高强度体外聚焦超声热疗治疗局部晚期胰腺癌的多中心临床研究

目的：探讨临床单用HIFU治疗局部晚期胰腺癌(local advanced pancreatic carcinoma，APC)的可能性。方法：4个中心共41例患者入选进行非随机病例对照研究，其中HIFU组24例，单用HIFU治疗；对照组17例，接受HIFU及吉西他滨综合治疗。比较两组的疗效、治疗费用及安全性，采用Cox回归分析进一步确定吉西他滨化疗对生存期的影响。结果：HIFU组临床受益率、平均生存期与对照组相似，分别为66．7％比76．5％(P=10．740)和141．5天比176．5天(P=0．3510)；而治疗费用较低，为20500元比51805元(P=0．000)；安全性更高。Cox回归分析显示仅体力状态、HIFU次数及临床受益进入方程(P=0．000)，化疗对生存期无影响。结论：单用HIFU治疗APC，其疗效等同于HIFU和吉西他滨的综合治疗，但较综合治疗经济、安全。推测可以单独应用HIFU治疗局部晚期胰腺癌．值得临床进一步验证。     

胰腺癌的辅助治疗

对于胰腺癌术后状态,研究表明进行吉西他滨全身化疗能够显著提高无瘤生存期和总生存期,而辅助放化疗则存在较大争议;局部介入化疗在小样本的研究中获得肯定,但仍缺乏大样本随机对照研究予以证实;新辅助治疗对于评价为可能切除的胰腺癌病灶提供了外科切除的可能.     

吉西他滨联合铂类药物治疗晚期胰腺癌的疗效观察

目的 观察吉西他滨(健择)联合顺铂/草酸铂(GP/GEM-OX方案)治疗晚期不能手术或手术后复发的胰腺癌患者的疗效与不良反应。方法 28例患者分别给予GP或GEM-OX方案2～13周期。按WHO标准评定疗效和不良反应。结果 26例可评价疗效，无一例完全缓解(CR，0％)，部分缓解(PR)7例(26．9％)，稳定(SD)10例(38．5％)，进展(PD)9例(34．6％)。可评价临床受益反应(CBR)27例，有效率为70．4％(19／27)。中位疾病进展时间为4．2个月，中位生存时间为9．3个月。结论 健择联合顺铂/草酸铂是治疗晚期胰腺癌患者的安全有效方案，并能较好改善疾病相关症状，毒副反应可以耐受。     

Enhancing Effects of Quinacrine on Development of Hepatopancreatic Lesions in N-Nitrosobis(2-oxopropyl)amine-initiated Hamsters

The modifying effects of quinacrine administration during the post-initiation phase of carcinogenesis were investigated in hamsters treated with N -nitrosobis(2-oxopropyl)amine (BOP). Female Syrian hamsters were given three weekly s.c. injections of BOP at a dose of 10 mg/kg and then 300 or 100 ppm quinacrine in their diet for 37 weeks. Additional groups of animals received the BOP injection alone, or only the 300 ppm quinacrine treatment as BOP-negative controls. At week 40 of the experiment, all surviving animals were killed and development of proliferative lesions was assessed histopathologically. The multiplicity of pancreatic adenocarcinomas and dysplastic lesions per hamster was significantly higher ( P <0.01 and P <0.05) in the BOP/Q100 group (1.92 and 1.78) than in the BOP-alone group (1.07 and 0.79). The incidence of hepatocellular adenomas plus carcinomas was also significantly elevated ( P <0.05) in the BOP/Q300 and BOP/Q100 groups. In contrast, the multiplicity of lung adenomas plus adenocarcinomas was significantly decreased ( P <0.05) by the Q300 treatment. Neither the incidence nor the multiplicity of renal cell tumors (adenomas and carcinomas) or nephroblastomas significantly differed between the BOP-treated groups. Electron microscopic examination revealed an abundance of myeloid lamellar bodies filling the cytoplasm of hepatocytes and pancreatic ductular and acinar cells, and epithelial cells of the gallbladder in the quinacrine-treated animals, the degree being dose-dependent. Our results indicate that quinacrine enhances pancreatic and hepatic carcinogenesis in hamsters induced by BOP.     

胞嘧啶脱氨酸基因治疗人胰腺癌的实验研究

探讨腺病毒介导的大肠杆菌胞嘧啶脱氨酶基因用于人胰腺癌基因疗法的可行性。方法将含癌胚抗原启动子的重组腺病毒感染人胰腺癌ＳＷ１９９０细胞和Ｃａｐａｎ－２细胞以及人宫颈癌Ｈｅｌａ细胞,用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）和Ｗｅｓｔｅｒｎｂｌｏｔ检测ＣＤ基因在细胞中的表达,以ＭＴＴ法比较细胞对５－氟胞嘧（５－ＦＣ）的敏感性差异。建立胰腺癌裸鼠皮下移植瘤模型,观察ＣＤ基因的原位治疗效应及安全性。结果腺病毒介     

罗非昔布抑制胰腺癌细胞ERK、AP-1信号转导通路

目的研究环氧合酶-2抑制剂-罗非昔布对胰腺癌细胞株BXPC-3增殖的信号转导作用的影响.方法用免疫组化法检测裸小鼠胰腺癌移植瘤中c-Fos的表达,免疫印迹法检测BXPC-3中c-Fos、ERK蛋白的改变,采用EMSA技术检测罗非昔布对胰腺癌细胞AP-1活化的影响.结果罗非昔布可抑制裸小鼠胰腺癌移植瘤c-Fos的表达.随着罗非昔布浓度的增加,胰腺癌细胞中c-Fos、ERK蛋白逐渐下降.EMSA分析显示,20%胎牛血清能刺激胰腺癌细胞BXPC-3中AP-1的活化增加,罗非昔布能抑制这种刺激作用.结论罗非昔布可通过抑制胰腺癌细胞ERK、AP-1信号转导通路,抑制胰腺癌细胞增殖.     

大鼠胰腺癌和非癌胰腺组织Skp2和p27表达研究

目的建立大鼠胰腺癌模型,研究大鼠胰腺癌和非癌胰腺组织中Skp2和p27表达及其意义。方法应用二甲基苯并蒽(DMBA)置入大鼠胰实质内(A组)及设立曲古霉素(TSA)干预组(B组),3~5个月内处死观察胰腺癌发生情况,应用SP免疫组化法研究胰腺癌和非癌胰腺组织中Skp2和p27表达。结果3~5个月内A组发癌率为48.7%(18/37),B组为33.3%(12/36),A组和B组各1例纤维肉瘤外,余均为胰腺导管癌;A组肿块最大径大于B组(P<0.05);非癌胰腺组织中A组导管上皮中至重度不典型增生者(52.6%)高于B组(33.3%),但差异无显著性(P>0.05);C组胰腺和A或B组鼠胰腺外主要脏器均无明显病变。A组和/或B组胰腺导管癌Skp2表达阳性率均明显高于A组和/或B组非癌胰腺组织(P<0.05);但胰腺导管癌p27表达阳性率明显低于非癌胰腺组织(P<0.01);Skp2阳性和p27阴性的非胰腺组织导管上皮均呈中至重度不典型增生;C组胰腺导管上皮Skp2均阴性表达和p27均阳性表达。结论DM-BA置入胰实质内可在短期获得较高的SD鼠胰腺癌发生率,TSA能抑制胰腺癌发生和生长。Skp2和p27表达水平与SD鼠胰腺癌发生发展有密切关系。     

胰腺移植中血管吻合重建的实验研究

目的:研究猪胰腺移植术中不同的血管吻合重建对术后移植胰功能恢复的影响。方法:采用健康小型猪18头体重30~50Kg,雌雄各半,随机分成A、B两组,均作带十二指肠袢的同种异体节段性胰腺移植。A组采用传统血管重建术;B组采用边灌注边吻合、先静脉后动脉的血管重建术。测定各组术后不同天数的胰液淀粉酶小时分泌量平均值、血清C-肽水平,了解移植胰的功能状况。结果:A组术后第5天始血清C-肽、AM分泌量低于B组,两组差异有统计学意义(P<0.05)。结论:胰腺移植术中采用改进后的血管吻合重建术可明显改善术后移植胰的功能。     

Diffusion‐weighted MRI monitoring of pancreatic cancer response to radiofrequency heat‐enhanced intratumor chemotherapy

The aim of this study was to evaluate the feasibility of using diffusion‐weighted MRI to monitor the early response of pancreatic cancers to radiofrequency heat (RFH)‐enhanced chemotherapy. Human pancreatic carcinoma cells (PANC‐1) in different groups and 24 mice with pancreatic cancer xenografts in four groups were treated with phosphate‐buffered saline (PBS) as a control, RFH at 42 °C, gemcitabine and gemcitabine plus RFH at 42 °C. One day before and 1, 7 and 14 days after treatment, diffusion‐weighted MRI and T₂‐weighted imaging were applied to monitor the apparent diffusion coefficients (ADCs) of tumors and tumor growth. MRI findings were correlated with the results of tumor apoptosis analysis. In the in vitro experiments, the quantitative viability assay showed lower relative cell viabilities for treatment with gemcitabine plus RFH at 42 °C relative to treatment with RFH only and gemcitabine only (37 ± 5% versus 65 ± 4% and 58 ± 8%, respectively, p < 0.05). In the in vivo experiments, the combination therapy resulted in smaller relative tumor volumes than RFH only and chemotherapy only (0.82 ± 0.17 versus 2.23 ± 0.90 and 1.64 ± 0.44, respectively, p = 0.003). In vivo, 14‐T MRI demonstrated a remarkable decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination therapy group. The apoptosis index in the combination therapy group was significantly higher than those in the chemotherapy‐only, RFH‐only and PBS treatment groups (37 ± 6% versus 20 ± 5%, 8 ± 2% and 3 ± 1%, respectively, p < 0.05). This study confirms that it is feasible to use MRI to monitor RFH‐enhanced chemotherapy in pancreatic cancers, which may present new options for the efficient treatment of pancreatic malignancies using MRI/RFH‐integrated local chemotherapy. Copyright © 2013 John Wiley & Sons, Ltd.