Application of caerulin in preparing sensitizing preparation of medicaments for intervening in pancreatic cancer animal model

An animal model, the technology of cerulein, applied in the field of experimental models, can solve the problems of long experimental period, tumor research limitations, and speed up the development of pancreatic ductal epithelial carcinoma, so as to shorten the modeling time, scientific and efficient platform tools, and improve the efficiency of pancreatic cancer. The effect of incidence

Inactive Publication Date: 2014-08-27
FUDAN UNIV SHANGHAI CANCER CENT
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  • Abstract
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  • Application Information

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Problems solved by technology

[0005] (1) Implanted tumor model: It is a kind of animal model widely used in preclinical research; this model can form tumor locally in a short period of time, and the tumor formation rate can reach almost 100%, and the model is easy to operate and observe However, because implanted tumors are often covered by connective tissue, they can only grow locally, limiting their invasion and metastasis; and after multiple passages of tumor cell lines cultured in vitro, the infiltration of inflammatory cells in the process of tumor formation The tumor microenvironment, such as the formation of blood vessels and the composition of interstitial components, is very different from the human tumor microenvironment. Therefore, it cannot well simulate the natural development process of human tumors and various biological behaviors of tumors, so it is not suitable for For the study of tumorigenesis;
[0006] (2) Genetic engineering mouse model: It is a tumor model established by knocking in or knocking out tumor-related genes in mouse somatic cells and giving mice carcinogen treatment; this type of model is mainly through the mutation of oncogene K-ras , activate and cause changes in related oncogenes or tumor suppressor genes, which can effectively simulate the development of human pancreatic tumors. However, high experimental costs, long experimental cycles, and low tumor formation efficiency are its main disadvantages ;
[0007] (3) Chemically induced pancreatic cancer model: After the in situ administration of chemical carcinogens by means of the pancreas, oncogenes or tumor suppressor genes are activated to induce pancreatic tumors in situ; the process of in situ induced tumors in the pancreas can simulate human pancreatic tumors The occurrence process of pancreatic cancer can well represent the early occurrence of pancreatic cancer; with the continuous development of research, more and more chemical carcinogens have been discovered, such as alkylating agents, nitrosamines, etc.; Dimethylbenzanthracene (DMBA) induces the occurrence of pancreatic tumors in mice, and has been applied in rat or mouse models of orthotopic induction of pancreatic tumors; however, this type of model has the disadvantages of low tumor incidence and long tumor formation time , After orthotopic implantation of DMBA pancreas, it is often 9 months before the visible pancreatic tumors can be induced. The experimental cycle is too long, and the use in tumor research has been significantly limited.
[0009] Another study shows that caerulein is an analog of cholecystokinin, which is now widely used in the establishment of pancreatitis mouse models. Caerulein can stimulate the secretion of pancreatic enzymes and cause acute and chronic pancreatitis in mice. Further accelerate the development of high-grade pancreatic ductal intraepithelial neoplasia (PanIN) and pancreatic ductal epithelial carcinoma; however, so far, there is no research on the effect of cerulein on DMBA-induced wild-type mouse pancreatic cancer models at home and abroad. research report

Method used

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  • Application of caerulin in preparing sensitizing preparation of medicaments for intervening in pancreatic cancer animal model
  • Application of caerulin in preparing sensitizing preparation of medicaments for intervening in pancreatic cancer animal model
  • Application of caerulin in preparing sensitizing preparation of medicaments for intervening in pancreatic cancer animal model

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Embodiment 1

[0068] 1. Experimental animals and drugs

[0069] (1) Selection and grouping of experimental animals 6-8 weeks old, 32 wild-type C57BL / 6J female mice weighing 18-20g, SPF grade, provided by the Experimental Animal Department of Shanghai Medical College, Fudan University; C57 mouse special feed, drinking water is distilled water; All mice are divided into four groups at random, blank control group (BC), negative control group (NC), chronic high-dose group (CIT), chronic low-dose group (CMT), 6 rats in BC group and NC group, 10 rats in CIT group and CMT group;

[0070] (2) Chemical carcinogen: Dimethylbenzanthracene (DMBA) (sigma) and toluene are prepared into 2.5% DMBA solution;

[0071] (3) Inflammation stimulant Caerulein (sigma) and saline were prepared into 0.02 mg / ml caerulein solution.

[0072] 2. Experimental method

[0073] (1) Establish an animal model of pancreatic cancer

[0074] After all the mice were anesthetized by intraperitoneal injection of 2% pentobarbita...

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Abstract

The invention belongs to the technical field of experimental models, relates to a medicament for intervening in an inflammation related chemically induced pancreatic cancer animal model, and in particularly relates to application of caerulin in preparing a sensitizing preparation for synergizing dimethylbenzanthracene (DMBA) to induce a pancreatic cancer animal model. According to the application, an effective sensitizing preparation is provided to a medicament DMBA for inducing a C57 wild type mouse pancreatic cancer model, and the prepared animal model is an ideal tool for further studying pancreatic precancerous lesions and pancreatic cancer; by virtue of the synergetic effect of caerulin, the experiment cycle can be shortened, the experiment efficiency can be improved, and the experiment cost can be saved; occurrence and development of multiple steps in the process of intervening in the pancreatic cancer animal model and changes of histology are extremely similar to the developing process of pancreatic cancer of human beings, so that normal pancreas ductal epithelium, atypical hyperplasia of pancreas ductal epithelium, carcinoma in situ of pancreas ductal epithelium and invasive pancreatic cancer in the pancreatic cancer developing process can reappear.

Description

technical field [0001] The invention belongs to the technical field of experimental models, and relates to drugs for intervening in inflammation-related chemically induced pancreatic cancer animal models, in particular to pancreatitis stimulating preparations that effectively assist pancreatic cancer animal models, and in particular to cerulein in the preparation of synergistic dimethylbenzanthracene (DMBA) induces the application in the sensitization preparation of pancreatic cancer animal model. Background technique [0002] According to reports, pancreatic cancer has become a common malignant tumor in the world. Due to its difficult early diagnosis, poor prognosis and high mortality rate, it is recognized as the "king of cancers" in the industry. At present, the incidence of pancreatic cancer in my country continues to rise at an alarming rate; according to data from the Shanghai Center for Disease Control and Prevention, the incidence of pancreatic cancer in Shanghai has...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/08A61K31/015
Inventor 李影奕梁晨王瑧王辰
Owner FUDAN UNIV SHANGHAI CANCER CENT
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