耐药对肺结核病治疗效果的影响

目的 评价耐药对地区肺结核病治疗效果的影响.方法 对上海地区2004年2月-9月新登记敏感及耐药肺结核病人1年治疗转归进行分析和比较.结果 在全市各区（县）结核病定点医院新登记1 597例肺结核病病人中,805例培养阳性,其中731例经菌型鉴定为结核分枝杆菌的病人纳入分析.731例病人的总耐药率为18.7%,耐多药率为6.7%.敏感组治疗成功率达到93.0%,非MDR的耐药病人治疗成功率达到85%以上,MDR组治疗成功率为71.4%.经x2检验,差别有统计学意义（x2=83.996 8,P＜0.01）.在68例治疗不成功的病人中,耐药病人占38.2%;而在30例治疗失败的病人中,耐药病人占60%.复治敏感病人的治疗成功率（92.0%）与初治敏感病人（93.1%）相当,但是复治耐药病人的治疗成功率远低于初治耐药病人.结论 （1）上海地区肺结核病病人治疗管理效果良好;（2）耐药是肺结核病治疗失败的重要因素,应加强和改进对耐药结核病的治疗措施;（3）耐药和敏感病人治疗效果存在较大差异,应分别评价.     

康泉合用地塞米松控制化疗所致的胃肠道反应

目的：比较康泉及康泉合用地塞米松预防急性白血病化疗所致的胃肠道反应的效果。方法：在同一方案的不同疗程，分别单用康泉或康泉合用地塞米松，随机对照，共观察１１０疗程。结果：康泉及康泉合用地塞米松对预防化疗所致急性呕吐有效率分别为６９．５％和９５．１％，有明显差异（Ｐ＜０．０１）；对于迟发性呕吐两组的有效率分别为７４．５５５％和９１．８３％，亦有明显差异。结论：康泉和地塞米松合用对控制急性和迟发性恶性呕吐优于康泉单用     

抗癌药物诱导人膀胱癌BIU—87和E—J细胞凋亡的作用

应用分子生物学方法，观察了丝裂霉素、喜树碱、顺铂和阿霉素对膀胱癌细胞系ＢＩＵ８７和ＥＪ体外生长和生存的影响，对抗癌药物诱导膀胱癌细胞凋亡作用进行了研究。结果：四种抗癌药均能在不同程度上抑制膀胱癌细胞生长，诱导膀胱癌细胞凋亡的能力与其生长抑制效应成正比。细胞形态学和ＤＮＡ分析显示喜树碱、顺铂处理的ＢＩＵ８７和丝裂霉素、阿霉素处理的ＥＪ细胞呈现典型的凋亡现象。揭示药物的抑癌作用是通过诱导肿瘤细胞凋亡实现的，它可能是抑制肿瘤生长的机理之一。不同膀胱癌细胞系对药物诱导凋亡的敏感性存在着差异。细胞凋亡现象为肿瘤化疗提供了新的领域。     

Does Additional Doxorubicin Chemotherapy Improve Outcome in Patients with Hepatocellular Carcinoma Treated by Liver Transplantation?

The aim of this prospective randomized study was to determine whether additional doxorubicin chemotherapy improves outcome in patients with hepatocellular carcinoma (HCCA) treated by liver transplantation. Stratification parameters were tumor stage (UICC I-IVa), gender, age 50 years, α-fetoprotein 20 ng/mL, cirrhosis and HbsAg status. For pre-operative chemotherapy doxorubicin (15 mg/m²) was given biweekly, intra-operative chemotherapy was a single dose administered before surgical manipulation. Post-operative chemotherapy from day 10 was as given preoperatively for a total dosage of 300 mg/m². Outcome parameters were overall survival (OS) and disease-free survival. Of the 75 consecutive patients who received liver transplantation for treatment of HCCA, 62 patients were enrolled. Thirty-four patients were randomized in the chemotherapy group; 28 patients were in the control group and transplanted only. OS rates at 5 years were 38% in the chemotherapy group and 40% in the control group, disease-free survival rates at 5 years 43% and 53%, respectively. Tumor stage and vascular invasion were identified as independent risk factors for recurrence of disease. Doxorubicin chemotherapy did not improve organ survival and disease-free survival in patients undergoing liver transplantation for HCCA.     

99Tcm-MIBI显像评价乳腺癌新辅助化疗疗效

目的 探讨^99Tc^m-甲氧基异丁基异腈（MIBI）显像评价乳腺癌新辅助化疗（NCT）疗效的价值。方法 35例局部进展期乳腺癌（LABC）患者术前化疗前后分别触诊估测肿瘤最大垂直长径及行^99Tc^m-MIBI显像，术后对乳腺癌标本行病理检查及P-糖蛋白（P-gP）、增殖细胞核抗原（PCNA）免疫组织化学染色。观察注射^99Tc^m-MIBI后60min显像图。采用目测法和半定量法，以病灶／本底（T／N）放射性比值降低〉35％为有效。临床疗效按WHO标准评价。化疗后肿瘤细胞病理形态学改变以Ⅱ、Ⅲ级定为显效，Ⅰ级定为弱效。结果 病理检查显效与弱效组间，显像目测法分析NCT有效率分别为75％和9％，差异有显著性（P〈0．01），灵敏度、特异性和准确性分别为75％、91％和80％；半定量法评价NCT疗效的灵敏度、特异性和准确性分别为84％、80％和83％；临床测量肿瘤最大垂直长径则分别为50％、64％和54％。^99Tc^m-MIBI显像评价疗效的灵敏度、准确性明显高于临床确诊。24例病理检查示显效的患者中，^99Tc^m-MIBI摄取与PCNA水平相关，与P-gP水平无关。结论 ^99Tc^m-MIBI显像可有效监测LABC患者术前NCT疗效。     

替尼泊苷和卡莫司汀对脑胶质瘤的治疗作用及耐药的研究

目的研究联合应用替尼泊苷、卡莫司汀对脑胶质瘤细胞的杀伤作用及联合用药的耐药机制.方法测定单独或联合应用替尼泊苷、卡莫司汀两种药物对20例胶质瘤细胞的体外敏感性,检测各标本中多药耐药基因(mdr-1)表达的情况.结果①替尼泊苷、卡莫司汀的敏感性为20%、15%,联合用药为45%,经统计学分析联合应用明显优于单独用药(P<0.05);②联合用药的耐药情况(8/20)与mdr-1基因表达(7/20)符合良好(P<0.05).结论亚硝脲类和鬼臼毒衍生物联合应用对胶质瘤有较好的治疗作用,联合用药的耐药性与mdr-1的表达有关.     

3H-胸苷酸掺入法对选择前列腺癌化疗方案的价值

目的为临床选择激素难治性前列腺癌(HRPC)的化疗方案提供参考.方法采用3H-胸苷酸(3H-TdR)掺入法检测了20例HRPC细胞对常用化疗药物的敏感性.结果HRPC对单药的体外敏感性依次为足叶乙苷(VP16)＞阿霉素(ADM)、5-氟尿嘧啶(5-FU)、雌二醇氮芥(EMP)＞长春花碱(VLB)＞顺铂(DDP);二药联合可使敏感性进一步提高,依次为EMP加VP1 6、5-FU加ADM＞EMP加VLB＞5-FU加DDP三药联用抑瘤作用更强,EMP加VLB加APM、5 FU加ADM加DDP＞EMP加VLB加DDP.结论3H-TdR掺入法有助于化疗方案的选择,对HRPC以联合化疗效果较好.     

Characterization of cell death events induced by anti-neoplastic drugs cisplatin, paclitaxel and 5-fluorouracil on human hepatoma cell lines: Possible mechanisms of cell resistance.

Two different hepatoma cell lines were incubated for 48h with chemotherapeutic drugs cisplatin, paclitaxel and 5-FU to determine their ability to induce cytotoxicity and DNA fragmentation as well as to modify the expression of some cell death-related genes that could be involved in the resistance to therapy. We observed that cisplatin and paclitaxel induced cytotoxicity, but significant differences between both cell lines, were found only in the case of paclitaxel. At 48h, apoptosis was clearly present in Hep3B cells treated with cisplatin and HepG2 cells treated with paclitaxel. 5-FU induced cytotoxicity in both cell lines but only at higher concentrations than the other two drugs, triggering apoptosis and necrosis in HepG2 cells and only necrosis in Hep3B. When a time course was performed for the first 8h of treatment to elucidate the initial mechanism of cell death responsible for DNA fragmentation, we observed that 5-FU in Hep3B, and cisplatin in both cell lines, induces primary necrosis, whereas at the concentration tested here, paclitaxel clearly triggers apoptosis in both cell lines. HepG2 cells were weakly sensitive to 5-FU in the first 8h of treatment, so the primary mechanism of cell death was not clear, but results seem to indicate that it could be apoptosis. At 48h, Bax was not up-regulated with any of the treatments, whereas cisplatin was able to induce Bcl-xL down-regulation in both cell lines. Treatment with 5-FU also down-regulated Bcl-xL in HepG2 cells. We also measured variations in the expression of survivin, an inhibitor of apoptosis that has also been involved in mitototic catastrophe. Hep3B cells seem to show an increase in protein levels with all treatments. Exposure to paclitaxel resulted in the highest effect. In the case of HepG2 cells, there was a decrease in survivin expression when cells were treated with 5FU and paclitaxel, both treatments showing complete loss of the protein. Using an antibody that recognizes unprocessed caspase-3, we observed that the enzyme was assumingly activated in HepG2 cells treated with 5FU and paclitaxel, but only weakly after treatment with cisplatin. Hep3B cells did not show activation since the levels of the pro-enzyme remained the same as that in the control. In conclusion, the three drugs tested in this study could induce cell death, with paclitaxel being more effective inducing apoptosis. 5FU was only effective at high doses and its mechanism seems to be primarily related to necrosis in Hep3B and probably apoptosis in HepG2. Cisplatin mechanism of cell death is probably mediated by the decrease in anti-apoptotic protein Bcl-xL whereas paclitaxel and 5FU are decreasing the apoptosis inhibitor survivin. According to pro-enzyme levels, caspase-3 was only activated in HepG2 cells, whereas in the case of Hep3B cells the mechanisms of toxicity appear to be caspase-3-independent at the time and concentrations tested in this study. The resistance of Hep3B cells to death induced by chemotherapy could be related to an increase in the expression of IAP survivin, which can decrease cell response to the treatment or even switch the type of death from apoptosis to another kind, making therapy less efficient.     

高能聚焦超声刀联合氟脲嘧啶、四氢叶酸治疗晚期胰腺癌临床疗效观察

目的探讨高能聚焦超声刀加氟脲嘧啶、四氢叶酸治疗晚期胰腺癌临床疗效及毒副作用。方法30例经病理学或细胞学确诊的晚期胰腺癌病人先用高能聚焦超声刀(HIFU)治疗，再予氟脲嘧啶、四氢叶酸联合化疗。氟脲嘧啶500mg／m^2加入5％GNS500ml静滴持续6小时以每天1次连用5天，CF(四氢叶酸)100mg／m^2加入生理盐水250ml静滴每天1次连用5天，28天为1周期，至少治疗2个周期。结果CR1例；PR9例；MR9例；NC5例；PD6例。总有效率63％。毒副作用主要消化道反应，其他副作用轻微。结论应用HIFU局部治疗胰腺癌同时合用四氢叶酸加氟脲嘧啶全身化疗近期疗效提高明显，止痛明显达75％，副反应小，值得应用。     

低浓度5-Fu24-小时持续化疗对BEL-7402肝癌细胞株的细胞周期的影响

目的研究低浓度5-Fu 24-小时持续化疗和高浓度5-Fu短时间化疗对BEL-7402肝癌细胞株的细胞周期的影响：方法用低浓度(1000．0μg/L)的5．Fu对BEL-7402肝癌细胞株进行持续24小时的培养(A组)，用高浓度(50000．0μg/L)的5-Fu对BEL-1 7402肝癌细胞株进行2小时培养(B组)，在培养后的不同时间点用流式细胞技术检测细胞周期的变化。结果A组结果显示：0h、4h、8h、12h、16h、20h和24h的S期细胞的百分数分别为25.23％、32．35％、39．28％、41．05％、46．02％、47．00％及47．14％。B组结果显示：0h、4h、8h、12h、16h、20h和24h的S期细胞的百分数分别为24．68％、68．43％、46．67％、43．67％、35．42％、33．22％及32．96％。结论5-Fu引起的S期细胞周期阻滞不但和浓度相关，也和作用时间相关。低浓度(1000．0μg/L)的5-Fu持续化疗较高浓度(50000．0μg/L)的5-Fu短时间(2小时)化疗更容易引起BEL-7402肝癌细胞株S期阻滞。