PMID- 36288875
OWN - NLM
STAT- MEDLINE
DCOM- 20221101
LR  - 20221101
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 42
IP  - 11
DP  - 2022 Nov
TI  - Oral-recombinant Methioninase in Combination With Rapamycin Eradicates 
      Osteosarcoma of the Breast in a Patient-derived Orthotopic Xenograft Mouse Model.
PG  - 5217-5222
LID - 10.21873/anticanres.16028 [doi]
AB  - BACKGROUND/AIM: Primary osteosarcoma of the breast is a very rare malignancy that 
      shares histological features with osteosarcoma. It is also highly sensitive to 
      methionine restriction due to methionine addiction. We previously established a 
      patient-derived orthotopic xenograft (PDOX) nude-mouse model derived from tumor 
      tissue of a patient with primary mammary osteosarcoma. In the present study, we 
      investigated the efficacy of oral-recombinant methioninase (o-rMETase), combined 
      with rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, on a 
      mammary osteosarcoma PDOX nude-mouse model. MATERIALS AND METHODS: The PDOX mouse 
      model was established by surgically transplanting a specimen of primary 
      osteosarcoma of the breast into the mammary gland of nude mice. Mice implanted 
      with tumors were randomly divided into four groups: Control group, N=5; 
      rapamycin-treated group, N=5; o-rMETase-treated group, N=5; and a group treated 
      with the combination of o-rMETase and rapamycin, N=5. Mice were treated for 2 
      weeks after transplantation, and tumor volume was measured during the treatment 
      period. RESULTS: Treatment with the combination of rapamycin and o-rMETase 
      eradicated the osteosarcoma of the breast compared to the untreated control 
      (p=0.000008). o-rMETase alone did not significantly inhibit tumor growth, and 
      rapamycin alone only partially inhibited the tumor (p=0.78 and p=0.018, 
      respectively) compared to the untreated control. There was not a significant 
      difference in mouse weight between the groups. CONCLUSION: The combination of 
      rapamycin and o-rMETase was highly effective against primary osteosarcoma of the 
      breast in a PDOX model, suggesting a future clinical strategy for this rare 
      cancer type that currently has no first-line treatment.
CI  - Copyright (c) 2022 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Masaki, Noriyuki
AU  - Masaki N
AD  - AntiCancer Inc, San Diego, CA, U.S.A.
AD  - Graduate School of Medicine, International University of Health and Welfare, 
      Tokyo, Japan.
AD  - Department of Surgery, University of California, San Diego, CA, U.S.A.
FAU - Han, Qinghong
AU  - Han Q
AD  - AntiCancer Inc, San Diego, CA, U.S.A.
FAU - Samonte, Carissa
AU  - Samonte C
AD  - AntiCancer Inc, San Diego, CA, U.S.A.
FAU - Wu, Nathaniel F
AU  - Wu NF
AD  - Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 
      U.S.A.
FAU - Hozumi, Chihiro
AU  - Hozumi C
AD  - AntiCancer Japan Inc, Narita, Japan.
FAU - Wu, Justin
AU  - Wu J
AD  - Department of General Surgery, Kaiser Permanente San Diego Medical Center, San 
      Diego, CA, U.S.A.
FAU - Obara, Koya
AU  - Obara K
AD  - AntiCancer Inc, San Diego, CA, U.S.A.
AD  - Department of Surgery, University of California, San Diego, CA, U.S.A.
FAU - Kubota, Yutaro
AU  - Kubota Y
AD  - AntiCancer Inc, San Diego, CA, U.S.A.
AD  - Department of Surgery, University of California, San Diego, CA, U.S.A.
FAU - Aoki, Yusuke
AU  - Aoki Y
AD  - AntiCancer Inc, San Diego, CA, U.S.A.
AD  - Department of Surgery, University of California, San Diego, CA, U.S.A.
FAU - Bouvet, Michael
AU  - Bouvet M
AD  - Department of Surgery, University of California, San Diego, CA, U.S.A.
FAU - Hoffman, Robert M
AU  - Hoffman RM
AD  - AntiCancer Inc, San Diego, CA, U.S.A.; all@anticancer.com.
AD  - Department of Surgery, University of California, San Diego, CA, U.S.A.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial, Veterinary
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - EC 4.4.- (Carbon-Sulfur Lyases)
RN  - EC 4.4.1.11 (L-methionine gamma-lyase)
RN  - AE28F7PNPL (Methionine)
RN  - 0 (Recombinant Proteins)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Bone Neoplasms/drug therapy
MH  - Carbon-Sulfur Lyases/pharmacology
MH  - Disease Models, Animal
MH  - Heterografts
MH  - Methionine
MH  - Mice, Nude
MH  - *Osteosarcoma/drug therapy/pathology
MH  - Recombinant Proteins/pharmacology/therapeutic use
MH  - Sirolimus/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Breast osteosarcoma
OT  - Hoffman effect
OT  - PDOX
OT  - combination therapy
OT  - efficacy
OT  - methioninase
OT  - nude mice
OT  - rapamycin
OT  - synergy
EDAT- 2022/10/27 06:00
MHDA- 2022/10/29 06:00
CRDT- 2022/10/26 20:53
PHST- 2022/09/03 00:00 [received]
PHST- 2022/09/23 00:00 [revised]
PHST- 2022/09/27 00:00 [accepted]
PHST- 2022/10/26 20:53 [entrez]
PHST- 2022/10/27 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
AID - 42/11/5217 [pii]
AID - 10.21873/anticanres.16028 [doi]
PST - ppublish
SO  - Anticancer Res. 2022 Nov;42(11):5217-5222. doi: 10.21873/anticanres.16028.