RESUMO
Vascular endothelial growth factor (VEGF) plays a significant role as a pro-angiogenic and pro-permeability factor within the kidney. Bevacizumab is a pharmaceutical monoclonal anti-VEGF antibody that inhibits the growth of new blood vessels, which blocks blood supply and thereby restricts tumor growth. Thus, we conducted a nationwide study to explore the risk of chronic kidney disease (CKD) development in Taiwan residents after bevacizumab therapy. We drew data from the extensive National Health Insurance Research Database (NHIRD), which encompasses data from >99% of Taiwan's population from 1995 onwards. Individuals who received bevacizumab between 2012-2018 were identified as the bevacizumab cohort, with the index date set at the first usage. We randomly selected dates within the study period for the control group to serve as index dates. We excluded patients with a history of CKD prior to the index date or those <20 years old. In both cohorts, patients' propensity scores matched in a 1:1 ratio based on sex, age, index year, income, urbanization level, comorbidities, and medications. We found patients treated with bevacizumab had a significantly higher risk of contracting CKD than patients without bevacizumab (adjusted hazard ratio = 1.35, 95% confidence interval = 1.35-1.73). The risk of CKD was 1.35-fold higher in participants with bevacizumab treatment than those in the control group. These findings suggest that close monitoring of CKD development after bevacizumab administration is needed.
Assuntos
Insuficiência Renal Crônica , Fator A de Crescimento do Endotélio Vascular , Humanos , Adulto Jovem , Adulto , Bevacizumab/efeitos adversos , Estudos Retrospectivos , Taiwan/epidemiologia , Insuficiência Renal Crônica/epidemiologiaRESUMO
To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog (PTEN) pathway to suppress the focal adhesion kinase (FAK)/Src signaling and downstream signal molecules, thus inhibiting cell migration and the formation of invadopodia in murine melanoma cancer cell line (B16-F10). Importantly, p17-induced formation of invadopodia could be reversed in cells transfected with the mutant PTENC124A. p17 protein was found to significantly reduce the expression levels of tyrosine kinase substrate 5 (TKs5), Rab40b, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), and matrix metalloproteinases (MMP9), suggesting that TKs5 and Rab40b were transcriptionally downregulated by p17. Furthermore, we found that p17 suppresses the formation of the TKs5/NCK1 complex. Coexpression of TKs5 and Rab40b in B16-F10 cancer cells reversed p17-modulated suppression of the formation of invadopodia. This work provides new insights into p17-modulated suppression of invadopodia formation by activating the p53/PTEN pathway, suppressing the FAK/Src pathway, and inhibiting the formation of the TKs5/NCK1 complex.
Assuntos
Movimento Celular , Quinase 1 de Adesão Focal , Orthoreovirus Aviário , Podossomos , Transdução de Sinais , Animais , Camundongos , Orthoreovirus Aviário/fisiologia , Orthoreovirus Aviário/genética , Linhagem Celular Tumoral , Podossomos/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Vírus Oncolíticos/fisiologia , Vírus Oncolíticos/genética , Quinases da Família src/metabolismo , Quinases da Família src/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Melanoma Experimental/terapia , Melanoma Experimental/patologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genéticaRESUMO
Viruses are the most abundant biological entities on Earth and play a significant role in the evolution of many organisms and ecosystems. In pathogenic protozoa, the presence of viruses has been linked to an increased risk of treatment failure and severe clinical outcome. Here, we studied the molecular epidemiology of the zoonotic disease cutaneous leishmaniasis in Peru and Bolivia through a joint evolutionary analysis of Leishmania braziliensis and their dsRNA Leishmania virus 1. We show that parasite populations circulate in tropical rainforests and are associated with single viral lineages that appear in low prevalence. In contrast, groups of hybrid parasites are geographically and ecologically more dispersed and associated with an increased prevalence, diversity and spread of viruses. Our results suggest that parasite gene flow and hybridization increased the frequency of parasite-virus symbioses, a process that may change the epidemiology of leishmaniasis in the region.