1.Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients.
Se Hoon LEE ; Boram LEE ; Joon Ho SHIM ; Kwang Woo LEE ; Jae Won YUN ; Sook Young KIM ; Tae You KIM ; Yeul Hong KIM ; Young Hyeh KO ; Hyun Cheol CHUNG ; Chang Sik YU ; Jeeyun LEE ; Sun Young RHA ; Tae Won KIM ; Kyung Hae JUNG ; Seock Ah IM ; Hyeong Gon MOON ; Sukki CHO ; Jin Hyoung KANG ; Jihun KIM ; Sang Kyum KIM ; Han Suk RYU ; Sang Yun HA ; Jong Il KIM ; Yeun Jun CHUNG ; Cheolmin KIM ; Hyung Lae KIM ; Woong Yang PARK ; Dong Young NOH ; Keunchil PARK
Cancer Research and Treatment 2019;51(1):211-222
PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes
;
Asian Continental Ancestry Group
;
DNA
;
Humans
;
Korea
;
Methods
;
Paraffin
;
Point Mutation
;
Precision Medicine
;
Prevalence
2.The Analysis of Tumor Aggressiveness accord- ing to Tumor Size in Occult Papillary Thyroid Carcinoma.
Hai Lin PARK ; Jin Young KWAK ; Seok Seon KANG ; Do Youn KIM ; Hyung Gon KANG ; Jung Yeon SHIM ; Yoori KIM ; Won Kun PARK ; Young Gil CHOI
Journal of the Korean Surgical Society 2007;73(6):470-475
PURPOSE: Occult papillary thyroid carcinomas (OPC) are defined as tumors measuring <15 mm. These tumors are believed to be a less aggressive subset of papillary cancers. They generally behave more like benign lesions and are often more conservatively treated. However, it is unclear if a cancer 1.0 to 1.5 cm in diameter will have a similar favorable clinical behavior as tumors <1.0 cm (micropapillary thyroid carcinoma). Therefore, a retrospective chart review study of patients with OPC in order was carried out in order to answer this question and characterize the biology and optimal treatment for OPCs. METHODS: From October 2001 to January 2007, Among the impalpable thyroid nodules detected incidentally during screening examinations, 260 patients underwent surgery for occult papillary thyroid cancer (OPC) at Kangnam Cha University hospital. The data from these patients was analyzed retrospectively. The mean follow up period was 25.6 +/- 14.5 (max: 63, min: 1) months. RESULTS: The mean age of these patients was 42.8 years, and 233 (89.5%) were female. 46.2% of patients underwent a total or neartotal thyroidectomy, and 54.6% underwent a central lymph node dissection. Of the 260 patients, 55 (21.2%) had lymph node metastases. The OPC presented with signs of aggressiveness including multifocality (34.2%), bilaterality (17.7%), capsular invasion (52.7%), and lymph node metastases (21.2%). A progressively increasing frequency of the signs of tumor aggressiveness was observed with increasing tumor size at presentation. LN metastases were associated with the tumor size (P=0.0063), extracapsular invasion (P=0.0015) and multfocallity (P=0.0020). However, there was no association with age and gender. With a follow-up of up to 63 months, 3 patients had a local recurrence (0.014%). No patients currently have active disease and no patients with OPC died during this period. CONCLUSION: In OPC patients, there is a progressively increasing frequency of the signs of tumor aggressiveness with increasing tumor size. Moreover, a small size itself cannot guarantee low risk and low recurrence rate. The prevalence of LN metastases and extracapsular invasion were higher in those with a tumor size >0.5 cm. A near-total or total thyroidectomy with a central lymph node dissection is the preferred treatment. The early detection and treatment of OPC might be warranted through the routine use of thyroid USG and USG-guided FNA.
Biology
;
Female
;
Follow-Up Studies
;
Humans
;
Lymph Node Excision
;
Lymph Nodes
;
Mass Screening
;
Neoplasm Metastasis
;
Prevalence
;
Recurrence
;
Retrospective Studies
;
Thyroid Gland*
;
Thyroid Neoplasms*
;
Thyroid Nodule
;
Thyroidectomy
3.The Effect of Plasma Treatment of Poly (Lactic-co-Glycolic)(PLGA) Scaffold on Adhesion and Bioactivity of Cultured Chondrocytes.
Ji Lak JEONG ; Hyung Gon SHIM ; Jae Gu PARK ; Young Min JU ; Dong Keun HAN ; Jong Won RHIE ; Sang Tae AHN
Journal of the Korean Society of Plastic and Reconstructive Surgeons 2003;30(4):491-497
The advantages of wielding synthetic polymer are that the pore size, physical strength and chemical composition can be easily controlled. However, the synthetic polymer has hydrophobic character and low affinity to cells and other bio molecules. This study was performed to investigate the effect of plasma glow's discharge on the surface modification of poly(lactic-co-glycolic acid)(PLGA) sponge on the adhesion and bio-activity of chondrocytes in vitro culture. PLGA sponges(lactic acid: glycolic acid = 85 : 15, pore size=200 - 300 mrcro m, dimension=15 x 2 mm) were prepared. The experimental group(n=8) was treated with a radiofrequency plasma glow-discharge(acrylic acid and oxygen: 50 W, 0.2 torr for 30 seconds) but the control group (n=8) was treated with nothing. 1 x 10(6)ml/20 microliter of P3 chondrocytes from rabbit ears were used for seeding. Eight hours after cell seeding, the total DNA amount of chondrocytes attached to the PLGA and the changes of actin were evaluated under a confocal microscope. Type I and II collagen expression were detected by RT-PCR three weeks after seeding for an evaluation of phenotypic maintenance. The total DNA amount of attached chondrocytes was remarkably increased in the experimental group(p < 0.05). After scrutinizing with a confocal microscope, the actin of cells was more spread out and finely arranged in the experimental group than in the control group. Both types of collagen expression were significantly increased in their assigned groups. Plasma treatment of the PLGA sponge could increase the adhesion property of chondrocytes, and provide suitable environment for maintaining the phenotype of chondrocytes.
Actins
;
Chondrocytes*
;
Collagen
;
DNA
;
Ear
;
Oxygen
;
Phenotype
;
Plasma*
;
Polymers
;
Porifera
4.Revascularization of Inferior Epigastric Islasnd Flap woth Limited Bed Contact.
Hyung Gon SHIM ; Ki Taik HAN ; Sang Tae AHN
Journal of the Korean Society of Plastic and Reconstructive Surgeons 1999;26(4):659-664
Island flaps have been widely used for the management of soft tissue defects in reconstructive surgery. The necrosis of the flap has been a catastrophe in clinical fields. It is well known that revascularization to the flap after ligation of its pedicle comes from the recipient bed and flap margins. The authors investigated the effects of the ischemic recipient bed on island flap survival after the ligation of its pedicle in the rats. One hundred and thirty inferior epigastric island flaps were divided into three groups (Group I, Group II, and Group III) according to the degree (0%,20%, and 60%) of interruption of contact of flap with the recipient bed, respectively. In Group I,the vascular pedicles were ligated before and on the 0, 2nd, 3rd, 4th and 5th days after flap elevation, and in Group II & III, the vascular pedicles were ligated on the 2nd, 3rd, 4th and 5th days after flap elevation. Flap survival was assessed on the 3rd day after pedicle ligation. Microangiographic studies were also performed on the 3rd day after pedicle ligation to study revascularization within the flap and the change of blood vessels around the flap margins. The results were as follows: 1. Flap survival was increased significantly in the flaps with pedicle ligation on the 4th and 5th postoperative days compared to those at the 2nd and 3rd postoperative days. 2. From the 3rd postoperative day, flap survival was not influenced significantly by the degree of limited bed contact and the date of pedicle ligation. 3. In spite of limited bed contact, the flap will likely survive with abundant revascularization from the flap margins. In conclusion, the flaps with limited bed contact were revascularized significantly from the flap margin by the 3rd postoperative day.
Animals
;
Blood Vessels
;
Ligation
;
Necrosis
;
Rats
;
Surgical Flaps
5.The Vocal Tract and Speech Intelligibility of Tracheoesophageal Shunt Patients after Total Laryngectomy.
Cheul Su KIM ; Soo Geun WANG ; Woo Young SHIM ; Hyung Jin PARK ; Chang Su KIM ; Jung Hwan PARK ; Hyeong Jun JANG ; Suk Hun LEE ; Suck Hong LEE ; Byung Gon YANG ; Moo Jin BAEK ; Cheol Woo JO
Korean Journal of Otolaryngology - Head and Neck Surgery 1999;42(9):1160-1168
BACKGROUND AND OBJECTIVES: In this paper, rehabilitation of voice after total laryngectomy has been suggested through the correct estimation and simulation of patients' vocal tract. Material and Methods: The author studied the shape of vocal tract during the phonation of five Korean vowels /u, o, a, e, i/ in tracheoesophageal shunt patients by magnetic resonance images (MRI). The same vocal tract was determined in each vowels from MRI. First, speech data produced by them were analyzed and also checked for speech intelligibility. Then the author tried to synthesize vowels from the vocal tract area of each vowels and from the expanded pharyngeal section of the vocal tract. RESULTS: The obtained results were as follows: 1) The sounds of /a/, /e/, /i/ were similar to natural sounds in actual patients' speech. The sound of /o/ was heard as /sigma/. The sound of /u/ was heard as strained /u/. 2) The synthesized vowels of /a/, /e/ from MRI were heard as natural sounds. The sounds of /u/, /o/, /i/ were heard as other sounds. 3) The synthesized vowel by the expanded pharyngeal section of 3 times in vowel /o/ was more naturally heard than that of 2 times. The synthesized vowel from Formfrek was more naturally heard than that from AreatoFormant. CONCLUSION: In conclusion, some of the synthesized sounds from MRI disagrees with the actual sounds produced by the subjects. This could be best identified by the synthesis from the area data. Future MRI studies should consider this problem for more accurate measurements. Also, pharyngeal areas with varied sizes should be experimented to secure better speech output because the correct shapes of vocal tract ensures correct vowel pronunciation.
Humans
;
Laryngectomy*
;
Magnetic Resonance Imaging
;
Phonation
;
Rehabilitation
;
Speech Intelligibility*
;
Voice
6.Lacrimal canalicular reconstruction with various materials.
Hyung Gon SHIM ; Jun Hee BYEON ; Jong Won RIE ; Chong Kun LEE ; Poong LIM
Journal of the Korean Society of Plastic and Reconstructive Surgeons 1998;25(4):622-627
This retrospective clinical study consists of 27 patients with lacrimal canalicular injury caused by various accidents and which were reconstructed with various materials in the department of plastic surgery at Catholic University Medical College from December 1987 to July 1996. These 27 patients were followed up at least 6 months after the canalicular reconstruction and their medical records were reviewed and analysed retrospectively in order to obtain the clinical pattern and understand the therapeutic results. The statistical items were the age and sex distribution, the causes of injury, the prevalent site of injury, the reconstruction materials, the duration of intubation and the results of treatment. The following results are obtained: 1. Males were more dominant than females by 4.4 : 1. 2. The patient age was from 6 to 73 years old and the prevalent age groups were the third and fourth decades(55.5%). 3. The most common cause of canalicular injury was the violence(29.6%) and was followed by traffic accident. 4. The left canaliculi, especially inferior canaliculi, was the prevalent injury site. 5. Regardless of the materials(P.V.C. tube, nylon and silicone tube) used in canalicular reconstruction, the longer duration of intubation was obtained the better result of treatment. 6. So the silicone tube with stainless steel(C-line canaliculus intubation set) was relatively inert and less complicating, it could be maintained more longer and had better results than other materials such as P.V.C. tube and nylon.
Accidents, Traffic
;
Aged
;
Female
;
Humans
;
Intubation
;
Male
;
Medical Records
;
Nylons
;
Retrospective Studies
;
Sex Distribution
;
Silicones
;
Surgery, Plastic
7.Clinical and MRI Findings of Acute Disseminated Encephalomyelitis Associated with Preceding Infections Confirmed Serologically.
Jung Yeon SHIM ; Tae Sung KO ; Hyung Nam MOON ; Chang Yee HONG ; Choong Gon CHOI ; Shi Joon YOO ; Dae Chul SUH
Journal of the Korean Pediatric Society 1998;41(4):505-513
PURPOSE: Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. The pathogenesis is not well known, but it is thought to be an immune-mediated disease and may follow a viral infection or vaccinations. MRI demonstrates decreased signal on T1 weighting and increased signal on T2-weighted image. We report clinical features and characteristic MRI findings in seven patients with ADEM who confirmed the preceding infections serologically. METHODS: Patients admitted to the Department of Pediatrics at Asan Medical Center as having ADEM were evaluated for the preceding infections : CSF findings, MRI findings, effects of high-dose steroids and follow-up on changes of neurological symtoms and MRI findings. RESULTS: The onset of neurological symptoms from preceding infection was between 1-3 weeks. The etiologies were Epstein-Barr virus in two, mycoplasma pneumoniae in three, and measles virus in two cases. All lesions found in MRI were cerebral white matter lesions of which there were subcortical white matter in three, corpus callosum in three, deep white matter in two, periventricular white matter in one, internal capsule in one, and cerebral peduncle in one case. There were a total of 3 cases with gray matter lesions. Two cases were treated with high- dose methyl prednisolone, one which showed a good clinical response with much improved lesions on follow-up T2-weighted image, but no clinical response in the other with aggravated MRI lesions. There was 1 patient with gadolinium enhancement lesion in acute phase and the lesion was completely resolved after steroid treatment. CONCLUSION: MRI shows various features in ADEM and may be useful in diagnosis and evaluation of clinical course.
Central Nervous System
;
Chungcheongnam-do
;
Corpus Callosum
;
Demyelinating Diseases
;
Diagnosis
;
Encephalomyelitis, Acute Disseminated*
;
Follow-Up Studies
;
Gadolinium
;
Herpesvirus 4, Human
;
Humans
;
Internal Capsule
;
Magnetic Resonance Imaging*
;
Measles virus
;
Mycoplasma pneumoniae
;
Pediatrics
;
Pneumonia, Mycoplasma
;
Prednisolone
;
Steroids
;
Tegmentum Mesencephali
;
Vaccination
8.A Case-Control Study on Risk Factors of CHD: Vegetable consumption and risk for CHD in Korean men.
Kyung Won OH ; Il SUH ; Kang Hee LEE ; Chung Mo NAM ; Suk Il KIM ; Hyung Gon KANG ; Sun Ha JEE ; Seung Yun CHO ; Won Heum SHIM
Korean Journal of Epidemiology 1998;20(2):234-245
The purpose of this study was to investigate the association of vegetable consumption with the incidence of CHD in Korean men by a case-control study. The case group consisted of 108 patients with EKG-confirmed myocardial infarct or angiographically-confirmed(>or=50% stenosis) angina pectoris admitted to a university teaching hospital in Seoul, Korea. Controls were 142 age-matched patients admitted to the departments of ophthalmology and orthopedic surgery at the same hospital. Dietary intake was assessed by a nutritionist using a semiquantitative food frequency method, while body mass index (BMI), tobacco use, and past history of cardiovascular disease were determined during an interview and examination. The consumption of vegetables was classified by the average frequency of intake(less than 3 times/week, 3~4 times/week, 5~6 times/week, more than once/day). The percentage of subjects who consumed vegetables less than 3 times per week was 29.6% for cases and 17.6% for controls; while men who consumed vegetavle more than once per day were 16.7% for cases and 32.4% for controls. After the adjustment for age, body mass index, and tobacco use, the odds ratio of men who consumed vegetables at least once per day was 0.38(95% confidence interval, 0.18-0.85) compared with men who consumed vegetables less than three times per week. These results suggested that in a population with a relatively low fat intake, consumption of vegetables at least once per day may reduce the risk of CHD in men.
Angina Pectoris
;
Body Mass Index
;
Cardiovascular Diseases
;
Case-Control Studies*
;
Coronary Disease
;
Hospitals, Teaching
;
Humans
;
Incidence
;
Korea
;
Male
;
Myocardial Infarction
;
Nutritionists
;
Odds Ratio
;
Ophthalmology
;
Orthopedics
;
Risk Factors*
;
Seoul
;
Tobacco Use
;
Vegetables*
9.THE EFFECT OF COLLAGEN SUBSTRATE IN CULTURE MEDIUM ON DNA AND PROTEIN SYNTHESIS OF DERMAL FIBROBLASTS.
Jong Won RHIE ; Hyung Gon SHIM ; Jun Hee BYEON ; Sung Il KWAK ; Chong Kun LEE
Journal of the Korean Society of Plastic and Reconstructive Surgeons 1997;24(2):229-236
Collagen is the major component of scar tissue. Considerable progress of fibroblast growth kinetics and of collagen synthesis has been achieved in the past decade. We have been interested in fibroblasts activities as they are expressed by cells cultured in collagen substrate. This study is to examine the effects of collagen substrate and peptide growth factors In culture medium on DNA and protein synthesis of human dermal fibroblasts. Collagen, interleukin-1(IL-1) and transforming growth factor-beta(TGF-beta) were added to fibroblast culture media according to the designed experiment model and DNA and protein synthesis were measured by [3H]-thymidine, [3H]-leucine, and [3H]-proline incorporation method. The morphological features of fibroblasts were observed by light microscope. The results were as follows ; 1) There were significant decreases of DNA and protein synthesis of cultured fibroblasts in the presence of collagen substrate compared with those in Control groups(p<0.01). 2) DNA and protein synthesis were decreased as dose dependant manner of collagen density in culture media. 3) Morphological features of fibroblasts became less stellate and flat, more spindle-like in the presence of collagen. 4) In responsiveness to IL-1, collagen non-treated groups responded to IL-1 but collagen treated groups were unresponsive to IL-1 (P<0.05). 5) Cells In collagen non-treated groups responded to TGF-beta as dose-related manner(P<0.01). Collagen treated groups desponded to TGF-beta but did not show TGF-beta dose-dependant relationship. In Conclusion, collagen substrate in the culture medium could lower the DNA and protein synthesis of fibroblasts. Cells in collagen substrate were unresponsive or less responsive to peptide growth factors than those in non-collagen substrate.
Cicatrix
;
Collagen*
;
Culture Media
;
DNA*
;
Fibroblasts*
;
Humans
;
Intercellular Signaling Peptides and Proteins
;
Interleukin-1
;
Kinetics
;
Transforming Growth Factor beta
10.Four-year change and tracking of serum lipids in Korean adolescents.
Kang Hee LEE ; Il SUH ; Sun Ha JEE ; Chung Mo NAM ; Sung Soon KIM ; Won Heum SHIM ; Jong Won HA ; Suk Il KIM ; Hyung Gon KANG
Korean Journal of Preventive Medicine 1997;30(1):45-60
It has been known that there is a tracking phenomenon in the level of serum lipids. However, no study has been performed to examine the change and tracking of serum lipids in Korean adolescents. The purpose of this study is to examine the changes of serum lipids in Korean adolescents from 12 to 16 years of age, and to examine whether or not there is a tracking phenomenon in serum lipids level during the period. In 1992 serum lipids(total cholesterol(TC), triglyceride(TG), LDL cholesterol(LDL-C), HDL cholesterol(HDL-C)) were measured in 318 males, 365 females who were 12 years of age in Kangwha county, Korea. These participants have been followed up to 1996 and serum lipids level were examined in 1994 and 1996. Among the participants 162 males and 147 females completed all three examinations in fasting state. To examine the effect of eliminating adolescents with incomplete data, we compared serum lipids, blood pressure and anthropometric measures at baseline between adolescents with complete follow-up and adolescents who were withdrawn. To examine the change of serum lipids we compared mean values of serum lipids according to age in males and females. Repeated analysis of variance was used to test the change according to age. We used three methods to examine the existence of tracking. First, we analyzed the trends in serum lipids over 4-year period within quartile groups formed on the basis of the first-year serum lipids level to see whether or not the relative ranking of the mean serum lipids among the quartile groups remained in the same group for 4-year period. Second, we quantified the degree of tracking by calculating Spearman's rank correlation coefficient between every tests. Third, the persistence extreme quartile method was used. This method divides the population into quartile groups according to the initial level of blood lipids and then calculates the percent of the subjects who stayed in the same group at follow-up measurement. The decreases in levels were noted during 4 years for TC, LDL-C, primarily for boys. The level of HDL-C decreased between baseline and first follow-up for both sexes and girls. Tracking, as measured by both correlation coefficients and persistence extreme quartiles, was evident for all of the lipids. The correlation coefficients of TC between baseline and 4 years later in boys and girls were 0.55 and 0.68, respectively. And the corresponding values for HDL-C were 0.58 and 0.69. More than 50% of adolescents who belonged to the highest quartile group in TC, HDL-C and LDL-C at the baseline were remained at the same group at the examination performed 2 years later for both sexes. The probability of remaining at the same group was more than 35% when examined 4 years later. The tracking phenomenon of TG was less evident compared with the other lipids. Percents of girls who stayed at the same group 2 years later and 4 years later were 42.9% and 25.7%, respectively. It was evident that serum lipid levels tracked in Korean adolescents. Researches with longer follow-up would be needed in he future to investigate the long-term change of lipids from adolescents to adults.
Adolescent*
;
Adult
;
Blood Pressure
;
Cholesterol, HDL
;
Cholesterol, LDL
;
Fasting
;
Female
;
Follow-Up Studies
;
Humans
;
Korea
;
Male
;
Triglycerides

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