• Journal of Genetic Medicine
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• v.6 no.1
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• pp.91-94
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• 2009

Werner syndrome (WRN), or adult progeria, is a very rare, autosomal recessive disorder characterized by the appearance of accelerated aging, including cataracts, gray hair, skin atrophy, and atherosclerosis. This syndrome is caused by mutations in the WRN gene and had a high risk of a spectrum of rare neoplasms including: i) non-epithelial malignant or pre-malignant tumors/conditions, osteosarcomas and soft tissue sarcomas, malignant melanomas, myeloid leukemia and myelodysplastic syndrome; ii) an epithelial neoplasm, thyroid carcinoma, and iii) meningiomas. Recently, authors experienced a case of Werner syndrome complicated by bone metastasis of rhabdomyosarcoma in a 20-year old Korean man. The patient revealed a painful mass on his right knee and progeroid features, short stature, scalp alopecia, abnormal dentition, craniofacial disproportion, hypothyroidsm, cataracts and osteoporosis. The onset of symptoms of Werner syndrome generally precedes any later symptoms of associated conditions, such as malignant tumor. Therefore, early recognition of Werner syndrome is important to assist identification of malignant tumors at an early stage in this patient group.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.10
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• pp.1399-1403
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• 2006

A total of 80 cows, including 40 top mastitis resistant and 40 top mastitis susceptible animals as Group I and Group II, were selected from a population of 520 cows based on clinical mastitis occurrence. PCR-SSCP analysis on four fragments within the 5'region and two fragments of Exons 4,15 of bovine lactoferrin (bLF) revealed that four fragments-P1,P4,E4,E15-had polymorphisms which totally included six base mutations, and only two of them had significant differences in allele frequencies between resistant and susceptible groups, P1 (53.7% vs. 70.0%, p<0.05) and P4 (55.0% vs. 68.8%, p<0.05). Further study on these two promising markers combined with the milk performance traits of cows demonstrated that their selection would result in higher fat percentage (p<0.05), lower Somatic Cell Score (SCS) (p<0.05) and Clinical Mastitis Residuals (CMR) (p<0.01) indicating higher mastitis resistance and lower milk yield (p<0.05). The putative transcription factor binding sites in the 5'region were also studied by using MatInspector 7.2.2 software, and two signal pathways regulating the expression of bLF including the NF-${\kappa}B$ pathway and nuclear hormone receptor pathway were predicted.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4033-4039
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• 2013

Links between cancer and metabolism have been suggested for a long time but compelling evidence for this hypothesis came from the recent molecular characterization of the LKB1/AMPK signaling pathway as a tumor suppressor axis. Besides the discovery of somatic mutations in the LKB1 gene in certain type of cancers, a critical emerging point was that the LKB1/AMPK axis remains generally functional and could be stimulated by pharmacological molecules such as metformin in cancer cells. In addition, AMPK plays a central role in the control of cell growth, proliferation and autophagy through the regulation of mTOR activity, which is consistently deregulated in cancer cells. Targeting of AMPK/mTOR is thus an attractive strategy in the development of therapeutic agents against non-small-cell lung cancer (NSCLC). In this review, the LKB1/AMPK/mTOR signaling pathway is described, highlighting its protective role, and opportunities for therapeutic intervention, and clinical trials in NSCLC.

• Development and Reproduction
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• v.7 no.2
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• pp.69-80
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• 2003

The zebrafish(Danio rerio) is a pre-eminent vertebrate model system for clarification of the roles of specific genes and signaling pathways in development. We show examples of positional cloning in two developmental mutants in zebrafish. headless: The severe head defects in headless(hdl) mutants are due to a mutation in T-cell factor-3(Tcf3). Loss of Tcf3 function in the hdl mutant reveals that Hdl represses Wnt target genes. The results provide genetic evidence that a component of the Wnt signaling pathway is essential in vertebrate head formation and patterning. mind bomb: Reduced lateral inhibition in mind bomb(mib) mutants permits too many neural precursors to differentiate as neurons. Positional cloning of mib revealed that it is a gene in the Notch pathway that encodes a ubiquitin E3 ligase. Mib interacts with the intracellular domain of Delta to promote its internalization. The results suggest a model for Notch activation where the Delta-Notch interaction is followed by endocytosis of Delta and transendocytosis of the Notch extracellular domain by the signaling cell.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.98-100
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• 2015

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare mitochondrial fatty-acid oxidation disorder that is inherited as an autosomal recessive pattern. SCAD deficiency is caused by mutations in the ACADS gene (Acyl-CoA Dehydrogenase, Short-chain, OMIM #606885), which encodes SCAD, the mitochondrial enzyme that catalyzes the first reaction in the beta-oxidation of fatty acids four to six carbons in length. Here, we describe one Korean pediatric case of SCAD deficiency, which was diagnosed during newborn screening through tandem mass spectrometry. An increased concentration of butyrylcarnitine was detected on the newborn screening test, and the urine organic acid analysis showed increased urinary excretion of ethylmalonic acid. The patient has been asymptomatic and has shown normal growth and development by 8 months of age without any intervention during follow-up period.

• Korean Journal of Veterinary Research
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• v.38 no.3
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• pp.606-613
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• 1998

Cadmium is one of the well-known environmental toxicants and induces cancer in rodents and human, but its carcinogenic mechanism has not been well demonstrated until now. Genotoxic effects of cadmium in Salmonella typhimurium TA98, TA100 and TA1535/pSK1002 or in WB-F344 rat liver epithelial cells were investigated to elucidate the tumor initiating effects of cadmium. TA98, TA100 and TA1535/pSK1002 tester strains were used to detect frameshift mutation, base-pair mutation and SOS repair response, respectively, in Salmonella mutation test. Reverse mutations from histidine to $histidin^+$ of Salmonella typhimurium TA98 and TA100 by $CdCl_2$ were not significantly different from control up to the maximum doses ($100{\mu}M$ and $200{\mu}M$ in TA98 and TA100, respectively) at which non-cytotoxicity was observed. DNA SOS repair responses(${\beta}$-galactosidase activity) generally did not show significant increases compared to control in both of the conditions with or without metabolic activation in Salmonella typhimurium TA1535/pSK1002 by $CdCl_2$. But the activities of ${\beta}$-galactosidase by $400{\mu}M$ of $CdCl_2$ in metabolic activation condition and by 130 and $400{\mu}M$ of $CdCl_2$ in non-metabolic activation condition were more decreased than those of control. DNA single strand breaks for 4hrs were observed only in WB-F344 rat liver epithelial cells treated with $200{\mu}M$ of $CdCl_2$. As a conclusion, $CdCl_2$ did not induce gene mutation in microbials but induce DNA single strand breaks in rat liver epithelial cells.

• BMB Reports
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• v.50 no.6
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• pp.308-317
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• 2017

Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth $factor-{\beta}$ ($TGF-{\beta}$) superfamily receptors, performing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids, and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD proteins-mediated signal transduction leading to the expression of target genes implicated in the development or differentiation of the embryo, organs and bones. In particular, genetic alterations of BMPR2 gene are associated with several clinical disorders, including representative pulmonary arterial hypertension, cancers, and metabolic diseases, thus demonstrating the physiological importance of BMPR2. In this mini review, we summarize recent findings regarding the molecular basis of BMPR2 functions in BMP signaling, and the versatile roles of BMPR2. In addition, various aspects of experimentally validated pathogenic mutations of BMPR2 and the linked human diseases will also be discussed, which are important in clinical settings for diagnostics and treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1999-2002
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• 2012

Background: DNA polymerase is a single-copy gene that is considered to be part of the DNA repair machinery in mammalian cells. The encoded enzyme is a key to the base excision repair (BER) pathway. It is evident that pol beta has mutations in various cancer samples, but little is known about ovarian cancer. Aim: Identification of any variant form of $pol{\beta}$ cDNA in ovarian carcinoma and determination of association between the polymorphism and ovarian cancer risk in Indian patients. We used 152 samples to isolate and perform RT-PCR and sequencing. Results: A variant of polymerase beta (deletion of exon 4-6 and 11-13, comprising of amino acid 63-123, and 208-304) is detected in heterozygous condition. The product size of this variant is 532 bp while wild type pol beta is 1 kb. Our study of association between the variant and the endometrioid type shows that it is a statistically significant factor for ovarian cancer [OR=31.9 (4.12-246.25) with p<0.001]. The association between variant and stage IV patients further indicated risk (${\chi}^2$ value of 29.7, and OR value 6.77 with 95% CI values 3.3-13.86). The correlation study also confirms the association data (Pearson correlation values for variant/stage IV and variant/endometrioid of 0.44 and 0.39). Conclusion: Individuals from this part of India with this type of variant may be at risk of stage IV, endometrioid type ovarian carcinoma.

• Journal of mucopolysaccharidosis and rare diseases
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• v.2 no.1
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• pp.19-22
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• 2016

Purpose: Mucolipidosis type II (ML II), also known as I-cell disease is an autosomal recessive inherited disorder of lysosomal enzyme transport caused by a deficiency of the uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase). Clinical manifestations are skeletal abnormalities, mental retardation, cardiac disease, and respiratory complications. A severely and rapidity progressive clinical course leads to death before 10 years of age. Methods/Results: In this study we diagnosed three cases of prenatal ML II in two different at-risk families. We compared two procedures -biochemical analysis and molecular analysis - for the prenatal diagnosis of ML II. Both methods require an invasive procedure to obtain specimens for the diagnosis. Biochemical analysis requires obtaining cell cultures from amniotic fluid for more than two weeks, and would result in a late diagnosis at 19 to 22 weeks of gestation. Molecular genetic testing by direct sequence analysis is usually possible when mutations are confirmed in the proband. Molecular analysis has an advantage in that it can be performed during the first-trimester. Conclusion: Molecular diagnosis is a preferable method when a prompt decision is necessary.