Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antineoplastic activity of 5-aza-2'-deoxycytidine (5-AZA-CdR) and docetaxel (Taxotere, Taxo) alone or in combination against human MDA-MB-231 breast, Calu-6 lung and DU-145 prostate carcinoma cell lines was evaluated by clonogenic assay. We also investigated by RT-PCR the capacity of these agents to re-activate the expression of E-cadherin and maspin, two tumor suppressor genes that were silenced by DNA methylation. 5-AZA-CdR and Taxo in combination produced a greater loss of clonogenicity than either agent alone. In MDA-MB-231 breast carcinoma cells, Taxo did not interfere with the re-activation of E-cadherin and maspin genes by 5-AZA-CdR. These results provide a rationale for clinical trials on the combination of 5-AZA-CdR and Taxo in patients with advanced cancer.
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PMID:Evaluation of antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and docetaxel (Taxotere) on human breast, lung and prostate carcinoma cell lines. 1507 73

The omega-6 polyunsaturated fatty acid gamma-linolenic acid (GLA; 18:3n-6) has raised recent interest as novel anti-cancer agent as it possesses effective tumoricidal properties while not inducing damage to normal cells or creating harmful systemic side effects. The taxane docetaxel (Taxotere) is currently one of the most active microtubule-interfering agents for breast cancer. Despite this encouraging therapeutical potential, the clinical use of taxanes involves problems related to the solubility, toxicity and development of drug resistance, which may be partially dependent on the expression of HER-2/neu oncogene. Current trends in the treatment of human tumors are for drug combinations that result in improved responses as well as the ability to use less toxic concentrations of the drugs. Here, we examined the cytotoxic effects of GLA in combination with docetaxel against estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231 and SK-Br3) human breast carcinoma cell lines. The cells were exposed simultaneously to GLA and docetaxel or sequentially to GLA followed by docetaxel for 24 h. Cytotoxicity was evaluated by the MTT assay, and the nature of the interactions between GLA and docetaxel (antagonism, additivity, and synergism) was analyzed by median effect and isobologram analyses. Interaction assessment showed that concurrent exposure to GLA plus docetaxel for 24 h resulted in synergism for MCF-7 and MDA-MB-231 cells, whereas an additive effect was observed in SK-Br3 cells. When exposure to GLA (24 and 48 h) was followed sequentially by docetaxel (24 h) a synergistic effect was observed in MDA-MB-231 and SK-Br3 cells, whereas an additive effect was found in MCF-7 cells. GLA-mediated increase in docetaxel cytotoxicity was only marginally abolished by Vitamin E, a lipid peroxidation inhibitor. Moreover, simultaneous exposure to GLA and docetaxel in the presence of the anti-oxidant Vitamin E also resulted in synergism, suggesting a limited influence of the oxidative status of GLA in achieving potentiation of docetaxel-induced cytotoxicity. Further experiments showed that GLA markedly decreased the expression of p185HER-2/neu oncoprotein in MCF-7 breast cancer cells (</=85%), and RT-PCR analysis revealed that HER-2/neu mRNA was selectively decreased in a concentration-dependent manner following GLA treatment. Therefore, our results show that the fatty acid GLA enhances the cytotoxicity of docetaxel in human breast cancer cells by mechanisms other than lipoperoxidation, and that GLA-induced transcriptional repression of HER-2/neu oncogene might be one component of the mechanisms of this interaction.
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PMID:Omega-6 polyunsaturated fatty acid gamma-linolenic acid (18:3n-6) enhances docetaxel (Taxotere) cytotoxicity in human breast carcinoma cells: Relationship to lipid peroxidation and HER-2/neu expression. 1513 62

Current therapies used in the treatment of breast cancer are limited by systemic toxicity, rapid drug metabolism and intrinsic and acquired drug resistance. We have previously shown that adenoviral-mediated transfer of the melanoma differentiation-associated gene-7 (mda-7) elicits growth inhibition and apoptosis in various tumor types. Here, we evaluate the effects of Ad-mda7, alone and in combination with other therapies, against a panel of nine breast tumor cell lines and their normal counterparts; we report selective Ad-mda7-mediated p53-independent growth inhibition, G2/M cell cycle arrest, and apoptosis. In vivo, Ad-mda7 induced p53-independent tumor growth inhibition (P<0.004) in multiple xenograft models. We then evaluated the combination of Ad-mda7 with agents commonly used to treat breast cancer: radiotherapy (XRT), Tamoxifen, Taxotere, Adriamycin, and Herceptin. These agents exhibit diverse modes of action, including formation of bulky adducts, inhibition of DNA replication (Adriamycin, XRT), damage to microtubules (Taxotere), nonsteroidal estrogen antagonists (Tamoxifen), or Her2/neu receptor blockade (Herceptin). Treated with conventional anticancer drugs or radiation, MDA-7-expressing cells display additive or synergistic cytotoxicity and apoptosis that correlates with decreased BCL-2 expression and BAX upregulation. In vivo, animals that received Ad-mda7 and XRT underwent significant reduction of tumor growth (P<0.002). This is the first report of the synergistic effects of Ad-mda7 combined with chemotherapy or radiotherapy on human breast carcinoma cells.
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PMID:mda-7 gene transfer sensitizes breast carcinoma cells to chemotherapy, biologic therapies and radiotherapy: correlation with expression of bcl-2 family members. 1628 87

Therapy with Docetaxel for hormone-refractory prostatic carcinoma has for the first time led to an increase in the survival time. Docetaxel has become established as a standard therapy for his indication. Since hormone-refractory prostatic carcinoma is not uniformly defined and is thus for prognosis not a homogeneous entity, the prospects at the start of chemotherapy are uncertain. In the summer of 2005 these questions were addressed in an interdisciplinary consensus conference. It was agreed that the 3-week scheme with 75 mg/m (2) as standard and the indication for symptomatic patients were above question. Opinions differed with regard to the use of chemotherapy in asymptomatic patients. In addition, recommendations for the performance and monitoring of the therapy were formulated.
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PMID:[Interdisciplinary recommendations concerning the therapy for hormone-refractory prostatic carcinoma]. 1673 22

Taxol (paclitaxel) and Taxotere (docetaxel) are considered as two of the most important anti-cancer chemotherapy drugs. The cytotoxic action of these drugs has been linked to their ability to inhibit microtubule depolymerization, causing growth arrest and subsequent cell death. Studies by a number of laboratories have also linked suppression of MEK1/2 signaling to enhanced Taxol toxicity in vitro and in vivo. The present study examined the interactions of the semi-synthetic taxane Taxotere with MEK1/2 inhibitors in epithelial tumor cells. In vitro colony formation studies demonstrated that Taxotere and the MEK1/2 inhibitor PD184352 interacted in a sequence dependent fashion to synergistically kill human mammary carcinoma cells (MDA-MB-231, MCF7) as well as in other tumor cell types; e.g. prostate and renal cell carcinoma. Athymic mice were implanted in the rear flank with either MDA-MB-231 or MCF7 cells and tumors permitted to form to a volume of approximately 100 mm3 prior to a two day exposure of either Vehicle, PD184352 (25 mg/kg), Taxotere (15 mg/kg) or the drug combination. Tumor volume was measured every other day and tumor growth determined over the following approximately 30 days. Transient exposure of MDA-MB-231 tumors or MCF7 tumors to PD184352 did not significantly alter tumor growth rate or the mean tumor volume in vivo approximately 15-30 days after drug administration. Transient Taxotere exposure of MDA-MB-231 or to a lesser extent MCF7, tumors modestly reduced the mean tumor volume in vivo approximately 15-30 days after drug administration. In contrast, combined treatment with PD184352 and Taxotere significantly reduced MDA-MB-231 and MCF7 tumor growth. The tumor control values for MDA-MB-231 cells and MCF7 cells were 0.43 and 0.71, respectively. Fractionated irradiation of MDA-MB-231 tumors during drug exposure or single dose irradiation prior to drug administration did not significantly further suppress tumor growth beyond that of cells exposed to Taxotere and MEK1/2 inhibitor. Single dose irradiation of tumors after drug exposure, however, caused a significant further suppression of tumor growth below that caused by drug exposure. These findings were also reflected in ex vivo colony formation analyses of isolated tumor cells. Collectively, these findings argue that Taxotere and MEK1/2 inhibitors have the potential to suppress mammary tumor growth in vivo which is enhanced by sequence-dependent exposure to ionizing radiation. Based on the cell lines used in these studies, our findings argue that the interaction of Taxotere and PD184352 is independent of p53 status, estrogen dependency, caspase 3 levels or oncogenic K-RAS expression.
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PMID:MEK1/2 inhibition promotes Taxotere lethality in mammary tumors in vivo. 1695 20

Malignant neoplasms of the salivary gland are uncommon entities in which surgical resection of the primary lesion has been accepted as a standard therapeutic option. The efficacy of radiation and systemic chemotherapy has been limited for patients with recurrent, metastatic, or unresectable disease because of unfavorable response rates and the short duration of the response. We treated one patient with recurrent adenoid cystic carcinoma arising from the sublingual gland and one patient with primary adenocarcinoma arising from the parotid gland with transfemoral intraarterial chemotherapy, based on full-dose cisplatin and docetaxel and concurrent external-beam radiotherapy. The doses of cisplatin and docetaxel in the two patients were 80-100 mg/m2 and 10-15 mg/m2, respectively. Docetaxel was infused first, followed by cisplatin. Both patients obtained complete responses. Although complications such as mucositis, anorexia, neutropenia, and ischemic colitis were observed, they were well tolerated and manageable. The concomitant chemoradiotherapy of cisplatin and docetaxel seemed to be a practicable option for patients with recurrent and unresectable salivary gland carcinomas.
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PMID:Salivary gland carcinoma treated with concomitant chemoradiation with intraarterial cisplatin and docetaxel. 1705 39

Multicellular tumor spheroids (MTS) are three-dimensional structural forms of tumors grown in vitro in the laboratory. In this study, the aim was to determine the regulation of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) expressions on MTS in response to treatment with the commonly used anti-cancer drugs Doxorubicin and Docetaxel. The spheroids were generated using the "liquid overlay" technique. The distribution of both iNOS and eNOS was detected using indirect immunohistochemistry, while the expression of both iNOS and eNOS was measured using Western blots. Additionally, S-phase analysis using 5-bromo-2'-deoxyuridine (BrdU) was done on the MTS after treatment with doxorubicin, docetaxel, and a combination of the two. The Griess method was used to measure nitric oxide (NO) production in the cells. An increase in iNOS immunoreactivity and a decrease in eNOS immunoreactivity were observed after doxorubicin treatment, when compared with the other groups. Furthermore, upregulation of iNOS and downregulation of eNOS were detected in doxorubicin-treated cells using Western blotting. Insignificant iNOS expression was observed in all of the groups, and it was particularly low in the control and drug combination groups. NO production was also found to be significantly high after docetaxel treatment, and cell proliferation decreased after doxorubicin treatment. In conclusion, chemotherapy influences NOS activity differently with the presence of different drugs. The results with iNOS show that doxorubicin is a more effective drug than docetaxel, and a drug combination may play a helpful role in the suppression of tumorigenicity and cancer metastasis. Interestingly, eNOS expression increased after the addition of both docetaxel and the drug combination, and it was found to negatively correlate with the histological grade of the tumor. Therefore, analyzing the expression of both iNOS and eNOS might be very useful for targeting the treatment of breast carcinoma and obtaining better information on prognosis.
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PMID:Chemotherapy influences inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) activity on 3D breast cancer cell line. 1712 Jun 17

In a phase I study, we determined the maximum tolerated dose (MTD) and the recommended dose (RD) of nedaplatin (CDGP) in combination chemotherapy with Docetaxel (DOC) and 5-fluorouracil (5-FU) for treatment of carcinoma of the head and neck. Then, in a phase II study, we examined the efficacy and safety of the RD of chemotherapy. Fresh patients with squamous cell carcinoma of the head and neck were enrolled in the study. The dosage of chemotherapy was as follows: DOC 60 mg/m(2) on day 1 by infusion over 2 hours; CDGP 20-30 mg/m(2)/day on day 1 to 5 by infusion over 1 hour, and 5-FU 600 mg/m(2)/day on day 1 to 5 by 5 days continuous infusion. For CDGP, an initial dose level was set at 20 mg/m(2), and 3 patients were enrolled for each level of dose escalation. The DLT was defined here as grade 4 neutropenia or grade> or =3 non-hematotoxic reactions. The dose at which DLT was observed in overall 33% cases was taken as MTD. The RD for phase II study was estimated to be DOC 60 mg/m(2), CDGP 20 mg/m(2)/day, 5-FU 600 mg/m(2)/day. Forty patients were enrolled in the phase II study. DLT of neutropenia was noted in 2 of 38 cases. DLT of non-hematotoxic reactions was found in less than 33% of the cases; 17 cases showed CR, and 12 cases showed PR. The response rate was 76.3%. The overall response rate in histological assessment was 55.3%. The combination chemotherapy with Low-Divided Dose of CDGP, DOC and 5-FU was suggested to be safe and effective.
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PMID:[Phase I/II clinical trial of induction chemotherapy with nedaplatin (CDGP), docetaxel (DOC) and 5-fluorouracil (5-FU) for squamous cell carcinoma of head and neck]. 1722 Jun 68

Docetaxel and paclitaxel are demonstrated to be effective for use as salvage therapy for advanced gastric cancer. Both drugs are taxane derivatives but there is only partial cross-resistance between them. For breast cancer and ovarian cancer, there have been several reports that showed docetaxel is effective for paclitaxel-resistant cancer, and vice versa. We experienced two cases of advanced gastric cancer effectively treated by sequential therapy of docetaxel and paclitaxel. One patient was a 43-year-old woman with a type 4 gastric carcinoma, and the other a 51-year-old woman who had suffered a recurrence of the gastric cancer after a total gastrectomy. At first, chemotherapy failed, so we chose docetaxel/high-dose 5-FU (HDFU) for the second-line therapy. After resistance to Docetaxel/HDFU, paclitaxel was effective for third-line treatment of both patients.
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PMID:[Two cases of advanced gastric cancer in which paclitaxel proved effective after resistance to docetaxel]. 1794 Mar 82

Docetaxel (DCTX) and paclitaxel (PTX) are very potent anti-cancer drugs, but the currently marketed formulations, Taxotere and Taxol, respectively, are associated with vehicle-related toxicity. An attractive alternative to formulate these hydrophobic cytotoxic agents are polymeric micelles. In this study, the loading of taxanes into oligomeric micelles composed of mPEG750-b-oligo(epsilon-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group was investigated. Next, the release characteristics and cytotoxicity of the loaded micelles were studied. MPEG750-b-OCL5 -OH micelles loaded with taxanes formed unstable particles with rapid leakage of the drug. In contrast, the presence of an aromatic end group (Bz or Np) resulted in the formation of small (10nm), almost monodisperse micelles with stable encapsulation of 10% (w/w) of PTX or DCTX. This was ascribed to a better compatibility between the micellar core and the drug as compared to the oligomers with the hydroxyl end group. 1H NMR studies showed that the micellar core was liquid, and that PTX was molecularly dissolved in the core. The in vitro stability was studied in PBS at 37 degrees C, which showed that leakage of PTX from 10% and 5% (w/w) loaded mPEG750-b-OCL5-Bz micelles started after 8 and 24h, respectively. The presence of albumin did not affect the stability, suggesting that the micelles are not destabilised and the drug was not extracted from the micellar core by this protein. The in vitro cytotoxic effect of the taxane-loaded micelles on C26 carcinoma cells was comparable to that of the commercial formulations, but the empty micelles were far less toxic than the Cremophor EL vehicle. The results show that mPEG-b-oligo(epsilon-caprolactone) micelles hold good promise for the formulation of taxanes.
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PMID:The effect of core composition in biodegradable oligomeric micelles as taxane formulations. 1794 56


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