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Weibin Hou,Zhigang Ji 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-
Renal cell carcinoma (RCC) is one of the 10 most common cancers worldwide, and to date, a strong systemic therapy has not been developed to treat RCC, even with the remarkable modern advances in molecular medicine mostly due to our incomplete understanding of its tumorigenesis. There is a dire unmet need to understand the etiology and progression of RCC, especially the most common subtype, clear cell RCC (ccRCC), and to develop new treatments for RCC. Genetically engineered mouse (GEM) models are able to mimic the initiation, progression, and metastasis of cancer, thus providing valuable insights into tumorigenesis and serving as perfect preclinical platforms for drug testing and biomarker discovery. Despite substantial advances in the molecular investigation of ccRCC and monumental efforts that have been performed to try to establish autochthonous animal models of ccRCC, this goal has not been achieved until recently. Here we present a review of the most exciting progress relevant to GEM models of ccRCC.
Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate
Xiang Wei,Peng Yongbo,Zeng Hongliang,Yu Chunping,Zhang Qun,Liu Biao,Liu Jiahao,Hu Xing,Wei Wensu,Deng Minhua,Wang Ning,Liu Xuewen,Xie Jianfei,Hou Weibin,Tang Jin,Long Zhi,Wang Long,Liu Jianye 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC.Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays.PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models.These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy.