清胰消积中药对实验性胰腺癌基因表达的影响

目的:研究中药清胰消积方对裸鼠体内人胰腺癌SW1990细胞移植瘤的抑瘤作用,并利用基因表达谱芯片探索其作用机理。方法:荷瘤裸小鼠随机分为对照组、5-FU组、中药不同剂量组,治疗后计算抑瘤率。提取对照组及中药中剂量组肿瘤组织mRNA,制备cDNA探针并分别用Cy3和Cy5两种荧光染料标记,与基因表达谱芯片进行杂交,经扫描、分析,得出药物作用后表达有差异的基因。结果:中药18g/kg、36g/kg、72g/kg剂量组抑瘤率分别为21.31%、38.16%及29.09%。筛选出癌基因、蛋白翻译合成、DNA合成和修复、细胞信号传导蛋白等表达下调的基因共7条。结论:清胰消积中药对人胰腺癌体内生长有抑制作用,调节癌基因及其相关的信号传导、改变肿瘤细胞蛋白合成等可能是其作用机制。     

The pancreatic ductal epithelium serves as a potential pool of progenitor cells

Abstract:  With the increasing success of islet transplantation, β-cell replacement therapy has had renewed interest. To make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must become readily available. The most promising sources are stem cells, whether embryonic or adult stem cells. Clearly identifiable adult pancreatic stem cells have yet to be characterized. Although considerable evidence suggests their possibility, recent lineage-tracing experiments challenge their existence. Even in light of these lineage-tracing experiments, we suggest that evidence for neogenesis or new islet formation after birth remains strong. Our work has suggested that the pancreatic duct epithelium itself serves as a pool for progenitors for both islet and acinar tissues after birth and into adulthood and, thus, that the duct epithelium can be considered 'facultative stem cells'. We will develop our case for this hypothesis in this perspective.     

Effect of HIF-1α on VEGF-C Induced Lymphangiogenesis and Lymph Nodes Metastases of Pancreatic Cancer

The effect of hypoxia inducible factor-1α(HIF-1α) on vascular endothelial growth factor C (VEGF-C) and the correlation between HIF-1αand lymphangiogenesis and lymph nodes metasta-ses (LNM) in pancreatic cancer were investigated. Immunohistochemical SP method was used to detect the protein expression of HIF-1αand VEGF-C, and Lymphatic vessel density (LVD) was determined by stain of VEGFR-3, collagen type IV in 75 pancreatic head cancers from regional pancre-atectomy (RP) during Dec. 2001 to Dec. 2003. The relationship between HIF-1αand VEGF-C, lymphangiogenesis, LNM was analyzed statistically. The results showed that the positive expression rate of HIF-1αand VEGF-C in pancreatic cancer tissues was 48.00 % (36/75) and 65.33 % (49/75) respectively. In positive group of HIF-1α, the positive rate of VEGF-C and LVD, and LVD rate was 80.56 % (29/36), 13.22±3.76 and 88.89 % (32/36) respectively, and in negative group of HEF-1α, positive rate of VEGF-C and LVD was 51.28 % (20/39), 5.98±2.17 and 66.67 % (26/39) respectively (P<0.01 or P<0.05). It was suggested that HIF-1αcould promote the expression of VEGF-C, lymphangiogenesis and LNM in pancreatic cancer.     

质子泵抑制剂对离体胰腺腺泡淀粉酶分泌的影响

目的探讨质子泵抑制剂(PPI)对胰腺外分泌是否有直接影响。方法首先,参照Williams方法制备离体胰腺腺泡悬液,加入蛙皮素(10-10M)刺激。①加入不同浓度的奥美拉唑(1×10-6M,2×10-6M,4×10-6M,8×10-6M)(10-8M~10-5M),取上清液以碘-淀粉比色法测量淀粉酶量;②将相同浓度的奥美拉唑(10-6M)加入蛙皮素刺激后的胰腺腺泡中作用30,60,90,120,150min后,测定其胰腺腺泡分泌率;③加入不同浓度善宁(10-9M~10-6M),取上清液测定其淀粉酶分泌程度。结果不同浓度善宁作用后的淀粉酶分泌率明显降低,有显著性差异(P<0.05);不同浓度奥美拉唑作用后的淀粉酶分泌率间无显著性差异(P>0.05);奥美拉唑(10-6M)作用30,60,90,120,150min后胰腺腺泡分泌率无显著性差异(P>0.05)。结论奥美拉唑对胰腺腺泡外分泌功能无直接抑制作用。     

Survivin在顺铂诱导Panc-1细胞凋亡中的作用

的 :体外观察顺铂是否具有诱导胰腺癌细胞株 (Panc-1)凋亡的作用 ,同时观察在此过程中凋亡抑制蛋白 Survivin的表达变化 ,为探讨胰腺癌的化疗耐药机制提供理论基础。方法 :用人 Panc-1株进行培养传代 ;MTT试验检测顺铂以不同浓度和不同时间对 Panc-1株生长的抑制作用 ;用 RT-PCR检测凋亡过程中 Survivin基因表达的动态变化。结果 :顺铂可明显抑制 Panc-1细胞增殖 ,其增殖抑制率呈浓度和时间依赖性 ;DNA电泳可以观察到凋亡的发生 ,而且呈药物浓度、作用时间依赖关系 ;Survivin表达水平随着顺铂作用浓度的增加而下降 ,当顺铂浓度为 5 0μg/ml时下降最明显 (61% ) ;Survivin c DNA/β-actin c DNA比值与细胞增殖抑制率和细胞凋亡率呈负相关 (P<0 .0 1)。结论 :顺铂可以有效诱导 Panc-1株的细胞凋亡 ,而且 Survivin基因的抑制在顺铂诱导 Panc-1株的细胞凋亡中起重要作用。     

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。