RT Journal Article
SR Electronic
T1 Oral Recombinant Methioninase Overcomes Colorectal-cancer Liver Metastasis Resistance to the Combination of 5-Fluorouracil and Oxaliplatinum in a Patient-derived Orthotopic Xenograft Mouse Model
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4667
OP 4671
DO 10.21873/anticanres.13648
VO 39
IS 9
A1 HIROMICHI OSHIRO
A1 YASUNORI TOME
A1 TASUKU KIYUNA
A1 SANG NAM YOON
A1 THINZAR M. LWIN
A1 QINGHONG HAN
A1 YUYING TAN
A1 KENTARO MIYAKE
A1 TAKASHI HIGUCHI
A1 NORIHIKO SUGISAWA
A1 YUKI KATSUYA
A1 JUN HO PARK
A1 ZHIYING ZANG
A1 SAHAR RAZMJOOEI
A1 MICHAEL BOUVET
A1 BRYAN CLARY
A1 SHREE RAM SINGH
A1 FUMINORI KANAYA
A1 KOTARO NISHIDA
A1 ROBERT M. HOFFMAN
YR 2019
UL http://ar.iiarjournals.org/content/39/9/4667.abstract
AB 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.