目的:研究TRAIL对卵巢癌COC1/DDP细胞生长的影响，以及化疗药物DDP等对TRAIL受体（DR4、DR5）表达的影响，揭示TRAIL与COC1/DDP细胞顺铂耐药性的关系。方法:用MTT法检测不同浓度TRAIL蛋白和TRAIL与DDP联合用药对COC1/DDP细胞生长的影响，用RTPCR方法检测DDP对TRAIL受体（DR4、DR5）表达的影响。结果:①TRAIL蛋白对COC1/DDP细胞生长有抑制作用，且随着TRAIL蛋白浓度升高，细胞抑制率逐渐上升。②DDP（2.5μg/mL）对COC1/DDP细胞生长抑制作用较弱（抑制率为3.31%），DDP在加入TRAIL蛋白后对细胞生长抑制率显著升高（Plt;0.05）。③DDP使COC1/DDP细胞的DR5表达水平显著增强为正常对照组的3.54倍（Plt;0.001）。结论:TRAIL蛋白对COC1/DDP细胞生长有抑制作用，DDP与TRAIL联合使用COC1/DDP细胞生长抑制更明显，TRAIL可逆转COC1/DDP细胞对DDP的耐药性，耐药性的逆转可能与DDP导致TRAIL受体DR5水平增高促进了肿瘤细胞的凋亡有关。
Objective To review the recent studies on the multidrug resistance of breast cancer. Methods The literatures of recent years on the studies of multidrug resistance, multidrug resistance protein and breast cancer resistance protein were reviewed. Results Multidrug resistance resulted from multiple factors. How to identify the sensibility of chemotherapy drugs and select individual therapeutic regime early were important to improve the survival rate and life quality of breast cancer patients. Conclusion These studies on multidrug resistance of breast cancer are helpful to predicting the effect and outcome of chemotherapy and overcoming the barrier of drug resistance.
Test of tissue tolerance to domastic prosthetic materials (carbon fiber mesh, siliconized velvet, silk cloth and dacron cloth) as a subcutaneos transplant was performed in the adcominal wall of rabbit. These implants and their surroundding tissues were excied for studies at second , fourth, eighth and the twelfth weeks after operation. Ratio of fibroblast count to inflammatory cells count which is a common parameter of tissue tolerance was calculated in these four groups. The result shows that fibroblastic cell reaction elicited by carbon fiber mesh is the greates among the four prosthetic materials, the second one is dasron cloth. The inflammatory cell reaction elicited by silk is the greatest among the four materials, the second is carbon fiber mesh, and the dacron cloth the least. Tissure tolerance of dacron cloth is the best in the four prosthetic materials for implantation while sick is the worst.
Objective To probe the relationship between the patients′prognosis and the gene of multidrugs and drug resistance in uveal melanoma.Methods The gene expression of cyclin D1, epithelial growth factor receptor (EGFR), non-metastasis gene 23 (nm 23), P glucose protein (P-gp ) , multidrug resistance relation protein (MRP) and lung resistance protein (LRP) expression in 96 cases of uveal melanoma were detected by depigment immunohistochemistry. The patients with complete anamnesis data were observed continuously, and the follow-up results were classified. Results Among the 96 cases of uveal melanoma, the epithelioid cell type was in 21, the mixed cell type in 56, and the spindle cell type in 19 ; including 76 at intraocular stage and 20 at extraocular stage. As the level of metastasis suppress gene nm 23 expression decreased and the level of cyclin D1 and EGFR expression increased, the expression level of drug resistance genes increased. The levels of LRP and MRP had negative correlation to the expressions of nm 23 and postive correlation to the expressions of nm 23, Cyclin D1 and EGFR. In 58 patients′who were observed continuously, 19 died in 5 years and 26 survived over 5 years.Conclusion There are significant as sociation between patients′prognosis and multidrug and drug resistance gene in uveal melanoma.(Chin J Ocul Fundus Dis，2003，19：1-4)
PURPOSE:Studying the multidrug resistance(MDR) phenotype occurring in retinoblastoma and its mechanism. METHODS:Using the procedure of stepwise increase in drug concentrations to obtain a retinoblastoma subline which resistant to 600ng/ml vincristine (HXO-RB/VCR). Characteristics of this drug-resistant cell line were investigated by cell counting,drugcontents determinatin,drug sensitivity evaluation and radiation sensitivity test. RESULTS:This cell line was cross-resistant to VDS,MMC VP16，ADM ,DDP,CBP,but not resistant to BCNU and 5-Fu. It was proved to be collaterally sensitive to MTX,and the response to 60Co gamma;-ray was modified slightly in HXO-RB/VCR cell line. Intracellular levels of VCR was much higher in HXO-RB44 cells than in the resistant subline. Those cross-resistances can be reversed by verapamil partly. CONCLUSIONS:MDR and radiation resistance of retinoblastoma can be induced by exposing to VCR and reversed by verapamil partly. （Chin J Ocul Fundus Dis,1997,13: 6-9）
Objective To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 mg, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 mg Yinhuang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher’s exact test were used for categorical variables.Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild adverse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after administration of single-doses (40-560 mg) and multi-doses (240-400 mg once a day for consecutive 7 days). The maximum-tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recommended for phase II study.
Objective To evaluate the safety and tolerance of medicinal charcoal enteric-coated tablets in healthy volunteers. Methods A total of 44 healthy volunteers were randomly divided into 6 single-dose groups (0.5 g, 2 g, 4 g, 6 g, 8 g and 10 g) and a multiple-dose group (3 g, 3 times a day, for 14 days). The safety profile and tolerance were evaluated by observing symptoms, vital signs, and laboratory tests. Results No serious adverse event was reported for any volunteer. Abdominal distension occurred in 2 volunteers in the 4 g dose group and the 6 g dose group. One volunteer in the 8 g dose group experienced nausea and vomiting. Transient decrease in white blood cell count was observed in one volunteer in the 10 g dose group. Abdominal distension occurred in 2 volunteers of the multiple-dose group. Conclusion Based on our findings, the maximum tolerated dose of medicinal charcoal enteric-coated tablets in Chinese healthy volunteers is 10 g. The recommended dose for subsequent clinical trials is 3 g, 3 times a day.
Objective To evaluate the safety and tolerance of pegfilgrastin (PEG-G-CSF) in Chinese healthy volunteers. Methods Thirty healthy volunteers were randomly divided into five single-dose groups to receive PEG-G-CSF 15, 30, 50, 60 or 75μg/kg by hypodermic injection. The safety profile and tolerability were evaluated by observing symptoms, vital signs, laboratory tests and electro cardiogram. Results No serious adverse event was reported for any volunteer. Transient dizziness occurred in one person in the 50 μg/kg dose group, and mild dizziness and ostalgia was found in all six people in the 75μg/kg dose group, of whom one experienced transient fever and two experienced mild diarrhea. No clinically significant changes in laboratory tests and electrocardiogram were found during the follow-up period. Conclusions The maximum tolerated dose of PEG-G-CSF injection in Chinese healthy volunteers is 60 μg/kg. Doses below 60μg/kg can be well tolerated. The recommended dose for phase II clinical trials is 60 μg/kgone, one dose for each cycle of chemotherapy.
目的 评价健康志愿受试者对通栓救心片的耐受性和安全性，为Ⅱ期临床试验给药方案提供依据。 方法 2009年1月－4月，选择健康受试者38例，随机进入5个单次给药组和2个连续给药组。单次给药组分别口服通栓救心片3、6、8、10、15片；连续给药组口服通栓救心片2片/次和3片/次，3次/d，服药7 d。观察生命体征、实验室检查指标、临床症状和不良反应。 结果 单次给药8片和15片组各有1例有轻微头痛、头昏；连续给药组有轻微头昏或恶心的不良反应，均未经处理自动消失。 结论 健康人体对通栓救心片耐受性较好，临床应用较安全，仅见轻微头昏、头痛或恶心。推荐Ⅱ期临床试验给药剂量范围是（2～3）片/次，3次/d 。
目的 总结静脉制剂Ⅰ期临床耐受性试验中的护理要点。方法 2011年10月－12月，采用随机、盲法、安慰剂平行对照试验设计，在健康志愿者中按剂量递增原则，逐组完成8个剂量单次静脉滴注给药耐受性试验。 结果 试验顺利完成。静脉制剂的Ⅰ期耐受性试验中，研究护士在临床试验前需认真学习试验方案，做好试验病房、监护急救设施设备的充分准备，针对可能出现的不良反应制定切实可行的处理预案，试验过程中密切监测，对出现的不良反应做好救治工作。特别针对静脉制剂，须做好受试者的心理疏导，保证静脉穿刺一次成功，减少受试者因情绪紧张、穿刺疼痛等因素干扰对试验药物耐受性的评价。 结论 Ⅰ期临床耐受性试验实施前准备充分，试验过程中为受试者提供良好的试验环境和心理护理，提高静脉穿刺一次成功率，密切监测，可使试验过程顺利，并获得客观、准确的试验结果。