Characterization of tetrandrine,a potent inhibitor of P-glycoprotein-mediated multidrug resistance

Multidrug resistance (MDR) is one of the main obstacles in tumor chemotherapy. A promising approach to solving this problem is to utilize a nontoxic and potent modulator able to reverse MDR, which in combination with anticancer drugs increases the anticancer effect. Experiments were carried out to examine the potential of tetrandrine (Tet) as a MDR-reversing agent. Survival of cells incubated with Tet at 2.5 mol/l for 72 h was over 90%. Tet at 2.5 mol/l almost completely reversed resistance to vincristine (VCR) in KBv200 cells. Tet at a concentration as low as 0.625 mol/l produced a 7.6-fold reversal of MDR, but showed no effect on the sensitivity of drug-sensitive KB cells in vitro. In the KBv200 cell xenograft model in nude mice, neither Tet nor VCR inhibited tumor growth. However, VCR and Tet combined inhibited tumor growth by 45.7%, 61.2% and 55.7% in three independent experimental settings. In the KB cell xenograft model in nude mice, Tet did not inhibit tumor growth, but VCR and the combination of VCR and Tet inhibited tumor growth by 40.6% and 41.6%, respectively. Mechanism studies showed that Tet inhibited [³H]azidopine photoaffinity labeling of P-gp and increased accumulation of VCR in MDR KBv200 cells in a concentration-dependent manner. The results suggest that Tet is a potent MDR-reversing agent in vitro and in vivo. Its mechanism of action is via directly binding to P-gp and increasing intracellular VCR accumulation.Abbreviations DMSO Dimethyl sulfoxide - FBS Fetal bovine serum - MDR Multidrug resistance - MTT 3-(4,5-Dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide - PBS Phosphate-buffered saline - P-gp P-glycoprotein - SDS Sodium dodecyl sulfate - Tet Tetrandrine - VCR Vincristine     

进展期胃癌S-1与5-FU基础化疗有效性和安全性Meta分析

目的 S-1被应用于进展期胃癌一线化疗中,其疗效也备受关注.本研究评估S-1基础化疗对比5-氟尿嘧啶(5-Fluorouracil,5-FU)基础化疗方案在进展期胃癌一线化疗中的有效性和安全性.方法 用“胃癌、替吉奥或S-1、5-氟尿嘧啶和随机对照研究”等检索词,在Pubmed、Embase、Cochrane Library、ASCO会议摘要、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)和中文科技期刊全文数据库(VIP)等检索相关的临床随机对照试验,检索时间截止至2016-10.提取总生存期、无疾病进展生存期、有效率、3～4级不良反应等数据.采用Revman 5.3和STATA 12.0进行数据分析.结果 共纳入18个随机对照研究,3 581例患者.结果显示,S-1基础化疗在总生存期(HR=0.92,95％CI为0.84～1.01,P=0.07)及无疾病进展生存期(HR=0.90,95％CI为0.76～1.07,P=0.25)方面与5-FU基础化疗方案差异无统计学意义,但有更高的有效率,RR=1.46,95％CI为1.22～1.74,P＜0.001.S-1基础化疗方案3～4级中性粒细胞减少(P＜0.001)、白细胞减少(P＜0.001)、血小板减少(P=0.01)、口腔炎(P＜0.001)和脱发(P=0.02)等不良反应较5-FU基础化疗发病率更低,差异有统计学意义.结论 相比于5-FU基础化疗,S-1基础化疗在进展期胃癌一线治疗中均是有效且更安全的化疗方案.     

食管癌的免疫治疗

肿瘤进展通常与免疫抑制或癌细胞逃避免疫监视相关.免疫治疗可提高免疫系统识别和清除肿瘤细胞的能力,且对正常组织影响轻微,是目前晚期食管癌研究的热点.食管癌的免疫治疗方法主要包括免疫检查点抑制剂、过继细胞免疫治疗、肿瘤疫苗和抗体治疗.目前大量临床试验正在进行中,以评价免疫治疗在食管癌中的作用.以Pembrolizumab和Nivolumab为代表的免疫检查点抑制剂在晚期食管癌治疗中已取得初步成功,为食管癌患者改善预后和生命质量带来希望.未来还需要对肿瘤异质性、疗效预测靶点、免疫治疗耐受等影响免疫治疗疗效的问题展开进一步的研究.     

Ⅲ期非小细胞肺癌的手术治疗

手术治疗在Ⅲ期非小细胞肺癌（NSCLC）综合治疗中有着举足轻重的地位。本文针对Ⅲa期和Ⅲb期不同类型手术方案的选择及手术疗效作一综述。对于T3N1M0的Ⅲ8期NSCLC来说，外科手术是最主要的治疗手段，手术指征很明确，而N2阳性患者治疗方案的选择是争论的焦点。肺切除术加系统性肺门纵隔淋巴结清扫术适用于“可切除”的N2期NSCLC，预后较佳，而“不可切除”的N2期NSCLC预后很差，不主张手术治疗。对于一般情况、心肺功能较好的部分T4N0M0患者，积极采取手术治疗，甚至应用体外循环技术，扩大切除受累的器官，可取得较好的治疗效果。目前多主张对于手术治疗的Ⅲ期NSCLC辅以术后化疗或实施新辅助化疗，而是否需采用放疗尚没有定论。     

ECX方案治疗晚期胃癌的临床观察

目的观察ECX方案（表阿霉素＋顺铂＋希罗达）治疗26例晚期胃癌的疗效和耐受性。方法表阿霉素50mg/m^2,静脉推注,第1天;顺铂30mg/m^2,静脉滴注,第1～2天;希罗达1000mg/m^2,口服,每天2次,第1～14天,每21～28天为1个周期。每例患者治疗至少2个周期,2个周期化疗即4周后评价疗效。结果在可评价疗效的该26例患者中,完全缓解（CR）1例（3.8%）,部分缓解（PR）11例（42.3%）,疾病稳定（SD）9例（34.4%）,疾病进展（PD）5例（19.5%）,总有效率（CR＋PR）46.1%,临床获益者（CR＋PR＋SD）共21例,占80.5%;平均肿瘤进展时间（TTP）为（6.04±2.20）个月,平均生存期（MST）为（12.04±2.14）个月。不良反应主要为恶心呕吐,骨髓抑制,腹泻,手足综合征。结论ECX方案治疗晚期胃癌疗效好,不良反应小,患者耐受性好。     

Frequent hypermethylation of RASSF1A and TSLC1, and high viral load of Epstein-Barr Virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues

We examined the promoter hypermethylation of tumor-suppressor genes RASSF1A and TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC) tissues (T tissues), and matched tumor-adjacent tissues outside 0.5 cm (P tissues) and outside 1.0 cm (Z tissues) to evaluate the role of promoter hypermethylation of RASSF1A and TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR) for RASSF1A and TSLC1 and quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, and Z tissues (n = 28) as well as chronic nasopharyngitis tissues (n = 8). Hypermethylated RASSF1A was frequently detected in the T (82%) and P tissues (75%), but less frequently in Z tissues (46%). he average quantities of EBV DNA (copies/microg DNA) in matched T, P, and Z tissues were 673,000, 90,000, and 7000. The differences of promoter hypermethylation of RASSF1A and EBV viral load among T, P, and Z tissues were statistically significant, with more frequent methylation and higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A and high EBV load might be important events in NPC pathogenesis, and they may be useful molecular diagnostic markers for this cancer.     

胸腺肽在晚期非小细胞肺癌化疗中的作用

背景与目的：肺癌的发生、发展与机体的免疫功能状况密切相关,恶性肿瘤患者存在明显的免疫功能紊乱,主要表现为细胞免疫功能下降.本研究评价胸腺肽联合化疗对晚期非小细胞肺癌的疗效、毒副反应、生活质量及免疫功能的影响.方法：42例非小细胞肺癌随机分为2组,治疗组：NP方案＋胸腺肽.长春瑞滨（NVB）25 mg/m^2,静脉滴注,第1、8天,顺铂（DDP）70～80 mg/m^2,静脉滴注,第1天.化疗后第3天每日静脉滴注胸腺肽200 mg,连续7～10 d.对照组：单化疗,用NP方案,剂量、用法同上.结果：治疗组化疗后CD4和NK细胞活性显著高于化疗前和对照组化疗后水平（P＜0.01）,对照组NK细胞活性化疗后显著低于化疗前水平（P＜0.05）.治疗组KPS提高率为61.9%（13/21）,而对照组为28.6%（6/21）,两组差异有显著性（P＜0.05）.治疗组有效率52.4%（11/21）,1年生存率为52.6%.对照组有效率42.9%（9/21）,1年生存率38.8%.两组间疗效、毒副反应及1年生存率比较差异无显著性（P＞0.05）.结论：胸腺肽联合化疗能提高肺癌化疗患者机体的免疫功能,改善患者生存质量.     

伴有钙化的乳腺浸润性导管癌病理特征及预后分析

目的 乳腺癌已成为世界范围内女性恶性肿瘤中最常见的死因,伴有钙化的乳腺癌占乳腺癌30％～50％.探讨伴有钙化的乳腺浸润性导管癌(invasive ductal carcinoma,IDC)的临床病理特征及预后的影响因素.方法 收集2012-06-01-2013-06-30新疆医科大学附属肿瘤医院收治的初治可手术女性乳腺癌患者307例的临床病理资料和随访资料,根据乳腺X射线图像特征分为钙化组与非钙化组,回顾性分析其临床病理特征及3年无病生存率(disease-free survival,DFS).结果 钙化组在病理类型(P＜0.001)、淋巴结转移(P=0.037)、人表皮生长因子受体2(human epidermal growth fator gene-2,HER2)过表达(P=0.005),组织学分级(P=0.043)、临床分期(P=0.021)与非钙化组比较差异有统计学意义.钙化是淋巴结转移及HER2过表达的相关风险因素.钙化组淋巴结转移的风险是非钙化组的1.736倍;钙化组HER2过表达的风险是非钙化组的2.297倍.钙化组和非钙化组3年DFS分别为87.5％和94.9％.肿瘤直径(P=0.025)和淋巴结(P=0.009)是影响乳腺IDC无病生存时间的独立预后因素.结论 钙化组乳腺IDC更具有肿瘤转移性,预后较非钙化组差.     

Ⅱ型糖尿病与结直肠癌的相关性研究

目的:探讨结直肠癌与Ⅱ型糖尿病的相关性,了解Ⅱ型糖尿病对结直肠癌的发病、围手术期并发症以及预后的影响。方法:选取2002年-2010年间经病理确诊的结直肠癌手术后患者256例,同时期的非肿瘤手术后患者372例作对照,比较两组年龄、性别、体重指数(body mass index,BMI)、病程、糖尿病病史、糖尿病家族史、并发症、肿瘤系列生化检查及环境因素如吸烟和饮酒等因素,同时还分析了结直肠癌的发生率,以及各组对手术后并发症和预后的影响。结果:结直肠癌患者中Ⅱ型糖尿病的患者发生率为30.1%;较非肿瘤患者高;其并发感染占6.6%。结论:多因素分析结果显示,结直肠癌与Ⅱ型糖尿病存在某种相关性,Ⅱ型糖尿病增加了感染机会,并且增加了结直肠癌的风险和结直肠癌根治手术后感染的风险。