二氢青蒿素对胰腺癌生长的抑制作用

Objective To investigate the anti-tumor activity of dihydroartemisinin in pancreatic cancer in vitro and in vivo. Methods For cultured cells,cell growth was determined by the MTT assay and apoptosis was evaluated by flow cytometry analysis stained with Annexin V-FITG/PI. The protein expression in BxPC-3 cells was analyzed by Western blot assay. BxPC-3 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors and the tumor volume was monitored after exposure to dihydroartemisinin. Ki-67 staining and TUNEL assay were used to assess tumor cell proliferation and apoptosis in tumor tissue. Results After treatment by dihydroartemisinin in vitro, the proliferative inhibition rates of pancreatic cancer cells BxPC-3 and AsPC-1 reached up to (76.2 ± 3.5) % and (79.5 ± 2.9) %, and the apoptosis rates were up to (55.5 ± 3.2)% and (40.0 ± 3.5)%, the differences were significantly (P ＜ 0.01) compared with control [(2.0 ± 1.3) % and (0.9 ± 0.4) %]. Dihydroartemisinin inhibited the growth of pancreatic xenograft tumors in nude mice. The proliferation index and apoptusis index were (49.1 ± 3.9)% and (50.2 ± 4.4)% respectively in dihydroarternisinin 50 mg/kg treatment group, compared to those of (72.1 ± 3.3) % and (9.4 ± 2.9) % in control, the differences were significantly (P ＜0.01). Western blot assay indicated that dihydroartemisinin up-regulates expression of proliferation-associated protein p21WAF1 and down-regulates expression of PCNA, increases expression of apoptosis-associated protein Bax and decreases expression of Bcl-2 and activates caspase-9 in BxPC-3 cells. Conclusions Dihydroartemisinin exerts anti-tumor activity in pancreatic cancer both in vitro and in vivo by proliferation inhibition and apoptusis induction. Dihydroartemisinin can be used as a potential anti-tumor drug in pancreatic cancer.     

钝性胰腺损伤合并主胰管损伤的诊断和治疗:附35例报告

目的探讨钝性胰腺损伤合并主胰管损伤的早期诊断和合理的外科治疗方法。方法回顾性分析1995年4月至2005年4月间35例胰腺钝性伤病人的临床资料，其早期诊断和损伤严重度的分级根据术前动态的淀粉酶及影像学检查（特别是动态螺旋CT和MRCP扫描）和早期外科手术的术中发现，就胰腺钝性伤的早期诊断方法、不同的手术处理方式及并发症等进行分析。结果22例Ⅲ级胰腺损伤病人中，14例行远端胰腺切除术和脾切除术，6例行远端胰腺切除术和保留脾脏手术，2例行单纯胰周引流术。8例Ⅳ级胰腺损伤病人中，2例行远端胰腺切除术和脾切除术，2例行胰尾切除术，4例行胰腺空肠Roux-en-Y吻合术。5例Ⅴ级胰腺损伤病人中，4例由于复合伤情较重且合并十二指肠损伤，根据伤害严重度（injury severity score，ISS）评分，首先应用损伤控制手术先进行止血和制止肠内容物的外溢、胰腺外引流等简化手术，于急诊ICU监护待血液动力学稳定后，于受伤后48-72h再次行彻底性手术，1例胰头严重毁损伤行Whipple手术，平均住院时间是40d（2～147d），总死亡率是14．3％（35例中5例），其余均治愈。结论对胰腺损伤病人，及时正确的诊断和合理的外科手术治疗是减少死亡率，改善预后的重要因素。     

5-氟尿嘧啶缓释剂瘤内注射治疗胰腺癌的实验研究

目的:观察5FU缓释剂瘤内注射对裸鼠胰腺癌肿瘤细胞的影响,探讨其作用机制。方法:体外培养胰腺癌细胞株PC3,以2×106个细胞分别接种于70只裸鼠。4周后挑选肿瘤大小一致的裸鼠60只,随机分成5组,即静脉NS对照组、5FU静注组(10mg/kg)、基质植入组、5FU缓释剂(4mg/kg)植入组及5FU缓释剂(1mg/kg)植入组。于治疗前及治疗后14d内测量肿瘤大小,计算肿瘤生长速度;观察组织学变化和细胞分裂指数;免疫组化法测定bcl2和Bax的蛋白表达水平;采用脱氧核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测凋亡指数(AI)。结果:5FU缓释剂瘤内注射组裸鼠移植瘤生长速度减慢(P<0.05),最终瘤重小于其他各组(P<0.05);细胞分裂指数亦均低于其他各组(P<0.05)。5FU缓释剂瘤内注射组肿瘤组织中炎症反应和血管内膜增厚程度明显高于其他各组(P<0.05)。5FU缓释剂瘤内注射组荷瘤裸鼠的bcl2基因蛋白表达明显低于其他各组,而Bax基因的蛋白表达明显高于其他各组,其肿瘤细胞的AI明显高于其他各组(P<0.05)。结论:5FU缓释剂瘤内注射可明显抑制裸鼠胰腺癌瘤体的生长,其作用机制与药物在肿瘤组织中引起的炎症反应和血管内膜增厚等因素有关,并可能与诱导肿瘤细胞的凋亡有关。     

重症胰腺炎动物模型制作及发病机理的研究

为探讨胰腺炎的发病机理，作者采用大鼠（ｎ＝５８只）十二指肠结扎法和犬（ｎ＝４６条）胰管内注射自身胆汁法制作重症胰腺炎的动物模型。该模型接近人类急性胰腺炎的发病因素，方法可靠，操作简便，费用便宜。前者适用于小动物实验，后者宜于大动物实验。作者认为胰管内压力增高和微生物是急性胰腺炎的重要条件；胰酶激活始动时间早在胰管内胆汁和肠液的反流后，胰酶激活的主要部位在腺泡细胞。     

The efficacy of density gradients for islet purification: a comparison of seven density gradients

Seven different density gradient-forming materials were compared as to their efficacy for rat islet purification. Continuous density gradients were used in order to determine the bouant densities of the different pancreatic tissue components. Hand-picked islets served as a control. A significant separation of large numbers of slets from the exocrine tissue band was only seen in the albumin, dextran-40, and metrizamide gradients. Pure islet preparations could not be obtained with any of the gradients studied as none of the gradients completely separated lymph nodes, vessels, and ducts from the islets. Gradients containing sucrose resulted in low islet yields. The islet yields obtained with the other gradients were in the same range as those obtained by hand-picking. Metrizamide gave significantly higher yields than the widely used Ficoll. Judged both in terms of numbers of islets and their in vitro function, the best results were obtained with metrizamide and dextran-40.     

紫杉醇诱导胰腺癌细胞凋亡Survivin表达的变化及意义

目的研究紫杉醇（PA）体外化疗对胰腺癌细胞凋亡抑制蛋白Survivin基因表达的影响。方法培养人胰腺癌细胞株SW1990，加入低浓度的PA，用流式细胞仪分别检测加药前和加药后24、48h的细胞凋亡率，用逆转录-聚合酶链反应（RT-PCR）和免疫印迹技术（Western blot）检测Survivin mRNA和蛋白的表达。结果SW1990细胞给予低浓度的PA后，加药前和加药后24、48h的细胞凋亡率分别为（2．59±0．35）％、（14．75±1．29）％、（22．65±2．80）％；其Survivin mRNA的表达则分别比加药前提高了1．1倍和2．9倍；Survivin蛋白的表达分别增加了1．3倍和3．6倍。结论应用PA化疗可促使胰腺癌细胞内Survivin表达的增加，抵抗化疗诱导的细胞凋亡。     

Aktuelle Indikationen zur pyloruserhaltenden Duodenopankreaskopfresektion beim Malignom

Zusammenfassung Die Pankreaskopfresektion in der Modifikation nach Traverso-Longmire, mit Erhaltung eines funktionierenden Pylorus, hat gegenüber der Kausch-Whipple-Operation die Vorteile, daß Anastomosenulzera vermieden werden und daß die Patienten postoperativ eine bessere und schnellere Gewichtszunahme haben. Indikationen waren bisher die Papillenkarzinome und periampulare Tumoren. Bei den Adenokarzinomen lassen sich mit der Pyloruserhaltung gleich gute Überlebensraten erzielen. Unsere Ergebnisse von 56 Pyloruserhaltungen, davon 32 beim duktalen Karzinom und 28 Kausch-Whipple-Operationen in den Jahren von 1985–1993, belegen gleiche Überlebensraten, wie dies bereits für das Papillenkarzinom gezeigt werden konnte. Die Überlebenskurven zeigen, daß die Radikalität nicht von der Magenteilentfernung, sondern von der Resektion an den posterioren und retroperitonealen Resektionsrändern abhängt.

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Current indications for pylorus preservation in duodenopancreatic head resection in malignancies

The Whipple procedure has been improved by preservation of a functioning pylorus. A functioning pylorus is important because marginal ulceration is avoided and, compared to the standard Whipple procedure with gastric resection, more patients can gain weight postoperatively. The most common indications are carcinomas of ampulla of Vater and periampullary tumors. In patients with pancreatic adenocarcinoma the pylorus-preserving variety results in equal or better survival rates. In 56 patients with pylorus preservation, 32 with ductal carcinoma, and 28 with Kausch-Whipple between 1985 and 1993, our results showed slightly better survival rates and better post-operative nutrition. The weakest aspect of the radical resection addresses the retroperitoneal margin of the pancreas head and not the gastric resection.

     

A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile

There are a large number of stable pancreatic ductal carcinoma cell lines (PDCL) that are used by researchers worldwide. Detailed data about their differentiation status and genetic alterations are present in the literature, but a systematic correlation with cell biological behavior is often lacking. PDCL (n=12) were clustered by source of tumor cell (ascites, primary tumor, metastasis), and the data of functional cell biology were correlated with the reported structural and genetic profiles. Major histocompatibility complex expression, chemosensitivity and aneuploidia appeared to be related to the source of PDCL, and proliferative capacity appeared to be related to the grade of differentiation. No correlation between genetic/structural features of PDCL and biological behavior was found. All the cell lines appeared generally insensitive to in vitro treatment with 5-fluorouracil and showed variable degrees of susceptibility to gemcitabine, raltitrexed and oxaliplatin. All the PDCL showed resistance to Fas-mediated apoptosis but were significantly sensitive to the pro-apoptotic effect of inflammatory cytokines [interleukin (IL)-1, tumor necrosis factor (TNF) and interferon ]. PDCL were characterized for the secretion of several factors relevant to the tumor-immune cross talk. Vascular endothelial growth factor, CCL2, CCL5 and transforming growth factor were the factors most frequently released; less frequent was the secretion of CXCL8, CCL22, IL-6 and sporadically CXCL12, IL-10 and hepatocyte growth factor. The cytokines IL-1 and TNF were always undetectable. In conclusion, a clear correlation between structural/genetic features and function could not be detected, suggesting the weakness of a morphological classification for the in vitro studies of pancreatic cancer.     

Metastatic Psammomatous Somatostatinoma of the Pancreas Causing Severe Ketoacidotic Diabetes Cured by Surgery

A case of somatostatin-producing pancreatic tumor associated with severe insulindependent diabetes mellitus and ketoacidotic coma is reported. The tumor, a 10-cm expansile mass arising from the pancreatic tail of a 70-yr-old woman, was first detected by ultrasonography, performed because of abdominal pain, and subsequently confirmed by computed tomography and fine-needle tumor aspiration. Pathologic investigation showed a predominatly solid-trabecular structure with scattered microacini and psammomatous bodies. A large proportion of tumor cells expressed somatostatin and/or calcitonin. Following resection of the primary tumor and three peripancreatic lymph nodes with metastases, the patient recovered rapidly from her diabetic syndrome and remained in substantially good health during a subsequent 8-yr follow-up period, without evidence of tumor recurrence.