RESUMEN
We observed efficacy and safety of ustekinumab in very early-onset inflammatory bowel disease, which has not been previously reported. Clinical remission at 52% was 75%, often persisting beyond 2 years. Further studies including larger numbers of cases are needed to confirm this observation.
Asunto(s)
Enfermedades Inflamatorias del Intestino , Inducción de Remisión , Ustekinumab , Humanos , Ustekinumab/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Femenino , Masculino , Edad de Inicio , Resultado del TratamientoRESUMEN
BACKGROUND: Kawasaki disease (KD) presents with gallbladder enlargement (GBE) or hydrops in the acute phase. Although GBE is highly specific to KD, epidemiological data on GBE have not been updated. In this study we evaluated the occurrence rate of GBE in KD and characterized the clinical features of patients who developed GBE. METHODS: The present study was a prospective, observational study. The maximum longitudinal area of the gallbladder and the common bile duct diameter in KD patients were measured by ultrasonography at the start of initial intravenous immunoglobulin (IVIG) therapy (day 0) and on days 7, 30, and 60 of therapy. The primary outcome was the complication rate of GBE (z- score ≥2.0) on day 0. The secondary outcome was the association of GBE with cholestasis, unresponsiveness to IVIG, and coronary artery lesions (CAL). RESULTS: Gallbladder enlargement occurred in 35% (35/101) of patients on day 0. Cholestasis and severe patients (Kobayashi score [KS] ≥5) were more common in the GBE group (20.6% vs. 1.6%, p = 0.002, and 54.3% vs. 15.2%, p < 0.001, respectively). In patients with a KS of ≤4, the non-responder rate was higher in the GBE group (44% vs. 20%, p = 0.0495) but did not differ in those with a KS of ≥5 (21% vs. 20%, p = 0.95). The rate of CAL occurrence did not differ significantly between the groups (8.6% vs. 6.1%, p = 0.64). CONCLUSIONS: Gallbladder enlargement occurred in 35% of KD patients and was associated with cholestasis. Gallbladder enlargement may not only be a diagnostic finding, but also a severity marker in KD patients.
Asunto(s)
Colestasis , Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Humanos , Lactante , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Vesícula Biliar/diagnóstico por imagen , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Osimertinib-the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs. METHODS: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR). RESULTS: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs. CONCLUSION: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Hepáticas , Neoplasias Pulmonares , Acrilamidas , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB , Humanos , Indoles , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Metástasis de la Neoplasia , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: The rapid deterioration of oral health in young adults is an alarming problem in Japan. The aim of the present study is to investigate the oral health status, subjective oral symptoms and oral health behaviors of dental students. METHODS: Participants were 108 first-year students attending dental school in 2018-2019. Oral examinations were performed to assess dental caries indices, oral hygiene status, gingival bleeding on probing (BOP) and pocket depth. A self-administered questionnaire was used to assess subjective oral symptoms and oral health behaviors. RESULTS: The prevalence of decayed teeth (DT) and gingivitis (BOP ≥ 10%) were 43.5% and 50.0%, respectively. Having DT and gingivitis were significantly associated with poorer oral hygiene. No association was observed between DT and subjective symptoms. Having gingivitis was significantly associated with xerostomia, mouth-breathing and less use of interdental cleaning tools. Multiple logistic regression analysis for gingivitis yielded an odds ratio of 1.41 (95% confidence interval: 1.19-1.67) for plaque score, and 2.75 (1.27-5.98) for xerostomia. CONCLUSION: Since a relatively high ratio of students had DT and gingivitis without clear subjective symptoms, they require regular dental visits for early treatment and oral hygiene maintenance from the start of their time at university.
Asunto(s)
Caries Dental , Gingivitis , Caries Dental/epidemiología , Gingivitis/epidemiología , Conductas Relacionadas con la Salud , Humanos , Japón/epidemiología , Salud Bucal , Estudiantes de Odontología , Encuestas y Cuestionarios , Universidades , Adulto JovenRESUMEN
We evaluated the value of UHRF1, a regulator of methylation, as a biomarker for lung cancer. UHRF1 is expressed at higher levels in both lung adenocarcinoma (AD) and squamous cell carcinoma (SQ); however, a meta-analysis showed that UHRF1 expression is correlated with worse survival in patients with AD but not in those with SQ. UHRF1 knockdown suppressed the growth of lung cancer cell lines through G1 cell cycle arrest in some cell lines. These results suggest that UHRF1 may server as a diagnostic marker for AD and SQ and as a prognostic marker for AD in lung cancer.
Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico , Biomarcadores de Tumor/análisis , Proteínas Potenciadoras de Unión a CCAAT/análisis , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Ubiquitina-Proteína Ligasas/análisis , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/mortalidad , Adenocarcinoma del Pulmón/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Biología Computacional , Metilación de ADN , Conjuntos de Datos como Asunto , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Pulmón/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Pronóstico , Interferencia de ARN , Análisis de Supervivencia , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Oncogenic EGFR signaling has been shown to upregulate vascular endothelial growth factor A (VEGFA) expression involved in tumor angiogenesis. However, the clinical benefits of bevacizumab plus cytotoxic chemotherapy for EGFR mutation-positive patients remain unclear. This study aimed to investigate VEGFA messenger RNA expression in patients with EGFR mutation, and to further compare the efficacy of bevacizumab combined with platinum-based chemotherapy between EGFR-mutant and wild-type patients. PATIENTS AND METHODS: Gene expression of various proangiogenic factors was analyzed in nonsquamous, non-small-cell lung cancer (NSCLC) patients using The Cancer Genome Atlas dataset. Additionally, clinical data of patients receiving carboplatin and pemetrexed (CPem; n = 104) or bevacizumab plus CPem (BevCPem; n = 55) at Nagoya University hospital were retrospectively assessed for progression-free survival and best overall response rate (ORR). RESULTS: Among various proangiogenic factors, only VEGFA expression was significantly higher in patients with advanced nonsquamous NSCLC with EGFR mutation compared to wild-type patients (P = .0476). Progression-free survival in the BevCPem group was significantly longer in patients with EGFR mutation than in wild-type patients (10.5 vs. 6.6 months; Wilcoxon P = .0278), while the difference in the CPem group was not significant (6.6 vs. 4.5 months; Wilcoxon P = .1822). The ORRs in the BevCPem group were 54.5% and 36.4% for EGFR-mutant and wild-type patients, respectively, and the ORRs in the CPem group were 35.5% and 28.8 % in EGFR-mutant and wild-type patients, respectively. CONCLUSION: VEGFA messenger RNA expression was significantly increased in advanced nonsquamous NSCLC harboring EGFR mutation, and BevCPem provided better clinical benefits to patients with EGFR mutation than wild-type carriers.
Asunto(s)
Adenocarcinoma del Pulmón/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Grandes/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adulto , Anciano , Carboplatino/administración & dosificación , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pemetrexed/administración & dosificación , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaAsunto(s)
Afatinib/uso terapéutico , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Mutación/genética , Adulto , Anciano , Anciano de 80 o más Años , Receptores ErbB/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
To identify novel therapeutic targets for non-small cell lung cancer (NSCLC), we conducted an integrative study in the following 3 stages: (i) identification of potential target gene(s) through shRNA functional screens in 2 independent NSCLC cell lines; (ii) validation of the clinical relevance of identified gene(s) using public databases; and (iii) investigation of therapeutic potential of targeting the identified gene(s) in vitro. A semi-genome-wide shRNA screen was performed in NCI-H358 cells, and was integrated with data from our previous screen in NCI-H460 cells. Among genes identified in shRNA screens, 24 were present in both NCI-H358 and NCI-H460 cells and were considered potential targets. Among the genes, we focused on eIF2ß, which is a subunit of heterotrimeric G protein EIF2 and functions as a transcription initiation factor. The eIF2ß protein is highly expressed in lung cancer cell lines compared with normal bronchial epithelial cells, and gene copy number analyses revealed that eIF2ß is amplified in a subset of NSCLC cell lines. Gene expression analysis using The Cancer Genome Atlas (TCGA) dataset revealed that eIF2ß expression is significantly upregulated in lung cancer tissues compared with corresponding normal lung tissues. Furthermore, high eIF2ß expression was correlated with poor survival in patients with lung adenocarcinoma, as shown in other cohorts using publicly available online tools. RNAi-mediated depletion of eIF2ß suppresses growth of lung cancer cells independently of p53 mutation status, in part through G1 cell cycle arrest. Our data suggest that eIF2ß is a therapeutic target for lung cancer.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Factor 2 Eucariótico de Iniciación/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Células A549 , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Anciano , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular , Línea Celular Tumoral , Factor 2 Eucariótico de Iniciación/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Interferencia de ARNRESUMEN
Expression of programmed death-ligand 1 (PD-L1) in tumor cells such as lung cancer cells plays an important role in mechanisms underlying evasion of an immune check point system. Lung cancer tissue with increased deposition of extracellular matrix is much stiffer than normal lung tissue. There is emerging evidence that the matrix stiffness of cancer tissue affects the phenotypes and properties of cancer cells. Nevertheless, the effects of substrate rigidity on expression of PD-L1 in lung cancer cells remain elusive. We evaluated the effects of substrate stiffness on PD-L1 expression in HCC827 lung adenocarcinoma cells by using polyacrylamide hydrogels with stiffnesses of 2 and 25â¯kPa. Expression of PD-L1 protein was higher on the stiffer substrates (25â¯kPa gel and plastic dish) than on the soft 2â¯kPa gel. PD-L1 expression was reduced by detachment of cells adhering to the substrate. Interferon-γ enhanced expression of PD-L1 protein cultured on stiff (25â¯kPa gel and plastic dishes) and soft (2â¯kPa gel) substrates and in the cell adhesion-free condition. As the stiffness of substrates increased, formation of actin stress fiber and cell growth were enhanced. Transfection of the cells with short interfering RNA for PD-L1 inhibited cell growth without affecting stress fiber formation. Treatment of the cells with cytochalasin D, an inhibitor of actin polymerization, significantly reduced PD-L1 protein levels. Taken together, a stiff substrate enhanced PD-L1 expression via actin-dependent mechanisms in lung cancer cells. It is suggested that stiffness as a tumor environment regulates PD-L1 expression, which leads to evasion of the immune system and tumor growth.