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1.
Front Med (Lausanne) ; 10: 1218106, 2023.
Article in English | MEDLINE | ID: mdl-37621457

ABSTRACT

Introduction: Sarcoidosis is a highly variable disease in terms of organ involvement, type of onset and course. Associations of genetic polymorphisms with sarcoidosis phenotypes have been observed and suggest genetic signatures. Methods: After obtaining a positive vote of the competent ethics committee we genotyped 1909 patients of the deeply phenotyped Genetic-Phenotype Relationship in Sarcoidosis (GenPhenReSa) cohort of 31 European centers in 12 countries with 116 potentially disease-relevant single-nucleotide polymorphisms (SNPs). Using a meta-analysis, we investigated the association of relevant phenotypes (acute vs. sub-acute onset, phenotypes of organ involvement, specific organ involvements, and specific symptoms) with genetic markers. Subgroups were built on the basis of geographical, clinical and hospital provision considerations. Results: In the meta-analysis of the full cohort, there was no significant genetic association with any considered phenotype after correcting for multiple testing. In the largest sub-cohort (Serbia), we confirmed the known association of acute onset with TNF and reported a new association of acute onset an HLA polymorphism. Multi-locus models with sets of three SNPs in different genes showed strong associations with the acute onset phenotype in Serbia and Lublin (Poland) demonstrating potential region-specific genetic links with clinical features, including recently described phenotypes of organ involvement. Discussion: The observed associations between genetic variants and sarcoidosis phenotypes in subgroups suggest that gene-environment-interactions may influence the clinical phenotype. In addition, we show that two different sets of genetic variants are permissive for the same phenotype of acute disease only in two geographic subcohorts pointing to interactions of genetic signatures with different local environmental factors. Our results represent an important step towards understanding the genetic architecture of sarcoidosis.

2.
Sci Rep ; 11(1): 12848, 2021 06 18.
Article in English | MEDLINE | ID: mdl-34145303

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.


Subject(s)
Disease Susceptibility , Gene Expression , Leukocytes/metabolism , Mitochondria/genetics , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/metabolism , Respiratory Mucosa/metabolism , Biomarkers , Computational Biology/methods , Female , Gene Expression Profiling , Humans , Kruppel-Like Factor 4 , Leukocytes/immunology , Leukocytes/pathology , Male , Mitochondria/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , Sex Factors , Transcriptome
3.
Eur Respir J ; 51(1)2018 01.
Article in English | MEDLINE | ID: mdl-29371378

ABSTRACT

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.


Subject(s)
Phenotype , Sarcoidosis/diagnosis , Sarcoidosis/physiopathology , Abdomen , Acute Disease , Adult , Aged , Europe , Eye/physiopathology , Eye Diseases/physiopathology , Female , Forced Expiratory Volume , Genotype , Humans , Joint Diseases/physiopathology , Lung/physiopathology , Lung Diseases/physiopathology , Lymph Nodes/physiopathology , Male , Middle Aged , Skin/physiopathology , Skin Diseases/physiopathology , Tertiary Healthcare , White People
4.
Eur Respir J ; 48(1): 92-103, 2016 07.
Article in English | MEDLINE | ID: mdl-27230444

ABSTRACT

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.


Subject(s)
Phenotype , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Emphysema/diagnostic imaging , Tomography, X-Ray Computed/standards , Adult , Aged , Europe , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Respiratory System/physiopathology , Spirometry
5.
Pathol Oncol Res ; 21(4): 1167-73, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26003189

ABSTRACT

UNLABELLED: In the past years the participation rate in conventional voluntary x-ray lung screening has been around 22 % in Somogy County in Hungary. Due to the high morbidity and mortality rates of lung cancer, low participation rate of the high risk individuals on the screening is a primary question in Hungary. To obtain an effectively high level of participation in our ongoing low dose CT screening program, we had to emphasize the benefits of participation for the targeted individuals. As a first step, our aim was to gather information on the aspects affecting the individuals' will for participation. We used the most accessible source of information: individuals over the age of 50, who attended the conventional voluntary lung screening, were approached to fill a questionnaire on their habits relating to smoking, health issues and their prior participation of lung screening. 1080 adults anonymously completed the questionnaire. Analyzing the results, beside other findings, we found a unique variable factor, which altered negatively the compliance for the screening: older individuals, who started participating in the screening in obligation to the health regulations, took part in the voluntary screening programs at a significantly lower rate. Our findings led us to better understanding the complexity of decision making affecting the individual's participation and attitudes toward health issues. TRIAL REGISTRATION: IG/03833/2012.


Subject(s)
Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Lung/pathology , Early Detection of Cancer/methods , Female , Humans , Hungary , Male , Middle Aged , Smoking/adverse effects , Surveys and Questionnaires , Tomography, X-Ray Computed/methods
6.
Orv Hetil ; 155(10): 383-8, 2014 Mar 09.
Article in Hungarian | MEDLINE | ID: mdl-24583559

ABSTRACT

INTRODUCTION: Lung cancer has the highest mortality rate of all types of cancers both in developed countries and Hungary. AIM: To obtain experience and facilitate the application of low-dose computed tomography-based lung cancer screening as a targeted public health screening procedure. METHOD: Volunteers without thoracic complaints above the age of 40 years (n = 963) were screened for lung cancer using digital chest radiography and low-dose computed tomography. RESULTS: Two lung cancers were found among the participants screened with digital chest radiography (0.2%). After informed consent, 173 individuals with normal chest radiography findings (n = 943) took the opportunity to voluntarily participate in low-dose computed tomography screening for lung cancer. After 3 or 12 months, 65 individuals had follow up control examinations based on the size and characteristics of the detected lesions. Among them, one participant was found to have lung cancer using low-dose computed tomography. CONCLUSIONS: These results indicate that low-dose computed tomography-based lung cancer screening as a public health screening procedure can enhance the success of screening with 50% (from 0.2% to 0.3%). The cost-benefit ratio can be raised if chest radiography is performed prior to the low-dose computed tomography examination.


Subject(s)
Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Mass Chest X-Ray , Mass Screening/methods , Radiation Dosage , Tomography, X-Ray Computed/methods , Adult , Aged , Early Detection of Cancer , Female , Humans , Hungary/epidemiology , Lung Neoplasms/prevention & control , Male , Middle Aged , Risk Factors
7.
BMC Public Health ; 13: 914, 2013 Oct 02.
Article in English | MEDLINE | ID: mdl-24088358

ABSTRACT

BACKGROUND: Lung cancer is the most common fatal malignancy and also the primary cause of cancer mortality. Participation in lung screening is an important step in diagnosing patient in early stage and it can promise better outcomes. The aim of this preliminary study was to determinate the differences in the participation rate of smokers and non-smokers in lung cancer screening and to determine the communication strategies to increase the participation rate. METHODS: In the given period of time (from May to August 2012) out of 1426 people who participated in the lung screening program 1,060 adult volunteers (331 males and 729 females, average age 54.0 ± 9.3 years), completed fully and anonymously author's questionnaire that contained 28 questions. 25.7% of the respondents were smokers (n=272), 64.6% have never smoked, while 9.7% were former smokers. RESULTS: Mostly former smokers considered lung screening as an effective method for early detection of pulmonary diseases (86.4%). The most important source (41.0%) of information was the general practitioner. The participation rate of non-smokers is higher in lung screening than the ratio of non-smokers in the population. The unclear data suggest that smokers need distinct, concise messages to know why they should regularly undergo lung screening and doctors have a major role in this. CONCLUSIONS: We found that smokers significantly more frequently took part in lung screening annually. It is positive that the participation rate of former smokers is higher than non-smokers, it is just a bit lower than the participation rate of smokers--both in annual and biannual participation. The participation rate of non-smokers is higher in lung screening than the rate of non-smokers in the population.


Subject(s)
Attitude to Health , Communication , Early Detection of Cancer , Lung Neoplasms/diagnosis , Mass Screening , Patient Acceptance of Health Care , Smoking , Adult , Female , General Practice , Humans , Male , Mass Screening/methods , Middle Aged , Surveys and Questionnaires , Voluntary Programs
8.
J Clin Oncol ; 30(17): 2070-8, 2012 Jun 10.
Article in English | MEDLINE | ID: mdl-22564989

ABSTRACT

PURPOSE: Sunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. PATIENTS AND METHODS: Patients previously treated with one to two chemotherapy regimens (including one platinum-based regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety. RESULTS: In all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P = .0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. CONCLUSION: In patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Indoles/administration & dosage , Lung Neoplasms/drug therapy , Pyrroles/administration & dosage , Quinazolines/administration & dosage , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Double-Blind Method , Erlotinib Hydrochloride , Female , Humans , Male , Middle Aged , Placebos , Proportional Hazards Models , Smoking , Sunitinib , Treatment Outcome
9.
Eur Respir J ; 40(4): 823-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22441733

ABSTRACT

The EvA study is a European Union-funded project under the Seventh Framework Programme (FP7), which aims at defining new markers for chronic obstructive pulmonary disease (COPD) and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes, are driven by different genes and have differential gene expression in the lung. To define these genes, patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography (CT) of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples, along with blood samples, are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoids, antibiotics and exacerbations or current smokers are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.


Subject(s)
Bronchial Diseases/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Emphysema/genetics , Aged , Bronchoscopy , Case-Control Studies , Gene Expression , Genetic Markers , Genetic Predisposition to Disease , Genotype , Humans , Inflammation/genetics , Middle Aged , Phenotype , Tomography, X-Ray Computed
10.
Orv Hetil ; 152(44): 1772-4, 2011 Oct 30.
Article in Hungarian | MEDLINE | ID: mdl-21997582

ABSTRACT

The 15 years history of lung transplantation in Hungary shows the medical, political and social characteristics of this period. The barely determined, open-ended legal, financial and ethical framework of transplantation has stayed nowadays in the same position. The Hungarian State Audit Office has also noted these problems. Joining of Hungary to Eurotransplant will beneficially influence the whole procedure.


Subject(s)
Lung Transplantation , Waiting Lists , Austria , European Union , Humans , Hungary , Lung Transplantation/economics , Lung Transplantation/legislation & jurisprudence , Lung Transplantation/statistics & numerical data , Medical Audit , Medical Tourism , Politics , Tissue and Organ Procurement/ethics , Tissue and Organ Procurement/legislation & jurisprudence , Tissue and Organ Procurement/statistics & numerical data , Tissue and Organ Procurement/trends
11.
Magy Onkol ; 54(4): 297-301, 2010 Dec.
Article in Hungarian | MEDLINE | ID: mdl-21163760

ABSTRACT

Histological subgroups of non-small cell lung cancer have different prognosis and they require different therapeutic approaches. Accordingly, there is a clinical need in this field to supplement conventional pathological diagnostics with protein and genetic biomarkers that can help to recognize patients responsive to these therapies. Methods for subgroup classification and target identification were developed using surgical samples (surgical lung tumor specimens are available only in 20% of all lung cancer cases). The majority of lung cancer patients, however, have tumors that are irresectable at the time of diagnosis. Therefore, their diagnosis is usually based on bronchoscopically removed tissue or needle biopsy samples analyzed mainly by cytology. Because of the growing need for immunohistochemistry and molecular pathology in lung cancer diagnosis, emphasis should be given to diagnostic bronchoscopic procedures providing tissue samples. Combination of the different biopsy techniques (histology, cytology, bronchial brush, BAL, TBNA etc.), embedding the cells (preparing cell blocks) and, moreover, the availability of immunohistochemical and molecular pathological facilities are all required to set up the proper diagnosis and therapeutic strategy in human lung cancer. Strausz J, Tímár J. Non-surgical biopsy in lung cancer: a paradigm shift.


Subject(s)
Biopsy, Needle/methods , Bronchoscopy , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Lymph Nodes/pathology , Humans , Immunohistochemistry , Prognosis
12.
Magy Onkol ; 54(2): 137-43, 2010 Jun.
Article in Hungarian | MEDLINE | ID: mdl-20576590

ABSTRACT

Major advancements have been made in the clinical management of non-small cell lung cancer (NSCLC) in the past decade. This development involved the introduction of pemetrexed and several targeted therapies (bevacizumab, erlotinib, gefitinib) in the first and second line treatments of NSCLC. Novel maintenance therapeutic strategies for NSCLC (erlotinib) and for non-squamous-NSCLC (pemetrexed, bevacizumab+erlotinib) have also been developed resulting in a significant improvement in patient's survival. These changes have modified registrations of various drugs and require continuous update of guidelines and reimbursement schemes as well. These advantages are based on refinement of differential diagnosis of NSCLC and on the development of molecular predictive markers. Our aim is to summarize the changes in the diagnosis and therapy of NSCLC and to present the altered therapeutic scheme.


Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , Mutation , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Drug Administration Schedule , ErbB Receptors/genetics , ErbB Receptors/metabolism , Erlotinib Hydrochloride , Gefitinib , Glutamates/administration & dosage , Guanine/administration & dosage , Guanine/analogs & derivatives , Humans , Lung Neoplasms/metabolism , Pemetrexed , Predictive Value of Tests , Prognosis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins p21(ras) , Quinazolines/administration & dosage , ras Proteins/genetics , ras Proteins/metabolism
13.
BMC Pulm Med ; 9: 44, 2009 Sep 09.
Article in English | MEDLINE | ID: mdl-19740418

ABSTRACT

BACKGROUND: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. METHODS: In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (Day 10-21 post-therapy). RESULTS: Of the 428 patients who received at least one dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. CONCLUSION: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP. TRIAL REGISTRATION: NCT00081575.


Subject(s)
Community-Acquired Infections/drug therapy , Levofloxacin , Minocycline/analogs & derivatives , Ofloxacin/adverse effects , Ofloxacin/therapeutic use , Pneumonia, Bacterial/drug therapy , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/microbiology , Diarrhea/chemically induced , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Minocycline/administration & dosage , Minocycline/adverse effects , Minocycline/therapeutic use , Nausea/chemically induced , Ofloxacin/administration & dosage , Prospective Studies , Severity of Illness Index , Tigecycline , Treatment Outcome , Vomiting/chemically induced , Young Adult
14.
Lancet Oncol ; 10(6): 549-58, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19428297

ABSTRACT

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a clinical management problem after treatment with highly emetogenic chemotherapy (HEC). We therefore designed and carried out a multicentre, randomised, double-blind, placebo-controlled trial to assess whether a three-drug antiemetic regimen of ondansetron, dexamethasone, and the neurokinin-1-receptor antagonist casopitant mesylate was able to prevent acute and delayed CINV events in patients naive to chemotherapy with a malignant solid tumour who were scheduled to receive cisplatin-based HEC regimens. METHODS: The study was done between Nov 6, 2006, and Oct 9, 2007, in 77 participating centres in 22 countries. All 810 patients enrolled in the trial received dexamethasone and ondansetron. Patients were randomly assigned to also receive placebo (n=269), single oral dose of casopitant mesylate (150 mg oral, n=271), or 3-day intravenous plus oral casopitant mesylate (90 mg intravenous on day 1 plus 50 mg oral on days 2 and 3, n=270). Randomisation was done using a central telephone system at the study level, because some centres were expected to recruit only a few patients during the study period. The primary endpoint was the proportion of patients achieving complete response (no vomiting, retching, or use of rescue medications) in the first 120 h after receiving HEC. Efficacy analysis was done on the modified intention-to-treat population (n=800), which included all patients who received placebo or study drug and HEC (n=265 control, n=266 single-dose oral casopitant mesylate, n=269 3-day intravenous and oral casopitant mesylate). Safety was reported in 802 patients who received either placebo or study medication. This study is registered with ClinicalTrials.gov, NCT00431236. FINDINGS: Significantly more patients in each casopitant group achieved complete response in cycle 1 of HEC treatment than did those in the control group (175 [66%] patients in the control group, 228 [86%] in the single-dose oral casopitant mesylate group [p<0.0001 vs control], and 214 [80%] in the 3-day intravenous plus oral casopitant mesylate group (p=0.0004 vs control]). This improvement was sustained over multiple cycles of HEC. Adverse events occurred in 205 (77%) patients in the single-dose oral casopitant mesylate group and 203 (75%) patients in the 3-day intravenous and oral casopitant mesylate group compared with 194 (73%) of patients in the control group. The most common serious adverse events were neutropenia (n=5 [3%] in the control group, n=3 [1%] in the single-dose oral casopitant mesylate group, and n=11 [4%] in the 3-day intravenous plus oral casopitant mesylate group), febrile neutropenia (n=1 [<1%] in the control group, n=4 [1%] in the single-dose oral casopitant mesylate group, and n=6 [2%] in the 3-day intravenous plus oral casopitant mesylate group), and dehydration (n=4 [2%] in the control group, n=2 [<1%] in the single-dose oral casopitant mesylate group, and n=1 [<1%] in the 3-day intravenous plus oral casopitant mesylate group). INTERPRETATION: A three-drug regimen including a single oral dose or 3-day intravenous plus oral regimen of casopitant mesylate plus dexamethasone and ondansetron significantly reduced CINV events in patients receiving HEC compared with a two-drug regimen of dexamethasone and ondansetron. FUNDING: GlaxoSmithKline.


Subject(s)
Antiemetics/therapeutic use , Cisplatin/therapeutic use , Nausea/prevention & control , Neoplasms/drug therapy , Neurokinin-1 Receptor Antagonists , Piperazines/therapeutic use , Piperidines/therapeutic use , Vomiting/prevention & control , Administration, Oral , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Infusion Pumps , Male , Middle Aged , Molecular Structure , Nausea/chemically induced , Piperazines/administration & dosage , Piperidines/administration & dosage , Vomiting/chemically induced , Young Adult
15.
Clin Cancer Res ; 15(5): 1741-6, 2009 Mar 01.
Article in English | MEDLINE | ID: mdl-19240177

ABSTRACT

PURPOSE: The newly identified bone marrow-derived cell population, called lymphatic/vascular endothelial progenitor cells (LVEPC), has been shown to contribute to lymph capillary growth in experimental tumor systems. The clinical significance of these cells has not yet been investigated in a human malignancy. Our aim was to study whether peripheral blood circulating LVEPCs participate in the progression of human small cell lung cancer (SCLC). EXPERIMENTAL DESIGN: A total of 88 patients with limited-stage SCLC and 32 tumor-free control subjects were included. Peripheral blood circulating LVEPC labeled with CD34 and vascular endothelial growth factor receptor-3 (VEGFR3) antibodies and the serum levels of the key lymphangiogenic molecule VEGF-C were measured by flow cytometry and ELISA, respectively. RESULTS: CD34-positive/VEGFR3-positive LVEPC levels were significantly increased in patients (versus controls; P<0.01), and there was also a significant relationship between LVEPC counts and lymph node metastasis (P<0.01). High pretreatment circulating LVEPC numbers correlated with poor overall survival (P<0.01). Although we observed significantly elevated VEGF-C concentrations in patients (versus controls; P<0.01), there was no significant correlation between VEGF-C and LVEPC levels. Moreover, no significant differences in peripheral blood VEGF-C levels were seen between patients subgrouped by clinicopathologic variables including tumor and lymph node stages and survival. CONCLUSIONS: Peripheral blood levels of bone marrow-derived LVEPCs are significantly increased in patients with SCLC and correlate with lymphatic involvement and prognosis. This is the first study that shows evidence of increased numbers of circulating LVEPC in patients with a malignant tumor.


Subject(s)
Endothelial Cells/metabolism , Lung Neoplasms/metabolism , Lymphatic Vessels/metabolism , Small Cell Lung Carcinoma/metabolism , Stem Cells/metabolism , Vascular Endothelial Growth Factor Receptor-3/blood , Adult , Aged , Bone Marrow/metabolism , Bone Marrow/pathology , Case-Control Studies , Disease Progression , Endothelial Cells/pathology , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Follow-Up Studies , Humans , Lung/metabolism , Lung/pathology , Lung Neoplasms/pathology , Lymphatic Metastasis , Lymphatic Vessels/pathology , Male , Middle Aged , Prognosis , Small Cell Lung Carcinoma/pathology , Stem Cells/pathology , Survival Rate , Vascular Endothelial Growth Factor C/blood
17.
Pathol Oncol Res ; 14(3): 313-9, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18543081

ABSTRACT

Noninvasive imaging methods can be valuable tools for diagnosing thoracic diseases, especially malignancies. The aim of this study was to compare the effectiveness of conventional and virtual bronchoscopy in the follow-up of patients with large airway stenosis. Twenty-three consecutive patients with stenoses of the trachea and/or the main bronchi were enrolled in this prospective observer study. The causes of stenosis included malignant or benign tumours, goiter, and postintubation stenoses. Patients were evaluated before and after treatment (which included mechanical dilation, laser photocoagulation, stent implantation, radiotherapy, chemotherapy, and surgical resection). The mean time between baseline and follow-up endoscopy was 140 days. No significant differences were observed between the estimated and measured data from bronchofibroscopy and virtual bronchoscopy. Exact measurement of stenoses was performed with virtual bronchoscopy.


Subject(s)
Airway Obstruction/therapy , Bronchoscopy/methods , Fiber Optic Technology , Tracheal Stenosis/therapy , User-Computer Interface , Adult , Aged , Airway Obstruction/diagnosis , Drug Therapy , Female , Follow-Up Studies , Humans , Light Coagulation , Male , Middle Aged , Prospective Studies , Radiotherapy , Stents , Tracheal Stenosis/diagnosis
18.
Orv Hetil ; 148(18): 829-31, 2007 May 06.
Article in Hungarian | MEDLINE | ID: mdl-17468065

ABSTRACT

At present, 8-10 million new cases of tuberculosis and 3 million tuberculosis related deaths occur worldwide. Approximately 90% of patients and deaths occur in the developing countries. In Hungary, 2024 new cases with tuberculosis were detected in 2005. This incidence corresponds to the epidemiological data of western European countries. However, the multidrug and extensively drug resistant bacteria challenged the otherwise effective antimicrobial therapy. In Hungary, 27 new multidrug-, and 3 new extensively drug resistant tuberculoses were detected in 2005. The recommendation of the World Health Organisation and the renewed guideline of the Hungarian Board of Pulmonology include all criteria necessary to the effective prevention, diagnosis and therapy of multidrug-, and extensively drug resistant tuberculoses.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Drug Resistance, Bacterial , Humans , Hungary/epidemiology , Incidence , Practice Guidelines as Topic , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology
19.
J Clin Oncol ; 25(12): 1545-52, 2007 Apr 20.
Article in English | MEDLINE | ID: mdl-17442998

ABSTRACT

PURPOSE: Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL). RESULTS: A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild). CONCLUSION: Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Quinazolines/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Erlotinib Hydrochloride , Female , Humans , Lung Neoplasms/pathology , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Probability , Prognosis , Quinazolines/adverse effects , Risk Assessment , Statistics, Nonparametric , Survival Analysis , Gemcitabine
20.
Magy Onkol ; 50(2): 121-5, 2006.
Article in Hungarian | MEDLINE | ID: mdl-16888675

ABSTRACT

Bronchoscopic imaging and diagnostics are tightly connected with radiological and pathological techniques. While computer tomography (virtual bronchoscopy) makes possible to mimic a realistic endobronchial situation, autofluorescent bronchoscopy holds significant potential to discover precancerous lesions not identifiable by standard bronchoscopy. Endoscopic ultrasound and fluoroscopy can be applied in order to obtain images and tissue samples from the extrabronchial areas. Electromagnetic navigation during flexible bronchoscopy, a novel technology that facilitates approaching peripheral lung lesions, involves creating an electromagnetic field around the thorax and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. In conclusion, parallel use of invasive and non-invasive imaging has the potential for considerable improvements in the diagnostic possibilities of routine bronchoscopic procedures.


Subject(s)
Bronchial Neoplasms/diagnosis , Bronchoscopy/methods , Endosonography , Fluorescence , Tomography, X-Ray Computed , Electromagnetic Phenomena , Fluoroscopy , Humans , Precancerous Conditions/diagnosis , User-Computer Interface
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