RESUMEN
OBJECTIVES: Recently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20-30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed. The present study explored the association between immunohistochemical biomarkers and clinical outcomes in UC patients treated with pembrolizumab. PATIENTS AND METHODS: A total of 85 patients with UC who received pembrolizumab after chemotherapy from January 2018 to May 2020 were retrospectively reviewed. Tumor tissues were obtained for immunohistochemical study from 47 out of 85 patients. The protein expressions of PD-L1, WT1, Nectin-4, CD4, CD8, Foxp3, and CD68 in tumor cells and/or tumor infiltrating lymphocytes were immunohistochemically examined. The associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed. RESULTS: Patients with positive PD-L1 in tumor cells showed significantly worse OS (Log-rank test: HR 5.146, p = 0.001, Cox regression analysis: HR 4.331, p = 0.014) and PFS (Log-rank test: HR 3.31. p = 0.022), along with significantly lower DCR (14.3%) compared to the PD-L1 negative patients (67.5%). In addition, patients with strong expression of Nectin-4 in tumor cells showed significantly higher DCR (100%) than the other patients (50%). CONCLUSION: PD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/biosíntesis , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/metabolismo , Moléculas de Adhesión Celular/biosíntesis , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We identified a novel mutation (CGC to T GC) at codon 31 of the Paired box 8 gene, an important transcription factor in the development of the thyroid gland. Mutations at this codon have been independently reported in 2 cases (CGC to CA C). These transitions are considered typical CpG-consequence mutations and account for hypermutability at this position.
Asunto(s)
Codón/genética , Proteínas de Unión al ADN/genética , Mutación Missense/genética , Proteínas Nucleares , Enfermedades de la Tiroides/congénito , Enfermedades de la Tiroides/genética , Transactivadores/genética , Adulto , Niño , Femenino , Humanos , Hipotiroidismo/sangre , Hipotiroidismo/genética , Factor de Transcripción PAX8 , Factores de Transcripción Paired Box , Reacción en Cadena de la Polimerasa , Tiroglobulina/sangre , Enfermedades de la Tiroides/sangre , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreAsunto(s)
Contaminación de Medicamentos , Fluorocarburos , Pseudomonas aeruginosa/crecimiento & desarrollo , Staphylococcus aureus/crecimiento & desarrollo , Recuento de Colonia Microbiana , Soluciones Oftálmicas , Pseudomonas aeruginosa/aislamiento & purificación , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
We evaluated 174 children with acute asthma and/or wheezing attending two different settings, the allergy clinic (AC) and the emergency room (ER), and compared clinical symptoms and spirometric findings with arterial oxygen saturation as measured by pulse oximetry (SpO2). Seventy-four children (4 months to 15 years old) seen at the AC and 100 children (2 months to 14 years old) seen at the ER for the treatment of acute asthma and/or wheezing were evaluated and a clinical score was attributed on the basis of their symptoms. In addition, the heart rate (HR) was recorded and SpO2 was measured. Among the children seen at the AC, 58 were able to perform pulmonary function tests, and the forced respiratory volume in 1 sec (FEV1) and forced expiratory flow between 25% and 75% of the forced vital capacity (FEF(25-75)) were determined. Children from both groups underwent treatment with a nebulized beta2-agonist (Fenoterol 0.5% solution, 0.08 mg/kg/dose, maximum 2.5 mg) and were re-evaluated after 30 min. Our results showed a significant correlation between decrease in clinical scores and increase of SpO2 following treatment with bronchodilator in both groups of children. SpO2 levels correlated positively with FEV1 and FEF(25-75) values, and negatively with clinical scores and heart rate. The data revealed that a clinical score greater than 3 and an SpO2 < 94% were associated with increased severity of the asthma attack. In addition, SpO2 levels < or = 92% were associated with a 6.3-fold greater relative risk for requiring additional treatment. We concluded that determination of oxygen saturation by pulse oximetry is helpful in monitoring the severity of an acute exacerbation of asthma and/or wheezing, and has a prognostic value.