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1.
N Engl J Med ; 381(10): 923-932, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31483963

RESUMO

BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte-macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 µg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or <75 mm Hg in symptomatic patients). Patients with severe pulmonary alveolar proteinosis (Pao2 <50 mm Hg) were excluded to avoid possible exacerbation of the disease in patients who were assigned to receive placebo. The primary end point was the change in the alveolar-arterial oxygen gradient between baseline and week 25. RESULTS: The change in the mean (±SD) alveolar-arterial oxygen gradient was significantly better in the GM-CSF group (33 patients) than in the placebo group (30 patients) (mean change from baseline, -4.50±9.03 mm Hg vs. 0.17±10.50 mm Hg; P = 0.02). The change between baseline and week 25 in the density of the lung field on computed tomography was also better in the GM-CSF group (between-group difference, -36.08 Hounsfield units; 95% confidence interval, -61.58 to -6.99, calculated with the use of the Mann-Whitney U test and the Hodges-Lehmann estimate of confidence intervals for pseudo-medians). Serious adverse events developed in 6 patients in the GM-CSF group and in 3 patients in the placebo group. CONCLUSIONS: In this randomized, controlled trial, inhaled recombinant human GM-CSF was associated with a modest salutary effect on the laboratory outcome of arterial oxygen tension, and no clinical benefits were noted. (Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.).


Assuntos
Doenças Autoimunes/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Proteinose Alveolar Pulmonar/tratamento farmacológico , Administração por Inalação , Adulto , Idoso , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico por imagem , Método Duplo-Cego , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/imunologia , Capacidade de Difusão Pulmonar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X , Teste de Caminhada
5.
Presse Med ; 48(7-8 Pt 2): e219-e231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447333

RESUMO

Image-guided ablation is performed by percutaneously introducing ablation probes to deliver energy into a tumor to destroy it in a controlled and localized fashion. Ablation modalities can be broadly classified as thermal or non-thermal based on the mechanism of tumor destruction and are performed using different types of image guidance for planning, delivering and follow-up of the treatment. Ablation is performed in a minimally invasive fashion, providing greater residual organ preservation with minimal morbidity to the patient. Image-guided ablation is being used in the clinic for the treatment of primary and metastatic tumors, and this article reviews state of the art for the treatment of malignancies in the liver, lung, kidney and musculoskeletal tissue.


Assuntos
Ablação por Cateter/métodos , Neoplasias/cirurgia , Cirurgia Assistida por Computador/métodos , Ablação por Cateter/efeitos adversos , Tecido Conjuntivo/patologia , Tecido Conjuntivo/cirurgia , Humanos , Rim/patologia , Rim/cirurgia , Fígado/patologia , Fígado/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Sistema Musculoesquelético/patologia , Sistema Musculoesquelético/cirurgia , Neoplasias/diagnóstico , Neoplasias/patologia , Especificidade de Órgãos , Complicações Pós-Operatórias/etiologia , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento
6.
Prev Vet Med ; 169: 104693, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31311630

RESUMO

Bayesian networks are used to evaluate the effectiveness of mixed autogenous vaccines in fattening lambs to prevent the ovine respiratory syndrome. An experiment was performed with 460 fattening lambs, which were clustered into four groups according to the kind of vaccine received (Pasteurella spp., Mycoplasma spp., Mixed Mycoplasma-Pasteurella or placebo). After slaughtering, lungs were collected, and macroscopic and microscopic studies were performed. A microbiological study was carried out to evaluate the presence of Mycoplasma spp. and Pasteurellaceae by conventional culture and identification by nested polymerase chain reaction. To the best of the authors' knowledge, Bayesian networks have not been used to evaluate the effect of vaccines on the absence/presence of lung consolidation. Our results revealed that the use of mixed autogenous vaccines can decrease lung consolidation from 15.75% (12.42-19.08) to 9.24% (6.59-11.89). Therefore, the use of these autogenous vaccines in farms could be considered an effective control tool against ovine respiratory syndrome.


Assuntos
Autovacinas/uso terapêutico , Teorema de Bayes , Pneumonia/veterinária , Doenças dos Ovinos/prevenção & controle , Animais , Pulmão/patologia , Mycoplasma/isolamento & purificação , Pasteurella/isolamento & purificação , Pneumonia/microbiologia , Pneumonia/prevenção & controle , Reação em Cadeia da Polimerase , Ovinos , Doenças dos Ovinos/microbiologia , Espanha
7.
Biomed Environ Sci ; 32(7): 508-519, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31331435

RESUMO

OBJECTIVE: The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS: Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1ß, IL-6, IL-10, and IL-17] were investigated. RESULTS: Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1ß increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1ß and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION: The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.


Assuntos
Cádmio/toxicidade , Pulmão/efeitos dos fármacos , Administração Oral , Animais , Cádmio/administração & dosagem , Leucócitos/metabolismo , Pulmão/imunologia , Pulmão/patologia , Masculino , Ratos , Staphylococcus epidermidis , Testes de Toxicidade Subcrônica
9.
APMIS ; 127(9): 616-626, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273840

RESUMO

There is no consensus on the classification of the diagnostic certainty of hypersensitivity pneumonitis (HP) based on the histopathological findings. This retrospective study aimed to describe the clinical and histopathological spectrum of HP. Herein, we also propose different grades of diagnostic certainty. Based on the histology, the cases were classified as: 'definite HP', 'probable HP', and 'possible HP'. Of the 47 subjects screened, 30 cases of histologically diagnosed HP (mean age 48.4 years; 50% women) were included. The findings of cellular bronchiolitis, interstitial pneumonia, interstitial granuloma, isolated interstitial multinucleated giant cells (MNGCs), airspace granulomas, isolated airspace MNGCs, and organizing pneumonia were present in 96.7%, 80%, 46.7%, 50%, 10%, 63.3%, and 16.7% cases, respectively. Based on the various combinations of histopathological findings, the cases were classified as 'definite', 'probable', and 'possible' HP in 56.7%, 33.3%, and 10%, respectively. Chronic HP was diagnosed in 56.7% cases based on the presence of fibrosis on histopathology. The histopathological diagnosis of subacute or chronic HP did not corroborate with the disease duration, and 17.6% of the subjects with duration of symptoms of <6 months had evidence of fibrotic disease on histopathology.


Assuntos
Alveolite Alérgica Extrínseca/diagnóstico , Alveolite Alérgica Extrínseca/patologia , Adolescente , Adulto , Doença Crônica , Feminino , Fibrose/diagnóstico , Fibrose/patologia , Células Gigantes/patologia , Granuloma/diagnóstico , Granuloma/patologia , Humanos , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Biomed Environ Sci ; 32(6): 419-426, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31262387

RESUMO

OBJECTIVE: Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang (1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II. METHODS: HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin (α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang (1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence. RESULTS: Ang (1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang (1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang (1-7) increased the levels of ACE2 and Ang (1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang (1-7) in fibroblasts stimulated by Ang II. CONCLUSION: Ang (1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang (1-7)-Mas axis.


Assuntos
Angiotensina II/sangue , Angiotensina I/uso terapêutico , Pulmão/metabolismo , Miofibroblastos/efeitos dos fármacos , Fragmentos de Peptídeos/uso terapêutico , Silicose/prevenção & controle , Actinas/metabolismo , Angiotensina I/sangue , Angiotensina I/farmacologia , Animais , Animais Recém-Nascidos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Pulmão/patologia , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Silicose/metabolismo , Silicose/patologia
11.
J Biol Regul Homeost Agents ; 33(4): 1023-1040, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309816

RESUMO

Viral dsRNA acts as the paramount pathogen-associated molecular pattern on infection and orchestrates inflammation or immune cascades of the host's tissues. The comparative effects or mechanisms of inflammation or immunity in different organs on viral infections are critical in immunology or virology. To outline the organ-based molecular mechanisms of inflammation or immunity on viral infection, we challenged mice with the viral mimic poly(I:C) and quantified inflammatory cytokines Il-1b and TNF-α in the brain and lung tissues. As cytokines showed differential expression, transcriptome screenings of mouse lung and brain tissues were analyzed. We identified 629 differentially expressed genes (DEGs) in lung and 137 DEGs in brain tissues with a few overlapping genes. Most of those DEGs were interferon-stimulated genes (ISGs) that are involved in the anti-viral defense mechanisms. The expression patterns of viral dsRNA stimulated genes, and consequently, their association with different molecular mechanisms of inflammation and immunity were specific to the organs. The effects of viral mimic were higher in the lung than in the brain in terms of the number of DEGs and ISGs. Interestingly ribosomal protein L29 (Rpl29), a cell surface heparin-binding protein, was upregulated in the brain and downregulated in the lung. The contrasting expression of Rpl29 gene might be responsible for tissue-specific inflammatory responses in lung and brain tissue on virus infection. In addition, the upregulation of Tlr13, a dsRNA and bacterial 23s rRNA receptor, in the poly(I:C)-stimulated mouse lungs suggests its important role in lung inflammatory responses. It is likely that the combined effects of these genes orchestrate the organ-specific inflammatory or immune responses. Our findings would be beneficial to explore new insights in inflammation and immunity against many critical viral diseases.


Assuntos
Encéfalo/patologia , Inflamação/metabolismo , Pulmão/patologia , Proteínas Ribossômicas/metabolismo , Receptores Toll-Like/metabolismo , Animais , Encéfalo/metabolismo , Citocinas/metabolismo , Inflamação/patologia , Pulmão/metabolismo , Camundongos
12.
Toxicol Lett ; 313: 178-187, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284023

RESUMO

Long-term inhalation of crystalline silica particles leads to silicosis characterized by pulmonary inflammation and interstitial fibrosis. The growth arrest-specific protein 6 (Gas6) and its tyrosine receptor Mer have been implicated to involve in the regulation of inflammation, innate immunity and tissue repair. However, the role of Gas6 or Mer in silica-induced lung inflammation and fibrosis has not been investigated previously. In this study, we observed a remarkable increase of Gas6 in bronchoalveolar lavage fluid (BALF) from wild-type C57BL/6 mice after silica intratracheal administration. Then, we investigated whether genetic loss of Gas6 or Mer could attenuate silica-induced lung inflammation and fibrosis. Our results showed that Gas6-/- and Mer-/- mice exhibited reduced lung inflammation response from days 7 to 84 after silica exposure. We also uncovered an overexpression of the suppressor of cytokine signaling protein 1 in silica-treated deficient mice. Moreover, Gas6 or Mer deficiency attenuated silica-induced collagen deposition by inhibiting the expression of transforming growth factor-ß. We conclude that gene absence of Gas6 or Mer is protective against silica-induced lung inflammation and fibrosis in mice. Targeting Gas6/Mer pathway may be a potential therapeutic approach to treat pulmonary fibrosis in patients with silicosis.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Pulmão/enzimologia , Pneumonia/prevenção & controle , Fibrose Pulmonar/prevenção & controle , Silicose/prevenção & controle , c-Mer Tirosina Quinase/deficiência , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular/genética , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pneumonia/enzimologia , Pneumonia/genética , Pneumonia/patologia , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Transdução de Sinais , Silicose/enzimologia , Silicose/genética , Silicose/patologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , c-Mer Tirosina Quinase/genética
13.
J Cancer Res Clin Oncol ; 145(9): 2325-2333, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31317326

RESUMO

PURPOSE: Nodal positive lung adenocarcinoma includes wide range of survival. Several methods for the classification of nodal-positive lung cancer have been proposed. However, classification considering the impact of targetable genetic variants are lacking. The possibility of genetic variants for the better stratification of nodal positive lung adenocarcinoma was estimated. METHODS: Mutations of 36 genes between primary sites and metastatic lymph nodes (LNs) were compared using next-generation sequencing. Subsequently, mutations in EGFR and BRAF, rearrangements in ALK and ROS1 were evaluated in 69 resected pN1-2M0 adenocarcinoma cases. Recurrence-free survival (RFS), post-recurrence survival (PRS), and overall survival (OS) were evaluated with respect to targetable variants and tyrosine kinase inhibitor (TKI) therapy after recurrence. RESULTS: About 90% of variants were shared and allele frequencies were similar between primary and metastatic sites. In 69 pN1-2M0 cases, EGFR/ALK were positive in primary sites of 39 cases and same EGFR/ALK variants were confirmed in metastatic LNs of 96.7% tissue-available cases. Multivariate analyses indicated positive EGFR/ALK status was associated with worse RFS (HR 2.366; 95% CI 1.244-4.500; P = 0.009), and PRS was prolonged in cases receiving TKI therapy (no post-recurrence TKI therapies, HR 3.740; 95% CI 1.449-9.650; P = 0.006). OS did not differ with respect to targetable variants or TKI therapy. CONCLUSIONS: Cases harbouring targetable genetic variants had a higher risk of recurrence, but PRS was prolonged by TKI therapy. Classification according to the targetable genetic status provides a basis for predicting recurrence and determining treatment strategies after recurrence.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Neoplasias Pulmonares/diagnóstico , Pulmão/metabolismo , Linfonodos/metabolismo , Mutação , Transcriptoma/genética , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Metástase Linfática , Masculino , Análise em Microsséries/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
14.
Medicine (Baltimore) ; 98(27): e16224, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277134

RESUMO

Pneumothorax is a common complication in computed tomography (CT)-guided percutaneous lung biopsy (CPLB). Whether the lobar location of lesions contributes to the incidence of pneumothorax should be further clarified.A total of 1452 consecutive patients who underwent CPLB between January 2010 and March 2018 were retrospectively analyzed. The incidence of pneumothorax was compared among 5 different lobe biopsies. Minor pneumothorax was defined as pneumothorax without chest tube placement and major pneumothorax was defined as pneumothorax with chest tube placement.The positive diagnosis rate of pathology for this cohort was approximately 84%, with 22.5% (326/1452) of the patients experiencing pneumothorax. The rates of pneumothorax were 19.5%, 24.5%, 33.9%, 21.4%, and 23.9% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe, respectively (P = .09). Chest tube placement was necessary in 19.0% (62/326) of the patients with pneumothorax. The rates of major pneumothorax were 5.3%, 2.6%, 10.2%, 4.7%, and 2.6% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe biopsies, respectively (P = .02). This result was further confirmed by the propensity score-matching method. Moreover, 8.7% (127/1452) of the patients experienced puncture of fissure, the rates of which were 13.5%, 5%, 10.2%, 9.1%, and 4.3% for the right upper lobe, right lower lobe, right middle lobe, left upper lobe, and left lower lobe, respectively (P < .001). Within the pneumothorax patient group, the rate of lobe fissure puncture (15.2%) was significantly lower in patients with minor pneumothorax than (51.6%) in those with major pneumothorax (P < .001).Upper and middle lobe lesion biopsies show a significantly high rate of major pneumothorax, which may be due to more puncture of fissure. It is crucial to carefully distinguish the fissure around lesions and bypass it to avoid major pneumothorax.


Assuntos
Biópsia Guiada por Imagem/efeitos adversos , Pneumopatias/diagnóstico , Pulmão/patologia , Tomografia Computadorizada Multidetectores/efeitos adversos , Pneumotórax/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumotórax/diagnóstico , Pneumotórax/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
15.
Cancer Sci ; 110(9): 2734-2747, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278886

RESUMO

Lung cancer has the highest morbidity and mortality among all cancers. Discovery of early diagnostic and prognostic biomarkers of lung cancer can greatly facilitate the survival rate and reduce its mortality. In our study, by analyzing Gene Expression Omnibus and Oncomine databases, we found a novel potential oncogene uridine-cytidine kinase 2 (UCK2), which was overexpressed in lung tumor tissues compared to adjacent nontumor tissues or normal lung. Then we confirmed this finding in clinical samples. Specifically, UCK2 was identified as highly expressed in stage IA lung cancer with a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). We also found that high UCK2 expression was related to poorer clinicopathological features, such as higher T stage and N stage and higher probability of early recurrence. Furthermore, we found that patients with high UCK2 expression had poorer first progression survival and overall survival than patients with low UCK2 expression. Univariate and multivariate Cox regression analyses showed that UCK2 was an independent risk factor related with worse DFS and OS. By gene set enrichment analysis, tumor-associated biological processes and signaling pathways were enriched in the UCK2 overexpression group, which indicated that UCK2 might play a vital role in lung cancer. Furthermore, in cytology experiments, we found that knockdown of UCK2 could suppress the proliferation and migration of lung cancer cells. In conclusion, our study indicated that UCK2 might be a potential early diagnostic and prognostic biomarker for lung cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia/diagnóstico , Uridina Quinase/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Uridina Quinase/genética
16.
Cancer Sci ; 110(9): 2711-2721, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294893

RESUMO

The percentage of programmed death ligand 1 (PD-L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti-PD-1/PD-L1 therapy in lung cancer. PD-L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD-L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD-L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD-L1 expression was negative in 169 patients (73.2%), 1%-49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD-L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD-L1 expression was associated with high-grade cancer cells and in higher stage cancer. PD-L2 was negative in 109 patients (47.2%), 1%-49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD-L2-positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty-five patients (15.2%) were positive for both PD-L1 and PD-L2, whereas 81 patients (35.1%) were negative for both PD-L1 and PD-L2. Log-rank analysis showed that progression-free survival and overall survival were significantly the longest in the PD-L1-negative and PD-L2-positive groups (P < .0001 and P = .0120). We observed lower PD-L1 or PD-L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD-L1 or PD-L2 expression specifically in cancer cells.


Assuntos
Adenocarcinoma de Pulmão/patologia , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/análise , Neoplasias Pulmonares/patologia , Proteína 2 Ligante de Morte Celular Programada 1/análise , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/imunologia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imuno-Histoquímica/métodos , Pulmão/citologia , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Resultado do Tratamento
17.
Cancer Sci ; 110(9): 3006-3011, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301084

RESUMO

Decreased cell adhesion has been reported as a significant negative prognostic factor of lung cancer. However, the molecular mechanisms responsible for the cell incohesiveness in lung cancer have not yet been elucidated in detail. We herein describe a rare histological variant of lung adenocarcinoma consisting almost entirely of individual cancer cells spreading in alveolar spaces in an incohesive pattern. A whole exome analysis of this case showed no genomic abnormalities in CDH1 or other genes encoding cell adhesion molecules. However, whole mRNA sequencing revealed that this case had an extremely high expression level of mucin 21 (MUC21), a mucin molecule that was previously shown to inhibit cell-cell and cell-matrix adhesion. The strong membranous expression of MUC21 was found on cancer cells using mAbs recognizing different O-glycosylated forms of MUC21. An immunohistochemical analysis of an unselected series of lung adenocarcinoma confirmed that the strong membranous expression of MUC21 correlated with incohesiveness. Thus, MUC21 could be a promising biomarker with potential diagnostic and therapeutic applications for lung adenocarcinoma showing cell incohesiveness.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/patologia , Glicoproteínas de Membrana/metabolismo , Mucinas/metabolismo , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Idoso , Antígenos CD/genética , Caderinas/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Tomografia Computadorizada por Raios X , Sequenciamento Completo do Exoma
18.
Cancer Sci ; 110(9): 2960-2972, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31301086

RESUMO

In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin-coupled microRNA capture were carried out to investigate the Ago2-dependent interaction of circCRIM1 and microRNA (miR)-93/miR-182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well-known tumor suppressor, by sponging miR-93 and miR-182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target.


Assuntos
Adenocarcinoma de Pulmão/genética , Biomarcadores Tumorais/metabolismo , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/genética , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , RNA/metabolismo , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/patologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Subunidade alfa de Receptor de Fator Inibidor de Leucemia/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Proteínas de Membrana/genética , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Prognóstico , RNA/genética , RNA Interferente Pequeno/metabolismo , Análise de Sobrevida , Análise Serial de Tecidos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Acta Vet Scand ; 61(1): 37, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349870

RESUMO

BACKGROUND: Pulmonary hypoplasia (PH) and congenital lobar emphysema (CLE) are very rare congenital pulmonary anomalies in veterinary medicine. PH refers to the incomplete pulmonary development due to embryologic imbalance of bronchial development between the lung buds, while CLE is defined as alveolar hyperinflation due to bronchial collapse during expiration caused by bronchial cartilage dysplasia, external bronchial compression, and idiopathic etiology. CLE may develop into pulmonary blebs or bullae that may rupture and induce a spontaneous pneumothorax. There are no reports on concurrent PH and CLE in animals. CASE PRESENTATION: A 7-month-old castrated male Italian Greyhound weighing 5.5 kg presented with vomiting and acute onset of severe dyspnea without any previous history of disease. After emergency treatment including oxygen supplementation and thoracocentesis, plain radiology and computed tomography scanning were performed and lobar emphysema with multiple bullae in the left cranial lung lobe associated with tension pneumothorax was identified. Since the pneumothorax was not resolved despite continuous suction of intrathoracic air for 3 days, a complete lobectomy of the left cranial lung lobe was performed. The excised lobe was not grossly divided into cranial and caudal parts, but a tissue mass less than 1 cm in size was present at the hilum and cranial to the excised lobe. Postoperatively, the dog recovered rapidly without air retention in the thoracic cavity. Histopathologically, the mass was identified as a hypoplastic lung tissue with collapsed alveoli, bronchial dysplasia, and pulmonary arterial hypertrophy. Additionally, the excised lung lobe presented CLE with marked ectasia of alveoli, various blebs and bullae, and general bronchial cartilage dysplasia. According to gross and histopathologic findings, the dog was diagnosed with concurrent PH and CLE in the left cranial lung lobe. During 16 months of follow-up, the dog was well and without any respiratory problems. CONCLUSIONS: This case report confirmed the clinical and histologic features of two different types of rare congenital pulmonary anomalies, PH and CLE, which occurred concurrently in a single lung lobe of a young dog. The condition was successfully managed with lobectomy.


Assuntos
Anormalidades Múltiplas/veterinária , Doenças do Cão/congênito , Pneumopatias/veterinária , Pulmão/anormalidades , Pneumotórax/veterinária , Enfisema Pulmonar/congênito , Animais , Cães , Pulmão/química , Pulmão/patologia , Pulmão/cirurgia , Pneumopatias/congênito , Masculino , Pneumotórax/etiologia , Pneumotórax/patologia , Pneumotórax/cirurgia , Enfisema Pulmonar/complicações , Enfisema Pulmonar/veterinária , Resultado do Tratamento
20.
Neumol. pediátr. (En línea) ; 14(2): 95-99, jul. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1015014

RESUMO

The diagnosis of primary ciliary dyskinesia (PCD) is complex and requires high clinical suspicion. The findings in the diagnostic images are nonspecific and can be seen in other conditions of the airway. In this review, we will describe the findings of PCD in chest radiography and computed tomography, with emphasis on some of the characteristics that differentiate it from cystic fibrosis and we will review the role of CT in the monitoring of changes of the PCD, since the CT findings correlate very well with the structural changes that occur in the course of PCD, especially bronchiectasis. However, using serial CTs should be decided on a case-by-case basis to avoid unnecessary radiation because they are pediatric patients.


El diagnóstico de la Discinesia ciliar primaria (DCP) es complejo y requiere alta sospecha clínica. Los hallazgos en la imágenes diagnósticas son inespecíficos y se pueden ver en otras afecciones de la vía aérea. En esta revisión describiremos los hallazgos de la DCP en Radiología simple y en Tomografía computada (TC), con énfasis en algunas de las características que permiten diferenciarla de la Fibrosis quística (FQ) y revisaremos el rol de la TC en la monitorización de la DCP ya que los hallazgos en la TC se correlacionan muy bien con los cambios estructurales que ocurren en el curso de la DCP, en especial las bronquiectasias. Sin embargo usar TC seriadas se debe decidir caso por caso para evitar la radiación innecesaria por ser pacientes pediátricos.


Assuntos
Humanos , Criança , Sistema Respiratório/metabolismo , Síndrome de Kartagener/fisiopatologia , Pulmão/diagnóstico por imagem , Sistema Respiratório/fisiopatologia , Sistema Respiratório/patologia , Espectroscopia de Ressonância Magnética , Tomografia Computadorizada por Raios X/métodos , Síndrome de Kartagener/metabolismo , Síndrome de Kartagener/microbiologia , Pulmão/metabolismo , Pulmão/patologia
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