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Tissue Cell ; 76: 101762, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35245856

RESUMEN

The new modalities for treating patients with high-grade non-muscle invasive bladder cancer (HGNMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. Since NMIBC is sensitive to immunotherapy, Toll-like receptors (TLRs) agonist compounds may represent a potential antitumor therapeutic approach. Our research group developed a synthetic compound, with antitumor and immunological properties, called OncoTherad® (MRB-CFI-1). To evaluate the effects of OncoTherad® (MRB-CFI-1) and its compounds (P14-16 and CFI-1), thirty-six female C57Bl/6 J mice were divided into six groups (n = 6): Control, Cancer, Cancer + BCG (40 mg), Cancer + OncoTherad® (20 mg/mL), Cancer + P14-16 (20 mg/mL) and Cancer + CFI-1 (20 mg/mL). NMIBC was chemically induced (N-ethyl-N-nitrosourea 50 mg/mL) and the treatments were followed for six weeks. The bladder was collected and routinely processed for immunohistochemical analyses of the Toll-Like receptors signaling pathway (TLR2, TLR4, MyD88, IRF-3, IKK-α, NF-kB, TNF-α, TRIF, IFN-γ, IL-6). The results obtained showed that the tumor progression was 100 % reduced on OncoTherad® (MRB-CFI-1) treated animals. Immunohistochemical analysis demonstrated that while the conventional BCG treatment stimulated the canonic pathway, OncoTherad® (MRB-CFI-1) stimulated the non-canonical pathway (increasing expression of TLR4, TRIF, IRF, and IFNγ). OncoTherad® (MRB-CFI-1) could be considered a promising therapy in the treatment of NMIBC.


Asunto(s)
Glicoproteínas , Mycobacterium bovis , Nanoestructuras , Fosfatos , Receptores Toll-Like , Neoplasias de la Vejiga Urinaria , Animales , Vacuna BCG/farmacología , Femenino , Glicoproteínas/farmacología , Humanos , Inmunoterapia/métodos , Ratones , Nanoestructuras/administración & dosificación , Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología
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