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BACKGROUND: The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value. METHODS: A prospective observational study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between July 2016 and December 2018. Blood samples were collected at days 1 and 3. Serum cytokine levels (e.g., tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]) and CD14+ monocyte human leukocyte antigen-D-related (HLA-DR) expression were measured to serve as immune markers. Classification of each immune status, namely systemic inflammatory response syndrome (SIRS), compensatory anti-inflammatory response syndrome (CARS), and mixed antagonistic response syndrome (MARS), was defined based on levels of immune markers. Changes of immune status were classified into four groups which were stabilization (SB), deterioration (DT), remission (RM), and non-remission (NR). RESULTS: A total of 174 septic patients were enrolled including 50 non-survivors. Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors. Patients with MARS had the highest mortality rate. Immune status of 46.1% patients changed from day 1 to day 3. Among four groups of immune status changes, DT had the highest mortality rate, followed by NR, RM, and SB with mortality rates of 64.7%, 42.9%, and 11.2%, respectively. CONCLUSIONS: Severe immune disorder defined as MARS or deterioration of immune status defined as DT lead to the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.
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Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.
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Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Inmunoterapia/efectos adversos , Neoplasias Pulmonares/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Periodo PerioperatorioRESUMEN
BACKGROUND: Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the potential for repairing injured sites and regulating autophagy. This study was to investigate the influence of BM-MSCs on autophagy of macrophages in the oxygen-glucose deprivation/restoration (OGD/R) microenvironment and to explore the potential mechanism. METHODS: We established a co-culture system of macrophages (RAW264.7) with BM-MSCs under OGD/R conditions in vitro. RAW264.7 cells were transfected with recombinant adenovirus (Ad-mCherry-GFP-LC3B) and autophagic status of RAW264.7 cells was observed under a fluorescence microscope. Autophagy-related proteins light chain 3 (LC3)-I, LC3-II, and p62 in RAW264.7 cells were detected by Western blotting. We used microarray expression analysis to identify the differently expressed genes between OGD/R treated macrophages and macrophages co-culture with BM-MSCs. We investigated the gene heme oxygenase-1 (HO-1), which is downstream of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. RESULTS: The ratio of LC3-II/LC3-I of OGD/R treated RAW264.7 cells was increased (1.27â±â0.20 vs. 0.44â±â0.08, t = 6.67, Pâ <â0.05), while the expression of p62 was decreased (0.77â±â0.04 vs. 0.95â±â0.10, tâ=â2.90, Pâ <â0.05), and PI3K (0.40â±â0.06 vs. 0.63â±â0.10, tâ=â3.42, Pâ <â0.05) and p-Akt/Akt ratio was also decreased (0.39â±â0.02 vs. 0.58â±â0.03, tâ=â9.13, Pâ <â0.05). BM-MSCs reduced the LC3-II/LC3-I ratio of OGD/R treated RAW264.7 cells (0.68â±â0.14 vs. 1.27â±â0.20, tâ=â4.12, Pâ <â0.05), up-regulated p62 expression (1.10â±â0.20 vs. 0.77â±â0.04, tâ=â2.80, Pâ <â0.05), and up-regulated PI3K (0.54â±â0.05 vs. 0.40â±â0.06, tâ=â3.11, Pâ <â0.05) and p-Akt/Akt ratios (0.52â±â0.05 vs. 0.39â±â0.02, tâ=â9.13, Pâ <â0.05). A whole-genome microarray assay screened the differentially expressed gene HO-1, which is downstream of the PI3K/Akt signaling pathway, and the alteration of HO-1 mRNA and protein expression was consistent with the data on PI3K/Akt pathway. CONCLUSIONS: Our results suggest the existence of the PI3K/Akt/HO-1 signaling pathway in RAW264.7 cells under OGD/R circumstances in vitro, revealing the mechanism underlying BM-MSC-mediated regulation of autophagy and enriching the understanding of potential therapeutic targets for the treatment of ALI.
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Células Madre Mesenquimatosas , Animales , Apoptosis , Autofagia , Médula Ósea , Glucosa , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Macrófagos/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Oxígeno , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Transducción de SeñalRESUMEN
OBJECTIVE: In the era of fast track surgery, early and accurately estimating whether postoperative length of stay (p-LOS) will be prolonged after lung cancer surgery is very important, both for patient's discharge planning and hospital bed management. Pulmonary function tests (PFTs) are very valuable routine examinations which should not be underutilized before lung cancer surgery. Thus, this study aimed to establish an accurate but simple prediction tool, based on PFTs, for achieving a personalized prediction of prolonged p-LOS in patients following lung resection. METHODS: The medical information of 1257 patients undergoing lung cancer surgery were retrospectively reviewed and served as the training set. p-LOS exceeding the third quartile value was considered prolonged. Using logistic regression analyses, potential predictors of prolonged p-LOS were identified among various preoperative factors containing PFTs and intraoperative factors. A nomogram was constructed and subjected to internal and external validation. RESULTS: Five independent risk factors for prolonged p-LOS were identified, including older age, being male, and ratio of residual volume to total lung capacity (RV/TLC) ≥ 45.0% which is the only modifiable risk factor, more invasive surgical approach, and surgical type. The nomogram comprised of these five predictors exhibited sufficient predictive accuracy, with the area under the receiver operating characteristic curve (AUC) of 0.76 [95% confidence interval (CI) 0.73-0.79] in the internal validation. Also its predictive performance remained fine in the external validation, with the AUC of 0.70 (95% CI 0.60-0.79). The calibration curves showed satisfactory agreements between the model predicted probability and the actually observed probability. CONCLUSIONS: Preoperative amelioration of RV/TLC may prevent lung cancer patients from unnecessary prolonged p-LOS. The integrated nomogram we developed could provide personalized risk prediction of prolonged p-LOS. This prediction tool may help patients perceive expected hospital stays and enable clinicians to achieve better bed management after lung cancer surgery.
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Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue factor pathway inhibitor (hTFPI) or hirudin fusion protein on CD31+ cells, including vascular endothelial cells (ECs). ALI was induced by intratracheal injection of LPS, and after 24 h the expression of TF and protease-activated receptors (PARs) on EC in lungs were assessed, alongside the extent of inflammation and injury. The expression of TF and PARs on the EC in lungs was upregulated after ALI. In the two strains of transgenic mice, expression of either of hTFPI or hirudin by EC was associated with significant reduction of inflammation, as assessed by the extent of leukocyte infiltration or the levels of proinflammatory cytokines, and promoted survival after LPS-induced ALI. The beneficial outcomes were associated with inhibition of the expression of chemokine CCL2 in lung tissues. The protection observed in the CD31-TFPI-transgenic strain was abolished by injection of an anti-hTFPI antibody, but not by prior engraftment of the transgenic strains with WT bone marrow, confirming that the changes observed were a specific transgenic expression of anticoagulants by EC. These results demonstrate that the inflammation in ALI is TF and thrombin dependent, and that expression of anticoagulants by EC significantly inhibits the development of ALI via repression of leukocyte infiltration, most likely via inhibition of chemokine gradients. These data enhance our understanding of the pathology of ALI and suggest a novel therapeutic strategy for treatment.
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Lesión Pulmonar Aguda/metabolismo , Células Endoteliales/metabolismo , Hirudinas/metabolismo , Inflamación/metabolismo , Lipoproteínas/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Animales , Coagulación Sanguínea/fisiología , Quimiocinas/metabolismo , Quimiotaxis de Leucocito/fisiología , Hirudinas/genética , Humanos , Inflamación/inducido químicamente , Sanguijuelas/química , Lipopolisacáridos , Lipoproteínas/genética , Pulmón/patología , Ratones Endogámicos C57BL , Ratones Transgénicos , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Pseudomonas aeruginosa/química , Receptores Proteinasa-Activados/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Trombina/metabolismo , Tromboplastina/metabolismoRESUMEN
Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.
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Autofagia/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Platino (Metal)/uso terapéutico , Polimorfismo Genético/genética , Adulto , Anciano , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Femenino , Genotipo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Enzimas Ubiquitina-Conjugadoras/genética , Proteínas de Transporte Vesicular/genéticaRESUMEN
BACKGROUND: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. METHODS: We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. RESULTS: Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. CONCLUSIONS: Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.
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Inflamación/metabolismo , Neoplasias Pulmonares/metabolismo , Factores de Transcripción MEF2/metabolismo , Células A549 , Carcinoma de Pulmón de Células no Pequeñas/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/genética , Inflamación/patología , Lipopolisacáridos/farmacología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Factores de Transcripción MEF2/deficiencia , Factores de Transcripción MEF2/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA) against versican to determine if knockdown of versican could restore the deposition of insoluble elastin. Versican siRNA treatment reduced versican expression and secretion by pulmonary fibroblasts from both COPD and non-COPD patients (P<0.01) and significantly increased deposition of insoluble elastin in the COPD cell cultures (P<0.05). The treatment, however, did not significantly affect production of soluble elastin (tropoelastin) in either the COPD or non-COPD cell cultures, supporting a role for versican in inhibiting assembly but not synthesis of tropoelastin. These results suggest that removal or knockdown of versican may be a possible therapeutic strategy for increasing deposition of insoluble elastin and stimulating repair of elastic fibers in COPD lung.
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Elastina/metabolismo , Fibroblastos/metabolismo , Pulmón/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/terapia , Interferencia de ARN , ARN Interferente Pequeño/genética , Tratamiento con ARN de Interferencia/métodos , Versicanos/genética , Estudios de Casos y Controles , Línea Celular , Regulación hacia Abajo , Elastina/genética , Fibroblastos/patología , Técnicas de Silenciamiento del Gen , Humanos , Pulmón/patología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , ARN Interferente Pequeño/metabolismo , Solubilidad , Factores de Tiempo , Transfección , Tropoelastina/genética , Tropoelastina/metabolismo , Versicanos/metabolismoRESUMEN
In this study, we utilized AQP3-knockout mice as the in vivo model and AQP3-knockdown human bronchial epithelial cells (HBECs) as the in vitro model. Airway injury was experimentally induced by intra-tracheal injection of naphthalene. HE staining, transmission and scanning electron microscope were performed to evaluate self-healing capacity in vivo. Transwell and wound-healing assays were performed to evaluate epithelial cell migration in vitro. We found that both the airway epithelial cells of AQP3-knockout mice and AQP3-knockdown HBECs exhibited an obviously impaired self-healing capacity with defective epithelial cell migration through AQP3-facilitated glycerol transport. In addition, glycerol supplementation could largely correct defective injury healing and epithelial cell migration. For the first time, we found evidence for distinct defects in AQP3-deficient airway epithelial cell migration. Mechanistic analysis showed AQP3-facillitated glycerol transport plays a role in airway epithelial self-healing after injury.
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Acuaporina 3/deficiencia , Epitelio/metabolismo , Cicatrización de Heridas/genética , Animales , Acuaporina 3/genética , Acuaporina 3/farmacología , Bronquios/citología , Bronquios/lesiones , Línea Celular Transformada , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Células Epiteliales/ultraestructura , Epitelio/ultraestructura , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Glicerol/metabolismo , Glicerol/farmacología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Microscopía Electrónica , Naftalenos/toxicidad , Factores de Tiempo , Cicatrización de Heridas/efectos de los fármacosRESUMEN
China is the largest producer and consumer of tobacco in the world. Consequently, the burden of tobacco-related diseases in China is enormous. Implementation of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) may lead to a significant reduction in tobacco-related morbidity and mortality both in China and globally. In this review, the authors summarize the epidemic of tobacco use and the progress made in implementing the WHO FCTC, including the promotion of legislation for smoke-free public places; smoking-cessation assistance; labeling of tobacco packaging; enforcement of bans on tobacco advertising, promotion, and sponsorship; increased taxes on tobacco products; increased tobacco prices; improvements in public awareness of the dangers of smoking; and identifying the barriers to implementing effective tobacco-control measures in China. Since the WHO FCTC officially took effect in China on January 9, 2006, China has taken some important steps, especially in promoting legislation for smoke-free public places. Because tobacco permeates the fabric of society, business, commerce, and politics in China, commitments and actions from the government are crucial, and implementing the WHO FCTC in China will be an arduous and long-term task.
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Fumar/efectos adversos , Tabaquismo/epidemiología , China , Política de Salud , Humanos , Cese del Hábito de Fumar , Tabaquismo/patología , Organización Mundial de la SaludRESUMEN
Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer.
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Neoplasias Pulmonares/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , China , Manejo de la Enfermedad , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/prevención & control , Neoplasias Pulmonares/terapia , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Enfermedad Pulmonar Obstructiva Crónica/terapia , Factores de RiesgoRESUMEN
BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China.
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Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Detección Precoz del Cáncer , Carcinoma Pulmonar de Células Pequeñas/sangre , Anciano , Antígenos de Neoplasias/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , China , Femenino , Humanos , Queratina-19/sangre , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/sangre , Proteínas Recombinantes/sangre , Serpinas/sangre , Carcinoma Pulmonar de Células Pequeñas/patologíaRESUMEN
The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment.
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Detección Precoz del Cáncer , Neoplasias Pulmonares/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Broncoscopía , China , Humanos , Neoplasias Pulmonares/etiología , Neoplasias Pulmonares/patología , Tamizaje Masivo , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/patología , Factores de Riesgo , Fumar/efectos adversosRESUMEN
BACKGROUND AND AIM: There is growing interest in how integrins play a role in cancer disease biology and what applications these may have in anti-cancer therapeutic development. This study investigates integrin αvß5 expression in non-small cell lung carcinoma (NSCLC) and its correlations with clinical information. METHODS: Tumor human tissue microarrays of 147 radically operated Chinese NSCLC patients were retrieved from the pathology archive, and sections were autoimmune stained along with positive and negative controls. Integrin αvß5 (P1F6) mouse monoclonal antibody were validated by both Western blotting and immunoreactivity on the same set of cell pellets, according to a precedent of expression levels in cell flow cytometry. The immunoreactivity of all patients' cases against integrin αvß5 antibody was graded in a semi-quantitative manner by two pathologists blind to any patient data. RESULTS: Overall survival significantly correlated to integrin αvß5 immunoreactivity by Cox regression analysis with P = 0.032. When applying Kaplan-Meier to analyze the comparison between positive and negative expression on lymph node metastasis patients, P = 0.082. Therefore, integrin αvß5 expression emerges as a significant prognostic factor for NSCLC. In total, 39 of 147 (26.5%) showed an integrin αvß5 immunoreactivity positive, as it ranged from 6.1% in squamous cell carcinoma to 19.7% in adenocarcinoma. This expression correlated significantly with histological subtypes (P = 0.007), tumor node metastasis classification of malignant tumors (P = 0.027) and lymph node metastases (P = 0.006). CONCLUSION: This study support the hypothesis that integrin αvß5 is a prognostic biomarker and correlates to metastasis with therapeutic development potential in NSCLC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Receptores de Vitronectina/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Análisis de SupervivenciaRESUMEN
Despite a number of studies on biomarkers in chronic obstructive pulmonary disease (COPD), only a few disease-related markers have been identified, yet we still have no satisfactory markers specific to innate immune system and neutrophil activation, which is essential in airway inflammation in COPD. Recent biological studies indicated that lipocalins (LCNs) might be involved in airway inflammation and innate immunity; however, results from available studies on the association of LCNs with COPD are not consistent. We carried out a multicenter prospective observational cohort study to investigate the differences in serum levels of LCN1 and LCN2 between subjects with COPD (n=58) and healthy controls (n=29). Several validated inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-8, were measured. The correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung function, symptoms, and disease category was also analyzed. When comparing with healthy controls, serum levels of LCN1 (66.35±20.26 ng/mL versus 41.16±24.19 ng/mL, P<0.001) and LCN2 (11.29±3.92 ng/mL versus 6.09±5.13 ng/mL, P<0.001) were both elevated in subjects with COPD after adjusting for age, sex, smoking habits, and inflammatory biomarkers. Smoking history and tobacco exposure, as quantified by pack-year, had no impact on systemic expressions of LCN1 and LCN2 in our study. Blood levels of LCN1 and LCN2, respectively, were negatively correlated to COPD Assessment Test and Modified Medical British Research Council score (P<0.001). Disease category by Global Initiative for Chronic Obstructive Lung Disease grade 1-4 or group A-D was not associated with levels of LCNs. Patient-reported exacerbations and body mass index were also tested, but no relationship with LCNs was found. In summary, serum concentrations of LCN1 and LCN2 were both elevated in patients with COPD, with their levels correlating to COPD Assessment Test and Modified Medical British Research Council score. These findings warrant large-scale and longitudinal studies to validate LCNs as circulating biomarkers for COPD.
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Lipocalina 1/sangre , Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Proteínas de Fase Aguda , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios de Casos y Controles , China , Estudios Transversales , Femenino , Humanos , Mediadores de Inflamación/sangre , Lipocalina 2 , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Índice de Severidad de la Enfermedad , Regulación hacia ArribaRESUMEN
Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People's Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD.
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Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Neumología/normas , China/epidemiología , Consenso , Progresión de la Enfermedad , Humanos , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/normas , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD. METHODS: In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s [FEV1]/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460. FINDINGS: Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1·16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1·49 exacerbations per patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495 patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo group. INTERPRETATION: Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I). FUNDING: Hainan Zambon Pharmaceutical.