RESUMEN
Glioblastoma multiforme (GBM) is the most common and lethal primary brain tumor of the central nervous system (CNS). As an attempt to identify drugs for GBM therapeutics, phenotypic assays were used to screen 1000 chemicals from a clinical compound library. GBM subtypes exhibited different capabilities to induce angiogenesis when cultured on Matrigel; proneural cells migrated and formed a tube-like structure without endothelial cells. Among the compounds screened, indatraline, a nonselective monoamine transporter inhibitor, suppressed these morphological changes; it dose dependently inhibited cell spreading, migration, and in vitro/in vivo tube formation. In addition to intracellular calcium concentration, indatraline increased the level of Rho GTPase and its activity. Moreover, indatraline downregulated angiogenesis-related genes such as IGFBP2, PTN, VEGFA, PDGFRA, and VEGFR as well as nestin, a stem cell marker. These findings collectively suggest that the activation of Rho GTPase and the suppression of angiogenesis-related factors mediate the antiangiogenic activity of indatraline in proneural GBM culture.
Asunto(s)
Proteínas Angiogénicas/metabolismo , Calcio/metabolismo , Glioblastoma/metabolismo , Indanos/farmacología , Metilaminas/farmacología , Neovascularización Patológica/metabolismo , Proteínas de Unión al GTP rho/metabolismo , Movimiento Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Glioblastoma/complicaciones , Humanos , Neovascularización Patológica/complicaciones , Células Tumorales CultivadasRESUMEN
BACKGROUND: Data concerning the rate of pulmonary embolism (PE) in Asian patients with chronic obstructive pulmonary disease (COPD) exacerbation are sparse, and no study has shown predictors of PE in these patients. OBJECTIVES: The purpose of the present study was to investigate the prevalence and predictors of PE in Korean patients with COPD exacerbation. METHODS: Hospitalized patients with COPD exacerbations were prospectively enrolled into this study and underwent computed tomography (CT) pulmonary angiography and indirect CT venography. RESULTS: The most common cause of COPD exacerbation was lower respiratory tract infection (82%; n = 84), followed by PE (5%; n = 5). Eight patients (8%) had venous thromboembolism, and deep vein thrombosis (DVT) was seen in 6%, with proximal DVT in 4%. On multivariate analysis, the absence of symptoms of respiratory infection and plasma D-dimer elevation (≥500 µg/l) were significant factors predicting PE in patients with COPD exacerbations (odds ratio 31, 95% confidence interval 2-563, p = 0.02, and odds ratio 25, 95% confidence interval 1-464, p = 0.03, respectively). CONCLUSIONS: PE comprises approximately 5% of the etiologies of COPD exacerbations in Koreans. The absence of symptoms suggestive of respiratory infection and elevated plasma D-dimer levels were significant predictors of PE in this population.
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Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Embolia Pulmonar/epidemiología , Trombosis de la Vena/epidemiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Embolia Pulmonar/etiología , República de Corea/epidemiología , Factores de Riesgo , Trombosis de la Vena/etiologíaRESUMEN
Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7) or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11)). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11)). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20), allelic risk = 1.54, 95% Confidence Interval (CI) 1.41-1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87), and 2.35 (95% CI: 1.95-2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.
Asunto(s)
Adenocarcinoma/genética , Cromosomas Humanos Par 5/genética , Predisposición Genética a la Enfermedad , Neoplasias Pulmonares/genética , Adenocarcinoma/etnología , Adulto , Anciano , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Neoplasias Pulmonares/etnología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
Asunto(s)
Adenocarcinoma/genética , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Adenocarcinoma del Pulmón , Asia , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Riesgo , FumarRESUMEN
BACKGROUND AND OBJECTIVES: This study was conducted to investigate the impact of polymorphisms in the AKT1 gene on the survival of early stage non-small cell lung cancer (NSCLC) patients. METHODS: Three hundred and ten patients with surgically resected NSCLC were enrolled. The rs3803300, rs1130214, rs3730358, rs1130233, and rs2494732 single nucleotide polymorphisms (SNPs) in the AKT1 gene were investigated. The genotype and haplotype associations with overall survival (OS) and disease free survival (DFS) were analyzed. RESULTS: The three SNPs (rs3803300, rs1130214, and rs2494732) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased in a dose-dependent manner as the number of bad genotypes increased (P(trend) = <1.0 × 10(-4) and 0.001, respectively). Patients with 2 bad genotypes had a significantly worse OS and DFS compared with those with 0 bad genotypes (adjusted hazard ratio (HR) = 3.08, 95% confidence interval (CI) = 1.61-5.89, P = 0.001; and adjusted HR = 2.04, 95% CI = 1.22-3.43, P = 0.01). CONCLUSIONS: These results suggest that the AKT1 polymorphisms could be used as prognostic markers for the patients with early-stage NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Haplotipos/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Proto-Oncogénicas c-akt/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Tasa de SupervivenciaRESUMEN
Data regarding parapneumonic pleural effusion in Mycoplasma pneumoniae pneumonia (MP) patients are limited. In this study MP patients with pleural effusion tended to be younger and had longer hospital stays and more common use of systemic steroids compared to those without pleural effusion. In 5 of the 6 patients for whom pleural fluid data were available, the pleural effusion was lymphocyte-predominant rather than polymorphonuclear leukocyte-predominant; these patients also had elevated adenosine deaminase levels. Taken together, these results indicate that MP patients with pleural effusion may have a more severe form compared to those without pleural effusion. M. pneumoniae should be considered an aetiological agent of lymphocyte-predominant pleural effusion.
Asunto(s)
Mycoplasma pneumoniae/aislamiento & purificación , Derrame Pleural/diagnóstico , Derrame Pleural/patología , Neumonía por Mycoplasma/complicaciones , Neumonía por Mycoplasma/patología , Adolescente , Adulto , Exudados y Transudados/citología , Femenino , Humanos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Genome-wide association studies (GWAS) have identified the three chromosomal regions, 5p15, 6p21 and 15q25, as being associated with lung cancer risk in European populations. This study was performed to confirm these associations in Korean patients with lung cancer. METHODS: The genotypes at rs2736100, rs402710, rs401681 and rs31489 at 5p15, rs9295740 at 6p22, which is in extensive linkage disequilibrium with the 6p21 region, as well as rs2036534 and rs6495309 at 15q25, were determined in 1094 patients with lung cancer and 1100 healthy control subjects, who were frequency matched for age and gender. RESULTS: The single-nucleotide polymorphisms (SNP) at 5p15 (rs2736100, adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.03-1.67, P = 0.025; rs402710, aOR 0.82, 95% CI 0.69-0.98, P = 0.025; rs401681, aOR 0.82, 95% CI 0.69-0.98, P = 0.026) and at 15q25 (rs2036534, aOR 0.75, 95% CI 0.61-0.93, P = 0.01; rs6495309, aOR 0.81, 95% CI 0.65-1.00, P = 0.052) were significantly associated with lung cancer risk. The magnitude of the effect was similar to that reported in previous studies, and the association was in the same direction. The effect of SNP in the 5p15 region on the risk of lung cancer was significant only for adenocarcinoma. The two SNP in the 15q25 region were significantly associated with lung cancer risk in ever-smokers and in patients with squamous-cell carcinoma. However, there was no association between the SNP at 6p22 and lung cancer risk. CONCLUSIONS: The association between SNP in the 5p15 and 15q25 regions and the risk of lung cancer was confirmed in a Korean population.
Asunto(s)
Adenocarcinoma/genética , Pueblo Asiatico/genética , Carcinoma de Células Escamosas/genética , Predisposición Genética a la Enfermedad/etnología , Estudio de Asociación del Genoma Completo , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Carcinoma Pulmonar de Células Pequeñas/genética , Adenocarcinoma/etnología , Carcinoma de Células Escamosas/etnología , Estudios de Casos y Controles , Humanos , Desequilibrio de Ligamiento , Neoplasias Pulmonares/etnología , Reproducibilidad de los Resultados , República de Corea , Carcinoma Pulmonar de Células Pequeñas/etnologíaRESUMEN
This study was conducted to determine the impact of a functional tandem repeat minisatellite (MNS16A) polymorphism in the telomerase reverse transcriptase (TERT) gene on the risk of lung cancer, as well as on survival of patients with non-small-cell lung cancer (NSCLC). The effect of the MNS16A variable number of tandem repeat (VNTR) polymorphism on the risk of lung cancer was evaluated in a case-control study that consisted of 937 lung cancer patients and 943 healthy controls. The effect of the polymorphism on survival outcome was evaluated in 703 patients with surgically resected NSCLC. Compared with the VNTR-302 allele, the VNTR-243 allele was associated with a significantly increased risk of lung cancer (adjusted odds ratio, 1.55; 95% confidence interval [CI], 1.07-2.25; P = 0.02). In addition, the genotypes carrying at least one VNTR-243 allele were associated with a significantly increased risk of lung cancer compared with the genotypes with no VNTR-243 allele (adjusted odds ratio, 1.61; 95% CI, 1.09-2.38; P = 0.02). In contrast to the effect of the polymorphism on the risk of lung cancer, the genotypes carrying at least one VNTR-243 allele were associated with a significantly better overall survival in patients with surgically resected NSCLC (adjusted hazard ratio, 0.51; 95% CI, 0.28-0.93; P = 0.03). These findings suggest that the MNS16A VNTR polymorphism in the TERT gene has dual, conflicting roles in lung carcinogenesis. This polymorphism may increase the risk of lung cancer development, and may improve survival in lung cancer patients.
Asunto(s)
Neoplasias Pulmonares/genética , Repeticiones de Minisatélite , Telomerasa/genética , Anciano , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/análisisRESUMEN
BACKGROUND: This study was conducted to evaluate the performance of a whole-blood interferon-gamma release assay in inpatients who were admitted to the emergency department (ED) with pulmonary infiltrates who required a differential diagnosis with pulmonary tuberculosis (TB). METHODS: The patients with pulmonary infiltrates who received a QuantiFERON (QFT) test in the ED were included as an inpatient group and were divided into TB and non-TB group based on the final diagnosis. Patients with pulmonary TB who were tested in the outpatient department served as a control group. RESULTS: In total, 377 QFT tests were analyzed. Of the 284 inpatient QFT tests, 29.6% had an indeterminate result (35.2% in the 196 patients with non-TB and 17.0% in the 88 patients with TB). In contrast, only 1.1% of the 93 outpatients with TB returned an indeterminate result (p<0.001). The indeterminate QFT results in the inpatient group were independently associated with lymphocytopenia, hypoalbuminemia, and high C-reactive protein levels. Non-positive QFT results in inpatients with TB were associated with lymphocytopenia and hypoalbuminemia, while non-positive QFT results in outpatients with TB were associated with high erythrocyte sedimentation rates and radiographically more severe diseases. CONCLUSIONS: QFT tests in ED-based inpatients with pulmonary infiltrate return indeterminate results relatively frequently. In addition, inpatients and outpatients with pulmonary TB may differ in terms of the risk factors on non-positive QFT results.
Asunto(s)
Técnicas y Procedimientos Diagnósticos , Interferón gamma/sangre , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Técnicas y Procedimientos Diagnósticos/instrumentación , Servicio de Urgencia en Hospital , Femenino , Humanos , Ensayos de Liberación de Interferón gamma , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Pacientes Ambulatorios , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Tuberculosis Pulmonar/sangreRESUMEN
This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNP) in DNA repair genes to determine the relationship between polymorphisms and the survival outcome of patients with early stage non-small-cell lung cancer (NSCLC). Three hundred and ten consecutive patients with surgically resected NSCLC were enrolled. Forty-eight SNP in 27 DNA repair genes were genotyped and their associations with overall survival (OS) and disease-free survival (DFS) were analyzed. Individually, six SNP exhibited significant associations with survival outcome. When the six SNP were combined, OS and DFS decreased as the number of bad genotypes increased (P(trend) <0.0001 for both). Patients with three, and four or five bad genotypes had a significantly worse OS and DFS compared with those carrying zero or one bad genotypes (adjusted hazard ratio [aHR] for OS=3.53, 95% confidence interval [CI]=1.25-9.97, P=0.02, and aHR for DFS=3.31, 95% CI=1.41-7.76, P=0.006; and aHR for OS=5.47, 95% CI=1.87-16.00, P=0.002, and aHR for DFS=4.42, 95% CI=1.82-10.74, P=0.001, respectively). These findings suggest that the six SNP identified can be used as prognostic markers for patients with surgically resected early stage NSCLC.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Reparación del ADN/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Supervivencia sin Enfermedad , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Proteína 2 Homóloga a MutS/genética , Estadificación de Neoplasias , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/genética , Pronóstico , Proteínas Supresoras de Tumor/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X , Proteína de la Xerodermia Pigmentosa del Grupo D/genéticaRESUMEN
Based on the important role of microRNA (miRNA) biosynthesis genes in carcinogenesis, we hypothesized that polymorphisms in the miRNA biosynthesis genes may modulate susceptibility to lung cancer. To test this hypothesis, we conducted a two-stage study to evaluate the associations between single nucleotide polymorphisms (SNPs) in the miRNA biosynthesis genes and the risk of lung cancer. In stage 1 of the study, 24 SNPs in the 11 miRNA biosynthesis genes (DROSHA, DGCR8, RAN, XPO5, DICER, AGO1, AGO2, HIWI, GEMIN3, GEMIN4, and TRBP) were genotyped in 100 lung cancer patients and 100 healthy controls using a sequenome mass spectrometry-based genotyping assay. One promising SNP (AGO1 rs636832A > G) was selected for stage 2 of the study, and genotyped by a melting-curve analysis using fluorescence-labeled hybridization probes in an independent set of 552 cases and 552 controls. The AGO1 rs636832A > G exhibited highly consistent results between the two stages of the study. In combined analysis, the 636832A > G was associated with a significantly decreased risk of lung cancer in a dose-dependent manner (P(trend) = 6.0 × 10(-4)). Individuals with at least one rs636832G allele were at a significantly decreased risk of lung cancer compared with those with the AA genotype (adjusted odds ratio = 0.67, 95% confidence interval = 0.53-0.84, P = 4.0 × 10(-4)). This finding suggests that the AGO1 rs636832A > G might be a useful marker for determining the susceptibility to lung cancer and that the AGO1 gene might be involved in the development of lung cancer.
Asunto(s)
Factores Eucarióticos de Iniciación/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Proteínas Argonautas , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Riesgo , FumarRESUMEN
PURPOSE: This study was conducted to determine the association between single-nucleotide polymorphisms (SNPs) in apoptosis-related genes and survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: Three hundred ten consecutive patients with surgically resected NSCLC were enrolled. Twenty-five SNPs in 17 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: Three SNPs (TNFRSF10B rs1047266, TNFRSF1A rs4149570, and PPP1R13L rs1005165) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased as the number of bad genotypes increased (P (trend) for OS and DFS = 7 × 10(-5) and 1 × 10(-4), respectively). Patients with one bad genotype, and patients with two or three bad genotypes had significantly worse OS and DFS compared with those with no bad genotypes [adjusted hazard ratio (aHR) for OS = 2.27, 95% confidence interval (CI) = 1.22-4.21, P = 0.01, aHR for DFS = 1.74, 95% CI = 1.08-2.81, P = 0.02; aHR for OS = 4.11, 95% CI = 2.03-8.29, P = 8 × 10(-5); and aHR for DFS = 2.89, 95% CI = 1.64-5.11, P = 3 × 10(-4), respectively]. CONCLUSION: Three SNPs in apoptosis-related genes were identified as possible prognostic markers of survival in patients with early-stage NSCLC. The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Proteínas Represoras/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , ADN de Neoplasias/genética , Femenino , Genotipo , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Tasa de SupervivenciaRESUMEN
PURPOSE: This study was conducted to investigate the impact of functional polymorphisms in the FAS and FASL genes on the survival of early stage non-small cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: Three hundred and thirty-eight consecutive patients with surgically resected NSCLC were enrolled. The FAS -1377G>A (rs2234767) and -670A>G (rs1800682) and FASL -844C>T (rs763110) polymorphisms were investigated. Immunohistochemistry was used to assess FAS protein expression in tumors. The genotype and haplotype associations with survival were analyzed using Cox proportional hazards model, Kaplan-Meier method, and the log-rank test. RESULTS: Patients with the GG and combined AG+GG genotypes of the FAS -670A>G locus had a significantly decreased survival when compared with patients with the AA genotype [adjusted hazard ratio=1.71, 95% confidence interval (95% CI)=1.06-2.77, and P=0.03; and adjusted hazard ratio=1.48, 95% CI=1.01-2.20, and P=0.047, respectively]. In addition, the FAS -1377G/-670G and -1377A/-670G haplotypes exhibited a significantly lower survival compared with the -1377G/-670A haplotype (adjusted hazard ratio=1.87, 95% CI=1.20-2.91, and P=0.006; and adjusted hazard ratio=1.31, 95% CI=1.05-1.65, P=0.02, respectively). Strongly positive FAS immunostaining was significantly less frequent in patients with the FAS -670 AG+GG genotype than in patients with the -670 AA genotype (4.5% versus 10.8%; P=0.04). CONCLUSION: The FAS -670A>G polymorphism may affect survival in early-stage NSCLC. The analysis of the FAS -670A>G polymorphism can help identify patients at high risk for a poor disease outcome.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Proteína Ligando Fas/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple/genética , Receptor fas/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/secundario , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/secundario , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundario , Proteína Ligando Fas/metabolismo , Femenino , Genotipo , Haplotipos/genética , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Receptor fas/metabolismoRESUMEN
Data regarding treatment outcomes and prognosis in pneumonia that occurs after lung cancer chemotherapy are lacking. We performed a retrospective study of 84 patients with clinically suspected bacterial pneumonia after cytotoxic chemotherapy for lung cancer. Small cell carcinoma was the most common histological type (36.9%, n = 31), followed by squamous cell carcinoma (35.7%, n = 30) and adenocarcinoma (21.4%, n = 18). The most frequent pathogen was Streptococcus pneumoniae (n = 14), followed by Klebsiella pneumoniae (n = 10), Staphylococcus aureus (n = 8), and Pseudomonas aeruginosa (n = 7). Of 84 patients, treatment outcome was determined for 80; the outcome was success in 52 (61.9%) and failure in 28 (33.3%); outcome remained undetermined for 4 patients (4.8%). Based on multivariate analysis, tachypnoea (respiratory rate ≥20/min) was the only significant predictor of treatment failure (odds ratio 4.79, 95% confidence interval 1.17-19.70; p = 0.030). In conclusion, bacterial pneumonia after cytotoxic chemotherapy for lung cancer was found to be caused more often by S. pneumoniae and K. pneumoniae than P. aeruginosa, and treatment failure leading to death was found to be high. Tachypnoea was independently associated with treatment failure in this population.
Asunto(s)
Adenocarcinoma , Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Neumonía Bacteriana/microbiología , Carcinoma Pulmonar de Células Pequeñas , Adenocarcinoma/complicaciones , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Klebsiella pneumoniae/aislamiento & purificación , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/mortalidad , Neumonía Bacteriana/fisiopatología , Pronóstico , Frecuencia Respiratoria , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Streptococcus pneumoniae/aislamiento & purificación , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: Although a few studies have been conducted to evaluate the association of polymorphisms in matrix metalloproteinase (MMP) genes with chronic obstructive pulmonary disease (COPD), the results have been inconsistent. OBJECTIVES: To investigate the association of 3 polymorphisms of MMP genes (MMP-1 -1607G-->GG, MMP-9 -1562C-->T and MMP-12 N357S), which have been reported to be associated with COPD-related phenotypes, with the risk of COPD in a Korean population. METHODS: The genotypes of the 3 polymorphisms were determined in 301 patients with COPD and 333 healthy controls. RESULTS: Of the 3 polymorphisms studied, only the distribution of the MMP-9 -1562C-->T genotypes was significantly different between the cases and controls (p = 0.01), with the frequency of the variant T allele being significantly lower in the cases than in the controls (10.4 vs. 15.7%; p = 0.006). Individuals with at least 1 variant T allele were at a significantly decreased risk of COPD when compared with those with homozygous wild-type alleles (adjusted odds ratio = 0.69; 95% CI = 0.45-0.98; p = 0.04). CONCLUSIONS: These findings suggest that the MMP-9 -1562C-->T polymorphism could be used as a marker for determining the genetic susceptibility to COPD in a Korean population.
Asunto(s)
Metaloproteinasas de la Matriz/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Anciano , Pueblo Asiatico , Estudios de Casos y Controles , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Fumar/efectos adversosRESUMEN
BACKGROUND: The clinical relevance of emboli limited to the segmental or sub-segmental pulmonary arteries and the role of anticoagulation in patients with these conditions remains to be clarified. OBJECTIVES: To determine the clinical characteristics and treatment outcomes of peripheral pulmonary embolism (PE), and in particular, isolated sub-segmental PE (ISSPE). METHODS: We reviewed the data for 334 patients who were diagnosed with a PE by computed tomographic (CT) pulmonary angiography and indirect CT venography. RESULTS: All patients were classified into one of three groups: central (245 patients, 73.4%); segmental (67 patients, 20.1%), and sub-segmental (22 patients, 6.6%). An incidental CT finding (63.6%) was the most common presentation in the segmental and sub-segmental groups. Compared with the central group, the sub-segmental group had less frequent proximal deep venous thrombosis (14 vs. 47%, Bonferroni's corrected p = 0.002), and greater preservation of oxygenation levels (p < 0.05) without hemodynamic instability. The recurrence of PE and deaths related to PE did not occur in the sub-segmental group, although approximately 30% of the patients did not receive anticoagulation therapy. CONCLUSIONS: Patients with ISSPE may have a more benign clinical presentation, as compared to the central type, and may follow a good clinical course without mortality or recurrence.
Asunto(s)
Embolia Pulmonar/mortalidad , Adulto , Anciano , Anticoagulantes/uso terapéutico , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/tratamiento farmacológico , Radiografía , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
In patients undergoing major orthopedic surgery, data of deep venous thrombosis (DVT) and pulmonary embolism (PE) are lacking as studied by computed tomographic (CT) pulmonary angiography and indirect CT venography (CTPA-CTV). A prospective observational study was performed for 363 Korean patients undergoing major orthopedic surgery to determine the incidence of venous thromboembolism (VTE), especially proximal DVT and PE. The incidence of VTE was 16.3% (n=59). Of them, 8 patients (2.2%) were symptomatic. The rate of VTE was the highest in patients who underwent total knee replacement (40.4%), followed by hip fracture surgery (16.4%), and total hip replacement (8.7%; P<0.001). The incidence of PE was 6.6% (n=24). Of them, 4 patients (1.1%) were symptomatic. Forty-one patients (11.3%) were in the proximal DVT or PE group. Based on multivariate analysis, total knee replacement and age > or =65 yr were significant risk factors for proximal DVT or PE in patients undergoing major orthopedic surgery (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.1; P=0.025; and OR, 2.1; 95% CI, 1.0-4.4; P=0.046, respectively). Taken together, the overall incidence of PE was 6.6% and rate of symptomatic PE rate was 1.1%. Knee joint replacement and age > or =65 yr were significant risk factors for proximal DVT or PE.
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Procedimientos Ortopédicos , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/epidemiología , Anciano , Artroplastia de Reemplazo de Rodilla , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Flebografía , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/cirugía , República de Corea , Factores de Riesgo , Tomografía Computarizada por Rayos X , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/cirugíaRESUMEN
Although TP53 mutations have been widely studied in lung cancer, the majority of studies have focused on exons 5-8 of the gene. In addition, TP53 mutations in Korean patients with lung cancers have not been investigated. We searched for mutations in the entire coding exons, including splice sites of the gene, in Korean patients with non-small cell lung cancer (NSCLC). Mutations of the gene were determined by direct sequencing in 176 NSCLCs. Sixty-nine mutations (62 different mutations) were identified in 65 tumors. Of the 62 mutations, 12 were novel mutations. TP53 mutations were more frequent in males, ever-smokers and squamous cell carcinomas than in females, never-smokers and adenocarcinomas, respectively (all comparisons, P<0.001). Missense mutations were most common (52.2%), but frameshift, nonsense, and splice-site mutations were frequently observed at frequencies of 18.8%, 15.9% and 10.1%, respectively. Of the 69 mutations, 9 (13.0%) were found in the oligomerization domain. In addition, the proportion of mutations in the oligomerization domain was significantly higher in adenocarcinomas than in squamous cell carcinomas (23.5% vs. 2.9%, P=0.01). Our study provides clinical and molecular characteristics of TP53 mutations in Korean patients with NSCLCs.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Proteína p53 Supresora de Tumor/genética , Femenino , Humanos , Incidencia , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
The clinicoradiologic features of Mycoplasma pneumoniae bronchiolitis in adults remain unclear. 29 patients with M. pneumoniae infection were collected and classified by computed tomographic findings (bronchiolitis (n=8) and pneumonia (n=21)). M. pneumoniae bronchiolitis is not rare in adults and is clinically similar to M. pneumoniae pneumonia, despite radiographic differences.
Asunto(s)
Bronquiolitis/diagnóstico por imagen , Bronquiolitis/patología , Mycoplasma pneumoniae/aislamiento & purificación , Neumonía por Mycoplasma/diagnóstico por imagen , Neumonía por Mycoplasma/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Anticuerpos Antibacterianos/sangre , Bronquiolitis/tratamiento farmacológico , Bronquiolitis/microbiología , Distribución de Chi-Cuadrado , Humanos , Persona de Mediana Edad , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/microbiología , Radiografía Torácica , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Although lung cancer is the most common malignancy diagnosed in patients with venous thromboembolism (VTE), data regarding pulmonary embolism (PE) in lung cancer patients are limited. OBJECTIVES: To investigate the clinicoradiological features, clinical course and survival of lung cancer patients with PE. METHODS: We performed a retrospective case-control study investigating the clinical course and survival of 40 lung cancer patients with PE (PE group). The control group (non-PE group) consisted of 80 lung cancer patients without VTE, treated during the same period. RESULTS: Adenocarcinoma (45.0%, n = 18) was the most common histological type of lung cancer and when PE was diagnosed, the majority of the lung cancer patients were in stages IIIB (37.5%, n = 15) and IV (47.5%, n = 19). Thirty-four patients (85.0%) were diagnosed with PE within 12 months of the diagnosis of lung cancer. The median survival from the diagnosis of PE was 3.5 months in the PE group, but the survival rates revealed no significant difference between the two groups (p = 0.249). In both groups, the most common cause of death was lung cancer progression (76.9 and 80.3%, respectively), followed by chemotherapy-related septic shock (19.2 and 16.7%, respectively). CONCLUSIONS: In lung cancer patients, PE may not be the main cause of death, but one of the various complications of lung cancer, despite suggesting a poor prognosis.