• A convolutional neural network uses microscopic images to differentiate between mouse and human cell lines and their radioresistant clones (Cancer Research, 2018, in press)

    In collaboration with the Department of Radiation Oncology, Osaka University (Prof. Kazuhiko Ogawa), Toratani et al. demonstrated that the utility of image recognition using the artificial intelligence (AI) technology for predicting minute differences among phase-contrast microscopic images of cancer cells and their radioresistant clones. This study demonstrates rapid and accurate identification of radioresistant tumor cells in culture using artifical intelligence, and this should have applications in future pre-clinical cancer research.

  • Block copolymer conjugate targets hepatocellular carcinoma stem cells (Oncogene, 2018)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki) and Tokyo Institute of Technology (Prof. Nobuhiro Nishiyama), Toshiyama et al. developed a block copolymer conjugate to increase the efficacy of reagents in cancer stem cells. The exposure increased the intracellular ROS concentration by inhibiting enzyme activity, permitting the induction of apoptosis and attenuation of cancer cell growth. This study demonstrated that it exerts a potent antitumor effect.

  • Computational trans-omics approach characterised methylomic and transcriptomic involvements and identified novel therapeutic targets for chemoresistance in gastrointestinal cancer stem cells (Scientific Reports, 2018, in press)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Konno et al. demonstrated by the computational trans-omics approach that the novel therapeutic targets are involved in the chemoresistance in gastrointestinal cancer stem cells. This mathematical method can be used to simultaneously quantify and identify chemoresistant potential targets in gastrointestinal cancer stem cells.

  • Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis (Scientific Reports, 2018, in press)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Koseki et al. studied the significance of mitochondrial metabolism in cancer cells by computational approach as well as wet experiments, and demonstrated the importance of the one-carbon folate metabolism in metabolic cycle of tetrahydrofolate in mitochondria, SHMT2, MTHFD2, and ALDH1L2, suggesting the rationale of drug discovery in cancer medicine.

  • Association with the prognosis of patients with pancreatic cancer of iron metabolic enzyme hepacidin expression levels (Oncology Letters, 2017, in press)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Toshiyama et al. demonstrated that the expressions of iron metabolic enzymes hepacidin and ferroportin are associated with the prognosis of patients with pancreatic cancer. Given that iron overload is a risk factor for cancer, possibly through the generation of reactive oxygen species, the present study indicates that iron metabolism plays a role in pancreatic cancer, and suggests the significance in novel diagnostic tools and efficient therapeutic targets.

  • Mitochondrial pyruvate carrier modulates the epithelial–mesenchymal transition in cholangiocarcinoma (Oncology Reports, in press)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Ohashi et al. demonstrated the mitochondrial pyruvate carrier (MPC) plays a role in the intrahepatic cholangiocarcinoma (ICC). ICC has a poor prognosis even after complete tumor resection. MPC is located in the mitochondrial inner membrane and is involved in the oxidative phosphorylation. The present study indicates that MPC is important in the control of epithelial–mesenchymal transition (EMT), which characterizes metastasis of tumor cells, and could be a novel therapeutic target in some cancers.

  • Oncogene c-Myc promotes epitranscriptome m6A reader YTHDF1 expression in colorectal cancer (Oncotarget, in press)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Nishizawa et al. demonstrated that epitranscriptome N6-methyladenosine (m6A) reader, YT521-B homology YTH domain family YTHDF1,  plays a role in the malignant behavior of colorectal cancer cells in an oncogene transcription factor c-Myc  dependent manner. Given that the m6A was first reported in RNA modification and is most common in the epitranscriptome issues of various RNAs, the present study indicated that YTHDF1 may be involved in the translation of numerous tumor related proteins. We are exploring further the transcription and ribosomal translation mechanism of epitranscriptome dependent pathway in the tumor microenvironment such as hypoxia.

  • Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA LINC00152 in colorectal cancer (Int J Oncol, in press)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Nishizawa et al. demonstrated a long noncoding RNA, LINC00152, plays a pivotal role in cellular processes of colorectal cancer cells via the cytoplasmic localization under hypoxic tumor microenvironment. The present study indicated that lncRNA networks could provide diagnostic tools and novel therapeutic targets.

  • Epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in pancreatic cancer cells (Int J Oncol, in press)

    In the collaboration with the Department of Radiation Oncology, Osaka University, Taketo, et al. investigated a Epitranscriptome N6-methyladenosine (m6A) writer, methyltransferase-like 3 (METTL3), and showed the significance in chemo- and radioresistance in pancreatic cancer cells. Given that m6A is the most abundant epitranscriptome modification in mammalian mRNA and recent years have seen major progress in m6A epitranscriptomics, the present study indicates as tumor biology its crucial roles in initiation and progression of cancer through the regulation and mechanism of RNA stabilities, mRNA splicing, microRNA processing, and mRNA translation. We are now studying which factors control m6A dynamically, what occurs as the resultant of written/erased/read process by RNA modification, and how significant m6A marking is for each of the numerous genes, in order to discover draggable targets against intractable pancreatic cancer.

  • MicroRNA profiles involved in trifluridine resistance (Oncotarget, 2017)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Tsunekuni et al. demonstrated the microRNA profiles involved in trifluridine (FTD) resistance.  FTD is a key component of the novel oral antitumor drug trifluridine/tipiracil, which was approved for the treatment of patients with metastatic colorectal cancer refractory to standard chemotherapies. A comprehensive analysis of microRNA profiles was performed in colorectal cell lines resistant to FTD, in order to explore the underlying mechanisms of resistance to the drug. The data indicate the significance of microRNA network and the candidacy of microRNAs as a potential predictive clinical marker of FTD treatment.