P14ARF基因联合氟尿嘧啶对人结肠癌LOVO细胞的作用

目的观察p14ARF基因转染联合氟尿嘧啶对人结肠癌LOVO细胞的作用.方法采用RT-PCR和Western blot方法检测转染前后LOVO细胞中p14ARF基因的表达.四唑蓝比色法（MTT法）检测细胞增殖,流式细胞术分析细胞周期,对比在不同浓度的氟尿嘧啶作用下转染前后LOVO细胞的增殖情况.结果LOVO细胞呈现p14ARF基因缺失变异.RT-PCR和Western blot法证实转染后LOVO细胞中有p14ARF基因的表达.p14ARF基因转染后细胞增殖受抑,流式细胞仪显示p14ARF基因诱发凋亡.在氟尿嘧啶0.1 g/mL的作用下,未转染的LOVO细胞的增殖速度未受影响,而转染后LOVO细胞较未用药时的抑制率增加;氟尿嘧啶1、10、100 μg/mL时,对转染前后LOVO细胞均有增殖抑制作用,且呈剂量相关性.氟尿嘧啶对转染后LOVO细胞的抑制率明显高于未转染的LOVO细胞.结论p14ARF基因转染可抑制LOVO细胞增殖.p14ARF基因和氟尿嘧啶联合用于LOVO细胞能够加强氟尿嘧啶的增殖抑制作用,明显提高LOVO细胞对氟尿嘧啶的敏感性.     

缓释氟尿嘧啶植入剂在大肠癌患者的药动学研究

目的:研究缓释氟尿嘧啶植入剂术中植入治疗大肠癌的体内药动学特征.方法:24例大肠癌患者根治术后,关腹前分多点植入缓释氟尿嘧啶,定时采集血样,以高效液相色谱法检测血中氟尿嘧啶浓度.结果:药动学为一室模型,Tmax=72 h,Cmax=(0.56±0.23)μg·mL-1,维持0.1 μg·mL-1以上浓度达20d,AUC达140μg·h·mL-1.24例患者均顺利完成实验,未见不良反应.结论:术中植入缓释氟尿嘧啶后,有典型的药动学特征,对指导临床用药具有积极意义.     

奥沙利铂联合羟基喜树碱和氟尿嘧啶及亚叶酸钙治疗晚期胃癌的临床研究

目的：观察以奥沙利铂（LOHP）、羟基喜树碱（HCPT）、氟尿嘧啶（5FU）及亚叶酸钙（LV）组成的HLOF方案和顺铂（DDP）、HCPT、5-FU及LV组成的HLPF方案治疗晚期胃癌的疗效与安全性。方法：61例患者随机分组，试验组32例给予HLOF方案化疗，L-OHP130mg／m^2，静脉滴入2h，d1；HCPT6mg／m^2，静脉滴入，d1～d3；5-FU500mg／m^2，静脉滴入．d1～d3；LV100mg／m^2，静脉滴入，d1～d3。对照组29例给予HLPF方案化疗，除用DDP替代L-OHP外余同对照组。DDP用法：30mg／m^2，静脉滴入，d1～d3。以上方案均每21～28d重复。每例至少完成2个周期化疗方可评价疗效。结果：试验组CR2例．PR17例，SD8例，PD5例，有效率为59．4％（19／32）；对照组PR12例．SD11例，PD6例，有效率为41．4％。两组总有效率差异无统计学意义，P〉0．05。不良反应HLOF组食欲下降、恶心、呕吐的发生率较对照纽低，P〈0．05；神经毒性发生率高于对照组。KPS评分HLOF组升高幅度高于对照，P〈0．05。两组疾病无进展时间（time to progress，TTP）及生存期比较，差异均无统计学意义，P〉0.05。结论：治疗晚期胃癌，两者均为有效、低毒的化疗方案。在改善生活质量和减轻消化道反应方面，HLOF优于HLPF方案。     

高效液相色谱法测定兔房水中氟脲嘧啶和丝裂霉素的含量

目的:测定壳聚糖膜和免眼房水中氟脲嘧啶(5-Fu)和丝裂霉素(MMC)的含量.方法:使用Waters HPLC仪,配有浸透限制固定相(RAM)直接进样,流动相为甲醇-水(10:90),流速为0.8 mL·imin-1,紫外二极管阵列检测器,测定溶液和房水中的5 Fu、MMC浓度.结果:5-Fu和MMC与房水中的蛋白质有良好的分离,保留时间分别为3.8 min和5.6 min.两种药物在规定的浓度范围内都显良好的线性关系,日内RSD＜4%,日间RSD＜7%,平均回收率分别为99.50%和99.04%.结论:RAM-HPLC法样品不经前处理,简单快速,精密度好,回收率高.当壳聚糖膜吸附了5-Fu和MMC置于兔眼内时,用本法已测定了其释放药物过程.     

卵巢癌术中腹腔内播撒缓释氟尿嘧啶的临床研究

目的评价卵巢癌患者术中腹腔内播撒氟尿嘧啶缓释剂后的疗效和安全性。方法 60例卵巢癌患者随机分为治疗组（术中播撒氟尿嘧啶缓释剂）和对照组（常规手术）各30例。比较2组患者治疗后1周内局部并发症和引流量情况,同时密切观察全身毒副反应。结果治疗组术后3~7 d腹腔引流量较对照组明显减少（P〈0.05）;并发症未见增多（P〉0.05）。同时2组患者全身毒副反应均能耐受,手术切口愈合良好。结论术中播撒氟尿嘧啶缓释剂简便、安全、有效,值得临床推广。     

Enrichment of Oct3/4‐positive cells from a human bronchial epithelial cell line

Most adult stem cells are in the G0 phase of the cell cycle, accounting for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. The anti‐tumor drug 5‐fluorouracil (5‐FU) selectively kills proliferating cells, sparing cells in the G0 phase. Thus, the objective of this study was to determine whether 5‐FU can be used to enrich stem cells in a human bronchial epithelial (HBE) cell population in vitro. Side population (SP) cells were isolated from untreated HBE cells or HBE cells treated with 5‐FU, and the resulting cells were subjected to colony formation assays, culturing of cell spheres, and tumorigenicity assays. Expression of Oct3/4, Sox2, PCK, and β‐catenin were examined by Western blot analysis and immunofluorescence. Treatment with 5‐FU increased the percentage of SP cells from 0.3% to 1.5%, and the clonogenic ability of 5‐FU‐treated cells was more than twofold higher than that of HBE cells. Cells that survived after 5‐FU treatment exhibited a higher capacity for sphere formation. Furthermore, spheres formed from 5‐FU‐treated cells possessed the capacity to generate differentiated progenies. Cells treated with 5‐FU also exhibited tumorigenic potential, based on tumor formation assays in nude mice, and Oct3/4‐positive cell aggregates were identified in the resulting tumors. In this study, we have shown that 5‐FU treatment enriched the population of cells expressing the putative embryonic markers Oct3/4 and Sox2 and exhibiting nuclear accumulation of β‐catenin. Furthermore, 5‐FU‐treated cells expressed low levels of the epithelial differentiation marker PCK. Analysis of epigenetic modifications suggested that Oct3/4‐positive cells possessed characteristics of stem cells. These results demonstrate that treatment with 5‐FU can enrich the stem cell population present in a human bronchial epithelial cell line, and implicate combined treatment with 5‐FU and serum‐free medium as a new method for isolation of stem‐like cells from the HBE cell line.     

S-1 monotherapy as second line chemotherapy in advanced gastric cancer patients previously treated with cisplatin/infusional fluorouracil

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.     

The Role of Interferons in the Treatment of Colorectal Cancer

Summary

There is a substantial body of evidence suggesting in vivo synergy between fluorouracil (FU) and interferons (IFNs). The mechanism(s) which is implicated in the expression of synergy with the combination of FU and IFNs is unknown. Although phase I sudies have demonstrated a pharmacokinetic advantage for this combination, subsequent phase II studies in patients with advanced colorectal cancer showed that only one-third of the patients responded partially to this treatment. Double modulation of FU with leucovorin and IFN does not appear to add any survival benefit to these patients compared to single modulation of FU by IFN. In conclusion, the role of IFNs in the treatment of colorectal cancer has not been defined yet. It is hoped that phase III trials which currently are in progress will clarify this issue.     

Relationship between Fas/FasL expression and apoptosis of colon adenocarcinoma cell lines

INTRODUCTIONFas/ FasL system has been identified as a keymediator of apoptosis in tumor cells[1-4]. Theoccurrence and development of neoplasm are closelyrelated to apoptosis[5-7] Most chemotherapeuticdrugs kill cancer cells mainly by inducingapoptosis[8-14].'