scholarly journals Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marta Cáceres ◽  
Rita Quesada ◽  
Mar Iglesias ◽  
Francisco X. Real ◽  
Maria Villamonte ◽  
...  

Abstract 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.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marta Cáceres ◽  
Rita Quesada ◽  
Mar Iglesias ◽  
Francisco X. Real ◽  
Maria Villamonte ◽  
...  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 945
Author(s):  
Ryota Sagami ◽  
Kentaro Yamao ◽  
Jun Nakahodo ◽  
Ryuki Minami ◽  
Masakatsu Tsurusaki ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.


1988 ◽  
Vol 118 (2) ◽  
pp. 227-232 ◽  
Author(s):  
L. G. Guijarro ◽  
E. Arilla

ABSTRACT Atrophy of the exocrine pancreas was induced in rabbits by pancreatic duct ligation. Somatostatin concentration and binding in cytosol from rabbit duodenal mucosa were studied after 6 and 14 weeks of pancreatic duct ligation. Somatostatin-like immunoreactivity was significantly increased in the duodenal mucosa in both periods. Scatchard analysis showed a parallel increase in the number of binding sites rather than a change in their affinity. The physiological significance of these findings remains to be clarified. J. Endocr. (1988) 118, 227–232


2001 ◽  
Vol 120 (5) ◽  
pp. A720
Author(s):  
Hong Sik Lee ◽  
Chang Duck Kim ◽  
Byung Won Hur ◽  
Chang Don Kang ◽  
Hoon Jai Chun ◽  
...  

1983 ◽  
Vol 117 (2) ◽  
pp. 281-286 ◽  
Author(s):  
GUNNAR ISAKSSON ◽  
INGEMAR IHSE ◽  
INGMAR LUNDQUIST

1995 ◽  
Vol 108 (4) ◽  
pp. A399
Author(s):  
M. Wada ◽  
R. Doi ◽  
R. Hosotani ◽  
J. Lee ◽  
M. Imamura

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