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Review
. 2013 Jun;144(6):1194-8.
doi: 10.1053/j.gastro.2013.01.070.

Relevance of animal models of pancreatic cancer and pancreatitis to human disease

Affiliations
Review

Relevance of animal models of pancreatic cancer and pancreatitis to human disease

Ashok K Saluja et al. Gastroenterology. 2013 Jun.
No abstract available

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Conflict of interest statement

Conflicts of interest

The authors disclose no conflicts.

Figures

Figure 1
Figure 1
Potential anticancer therapies should be evaluated in multiple animal models. Thus, novel therapies should be evaluated in more than one model because the results and conclusions gained from testing drugs in multiple complementary models will be more reliable. For example, Minnelide, a novel water-soluble analog of a natural compound triptolide, was evaluated in multiple animal models in preclinical studies. (A) Kaplan–Meier curve showing that Minnelide increased survival of mice with pancreatic cancer in an orthotopic xenograft model with pancreatic cancer cell line AsPc-1. In this model AsPC-1 cells (2 × 105) were injected into the tail of the pancreas of athymic nu/nu mice. On day 7, mice were randomized to Minnelide (0.42 mg/kg) or the saline group. On day 100, the Minnelide-treated cohort (n = 10) was divided into 2 groups. One group (n = 5) continued to receive Minnelide (0.42 mg/kg), but treatment was terminated in the second group (n = 5; D/C; stop Minnelide). All the animals in the Minnelide-treated group were alive at day 385 when the experiment was terminated. Survival lines are superimposed. *Censored because deaths were unrelated to pancreatic cancer. (B) In another similar orthotopic xenograft model with pancreatic cancer cell line S2-013, Minnelide markedly reduced locoregional spread. Macroscopic analysis of metastasis in control and Minnelide-treated groups is shown. (C) Minnelide decreases tumor size in a human subcutaneous xenograft model of pancreatic cancer. A de-identified patient pancreatic tumor was implanted into severe combined immunodeficient animals that were randomized to Minnelide (0.42 mg/kg) or the saline group when the tumor reached a size of 300 mm3. In the Minnelide group the treatment was stopped on day 55 (Minnelide D/C). Even when Minnelide was stopped, the tumor did not recur. In the saline group, when the tumor reached 1000 mm3 the animals were started on Minnelide. This was associated with marked decreases in the tumor volume. (D) Tumor in the subcutaneous human xenograft model retains its original architecture. The neoplastic glands are surrounded by fibrous stromal tissue.

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