Jung Han Yoon Park

Mutational analysis of OGG1, MYH, MTH1 in FAP, HNPCC and sporadic colorectal cancer patients: R154H OGG1 polymorphism is associated with sporadic colorectal cancer patients

MYH, OGG1 and MTH1 are members of base excision repair (BER) families, and MYH germline mutations were recently identified in patients with multiple adenomas or familial adenomatous polyposis (FAP). A total of 20 APC-negative Korean FAP patients were analyzed for OGG1, MYH and MTH1 germline mutations. A total of 19 hereditary nonpolyposis colorectal cancer (HNPCC), 86 suspected HNPCC, and 246 sporadic colorectal cancer cases were investigated for OGG1 and MYH mutations. A total of 14 R154H OGG1 polymorphisms were identified in hereditary, sporadic colorectal cancers, and normal controls. For the case-control analysis of OGG1 R154H, a total of 625 hereditary or sporadic colorectal cancer patients and 527 normal controls were screened. R154H was a rare polymorphism associated with sporadic colorectal cancer patents (OR: 3.586, P= 0.053). R154H does not segregate with cancer phenotypes. Upon examining the possibility of recessive inheritance of R154H, we could not identify any complementary mutations in OGG1, MYH or MTH1. Samples with R154H were further screened for mutations of K-ras, β-catenin, APC, p53, BRAF and the microsatellite instability (MSI) status. Eight somatic mutations were identified in these genes and G:C to T:A transversion mutations were not dominant in samples harboring R154H. This result raises the possibility that OGG1 R154H may function as a low/moderate-penetrance modifier for colorectal cancer development.

A novel germline mutation in the MET extracellular domain in a Korean patient with the diffuse type of familial gastric cancer.

Gastric cancer is one of the most deadly cancers world wide. Although its incidence has declined in recent years, it is still the most prevalent cancer in Asian countries such as Korea and Japan.1 Germline mutations of the cell to cell adhesion molecule E-cadherin ( CDH1 ) have been reported in patients with the diffuse type of familial gastric cancer.2,3 However, the frequency of CDH1 mutations is low overall4 and the observed mutations differ between western and Asian patients.5 Truncating mutations (that is, nonsense, frameshift, and alternative splicing mutations) predominate in patients of western origin,2,3 whereas only a few missense mutations have been found in patients of Asian extraction.5,6 This suggested that CDH1 does not play a major role in gastric cancer development in Asian countries, and prompted researchers to investigate other gastric cancer causing genes. One such gene is that for the MET receptor tyrosine kinase. MET transduces motility, proliferation, and morphogenic signals of hepatocyte growth factor/scatter factor (HGF/SF) in epithelial cells.7 Similar to other receptor tyrosine kinase genes such as RET , the MET gene encodes a protein with an extracellular domain (exon 2–13), a transmembrane domain (exon 13), and a tyrosine kinase domain (exon 15–21).8,9 MET germline mutations have been reported in patients with hereditary papillary renal carcinoma (HPRC).7 Most of the MET mutations associated with HPRC or sporadic papillary renal carcinomas7 were missense mutations in the tyrosine kinase domain,10,11 and overexpression of MET has been reported in human diseases such as breast, prostate, gastric, and ovarian cancers.12,13 In the specific context of gastric cancers, a MET germline missense mutation was found in a Korean patient suffering from intestinal gastric cancer.11 The mutation, located at the juxtamembrane domain (exon 14), …

Germline mutations of the MEN1 gene in Korean families with multiple endocrine neoplasia type 1 (MEN1) or MEN1-related disorders.

Multiple endocrine neoplasia type 1 (MEN1) is a familial cancer syndrome characterized by the combined occurrence of tumours of the parathyroid glands, pancreatic islet cells and anterior pituitary gland. Mutation analysis of the MEN1 gene has enabled the genetic diagnosis of patients with MEN1. Two MEN1‐related disorders – familial isolated hyperparathyroidism (FIHP) and familial pituitary adenoma – are considered to be variants of MEN1, or at least to be incompletely expressed variants. Germline mutations of the MEN1 gene have been reported in some with FIHP, but familial pituitary adenoma usually lacks the MEN1 mutation and has been described as a genetically distinct disorder. In this work, we investigated five Korean families with MEN1, one family with FIHP and one family with familial pituitary adenoma. Polymerase chain reaction (PCR)‐based single‐strand conformation polymorphism (PCR‐SSCP) analysis, denaturing high‐performance liquid chromatography (DHPLC) and sequencing were used to detect the MEN1 mutations. Screening of the genetic variations of the MEN1 gene revealed four germline mutations in five typical MEN1 families. All four germline mutations led to truncated proteins or a change in the amino acids of the functional domains. In this study, we identified three novel MEN1 germline mutations (969C >A, 973G >C and 1213C >T) and one previously reported mutation (200–201insAGCCC). The frequency of the MEN1 germline mutation in Korean MEN1 families (four of five; 80%) was similar to those reported previously. In accordance with previous studies, no MEN1 germline mutation was detected in two families with FIHP or familial pituitary adenoma.

Burden of disease attributable to obesity and overweight in Korea.

Objective:To estimate the burden of disease attributable to overweight and obesity using disability-adjusted life-year (DALY) in Korea.Research methods:Firstly, overweight and obesity-related diseases and their relative risk (RR) were selected by the systematic review. Secondly, population-attributable fractions (PAFs) were computed by using the formula including RR and the prevalence of exposure (Pe) of overweight and obesity. Thirdly, DALYs of overweight and obesity-related diseases in Korea were estimated. Finally, the attributable burden (AB) of diseases due to overweight and obesity was calculated as the sum of the products from multiplying DALYs of overweight and obesity-related diseases by their PAFs.Results:The disease burden attributable to overweight was 827.1 person years (PYs) overall, 732.6 for men, 922.9 for women per 100 000 persons. The disease burden attributable to obesity was 260.0 PYs overall, 144.2 for men, 377.3 for women. Diabetes attributable to overweight and obesity accounts for highest burden among other diseases in both genders. The disease burden attributable to overweight was 3.2 times higher than that attributable to obesity.Conclusion:Most proportion of disease burden attributable to high body mass index (BMI) occurred among those with only moderately raised levels such as overweight, not the extremes such as obesity. It suggests that population-based, public health intervention rather than high-risk group-focused strategies are more effective to reduce the burden of disease attributable to overweight and obesity in Korea.

High-fat diet-induced obesity increases lymphangiogenesis and lymph node metastasis in the B16F10 melanoma allograft model: roles of adipocytes and M2-macrophages.

To examine the effects of high‐fat diet (HFD) on melanoma progression, HFD‐fed C57BL/6N mice were subcutaneously injected with syngeneic B16F10 melanoma cells. At 3 weeks post‐injection, the tumors were resected; the mice were then sacrificed at 2 weeks post‐resection. HFD stimulated melanoma growth and lymph node (LN) metastasis as well as tumor and LN lymphangiogenesis. Lipid vacuoles in the tumor and M2‐macrophage (MΦ)s in the adipose and tumor tissues were increased in HFD‐fed mice. CCL19 and CCL21 contents were higher in LNs than in tumors. HFD increased both CCL19 and CCL21 levels in LNs and CCR7 in tumors. Adipose tissue‐conditioned media (CM) from HFD‐fed mice enhanced lymphangiogenesis, and mature adipocyte (MA)/M2‐MΦ co‐culture CM markedly stimulated the tube formation of lymphatic endothelial cell (LEC)s and B16F10 migration. Monocyte migration was moderately stimulated by B16F10 or MA CM, but tremendously stimulated by B16F10/M2‐MΦ co‐culture CM, which was enhanced by MA/B16F10/M2‐MΦ co‐culture CM. The co‐culture results revealed that MAs increased CCL2, M‐CSF and CCR7 mRNAs in B16F10s; vascular endothelial growth factor (VEGF)‐D mRNA in M2‐MΦs; and CCL19, CCL21 and VEGF receptor (VEGFR)3 mRNA in LECs. M2‐MΦs increased CCL2, M‐CSF and VEGF‐A mRNAs in B16F10s, whereas B16F10s increased VEGF‐C mRNAs in M2‐MΦs and VEGFR3 mRNA in LECs. These results indicate that in HFD‐fed mice, MA‐induced CCL2 and M‐CSF in tumor cells increase M2‐MΦs in tumor; the crosstalk between tumor cells and M2‐MΦs further increases cytokines and angiogenic and lymphangiogenic factors. Additionally, MA‐stimulated CCL19, CCL21/CCR7 axis contributes to increased LN metastasis in HFD‐fed mice.

A new AMS facility in Korea

Abstract A new accelerator mass spectrometry (AMS) facility has been installed at the Inter-University Center for Natural Science Research Facilities (ICNSRF) of Seoul National University. In this report, an overview of the facility with its current status and prospects for the future will be presented.

Identification of a novel BMPR1A germline mutation in a Korean juvenile polyposis patient without SMAD4 mutation

Juvenile polyposis (JP) is characterized by the development of multiple hamartomatous polyps and is inherited as an autosomal dominant trait. Germline mutations of the SMAD4 gene have been reported in JP. We have previously identified three SMAD4 germline mutations in five Korean JP patients. Recently, germline mutations of the BMPR1A (ALK3) gene were reported in JP cases without SMAD4 mutations. In order to determine whether BMPR1A could be involved in the development of JP, we screened all five patients using denaturing high‐performance liquid chromatography (DHPLC) analysis. We found that one patient had a BMPR1A germline mutation without a SMAD4 mutation. This patient harbored a novel missense mutation (M470T) in exon 10. After close clinico‐pathological examination, one patient who was previously diagnosed to have JP was excluded from the JP group. In total, all four Korean JP patients had either the SMAD4 or the BMPR1A mutation, with three having SMAD4 germline mutations and one carrying a BMPR1A germline mutation.

Progress in sample preparation system for the Seoul National University AMS facility

Abstract The Seoul National University AMS Laboratory has developed a sample preparation system for AMS measurement. Graphite targets are prepared via the reduction of carbon dioxide over a Fe catalyst. The carbon dioxide gases are produced by combusting pretreated organic samples with CuO and silver wire in a sealed quartz tube. Each combustion produces ca. 2 mg of graphite that is loaded into the target. So far we have been successful in extracting and analyzing 12C− current up to 10 mA in stable condition by Cs sputtering onto the targets.

Helical CT anatomy of pancreatic arteries

Abstract.Background: To assess the frequency of visualization of pancreatic arteries in the arterial phase of helical computed tomography (CT). Methods: The visibility of pancreatic and peripancreatic arteries in helical CT images was evaluated in 20 consecutive patients who had no evidence of pancreatic disease. CT examinations were performed by using a continuously rotating CT scanner and intravenous injection of contrast media. The scans were taken 35 s after the start of injection and with a table speed of 3 mm/s. Images were reconstructed in 3-mm section increments. Results: Frequently visualized arteries were the gastroduodenal, anterior and posterior superior pancreaticoduodenal, and right gastroepiploic arteries. Infrequently visualized arteries were the dorsal pancreatic, pancreatica magna, caudal pancreatic, transverse pancreatic, and common, anterior, and posterior inferior pancreaticoduodenal arteries. Conclusion: Helical CT enabled us to recognize small pancreatic arteries, and the evaluation of these arteries should be considered in the staging of pancreatic carcinoma.

Determination of tadalafil and N-desmethylsibutramine in health and dietary supplements using ultra-performance liquid chromatography (UPLC) coupled with quadrupole-time-of-flight mass spectrometry (Q-TOF MS)

The adulteration of dietary supplements with drugs is potentially dangerous for human health. In this study, a method was used to test simultaneously for the presence of three synthetic PDE-5 inhibitors (sildenafil, vardenafil and tadalafil), and sibutramine and its two major metabolites (N-desmethylsibutramine and N-didesmethylsibutramine) using ultra-performance liquid chromatography (UPLC) coupled with quadrupole-time-of-flight mass spectrometry (Q-TOF MS) in dietary supplements. This approach with UPLC/Q-TOF MS uses the high accurate mass of six compounds for identification and has a short run time. The recovery was from 87% to 113%; precision was less than 12.8%. The limit of detection and limit of quantification were from 0.4 to 2.0 µg kg−1 and from 1.3 to 6.0 µg kg−1, respectively. This method allows easy and fast analysis and detection of diverse adulterants.