Min-Woong Kang

Clinical Features of Deep Neck Infections and Predisposing Factors for Mediastinal Extension

Background Deep neck infections (DNI) can originate from infection in the potential spaces and fascial planes of the neck. DNI can be managed without surgery, but there are cases that need surgical treatment, especially in the case of mediastinal involvement. The aim of this study is to identify clinical features of DNI and analyze the predisposing factors for mediastinal extension. Materials and Methods We reviewed medical records of 56 patients suffering from DNI who underwent cervical drainage only (CD group) and those who underwent cervical drainage combined with mediastinal drainage for descending necrotizing mediastinitis (MD group) from August 2003 to May 2009 and compared the clinical features of each group and the predisposing factors for mediastinal extension. Results Forty-four out of the 56 patients underwent cervical drainage only (79%) and 12 patients needed both cervical and mediastinal drainage (21%). There were no differences between the two groups in gender (p=0.28), but the MD group was older than the CD group (CD group, 44.2±23.2 years; MD group, 55.6±12.1 years; p=0.03). The MD group had a higher rate of co-morbidity than the CD group (p=0.04). The CD group involved more than two spaces in 14 cases (32%) and retropharyngeal involvement in 12 cases (27%). The MD group involved more than two spaces in 11 cases (92%) and retropharyngeal involvement in 12 cases (100%). Organism identification took place in 28 cases (64%) of the CD group and 3 cases of (25%) the MD group (p=0.02). The mean hospital stay of the CD group was 21.5±15.9 days and that of the MD group was 41.4±29.4 days (p=0.04). Conclusion The predisposing factors of mediastinal extension in DNI were older age, involvement of two or more spaces, especially including the retropharyngeal space, and more comorbidities. The MD group had a longer hospital stay, higher mortality, and more failure to identify causative organisms of causative organisms than the CD group.

The C-terminus of Hsp70-Interacting Protein Promotes Met Receptor Degradation

Introduction: The tyrosine kinase Met receptor regulates a complex array of cellular behaviors known collectively as invasive growth. Although essential for normal development and wound repair, this pathway is frequently deregulated in tumors to promote their growth, motility, and invasion. Accordingly, Met is overexpressed in a variety of human tumors, and this aberrant expression correlates with a poor patient prognosis. Previous studies have shown that Met receptor levels are governed in part by Cbl-mediated ubiquitination and degradation, and the uncoupling of Met from this pathway promotes its transforming activity. Methods: Here, we describe a novel mechanism of Met degradation in Non Small Cell Lung Cancer Cells and HeLa cells using western blot, immunocytochemistry, immunoprecipitation assay, invasion assay, cell viability assay and in vivo tumor growth model. Results: Met receptor interacted with the C-terminus of heat shock protein 70-interacting protein (CHIP), leading to proteasomal degradation of the receptor in vitro. In addition, CHIP overexpression destabilized endogenous Met receptor in lung cancer cells, whereas CHIP knockdown increased Met receptor expression, indicating an essential role for CHIP in the regulation of Met degradation. CHIP overexpression inhibited Met-mediated lung cancer cell growth and invasion. Finally, we confirmed these results by tumor xenograft model. Conclusion: Based on these findings, we conclude that CHIP is a suppressor of Met function, serving to regulate cellular receptor levels by promoting Met receptor degradation.

Benign Metastasizing Leiomyoma: Metastasis to Rib and Vertebra

Benign metastasizing leiomyoma is very rare and characterized by the presence of pelvic, peritoneal, nodal, or pulmonary nodules in women with a history of uterine leiomyomas. We report a case of benign metastasizing leiomyoma in a 30-year-old woman who had undergone a prior myomectomy due to uterine cellular leiomyoma 3 years earlier. The patient had a mass on the right sixth rib and 2 masses in the sixth thoracic vertebra. Pathologically, these masses were diagnosed as cellular leiomyomas. Estrogen and progesterone receptors were both positive in the metastatic tumors as well as in the uterine leiomyomas. The diagnosis of benign metastasizing leiomyoma can only be made after careful examination of the primary tumor to exclude small foci of malignant change.

Roles of endoplasmic reticulum stress-mediated apoptosis in M1-polarized macrophages during mycobacterial infections

Alteration of macrophage function has an important regulatory impact on the survival of intracellular mycobacteria. We found that macrophages infected with attenuated Mycobacterium tuberculosis (Mtb) strain H37Ra had elevated expression of M1-related molecules, whereas the M2 phenotype was dominant in macrophages infected with virulent Mtb H37Rv. Further, the TLR signalling pathway played an important role in modulating macrophage polarization against Mtb infection. Interestingly, endoplasmic reticulum (ER) stress was significantly increased in M1 polarized macrophages and these macrophages effectively removed intracellular Mtb, indicating that ER stress may be an important component of the host immune response to Mtb in M1 macrophages. This improved understanding of the mechanisms that regulate macrophage polarization could provide new therapeutic strategies for tuberculosis.

Nafamostat Mesilate Inhibits TNF-α-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production.

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-α (TNF-α). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-α for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 µg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-α (3 ng/mL), and it dose dependently prevented the TNF-α-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-α-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-α-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

An Isolated True Aneurysm of the Superficial Femoral Artery in a Young Woman - A case report -

A 39-year-old woman was admitted to the hospital due to a pulsatile mass on her right inner thigh that was evident for two months. She did not exhibit any risk factors of atherosclerosis, no evidence of vasculitis, or any signs of previous trauma history. Ultrasound and computed tomography revealed an adult fist-sized aneurysm on the distal superficial femoral artery. The aneurysm was resected and peripheral circulation was restored with the interposition of a saphenous vein graft. The resected aneurysm had three layers that showed atherosclerosis on histological examination.

Stress-induced Cardiomyopathy during Pulmonary Resection (Takotsubo Syndrome) − A case report −

Stress-induced cardiomyopathy is caused by emotional or physical stressors and mimics acute myocardial infarction, though Stress-induced cardiomyopathy is characterized by reversible left ventricular (LV) apical ballooning in the absence of significant coronary artery disease. We describe a 51-year-old male who underwent left upper lobectomy for non-small cell lung cancer, and during which cardiogenic arrest occurred due to stress-induced cardiomyopathy, successfully managed by intra-aortic balloon pumping and extracorporeal membrane oxygenation.

Differential gene expression during colon-to-lung metastasis.

Primary tumors in certain metastatic cases have potential dissemination mechanisms. However, they often lack the potential to colonize distant microenvironments, and consequently the disseminated cancer cells enter into a state of latency which can last for years. In order to investigate the metastatic colonization potential at the gene expression level, we compared such primary tumors with their matching, actively proliferating metastatic tumors. Six pairs of colon-to-lung metachronous tumor samples were examined for the expression levels of 84 well-known metastatic genes using the quantitative RT-PCR-based PCR Array technology. The unsupervised hierarchical clustering of all 12 samples together, resulted in the formation of one closely related cluster by the primary tumors, but highly diversified ones by the metastatic tumors. A pair-wise comparison of the matching primary-metastatic tumors showed that different groups of genes were activated in the lung metastases. Therefore we charted specific genes involved in the genetic diversification processes. A number of these genes showed similar differential expression (ΔCt) patterns in all the patients. These were the cancer cell-, the microenvironment- and the stem cell-specific gene groups. In conclusion, the results suggest that the primary colorectal cancer cells are diversified as regards colonization of the lung, which could explain why the effective therapies for primary colorectal cancers are often not appropriate for controling the growth of pulmonary metastases.

Stage III Thymic Epithelial Neoplasms are Not Homogeneous with Regard to Clinical, Pathological, and Prognostic Features

Introduction: The main therapeutic approach to a Masaoka stage III thymic epithelial neoplasm (TEN) is surgical resection, and the 5-year survival rate is approximately 60%. According to the Masaoka staging system, invasion of neighboring organs is classified as stage III disease, regardless of the number of organs involved or the size of the tumor. We retrospectively analyzed the prognostic significance associated with the extent of disease in patients with Masaoka stage III TENs. Methods: From 1995 to 2006, 241 patients were identified with thymomas. Among these patients, 59 were diagnosed with Masaoka stage III disease. The patients with a stage III TEN were advised to have extended thymectomy with en bloc resection of the invaded structures as the initial treatment. The prognostic significance of the size, organs invaded, and other factors were analyzed. Results: The overall survival rates for the stage III patients were 83% and 64%, and the recurrence-free survival rates were 56% and 51%, at 5 and 8 years, respectively. Patients with a low-grade World Health Organization classification (p = 0.0202) or a complete resection (p < 0.0001) had a better overall survival. In addition, patients with tumors less than 6.5 cm (p = 0.0311) or with pericardium invasion (p = 0.0299) had a better recurrence-free survival. The patients with limited disease had a better prognosis for a recurrence-free survival than did patients with extensive disease (p = 0.0007). Conclusions: Heterogeneous prognostic subgroups based on tumor size and organs invaded were identified in patients with Masaoka stage III TENs. Therapeutic plans, based on these subgroups, will potentially improve patient management and treatment outcomes.

Upregulation of APE/ref-1 in recurrence stage I, non small cell lung cancer

Lung cancer, the leading cause of cancer-related death, still lacks reliable biomarkers. Apurinic/apyrimidinic endonuclease 1/Ref-1 is a multifunctional protein involved in the base excision repair of DNA damaged by oxidative stress or alkylating compounds, as well as in the regulation of multiple transcription factors. To validate apurinic/apyrimidinic endonuclease 1/Ref-1 as a biomarker for prediction of lung cancer recurrence, we studied 42 patients who received curative resection and mediastinal lymph node dissection for stage I non-small-cell lung cancer. They were divided into 2 groups based on recurrence, and compared by immunohistochemistry staining of paraffin-embedded tissues and Western blot analysis. Immunohistochemical staining showed a significant difference between the cytoplasm and nucleus in patients who had a recurrence compared to those with nonrecurrent adenocarcinoma. In Western blot analysis, the recurrent adenocarcinoma group showed increased expression of apurinic/apyrimidinic endonuclease 1/Ref-1 in cytoplasm, nucleus, and in total. This indicates that apurinic/apyrimidinic endonuclease 1/Ref-1 is unregulated in recurrent stage I adenocarcinoma. For clinical application as a prognostic marker for non-small-cell lung cancer, further investigation into the role of apurinic/apyrimidinic endonuclease 1/Ref-1 in carcinogenesis is needed in an expanded prospective study.