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2.
Mol Oncol ; 18(4): 1012-1030, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38217262

RESUMO

Triple-negative breast cancer (TNBC) is a leading cause of cancer mortality and lacks modern therapy options. Modulated electro-hyperthermia (mEHT) is an adjuvant therapy with demonstrated clinical efficacy for the treatment of various cancer types. In this study, we report that mEHT monotherapy stimulated interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) expression, and consequently cyclooxygenase 2 (COX-2), which may favor a cancer-promoting tumor microenvironment. Thus, we combined mEHT with nonsteroid anti-inflammatory drugs (NSAIDs): a nonselective aspirin, or the selective COX-2 inhibitor SC236, in vivo. We demonstrate that NSAIDs synergistically increased the effect of mEHT in the 4T1 TNBC model. Moreover, the strongest tumor destruction ratio was observed in the combination SC236 + mEHT groups. Tumor damage was accompanied by a significant increase in cleaved caspase-3, suggesting that apoptosis played an important role. IL-1ß and COX-2 expression were significantly reduced by the combination therapies. In addition, a custom-made nanostring panel demonstrated significant upregulation of genes participating in the formation of the extracellular matrix. Similarly, in the B16F10 melanoma model, mEHT and aspirin synergistically reduced the number of melanoma nodules in the lungs. In conclusion, mEHT combined with a selective COX-2 inhibitor may offer a new therapeutic option in TNBC.


Assuntos
Benzenossulfonamidas , Hipertermia Induzida , Melanoma , Pirazóis , Neoplasias de Mama Triplo Negativas , Humanos , Melanoma/tratamento farmacológico , Ciclo-Oxigenase 2 , Neoplasias de Mama Triplo Negativas/terapia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Aspirina/farmacologia , Aspirina/uso terapêutico , Microambiente Tumoral
3.
J Mater Sci Mater Med ; 25(4): 1137-48, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24378848

RESUMO

Mineralized poly(ε-caprolactone)/gelatin core-shell nanofibers were prepared via co-axial electrospinning and subsequent incubation in biomimetic simulated body fluid containing ten times the calcium and phosphate ion concentrations found in human blood plasma. The deposition of calcium phosphate on the nanofiber surfaces was investigated through scanning electronic microscopy and X-ray diffraction. Energy dispersive spectroscopy results indicated that calcium-deficient hydroxyapatite had grown on the fibers. Fourier transform infrared spectroscopy analysis suggested the presence of hydroxyl-carbonate-apatite. The results of a viability assay (MTT) and alkaline phosphatase activity analysis suggested that these mineralized matrices promote osteogenic differentiation of human adipose-derived stem cells (hASCs) when cultured in an osteogenic medium and have the potential to be used as a scaffold in bone tissue engineering. hASCs cultured in the presence of nanofibers in endothelial differentiation medium showed lower rates of proliferation than cells cultured without the nanofibers. However, endothelial cell markers were detected in cells cultured in the presence of nanofibers in endothelial differentiation medium.


Assuntos
Tecido Adiposo/citologia , Células-Tronco Adultas/citologia , Materiais Biocompatíveis/química , Nanofibras/química , Células-Tronco Adultas/enzimologia , Fosfatase Alcalina/metabolismo , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Células Endoteliais/citologia , Gelatina/química , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Minerais/química , Nanofibras/ultraestrutura , Osteogênese , Poliésteres/química
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