RESUMEN
OBJECTIVES: The major cause of mucosal squamous cell carcinomas of the head and neck (HNSCCs) has been attributed to human papillomavirus (HPV) infection. Here we investigate if microRNA expression in HNSCC can be used as a prognostic tool with or without HPV status. MATERIALS AND METHODS: We performed a discovery miRNA microarray (miRBase v.21) profiling of 52 tonsillar SCCs with TaqMan real-time PCR validation of 228 HNSCCs. Patients had a histologically confirmed primary SCC of the oropharynx, oral cavity, hypopharynx or larynx. Logistic regression models were used to estimate the magnitude of the effect of association with clinical factors and miRNAs associated with HPV status. For recurrence and survival analysis, we used unadjusted and multivariable adjusted Cox proportional hazard regression models. RESULTS: Seventeen miRNAs were significantly associated with better prognosis in the discovery phase and were validated in the extended dataset. The best fitting model (AUC = 0.92) for HPV status included age, smoking, and miRNAs: miR-15b, miR-20b, miR-29a, miR-29c, miR-142, miR-146a and miR-205. Using Cox regression model for recurrence, miR-29a was associated with 49% increased risk of recurrence while miR-30e and miR-342 were associated with decreased risk of recurrence with HRs 0.92 (95% CI 0.85-0.99) and 0.84 (95% CI 0.73-0.98), respectively. Our best fitting model for survival included age, gender, alcohol consumption, N stage, recurrence, HPV status, together with miRNAs-20b, 29a, and 342. CONCLUSION: miRNAs show potential to serve as usual biomarkers to predict the clinical course of patients with mucosal HNSCC.
Asunto(s)
MicroARNs/metabolismo , Papillomaviridae/patogenicidad , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
It has been known for over 100 years that trace elements play an essential role in metabolism. Some 24 elements are now acknowledged as being essential to life. Many conditions have been examined in recent years from a trace element viewpoint. Alzheimer's disease and the part played by aluminium has received much attention, particularly since Crapper's work in the early 1970's. Extremely low levels of elements of interest and inappropriate methods of analysis are problems common to elemental tissue studies. Many early studies are now known to have reported falsely high levels of elements in tissues for just these reasons. Much research in recent years has been directed to looking at a range of trace elements thought to play a part in neurological disorders, particularly Alzheimer's disease. Inductively Coupled Plasma Source Mass Spectrometry (ICP-MS) is an ultra-sensitive, multi-element technique which can determine up to 90% of the elements in the periodic table, many at the sub ng.g-1 level. Developed and adopted commercially within the last 10 years, ICP-MS has to date been applied mainly to geological and environmental studies. Its suitability for use in biological investigations is now being exploited to examine the levels of 20 elements in brain tissue, cerebrospinal fluid, serum and aqueous humour from Alzheimer victims and matched control subjects.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Oligoelementos/metabolismo , HumanosRESUMEN
BACKGROUND: Despite increasing awareness of peanut allergy, little is known of its prevalence. We report on a two-stage interview survey conducted in Great Britain. METHODS: A total of 16434 adults (aged 15+ years) reported their own allergies and atopies and named cohabitants with peanut allergy (stage 1). Follow-up interviews were conducted with identified sufferers from peanut allergy (stage 2). RESULTS: At stage 1, peanut allergy was reported in 58 respondents and 205 other household members. When we accounted for cases where peanut allergy was unconfirmed or newly reported at stage 2, the prevalence, based on 124 confirmed sufferers, was estimated as 0.48% (95% confidence interval 0.40%-0.55%). The prevalence in children (0.61%, 0.41%-0.82%) was slightly higher than in adults; age-of-onset was strikingly earlier. Prevalence was strongly associated with other atopies, particularly tree-nut allergy. Cases tended significantly to cluster in households. Half of cases had never consulted a doctor. Exactly 7.4% reported being hospitalized after a reaction. CONCLUSIONS: Peanut allergy is reported by 1 in 200 of the population and is commoner in those reporting other atopies. The fact of similar rates in children and adults argues against a recent marked rise in prevalence. The frequency and potential lethality of this disorder emphasize the need for sufferers to demographic factors, other food allergies, atopic conditions, and allergy in family/household members. Our study comprised a screening survey and detailed interviews with sufferers identified. The frequency and potential lethality of this disorder emphasize the need for sufferers to receive correct medical advice on management [corrected].