ABSTRACT
BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterized by the overlapping clinical features of asthma and COPD. To evaluate the appropriateness of different sets of ACO definition, we compared the clinical characteristics of the previously defined diagnostic criteria and the specialist opinion in this study. METHODS: Patients enrolled in the KOrea COpd Subgroup Study (KOCOSS) were evaluated. Based on the questionnaire data, the patients were categorized into the ACO and non-ACO COPD groups according to the four sets of the diagnostic criteria. RESULTS: In total 1,475 patients evaluated: 202 of 1,475 (13.6%), 32 of 1,475 (2.2%), 178 of 1,113 (16.0%), and 305 of 1,250 (24.4%) were categorized as ACO according to the modified Spanish Society of Pneumonology and Thoracic Surgery (SEPAR), American Thoracic Society (ATS) Roundtable, Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and the specialists diagnosis, respectively. The ACO group defined according to the GINA/GOLD criteria showed significantly higher St. George's Respiratory Questionnaire and COPD Assessment Test scores than the non-ACO COPD group. When the modified SEPAR definition was applied, the ACO group showed a significantly larger decrease in the forced expiratory volume in 1 second (FEV1, %). The ACO group defined by the ATS Roundtable showed significantly larger decrease in the forced vital capacity values compared to the non-ACO COPD group (-18.9% vs. -2.2%, p=0.007 and -412 mL vs. -17 mL, p=0.036). The ACO group diagnosed by the specialists showed a significantly larger decrease in the FEV1 (%) compared to the non-ACO group (-5.4% vs. -0.2%, p=0.003). CONCLUSION: In this study, the prevalence and clinical characteristics of ACO varied depending on the diagnostic criteria applied. With the criteria which are relatively easy to use, defining ACO by the specialists diagnosis may be more practical in clinical applications.
ABSTRACT
BACKGROUND: Few reports have investigated the efficacy of using inhaled corticosteroid (ICS)-containing inhalers to treat patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). OBJECTIVE: To investigate the effect of ICS treatment on patients with ACO using 5 sets of diagnostic criteria. METHODS: Patients with stable COPD enrolled in the Korean COPD subgroup study cohort were assessed for asthma overlap. Patients who were prospectively followed up for 1 year were included in an exacerbation analysis. RESULTS: Among 1067 patients with COPD, 138 (12.9%), 32 (3.0%), 171 (16%), 221 (20.7%), and 264 (24.7%) were classified as having ACO by the Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, the American Thoracic Society roundtable criteria, the modified Spanish criteria, the updated Spanish criteria, and specialists' diagnoses, respectively. According to the specialists' diagnoses, the ACO exacerbation rate was higher than that for COPD alone (incidence rate ratio [IRR] = 1.65; P < .01), even after adjustment for covariates. Patients with ACO who used ICSs experienced less exacerbation, according to the specialists' diagnoses and the GINA/GOLD criteria (IRR = 0.55, P = .026; IRR = 0.69, P = .046, respectively). The only factor associated with a decrease in ACO exacerbation after ICS use was a blood eosinophil count of ≥300 cells/µL (IRR = 0.52, P = .03) irrespective of the diagnosis of ACO by any set of criteria. CONCLUSIONS: This study suggests that ICS treatment can decrease the risk of exacerbation in patients with ACO, and that a blood eosinophil count of ≥300 cells/µL can predict the response to ICS treatment.
Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Adrenal Cortex Hormones/therapeutic use , Asthma/diagnosis , Asthma/drug therapy , Asthma/epidemiology , Eosinophils , Humans , Leukocyte Count , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiologyABSTRACT
PURPOSE: Although decreased natural killer cell activity (NKA) has been observed in many solid cancers, clinical implication of NKA has been scarcely investigated in lung cancer. The objective of this study was to evaluate the potential of using NKA to support diagnosis of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We prospectively evaluated and compared peripheral blood NKA using a novel interferon-gamma releasing assay in healthy population (n=40), patients with benign lung disease (n=40), and those with NSCLC (n=71). We explored the correlation between NKA and clinical parameters and assessed diagnostic performance of NKA for NSCLC using receiver operating characteristic curve analysis. RESULTS: Median NKA values in healthy population, patients with benign lung disease, and those with NSCLC were 1,364.2, 1,438.2, and 406.3 pg/mL, respectively. NKA in NSCLC patients was significantly lower than that in the other two control groups (both P<0.001). At a cutoff value of NKA at 391.0 pg/mL, the area under the curve was 0.762 (95% CI: 0.685-0.838, P<0.001), with a sensitivity of 52.3%, a specificity of 91.0%, a positive predictive value of 85.3%, and a negative predictive value of 65.4% for the diagnosis of NSCLC. Multivariate analysis demonstrated that diagnosis of NSCLC is the only clinical parameter that was significantly associated with NKA (P<0.001). CONCLUSION: This pilot study showed that patients with low NKA were more likely to have lung cancer. Further studies are warranted in order to establish the clinical utility of NKA test for diagnosing lung cancer.
ABSTRACT
Airway sensory nerves are known to express several receptors and channels that are activated by exogenous and endogenous mediators that cause coughing. Toll-like receptor (TLR) s are expressed in nociceptive neurons and play an important role in neuroinflammation. However, there have been very few studies of TLR expression in lung-derived sensory neurons or their relevance to respiratory symptoms such as cough. We used the bleomycin-induced pulmonary fibrosis model to investigate the change in TLR expression in pulmonary neurons and the association of TLRs with transient receptor potential (TRP) channels in pulmonary neurons. After 2 weeks of bleomycin or saline administration, pulmonary fibrosis changes were confirmed using tissue staining and the SIRCOL collagen assay. TLRs (TLR 1-9) and TRP channel expression was analyzed using single cell reverse transcription polymerase chain reaction (RT-PCR) in isolated sensory neurons from the nodose/jugular ganglion and the dorsal root ganglion (DRG). Pulmonary sensory neurons expressed TLR2 and TLR5. In the bleomycin-induced pulmonary fibrosis model, TLR2 expression was detected in 29.5% (18/61) and 26.9% (21/78) of pulmonary nodose/jugular neurons and DRG neurons, respectively. TLR5 was also detected in 55.7% (34/61) and 42.3% (33/78) of pulmonary nodose/jugular neurons and DRG neurons, respectively, in the bleomycin-induced pulmonary fibrosis model. TLR5 was expressed in 63.4% of TRPV1 positive cells and 43.4% of TRPM8 positive cells. In conclusion, TLR2 and TLR5 expression is enhanced, especially in vagal neurons, in the bleomycin-induced fibrosis model group when compared to the saline treated control group. Co-expression of TLR5 and TRP channels in pulmonary sensory neurons was also observed. This work sheds new light on the role of TLRs in the control and manifestation of clinical symptoms, such as cough. To understand the role of TLRs in pulmonary sensory nerves, further study will be required.
Subject(s)
Gene Expression , Lung/metabolism , Pulmonary Fibrosis/genetics , Sensory Receptor Cells/metabolism , Toll-Like Receptors/genetics , Animals , Bleomycin , Ganglia, Spinal/metabolism , Lung/innervation , Lung/pathology , Nodose Ganglion/metabolism , Protein Isoforms/genetics , Pulmonary Fibrosis/chemically induced , Rats, Sprague-Dawley , TRPA1 Cation Channel/genetics , Toll-Like Receptor 2/genetics , Toll-Like Receptor 5/geneticsABSTRACT
PURPOSE: NANOG is a master transcription factor that regulates stem cell pluripotency and cellular reprograming. Increased NANOG expression has been associated with poor survival in several human malignancies. However, the clinical significance of NANOG overexpression in lung cancer has been scarcely evaluated. The aim of this study was to investigate whether NANOG levels are associated with clinical outcomes of patients with non-small cell lung cancer (NSCLC) who were treated with platinum-based chemotherapy. METHODS: NANOG levels were evaluated immunohistochemically using the histologic score (H-score) in tumor tissues from patients with advanced NSCLC who received platinum-based doublet treatment. We performed survival analyses according to the NANOG levels and evaluated the association between clinicopathological parameters and levels of NANOG. RESULTS: Multivariate analyses using 112 tumor specimens showed that high NANOG levels were independently associated with short progression-free survival (hazard ratio [HR] =3.09, 95% confidence interval [CI]: 2.01-4.76) and with short overall survival (HR =3.00, 95% CI: 1.98-4.54). Similar results were shown in the subgroup analyses for patients with adenocarcinoma and squamous cell carcinoma. NANOG expression was not associated with any clinicopathological parameter such as age, gender, smoking status, stage, differentiation, or histological subtypes. CONCLUSION: NANOG overexpression was associated with poor response and short overall survival in patients with advanced NSCLC who were treated with platinum-based chemotherapy, suggesting that NANOG could be a potential adverse predictive marker in this setting.
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INTRODUCTION: To date, no prospective phase III trials have directly compared the efficacy of pemetrexed plus cisplatin (Pem-Cis) with docetaxel plus cisplatin (Doc-Cis) in patients with nonsquamous non-small-cell lung cancer. MATERIALS AND METHODS: A total of 148 chemotherapy-naive patients lacking driver mutations were randomized into 21-day regimens of cisplatin 70 mg/m2 with either docetaxel 60 mg/m2 (n = 71) or pemetrexed 500 mg/m2 (n = 77) for ≤ 4 cycles. The primary objective was to assess the noninferiority of progression-free survival (PFS) for patients receiving the Doc-Cis regimen. The secondary endpoints were the response rates, overall survival, and toxicity profiles. RESULTS: Partial remission was observed in 24 (31.2%) and 24 (33.8%) patients in the Pem-Cis and Doc-Cis groups, respectively. The median PFS was 4.7 months (95% confidence interval [CI], 4.4-5.0) in the Pem-Cis arm and 4.4 months (95% CI, 3.7-5.1) in the Doc-Cis arm (P > .05). The median overall survival was longer in the Doc-Cis arm (13.3 months; 95% CI, 8.1-18.5) than in the Pem-Cis arm (11.7 months; 95% CI, 8.6-14.8; P > .05). Between the 2 arms, no significant difference was found in the subsequent treatments after failure of first-line treatment. The rate of grade 3 or 4 neutropenia and febrile neutropenia was greater in the Doc-Cis arm than in the Pem-Cis arm. CONCLUSION: In nonsquamous non-small-cell lung cancer patients lacking driver mutations, the PFS and response rates were similar between the 2 arms, and toxicity was tolerable, although adverse events and more severe toxicities were observed more frequently in the Doc-Cis arm.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Pemetrexed/therapeutic use , Taxoids/therapeutic use , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Docetaxel , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Neutropenia/etiology , Survival Analysis , Treatment OutcomeABSTRACT
Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (nâ=â53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (nâ=â91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3âng/mL, which was significantly higher than that in benign pleural effusions (Pâ<â0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0âng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750-0.886), which was significantly better than that of cytokeratin 19 fragments (Pâ<â0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion.
Subject(s)
Adenocarcinoma/diagnosis , Carcinoma, Squamous Cell/diagnosis , Lung Neoplasms/diagnosis , Membrane Proteins/analysis , Mitochondrial Proteins/analysis , Pleural Effusion, Malignant/chemistry , Adult , Aged , Antigens, Neoplasm/analysis , Biomarkers/analysis , Carcinoembryonic Antigen/analysis , Female , Humans , Keratin-19/analysis , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ROC CurveABSTRACT
PURPOSE: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. MATERIALS AND METHODS: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. RESULTS: A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. CONCLUSION: Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.
Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Membrane Proteins/metabolism , Mitochondrial Proteins/metabolism , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/drug therapy , Female , Gene Expression , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lung Neoplasms/diagnosis , Lung Neoplasms/drug therapy , Male , Membrane Proteins/genetics , Middle Aged , Mitochondrial Proteins/genetics , Neoplasm Grading , Neoplasm Staging , Platinum/administration & dosage , Prognosis , Treatment OutcomeABSTRACT
PURPOSE OF THE STUDY: Inactivation of NF-κB with IKKß knockout mice reduces tobacco smoke-induced pulmonary inflammation. In this study, we investigated whether the IKKß inhibitor PS-1145 could attenuate the pulmonary inflammation induced by tobacco smoke. MATERIALS AND METHODS: We divided 30 mice into three groups: a control group, a smoking group, and a PS-1145 group. Mice from the smoking and PS-1145 groups were exposed for 2 weeks to tobacco smoke. PS-1145 was injected intraperitoneally before every tobacco smoke exposure. After 2 weeks, bronchoalveolar lavage (BAL) was performed for cell counting and measuring of inflammatory chemokines. We analyzed the correlation between NF-κB and NF-κB-regulated chemokines in BAL fluid and measured the neutrophils and macrophages by immunostaining in lung tissues. RESULTS: The PS-1145 group showed a significant reduction in the number of total cells, neutrophils, and macrophages, as well as the KC and MCP-1 level, in the BAL fluid compared to the smoking group. There was no significant difference in the level of MIP-1α. The level of NF-κB in BAL fluid was significantly positively correlated with KC and MCP-1 levels, but not with MIP-1α level. The PS-1145 group also showed a significant fewer neutrophils and macrophages in the lung tissue. CONCLUSIONS: We conclude that the IKKß inhibitor PS-1145 suppressed the NF-κB signaling pathway and reduced the recruitment of inflammatory cells and chemokines in pulmonary inflammation induced by tobacco smoke. IKKß inhibition offers a potential therapeutic target for tobacco smoke-induced pulmonary inflammation.
Subject(s)
I-kappa B Kinase/antagonists & inhibitors , Pneumonia/etiology , Protein Kinase Inhibitors/pharmacology , Tobacco Smoke Pollution/adverse effects , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Chemokines/drug effects , Chemokines/metabolism , Heterocyclic Compounds, 3-Ring/administration & dosage , Heterocyclic Compounds, 3-Ring/pharmacology , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/pathology , Mice , NF-kappa B/drug effects , NF-kappa B/metabolism , Neutrophils/drug effects , Neutrophils/pathology , Pneumonia/pathology , Protein Kinase Inhibitors/administration & dosage , Pyridines/administration & dosage , Pyridines/pharmacologyABSTRACT
BACKGROUND: Acute exacerbation and bacterial pneumonia are major life-threatening conditions in patients with interstitial lung disease (ILD). The rapid recognition of these 2 different conditions is important for their proper treatment. An elevated procalcitonin (PCT) level is commonly detected in patients with bacterial infections. This study assessed the usefulness of the serum PCT level as a biomarker for the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. MATERIALS AND METHODS: In this prospective observational study, we enrolled patients with ILD who had experienced recently progressive dyspnea and exhibited new infiltrations on chest radiographs. We classified these patients into an acute exacerbation group and a bacterial pneumonia group and compared their baseline characteristics and laboratory parameters, including the PCT level. RESULTS: Of 21 patients with ILD, 9 patients had bacterial pneumonia. Both the groups showed similar baseline characteristics. The bacterial pneumonia group demonstrated a high PCT level. The PCT level in the acute exacerbation group was significantly lower than that in the bacterial pneumonia group (0.05 versus 0.91ng/mL, respectively; P < 0.001). Other parameters, such as the C-reactive protein level, leukocyte count and body temperature, were also lower in the acute exacerbation group. At a cutoff value of 0.1ng/mL, the sensitivity, specificity and negative predictive values of the serum PCT level were 88.9%, 100.0% and 92.3%, respectively. CONCLUSIONS: These findings suggest that the serum PCT level is useful in the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD.
Subject(s)
Calcitonin/blood , Lung Diseases, Interstitial/diagnosis , Pneumonia, Bacterial/diagnosis , Aged , Biomarkers/blood , Diagnosis, Differential , Disease Progression , Female , Humans , Lung Diseases, Interstitial/microbiology , Male , Middle Aged , Pneumonia, Bacterial/microbiology , Prospective Studies , Republic of KoreaABSTRACT
Bronchial mucous gland adenoma is a very rare benign tumor that arises from the bronchial mucous-secreting glands. Its detection and appearance using F-FDG PET/CT has not been well characterized. We present a case of a 59-year-old man with FDG-avid mucous gland adenoma that mimicked lung cancer on F-FDG PET/CT.
Subject(s)
Adenoma/diagnostic imaging , Bronchi/diagnostic imaging , Fluorodeoxyglucose F18 , Lung Neoplasms/diagnostic imaging , Positron-Emission Tomography , Radiopharmaceuticals , Tomography, X-Ray Computed , False Positive Reactions , Humans , Male , Middle Aged , Multimodal ImagingSubject(s)
Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Lung Diseases/etiology , Lymphoma, T-Cell, Peripheral/surgery , Biopsy , Graft vs Host Disease/diagnosis , Humans , Lung Diseases/diagnosis , Lymphoma, T-Cell, Peripheral/diagnosis , Male , Middle Aged , Tomography, X-Ray Computed , Transplantation, Autologous , Treatment OutcomeABSTRACT
UNLABELLED: Quercetin is a bioflavonoid known for antioxidation and antiproliferation activities. We demonstrated that quercetin inhibited cancer cell growth and sensitized cancer cells to gemcitabine treatment by promoting apoptosis via inhibiting heat shock protein 70 expression. Our results suggest that quercetin might have potential to increase sensitivity to chemotherapy and that heat shock protein 70 could be a new target for lung cancer treatment. BACKGROUND: Quercetin is a bioflavonoid with antiproliferative and proapoptotic activity in various cancer cells. However, little is known about the mechanism by which quercetin inhibits cancer growth or its potential role as a chemosensitizer in lung cancer cells. We investigated whether quercetin-induced inhibition of heat shock protein 70 (HSP70) is involved in its anticancer activity and whether it could modulate the responsiveness of lung cancer cells to chemotherapy. MATERIALS AND METHODS: Various concentrations of quercetin and gemcitabine, either alone or in combination, were applied to lung cancer cells (A549 and H460 cells). We evaluated cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt assay, apoptotic activity by determining caspase-3 and caspase-9 activities, and HSP70 expression using Western blot analysis after treatment. RESULTS: Quercetin reduced cell viability and suppressed HSP70 expression in both cell lines dose-dependently. Adding a fixed quercetin dose enhanced gemcitabine-induced cell death, which was related to increased caspase-3 and caspase-9 activities. Combination treatment with quercetin and gemcitabine downregulated HSP70 expression more prominently than treatment with quercetin or gemcitabine alone. CONCLUSION: Quercetin-induced HSP70 inhibition was involved in growth inhibition and sensitization to chemotreatment in lung cancer cells. Quercetin might have potential as a chemosensitizer in lung cancer treatment.
Subject(s)
Adenocarcinoma/drug therapy , Biomarkers, Pharmacological/metabolism , Deoxycytidine/analogs & derivatives , HSP70 Heat-Shock Proteins/metabolism , Lung Neoplasms/drug therapy , Quercetin/pharmacology , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Apoptosis/drug effects , Caspases/metabolism , Cell Line, Tumor , Deoxycytidine/pharmacology , Gene Expression Regulation/drug effects , HSP70 Heat-Shock Proteins/genetics , Humans , Lung Neoplasms/pathology , GemcitabineABSTRACT
OBJECTIVES: Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Romo1 is overexpressed in most cancer cell lines and related to invasiveness and chemoresistance in vitro. However, little information is available on its clinical implications. We investigated the association between Romo1 expression and the clinical outcomes of non-small cell lung cancer (NSCLC) patients who underwent surgical resection. MATERIALS AND METHODS: Romo1 protein expressions were evaluated immunohistochemically in resected tumor specimens. Survival analyses for overall population (n=110) and early-stage patients (n=97) were performed according to clinical parameters including level of Romo1 expression. RESULTS: Multivariate analyses showed that high Romo1 expression in tumor tissues was significantly associated with short disease-free survival (hazard ratio [HR]=3.16, 95% confidence interval [CI]: 1.21-8.22), and with short overall survival (HR=3.22, 95% CI: 1.02-10.21). Stronger associations were observed between Romo1 expression and disease-free survival (HR=3.69, 95% CI: 1.39-9.97) and overall survival (HR=4.21, 95% CI: 1.12-14.67) in stage I and II patients than in the overall population. Romo1 expression was not associated with any clinical parameter including age, gender, smoking status, stage, differentiation, or tumor histology. CONCLUSIONS: Increased Romo1 expression in surgically resected NSCLC was found to be significantly associated with early recurrence and poor survival. Romo1 overexpression could be a potential adverse prognostic marker in this setting.
Subject(s)
Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Lung Neoplasms/metabolism , Lung Neoplasms/mortality , Membrane Proteins/metabolism , Mitochondrial Proteins/metabolism , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/surgery , Combined Modality Therapy , Female , Gene Expression , Humans , Immunohistochemistry , Lung Neoplasms/diagnosis , Lung Neoplasms/surgery , Male , Membrane Proteins/genetics , Middle Aged , Mitochondrial Proteins/genetics , Neoplasm Grading , Neoplasm Staging , Prognosis , Treatment OutcomeSubject(s)
Air Pollutants/toxicity , Disinfectants/toxicity , Guanidines/toxicity , Lung Diseases, Interstitial/chemically induced , Aerosols/toxicity , Animals , Disease Models, Animal , Environmental Exposure , Household Articles , Household Products , Humans , Nebulizers and Vaporizers , Rats , Rats, Sprague-Dawley , Republic of KoreaABSTRACT
BACKGROUND: NBS LabChip G2-3 is a novel, ultrafast, chip-type portable real-time polymerase chain reaction (PCR) system. We evaluated the clinical usefulness of this system in detecting pulmonary TB and assessed its diagnostic performance compared with a conventional tube-type PCR system. METHODS: A total of 247 sputum samples were collected from patients suspected of having pulmonary TB. After the decontamination process, these samples were examined by fluorescence staining for acid-fast bacilli, cultures with both solid and liquid media, and real-time PCR with the NBS LabChip and a conventional tube-type system. The diagnostic accuracy of the NBS LabChip system and the agreement between the two assays were evaluated. RESULTS: Considering mycobacterial culture results as a gold standard, the overall sensitivity and specificity of the NBS LabChip was 83.8% (95% CI, 73.8%-91.1%) and 94.0% (95% CI, 89.3%-97.1%), respectively. For the detection of TB from the smear-positive samples, the sensitivity and specificity of the NBS LabChip was 96.0% (95% CI, 86.3%-99.5%) and 83.3% (95% CI, 72.3%-95.7%), respectively. For the smear-negative samples, the sensitivity and specificity of the NBS LabChip was 63.3% (95% CI, 43.9%-80.1%) and 95.0% (95% CI, 90.4%-97.8%), respectively. There were no significant differences in the sensitivity and specificity between the NBS LabChip and a conventional tube-type system, although the NBS LabChip shortened the PCR time (27 min for 45 cycles). CONCLUSIONS: The NBS LabChip G2-3 system has potential as an ultrafast, cost-effective diagnostic tool for pulmonary TB with high sensitivity and specificity.
Subject(s)
DNA, Bacterial/genetics , Mycobacterium tuberculosis/genetics , Real-Time Polymerase Chain Reaction/instrumentation , Sputum/microbiology , Tuberculosis, Pulmonary/diagnosis , Diagnosis, Differential , Equipment Design , Humans , Mycobacterium tuberculosis/isolation & purification , ROC Curve , Reproducibility of Results , Time Factors , Tuberculosis, Pulmonary/microbiologyABSTRACT
OBJECTIVES: Reactive oxygen species modulator 1 (Romo1) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. Romo1 is increased in most cancer cell lines and is related with resistance to chemotherapy in vitro. However, data on its expression in patients with malignancy is very limited. We evaluated the usefulness of serum Romo1 as a potential diagnostic biomarker in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We initially assessed the expression of Romo1 using Western blotting and enzyme-linked immunosorbent assay in paired lung tissue and serum specimen from NSCLC patients who underwent surgical resection. Then we evaluated and compared serum Romo1 level in a healthy population (n=55), patients with benign lung diseases (n=63) and NSCLC patients (n=58). We explored the correlation between Romo1 expression and clinical parameters and assessed diagnostic performance of serum Romo1 for NSCLC using receiver operating characteristic (ROC) curve analysis. RESULTS: Romo1 expression in lung cancer tissues was significantly increased compared with non-tumorous tissues (p<0.001). Romo1 expression in cancer tissues positively correlated with that in serum (r=0.68, p=0.009). Serum Romo1 level in NSCLC patients significantly increased compared with that of healthy population or patients with benign lung diseases (both p<0.001). ROC curve analysis using an optimal cutoff value of 329.7 pg/mL revealed sensitivity and specificity for the diagnosis of NSCLC of 81.9% and 89.8%, respectively, with an area under the curve of 0.847 (95% confidence interval: 0.789-0.892, p<0.001). Serum Romo1 level was not related with age, gender, smoking status, tumor differentiation, histological type or stage. CONCLUSIONS: Serum Romo1 discriminated NSCLC patients from the population without cancer with considerable sensitivity and specificity. Serum Romo1 could be a potential diagnostic biomarker for NSCLC.
Subject(s)
Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/blood , Lung Neoplasms/diagnosis , Membrane Proteins/blood , Mitochondrial Proteins/blood , Aged , Aged, 80 and over , Female , Humans , Lung Diseases/blood , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , ROC Curve , Risk Factors , Sensitivity and Specificity , SmokingABSTRACT
Immunoglobulin (Ig) G4-related disease is a recently recognized systemic fibroinflammatory condition characterized by a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells with elevated circulating levels of IgG4. The disease can either be localized to one or two organs, or present as diffuse multi-organ disease. Furthermore, lesions in different organs can present simultaneously or metachronously. In the pulmonary manefestations, lesions associated with IgG4-related disease have been described in the lung parenchyma, airways and pleura, as well as the mediastinum. We report a case of IgG4-related disease presenting as massive pleural effusion and thrombophlebitis.