• Micro-RNA-130a-3p regulates gemcitabine-resistance via PPARG in cholangiocarcinoma (Annal. Surg. Oncol., 2017)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Asukai et al. demonstrated that miR-130a-3p was upregulated in gemcitabine-resistant cholangiocancinoma (CCA) cell lines, and its expression levels were closely related to prognosis of CCA patients. The data support that CCA patients with PPARγ positive were more effective for gemcitabine than those with negative.

  • MicroRNA miR-374, a potential radio sensitizer for carbon ion beam radiotherapy (Oncology reports, 2016)
    In the collaboration with the Department of Radiation Oncology, Osaka University (Prof. Ogawa, K.), Baek et al.
    studied microRNA (miRNA) profiles of a control and X-ray- and carbon ion beam-resistant cells to identify miRNAs that can be used as radio sensitizers and biomarkers. Expression of miRNAs shown to be upregulated or downregulated in the microarray analysis was studied. miRNA miR-374 has the potential to be a new radio sensitizer for carbon ion beam radiotherapy and a new biomarker to determine the optimal treatment for cancer.

  • Metabolic adaptation to nutritional stress in human colorectal cancer ( Scientific Reports, 2016 )
    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Miyo and Konno et al.
    demonstrated that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained tricarboxylic acid cycle activity and ATP production under such conditions. The study showed that pivotal roles of GLUD1 and SLC25A13 in nutritional stress. Thus GLUD1 and SLC25A13 may serve as new targets in treating refractory colorectal cancer which survive in malnutritional microenvironments.

  • The one-carbon metabolism pathway highlights therapeutic targets for gastrointestinal cancer (Int J Oncol, 2017)
    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Konno et al.
    demonstrated the importance of one-carbon metabolism pathway in drug discovery. In this review, they focused on the understanding of the one-carbon metabolism pathway to unravel the link between the causes and effects of cancer phenotypes. The characterization of one-carbon metabolism is indispensable to the development of precision medicine in the context of cancer diagnostics and therapeutics. They review the historical issues associated with one-carbon metabolism and highlight the recent advances in cancer research.

  • Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer (Scientific Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Colvin et al. demonstrate that in colorectal cancer cells that even in the absence of isocitrate dehydrogenase (IDH) mutation, the levels of the oncometabolite D-2 hydroxyglutarate (D-2HG) and its enantiomer L-2HG were elevated through glutamine anaplerosis. D-2HG, but not L-2HG, increased the trimethylation of histone H3 lysine 4 of the promoter region of ZEB1 , the master regulator of epithelial-mesenchymal transition (EMT), also increased the expression of the ZEB1 gene to directly induce EMT in colorectal cancer cells. Furthermore, they demonstrated that D-2HG levels to be elevated in colorectal cancer specimens, particularly in those associated with distant metastasis, supporting the observations in vitro and implicating the contribution of D-2HG in metastasis, the major cause of death in this disease.

  • Cell-free culture conditioned medium elicits pancreatic β-cell lineage-specific epigenetic reprogramming (Oncology Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Kawamoto and Ohashi et al. demonstrate that cell-free culture conditioned medium elicits pancreatic β-cell lineage-specific epigenetic reprogramming in mice. The study showed that the transfer of epigenetic phenotypes was achieved in the cell-free system of pancreatic insulinoma cell culture. These findings provide further support for the utility of cell-free conditioned medium for cellular reprogramming and the regenerative medicine.

  • The importance of one carbon (C1) metabolism: mitochondrial folate enzymes in human colorectal cancer ( Oncology Reports, 2016)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Miyo et al. demonstrate that the importance of mitochondrial folate enzymes of one carbon (C1) metabolism in human colorectal cancer. The data indicate that three mitochondrial folate metabolic enzymes, serine hydroxymethyl transferase (SHMT2), methylenetetrahydrofolate dehydrogenase (MTHFD2), and aldehyde dehydrogenase 1 family member L2 (ALDH1L2), play a role in human colorectal tumor tissues. The present study demonstrates that C1 metabolic enzymes could provide a potential therapeutic strategy for treating colorectal cancer.

  • Clinical significance of histone demethylase NO66 in invasive colorectal cancer (Annal. Surg. Oncology, 2016)
    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Nishizawa et al. demonstrate that the oncogene-regulated histone demethylase, nucleolar protein 66 (NO66), which is known to work coordinately with the well-characterized oncogene c-MYC, are critical for the determination of biological behavior of invasive colorectal cancer. This would facilitate new drug discovery for the intractable cancer.

  • c-Met affects gemcitabine resistance in mouse model of pancreatic cancer (Oncology Letters, 2016 )
    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Noguchi et al. studied a  mouse Kras/Met   model of pancreatic cancer stem cells (CSCs) and  showed that  c-Met inhibition in Kras mice significantly decreased pancreatic intraepithelial neoplasia (PanIN)  lesions, suggesting that complete c-Met signal inhibition with chemotherapy could be useful for control of pancreatic malignant features.

  • Fetal-hepatocyte-derived culture medium elicits adipocyte differentiation into bile-duct-cell lineage in mouse (Biomedical Reports, 2016 )

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Ogawa et al.  studied fetal tissues of mouse and showed that fetal-hepatocyte-derived factors elicit the differentiation to bile-duct-cell lineages, suggesting that fetal cells possess multiple potentials that are absent in adults.