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排序方式: 共有6167条查询结果,搜索用时 406 毫秒
81.
Alex Sparreboom Charity D Scripture Vuong Trieu Paul J Williams Tapas De Andrew Yang Bridget Beals William D Figg Michael Hawkins Neil Desai 《Clinical cancer research》2005,11(11):4136-4143
PURPOSE: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophor-ethanol (Taxol). EXPERIMENTAL DESIGN: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m(2), 30 minutes; n = 14) or Taxol (175 mg/m(2), 3 hours; n = 13), with cycles repeated every 3 weeks. RESULTS: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m(2) (P = 0.048) and 663.8 versus 433.4 L/m(2) (P = 0.040), respectively]. CONCLUSIONS: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel-sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness. 相似文献
82.
Konstantin H Dragnev W Jeffrey Petty Sumit Shah Adrian Biddle Neil B Desai Vincent Memoli James R Rigas Ethan Dmitrovsky 《Journal of clinical oncology》2005,23(34):8757-8764
PURPOSE: The epidermal growth factor receptor (EGFR) and cyclin D1 are overexpressed in lung carcinogenesis. The rexinoid, bexarotene, represses cyclin D1 and EGFR expression in vitro. It was hypothesized that combining bexarotene with the EGFR inhibitor, erlotinib, would augment clinical activity. PATIENTS AND METHODS: In vitro studies and a phase I clinical trial were performed. Twenty-four patients with advanced aerodigestive tract cancers were enrolled; 79% had non-small-cell lung cancer (NSCLC). The primary objective was to determine the maximum-tolerated dose. Clinical activity was a secondary objective. RESULTS: Combining erlotinib with bexarotene enhanced growth suppression in vitro compared with each single-agent treatment. This cooperatively repressed cyclin D1 expression. Clinically, the most frequent toxicities were mild hypertriglyceridemia and skin rash. Two serious treatment-related adverse events occurred (creatine phosphokinase elevation attributed to antilipid therapy and a case of generalized pain). Five objective responses (four partial and one minor) were observed in NSCLC patients. Responses were observed in males and smokers. EGFR sequence analyses did not reveal activating mutations in tumors from assessable responding patients. Median time to progression was 2.0 months; overall survival time was 14.1 months; and 1-year survival rate was 73.8%. CONCLUSION: The recommended phase II doses are erlotinib 150 mg/d and bexarotene 400 mg/m2/d orally. These agents can be administered in combination at the recommended single-agent doses without added toxicity. Overall survival and clinical features of responding patients differ from prior reports of single-agent erlotinib treatment. These findings are encouraging and warrant further investigation of this regimen. 相似文献
83.
B. R. Prashantha Kumar S. Sopna Jenson Verghese Bijoy Desai M. J. Nanjan 《Medicinal chemistry research》2012,21(5):624-633
We report both automated rigid and flexible ligand docking simulations performed on fifty peroxisome proliferator-activated
receptor (PPAR-γ) agonists, namely, glitazones. The binding conformations and binding affinities of these agonists were obtained
by the use of the Autodock 4.1 with Lamarckian genetic algorithm (LGA). All the 50 flexible docks are considered as well-docked
as all of them were bound to the ligand binding domain of PPAR-γ. The predicted binding affinity values (pKa) were found to
have some degree of correlation with their experimental in vivo activity values. The head group hydrogen bond interactions
via H323 and H449 histidine residues were found to play a significant role. The results obtained will be valuable in designing
newer selective PPAR-γ agonists. 相似文献
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Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia, and abnormally oriented and misshapen hippocampi have been described with SOX2 gene mutations. A neocortical malformation is presented here in association with SOX2 deletion that over time underwent spontaneous evolution and decrease in size. 相似文献
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Zhand Naista Desai Nimisha Park Angela Dick Matthew 《International journal of clinical pharmacy》2022,44(4):1083-1086
International Journal of Clinical Pharmacy - Schizophrenia is a severe, debilitating disorder that is associated with a significant burden of illness. Antipsychotic medications remain the mainstay... 相似文献
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