Background/aim: A major challenge in treating soft-tissue sarcoma is the development of drug resistance. Eribulin, an anti-tubulin agent, is used as a second-line chemotherapy for patients with unresectable or metastatic soft-tissue sarcoma. However, most patients with advanced soft-tissue sarcoma are resistant to eribulin and do not survive. Recombinant methioninase (rMETase) targets the fundamental and general hallmark of cancer, methionine addiction, termed the Hoffman Effect. The present study aimed to show how much rMETase could increase the efficacy of eribulin on eribulin-resistant fibrosarcoma cells in vitro.
Materials And Methods: HT1080 human fibrosarcoma cells were exposed to step-wise increasing concentrations of eribulin from 0.15-0.4 nM to establish eribulin-resistant HT1080 (ER-HT1080). ER-HT1080 cells were cultured in vitro and divided into four groups: untreated control; eribulin treated (0.15 nM); rMETase treated (0.75 U/ml); and eribulin (0.15 nM) plus rMETase (0.75 U/ml) treated.
Results: The IC of eribulin on ER-HT1080 cells was 0.95 nM compared to the IC of 0.15 nM on HT1080 cells, a 6-fold increase. The IC of rMETase on ER-HT1080 and HT1080 was 0.87 U/ml and 0.75 U/ml, respectively. The combination of rMETase (0.75 U/ml) and eribulin (0.15 nM) was synergistic on ER-HT1080 cells resulting in an inhibition of 80.1% compared to eribulin alone (5.0%) or rMETase alone (47.1%) (p<0.05). rMETase thus increased the efficacy of eribulin 16-fold on eribulin-resistant fibrosarcoma cells.
Conclusion: The present study showed that the combination of eribulin and rMETase can overcome high eribulin resistance of fibrosarcoma. The present results demonstrate that combining rMETase with first- or second-line therapy for soft-tissue sarcoma has the potential to overcome the intractable clinical problem of drug-resistant soft-tissue sarcoma.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.21873/anticanres.17202 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS.
Cancer Med
January 2025
Department for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
Background: The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established.
View Article and Find Full Text PDFNew insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products.
Int J Biol Sci
January 2025
Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100029, China.
Anthracyclines (ANTs) are widely used in cancer therapy, particularly for lymphoma, sarcoma, breast cancer, and childhood leukemia, and have become the cornerstone of chemotherapy for various malignancies. However, it is associated with fatal and dose-dependent cardiovascular complications, especially cardiotoxicity. Mitochondrial quality control mechanisms, encompassing mitophagy, mitochondrial dynamics, and mitochondrial biogenesis, maintain mitochondrial homeostasis in the cardiovascular system.
View Article and Find Full Text PDFFrequency and treatment outcomes of chest wall masses: a 10-year report.
Kardiochir Torakochirurgia Pol
December 2024
Endoscopic and Minimally Invasive Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Introduction: Chest wall tumors, though rare, represent a significant subset of thoracic neoplasms, accounting for approximately 5% of thoracic and 2% of overall body neoplasms. Their management has historically posed challenges for surgeons, often leading to misdiagnosis, incomplete resection, and high complication rates. An individualized surgical approach, tailored to the specific characteristics of the disease, is crucial for optimizing outcomes.
View Article and Find Full Text PDFIncome and Insurance-Based Disparities in Primary Soft Tissue Sarcoma of the Extremities.
J Surg Oncol
January 2025
Department of Orthopaedic Surgery, University of California, Los Angeles, California, USA.
Background And Objectives: Soft tissue sarcomas (STSs) are rare but can be devastating. Paradigm shifts in adjuvant treatment have expanded the availability of limb salvage; however, a subset of patients still require amputation. The aim of this study was to examine the impact of patient, disease, and practice-related factors on rates of amputation in STS.
View Article and Find Full Text PDFImplant failure of the Compress prosthesis: a case report.
J Med Case Rep
January 2025
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Aichi, 466-8550, Japan.
Background: The Compress is designed to achieve bone formation and stability by applying pressure at the bone-implant interface, minimizing the likelihood of aseptic loosening, which is a complication of stem implants. Herein, we report two cases of implant failure using the Compress.
Case Presentation: Case 1 describes a 36 year-old Japanese man who underwent extraarticular tumor resection, Compress arthroplasty, and reconstruction with a gastrocnemius flap after preoperative chemotherapy for a secondary malignant giant cell tumor in the right distal femur.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!