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검색결과 650건 처리시간 0.031초

Modification of ERα by UFM1 Increases Its Stability and Transactivity for Breast Cancer Development

  • Yoo, Hee Min;Park, Jong Ho;Kim, Jae Yeon;Chung, Chin Ha
    • Molecules and Cells
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    • 제45권6호
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    • pp.425-434
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    • 2022
  • The post-translational modification (e.g., phosphorylation) of estrogen receptor α (ERα) plays a role in controlling the expression and subcellular localization of ERα as well as its sensitivity to hormone response. Here, we show that ERα is also modified by UFM1 and this modification (ufmylation) plays a crucial role in promoting the stability and transactivity of ERα, which in turn promotes breast cancer development. The elevation of ufmylation via the knockdown of UFSP2 (the UFM1-deconjugating enzyme in humans) dramatically increases ERα stability by inhibiting ubiquitination. In contrast, ERα stability is decreased by the prevention of ufmylation via the silencing of UBA5 (the UFM1-activating E1 enzyme). Lys171 and Lys180 of ERα were identified as the major UFM1 acceptor sites, and the replacement of both Lys residues by Arg (2KR mutation) markedly reduced ERα stability. Moreover, the 2KR mutation abrogated the 17β-estradiol-induced transactivity of ERα and the expression of its downstream target genes, including pS2, cyclin D1, and c-Myc; this indicates that ERα ufmylation is required for its transactivation function. In addition, the 2KR mutation prevented anchorage-independent colony formation by MCF7 cells. Most notably, the expression of UFM1 and its conjugating machinery (i.e., UBA5, UFC1, UFL1, and UFBP1) were dramatically upregulated in ERα-positive breast cancer cell lines and tissues. Collectively, these findings implicate a critical role attributed to ERα ufmylation in breast cancer development by ameliorating its stability and transactivity.

Betulin, an Anti-Inflammatory Triterpenoid Compound, Regulates MUC5AC Mucin Gene Expression through NF-kB Signaling in Human Airway Epithelial Cells

  • Hossain, Rajib;Kim, Kyung-il;Jin, Fengri;Lee, Hyun Jae;Lee, Choong Jae
    • Biomolecules & Therapeutics
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    • 제30권6호
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    • pp.540-545
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    • 2022
  • Betulin is a triterpenoid natural product contained in several medicinal plants including Betulae Cortex. These medicinal plants have been used for controlling diverse inflammatory diseases in folk medicine and betulin showed anti-inflammatory, antioxidative, and anticancer activities. In this study, we tried to examine whether betulin exerts a regulative effect on the gene expression of MUC5AC mucin under the status simulating a pulmonary inflammation, in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with betulin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h or the indicated periods. The MUC5AC mucin mRNA expression and mucin glycoprotein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. To elucidate the action mechanism of betulin, effect of betulin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated by western blot analysis. The results were as follows: 1) Betulin significantly suppressed the production of MUC5AC mucin glycoprotein and down-regulated MUC5AC mRNA expression induced by PMA in NCI-H292 cells. 2) Betulin inhibited NF-κB activation stimulated by PMA. Suppression of inhibitory kappa B kinase (IKK) by betulin led to the inhibition of the phosphorylation and degradation of inhibitory kappa B alpha (IκBα), and the nuclear translocation of NF-κB p65. This, in turn, led to the down-regulation of MUC5AC glycoprotein production in NCI-H292 cells. These results suggest betulin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

High-velocity ballistics of twisted bilayer graphene under stochastic disorder

  • Gupta, K.K.;Mukhopadhyay, T.;Roy, L.;Dey, S.
    • Advances in nano research
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    • 제12권5호
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    • pp.529-547
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    • 2022
  • Graphene is one of the strongest, stiffest, and lightest nanoscale materials known to date, making it a potentially viable and attractive candidate for developing lightweight structural composites to prevent high-velocity ballistic impact, as commonly encountered in defense and space sectors. In-plane twist in bilayer graphene has recently revealed unprecedented electronic properties like superconductivity, which has now started attracting the attention for other multi-physical properties of such twisted structures. For example, the latest studies show that twisting can enhance the strength and stiffness of graphene by many folds, which in turn creates a strong rationale for their prospective exploitation in high-velocity impact. The present article investigates the ballistic performance of twisted bilayer graphene (tBLG) nanostructures. We have employed molecular dynamics (MD) simulations, augmented further by coupling gaussian process-based machine learning, for the nanoscale characterization of various tBLG structures with varying relative rotation angle (RRA). Spherical diamond impactors (with a diameter of 25Å) are enforced with high initial velocity (Vi) in the range of 1 km/s to 6.5 km/s to observe the ballistic performance of tBLG nanostructures. The specific penetration energy (Ep*) of the impacted nanostructures and residual velocity (Vr) of the impactor are considered as the quantities of interest, wherein the effect of stochastic system parameters is computationally captured based on an efficient Gaussian process regression (GPR) based Monte Carlo simulation approach. A data-driven sensitivity analysis is carried out to quantify the relative importance of different critical system parameters. As an integral part of this study, we have deterministically investigated the resonant behaviour of graphene nanostructures, wherein the high-velocity impact is used as the initial actuation mechanism. The comprehensive dynamic investigation of bilayer graphene under the ballistic impact, as presented in this paper including the effect of twisting and random disorder for their prospective exploitation, would lead to the development of improved impact-resistant lightweight materials.

Effect of peanut shell extract supplementation on the growth performance, carcass characteristics and meat quality of broilers

  • Narae, Han;Byong Won, Lee;Jung Min, Heo;Samooel, Jung;Mihyang, Kim;Jin Young, Lee;Yu-Yong, Lee;Moon Seok, Kang;Hyun-Joo, Kim
    • 농업과학연구
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    • 제49권3호
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    • pp.547-560
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    • 2022
  • The present study investigated the effects of dietary supplementation of peanut shell extract on the growth performance and physiological properties of broiler chicks. Two diet energy levels (Positive and Negative) and four additives (0.0, 0.05, and 0.1% peanut shell extract and commercial antioxidant) were factorially arranged for eight treatments. The overall weight gain of the broilers was slightly improved at 0.05% for the antioxidant treatments regardless of the diet energy levels, but there was no statistical difference among the treatments (p > 0.05). The carcass characteristics of the broilers, such as cooking loss, crude protein content, antioxidant activity, and thiobarbituric acid reactive substances (TBARS) values, were improved by the feeding diets containing the 0.05% peanut shell extract. Furthermore, it was confirmed that the dietary supplementation of peanut shell extract did not have a negative effect on the immune responses of the broilers show by the lack of statistical differences in the liver and bursa Fabricious weight and cytokine level among the treatments. From the economic analysis, dietary supplementation of peanut shell extract significantly influenced the compensatory growth and food efficiency and, in turn, led to a decrease in the duration needed to reach 1.5 kg compared to the control. These results suggest the possibility that the peanut shell extract could be used as a functional feed additive by improving the growth performance and carcass characteristics with no detrimental effects on broilers.

취수원 수질예측을 위한 성층 물리변수 활용 데이터 기반 모델링 연구 (A Study on Data-driven Modeling Employing Stratification-related Physical Variables for Reservoir Water Quality Prediction)

  • 장현준;정지영;주경원;이충성;김성훈
    • 한국수자원학회:학술대회논문집
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    • 한국수자원학회 2023년도 학술발표회
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    • pp.143-143
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    • 2023
  • 최근 대청댐('17), 평림댐('19) 등 광역 취수원에서 망간의 먹는 물 수질기준(0.05mg/L 이하) 초과 사례가 발생되어, 다수의 민원이 제기되는 등 취수원의 망간 관리 중요성이 부각되고 있다. 특히, 동절기 전도(Turn-over)시기에 고농도 망간이 발생되는 경우가 많은데, 현재 정수장에서는 망간을 처리하기 위해 유입구간에 필터를 설치하고 주기적으로 교체하는 방식으로 처리하고 있다. 그러나 단기간에 고농도 망간 다량 유입 시 처리용량의 한계 등 정수장에서의 공정관리가 어려워지므로 사전 예측에 의한 대응 체계 고도화가 필요한 실정이다. 본 연구는 광역취수원인 주암댐을 대상으로 망간 예측의 정확도 향상 및 예측기간 확대를 위해 다양한 머신러닝 기법들을 적용하여 비교 분석하였으며, 독립변수 및 초매개변수 최적화를 진행하여 모형의 정확도를 개선하였다. 머신러닝 모형은 수심별 탁도, 저수위, pH, 수온, 전기전도도, DO, 클로로필-a, 기상, 수문 자료 등의 독립변수와 화순정수장에 유입된 망간 농도를 종속변수로 각 변수에 해당하는 실측치를 학습데이터로 사용하였다. 그리고 데이터기반 모형의 정확도를 개선하기 위해서 성층의 수준을 판별하는 지표로서 PEA(Potential Energy Anomaly)를 도입하여 데이터 분석에 활용하고자 하였다. 분석 결과, 망간 유입률은 계절 주기에 따라 농도가 달라지는 것을 확인하였고 동절기 전도시점과 하절기 장마기간 난류생성 시기에 저층의 고농도 망간이 유입이 되는 것을 분석하였다. 또한, 두 시기의 망간 농도의 변화 패턴이 상이하므로 예측 모델은 각 계절별로 구축해 학습을 진행함으로써 예측의 정확도를 향상할 수 있었다. 다양한 머신러닝 모델을 구축하여 성능 비교를 진행한 결과, 동절기에는 Gradient Boosting Machine, 하절기에는 eXtreme Gradient Boosting의 기법이 우수하여 추론 모델로 활용하고자 하였다. 선정 모델을 통한 단기 수질예측 결과, 전도현상 발생 시기에 대한 추종 및 예측력이 기존의 데이터 모형만 적용했을 경우대비 약 15% 이상 예측 효율이 향상된 것으로 나타났다. 본 연구는 머신러닝 모델을 활용한 망간 농도 예측으로 정수장의 신속한 대응 체계 마련을 지원하고, 수처리 공정의 효율성을 높이는 데 기여할 것으로 기대되며, 후속 연구로 과거 시계열 자료 활용 및 물리모형과의 연결 등을 통해 모델의 신뢰성을 제고 할 계획이다.

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Korean red ginseng suppresses mitochondrial apoptotic pathway in denervation-induced skeletal muscle atrophy

  • Ji-Soo Jeong;Jeong-Won Kim;Jin-Hwa Kim;Chang-Yeop Kim;Je-Won Ko;Tae-Won Kim
    • Journal of Ginseng Research
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    • 제48권1호
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    • pp.52-58
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    • 2024
  • Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

형광스펙트럼을 이용한 유역 하류 저수지의 유입 유기물 내 유기인 기여도 평가 (Estimating the Relative Contribution of Organic Phosphorus to Organic Matters with Various Sources Flowing into a Reservoir Via Fluorescence Spectroscopy)

  • 이미희;이승윤;허진
    • 한국물환경학회지
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    • 제40권2호
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    • pp.67-78
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    • 2024
  • The introduction of a significant amount of phosphorous into aquatic environments can lead to eutrophication, which can in turn result in algal blooms. For the effective management of watersheds and the prevention of water quality problems related to nonpoint organic matter (OM) sources, it is essential to pinpoint the predominant OM sources. Several potential OM sources were sampled from upper agricultural watersheds, such as fallen leaves, riparian reeds, riparian plants, paddy soil, field soil, riparian soil, cow manure, and swine manure. Stream samples were collected during two storm events, and the concentrations of dissolved organic carbon (DOC) and phosphorous (DOP) from these OM sources and stream samples were assessed. DOM indicators using fluorescence spectroscopy, including HIX, FI, BIX, and EEM-PARAFAC, were evaluated in terms of their relevance in discerning DOM sources during storm events. Representative DOM descriptors were chosen based on specific criteria, such as value ranges and pronounced differences between low and high-flow periods. Consequently, the spectral slope ratio (SR) paired with fluorescence index (FI) using end-member mixing analysis (EMMA) proved to be suitable for estimating the contribution of organic carbon (OC). The contribution of each organic phosphorous (OP) in stream samples was determined using the phosphorous-to-carbon (P/C) ratio in conjunction with the OC contribution. Notably, OP derived from swine manure in stream samples was found to make the most dominant contribution, ranging from 61.3% to 94.2% (average 78.1% ± 12.7%). The results of this research offer valuable insights into the selection of suitable indicators to recognize various OM sources and highlight the main sources of OP in forested-agricultural watersheds.

압력조절환기법에서 압력상승시간(Pressure Rise Time)이 흡기 일환기량 및 가스교환에 미치는 영향 (Effect of Pressure Rise Time on Tidal Volume and Gas Exchange During Pressure Control Ventilation)

  • 정병오;고윤석;심태선;이상도;김우성;김동순;김원동;임채만
    • Tuberculosis and Respiratory Diseases
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    • 제48권5호
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    • pp.766-772
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    • 2000
  • 배경 : 압력조절환기법(pressure control ventilation mode, PCV)에서 설정된 기도압의 달성은 기도저항이 일정한 조건에서 초기 흡기 유량 (inspiratory flow)에 의해 결정되며 압력상승시간(pressure rise time) 조절은 이 흡기 유량을 변동시킨다. 압력조절환기법에서 흡기 일환기량은 흡기 시간과 흡기 시간내 평균 흡기 유량에 따라 결정되므로 압력 도달 시간을 짧게 하면 초기 유량이 많아지게 되고 따라서 흡기되는 용적이 증가할 것으로 예상된다. 본 연구는 압력조절환기 법에서 압력상승시간을 줄이는 것이 흡기 일환기량 및 가스교환을 호전시키는지 알아보고자 하였다. 방법 : 호흡부전으로 기계호흡 중인 환자 13명(58$\pm$16세, 남 : 여=7 : 6)에서 Servo 300 (Simens-Elema, Solna, Sweden) 상의 압력상승시간 10%. 5% 및 30분 간 씩 적용하고 동맥혈 검사, 혈역동학적 지표(혈압, 분당맥박수) 및 호흡 지표(일회 호흡량, 최대 흡기유량, 최대 흡기압, 평균 기도압, 기도저항, 탄성도, 호기말 이산화탄소, 동맥혈가스)를 측정하였다. 결과 : 1) 압력상승시간이 10%, 5%, 0%로 변경시 일회 호흡량은 425$\pm$94 ml, 439$\pm$101 ml, 456$\pm$106ml로 증가되었다(p<0.001). 압력상승시간 단축에 따라 평균기도압 역시 증가되었다(각각 11.2$\pm$3.7cm $H_2O$, 12.0$\pm$3.7 cm $H_2O$, 12.5$\pm$3.8 cm $H_2O$; p<0.001). 2) pH는 10% 와 5% 보다 0%에서 높았으며(각각 7.40$\pm$0.08, 7.40$\pm$0.92, 7.41$\pm$0.96 ; p<0.0), $PaCO_2$도 10%와 5%에서 보다 0%에서 낮았다(각각 47.4$\pm$15.8 mm Hg, 47.2$\pm$15.7 mm Hg, 44.6$\pm$16.2 mm Hg ; p<0.01). 결론 : 압력조절환기법에서 압력상승시간의 단축은 일환기량과 평균기도압을 증가시키고, 동맥혈이산화탄소분압 저하 및 이에 따른 pH 상승 효과가 있었다. 압력조절 환기법에서 압력상승시간은 일환기량을 조절할 수 있는 한 변수로 사료된다.

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독거노인의 사회안전망에 대한 활성화 방안 - 광양시 무선페이징시스템 대상자 중심으로 - (Activation plan of social safety network of the aged living alone - Focused on the aged using wireless paging system in Gwangyang-si -)

  • 이재민
    • 한국응급구조학회지
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    • 제13권3호
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    • pp.41-58
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    • 2009
  • Objective : The purpose of this study is to identify actual operations and issues of wireless paging system operation for the aged living alone as the end users of wireless paging system primarily in Gwangyang city, and thereby to explore possible advanced and integrated ways to promote social safety network for the aged. Methods : The survey tool used in this study was a structured questionnaire form consisting of question items. The researcher hereof conducted this survey by means of direct visit and interview during two seasons, i.e. from February to August, 2008 and from December 2008 to March 2009, respectively. Results : 1) For general demographic characteristics, it was found that 90.9% of all respondents were women and 61.2% of all respondents were at age 75 to 84. for health conditions, it was found that more than 90% of all respondents often took medicines due to their unhealthy body, and most of respondents suffered from musculoskeletal diseases 79.3% and circulatory diseases 61.6%. for walking capacity, it was found that 45.5% of all respondents used walking aids, and disable respondents (11.5% of all respondents) were represented primarily by those with physical disability (52.6% of disable respondents). for actual use of medical institutions, it was found 47.3% of all respondents relied on local clinics, since they preferred neighborhood hospitals or clinics they can trust for medical care. for social activities and supports, it was found that 43.6% respondents had 'needs for assistance at times' and 33.9% respondents have 'no need for assistance'. And it was found that the major difficulties in living alone at old age were represented primarily by health problems 37.8% and economic difficulties 33.5%. 2) For characteristics related to wireless paging system, it was found that 90.3% respondents used wireless paging system recommended by firemen, and 28.5% respondents used this system. and it was found that 59.6% respondents used this system once, and 85.2% respondents used it because of acute or chronic diseases. more than 90% respondents thought that they knew about wireless paging system and considered themselves safe, but 83.6% respondents didn't attach a remote control on their upper clothes, and even 49.1% respondents turned off the power of wireless paging system due to their concern about electricity bill and noise. 3) It was found that 83.6% respondents felt it necessary to use wireless paging system, and wireless paging users felt more satisfied with using the system than non-users, and 50.7% showed high satisfaction at certain psychological benefits like 'confidence in coping with critical situations' and 'a sense of relief'. In addition, it was found that some respondents who answered that 'they didn't turn off the paging system as they knew how it works' and those who answered that they knew 'how to use it' showed relatively high satisfaction. And some respondents who kept it well and felt it necessary also showed high satisfaction. 4) It was found that the level of satisfaction our respondents felt with using wireless paging system varied significantly availability($x^{2}$ = 12.759, p = .002), psychological advantages($x^{2}$ = 12.174, p = .002), knowledge about how to use system($x^{2}$ = 7.021, p = .016), power on/off($x^{2}$ = 13.221, p = .001), level of knowledge about system($x^{2}$ = 21.002, p = .000), maintenance($x^{2}$ = 9.871, p = .007) and level of necessity($x^{2}$ = 34.939, p = .000) on the statistical basis.

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비소세포성 폐암종의 CD44s 및 CD44v6의 발현에 대한 연구 -CD44의 발현에 대한 연구- (A Study on the Expression of CD44s and CD44v6 in Non-Small Cell Lung Carcinomas)

  • 장운하;오태윤;김정태
    • Journal of Chest Surgery
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    • 제39권1호
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    • pp.1-11
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    • 2006
  • 배경: CD44는 세포상호간 그리고 세포와 기질 사이의 부착을 조절하는 세포표면당단백질로 표준형인 CD44s와 여러 동종변형이 있다. CD44는 림프구와 단핵구를 활성화할 뿐만 아니라, 여러가지 상피성 종양의 진행과정에 참여하여 종양의 침습과 전이를 도와줄 것이라는 연구결과가 나오고 있다. 그러나, 종양의 종류에 따라 CD44의 표준형과 여러 동종변형의 발현양상이 다르고, 종양의 생물학적 특성과의 관련성에 대해서도 아직은 잘 알려져 있지 않다. 폐장에는 많은 종류의 원발성 악성종양과 전이성종양이 발생하기 때문에 폐암조직에서 CD44 당단백의 발현양상에 대해 연구하는 것이 폐암의 생물학적 특성뿐만 아니라 다른 종양의 전이에 관한 이해의 폭을 넓히는데 도움이 될 것으로 생각하여 본 연구를 시행하였다. 대상 및 방법: 1985년부터 1994년까지 비소세포성폐암으로 진단한 후 절제하여 의뢰된 48예의 편평세포암종, 33예의 선암종, 8예의 미분화성대세포암종을 합한 총 89예의 폐암조직을 대상으로 연구하였다. CD44 당단백질은 표준형인 CD44s와 동종변형인 CD44v6에 대해 면역조직화학염색을 시행하여 발현정도를 평가하였다. 종양의 미세혈관분포는 혈관내피세포 표지자인 CD34에 대한 면역조직화학염색을 시행하여 200배 및 400배 현미경 시야에서 혈관의 수를 헤아렸다. CD44s와 CD44v6의 발현정도와 미세혈관의 수 사이에 연관성을 검정하였다. 이 결과를 환자의 나이, 성별, 병기, 종양의 크기, 림프절 전이 여부, 종양의 병리조직학적 유형 및 생존율과 비교하였다. 결과: CD44s와 CD44v6는 89예의 비소세포폐암종 중 각각 71예(79.8$\%$)와 64예(71.9$\%$)에서 발현하였다. 이 두 당단백의 발현은 상호 관련성이 있었다(p < 0.0001). CD44s와 CD44v6모두 편평세포암종에서 각각 95.8$\%$로 가장 높은 발현율을 보였다(p < 0.0001). CD44s의 발현은 편평세포암종의 분화도와 관련이 있었는데 (p=0.008), 불량한 분화를 보이는 암종이 양호한 분화의 암종보다 발현율이 높았으며(p=0.002), 중등도 분화를 보인 암종과는 유의한 차이가 없었다. CD44v6의 발현은 편평세포암종과 선암종의 분화도와 관련이 없었다. CD44s의 발현은 종양의 미세혈관의 수와 상관관계를 보였다(p=0.019 및 p=0.007). 종양의 미세혈관의 수는 종양의 크기와 상관 관계가 있었다 (각각 p=0.043). 그러나, 나이, 성별, 병기, 림프절 전이 및 생존율과는 관련성이 없었다. 결론: 이상의 결과에서, 종양의 미세혈관의 수가 CD44s의 발현과 상관관계가 있고, 종양의 크기와도 상관관계를 보이는 점으로 미루어 CD44s가 종양의 성장과 혈관 형성에 관련되어 있을 가능성을 시사한다. CD44s와 CD44v6의 발현이 편평세포암종에서 가장 높은 발현율을 보이는 것으로 보아 조직형태학적 특성과 관련이 있을 것으로 생각한다.