Associate Chief Physician
Diabetes, thyroid disease, pituitary and adrenal diseases, gout and other endocrine and metabolic diseases
Doctorate, Ludwig-Maximilians-Universität München (LMU, Munich University), Germany, 2010/9 to 2013/8
Master of Clinical Medicine, Zhejiang University School of Medicine, China, 2003/9 to 2010/6
For many tumor types, neuroendocrine phenotype indicates higher malignancy and worse clinical prognosis. Although the mTOR inhibitors, represented by RAD001(Everolimus), can significantly inhibit the proliferation of neuroendocrine tumor cells in vitro and prolong the progression free survival of the patients in clinical trails, the resistance of the tumor cells induced by the treatment impairs the anti-tumor effects in vivo. Up to now, the resistance mechanism of neuroendoctine tumor cells to mTOR inhibitors has not been fully illustrated. We have previously screened the resistance-related genes based on a new mouse model system for gastric neuroendocrine tumor (CEA424-SV40 T Antigen transgenic mouse model system). A significant up-regulated expression of Prap1 gene, which is the most strongly up-regulated gene identified by the array, was observed in the RAD001 resistant tumor cells both in vitro and in vivo. Preliminary experiment showed that down-regulating Prap1 expression in the RAD001 resistant gastric neuroendocrine tumor cells significantly enhanced the anti-proliferation effect induced by RAD001 treatment. With special emphasis on the molecularly targeted therapy for high grade gastric cancer with a neuroendocrine phenotype, we try to clarify the possible role of Prap1 gene during the process of RAD001 resistance of neuroendocrine tumor cells, to evaluate the prospect of Prap1 as a promising target for anti-resistance strategy, and to proclaim the underlying gene regulating mechanisms involved by this gene to RAD001 resistance induced by long term treatment. We hope our study will provide valuable preclinical experience for the treatment of neuroendocrine tumors and contribute to the establishment of more effective clinical management.
Penate Medina T, Pan J, Damoah C, Humbert J, Köpnick AL, Will O, Sebens S, Penate Medina O*, Utilizing Sphingomyelinase Sensitizing Liposomes in Imaging Intestinal Inflammation in Dextra n Sulfate Sodium-Induced Murine Colitis, Biomedicines, 2022, 10(2): 1-15.
Pan J*, Bao Q, Enders G. The altered metabolic molecular signatures contribute to the RAD001 resistance in gastric neuroendocrine tumor. Front Oncol, 2020 Apr 21;10:546. doi: 10.3389/fonc.2020.00546. eCollection 2020.
Liu Y#, Pan J#, Pan X#, Wu L, Bian J, Lin Z, Xue M, Su T, Lai S, Chen F, Ge Q, Chen L, Ye S, Zhu Y, Chen S*, Wang L*, Klotho-mediated targeting of CCL2 suppresses the induction of colorectal cancer progression by stromal cell senescent microenvironments, Mol Oncol, 2019, 13(11):2460-2475.
Liu Y, Ye S, Zhu Y, He X, Pan J, Chen S, Ye B, Wang L*, Impact of tumour size on metastasis and survival in patients with pancreatic neuroendocrine tumours (PNETs): A population based study, J Cancer, 2019, 10(25):6349-6357.
Wang C, Shou Y, Pan J, Du Y, Liu C, Wang H*, The Relationship between Cholesterol Level and Alzheimer's Disease-Associated APP Proteolysis/Aβ Metabolism, Nutr Neurosci, 2018, 11:1-11.
Liu Y, He X, Pan J, Chen S, Wang L*, Prognostic role of Glasgow prognostic score in patients with colorectal cancer: evidence from population studies, Sci Rep, 2017, 7(1):6144.
Wu L, Fu J, Wan L, Pan J, Lai S, Zhong J, Chung DC, Wang L*, Survival outcomes and surgical intervention of small intestinal neuroendocrine tumors: a population based retrospective study, Oncotarget, 2017, 8(3):4935-4947.
He X#, Pan J#, Pan M#, Wang J, Dong J, Yuan H, Zhou L, Chen M, Chen Y, Lu Y, Gu H, Chen Y, Wu L, Chen Y, Jin F, Li B, Gu W*, Dietary and physical activity of adult patients with type 2 diabetes in Zhejiang province of eastern China: Data from a cross-sectional study, J Diabetes Investig, 2016, 7(4):529-38.
Bao Q#, Pan J#, Qi H, Wang L, Qian H, Jiang F, Shao Z, Xu F, Tao Z, Ma Q, Nelson P, Hu X*, Aging and age-related diseases-From endocrine therapy to target therapy, Mol Cell Endocrinol, 2014, 394(1-2):115-118.
Ihler F*, Vetter EV, Pan J, Kammerer R, Debey-Pascher S, Schultze JL, Zimmermann W, Enders G, Expression of a neuroendocrine gene signature in gastric tumor cells from CEA 424-SV40 large T antigen-transgenic mice depends on SV40 large T antigen, PLoS One, 2012, 7(1):e29846.
Pan J, Zhong J, Gan LH, Chen SJ, Jin HC, Wang X, Wang LJ*. Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer. Tumour Biol. 2011 Aug;32(4):729-35.
Wang L, Wang X, Wang X, Pan J, Lu H, Zhang S, Lin X, Lam EK, Cui Y, Yu J, Jin H*, Klotho is silenced through promoter hypermethylation in gastric cancer, Am J Cancer Res, 2011, 1(1):111-119.
Gan LH, Pan J, Chen SJ, Zhong J, Wang LJ*. DNA methylation of ZIC1 and KLOTHO gene promoters in colorectal carcinomas and its clinicopathological significance. Zhejiang Da Xue Xue Bao Yi Xue Ban，2011，40(3)：309-314
Study on the involvement of Prap1 in the resistance to RAD001 of gastric neuroendocrine tumor cells and the Mad1-related mechanisms. Funding source: National Natural Science Foundation of China
The role of cellular senescence in the induction of resistance against RAD001 treatment in neuroendocrine tumor cells. Funding source: Zhejiang Provincial Natural Science Foundation
The role of neuroendocine hormones in aging and cancer. Funding source: Zhejiang Province Key Science and Technology Innovaion Team