Shao Hua Ge

Tianjin Medical University Cancer Institute and Hospital

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Ting Deng

Hunan University

Yi Ba

Tianjin Medical University Cancer Institute and Hospital

Xia Wang

Sichuan University

Hong Li Li

Tianjin Medical University Cancer Institute and Hospital

Huang Ding

Hunan University of Traditional Chinese Medicine

Li Zhou

The First Affiliated Hospital, Sun Yat-sen University

Jing Ya Wang

Tianjin Medical University Cancer Institute and Hospital

Haiyang Zhang

Institute of Hydrobiology

Hai Yan Wang

Second Military Medical University

Rui Liu

Tianjin University

Cooperative Institutions

Tianjin Medical University Cancer Institute and Hospital

Tianjin Medical University

National Clinical Research

China Medical University

Chinese Academy of Sciences

Peking University

Sun Yat-sen University

Chinese Academy of Medical Sciences & Peking Union Medical College

Shandong First Medical University

Peking University Cancer Hospital

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Gemcitabine sensitivity factors, hENT1 and RRM1 as potential prognostic biomarker for advanced biliary tract cancer.

PubMed (2014)

Ting Deng Hong Pan Ru Han Huang Ding Hong Li Li

Biliary tract caner (BTC) is one of rare malignant disease with poor prognosis. Gemcitabine has been widely used as chemotherapeutic agent for advanced BTC treatment. Several molecules involved in gemcitabine metabolism, including human equilibrative nucleoside transporter (hENT1) and ribonucleotide reductase subunit M1 (RRM1), have been investigated as predictive biomarkers of chemotherapy efficacy. The aim of present study is to determine whether hENT1 and RRM1 could be used as the biomarkers to assess the efficacy of chemotherapy and predict survival in patients with advanced BTC.The analysis was performed on samples from 44 patients with unresectable or recurrent BTC who were treated with gemcitabine as first-line therapy. We determined levels of hENT1 and RRM1 with immunohistochemistry (IHC). Also, its prognostic and predictive role on tumor response and several clinical factors for survival were evaluated with Kaplan-Meier or Cox analysis.The patients who were clinical benefit (partial response [PR] or stable disease [SD]) had high level of hENT1 (P = 0.046) and low level of RRM1 (P = 0.033). Moreover, hENT1 expression was a significant factor for progression free survival (PFS) (P = 0.005) and overall survival (OS) (P = 0.048) in Cox univariate analysis. Also, hENT1 was an independent prognostic factor of OS based on Cox multivariate analysis (P = 0.005).The expression of hENT1 and RRM1 was associated with gemcitabine efficacy. hENT1 was one of reliable predictive marker of survival in patients with advanced BTC patients.

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Tumor microenvironment interruption: a novel anti-cancer mechanism of Proton-pump inhibitor in gastric cancer by suppressing the release of microRNA-carrying exosomes.

PubMed (2017)

Xu Guan Fang Zhao Jing Ya Wang Hai Yan Wang Shao Hua Ge

Poor prognosis of gastric cancer is related to not only malignancy of gastric cancer cells, but also the tumor microenvironment. Thus drugs, which can inhibit both of them, are urgently needed to be explored. Studies on effect of Proton-pump inhibitors (PPIs) in anti-neoplasms are increasing, but is rare in gastric in gastric cancer. Here we investigated how the gastric cancer microenvironment is regulated by PPIs. The objective response rate of gastric cancer patients in our hospital treated by PPIs is investigated. PPIs' effects were further explored by observing the change of microRNAs, cytokines, cellular apoptosis. Bioinformatic pathway analysis of microarray was used to discover the pathway involved in PPIs' regulation of gastric cancer microenvironments. Immunoblotting assays and qRT-PCR were used to define molecular events with PPIs treatment. We report here that PPIs can improve the prognosis of advanced gastric cancer patients; and inhibit the progress of gastric cancer both in vivo and in vitro. Moreover, high dose of PPIs can regulate the pathway associated with tumor malignancy and microenvironment via inhibiting the release of exosomes, which packed microRNAs. PPIs can inhibit the transformation of CAFs (cancer associated fibroblasts) and cytokines released from CAFs. In addition, PPIs inhibit the malignancy of gastric cancer through regulating HIF-1α-FOXO1 axis. High dose of PPIs can inhibit malignancy of gastric cancer and regulate its surrounding tumor microenvironment. This finding suggests that PPIs maybe of potential value as a therapeutic tool for treatment of gastric cancer.

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