The protective activity of ICRF-187 against doxorubicin-induced cardiotoxicity in the rat

Summary The protective activity of the bisdioxopiperazine ICRF-187 against the cardiotoxicity of doxorubicin was evaluated in the rat using both functional and histological assays. Animals that had received a single i. v. dose of doxorubicin (4 mg/kg) alone were compared with those that had been pretreated with a single i. v. injection of saline or ICRF-187 (40 or 60 mg/kg). All rats showed a transient reduction in body weight during the first 3 weeks after drug administration. The greatest reduction (16%) was observed in animals that had received a combination of ICRF-187 (40 or 60 mg/kg) and doxorubicin. Deaths related to cardiotoxicity were observed only in rats that had received doxorubicin alone and in those treated with saline; most of the deaths occurred at between 8 and 13 weeks after drug administration. Sequential assessments of heart function showed a persistent depression of cardiac output in animals that had received doxorubicin, with or without pretreatment with ICRF-187. The reduction in cardiac output observed in rats that had been pretreated with ICRF-187 (40 or 60 mg/kg) amounted to 15% and 30% after 12 and 20 weeks, respectively, indicating that cardioprotection was only partial. Nevertheless, this represented a marked improvement as compared with the 35% reduction in cardiac output measured at 12 weeks in animals that had received doxorubicin but without pretreatment with ICRF-187. Histological examination of animals that had died during the course of the study and had received doxorubicin after pretreatment with saline revealed severe myocardial lesions typical of doxorubicin-induced damage. In contrast, animals that had been pretreated with ICRF-187 and survived for up to 20 weeks after treatment showed a marked amelioration of these lesions. The present findings may be interpreted as a true cardioprotection or a delay in the onset of the cardiotoxicity of doxorubicin resulting from pretreatment with the bisdioxopiperazine ICRF-187. Although prior and ongoing clinical trials clearly indicate that ICRF-187 protects patients well against doxorubicin-induced heart damage, further investigations are required beforehigh doses of ICRF-187 can be used as a means of increasing the protective activity of this drug against doxorubicin-induced cardiotoxicity.This work was supported by the Cancer Research Campaign     

大孔吸附树脂富集茵陈蒿汤中蒿属香豆素的工艺研究

目的 研究大孔吸附树脂富集茵陈蒿汤中蒿属香豆素的工艺条件及参数。方法 以蒿属香豆素为指标，考察大孔吸附树脂富集茵陈蒿汤中蒿属香豆素的最佳工艺条件。结果提取液上大孔吸附树脂柱，吸附30min后，以5倍树脂量的蒸馏水洗去杂质，再以3～4倍树脂量的70％乙醇洗脱蒿属香豆素为最佳工艺。结论 此法可较好地富集茵陈蒿汤中的主要有效成分蒿属香豆素。     

中药药效方法学研究初探（I）

对目前中药药效的研究方法进行全面论述，找出存在问题，并对中药药效方法学进行初步探讨。提出中医学发展是中药药效方法学研究的基础和前提，尤其是藏象经络学说和中药的归经理论的现代研究的突破对中药药效方法学研究起着主导作用；中药药效方法学研究四维系统论，在药效作用物质基础和药物作用机制两维的基础上增加时间维和人体精神维。     

HPLC法测定傣药雅路哈中槲皮素的含量

目的:建立傣药雅路哈(接骨1号)中槲皮素的含量测定方法。方法:采用高效液相色谱法,C18色谱柱(4.6mm×200mm,5μm);流动相:甲醇-0.4%磷酸溶液(52∶48);检测波长:360nm;流速:1.0mL/min;柱温:30℃。结果:槲皮素在10.56～528μg范围内线性关系良好(r=0.9999),回收率98.21%,RSD为l.87%。结论:为傣药雅路哈(接骨1号)质量标准的研究,提供准确、可靠的方法。     

肝内胆管癌30例的临床病理特征及预后分析

目的 :探讨肝内胆管癌 (intra hepaticcholangiocarcinoma ,ICC)的临床病理特征及治疗与预后的关系。方法 :回顾性分析 1991～ 1999年山东省立医院、济宁医学院附属医院 3 0例ICC患者病理、临床资料。结果 :ICC比肝细胞癌少见且预后不良 ,手术切除是目前较理想治疗方式 ,影响预后的因素是肿瘤边缘、淋巴结转移与组织病理情况。根治切除术后 1年生存率 5 3 3 % ,3年生存率 3 3 3 %。结论 :根治性切除是最有效的治疗方法。     

A23187诱导恶性黑色素瘤患者的外周血单核细胞向树突状细胞分化

A23187为一种钙离子载体(calcium ionophore,CI),可提高胞浆内游离钙水平,模拟某些细胞内信号转导事件,导致多基因活化[1-2].我们先前曾探讨了A23187对正常人外周血单核细胞(peripheral monotytes,PBMC)来源的DC的影响[3],最近,我们进行了有关A23187诱导MMe患者的PBMC向DC分化的实验研究.     

dbcAMP诱导的EoL-1分化和凋亡与bcl-2家族的关系

目的:探讨dbcAMP(dbutyryl cyclicAMP)诱导的EoL-1(eosinophilic leukemia cell line)分化和凋亡与bcl-2家族的关系.方法:通过免疫印记和流式细胞仪调查bcl-2家族蛋白在dbcAMP刺激的EoL-1细胞中的表达.结果:EoL-1在正常培养条件下表达高水平的bcl-2、bcl-xL和中等水平的bax,但未表达bcl-xs.dbcAMP诱导了EoL-1细胞下调表达bcl-2和bax及上调表达bcl-xs.结论:dbcAMP诱导EoL-1分化和凋亡与bcl-2的降低以及bcl-xs的升高有关.     

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

PURPOSE: To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). RESULTS: All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). CONCLUSION: There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.     

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.