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)

Survival of patients with advanced stage malignant mixed mullerian tumor of the ovary is poor and the best treatment remains unknown. A 62-year-old woman diagnosed with stage IIIC heterologous malignant mixed mullerian tumor of the ovary underwent optimal cytoreductive surgery followed by paclitaxel (135 mg/m2 over 24 hours) and cisplatin (75 mg/m2) every 4 weeks for 6 courses. The patient tolerated chemotherapy well, had complete clinical response and remained without disease for 21 months following diagnosis. Paclitaxel and cisplatin may be effective in malignant mixed mullerian tumors of the ovary.
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PMID:Good response of malignant mixed mullerian tumor of the ovary to paclitaxel and cisplatin chemotherapy. 1060 93

The efficacy of systemic chemotherapy for non-small cell lung cancer (NSCLC) has improved with newer agents. However, the response rates and prolonged survival times achieved by chemotherapy remain modest, and these small gains are obtained at the cost of significant toxicity. In this study, the efficacy of a controlled release formulation of paclitaxel was compared with conventional paclitaxel in animals with human lung cancer xenografts. Paclitaxel (10%) was encapsulated in a proprietary polymer in the form of microspheres (PACLIMER Delivery System). Tumor nodules comprised of two different cell lines (A549 and H1299) were treated by a single i.p. or intratumoral administration of conventionally formulated paclitaxel or a single intratumoral injection of the PACLIMER Delivery System. In vitro testing demonstrated that paclitaxel was released slowly from the microspheres with >80% released after 90 days. Direct comparison of the highest dose for all formulations (24 mg/kg) showed that for nodules comprised of either NSCLC cell line, growth of the PACLIMER Delivery System-treated nodules were inhibited significantly more than the groups treated with conventional paclitaxel or the vehicle controls. Tumor volume doubling times for A549 and H1299 nodules treated with PACLIMER Delivery System were 60 and 35 days, respectively, compared with 10 and 11 days, respectively, in the nodules treated with the conventional paclitaxel by intratumoral administration. We conclude that intratumoral administration of the PACLIMER Delivery System may substantially increase the efficacy of paclitaxel for the therapy of local-regional NSCLC.
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PMID:Enhanced efficacy of a novel controlled release paclitaxel formulation (PACLIMER delivery system) for local-regional therapy of lung cancer tumor nodules in mice. 1063 66

Despite the generally high cure rate in patients with metastatic testicular cancer, 20% to 30% of treated patients will become candidates for salvage chemotherapy. We reviewed the recent salvage chemotherapy trials of refractory diseases. CPT-11 is a new derivative of camptothecin and has activity in a variety of solid tumors. We evaluated the antitumor effect of combination chemotherapy using CDDP and CPT-11 against refractory testicular cancer. Fourteen patients who failed to achieve complete remission with salvage chemotherapy were treated with combination chemotherapy with CPT-11 and CDDP or 254-S (nedaplatin) as third line chemotherapy. Six patients remain alive and disease-free and 5 patients died of disease. The combination of CPT-11 and either CDDP or nedaplatin was significantly more effective than other salvage therapy regimens such as VIP. Paclitaxel, ifosfamide, etoposide regimens were also effective in patients with refractory testicular tumors. We concluded that these combination regimens demonstrated significant activity against refractory testicular tumor and further investigation is warranted.
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PMID:[The salvage chemotherapy for refractory testicular cancer with novel anticancer agents]. 1063 49

Paclitaxel is a frontline therapy for ovarian cancer. Our laboratory has shown that paclitaxel induces IL-8, a member of the C-X-C family of chemokines, in subsets of human ovarian cancer cells. However, the critical issue concerns the biological significance of this chemokine in human ovarian cancer. To study the influence of IL-8 on tumor growth, human ovarian cancer cell lines were transfected with an expression vector for human IL-8 and tested for their ability to form tumors in nude mice. IL-8 expression by the transfected cells did not alter their growth properties in vitro. In contrast, tumor growth in vivo was significantly attenuated in animals receiving IL-8-expressing cells when compared with mice injected with control cells. As additional evidence that IL-8 is a crucial factor in tumor growth, it was noted that ovarian cell lines in which constitutive IL-8 expression is elevated did not form tumors. Injection of neutralizing Ab to IL-8 reverted the phenotype and caused tumor growth in vivo. Examination of tissue from the inoculation site revealed a dramatically elevated cellularity, containing neutrophils and macrophages, in mice receiving IL-8-expressing tumor cells. These results suggest that IL-8 production by human ovarian tumor cells can play a role in reducing the rate of tumor growth; this effect may be mediated by the increased targeting of neutrophil and other mononuclear cells to the tumor injection site. These studies indicate a role for IL-8 in ovarian cancer control and suggest that chemotherapy-induced IL-8 may have a positive role in controlling tumor growth.
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PMID:IL-8 reduced tumorigenicity of human ovarian cancer in vivo due to neutrophil infiltration. 1067 19

We report here the toxicity and therapeutic effects of 2'-alpha-bromohexadecanoyl paclitaxel (BrC16HT), a prodrug form of paclitaxel, in mice. Paclitaxel is the active ingredient of Taxol. The maximum tolerated dose, at a one dose per day for 5-day schedule, was 37.5 mg/kg for BrC16HT compared to 12.5 for Taxol administered IP, and was 12.5-25 mg/kg for either agent administered IV. Dose-dependent therapeutic effects were found for BrC16HT against a human ovarian tumor (OVCAR-3) grown in SCID mice. IP treatments with BrC16HT against early or established IP-implanted OVCAR-3 tumor increased mean survival times more than treatment with Taxol. Long-term survivors were found only in groups treated with BrC16HT. Intravenously administered BrC16HT was more effective than Taxol against SC OVCAR-3 tumor. Early treatment (25 mg/kg x 5) completely inhibited tumor growth through 120 days after tumor implantation. Pharmacokinetic studies suggest that BrC16HT is slowly hydrolyzed to paclitaxel and circulates longer than paclitaxel from Taxol. Thus, BrC16HT may provide sustained levels of paclitaxel, which may contribute to the increased efficacy of BrC16HT compared to Taxol.
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PMID:Growth inhibition of a human ovarian tumor by a novel paclitaxel derivative in SCID mice. 1069 Oct 29

Paclitaxel and cisplatin are associated with dose-limiting neurotoxicity that may result from their differing effects on microtubule stability in peripheral nerves. We hypothesized that such different actions of paclitaxel and cisplatin could be exploited to minimize their neurotoxicity by giving them in combination. Paclitaxel (9-18 micromol/kg/week or 7.7-15.4 mg/kg/week) and cisplatin (5-10 micromol/kg/week or 1.5-3 mg/kg/week) were given alone and in combination to female Wistar rats. Treatment was given once per week for a total of 7-10 weeks. Paclitaxel and cisplatin were given 24 h apart when they were given in combination. Changes in sensory nerve conduction velocity (SNCV) and dorsal root ganglia (DRG) morphology were measured. The nature of their interaction was analyzed using an isobologram. Their antitumor activity alone or in combination was also determined in C57B1/6 mice bearing colon 38 tumors. Reductions in SNCV occurred with paclitaxel alone (P = 0.009), cisplatin alone (P = 0.012), and cisplatin given 24 h before paclitaxel (P < 0.0001). In contrast, there was no significant change in SNCV with paclitaxel given 24 h before cisplatin (P = 0.11). An isobologram showed that the SNCV effects of the drug combinations were less than additive or antagonistic. Cisplatin-induced morphometric changes in DRG neurons were less marked when cisplatin was given with paclitaxel (P = 0.004). Concentrations of platinum in dorsal root ganglia, sural nerves, and sciatic nerves were not altered by giving paclitaxel before cisplatin. Tumor growth delays (TGD) were greater after treatment with paclitaxel (23.4 micromol/kg or 20 mg/kg) given 24 h before cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 7.5 days) than after paclitaxel (23.4 micromol/kg or 20 mg/kg) (TGD = 2.0 days) or cisplatin (23.3 micromol/kg or 7 mg/kg) (TGD = 3.5 days) alone. Paclitaxel and cisplatin antagonized each other's neurotoxicity in Wistar rats. Combining cytotoxic agents with opposing effects on peripheral nerves has potential for minimizing neurotoxicity in patients.
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PMID:Neuroprotective interactions in rats between paclitaxel and cisplatin. 1069 Oct 31

Rob Paclitaxel (Taxol; Bristol-Myers Squibb Company Princeton, NJ) showed antitumor activity in patients with germ cell tumors resistant to combination cisplatin-containing chemotherapy and was included in two risk-directed first-line combination salvage programs. Patients with relapsed germ cell tumors originating from a testis primary site were treated in a phase I/II trial with conventional-dose paclitaxel, ifosfamide, and cisplatin. Fifteen of 21 evaluable patients (71%) achieved a complete or partial response with normal serum tumor markers; 12 patients (57%) remain progression free with a median follow-up period of 15 months. Accrual to this trial continues to further define efficacy and toxicity. In a second trial, patient with cisplatin-resistant germ cell tumors and unfavorable prognostic features (prior incomplete response or an extragonadal primary site) were treated with a dose-intensive program consisting of rapid recycling of paclitaxel plus ifosfamide followed by carboplatin plus etoposide with stem cell support. Twenty-one of 37 assessable patients (57%) achieved a complete response and two (5%) achieved a partial response with negative serum tumor markers; 15 (41%) of these patients remain in durable response with a median follow-up period of 30 months.
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PMID:Paclitaxel (Taxol) combination therapy for resistant germ cell tumors. 1069 42

The purpose of this study was to retrospectively predict the chemotherapy response to paclitaxel in non-small cell lung cancer (NSCLC) using technetium-99m methoxyisobutylisonitrile (Tc-99m MIBI) chest single-photon-emission computed tomography (SPECT) to detect the expression of multidrug-resistance-mediated Mr 170,000 P-glycoprotein. Before chemotherapy with Paclitaxel (Taxol), 30 patients with stage IIIb or IV NSCLC were enrolled in this study. Early chest SPECT 10 min after i.v. injection of Tc-99m MIBI was performed to qualitatively interpret Tc-99m MIBI chest SPECT visually and quantitatively calculate early tumor:normal lung ratios (T:NL) for quick assessment of multidrug-resistant P-glycoprotein expression in NSCLC. On the basis of qualitatively visual interpretation of early Tc-99m MIBI chest SPECT, all of 15 (100%) cases with good response to chemotherapy with Taxol could be detected but 10 (67%) of 15 cases with poor response could not be detected. Early Tc-99m MIBI chest SPECT could correctly predict chemotherapy response in 25 (83%) of 30 of cases. The early T:NL were 3.30 +/- 0.82 for 15 patients with good response and 2.02 +/- 0.19 for 5 patients with poor response. The differences were significant (P < 0.05) by independent Student t tests. However, no significant differences were found for other prognostic factors (age, sex, tumor size, tumor location, stage, and cell type) between good-response and poor-response patients. Early Tc-99m MIBI chest SPECT has the potential to predict chemotherapy response to Paclitaxel.
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PMID:Quickly predicting chemotherapy response to paclitaxel-based therapy in non-small cell lung cancer by early technetium-99m methoxyisobutylisonitrile chest single-photon-emission computed tomography. 1074 2

Paclitaxel (Taxol) kills tumor cells by inducing both cellular necrosis and apoptosis. A major impediment to paclitaxel cytotoxicity is the establishment of multidrug resistance whereby exposure to one chemotherapeutic agent results in cross-resistance to a wide variety of other drugs. For example, selection of MCF-7 breast cancer cells for resistance to doxorubicin (MCF-7ADR cells) results in cross-resistance to paclitaxel. This appears to involve the overexpression of the drug transporter P-glycoprotein which can efflux both drugs from tumor cells. However, MCF-7ADR cells possess a deletion mutation in p53 and have considerably reduced levels of the Fas receptor, Fas ligand, caspase-2, caspase-6, and caspase-8, suggesting that paclitaxel resistance may also stem from a bona fide block in paclitaxel-induced apoptosis in these cells. To address this issue, we examined the ability of the P-glycoprotein inhibitor valspodar to restore paclitaxel accumulation, paclitaxel cytotoxicity, and paclitaxel-induced apoptosis. Compared to drug sensitive MCF-7 cells, MCF-7ADR cells accumulated >6-fold less paclitaxel, were approximately 100-fold more resistant to killing by the drug, and were highly resistant to paclitaxel-induced apoptosis. In contrast, MCF-7ADR cells pretreated with valspodar were indistinguishable from drug-sensitive cells in their ability to accumulate paclitaxel, in their chemosensitivity to the drug, and in their ability to undergo paclitaxel-induced apoptosis. Valspodar, by itself, did not affect these parameters. This suggests that the enhancement of paclitaxel toxicity in MCF-7ADR cells involves a restoration of apoptosis and not solely through enhanced drug-induced necrosis. Morever, it appears that changes in the levels/activity of p53, the Fas receptor, Fas ligand, caspase-2, caspase-6, or caspase-8 activity have little effect on paclitaxel-induced cytotoxicity and apoptosis in human breast cancer cells.
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PMID:Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells. 1083 93

Paclitaxel (Taxol) and docetaxel (Taxotere) are the first representatives of a new class of antitumor compounds. These two taxoids are clinically active against breast, ovarian and lung cancers. Taxoids are highly complex diterpenoids form natural origin. Preclinical and clinical developments have been made possible after a long and sustained chemical effort: paclitaxel is extracted from the barks of the Pacific yew tree Taxus brevifolia whereas docetaxel is prepared by hemisynthesis starting from 10-deacetyl-baccatin III, an inactive precursor found in the needles of the European yew tree Taxus baccata. These two drugs are active in various in vitro and in vivo preclinical models (cell lines, cloning of human tumor stem cells, murine grafted tumors, human xenografts). Taxoids constitute a new class of antimitotic agents different from vinca-alkaloids: on the one hand, paclitaxel and docetaxel can be considered as inhibitors of the reaction of depolymerization of microtubules into tubulin; on the other hand, vinca-alkaloids inhibit reaction of polymerization of tubulin into microtubules. An active program of medicine chemistry is done in various pharmaceutical and academic Institutions with two objectives: knowledge of structure-activity relationships and selection of new candidates for clinical trials.
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PMID:[Taxoids: structural and experimental properties]. 1084 36


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