Hiromichi Oshiro1,2,3, Yasunori Tome4, Tasuku Kiyuna3, Sang Nam Yoon1,2, Thinzar M Lwin2, Qinghong Han1, Yuying Tan1, Kentaro Miyake1,2, Takashi Higuchi1,2, Norihiko Sugisawa1,2, Yuki Katsuya1,2, Jun Ho Park1,2, Zhiying Zang1, Sahar Razmjooei1, Michael Bouvet5, Bryan Clary2, Shree Ram Singh6, Fuminori Kanaya3, Kotaro Nishida3, Robert M Hoffman7,2. 1. AntiCancer Inc., San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. 4. Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov. 5. Department of Surgery, University of California, San Diego, CA, U.S.A. all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov. 6. Basic Research Laboratory, National Cancer Institute, Frederick, MD, U.S.A. all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov. 7. AntiCancer Inc., San Diego, CA, U.S.A. all@anticancer.com yash_toume@hotmail.com mbouvet@ucsd.edu singhshr@mail.nih.gov.
Abstract
BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS: Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis. Copyright
BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS:Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis. Copyright
Authors: Yoshihiko Tashiro; Hannah M Hollandsworth; Hiroto Nishino; Jun Yamamoto; Siamak Amirfakhri; Filemoni Filemoni; Norihiko Sugisawa; Takeshi Aoki; Masahiko Murakami; Robert M Hoffman; Michael Bouvet Journal: In Vivo Date: 2020 Sep-Oct Impact factor: 2.155
Authors: Hye In Lim; Kazuyuki Hamada; Jun Yamamoto; Qinhong Han; Yuying Tan; Hee Jun Choi; Seok Jin Nam; Michael Bouvet; Robert M Hoffman Journal: In Vivo Date: 2020 Sep-Oct Impact factor: 2.155
Authors: Hiroto Nishino; Hannah M Hollandsworth; Norihiko Sugisawa; Jun Yamamoto; Yoshihiko Tashiro; Sachiko Inubushi; Kazuyuki Hamada; Y U Sun; Hyein Lim; Siamak Amirfakhri; Filemoni Filemoni; Robert M Hoffman; Michael Bouvet Journal: In Vivo Date: 2020 Nov-Dec Impact factor: 2.155
Authors: Hye In Lim; Jun Yamamoto; Qinhong Han; Y U Sun; Hiroto Nishino; Yoshihiko Tashiro; Norihiko Sugisawa; Yuying Tan; Hee Jun Choi; Seok Jin Nam; Michael Bouvet; Robert M Hoffman Journal: In Vivo Date: 2020 Nov-Dec Impact factor: 2.155