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// Yiming Qi 1, * , Yu Hu 1, * , Hua Yang 2, * , Rongyuan Zhuang 3, * , Yingyong Hou 4 , Hanxing Tong 2 , Yi Feng 3 , Yuan Huang 5 , Quan Jiang 2 , Qunsheng Ji 6 , Qingyang Gu 6 , Zhixiang Zhang 6 , Xuzhen Tang 6 , Weiqi Lu 2 and Yuhong Zhou 3 1 Departments of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China 2 Departments of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China 3 Departments of Oncology, Zhongshan Hospital, Fudan University, Shanghai, China 4 Departments of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China 5 Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, China 6 Oncology BU, Research Service Division, WuXi AppTec, Shanghai, China * These authors contributed equally to this work Correspondence to: Yuhong Zhou, email: zhou.yuhong@zs-hospital.sh.cn Weiqi Lu, email: lu.weiqi@zs-hospital.sh.cn Keywords: liposarcoma, MRCL, PDX model, PIK3CA mutation, PI3K/mTOR pathway Received: September 18, 2016 Accepted: April 10, 2017 Published: April 21, 2017 ABSTRACT Myxoid and round cell liposarcoma (MRCL) is a common type of soft tissue sarcoma. The lack of patient-derived tumor xenograft models that are highly consistent with human tumors has limited the drug experiments for this disease. Hence, we aimed to develop and validate a patient-derived tumor xenograft model of MRCL. A tumor sample from a patient with MRCL was implanted subcutaneously in an immunodeficient mouse shortly after resection to establish a patient-derived tumor xenograft model. After the tumor grew, it was resected and divided into several pieces for re-implantation and tumor passage. After passage 1, 3, and 5 (i.e. P1, P3, and P5, respectively), tumor morphology and the presence of the FUS-DDIT3 gene fusion were consistent with those of the original patient tumor. Short tandem repeat analysis demonstrated consistency from P1 to P5. Whole exome sequencing also showed that P5 tumors harbored many of the same gene mutations present in the original patient tumor, one of which was a PIK3CA mutation. PF-04691502 significantly inhibited tumor growth in P5 models (tumor volumes of 492.62 ± 652.80 vs 3303.81 ± 1480.79 mm 3 , P < 0.001, in treated vs control tumors, respectively) after 29 days of treatment. In conclusion, we have successfully established the first patient-derived xenograft model of MRCL. In addition to surgery, PI3K/mTOR inhibitors could potentially be used for the treatment of PIK3CA -positive MRCLs.

The protein 3-phosphoinositide-dependent protein kinase 1 (PDK1) is upregulated in cancer. Here we showed that PDK1 stimulated cell proliferation, invasion and metastasis in gallbladder cancer (GBC), by inducing JunB and epithelial-mesenchymal transition. JunB levels were increased in GBC samples and positively correlated with PDK1 levels in tumors. High levels of JunB predicted poor overall survival in GBC patients. Thus, PDK1 functions as a tumor promoter in human GBC by upregulating JunB.

// Yebo Shao 1, * , Yong Zhang 1, * , Yingyong Hou 2, * , Hanxing Tong 1 , Rongyuan Zhuang 3 , Zhengbiao Ji 4 , Binliang Wang 5 , Yuhong Zhou 3 , Weiqi Lu 1 1 Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China 2 Department of Medical Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China 3 Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China 4 Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, China 5 Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China * These authors contributed equally to this work Correspondence to: Weiqi Lu, email: lu.weiqi@zs-hospital.sh.cn Yuhong Zhou, email: zhou.yuhong@zs-hospital.sh.cn Keywords: LncRNA-PILRLS, proliferation, MDM2, P53 signaling pathway, retroperitoneal liposarcoma Received: September 20, 2016 Accepted: December 27, 2016 Published: January 25, 2017 ABSTRACT It is becoming evident that lncRNAs may be an important class of pervasive genes involved in carcinogenesis and metastasis. However, the biological and molecular mechanisms of lncRNAs in retroperitoneal liposarcoma have never been reported. In our study, we found a novel lncRNA PILRLS (Proliferation Interacting LncRNA in Retroperitoneal Liposarcoma), which as an oncogene significantly overexpressed in retroperitoneal liposarcoma. Functions of PILRLS on tumor progression both in vitro and in vivo have verified in this study which PILRLS knockdown significantly inhibited cell proliferation and colony formation. RNA pull-down assay found PILRLS can specific binding with TCL1A which also regulate the expression level of TCL1A. Our work for the first time demonstrated PILRLS can activating the MDM2 by binding with TCL1A which suppress the P53 pathway to promote the unlimited growth of retroperitoneal Liposarcoma cells. It suggests that PILRLS may be an important targets for retroperitoneal liposarcoma therapy.