Animal models of pancreatic cancer for drug research

Kapischke, Matthias; Pries, Alexandra

doi:10.1517/17460441.3.10.1177

Cited by 5 publications

(5 citation statements)

References 82 publications

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“…Overall, 40 BALBc nu/nu mice were orthotopically inoculated with 1x10 6 SUIT-2 cells (day 0). The mice were randomly divided into three groups: the vehicle group (n=20), gemcitabine day 7 group (n=10, weekly intravenous injection started 7 days after inoculation; 240 mg/kg/week, weekly) (Teva Pharmaceutical Industries Netanya, Israel), and gemcitabine day 14 group (n=10, weekly intravenous injection was started 14 days after inoculation; 240 mg/kg/week, weekly).…”

Section: Methodsmentioning

confidence: 99%

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Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT‑2 pancreatic cancer mouse model

et al. 2017

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Abstract. Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer.

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Section: Methodsmentioning

confidence: 99%

“…Therefore, several mouse models are used, including orothotopically, heterotopically, syngenic, xenografted (6); patient-derived tumor xenografted or genetically engineered cancer models (7,8). These models have varied advantages pertaining to ease, cost, reproducibility, etc.…”

Section: Introductionmentioning

confidence: 99%

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT‑2 pancreatic cancer mouse model

et al. 2017

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“…The evaluation of therapies in tissue culture along with the analysis in an orthotopic cancer model combines the advantages of in vitro studies with the advantages of a clinically relevant animal model [ 5 , 6 ]. Tissue culture allows the evaluation of combinatorial therapies on isolated cancer cells in a fast and cost efficient way, whereas a syngeneic orthotopic cancer model allows the in vivo evaluation of therapies while considering clinically relevant factors such as a desmoplastic reaction, an intact immune system, and pharmacokinetic aspects of applied therapies [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of novel carcinoma cell lines for the analysis of therapeutical strategies fighting pancreatic cancer

et al. 2015

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BackgroundPreclinical evaluations of chemotherapies depend on clinically relevant animal models for pancreatic cancer. The injection of syngeneic murine adenocarcinoma cells is one efficient option to generate carcinomas in mice with an intact immune system. However, this option is constrained by the paucity of appropriate cell lines.ResultsThe murine pancreatic adenocarcinoma cell lines 6606PDA and 7265PDA were compared to the 6606l cell line isolated from a liver metastasis from mice suffering from pancreatic cancer. In tissue culture 6606PDA and 6606l proliferated faster than 7265PDA. 7265PDA cells were, however, significantly more sensitive to gemcitabine as assessed by BrdU-incorporation and trypan blue exclusion assays in vitro. Within 1 week after injection of either one of these three cell lines into the pancreas of C57BL/6J mice, carcinomas were observed by T2 weighted magnetic resonance imaging and histology. Three weeks after injecting 6606PDA or 6606l cells large carcinomas could be characterized, which were surrounded by extensive desmoplastic reaction. After injection of 7265PDA cells, however, remission of cancer was observed between the first and the third week. Compared to 6606PDA cell derived carcinomas a higher apparent diffusion coefficient was quantified by diffusion weighted magnetic resonance imaging in these tumors. This correlated with reduced cancer cell density observed on histological sections.ConclusionAll three cell lines can be used in vitro for testing combinatorial therapies with gemcitabine. The 6606PDA and 6606l cell lines but not the 7265PDA cell line can be used for evaluating distinct therapies in a syngeneic carcinoma model using C57BL/6J mice. Diffusion-weighted MRI proved to be an appropriate method to predict tumor remission.

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“…2006). However, successful translation of preclinical studies in mouse models toward the effective treatment of human disease has been inefficient (Kapischke and Pries 2008). To address this fundamental problem, it is necessary to develop a new platform that can significantly accelerate preclinical drug development.…”

Section: Introductionmentioning

confidence: 99%

Zebrafish model of KRAS-initiated pancreatic endocrine tumor

Park

2019

Animal Cells and Systems

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Pancreatic cancer constitutes a genetic disease in which somatic mutations in the KRAS proto-oncogene are detected in 95% of cases. Activation of the KRAS proto-oncogene represents an initiating event in pancreatic tumorigenesis. Here, we established a zebrafish pancreatic neoplasia model that recapitulates human pancreatic tumors. Toward this end, we generated a stable CRE/Lox-based zebrafish model system to express oncogenic KRAS G12D in the elastase3I domain of the zebrafish pancreas. Lineage tracing experiments showed that early KRAS G12D -responsive pancreatic progenitors contribute to endocrine in addition to exocrine cells. In this system, 10% and 40% of zebrafish developed pancreatic tumors by 6 and 12 months, respectively. The histological profiles of these experimental tumors bore a striking resemblance to those of pancreatic endocrine tumors. Immunohistochemical analysis including the endocrine cell-specific marker confirmed the pancreatic tumor region as a characteristic endocrine tumor. Taken together, our zebrafish model data revealed that pancreatic endocrine tumors originate from early KRAS G12D -responsive pancreatic progenitor cells. These findings demonstrated that this zebrafish model may be suitable as an experimental and preclinical system to evaluate different strategies for targeting pancreatic endocrine tumors and ultimately improve the outcome for patients with pancreatic endocrine tumors.

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Animal models of pancreatic cancer for drug research

Cited by 5 publications

References 82 publications

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT‑2 pancreatic cancer mouse model

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT‑2 pancreatic cancer mouse model

Characterization of novel carcinoma cell lines for the analysis of therapeutical strategies fighting pancreatic cancer

Zebrafish model of KRAS-initiated pancreatic endocrine tumor

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