The effect of dexamethasone on the uptake of cisplatin in 9L glioma and the area of brain around tumor

The negative influence of dexamethasone (Dex) on the uptake of cisplatin in brain tumors was investigated in rats bearing 9L glioma. Dex or saline was given intraperitoneally prior to intravenous administration of cisplatin 5 mg/kg. Total Platinum (Pt) concentration was quantified with atomic absorption spectroscopy (AAS) in tumor, brain around tumor (BAT), normal brain and plasma. In the second experiment DNA-adducts of cisplatin were determined in tumor and BAT by AAS. In tumor, there was no difference in the Pt concentration and in the DNA-adduct level between the two treatment groups. In BAT, the Pt level in the Dex group was 0.20 µg/g (SD = 0.10 µg/g), which was significantly lower than in the controls (0.53 µg/g (SD=0.21 µg/g); p < 0.001). In addition, the DNA-adduct level in BAT was 23% lower in the Dex treated rats (p=0.05). In normal brain the Pt concentration was 10-fold lower than in tumor tissue. Thus, Dex did not significantly limit the uptake of cisplatin in brain tumor nor did it influence the uptake in normal brain parenchyma. In contrast, in BAT that has a partially disrupted BBB, the concentrations of Pt and DNA-adduct formation were significantly decreased following pretreatment with Dex. The influence of Dex on limiting the effects of chemotherapy for brain tumors needs further study.     

Advanced colorectal cancer in the elderly: results of consecutive trials with 5-fluorouracil-based chemotherapy

To evaluate toxicity and efficacy of chemotherapy in elderly patients (≥65 years of age) with advanced colorectal cancer, data from two consecutive trials conducted between 1984 and 1995 at the National Institute for Cancer Research were analysed comparing the results of treatment in those 65 years of age or older and in those younger than 65 years. Of 215 patients recruited, 82 elderly patients (median age 70 years, median performance status 1) received one of the following regimens based on 5-fluorouracil (5-FU): (1) weekly 5-FU 600 mg/m² i.v. bolus (30 patients); (2) weekly 5-FU 600 mg/m² bolus plus leucovorin (LV) 500 mg/m² 2-h i.v. infusion (28 patients); (3) Weekly 5-FU 2600 mg/m² 24-h continuous i.v. infusion plus LV 100 mg 4-h i.v. infusion and 50 mg orally every 4 h for five doses (24 patients). Overall, 1071 chemotherapy cycles were administered with a median number of 12 courses per patient. The main side effects were diarrhoea, observed in 38% of patients, stomatitis in 24% of patients and hand-foot syndrome in 13% of patients, and haematological toxicity affected only 15% of patients. No patient suffered grade IV toxicity. In three patients chemotherapy was discontinued because of toxicity (two patients suffered grade III diarrhoea, one patient grade III hand-foot syndrome). No significant difference in toxicity was evident between patients older than or younger than 65 years. Analysis of median dose intensity demonstrated no difference between the two groups. Overall objective response was observed in 18% (95% confidence limits 11–29) of elderly patients (15/82) in comparison with 23% (95% CL 17–32) of patients <65 years of age (31/133 pts). In conclusion, chemotherapy in elderly patients with advanced colorectal cancer is a safe and effective treatment with acceptable toxicity and comparable objective response rates. Received: 6 January 1998 / Accepted: 27 February 1998     

Allogeneic bone marrow transplantation for adult acute lymphoblastic leukemia: a single-centre experience.

Between 1990 and 1997, we performed 29 allogeneic BMTs for acute lymphoblastic leukemia (ALL) patients with HLA-identical sibs. Their median age was 31 years (range 15 to 43); there were 15 males and 14 females. The conditioning protocol was Cy-TBI (n = 15), VP16-Cy-TBI(n = 12), CBV (n = 1) and Bu-Cy (n = 1). Cyclosporin and methotrexate were used for GVHD prophylaxis. The median disease-free survival (DFS) was 12 months (range 1 to 92) with an actuarial 4-years DFS of 42.3 per cent. Three patients died of transplant-related complications before 100 days. Relapse occurred in 11 cases at a median time of 5 months (range 3 to 14). All nine patients relapsing within one year died form resistant leukemia. Three patients died of late treatment-related complications. There were 13 survivors (median follow-up 38 months, range 12-98), with 12 in remission. Only four had limited cGVHD, and all had 100 per cent performance scores. One patient also cleared her chronic hepatitis B carrier status due to acquired immunity. The DFS rates amongst CR1 cases and R1/CR2 cases were comparable (p = 0.39). No long-term DFS is obtained from patients with resistant disease (n = 4). The survival results for BMT at CR1 were superior to those using intensive chemotherapy consolidation (p = 0.29), mainly due to poor late results in the chemotherapy arm. For young ALL patients with HLA-matched siblings, the option of BMT should be considered in light of local consolidation survival results.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

ras基因的表达与胃癌细胞生物学特性的相关研究

为研究ｒａｓ基因在胃癌中的表达，采用组织化学、免疫化学和自动图像分析方法，检测了５４例胃癌切除标本的ｒａｓ基因表达、癌细胞核形态参数和ＤＮＡ含量及倍体分布类型。发现胃癌细胞ｐ２１表达水平随着ＤＮＡ含量不断增多、倍体成倍增加而逐渐下降。表明ｒａｓ过度表达主要出现在细胞表型发生明显转化之前。此外，发现胃癌细胞ｐ２１的表达水平与癌细胞核形态参数、癌肿大小、有无淋巴结转移均无关。     

川芎嗪抗缺氧致脑细胞损伤作用的实验研究

目的:观察川芎嗪对缺氧状态下离体大脑皮层细胞脂质过氧化物(LRO)含量及超氧化物歧化酶(SOD)活性的影响。方法:将4～5日龄 Wistar 大鼠大脑皮层分离并制成细胞悬液(5×10~6个细胞/ml),在 CO_2培养箱内孵育2h 之后观测单纯缺氧1h(细胞悬液通以95％N_2加5％CO_2),以及预先向细胞悬液加入磷酸川芎嗪(分10~(-5)、10~(-4)和10~(-3)mol/L3个剂量组),再缺氧1h 细胞 LPO 含量与 SOD 活性的改变。结果:缺氧可使 LPO 显著增加、SOD 活性明显降低;预先加入川芎嗪能有效防止缺氧所致的 LPO 升高和 SOD 活性降低。结论:川芎嗪对缺氧致细胞脂质过氧化损伤具有保护作用,其机制可能是通过增强内源性 SOD 活性、清除氧自由基,进而降低了细胞脂质过氧化程度。     

通脉疏络胶囊预防脑血栓形成药效学研究

目的:探讨通脉疏络胶囊预防脑血栓形成药效学机理。方法:用通脉疏络胶囊给动物灌胃,观察有关指标。结果:用通脉疏络胶囊后小鼠血凝时间较对照组明显延长,用二磷酸腺苷诱导的大鼠血小板聚集明显降低,降低小鼠脑组织中因脑缺血所致的乳酸脱氢酶及肌酸激酶活性含量升高。结论:通脉疏络胶囊具有预防脑血栓形成的作用,其作用机理与延长血凝时间,降低血小板聚集,保护缺血脑细胞有关。     

健脾益气和胃法防治大鼠胃缺血再灌注损伤的实验研究

目的:探讨大鼠胃缺血后再灌注胃粘膜损伤与氧自由基脂质过氧化的相关性及以健脾益气和胃法防治其胃粘膜损伤的细胞保护作用机制。方法:采用腹腔动脉结扎法,造成胃缺血20min,解除结扎,再灌注60min 后,取出胃粘膜,观察正常对照组、病理模型组和用药各组中胃粘膜之氧自由基脂质过氧化物及清除酶系诸指标的变化。结果:大鼠胃缺血后再灌注,胃粘膜脂质过氧化物(LPO)含量比正常对照组明显增加,超氧化物歧化酶(SOD)、非蛋白巯基(NPSH)、谷胱甘肽过氧化物酶(GSH-Px)含量则明显降低(P<0.01);术前口服健脾益气和胃中药各组胃粘膜 LPO 含量明显低于病理组,SOD、NPSH、GSH-Px 水平则明显高于病理组(P<0.05,P<0.01);而过氧化氢酶(CAT)和前列腺素 E_2(PGE_2)在实验各组的比较无统计学意义(P>0.05)。结论:氧自由基脂质过氧化参与胃缺血再灌注的胃粘膜损伤过程,健脾益气和胃法的治疗对胃缺血再灌注损伤具有保护作用。此作用可能是通过抑制氧自由基过氧化损伤,提高胃粘膜 SOD、GSH-Px、NPSH 活性,增强其抗氧化能力而实现的。     

小柴胡汤对鼠实验性肝纤维化的影响

目的:探讨小柴胡汤对鼠肝纤维化的抑制作用及该抑制作用与活性伊东细胞间的相互关系。方法:分别腹腔注射二甲基亚硝基胺和猪血清复制两种肝纤维化动物模型并投予小柴胡汤观察其预防与治疗作用。结果:小柴胡汤可促进肝维生素 A 含量恢复;降低肝胶原含量和明显抑制肝前α-Ⅰ型胶原的基因表达;显著减少Ⅰ、Ⅲ型胶原在肝脏沉积,明显减少。α-平滑肌原纤维阳性的伊东细胞的数目。结论:小柴胡汤可防治鼠肝纤维化的发生与发展。     

复方茵陈蒿汤对兔奥狄氏括约肌肌电活动及胆总管压力的影响

目的:揭示奥狄氏括约肌肌电活动与机械收缩的关系和复方茵陈蒿汤治疗胆石症的作用机制。方法:采用同步记录技术,动态观察灌胃前后兔奥狄氏括约肌肌电活动及胆总管压力的变化。结果:胆总管压力波动与括约肌肌电发放在时程上一致,药后30～75min,括约肌肌电脉冲频数明显增加,其增值明显高于相应时间的给予等量水灌胃的对照组(P<0.05,60min,P<0.01),胆总管压力无相应的升高。结论:奥狄氏括约肌肌电活动与机械收缩相藕联,复方茵陈蒿汤通过兴奋括约肌肌电活动,增强括约肌的节律性舒缩,促进胆汁排放。