CAPS1 Suppresses Tumorigenesis in Cholangiocarcinoma.


  • 影响因子:2.46
  • DOI:10.1007/s10620-019-05843-9
  • 作者列表:"Weng S","Janssen HLA","Zhang N","Tang W","Bai E","Yang B","Dong L
  • 发表时间:2020-04-01

BACKGROUND:CAPS1 (calcium-dependent activator protein for secretion) is a multi-domain protein involved in regulating exocytosis of synaptic vesicles and dense-core vesicles. However, the expression and function of CAPS1 in cholangiocarcinoma (CCA) remains unclear. In the present study, we explored the role of CAPS1 in CCA carcinogenesis. METHODS:CAPS1 expression was explored using western blotting and immunohistochemistry in four CCA cell lines and clinical samples from 90 cases of CCA. The clinical significance of CAPS1 was analyzed. The biological function of CAPS1 in CCA cells was detected in vitro and in vivo. The underlying mechanism of CAPS1 function was explored by detecting the expression of critical molecules in its associated signaling pathways. The mechanism of CAPS1 downregulation in tumor tissues was explored using in silico prediction and luciferase reporter assays. RESULTS:CAPS1 expression was reduced in CCA cell lines and human tumor tissues. Loss of CAPS1 in tumor tissues was closely associated with poor prognosis of patients with CCA. Moreover, CAPS1 expression correlated significantly with tumor-node-metastasis stage, lymph node metastasis, and vascular invasion. Lentivirus-mediated CAPS1 overexpression substantially prevented clone formation, cell proliferation, and cell cycle progression. CAPS1 overexpression also suppressed carcinogenesis in nude mice. Mechanistically, CAPS1 overexpression greatly accelerated the ERK and p38 MAPK signal pathways. In addition, microRNA miR-30e-5p negatively regulated CAPS1 expression. CONCLUSION:These data showed that CAPS1 functions as a tumor suppressor in CCA. Reduced CAPS1 expression could indicate poor prognosis of patients with CCA.


背景: CAPS1 (分泌的钙依赖激活蛋白) 是一种多结构域蛋白,参与调节突触囊泡和致密核心囊泡的胞吐作用。然而,CAPS1在胆管癌 (CCA) 中的表达和功能仍不清楚。在本研究中,我们探讨了CAPS1在CCA致癌中的作用。 方法: 采用免疫印迹和免疫组织化学方法检测90例CCA患者4种CCA细胞系和临床标本中CAPS1的表达。分析CAPS1的临床意义。在体外和体内检测CAPS1在CCA细胞中的生物学功能。通过检测相关信号通路中关键分子的表达,探索CAPS1功能的潜在机制。使用计算机模拟预测和荧光素酶报告基因测定探索了肿瘤组织中CAPS1下调的机制。 结果: CAPS1在CCA细胞系和人肿瘤组织中表达降低。肿瘤组织中CAPS1的丢失与CCA患者的不良预后密切相关。此外,CAPS1表达与肿瘤淋巴结转移分期、淋巴结转移和血管浸润显著相关。慢病毒介导的CAPS1过表达基本上阻止了克隆形成、细胞增殖和细胞周期进程。CAPS1过表达还抑制裸鼠的癌变。在机理上,CAPS1过表达极大地加速了ERK和p38 MAPK信号通路。此外,microRNA miR-30e-5p负调控CAPS1表达。 结论: 这些数据表明CAPS1在CCA中起肿瘤抑制作用。CAPS1表达降低提示CCA患者预后不良。



作者列表:["Dong Y","Xu B","Cao Q","Zhang Q","Qiu Y","Yang D","Yu L","Wang WP"]

METHODS:AIM:To investigate the value of contrast enhanced ultrasound with high resolution linear transducers (HF-CEUS) for differential diagnosis of focal fundal gallbladder (GB) wall thickening. METHODS:A total of 32 patients with incidentally detected focal fundal GB wall thickening were included. After conventional B mode ultrasound (BMUS) examinations, HF-CEUS were performed with a 7.5-12 MHz 9L4 linear transducer (S2000 HELX OXANA unit, Siemens). Two radiologists independently reviewed the HF-CEUS enhancement patterns to determine the differential features between malignancy and benignity with a five-point confidence scale. The diagnostic accuracy of BMUS and HF-CEUS for GB wall thickening was compared. The final gold standard was surgery with histological examination. RESULTS:Final diagnoses included GB adenocarcinoma (n = 16), adenomyomatosis (n = 12), Xanthogranulomatous (n = 2) and cholecystitis (n = 2). HF-CEUS features associated with GB adenocarcinoma including arterial phase inhomogeneous hyperenhancement, venous phase hypoenhancement and disruption of GB wall layer structure (P < 0.05). Two small (5 mm) liver metastasis were confirmed by HF-CEUS during the late phase liver sweep as hypoenhanced lesions. Nonenhanced Rokitansky-Aschoff sinuses were clearly observed in 83.3% focal adenomyomatosis. Overall sensitivity, specificity and accuracy for differentiation between malignant and benign focal fundal GB wall thickening of HF-CEUS and BMUS were 84.3% vs 53.1%, 90.6% vs 59.3% and 87.5% vs 56.2% (P < 0.005). CONCLUSIONS:CEUS performed with high frequency linear transducers could be a useful alternative in the differential diagnosis of focal fundal GB wall thickening on conventional ultrasound.

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来源期刊:Surgery today
作者列表:["Yoshizumi T","Mori M"]

METHODS::Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT.

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作者列表:["Khan MS","Shahzad N","Arshad S","Shariff AH"]

METHODS:BACKGROUND:Seasonal variation in the occurrence of medical illnesses reflects the effect of the environment, provides insight into pathogenesis, and can assist health care administrators in allocating resources accordingly. Seasonal variation has been reported in various infectious and surgical diseases, but has been rarely studied in acute cholecystitis. Our objective was to study seasonal variation in acute cholecystitis at our institution. METHODS:We performed a retrospective analysis of patients who underwent cholecystectomy for acute cholecystitis from January 1988 to December 2018. Chi-square goodness-of-fit test was used to analyze seasonality of acute cholecystitis adjusting for variation in number of days between seasons. The number of days for seasons were taken as 92, 92, 91, and 90.25 for spring, summer, fall, and winter, respectively. RESULTS:Overall, 3924 patients underwent cholecystectomy for acute cholecystitis during the study period. The frequency of cholecystectomies performed varied between months (minimum February n = 259, maximum July n = 372, P < 0.001) and seasons (minimum winter n = 789, maximum summer n = 1101 P < 0.001). Age and gender distribution across months and seasons was similar (P > 0.05). CONCLUSIONS:Our findings confirm seasonal variation in occurrence of acute cholecystitis with summer season witnessing the most and the winter season encountering the least patients with acute cholecystitis. Validation of our findings through prospectively collected data at national level is the way forward.

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