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  • Open Access

    ARTICLE

    Reactive Oxygen Species-Mediated Cezanne Inactivation by Oxidation of its Catalytic Cysteine Residue in Hepatocellular Carcinoma

    Zhongyuan Yin*, Lin Yang, Feng Wu, Jinshuo Fan, Juanjuan Xu, Yang Jin, Guanghai Yang§

    Oncology Research, Vol.27, No.9, pp. 1069-1077, 2019, DOI:10.3727/096504019X15566157027506

    Abstract Cysteine oxidation occurs at the active site of deubiquitinases (DUBs) during many biologic signaling cascades. Here we report that hepatocellular carcinoma cells (HCCs) generated higher levels of endogenous reactive oxygen species (ROS). This elevated ROS production was inhibited by NADPH oxidase inhibitor diphenylene iodonium (DPI) and mitochondria electron chain inhibitor rotenone in HCC cells. Moreover, we found that H2O2 could activate NF- B-dependent inflammatory effect through increased induction of matrix metalloproteinase 2 (MMP2), MMP9, and intercellular adhesion molecule 1 (ICAM1) expression levels. In addition, we found that H2O2 could prolong NF- B activation by suppressing the More >

  • Open Access

    ARTICLE

    CRISPR/Cas9-Mediated Gene Knockout of ARID1A Promotes Primary Progesterone Resistance by Downregulating Progesterone Receptor B in Endometrial Cancer Cells

    Haizhen Wang*, Zhenghua Tang*, Ting Li*, Menglu Liu*, Yong Li, Baoling Xing*

    Oncology Research, Vol.27, No.9, pp. 1051-1060, 2019, DOI:10.3727/096504019X15561873320465

    Abstract Medroxyprogesterone (MPA) is used for the conservative treatment of endometrial cancer. Unfortunately, progesterone resistance seriously affects its therapeutic effect. The purpose of the current study was to investigate the influence of deletion of AT-rich interactive domain 1A (ARID1A) in progesterone resistance in Ishikawa cells. Ablation of ARID1A was conducted through the CRISPR/Cas9 technology. Acquired progesterone-resistant Ishikawa (Ishikawa-PR) cells were generated by chronic exposure of Ishikawa cells to MPA. The sensitivity of the parental Ishikawa, Ishikawa-PR, and ARID1A-deficient cells to MPA and/or LY294002 was determined using the Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis.… More >

  • Open Access

    ARTICLE

    High Blood miR-802 Is Associated With Poor Prognosis in HCC Patients by Regulating DNA Damage Response 1 (REDD1)-Mediated Function of T Cells

    Chao Jiang*, Xueyan Liu, Meng Wang*, Guoyue Lv*, Guangyi Wang*

    Oncology Research, Vol.27, No.9, pp. 1025-1034, 2019, DOI:10.3727/096504018X15456687424096

    Abstract miR-802 has been reported to be dysregulated in multiple tumors and contribute to tumor progression. However, its role in HCC was still largely unknown. The aim of this study is to investigate the function and mechanism of miR-802 in HCC progression. The results showed that miR-802 was upregulated in the peripheral blood and tumor tissue of HCC patients, and high levels of blood miR-802 predicted poor prognosis. miR-802 had no effect on the proliferation and migration of HCC cell lines. Interestingly, the levels of CD8/CD28 and regulated in development and DNA damage response 1 (REDD1) More >

  • Open Access

    ARTICLE

    Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI

    Jian-Wei Wang, Xiao-Feng Wu, Xiao-Juan Gu, Xing-Hua Jiang

    Oncology Research, Vol.27, No.9, pp. 979-986, 2019, DOI:10.3727/096504018X15336368805108

    Abstract Cancer-associated fibroblasts (CAFs) play a predominant role in regulating tumor progression. Understanding how CAFs communicate with osteosarcoma is crucial for developing novel approaches for osteosarcoma therapy. Exosomes are able to transmit messages between cells. In this study, we demonstrated that CAFs transfer exosomes to osteosarcoma cells, which promotes osteosarcoma cell migration and invasion. Using a miRNA microarray analysis, we identified 13 miRNAs that are significantly increased in exosomes derived from cancer-associated fibroblasts (CAFs) and corresponding paracancer fibroblasts (PAFs). In vitro studies further validated that the levels of microRNA-1228 (miR-1228) were increased in CAFs, its secreted More >

  • Open Access

    ARTICLE

    Upregulation of Mobility in Pancreatic Cancer Cells by Secreted S100A11 Through Activation of Surrounding Fibroblasts

    Yosuke Mitsui*†, Nahoko Tomonobu*, Masami Watanabe, Rie Kinoshita*, I Wayan Sumardika*‡, Chen Youyi*, Hitoshi Murata*, Ken-ichi Yamamoto*, Takuya Sadahira, Acosta Gonzalez Herik Rodrigo*†, Hitoshi Takamatsu*, Kota Araki, Akira Yamauchi, Masahiro Yamamura#, Hideyo Fujiwara**, Yusuke Inoue††, Junichiro Futami‡‡, Ken Saito§§, Hidekazu Iioka§§, Eisaku Kondo§§, Masahiro Nishibori¶¶, Shinichi Toyooka§, Yasuhiko Yamamoto##, Yasutomo Nasu, Masakiyo Sakaguchi*

    Oncology Research, Vol.27, No.8, pp. 945-956, 2019, DOI:10.3727/096504019X15555408784978

    Abstract S100A11, a member of the S100 family of proteins, is actively secreted from pancreatic ductal adenocarcinoma (PDAC) cells. However, the role of the extracellular S100A11 in PDAC progression remains unclear. In the present study, we investigated the extracellular role of S100A11 in crosstalking between PDAC cells and surrounding fibroblasts in PDAC progression. An abundant S100A11 secreted from pancreatic cancer cells stimulated neighboring fibroblasts through receptor for advanced glycation end products (RAGE) upon S100A11 binding and was followed by not only an enhanced cancer cell motility in vitro but also an increased number of the PDAC-derived… More >

  • Open Access

    ARTICLE

    Anticancer Effects of Gleditsia sinensis Extract in Rats Transplanted With Hepatocellular Carcinoma Cells

    Yue Cai*†‡, Chizhi Zhang*†‡, Lei Zhan*†, Liangbin Cheng*†, Dingbo Lu*†, Xiaodong Wang*†, Hanlin Xu§, Shuxue Wang, Deng Wu*†, Lianguo Ruan#

    Oncology Research, Vol.27, No.8, pp. 889-899, 2019, DOI:10.3727/096504018X15482423944678

    Abstract The thorns of Gleditsia sinensis have been historically used in Chinese medicine and are considered one of the fundamental therapeutic herbs. Its anticancer effects are currently being explored. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and still requires the development of new drugs with higher efficiency. By using a rat HCC model implanted with cancerous Walker-256 cells, the therapeutic effects of G. sinensis extract (GSE) were assessed, as well as its regulatory effects on miRNAs. GSE significantly restored liver morphology and dramatically induced cell apoptosis in HCC rats. In addition, miR-21/181b/183 was More >

  • Open Access

    ARTICLE

    MicroRNA-510 Plays Oncogenic Roles in Non-Small Cell Lung Cancer by Directly Targeting SRC Kinase Signaling Inhibitor 1

    Wei Wu*, Linyan He†‡, Yan Huang*, Likun Hou*, Wei Zhang*, Liping Zhang*, Chunyan Wu*

    Oncology Research, Vol.27, No.8, pp. 879-887, 2019, DOI:10.3727/096504018X15451308507747

    Abstract An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues. miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510 suppressed NSCLC cell More >

  • Open Access

    REVIEW

    The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer

    Jie Wei*†1, Yuanliang Yan*†1, Xi Chen*†, Long Qian*†, Shuangshuang Zeng*†, Zhi Li, Shuang Dai*†, Zhicheng Gong*†,Zhijie Xu§

    Oncology Research, Vol.27, No.7, pp. 849-858, 2019, DOI:10.3727/096504018X15447833065047

    Abstract Over the past decade, natural compounds have been proven to be effective against many human diseases, including cancers. Triptolide (TPL), a diterpenoid triepoxide from the Chinese herb Tripterygium wilfordii Hook F, has exhibited attractive cytotoxic activity on several cancer cells. An increasing number of studies have emphasized the antitumor effects of TPL on non-small cell lung cancer (NSCLC). Here we mainly focused on the key molecular signaling pathways that lead to the inhibitory effects of TPL on human NSCLC, such as mitogen-activated protein kinases (MAPKs) modulation, inhibition of NF- B activation, suppression of miRNA expression, More >

  • Open Access

    ARTICLE

    Nonsteroidal Anti-inflammatory Drugs Sensitize CD44-Overexpressing Cancer Cells to Hsp90 Inhibitor Through Autophagy Activation

    Hyun-Jung Moon,1 So-Young Park,1 Su-Hoon Lee, Chi-Dug Kang, Sun-Hee Kim

    Oncology Research, Vol.27, No.7, pp. 835-847, 2019, DOI:10.3727/096504019X15517850319579

    Abstract Recently, novel therapeutic strategies have been designed with the aim of killing cancer stem-like cells (CSCs), and considerable interest has been generated in the development of specific therapies that target stemnessrelated marker of CSCs. In this study, nonsteroidal anti-inflammatory drugs (NSAIDs) significantly potentiated Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-mediated cytotoxicity through apoptotic and autophagic cell death induction, but COX-2-inhibitory function was not required for NSAIDinduced autophagy in CD44-overexpressing human chronic myeloid leukemia K562 (CD44highK562) cells. Importantly, we found that treatment with NSAIDs resulted in a dose-dependent increase in LC3-II level and decrease in p62 level and simultaneous reduction… More >

  • Open Access

    ARTICLE

    E2-Induced Activation of the NLRP3 Inflammasome Triggers Pyroptosis and Inhibits Autophagy in HCC Cells

    Qing Wei1, Rui Zhu1, Junying Zhu, Rongping Zhao, Min Li

    Oncology Research, Vol.27, No.7, pp. 827-834, 2019, DOI:10.3727/096504018X15462920753012

    Abstract Emerging evidence suggests that 17β-estradiol (E2) and estrogen receptor (ER) signaling are protective against hepatocellular carcinoma (HCC). In our previous study, we showed that E2 suppressed the carcinogenesis and progression of HCC by targeting NLRP3 inflammasome activation, whereas the molecular mechanism by which the NLRP3 inflammasome initiated cancer cell death was not elucidated. The present study aimed to investigate the effect of NLRP3 inflammasome activation on cell death pathways and autophagy of HCC cells. First, we observed an increasing mortality in E2-treated HCC cells, and then apoptotic and pyroptotic cell death were both detected. The… More >

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