Suk Woo Lee

Gastrokine 1 regulates NF-κB signaling pathway and cytokine expression in gastric cancers.

Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. In this study, we examined the effect of GKN1 on the expression of inflammatory mediators, including NF‐κB, COX‐2, and cytokines in GKN1‐transfected AGS cells and shGKN1‐transfected HFE‐145 cells. Lymphocyte migration and cell viability were also analyzed after treatment with GKN1 and inflammatory cytokines in AGS cells by transwell chemotaxis and an MTT assay, respectively. In GKN1‐transfected AGS cells, we observed inactivation and reduced expression of NF‐κB and COX‐2, whereas shGKN1‐transfected HFE‐145 cells showed activation and increased expression of NF‐κB and COX‐2. GKN1 expression induced production of inflammatory cytokines including IL‐8 and ‐17A, but decreased expression of IL‐6 and ‐10. We also found IL‐17A expression in 9 (13.6%) out of 166 gastric cancer tissues and its expression was closely associated with GKN1 expression. GKN1 also acted as a chemoattractant for the migration of Jurkat T cells and peripheral B lymphocytes in the transwell assay. In addition, GKN1 significantly reduced cell viability in both AGS and HFE‐145 cells. These data suggest that the GKN1 gene may inhibit progression of gastric epithelial cells to cancer cells by regulating NF‐κB signaling pathway and cytokine expression. J. Cell. Biochem. 114: 1800–1809, 2013.

TNF-α and TNF-β Polymorphisms are Associated with Susceptibility to Osteoarthritis in a Korean Population.

Background The tumor necrosis factor (TNF) is believed to play an important role in the pathophysiology of osteoarthritis (OA). Evidence shows that genetic polymorphisms make substantial contributions to the etiology of OA. Methods We investigated the genotypes TNF-α and TNF-β in 301 OA patients and 291 healthy subjects as controls. We employed a polymerase chain reaction-restriction fragment length polymorphism and a polymerase chain reaction-single strand conformation polymorphism assay to identify the genotypes TNFA -G308A and TNFB +G252A, respectively. Results For TNFA -G308A, the percentages of genotypes GG, AG, and AA were 26.3% (79/301), 62.5% (188/301), and 11.3% (34/301) in OA patients and 88.7% (258/291), 11.3% (33/291), and 0% (0/291) in controls. For TNFB +G252A, the percentages of genotypes GG, AG, and AA were 15.3% (46/301), 41.9% (126/301), and 42.9% (129/301) in OA patients and 12% (35/291), 52.6% (153/291), and 35.4% (103/291) in controls. There were significant differences in genotypes and alleles of TNFA -308 between OA patients and controls (p<0.0001) and in alleles of TNFB +252 (p=0.0325). The risk of OA was significantly higher for carriers of the TNFA -308A allele and the TNFB +252 AA homozygote (p=0.0224). Conclusions The results suggest close relationships between TNFA -G308A and TNFB +G252A polymorphisms and individual susceptibility to OA in the Korean population.

Association of SOD1 and SOD2 single nucleotide polymorphisms with susceptibility to gastric cancer in a Korean population

Oxidative stress is accepted as one of the main factors involved in the development and progression of cancer. Superoxide dismutases (SODs) are important in avoiding oxidative stress by eliminating reactive oxygen species (ROS). To determine whether single nucleotide polymorphisms at G7958A within SOD1 and at T5482C within SOD2 are associated with an increased susceptibility to gastric cancer, we investigated the genotype and allele frequencies of the genes from 294 gastric cancer patients and 300 healthy individuals. A polymerase chain reaction‐single strand conformation polymorphism assay was used to identify the SOD1 G7958A and the SOD2 T5482C genotypes. Statistically significant differences in the genotype and allele frequencies of SOD2 T5482C were found between the healthy controls and gastric cancer patients (p = 0.0001 and p < 0.0001, respectively). When the data were stratified according to gastric cancer histological subtypes, the risk of both diffuse‐ and intestinal‐type gastric cancer was statistically higher for carriers of the C allele compared with carriers of the T allele. However, there were no statistically significant differences in genotype distribution (p = 0.5069) and allele frequencies (p = 0.3714) of SOD1 G7958A between gastric cancer patients and controls. Our findings suggest that polymorphism of the SOD2 T5482C may be closely associated with an increased susceptibility to the development and differentiation of gastric cancer in the Korean population.

The single nucleotide polymorphism (SNP) of the estrogen receptor-β gene, rs1256049, is associated with knee osteoarthritis in Korean population

BACKGROUND Estrogens affect articular cartilage metabolism via estrogen receptors (ER) in chondrocytes and are believed to play an important role in the pathophysiology of osteoarthritis (OA). The aim of this study is to determine whether the single nucleotide polymorphism (SNP) of the estrogen receptor-β (ER-β) is associated with an increased susceptibility to knee OA. METHODS The possible influence of the SNP of the ER-β was investigated in 286 OA patients and 294 healthy subjects as controls. A polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay and a PCR-single strand conformation polymorphism (SSCP) assay were used to identify the Rsa polymorphism genotype among healthy controls and OA patients, respectively. RESULTS For rs1256049 (Rsa), frequencies of genotypes GG, GA, and AA were 49.0% (144/294), 43.5% (128/294), and 7.5% (22/294) in healthy controls, and 35.3% (101/286), 45.5% (130/286), and 19.2% (55/286) in OA patients. Frequencies of alleles G and A among healthy controls were 70.7% (416/588) and 29.3% (172/588); whereas those among OA patients were 58.0% (332/572) and 42.0% (240/572). Statistically significant differences in allele and genotype frequencies of rs1256049 were observed between OA patients and controls (P<0.0001). In particular, the risk of OA was significantly increased in carriers with the rs1256049A allele and rs1256049 AA homozygotes. CONCLUSIONS These results suggest a close association of rs1256049 ER-β polymorphisms with susceptibility to OA in the Korean population. CLINICAL RELEVANCE The rs1256049 polymorphism of the estrogen receptor-β gene can potentially be used to identify genetically high-risk subgroup of osteoarthritis in advance and to understand pathogenesis of osteoarthritis.

Predictive Markers of Tubo-Ovarian Abscess in Pelvic Inflammatory Disease

Background/Aims: The purpose of this study was to identify predictive markers for tubo-ovarian abscess (TOA) through a comparison of clinical and laboratory data in patients diagnosed with pelvic inflammatory disease (PID). Methods: We reviewed the medical charts of 499 females who were admitted to hospital with clinical, surgical, imaging-based diagnoses of PID between 2001 and 2011. The patients were divided into the following two groups: (1) PID with TOA and (2) PID without TOA. Results: The TOA and non-TOA groups were comprised of 69 and 430 females, respectively. Mean age, history of intrauterine device (IUD) insertion and inflammatory markers, including erythrocyte sedimentation rate, C-reactive protein (CRP) and CA-125 levels, were higher in the TOA group than the non-TOA group. Independent factors that predicted TOA were older age, IUD insertion, increased CRP and CA-125, and chlamydia infection. CA-125 was found to have the highest predictive value for TOA. TOA size was associated with increased surgical therapy compared to patients with smaller abscesses. Conclusions: Increased age, IUD insertion, chlamydia infection, and increased CRP and CA-125 level were the independent factors predictive of TOA in acute PID. These predictive values will be expected to help decrease gynecological morbidity by early diagnosis and appropriate treatment of TOA.

A laparoscopic sacrohysteropexy to manage uterine prolapse after surgical failure via a vaginal approach.

Case report A 22-year-old woman G2P2 presented to the emergency department with intra-abdominal bleeding following blunt abdominal trauma. Splenectomy was done because of bleeding from splenic lacerations and two prophylactic silicone peritoneal drains were placed: one in the left subdiaphragmatic space and the other in the pouch of Douglas. Following the removal of the left subdiaphragmatic drain on the third postoperative day, she developed abdominal pain and tenderness. At repeat laparotomy, the bleeding sites at the splenectomy location were controlled. Additionally, the right fallopian tube was noticed to be suctioned into the drain passing through one side hole and exiting through the opposite one (Figure 1). Th e drain was incised and the tube was released without apparent injury.

Abstract 21: Gastrokine 1 functions as a tumor suppressor by regulating inflammatory mediators

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanisms and also acts as a functional gastric tumor suppressor. The specific aim of this study was to determine the inflammatory mediator regulation underlying GKN1 activity in the tumor development/progression of gastric cancer. We examined the effect of GKN1 on expression of inflammatory mediators including NF-κB, COX-2, and cytokines in GKN1-transfected and recombinant GKN1-treated AGS gastric cancer cells by western blot and real time RT-PCR. Lymphocyte migration and cell viability were also analyzed in AGS cells after being treated with GKN1 and inflammatory mediators by transwell chemotaxis and MTT assay, respectively. In GKN1-transfected AGS cells, we observed inactivation and reduced expression of NF-κB and COX-2. Ectopic GKN1 expression induced the production of inflammatory mediators including IL-8 and -17A, but decreased IL-6 and IL-10 expressions. GKN1 also functions as a chemoattractant in migration of Jurkat T cells and peripheral B lymphocytes in transwell assay. In addition, GKN1 significantly inhibited cell viability, whereas treatment of IL-10, IL-17 and TNF-α in AGS cells did not show significant difference in cell viability. These data suggest that the GKN1 gene may play an important role in the regulation of inflammatory mediators in the tumor development/progression of gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 21. doi:1538-7445.AM2012-21

Use of heteroatom-containing small cyclic compounds for enzyme inhibitor design

Varied mode of inhibitors for carboxypeptidase A were designed using heteroatom-containing small rings which interact with the catalytic center to modify it covalently. Substrate analogs having an oxirane ring and those having 2-oxo-1,3- oxazolidine moiety inhibited the enzyme irreversibly, but those bearing P-lactam ring were shown to be reversible competitive inhibitors. Enzyme inhibitors are important not only as therapeutic agents but also as tools for studying enzymic action. A majority of medicinal agents which are being used clinically manifest their therapeutic effects by inhibiting the catalytic action of the enzyme which is involved in the physiology related to the particular disease. Bioorganic and medicinal chemists are increasingly successful in de novo designing of ever potent and efficient inhibitors. Chemistry of heteroatom-containing small ring compounds is characterized by their enhanced chemical reactivity mostly arising from their large ring strain. Furthermore, they are in general small in size enough to be fit in the active site of enzyme. These chemical and physical properties of heteroatom-containing small rings are thought to be of value for designing inhibitors of enzyme by incorporating them in substrate analogs as a reactive group which interacts with the catalytic center in the enzyme.