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91.
92.
Maria G Beconi Ann Mao David Q Liu Christopher Kochansky Tony Pereira Conrad Raab Paul Pearson Shuet-Hing Lee Chiu 《Drug metabolism and disposition》2003,31(10):1269-1277
The pharmacokinetics and metabolism of the l-threo isoleucine thiazolidide dipeptidyl peptidase IV inhibitor, di-[2S,3S]-2-amino-3-methyl-pentanoic-1,3-thiazolidine fumarate (ILT-threo) and its allo stereoisomer (ILT-allo) were evaluated in rats, dogs, and monkeys. Both compounds were well absorbed (>80%) in all species, and most of the dose (>60%) was recovered in urine. Metabolites identified in all species included a sulfoxide (M1), a sulfone (M2), and a carbamoyl glucuronide (M3). For both compounds, parent drug had moderate systemic clearance in rats and dogs ( approximately 20-35 ml/min/kg in both species) and lower clearance in monkeys ( approximately 6-9 ml/min/kg). In rats, M1 was present in systemic circulation in concentrations similar to that of parent drug, whereas in dogs and monkeys, exposures to M1 were higher than for parent drug. In dogs, exposures to the sulfoxide metabolite were approximately 2 to 3 times higher after administration of ILT-allo than after administration of ILT-threo. Carbamoyl glucuronidation was an important biotransformation pathway in dogs. Circulating levels of M3 were significant in the dog, and present only in trace levels in rats and monkeys. M3 could be produced in in vitro systems in a NaHCO3 buffer under a CO2-saturated atmosphere and in the presence of UDP-glucuronic acid and alamethicin. 相似文献
93.
毛遐先 《针灸推拿医学(英文版)》2004,2(3):20-21
取双侧肾俞、足三里和曲池,进行温针,并配合内服中药治疗类风湿性关节炎患者30例,以西药常规治疗30例为对照.治疗3个月后,两组有效率分别为86.7%和60.0%,疗效差异有统计意义(P<0.05). 相似文献
94.
Expression of hepatoma-derived growth factor is a strong prognostic predictor for patients with early-stage non-small-cell lung cancer. 总被引:5,自引:0,他引:5
Hening Ren Ximing Tang J Jack Lee Lei Feng Allen D Everett Waun Ki Hong Fadlo R Khuri Li Mao 《Journal of clinical oncology》2004,22(16):3230-3237
PURPOSE: Hepatoma-derived growth factor (HDGF), which is unrelated to hepatocyte growth factor, can stimulate DNA synthesis and cell proliferation on entering the nucleus. We hypothesize that HDGF plays an important role in biologic behavior of early-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-eight patients with pathologic stage I NSCLC who underwent curative surgery were studied. Immunohistochemistry was used to determine the expression level of HDGF in the tumor specimens. The intensity of the protein staining and percentage of stained tumor cells were used to determine a labeling index. Statistical analyses, all two-sided, were performed to determine the prognostic effect of HDGF expression levels on clinical parameters and outcomes. RESULTS: The mean +/- standard deviation HDGF labeling index in the 98 tumors was 185 +/- 41. Patients whose tumors had higher HDGF indexes (>/= 185) had a significantly poorer probability of overall survival at 5 years after surgery than did those with lower HDGF indexes (0.26 v 0.82; P <.0001). Similarly, the 5-year disease-specific and disease-free survival probabilities were lower in those with higher HDGF indexes (0.42 v 0.92, and 0.34 v 0.71; P <.0001 and P =.0008; respectively). Multivariate analysis indicated that HDGF level was an independent predictor of overall, disease-specific, and disease-free survivals. CONCLUSION: Overexpression of HDGF is common in early-stage NSCLC. The expression level in tumor cells is strongly correlated with poor overall, disease-specific, and disease-free survivals, suggesting HDGF may be a powerful prognostic marker for patients with early-stage NSCLC. 相似文献
95.
96.
目的:探讨MGMT蛋白在乳腺癌中的表达及其与乳腺癌预后的关系。方法:应用免疫组化法检测135例乳腺癌患者MGMT蛋白的表达,并探讨其与乳腺癌临床特征及预后的关系。结果:135例乳腺癌中MGMT蛋白总阳性率为84.4 %(114/135),但存在异质性。MGMT蛋白的阳性表达与患者年龄、月经状态、原发肿瘤大小、淋巴结转移情况及肿瘤的临床分期无明显相关性(P>0.05),与生存期无明显相关性(P>0.05),但与ER状况相关(P<0.025)。结论:MGMT蛋白的表达不能作为乳腺癌的一个预后指标。 相似文献
97.
Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication. 总被引:12,自引:0,他引:12
Shyh-Kuan Tai Janet I Lee K Kian Ang Adel K El-Naggar Khaled A Hassan Diane Liu J Jack Lee Hening Ren Waun K Hong Li Mao 《Clinical cancer research》2004,10(16):5554-5557
PURPOSE: Abnormalities of FHIT, a candidate tumor suppressor gene, have frequently been found in multiple malignancies, including head and neck squamous cell carcinoma (HNSCC). To define its role in HNSCC treated with surgery and postoperative radiotherapy (PORT), the Fhit protein expression status was investigated in 80 patients enrolled in a prospective Phase III clinical trial addressing the dose and fractionation regimen of PORT. EXPERIMENTAL DESIGN: Immunohistochemical staining of HNSCC tissue sections for Fhit expression was performed. The Fhit expression status was correlated with the clinicopathological characteristics and clinical course. The median follow-up duration was 4.9 years. RESULTS: Loss of Fhit expression was found in 52 of the 80 study patients (65%). There was not a significant association between Fhit expression and clinical characteristics. Patients whose tumor exhibited negative Fhit expression had a significantly worse 5-year overall survival duration [hazard ratio = 0.49; 95% confidence interval, 0.23-1.03; P = 0.05 (log-rank test)] than did those whose tumor exhibited positive Fhit expression. One third of the patients with a Fhit-negative tumor had distant metastasis during the follow-up period. Paradoxically, patients classified as high risk who had a Fhit-negative tumor experienced locoregional recurrence less often (18%) than did high-risk patients who had a Fhit-positive tumor (33%). CONCLUSIONS: Loss of Fhit expression is a poor prognostic indicator in patients with HNSCC. However, tumors lacking Fhit expression may be more sensitive to PORT and therefore more susceptible to locoregional control. 相似文献
98.
99.
阻断致瘤病毒复制的抗肿瘤药物筛选策略 总被引:2,自引:0,他引:2
许多病毒与人类恶性肿瘤的发生有关,阻断病毒与靶细胞的结合和融合、干扰病毒的复制和表达,抑制与病毒复制有关的酶等多个环节,将为抗肿瘤药物的筛选提供相关策略。 相似文献
100.