Choong-Sik Lee

A climatology of medium‐scale gravity wave activity in the midlatitude/low‐latitude daytime upper thermosphere as observed by CHAMP

We report on a detailed global climatology of medium-scale (150–600 km) thermospheric gravity wave (GW) activity using mass density observations onboard the CHAMP satellite from 2001 to 2010. Our study focuses mainly on daytime (09–18 h in local time) and midlatitude/low-latitude upper thermosphere between 300 km and 400 km altitudes. Midlatitude GW activity is strongest in the winter hemisphere. GW activity during June solstice adjacent to the Andes and Antarctic Peninsula is stronger than in any other season or location. GW activity in the low-latitude summer hemisphere is stronger above continents than above oceans: especially during December solstice and equinoxes. In terms of relative density variation, GW activity is stronger during solar minimum than solar maximum. These results agree well with the characteristics of stratospheric GWs, implying that the CHAMP GWs are mainly caused by GWs from tropospheric/stratospheric processes. Using mesosphere/lower thermosphere wind observations at a Korean Antarctic station, we investigated at which altitudes the upper thermospheric GW climatology becomes visible. While the correlation is insignificant at z=82–88 km, it becomes significant for most cases at z=90–98 km, suggesting that the upper thermospheric GW climatology may start to emerge at z≥90 km.

Hippo pathway effector YAP inhibition restores the sensitivity of EGFR-TKI in lung adenocarcinoma having primary or acquired EGFR-TKI resistance.

The efficacy of EGFR-tyrosine kinase inhibitors (TKIs) is significantly limited by various resistance mechanisms to those drugs. The resistance to EGFR-TKI is largely divided by two classes; acquired resistance after EGFR-TKI treatment, and primary resistance marked by cancer cells dependence on other oncogene, such as KRAS. YAP has emerged as critical oncogene in conferring drug resistance against targeted therapy. In this study, we evaluated the role of YAP in primary and acquired EGFR-TKI resistance using gefitinib-resistant A549 and PC9 cells and their parental cell lines. Our study revealed that EGFR-TKI resistance is associated with enhanced YAP activity. Notably, YAP activation was independent of the Hippo pathway. We confirmed that AXL is a downstream target of YAP that confers EGFR-TKI resistance. And our results showed that YAP can induce ERK activation in lung adenocarcinoma. The combination of YAP inhibition with EGFR-TKI overcomes primary and acquired EGFR-TKI resistance. We also found increased YAP expression in human lung cancer after acquiring EGFR-TKI resistance. Collectively, we suggest a novel EGFR-TKI resistance mechanism involving YAP activation and suggest targeting YAP and EGFR simultaneously may be a breakthrough treatment of primary and acquired EGFR-TKI resistant lung cancer.

Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours

Kang G H, Lee E J, Jang K T, Kim K‐M, Park C K, Lee C‐S, Kang D Y, Lee S H, Sohn T S & Kim S
(2010) Histopathology 56, 694–701
Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours

Genistein supplementation inhibits atherosclerosis with stabilization of the lesions in hypercholesterolemic rabbits.

The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was increased mildly by genistein (0.997 mm2), and decreased by normal diet (0.228 mm2). The ratio of macrophages to smooth muscle cells in the lesion was not changed by genistein supplementmentation. The western blotting showed reduction of MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of atherogenesis by genistein was might be due to improve the endothelial dysfunction rather than direct action on macrophages and/or smooth muscle cells in the lesion, since endothelial dysfunction by lipid peroxidation was the main atherogenic factor in the hypercholesterolemicrabbits. The genistein supplementmentation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.

Pulmonary Artery Angiosarcoma Confused with Acute Pulmonary Thromboembolism: Focusing on Clinical and Echocardiographic Features in the Differentiation of Two Categories

Although pulmonary artery angiosarcoma is rare, it can be misdiagnosed as pulmonary embolism because of its similar clinical and diagnostic features. The diagnosis is often delayed and the misdiagnosis brings unnecessary treatment. Because we made a wrong diagnosis of pulmonary artery angiosarcoma as an acute pulmonary embolism, we did thrombolytic therapy which could be dangerous to the patient. In this case report, we focused on the clinical and echocardiographic features of pulmonary artery angiosarcoma which can be used in differentiating the diagnosis from pulmonary embolism.

Association of castration-dependent early induction of c-myc expression with a cell proliferation of the ventral prostate gland in rat

The protooncogene c-myc is known to be associated with both cell proliferation and apoptosis. The possible cellular affects of castration on the ventral prostate gland of rat as well as the relationship to a castration induced c-myc expression were examined. Levels of c-myc mRNA in the ventral prostate gland peaked at 6 h (early induction) and 48 h (late induction) after castration, respectively. Castration-induced DNA fragmentation was not observed at an early induction of c-myc mRNA. DNA fragmentation appeared to be testosterone-dependent. On the other hand, cellular DNA synthesis measured by [3H]thymidine uptake in the ventral prostate gland was increased to maximum at 6 h after castration. These results suggest that an early induction of c-myc mRNA in ventral prostate gland after castration is closely associated with cell proliferation of the gland.

The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation

Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIPs effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenografts tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance.

Expression Pattern of the Hippo Pathway Effector TAZ in Cellular and Fibrotic Nonspecific Interstitial Pneumonia

Interstitial lung disease (ILD) is a comprehensive term referring to a group of lung diseases affecting the interstitium of the lung. Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic ILD, and nonspecific interstitial pneumonia (NSIP) is the second most common. As the name suggests, NSIP is diagnosed after many other diseases are excluded. The main pathological finding in NSIP is homogeneous interstitial inflammation with or without fibrosis.[1] NSIP can be categorized by cellular type or fibrotic type, according to the grade of inflammation and fibrosis. The cellular type has mostly inflammatory lesions with good responses to steroid, but the fibrotic type has a large proportion of fibrosis mixed with inflammatory lesions and a relatively poor response to steroid treatment.[1] So far, the exact mechanism underlying idiopathic ILD has not been clarified. Determining key regulators of these ILDs will be helpful in the diagnosis and development of novel drugs for ILD.

Voice Change Due to Paratracheal Air Cysts

Paratracheal air cysts are a rare entity in which cystic formation occurs adjacent to the trachea. Most patients with paratracheal air cysts are asymptomatic, and the cysts are detected incidentally on chest radiograph or computed tomography (CT) scan. Most symptomatic patients complain of pulmonary symptoms or repeated respiratory infection. Rarely, the air cysts can lead to paralysis of the recurrent laryngeal nerve as a result of direct compression. We report a case of a 59-year-old male patient who presented with voice change, and the cause was identified as paratracheal air cysts on a chest CT scan. Surgical resection via video-assisted mediastinoscopy was performed, and the voice recovered immediately after the operation.

Solitary pulmonary plasmacytoma

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. A 79-year-old woman presented with a pulmonary nodule, which was incidentally found during regular health examination. Chest computed tomography revealed a solitary nodule of 1.4 cm in diameter located in the upper lobe of the right lung (A). Percutaneous needle biopsy of the nodule revealed extensive infiltration of plasma cells (B, C). Immunohistochemically, the cells were positive for CD138 and were restricted to kappa light chain (D). Complete blood count, routine chemistry (including BUN, creatinine and calcium) and urine analysis were nonspecific. Serum and urine protein electrophoresis and immunofixation did not show the presence of paraprotein, and serum kappa and lambda free light chains were within normal limits. Bone marrow plasma cells were less than 1%. Skeletal X-ray survey was negative. She was diagnosed with solitary pulmonary plasmacytoma and was placed on curative radiotherapy (36 Gy over 4 weeks). This case illustrates that plasmacytoma can be presented as a solitary pulmonary nodule.