Increasing experimental evidence suggests that IGF-1 may modulate tumor angiogenesis via activation of the expression of VEGF in Ewing sarcomas and rhabdomyosarcomas. This study investigates the effects of the PEGylated Adnectins™ CT-322, a VEGFR2-inhibitor and AT580Peg40, an IGF-1R inhibitor, as monotherapy and in combination in a murine A673 xenograft tumor model. The combination of Adnectins CT-322 and AT580Peg40 revealed a 83% reduction in tumor growth, a nearly 5 times lower vessel density, less necrotic areas and less appearance of intussusceptive angiogenesis. Monotherapy with IGF-1R or CT-322 revealed equally a significant inhibition of tumor and vessel growth. Combinatory inhibition of IGF-1R and VEGFR2 shows a downregulation of IGF-binding protein 2 and a compensatory upregulation of VEGF levels. Immunohistological analysis showed remodeling vascular effects of CT-322-treatment or combination therapy. The vascular architecture in Adnectin-treated tumors was characterized by a strong normalization of vasculature. 3D-evaluation in microvascular corrosion casts showed significantly higher intervascular and interbranching distances in Adnectin-treated tumors. CT-322-treatment and combinatory inhibition reveal a significant reduction of intussusceptive angiogenesis. These pronounced effects on tumor vasculature suggest potential therapeutic benefit of combinatorial IGF1- and VEGF-pathways inhibition in Ewing's sarcoma.
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http://dx.doi.org/10.1007/s10456-012-9294-9 | DOI Listing |
Rofo
January 2025
University Medical Center Rostock, Institute of Diagnostic and Interventional Radiology, Pediatric Radiology and Neuroradiology, Rostock, Germany.
Cureus
December 2024
Department of Orthopaedics and Traumatology, Cerrahpasa Faculty of Medicine, Istanbul University - Cerrahpasa, Istanbul, TUR.
Extraskeletal Ewing sarcoma (EES) is a rare and aggressive malignancy originating in soft tissues, distinct from osseous Ewing sarcoma. It commonly affects adolescents and young adults but can occur at any age. Due to its rarity and overlapping clinical features with other malignancies, EES poses significant diagnostic and therapeutic challenges.
View Article and Find Full Text PDFSkeletal Radiol
January 2025
Department of Radiology, Moffit Cancer Center Florida, Tampa, FL, USA.
The sacrum can harbor a diverse group of both benign and malignant tumors, including metastases. Primary tumors of the sacrum can arise from bone, cartilage, marrow, notochordal remnants, or surrounding nerves and vessels. Among a variety of primary tumors of the spine, chordoma, germ cell tumors and Ewing's sarcoma are recognized for their propensity to occur in the sacrum.
View Article and Find Full Text PDFJBJS Case Connect
January 2025
Department of Orthopaedic Surgery, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Case: Triple pelvic osteotomy (TPO) is used to treat developmental dysplasia of the hip in a pediatric population. This case report highlights a new indication for this procedure. Acetabular coverage was restored in a 9-year-old patient who experienced instability following hip hemiarthroplasty and proximal femur composite allograft implantation for the treatment of Ewing sarcoma.
View Article and Find Full Text PDFEcancermedicalscience
November 2024
Department of Radiation Oncology, Government Medical College and Hospital, Chandigarh 160030, India.
Background: There is limited data from India on Ewing sarcoma (ES) patients. We analysed the demographic and clinical profile of ES patients, the systemic chemotherapy, local treatment and outcomes in patients with localised, metastatic and recurrent disease.
Methods: Data of ES patients reporting from 2010 to 2019 to a tertiary care referral centre in north India was evaluated.
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