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1.
Inj Epidemiol ; 11(Suppl 1): 44, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39237989

RESUMO

BACKGROUND: Head injuries are the most common cause of death in some motorized vehicles for which helmet use can significantly decrease the risk. Our objective was to determine rural adolescents' attitudes regarding helmets and their use while riding ATVs, motorcycles and dirt bikes. METHODS: A convenience sample of 2022 Iowa FFA (formerly Future Farmers of America) Leadership Conference attendees were surveyed. After compilation, data were imported into the statistical program, R ( https://www.R-project.org/ ). Descriptive statistics, contingency table, logistic regression and non-parametric alternatives to ANOVA analyses were performed. RESULTS: 1331 adolescents (13-18 years) participated. One half lived on a farm, 21% lived in the country/not on a farm and 28% were from towns. Nearly two-thirds (65%) owned an ATV with 77% of all having ridden one in the past year. Farm residents had the highest ATV ownership (78%) and having ridden (80%) proportions, both p < 0.001. Overall, ownership and ridership for motorcycles (22% and 30%, respectively) and dirt bikes (29% and 39%, respectively) was significantly less than ATVs, all p < 0.001. Of ATV riders, those living on farms or in the country/not on a farm rode them more frequently than those from towns, p < 0.001. Higher percentages always/mostly wore helmets when riding dirt bikes (51%) and motorcycles (57%) relative to ATVs (21%), p < 0.001. Those from farms had lower proportions wearing helmets versus those living elsewhere for all vehicles. Helmet use importance ratings (1-10, 10 high) were not different for motorcycles (mean 8.6, median 10) and dirt bikes (mean 8.3, median 10), but much lower for ATVs (mean 6.1, median 6). Females, non-owners, and helmet law supporters all had higher helmet use importance ratings. Males, those from farms, and owners and riders of the vehicles all had lower proportions that supported helmet laws. Support for helmet laws was significantly lower for ATVs (30.7%) than dirt bikes (56.3%) or motorcycles (72.3%), both p < 0.001. Those whose families had strict ATV "No Helmet, No Riding" rules had much higher helmet use and helmet importance ratings. CONCLUSIONS: Our study indicates that the safety culture surrounding helmet use is relatively poor among rural adolescents, especially on farms, and deserves targeted interventions.

2.
Surgery ; 171(1): 245-251, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34362588

RESUMO

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.


Assuntos
Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Células-Tronco Neoplásicas/metabolismo , Câncer Papilífero da Tireoide/mortalidade , Glândula Tireoide/patologia , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/patologia , Estudos Retrospectivos , Medição de Risco/métodos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Glândula Tireoide/citologia , Neoplasias da Glândula Tireoide/patologia
3.
Mol Cancer Res ; 19(7): 1156-1167, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33753551

RESUMO

Activating protein 2 alpha (AP-2α; encoded by TFAP2A) functions as a tumor suppressor and influences response to therapy in several cancer types. We aimed to characterize regulation of the transcriptome by AP-2α in colon cancer. CRISPR-Cas9 and short hairpin RNA were used to eliminate TFAP2A expression in HCT116 and a panel of colon cancer cell lines. AP-2α target genes were identified with RNA sequencing and chromatin immunoprecipitation sequencing. Effects on cell cycle were characterized in cells synchronized with aphidicolin and analyzed by FACS and Premo FUCCI. Effects on invasion and tumorigenesis were determined by invasion assay, growth of xenografts, and phosphorylated histone H3 (PHH3). Knockout of TFAP2A induced significant alterations in the transcriptome including repression of TGM2, identified as a primary gene target of AP-2α. Loss of AP-2α delayed progression through S-phase into G2-M and decreased phosphorylation of AKT, effects that were mediated through regulation of TGM2. Buparlisib (BKM120) repressed in vitro invasiveness of HCT116 and a panel of colon cancer cell lines; however, loss of AP-2α induced resistance to buparlisib. Similarly, buparlisib repressed PHH3 and growth of tumor xenografts and increased overall survival of tumor-bearing mice, whereas, loss of AP-2α induced resistance to the effect of PI3K inhibition. Loss of AP-2α in colon cancer leads to prolonged S-phase through altered activation of AKT leading to resistance to the PI3K inhibitor, Buparlisib. The findings demonstrate an important role for AP-2α in regulating progression through the cell cycle and indicates that AP-2α is a marker for response to PI3K inhibitors. IMPLICATIONS: AP-2α regulated cell cycle through the PI3K cascade and activation of AKT mediated through TGM2. AP-2α induced sensitivity to Buparlisib/BKM120, indicating that AP-2α is a biomarker predictive of response to PI3K inhibitors.


Assuntos
Aminopiridinas/farmacologia , Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Morfolinas/farmacologia , Fase S/genética , Fator de Transcrição AP-2/genética , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Perfilação da Expressão Gênica/métodos , Técnicas de Inativação de Genes , Células HCT116 , Humanos , Camundongos , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Interferência de RNA , RNA-Seq/métodos , Fator de Transcrição AP-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
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