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1.
Int J Mol Sci ; 21(7)2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32290096

RESUMO

Synovial sarcoma, an uncommon cancer, typically affects young adults. Survival rates range from 36% to 76%, decreasing significantly when metastases are present. Synovial sarcomas form in soft tissues, often near bones, with about 10% demonstrating ossification in the tumor. The literature is inconclusive on whether the presence of ossification portends a worse prognosis. To this end, we analyzed our genetic mouse models of synovial sarcoma to determine the extent of ossification in the tumors and its relationship with morbidity. We noted higher ossification within our metastatic mouse model of synovial sarcoma. Not only did we observe ossification within the tumors at a frequency of 7%, but an even higher frequency, 72%, of bone reactivity was detected by radiography. An enrichment of bone development genes was associated with primary tumors, even in the absence of an ossification phenotype. In spite of the ossification being intricately linked with the metastatic model, the presence of ossification was not associated with a faster or worse morbidity in the mice. Our conclusion is that both metastasis and ossification are dependent on time, but that they are independent of one another.


Assuntos
Ossificação Heterotópica , Fenótipo , Sarcoma Sinovial/patologia , Animais , Biomarcadores Tumorais , Biópsia , Osso e Ossos/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Fusão Gênica , Genótipo , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Camundongos , Metástase Neoplásica , Prognóstico , Sarcoma Sinovial/etiologia , Sarcoma Sinovial/metabolismo , Sarcoma Sinovial/mortalidade
2.
Pharmaceuticals (Basel) ; 15(6)2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35745569

RESUMO

Synovial sarcoma (SS) is a pediatric muscle cancer that primarily affects adolescents and young adults and has few treatment options. Complicating the treatment of synovial sarcoma is the low mutational burden of SS. Inflammatory pathways have been identified as being upregulated in some SS, leading to the discovery of upregulated oncostatin M receptor (OSMR). It was found that OSMR is upregulated in SS by RNAseq analysis and quantitative PCR, highlighting its potential in the treatment of SS. Also, OSMR is upregulated in mouse models for synovial sarcoma as demonstrated by western blot and immunohistochemistry, and the protein is present in both primary and metastatic sites of disease. Using a radioimmune therapy drug model, targeted therapy was synthesized for use in OSMR expressing SS and it was demonstrated that this drug is stable, while capable of efficient OSMR binding and isotope capture. Finally, this antibody conjugate exhibited ideal pharmacokinetics and targeted sites of disease in our mouse model and was taken up in both primary and metastatic diseased tissue. This suggests OSMR as an ideal target for therapy and this radioimmune therapy provides a novel treatment option for a disease with few therapy choices.

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