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  • Open Access

    ARTICLE

    Pyrotinib Sensitizes 5-Fluorouracil-Resistant HER2+ Breast Cancer Cells to 5-Fluorouracil

    Jianing Yi*, Shuai Chen*, Pingyong Yi, Jinlin Luo*, Meng Fang*, Yang Du*, Lianhong Zou*, Peizhi Fan*

    Oncology Research, Vol.28, No.5, pp. 519-831, 2020, DOI:10.3727/096504020X15960154585410

    Abstract 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for breast cancer. However, acquired chemoresistance leads to a loss of its efficacy; methods to reverse are urgently needed. Some studies have shown that pyrotinib, an ErbB receptor tyrosine kinase inhibitor, is effective against HER2+ breast cancer. However, whether pyrotinib sensitizes 5-FU-resistant breast cancer cells to 5-FU is unknown. We hypothesized that the combination of pyrotinib and 5-FU would show synergistic antitumor activity, and pyrotinib could reverse 5-FU resistance in HER2+ breast cancer cells in vitro and in vivo. Our data showed that pyrotinib inhibited the growth… More >

  • Open Access

    CORRECTION

    Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN

    Jianjun Shen*1, Weina Niu†1, Hongbo Zhang*, Ma Jun*, Hongyan Zhang*

    Oncology Research, Vol.28, No.9, pp. 961-963, 2020, DOI:10.3727/096504022X16414984936746

    Abstract Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. This study aimed to investigate the expression patterns, biological roles, and underlying mechanisms of microRNA-147 (miR-147) in gastric cancer. The present study demonstrated that miR-147 was significantly upregulated in gastric cancer tissues and cell lines. Downregulation of miR-147 decreased cell proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-fluorouracil (5-FU) through the cell apoptosis pathway. In addition, phosphatase and tensin homolog (PTEN) was mechanically identified as the direct target of miR-147 in gastric cancer. PTEN knockdown More >

  • Open Access

    ARTICLE

    MicroRNA-623 Targets Cyclin D1 to Inhibit Cell Proliferation and Enhance the Chemosensitivity of Cells to 5-Fluorouracil in Gastric Cancer

    Lihua Jiang*1, Wenchuan Yang*1, Weishi Bian, Hailin Yang*, Xia Wu*, Yuhua Li*, Wen Feng*, Xuejian Liu*

    Oncology Research, Vol.27, No.1, pp. 19-27, 2019, DOI:10.3727/096504018X15193469240508

    Abstract The dysregulation of microRNAs (miRNAs) plays an important function in the onset and progression of gastric cancer (GC). In addition, aberrantly expressed miRNAs affect the chemosensitivity of GC cells to chemotherapeutic drugs. Hence, miRNA-based targeted therapy might be applied to treat patients with GC exhibiting chemotherapeutic resistance. In this study, miRNA-623 (miR-623) expression was downregulated in GC tissues and cell lines. Functional analysis showed that the restored miR-623 expression could inhibit the proliferation of GC cells and enhance their chemosensitivity to 5-FU via the cell apoptosis pathway. Cyclin D1 (CCND1) was identified as a direct More >

  • Open Access

    ARTICLE

    PAR2 Inhibition Enhanced the Sensitivity of Colorectal Cancer Cells to 5-FU and Reduced EMT Signaling

    Qiuying Quan*1, Fengyun Zhong†1, Xinwei Wang, Kai Chen§, Lingchuan Guo*

    Oncology Research, Vol.27, No.7, pp. 779-788, 2019, DOI:10.3727/096504018X15442985680348

    Abstract The aim of this study was to investigate the underlying mechanisms that transforming growth factor- (TGF- )-mediated epithelial-to-mesenchymal transition (EMT) in tumor cells contributes to 5-FU resistance. A series of experiments involving cell viability and caspase activity analyses, siRNA transfection, RNA isolation, and quantitative-PCR (qPCR) assay, cell migration analysis, Western blotting analysis of total protein and membrane protein were performed in this study. Mouse xenograft model was used to determine the effect of the PAR2 inhibitor in vivo. In this study, we found that protease-activated receptor 2 (PAR2) induction in 5-FU therapy is correlated with… More >

  • Open Access

    ARTICLE

    Downregulation of MicroRNA-147 Inhibits Cell Proliferation and Increases the Chemosensitivity of Gastric Cancer Cells to 5-Fluorouracil by Directly Targeting PTEN

    Jianjun Shen*1, Weina Niu†1, Hongbo Zhang*, Ma Jun*, Hongyan Zhang*

    Oncology Research, Vol.26, No.6, pp. 901-911, 2018, DOI:10.3727/096504017X15061902533715

    Abstract Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. This study aimed to investigate the expression patterns, biological roles, and underlying mechanisms of microRNA-147 (miR-147) in gastric cancer. The present study demonstrated that miR-147 was significantly upregulated in gastric cancer tissues and cell lines. Downregulation of miR-147 decreased cell proliferation and enhanced the chemosensitivity of gastric cancer cells to 5-fluorouracil (5-FU) through the cell apoptosis pathway. In addition, phosphatase and tensin homolog (PTEN) was mechanically identified as the direct target of miR-147 in gastric cancer. PTEN knockdown More >

  • Open Access

    CORRECTION

    The Inhibitory Effects of HYDAMTIQ, a Novel PARP Inhibitor, on Growth in Human Tumor Cell Lines With Defective DNA Damage Response Pathways

    Enrico Mini*, Ida Landini*, Laura Lucarini, Andrea Lapucci*, Cristina Napoli, Gabriele Perrone*, Renato Tassi*, Emanuela Masini, Flavio Moroni, Stefania Nobili

    Oncology Research, Vol.26, No.2, pp. 333-334, 2018, DOI:10.3727/096504018X15187172557369

    Abstract The poly(ADP-ribose) polymerase (PARP) enzymes play a key role in the regulation of cellular processes (e.g., DNA damage repair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells having dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug-induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP-1 activity. The aim of this study was to evaluate the inhibitory effects of a novel PARPI, HYDAMTIQ, on growth in human tumor cell lines characterized by different features with regard… More >

  • Open Access

    ARTICLE

    The Inhibitory Effects of HYDAMTIQ, a Novel PARP Inhibitor, on Growth in Human Tumor Cell Lines With Defective DNA Damage Response Pathways

    Enrico Mini*, Ida Landini*, Laura Lucarini, Andrea Lapucci*, Cristina Napoli, Gabriele Perrone*, Renato Tassi*, Emanuela Masini, Flavio Moroni, Stefania Nobili

    Oncology Research, Vol.25, No.9, pp. 1441-1451, 2017, DOI:10.3727/096504017X14926854178616

    Abstract The poly(ADP-ribose) polymerase (PARP) enzymes play a key role in the regulation of cellular processes (e.g., DNA damage repair, genomic stability). It has been shown that PARP inhibitors (PARPIs) are selectively cytotoxic against cells having dysfunctions in genes involved in DNA repair mechanisms (synthetic lethality). Drug-induced PARP inhibition potentiates the activity of anticancer drugs such as 5-fluorouracil in enhancing DNA damage, whose repair involves PARP-1 activity. The aim of this study was to evaluate the inhibitory effects of a novel PARPI, HYDAMTIQ, on growth in human tumor cell lines characterized by different features with regard… More >

  • Open Access

    ARTICLE

    Three Combined Treatments, a Novel HDAC Inhibitor OBP-801/YM753, 5-Fluorouracil, and Paclitaxel, Induce G2 Phase Arrest Through the p38 Pathway in Human Ovarian Cancer Cells

    Makoto Akiyama*†, Yoshihiro Sowa*, Tomoyuki Taniguchi*, Motoki Watanabe*, Shingo Yogosawa, Jo Kitawaki,Toshiyuki Sakai*

    Oncology Research, Vol.25, No.8, pp. 1245-1252, 2017, DOI:10.3727/096504017X14850164661097

    Abstract Ovarian cancer is the most lethal disease among gynecological malignancies. More effective therapy is required to counter high recurrence rates and chemotherapy resistance. We investigated the efficacy and molecular mechanisms of three combined treatments (TCTs)—a novel histone deacetylase (HDAC) inhibitor OBP-801/YM753, 5-fluorouracil (5-FU), and paclitaxel (PTX)—in human ovarian cancer SKOV-3 and OVCAR-3 cells. The inhibition of cell growth was stronger with TCTs than with each single agent and with two combined treatments. The TCTs significantly induce G2 phase arrest in both cell lines. We then analyzed the molecular mechanisms and found that the TCTs increased the More >

  • Open Access

    ARTICLE

    Simultaneous, But Not Consecutive, Combination With Folinate Salts Potentiates 5-Fluorouracil Antitumor Activity In Vitro and In Vivo

    Antonello Di Paolo1, Paola Orlandi1, Teresa Di Desidero, Romano Danesi, Guido Bocci

    Oncology Research, Vol.25, No.7, pp. 1129-1140, 2017, DOI:10.3727/096504017X14841698396900

    Abstract The combination of folinate salts to 5-fluoruracil (5-FU)-based schedules is an established clinical routine in the landscape of colorectal cancer treatment. The aim of this study was to investigate the pharmacological differences between the sequential administration of folinate salts (1 h before, as in clinical routine) followed by 5-FU and the simultaneous administration of both drugs. Proliferation and apoptotic assays were performed on human colon cancer cells exposed to 5-FU, calcium (CaLV), or disodium (NaLV) levofolinate or their simultaneous and sequential combination for 24 and 72 h. TYMS and SLC19A1 gene expression was performed with… More >

  • Open Access

    CORRECTION

    The Novel HDAC Inhibitor OBP-801/YM753 Enhances the Effects of 5-Fluorouracil With Radiation on Esophageal Squamous Carcinoma Cells

    Akinobu Furutani*†, Yoshihiro Sowa*, Hitoshi Fujiwara, Eigo Otsuji, Toshiyuki Sakai*

    Oncology Research, Vol.23, No.1-2, pp. 87-87, 2015, DOI:10.3727/096504016X14514194509664

    Abstract Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5-fluorouracil (5-FU) against various cancer cells; however, no report has shown that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore, we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells. The inhibition of the cell growth was significantly stronger with the combination of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore, inhibition of the colony formation was the most effective with the combined treatment of More >

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