| Koshi Mimori | Last modified date：2023.11.27 |
Professor /
Kyushu University Hospital
Administration Post
Other
Other
Homepage
https://kyushu-u.elsevierpure.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.
(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.
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.
(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
Membership in Academic Society
- Identification of the novel drivers to eradicate pancreatic cancer. Particular attention is paid to the gene expression control regions in enhancer promoters.
keyword : Whole genome sequencing
2022.08～2022.08. - 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.
- 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.)
Papers
Presentations
- The European Liquid Society
- American Association for Cancer Research
- Society of Surgical Oncology
- 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.
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.
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.
Unauthorized reprint of the contents of this database is prohibited.