Yu Ji Cho

Curcumin attenuates radiation-induced inflammation and fibrosis in rat lungs.

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-κ B (NF-κB) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

Endobronchial Aspergilloma: Report of 10 Cases and Literature Review

Purpose A retrospective investigation of the clinical and radiologic features as well as the bronchoscopic appearance was carried out in patients with endobronchial aspergilloma. Materials and Methods Ten patients with endobronchial aspergilloma diagnosed by bronchoscopy and histological examination were identified at the Gyeongsang University Hospital of Korea, from May 2003 to May 2009. Results The patients included 9 men and 1 woman, and the age of the patients ranged from 36 to 76 (median, 58 years). The associated diseases or conditions were: previous pulmonary tuberculosis in 7 patients, lung cancer in 2 patients, pulmonary resection in 1 patient, and foreign body of the bronchus in 1 patient. The chest radiologic finding showed fibrotic changes as a consequence of previous tuberculosis infection in 6 patients and a mass-like lesion in 2 patients. Two patients had a co-existing fungus ball, and an endobronchial lesion was suspected in only 2 patients on the CT scan. The bronchoscopic appearance was a whitish to yellow necrotic mass causing bronchial obstruction in 7 patients, foreign body with adjacent granulation tissue and whitish necrotic tissue in 1 patient, whitish necrotic tissue at an anastomosis site in 1 patient, and a protruding mass with whitish necrotic tissue in 1 patient. Conclusion An endobronchial aspergilloma is a rare presentation of pulmonary aspergilosis and is usually incidentally found in immunocompetent patients with underlying lung disease. It usually appears as a necrotic mass causing bronchial obstruction on bronchoscopy and can be confirmed by biopsy.

Anti-inflammatory effects of celecoxib in rat lungs with smoke-induced emphysema

Chronic airway inflammation is a characteristic feature of destructive cigarette smoking (CS)-induced lung disease, particularly in patients with emphysema. Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is widely used to treat inflammation. However, the exact mechanisms underlying this drugs anti-inflammatory effects have not yet been determined in pulmonary emphysema. Here, we explore whether celecoxib attenuates CS-induced inflammation in rat lungs. Rats were exposed to smoke and received celecoxib via intragastric feeding daily for 20 wk. We found that celecoxib inhibited interalveolar wall distance and pulmonary inflammation in the lungs of CS-treated rats. Celecoxib inhibited serum NO production, iNOS, COX-2 expression, and PGE(2) production in CS-treated lung tissues. Our immunohistochemical data showed that CS-induced CD68 and COX-2 expression were inhibited by celecoxib. Furthermore, celecoxib attenuated the activation of phospho-IkappaBalpha and NF-kappaB in CS-treated rat lung. In addition, there was an inhibitory effect of celecoxib on the COX-2 expression and NF-kappaB activation in LPS-stimulated RAW 264.7 macrophages. Celecoxib also attenuated NF-kappaB activation in COX-2 siRNA-transfected RAW 264.7 macrophages. Thus, our findings suggest that the anti-inflammatory effects of celecoxib are mediated by its effects on NF-kappaB-regulated gene expression, which ultimately reduces the progression of CS-induced pulmonary emphysema.

Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy

BACKGROUND First-line platinum-based chemotherapy is currently considered the standard treatment for unresectable non-small cell lung cancer (NSCLC). However, resistance to platinum-based chemotherapy results in poor prognoses. The DNA repair pathway is a crucial molecular mechanism potentially involved in resistance to platinum-based chemotherapy. ERCC2 plays an integral role in the nucleotide excision repair pathway. Furthermore, single nucleotide polymorphisms (SNPs) and haplotypes in the ERCC2 gene are thought to be associated with the risk of developing lung cancer and clinical outcomes. Therefore, we evaluated the impact of ERCC2 haplotype-tagging SNPs (htSNPs) on the clinical parameters of first-line platinum-based chemotherapy in unresectable NSCLC. PATIENTS AND METHODS We genotyped 8 ERCC2 htSNPs for 129 unresectable NSCLC (stage IIIA, 12; stage III, 36; stage IV, 82) cases treated with first-line platinum-based chemotherapy. Clinical characteristics, treatment outcomes, hematological and non-hematological toxicities, and predictive value of the htSNPs in patient response, survival, and adverse events related to platinum-based chemotherapy were analyzed according to each ERCC2 htSNP using the chi-square test, Kaplan-Meier method, and Cox proportional hazard model. RESULTS No differences were observed in patient or disease characteristics and response according to ERCC2 htSNPs. In a survival analysis, rs50872 was significantly related to overall survival (OS) (log-rank test, p=0.014). The median survival duration of rs50872 G/G, A/G, and A/A genotypes was 35.75 (95% confidence interval [CI] 21.05-50.45), 36.07 (hazard ratio [HR] 1.02, 95% CI 25.20-46.94), and 16.75 (HR 3.49, 95% CI 5.73-27.77) months, respectively. A significant association was observed between grades 3 and 4 infections and poor survival: OS in patients with a grade 0-2 infection: 35.75 months (95% CI 28.15-43.35); OS in patients with a grade 3-4 infection: 12.86 months (95% CI 8.99-16.72, HR 3.57) (log-rank test, p<0.001). In a subgroup analysis based on taxane-platinum vs. gemcitabine-platinum doublets, the rs238405 genotype was significantly related to OS in the taxane-platinum doublets group. However, the rs238416 genotype was significantly associated with OS in the gemcitabine-based group. CONCLUSIONS ERCC2 htSNPs rs50872 (overall), rs238405 (taxane-platinum doublets group), and rs238416 (gemcitabine-platinum doublets group) and infection related to first-line chemotherapy were associated with OS in unresectable NSCLC patients treated with first-line platinum-based chemotherapy. However, additional large prospective studies focusing on the role of ERCC2 htSNPs in unresectable NSCLC are needed.

Hypoxia-inducible factor-1α and excision repair cross-complementing 1 in patients with small cell lung cancer who received front-line platinum-based chemotherapy: a retrospective study.

Introduction: Hypoxia-inducible factor-1&agr; (HIF-1&agr;), which plays an essential role in the adaptive response of cells to hypoxia, is associated with aggressive tumor behavior. Furthermore, a relationship between excision repair cross-complementing 1 (ERCC1) expression and platinum resistance has been reported in patients with various malignancies. The aim of this study was to investigate the expression of HIF-1&agr; and ERCC1 and to elucidate the clinical significance of their expression in patients with small cell lung cancer (SCLC) treated with front-line platinum-based chemotherapy. Methods: SCLC biopsy samples were obtained before front-line platinum-based chemotherapy from 111 patients with SCLC (limited disease, 29; extensive disease [ED], 82) between January 2002 and December 2009 at Gyeongsang National University Hospital. The expression levels of HIF-1&agr; and ERCC1 were assessed by immunohistochemistry. Results: High expression levels of ERCC1 and HIF-1&agr; were observed in 49 (44.1%) and 71 (64.0%) of 111 patients, respectively. Expression of ERCC1 and HIF-1&agr; was not significantly associated with age, sex, Eastern Cooperative Oncology Group performance status, weight loss, or response to treatment, regardless of stage. In ED-SCLC, low expression in the HIF-1&agr; group showed statistically better survival compared with high expression in the HIF-1&agr; group (p = 0.018). Multivariate analysis revealed that response to front-line platinum-based chemotherapy (p < 0.001), good Eastern Cooperative Oncology Group performance status (0–1) (p = 0.002), and low expression of HIF-1&agr; (p = 0.004) were independent predictors of better overall survival in ED-SCLC. Conclusions: Low expression of HIF-1&agr; may be a useful predictor of better overall survival in ED-SCLC patients treated with front-line platinum-based chemotherapy.

Factors Influencing Pleural Adenosine Deaminase Level in Patients With Tuberculous Pleurisy

Background:Adenosine deaminase (ADA) activity is useful for diagnosing tuberculous (TB) pleurisy in regions with a high prevalence of tuberculosis. However, some cases of TB pleural effusion show decreased ADA activity. Therefore, we evaluated factors influencing pleural ADA levels in patients with TB pleurisy. Methods:We retrospectively evaluated 182 patients with TB pleural effusion who were admitted to Gyeongsang National University Hospital from January 2004 to September 2008. Patients were dichotomized into 2 groups: a low-ADA (<40 IU/L) group (n = 22) and a high-ADA (≥40 IU/L) group (n = 160). Age, sex, ADA level of pleural effusion, smoking status, history of tuberculosis and comorbid diseases were evaluated in each group. Results:The median age of the patients was 50.5 years, with a male to female ratio of 1.72:1. Patients with a low-ADA level were significantly older than those with a high ADA level (66.9 ± 12.0 versus 49.4 ± 21.2 years, P < 0.001). A history of tuberculosis and hypertension was more common in the low-ADA group than in the high-ADA group (31.8% versus 15.0%, P = 0.049 and 36.4% versus 16.9%, P = 0.03, respectively). A multivariate analysis revealed that older age and current smoking were predictive of TB pleurisy with a low ADA level (odds ratios, 1.053 and 4.848; P = 0.002 and 0.028, respectively). Conclusions:Physicians should be careful when interpreting pleural ADA levels in elderly patients and/or current smokers for the diagnosis of TB pleurisy.

Serum angiopoietin-2 levels are elevated during acute exacerbations of COPD

Background and objective:  Recently, angiopoietin‐2 (Ang‐2) was identified as a ligand of the endothelial receptor tyrosine kinase, Tie‐2. Ang‐2 is an angiopoietin‐1 antagonist that plays a role in vascular destabilization and remodelling, which may increase in some diseases. However, serum Ang‐2 levels have not been evaluated in patients with COPD. In this study, we examined serum Ang‐2 concentrations in patients experiencing COPD exacerbations and in patients with stable COPD.

Comparison between systemic and catheter thrombolysis in patients with pulmonary embolism.

BACKGROUND Although systemic thrombolysis (ST) or catheter-directed therapy (CDT) is performed in patients with acute massive or submassive pulmonary embolism (PE), clinical data comparing between both therapies remain limited. We compared clinical outcomes between ST and CDT in patients with acute massive and submassive PE. METHODS From January 2005 to June 2015, clinical outcomes of patients with acute massive or submassive PE receiving ST or CDT were evaluated and compared retrospectively. RESULTS Of 72 patients, 44 were treated with ST; and 28, with CDT. The mean age was 63.9 ± 17 years old. The proportion of male sex was higher in patients receiving CDT compared to that with ST (46.4% vs 20.5%; P = .02). Half of patients presented with massive PE, and cardiac arrest occurred in 11 patients (15.3%). No difference was observed between the 2 groups with respect to 7-day mortality (13.6% in ST vs 10.7% in CDT), inhospital mortality (13.6% in ST vs 14.3% in CDT), and major bleeding complication (16.7% in ST vs 16.7% in CDT). Cardiac arrest (odds ratio, 6.286; 95% confidence interval, 1.081-36.555; P = .041) was associated with 14-day mortality. CONCLUSIONS Similar clinical outcomes were shown between ST and CDT in patients with acute massive or submassive PE.

A case of anaphylaxis after the ingestion of yacon.

Anaphylaxis is a potentially life-threatening systemic allergic reaction, often with an explosive onset; the symptoms range from mild flushing to upper respiratory obstruction, with or without vascular collapse. Foods are common offending allergens and remain the leading cause of outpatient anaphylaxis in most surveys. Yacon (Smallanthus sonchifolius) is a plant native to the Andes region, where its root is cultivated and consumed mainly as food. Unlike most edible roots, yacon contains large amounts of ructooligosaccharides. Traditionally, yacon tubers have been used as a source of natural sweetener and syrup for people suffering from various disorders. We report the case of a 55-year-old woman who developed syncope and generalized urticaria after ingesting yacon roots. The patient had positive skin prick and intradermal tests to yacon extract. An open food challenge test was performed to confirm food anaphylaxis and was positive 10 minutes after the consumption of yacon roots. To our knowledge, this is the first reported case of anaphylaxis after the ingestion of yacon roots.

Usefulness of neutrophil to lymphocyte ratio in patients with chronic obstructive pulmonary disease: a prospective observational study

Background/Aims: Neutrophil to lymphocyte ratio (NLR) in peripheral blood is a useful systemic inflammatory response biomarker. However, NLR has not been studied in patients with chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the usefulness of NLR in patients with COPD. Methods: NLR was prospectively measured and compared in patients with COPD exacerbation (n = 59), patients with stable COPD (n = 61), and healthy controls (n = 28). NLR in patients with COPD exacerbation was repeatedly measured in the convalescent period. The correlation between NLR and clinical parameters was evaluated, and the predictors for respiratory hospitalization were analyzed by multivariate logistic regression. Results: NLR values were significantly higher in patients with COPD exacerbation compared with stable COPD patients and controls (12.4 ± 10.6, 2.4 ± 0.7, 1.4 ± 0.5, respectively; p < 0.001). NLR was significantly decreased during the convalescent period in patients with COPD exacerbation (4.5 ± 4.6 vs. 11.5 ± 8.8, p < 0.001). NLR exhibited a significant correlation with the body mass index, degree of airway obstruction, dyspnea, and exercise capacity (BODE) index, the 6-minute walk test, and the modified Medical Research Council scale. NLR ≥ 2.8 was an independent predictor with a borderline significance for respiratory hospitalization (odds ratio, 2.083; p = 0.079). Body mass index and forced expiratory volume in 1 second were independent predictors for respiratory hospitalization. Conclusions: NLR is a straightforward and effective biomarker of COPD exacerbation that may serve as a predictor for respiratory hospitalization in patients with COPD.