Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice.
Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice.
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DOI：
10.1038/s41598-020-74947-4
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发表时间：
2020-10-27
影响因子：
4.6
通讯作者：
Burdío F
中科院分区：
文献类型：
--
作者：
Cáceres M;Quesada R;Iglesias M;Real FX;Villamonte M;de Villarreal JM;Pérez M;Andaluz A;Moll X;Berjano E;Dorcaratto D;Sánchez-Velázquez P;Grande L;Burdío F
在小鼠模型中，胰管结扎术(PDL)被描述为一种外分泌性胰腺萎缩诱导过程。然而，它对癌前病变的影响很少被描述。本研究描述了胰腺导管腺癌癌前病变的组织学变化和PDL方法建立的胰腺导管腺癌模型中的基因表达。Ptf1a-Cre(+/KI)、K-ras LSLG12Vgeo(+/KI)小鼠(PDL-Kras小鼠)选择性结扎胰腺。实验分为三组：PDL组、对照组和假手术组。研究每组胰腺近端(PP)和远端(DP)癌前病变(Panin1-3和非典型扁平病变-AFL)的存在和数量。用微阵列技术分析PP和PD之间的差异表达基因。临床标本的胰腺十二指肠切除后，导管闭塞也进行了评估。PDL-Kras小鼠在DP中表现出强烈的萎缩模式，萎缩到组织的最小部分。与PDL-Kras小鼠相比，对照组和假手术组小鼠患高级别Panin2和3以及AFL的风险分别增加了7倍和10倍。此外，与PP相比，PDL-Kras小鼠在DP中的Panin 1和2以及AFL损伤显著减少。比较PP和PD，我们鉴定出38个角。其中一些基因与蛋白质的分泌和消化有关，而另一些基因如Nupr1则与Panin和PDAC有关。Ptf1a-Cre(+/Ki)；K-ras LSLG12Vgeo(+/Ki)小鼠的PDL可减少结扎的DP中癌前病变的出现。这可能是一些癌症风险患者感兴趣的潜在研究方向。
Pancreatic duct ligation (PDL) in the murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has scarcely been described on premalignant lesions. This study describes the histological changes of premalignant lesions and the gene expression in a well-defined model of pancreatic ductal adenocarcinoma by PDL. Selective ligation of the splenic lobe of the pancreas was performed in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice (PDL-Kras mice). Three experimental groups were evaluated: PDL group, controls and shams. The presence and number of premalignant lesions (PanIN 1–3 and Atypical Flat Lesions—AFL) in proximal (PP) and distal (DP) pancreas were studied for each group over time. Microarray analysis was performed to find differentially expressed genes (DEG) between PP and PD. Clinical human specimens after pancreaticoduodenectomy with ductal occlusion were also evaluated. PDL-Kras mice showed an intense pattern of atrophy in DP which was shrunk to a minimal portion of tissue. Mice in control and sham groups had a 7 and 10-time increase respectively of risk of high-grade PanIN 2 and 3 and AFL in their DP than PDL-Kras mice. Furthermore, PDL-Kras mice had significantly less PanIN 1 and 2 and AFL lesions in DP compared to PP. We identified 38 DEGs comparing PP and PD. Among them, several mapped to protein secretion and digestion while others such as Nupr1 have been previously associated with PanIN and PDAC. PDL in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice induces a decrease in the presence of premalignant lesions in the ligated DP. This could be a potential line of research of interest in some cancerous risk patients.
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影响因子：
12.4
作者：
通讯作者：
--
影响因子：
6.7
作者：
Kontos, Christos K.;Mavridis, Konstantinos;Scorilas, Andreas
通讯作者：
Scorilas, Andreas
影响因子：
3.1
作者：
Burdio, Fernando;Dorcaratto, Dimitri;Berjano, Enrique
通讯作者：
Berjano, Enrique
DOI：
10.1097/pas.0000000000000533
发表时间：
2015-12
期刊：
The American journal of surgical pathology
影响因子：
--
作者：
Basturk O;Hong SM;Wood LD;Adsay NV;Albores-Saavedra J;Biankin AV;Brosens LA;Fukushima N;Goggins M;Hruban RH;Kato Y;Klimstra DS;Klöppel G;Krasinskas A;Longnecker DS;Matthaei H;Offerhaus GJ;Shimizu M;Takaori K;Terris B;Yachida S;Esposito I;Furukawa T;Baltimore Consensus Meeting
通讯作者：
Baltimore Consensus Meeting
DOI：
10.1159/000161012
发表时间：
2008
期刊：
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
影响因子：
--
作者：
Cheung W;Darfler MM;Alvarez H;Hood BL;Conrads TP;Habbe N;Krizman DB;Mollenhauer J;Feldmann G;Maitra A
通讯作者：
Maitra A