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Koshi Mimori Last modified date:2021.05.28



Administration Post
Other


Homepage
https://kyushu-u.pure.elsevier.com/en/persons/koshi-mimori
 Reseacher Profiling Tool Kyushu University Pure
Phone
0977-27-1645
Fax
0977-27-1651
Academic Degree
MEDICAL DOCTOR
Country of degree conferring institution (Overseas)
No
Field of Specialization
gastro intestinal surgery
Total Priod of education and research career in the foreign country
00years00months
Outline Activities
Based on the basic concept that "the truth lies in the primitive, and various organisms have fractal relationships," we are trying to elucidate the true mechanism of the process from carcinogenesis to cancer progression and recurrence, analogous to the theory of biological evolution. In addition, we aim to solve clinical problems while improving the knowledge and techniques of basic research (dry analysis and wet analysis) with the goal of "significantly prolonging the life prognosis of cancer patients" and "solving individual patient or comprehensive disease problems in various clinical aspects".

Evolution in solid tumors: In advanced colorectal cancer, many driver mutations existed clonally (Uchi R., Takahashi Y., et al. PLoS Genet 2016). On the other hand, when we analyzed the evolutionary process of early-stage colorectal cancer using a similar approach, we found that driver mutations were scattered in subclonal regions. Copy number mutations (chromosomal amplifications and deletions) were significantly more common in advanced cancers than in early-stage cancers (Saito T., Nat Commun 2018).
We identified the risk alleles of ALDH2 and ADH1B polymorphisms involved in esophageal carcinogenesis (Tanaka F., GUT 2010), and for somatic mutations, we identified a comprehensive genetic mutation profile of Japanese esophageal cancer (Sawada G., 201). (Sawada G., 201), and recently, Professor Seiji Ogawa and his colleagues at Kyoto University reported a paper using the same data to clarify the evolution of esophageal cancer (Yokoyama A., Ogawa S., et al, Nature 2019).
In addition, evolutionary analysis of intrahepatic cholangiocarcinoma, pancreatic cancer, and breast cancer is ongoing with the aim of searching for true therapeutic targets that are clinically useful.

In addition, we are continuing our evolutionary studies of intrahepatic cholangiocarcinoma, pancreatic cancer, and breast cancer to identify clinically useful therapeutic targets. In particular, we have focused on mutated genes localized on chromosome 7 as genomic regions that undergo clonal amplification in colorectal cancer. In particular, we found a gene, 5MP1, which causes "dysregulation of protein translation start site" as a new mechanism of colorectal carcinogenesis (Sato K, EBioMed 2019). (Sato K, EBioMed 2019). We also clarified the clinical significance of the DDX56 gene, which regulates the transcription mechanism (Kouyama Y, Cancer Sci 2019). In addition, the development of

SK-818 is a drug approved by Sanwa Kagaku Co., Ltd. for the treatment of chronic hepatitis B. It has been used for 20 years, and its safety has been assured to some extent. In addition, it is economically viable from the perspective of drug repositioning (expansion of indications for inexpensive drugs). The safety study was successfully completed at the end of last fiscal year. Currently, we are trying to elucidate the mechanism of action of SK818 as it shows efficacy as a single agent. We are also working hard to identify candidate drugs for various other carcinomas.

Liquid Biopsy
(1) Characteristics of ctDNA detected in the blood of gastrointestinal cancers: The characteristics of clones in which ctDNA mutations are detected are not clear. (1) Characteristics of ctDNA detected in blood of gastrointestinal cancers: The characteristics of clones in which ctDNA mutations are detected are not clear. We are conducting basic research to clarify the characteristics of clones in which mutations are detected in ctDNA at the time of cancer recurrence from the viewpoint of tumor immune response.
(2) Chronic inflammation and gastric cancer: There is a classification method called the Kimura-Takemoto classification that classifies the extent of atrophy of the gastric mucosa based on upper gastrointestinal endoscopy. The more advanced the atrophy, the higher the risk of gastric cancer. We identified microRNAs in the serum of patients with gastric precancerous lesions.
(3) Risk prediction by gene polymorphism: The prognosis of patients with advanced or recurrent solid tumors has been dramatically improved by the advent of molecular targeted drugs. However, the establishment of biomarkers is an urgent and long-standing issue because some patients have to reduce, discontinue, or change their medication due to adverse events, and some patients do not show the expected antitumor effect. The establishment of biomarkers is an urgent and long-standing issue. In addition, personalized medicine based on genomic mutation information is becoming more practical as the precise genomic information of each patient becomes available for analysis. We will clarify the importance of genetic polymorphism information and somatic mutation information for early detection of disease onset. Although whole genome sequencing is expected to become common in the near future, we would like to construct a community-wide disease onset detection system using clearly annotated genetic polymorphism information for the realization of truly personalized medicine.

(6) Major joint research projects
Representative research
AMED Research Project for Creation of Next-Generation Cancer Medicine
Research and Development Project: Establishment of a ctDNA detection method targeting intractable cancer-specific epigenetic mutations
 Cancer genome medicine has started to recommend therapies based on mutation information for solid tumors. However, access to solid tumors is often difficult for refractory cancers such as pancreatic cancer, bile duct cancer, and recurrent colorectal cancer. Therefore, there is an urgent need to establish minimally invasive, low-cost, and highly implementable liquid biopsy (LB) with high cancer type specificity. We will focus on cancer type-specific epigenomic mutations in ctDNA for these three intractable cancers and clarify the usefulness of detection. The most important feature of LB is that it can be used to monitor tumor burden over time. In this study, we will use recurrent colorectal cancer as a model to clarify its clinical significance.

Contributing research
(1) PRISM
Principal Investigator] Dr. Yoshihiro Yamanishi, Professor, Kyushu Institute of Technology
Title of Research and Development: Search for tool substances to verify the authenticity of drug target molecules
We will develop an in silico method to search for tool compounds that can be used for verification experiments of the "certainty" of drug target candidates for target diseases based on pharmaceutical big data. We will collect multi-omics data and molecular network data on various cancer types and organ fibrosis, as well as structural and experimental data of large-scale compounds including already approved drugs, discontinued development compounds, synthetic compounds, and natural compounds. We will develop statistical methods for fusion analysis of disease data and compound data, and machine learning methods that can effectively utilize diverse omics-related data to efficiently screen compounds. Finally, we will predict in silico the candidate tool compounds that regulate the candidate drug target molecules found for idiopathic pulmonary fibrosis and lung cancer.
Project Title: Identification and experimental validation of molecular target drugs for gefitinib-resistant lung cancer.
 Screening was completed and candidate compounds were identified. The point of action is being elucidated.

(2) AMED Research Project for Practical Application of Innovative Cancer Medicine
(2) AMED Innovative Cancer Medicine Research Project: [Principal Investigator] Dr. Tatsuhiro Shibata, Director, Division of Cancer Genomics, National Cancer Center Research Institute
(2) AMED Innovative Cancer Medicine Project: [Principal Investigator] Dr. Tatsuhiro Shibata, Director, Division of Cancer Genomics, National Cancer Center Research Institute
Title of Project: Construction and data sharing of Japanese cancer genomics database with new genome technology
 In particular, we are working to elucidate the mechanisms of omics evolution in intrahepatic cholangiocarcinoma and to study tumor immune responses and metabolites as evolutionary selection pressures.

(3) AMED Research Project for Practical Application of Innovative Cancer Medicine
Dr. Masanobu Oshima, Professor, Institute for Cancer Research, Kanazawa University
Title of Research and Development: Establishment of novel preventive treatment strategies by understanding the mechanism of colorectal cancer micrometastasis formation
Elucidation of the role of fibrous niche in micrometastases 2. Elucidation of the involvement of HSCs and Kupffer cells 3. Elucidation of the interaction between cancer cells and HSCs 4. Search and validation of candidate genes 5. Validation in human colon cancer cells
The above five items will be clarified by a two-person team.
Research
Research Interests
  • liquidbiopsy
    keyword : liquidbiopsy
    2019.04~2023.03.
  • Clinical Trial for the Safety Evaluation of SK-818 for Breast Cancer Patients Conducting Curative Operations.
    keyword : Drug repositioning
    2018.06~2018.06.
  • Genomic analysis of hereditary GI tract tumors.
    keyword : Lynch、〜analysis
    2017.04~2019.03.
  • evolutional pathway of Colorectal cancers
    keyword : Evolution, colorectal cancer
    2018.06~2018.06.
  • Evolution of Early Colorectal Cancer via Genomic Aberrations Hampering the Tumor Immune Response
    keyword : RNAseq
    2018.06~2018.06.
Current and Past Project
  • Identification of the Bone-Fide Cancer Metastasis Regulating Factors in Solid Cancers.
    Purpose: Identification of microRNA in BM expressing specifically in metastatic cases of CRC as well as GC
    Patients and Method:
    Subset A:20 cases of metastasis (+) CRC, and GC
    Subset B:20 advanced CRC and GC metastasis(-) cases. Bone marrow is 6ml from sternum and AGPC method to ext. total RNA, stored at -80 degree. Extraction of RNA: @Kyushu University in Beppu. Then, we send total RNA to microRNA microarry. Microarray: microRNA microarray between A vs B
    Expecting Results:
    Establishment of expression profile of miRNA expressing specifically in BM from metastasis (+) cases.
    1) Then, we can identify target genes to control metastasis. 2) Validation of the identified miRNA and/or genes by in vitro and in vivo experiment. 3) Clinical significance of the identified genes in 810 cases of GC and 600 CRC cases. 4)Comparison data with the CGH array in 80 cases of CRC. (In those cases, Laser microdissection was applied, therefore, CGH data is extremely specific for cancer cell.)
Academic Activities
Papers
1. Koshi Mimori, Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis, Cancer Res, 73, 7, 2059-2069, 2013.04.
2. Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M., MicroRNA-125a-5p is an independent prognostic factor in gastric cancer,and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab., Clin Cancer Res., 17, 9, 2725-33, 2011.05.
3. Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M., MicroRNA-125a-5p is an independent prognostic factor in gastric cancer,and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab., Clin Cancer Res., 17, 9, 2725-33, 2011.05.
4. Mimori K, Druck T, Inoue H, Hansjuerg A, Berk L, Mori M, Huebner K, Croce CM. , Cancer-specific chromosome alterations in the constitutive fragile region FRA3B., Proc Natl Acad Sci (USA), 10.1073/pnas.96.13.7456, 96, 13, 7456-7461, 1999.06.
5. Mimori K, Druck T, Inoue H, Alder H, Berk L, Mori M, Huebner K and Croce CM, Cancer-specific chromosome alterations in the constitutive fragile region FRA3B.
, Proc Natl Acad Sci (U.S.A) , 10.1073/pnas.96.13.7456, 96, 13, 7456-7461, 96: 7456-61, 1999, 1999.06.
Presentations
1. Identification of non coding RNA as carcinogenic or recurrence/metastatic markers by Next Generation Sequencer, and the magnitude for surgeons..
2. MAL expression is diminished in esophageal cancer cases and cell lines.
MAL expression in tumor cells exerts an anti-tumorigenic effect by Fas and/or by keratins of esophageal epithelium.
MAL expression is diminished in pre-cancerous lesions in a rat carcinogenic model, as well as in dysplastic lesions of esophageal cancer. .
3. INTRODUCTION The fragile histidine triad (FHIT) functions as a tumor suppressor and clinical benefits of adenoviral-FHIT (Ad-FHIT) may be expected. However, the pathways through which FHIT induces apoptosis and inhibits cancer cell growth are not known. To determine appropriate targets for Ad-FHIT mediated therapy, we performed microarray analysis between Ad-FHIT transfected cells and control cells using 3 kinds of squamous cancer cell lines. For this purpose, 1) we identified clusters of more repressed genes in Ad-FHIT cells compared to control cells, and 2) we compared clustered genes in apoptosis induced cells H1299 and TE4 by Ad-FHIT infection with genes in non apoptotic non-induced cell line, TE2.
METHOD Three cell lines, H1299, TE4 and TE2 were transfected individually with full length FHIT and lacZ cDNA as a control. Total RNAs extracted from Ad-FHIT or AdlacZ infected samples were labeled with Cy3-dCTP or Cy5-dCTP and hybridized with a chip printed with 19,200 oligos. 1) The Ad-FHIT/Ad-control expression ratio was derived by using a random permutation test with high reproducibility from 7 repetitive
Experiments, and 4 spots per gene on a chip. 2) The expression ratio of TE4/TE2 for eachgene was calculated to determine what genes are dominant in Ad-FHIT induced apoptotic cells.
RESULTS 1) We identified clusters of genes reduced in Ad-FHIT, such as arachidonicacid metabolism (Table 1A) and matrix metalloprotease (MMP) related genes (Table 1B). We confirmed a reduction of PGE2 synthesis to 0.75 times control cells (range 0.35 to 0.98) by ELISA assays after exposure to LPS, IL-1 beta, or PMA stimulation in FHIT expressing cells. 2) The expression ratio of TE4 (apoptosis induced) /TE2 (non-apoptosis induced), disclosed that c-Src tyrosine kinase, tyrosine-protein kinase JAK-1 and EST (#Hs.268892) were associated with apoptosis, with ratios of 2.1, 2.4 and 6.6, respectively(Table 2).

CONCLUSION 1) We anticipate that Ad-FHIT may be effective in certain pre-malignant cases involving inflammatory carcinogens, such as COX-2 which leads to the inhibition of apoptosis; invasion, cell proliferation, angiogenesis mediated by the PGE2 receptor Ep4; IL-1 beta which stimulates the release of prostaglandin; and ERG-1 which is a transcription factor for mPGES. Moreover, the MMP family could be a target of the Ad-FHIT gene. 2) Therefore we predict the induction of apoptosis by Ad-FHIT on far advanced esophageal cancer cases with activation of those signal pathways..
Membership in Academic Society
  • The European Liquid Society
  • American Association for Cancer Research
  • Society of Surgical Oncology
Awards
  • Technical assistance of miR assay
Educational
Educational Activities
Annual lectures for graduate students in Kyushu University.
Contributing to the completion of degrees among the department's medical staff.
Social
Professional and Outreach Activities
2012-13: 28 Small Lectures in community centers in Beppu city

2016.11.14 The 1st Remote Lecture for Ritsumeikan Asia Pacific University(APU)   “a real and vivid information” by native foreign doctors coming from abroad. The first communicator was Dr. Mohamed who gave a great talk entitled “Health issues, morbidity and mortality in Egypt”. We have learned and moved actual life of people in Egypt from what he insisted in his talk rather than the general knowledge of Egypt. This communication was really significant one for us. We have six intercollegiate meetings.