• 대한두경부종양학회지
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• 제30권2호
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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.

• 생명과학회지
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• 제23권1호
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• pp.1-7
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• 2013

작물의 생산성 증가를 위해 염해 저항성 메커니즘을 이해하는 것이 중요하다. 식물의 염해 저항성에 관련된 유전자를 확보하기 위한 여러 가지의 선별방법이 개발되었다. 본 논문에서는 애기장대의 cDNA 라이브리를 염해감수성 효모인 cnb 돌연변이체에 삽입하여 염해 감수성 표현형을 회복하는 콜로니를 선발하였다. 이 선별방법을 통하여 34종의 cnb 돌연변이체의 염해 감수성을 회복하는 콜로니를 선별하였으며, 염기서열분석을 통하여 CaS와 AtSUMO1, AtHB-12 등 9종의 유전자임을 확인하였다. 이들 유전자 중 CaS의 발현이 염해 저항성을 증가시키는 것과 염해 처리에 의해 CaS의 유전자의 발현이 증가되는 것을 확인하였다. CaS 발현억제 형질전환체는 100 mM 염처리에 의하여 뿌리생장이 저해되었다. 또한 150 mM 염처리에 의하여 CaS 발현억제 형질전환체의 잎에서 백화현상을 나타내었다. 이러한 결과를 통하여 CaS 유전자가 효모와 식물에서 염해 저항성에 중요한 유전자임을 증명하였다.

• 대한소아치과학회지
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• 제31권2호
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• pp.262-266
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• 2004

부갑상선 호르몬은 혈중 인농도를 낮추고, 칼슘농도를 증가시키는 호르몬으로 부갑상선기능저하증은 부갑상선이 존재하지 않거나 비정상적으로 기능하여 이 호르몬의 분비가 감소되는 질환이며, 가성부갑상선기능저하증은 부갑상선 호르몬 분비는 정상이나, 이 호르몬에 대한 골과 신장의 반응이상으로 혈중 칼슘 농도가 감소되고 인농도가 증가되는 질환이다. 가성부갑상선기능저하증은 임상적으로 성장 및 발육부전, 둥근 얼굴, 조기 골단폐쇄로 인한 단지증, 이소성 연조직 석회화, 비만, 두개관의 비후, 정신지체, 백내장 등이 나타난다. 구강내 소견으로는 치아의 맹출지연, 법랑질형성부전이 가장 큰 특징이며, 그 외에 결손치, 부정교합, 높은 구개궁, 확장된 치근관과 짧은 치근, 치수강 내 석회화, 높은 우식 이환율 치근막의 비후 등이 관찰된다. 본 증례에서 환아의 구강내 소견은 맹출한 하악 4전치와 상악 좌우측 영구 중절치, 상악 우측 영구 측절치, 상, 하악 제 1대구치에서 법랑질형성부전을 보였고, 다수의 유치에서 심한 동요도를 보였다. 방사선 소견으로는 대부분의 미맹출된 영구치들도 법랑질형성부전이 관찰되었으며, 특히 영구 견치의 경우 심한 치관의 형태이상을 볼 수 있었다. 또한 유치의 비정상적인 치근흡수가 나타났고, 하악 전치의 경우 치근형태가 짧고, 치근단이 둥근 형태로 나타났다. 이에 저자는 가성부갑상선기능저하증인 환아의 구강내 소견에 대해 보고하고자 한다.

• Molecules and Cells
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• 제41권9호
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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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• 제26권2호
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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.

• 지역사회간호학회지
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• 제7권1호
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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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• 제19권3호
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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).

• 대한소아치과학회지
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• 제29권3호
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• pp.444-449
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• 2002

치아의 맹출은 치아가 구강내 교합평면에 도달하여 기능적인 위치를 차지할 때까지의 치아 이동 및 골조직 내에서의 발달로 이루어지는 생리학적인 양상으로 이해되어진다. 그러나 치아가 정상적으로 맹출해야 하는 시기를 지나서도 골조직 내에서 맹출하지 않을 수 있으며, 이러한 치아를 매복치라 일컫는다. 이러한 치아 매복의 주된 요인은 국소적인 것으로 악궁내 공간 부족, 치아 위치 이상, 과잉치, 맹출 경로의 감염, 낭종 및 안면 외상으로 인한 치배의 영향 등이 있다. 또한 쇄골두개이골증, 골다공증 등의 전신적 그리고 유전적 질환도 맹출 장애와 맹출 지연 등과 관련이 있다. 현재까지 매복치의 대부분은 영구치로 보고되었으며 반면에 유치의 매복에 대한 것은 극히 소수에 불과하고, 매복된 유치의 대다수는 제 2 유구치이다. 유치의 매복은 유착에 의해 이차적으로 생긴 저위교합과는 구별되어야 하며, 유치의 매복에 대한 병인은 유치 치배의 비정상적인 발달로 인해 조기에 유착이 일어나는 것으로 추측되어지고 있으나, 아직까지 정확하게 밝혀진 바는 없다. 유치의 맹출 실패로 나타날 수 있는 문제점으로는 계승 영구치 발달 및 맹출 방해, 낭종 형성이나 감염의 발생 등을 생각해 볼 수 있다. 본 증례들은 연세대학교 치과대학병원 소아치과에 내원한 환아의 구강 및 방사선학적 검사에서 유구치의 매복이 관찰되었기에 이에 보고하는 바이다.

• BMB Reports
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• 제53권6호
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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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• 제26권3호
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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.