SHH mRNA在人胰腺癌组织及细胞系中的表达及意义

目的检测Sonic Hedgehog(SHH)mRNA在人胰腺癌组织及细胞系中的表达,探讨SHH mRNA在胰腺癌发生和发展中的作用。方法收集本实验室保存的6株人胰腺癌细胞系及30例胰腺癌和相应癌旁正常胰腺组织,应用半定量RT-PCR方法检测SHH mRNA的表达。结果6株人胰腺癌细胞系中均有SHH mRNA高表达;胰腺癌组织SHH mRNA表达率为86.7%,表达强度为0.785±0.070,癌旁正常胰腺组织SHH mRNA表达率为40.0%,表达强度为0.463±0.055,两者具有显著性差异(P<0.01)。SHH mRNA的表达水平与胰腺癌的肿瘤大小、分化程度、淋巴结转移均无相关性。结论胰腺癌存在SHH mRNA的高表达,这可能是胰腺癌发生的早期事件。     

载脂蛋白E和补体C4b1在人胰腺癌组织中的表达及意义

目的 检测载脂蛋白E(ApoE)和补体C4b1在人胰腺癌组织中的表达,探讨其意义.方法 应用免疫组化法检测38例胰腺癌和相应癌旁正常胰腺组织ApoE、C4b1蛋白表达;应用RT-PCR法检测20例胰腺癌和相应癌旁正常胰腺组织ApoE、C4b1 mRNA表达.分析ApoE、C4b1的表达与胰腺癌生物特征的相关性.结果 胰腺癌组织ApoE、C4b1蛋白表达阳性率分别为86.8%(33/38)和76.3%(29/38),显著高于癌旁正常胰腺组织的42.1%(16/38)和26.3%(10/38)(P值均＜0.01);有淋巴结转移的胰腺癌组织ApoE、C4b1蛋白表达阳性率分别为78.3%(18/23)和73.9%(17/23),明显高于无转移者的33.3%(5/15)和40.0%(6/15)(P值均＜0.05).胰腺癌ApoE、C4b1 mRNA表达量分别为4.83±0.65、7.94±0.95,明显高于癌旁正常胰腺组织的1.78±0.74、1.22±0.57(P值均＜0.01);有淋巴结转移的胰腺癌组织ApoE、C4b1 mRNA的表达量为5.05±0.71、8.24±1.07,显著高于无转移者的4.42±0.25、7.39±0.15(P值均＜0.05).结论 ApoE、C4b1在胰腺癌组织中高表达,并与胰腺癌淋巴结转移相关.     

Plk1在胰腺癌中的表达及临床意义

目的 研究胰腺癌组织标本及细胞系中Plk1的表达及临床意义.方法 应用免疫组化EnVision两步法检测33例胰腺癌及其癌旁组织、3例胰腺浆液性囊腺瘤、3例黏液性囊腺瘤、5例慢性胰腺炎的石蜡标本中Plk1的表达.用半定量RT-PCR检测5例新鲜胰腺癌组织及其癌旁组织中Plk1 mRNA的表达.用Western blot检测两株胰腺癌细胞PANC1和CFPAC1中Plk1表达.结果 胰腺癌组织中Plk1的阳性表达率为72.7%(24/33),其表达与胰腺癌患者的年龄、性别、临床分期、组织学分级、淋巴结转移、肿瘤的部位无显著相关(P ＞ 0.05).癌旁组织、慢性胰腺炎和良性胰腺肿瘤组织中Plk1的表达均为阴性.5例新鲜胰腺癌组织中都有Plk1 mRNA的高表达,两株胰腺癌细胞中也有Plk1蛋白的表达.结论 Plk1在胰腺癌中的表达具有一定肿瘤特异性,有可能成为胰腺癌诊治的理想靶标.     

Toll样受体9在胰腺癌组织中的表达及临床意义

目的 检测Toll样受体9(TLR9)在胰腺癌组织中的表达,探讨其临床意义.方法 采用实时定量PCR法、蛋白质印迹法及免疫组化法检测30例胰腺癌及其相应癌旁组织、10例正常胰腺组织中TLR9的表达,分析胰腺癌组织TLR9表达与临床病理参数的关系.结果 以正常胰腺组织作为对照,胰腺癌组织TLR9 mRNA表达倍数为2.32(1.41～3.22),癌旁组织为1.23(1.18～1.28),两组间比较差异有统计学意义(P＜0.05).胰腺癌组织TLR9蛋白阳性表达率为73.3%(22/30),癌旁组织为33.3%(10/30),正常胰腺组织为20.0%(2/10),三者的TLR9相对表达量分别为0.780±0.026、0.400±0.018、0.173±0.043,三组间比较差异有统计学意义(P值均＜0.01).胰腺癌组织TLR9高表达与肿瘤分化程度、TNM分期、淋巴结转移呈正相关.结论 胰腺癌组织高表达TLR9,它可能参与胰腺癌的恶性转化过程.     

TMPRSS4在胰腺癌组织中的表达及其临床意义

目的 检测Ⅱ型跨膜丝氨酸蛋白酶4( TMPRSS4)在胰腺癌组织中的表达及其与临床病理特征的关系.方法 采用实时PCR法和蛋白质印迹法检测16例胰腺癌和配对癌旁组织TMPRSS4 mRNA和蛋白表达;采用免疫组织化学法检测61例胰腺癌标本、26例配对癌旁组织、4例正常胰腺组织TMPRSS4蛋白的表达,分析其与临床病理特征的相关性.结果 胰腺癌组织TMPRSS4mRNA和蛋白表达明显高于配对癌旁组织(9.09±7.01比1.27±0.72;1.223±0.125比0.667 ±0.106,P值均＜0.01),胰腺癌组织TMPRSS4蛋白阳性表达率为67.2％ (41/61),显著高于癌旁组织3.8％ (1/26)的阳性表达率(P＜0.01).正常胰腺组织未见TMPRSS4蛋白表达.胰腺癌TMPRSS4表达与患者年龄、性别及肿瘤部位、肿瘤大小无关,而与肿瘤分化程度、淋巴结转移、临床分期密切相关(P值均＜0.05).结论 胰腺癌组织高表达TMPRSS4,其表达与肿瘤的恶性程度相关.     

Plk1在胰腺癌中的表达及临床意义

目的 研究胰腺癌组织标本及细胞系中Plk1的表达及临床意义。方法 应用免疫组化EnVision两步法检测33例胰腺癌及其癌旁组织、3例胰腺浆液性囊腺瘤、3例黏液性囊腺瘤、5例慢性胰腺炎的石蜡标本中Plk1的表达。用半定量RT—PCR检测5例新鲜胰腺癌组织及其癌旁组织中Plk1 mRNA的表达。用Westernblot检测两株胰腺癌细胞PANC1和CFPAC1中Plk1表达。结果 胰腺癌组织中Plk1的阳性表达率为72、7％（24／33），其表达与胰腺癌患者的年龄、性别、临床分期、组织学分级、淋巴结转移、肿瘤的部位无显著相关（P〉0.05）。癌旁组织、慢性胰腺炎和良性胰腺肿瘤组织中Plk1的表达均为阴性。5例新鲜胰腺癌组织中都有Plk1mRNA的高表达，两株胰腺癌细胞中也有Plk1蛋白的表达。结论 Plk1在胰腺癌中的表达具有一定肿瘤特异性，有可能成为胰腺癌诊治的理想靶标。     

Mesothelin在胰腺癌组织的表达及其临床意义

目的研究胰腺癌组织mesothelin的表达及其与临床肿瘤指标的关系.方法 (1)通过逆转录-聚合酶链反应(RT-PCR)方法检测5株胰腺癌细胞株mesothelin mRNA的表达;(2)收集54例手术切除的胰腺癌及42例相应癌旁胰腺组织石蜡标本,利用EnVision免疫组化法分别检测癌组织和癌旁胰腺组织Mesothelin的表达情况.结果 5株胰腺癌细胞株均有mesothelin mRNA表达;54例胰腺癌中mesothelin阳性表达41例(75.9%),2例癌旁胰腺组织中均无阳性表达;mesothelin阳性率与肿瘤分化程度相关(P ＜ 0.005),与肿瘤大小、淋巴及远处转移无关(P ＞ 0.05).结论 Mesothelin在胰腺癌组织中有较高的阳性表达率,检测其表达有助于胰腺癌的诊断,并可作为判断胰腺癌恶性程度的重要指标.     

胰淀粉样多肽在糖尿病及胰腺癌患者胰腺组织中的表达

目的 检测胰淀粉样多肽(IAPP)在胰腺癌患者胰腺组织中的表达,探讨胰腺癌与糖尿病的相关性.方法 收集28例手术切除的胰腺癌及其相应癌旁正常胰腺组织,其中12例患者合并糖尿病,16例不合并糖尿病.采用免疫组化和蛋白质印迹法(Western blotting)检测组织标本中IAPP的表达.结果 IAPP定位表达于人胰腺的胰岛细胞胞质内.合并糖尿病的胰腺癌组织及癌旁胰腺组织、不合并糖尿病的胰腺癌组织及癌旁胰腺组织IAPP表达的免疫组化指数分别为283 305±91 627、122 874±86 917、154 032±81 097和105 797±67 593;IAPP相对表达量分别为(173.1±23.5)%、(1 19.4±18.4)%、(148.7±28.3)%和100%.胰腺癌组织的IAPP表达均显著高于相应癌旁正常胰腺组织(P＜0.01);合并糖尿病的胰腺癌组织的IAPP表达显著高于不合并糖尿病的胰腺癌组织(P＜0.01);合并糖尿病的痛旁胰腺组织的IAPP表达高于不合并糖尿病的痛旁胰腺组织(P＜0.05).结论 IAPP与糖尿病及胰腺癌的发病密切相关,很可能为两种疾病的共同发病机制之一.     

胰腺癌组织中SMO mRNA的表达及其临床意义

目的研究胰腺癌组织SMO mRNA的表达及其与临床肿瘤指标的关系.方法收集28例手术切除的新鲜胰腺癌及癌旁胰腺组织,利用RT-PCR方法分别检测癌组织和癌旁胰腺组织SMO mRNA的表达情况.结果 28例胰腺癌组织中20例胰腺癌组织有SMO mRNA表达(阳性率71.4%);28例癌旁胰腺组织中无SMO mRNA的表达;胰腺癌组织和癌旁组织SMO mRNA阳性表达率差异有显著性(P＜ 0.01);SMO mRNA阳性表达率与肿瘤分化程度有关(P＜ 0.05),与肿瘤的大小、淋巴结及远处转移无关(P ＞ 0.05).结论 SMO mRNA在胰腺癌组织中有较高的阳性表达率,检测其表达有助于胰腺癌的诊断,并可作为判断胰腺癌恶性程度的重要指标.     

酪氨酸激酶受体RON在胰腺癌中的表达及意义

目的:研究酪氨酸激酶RON(recepteur d'origine nantais)在胰腺癌组织中的表达及其意义.方法:收集胰腺癌组织及相关癌旁组织31例.正常胰腺组织8例,采用免疫组织化学技术检测组织中RON的表达.结果:RON在正常胰腺组织、癌旁组织、胰腺癌组织中均见阳性表达,胰腺癌及癌旁中的表达强度高于正常胰腺组织,胰腺癌RON的表达强度强于癌旁组织(P＜0.05).RON表达与患者年龄、肿瘤大小、组织学类型和肿瘤部位等均无关,与胰腺癌临床分期、分化程度及淋巴结转移相关(P＜0.05).结论:RON表达量的增多与胰腺癌的发生、发展有关.     

Experimental pancreatic carcinoma as a model of human pancreatic carcinoma

Experimental pancreatic carcinoma induced by BHP in hamsters and by DMBA in rats are compared with human pancreatic carcinoma. Tubular adenocarcinoma and papillary adenocarcinoma in human pancreas and hamster pancreas appeared to be similar. However, poorly differentiated adenocarcinoma and acinar cell carcinoma were not observed in the experimental hamster model. Poorly differentiated adenocarcinoma and acinar cell carcinoma in human and rat pancreas were similar but experimentally induced papillary adenocarcinoma and cystoadenocarcinoma were not observed in the rat. Mucin producing cells were usually observed in human and experimental pancreatic carcinoma in the hamster but were rarely noted in the rat. These results indicate that experimental pancreatic carcinoma either in rats or hamsters is a good model for the understanding of both the histogenesis and the carcinogenesis of human pancreatic carcinoma.     

Solitary pancreatic tuberculosis mimicking advanced pancreatic carcinoma

A 40-year-old woman was referred for pancreatic head carcinoma invading the portal vein. The dichotomy between the radiological findings and the general condition of the patient, as well as the laboratory results (no evidence of cholestasis), cast doubt on the diagnosis. There was no history of tuberculosis. The chest radiograph revealed no pathological findings. The anatomic relationships of the lesion entailed a high risk of vascular injury if tissue biopsy were to be done; therefore, diagnostic laparotomy was performed. Biopsy revealed granulomas with caseous necrosis, consistent with tuberculosis. After 6 months of antituberculosis treatment, the lesions had completely resolved. Tuberculosis should be considered in the differential diagnosis of pancreatic masses, particularly in regions where the disease is endemic. The condition usually resembles an advanced pancreatic tumor. Performing a biopsy of inoperable lesions and maintaining a reasonable skepticism in regard to the evaluation of operable lesions (attention to nonexclusive but helpful clues, such as young patient age, history of tuberculosis, absence of jaundice) will lead to the diagnosis in most patients. Diagnostic laparotomy may be required in a small subset of patients. The response to antituberculosis treatment is very favorable. The role of resection (e.g., pancreatoduodenectomy) is very limited.     

Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma

In this study, two cases of biopsy-proven pancreatic tuberculosis are reported. The patients presented with fever, anorexia, fatigue, abdominal pain and weight loss. A differential diagnosis of fever of unknown origin was conducted. Computed tomography (CT) revealed a cystic mass image in the pancreatic head in one patient, and a hypodense lesion in the pancreatic head in the other. The first patient was diagnosed by a wedge biopsy specimen obtained in the exploratory laparotomy. The other patient was diagnosed by percutaneous fine-needle aspiration biopsy. Both patients were successfully treated with quadruple antituberculous therapy for 12 months. We concluded that especially in young patients who present with a mass in the pancreas, pancreatic tuberculosis should be considered among the differential diagnoses, particularly in developing countries and immunosuppressed individuals.     

Anti-angiogenesis therapy in pancreatic carcinoma

Pancreatic adenocarcinoma is a leading cause of cancer death in the United States and represents a challenging chemotherapeutic problem. The treatment of advanced pancreatic cancer with gemcitabine has only modest activity with a small survival benefit, and toxicity continues to be a major obstacle. New therapeutic strategies that notably lack cross resistance with established treatment regimens are much needed in pancreatic cancer. One such approach is the pharmacological control of angiogenesis that represents a novel approach to the management of pancreas cancer, since the pathological development of vascular supply is a critical step for tumor growth and may affect its prognosis. Since pancreatic carcinoma show strong tumor neoangiogenesis, overexpression of vascular endothelial growth factor (VEGF), a key mediator of angiogenesis, in pancreatic cancer and consequently are highly vascularized, the role of anti-angiogenic therapies is under exploration at present. Hence, this review covers the summary of the development of anti-angiogenesis as anti-antitumor therapy in pancreatic carcinoma, including matrix-metalloproteinase inhibitors (MMPIs), such as marimastat and BAY 12-9566, anti-VEGF agent, bevacizumab (Avastin, Genentech, South San Francisco, CA, USA), celecoxib (a cyclooxygenase-2 inhibitor), thalidomide and others. Role of markers of angiogenesis in predicting response to therapy is also discussed.     

Modern management of pancreatic carcinoma

Pancreatic cancer remains a fearsome disease. New insights into the molecular pathogenesis may influence choice of treatment modalities and provide avenues for novel therapeutic strategies for testing in the clinic. The survival rate of patients with all stages of disease is poor and clinical trials are appropriate alternatives for treatment and should be considered. Surgical resection, when possible, remains the primary treatment modality and can result in long-term cure. Less invasive techniques such as laparoscopy may reduce the rate of unnecessary laparotomies. The role of adjuvant therapy is re-emerging. Patients with unresectable and metastatic disease are incurable and optimal palliation is the goal. These patients may benefit from palliative bypass of biliary or duodenal obstruction if symptomatic. Pain associated with local tumour infiltration may be palliated with radiation, with or without chemotherapy, or with coeliac nerve blocks or local neurosurgical procedures. Chemotherapy with gemcitabine has modest objective response rates but has been shown to improve symptoms.