| Summary: | 碩士 === 中山醫學大學 === 醫學研究所 === 104 === Pancreatic cancer is one of the worldwide major causes of malignant tumor deaths. The location of the pancreas is privacy, and it''s not easy to be found at the beginning. It always causes a definite diagnosis with low survival rate at the last stage. However, the development of pancreatic cancer at the early stage of development is still unclear. Therefor we used 3,6,12 and 24 week-old PDX-1-Cre;LSL-Kras G12D (KC) mice that can develop to murine PanIN lesions with 100% penetrance, and progress to PDAC with a long latency, to understand the progress of early pancreatic cancer in sequence. In addition, the researcher also pointed out that Porphyromonas gingivalis (P.gingivalis) was associated with a twofold increased risk of pancreatic cancer. However, compared to the traditional caerulein induced acute pancreas inflammation animal model, which can promote the pancreatic cancer, while the assessment of mice infected with P.gingivalis, whether the acceleration caused by pancreatic cancer gotten worse. We found mice without using caerulein or P.gingivalis, the mice body weight, spleen and pancreas weight were not obvious in difference, but at 24 week-old Kras transgenic mice (KC mice) were using P.gingivalis that induced the spleen and pancreas were obviously lower with caerulein inducing by weight. On the other hand, the spontaneous mice development of pancreatic cancer, the pancreas weight in KC mice in 24 week-old will emerge the gender differences, female mice will be higher than the male mice. In pancreas tissue sections, we found that KC female mice without caerulein or P.gingivalis induction were more severe than male mice. Besides, we also found that KC mice with caerulein induction were more severe than those by P.gingivalis. The pancreas lesion occur together with a typical ductal hyperplasia, and the cell proliferation index indicated the PCNA expression without induction in KC female mice at 12 week-old and male mice at 24 week-old began to increase. Caerulein-induced acute inflammatory may increase the progression of pancreatic cancer and it has been identified from the literature. In our experiment we also found that the co-culture with P.gingivalis will stimulate the secretion of IL-1β,IL-6 and TNF-α inflammatory cytokines of spleen and Raw264.7 cells. Although chronic low infection caused by P.gingivalis-induced is not more obvious than by caerulein-induced which lead to the development of pancreatic cancer. It makes the time of occurrence of the lesion more forward than the mice that was not induced. Cancer-associated fibroblasts (CAFs) can significantly promote tumorigenesis, and epithelial-mesenchymal-transition is one of the mechanisms of tumor metastasis; so as time increases and induced by P.gingivalis or caerulein will increase α-SMA, N-cadherin, SNAIL and twist in pancreatic tissue performance. In in vitro experiments also found that P.gingivalis itself mainly stimulating the immune system to produce inflammation. By speculating the macrophage cells may not secreted IL-6 and the TNF-α may producing cells. As the results above, we believe that the inflammation caused by P.gingivalis would accelerate the deterioration degree of pancreatic cancer.
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