Vaccination with Polyclonal Antibody Stimulator (PAS) Prevents Pancreatic Carcinogenesis in the KRAS Mouse Model

PURPOSE: To evaluate the effects of alcohol and caffeine in a pancreatic carcinogenesis mouse model induced by 7,12-dimethylbenzantracene (DMBA), according to the PanIN classification system. METHODS: 120 male, Mus musculus, CF-1 mice were divided into four groups. Animals received either water or caffeine or alcohol or alcohol + caffeine in their drinking water. In all animals, 1 mg of DMBA was implanted into the head of the pancreas. After 30 days, euthanasia was performed; excised pancreata were then fixed in formalin, stained with hematoxylin-eosin and categorized as follows: normal ducts, reactive hyperplasia, PanIN-1A, PanIN-1B, PanIN-2, PanIN-3 or adenocarcinoma. RESULTS: PanIN lesions were verified in all groups. Adenocarcinoma was detected in 15% of animals in the caffeine group, 16.6% in the water group, 23.8% in the alcohol + caffeine group and 52.9% in the alcohol group (P<0.05). CONCLUSIONS: The experimental pancreatic carcinogenesis mouse model using DMBA effectively induces PanIN lesions and pancreatic adenocarcinoma. This study verified the association between alcohol use and pancreatic adenocarcinoma; caffeine did not present the same effect.

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Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

Scientific Reports ◽

10.1038/s41598-021-94566-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sophie Liot ◽

Naïma El Kholti ◽

Jonathan Balas ◽

Laurent Genestier ◽

Bernard Verrier ◽

...

Keyword(s):

Adverse Effect ◽

Mouse Model ◽

Clinical Signs ◽

Genetically Engineered ◽

Ductal Adenocarcinoma ◽

Pancreatic Carcinogenesis ◽

Pancreatic Cancers ◽

Thymic Tumor ◽

Genetically Engineered Mouse Model ◽

Lung Malignancies

AbstractPancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.

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Development of thymic tumor in [LSL:KrasG12D;Pdx1-CRE ] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

10.21203/rs.3.rs-383266/v1 ◽

2021 ◽

Author(s):

Sophie Liot ◽

Naïma El Kholti ◽

Bernard Verrier ◽

Ulrich Valcourt ◽

Elise Lambert

Keyword(s):

Adverse Effect ◽

Mouse Model ◽

Clinical Signs ◽

Genetically Engineered ◽

Ductal Adenocarcinoma ◽

Pancreatic Carcinogenesis ◽

Pancreatic Cancers ◽

Thymic Tumor ◽

Genetically Engineered Mouse Model ◽

Lung Malignancies

Abstract Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.

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