Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group.

BACKGROUND: In the present phase II multicenter study, we assessed the efficacy and tolerability of the combination of gemcitabine and carboplatin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients with previously untreated, locally advanced or metastatic pancreatic cancer were treated with gemcitabine 800 mg/m(2) on days 1 and 8 and carboplatin at an AUC of 4 on day 8 of a 3-week cycle, for a total of six cycles. Primary end points were response rate and clinical benefit; secondary end points were, survival, time to progression (TTP) and toxicity. RESULTS: A total of 50 patients were enrolled in the study, 47 of whom were eligible for treatment. The median age was 63 years (range 34-76) and the median Karnofsky performance status (PS) was 80%. Patients received a median of six cycles (range 1-11). Among 35 patients evaluable for response, eight (17%) achieved partial response; 15 (32%) and 12 (25%) patients had stable and progressive disease, respectively. The median overall survival was 7.4 months; the median TTP was 4.4 months and the 1-year survival was 28%. The observed clinical benefit response was remarkable. After the second cycle of chemotherapy, 21 of 31 (68%) patients experienced pain improvement and reduced analgesic consumption. At the same time, 35% and 56% of our patients significantly improved their Karnofsky PS and weight, respectively. Overall, the treatment was well tolerated. The most common grade 3-4 toxicities were hematological, including 8% anemia, 6% neutropenia and 13% thrombocytopenia. CONCLUSIONS: The combination of gemcitabine plus carboplatin is a moderately active treatment for patients with locally advanced and metastatic pancreatic cancer. This regimen has an acceptable toxicity profile and provides a significant clinical benefit, and hence warrants further investigation.     

复方丹参滴丸在41例中晚期胰腺癌化疗中的应用

[目的]对比分析复方丹参滴丸联合化疗和单纯化疗对中晚期胰腺癌疗效及生存质量的影响.[方法]81例中晚期胰腺癌患者随机分为A、B两组,A组(41例)采用复方丹参滴丸加健择 顺铂(GP方案)治疗,B组(40例)采用单纯GP方案化疗,对其疗效、生存质量及不良反应进行评价.[结果] A、B两组的有效率(CR PR)分别为46.3%和35.0%(P＞0.05),A、B两组的临床获益率(CR PR SD)分别为73.2%和50.0%(P＜0.05),A组治疗后T淋巴细胞亚群中CD4/CD8比值有明显提高(P＜0.01),而B组治疗后T淋巴细胞亚群中的CD4/CD8比值有明显降低(P＜O.01),生存质量A组高于B组(P＜0.05),恶心呕吐和白细胞减少B组高于A组(P＜0.05).[结论]复方丹参滴丸与化疗同时应用治疗胰腺癌能提高患者的治疗临床获益率、改善生存质量、减轻化疗不良反应.     

胃肠胰脂肪酶抑制剂对肥胖症患者胆囊运动功能的影响

目的:研究胃肠胰脂肪酶抑制剂对肥胖症患者胆囊运动功能和胆固醇结石形成的影响,以期为临床合理用药提供参考.方法:通过查阅近期国内外相关文献,并结合笔者临床经验进行综述.结果与结论:已有研究证实短期(1月)和长期(1年)胃肠胰脂肪酶抑制剂奥利司他(120mg,1日3次)配合合理的饮食控制治疗对肥胖症患者胆囊运动功能均有加大抑制作用,同时伴有血浆胆囊收缩素水平的降低.今后仍需更大样本量和更长观察时间的试验来动态观察减重对胆囊运动功能、血浆胆囊收缩素水平和胰岛素抵抗程度的改变,以进一步证实减肥药物对肥胖症患者胆囊运动功能的加大抑制作用.     

奥曲肽选择性动脉介入治疗重症急性胰腺炎的临床观察

目的 观察奥曲肽选择性动脉介入治疗重症急性胰腺炎(SAP)的疗效。方法 将67例SAP患者分为对照组和治疗组,对照组35例采用常规治疗,治疗组32例除常规治疗外,采用数字减影(DSA)装置,以奥曲肽25 μg·h~(-1)直接经胰腺供血动脉连续输注24～48 h。两组疗效进行对比。结果 治疗组血液淀粉酶较对照组下降迅速,胃肠减压量治疗组与对照组相比差异显著(P<0.05),临床治愈时间治疗组比对照组明显缩短(P=0.02),并发症发生率和死亡率,治疗组分别为15.6％和6.3％、对照组分别为45.7％和25.7％,均达统计学意义。结论 奥曲肽介入治疗SAP疗效显著且优于常规治疗。     

大鼠胰岛细胞原代培养模型的研究

目的：建立一种客观的用于糖尿病和降血糖药物研究的大鼠胰岛细胞原代培养模型。方法：大鼠胰腺经胶原酶消化后，利用细胞贴壁时间、紧密程度及存活时间的差异，获得较为纯净的胰岛细胞。通过胰岛素含量测定，葡萄糖刺激实验及移植实验评价该细胞的功能。结果：分离得到的胰岛细胞成活率可达95％以上；双硫腙染色表明大部分细胞团为含有β细胞的胰岛细胞团；经RPMI 1640培养的细胞，其上清及细胞内的胰岛素含量均高于DMEM组，且对葡萄糖刺激的敏感性优于DMEM组：培养的胰岛细胞移植入1型糖尿病模型小鼠体内，可使糖尿病小鼠的血糖降至正常。结论：利用该方法得到的胰岛细胞活力和纯度均较高，体外培养后细胞功能正常，有望成为一种实用的降糖药研究的细胞模型。     

经动脉灌注吉西他滨和5-氟尿嘧啶联合热疗治疗中晚期胰腺癌的临床分析

目的：探讨经动脉灌注吉西他滨（Gemcitabine,商品名健择）和5-氟尿嘧啶（5-FU）联合内生场热疗治疗中晚期胰腺癌的临床疗效。方法：18例中晚期胰腺癌患者,采用改良Seldinger技术,动脉插管后选择性置管于胰腺癌的供血动脉,灌注吉西他滨1000mg／m^2;之后行内生场热疗,热疗同时经动脉留置导管灌注卡铂400mg／m^2;热疗后,用输液泵经动脉留置管灌注5-FU 1g,连用2d。随访观察客观疗效、临床受益反应、患者的生存期及不良反应等。结果：18例患者的客观缓解率为22．20％,临床受益反应为44．40％,Kaplan-Meier法计算6、9和12个月的累积生存率分别为83．33％、66．67％和33．33％,频数分布法计算中位生存期为11个月。结论：经动脉灌注吉西他滨和5-FU联合内生场热疗治疗中晚期胰腺癌可获得较好的临床疗效,患者耐受良好,值得进一步研究。     

Expression of MTA1 promotes motility and invasiveness of PANC-1 pancreatic carcinoma cells

The human metastasis-associated protein 1 (MTA1) is a constituent of the nucleosome-remodelling and -deacetylation complex. Its expression has been correlated with the invasion and metastasis of epithelial neoplasms. To address the functional consequences of MTA1 expression in pancreatic carcinoma cells, we have established PANC-1 pancreatic carcinoma cells that stably express MTA1 as an enhanced green fluorescent fusion protein (EGFP-MTA1). Here, we demonstrate that heterologous expression of EGFP-MTA1 markedly enhanced the cellular motility and the invasive penetration of epithelial barriers by the cells. Expression of EGFP-MTA1 had no effect on substrate-independent growth, but reduced substrate-dependent cell proliferation. In addition, the organisation of the cytokeratin filament system and the localisation of the actin cytoskeleton-associated protein IQGAP1 were distinctly altered in EGFP-MTA1-expressing cells. These results indicate that enhanced expression of MTA1 promotes the acquisition of an invasive, metastatic phenotype, and thus enhances the malignancy of pancreatic adenocarcinoma cells by modulation of the cytoskeleton.     

Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF‐1/IGF‐1R signaling

Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor‐induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin‐like growth factor‐1 (IGF‐1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF‐1‐dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF‐1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF‐1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF‐1/IGF‐1R‐induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF‐1/IGF‐1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies.     

微管相关蛋白2在胰腺神经内分泌肿瘤组织中的表达及预后意义

  目的   探索微管相关蛋白2（microtubule-associated protein 2,MAP2）与微管相关蛋白1B（microtubule-associated protein 1B,MAP1B）在预测胰腺神经内分泌肿瘤（pancreatic neuroendocrine tumors,PNETs）患者预后中的意义。   方法   收集1999年12月至2016年12月来自于北京协和医院、中山大学附属第一医院、复旦大学上海癌症中心和Cedars-Sinai医学中心（洛杉矶）193例患者的193个原发肿瘤标本。免疫组织化学染色法分别检测193例、120例PNETs组织中MAP2、MAP1B的表达,随后分析蛋白表达与患者临床病理特征及预后的关系。   结果   MAP2和MAP1B在PNETs患者中的阳性率分别为45.6%（88/193）和64.2%（77/120）。MAP2表达阳性的患者的总生存好于阴性患者（P=0.012）。另外,MAP2阳性Ⅱ、Ⅲ期患者的总生存也优于阴性者（P=0.017）。然而,MAP1B的表达与肿瘤大小、转移、肿瘤组织学分级、临床分期、总生存、无病生存均无相关性（P > 0.05）。   结论   MAP2为潜在的预测PNETs患者预后的指标。      

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.