to administer the drug. In vitro. Taxol liposomes retain the growth-inhibitory activity of free Taxol against a variety of tumor cell lines. In vivo, preliminary results showed no effect of free Taxol (in Cremophor EL) on the growth of Colon-26, a Taxol-resistant murine tumor, when given at doses that included or exceeded the maximum tolerated dose (MTD). In contrast, Taxol liposomes delayed tumor progression at a dose that exceeded the MTD of free Taxol.
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PMID:Novel Taxol formulations: Taxol-containing liposomes. 791 32


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