• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• Journal of Life Science
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• v.23 no.1
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• pp.1-7
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• 2013

Understanding salt tolerance mechanisms is important for the increase of crop yields, and so, several screening approaches were developed to identify plant genes which are involved in salt tolerance of plants. Here, we transformed the Arabidopsis cDNA library into a salt-sensitive calcineurin (CaN)-deficient ($cnb{\Delta}$) yeast mutant and isolated the colonies which can suppress salt-sensitive phenotype of $cnb{\Delta}$ mutant. Through this functional complementation screen, a total of 34 colonies functionally suppressed the salt-sensitive phenotype of $cnb{\Delta}$ yeast cells, and sequencing analysis revealed that these are 9 genes, including CaS, AtSUMO1 and AtHB-12. Among these genes, the ectopic expression of CaS gene increased salt tolerance in yeast, and CaS transcript was up-regulated under high salinity conditions. CaS-antisense transgenic plants showed reduced root elongation under 100 mM NaCl treatment compared to the wild type plant, which survived under 150 mM NaCl treatment, whereas CaS-antisense transgenic plant leaves turned yellow under 150 mM NaCl treatment. These results indicate that the expression of CaS gene is important for stress tolerance in yeast and plants.

• Journal of the korean academy of Pediatric Dentistry
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• v.31 no.2
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• pp.262-266
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• 2004

The parathyroid hormone plays a major role in the metabolism of calcium and phosphorus. In hypoparathyroidism the parathyroid glands are atrophied or absent associated with autoantibodies against parathyroid tissue. Pseudohypoparathyroidism is a metabolic disease caused by the disturbance in peripheral action of parathormone, but parathormone level is normal. In general, patients with pseudohypoparathyroidism have short stature, round face, brachydactylia, obesity, mental retardation, cataracts & ectopic calcifications on soft tissues. Dental manifestations are enamel hypoplasia, delayed eruption, blunting of root apex, hypodontia, pulp calcification, thickened lamina dura, excessive caries & malocclusion. In this case, intraoral examination showed enamel hypoplasia on the erupted permanent teeth & hypermobility on the remaining deciduous teeth. From the radiographic view severe dental anomalies were observed on canines and shortening and blunting of root apex was observed on mandibular incisors. Pathologic root resorption was also observed on deciduous teeth.

• Molecules and Cells
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• v.41 no.9
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• pp.830-841
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• 2018

Recent studies have indicated that microRNAs (miRNAs) play an important role in hepatocellular carcinoma (HCC) progression. In this study, we showed that miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and its low expression level was significantly correlated with tumour size, TNM stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression inhibited HCC cell proliferation, colony formation, migration and invasion. In addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an inverse correlation between miR-766-3p and Wnt3a expression was observed. Moreover, Wnt3a up-regulation reversed the effects of miR766-3p on HCC progression. In addition, our study showed that miR-766-3p up-regulation decreased the nuclear ${\beta}-catenin$ level and expression of Wnt targets (TCF1 and Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1). However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In addition, PRC1 upregulation increased the nuclear ${\beta}-catenin$ level and protein expression of TCF1 and Survivin. iCRT3, which disrupts the ${\beta}-catenin-TCF4$ interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken together, our results suggest that miR-766-3p down-regulation promotes HCC cell progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may serve as a potential therapeutic target in HCC.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.2
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• pp.239-249
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• 1999

The role of amino acids in culture media for IVF-ET was examined in a total of 76 cycles. Patients received clomiphene citrate (CC) followed by hMG or GnRH-a combined with gonadotropins (FSH/hMG) for controlled ovarian hyperstimulation. Severe male (<$4{\times}10^6$ motile sperm) or age factor (>39 y) patients were excluded in this study. Pregnancy was classified as clinical if a gestational sac or fetal cardiac activity was seen on ultrasound. No significant differences were found in age, duration of infertility, follicle size, the level of $E_2$ on the day of hCG injection, the mean number of oocytes retrieved, total motile sperm count, fertilization rate and the mean number of embryos transferred between bHTF (without amino acids) and mHTF (with amino acids) groups. However, total ampules of gonadotropins were higher (p<0.01) in mHTF group than bHTF group. Significantly (p<0.05) more clinical pregnancies were recorded in mHTF group (13/30) compared with bHTF group (9/46). The multiple pregnancy rates were 11.1% in bHTF group and 7.7% in mHTF group. There were one ectopic pregnancy in mHTF group and one heterotopic pregnancy in bHTF group. Abortion rates were 22.2% in bHTF group and 7.7% in mHTF, respectively. The ongoing pregnancy or livebirth rate was significantly (p<0.05) higher in mHTF group (12/30) than bHTF group (7/46). These results suggest that the addition of amino acids in culture media is essential for culture of zygotes in vitro and adjustment of energy substrates in phosphate-free culture media appears to be beneficial for human IVF-ET procedure.

• Research in Community and Public Health Nursing
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• v.7 no.1
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• pp.138-153
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• 1996

Intending to offer basic information for a prospective health services in Korea, this study is to investigate the complication caused by sterilization in goverment family planning program from 1962 to 1995. The results are as follows: 1. Total number of sterilization performed during the period from 1962 to 1995 were 1.367,772 cases of male sterilization and 2,889,635 cases of female sterilization. 2. Incidence of the complication caused by sterilization operation from 1980 to 1995 were 1,883(0.20%) out of 925,801 cases in vasectomies and 15,866(0.70%) out of 2,256,020 cases in tubal sterilizations. 3. Major complications in vasectomy were epididymities of 658 cases (34.9%), vas recanalization of 326 cases(17.3%), hematoma of 266 cases(14.1%), scrotal abscess of 184 cases(9.8%), sperm granuloma of 76 cases(4.0%),and other of 373 cases(19.8%). On the other hand, in tubal sterilization, ectopic pregnancy was the most significant complication of 15,078 cases (95.0%) among 15,866 total complications, followed by pelvic inflammatory diseases of 155 cases(0.9%), peritonities of 96 cases(0.6%), ovarian & tubal bleeding of 31 cases(0.2%), intestinal perforation of 16 cases (0.1%), uterine bleeding of 14 cases(0.1%), uterine cervix laceration of 1 case (0.1%), and other of 271 cases(1.7%), while 161 pregnancies(0.1%) were terminated and 43 cases(0.3%) with normal delivery. 4. The occurrence rate of the complication for each period showed that most of the complication cases by vasectomy occurred in a year after the operation -the cases were 1,256 (66.7%). 254 cases(13.5%) occurred between the next year and the 2nd year, 138 cases (7.3%) between the 2nd year and the 3rd year, 73 cases(3.9%) between the 3rd year and the 4th year, 52 cases(2.8%) between the 4th year and the 5th year, 31 cases(1.6%) between the 5th year and the 6th year, 79 cases(4.2%) over the 6th year. Tubal sterilization indicated that the occurred complication cases in a year were 2,175 cases(13.7%), 2,113 cases(13.3%) occurred between the next year and the 2nd year, 2,082 cases(13.1%) between the 2nd year and the 3rd year, 2,049 cases (12. 9%) between the 3rd year and the 4th year, 1,819 cases(11.5%) between the 4th year and the 5th year, 621 cases(10.2%) between the 5th year and the 6th year, 4,007 cases(25.3%) over the 6th year. 5. For the cost of complication treatment, total \7,928,229,000 were paid as medical expenditure in which \609,438,000 for vasectomy and \7,318,791,000 for tubal sterilization. Accordingly per capita expenses were \345,000 for vasectomy and \467,000 for tubal sterilization. As the proportion of government sterilization program was decreased after 1988, that of private sterilization program would be increased. So it is recommended to set a guideline for the private sterilization program and to continue government sterilization program for the lower class.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.19 no.3
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• pp.265-286
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• 1997

Bone morphogenetic proteins(BMPs) are a group of transforming growth factor beta(TGF-${\beta}$)-related factors and multifunctional proteins, especially the only known biologic factors capable of inducing endochondral bone formation at an extraskeletal site. This study was performed to investigate the effect of the partially purified porcine BMP(pBMP) at an ectopic site. PBMP was partially purified from porcine bone matrix and its activity was monitored by an in vivo bioassay. The purification method utilized extraction of the bone-inducing activity with 4M guanidine, followed by chromatography on heparin-Sepharose. Active fractions were assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. And the fractions were reconstituted with inactive insoluble collagenous bone matrix from rats, acid soluble type I collagen from rat tail and chondroitin-6-sulfate sodium salt and implanted into the pectroralis muscle pouches of Sprague-Dawley rats. And the carrier complex was implanted on the opposite side as control. The rats were sacrificed at the day of 1st, 3rd, 5th, 7th, 11th, 14th and 21st after implantation and examined histologically, radiologically and biochemically. And alkaline phosphatase activity and calcium content were used as indices of bone formation. The results were as follows ; 1. Active fractions were localized in a zone between 31 and 40 KDa on SDS-PAGE. 2. The implanted 3.0mg of the partially purified pBMP induced cartilage and bone in the muscle tissue of rats through an endochondral ossification process. 3. Inactive insoluble bone matrix, type I collagen and chondroitin-6-sulfate have functioned as carriers for pBMP, but revealed some foreign body reactions. 4. Soft X-ray didn't reveal significant change between the experimental and the control group. 5. The alkaline phosphatase activities in the experimental group of 5th, 7th, 11th, 14th and 21st were increased significantly compared with control (p<0.01) with the peak in the group of 11th day. 6. With time, the calcium content of the experimental group increased. And the calcium contents in the experimental group of 11th, 14th and 21st were increased significantly compared with control (p<0.01).

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.3
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• pp.444-449
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• 2002

The term 'impaction' is used to designate a tooth which remains unerupted in the jaw beyond the time at which it should normally be erupted. The main causal factors are local (lack of space, ectopic positions of teeth, supernumerary teeth, cyst, the occurrence of infectious process in the eruption path, traumatic facial injury etc.). Systemic and genetic disorders, however, may have primary failure of eruption and retarded eruption as additional symptoms (cleidocranial dysplasia, osteopetrosis etc.). Most cases of impacted teeth reported in the literature are of permanent teeth. The absence of primary teeth occur rarely whereas impaction of second primary molars is more numerous than all other impactions. Impaction due to primary failure of eruption must be distinguished from the secondary infraocclusion. The etiology of impaction of primary teeth is probably related to early ankylosis of primary teeth, but it is not clear. Failure of eruption of primary teeth may cause a number of complications, such as interference with development and eruption of succedaneous teeth, formation of cyst, and damage to adjacent teeth. This study is to report cases of primary failure of eruption in the primary dentition.

• BMB Reports
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• v.53 no.6
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• pp.323-328
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• 2020

Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNFα) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNFα and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNFα is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNFα-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-κB) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNFα. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNFα-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNFα-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNFα-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression.

• Clinical and Experimental Reproductive Medicine
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• v.26 no.3
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• pp.331-338
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• 1999

The purposes of this study were to evaluate the effects of insulin-like growth factor (IGF)s in peritoneal fluid (PF) from patients with and without endometriosis on the proliferation of endometrial stromal cells and to investigate the effects of type I IGF receptor antibody on the response of endometrial stromal cells to PF from patients with endometriosis. IGFs in PF from patients with endometriosis (n=14) and without endometriosis (n=10) were measured by immunoradiometric assay and PF samples were divided into low IGF-I PF group (less than 85 ng/ml) and high IGF-I PF group (more than 85 ng/ml). Endometrial stromal cells from patients without endometriosis were cultured in serum free media in the presence or absence of 1 % PF and thymidine incorporation test were used to evaluate the proliferation of endometrial stromal cells. Also cultures were incubated with type I IGF receptor monoclonal antibody (${\alpha}IR_3$) before adding PF. PF from patients with endometriosis and without endometriosis increased thymidine incorporation in endometrial stromal cells. In patients with endometriosis, high IGF-I PF group had high IGF-II levels and resulted in higher thymidine incorporation than low IGF-I PF group but no significant difference in increase in thymidine incorporation between high IGF-I and low IGF-I PF group was noted in patients without endometriosis. There was not a significant correlation between increase in thymidine incorporation and IGF-I levels in PF from patients without endometriosis but in PF from patients with endometriosis. Preincubation with ${\alpha}IR_3$ significantly inhibited the mitogenic response of endometrial stromal cells to PF. Our data indicate that IGF-I in PF may be involved in the growth of ectopic endometrium in patients with endometriosis.