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1.
J Craniofac Surg ; 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283094

RESUMO

The aim of this study was to prospectively evaluate the diagnostic accuracy between the position of the disc in the temporomandibular joint (TMJ) according to findings on magnetic resonance (MRI) imaging and the position of the disc depending on the "roofing" in arthroscopic evaluation in patients who underwent arthroscopy for a temporomandibular disorder (TMD). This relationship was analyzed in 298 patients diagnosed with internal derangements. The concordance between the 2 methods was evaluated using the κ coefficient. A significant agreement was observed between the findings in MRI and roofing in arthroscopy with an excellent concordance between the variables (κ=0.83, P<0.05). This indicates that both diagnostic methods are equally valid in the precise description and evaluation of the disc position for patients with a TMD undergoing arthroscopy.

2.
Clin Transl Med ; 14(5): e1670, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38689429

RESUMO

BACKGROUND: Treatment for osteosarcoma, a paediatric bone cancer with no therapeutic advances in over three decades, is limited by a lack of targeted therapies. Osteosarcoma frequently metastasises to the lungs, and only 20% of patients survive 5 years after the diagnosis of metastatic disease. We found that WNT5B is the most abundant WNT expressed in osteosarcoma tumours and its expression correlates with metastasis, histologic subtype and reduced survival. METHODS: Using tumor-spheroids to model cancer stem-like cells, we performed qPCR, immunoblotting, and immunofluorescence to monitor changes in gene and protein expression. Additionally, we measured sphere size, migration and forming efficiency to monitor phenotypic changes. Therefore, we characterised WNT5B's relevance to cancer stem-like cells, metastasis, and chemoresistance and evaluated its potential as a therapeutic target. RESULTS: In osteosarcoma cell lines and patient-derived spheres, WNT5B is enriched in stem cells and induces the expression of the stemness gene SOX2. WNT5B promotes sphere size, sphere-forming efficiency, and cell proliferation, migration, and chemoresistance to methotrexate (but not cisplatin or doxorubicin) in spheres formed from conventional cell lines and patient-derived xenografts. In vivo, WNT5B increased osteosarcoma lung and liver metastasis and inhibited the glycosaminoglycan hyaluronic acid via upregulation of hyaluronidase 1 (HYAL1), leading to changes in the tumour microenvironment. Further, we identified that WNT5B mRNA and protein correlate with the receptor ROR1 in primary tumours. Targeting WNT5B through inhibition of WNT/ROR1 signalling with an antibody to ROR1 reduced stemness properties, including chemoresistance, sphere size and SOX2 expression. CONCLUSIONS: Together, these data define WNT5B's role in driving osteosarcoma cancer stem cell expansion and methotrexate resistance and provide evidence that the WNT5B pathway is a promising candidate for treating osteosarcoma patients. KEY POINTS: WNT5B expression is high in osteosarcoma stem cells leading to increased stem cell proliferation and migration through SOX2. WNT5B expression in stem cells increases rates of osteosarcoma metastasis to the lungs and liver in vivo. The hyaluronic acid degradation enzyme HYAL1 is regulated by WNT5B in osteosarcoma contributing to metastasis. Inhibition of WNT5B with a ROR1 antibody decreases osteosarcoma stemness.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Osteossarcoma , Proteínas Wnt , Osteossarcoma/patologia , Osteossarcoma/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Wnt/metabolismo , Proteínas Wnt/genética , Animais , Camundongos , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/tratamento farmacológico , Metástase Neoplásica/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Linhagem Celular Tumoral
3.
Int Forum Allergy Rhinol ; 14(7): 1253-1257, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38343159

RESUMO

KEY POINT: Social determinants of health interactively influence sinonasal cancer care and prognosis. Housing-transportation and socioeconomic status showed the largest associations with disparities. The social vulnerability index can reveal the social determinants of sinonasal cancers.


Assuntos
Neoplasias dos Seios Paranasais , Humanos , Estados Unidos/epidemiologia , Prognóstico , Neoplasias dos Seios Paranasais/epidemiologia , Neoplasias dos Seios Paranasais/terapia , Masculino , Feminino , Determinantes Sociais da Saúde , Pessoa de Meia-Idade , Idoso , Classe Social , Disparidades em Assistência à Saúde , Adulto , Fatores Socioeconômicos , Populações Vulneráveis/estatística & dados numéricos
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