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排序方式: 共有3517条查询结果,搜索用时 625 毫秒
31.
Purpose: In an attempt to increase the local concentration of tamoxifen in estrogen receptor positive breast cancer cells, we have prepared and characterized poly (ε-caprolactone) (PCL) nanoparticle formulation. Methods: PCL (mol wt 14,800 daltons) nanoparticles were prepared by the solvent displacement method in acetonewater system in the presence of Pluronic F-68. PCL nanoparticles, labeled with rhodamine 123, were incubated with MCF-7 estrogen receptor positive breast cancer cells to determine uptake, intracellular distribution, and localization as a function of time. Intracellular drug concentrations over a specified period of time using different initial doses were examined using tritiated [3H]-tamoxifen. Results: A significant fraction of the administered rhodamine 123-loaded PCL nanoparticles was found in the perinuclear region of the MCF-7 cells, where estrogen receptors are also localized, after 1 hour of incubation. Measurements of the intracellular concentrations revealed that most of the administered nanoparticle dose was internalized within the first 30 minutes of incubation, and the uptake followed saturable transport kinetics. Conclusion: Results of this study show that PCL nanoparticles were rapidly internalized in MCF-7 cells and intracellular tamoxifen concentrations followed a saturable process. This approach may provide better therapeutic benefit by delivering the drug locally, near the tumor cells, for a longer period of time. 相似文献
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Obstetric outcome in 232 ovum donation pregnancies 总被引:3,自引:0,他引:3
Hossam I. Abdalla Consultant Anne Billett Clinical Research Fellow rew K. S. Kan Clinical Research Fellow Sabah Baig Clinical Research Fellow Marie Wren Infertility Specialist Lena Korea Ovum Donation Co-ordinator John W. W. Studd Consultant 《BJOG : an international journal of obstetrics and gynaecology》1998,105(3):332-337
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Vlastos G Fornage BD Mirza NQ Bedi D Lenert JT Winchester DJ Tolley SM Ames FC Ross MI Feig BW Hunt KK Buzdar AU Singletary SE 《American journal of surgery》2000,179(6):446-452
BACKGROUND: The goal of this study was to examine the role of ultrasonography in detecting axillary lymph node metastases in stage II breast cancer patients after induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0-1, M0 breast cancer registered in a prospective IC trial, a subset of 130 evaluable patients were chosen, with (1) both physical and ultrasonographic examinations of the axilla before and after IC; (2) exactly four cycles of IC; (3) no presurgical radiation therapy; and (4) an axillary lymph node dissection. RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by both physical and ultrasonographic examinations. After IC, this number increased to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast cancer patients who were or became node negative by both ultrasonographic and physical examinations after IC had a 48% incidence of nodal metastases. Because the residual tumor was minimal, irradiation may be sufficient for adequate local control of the axilla. 相似文献
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Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naive advanced non-small-cell lung cancer. 总被引:2,自引:0,他引:2
Francisco Robert George Blumenschein Roy S Herbst Frank V Fossella Jennifer Tseng Mansoor N Saleh Michael Needle 《Journal of clinical oncology》2005,23(36):9089-9096
PURPOSE: This multicenter, open-label, phase I/IIa study was undertaken to establish the safety/toxicity profile of cetuximab in combination with gemcitabine and carboplatin in patients with chemotherapy-na?ve, epidermal growth factor receptor-positive, stage IV non-small-cell lung cancer. Secondary objectives were to gather preliminary evidence of efficacy including tumor response rate, time to progression, and overall survival. PATIENTS AND METHODS: Thirty-five patients received a total of 264 3-week cycles of treatment with cetuximab, carboplatin, and gemcitabine. An initial dose of cetuximab 400 mg/m2 intravenously was administered the first week, followed by weekly doses of 250 mg/m2. Carboplatin (area under the curve = 5, day 1) and gemcitabine 1,000 mg/m2 on days 1 and 8 were administered every 3 weeks. Patients were evaluated for tumor response after every two cycles of therapy. RESULTS: The most frequently reported adverse events related to cetuximab included an acne-like rash (88.6%), dry skin (34.3%), asthenia and skin disorders (31.4%), mucositis/stomatitis (25.7%), fever/chills (20%), and nausea/vomiting (17.1%). The majority of these toxicities were mild to moderate. One patient withdrew from the study because of a grade 3 allergic reaction. Myelosuppression was the most frequently observed toxicity related to chemotherapy. Responses among 35 assessable patients included 10 partial responses (28.6%). Twenty-one patients had stable disease. The median time to progression was 165 days, and the median overall survival was 310 days. CONCLUSION: The combination of cetuximab, carboplatin, and gemcitabine was well tolerated with an acceptable toxicity profile. Most grade 3 adverse events were attributable to chemotherapy. The response rate and median survival are encouraging and warrant additional investigation. 相似文献
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Dharamainder Choudhary Ingela Jansson Ivaylo Stoilov Mansoor Sarfarazi John B Schenkman 《Drug metabolism and disposition》2004,32(8):840-847
The cytochrome P450 family 1 (CYP1) is considered to be one of the xenobiotic-metabolizing enzyme families and is responsible for oxidative metabolism of polycyclic aromatic hydrocarbons. For example, mouse Cyp1b1 was originally identified as the enzyme responsible for oxidative metabolism of 7,12-dimethylbenz(alpha)anthracene (DMBA). A comparison of the kinetics of this metabolism by mouse and human CYP1B1 orthologs revealed the mouse enzyme to have a more favorable metabolism of DMBA, with a catalytic efficiency ratio (CER) of 0.23. However, CYP1 enzymes are also capable of metabolism of endobiotics, and in the present study, the metabolism of retinoids and lipid endobiotics by human CYP1B1 and mouse Cyp1b1 orthologs was compared. Both hemoproteins oxidized retinol to retinal and retinal to retinoate, but did not oxidize retinoate. The CYP1B1 to Cyp1b1 CERs were 13 and 26 for the two steps, respectively; the Cyp1b1 K(m(app)) values for retinoids were 20-fold higher. Human family 1 cytochromes P450 had unique regional specificities for arachidonate oxidation: the major metabolites of CYP1A1, CYP1A2, and CYP1B1 were 75% terminal hydroxyeicosatetraenoic fatty acids (HETEs), 52% epoxyeicosatrienoic fatty acids (EETs), and 54% mid-chain HETEs, respectively. CYP1A1 and CYP1B1 K(m(app)) values for arachidonate were about 30 microM, whereas CYP1A2 K(m(app)) was 95 microM. The major metabolites of arachidonic acid by Cyp1b1 were EETs (50%) and midchain HETEs (37%). The mouse ortholog had a CER for metabolite production of 64 due to a K(m(app)) of 0.5 mM for arachidonate. 相似文献
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Akhtar Siddiqui Ziyaur Rahman Vilayat A. Sayeed Mansoor A. Khan 《Journal of pharmaceutical sciences》2013,102(11):4024-4035
The objective of this study was to assess the performance of the chemometric model to predict the proportion of the recrystallized polymorphs of nimodipine from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I, the two polymorphs mixtures were prepared and characterized spectroscopically using Fourier transformed infrared spectroscopy (FTIR), near-infrared spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated to construct multivariate calibration model using principal component regression (PCR) and partial least square regression approaches. Treated data showed better model fitting than without treatment, which demonstrated higher correlation coefficient (R2) and lower root mean square of standard error (RMSE) and standard error (SE). Multiple scattering correction and standard normal variate exhibited higher R2 and lower RMSE and SE values than second derivative. Goodness of fit for FTIR and NIR (R2 ~ 0.99) data was better than Raman (R2 ~ 0.95). Furthermore, the models were applied on the recrystallized polymorphs obtained by storing nimodipine-cosolvent formulations at selected stability conditions. The relative composition of the polymorphs differed with storage conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15°C qualitatively corroborated the model-based prediction of the two polymorphs. Therefore, these studies strongly suggest the importance of the potential utility of the chemometric model in predicting nimodipine polymorphs. 相似文献
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