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1.
Eur Radiol ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37921926

RESUMO

OBJECTIVES: The introduction of low-dose CT (LDCT) altered the landscape of lung cancer (LC) screening and contributed to the reduction of mortality rates worldwide. Here we report the final results of HUNCHEST-II, the largest population-based LDCT screening program in Hungary, including the screening and diagnostic outcomes, and the characteristics of the LC cases. METHODS: A total of 4215 high-risk individuals aged between 50 and 75 years with a smoking history of at least 25 pack-years were assigned to undergo LDCT screening. Screening outcomes were determined based on the volume, growth, and volume doubling time of pulmonary nodules or masses. The clinical stage distribution of screen-detected cancers was compared with two independent practice-based databases consisting of unscreened LC patients. RESULTS: The percentage of negative and indeterminate tests at baseline were 74.2% and 21.7%, respectively, whereas the prevalence of positive LDCT results was 4.1%. Overall, 76 LC patients were diagnosed throughout the screening rounds (1.8% of total participants), out of which 62 (1.5%) patients were already identified in the first screening round. The overall positive predictive value of a positive test was 58%. Most screen-detected malignancies were stage I LCs (60.7%), and only 16.4% of all cases could be classified as stage IV disease. The percentage of early-stage malignancies was significantly higher among HUNCHEST-II screen-detected individuals than among the LC patients in the National Koranyi Institute of Pulmonology's archive or the Hungarian Cancer Registry (p < 0.001). CONCLUSIONS: HUNCHEST-II demonstrates that LDCT screening for LC facilitates early diagnosis, thus arguing in favor of introducing systematic LC screening in Hungary. CLINICAL RELEVANCE STATEMENT: HUNCHEST-II is the so-far largest population-based low-dose CT screening program in Hungary. A positive test's overall positive predictive value was 58%, and most screen-detected malignancies were early-stage lesions. These results pave the way for expansive systematic screening in the region. KEY POINTS: • Conducted in 18 medical facilities, HUNCHEST-II is the so far largest population-based low-dose CT screening program in Hungary. • The vast majority of screen-detected malignancies were early-stage lung cancers, and the overall positive predictive value of a positive test was 58%. • HUNCHEST-II facilitates early diagnosis, thus arguing in favor of introducing systematic lung cancer screening in Hungary.

2.
Orv Hetil ; 164(27): 1077-1083, 2023 Jul 09.
Artigo em Húngaro | MEDLINE | ID: mdl-37422888

RESUMO

Mesenchymal tumors of the lungs are rare, mostly aggressive, with a high metastatic rate, representing only 0.013-1.1% of all pulmonary malignancies. Primary pulmonary myxoid sarcoma is an extremely rare type of lung sarcoma and stands as a separate entity in the 2015 WHO classification, characterized by EWSR1-CREB fusion gene. So far, 37 myxoid sarcoma cases have been reported. We offer an overview of the most important characteristics of pulmonary myxoid sarcoma and differential diagnosis, while reviewing the reported cases. We present the case of a 47-year-old patient with pulmonary myxoid sarcoma, who was diagnosed with a right central pulmonary mass, showing rapid endobronchial progression, complicated by empyema. EWSR1 gene translocation could not be detected. During chemotherapy, tumor progression occurred. Molecular genetic examinations revealed MET gene exon 14 skipping mutation, based on which tyrosine-kinase inhibitor treatment was administered. Pulmonary myxoid sarcoma can be classified as a nonvascular, spindle cell entity of mesenchymal tumors, with the characteristic EWSR1-CREB1 gene translocation. The male-female ratio is similar, with a slightly higher incidence in middle-aged women (1.5 : 1). Patients' average age is 44 years; with predilection in the right upper lobe (62%), or endobronchially (85%). Without specific symptoms, diagnosis is often cumbersome. Immunohistochemical methods, typical hystological image and molecular genetic tests confirm the diagnosis. Pulmonary myxoid sarcoma is a rare entity, without specific symptoms. In our case, myxoid sarcoma was complicated by empyema, which was drained. Because of advanced stage, surgical resection was not an option. Radical surgery offers the best results, in inoperable cases therapeutic recommendations for sarcomas are the guiding principles. Our case belongs to the rare group of myxoid sarcomas, where MET activating mutation was detected, making it eligible for targeted treatment. Orv Hetil. 2023; 164(27): 1077-1083.


Assuntos
Neoplasias Pulmonares , Sarcoma , Neoplasias de Tecidos Moles , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Adulto , Sarcoma/diagnóstico , Sarcoma/genética , Sarcoma/cirurgia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Diagnóstico Diferencial , Biomarcadores Tumorais
3.
Mol Cell Proteomics ; 22(7): 100580, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37211046

RESUMO

Current proteomic technologies focus on the quantification of protein levels, while little effort is dedicated to the development of system approaches to simultaneously monitor proteome variability and abundance. Protein variants may display different immunogenic epitopes detectable by monoclonal antibodies. Epitope variability results from alternative splicing, posttranslational modifications, processing, degradation, and complex formation and possesses dynamically changing availability of interacting surface structures that frequently serve as reachable epitopes and often carry different functions. Thus, it is highly likely that the presence of some of the accessible epitopes correlates with function under physiological and pathological conditions. To enable the exploration of the impact of protein variation on the immunogenic epitome first, here, we present a robust and analytically validated PEP technology for characterizing immunogenic epitopes of the plasma. To this end, we prepared mAb libraries directed against the normalized human plasma proteome as a complex natural immunogen. Antibody producing hybridomas were selected and cloned. Monoclonal antibodies react with single epitopes, thus profiling with the libraries is expected to profile many epitopes which we define by the mimotopes, as we present here. Screening blood plasma samples from control subjects (n = 558) and cancer patients (n = 598) for merely 69 native epitopes displayed by 20 abundant plasma proteins resulted in distinct cancer-specific epitope panels that showed high accuracy (AUC 0.826-0.966) and specificity for lung, breast, and colon cancer. Deeper profiling (≈290 epitopes of approximately 100 proteins) showed unexpected granularity of the epitope-level expression data and detected neutral and lung cancer-associated epitopes of individual proteins. Biomarker epitope panels selected from a pool of 21 epitopes of 12 proteins were validated in independent clinical cohorts. The results demonstrate the value of PEP as a rich and thus far unexplored source of protein biomarkers with diagnostic potential.


Assuntos
Biomarcadores Tumorais , Neoplasias , Humanos , Proteoma , Proteômica/métodos , Epitopos , Anticorpos Monoclonais/química
4.
Cancers (Basel) ; 12(12)2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33317143

RESUMO

The human serum N-glycome is a valuable source of biomarkers for malignant diseases, already utilized in multiple studies. In this paper, the N-glycosylation changes in human serum proteins were analyzed after surgical lung tumor resection. Seventeen lung cancer patients were involved in this study and the N-glycosylation pattern of their serum samples was analyzed before and after the surgery using capillary electrophoresis separation with laser-induced fluorescent detection. The relative peak areas of 21 N-glycans were evaluated from the acquired electropherograms using machine learning-based data analysis. Individual glycans as well as their subclasses were taken into account during the course of evaluation. For the data analysis, both discrete (e.g., smoker or not) and continuous (e.g., age of the patient) clinical parameters were compared against the alterations in these 21 N-linked carbohydrate structures. The classification tree analysis resulted in a panel of N-glycans, which could be used to follow up on the effects of lung tumor surgical resection.

5.
Curr Mol Med ; 20(10): 765-772, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321401

RESUMO

BACKGROUND: Immunoglobulin G and A, transferrin, haptoglobin and alpha-1- antitrypsin represent approximately 85% of the human serum glycoproteome and their N-glycosylation analysis may lead to the discovery of important molecular disease markers. However, due to the labile nature of the sialic acid residues, the desialylated subset of the serum N-glycoproteome has been traditionally utilized for diagnostic applications. OBJECTIVE: Creating a five-protein model to deconstruct the overall N-glycosylation fingerprints in inflammatory and malignant lung diseases. METHODS: The N-glycan pool of human serum and the five high abundant serum glycoproteins were analyzed. Simultaneous endoglycosidase/sialidase digestion was followed by fluorophore labeling and separation by CE-LIF to establish the model. Pooled serum samples from patients with COPD, lung cancer (LC) and their comorbidity were all analyzed. RESULTS: Nine significant (>1%) asialo-N-glycan structures were identified both in human serum and the standard protein mixture. The core-fucosylated-agalacto-biantennary glycan differentiated COPD and LC and both from the control and the comorbidity groups. Decrease in the core-fucosylated-agalacto-biantennary-bisecting, monogalacto and bigalacto structures differentiated all disease groups from the control. The significant increase of the fucosylated-galactosylated-triantennary structure was highly specific for LC, to a medium extent for COPD and a lesser extent for comorbidity. Also, some increase in the afucosylated-galactosylated-biantennary structure in all three disease types and afucosylated-galactosylated-triantennary structures in COPD and LC were observed in comparison to the control group. CONCLUSION: Our results suggested that changes in the desialylated human serum Nglycome hold glycoprotein specific molecular diagnostic potential for malignant and inflammatory lung diseases, which can be modeled with the five-protein mixture.


Assuntos
Biomarcadores/sangue , Neoplasias Pulmonares/diagnóstico , Modelos Biológicos , Polissacarídeos/sangue , Ácidos Siálicos/química , Idoso , Estudos de Casos e Controles , Feminino , Glicômica , Glicosilação , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica
6.
Orv Hetil ; 161(4): 123-128, 2020 Jan.
Artigo em Húngaro | MEDLINE | ID: mdl-31955582

RESUMO

Chronic obstructive pulmonary disease (COPD) is worldwide a significant representative of morbidity and mortality statistics. COPD is a preventable and treatable disease and smoking is the main risk factor of disease development. Prevention is crucial, but it has its limitations, so risk estimation and early non-invasive diagnostics are essential to decrease COPD mortality. Although diagnostic techniques are evolving, the perfect screening tool is lacking. Discovery of properly sensitive and specific biomarkers is important. They could be effective diagnostic, differential diagnostic, phenotyping and prognostic tools to clinicians. The manuscript is focusing on recently discovered potential protein and glycan biomarkers for COPD. Orv Hetil. 2020; 161(4): 123-128.


Assuntos
Glicômica , Proteômica , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Biomarcadores , Humanos
7.
Orv Hetil ; 161(3): 95-102, 2020 Jan.
Artigo em Húngaro | MEDLINE | ID: mdl-31928062

RESUMO

Introduction: Chronic obstructive pulmonary disease (COPD) is a health burden for the patient and the society. We have sought to find the optimal education content to alleviate this burden. Aim: (1) To create patient education content based on the pulmonologists' opinion; (2) to understand the pulmonologists' attitudes and perceptions; (3) to evaluate the options to improve patient adherence. Method: We have performed 20 interviews with pulmonologists working in inpatient, outpatient and rehabilitation settings. The structure of the interviews has been designed to determine the key elements of a patient education programme and to discover perception and therapeutic attitudes. Results: The average COPD patient is a smoker, male, under-socialized, coughs, has dyspnoea and is older than 40 years. He does not take his illness seriously, and seeks medical attention only in case of worsening of the disease, and improvement in adherence is only present in such cases. The latter phenomenon is frequently transient, and limited to worse periods. Three adherence groups can be defined: marginal good adherence (approx. 10%), the average is around 30-40%, and minimal adherence (60%). Correct inhaler use should be taught in maximum three steps, which should be easily reproduced and explained. Conclusion: The aspects defining the framework of the education programme are the adequate patient profile (tailor-making), on-the-spot education in the pulmonology centre, the relationship between the patient and the doctors, patient attitudes and lifestyle changes (smoking cessation), and choosing the adequate inhaler. Orv Hetil. 2020; 161(3): 95-102.


Assuntos
Educação de Pacientes como Assunto , Relações Médico-Paciente , Doença Pulmonar Obstrutiva Crônica/terapia , Pneumologistas/psicologia , Atitude , Dispneia , Humanos , Masculino , Adesão à Medicação , Percepção , Pneumologia , Abandono do Hábito de Fumar
8.
Curr Med Chem ; 27(20): 3302-3313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30332938

RESUMO

Lung adenocarcinoma is one of the leading causes of mortality among cancer patients worldwide and Chronic Obstructive Pulmonary Disease (COPD) is also high in death statistics. In addition, patients with Chronic Obstructive Pulmonary Disease (COPD) have a high risk of developing primary lung cancer. Prevention, risk estimation and a non-invasive diagnostics are essential to decrease COPD and lung cancer mortality. Therefore, better and more accurate molecular diagnostic markers (biomarkers) are needed for the early differential diagnosis of these lung diseases to help clinicians make better therapeutic decisions. This review focuses on recently discovered adenocarcinoma and COPD biomarkers at the proteome and glycome level. In the first part, the protein markers are summarized, while the second part is focused on glycan markers. Their use to differentiate between chronic inflammation (COPD) and malignant (adenocarcinoma) diseases is discussed in detail.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Biomarcadores , Glicômica , Humanos , Proteômica
9.
Curr Mol Med ; 20(3): 185-193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31644407

RESUMO

BACKGROUND: A number of human inflammatory diseases and tumors have been shown to cause alterations in the glycosylation pattern of plasma proteins in a specific manner. These highly variable and versatile post-translational modifications finetune protein functions by influencing sorting, folding, enzyme activity and subcellular localization. However, relatively little is known about regulatory factors of this procedure and about the accurate causative connection between glycosylation and disease. OBJECTIVE: The aim of the present study was to investigate whether certain single nucleotide polymorphisms (SNPs) in genes encoding glycosyltransferases and glycosidases could be associated with elevated risk for chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma. METHODS: A total of 32 SNPs localized in genes related to N-glycosylation were selected for the association analysis. Polymorphisms with putative biological functions (missense or regulatory variants) were recruited. SNPs were genotyped by a TaqMan OpenArray platform. A single base extension-based method in combination with capillary gel electrophoresis was used for verification. RESULTS: The TaqMan OpenArray approach provided accurate and reliable genotype data (global call rate: 94.9%, accuracy: 99.6%). No significant discrepancy was detected between the obtained and expected genotype frequency values (Hardy-Weinberg equilibrium) in the healthy control sample group in case of any SNP confirming reliable sampling and genotyping. Allele frequencies of the rs3944508 polymorphism localized in the 3' UTR of the MGAT5 gene significantly differed between the sample groups compared. CONCLUSION: Our results suggest that the rs34944508 SNP might modulate the risk for lung cancer by influencing the expression of MGAT5. This enzyme catalyzes the addition of N-acetylglucosamine (GlcNAc) in beta 1-6 linkage to the alpha-linked mannose of biantennary N-linked oligosaccharides, thus, increasing branching that is the characteristic of invasive malignancies.


Assuntos
Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade
10.
Artigo em Inglês | MEDLINE | ID: mdl-31881512

RESUMO

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are prevalent ailments with a great challenge to distinguish them based on symptoms only. Since they require different treatments, it is important to find non-invasive methods capable to readily diagnose them. Moreover, COPD increases the risk of lung cancer development, leading to their comorbidity. In this pilot study the N-glycosylation profile of pooled human serum samples (90 patients each) from lung cancer, COPD and comorbidity (LC with COPD) patients were investigated in comparison to healthy individuals (control) by capillary gel electrophoresis with high sensitivity laser-induced fluorescence detection. Sample preparation was optimized for human serum samples introducing a new temperature adjusted denaturation protocol to prevent precipitation and increased endoglycosidase digestion time to assure complete removal of the N-linked carbohydrates. The reproducibility of the optimized method was <3.5%. Sixty-one N-glycan structures were identified in the pooled control human serum sample and the profile was compared to pooled lung cancer, COPD and comorbidity of COPD with lung cancer patient samples. One important finding was that no other sugar structures were detected in any of the patient groups, only quantitative differences were observed. Based on this comparative exercise, a panel of 13 N-glycan structures were identified as potential glycobiomarkers to reveal significant changes (>33% in relative peak areas) between the pathological and control samples. In addition to N-glycan profile changes, alterations in the individual N-glycan subclasses, such as total fucosylation, degree of sialylation and branching may also hold important glycobiomarker values.


Assuntos
Eletroforese Capilar/métodos , Neoplasias Pulmonares , Polissacarídeos , Doença Pulmonar Obstrutiva Crônica , Comorbidade , Glicômica , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/metabolismo , Projetos Piloto , Polissacarídeos/sangue , Polissacarídeos/química , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Reprodutibilidade dos Testes
11.
Electrophoresis ; 38(17): 2115-2123, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28116769

RESUMO

Multiple myeloma (MM) is an immedicable malignancy of the human plasma cells producing abnormal antibodies (also referred to as paraproteins) leading to kidney problems and hyperviscosity syndrome. In this paper, we report on the N-glycosylation analysis of paraproteins from total human serum as well as the fragment crystallizable region (Fc ) and fragment antigen binding (Fab ) κ/λ light chain fractions of papain digested immunoglobulins from multiple myeloma patients. CE-LIF detection was used for the analysis of the N-glycans after endoglycosidase (PNGase F) mediated sugar release and fluorophore labeling (APTS). While characteristic N-glycosylation pattern differences were found between normal control and untreated, treated and remission stage multiple myeloma patient samples at the global serum level, less distinctive changes were observed at the immunoglobulin level. Principal component analysis adequately differentiated the four groups (control and three patient groups) on the basis of total serum N-glycosylation analysis. 12 N-glycan features showed statistically significant differences (p <0.05) among various stages of the disease in comparison to the control at the serum level, while only six features were identified with similar significance at the immunoglobulin level, including the analysis of the partitioned Fc fragment as well as the Fab κ and Fab λ chains.


Assuntos
Eletroforese Capilar/métodos , Mieloma Múltiplo/sangue , Paraproteínas/análise , Paraproteínas/química , Polissacarídeos/sangue , Feminino , Glicosilação , Humanos , Masculino , Mieloma Múltiplo/metabolismo , Paraproteínas/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo
12.
Orv Hetil ; 153(14): 553-8, 2012 Apr 08.
Artigo em Húngaro | MEDLINE | ID: mdl-22450144

RESUMO

The authors present the case of a 72-year-old woman who underwent coronary bypass grafting. Left sided chylothorax due to accidental dissection of a thoracic duct branch developed 2 months after sternotomy. As conservative therapy has failed, surgical pleurodesis was performed successfully. Chylothorax is a rare and underestimated complication of coronary bypass grafting. The worldwide increasing number of coronary artery bypass grafting surgeries makes it important to pay attention to this condition. Thus diagnosis of the chyle is relatively easy by its high chylomicron and triglyceride content, but identification of the etiology and its treatment is sometimes challenging for the physician. The treatment of chylothorax is usually conservative. The main goal is to keep the volume of the chyle under control. The number of surgical interventions because of chylothorax is increasing due to an increase of iatrogenic etiology.


Assuntos
Quilotórax/etiologia , Quilotórax/cirurgia , Ponte de Artéria Coronária/efeitos adversos , Pleurodese , Idoso , Quilotórax/diagnóstico , Quilotórax/terapia , Feminino , Humanos , Doença Iatrogênica , Toracotomia , Tomografia Computadorizada por Raios X
13.
Mol Cell Proteomics ; 10(12): M111.010298, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21947365

RESUMO

A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody proteomics for discovery of a panel of biomarkers for early detection (stage I) of non-small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totaling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies. The monoclonal antibodies recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83% sensitivity at 95% specificity for stage I NSCLC.


Assuntos
Anticorpos Monoclonais/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/sangue , Proteoma/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos Monoclonais/química , Especificidade de Anticorpos , Área Sob a Curva , Biomarcadores Tumorais/imunologia , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Estudos de Casos e Controles , Fator H do Complemento/imunologia , Fator H do Complemento/metabolismo , Feminino , Glicoproteínas/sangue , Glicoproteínas/imunologia , Haptoglobinas/imunologia , Haptoglobinas/metabolismo , Humanos , Imunoensaio/métodos , Neoplasias Pulmonares/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Proteômica , Curva ROC , Adulto Jovem , alfa 1-Antiquimotripsina/sangue , alfa 1-Antiquimotripsina/imunologia
14.
BMC Med Genet ; 11: 152, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-21044285

RESUMO

BACKGROUND: In addition to smoking, genetic predisposition is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Genetic association studies of new candidate genes in COPD may lead to improved understanding of the pathogenesis of the disease. METHODS: Two proposed casual single nucleotide polymorphisms (SNP) (rs1051740, rs2234922) in microsomal epoxide hydrolase (EPHX1) and three SNPs (rs1801282, rs1800571, rs3856806) in peroxisome proliferator-activated receptor gamma (PPARG), a new candidate gene, were genotyped in a case-control study (272 COPD patients and 301 controls subjects) in Hungary. Allele frequencies and genotype distributions were compared between the two cohorts and trend test was also used to evaluate association between SNPs and COPD. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested in logistic regression analysis. Association between haplotypes and COPD outcome was also assessed. RESULTS: The distribution of imputed EPHX1 phenotypes was significantly different between the COPD and the control group (P = 0.041), OR for the slow activity phenotype was 1.639 (95% CI = 1.08- 2.49; P = 0.021) in our study. In logistic regression analysis adjusted for both variants, also age and pack-year, the rare allele of His447His of PPARG showed significant association with COPD outcome (OR = 1.853, 95% CI = 1.09-3.14, P = 0.0218). In haplotype analysis the GC haplotype of PPARG (OR = 0.512, 95% CI = 0.27-0.96, P = 0.035) conferred reduced risk for COPD. CONCLUSIONS: The "slow" activity-associated genotypes of EPHX1 were associated with increased risk of COPD. The minor His447His allele of PPARG significantly increased; and the haplotype containing the minor Pro12Ala and the major His447His polymorphisms of PPARG decreased the risk of COPD.


Assuntos
Epóxido Hidrolases/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , PPAR gama/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/efeitos adversos , Fumar/genética
15.
Exp Lung Res ; 35(8): 646-64, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19895320

RESUMO

Expression of microRNAs (miRNAs) is characteristically altered in cancer, and they may play a role in cancer development and progression. The authors performed microarray and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses to determine the miRNA expression profile of primary small cell lung cancer. Here we show that at least 24 miRNAs are differentially expressed between normal lung and primary small cell lung cancer (SCLC) tumors. These include miR-301, miR-183/96/182, miR-126, and miR-223, which are microRNAs deregulated in other tumor types as well; and other miRNAs, such as miR-374 and miR-210, not previously reported in association with lung cancer. The aberrant miRNA profile of SCLC may offer new insights in the biology of this aggressive tumor, and could potentially provide novel diagnostic markers.


Assuntos
Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Carcinoma de Pequenas Células do Pulmão/genética , Adulto , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Carcinoma de Pequenas Células do Pulmão/patologia , Fumar
16.
Electrophoresis ; 28(23): 4401-6, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18041035

RESUMO

We define mAb proteomics as the global generation of disease specific antibodies that permit mass screening of biomarkers. An integrated, high-throughput, disease-specific mAb-based biomarker discovery platform has been developed. The approach readily provided new biomarker leads with the focus on large-scale discovery and production of mAb-based, disease-specific clinical assay candidates. The outcome of the biomarker discovery process was a highly specific and sensitive assay, applicable for testing of clinical validation paradigms, like response to treatment or correlation with other clinical parameters. In contrast to MS-based or systems biology-based strategies, our process produced prevalidated clinical assays as the outcome of the discovery process. By re-engineering the biomarker discovery paradigm, the encouraging results presented in this paper clearly demonstrate the efficiency of the mAb proteomics approach, and set the grounds for the next steps of studies, namely, the hunt for candidate biomarkers that respond to drug treatment.


Assuntos
Anticorpos Monoclonais/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Anticorpos Monoclonais/biossíntese , Antineoplásicos , Biomarcadores/análise , Proteínas Sanguíneas , Cromatografia Líquida de Alta Pressão , Biologia Computacional , Ensaio de Imunoadsorção Enzimática , Humanos , Técnicas de Diagnóstico Molecular/tendências , Análise Serial de Proteínas , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas em Tandem
17.
Orv Hetil ; 147(43): 2069-74, 2006 Oct 29.
Artigo em Húngaro | MEDLINE | ID: mdl-17297753

RESUMO

Lung transplantation is now generally accepted as a useful modality of care for patients with severe life-threatening respiratory diseases that are refractory to conventional therapies. Lung transplantation is indicated for patients with end stage lung diseases, who demonstrate declining function despite maximal therapy. The author reports own experience of selection, timing referrals for lung transplantation, and the management of patients on the waiting list. Eleven patients were selected for lung transplantation. Eight of them suffered from end stage pulmonary fibrosis, two of them cystic fibrosis, and one patient had pulmonary hypertension. Seven patients underwent a successful lung transplantation and four patients died during the investigations, before the operation, due to respiratory failure, and pulmonary heart disease. It is generally recommended to consider transplantation when patients who suffer in the end stage pulmonary disease are symptomatic during daily activities too, due to pulmonary status and the expected survival is to be strongly limited, less than two years.


Assuntos
Pneumopatias/terapia , Transplante de Pulmão , Seleção de Pacientes , Listas de Espera , Adulto , Contraindicações , Fibrose Cística/terapia , Feminino , Humanos , Hipertensão Pulmonar/terapia , Pneumopatias/complicações , Pneumopatias/diagnóstico , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/terapia , Fibrose Pulmonar/terapia , Índice de Gravidade de Doença
18.
Orv Hetil ; 147(43): 2091-6, 2006 Oct 29.
Artigo em Húngaro | MEDLINE | ID: mdl-17297756

RESUMO

The role of volume reduction surgery in the therapy of early stage chronic obstructive pulmonary disease. COPD is a leading cause of morbidity and mortality worldwide. Assessment of COPD severity is based on the level of patient's symptoms, the severity of the spirometric abnormality and the presence of complications, such as respiratory failure, and right heart failure. Management of mild to moderate COPD is complex, involves the avoidance of risk factors to prevent disease progression, pharmacotherapy as needed to control symptoms, physiotherapy, and rehabilitation. The bases of pharmacotherapy are bronchodilators, which represent the first line symptom based pharmacologic intervention in COPD. Surgical treatment of emphysema was basically designed to improve subjective dyspnoea, respiratory function and quality of life in severely disabled patients. Three surgical options are currently employed, namely bullectomy, lung volume surgery and lung transplantation. During volume reduction surgery the hyperinflated areas are resected, so the functional residual volume is getting reduced, the respiratory muscle function is increased; the quality of life is improved. The authors are report a young early stage COPD patient who underwent a volume reduction surgery because of decline in physical condition, improving her disability. In conclusion in properly selected patients, lung volume surgery can offer prolonged functional benefit and satisfactory long term survival, even in early stage. The invasive options has a risk of both mortality and morbidity, they are directed only at patients who remain symptomatic despite optimal medical treatment.


Assuntos
Pneumonectomia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/cirurgia , Fatores Etários , Broncodilatadores/uso terapêutico , Contraindicações , Feminino , Humanos , Transplante de Pulmão/normas , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/patologia , Qualidade de Vida , Testes de Função Respiratória , Terapia Respiratória , Índice de Gravidade de Doença , Espirometria , Tomografia Computadorizada por Raios X
19.
Orv Hetil ; 146(17): 803-6, 2005 Apr 24.
Artigo em Húngaro | MEDLINE | ID: mdl-17918637

RESUMO

The authors present a case report of a 17 years old female patient who had a peripheral round shadow on the chest X-ray. After the operation the histological examination verified cystic adenomatoid malformation. The cystic adenomatoid malformation is an abnormal growth of the terminal bronchiolar structures. It is a rare disease, but often associates with other developmental abnormalities. It is important in the differential diagnosis to separate this disease from other cystic pulmonary lesions or sequestration. It is usually recognized in antenatal period or early childhood, but rarely in adulthood. It is possible that there is a connection between the adenoid malformation and lung cancer.


Assuntos
Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico , Malformação Adenomatoide Cística Congênita do Pulmão/cirurgia , Nódulo Pulmonar Solitário/diagnóstico , Adolescente , Sequestro Broncopulmonar/diagnóstico , Malformação Adenomatoide Cística Congênita do Pulmão/diagnóstico por imagem , Malformação Adenomatoide Cística Congênita do Pulmão/patologia , Diagnóstico Diferencial , Feminino , Humanos , Nódulo Pulmonar Solitário/cirurgia , Tomografia Computadorizada por Raios X
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