1-氨基茚的合成

目的：合成1-氨基茚。方法：以苯丙酰氯为初始原料，经3步反应合成1-氨基茚。由TLC确定每步反应终点。结果：目标化合物结构经MS确证，纯度经GSMS测定达97．8％。结论：该法合成了1-氨基茚，收率达39．2％。     

注射用重组改构人肿瘤坏死因子治疗恶性肿瘤Ⅲ期临床观察

目的评价注射用重组改构人肿瘤坏死因子(rmhTNF)与化疗联合治疗恶性肿瘤的有效性及不良反应.方法共入选52例患者,随机分为试验组39例,对照组13例,试验组用rmhTNh 400万u·m-2,im,d1～7,d11～17,同时联合应用化疗药物,21d为1个周期,连用2个周期;对照组联合化疗方案同实验组,但不加用rmhTNh.结果45例患者可评价疗效.试验组33例中有效率为36.36%(12/33);对照组有效率为8.33%(1/12).试验组有效率高于对照组,但两组之间无统计学差异(P=0.070).不同病种疗效分析显示试验组肺癌的有效率44.44%(8/18)高于对照组10%(1/10),而试验组3例头颈部肿瘤患者均有效.与rmhTNh有关的不良反应发生率为72.73%(24/33),主要为轻度注射部位疼痛72.73%(24/33),红肿硬结45.45%(15/33),少数患者出现发热,感冒样症状.结论rmhTNh与化疗药物联合应用治疗恶性肿瘤,显示对肺癌、头颈部肿瘤有较好的疗效,且毒性反应较轻.     

Metabolism and pharmacokinetics of a dipeptidyl peptidase IV inhibitor in rats, dogs, and monkeys with selective carbamoyl glucuronidation of the primary amine in dogs.

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.     

Treatment of 30 cases of rheumatoid arthritis by needle-warming therapy

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).     

Expression of hepatoma-derived growth factor is a strong prognostic predictor for patients with early-stage non-small-cell lung cancer.

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.     

Loss of Fhit expression in head and neck squamous cell carcinoma and its potential clinical implication.

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.     

阻断致瘤病毒复制的抗肿瘤药物筛选策略

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。     

关白附新工艺最佳技术参数优选

通过对关白附不同炮制品有效成分总生物碱、关附甲素及有毒成分次乌头碱含量测定,急性毒性实验,结合药典对关白附炮制品的法定标准要求(饮片表面特征、断面色泽、气味)及饮片收得率等指标考查,确定关白附新工艺技术参数为清蒸4小时为佳。