Hye In Lim1,2,3, Jun Yamamoto4,2, Qinhong Han4, Y U Sun4,2, Hiroto Nishino4,2, Yoshihiko Tashiro4,2, Norihiko Sugisawa4,2, Yuying Tan4, Hee Jun Choi5, Seok Jin Nam6, Michael Bouvet2, Robert M Hoffman1,2. 1. AntiCancer Inc, San Diego, CA, U.S.A. all@anticancer.com vastprogress@naver.com. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Surgery, Chinjujeil Hospital, Jinju, Republic of Korea. 4. AntiCancer Inc, San Diego, CA, U.S.A. 5. Department of Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea. 6. Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Abstract
BACKGROUND/AIM: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. MATERIALS AND METHODS: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. RESULTS: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm3 in the control group; 160.0 mm3 in the o-rMETase 100 U group; and 245.3 mm3 in the o-rMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p<0.05). CONCLUSION: The TNBC liver metastasis was highly aggressive resulting in re-metastasis and ascites. o-rMETase tended to inhibit the liver metastasis and significantly improved the mouse body-condition score. This new PDOX model of TNBC liver metastasis will be useful for identifying effective agents for this recalcitrant disease. Copyright
BACKGROUND/AIM: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. MATERIALS AND METHODS: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. RESULTS: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm3 in the control group; 160.0 mm3 in the o-rMETase 100 U group; and 245.3 mm3 in the o-rMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p<0.05). CONCLUSION: The TNBC liver metastasis was highly aggressive resulting in re-metastasis and ascites. o-rMETase tended to inhibit the liver metastasis and significantly improved the mouse body-condition score. This new PDOX model of TNBC liver metastasis will be useful for identifying effective agents for this recalcitrant disease. Copyright
Authors: Rebecca Dent; Maureen Trudeau; Kathleen I Pritchard; Wedad M Hanna; Harriet K Kahn; Carol A Sawka; Lavina A Lickley; Ellen Rawlinson; Ping Sun; Steven A Narod Journal: Clin Cancer Res Date: 2007-08-01 Impact factor: 12.531
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