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AIMS: The aim of the study was to analyse the prognostic and predictive value of LC3A positive' 'Stone Like Structures'' (SLSs) in a large cohort of patients with non-small cell lung carcinoma (NSCLC) and to check its relationship with tumor infiltrating lymphocytes (TILs) and PD-L1 expression. METHODS: Tissue microarrays from 1015 patients diagnosed at the Institute of Pathology and Molecular Pathology, University Hospital Zurich, Switzerland, were stained for LC3A, PD-L1, CD3 and CD68 using automated tissue stainer Ventana Benchmark Ultra (Roche). TILs were assessed in matched haematoxylin and eosin stained slides. RESULTS: LC3A positive SLSs, were significantly associated with worse overall (OS) and disease-free survival (DFS) outcomes in patients with lung adenocarcinoma (LADC) (HR = 2.4, 95 %CI(.994-1.008, p = 0.029) and HR = 3.9, 95 %CI (1.002-1.014), p = 0.002 respectively), whilst it was associated with better OS and DFS in patients with lung squamous cell carcinoma (LUSC), with marginal significance (HR = .99, 95 %CI(.975-1.011),p = 0.042 and HR = .99, 95 %CI (.975-1.008), p = 0.026). Multivariate analysis showed that LC3A SLSs are independent poor prognostic factor only in patients with LADC. In addition, LC3A SLSs, were negatively associated with CD68 count in LADC, whilst there was a positive correlation in LSCC. CONCLUSIONS: LC3A SLSs are differentially associated with the survival outcomes and CD68 count in LADC and LSCC. Further studies are justified for the understanding the underlying biological mechanisms of this phenomenon.
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Adenocarcinoma del Pulmón , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Macrófagos , Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Antígeno B7-H1 , Humanos , Linfocitos Infiltrantes de Tumor , Proteínas Asociadas a Microtúbulos , Pronóstico , SuizaRESUMEN
BACKGROUND: Clear cell renal carcinoma (ccRC) accounts for 65-70% of renal carcinomas with peak occurrence at the 6th and 7th age decade, predominantly in males. At the time of diagnosis, especially pulmonary metastases can be found in one-third of patients. There have also been described as late metastases for several decades after nephrectomy. In our case report, clinical course indicated primary lung tumour. Histological differential diagnosis included malignant pleural mesothelioma, lung adenocarcinoma and squamous cell carcinoma with clear cell differentiation or primary clear cell adenocarcinoma of the lung. However, using immunohistochemistry, all these possible diagnoses were excluded. CASE REPORT: We present a case of 62-year old man with 3 months history of progressive dyspnea accompanied with a cough and recurrent pleural effusions. PET/CT scan revealed metastatic tumour spread with right-sided pleural thickening, multiple pulmonary tumour foci, mediastinal, cervical, abdominal para-aortic and pelvic lymph node involvement and skeletal metastasis. The patient died one day after administration of palliative chemotherapy. The autopsy showed the majority of changes in the right hemithorax, was caused by a diffuse yellowish, extremely tough tumour infiltrating parietal and visceral pleura with adhesions and obliteration of truncus pulmonalis. In left lung and both renal cortices we could see scant nodules, mimicking primary lung tumour metastasis. In close proximity to the left renal hilum we found unusual homogeneous white round to oval tissue of 80 × 86 × 72mm in diameter, with identical histological pattern. Extensive immunohistochemical profile (positivity of CK18, PAX8, vimentin, androgen receptor, napsin A; negativity of mesothelial markers, TTF-1, CK7, CK20, CDX-2, CD10, PSA, CK34B12 and PAS-D) was compatible with metastatic ccRC. CONCLUSION: We present an extremely rare case of morphologically verified metastatic ccRC without evidence of primary lesion in the kidneys. There is speculated the possibility of spontaneous regression of primary tumour. In our case, however, we cannot exclude the possibility of generalized primary tumour of ectopic kidney. This hypothesis is based on the finding of isolated tumour mass adjacent to left renal hilum.
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Carcinoma de Células Renales/secundario , Diagnóstico Diferencial , Neoplasias Renales/patología , Neoplasias Pulmonares/patología , Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Resultado Fatal , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
Silicosis, caused by inhaling dust containing free crystalline silica, typically has a chronic course, with the numbers of silicosis patients declining globally. Much rarer are the acute and subacute forms. Presented is a case of severe subacute (accelerated) silicosis. The condition resulted from ~2 years of very intense exposure without appropriate personal protective equipment while sandblasting. The patient's initial symptoms were progressive cough, dyspnoea and weight loss. Given his occupational history, typical clinical manifestations and radiological findings, an initial diagnosis of accelerated silicosis was proposed and histologically confirmed. The patient was a candidate for lung transplantation. The case demonstrates a rare but largely preventable disease with serious health effects and a poor prognosis.
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Silicosis/complicaciones , Adulto , Tos/etiología , Disnea/etiología , Humanos , Masculino , Exposición Profesional/efectos adversos , Pletismografía/métodos , Dióxido de Silicio/efectos adversos , Silicosis/etiologíaRESUMEN
Sleep apnoea (SA) is common in patients with hypertension. Nowadays, limited data on the prevalence of SA in nocturnal hypertension (NH) exist. Therefore, we studied the occurrence of SA in Czech patients and its association with 24-h ambulatory blood pressure monitoring (ABPM), breathing disturbances in sleep, anthropometric data, Mallampati score and Epworth sleepiness scale (ESS) using the Apnea Link device. Undiagnosed SA was found in 72.9 % patients (29.3 % mild, 26.6 % moderate, 17.0 % severe) of 188 patients with NH measured by ABPM. The median of the apnoea-hypopnoea index (AHI) was 12.0 (25th-75th percentile 5.0-23.8). Moderate/severe SA (AHI>/=15) was associated with BMI, waist circumference, mean night saturation (SpO(2)), t90, oxygen desaturation index (ODI), ESS (daytime BP only) (p=0.032), but not ABPM parameters and Mallampati score (p>0.09). A likelihood of moderate/severe SA was enhanced by ODI>14.5 events/h (odds ratio=57.49, 95 % CI=22.79-145.01), t90>6.5 % (8.07, 4.09-15.92), mean night SpO(2)<93.5 % (3.55, 1.92-6.59), BMI>29.05 kg/m(2) (6.22, 3.10-12.49), circum waist>105.5 cm (3.73, 1.57-8.83), but not by any ABPM parameter. In conclusion, a high incidence of SA (72.9 %) was observed in Czech patients with NH. SA severity was associated with body characteristics and oxygenation parameters, but not with ABMP parameters and Mallampati score.
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Hipertensión/epidemiología , Síndromes de la Apnea del Sueño/epidemiología , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Índice de Masa Corporal , Estudios de Cohortes , República Checa/epidemiología , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Polisomnografía , Prevalencia , Mecánica Respiratoria , Síndromes de la Apnea del Sueño/complicaciones , Fases del Sueño , Circunferencia de la CinturaRESUMEN
BACKGROUND: Estrogens are steroid hormones that affect a number of physiological functions in cells; these compounds play an irreplaceable role in the reproductive system. Their effects are mediated by the estrogen receptor (ER), of which there are two subtypes - ERα and ERβ. ERs are expressed in regions outside the reproductive system, including bone, brain, intestine, endothelium, kidney, and lung. Expression of ER by lung cancer (LC) cells was first described in the early 1980s. The experimental literature also describes co-expression of ERβ and an epidermal growth factor activating mutation, and the additive antiproliferative effects of anti-estrogens plus tyrosine kinase inhibitors during treatment of lung adenocarcinoma. However, coincident expression of ER and ALK translocation were not decribed. The 4-year survival for generalized non-small cell lung cancer indicates the possibility that both molecular features (ER and ALK positivity) may be a favorable prognostic biomarker for this tumor. CASE: A 69-year-old patient presented with generalized lung adenocarcinoma that was positive for ERb and the ALK-EML4 fusion gene. The tumor was stage IV. Additional examinations excluded malignancy of the gynecological area. The patient was treated with chemotherapy and a tyrosine kinase ALK inhibitor. CONCLUSION: The role of individual ER subtypes in LC carcinogenesis, and the possible therapeutic effects, is unclear. This is the first documented case of co-occurrence of ALK-EML4 and ERβ in LC. Key words non-small cell lung cancer - estrogen receptors - ALK translocation - prognosis - treatment This work was supported by Ministry of Health of the Czech Republic, grant AZV 16-32318A, and by Ministry of Education, Youth and Sports of the Czech Republic, grant NPU I LO1304. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 23. 9. 2018 Accepted: 25. 10. 2018.
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AIM: Catamenial pneumothorax is menstrual cycle dependent and represents the most common form of thoracic endometriosis syndrome. Recurrences are very common even after surgical resection. DESIGN: Case reports and literature overview. SETTING: Department of Respiratory Medicine, Department of Surgery I, Department of Obstetrics and Gynecology, University Hospital, Palacky University, Olomouc. CASE REPORT: Two cases of catamenial pneumothorax are presented with repeated recurrences of right-sided pneumothorax even after surgical treatment. Histopathologic finding of pelvic endometriosis was shown in both patients. CONCLUSION: Catamenial pneumothorax is usually connected with thoracic endometriosis and also includes catamenial hemothorax, recurrent catamenial hemoptysis, catamenial pleural pain as well as endometriosis lung nodules. Multidisciplinary approach including pneumologist, thoracic surgeon and gynecologist with early postoperative hormonal treatment that deals with the main chronic systemic disease may lead to improved results, mainly reduced recurrence rates of catamenial and/or endometriosis related pneumothorax.
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Endometriosis/complicaciones , Neumotórax/etiología , Enfermedades Torácicas/complicaciones , Dismenorrea , Endometriosis/patología , Femenino , Humanos , RecurrenciaRESUMEN
BACKGROUND: This article is a joint statement of the Czech Pneumological and Physiological Society and the Czech Society for Radiation Oncology, Biology and Physics, and reviews current opinions on radiotherapy in patients with idiopathic pulmonary fibrosis (IPF). In general, radiotherapy of lung tumours is associated with risk of radiation pneumonitis (RP); moreover, IPF may be complicated by acute exacerbations (AE-IPF). Both complications may immediately threaten patients lives. MATERIAL AND METHODS: Assessment of individual radiotherapy modalities has shown that conventional radiotherapy is not appropriate, especially in large tumours. Up to 30% of patients are at risk of developing AE-IPF. As a result, as many as 83% of patients die within 3 months of initiation of lung cancer treatment. Fatal RP is most commonly observed within 2 months of radiotherapy. In IPF accompanied by early-stage non-small cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) may be considered. NSCLC should be treated with chemotherapy. Several cases report severe exacerbations of subclinical IPF after SBRT even with minimal signs of previous interstitial involvement. Grade 2 RP has been reported in up to 50% of cases with any level of interstitial change detected by lung CT prior to radiotherapy. In palliative radiotherapy, external radiation may be considered as an exception if the main bronchi are involved. Similarly, brachytherapy may be indicated for certain cases of bronchial stenosis. RESULTS: The presence of any level of interstitial change suggests a risk for fatal RP and AE-IPF. This is also supported by the fact that, at the present time, there are no dose limitations for radiation therapy of lung cancer in IPF, irrespective of whether conventional fractionated radiotherapy or SBRT is used. Moreover, there are no reliable predictive factors for lung involvement. In some studies, RP was more frequently associated with high CRP and LDH levels, PS 2 and interstitial changes of 10% or more. Treatment depends on the severity of the involvement. In more severe forms, corticosteroids, antibiotics and oxygen therapy should be administered. Ventilation support is often needed. CONCLUSION: Radiotherapy for patients with IPF and lung cancer or other chest tumours requires an individual approach depending on the local findings, the patients lung function and general condition, and the prognosis of the primary disease. Decision-making should take into consideration potential benefits and risks, and be carried out by a multidisciplinary team comprising a pulmonologist and clinical and radiation oncologists. Treatment should always be thoroughly discussed with the patient signing an informed consent form.Key words: idiopathic pulmonary fibrosis - chest radiotherapy - indications - radiation pneumonitis - acute exacerbation of idiopathic pulmonary fibrosis - treatment This work was supported by grant AZV 16-32-318 A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 4. 5. 2017Accepted: 18. 5. 2017.
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Fibrosis Pulmonar Idiopática/fisiopatología , Neoplasias Pulmonares/radioterapia , Neumonitis por Radiación/etiología , Radioterapia/efectos adversos , Enfermedad Aguda , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Progresión de la Enfermedad , Humanos , Fibrosis Pulmonar Idiopática/etiología , Neoplasias Pulmonares/fisiopatología , Neumonitis por Radiación/fisiopatología , Radiocirugia/efectos adversosRESUMEN
BACKGROUND: There is still a lack of evidence as to which method of biological sample collection is optimal for identifying bacterial pathogens causing hospital-acquired pneumonia (HAP). Much effort has been made to find an easy and valid approach to be used in clinical practice. METHODS: The primary endpoint of this prospective, observational study was to determine the predictive value of oropharyngeal swab (OS) and gastric aspiration (GA) as simple and non-invasive methods for diagnosing HAP. Their efficacy was compared to endotracheal aspiration (ETA) and protected specimen brushing (PSB), the standard methods approved for HAP diagnosis. RESULTS: Initially, 56 patients were enrolled. Significant amounts of bacterial pathogens were detected in 48 patients (79 isolates) in Round A and in 39 patients (45 isolates) in Round B (after 72 hours). The sensitivity rates were: ETA 98%, PSB 31%, OS 64% and GA 67% in Round A and ETA 87%, PSB 32%, OS 74% and GA 42% in Round B. Strains of 12 bacterial species were identified in the samples. The three most common etiological agents (both rounds together) were Klebsiella pneumoniae (23.7%), Burkholderia multivorans (21.1%) and Pseudomonas aeruginosa (15.8%). CONCLUSIONS: Blind ETA is an optimum method for obtaining biological samples for identification of etiological agents causing HAP in intubated patients. Microbial etiological agents were more frequently detected in ETA samples than in those collected by PSB. If ETA/PSB results are negative, samples may be collected by OS and/or GA as these techniques followed ETA in terms of the frequency of pathogen detection.
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Bacterias , Infección Hospitalaria , Técnicas Microbiológicas , Neumonía Bacteriana , Bacterias/aislamiento & purificación , Cuidados Críticos , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/microbiología , Humanos , Técnicas Microbiológicas/normas , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
An actin-binding protein filamin A connects the actin filament network to cell membrane receptors, and acts as a scaffold for various signaling pathways related to cancer growth and progression. Recently, it has been reported that filamin A is required for efficient regulation of early stages of DNA repair process. Moreover, some in vitro studies showed that the overexpression of filamin A determines resistance to various cytotoxic drugs, including cisplatin. We aimed to analyse the expression of filamin A protein in resected NSCLC (Non Small Cell Lung Cancer) specimens, to investigate the association of the level of filamin A protein expression and other clinicopathological features, and possible relationship between the expression of filamin A and survival outcome in NSCLC patients, treated with platinum-based combination chemotherapy. We performed filamin A protein immunohistochemistry on formalin-fixed and paraffin-embedded (FFPE) tissue sections from 135 NSCLC patients, using EP2405Y antibody against C-terminus of filamin A. Cytoplasmic, membranous and nuclear positivity of filamin A was evaluated semi-quantitatively and correlated with available clinicopathological data. Patients were divided into two groups for survival analysis (I group - patients treated with adjuvant platinum-based chemotherapy, II group - patients with surgical treatment only). We found significant positive correlation between filamin A protein expression and NSCLC stage (r=0.249; p<0,05), presence of lymph node (N)(r=0.205; p<0,05) and distant metastases (M) (r=0.332; P<0.01). Increased filamin A protein expression was significantly related with poor survival outcomes in patients with adjuvant platinum-based chemotherapy: OS (HR=1.005, 95%CI[1.000;1.010], p=0.037), DFS (HR=1.004, 95%CI [1.001:1.008], p=0,017). Multivariate Cox proportional hazards regression analysis also showed that overexpression of filamin A represents an independent risk factor for disease relapse, in addition to tumor size, stage, and metastases status (HR=1.723, 95%CI [1.021:2.909], p<0.05). Thus, filamin A expression might be a new prognostic marker in patients with NSCLC.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/biosíntesis , Carcinoma de Pulmón de Células no Pequeñas/patología , Cisplatino/uso terapéutico , Filaminas/biosíntesis , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Femenino , Filaminas/genética , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/mortalidad , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Resultado del TratamientoRESUMEN
BACKGROUND: Adjuvant chemotherapy became a standard of treatment in completely resected non-small cell lung cancer (NSCLC) based on results of big trials meta-analyses, which proved its influence on the decrease of relative mortality risk and absolute improvement of survival. Adjuvant chemotherapy is routinely used according to tumor stage evaluation, performance status (PS) and age of the patients. It is indicated in stage II and IIIA of NSCLC- in frame of clinical studies also in stage IB, in PS 0-1 and in patients under 75 years. Therapy with cisplatin and vinorelbine is a preferred regimen, as well as other drugs, such as paclitaxel, docetaxel, gemcitabine and pemetrexed. The problem is a relatively small dose intensity applied, due to toxic side effects. AIM: The present work is evaluating contemporary trends of adjuvant therapy in NSCLC according to latest clinical studies, which are finished or running. Efforts are directed to the improvement of treatment effectiveness, decrease of side effects and refinement of patients selection. Potential treatment benefit of better tolerable carboplatin is verified and results of trials with biologically targeted therapy are expected. Large clinical studies are evaluating the effect of tyrosine kinase inhibitors and angiogenesis inhibitors used either in various combinations with chemotherapy or as monotherapy. Application of vaccines is tested. CONCLUSION: Contemporary trend of adjuvant therapy is leading to the appropriate patient selection with regard to analysis of several prognostic and predictive biomarkers; it is proposed that future adjuvant therapy will be more and more personalized.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Factores de Edad , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Docetaxel , Medicina Basada en la Evidencia , Humanos , Neoplasias Pulmonares/cirugía , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Pronóstico , Taxoides/administración & dosificación , Taxoides/efectos adversos , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/análogos & derivados , Vinorelbina , GemcitabinaAsunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Sistema de Registros , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Bevacizumab , República Checa , Clorhidrato de Erlotinib , Gefitinib , Glutamatos/uso terapéutico , Guanina/análogos & derivados , Guanina/uso terapéutico , Humanos , Pemetrexed , Quinazolinas/uso terapéuticoRESUMEN
Several expert systems were developed for assessment of community-acquired pneumonia (CAP) and its severity in individual patients. Scoring systems PSI, CURB-65, and CRB-65 are widely used. They were primarily designed for easier decision on need of CAP patients hospitalization. Newer scoring systems evaluate especially severity of CAP and need of intensive care. This group of systems comprise ATS/IDSA recommendations, CURXO-8O, SMART-COP, and SMRT-CO. The last one appears to be the most appropriate for common practice but more studies are necessary to confirm this opinion. Regardless of the scoring systems the authors recommend more extensive usage of pulse oxymetry in the care of CAP patients.
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Neumonía/clasificación , Infecciones Comunitarias Adquiridas , Humanos , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor ß, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes.
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Sarcoidosis Pulmonar/metabolismo , Proteínas de Dominio T Box/metabolismo , Células TH1/metabolismo , Regulación hacia Arriba , Adulto , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CCL5/genética , Quimiocina CCL5/metabolismo , Femenino , Expresión Génica , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Pulmón/metabolismo , Ganglios Linfáticos/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Receptores CXCR6 , Receptores de Quimiocina/genética , Receptores de Quimiocina/metabolismo , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/metabolismo , Receptores Virales/genética , Receptores Virales/metabolismo , Sarcoidosis Pulmonar/genética , Sarcoidosis Pulmonar/inmunología , Células TH1/inmunologíaRESUMEN
In the recent genome-wide association study the polymorphisms of annexin A11 (ANXA11) gene were associated with susceptibility to sarcoidosis. Beside the replication of this finding and analysis of local ANXA11 expression in bronchoalveolar lavage cells, we wondered whether 'leading' ANXA11 rs1049550 (R230C) variant might also be related to the clinical manifestation of sarcoidosis. The study included 245 Czech patients with sarcoidosis and 254 healthy control subjects. The frequency of ANXA11(*)T allele was significantly lower in patients with sarcoidosis (35%) compared with controls (42%, P=0.04, odds ratio=0.77). Furthermore, ANXA11(*)T allele was less frequent in patients with the infiltration of lung parenchyma by comparison with those with isolated hilar lymphadenopathy (P=0.01). In line with the previous observation, ANXA11 mRNA expression was not deregulated in sarcoidosis and was independent from rs1049550 variant. In conclusion, ANXA11 rs1049550 single nucleotide polymorphism is the susceptibility marker in sarcoidosis, at least in Caucasians. Its role as a disease modifier should be independently replicated.
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Anexinas/genética , Predisposición Genética a la Enfermedad , Sarcoidosis/genética , Adulto , Anexinas/metabolismo , Biomarcadores , Femenino , Estudio de Asociación del Genoma Completo , Granuloma/genética , Humanos , Pulmón/patología , Enfermedades Pulmonares/genética , Enfermedades Linfáticas/genética , Enfermedades Linfáticas/patología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Mensajero/biosíntesis , Sarcoidosis/metabolismoRESUMEN
INTRODUCTION: Lung cancer takes first place in both incidence and mortality in the Czech Republic. This is associated with the disease being diagnosed in late stages, which limits the possibility of radical therapy. Five-year survival of patients operated on with stage IIIA is low and doesn't even reach 20%. These poor results and the development of systemic chemotherapy in the 1990's led to an effort to treat locally advanced disease by administering chemotherapy before the surgical procedure- induction chemotherapy. Its benefit, however, unlike that of adjuvant chemotherapy, remains unclear. AIM: To analyze and compare the results between a set of patients with non-small cell lung cancer (NSCLC) with stage III A-B, operated on at the I. Department of Surgery at the University Hospital and Palacky Medical Faculty in Olomouc between the years 2000-2008, who underwent preoperative chemotherapy with the results of patients with stage III A-B diagnosed after the operation based on histological findings. Three- and five-year survivals, as well as survival median, were evaluated in both groups. RESULTS: A statistically significant difference in survival between the two groups was not observed. CONCLUSION: Neoadjuvant chemotherapy remains controversial in the treatment of NSCLC. The initially promising results have not been unequivocally confirmed in later studies and its role remains a question to be answered in future extensive randomized studies.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Terapia Neoadyuvante , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Neumonectomía , Tasa de SupervivenciaRESUMEN
The objective of this study was to assess protein levels for candidate cytokines, chemokines, growth factors, matrix metalloproteinases and their inhibitors in bronchoalveolar lavage fluid (BALF) in patients with polar forms of pulmonary sarcoidosis, i.e. Löfgren's syndrome (LS) and more advanced chest X-ray (CXR) stage III disease. Twenty-four inflammatory molecules were analysed in unconcentrated BALF samples from 10 sarcoidosis patients with CXR stage III and 10 patients with LS by semiquantitative protein array. Four novel molecules [CC chemokine ligand (CCL)15, CCL16, macrophage migration inhibitory factor (MIF) and macrophage stimulating protein (MSP)], detected for the first time in association with sarcoidosis, were then quantified by enzyme-linked immunosorbent assay in a second cohort of 68 sarcoidosis patients and 17 control subjects. The protein levels of CCL15, CCL16, CCL24, CXCL8, CXCL9, CXCL10, interleukin-16, MIF, MSP and matrix metallopeptidase 1 were increased in CXR stage III patients when compared with patients with LS. CCL15 and MSP up-regulation in CXR stage III patients in comparison with LS patients and controls was confirmed by enzyme-linked immunosorbent assay. Moreover, MSP was associated with treatment requirement (P = 0.001) and CCL15 was elevated in patients with disease progression at 2-year follow-up (P = 0.016). CCL16 levels were increased in sarcoidosis versus controls (P < 0.05), but no difference was observed between patient subgroups. MIF up-regulation was not confirmed in a larger patient group. In conclusion, chemokines CCL15, CCL16 and MSP were found elevated for the first time in BALF from sarcoidosis patients; our results showed that CCL15 and MSP may affect disease course.
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Quimiocinas CC/análisis , Factor de Crecimiento de Hepatocito/análisis , Proteínas Inflamatorias de Macrófagos/análisis , Proteínas Proto-Oncogénicas/análisis , Sarcoidosis Pulmonar/inmunología , Regulación hacia Arriba , Adulto , Análisis de Varianza , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Inflamación , Oxidorreductasas Intramoleculares/análisis , Factores Inhibidores de la Migración de Macrófagos/análisis , Masculino , Metaloproteinasas de la Matriz/análisis , Persona de Mediana Edad , Adulto JovenRESUMEN
Idiopathic pulmonary fibrosis (IPF), a severe lung disease with unknown aetiology, is thought to have an important genetic component. Single nucleotide polymorphism, C5507G, of the complement receptor 1 (CR1) gene, which affects the number of CR1 molecules on erythrocytes, has been associated with susceptibility to IPF in a single European population. To replicate this finding, 53 Czech IPF patients with 203 Czech healthy control subjects and 70 English IPF patients with 149 English controls were investigated. In both populations, there were no significant differences in distribution of CR1 C5507G variants between IPF patients and their appropriate control groups. In conclusion, the association of the CR1 C5507G polymorphism with susceptibility to IPF was not reproducible in Czech and English populations.