RESUMO
Cutaneous melanoma is an aggressive and highly metastatic skin cancer. In recent years, immunotherapy and targeted small-molecule inhibitors have improved the overall survival of patients. Unfortunately, most patients in advanced stages of disease exhibit either intrinsically resistant or rapidly acquire resistance to these approved treatments. However, combination treatments have emerged to overcome resistance, and novel treatments based on radiotherapy (RT) and targeted radionuclide therapy (TRT) have been developed to treat melanoma in the preclinical mouse model, raising the question of whether synergy in combination therapies may motivate and increase their use as primary treatments for melanoma. To help clarify this question, we reviewed the studies in preclinical mouse models where they evaluated RT and TRT in combination with other approved and unapproved therapies from 2016 onwards, focusing on the type of melanoma model used (primary tumor and or metastatic model). PubMed® was the database in which the search was performed using mesh search algorithms resulting in 41 studies that comply with the inclusion rules of screening. Studies reviewed showed that synergy with RT or TRT had strong antitumor effects, such as tumor growth inhibition and fewer metastases, also exhibiting systemic protection. In addition, most studies were carried out on antitumor response for the implanted primary tumor, demonstrating that more studies are needed to evaluate these combined treatments in metastatic models on long-term protocols.
Assuntos
Melanoma , Neoplasias Cutâneas , Animais , Camundongos , Melanoma/tratamento farmacológico , Melanoma/radioterapia , Melanoma/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Terapia Combinada , Imunoterapia/métodos , Radioisótopos/uso terapêuticoRESUMO
Evaluate the anti-inflammatory activity in vivo and in vitro of cis-(±)-acetate of 4-chloro-6-(naphtalene-1-yl)-tetrahydro-2H-pyran-2-yl) methyl 2-(2-(2,6-diclorofenylamine) phenyl (LS19). Male Swiss mice were analyzed in the paw edema, ear edema, and air pouch tests, and in vitro COX inhibition, cytotoxicity evaluation, and cytokine and nitric oxide determination tests. The compound showed effect on the carrageenan- and bradykinin-induced paw edema and capsaicin-induced ear edema tests. In addition, the compound was able to inhibit leukocyte migration to decrease the levels of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) and to increase the levels of the anti-inflammatory cytokine IL-10. The compound was also able to reduce levels of TNF-α, IL-6, and nitric oxide in the RAW 264.7 cell line and to inhibit COX activity. LS19 did not induce any significant changes in the viability of RAW 264.7 cells, demonstrating safety for these cell lines. The compound LS19 did not reduce the production of gastric mucus and induced a smaller increase in the extent of gastric lesions than that developed by the administration of diclofenac. In summary, the new compound proved to be safer and it had additional mechanisms compared to diclofenac.
Assuntos
Anti-Inflamatórios não Esteroides , Anti-Inflamatórios , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Masculino , Camundongos , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfaRESUMO
The pressure injury environment is characterized by overproduction of reactive oxygen species and exacerbated inflammation, which impair the healing of these lesions. Mediterranean-like diet may be a good intervention to improve the healing of pressure injury owing to its anti-inflammatory and antioxidant components. Thus, this study evaluated the hypothesis that olive oil, as a main source of lipid in Mediterranean diet, could improve cutaneous wound healing of pressure injury in mice. Male Swiss mice were randomly divided into standard, olive oil, or soybean oil plus olive oil groups and fat represented 10% of total calories in all groups. Four weeks after the beginning of diet administration, 2 cycles of ischemia-reperfusion (IR) by external application of 2 magnets disks were performed in the dorsal skin to induce pressure injury formation. Fourteen days after the end of the second IR cycle, olive oil-based diet reduced neutrophils cells and cyclooxygenase-2 protein expression and increased nitric oxide synthase-2 and protein and lipid oxidation. Olive oil based-diet also increased nuclear factor erythroid 2-related factor 2 protein expression and collagen type I precursor protein expression. In addition, administration of olive oil-based diet promoted wound closure at 7, 10, and 14 days after the end of the second IR cycle. These findings support the hypothesis that olive oil-based diet improves cutaneous wound healing of pressure injury in mice through the reduction of inflammation and stimulation of redox equilibrium.
Assuntos
Lesões por Esmagamento , Dieta , Fator 2 Relacionado a NF-E2 , Óxido Nítrico Sintase Tipo II , Azeite de Oliva , Úlcera por Pressão , Pele , Cicatrização , Animais , Masculino , Camundongos , Colágeno Tipo I/metabolismo , Lesões por Esmagamento/terapia , Ciclo-Oxigenase 2/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Azeite de Oliva/farmacologia , Distribuição Aleatória , Espécies Reativas de Oxigênio/metabolismo , Pele/lesões , Úlcera por Pressão/terapiaRESUMO
Downhill running-based overtraining model increases the hypothalamic levels of IL-1ß, TNF-α, SOCS3, and pSAPK-JNK. The aim of the present study was to verify the effects of 3 overtraining protocols on the levels of BiP, pIRE-1 (Ser724), pPERK (Thr981), pelF2α (Ser52), ATF-6, GRP-94, caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) proteins in the mouse hypothalamus. The mice were randomized into the control, overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. After the overtraining protocols (i.e., at the end of week 8), hypothalamus was removed and used for immunoblotting. The OTR/down group exhibited increased levels of all of the analyzed endoplasmic reticulum stress markers in the hypothalamus at the end of week 8. The OTR/up and OTR groups exhibited increased levels of BiP, pIRE-1 (Ser724), and pPERK (Thr981) in the hypothalamus at the end of week 8. There were no significant differences in the levels of caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) between the experimental groups at the end of week 8. In conclusion, the 3 overtraining protocols increased the endoplasmic reticulum stress at the end of week 8.
Assuntos
Transtornos Traumáticos Cumulativos/metabolismo , Estresse do Retículo Endoplasmático , Hipotálamo/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Condicionamento Físico Animal/efeitos adversos , Esforço Físico , Animais , Apoptose , Biomarcadores/metabolismo , Western Blotting , Transtornos Traumáticos Cumulativos/etiologia , Transtornos Traumáticos Cumulativos/imunologia , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Hipotálamo/enzimologia , Hipotálamo/imunologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Neurônios/enzimologia , Neurônios/imunologia , Fosforilação , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/metabolismo , Distribuição Aleatória , Resposta a Proteínas não Dobradas , eIF-2 Quinase/metabolismoRESUMO
In the Guianese rainforest, we examined the impact of the presence of guano in and around a bat roosting site (a cave). We used ant communities as an indicator to evaluate this impact because they occupy a central place in the functioning of tropical rainforest ecosystems and they play different roles in the food web as they can be herbivores, generalists, scavengers or predators. The ant species richness around the cave did not differ from a control sample situated 500m away. Yet, the comparison of functional groups resulted in significantly greater numbers of detritivorous fungus-growing and predatory ant colonies around the cave compared to the control, the contrary being true for nectar and honeydew feeders. The role of bats, through their guano, was shown using stable isotope analyses as we noted significantly greater δ(15)N values for the ant species captured in and around the cave compared to controls.