RESUMO
OBJECTIVE: To determine the balance of metabolism of free bisphenol A (BPA) to the inactive conjugate, BPA glucuronide (BPAG), in neonates. STUDY DESIGN: Free BPA and BPAG concentrations were measured in 78 urine samples collected between December 2012 and August 2013 from a cohort of 44 healthy full term (≥ 37 weeks' gestation) neonates at 2 intervals (3-6 days and 7-27 days of age). A questionnaire was administered at the time of sample collection. Neonates recruited into the study were born in an urban, tertiary care hospital. RESULTS: Only BPAG was detected in the urine samples; concentrations ranged from <0.1 µg/L to 11.21 µg/L (median: 0.27 µg/L). Free BPA concentrations were below the limit of quantification of 0.1 µg/L. Age, but not sex or type of diet, was significantly associated with urinary BPAG concentration (P = .002). CONCLUSIONS: Our results illustrate widespread BPA exposure in healthy full-term neonates and efficient conjugation of BPA to its readily excretable and biologically inactive form (BPAG) as early as 3 days of age. Factors other than type of diet may be important contributors to BPA exposure in neonates.
Assuntos
Compostos Benzidrílicos/urina , Glucuronídeos/urina , Fenóis/urina , Fatores Etários , Aleitamento Materno , Feminino , Humanos , Fórmulas Infantis , Recém-Nascido , Masculino , Fatores SexuaisRESUMO
DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia) in paraffin embedded samples of triple negative breast cancer (TNBC) compared to luminal A breast cancer (LABC). Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.
Assuntos
Reparo do DNA/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia de Fanconi/genética , Feminino , Recombinação Homóloga/genética , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estrogênio/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
Infants are exposed to the endocrine disruptor bisphenol A (BPA) through breast milk and baby formula. Detoxication by conjugation of BPA may be limited in infants. We demonstrate BPA exposure in 11 neonates and 1 young infant, but find no evidence of a low capacity for BPA conjugation.
Assuntos
Compostos Benzidrílicos/urina , Glucuronídeos/urina , Fenóis/urina , Aleitamento Materno , Cromatografia Líquida de Alta Pressão/métodos , Exposição Ambiental , Feminino , Humanos , Lactente , Fórmulas Infantis , Recém-Nascido , Terapia Intensiva Neonatal , Masculino , Triagem Neonatal , Isoformas de Proteínas , Espectrometria de Massas em Tandem/métodos , Fatores de TempoRESUMO
PURPOSE: To determine the prognostic importance of p16 and human papillomavirus (HPV) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial. PATIENTS AND METHODS: Patients with stage III or IV head and neck squamous cell cancer were randomly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine. In this substudy, analyses were restricted to patients with oropharyngeal cancer. p16 was detected by immunohistochemistry, and HPV was detected by in situ hybridization and polymerase chain reaction. RESULTS: Slides were available for p16 assay in 206 of 465 patients, of which 185 were eligible, and p16 and HPV were evaluable in 172 patients. One hundred six (57%) of 185 were p16-positive, and in patients evaluable for both p16 and HPV, 88 (86%) of 102 p16-positive patients were also HPV-positive. Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group (ECOG) performance status. p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival (91% v 74%; hazard ratio [HR], 0.36; 95% CI, 0.17 to 0.74; P = .004) and failure-free survival (87% v 72%; HR, 0.39; 95% CI, 0.20 to 0.74; P = .003). p16 was a significant prognostic factor on multivariable analysis (HR, 0.45; 95% CI, 0.21 to 0.96; P = .04). p16-positive patients had lower rates of locoregional failure and deaths due to other causes. There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients (HR, 0.33; 95% CI, 0.09 to 1.24; P = .13). CONCLUSION: HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy.