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1.
Int J Mol Sci ; 23(14)2022 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-35886983

RESUMEN

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.


Asunto(s)
Antineoplásicos , Galectina 3 , Melanoma , Neoplasias Cutáneas , Animales , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Dacarbazina/metabolismo , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Galectina 3/metabolismo , Galectina 3/farmacología , Galectina 3/uso terapéutico , Ligandos , Melanoma/tratamiento farmacológico , Melanoma/metabolismo , Ratones , Recurrencia Local de Neoplasia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/metabolismo , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/fisiología
2.
Int J Biol Macromol ; 185: 551-561, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34216657

RESUMEN

Advanced melanoma patients that are not included in common genetic classificatory groups lack effective and safe therapeutic options. Chemotherapy and immunotherapy show unsatisfactory results and devastating adverse effects for these called triple wild-type patients. New approaches exploring the intrinsic antitumor properties of gold nanoparticles might reverse this scenario as a safer and more effective alternative. Therefore, we investigated the efficacy and safety of a composite made of gum arabic-functionalized gold nanorods (GA-AuNRs) against triple wild-type melanoma. The natural polymer gum arabic successfully stabilized the nanorods in the biological environment and was essential to improve their biocompatibility. In vivo results obtained from treating triple wild-type melanoma-bearing mice showed that GA-AuNRs remarkably reduced primary tumor growth by 45%. Furthermore, GA-AuNRs induced tumor histological features associated with better prognosis while also reducing superficial lung metastasis depth and the incidence of intrapulmonary metastasis. GA-AuNRs' efficacy comes from their capacity to reduce melanoma cells ability to invade the extracellular matrix and grow into colonies, in addition to a likely immunomodulatory effect induced by gum arabic. Additionally, a broad safety investigation found no evidence of adverse effects after GA-AuNRs treatment. Therefore, this study unprecedentedly reports GA-AuNRs as a potential nanomedicine for advanced triple wild-type melanomas.


Asunto(s)
Oro/administración & dosificación , Goma Arábiga/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Melanoma/tratamiento farmacológico , Animales , Células 3T3 BALB , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Matriz Extracelular/metabolismo , Oro/química , Oro/farmacología , Humanos , Neoplasias Pulmonares/metabolismo , Melanoma/metabolismo , Nanopartículas del Metal , Ratones , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Carbohydr Polym ; 225: 115203, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31521290

RESUMEN

A fucomannogalactan (FMG-Hm), with a molecular weight of 17.1 kDa, obtained from fruiting bodies of Hypsizygus marmoreus exhibited promising in vitro antimelanoma effects. FMG-Hm was not cytotoxic, nor did it alter the cell morphology and proliferation, but was able to inhibit colony-forming ability and cell migration in B16-F10 murine melanoma cells. An analysis of the monosaccharide composition indicated that FMG-Hm was composed of fucose, mannose, and galactose in a ratio of 1.00:1.08:3.17. The FMG-Hm was structurally characterized based on methylation analysis, partial acid hydrolysis, and NMR experiments. The results indicated that FMG-Hm contained a α-(1→6)-linked galactopyranosyl main chain, partially substituted at O-2 by non-reducing ends of α-L-fucopyranose and ß-D-mannopyranose. The predicted structure of the heteropolysaccharide was established as.


Asunto(s)
Agaricales/metabolismo , Galactanos/química , Galactanos/aislamiento & purificación , Galactanos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Cuerpos Fructíferos de los Hongos/metabolismo , Estructura Molecular , Peso Molecular
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