RESUMEN
PURPOSE: In light of continued innovation in cancer immunotherapy regimens and surgical management, no studies currently exist assessing the effect of these advances on global disparities in lip and oral cavity cancer disease burden. The purpose of this study is to characterize longitudinal trends in disease burden caused by lip and oral cavity cancers globally. MATERIALS AND METHODS: This retrospective, longitudinal cohort study extracted data on lip and oral cavity cancer disease burden from The Global Health Data Exchange for 1990-2017. The primary predictor variable was country human development index (HDI). The primary outcome variable was disease burden, measured by age-standardized disability-adjusted life years (DALYs) per 100,000 population, listed for each individual country. Additional variables assessed include country-level data on alcohol consumption and tobacco smoking. Concentration indices were also calculated. Mann-Whitney U and Kruskal-Wallis one-way analysis of variance tests with Bonferroni correction were utilized with a significance threshold of 0.008. RESULTS: A total of 185 countries met inclusion criteria. Global age-standardized DALYs increased from 44.5 ± 35.7 to 51.1 ± 41.1 from 1990 to 2017. High HDI and medium HDI countries showed a +37.6% and +22.4% median increase in DALYs, respectively, which is significantly greater than very-high HDI (+3.8%) and low HDI countries (-0.5%) (P < .001). The concentration index for lip and oral cavity cancer became increasingly negative from -0.064 to -0.077 from 1990 to 2015. In 2017, disease burden was concentrated in South Asia and Eastern Europe. CONCLUSIONS: High and medium HDI countries experienced a disproportionate growth in lip and oral cavity cancer disease burden. These findings may have resulted from increased life expectancy among these countries. Global and public health policy initiatives should focus on understanding the mechanisms driving these disparities with the goal of reducing disease burden globally.
Asunto(s)
Labio , Neoplasias de la Boca , Humanos , Estudios Longitudinales , Neoplasias de la Boca/epidemiología , Años de Vida Ajustados por Calidad de Vida , Estudios RetrospectivosRESUMEN
Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in individual cells detaching and assuming a migratory and invasive phenotype. Epithelial scattering recapitulates cancer progression and studies have implicated HGF signaling as a driver of cancer metastasis. Inhibitors of HGF signaling have been proposed to act as anti-cancer agents. We previously screened a small molecule library for compounds that block HGF-induced epithelial scattering. Most hits identified in this screen exhibit anti-mitotic properties. Here we assess the biological mechanism of a compound that blocks HGF-induced scattering with limited anti-mitotic activity. Analogs of this compound have one of two distinct activities: inhibiting either cell migration or cell proliferation with cell cycle arrest in G2/M. Each activity bears unique structure-activity relationships. The mechanism of action of anti-mitotic compounds is by inhibition of microtubule polymerization; these compounds entropically and enthalpically bind tubulin in the colchicine binding site, generating a conformational change in the tubulin dimer.
Asunto(s)
Amidas/farmacología , Antineoplásicos/farmacología , Células Epiteliales/efectos de los fármacos , Factor de Crecimiento de Hepatocito/antagonistas & inhibidores , Piridinas/farmacología , Pirimidinas/farmacología , Amidas/síntesis química , Amidas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células Epiteliales/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Humanos , Células MCF-7 , Estructura Molecular , Piridinas/síntesis química , Piridinas/química , Pirimidinas/síntesis química , Pirimidinas/química , Relación Estructura-ActividadRESUMEN
PURPOSE: Oral diseases pose a serious global health challenge. As such, dental education must integrate global health with emphasis on scalable and sustainable solutions. The aim of our study was to capture the scope of global health programs offered to dental students in the United States and identify ways in which dental schools may modify their curricula to improve global health knowledge and accessibility for students. MATERIALS AND METHODS: For this cross-sectional, cohort study, the investigators sent a confidential and electronic survey to 213 faculty members at the 67 accredited dental schools in the United States. This voluntary survey was distributed in September and October of 2020 with answers being self-reported. RESULTS: A total of 40 different schools are represented in this study, representing 59.7% of accredited dental schools in the United States. Using descriptive statistics, the results present existing global health opportunities, barriers preventing schools from expanding global health education, and necessary resources that schools without a program need to establish one. CONCLUSION: Our results demonstrate promising findings, in relation to global health being a vital part of dental education. However, there is an urgent need for enhanced and more structured education in this space. As the global burden of oral disease contributes to the degree and severity of noncommunicable diseases worldwide, the development of a sustainable, preventive primary care approach must integrate oral health, making future dental professionals a crucial component of global health.