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Lipase levels as compared to the placebo control (Fig. 3b).Endpoint therapeutic evaluation of proliferation, tumor vascularity, and apoptosis shows that oxaliplatin induces cell death in PACCThe endpoint tumors were analyzed via IHC for proliferation (Ki-67), tumor vascularity (CD31) and programmed cell death (cleaved caspase 3, CC3). Ki-67 percent positive expression remained similar in all treatment groups, which suggested that proliferation was similar at the time of collection (Fig. 4a). CD31 percent positive expression was increased in oxaliplatin, erlotinib, and doxorubicin groups as compared to placebo control, but only erlotinib treatment was statistically significant (P = 0.044) (Fig. 4b). On the other hand, CC3 staining significantlyAn IF and IHC panel for BRCA1 and BRCA2 expression was performed on normal pancreas, pancreatic ductal adenocarcinoma (PDAC), and the PACC PDTX model. Both techniques demonstrate that nuclear BRCA1 is present in all tissue samples along with some cytoplasmic expression (Fig. 6a panel i; Additional file 3: Figure S2 panel i). Immunofluorescence shows that the PDTX model has no co-localization of BRCA2 and DAPI nuclear stain (Fig. 6a, panel ii). IHC on patient PACC tissue and its PDTX (PA-018) also show a lack of BRCA2 nuclear expression. Instead, only cytoplasmic expression in the islets and PACC tissue were observed (Additional file 3: Figure S2 panel ii). Mutational gene analysis of PA-018 PDX tissue was used to identify a 5 base pair deletion in BRCA2 (c.1755_1759del5) (Fig. 6b; Additional file 4: Figure S3). All sequence reads contained the mutated allele, indicating that there was no wild type BRCA2 allele present. This suggests a loss of heterozygosity (LOH) occurred in the tumor.Discussion The rarity of pancreatic acinar cell carcinoma (PACC) has contributed to the lack of an effective standard treatment for this deadly disease. One way to understand a disease and test potential treatments is to have an in vivo laboratory model. To date, only a few recorded studies have been able to recapitulate PACC in mice. The oldest PACC model was formed by creating a transgenic mouse that expresses the transforming gene (T-antigen)Hall et al. J Transl Med (2016) 14:Page 9 ofFig. 4 Endpoint therapeutic effects on proliferation, tumor vascularity, and apoptosis. a Ki67 for proliferation index was scored by positive counts per core section and plotted as mean percent positive ?standard deviation Nelfinavir (Mesylate) with no change observed at endpoint. b CD31 for blood vessel density was scored by positive pixel count over area and plotted as mean percent ?standard deviation, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 only erlotonib had a significant change observed at endpoint (P = 0.44). c Cleaved caspase3 (CC3) for apoptotic index was scored by positive pixel count over area and plotted as mean percent ?standard deviation. Oxaliplatin treatment yielded significant apoptosis (P = 0.0109) compared to placebo. d Representative CC3 IHC was shown for placebo and oxaliplatin groups. Asterisk indicated P < 0.05 for treatment group as compared to placebo, n =of the SV40 virus under the control of elastase I, a pancreas specific promoter [36]. This model had been modified to express luciferase to record tumor burden and can be used to test chemotherapeutics [2]. Recently, another mouse model had been made by deleting a gene that blocked mTOR signaling [37]. The importance of mTOR was corroborated by the decreased tumor burden in both of these PACC mouse models when tre.

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