Background: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis has emerged as a novel target for cancer therapy. Agents that inhibit this pathway are currently under development for lung cancer treatment. In the present study, we have tested whether dual inhibition of PI3K/Akt/mTOR signaling can lead to enahnced antitumor effects. We have also examined the role of autophagy during this process. Methods: We analyzed the combination effect of the mTOR inhibitor, temsirolimus, and the Akt inhibitor,GSK690693, on the survival of NCI-H460 and A549 non-small cell lung cancer cells. Cell proliferation was determined by MTT assay and apoptosis induction was evaluated by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Autophagy induction was also evaluated by acridine orange staining. Changes of apoptosis or autophagy-related proteins were evaluated by western blot analysis. Results: Combination treatment with temsirolimus and GSK690693 caused synergistically increased cell death in NCI-H460 and A549 cells. This was attributable to increased induction of apoptosis. Caspase 3 activation and poly(ADP-ribose) polymerase cleavage accompanied these findings. Autophagy also increased and inhibition of autophagy resulted in increased cell death, suggesting its cytoprotective role during this process. Conclusion: Taken together, our results suggest that the combination of temsirolimus and GSK690693 could be a novel strategy for lung cancer therapy. Inhibition of autophagy could also be a promising method of enhancing the combination effect of these drugs.
Background: The purpose of this study was to evaluate whether measuring the ratio of descending aortic enhancement (DAE) to main pulmonary artery enhancement (MPAE) on pulmonary computed tomography angiography (PCTA) can predict poor outcome in patients with acute massive or submassive pulmonary embolism (PE). Methods: We retrospectively, reviewed computed tomgraphy findings and charts of 37 patients with acute PE and right ventricular dysfunction. We divided the enrolled patients into 3 groups; group Ia (n=8), comprised of patients with major adverse event (MAE); group Ib (n=5), consisted of those with PE-related MAE; and group II (n=29),those without MAE. We analyzed the right ventricular diameter (RVD)/left ventricular diameter (LVD) and DAE/MPAE on PCTA. Results: For observer 1, RVD/LVD in group Ia (1.9.36 vs. 1.44.38, p=0.009) and group Ib (1.87.37 vs. 1.44.38, p=0.044) were significantly higher than that of group II. For observer 2, RVD/LVD in group Ia (1.71.18 vs. 1.41.47, p=0.027) was significantly greater than that of group II, but RVD/LVD of group Ib was not (1.68.2 vs. 1.41.47, p=0.093). For both observers, there was a significant difference of DAE/MPAE between group Ib and group II (0.32.15 vs. 0.64.24, p=0.005; 0.34.16 vs. 0.64.22, p=0.004), but no significant difference of DAE/MPAE between group Ia and group II (0.51.3 vs. 0.64.24, p=0.268; 0.53.29vs. 0.64.22, p=0.302). Intra-class correlation coefficient (ICC) for the measurement of DAE/MPAE (ICC=0.97)was higher than that of RVD/LVD (ICC=0.74). Conclusion: DAE/MPAE measured on PCTA may predict PE-related poor outcomes in patients with massive or submassive PE with an excellent inter-observer agreement.
Background: Carbapenem-resistance is rapidly evolving among the pathogenic microbes in intensive care units (ICUs). This study aimed to determine annual trend of carbapenem-resistance in the ICU for 4 years, since the opening of a university-affiliated hospital in South Korea. Methods: From 2005 to 2008, microbial samples from consecutive 6,772 patients were screened in the ICU. Three hundred and ninety-seven patients (5.9%) and their first isolates of carbapenem-resistant pathogens were analyzed. Results: The percentage of patients infected with carbapenem-resistant organisms increased constantly during the initial three years (2.3% in 2005, 6.2% in 2006, 7.8% in 2007), then it declined to 6.5% in 2008. Acute Physiology and Chronic Health Evaluation (APACHE) III score at admission was 58.03.5, the median length of the ICU stay was 37 days, and the mortality rate was 37.5%. The sampling sites were endotracheal suction (67%),catheterized urine (17%), wound (6%) and others (10%). Bacteria with carbapenem-resistance were Pseudomonas aeruginosa (247 isolates, 62%), Acinetobacter baumannii (117 isolates, 30%), Enterobacteriaceae (12 isolates, 3%),and others (21, 5%). Of note, peak isolation of carbapenem-resistant microorganisms in medical ICU was followed by the same epidemic at surgical ICU. Conclusion: Taken together, carbapenem-resistant pathogens are of growing concern in the ICU.
Background: Chronic obstructive pulmonary disease (COPD) is now regarded as a heterogenous disease, with variable phenotypes. Acute exacerbation of COPD is a major event that alters the natural course of disease. The frequency of COPD exacerbation is variable among patients. We analyzed clinical features, according to the frequency of acute exacerbation in COPD. Methods: Sixty patients, who visited Gyeongsang National University Hospital from March 2010 to October 2010,were enrolled. Patients were divided into two groups, according to their frequency of acute exacerbation. Frequent exacerbator is defined as the patient who has two or more exacerbation per one year. We reviewed patients’medical records and investigated modified Medical Research Council (MMRC) dyspnea scale, smoking history and frequency of acute exacerbation. We also conducted pulmonary function test and 6-minute walking test, calculated body mass index, degree of airway obstruction and dyspnea and exercise capacity (BODE) index and measured CD146 cells in the peripheral blood. Results: The number of frequent exacerbators and infrequent exacerbators was 20 and 40, respectively. The frequent exacerbator group had more severe airway obstruction (forced expiratory volume in one second [FEV1], 45% vs. 65.3%, p=0.001; FEV1/forced vital capacity, 44.3% vs. 50.5%, p=0.046). MMRC dyspnea scale and BODE index were significantly higher in the frequent exacerbator group (1.8 vs. 1.1, p=0.016; 3.9 vs. 2.1, p=0.014, respectively). The fraction of CD146 cells significantly increased in the frequent exacerbator group (2.0 vs. 1.0, p＜0.001). Conclusion: Frequent exacerbator had more severe airway obstruction and higher symptom score and BODE index. However, circulating endothelial cells measured by CD146 needed to be confirmed in the future.
Background: Delivery of Bacille Calmette-Guréin (BCG) Tokyo vaccine, with the multipuncture device, has been much preferred over BCG Pasteur, with the intradermal method, possibly due to the easier manner of administration, a desire to avoid any trouble with scars, as well as side effects and higher profits to providers in South Korea. Methods: To determine BCG scar status in 0∼6 year old children vaccinated with two BCG vaccines (Pasteur BCG vaccine with intradermal method and BCG Tokyo vaccine with percutaneous method), the data from the national BCG scar survey in 2006 was analyzed. Results: Based on the national survey, the high proportion that were vaccinated with BCG Tokyo vaccines with the multipuncture method (64.5%) was noted in 0∼6 year old Korean children. From inspection of scar formation,as an indicator of vaccination, the median number of the visible pin scars from the percutaneous method was 16 (interquartile range, 12∼18) in the Korean children, and pin scars decreased as the age of the children increased (p＜0.001). Conclusion: The findings in this survey clearly showed a growing preference of parents for the BCG Tokyo vaccines by the multipuncture method in South Korea.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths. Most patients were presented with advanced disease at the time of diagnosis. In advanced NSCLC, it is almost impossible to anticipate complete remission by using only cytotoxic chemotherapy or molecularly targeted agents. In our case, two patients were diagnosed as advanced NSCLC and received chemotherapy. They achieved complete response (CR). After finishing treatment, disease recurred. They were retreated with the same regimens and achieved second CR. Until now,they have received each regimen, continuously, and the CR state has been maintained.
Diffuse alveolar damage (DAD) is a histological change in lung tissue, and is generally caused by an acute lung injury, which is characterized by bilateral and widespread damages. Localized DAD occurs very rarely. The causes for DAD are numerous, but the chief cause is acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia, in cases of idiopathic manifestation. The 82-year-old patient, in this case study, showed a DAD lesion in only 1 lobe. The patient was otherwise healthy, with no previous symptoms of DAD. He was admitted to our medical center owing to localized infiltration, observed on his chest radiograph. Laboratory studies showed no signs of infections. DAD was confirmed by a surgical lung biopsy. The patient received corticosteroid treatment and had gradually improved. We report the case of a patient with localized, idiopathic DAD that cannot be classified as acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia.