Hak Ryul Kim

Association between Elevated Pleural Interleukin-33 Levels and Tuberculous Pleurisy

Background Interferon-γ (IFN-γ) plays a crucial role in Mycobacterium tuberculosis induced pleural responses. Interleukin (IL)-33 up-regulates the production of IFN-γ. We aimed to identify whether an association between pleural IL-33 levels and tuberculous pleurisy exists and determine its diagnostic value. Methods Pleural IL-33, ST2 (a receptor of IL-33), adenosine deaminase (ADA), and IFN-γ, as well as serum IL-33 and ST2 were measured in 220 patients with pleural effusions (PEs). Patients with malignant (MPEs), parapneumonic (PPEs), tuberculous (TPEs), and cardiogenic (CPEs) pleural effusions were included. Results Pleural and serum IL-33 levels were highest or tended to be higher in patients with TPEs than in those with other types of PEs. The median pleural fluid-to-serum IL-33 ratio was higher in TPE cases (≥ 0.91) than in other PE cases (≤ 0.56). Pleural IL-33 levels correlated with those of pleural ADA and IFN-γ. However, the diagnostic accuracies of pleural IL-33 (0.74) and pleural fluid-to-serum IL-33 ratio (0.75) were lower than that of ADA (0.95) or IFN-γ (0.97). Pleural ST2 levels in patients with MPEs were higher than in patients with TPEs. Serum ST2 levels did not differ among the groups. Conclusions We identified an association between elevated pleural IL-33 levels and tuberculous pleurisy. However, we recommend conventional pleural markers (ADA or IFN-γ) as diagnostic markers of TPE.

Arsenic Trioxide Induces Apoptosis of HL-60 Cells via Activation of Intrinsic Caspase Protease with Mitochondrial Dysfunction

PURPOSEnArsenic trioxide (As2O3) was introduced into the treatment of refractory or relapsed acute promyelocytic leukemia and showed a striking effectiveness in China and United States multicenter study. However, the mechanistic basis for the carcinogenic or therapeutic effects of arsenics is still poorly understood. So, this study is performed to determine whether As2O3 induces apoptosis through intrinsic caspase cascades in acute promyelocytic leukemia HL-60 cells.nnnMATERIALS AND METHODSnHL-60 cells were treated with As2O3 to investigate apoptosis through signaling of caspase cascades and mitochondrial dysfunction.nnnRESULTSnAs2O3 (>0.5 uM) decreased the viability of HL-60 cells in a dose-dependent manner, which was revealed as apoptosis shown chromatin condensation and ladder pattern DNA fragmentation. As2O3 increased the catalytic activity of caspase family cysteine proteases including caspase-3 and -9 proteases. Consistently, PARP, an intracellular biosubstrate of caspase-3 protease, was cleaved from 116 kDa to 85 kDa fragments. It also induced the change of mitochondrial membrane potential. Morever, As2O3 resulted in the increase of Bak.nnnCONCLUSIONnThese data suggest that As2O3 induces apoptosis of HL-60 cells through activation of intrinsic caspase protease with mitochondrial dysfunction.

Elevated Prx1 Provides Resistance to Docetaxel, But Is Not Associated with Predictive Significance in Lung Cancer

Background This study was conducted in order to elucidate the effects of docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors and further tested the role of Prx1 as a predictor for how a patient would respond to docetaxel treatment. Methods Effects of docetaxel on the growth of scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured. Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin-embedded tissues from 24 non-small cell lung cancer patients who had received docetaxel-cisplatin regimens as a first-line treatment. Results Docetaxel treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth compared with other groups. Prx1 knockdown increased the production of cleaved caspases-8 and -9 in the control itself compared to scramble tumors. Moreover, docetaxel treatment in Prx1 knockdown tissue led to an increased protein band. Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was detected in the docetaxel treatment group. On the other hand, Prx1 knockdown completely suppressed the Akt-FOXO1 axis. The median progression-free survival (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval [CI], 6.0-7.7), whereas the median progression-free survival of patients with high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1 expression was not associated with decreased PFS (p=0.114). Conclusion Our findings suggest that elevated Prx1 provides resistance to docetaxel treatment through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may not be related with the predictive significance for response to docetaxel treatment.

History of pneumonia is a strong risk factor for chronic obstructive pulmonary disease (COPD) exacerbation in South Korea: the Epidemiologic review and Prospective Observation of COPD and Health in Korea (EPOCH) study

BACKGROUNDnIn South Korea, chronic obstructive pulmonary disease (COPD) is one of the ten leading causes of death. COPD exacerbations are significantly associated with mortality in COPD patients. This study was conducted to investigate the epidemiology of COPD in South Korea, specifically the clinical characteristics of South Korean COPD patients, the COPD exacerbation rate and the risk factors associated with COPD exacerbations.nnnMETHODSnThis study covers a 2-year interval. One year was data collected retrospectively and the second year was prospectively obtained data.nnnRESULTSnA total of 1,114 subjects were enrolled in the study. These subjects were observed for a period of 1 year from the enrollment, and a total of 920 subjects completed the study. A total of 1,357 COPD exacerbations occurred in 711 subjects (63.8%) out of the total of 1,114 subjects during the study period of 2 years. Multivariate logistic regression results showed that if patients had had a pneumonia before the retrospective year of analysis, they had a 18 times greater chance of having an exacerbation during the prospective year when other variables were controlled. Also, the subjects who had a history of two or more exacerbations during the retrospective year were approximately 6 times more likely to experience the COPD exacerbation compared to those who did not.nnnCONCLUSIONSnThis study examined the demographic and clinical characteristics of South Korean COPD patients and found that a history of pneumonia and two or more occurrences of exacerbation within 1 year was significantly associated with a higher rate of COPD exacerbation.

Safety and Effectiveness of Indacaterol in Chronic Obstructive Pulmonary Disease Patients in South Korea

Background Inhaled indacaterol (Onbrez Breezhaler), a long-acting β2-agonist, is approved in over 100 countries, including South Korea, as a once-daily bronchodilator for maintenance and treatment of chronic obstructive pulmonary disease (COPD). Here, we present an interim analysis of a post-marketing surveillance study conducted to evaluate the real-world safety and effectiveness of indacaterol in the Korean population. Methods This was an open-label, observational, prospective study in which COPD patients, who were newly prescribed with indacaterol (150 or 300 µg), were evaluated for 12 or 24 weeks. Safety was assessed based on the incidence rates of adverse events (AEs) and serious adverse events (SAEs). Effectiveness was evaluated based on physicians assessment by considering changes in symptoms and lung function, if the values of forced expiratory volume in 1 second were available. Results Safety data were analyzed in 1,016 patients of the 1,043 enrolled COPD patients receiving indacaterol, and 784 patients were included for the effectiveness analysis. AEs were reported in 228 (22.44%) patients, while 98 (9.65%) patients reported SAEs. The COPD condition improved in 348 patients (44.4%), while the condition was maintained in 396 patients (50.5%), and only 40 patients (5.1%) exhibited worsening of ailment as compared with baseline. During the treatment period, 90 patients were hospitalized while nine patients died. All deaths were assessed to be not related to the study drug by the investigator. Conclusion In real-life clinical practice in South Korea, indacaterol was well tolerated in COPD patients, and can be regarded as an effective option for their maintenance treatment.

Primary Malignant Fibrous Histiocytoma of the Pleura

Malignant fibrous histiocytoma, a type of sarcoma, is a malignant neoplasm with uncertain origin that arises in both the soft tissues and the bone. The occurrence of primary malignant fibrous histiocytoma of the pleura is extremely rare. We report a case of a 65-year-old Korean man who is being diagnosed with primary malignant fibrous histiocytoma of the pleura.

Response Evaluation of Chemotherapy for Lung Cancer

Assessing response to therapy allows for prospective end point evaluation in clinical trials and serves as a guide to clinicians for making decisions. Recent prospective and randomized trials suggest the development of imaging techniques and introduction of new anti-cancer drugs. However, the revision of methods, or proposal of new methods to evaluate chemotherapeutic response, is not enough. This paper discusses the characteristics of the Response Evaluation Criteria In Solid Tumor (RECIST) version 1.1 suggested in 2009 and used widely by experts. It also contains information about possible dilemmas arising from the application of response assessment by the latest version of the response evaluation method, or recently introduced chemotherapeutic agents. Further data reveals the problems and limitations caused by applying the existing RECIST criteria to anti-cancer immune therapy, and the application of a new technique, immune related response criteria, for the response assessment of immune therapy. Lastly, the paper includes a newly developing response evaluation method and suggests its developmental direction.

Computed tomography findings associated with bacteremia in adult patients with a urinary tract infection

The use of computed tomography (CT) in the diagnosis of urinary tract infection (UTI) has rapidly increased recently at acute stage, but the CT findings associated with bacteremia in UTI patients are unknown. 189 UTI patients were enrolled who underwent a CT scan within 24xa0h after hospital admission. We classified CT findings into eight types: a focal or multifocal wedge-shaped area of hypoperfusion, enlarged kidneys, perinephric fat stranding, ureteritis or pyelitis, complicated renal cyst, renal papillary necrosis, hydronephrosis, and renal and perirenal abscess. A retrospective analysis was conducted to evaluate the CT findings associated with bacteremia. The mean age of these patients was 60u2009±u200917.2xa0years, and 93.1xa0% were women. Concurrent bacteremia was noted in 40.2xa0% of the patients. Abnormal CT findings were noted in 96.3xa0% of the patients and 62.4xa0% had two or more abnormal findings. The most frequent abnormal CT finding was a focal or multifocal wedge-shaped area of hypoperfusion (77.2xa0%), followed by perinephric fat stranding (29.1xa0%). Perinephric fat stranding, hydronephrosis, and the presence of two or more abnormal CT findings were significantly associated with bacteremia in patients with community-acquired UTI. In the multivariate logistic regression analysis, age [odds ratio (OR) 1.03; 95xa0% confidence interval (CI) 1.009–1.062], two or more abnormal CT findings (OR 3.163; 95xa0% CI 1.334–7.498), and hydronephrosis (OR 13.160; 95xa0% CI 1.048–165.282) were significantly associated with bacteremia. Physicians should be aware that appropriate early management is necessary to prevent fatality in patients with these CT findings.

Abstract 1043: Autophagy induces cytoprotection in cisplatin-treated lung cancer cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCnnPurpose: Most of lung cancer patients had received the systemic chemotherapy because they had diagnosed the advanced stage at presentation. Cislplatin-based chemotherapy is main regimen for advanced lung cancer. But serious adverse reaction (SAE) had occurred after chemotherapy. This is main reason for chemotherapy withdrawal. If we will use the reduced dose of cispaltin, cisplatin-based the chemotheray will be continued. To figure out whether the effect of low dose of cisplatin will be synergistically enhance by autophagy inhibiton, even though the reduced dose of cisplatin less effect for treatment response, We investigated that role of autophagy by 3-methyladenine, class III PI3kinase inhibitor in cisplatin-treated lung cancer cells. Methods: Lung cancer cells were incubated with normal media and treated the 5uM (LD20) and 20uM(LD50) of cislpaltin according to time dependent. We examined the sensitivity to low or high doses of cisplatin treatment using the MTT cell viability assay and compared apoptosis and autophagy by nuclear stianing, apoptotic or autophagic related proteins or autophagic vacuoles. autophagy is also displayed the development of acidic vascular organelles by acridine orange and the fluorescent expression of GFP-LC3 protein in the GFP-LC3 transfected cells. Result: Low dose of cisplatin-treated lung cancer cells is relatively less sensitive to cell death rather than high dose treated cells in a time-dependent manners. We didnot find out the nuclear fragmentation in lower dose even though detected its in high dose. PARP cleavages also were not detected in low dose of cisplatin exception 24H. We observed that massive vacuolization in the cytoplasm were seen at lower dose treated cells. Acridine orange stain-positive cells also were increased according to time dependent. We figured out that the autophagosome-incorporated LC3 II protein expression more increased in low dose treated cells (24H to 48H) in spite of no detection of LC3 II in high dose treated cells. The expression of GFP-LC3 were increased in 5uM treated cells by time-dependent manner. When 3-methyladenine, class III PI3kinase inhibitor, was pretreated in 5uM cisplatin-treated lung cancer cells, cell survival significantly were decreased. Conclusion: Autophagy induces cytoprotection in lower dose of cisplatin-treated lung cancer cells.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1043.

A Case of Meigs' Syndrome

Meigs syndrome is defined as presence of pleural effusion, with ovarian tumor associated ascites, which spontaneously resolve soon after the removal of the tumor. The pathogenesis of the pleural effusion, in patients with Meigs syndrome, is thought to be the passage of fluid from the peritoneal cavity into the pleural cavity, through small holes in the diaphragm. A case of Meigs syndrome, in a 63-year-old woman, who had been referred for control of pleural effusion is reported. (Tuberculosis and Respiratory Diseases 2004, 56:415-419)