Home / Journals / OR / Vol.28, No.4, 2020
  • Open Access

    ARTICLE

    A Novel BCL-2 Inhibitor APG-2575 Exerts Synthetic Lethality With BTK or MDM2-p53 Inhibitor in Diffuse Large B-Cell Lymphoma

    Qiuyun Luo*†1, Wentao Pan*†‡1, Suna Zhou*†1, Guangfeng Wang, Hanjie Yi, Lin Zhang, Xianglei Yan*†, Luping Yuan*†, Zhenyi Liu#, Jing Wang**, Haibo Chen#, MiaoZhen Qiu*††, DaJun Yang*†‡, Jian Sun*‡‡
    Oncology Research, Vol.28, No.4, pp. 331-344, 2020, DOI:10.3727/096504020X15825405463920
    Abstract Despite therapeutic advances, the effective treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) remains a major clinical challenge. Evasion of apoptosis through upregulating antiapoptotic B-cell lymphoma-2 (BCL-2) family members and p53 inactivation, and abnormal activation of B-cell receptor signaling pathway are two important pathogenic factors for DLBCL. In this study, our aim is to explore a rational combination of BCL-2 inhibitor plus Bruton’s tyrosine kinase (BTK) blockade or p53 activation for treating DLBCL with the above characteristics. We demonstrated that a novel BCL-2 selective inhibitor APG-2575 effectively suppressed DLBCL with BCL-2 high expression via activating the mitochondrial apoptosis… More >

  • Open Access

    ARTICLE

    EIF5A2 Is Highly Expressed in Anaplastic Thyroid Carcinoma and Is Associated With Tumor Growth by Modulating TGF-β Signals

    Fengyun Hao*1, Qingli Zhu, Lingwei Lu, Shukai Sun, Yichuan Huang§, Jinna Zhang, Zhaohui Liu†#, Yuanqing Miao**, Xuelong Jiao††, Dong Chen††1
    Oncology Research, Vol.28, No.4, pp. 345-355, 2020, DOI:10.3727/096504020X15834065061807
    Abstract Anaplastic thyroid carcinoma (ATC) is resistant to standard therapies and has no effective treatment. Eukaryotic translation initiation factor 5A2 (EIF5A2) has shown to be upregulated in many malignant tumors and proposed to be a critical gene involved in tumor metastasis. In this study, we aimed to investigate the expression status of EIF5A2 in human ATC tissues and to study the role and mechanisms of EIF5A2 in ATC tumorigenesis in vitro and in vivo. Expression of EIF5A2 protein was analyzed in paraffin-embedded human ATC tissues and adjacent nontumorous tissues (ANCT) (n = 24) by immunochemistry. Expressions of EIF5A2 mRNA and protein… More >

  • Open Access

    ARTICLE

    miR-4792 Inhibits Acute Myeloid Leukemia Cell Proliferation and Invasion and Promotes Cell Apoptosis by Targeting Kindlin-3

    Yun Qin*, Yu Wang†‡§, Dongbo Liu
    Oncology Research, Vol.28, No.4, pp. 357-369, 2020, DOI:10.3727/096504020X15844389264424
    Abstract It has been reported that kindlin-3 expression is closely associated with progression of many cancers and microRNA (miRNA) processing. However, the effects and precise mechanisms of kindlin-3 in acute myeloid leukemia (AML) have not been well clarified. Our study aimed to explore the interaction between kindlin-3 and miR-4792 in AML. In our study, we found that the expression of kindlin-3 was dramatically increased in AML samples and cell lines, and the miR-4792 level was significantly downregulated. Interestingly, the low miR-4792 level was closely associated with upregulated kindlin-3 expression in AML samples. Moreover, introduction of miR-4792 dramatically suppressed proliferation and invasion… More >

  • Open Access

    ARTICLE

    Corosolic Acid Inhibits Cancer Progress Through Inactivating YAP in Hepatocellular Carcinoma

    Ming Jia*1, Yulin Xiong†1, Maoshi Li*, Qing Mao*
    Oncology Research, Vol.28, No.4, pp. 371-383, 2020, DOI:10.3727/096504020X15853075736554
    Abstract Chemotherapy is critical for the treatment of hepatocellular carcinoma (HCC). Despite the proapoptotic effects of corosolic acid (CA) treatment, its underlying mechanism is not completely clear. The aim of this study was to determine the molecular mechanism of CA in HCC treatment. MTT assay was used to determine the IC50 of CA. Immunoprecipitation and immunofluorescence were used to detect the interaction and subcellular localization of Yes-associated protein (YAP) and mouse double minute 2 (MDM2). In addition, in vivo xenotransplantation was performed to assess the effects of CA, YAP, and MDM2 on tumorigenesis. The IC50 of CA was about 40 µM… More >

  • Open Access

    ARTICLE

    Cylindromatosis Is Required for Survival of a Subset of Melanoma

    Ting La*†, Lei Jin*‡, Xiao Ying Liu*, Ze Hua Song*, Margaret Farrelly, Yu Chen Feng, Xu Guang Yan, Yuan Yuan Zhang*,† Rick F. Thorne*,*§ Xu Dong Zhang*†, Liu Teng*
    Oncology Research, Vol.28, No.4, pp. 385-398, 2020, DOI:10.3727/096504020X15861709922491
    Abstract The deubiquitinase cylindromatosis (CYLD) functions as a tumor suppressor inhibiting cell proliferation in many cancer types including melanoma. Here we present evidence that a proportion of melanoma cells are nonetheless addicted to CYLD for survival. The expression levels of CYLD varied widely in melanoma cell lines and melanomas in vivo, with a subset of melanoma cell lines and melanomas displaying even higher levels of CYLD than melanocyte lines and nevi, respectively. Strikingly, although short hairpin RNA (shRNA) knockdown of CYLD promoted, as anticipated, cell proliferation in some melanoma cell lines, it reduced cell viability in a fraction of melanoma cell… More >

  • Open Access

    ARTICLE

    miR-202 Suppresses Hepatocellular Carcinoma Progression via Downregulating BCL2 Expression

    Donghai Zhuang1, Li Liang1, Hongzhan Zhang, Xianguang Feng
    Oncology Research, Vol.28, No.4, pp. 399-408, 2020, DOI:10.3727/096504020X15864296270581
    Abstract miRNAs play an important role in progression of hepatocellular carcinoma (HCC). In this work, we assessed the function of miR-202 in human HCC and identified BCL2 as its target. We found miR-202 expression was found significantly downregulated, while BCL2 expression was markedly upregulated in HCC tissues and cell lines (HepG2, Hep3B, and HCCLM3). Both miR-202 and BCL2 were closely correlated with major vascular invasion and advanced TNM stage as well as overall survival of HCC patients. Overexpression of miR-202 significantly inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G0/G1 phase, and prevented tumor formation in a xenograft… More >

  • Open Access

    ARTICLE

    Tripartite Motif-Containing 46 Promotes Viability and Inhibits Apoptosis of Osteosarcoma Cells by Activating NF-kB Signaling Through Ubiquitination of PPARα

    Wenwei Jiang*, Xinyu Cai*, Tianyang Xu*, Kaiyuan Liu*, Dong Yang*, Lin Fan*, Guodong Li*, Xiao Yu
    Oncology Research, Vol.28, No.4, pp. 409-421, 2020, DOI:10.3727/096504020X15868639303417
    Abstract Osteosarcoma (OS), the most common bone cancer, causes high morbidity in children and young adults. TRIM46 is a member of the family of tripartite motif (TRIM)-containing proteins that serve as important regulators of tumorigenesis. Here we investigate the possible role of TRIM46 in OS and the underlying molecular mechanism. We report an increase in the expression of TRIM46 in OS and its association with tumor size, Enneking’s stage, and patient prognosis. TRIM46 knockdown inhibits OS cell viability and cell cycle progression and induces apoptosis, while TRIM46 overexpression exerts inverse effects, which are inhibited by peroxisome proliferator-activated receptor alpha (PPAR )… More >

  • Open Access

    ARTICLE

    The AKT/GSK3β-Mediated Slug Expression Contributes to Oxaliplatin Resistance in Colorectal Cancer via Upregulation of ERCC1

    Wei Wei*1, Xiao-Dong Ma†1, Guan-Min Jiang, Bin Shi§, Wen Zhong, Chun-Lei Sun§, Liang Zhao*, Yan-Jiao Hou*, Hao Wang*
    Oncology Research, Vol.28, No.4, pp. 423-438, 2020, DOI:10.3727/096504020X15877284857868
    Abstract Although oxaliplatin serves as one of the first-line drugs prescribed for treating colorectal cancer (CRC), the therapeutic effect is disappointing due to drug resistance. So far, the molecular mechanisms mediating oxaliplatin resistance remain unclear. In this study, we found the chemoresistance in oxaliplatin-resistant HCT116 cells (HCT116/OXA) was mediated by the upregulation of ERCC1 expression. In addition, the acquisition of resistance induced epithelial–mesenchymal transition (EMT) as well as the Slug overexpression. On the contrary, Slug silencing reversed the EMT phenotype, decreased ERCC1 expression, and ameliorated drug resistance. Further mechanistical studies revealed the enhanced Slug expression resulted from the activation of AKT/… More >

  • Open Access

    REVIEW

    Sulforaphane: Expected to Become a Novel Antitumor Compound

    Geting Wu*1, Yuanliang Yan†‡1, Yangying Zhou§, Yumei Duan*, Shuangshuang Zeng†‡, Xiang Wang†‡, Wei Lin*, Chunlin Ou*, Jianhua Zhou*, Zhijie Xu*‡
    Oncology Research, Vol.28, No.4, pp. 439-446, 2020, DOI:10.3727/096504020X15828892654385
    Abstract Natural products are becoming increasingly popular in a variety of traditional, complementary, and alternative systems due to their potency and slight side effects. Natural compounds have been shown to be effective against many human diseases, especially cancers. Sulforaphane (SFE) is a traditional Chinese herbal medicine. In recent years, an increasing number of studies have been conducted to evaluate the antitumor effect of SFE. The roles of SFE in cancers are mainly through the regulation of potential biomarkers to activate or inhibit related signaling pathways. SFE has exhibited promising inhibitory effects on breast cancer, lung cancer, liver cancer, and other malignant… More >

  • Open Access

    ERRATUM

    The Downregulation of MicroRNA-10b and its Role in Cervical Cancer

    Dongling Zou*, Qi Zhou, Dong Wang, Lili Guan*, Li Yuan*†, Shaolin Li*
    Oncology Research, Vol.28, No.4, pp. 447-449, 2020, DOI:10.3727/096504020X15970683241756
    Abstract It has been demonstrated that microRNAs (miRNAs) act as oncogenes or tumor suppressors in a variety of cancers. Our previous work suggested that miR-10a/b functioned as a tumor suppressor in gastric cancer, and miR-10b was also reported to be significantly downregulated in advanced stage cervical cancer tissues. However, the aberrant expression of miR-10b in cervical cancer and its possible role in cervical carcinogenesis was largely unknown. In this study, we investigated the expression of miR-10b in cervical cancer tissues, carcinoma in situ tissues, mild dysplasia, moderate dysplasia, severe dysplasia tissues, and normal controls. We found that miR-10b was significantly downregulated… More >

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