ArticleIn vivo (Athens, Greece)
Oral-recombinant Methioninase Lowers the Effective Dose and Eliminates Toxicity of Cisplatinum for Primary Osteosarcoma of the Mammary Gland in a Patient-derived Orthotopic Xenograft Mouse Model.
Article in In vivo (Athens, Greece). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- How to efficiently establish animal models of cholangiocarcinoma: challenges and inspiration.Medical review (2021) · 2026Review
- A perspective on patient-derived orthotopic xenograft (PDOX) mouse models for identification of novel and individualized treatment for sarcoma.International journal of clinical oncology · 2025Review
- Article
- Rescue of Methionine Dependence by Cobalamin in a Human Colorectal Cancer Cell Line.Nutrients · 2024Article
- Recombinant Methioninase Lowers the Effective Dose of Regorafenib Against Colon-Cancer Cells: A Strategy for Widespread Clinical Use of a Toxic Drug.Cancer diagnosis & prognosisArticle
- Induction of the DNA-Repair Gene POLQ only in BRCA1-mutant Breast-Cancer Cells by Methionine Restriction.Cancer genomics & proteomicsArticle
- Complete Response (CR) in a Previously-progressing Chronic Lymphocytic Leukemia (CLL) Patient Treated With Methionine Restriction in Combination With First-line Chemotherapy.Cancer diagnosis & prognosisArticle
- Prostate Cancer Patient With Lymph-node Metastasis Treated Only With Methionine Restriction Has Stable Disease for Two Years Demonstrated With PET/CT and PSMA-PET Scanning and PSA Testing.Cancer diagnosis & prognosisArticle
- Ultra-low Concentrations of Cisplatinum Down to the ICIn vivo (Athens, Greece)Article
- Synergy of Combining Methionine Restriction and Chemotherapy: The Disruptive Next Generation of Cancer Treatment.Cancer diagnosis & prognosisReview
- Synergy of a Low-methionine Diet and Reduced-dose Cisplatinum Eradicates Experimental Lung-cancer Bone Metastases in a Nude-mouse Model.In vivo (Athens, Greece)Article
- Precise and Facile Endotracheal Lung-tumor-implantation Mouse Model Visualized by GFP Expression.In vivo (Athens, Greece)Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimPrimary osteosarcoma of the mammary gland is a very rare disease, accounting for under 1% of all mammary gland malignancies. There is no established first-line treatment, and prognosis is poor compared to conventional breast cancer. We previously demonstrated the efficacy of cisplatinum and eribulin in a patient-derived orthotopic xenograft (PDOX) mouse model of primary breast osteosarcoma. However, these drugs show significant clinical toxicity. All cancers are addicted to methionine (Hoffman effect). In the present study, we determined whether methionine restriction with oral recombinant methioninase (o-rMETase) would lower the effective dose of cisplatinum in a PDOX model of primary osteosarcoma of the mammary gland, thereby reducing its toxicity. MATERIALS AND
methodsMouse PDOX models of primary osteosarcoma of the breast were randomized into the following groups: control; cisplatinum (weekly at 3 or 6 mg/kg); twice-daily o-rMETase; or o-rMETase combined with 3 mg/kg cisplatinum, with treatment for 2 weeks.
resultsCisplatinum at 6 mg/kg significantly inhibited breast osteosarcoma growth compared with the untreated control and mice treated with 3 mg/kg cisplatinum (p=0.01 and 0.009, respectively). There was no significant difference in tumor growth between mice treated with cisplatinum at 3 mg/kg and the control (p=0.16). Combination therapy with cisplatinum at 3 mg/kg and twice daily o-rMETase regressed the osteosarcoma of the mammary gland (p=0.009), similar to the inhibition by cisplatinum at 6 mg/kg alone. Cisplatinum at 6 mg/kg caused a significant loss of mouse body weight, compared to the control (p=0.02). There was no significant body-weight loss with the combination therapy of o-rMETase and cisplatinum at 3 mg/kg, compared to the untreated control.
conclusiono-rMETase halved the effective dose of cisplatinum, thereby eliminating cisplatinum toxicity, demonstrating a future clinical strategy for therapy of osteosarcoma of the breast.
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