Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Transl Oncol ; 41: 101887, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262112

RESUMO

BACKGROUND: The progression and metastasis of tumors are typically accompanied by angiogenesis. Crucially, vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a significant role in tumor-associated angiogenesis. In this study, the aim was to investigate the antitumor effect of combining bevacizumab (Bev) with anlotinib (An) on colorectal cancer (CRC). METHODS: The CCK-8 assay, EdU assay, and Annexin V staining were conducted to evaluate the proliferation and apoptosis of CRC cells in vitro. The migration capability of CRC cells and HUVECs was assessed using the Transwell assay. Additionally, the tube formation capability of HUVECs was investigated. Furthermore, the antitumor and antiangiogenic effects were evaluated in the BALB/c mice model using immunohistochemistry, TUNEL staining, and 18F-FDG PET/CT imaging. Finally, we analyzed the inhibitory effect of Bev and/or An on related signaling effectors through western blotting. RESULTS: The in vivo CRC mice model revealed that the combination of Bev + An significantly suppressed tumor formation and angiogenesis. Bev + An inhibited tumor glucose metabolism and increased the median survival period in tumor-bearing mice. Mechanistically, the expressions of VEGF, VEGFR2, PDGFR, and FGFR, as well as the phosphorylation levels of AKT, were inhibited after Bev+An treatment. In conclusion, the dual vertical targeting of VEGF and VEGFR in the CRC mice model strongly inhibited tumor growth and angiogenesis, with the suppression of the AKT signaling pathway playing a partial role.

2.
Front Cell Neurosci ; 18: 1458720, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39355176

RESUMO

Background: A number of drugs are toxic to the cochlear sensory cells known as hair cells (HCs), resulting in hearing loss. Treatment with survival-promoting growth factors, antioxidants, and inhibitors of cell death pathways or proteinases have been shown to reduce HC damage in in vivo and/or in vitro animal models. Conversely, translation to humans has often been disappointing. This may be due to the complexity of intracellular damage processes. We hypothesized that combining treatments targeting different cellular processes would be more effective. Methods: Using an in vitro model of gentamicin ototoxicity for murine cochlear hair cells, we screened all 56 possible combinations of inhibitors targeting five different cell damage mechanisms, plus the activator of one cell survival pathway, each of which have been shown to be singly effective in preventing HC loss in experimental studies. A high dose of gentamicin (200 µM) was used over three days in culture. All compounds were added at a dosage below that required for significant protection in the assay, and only this single dose was then employed. This was done so that we could more easily detect interactive, as opposed to additive, effects. Results: Increasing protection of hair cells was observed as combinations of compounds were increased from two to four factors, although not all combinations were equally protective. The optimal combination of four compounds consisted of an anti-oxidant, an apoptosis inhibitor, an autophagy inhibitor and a protective growth factor. Increasing the number of factors to five or six resulted in decreased protection. Conclusion: The results support the hypothesis that targeting multiple cellular damage or survival pathways provides more an effective hair cell protection approach. The results help to identify critical interactions among the cellular processes that operate in gentamicin ototoxicity. They also suggest that inhibiting too many biological processes impairs functions critical to HC survival, resulting in decreased protection.

3.
Front Cell Dev Biol ; 11: 1309719, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38161332

RESUMO

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte's programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI.

4.
J Drug Target ; 28(9): 961-969, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32374627

RESUMO

Angiogenesis is involved in the proliferation and metastasis of solid tumours; hence, it is an attractive therapeutic target. However, most patients who undergo anti-angiogenic drug treatment do not achieve complete tumour regression, resulting in drug resistance. The objective of this research is to explore the therapeutic effect of combining bevacizumab (Bev), an anti-vascular endothelial growth factor (VEGF)-A antibody, with apatinib (Apa), a VEGR receptor (VEGFR)-2-targeting tyrosine kinase inhibitor, in non-small cell lung cancer (NSCLC). In vitro, we assessed the influence which Bev + Apa treatment exerts upon the proliferation as well as apoptosis of Lewis lung carcinoma (LLC) cells in virtue of the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide as assay as well as Annexin V staining, respectively. For in vivo assessment, we established a tumour-bearing mouse model with LLC cells and investigated the anti-angiogenic and antitumor effects of Bev + Apa by 18F-FDG PET/CT imaging, immunohistochemistry and TUNEL staining. Bev + Apa treatment significantly inhibited LLC cell growth and proliferation in a larger scale compared to therapy of either of the only agent. Bev + Apa inhibited tumour growth and extended the median survival time of tumour-bearing mice. Mechanistically, Bev + Apa reduced angiogenesis by inhibiting VEGF and VEGFR-2 expression and reducing glucose metabolism in tumour tissues. Thus, Bev and Apa inhibited tumour angiogenesis synergistically, indicating their potential clinical utility for NSCLC treatment.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Bevacizumab/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA