The Discovery Of A New Therapeutic Target And Application Of Minimal Invasive Surgery In Pancreatic Tumors

Objects: This paper studies two representative pancreatic tumors,in order to find new therapeutic targets of pancreatic ductal adenocarcinoma and to compare the safety and efficacy of RDP and LDP for pancreatic neuroendocrine tumors.two representative.Methods: In the first part,64 patients with PDAC were enrolled in this study from April2013 to January 2016.Human PC cell lines were assigned to blank,negative-control,sh CUL4 B,PLOC,PLOC-CUL4 B and PLOC-CUL4B+si RNA-?-catenin groups.The m RNA and protein expression levels of CUL4 B in PDAC tissues,adjacent tissues and PC cell lines,as well as the m RNA and protein expression levels of Wnt/?-catenin signaling pathway-related proteins and EMT-related proteins,were detected by q RT-PCR and western blotting,respectively.MTT assay was performed to analyze cell proliferation,and flow cytometry was performed to analyze the cell cycle.Cell migration and invasion ability was assessed using the scratch test and transwell assay,respectively.HE staining was performed to observe liver metastasis in the nude mouse model of PC.CUL4B-positvity was detected using immunohistochemistry.In the second part,from September 2010 to January 2017,operative parameters and perioperative outcomes in an initial experience with 43 consecutive patients undergoing RDP were collected and compared with those in 31 patients undergoing LDP.Results: In the first part,CUL4 B and ?-catenin were expressed at higher levels in PC tissues than in adjacent tissues.CUL4 B and ?-catenin expression was associated with differentiation,lymph node metastasis and half-year survival.The PLOC-CUL4 B group showed increased CUL4 B,Wnt,?-catenin,LEF-1,c-Jun,Cyclin D1,N-cadherin,Vimentin,Snail and ZEB1 expression;decreased E-cadherin expression;accelerated cellproliferation;increased S-phase cell percentages;increased cell migration ability;and more liver metastases compared with the PLOC and PLOC-CUL4B+si RNA-?-catenin groups.The sh CUL4 B group showed decreased CUL4 B,Wnt,?-catenin,LEF-1,c-Jun,Cyclin D1,N-cadherin,Vimentin,Snail and ZEB1 expression;increased E-cadherin expression;shorter cell migration distances;decelerated cell proliferation;decreased S-phase cell percentages;decreased cell migration ability and less liver metastases compared with the blank and negative-control groups.In the second part,Patients undergoing RDP and LDP demonstrated equivalent age,sex,ASA score,tumor location and tumor size.Operating time,length of resected pancreas,postoperative length of hospital stay and rates of conversion to open,pancreatic fistula,transfusion and reoperation were not statistically different.Patients in the RDP group were associated with significantly higher overall(P=0.006)and Kimura spleen preservation rates(P<0.001)and had reduced risk of excessive blood loss(P<0.001).Oncological outcomes in this series were superior for the RDP group with more lymph node harvest for G2 and G3 PNETs(P=0.034).Conclusion: CUL4 B promotes PDAC growth by inducing EMT via the Wnt/?-catenin signaling pathway,which indicates that CUL4 B may take as a target for treatment of PDAC.Besides,both RDP and LDP are efficacious and safe methods in treating PNETs located in the body or tail of pancreas.Robotic approach offers advantages with less intraoperative blood loss,higher spleen preservation rate and more lymph node harvest.It may be sensible to choose RDP for patients who fit indications for scheduled spleen preservation.