RESUMEN
17-ß-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-ß-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-ß-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-ß-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-ß-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-ß-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-ß-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-ß-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-ß-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17ß-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17ß-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-ß-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.
Asunto(s)
Androstenodiona , Amianto , Biomarcadores de Tumor , Estradiol , Neoplasias Pulmonares , Mesotelioma Maligno , Exposición Profesional , Humanos , Estradiol/sangre , Masculino , Biomarcadores de Tumor/sangre , Androstenodiona/sangre , Amianto/toxicidad , Amianto/efectos adversos , Femenino , Persona de Mediana Edad , Exposición Profesional/efectos adversos , Anciano , Mesotelioma Maligno/sangre , Mesotelioma Maligno/diagnóstico , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Mesotelioma/sangre , Mesotelioma/diagnóstico , Mesotelioma/inducido químicamente , Neoplasias Pleurales/sangre , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/inducido químicamente , Deshidroepiandrosterona/sangre , Estudios de Casos y Controles , Detección Precoz del Cáncer/métodosRESUMEN
BACKGROUND: Regardless of the device used, many patients have difficulty maintaining proper inhaler technique over time. Repeated education from caregivers is required to ensure persistence of correct inhaler technique, but no information is available to evaluate the time required to rectify inhaler errors in experienced users with a baseline faulty technique and whether this time of re-education to restore inhaler mastery can differ between devices. METHODS: This was a multi-center, single-visit, open-label, cross-sectional study in a large group of 981 adult subjects (mean ± SD age 64 ± 15 y) experienced with inhaler use, mainly suffering from COPD and asthma, who showed faulty inhaler technique at a follow-up visit in chest clinics. These subjects received face-to-face practical education from trained caregivers until proper inhaler use could be demonstrated, and the time of instruction was recorded. RESULTS: The mean times (95% CIs) in minutes of instruction required for rectifying misuse and demonstrating inhaler mastery were 5.0 (3.6-6.4) min for the Diskus (n = 199), 5.3 (3.7-6.8) min for the HandiHaler (n = 219), 8.1 (5.6-10.5) min for the metered-dose inhaler (MDI) (n = 532), and 6.0 (5.0-7.0) min for the Turbuhaler (n = 169). The time to demonstrate good inhaler use for MDIs was higher (P < .05) than for all dry powder inhalers (DPIs). Between the DPIs, only the HandiHaler required more time for achieving mastery than the Diskus (P = .005). The variables associated with increasing time for correcting inhaler errors were an older age (0.05 min/y, 95% CI 0.03-0.07), a lower level of education (0.4 min/schooling level, 95% CI 0.7-0.1), and no reported previous instruction in inhaler use (1.96 min, 95% CI 1.35-2.58). CONCLUSIONS: In experienced subjects with baseline faulty inhaler use, the mean time of education required to achieve and demonstrate mastery with DPIs was lower than with MDIs.
Asunto(s)
Asma/terapia , Inhaladores de Polvo Seco , Inhaladores de Dosis Medida , Educación del Paciente como Asunto/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Factores de Tiempo , Anciano , Asma/psicología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto/métodos , Enfermedad Pulmonar Obstructiva Crónica/psicologíaRESUMEN
BACKGROUND: TP53 gene mutations can lead to the expression of a dysfunctional protein that in turn may enable genetically unstable cells to survive and change into malignant cells. Mutant p53 accumulates early in cells and can precociously induce circulating anti-p53 antibodies (p53Abs); in fact, p53 overexpression has been observed in pre-neoplastic lesions, such as bronchial dysplasia, and p53Abs have been found in patients with chronic obstructive pulmonary disease, before the diagnosis of lung and other tobacco-related tumors. METHODS: A large prospective study was carried out, enrolling non-smokers, ex-smokers and smokers with or without the impairment of lung function, to analyze the incidence of serum p53Abs and the correlation with clinicopathologic features, in particular smoking habits and impairment of lung function, in order to investigate their possible role as early markers of the onset of lung cancer or other cancers. The p53Ab levels were evaluated by a specific ELISA in 675 subjects. RESULTS: Data showed that significant levels of serum p53Abs were present in 35 subjects (5.2%); no difference was observed in the presence of p53Abs with regard to age and gender, while p53Abs correlated with the number of cigarettes smoked per day and packs-year. Furthermore, serum p53Abs were associated with the worst lung function impairment. The median p53Ab level in positive subjects was 3.5 units/ml (range 1.2 to 65.3 units/ml). Only fifteen positive subjects participated in the follow-up, again resulting positive for serum p53Abs, and no evidence of cancer was found in these patients. CONCLUSION: The presence of serum p53Abs was found to be associated with smoking level and lung function impairment, both risk factors of cancer development. However, in our study we have not observed the occurrence of lung cancer or other cancers in the follow-up of positive subjects, therefore we cannot directly correlate the presence of serum p53Abs with cancer risk.