• Cancer stem cells: the potential of carbon ion beam radiation and new radiosensitizers (Review) （Oncology Rep., 2015 ）

    In  the collaboration with the Department of Radiation Oncology, Osaka University (Prof. Ogawa, K.), Baek , et al. update the information regarding  carbon ion beam radiation and new radio sensitizers. Given that cancer stem cells (CSCs) are a small population of cells in cancer with stem-like properties such as cell proliferation, and CSCs are therapy-resistant and cause cancer metastasis and recurrence, one key issue in cancer therapy may be the carbon ion beam radiotherapy, being a promising treatment for CSCs. Evidence indicates that the carbon ion beam is more effective against CSCs than the conventional X-ray beam. Combination therapies of radiosensitizing microRNAs and carbon ion beam radiotherapy may be a promising cancer strategy.

  • Susceptibility of pancreatic cancer stem cells to reprogramming. (Cancer Sci, 2015)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Noguchi et al. studied the susceptibility of pancreatic cancer stem cells (CSCs) to reprogramming. Given that previous reports have indicated that reprogramming technologies may be useful for altering the malignant phenotype of epithelial cancer cells, the study may be useful for extensive modification of malignant features of pancreatic CSCs. The study focused on c-Met signaling, which has been identified as a marker of CSCs. The present study indicates that cells that expressed high levels of c-Met showed  higher CSC properties, such as tumor-initiating capacity,  and resistance to gemcitabine. Although further studies are necessary, it suggests the novel approach may be possible for cancer cell reprogramming .

  • Tumour-suppressive function of SIRT4 in human colorectal cancer  (Br. J. Cancer, 2015)

    SIRT4, which is localized in the mitochondria, is one of the least characterized members of the sirtuin family of nicotinamide adenine dinucleotide?dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. In collaboration with  the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki) , Miyo et al. studied the significance of SIRT4 in human colorectal cancer. SIRT4 expression decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis. SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.

  • MicroRNAs induce epigenetic reprogramming and suppress malignant phenotypes of human colon cancer cells  (PLOS ONE, 2015)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Ogawa et al. showed the data that  cancer reprogramming may be a useful treatment for chemo- or radiotherapy-resistant cancer cells. The introduction of microRNA (miR) resulted in epigenetic reprogramming of DNA demethylation and histone modification events. In vivo administration of the ribonucleotides in mice elicited the induction of cancer cell apoptosis. The present study shows that the introduction of miRs could induce cellular reprogramming and modulate malignant phenotypes of human colorectal cancer, suggesting that the appropriate delivery of functional small-sized ribonucleotides may open a new avenue for therapy against human malignant tumors.

  • Cyclin G2: a new prognosis marker in pancreatic cancer (Oncol. Lett., 2014)

    Although  a family of cyclins positively regulates the cell cycle to a large extent,  Hasegawa et al. found that  unexpectedly cyclin G2 has been shown to regulate cell proliferation as a tumor suppressor gene,  as the collaboration with the Department of Surgery, Osaka University (Profs. Nagano, Mori and Doki), Research Institute for Microbial Diseases, Osaka University (Prof. Nojima) , and   Cancer Research Institute of Kanazawa University (Prof. Gotoh), Japan. The study demonstrates the candidacy of  decreased CCNG2 expression as a marker for poor prognosis  in pancreatic cancer.

  • Mathematical analysis predicts imbalanced IDH1/2 expression associates with 2-HG-inactivating pathway in colorectal cancer (Int J Oncol, 46, 1181-1191, 2014)

    Bioinformatics and computational modeling offer innovative approaches to investigate cancer metabolism and predict the secondary and tertiary cellular responses. A significant proportion of patients with glioblastoma and hematological malignancies harbor the mutated forms of the oxidative phosphorylation (OxPhos) enzymes, isocitrate dehydrogenase (IDH) 1 or 2. The mutated forms of IDH1 and IDH2 produce an oncogenic metabolite, D-2-hydroxyglutarate (D2HG). We computationally analyzed gene expression in colorectal cancer (CRC), and identified novel sets of genes that are associated with patient survival. The study of OxPhos-related genes revealed that an imbalance between the expression of IDH1 and IDH2, defined as over expression of one isoform in relation to the other, was associated with worse prognosis in CRC patients. This effect was accentuated by reduced expression of the 2-HG-inactivating pathway. These findings suggest a yet uncharacterized mechanism to discover novel therapeutic targets for the treatment of CRC.

  • A proposed linkage of cancer metabolism and epigenetic alterations (Proc. Natl. Acad. Sci. USA, 111, 15526, 2014)

    In collaboration with the Department of Surgery, Osaka University (Profs. Masaki Mori and Yuichiro Doki), Hamabe et al. showed that pyruvate kinase M2 (PKM2), an alternatively spliced variant of the pyruvate kinase gene, mediates epithelial?mesenchymal transition (EMT), which is critical for aggressive cancer phenotypes. The study demonstrates that EMT stimulates nuclear translocation of PKM2 and controls transcription mechanism. The present study shows a role of pyruvate kinase M2 in transcriptional regulation leading to EMT. The precise understanding of nuclear PKM2 function suggests the potential for a model preventing metastasis of colorectal cancer.