Assuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Pneumologia/métodos , Pneumologia/tendências , Algoritmos , Biópsia , Diagnóstico Diferencial , Prática Clínica Baseada em Evidências/normas , Prática Clínica Baseada em Evidências/tendências , França , Humanos , Pulmão/patologia , Pneumologia/normas , Radiografia Torácica , Tomografia Computadorizada por Raios XAssuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Pneumologia/métodos , Pneumologia/tendências , Algoritmos , Biópsia , Lavagem Broncoalveolar , Diagnóstico Diferencial , Prática Clínica Baseada em Evidências/normas , Prática Clínica Baseada em Evidências/tendências , França , Humanos , Pulmão/patologia , Pneumologia/normas , Radiografia Torácica , Tomografia Computadorizada por Raios XAssuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Pneumologia/métodos , Pneumologia/tendências , Algoritmos , Biópsia , Lavagem Broncoalveolar , Diagnóstico Diferencial , Prática Clínica Baseada em Evidências/normas , Prática Clínica Baseada em Evidências/tendências , França , Humanos , Pulmão/patologia , Pneumologia/normas , Radiografia Torácica , Tomografia Computadorizada por Raios XRESUMO
This report describes the case of a 44-year-old man with pulmonary nodules whose histological analysis initially suggested tuberculosis. The Mycobacterium tuberculosis (MT) culture was negative and a questionnaire revealed a professional activity of brushing and polishing surgical instruments without any protection for 7 years. A mineralogical analysis by optical and electron microscopy was performed on both a healthy lung tissue biopsy and a lung nodule in a paraffin block. Electron microscopy analysis revealed the presence of metal particles (iron oxide, titanium oxide, aluminum oxide and steel) in both samples. This study suggests that mineralogical analysis combined with a questionnaire on dust exposure could help redirect the diagnosis of a dust-related disease.
Assuntos
Poeira , Granuloma do Sistema Respiratório/induzido quimicamente , Metais/efeitos adversos , Nódulos Pulmonares Múltiplos/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Saúde Ocupacional , Ocupações , Sarcoidose Pulmonar/induzido quimicamente , Instrumentos Cirúrgicos/efeitos adversos , Adulto , Biópsia , Diagnóstico Diferencial , Poeira/análise , Desenho de Equipamento , Compostos Férricos/efeitos adversos , Granuloma do Sistema Respiratório/diagnóstico , Humanos , Exposição por Inalação/efeitos adversos , Masculino , Metais/análise , Microscopia Eletrônica , Nódulos Pulmonares Múltiplos/diagnóstico , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Valor Preditivo dos Testes , Sarcoidose Pulmonar/diagnóstico , Aço/efeitos adversos , Titânio/efeitos adversosRESUMO
AIM: To generate a national biobank made up of samples of the highest quality for the purpose of inciting basic research on gestational trophoblastic diseases (GTD). MATERIAL AND METHODS: Three priority axes of research were defined to optimize the nature, method of collection, and storage of the samples. These are: to enhance our understanding of GTD, develop new diagnostic tests, and identify new therapeutic targets. The protocol for patient inclusion and sample processing was determined after extensive literature review and collaboration with international experts in the field of GTD. RESULTS: For each patient with a GTD and for control patients (legally induced abortions), chorionic villi, decidua and tumor samples (fresh, immersed in RNA-protective solution and fixed in formaldehyde), blood (serum, plasma, RNA, and peripheral blood mononuclear cells), urine (supernatant), and cell cultures of villous cytotrophoblasts are prospectively collected. Associations are then made between the collected samples and numerous clinical and biological data, such as human chorionic gonadotropic plasma levels following curettage in the case of a hydatidiform mole. CONCLUSION: Such a collection of high quality samples and their associated data open up new perspectives for both national and international collaborative research projects.
Assuntos
Doença Trofoblástica Gestacional , Bancos de Tecidos , Adulto , Feminino , Humanos , GravidezRESUMO
INTRODUCTION: Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting mainly young women. BACKGROUND: The respiratory manifestations are characterized by a progressive cystic destruction of the lung parenchyma. Extrapulmonary involvement includes benign renal tumours called angiomyolipomas and abdominal lymphatic masses called lymphangioleiomyomas. At the pathological level, the cellular proliferation found in LAM is in part due to the presence of mutations in the tumour suppressor genes TSC1 and TSC2 (Tuberous Sclerosis Complex). These mutations lead to the activation of the mTOR pathway, which is currently the main therapeutic target. mTOR inhibitors such as sirolimus or everolimus have shown a beneficial effect on the decline in pulmonary function and a reduction of angiomyolipoma size, but are necessary in only some patients. PERSPECTIVES: LAM cells have migratory properties mediated by the formation of new lymphatic vessels. They are also able to secrete metalloproteases, which enhance their invasiveness. Moreover, the expression of estrogen and progesterone receptors by LAM cells suggests a possible role for sex hormones in the pathogenesis of the disease. CONCLUSION: A better understanding of mTOR-independent mechanisms would allow the development of novel therapeutic approaches.
Assuntos
Neoplasias Pulmonares , Linfangioleiomiomatose , Adulto , Feminino , História do Século XX , História do Século XXI , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/terapia , Linfangioleiomiomatose/diagnóstico , Linfangioleiomiomatose/epidemiologia , Linfangioleiomiomatose/etiologia , Linfangioleiomiomatose/terapiaRESUMO
BACKGROUND: Pulmonary sarcomatoid carcinomas (SC) are tumors characterized by poor prognosis and resistance to conventional platinum-based chemotherapy. This study sought to describe the mutational profile of SC using high-throughput genotyping technology. PATIENTS AND METHODS: We used mass spectrometry to test 114 surgical biopsies from 81 patients with SC for 214 mutations affecting 26 oncogenes and tumor suppressor genes. RESULTS: In total, 75 (92.6%) patients were smokers. Within the total 81 tumors, 67 distinct somatic alterations were identified, with 56 tumors (69.1%) harboring at least one mutation. The most frequent mutations were KRAS (27.2%), EGFR (22.2%), TP53 (22.2%), STK11 (7.4%), NOTCH1 (4.9%), NRAS (4.9%), and PI3KCA (4.9%). The EGFR mutations were almost always rare mutations (89%). In 32 tumors (39.5%), two or more mutations co-existed, with up to four mutations in a single case. In six different cases, comparative genetic analysis of different histological areas from the same tumor (giant, spindle, or epithelial component) revealed a 61% concordance rate for all the mutations with a 10% detection threshold, compared with 91.7% with a 20% detection threshold. CONCLUSION: Our results demonstrated a high mutation rate and frequent co-mutations. Despite SC tumors exhibiting a high histological heterogeneity, some intratumoral molecular homogeneity was found. Now with newly developed targeted therapies, SC patients may be eligible for new target mutations, and can now therefore be screened for clinical trials.
Assuntos
Carcinoma de Células Gigantes/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinossarcoma/genética , Neoplasias Pulmonares/genética , Quinases Proteína-Quinases Ativadas por AMP , Adulto , Idoso , Carcinoma/genética , Estudos de Coortes , Receptores ErbB/genética , Feminino , GTP Fosfo-Hidrolases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptor Notch1/genética , Estudos Retrospectivos , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.
Assuntos
Mesotelioma , Neoplasias Pleurais , França , Humanos , Mesotelioma/patologia , Patologia Clínica , Neoplasias Pleurais/patologia , Encaminhamento e Consulta , Sociedades Médicas , Fatores de TempoAssuntos
Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/terapia , Acetilcisteína/uso terapêutico , Corticosteroides/uso terapêutico , Anticorpos/uso terapêutico , Anticoagulantes/uso terapêutico , Colchicina/uso terapêutico , Técnicas de Diagnóstico do Sistema Respiratório , França , Testes Genéticos , Humanos , Fibrose Pulmonar Idiopática/genética , Comunicação Interdisciplinar , Equipe de Assistência ao Paciente , VacinaçãoRESUMO
INTRODUCTION: Bronchiolo-alveolar carcinoma is a controversial indication for lung transplantation because of the risk of recurrence. We report three cases and propose some risk factors for recurrence. CASE REPORTS: Our study concerns three patients transplanted at the Louis-Pradel Hospital between 1991 and 2010. The first patient relapsed 86 months after transplantation, benefited from surgical treatment, then died of renal failure. A second patient died of infection, without recurrence, 72 months after transplantation. The third had an early recurrence at 7 months and died 27 months after transplantation. The risk factors for recurrence appear to be: clinically "aggressive" presentation and histological stromal pulmonary invasion by the carcinoma. CONCLUSION: Diffuse bronchiolo-alveolar carcinoma is a possible indication of lung transplantation. The risk of recurrence imposes some requirements: a precise histological diagnosis and a slow clinical course.
Assuntos
Adenocarcinoma Bronquioloalveolar/cirurgia , Neoplasias Pulmonares/cirurgia , Transplante de Pulmão , Adenocarcinoma Bronquioloalveolar/patologia , Adulto , Evolução Fatal , Feminino , Humanos , Neoplasias Pulmonares/patologia , Transplante de Pulmão/mortalidade , Transplante de Pulmão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Fatores de RiscoRESUMO
UNLABELLED: A 71 year-old man with primary Sjögren's syndrome developed pulmonary opacities within two years of the diagnosis. Videothoracoscopic lung biopsy demonstrated high grade, B-cell, CD20+, large-cell lymphoma, associated with Epstein-Barr virus (RNA EBERs of the virus were expressed by the lymphoma cells). The condition initially improved with rituximab-CHOP treatment, but recurrence of the lymphoma was fatal. CONCLUSION: High-grade B-cell lymphoma associated with EBV can occur in Sjögren's syndrome in the absence of long-term immunosuppressive therapy.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Neoplasias Pulmonares/virologia , Linfoma de Células B/virologia , Síndrome de Sjogren/complicações , Idoso , Humanos , MasculinoAssuntos
Bronquiectasia/etiologia , Crioglobulinemia/etiologia , Insuficiência Respiratória/etiologia , Macroglobulinemia de Waldenstrom/diagnóstico , Bronquiectasia/patologia , Bronquiectasia/fisiopatologia , Feminino , Humanos , Imunoglobulina M/metabolismo , Cadeias kappa de Imunoglobulina/metabolismo , Pessoa de Meia-Idade , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/fisiopatologiaRESUMO
Ovine pulmonary adenocarcinoma (OPA) is a lung cancer strikingly similar to the pneumonic-type mixed invasive adenocarcinoma with a predominant bronchioloalveolar component in humans. Telomerase activity in OPA and the potential involvement of the kinase Akt in telomerase activation and regulation of cell proliferation were investigated. Lung tissues were collected from sheep with a histopathological diagnosis of OPA or controls. Epithelial cell cultures were derived in vitro from lung tissues. Telomerase activity was evaluated using the telomeric repeat amplification protocol method. Phosphorylation of Akt was detected by Western blotting. Telomerase activity was significantly higher in OPA lung tissues compared to control lung tissues. A high telomerase activity was detected in eight out of 12 (67%) primary cell cultures derived from tumours. A high level of expression of phosphorylated Akt was found in 10 out of 27 (37%) tumours, with abolition of Akt activation in response to epidermal growth factor stimulation demonstrated in primary cell cultures derived from tumours. Telomerase activation takes place in ovine pulmonary adenocarcinoma tumour cells and may be partly attributable to Akt activation. Telomerase may inhibit cellular senescence and contribute to the accumulation of tumour cells in mixed adenocarcinoma with a bronchioloalveolar component. Further work is necessary to identify alternative signalling pathways of telomerase activation in tumours.
Assuntos
Adenocarcinoma Bronquioloalveolar/genética , Adenocarcinoma/genética , Modelos Animais de Doenças , Retrovirus Jaagsiekte de Ovinos/genética , Neoplasias Pulmonares/genética , Adenomatose Pulmonar Ovina/genética , Telomerase/genética , Adenocarcinoma Bronquioloalveolar/patologia , Animais , Divisão Celular/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Senescência Celular/genética , Ativação Enzimática/genética , Regulação da Expressão Gênica/genética , Humanos , Pulmão/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Alvéolos Pulmonares/patologia , Ovinos , Transdução de Sinais/genética , Células Tumorais Cultivadas/patologiaRESUMO
BACKGROUND: Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. METHODS AND RESULTS: Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1beta (MIP-1beta), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. CONCLUSIONS: We have demonstrated that the upregulation of MIP-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection.
Assuntos
Caderinas/genética , Rejeição de Enxerto/genética , Transplante de Coração/efeitos adversos , Proteínas Inflamatórias de Macrófagos/genética , Animais , Antígenos CD , Caderinas/análise , Quimiocina CCL4 , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas Inflamatórias de Macrófagos/análise , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Modelos Animais , Análise de Sequência com Séries de Oligonucleotídeos , Transplante Homólogo , Transplante Isogênico , Regulação para CimaRESUMO
To develop an MRI method for the evaluation of contrast enhancement in early atherosclerotic plaque development in the abdominal aorta of a mouse model. Male apoE-/- mice from three groups, respectively 4 (n = 6), 8 (n = 11) and 16 (n = 4) weeks were included. Axial T1 spin echo images of the abdominal aorta were obtained above and below the renal arteries (90 microm spatial resolution) before and over 1 h after the injection of a macromolecular contrast agent. Signal enhancement was measured in the vessel wall and compared to histological features. Maximal arterial wall signal enhancement was obtained from 16 to 32 min post injection. During this time, the signal-to-noise ratio increased by a factor up to 1.7 in 16 week mice and 2.7 and 2.4 in 8 and 4 weeks mice, respectively. The enhancement of the arterial wall appeared less pronounced in the oldest mice, 16 weeks old, exhibiting more advanced lesions. Using a macromolecular gadolinium agent, contrast uptake in atherogenesis varies with lesion stage and may be related to vessel-wall permeability. Dynamic contrast-enhanced MRI may be useful to evaluate the atherosclerotic plaque activity in mice.
Assuntos
Apolipoproteínas E/deficiência , Arteriosclerose/diagnóstico , Meios de Contraste , Modelos Animais de Doenças , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Compostos Organometálicos , Animais , Arteriosclerose/metabolismo , Arteriosclerose/patologia , Interpretação de Imagem Assistida por Computador/métodos , Magnetismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Myocardial dysfunction is common in grafted hearts from brain-dead donors, but the mechanisms involved remain unclear, although apoptosis has been suggested to play an important role. In this study, we investigated the presence of apoptotic myocardial cells in donor hearts as compared to control hearts to determine whether pre-existing apoptosis can predict donor heart dysfunction. Apoptosis was studied by in situ DNA fragmentation assay and by Western Blotting for caspase-3, the pivotal executive caspase of the apoptotic pathway. We show that brain-death induced myocardial apoptosis was not predictive of myocardial dysfunction in transplanted hearts.