Yoshihiko Maehara1, Yuji Soejima2,3, Tomoharu Yoshizumi2, Naoyuki Kawahara2, Eiji Oki2, Hiroshi Saeki2,4, Tomohiko Akahoshi2,5, Toru Ikegami2, Yo-Ichi Yamashita2,6, Tadashi Furuyama2, Keishi Sugimachi2,7, Noboru Harada2, Tetsuzo Tagawa2, Norifumi Harimoto2,4, Shinji Itoh2, Hideto Sonoda2,8, Koji Ando2, Yuichiro Nakashima2, Yoshihiro Nagao2, Nami Yamashita2, Yuta Kasagi2,9, Takafumi Yukaya2,10, Takeshi Kurihara2, Ryosuke Tsutsumi2, Shinkichi Takamori2, Shun Sasaki2, Tetsuo Ikeda11, Yoshikazu Yonemitsu12, Takasuke Fukuhara13, Hiroyuki Kitao14, Makoto Iimori14, Yuki Kataoka14,15, Takeshi Wakasa14,15, Masami Suzuki16, Koji Teraishi12,17, Yasuto Yoshida18, Masaki Mori2. 1. Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers, Fukuoka, Japan. maehara@kyushu-ctr-hsp.com. 2. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 3. Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan. 4. Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan. 5. Department of Advanced Medical Initiatives, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 6. Department of Gastroenterological Surgery, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. 7. Department of Hepatobiliary-Pancreatic Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 8. Department of Surgery, Imari Arita Kyoritsu Hospital, Saga, Japan. 9. Department of Surgery, Fukuoka Higashi Medical Center, Fukuoka, Japan. 10. Department of Surgery, Iizuka Hospital, Iizuka, Fukuoka, Japan. 11. Endoscopy and Endoscopic Surgery, Fukuoka Dental College, Fukuoka, Japan. 12. R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharma-Ceutical Sciences, Kyushu University, Fukuoka, Japan. 13. Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 14. Department of Molecular Cancer Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. 15. Taiho Pharmaceutical Co. Ltd., Tokyo, Japan. 16. Chugai Pharmaceutical Co., Ltd., Kanagawa, Japan. 17. Ono Pharmaceutical Co., Ltd., Osaka, Japan. 18. Yakult Central Institute, Tokyo, Japan.
Abstract
INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.
INTRODUCTION: According to the latest Japanese nationwide estimates, over a million Japanese people are newly diagnosed with cancer each year. Since gastrointestinal cancers account for more than 40% of all cancer-related deaths, it is imperative to formulate effective strategies to control them. MATERIALS AND METHODS, AND RESULTS: Basic drug discovery research Our research has revealed that the abnormal expression of regulators of chromosomal stability is a cause of cancers and identified an effective compound against cancers with chromosomal instability. We revealed the molecular mechanism of peritoneal dissemination of cancer cells via the CXCR4/CXCL12 axis to CAR-like cells and identified an MEK inhibitor effective against these tumors. Residual tumor cells after chemotherapy in colorectal cancer are LGR5-positive cancer stem cells and their ability to eliminate reactive oxygen species is elevated. The development of surgical procedures and devices In cases of gastric tube reconstruction for esophageal cancer, we determined the anastomotic line for evaluating the blood flow using ICG angiography and measuring the tissue O2 metabolism. We established a novel gastric reconstruction method (book-binding technique) for gastric cancer and a new rectal reconstruction method focusing on the intra-intestinal pressure resistance for rectal cancer. We established a novel tissue fusion method, which allows contact-free local heating and retains tissue viability with very little damage, and developed an understanding of the collagen-related processes that underpin laser-induced tissue fusion. Strategy to prevent carcinogenesis We succeeded in cleaving hepatitis B virus DNA integrated into the nucleus of hepatocytes using genome editing tools. The development of HCC from non-alcoholic steatohepatitis (NASH) may be prevented by metabolic surgery. CONCLUSION: We believe that these efforts will help to significantly improve the gastrointestinal cancer treatment and survival.
Entities:
Keywords:
Biomaterial collagen; Cancer odors; Chromosomal instability; Drug discovery; Gastrointestinal cancers; Metabolic surgery; Reconstruction after gastrointestinal surgery
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