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Amiodarone is an anti-arrhythmic drug widely used, but its administration can be associated with several adverse side-effects. Among these, amiodarone-induced pulmonary toxicity (APT) occurs in 4-17% of cases and, if not early diagnosed and treated, may evolve towards pulmonary fibrosis and respiratory failure. A 76 years-old-man went to the hospital for accidental trauma. The patient did not report respiratory symptoms but was suffering from atrial fibrillation treated with amiodarone 200 mg/day from three years (cumulative dose >150 gr). HRCT showed ground-glass opacities and nodules in both lungs. The patient underwent fibreoptic bronchoscopy with BAL. Cytologic examination of BALF sediment put in evidence foamy macrophages. The electronic microscopy revealed into the alveolar macrophages " the presence of multilamellar intracytoplasmic bodies and lysosomes, loads of lipid material". LFTs showed a restrictive syndrome and an impairment of DLCO. Amiodarone discontinuation and steroid administration led to the regression of radiological lesions and the recovery of lung function. Patients taking amiodarone can experience APT. They should perform a basal chest x-ray with LFTs before starting therapy. Monitoring could reveal early the pulmonary toxicity, and patients can respond favourably to the treatment.
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In non-small cell lung cancer (NSCLC), there is a consensus regarding the use of liquid biopsy, generally, to detect "druggable" mutations and, in particular, to monitor tyrosine kinase inhibitor (TKI) treatments. However, whether circulating tumor cells (CTCs) are better tools than cell-free DNA (cfDNA), is still a matter of debate, mainly concerning which antigen(s) we should use to investigating simultaneously both epithelial and epithelial-to-mesenchymal transient (EMT) phenotype in the same sample of CTCs. To address this item, we exploited here a single-tube liquid biopsy, to detect both epithelial cell adhesion molecule (EpCAM)-positive CTCs and EpCAM-low/negative CTCs, because down-modulation of EpCAM is considered the first step in EMT. Furthermore, we analyzed the DNA from CTCs of four different phenotypes (ctcDNA), according to their EpCAM expression and cytokeratin pattern, and circulating tumor DNA (ctDNA) by droplet digital PCR (ddPCR), in order to disclose activating and resistance-driving mutations. Liquid biopsy reflected spatial and temporal heterogeneity of the tumor under treatment pressure. We provide the proof-of-concept that the complementary use of ctDNA and ctcDNA represents a reliable, minimally invasive and dynamic tool for a more comprehensive view of tumor evolution.
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INTRODUCTION: Lipoid pneumonia is a clinical condition that may be initially asymptomatic or confused with an infectious or malignant lung disease. OBJECTIVES: We report four cases of this pathological condition. METHODS: The first case concerned an 85-year old woman with bilateral confluent pulmonary opacities, ground-glass type. Diagnosis was based on the cytology of the bronchoalveolar lavage (BAL) fluid followed by its ultrastructural examination. The second case was a 47-year-old man with an isolated pulmonary nodule, which was surgically removed; the diagnosis of lipoid pneumonia was formulated on the basis of the histological and electron microscopy examination. The third case concerned a 73-year-old woman, with bilateral hypodense areas at the bases of the lungs where FDG PET/CT scan showed an increased uptake. Diagnosis was formulated by BAL cytology and electron microscopy examination. The fourth case was a 69-year-old man, who performed a virtual colonoscopy for diverticulosis putting in evidence a round mass (3 cm in diameter) with two small peripheral nodules, located in the pulmonary left lower lobe. The histopathological examination of transthoracic biopsy confirmed a lipoid pneumonia. RESULTS AND CONCLUSION: In all four cases, it was put in evidence a prolonged use of a nasal decongestant containing mineral oils. In literature, the most cases described are characterized by a subclinical evolution and were presented as ground glass opacities which evolve, in the later phases, in an interstitial involvement or in a peripheral mass, simulating a lung tumour.
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Neoplasias Pulmonares/patología , Pulmón/patología , Descongestionantes Nasales/efectos adversos , Neumonía Lipoidea/inducido químicamente , Nódulo Pulmonar Solitario/patología , Anciano , Anciano de 80 o más Años , Lavado Broncoalveolar/métodos , Colonoscopía/métodos , Diverticulosis del Colon/diagnóstico por imagen , Diverticulosis del Colon/patología , Femenino , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Aceite Mineral/efectos adversos , Neumonía Lipoidea/diagnóstico por imagen , Neumonía Lipoidea/patología , Neumonía Lipoidea/fisiopatología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Nódulo Pulmonar Solitario/cirugía , Nódulo Pulmonar Solitario/ultraestructura , Tomografía Computarizada por Rayos XRESUMEN
The present study reports two cases of lung cancer with the involvement of the pleura. The diagnosis of adenocarcinoma with epidermal growth factor receptor (EGFR) mutation was made following repeated thoracentesis with cytology of pleural fluid and thoracoscopy with pleural biopsies. Talc pleurodesis was successfully performed in both cases subsequent to diagnosis. Following talc pleurodesis, the first patient (62 years old; male; non-smoker) underwent 3 cycles of cisplatin/vinorelbine chemotherapy, with a poor response. Concurrently, due to the presence of an EGFR mutation, treatment with gefitinib was initiated, with the patient achieving a good response for ~12 months. The residual tumor was treated with stereotactic radiotherapy and the patient continued gefitinib treatment. The patient is presently in good health, has not exhibited any signs of relapse and is continuing gefitinib treatment without side effects. The second patient (53 years old; male ex-smoker) underwent treatment with gefitinib subsequent to talc pleurodesis for a total of 15 months. In addition, radiotherapy (60 Gy) on the residual lesion was performed. Subsequently, second-line therapy with cisplatin/premetrexed was prescribed and followed by maintenance treatment with premetrexed. Three years after diagnosis, the patient did not exhibit any signs of recurrence. These two cases highlight the difficulty in treating advanced stage lung cancer, despite the presence of EGFR mutation. Each lung cancer is different and requires the physician to possess a wide range of knowledge of the therapeutic options available, in addition to careful monitoring in order to adjust the treatment over time. A multidisciplinary approach, involving surgeons, radiation oncologists, pulmonologists and oncologists, is required to optimize the survival and quality of life of patients with lung cancer.
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BACKGROUND: Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. Increasing evidence show that NT and their receptor are expressed in lung tissues suggesting a possible role in lung health and disease. Here we investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts. METHODS: Lung fibroblast were isolated from IPF patients and characterized for the expression of mesenchymal markers in comparison to normal lung fibroblasts isolated from non-IPF controls. RESULTS: BDNF treatment promoted mesenchymal differentiation and this effect was counteracted by the TrkB inhibitor K252a. In this regard, we showed that K252a treatment was able to control the expression of transcription factors involved in epithelial to mesenchymal transition (EMT). Accordingly, K252a treatment reduced matrix metalloproteinase-9 enzyme activity and E-cadherin expression while increased cytoplasmic ß-catenin expression. CONCLUSIONS: Our results suggest that BDNF/TrkB axis plays a role in EMT promoting the acquisition of (myo)fibroblast cell phenotype in IPF. Targeting BDNF/TrkB seems to represent a viable approach in order to prevent EMT dependent lung fibrosis.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Transición Epitelial-Mesenquimal , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Receptor trkB/metabolismo , Transducción de Señal , Biomarcadores/metabolismo , Carbazoles/farmacología , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Alcaloides Indólicos/farmacología , Pulmón/patología , Masculino , Persona de Mediana Edad , Transducción de Señal/efectos de los fármacosRESUMEN
Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways ß-catenin and YAP/TAZ. Here we first show that SCD1 expression, either alone or in combination with a variety of CSCs markers, correlates with poor prognosis in adenocarcinoma (ADC) of the lung. Treatment of lung ADC cell cultures with cisplatin enhances the formation of larger 3D tumor spheroids and upregulates CSCs markers. In contrast, co-treatment with cisplatin and the SCD1 inhibitor MF-438 reverts upregulation of CSCs markers, strongly synergizes in the inhibition of 3D spheroids formation and induces CSCs apoptosis. Mechanistically, SCD1 inhibition activates endoplasmic reticulum stress response and enhances autophagy. These data all together support the use of combination therapy with SCD1 inhibitors to achieve better control of lung cancer.
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Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Células Madre Neoplásicas/efectos de los fármacos , Piridazinas/farmacología , Estearoil-CoA Desaturasa/antagonistas & inhibidores , Tiadiazoles/farmacología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/enzimología , Adenocarcinoma/patología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Quimioterapia Combinada , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Estadificación de Neoplasias , Células Madre Neoplásicas/enzimología , Células Madre Neoplásicas/patología , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
We report two cases of solitary fibrous tumor of the pleura (SFTP). The first appeared in a young, new mother as a large mass in the upper lobe of the left lung that caused compression of lung parenchyma without significant respiratory symptoms but with polyarticular paraneoplastic syndrome; the other was documented by an occasional chest x-ray in a man affected by chronic obstructive pulmonary disease (COPD) as a small peripheral mass 4 years before and no longer controlled. Both patients underwent surgical resection with quick and full recovery. SFTP is a benign, slow growing neoplasm that is mostly localized. It appears in adult or elderly patients often with few symptoms. The computed tomography (CT) of the chest with contrast medium is important in order to see the shape of the mass and relationships with adjacent structures but only histology can provide the diagnosis. Surgery is the best treatment.
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BACKGROUND: Lung cancer is the leading cause of cancer related deaths and Malignant Pleural Effusion (MPE) is a frequent complication. Current therapies suffer from lack of efficacy in a great percentage of cases, especially when cancer is diagnosed at a late stage. Moreover patients' responses vary and the outcome is unpredictable. Therefore, the identification of patients who will benefit most of chemotherapy treatment is important for accurate prognostication and better outcome. In this study, using malignant pleural effusions (MPE) from non-small cell lung cancer (NSCLC) patients, we established a collection of patient-derived Adenocarcinoma cultures which were characterized for their sensitivity to chemotherapeutic drugs used in the clinical practice. METHODS: Tumor cells present in MPEs of patients with NSCLC were isolated by density gradient centrifugation, placed in culture and genotyped by next generation sequencing. In a subset of cases patient derived xenografts (PDX) were obtained upon tumor cell inoculation in rag2/IL2 knock-out mice. Isolated primary cultures were characterized and tested for drug sensitivity by in vitro proliferation assays. Additivity, antagonism or synergy for combinatorial treatments were determined by analysis with the Calcusyn software. RESULTS: We have optimized isolation procedures and culture conditions to expand in vitro primary cultures from Malignant Pleural Effusions (MPEs) of patients affected by lung adenocarcinomas, the most frequent form of non small cell lung cancer. Using this approach we have been able to establish 16 primary cultures from MPEs. Cells were banked at low passages and were characterized for their mutational pattern by next generation sequencing for most common driver mutations in lung cancer. Moreover, amplified cultures were shown to engraft with high efficiency when injected in immunocompromised mice. Cancer cell sensitivity to drugs used in standard chemotherapy regimens was assessed either individually or in combination. Differential chemosensitivity and different mutation profiles were observed which suggests that this isolation method could provide a platform for predicting the efficacy of chemotherapy in the clinical setting. Most importantly for six patients it was possible to establish a correlation between drug response in vitro and response to therapy in the clinic. CONCLUSIONS: Results obtained using primary cultured cells from MPEs underscore the heterogeneity of NSCLC in advanced stage as indicated by drug response and mutation profile. Comparison of data obtained from in vitro assays with patients' responses to therapy leads to the conclusion that this strategy may provide a potentially useful approach for evaluating individual chemosensitivity profile and tailor the therapy accordingly. Furthermore, combining MPE-derived primary cultures with their genomic testing allows to identify patients eligible to trials with novel targeted agents.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Modelos Biológicos , Derrame Pleural Maligno/tratamiento farmacológico , Adenocarcinoma/complicaciones , Adenocarcinoma/genética , Adenocarcinoma del Pulmón , Anciano , Antineoplásicos/farmacología , Bioensayo , Proliferación Celular/efectos de los fármacos , Análisis Mutacional de ADN , Clorhidrato de Erlotinib/farmacología , Clorhidrato de Erlotinib/uso terapéutico , Exoma/genética , Femenino , Heterogeneidad Genética , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/genética , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Mutación/genética , Derrame Pleural Maligno/complicaciones , Derrame Pleural Maligno/genética , Derrame Pleural Maligno/patología , Transducción de Señal/efectos de los fármacos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The purpose of this study was to compare functional and oncologic outcome of sleeve lobectomy (SL) with that of standard lobectomy (STL) in patients with non-small cell lung cancer. METHODS: Between January 2009 and April 2013, 44 consecutive patients undergoing upper SL (29 right side, 15 left side) were prospectively enrolled to be compared with 44 patients with the same side distribution who were randomly selected from patients undergoing upper STL during the study period. Functional and oncologic results of the two groups were compared. RESULTS: Pathologic tumor stage ranged between I and IIIa with similar patient distribution between the two groups. Postoperative complication rates were 20.5% in the SL group and 16% in the STL group. There was no postoperative mortality in either group. Mean postoperative decrease in forced expiratory volume in 1 second at 3 months postoperatively was 17.5% ± 6.2% in the SL group and 19% ± 14.8% in the STL group (p = 0.52). There also was no significant difference (p = 0.15) in mean postoperative decrease in 6-minute walk test (64.3 ± 2.5 m versus 69.1 ± 21.4 m) between the two groups. Evaluation of postoperative changes in quality of life at 3 and 6 months based on a standardized questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire) did not show significant differences between the SL group and the STL group (p > 0.05) in terms of global health status, physical functioning, and fatigue. Actuarial survival rates at 3 and 5 years, respectively, were 85.3% and 60.1% in the SL group and 88.7% and 58.2% in the STL group, without significant difference (p = 0.68). CONCLUSIONS: Functional and oncologic results of SL are comparable to those of STL in patients with non-small cell lung cancer.
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Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/fisiopatología , Carcinoma de Pulmón de Células no Pequeñas/psicología , Femenino , Volumen Espiratorio Forzado , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/fisiopatología , Neoplasias Pulmonares/psicología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Calidad de Vida , CaminataRESUMEN
The regulatory role of dopamine (DA) in endocrine, cardiovascular and renal functions has been extensively studied and used for clinical purposes. More recently DA has been indicated as a regulatory molecule for immune cells and malignant cell proliferation. We assessed the expression and the functional role DA, DA receptors, and transporters in primary small cell lung cancer (SCLC). By HPLC DA plasma levels were more elevated in SCLC patients in comparison with NSCLC patients and healthy controls. SCLC cell expressed DA D1- and D2-like receptors and membrane and vesicular transporters at protein and mRNA levels. We also investigated the effects of independent D1- or D2-like receptor stimulation on SCLC cell cultures. DA D1 receptor agonist SKF38393 induced the increase of cAMP levels and DARPP-32 protein expression without affecting SCLC growth rate. Cell treatment with the DA D1 receptor antagonist SCH23390 inhibited SKF38393 effects. In contrast, the DA D2 receptor agonist quinpirole (10 µM) counteracted, in a dose and time dependent way, SCLC cell proliferation, it did not affect cAMP levels and decreased phosphorylated AKT that was induced by DA D2 receptor antagonist sulpiride. However, in only one SCLC line, stimulation of DA D2 receptor failed to inhibit cell proliferation in vitro. This effect was associated to the existence of rs6275 and rs6277 polymorphisms in the D2 gene. These results gave more insight into DA control of lung cancer cell behavior and suggested the existence of different SCLC phenotypes.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Receptores Dopaminérgicos/genética , Receptores Dopaminérgicos/metabolismo , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Adenilil Ciclasas/metabolismo , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Dopamina/sangre , Fosfoproteína 32 Regulada por Dopamina y AMPc/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosforilación , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Receptores de Dopamina D1/genética , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismoRESUMEN
Chronic Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease, characterized by persistent airflow limitation not fully reversible. However, a number of patients with COPD respond to bronchodilator agents. Some studies have shown polymorphisms in the b2-adrenergic (ADRb2) and muscarinic M2 and M3 receptors (CHRM) that may participate in the modulation of the receptor responses. This study was designed to investigate the existence and the role of adrenergic and muscarinic receptor polymorphisms and their functional impact in COPD. Eighty-two patients with COPD and 17 healthy smokers were recruited and screened for ADRb2 (T164I and R175R), for CHRM2 (rs1824024) and for CHRM3 (-513C/A and -492C/T). Among the polymorphisms studied our results was not able to demonstrate statistically significant association between the polymorphisms studied and COPD risk. Contrarily, we identified, in our COPD population, a significant association with the CHRM2 (rs1824024) polymorphism and disease severity, with lower lung function test values, frequent exacerbations, and poor response to anti-cholinergic drugs. These results suggest the potential role of receptor polymorphism assessment to discriminate newly COPD phenotypes. J. Cell. Physiol. 231: 1745-1751, 2016. © 2015 Wiley Periodicals, Inc.
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Polimorfismo de Nucleótido Simple , Enfermedad Pulmonar Obstructiva Crónica/genética , Receptor Muscarínico M2/genética , Anciano , Anciano de 80 o más Años , Broncodilatadores/uso terapéutico , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/uso terapéutico , Fenotipo , Reacción en Cadena de la Polimerasa , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Receptor Muscarínico M2/antagonistas & inhibidores , Receptor Muscarínico M3 , Receptores Adrenérgicos beta 2/genética , Receptores Muscarínicos/genética , Pruebas de Función Respiratoria , Factores de Riesgo , Análisis de Secuencia de ADN , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Lymphocytes possess an independent cholinergic system. We assessed the expression of muscarinic cholinergic receptors in lymphocytes from 49 asthmatic children and 10 age matched controls using Western blot. We demonstrated that CD4+ and CD8+ T cells expressed M2 and M4 muscarinic receptors which density were significantly increased in asthmatic children in comparison with controls. M2 and M4 receptor increase was strictly related with IgE and fraction of exhaled nitric oxide (FeNO) measurements and with impairment in objective measurements of airway obstruction. Increased lymphocyte muscarinic cholinergic receptor expression may concur with lung cholinergic dysfunction and with inflammatory molecular framework in asthma.
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Asma/metabolismo , Asma/patología , Regulación de la Expresión Génica/fisiología , Linfocitos/metabolismo , Receptores Muscarínicos/metabolismo , Administración por Inhalación , Adulto , Factores de Edad , Asma/sangre , Asma/diagnóstico , Broncodilatadores/administración & dosificación , Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , Estudios de Casos y Controles , Niño , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Modelos Lineales , Linfocitos/efectos de los fármacos , Masculino , Óxido Nítrico/administración & dosificación , Receptores Muscarínicos/genética , Índice de Severidad de la Enfermedad , Estadísticas no ParamétricasRESUMEN
INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disorder characterized by multiple noncaseating granulomas involving intrathoracic lymph nodes and lung parenchyma. Recently, the use of anti-tumor necrosis factor alpha (anti-TNFα) agents has been introduced for therapy of chronic and refractory sarcoidosis with controversial results. Infliximab (Remicade) is a chimeric monoclonal antibody (mAb) that recognizes and binds TNFα, neutralizing its biological effects. In the present study, (99m)Tc labelled infliximab was used to study the expression of TNFα in sarcoid lesions and to evaluate its role as a predictive marker in response to therapy with Remicade. MATERIAL AND METHODS: A total of 10 patients with newly diagnosed sarcoidosis were enrolled together with 10 control patients affected by rheumatoid arthritis. All patients were studied by planar imaging of the chest with (99m)Tc-infliximab at 6 h and 24 h and total body [(18)F]-FDG PET/CT. Regions of interest were drawn over the lungs and the right arm and target-to-background ratios were analysed for (99m)Tc-infliximab. SUV mean and SUV max were calculated over lungs for FDG. RESULTS AND DISCUSSION: Image analysis showed low correlation between T/B ratios and BAL results in patients despite positivity at [(18)F]-FDG PET. CONCLUSION: In conclusion, patients with newly diagnosed pulmonary sarcoidosis, with FDG-PET and BAL positivity, showed a negative (99m)Tc-infliximab scintigraphy.
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Pulmón/diagnóstico por imagen , Pulmón/metabolismo , Sarcoidosis Pulmonar/diagnóstico por imagen , Sarcoidosis Pulmonar/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Adulto , Femenino , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiografía , Tecnecio , Tomografía Computarizada de EmisiónRESUMEN
Non-small cell lung cancer (NSCLC) accounts for ~80% of all cases of lung cancer, and is the leading cause of cancer-related mortality worldwide. The majority of NSCLC cases of are diagnosed at an advanced stage. The outcome of patients with advanced NSCLC is poor with a median survival time of ~12 months in European and American populations. Lymphoproliferative disorders (LPDs) represent a heterogeneous group of expanding lymphoid cells, which occurs as a result of immune dysfunction. LPDs are often associated with primary solid cancers. We report two cases of LPD diagnosed concurrently and successively to NSCLC. The first case presents a 65-year-old female patient with advanced IV stage lung cancer, according to the International Association for the Study of Lung Cancer TNM staging system. The patient developed a concurrent lymphoma and was treated with first-line therapy including six cycles of gemcitabine and cisplatin, however, the patient experienced an adverse drug reaction to bevacizumab, which was administered after gemcitabine and prior to cisplatin. The second case presented a 74-year-old male patient diagnosed with large B cell lymphoma. The patient acheived remission of the illness, however, after one year the patient was diagnosed with squamous cell lung cancer. After three years, the patient underwent surgery, however disease recurrence was identified. Subsequently, the patient was treated with sterotactic radiotherapy and oral chemotherapy. A review of the associated literature was also conducted.
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BACKGROUND: Studies of Idiopathic Pulmonary Fibrosis (IPF) epidemiology show regional variations of incidence and prevalence; no epidemiological studies have been carried out in Italy. OBJECTIVE: To determine incidence and prevalence rates of IPF in the population of a large Italian region. METHODS: in this cross-sectional study study data were collected on all patients of 18 years of age and older admitted as primary or secondary idiopathic fibrosing alveolitis (ICD9-CM 516.3) to Lazio hospitals, from 1/1/2005 to 31/12/2009, using regional hospital discharge, population and cause of death databases. Reporting accuracy was assessed on a random sample of hospital charts carrying the ICD9-CM 516.3, 516.8, 516.9 and 515 codes, by reviewing radiology and pathology findings to define cases as IPF "confident", "possible" or "inconsistent". RESULTS: Annual prevalence and incidence of IPF were estimated at 25.6 per 100,000 and 7.5 per 100,000 using the ICD9-CM code 516.3 without chart audit while they were estimated at 31.6 per 100,000 and at 9,3 per 100,000 for the IPF "confident" definition after hospital chart audit. CONCLUSION: The data provide a first estimate of IPF incidence in Italy and indicate that incidence and prevalence in southern European regions may be similar to those observed in northern Europe and North America.
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Fibrosis Pulmonar Idiopática/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Bases de Datos Factuales , Femenino , Encuestas Epidemiológicas , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/mortalidad , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Admisión del Paciente , Prevalencia , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: No biological marker is currently available for evaluating pulmonary involvement and/or for monitoring the clinical course of sarcoidosis. The present pilot study focused on possible relationships between circulating plasma levels of surfactant protein type B (SP-B) and plasma receptor for advanced glycation end products (RAGE) and lung function abnormalities in patients with pulmonary sarcoidosis, since both SP-B and RAGE have been previously suggested as lung injury markers. The plasmatic levels of these two proteins were also investigated with respect to functional capacity, as assessed by a cardiopulmonary exercise test (CPET). METHODS: Thirty pulmonary sarcoidosis outpatients and fifteen volunteers (Control Group) underwent lung function tests and CPET. Resting SP-B and RAGE plasma levels were also determined. Patients were then categorized according to the severity of their pulmonary involvement, as assessed in terms of lung diffusion for carbon monoxide (DLCO) values. RESULTS: Group B showed SP-B levels higher and RAGE levels lower than Group A and Control Group (p < 0.01). Group A showed lower RAGE levels than Control Group (p < 0.01), whereas SP-B levels did not differ between these two groups. A significant univariate relationship was found between both SP-B and RAGE and several lung function data, particularly with DLCO (SP-B Vs DLCO: r: -0.437, p = 0.016; RAGE Vs DLCO: r: -0.451, p = 0.012). CONCLUSIONS: Circulating plasma levels of SP-B and RAGE showed an opposite behavior in patients with pulmonary sarcoidosis. SP-B values are directly related to alveolar unit damage, supporting a possible role of SP-B as a marker of disease severity in these patients. Differently, RAGE decreases in severe sarcoidosis, suggesting more complex underlying mechanisms.
Asunto(s)
Proteína B Asociada a Surfactante Pulmonar/sangre , Receptores Inmunológicos/sangre , Sarcoidosis Pulmonar/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Prueba de Esfuerzo/métodos , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Capacidad de Difusión Pulmonar/fisiología , Receptor para Productos Finales de Glicación Avanzada , Sarcoidosis Pulmonar/diagnóstico , Sarcoidosis Pulmonar/fisiopatología , Capacidad Vital/fisiologíaRESUMEN
This study aimed to present the atypical clinical presentation and management of a metastatic lung cancer that had spread to an atypical location. Lung cancer is the most common cause of cancer-related mortality worldwide. The brain, liver, adrenal glands and bone are the most common sites of metastatic disease in patients with lung cancer. The reported incidence of symptomatic gastrointestinal metastases is 0.2-0.5%. Early diagnosis should be based on the observation of clinical symptoms and computed tomography (CT) imaging. In the present study, we describe the case of a 43-year-old male with a primary adenocarcinoma of the lung located in the lower right lobe. Following diagnosis, the patient underwent five lines of chemotherapy with a significant tumor reduction. Two years later, a mass located in the sigmoid colon was detected in the patient following a PET/CT scan. The clinical presentation was unusual with vomiting, headache, dyspnea and laboratory hyponatremia. A rare form of metastatic ulcerating adenocarcinoma was identified with colonoscopy, which was confirmed by immunohistochemical findings. A surgical approach was not performed due to the worsening condition of the patient. The patient demonstrated severe anemia and blood hypoxia, and one month later, the patient succumbed to disease. The metastasis may suggest an increase in tumor aggressiveness.
RESUMEN
Lung cancer is the leading cause of cancer-related mortality worldwide. Recent evidence indicates that tumors contain a subpopulation of cancer stem cells (CSCs) that are responsible for tumor maintenance and spread. CSCs have recently been linked to the occurrence of epithelial-to-mesenchymal transition (EMT). Neurotrophins (NTs) are growth factors that regulate the biology of embryonic stem cells and cancer cells, but still little is known about the role NTs in the progression of lung cancer. In this work, we investigated the role of the NTs and their receptors using as a study system primary cell cultures derived from malignant pleural effusions (MPEs) of patients with adenocarcinoma of the lung. We assessed the expression of NTs and their receptors in MPE-derived adherent cultures vs. spheroids enriched in CSC markers. We observed in spheroids a selectively enhanced expression of TrkB, both at the mRNA and protein levels. Both K252a, a known inhibitor of Trk activity, and a siRNA against TrkB strongly affected spheroid morphology, induced anoikis and decreased spheroid forming efficiency. Treatment with neurotrophins reversed the inhibitory effect of K252a. Importantly, TrkB inhibition caused loss of vimentin expression as well as that of a set of transcription factors known to be linked to EMT. These ex vivo results nicely correlated with an inverse relationship between TrkB and E-cadherin expression measured by immunohistochemistry in a panel of lung adenocarcinoma samples. We conclude that TrkB is involved in full acquisition of EMT in lung cancer, and that its inhibition results in a less aggressive phenotype.
Asunto(s)
Adenocarcinoma/metabolismo , Neoplasias Pulmonares/metabolismo , Derrame Pleural Maligno/metabolismo , Receptor trkB/metabolismo , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Anoicis/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/farmacología , Cadherinas/metabolismo , Carbazoles/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Inmunohistoquímica , Alcaloides Indólicos/farmacología , Neoplasias Pulmonares/patología , Derrame Pleural Maligno/patología , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptor trkB/antagonistas & inhibidores , Receptor trkB/genética , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Factores de Transcripción/metabolismo , Células Tumorales Cultivadas , Regulación hacia Arriba/efectos de los fármacos , Vimentina/metabolismoRESUMEN
Autophagy is the main cellular pathway for degradation of long-lived proteins and organelles and regulates cell fate in response to stress. Beclin 1 is a key regulator of this process. In some settings autophagy and apoptosis seem to be interconnected. Recent reports indicate that fibroblasts in idiopathic pulmonary fibrosis (IPF) acquire resistance to apoptosis. Here, we examined the expression of beclin 1, and of the anti apoptotic protein Bcl-2 in human IPF fibroblasts using immunohistochemistry and molecular biology in bioptic sections, in primary cultures of fibroblasts taken from patients with IPF and in fibroblast cell lines. Expression of beclin 1 in fibroblasts from IPF was down-regulated in comparison with fibroblasts from normal lungs while the anti-apoptotic protein Bcl-2 expression was over-expressed. Treatment of fibroblast cell cultures with cisplatin induced a significant increase in beclin 1 and caspase 3 protein levels but a reduction in Bcl-2 expression. These observations were confirmed by the analysis of acid compartments and transmission electron microscopy. Our results demonstrate a modified expression of the apoptotic beclin 1 Bcl-2 proteins in human IPF fibroblasts suggesting the existence of an autophagy/apoptosis system dysfunction.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Fibrosis Pulmonar Idiopática/metabolismo , Proteínas de la Membrana/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Autofagia/efectos de los fármacos , Autofagia/fisiología , Beclina-1 , Estudios de Casos y Controles , Línea Celular , Células Cultivadas , Cisplatino/farmacología , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Fibrosis Pulmonar Idiopática/patología , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismoRESUMEN
BACKGROUND: Lung diffusion for carbon monoxide (DLCO) has been shown to associate with the risk of pulmonary arterial hypertension development and, most likely, with right ventricular (RV) myocardial dysfunction in sarcoidosis patients. Besides its known role as a marker of left ventricular dysfunction, experimental evidence suggests a role of NT-proAtrial Natriuretic Peptide (NT-proANP) also in modulating pulmonary circulation. We therefore investigated possible relationships between NT-proANP, lung diffusion impairment and RV dysfunction. METHODS: Thirty-two pulmonary sarcoidosis outpatients and eighteen volunteers underwent full clinical assessment, including full lung function tests and Doppler echocardiography integrated with tissue Doppler imaging (TDI) study. Resting circulating NT-proBNP and NT-proANP plasma levels were also determined. RESULTS: NT-proANP and RV-myocardial performance index (RV-MPI) were significantly higher in those patients with the greatest DLCO impairment, whereas no differences were found for NT-proBNP values. At multivariable analysis, only DLCO (ß: -0.496; standard error: 3.38; p=0.000) and RV-MPI (ß: 0.373; standard error: 6.56; p=0.031) remained significantly associated with NT-proANP levels. CONCLUSIONS: Our finding may support a key role of NT-proANP in the complex mechanisms underlying modulation of lung function. An early increase in pulmonary vascular resistance may stimulate NT-proANP increase, thus explaining its association with signs of early RV myocardial dysfunction. This hypothesis warrants further confirmation.