Modulating effect of Hypericum perforatum extract on astrocytes in MPTP induced Parkinson's disease in mice

The present study has been evaluated the neuroprotective effect of Hypericum perforatum extract on the reaction of astrocytes in mice brain treated with an intraperitoneal injection of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (20 mg/kg with 2 hr intervals). Treatment with Hypericum perforatum extract (HPE) resulted in an inhibition of monoamine oxidase-B (MAO-B) activity and reduced astrocyte activation in striatal area induced by MPTP. The results show that HPE has neuromodulating effect against MPTP induced Parkinson's disease in mice.     

田基黄成分及药理应用研究进展

田基黄植物全草中主要化学成分为黄酮类、口山酮类、间苯三酚类等化合物,具有保肝护肝、退黄、抗菌、抗病毒、抗氧化以及抗肿瘤等药理作用。在检索国内外相关文献的基础上,对田基黄植物化学成分和药理作用以及临床应用进行了综述。     

银耳孢糖合用氟尿嘧啶对肉瘤S180和肝癌H22小鼠的抗肿瘤作用

目的对银耳孢糖与氟尿嘧啶(5-FU)合用的抗肿瘤作用进行研究.方法采用小鼠肉瘤S180和肝癌H22肿瘤模型,连续给药7 d后,剥出瘤块、胸腺及脾脏称取质量,计算抑瘤率和免疫器官指数;采用碳粒廓清实验测定吞噬指数.结果银耳孢糖合用5-FU(5,10,20 mg·kg-1)对小鼠肉瘤S180和肝癌H22有明显的抑制作用,对肉瘤S180的抑瘤率分别为41.7%,50.1%,68.8%,对肝癌H22的抑瘤率分别为42.3%,58.4%,69.8%.银耳孢糖合用5-FU能增加H22肝癌小鼠的免疫器官指数和吞噬指数.结论银耳孢糖与5-FU合用抗肿瘤具有增效作用,银耳孢糖对5-FU所致的免疫功能损伤有保护作用.     

TM208与5-氟尿嘧啶联合应用对小鼠肝癌H22移植瘤的抗肿瘤作用及其机制研究（英文）

4-甲基哌嗪-1-二硫代甲酸-（3-氰基-3,3-二苯基）丙酯盐酸盐（TM208）是一种新合成的氨基二硫代甲酸酯类化合物,具有良好的体内抗肿瘤作用,且毒性较低。探讨TM208与临床已知抗癌药联用能否提高疗效并降低毒性,可为TM208的临床试验提供依据。本实验通过小鼠肝癌H₂₂移植瘤模型考察了TM208与顺铂（DDP）、环磷酰胺（CTX）、5-氟尿嘧啶（5-Fu）分别联合用药的体内抗肿瘤作用及毒性。体内实验结果证实,5-Fu（5 mg/kg/2d）与TM208（100 mg/kg/d）联用后可显著增强对H₂₂肿瘤的抑制作用（P<0.01）,且几乎不增加毒性;而DDP和CTX则不能。进一步研究表明,TM208与5-Fu联用可通过下调cyclin B1,cdc2,cdk7和上调p21,p53的表达引起H₂₂实体瘤细胞发生G₂/M周期阻滞。同时此联合用药方案也可下调cyclin D1,cyclin E的表达,对cdk4,cdk2的表达则没有影响。Cdc2 mRNA的表达与其蛋白表达趋势一致,而cyclin B1mRNA表达在各组间没有差异。总之,TM208与5-Fu联用可提高抗肿瘤疗效,毒性不变,其抗肿瘤作用与细胞周期阻滞及其相关蛋白的表达变化有关。     

Chemosensitizing effect of vitamin C in combination with 5-fluorouracil in vitro

The antiproliferative effect and apoptosis-inducing action of 5-fluorouracil (5-FU) in combination with vitamin C were tested in vitro against the chemosensitive mouse lymphoma, the chemoresistant HEp-2 and a human lung fibroblast cell line. Vitamin C itself had no antiproliferative effect on the fibroblasts, but increased the anticancer effect of 5-FU dose-dependently. In the case of the chemoresistant cell line, only a high concentration of vitamin C increased the cytotoxicity of 5-FU. A combination of 5-FU and vitamin C exerted a significantly enhanced apoptotic effect on the mouse lymphoma cell line, whereas for the HEp-2 cell line this effect was less marked and was achieved only at a high concentration of vitamin C. These findings suggest that the administration of a high dose of vitamin C in combination with 5-FU chemotherapy enhances the chemoresponsiveness of cancer cells and serves as a potential sensitizer, especially in chemo-resistant cell lines. One of the mechanisms by which vitamin C potentiates cytostatics could be apoptosis induction.     

Transdermal delivery of 5-fluorouracil for induced ehrlich ascites carcinoma tumor in BALB/c mice and pharmacokinetic study

The purpose of this study was to determine the permeation of the hydrophilic compound 5-fluorouracil through human epidermal membranes, Ehrlich Ascites Carcinoma (EAC) cells were used as a model cell line to evaluate the cytotoxic concentration and anti-tumor activity of 5-fluorouracil (5-FU) through transdermal drug delivery for tumors. Cytotoxicity was assessed by exposing cell suspension to increased concentration of drug from 20-100 microg/ml and measuring the viable cell count by tryphan blue exclusion method. Results confirmed that 100 microg/ml of 5-FU was cytotoxic. The increase in the life span (ILS) was 87.05% with maximum survival time of 30.5+/-1.87 days. For 5-fluorouracil monolithic matrix transdermal patch, the results were statistically significant (p<0.05) compared to untreated control, anti-tumor activity was very effective compared to intravenous therapy. Patches did not show any sign of erythema, vesiculations or bullaous reaction. Mean cumulative skin irritation and adherence scoring for both animal and humans proved that none of the irritation sensitization reactions score were zero and less than one, while good adherence score was 0, with complete adherence to the skin, without leaving any adhesive residue on skin with scores = 0 in human subjects. Transdermal patches showed 100% flatness, thickness 150+/-0.03 mm, good content uniformity, folding endurance (>500 foldings), smoothness, transparency, flexibility and appearance. Pharmacokinetic studies of 5-FU transdermal patch in rabbits showed half-life 95+/-0.5 min, C(max) (ng/ml) 863.25,AUC(0-infinity) (ng/ml/h)1567+/-36 and T(max) (h) 1.5 with controlled release for 24 h which was very significant (p<0.001) compared to intravenous route. Recent patents has been reported for suitable treatment of tumors and cancer, by topical and transdermal applications. Velcro protection jackets were suitable for this study and protected our applied transdermal patched from being licked, scratched and rubbed off.     

奥沙利铂联合亚叶酸钙和氟尿嘧啶治疗晚期大肠癌的临床观察

目的评价奥沙利铂联合亚叶酸钙和大剂量氟尿嘧啶（5-FU）持续48 h静脉滴注治疗晚期大肠癌的疗效和安全性。方法32例大肠癌患者采用静脉滴注奥沙利铂100 mg/m^2,亚叶酸钙200 mg/m^2,亚叶酸钙滴注之后用5-FU 0．5 g静注,接着用5-FU 3．0 g/m^2持续静脉滴注48h,每2周1次,2次为1个周期。结果32例病例中,平均疗程数为4个周期,其中完全缓解（CR）1例,部分缓解（PR）15例,稳定（SD）12例,进展（PD）4例,总有效率（CR＋PR）为50%。不良反应为恶心、呕吐和骨髓抑制,但多为Ⅰ～Ⅱ度,一过性感觉异常。结论奥沙利铂联合亚叶酸钙和氟尿嘧啶治疗晚期大肠癌疗效较高,不良反应轻而且安全,患者容易耐受,值得推广使用。     

核桃提取物急性毒性和遗传毒性的实验研究

目的　观察核桃提取物对动物的毒性安全性并对其进行评价。方法　通过大鼠急性毒性实验 ,大鼠亚急性毒性实验 ,Am es试验以及小鼠睾丸染色体畸变试验 ,小鼠骨髓微核试验和小鼠单细胞凝胶电泳试验对其毒性安全性进行实验和评价。结果　急性毒性实验中 ,核桃提取物经口半数致死量 ( L D50 ) >10 g/ kg体重 ;亚急性毒性试验结果显示 :各项生化指标均在正常范围之内 ,而且各组之间差异无显著性 ,各组脏体比及体重增长差异无显著性 ;Am es试验结果显示 :自发回变组与各剂量组之间差异无显著性 ,而与阳性对照组差异有显著性 ;小鼠骨髓微核试验显示 :阴性对照组与各剂量组之间差异无显著性 ,阳性对照组与阴性对照组及各剂量组之间差异有显著性 ;小鼠睾丸染色体试验与单细胞凝胶电泳试验结果和微核试验相一致。结论　核桃提取物在急性毒性试验、亚急性毒性试验及遗传毒性试验中均未显示有毒性作用 ,符合《食品安全性毒理学评价程序和方法》GB15 193 .1- 94的要求 ,初步认为用于人体是安全的     

An evaluation of combination 5-fluorouracil and spirogermanium in the treatment of advanced colorectal carcinoma

Summary Seventeen patients with advanced colorectal carcinoma were treated with a combination of 5-fluorouracil and spirogermanium, a recently developed azaspiran-germanium compound remarkable for its lack of hematologic, gastrointestinal, renal or hepatic toxicity. Response to treatment and the incidence and severity of toxicity were evaluated. No patient achieved a complete response; there were three partial responses. Toxicity was unexpectedly frequent and severe; one patient was removed from study early due to intractable diarrhea, and there were two toxic deaths, both attributable to neutropenia and sepsis. Significant toxicity occurred in all seventeen patients, including three instances of Grade 3 or 4 hematologic toxicity. Given the low response rate and high incidence of life-threatening toxicity, we do not recommend further evaluation of this schedule of 5-fluorouracil and spirogermanium in the treatment of colorectal carcinoma.     

杂氮硅三环与5-氟尿嘧啶结合物的合成

杂氮硅三环具有免疫增强和抗肿瘤作用，依据药物设计的拼合原理设计了杂氮硅三环与5-氟尿嘧啶结合的协同前药，以期寻找高效低毒的抗肿瘤化合物。合成了2个未见报道的杂氮硅三环与5-氟尿嘧啶的结合物。其结构经质谱、核磁共振氢谱及元素分析确证。     

黄芪总提取物抗肿瘤作用的实验研究

目的研究TAE对小鼠HepA肝癌细胞的抗肿瘤作用。方法复制HepA肝癌小鼠抑制瘤模型,将60只接种HepA肝癌细胞昆明小鼠随机分为4组：模型对照组、黄芪总提取物高、中、低剂量组,实验12d末次给药后lh自眼球动脉采血,分离血清测定ALT、AST及ALP等所有肝功能指标,采血后处死全部小鼠,剥离皮下肿瘤,称小鼠肿瘤重量,计算出抑瘤率,并采用MTr法检测T淋巴细胞增殖反应的抑制作用。结果随着黄芪剂量增加,抑瘤率逐渐增加（P〈0．05）,TAE高、中剂量组可显著降低血清中ALT、AST及ALP含量（P〈0．05）,TAE高剂量组可显著升高淋巴细胞含量（P〈0．05）。结论TAE对小鼠HepA肝癌移植瘤有抑制作用。     

Synergistic antitumour effect of raltitrexed and 5-fluorouracil plus folinic acid combination in human cancer cells

5-Fluorouracil, usually in combination with folinic acid, is widely used in the treatment of both colorectal and head and neck squamous cell cancer patients. Since 5-fluorouracil plus folinic acid and the antifolate thymidylate synthase inhibitor; raltitrexed have distinct mechanisms of action and toxicity profiles, we have evaluated the potential synergistic antitumor interaction between these two agents combined with a sequential schedule of administration in KB (wt-p53) and Cal27 (mut-p53) head and neck squamous cell carcinomas, and LoVo (wt-p53) and HT29 (mut-p53) colorectal cell lines. The combination between a 24-h exposure to raltitrexed followed by a 4-h exposure to 5-fluorouracil plus folinic acid was globally synergistic, as assessed by the median effect principle and combination index. A specific contribution of folinic acid to the cytotoxic effect of the raltitrexed/5-fluorouracil combination was clearly demonstrated by the evaluation of the potentiation factor. In all cell lines, a 1.5- up to 17-fold reduction in the IC50 of both raltitrexed and 5-fluorouracil plus folinic acid was observed in the combination setting compared with the concentrations of the each drug used alone. Moreover, we demonstrated that raltitrexed/5-fluorouracil plus folinic acid induced a distinct S-phase block of the cell cycle, as well as a potentiation of the apoptotic cell death, compared with 5-fluorouracil plus folinic acid or raltitrexed/5-fluorouracil combination. This preclinical work represents, at least to our knowledge, the first demonstration of a synergistic interaction between raltitrexed and 5-fluorouracil modulated by folinic acid, and could represent a rationale for further clinical investigation of raltitrexed/5-fluorouracil plus folinic acid combination.     

奥沙利铂联合5-氟尿嘧啶和亚叶酸钙治疗晚期胃癌的临床研究

目的观察奥沙利铂联合5-氟尿嘧啶(5-FU)和亚叶酸钙(CF)治疗晚期胃癌临床疗效及其不良反应。方法奥沙利铂100 m g/m 2,静脉滴注2 h,第1天;CF 400 m g/m 2,静脉滴注,第1天;5-FU 400 m g/m 2,静脉推注,第1天;后续5-FU 2600 m g/m 2,静脉持续输注46 h;每2周重复,应用4次奥沙利铂(8周)后判断疗效。结果46例患者中,完全缓解(CR)5例(11%),部分缓解(PR)18例(39%),稳定(SD)16例(35%),进展(PD)7例(15%),CR+PR共23例,近期客观有效率为50%。26例初治患者中,CR 5例,PR10例,SD 8例,PD 3例,有效率58%;20例复治患者中,CR 0例,PR 8例,SD 8例,PD 4例,有效率40%,中位缓解时间为5个月,中位生存期为9个月。主要毒副反应为神经毒性,恶心、呕吐、白细胞和血小板减少程度较轻。结论奥沙利铂联合5-FU/CF治疗晚期胃癌有较好的近期疗效,毒副反应轻而且安全。     

山药多糖对糖尿病小鼠降血糖作用的研究

目的 探讨山药多糖对糖尿病小鼠的降血糖作用.方法 将90只小鼠随机分成山药多糖组、 格列苯脲组和健康对照组,各30只.小鼠经腹腔注射200 mg/kg四氧嘧啶建立糖尿病小鼠模型,用山药多糖？ 连续给小鼠模型灌胃给药12 d,以格列苯脲作阳性对照.结果 山药多糖组对糖尿病小鼠的血糖有明显降低 作用,与格列苯脲组比较差异无统计学意义（P＞0.05）.结论 山药多糖具有显著的降血糖作用.     

偏痛胶囊流浸膏镇痛抗炎作用实验研究

目的:研究偏痛胶囊流浸膏镇痛、抗炎药效学作用.方法:热板法、醋酸扭体法观察偏痛胶囊流浸膏对小鼠的镇痛作用,二甲苯致小鼠耳肿胀、蛋清致大鼠足肿胀的方法研究偏痛胶囊流浸膏的抗炎作用.结果:偏痛胶囊流浸膏能明显减少醋酸致小鼠扭体次数,显著提高小鼠痛阈值(P＜0.01或P＜0.05);明显抑制小鼠耳肿胀,减少耳重差,对大鼠足跖肿胀有显著抑制作用(P＜0.01或P＜0.05).结论:偏痛胶囊流浸膏具有较好的镇痛、抗炎作用.     

Poloxamer 188 and propylene glycol-based rectal suppository enhances anticancer effect of 5-fluorouracil in mice

The tumoricidal and apoptosis-inducing activities of 5-fluorouracil (5-FU) have been demonstrated in experimental and clinical investigations. Clinically, the 5-FU suppository form has been widely adopted for its advantages of less systemic toxicity, higher local tissue concentrations, and reduced first-pass effect. In this study, we investigated the feasibility of rectal administration of 5-FU suppository based on poloxamer 188 (P188) and propylene glycol (PG) and its anticancer effect on the murine experimental cancer models. The rectal suppository was made with 70% P188 and 30% PG, which was a solid phase at room temperature and instantly melted at physiological temperature. The treatment with the 5-FU suppository was more effective than the oral route in decreasing the volume of rectal cancer in mice. In addition, the survival rate of the mice with rectal cancer was higher in the group treated with the 5-FU suppository than in the group treated with 5-FU orally. Furthermore, in mice skin cancers induced by inoculation of murine CT-26 colon carcinoma cells, the anticancer effect of 5-FU was significantly enhanced by the rectal administration of the suppository than by oral treatment. Taken together, the results suggest that a poloxamer gel system with 5-FU/P188/PG is an effective rectal dosage form for the treatment of both rectal and non-rectal cancers.     

Double-blind randomised placebo-controlled phase III study of an E. coli extract plus 5-fluorouracil versus 5-fluorouracil in patients with advanced colorectal cancer

The primary aim of this study was to evaluate the toxicity (mucositis, diarrhea and leucopenia) of a therapy with 5-fluorouracil (CAS 51-21-8; 5-FU) plus an E. coli extract (LC-Extract, Laves coli extract, Colibiogen inject, cell-free soluble fraction from lysed E. coli, Laves strain) in comparison with 5-FU plus placebo. Secondary endpoints included general toxicity, response rate according to WHO, survival time and quality of life. 164 patients with advanced colorectal cancer were enrolled in this randomised, placebo-controlled, double-blind, multicenter phase III study. The treatment consisted of 0.167 ml/kg/d LC-Extract or placebo followed by 500-750 mg/m2/d 5-FU on five consecutive days, repeated every three weeks for up to six treatment cycles. 158 (77 verum, 81 placebo) patients were evaluable for toxicity, 144 (72 verum, 72 placebo) evaluable for response. The therapy with LC-Extract was well tolerated. Adverse events that occurred during the study were mainly judged as 5-FU- or tumor-related. Toxicity from treatment with 600 mg/m2/d 5-FU in both treatment groups was very low. After treatment with 750 mg/m2/d 5-FU patients in the placebo-group experienced a higher CTC toxicity than in the LC-Extract groups. Remission rate and survival time showed a slight trend in favour of LC-Extract. These results suggest a positive benefit-risk ratio of the additional application of LC-Extract to 5-FU in the treatment of advanced colorectal cancer especially for administration of high doses of 5-FU.     

硫酸壳聚糖体内抗肿瘤作用的实验研究

目的：研究硫酸壳聚糖的体内抗肿瘤作用。方法：用高、低（200、100mg/kg）两个剂量的硫酸壳聚糖分别腹腔注射治疗肉瘤180（S180）小鼠和艾氏腹水癌（EAC）小鼠10d,然后测定其抑瘤率、重要器官的内脏指数和生命延长率,同时设生理盐水组（空白对照组）和氟尿嘧啶组（阳性对照组）进行比较。结果：硫酸壳聚糖高、低剂量组和氟尿嘧啶组的抑瘤率分别为38.67%、30.19%和43.27%,3组的生命延长率分别为65.38%、69.23%和54.93%。和生理盐水组、氟尿嘧啶组相比,硫酸壳聚糖高、低剂量组的S180小鼠的胸腺指数均有明显增加（P〈0.05）。结论：硫酸壳聚糖能有效抑制S180小鼠肿瘤的生长和延长EAC小鼠的生存时间,其作用机制可能与其提高机体的免疫力有关。