ABSTRACT
The aim of this survey of practice was to define, in the absence of guideline, the management in France of asymptomatic men bearing a mutation of BRCA1 or 2 genes. A questionnaire was addressed to 90 oncogenetics centers. We obtained the answers of 34 practitioners working in 58 centers. Among the responders, 85.3% offered a systematic genetic test in all cases to determine the risk of transmission to the children and to offer a personal follow-up in 79.4 % of cases. This screening was directed towards prostate cancer, breast cancer and pancreatic cancer in respectively 94.1, 67.6 and 47.1% of cases. The screening of prostate cancer was mainly proposed to men bearing a BRCA2 mutation and from the age of 40 years. It was based on clinical examination and testing of prostate specific antigen. The screening of breast cancer was mainly proposed to men bearing a BRCA2 mutation and based on clinical examination and self-palpation without stating a started age. The screening of pancreatic cancer was mainly proposed to men with familial history of pancreatic cancer and from the age of 40 years. It was based on tomography and MRI. For the majority of answerers, the general practitioner was the best to perform all these screenings. These experts' opinions can help to establish guidelines for the global management of asymptomatic men carriers of BRCA1 or 2 mutations.
Subject(s)
Breast Neoplasms, Male/genetics , Genes, BRCA1 , Genes, BRCA2 , Mutation/genetics , Pancreatic Neoplasms/genetics , Prostatic Neoplasms/genetics , Adult , Age Factors , Breast Neoplasms, Male/diagnosis , France , Health Care Surveys , Humans , Male , Pancreatic Neoplasms/diagnosis , Practice Guidelines as Topic , Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosisABSTRACT
Intrauterine infection is a major cause of spontaneous preterm birth. Amniotic epithelial cells represent the first line of defense against intra-amniotic bacteria. We hypothesize that this epithelial cell barrier is able to recognize and respond to pathogens through the function of TLRs, which are crucial regulators of the innate immune system. In this study, we describe the expression of transcripts for TLR1-TLR10 in human amniotic epithelial cells. We show that amniotic epithelial cells express functional TLR5, TLR6/2, and TLR4. Activation by TLR5 and TLR6/2 agonists produces IL-6 and IL-8, concomitantly with the activation of NF-κB signaling pathway, matrix metalloproteinase-9 induction, and PTGS2 expression. In contrast, TLR4 activation reduced amniotic epithelial cell viability and induced cell apoptosis evidenced by an elevated Bax/Bcl-2 ratio and cleavage of caspase-3. These data suggest specific TLR-mediated functions in human amniotic epithelial cells for initiating different immune responses, which ultimately may lead to preterm birth.
