Objective: The biological activities of interleukin-17 (IL-17), a newly cloned cytokine, have not been fully elucidated. The present study was designed to assess the in vitro and in vivo effect of transfecting the IL-17 gene into tumor cells. Methods: A complementary DNA (cDNA) encoding human IL-17 (hIL-17) was obtained by polymerase chain reaction amplification from the human CD4+ T cell cDNA library and inserted into the plasmid pRc/cytomegalovirus to construct an expression vector for the hIL-17 gene. Murine Meth-A fibrosarcoma cells were transfected with the hIL-17 gene using the lipofectin method. The hIL-17 gene-expressing clone (Meth-A/IL-17) was selected and analyzed for cytokine expression by Northern blot. Results: There was no significant difference in the in vitro proliferation rate among parent Meth-A, cells transfected with vector alone and Meth-A/IL-17 cells. When the tumor cells were transplanted subcutaneously into BALB/c nude (nu+/nu+) mice, there was no difference in in vivo growth rates among the three cell lines. Challenge with tumor cells in conventional BALB/c mice, however, resulted in the rejection of Meth-A/IL-17 cells, but the other two lines did grow. After immunization with Meth-A/IL-17 cells, the mice were rechallenged by parent Meth-A or syngeneic MOPC-104E plasmacytoma cells; the immunized mice rejected the Meth-A cells, but not the MOPC-104E cells. Injecting the anti-thy 1,2 (CD90), anti-CD4 or anti-CD8 monoclonal antibody into conventional BALB/c mice resulted in the resumption of in vivo growth of Meth-A/IL-17 cells, but injecting the anti-asialo GM1 antibody did not. Furthermore, flow cytometric analysis demonstrated a significant increase in the expression of major histocompatibility complex (MHC) class I and class II antigens and lymphocyte function-associated antigen-1 on Meth-A/IL-17 cells. Conclusion: Meth-A cells transfected with the hIL-17 gene can induce tumor-specific antitumor immunity by augmenting the expression of MHC class I and II antigens, and both CD4+ and CD8+ T cells may play important roles in inducing antitumor immunity, suggesting the possibility of developing a tumor vaccine incorporating IL-17-transfected tumor cells.

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BackgroundThe significance of pneumatosis intestinalis (PI) and portal venous gas (PVG) is controversial. This retrospective study evaluated the risk factors for bowel necrosis in patients with PI and/or PVG.MethodsBetween 2002 and 2015, 52 patients were diagnosed with PI and/or PVG and were included in this study. The patients were classified according to the presence or absence of bowel necrosis in surgical findings or at autopsy. Patient characteristics and clinical findings related to bowel necrosis were investigated.ResultsBowel necrosis was diagnosed in 17 (32.7 %) patients. Amongst these 17, 10 patients received salvage surgical intervention, and seven of those diagnosed with bowel necrosis survived after the operation. The remaining 35 patients received conservative treatment with or without exploratory laparotomy. Between patients with and without bowel necrosis, laboratory data revealed significant differences in the levels of C-reactive protein (P = 0.0038), creatinine (P = 0.0054), and lactate (P = 0.045); clinical findings showed differences in abdominal pain (P = 0.019) and peritoneal irritation signs (P = 0.016); computed tomography detected ascites (P = 0.011) and changes of bowel wall enhancement (P = 0.03) that were significantly higher in patients with bowel necrosis. The rate of PI and/or PVG detected in patients postoperatively was significantly higher in patients with bowel necrosis (P < 0.0001). Multivariate analysis showed that bowel necrosis was significantly more likely when PI or PVG was detected in postoperative patients than in patients who had not had surgery (P = 0.003).ConclusionsPI and/or PVG, alone, are not automatically indicative of bowel necrosis. However, when these conditions occur postoperatively, they indicate bowel necrosis requiring reoperation.

Thymidine synthase (TS) is a key enzyme in the synthesis of pyrimidine in the de novo pathway of DNA synthesis and a major target of 5-fluorouracil (5-FU), but the implications of TS regarding human pancreatic cancer have not been reported. We assessed the expression of TS in invasive ductal carcinoma (IDC) of the pancreas by immunostaining and evaluated its clinicopathological significance, especially its implications regarding the efficacy of chemotherapy with 5-FU or its derivatives. The expression of TS in the nuclei of pancreatic cancer cells in 72 primary lesions of resectable IDC and 30 distant metastases of unresectable IDC was examined by immunostaining using anti-TS polyclonal antibody and immunoreactivity was classified into three categories: negative (-), low (+) and high (2+). High TS immunoreactivity was detected in 43% (31 of 72) of the primary lesions of the resectable IDCs and in 47% (18 of 38) of the metastatic lesions of the unresectable IDCs. The high TS in primary lesions showed a significantly inverse correlation with the level of nodal involvement. High TS immunoreactivity had a significant influence on the outcome of patients with resectable IDC and the rate of survival of the high TS immunoreactivity group was significantly higher than that of the negative or low reactivity groups, although high TS immunoreactivity did not have a significant influence on survival of the patients with unresectable IDC. The implications of TS immunoreactivity regarding the efficacy of 5-FU-based adjuvant chemotherapy (ACT) was also assessed. The high TS immunoreactivity group showed significantly better survival in both the patients who received ACT and those who were treated by surgery alone, in the resectable IDC among patients with resectable IDC. In cases of unresectable IDC, there were no differences in survival between the high and low TS groups among the patients who received ACT and those who were treated by surgery. In conclusion, high TS immunoreactivity was found to be cogent in predicting the prognosis of patients with pancreatic IDC, but its implications regarding the efficacy of 5-FU-based ACT are still unclear.

A p53 abnormality was not an independent factor for evaluating the prognosis of patients with pancreatic cancer, but was a beneficial indicator for selecting a reasonable strategy of adjuvant chemotherapy against pancreatic cancer.