• Tuberculosis and Respiratory Diseases
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• v.62 no.3
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• pp.203-210
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• 2007

Background: The incidence of adenocarcinoma of the lung has been increasing worldwide, and it has been generally been accepted to be relatively unrelated to smoking with a female preponderance. The aim of this study was to examine the gender-related pathological and survival differences in patients with an adenocarcinoma of the lung. Material and Method: A retrospective review of the clinical information of patients diagnosed with an adenocarcinoma of the lung at Kosin Medical Center from January 1999 to September 2005 was performed. The patient's demographics (age, gender), smoking history, stage, serum tumor marker, pathology classification, EGFR mutation, K-ras mutation, treatment methods, and survival time were analyzed. Result: Of the 438 patients, 179 (40.9%) were female. The median age at the diagnosis was 58 years for females and 59 years for males. However, 25.8% of women and only 17.7% of men were under 50 years of age (p=0.02). The distribution of the disease stage was similar in both men and women. The bronchioloalveolar carcinoma component was diagnosed more often in women (11.2%) than in men (5.0%). The overall survival rate was higher in women than in men (p=0.01), and women had a superior therapeutic response to a combined treatment of surgery and chemotherapy. Conclusion: This study showed significant genders differences in terms of the smoking history, bronchioloalveolar carcinoma component, overall survival, and survival after combined treatment of surgery and chemotherapy. Therefore, gender differences should be considered when diagnosing and treating adenocarcinomas of the lung.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.3
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• pp.87-94
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• 2018

We present the case of long-term observation of a patient with chronic kidney disease (CKD) caused by advanced focal segmental glomerulosclerosis (FSGS) resulting from underlying congenital chloride diarrhea (CLD). A 20-year-old woman was admitted for prolonged proteinuria despite conservative treatment for CLD. She was diagnosed with CLD and started taking KCl salt supplementation from the time of birth. Mild proteinuria was first found at 12 years of age, which progressed to moderate proteinuria at 16 years of age. At 16 years of age, CKD stage 2 with FSGS was diagnosed based on the initial assessment of the glomerular filtration rate (GFR) and kidney histology. On admission, we re-assessed her renal function, histology and genetic analysis. GFR had deteriorated to CKD stage 4 and renal histology revealed an advanced FSGS combined with tubulointerstitial fibrosis. A homozygous mutation in the SLC26A3 gene (c.2063-1G>T) was found by diagnostic exome sequencing and may have been inherited from both parents. CLD patients can be more vulnerable to renal injury, which may also cause progression of renal failure. Therefore, even if there is an early diagnosis and adequate salt supplementation, close monitoring of renal function and tailored treatment should be emphasized for renal protection and favorable CLD prognosis.

• Journal of Life Science
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• v.29 no.5
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• pp.537-544
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• 2019

Genome editing technology employing gene scissors has generated interest in molecular breeding in various fields, and the development of the third-generation gene scissors of the clustered, regularly interspaced short palindromic repeat (CRISPR) system has accelerated the field of molecular breeding through genome editing. In this study, we analyzed the possibility of silkworm molecular breeding using gene scissors by genomic and phenotypic analysis after editing the biogenesis of lysosome-related organelles (BmBLOS) gene of Bakokjam using the CRISPR/Cas9 system. Three types of guide RNAs (gRNA) were synthesized based on the BmBLOS gene sequence of Bakokjam. Complexes of the prepared gRNA and Cas9 protein were formed and introduced into Bombyx mori BM-N cells by electroporation. Analysis of the gene editing efficiency by T7 endonuclease I analysis revealed that the B4N gRNA showed the best efficiency. The silkworm genome was edited by microinjecting the Cas9/B4N gRNA complex into silkworm early embryos and raising the silkworms after hatching. The hatching rate was as low as 18%, but the incidence of mutation was over 40%. In addition, phenotypic changes were observed in about 70% of the G0 generation silkworms. Sequence analysis showed that the BmBLOS gene appeared to be a heterozygote carrying the wild-type and mutation in most individuals, and the genotype of the BmBLOS gene was also different in all individuals. These results suggest that although the possibility of silkworm molecular breeding using the CRISPR/Cas9 system would be very high, continued research on breeding and screening methods will be necessary to improve gene editing efficiency and to obtain homozygotes.

• Radiation Oncology Journal
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• v.26 no.4
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• pp.204-212
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• 2008

Purpose: This study was performed to evaluate the disease-free survival and risk factors of recurrence in early breast cancer patients who have undergone breast conserving surgery and radiation therapy. Materials and Methods: From March 1997 to December 2002, 77 breast cancer patients who underwent breast conserving surgery and radiation therapy were reviewed retrospectively. The median follow-up time was 58.4 months (range $43.8{\sim}129.4$ months) and the mean subject age was 41 years. The frequency distribution of the different T stages, based on the tumor characteristics was 38 (49.3%) for T1, 28 (36.3%) for T2, 3 for T3, 7 for T is and 1 for an unidentified sized tumor. In addition, 52 patients (67.5%) did not have axillary lymph metastasis, whereas 14 patients (18.1%) had $1{\sim}3$ lymph node metastases and 3 (0.03%) had more than 4 lymph node metastases. The resection margin was negative in 59 patients, close (${\leq}2\;mm$) in 15, and positive in 4. All patients received radiation therapy at the intact breast using tangential fields with a subsequent electron beam boost to the tumor bed at a total dose ranging from 59.4 Gy to 66.4 Gy. Patients with more than four positive axillary lymph nodes received radiation therapy ($41.4{\sim}60.4\;Gy$) at the axillary and supraclavicular area. Chemotherapy was administered in 59 patients and tamoxifen or fareston was administered in 29 patients. Results: The 5 year overall survival and disease-free survival rates were 98.08% and 93.49%, respectively. Of the 77 patients, a total of 4 relapses (5.2%), including 1 isolated supraclavicular relapse, 1 supraclavicular relapse with synchronous multiple distant relapses, and 2 distant relapses were observed. No cases of local breast relapses were observed. Lymph node metastasis or number of metastatic lymph nodes was not found to be statistically related with a relapse (p=0.3289) nor disease-free survival (p=0.1430). Patients with positive margins had a significantly shorter disease-free survival period (p<0.0001) and higher relapse rates (p=0.0507). However, patients with close margins were at equal risk of relapse and disease-free survival as with negative margins (p=1.000). Patients younger than 40 years of age had higher relapse rates (9.3% vs. 0%) and lower disease-free survival periods, but the difference was not statistically significant (p=0.1255). The relapse rates for patients with tumors was 14% for tumor stage T2, compared to 0% for tumor stage T1 tumors (p=0.0284). A univariate analysis found that disease-free survival and relapse rates, T stage, positive resection margin and mutation of p53 were significant factors for clinical outcome. Conclusion: The results of this study have shown that breast conservation surgery and radiation therapy in early breast cancer patients has proven to be a safe treatment modality with a low relapse rate and high disease-free survival rate. The patients with a positive margin, T2 stage, and mutation of p53 are associated with statistically higher relapse rates and lower disease-free survival.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.104-108
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• 2001

Aging is a senescence and defined as a normal physiologic and structural alterations in almost all organ systems with age. As Leonard Hayflick, one of the first gerontologists to propose a theory of biologic aging, indicated that a theory of aging or longevity satisfies the changes of above conditions to be universal, progressive, intrinsic and deleterious. Although a number of theories have been proposed, it is now clear that cell aging (cell senescence) is multifactorial. No single mechanism can account for the many varied manifestations of biological aging. Many theories have been proposed in attempt to understand and explain the process of aging. Aging is effected in individual by genetic factors, diet, social conditions, and the occurrence of age-related diseases as diabetes, hypertension, and arthritis. It involves an endogenous molecular program of cellular senescence as well as continuous exposure throughout life to adverse exogenous influences, leading to progressive infringement on the cell's survivability so called wear and tear. So we could say the basic mechanism of aging depends on the irreversible and universal processes at cellular and molecular level. The immediate cause of these changes is probably an interference in the function of cell's macromolecules-DNA, RNA, and cell proteins-and in the flow of information between these macromolecules. The crucial questions, unanswered at present, concerns what causes these changes in truth. Common theories of aging are able to classify as followings for the easy comprehension. 1. Biological, 1) molecular theories - a. error theory, b. programmed aging theory, c. somatic mutation theory, d. transcription theory, e. run-out-of program theory, 2) cellular theories - a. wear and tear theory, b. cross-link theory, c. clinker theory, d. free radical theory, e. waste product theory, 3) system level theory-a. immunologic/autoimmune theory, 4) others - a. telomere theory, b. rate of living theory, c. stress theory, etc. Prevention of aging is theoretically depending on the cause or theory of aging. However no single theory is available and no definite method of delaying the aging process is possible by this moment. The most popular action is anti-oxidant therapy using vitamin E and C, melatonin and DHEA, etc. Another proposal for the reverse of life-span is TCP-17 and IL-16 administration from the mouse bone marrow B cell line study for the immunoglobulin VDJ rearrangement with RAG-1 and RAG-2. Recently conclusional suggestion for the extending of maximum life-span thought to be the calory restriction.

• Biomedical Science Letters
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• v.1 no.1
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• pp.9-18
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• 1995

Genetic polymorphisms due to variation in the number of tandem repeats of DNA sequences(VNTRs) provides a useful means for discrimination between individuals. Allele and genotype frequencies of the highly polymorphic Human Thyroid Peroxidase(TPO) gene were determined in Korean population samples by using PCR followed by polyacrylamide gel electrophoresis, a procedure called the amplified fragment length polymorphism(Amp-FLP) technique. In 123 unrelated Korean individuals 10 different alleles and 29 genotypes were observed. The TPO gene demonstrated a heterozygosity of 0.707 and the power of exclusion(POE) was 0.945. The probability of having the same DNA band within two unrelated individuals was 14.6$\times10^{-2}$. The distribution of observed genotypes conformed to Hardy-Weinberg equilibrium($x^2$=4.48, 0.05

• Applied Biological Chemistry
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• v.51 no.3
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• pp.212-218
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• 2008

This study was performed to determine the antimutagenic and anticancer effects of ethanol extract of buckwheat sprout using Ames test and SRB assay, respectively. An ethyl acetate fraction (200 ${\mu}/plate$) from the ethanol extract of buckwheat sprout showed inhibition rate of 80.6% against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in Salmonella typhimurium TA100 strain. Also the ethyl acetate fraction (200 ${\mu}/plate$) showed higher antimutagenic activity than other fractions against the mutagenesis induced by 4-nitroquinoline-1-oxide (4NQO) in Salmonella typhimurium TA98 and TA100. In addition, the ethyl acetate fraction (200 ${\mu}/plate$) showed high antimutagenic effect of 80.9% and 85.9% against the mutation of TA98 and TA100 strains induced by 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxic effects of each solvent fraction from the ethanol extract of buckwheat sprout against human cancer cell lines including lung carcinoma (A549), gastric carcinoma (AGS), breast adenocarcinoma (MCF-7), hepatocellular carcinoma (Hep3B), and colon adenocarcinoma (Colo 205) were investigated. The ethyl acetate fraction of buckwheat sprout ethanol extract at the concentration of 1.0 mg/ml showed strong cytotoxic activities of 70.3, 94.8, 79.6, 82.3, and 73.2% against A549, AGS, MCF-7, Hep3B and Colo 205 cancer cell lines, respectively.

• Journal of Environmental Impact Assessment
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• v.26 no.1
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• pp.44-56
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• 2017

Sustainable development is important because the ultimate objective is efficient development combining the economic, social, and environmental aspects of urban conservation. Despite Korea's rapid urbanization and economic development, the distribution of resources is inefficient, and land-use is not an exception. Land use distribution is difficult, as it requires considering a variety of purposes, whose solutions lie in a multipurpose optimization process. In this study, Yangpyeong-eup, Yangpyeong, Gyeonggi-do, is selected, as the site has ecological balance, is well-preserved, and has the potential to support population increases. Further, we have used the genetic algorithm method, as it helps to evolve solutions for complex spatial problems such as planning and distribution of land use. This study applies change to the way of mutation. With four goals and restrictions of area, spatial objectives, minimizing land use conversion, ecological conservation, maximizing economic profit, restricting area to a specific land use, and setting a fixed area, we developed an optimal planning map. No urban areas at the site needed preservation and the high urban area growth rate coincided with the optimization of purpose and maximization of economic profit. When the minimum point of the fitness score is the convergence point, we found optimization occurred approximately at 1500 generations. The results of this study can support planning at Yangpyeong-eup.ausative relationship between the perception of improving odor regulation and odor acceptance.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.3
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• pp.203-206
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• 2003

Objectives: Controversial arguments exists on both the case for and against on the accumulation of mitochondrial DNA (mtDNA) deletion in association to tissue and age. The debate continues as to whether this mutation is a major contributor to the phenotypic expression of aging and common degenerative diseases or simply a clinical insignificant epiphenomenon. The objective of this study was to determine whether the accumulation of mtDNA deletion is correlated with age-related and tissue-specific variation. Materials and Methods: One hundred and fifty-seven tissues from blood, ovary, uterine muscle, and abdominal muscle were obtained from patients ranging in age from 31$\sim$60 years. After reviewing the clinical reports, patients with mitochondrial disorder were excluded from this study. The tissues were obtained at gynecological surgeries with the consent of the patient. Total DNA isolated from blood, ovary, uterine muscle, and abdominal muscle was amplified by two rounds of PCR using two pairs of primers corresponding to positions 8225-8247 (sense), 13551-13574 (antisense) for the area around deleted mtDNA and 8421-8440 (sense), 13520-13501 (antisense) for nested PCR product. A statistical analysis was performed by $x^2$-test. Results: About 0% of blood, 94.8% of ovary, 71.4% of uterine muscle, and 86.1% abdominal muscle harbored mtDNA deletion. When we examined the proportion of deleted mtDNA according to age deletion rate was 90% of ovary, 63.6% of uterine muscle, 77.7% of abdominal muscle in thirties and 100% of all tissue in fifties. Conclusion: The findings of this study suggest that the mtDNA deletion is varied in tissue-specific pattern and increases with aging.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7651-7656
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• 2013

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.