Journal of the Pancreas最新文献

英文中文

The Role of Real Time Endoscopic Ultrasound Guided Elastography for Targeting EUS-FNA of Suspicious Pancreatic Masses: A Review of the Literature and A Single Center Experience. 实时内镜超声引导弹性成像在可疑胰腺肿块EUS-FNA定位中的作用:文献综述和单中心经验。

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2016-09-01

Mikram Jafri, Amit H Sachdev, Lauren Khanna, Frank G Gress

Background: Endoscopic ultrasound guided elastography is an imaging modality that can be used to evaluate tissue stiffness and to assess solid pancreatic lesions. It can also assist in optimizing the diagnostic yield of endoscopic ultrasound guided fine needle aspiration biopsies.

Aims: To review the literature on solid pancreatic lesions, the use of EUS guided fine needle aspiration and endoscopic ultrasound guided elastography and to present a single center experience using elastography to direct fine needle aspiration biopsies of solid pancreatic lesions.

Methods: We present a review of the literature and a single center experience describing the use of EUS guided elastography in directing fine needle aspiration biopsies of solid pancreatic lesions.

Results: Thirteen male veterans with an average age of 62.3 (SD±11.8) years were enrolled in the study. The mean pancreatic mass size on EUS was 5.1×5.2 (SD±4.4×4.5) cm. A total of 13 lesions were identified during elastography. The lesions were most commonly found in the body (n=5), followed by multifocal lesions (n=4), pancreatic head (n=3) and tail (n=1). The seven concerning pancreatic lesions were stratified based on color pattern identified on EUS and EUS-elastography. Three lesions were homogenously blue, and four lesions were heterogeneously blue. The remaining six lesions which were less concerning were predominantly green. Of the three lesions, that were homogenously blue, two were diagnosed as adenocarcinoma (n=2) and chronic pancreatitis (n=1) respectively. Of the four heterogeneously blue lesions two were adenocarcinomas, while the other two represented a large B-cell lymphoma and chronic pancreatitis. Patients whose lesions were characterized as homogenous or heterogeneous green were benign and remained disease free after a median of two years of regular follow up.

Limitations: Relatively small number of patients studied.

Conclusions: In our single center experience we found that the use of real time endoscopic ultrasound guided elastography for targeting fine needle aspiration of suspicious pancreatic lesions may be beneficial as an adjunct modality to complement conventional EUS. Larger prospective studies need to be conducted to evaluate the utility of this modality in targeting pancreatic lesions.

背景:内镜超声引导弹性成像是一种成像方式，可用于评估组织刚度和评估实体胰腺病变。它还可以帮助优化内镜超声引导细针穿刺活检的诊断率。目的:回顾EUS引导下细针穿刺和内镜下超声引导下弹性成像在实性胰腺病变中的应用文献，介绍用弹性成像指导细针穿刺活检实性胰腺病变的单中心经验。方法:我们回顾了文献和单中心经验，描述了使用EUS引导弹性成像指导细针穿刺活检实体胰腺病变。结果:13例男性退伍军人入组，平均年龄62.3 (SD±11.8)岁。EUS检查胰腺肿块平均大小为5.1×5.2 (SD±4.4×4.5) cm。在弹性成像中共发现13个病变。病变最常见于身体(n=5)，其次是多灶性病变(n=4)，胰腺头部(n=3)和尾部(n=1)。根据EUS和EUS弹性成像确定的颜色模式对7例胰腺病变进行分层。3个病灶呈均匀蓝色，4个病灶呈非均匀蓝色。其余6个不太值得关注的病变以绿色为主。在均匀蓝色的三个病变中，两个分别被诊断为腺癌(n=2)和慢性胰腺炎(n=1)。在四个不均匀的蓝色病变中，两个是腺癌，而另外两个代表大b细胞淋巴瘤和慢性胰腺炎。病变特征为同质或异质绿色的患者是良性的，在中位数为两年的常规随访后仍无疾病。局限性:研究的患者数量相对较少。结论:在我们的单中心经验中，我们发现使用实时内镜超声引导弹性成像瞄准可疑胰腺病变的细针穿刺可能是一种有益的辅助方式，以补充传统的EUS。需要进行更大规模的前瞻性研究来评估这种方式在靶向胰腺病变中的效用。

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引用次数: 0

Hepatic Artery Chemotherapy for Advanced Adenocarcinoma of the Pancreas 晚期胰腺腺癌的肝动脉化疗

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2016-05-20 DOI: 10.1200/JCO.2016.34.15_SUPPL.E15733

R. Levin, P. Sirijintakarn, J. Grutsch

Context Seventy patients with adenocarcinoma of the pancreas with liver metastases, received chemotherapy every four weeks and their outcomes are reported in this retrospective series. Objective Advanced adenocarcinoma of the pancreas has a poor prognosis with only 2% 5-year survival reported by SEER (Surveillance, Epidemiology and End Results of the NCI). Chemotherapy given as intra-arterial perfusions is more intense than intravenous chemotherapy. Responses in perfused tumor is expected to be better than that obtained with only intravenous chemotherapy. Design Hepatic artery therapy is given monthly as a 5 hour perfusion of the hepatic artery using DDP and MIC. Also given is monthy Intravenous (IV) therapy with four hours of Leucovorin (LV), with an injection of FUDR during the last hour of LV, daily x 5 days. Setting all therapy was given at Midwestern Regional Medical Center. Patients Thirty seven patients had no prior chemotherapy, while 33 patients had progressed after prior IV chemotherapy. Intervention Hepatic artery therapy with IV LV-FUDR was given for up to six months depending upon marrow tolerance and response. At that point, if response was ongoing or improving, therapy was continued monthly with only IV LV-FUDR; all therapy was stopped whenever progressive disease was evident. Results of those without prior chemotherapy, the mean overall survival (OS) was 17.3 ± 30.2 months (mean±SD), ranging up to 13 years. Six patients survived more than three years with four are living in continuing complete remission for more than five years. Conclusion This therapy offers the opportunity for long term survival in a subset of patients with metastatic adenocarcinoma of the pancreas who have liver metastases, and some patients can be cured.

70例胰腺腺癌合并肝转移患者每4周接受一次化疗，并报道了他们的预后。目的根据美国国家癌症协会(NCI)的监测、流行病学和最终结果，晚期胰腺腺癌预后较差，5年生存率仅为2%。以动脉灌注方式给予的化疗比静脉化疗更强烈。灌注肿瘤的反应预期比单纯静脉化疗更好。肝动脉治疗每月给予肝动脉灌注5小时，使用DDP和MIC。同时给予每月静脉(IV)治疗4小时的亚叶酸素(LV)，并在LV的最后一小时注射FUDR，每天x 5天。所有治疗均在中西部地区医疗中心进行。37例患者既往无化疗，33例患者既往静脉化疗后有进展。根据骨髓耐受和反应，给予肝动脉静脉LV-FUDR治疗长达6个月。此时，如果反应持续或改善，则每月仅继续IV LV-FUDR治疗;当疾病进展明显时，停止所有治疗。结果既往未接受化疗的患者，平均总生存期(OS)为17.3±30.2个月(mean±SD)，最长可达13年。6名患者存活超过3年，4名患者持续完全缓解超过5年。结论:该疗法为部分肝转移的胰腺转移性腺癌患者提供了长期生存的机会，并且一些患者可以治愈。

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引用次数: 0

Diabetes Type 2 and Pancreatic Cancer: A History Unfolding. 2型糖尿病和胰腺癌:一个历史的展开。

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2016-03-01

Andre De Souza, Khawaja Irfan, Faisal Masud, Muhammad Wasif Saif

Pancreatic Cancer is the fourth cause of cancer-related deaths in the United States. Up to 80% of pancreatic cancer patients present with either new-onset type 2 diabetes or impaired glucose tolerance at the time of diagnosis. Recent literature suggests that diabetes mellitus type 2 is a risk factor, a manifestation and a prognostic factor for pancreatic cancer. This article is intended to clarify the evidence about diabetes as a risk factor for pancreatic cancer.

胰腺癌是美国癌症相关死亡的第四大原因。高达80%的胰腺癌患者在诊断时伴有新发2型糖尿病或糖耐量受损。最近的文献表明，2型糖尿病是胰腺癌的危险因素、表现和预后因素。本文旨在阐明糖尿病作为胰腺癌危险因素的证据。

引用次数: 0

Spleen Autotransplantation Following Laparoscopic Distal Pancreatosplenectomy and Cholecystectomy 腹腔镜远端胰脾和胆囊切除术后自体脾移植

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/3000

Sung Hwan Lee, D. H. Kim, H. Hwang, C. Kang, W. Lee

Context The lifelong risk of post-splenectomy overwhelming sepsis is major complication after splenectomy. Laparoscopic distal pancreatectomy is an accepted as safe, and adequate procedure for pancreatic pathologies requiring resection of the distal part of the pancreas. However, attempts to preserve the spleen are not always successful and sometimes require unnecessary splenectomy. Spleen autotransplantation can be regarded as inducing iatrogenic splenosis in the abdominal cavity. Case report In this report, we present a case of spleen autotransplantation (about 30 g of splenic tissue) following laparoscopic distal pancreatectomy and inadvertent splenectomy for benign intraductal papillary tumor of the pancreas. Conclusion This procedure may be the last option spleen preservation considered in the era of laparoscopic distal pancreatectomy. Image: Laparoscopic view after completion of spleen autotransplantation.

脾切除术后压倒性败血症的终生风险是脾切除术后的主要并发症。对于需要切除胰腺远端部分的胰腺病变，腹腔镜远端胰腺切除术是一种公认的安全、适当的手术。然而，保存脾脏的尝试并不总是成功的，有时需要不必要的脾切除术。自体脾移植可视为诱发医源性腹腔脾功能减退。病例报告在本报告中，我们报告一例自体脾移植(约30g脾组织)后腹腔镜远端胰腺切除术和无心脾切除术良性胰腺导管内乳头状瘤。结论该手术可能是腹腔镜远端胰腺切除术时代保留脾脏的最后选择。图片:自体脾移植完成后的腹腔镜视图。

引用次数: 2

Carcinosarcoma of the Pancreas: How a Common Blood Disorder Can Hide an Extremely Rare Tumour 胰腺癌肉瘤:一种常见的血液疾病如何隐藏极其罕见的肿瘤

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/3003

A. Katsourakis, C. Svoronos, E. Chatzitheoklitos, Iosif Hadjis, M. Alatsakis, C. Mirelis, A. Sovatzidis, G. Noussios

Context Sarcomas represent a relatively rare malignancy. Primary sarcomas of the pancreas represent an extremely rare pathology. Case report We report a case of primary pancreatic carcinoma that presented with anaemia. The patient underwent a Kausch-Whipple operation, and, 16 months after the operation, the patient is disease free. Conclusion This unique case describes an extremely rare gastrointestinal tumour that was found during the patient's anaemia assessment. Image: Gastro-duodenoscopy demonstrating a tumor at the ampulla of Vater.

肉瘤是一种相对罕见的恶性肿瘤。原发性胰腺肉瘤是一种极为罕见的病理。病例报告我们报告一例原发性胰腺癌的贫血。患者接受了Kausch-Whipple手术，手术后16个月，患者痊愈了。结论:这个独特的病例描述了一个极其罕见的胃肠道肿瘤，是在病人贫血评估期间发现的。图:胃十二指肠镜显示水腹侧肿瘤。

引用次数: 4

Hydropic Gallbladder in Three Patients with Poorly Controlled Diabetes Mellitus: What Constitutes Optimal Management? 3例控制不良的糖尿病患者胆囊积液:什么是最佳管理?

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/2998

Yezaz A Ghouri, Idrees Mian, Gitanjali Bhattacharjee, Modushudan Bhattacharjee

Context Long-standing diabetes mellitus results in autonomic nervous system dysfunction, leading to gastroparesis and cholecystoparesis. The latter can result in hydropic gallbladder, a condition that arises from the accumulation of mucinous secretions within the gallbladder, usually caused by obstruction of the cystic duct, but not in the case of the patients with diabetes that we have illustrated. Case report We describe three patients who presented with non-specific abdominal discomfort at the time of admission for complications of poorly controlled diabetes and were subsequently found to have hydropic gallbladder. We theorize that hydropic gallbladder may be a result of a natural progression of gallbladder dysfunction in poorly controlled diabetics with autonomic neuropathy. In our cases the risk of perioperative mortality was high at the time of presentation. No surgical intervention was performed except in one case with the most significant sized gallbladder, and underwent a temporizing cholecystostomy. Conclusions The development of hydropic gallbladder in patients with non-obstructed cystic ducts highlights the complexities of management of patients with functional biliary pain. The rome committee on functional biliary and pancreatic disorders has defined the characteristics of this pain. There is a need for guidelines to direct appropriate assessment of hydropic gallbladder in diabetics and also to determine the indications for cholecystectomy. Image: HIDA scan showing a low ejection fraction of the gallbladder after administration of CCK.

背景长期糖尿病可导致自主神经系统功能障碍，导致胃轻瘫和胆囊截瘫。后者可导致胆囊积水，这是一种由胆囊内粘液分泌物积聚引起的疾病，通常由胆囊管阻塞引起，但在我们所说明的糖尿病患者中不会出现这种情况。病例报告我们描述了3例患者，他们在入院时因控制不良的糖尿病并发症而出现非特异性腹部不适，随后被发现患有胆囊积液。我们推测，胆囊积水可能是控制不良的糖尿病伴自主神经病变患者胆囊功能障碍自然发展的结果。在我们的病例中，围手术期死亡的风险在出现时很高。没有手术干预，除了一个病例最显著的胆囊大小，并进行了暂时性胆囊造瘘。结论胆囊管未梗阻患者发生胆囊积水，凸显了功能性胆道疼痛患者治疗的复杂性。功能性胆道和胰腺疾病罗马委员会定义了这种疼痛的特征。有必要制定指南来指导糖尿病患者胆囊积水的适当评估，并确定胆囊切除术的适应症。图像:hda扫描显示CCK给药后胆囊射血分数低。

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引用次数: 2

Pancreatic Panniculitis: A Rare Manifestation of Acute Pancreatitis 胰膜炎:急性胰腺炎的一种罕见表现

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/3001

R. Patel, Ali Khan, Sami Naveed, Jason Brazleton, Mel C. Wilcox

Context Pancreatic panniculitis is a very rare complication associated with pancreatic disease and perhaps even a presage to pancreatic pathology. Case report We present a case of pancreatic panniculitis in a 61 year old patient who was treated for sudden onset of abdominal pain associated with nausea and vomiting secondary to acute pancreatitis of unknown etiology. He subsequently developed skin lesions consistent with pancreatic panniculitis which gradually improved after resolution of his acute condition and treatment with topical steroid cream. Conclusion We discuss and review the literature along with highlighting for the readers the important clinical and histopathologic features of acute pancreatitis associated pancreatic panniculitis. Image: Initial dermatologic manifestation on lower extremities.

胰腺膜炎是一种非常罕见的与胰腺疾病相关的并发症，甚至可能是胰腺病理的先兆。病例报告:我们报告一例61岁的胰腺胰膜炎患者，因不明原因的急性胰腺炎并发突然腹痛并伴有恶心和呕吐而接受治疗。随后，他出现了与胰膜炎相符的皮肤病变，在急性病情缓解和局部类固醇乳膏治疗后逐渐改善。结论我们讨论和回顾文献，并为读者强调急性胰腺炎相关性胰腺膜炎的重要临床和组织病理学特征。图像:下肢最初的皮肤病表现。

引用次数: 2

A Lower Cyst Fluid CEA Cut-Off Increases Diagnostic Accuracy In Identifying Mucinous Pancreatic Cystic Lesions 较低的囊肿液CEA切点可提高胰腺粘液性囊性病变的诊断准确性

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/2994

D. Jin, A. Small, C. Vollmer, N. Jhala, E. Furth, G. Ginsberg, M. Kochman, N. Ahmad, V. Chandrasekhara

Context Carcinoembryonic antigen analysis of pancreatic cyst fluid is the tumor marker of choice for preoperatively differentiating mucinous from non-mucinous cystic lesions. Objective We aim to determine the most accurate cyst carcinoembryonic antigen cut-off value for distinguishing mucinous cysts from non-mucinous cysts with a focus on discriminating intraductal papillary mucinous neoplasms. Methods The results of pancreatic cyst aspiration carcinoembryonic antigen levels from a single center were retrospectively collected and evaluated for a diagnosis of a mucinous cyst and an assessment of malignancy using surgical histology as the diagnostic standard in 86 patients. Results The median cyst carcinoembryonic antigen level (ng/mL) was significantly higher in mucinous cysts compared with non-mucinous cysts (218 vs. 4.4; P=0.0006) and in intraductal papillary mucinous neoplasms compared with non-mucinous cysts (135 vs. 4.4; P=0.0027). A cyst carcinoembryonic antigen cut-off of 30.7 ng/mL was most accurate (87.2%) for differentiating mucinous from non-mucinous cysts and specifically for differentiating intraductal papillary mucinous neoplasms from non-mucinous cysts (82.7%). Cyst carcinoembryonic antigen levels were not significantly different between malignant and non-malignant mucinous cysts (68.5 vs. 238.1; P=0.51). Conclusions Pancreatic cyst fluid carcinoembryonic antigen can accurately differentiate histologically verified mucinous lesions, including intraductal papillary mucinous neoplasms, from non-mucinous lesions with an optimal cut-off that is much lower than previously reported values. Cyst carcinoembryonic antigen levels are not a reliable predictor of malignancy. Image: Sensitivity and specificity curves of cyst fluid CEA levels for differentiating mucinous from non-mucinous cysts.

背景:胰腺囊肿液癌胚抗原分析是术前鉴别粘液性和非粘液性囊性病变的肿瘤标志物。目的探讨鉴别导管内乳头状黏液性肿瘤的最准确的囊肿癌胚抗原切断值。方法回顾性收集86例胰腺囊肿单中心抽吸癌胚抗原检测结果，并以手术组织学为诊断标准，评价其对粘液囊肿的诊断和恶性程度的判断。结果黏液囊肿中囊癌胚抗原水平(ng/mL)明显高于非黏液囊肿(218∶4.4;P=0.0006)，导管内乳头状黏液性肿瘤与非黏液性囊肿相比(135 vs 4.4;P = 0.0027)。囊肿癌胚抗原切断值为30.7 ng/mL，区分黏液性囊肿和非黏液性囊肿最准确(87.2%)，特别是区分导管内乳头状黏液性肿瘤和非黏液性囊肿(82.7%)。恶性和非恶性黏液囊肿癌胚抗原水平无显著差异(68.5比238.1;P = 0.51)。结论胰腺囊肿液癌胚抗原可以准确区分组织学证实的粘液性病变，包括导管内乳头状粘液性肿瘤和非粘液性病变，其最佳临界值远低于先前报道的值。囊肿癌胚抗原水平不是恶性肿瘤的可靠预测指标。图像:囊肿液CEA水平鉴别黏液囊肿与非黏液囊肿的敏感性和特异性曲线。

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引用次数: 20

Advances in Pancreatic Cancer: The Role of Metabolomics 代谢组学在胰腺癌中的作用

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/2990

V. Nguyen, S. Hurton, S. Ayloo, M. Molinari

Metabolomics is an emerging scientific field focusing on compounds, also known as metabolomes that are produced by biologic systems. Metabolomes represent phenotypic end-products of living entities, and are of particular interest as they represent a novel group of biomarkers that can be used for diagnosis, monitoring response to treatments, and more recently as potential therapeutic agents for benign but more so for malignant diseases. One of the main factors associated with improved survival of patients affected by malignancies is early diagnosis, particularly for those tumors with poor prognosis such as pancreatic cancer. Currently, there are no diagnostic tests for the screening of pancreatic cancer, and although novel biomarkers continue to be discovered, none has yet to be proven useful for this purpose. The main aims of this paper are to review the current literature and to summarize the most relevant advances in the field of metabolomics applied to pancreatic adenocarcinoma. Image: Dalhousie University. Halifax, Nova Scotia, Canada.

代谢组学是一个新兴的科学领域，主要研究由生物系统产生的化合物，也称为代谢组。代谢组学代表了生物实体的表型最终产物，并且特别令人感兴趣，因为它们代表了一组新的生物标志物，可用于诊断，监测对治疗的反应，最近作为良性疾病的潜在治疗剂，但更多的是用于恶性疾病。与恶性肿瘤患者生存率提高相关的主要因素之一是早期诊断，特别是对于那些预后不良的肿瘤，如胰腺癌。目前，没有用于筛查胰腺癌的诊断测试，尽管新的生物标志物不断被发现，但尚未证明对这一目的有用。本文的主要目的是回顾目前的文献，并总结代谢组学应用于胰腺腺癌领域的最新进展。图片来源:达尔豪斯大学。加拿大新斯科舍省哈利法克斯。

引用次数: 8

Acquired 5-Fluorouracil Resistance in Human Pancreatic Carcinoma Cells. A Paradigm for Chemoresistance Mechanisms in Pancreatic Cancer 人胰腺癌细胞获得性5-氟尿嘧啶耐药胰腺癌化疗耐药机制的一个范例

IF 0.2 Q4 GASTROENTEROLOGY & HEPATOLOGY

Journal of the Pancreas

Pub Date : 2015-05-20 DOI: 10.6092/1590-8577/2992

M. Schober, R. Jesenofsky, R. Faissner, S. Krug, C. Weidenauer, W. Hagmann, S. Haas, R. Heuchel, M. Löhr

Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amongst solid tumors. Its ability to develop chemoresistance mechanisms towards cytotoxic drugs is the main cause of treatment failure. Objective Here, we have established a drug-resistance model for pancreatic cancer in which Capan-1 pancreatic carcinoma cells (designated Capan-1 5-FU2000) acquired 5-fluorouracil (5-FU) resistance and were used as a paradigm to reveal alterations in intracellular signaling cascades that. Those alterations may contribute to the circumvention of apoptosis during the course of the disease, culminating in treatment failure. Methods We made use of 2-D-gelelectrophoresis, mass-spectrometry, sandwich-ELISA and western blotting to compare the proteomic expression patterns of respective mediators involved in pro- and antiapoptotic as well as inflammatory processes in both cell lines. An ATP-based chemosensitivity assay validated the chemoresistant phenotype of the Capan-1 5-FU2000 clones. Results We detected specific changes in our resistant cell clones in particular a decreased expression of S100A4. We also found a decreased basal phosphorylation of SAPK/JNK and P38. The expression of the pro-apoptotic mediators Bok and Bad was down- and up-regulated in these cells, respectively. In case of NfkB p65 and IkB-alpha treatment with 5-FU (2,000 µg/mL for 96 h) markedly induced phosphorylation in native Capan-1 cells. In contrast in resistant clones it decreased phosphorylation of NfkB p65 and did not affect IkB-alpha phosphorylation. Basal phosphorylation of S6-ribosomal-protein was markedly increased in resistant clones, treatment with 5-FU decreased this phosphorylation, while in native Capan-1 cells it was vice versa. Conclusion Thus we can conclude that several pathways were found to be altered in chemoresistant Capan-1 5-FU2000 cells. Moreover these alterations are most likely the consequence of a multistep adaption towards gradual cytotoxic exposure finally culminating in a chemoresistant phenotype. Interfering with these pathways may possibly reverse the phenotype and thus open up alternative treatment options. Image: Effect of 5-FU treatment on NfkB p65 phosphorylation in native and 5-FU resistant cells.

胰腺导管腺癌是一种预后最差的实体肿瘤之一。它对细胞毒性药物产生化学耐药机制的能力是治疗失败的主要原因。在此，我们建立了一个胰腺癌耐药模型，其中Capan-1胰腺癌细胞(指定为Capan-1 5-FU2000)获得5-氟尿嘧啶(5-FU)耐药性，并作为一个范例来揭示细胞内信号级联反应的变化。这些改变可能有助于在疾病过程中规避细胞凋亡，最终导致治疗失败。方法采用二维凝胶电泳、质谱、夹心elisa和western blotting等方法比较两种细胞系中参与促凋亡和抗凋亡以及炎症过程的介质的蛋白质组学表达模式。基于atp的化学敏感性试验验证了Capan-1 5-FU2000克隆的化学耐药表型。结果我们在抗性细胞克隆中检测到特异性变化，特别是S100A4的表达降低。我们还发现SAPK/JNK和P38的基础磷酸化降低。促凋亡介质Bok和Bad在这些细胞中的表达分别下调和上调。在NfkB p65和IkB-alpha中，5-FU(2000µg/mL，作用96小时)显著诱导天然Capan-1细胞磷酸化。相反，在抗性克隆中，它降低了NfkB p65的磷酸化，而不影响ikb - α的磷酸化。s6 -核糖体蛋白的基础磷酸化在抗性克隆中显著增加，5-FU处理降低了这种磷酸化，而在天然Capan-1细胞中则相反。结论在化疗耐药的Capan-1 5-FU2000细胞中，多种通路发生了改变。此外，这些改变很可能是逐渐暴露于细胞毒性的多步骤适应的结果，最终导致耐药表型。干扰这些途径可能会逆转表型，从而开辟替代治疗方案。图片:5-FU处理对天然细胞和5-FU耐药细胞中NfkB p65磷酸化的影响。

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引用次数: 3

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