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      • 간호대생과 의대생의 간호사 이미지 비교

        구민진,김수영,방정민,서아영,양희진,윤소람,이윤재,이재은,이지연,정윤경,최수정 이화여자대학교 간호과학대학 2014 이화간호학회지 Vol.- No.48

        Purpose: This study aims to analyze the difference in the perception that nursing students and medical students have regarding the image of nurses. Method: The sampling group for this study was made up of 111 nursing students and 117 medicine students, conducted from the 19th August 2013 to 3rd September 2013. The tool used for this study is the “Nurse Image Scale”. The data is analyzed using the SPSS 21.0 program, technical stats, t-test and ANOVA with Scheffe test. Result: There was a notable difference in the results(t=6.94, p<001), with the average image perception score of nurses at 3.84±0.34 amongst nursing students being higher than the 3.50±0.38 amongst Medicine students. The average score of the 4 areas tested, “Qualification of a Nurse”, “Role of a Nurse”, “Social Participation of a Nurse” and “Interpersonal Skills of a Nurse” were all marked higher by the nursing students than the medicine students. The average score became notably higher as the period of practice became shorter with nursing students (F=4.21, p=.043). Furthermore, the average score for the “Qualification of a Nurse” was notably higher as the period of practice became shorter (F=3.98, p=.049). Medical students gave an average score for the “Qualification of a Nurse”(F=3.72, p=.027) and the “Interpersonal Skills of a Nurse”(F=4.11, p=.019) which was relative to the development of a nurse's image, while the average score for the “Role of a Nurse” was notably higher with a longer period of practice(F=6.65, p=.011). Conclusion: The results of this study suggest that the image perception of a nurse can vary depending on the experience in period of practice. Therefore, together with this study conducted with nursing students and medicine students, there is a need for further studies conducted on image perception of nurses with various experience in period of practice.

      • SCIESCOPUSKCI등재후보

        Viator vitreocola gen. et sp. nov. (Stylonematophyceae), a new red alga on drift glass debris in Oregon and Washington, USA

        Hansen,,Gayle,I.,West,,John,A.,Yoon,,Hwan,Su,Goodman,,Christopher,D.,Goer,,Susan,Loiseaux-de,Zuccarello,,Giuseppe,C. The Korean Society of Phycology 2019 ALGAE Vol.34 No.2

        A new encrusting red alga was found growing abundantly on glass debris items that drifted ashore along the coasts of Oregon and Washington. These included discarded fluorescent tubes, incandescent light bulbs, capped liquor bottles, and ball-shaped fishing-net floats. Field collections and unialgal cultures of the alga revealed that it consisted of two morphological phases: a young loosely aggregated turf and a mature consolidated mucilaginous crust. The turf phase consisted of a basal layer of globose cells that produced erect, rarely branched, uniseriate to multiseriate filaments up to $500{\mu}m$ long with closely spaced cells lacking pit-plugs. These filaments expanded in size from their bases to their tips and released single cells as spores. At maturity, a second phase of growth occurred that produced a consolidated crust, up to $370{\mu}m$ thick. It consisted of a basal layer of small, tightly appressed ellipsoidal-to-elongate cells that generated a mucilaginous perithallial matrix containing a second type of filament with irregularly spaced cells often undergoing binary division. At the matrix surface, the original filaments continued to grow and release spores but often also eroded. Individual cells, examined using confocal microscopy and SYBR Green staining, were found to contain a central nucleus, a single highly lobed peripheral chloroplast without a pyrenoid, and numerous chloroplast nucleoids. Morphological data from field and culture isolates and molecular data (rbcL, psbA, and SSU) show that this alga is a new genus and species which we name Viator vitreocola, "a traveller on glass."

      • KCI등재

        Development of Sensitive Analytical Method of Rhodanthpyrone A by a LC-MS/MS and its Application to Bioavailability Study in Rats

        Bitna,Kang,Jeong,A,Yoon,송임숙,Young,Taek,Han,Min-Koo,Choi 사단법인 한국질량분석학회 2019 Mass spectrometry letters Vol.10 No.3

        A sensitive analytical method of rhodanthpyrone A in rat plasma was developed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rhodanthpyrone A and rhodanthpyrone B (internal standard) in rat plasma were extracted by a liq-uid-liquid extraction method with ethyl acetate. This extraction method gave results in high and reproducible extraction recovery in the range of 73.75-79.90% with no interfering peaks around the peak elution time of rhodanthpyrone A and B. The standard calibra- tion curves for rhodanthpyrone A ranged from 0.5 to 2000 ng/mL were linear with r 2 > 0.994 and the inter- and intra-day accuracy and precision and the stability were within acceptance criteria. Using this validated analytical method, pharmacokinetics of rhodanth-pyrone A following intravenous and oral administration of rhodanthpyrone A at doses of 2 mg/kg and 30 mg/kg, respectively, were investigated. Rhodanthpyrone A in rat plasma showed multi-exponential elimination pattern with high clearance and volume of dis-tribution values. The absolute oral bioavailability of this compound was calculated as 3.7%. Collectively, the newly developed sensi-tive LC-MS/MS analytical method of rhodanthpyrone A could be successfully applied to investigate the pharmacokinetic properties of this compound and would be useful for the further studies on the efficacy, toxicity, and biopharmaceutics of rhodanthpyrone A

      • SCISCIESCOPUS

        A ratiometric fluorescent probe for Zn<sup>2+</sup> based on pyrene-appended naphthalimide-dipicolylamine

        Yoon,,Shin,A,Lee,,Jinju,Lee,,Min,Hee Elsevier 2018 Sensors and actuators. B Chemical Vol.258 No.-

        <P><B>Abstract</B></P> <P>A pyrene-appended naphthalimide-dipicolylamine was developed as a ratiometric fluorescent probe for Zn<SUP>2+</SUP> ions. This probe displayed a ratiometric change in the fluorescent intensities at 385 and 530nm corresponding to the emissions of pyrene and naphthalimide units for Zn<SUP>2+</SUP> over other metal ions, allowing for a precise quantitative analysis of the Zn<SUP>2+</SUP> ion. The fluorescent color change was also visualized from blue to green. We demonstrated that probe recognized Zn<SUP>2+</SUP> ions based on a 1:1 stoichiometric binding event and it showed a high sensitivity (limit of detection: 10.5nM) and a rapid detection time for the Zn<SUP>2+</SUP> ion. In addition, the ratiometric change was found to be highly selective for the Zn<SUP>2+</SUP> ions even in the existence of other competitive metal ions including Cd<SUP>2+</SUP>, Pb<SUP>2+</SUP>, Hg<SUP>2+</SUP>, Ni<SUP>2+</SUP>, Co<SUP>2+</SUP> and Cu<SUP>2+</SUP> ions. Moreover, this probe was able to detect Zn<SUP>2+</SUP> ion in a wide pH range of 4–11 and it could be efficiently recycled by treating ethylenediaminetetraacetic acid (EDTA). Furthermore, this probe was successfully utilized for measurement of Zn<SUP>2+</SUP> concentration contained in drug commercially available zinc supplement.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A pyrene-appended naphthalimide-dipicolylamine was synthesized. </LI> <LI> This exhibited a selective ratiometric fluorescence change for Zn<SUP>2+</SUP> ion. </LI> <LI> This showed a 10.5nM of detection limit and a rapid response time for the Zn<SUP>2+</SUP>. </LI> <LI> Probe displayed a good reusability for the Zn<SUP>2+</SUP> upon treatment of EDTA reagent. </LI> <LI> Probe was applied to measurement of Zn<SUP>2+</SUP> concentration contained in drug. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • SCOPUSKCI등재

        Development of Sensitive Analytical Method of Rhodanthpyrone A by a LC-MS/MS and its Application to Bioavailability Study in Rats

        Kang,,Bitna,Yoon,,Jeong,A,Song,,Im-Sook,Han,,Young,Taek,Choi,,Min-Koo Korean Society for Mass Spectrometry 2019 Mass spectrometry letters Vol.10 No.3

        A sensitive analytical method of rhodanthpyrone A in rat plasma was developed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rhodanthpyrone A and rhodanthpyrone B (internal standard) in rat plasma were extracted by a liquid-liquid extraction method with ethyl acetate. This extraction method gave results in high and reproducible extraction recovery in the range of 73.75-79.90% with no interfering peaks around the peak elution time of rhodanthpyrone A and B. The standard calibration curves for rhodanthpyrone A ranged from 0.5 to 2000 ng/mL were linear with $r^2$ > 0.994 and the inter- and intra-day accuracy and precision and the stability were within acceptance criteria. Using this validated analytical method, pharmacokinetics of rhodanthpyrone A following intravenous and oral administration of rhodanthpyrone A at doses of 2 mg/kg and 30 mg/kg, respectively, were investigated. Rhodanthpyrone A in rat plasma showed multi-exponential elimination pattern with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 3.7%. Collectively, the newly developed sensitive LC-MS/MS analytical method of rhodanthpyrone A could be successfully applied to investigate the pharmacokinetic properties of this compound and would be useful for the further studies on the efficacy, toxicity, and biopharmaceutics of rhodanthpyrone A.

      • KCI등재SCIESCOPUS

        A Novel Method to Differentiate Tonsil-Derived Mesenchymal Stem Cells In Vitro into Estrogen-Secreting Cells

        Kim,Hee-Yeon,Lee,Younghay,Yoon,Hee-Soo,Kim,Yu-Hee,Cho,Kyong-A,Woo,So-Youn,김한수,박보영,Jung,Sung-Chul,Jo,Inho,Park,Woo-Jae,Park,Joo-Won,유경하 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.2

        BACKGROUND: The advantages of tonsil-derived mesenchymal stem cells (TMSCs) over other mesenchymal stem cells (MSCs) include higher proliferation rates, various differentiation potentials, efficient immune-modulating capacity, and ease of obtainment. Specifically, TMSCs have been shown to differentiate into the endodermal lineage. Estrogen deficiency is a major cause of postmenopausal osteoporosis and is associated with higher incidences of ischemic heart disease and cerebrovascular attacks during the postmenopausal period. Therefore, stem cell-derived, estrogen-secreting cells might be used for estrogen deficiency. METHODS: Here, we developed a novel method that utilizes retinoic acid, insulin-like growth factor-1, basic fibroblast growth factor, and dexamethasone to evaluate the differentiating potential of TMSCs into estrogen-secreting cells. The efficacy of the novel differentiating method for generation of estrogen-secreting cells was also evaluated with bone marrow- and adipose tissue-derived MSCs. RESULTS: Incubating TMSCs in differentiating media induced the gene expression of cytochrome P450 19A1 (CYP19A1), which plays a key role in estrogen biosynthesis, and increased 17β-estradiol secretion upon testosterone addition. Furthermore, CYP11A1, CYP17A1, and 3β-hydroxysteroid dehydrogenase type-1 gene expression levels were significantly increased in TMSCs. In bone marrow-derived and adipose tissue-derived MSCs, this differentiation method also induced the gene expression of CYP19A1, but not CYP17A1, suggesting TMSCs are a superior source for estrogen secretion. CONCLUSION: These results imply that TMSCs can differentiate into functional estrogen-secreting cells, thus providing a novel, alternative cell therapy for estrogen deficiency. BACKGROUND: The advantages of tonsil-derived mesenchymal stem cells (TMSCs) over other mesenchymal stem cells (MSCs) include higher proliferation rates, various differentiation potentials, efficient immune-modulating capacity, and ease of obtainment. Specifically, TMSCs have been shown to differentiate into the endodermal lineage. Estrogen deficiency is a major cause of postmenopausal osteoporosis and is associated with higher incidences of ischemic heart disease and cerebrovascular attacks during the postmenopausal period. Therefore, stem cell-derived, estrogen-secreting cells might be used for estrogen deficiency. METHODS: Here, we developed a novel method that utilizes retinoic acid, insulin-like growth factor-1, basic fibroblast growth factor, and dexamethasone to evaluate the differentiating potential of TMSCs into estrogen-secreting cells. The efficacy of the novel differentiating method for generation of estrogen-secreting cells was also evaluated with bone marrow- and adipose tissue-derived MSCs. RESULTS: Incubating TMSCs in differentiating media induced the gene expression of cytochrome P450 19A1 (CYP19A1), which plays a key role in estrogen biosynthesis, and increased 17β-estradiol secretion upon testosterone addition. Furthermore, CYP11A1, CYP17A1, and 3β-hydroxysteroid dehydrogenase type-1 gene expression levels were significantly increased in TMSCs. In bone marrow-derived and adipose tissue-derived MSCs, this differentiation method also induced the gene expression of CYP19A1, but not CYP17A1, suggesting TMSCs are a superior source for estrogen secretion. CONCLUSION: These results imply that TMSCs can differentiate into functional estrogen-secreting cells, thus providing a novel, alternative cell therapy for estrogen deficiency.

      • SCIEKCI등재

        ORIGINAL ARTICLE : The association between an abnormal post-voiding urine volume and a lower estimated glomerular filtration rate in patients with type 2 diabetes with no voiding symptoms

        ( A Jin Cho ), ( Sung Tae Cho ), ( Young Ki Lee ), ( Jieun Oh ), ( Sung Gyun Kim ), ( Jang Won Seo ), ( Jong Woo Yoon ), ( Ja Ryong Koo ), ( Hyung Jik Kim ), ( Yong Seong Lee ), ( Young Goo Lee ), ( Jung Woo Noh) 대한내과학회 2015 The Korean Journal of Internal Medicine Vol.30 No.1

        Background/Aims: Diabetic cystopathy is a frequent complication of diabetes mellitus. This study assessed the association between the post-voiding residual (PVR) urine volume and diabetic nephropathy in type 2 diabetics with no voiding symptoms. Methods: This study investigated 42 patients with type 2 diabetes who were followed regularly at our outpatient clinic between July 1, 2008 and June 30, 2009. No patient had voiding problems or International Prostate Symptom Scores (IPSSs) ≥12. An urologist performed the urological evaluations and the PVR was measured using a bladder scan. A PVR > 50 mL on two consecutive voids was considered abnormal, which was the primary study outcome. Results: The mean patient age was 60 ± 10 years; the IPSS score was 3.7 ± 3.3; and the diabetes duration was 11.9 ± 7.8 years. Seven of the 42 patients (16.7%) had a PVR > 50 mL. The presence of overt proteinuria or microalbuminuria was associated with an increased risk of a PVR > 50 mL (p < 0.01). Patients with a PVR > 50 mL had a significantly lower estimated glomerular filtration rate (eGFR) compared with those with a PVR ≤50 mL (59.2 ± 27.1 mL/min/1.73 m2 vs. 28.7 ± 23.3 mL/ min/1.73 m2; p < 0.001). Multivariate logistic analysis revealed that a lower eGFR (odds ratio, 0.94; 95% confidence interval, 0.88 to 0.99; p = 0.04) was a significant risk factor for a PVR > 50 mL. Conclusions: Patients with diabetic nephropathy had a significantly higher PVR and a lower eGFR was associated with an abnormal PVR.

      • KCI등재

        서비스디자인 측면의 공공공간 특성 연구: 국내외 국제공항 중심으로

        윤정아 ( Jung A Yoon ), 박영호 ( Young Ho Park ), 이돈일 ( Don Il Lee ) 한국기초조형학회 2015 기초조형학연구 Vol.16 No.1

        세계가 정보화, 글로벌화 되면서 산업구조는 다변화되고 있으며, 시스템의 고도화로 서비스디자인에 대한 needs가다양하게 요구되고 있다. 최근 생활수준 향상으로 인해 국가의 방문 목적이 다양해지고, 방문객들의 서비스에 대한 욕구도 높아짐에 따라 그 나라의 관문역할을 하는 국제공항 내 공공공간의 기능이 중요해지고 있다. 현재 국제공항은 기본적인 기능 외에 문화·예술성과 사용자 만족에 따른 융·복합공간으로 발전되고 있는 추세로 매력적이고 소통이 가능한 체계적인 공간계획이 요구된다. 본 연구는 공공공간과 서비스디자인의 선행연구를 통한 서비스디자인측면의 공공공간의 특성을 연구하고, 공항의 공공공간을 서비스시스템적 측면의 물리적 공간과 멀티스페이스적 측면의 경험적 공간과 장소브랜딩적 측면의 상징적 공간으로 구분하여 그에 따른 공간 특성을 복합성, 연계성, 개방성, 문화성, 장소성, 지역성으로 나누어 세부요소를 제시하였다. 국내외 선진 국제공항의 사례를 공공공간을 위한 서비스디자인 분석 요소에 따른 평가와 직접 방문 경험이 있는 이용자를 대상으로 인터뷰 및 평가지를 실시한 결과, 지리적 특성상의 접근성은다소 부족하였으나 문화성, 개방성, 지역성을 중점으로 모든 요소들이 고르게 나타났다. 이에 따라, 공공공간의 특성에 따른 적합한 서비스디자인 요소들의 상호작용을 통하여 공간운영이 효율적이고 이용 고객의 서비스 만족도가 높은공항으로 성장가능하다. 따라서 본 논문은 공항의 공공공간을 위한 서비스디자인의 방향성을 제시하고 향후, 통합적인 서비스디자인 측면의 공공공간을 위한 기초 연구로서 의의를 가지며 디자인 계획의 기본 방향으로 활용될 수 있을것이다. As the world has become globalization and information, Industrial structure has been diversified all everything. Also, there is a needs for a variety of service by the upgrading system. Recently, due to the improved living standard, the purpose of visiting to the country is getting various and more important for the public space that acts as a gateway role at the international airport. The current trend is required to develop complex financial and space according to the culture and artistic addition to the basic feature and user`s satisfaction so that the international airport is attractive and can communicate this systematic spatial planning. This study researches on the characteristics of public space aspects of the service design throughout a prior study of the public space and service design and Airport in the public space is divided into a physical space of the public service-system and empirical spatial aspects of multi-space, symbolic space of the place-branding side aspects of airport space. Each spatial characteristics are divided into a complexity, connectivity, openness, Ministry of Culture, of place, locality and given a detailed elements accordingly. It was derived from Domestic and foreign advanced international airport in the case by conducting interviews and assessment aimed at users with evaluation of the service design element analysis and experience in person. As a result, it is a little lack of accessibility of geographic nature though, all the factors all equally appeared focus on the Ministry of Culture, Openness, Locality. Therefore, leading airports has grown into a highly profitable by interacting with each other appropriate service components according to the characteristics, so that space operations are efficient and the satisfaction of customer service is high. This suggests the direction of the service design for the public space of the airport. The study has the meaning of the significance as a basic for the public space design aspects of future integrated services. Also it could be used as the primary direction of the design plan.

      • KCI등재

        조기분만진통 임부와 만삭 전 조기양막파열 임부의 정맥혈장내 산화 스트레스 지표

        김윤하 ( Yoon Ha Kim ), 노은지 ( Eun Ji Noh ), 백주아 ( Ju A Back ), 김종운 ( Jong Woon Kim ), 송태복 ( Tae Bok Song ) 대한주산의학회 2015 大韓周産醫學會雜誌 Vol.26 No.4

        목적: 조기분만진통 및 만삭 전 조기양막파열 임부의 정맥혈장내 산화능과 항산화능의 차이를 비교하고 산화 스트레스가 조기양막파열의 병태생리에 어떤 역할을 하는가를 규명하고자 하였다.방법: 75명의 임부를 대상으로 정맥혈을 채취하고 원심분리 후 혈장을 얻었다. (1) A군, 정상 임부 24명, (2) B군, 조기분만진통 임부 25명, (3) C군, 만삭 전 조기양막파열 임부 26명. thiobarbituric acid 반응을 이용하여 지질과산화물 농도를 측정하였고, 2,4-dinitrophenylhydrazine 방법을 이용하여 단백질의 carbonyl 기 함량을 측정하였으며, oxygen radical absorbance capacity assay (ORAC)로 총 항산화능을 측정하였다. Mann-Whitney U test, Kruskal Wallis test를 이용하여 분석하였다. 결과: B군과 C군의 정맥혈장내 지질과산화 치는 A군에 비해 의미있게 높았으며(B군: 4.59±0.30, C군: 5.40±0.22 vs. A군: 3.90±0.26 nmol/mg protein, P<0.05), C군의 정맥혈장내 지질과산화 치는 B군에 비해 의미있게 높았다. C군의 정맥혈장내 carbonyl기 함량은 A군에 비해 의미있게 높았으며(C군: 5.68±0.42 vs. A군: 5.43±0.41 nmol/mg protein, P<0.05), A군과 B군간의 carbonyl기 함량에는 차이가 없었다. 항산화능에 있어서는 B군과 C군이 A군에 비해 의미있게 낮았으며(B군: 117.91±0.48, C군: 111.68±1.23 vs. A군: 119.14±1.12 mM/mL, P<0.05), C군이 B군에 비해 의미있게 낮았다(P<0.05). 결론: 만삭 전 조기양막파열시 조기분만진통에 비해 정맥혈장에서 산화적 변화가 증가되어 있었으며 항산화능은 감소되어 있었다. 이는 조기양막파열시 산화적 스트레스가 증가되어 있을 가능성을 시사한다. Purpose: This study was performed to investigate the oxidation and antioxidation capacity in the maternalvenous plasma of preterm labor with intact membranes, and premature rupture of membranes (PPROM), andalso to evaluate their roles in the pathophysiology of PPROM. Methods: Seventy five women in the following categories had venous blood retrieved: (1) Group A, normal pregnancy (n=24). (2) Group B, preterm labor with intact membranes (n=25). (3) Group C, preterm premature rupture of membranes (n=26). Malondialdehyde (MDA) levels as a marker of lipid peroxidation by thiobarbituric acid reaction, protein carbonyl content by 2,4-dinitrophenylhydrazine reaction, and total antioxidant capacity by oxygen radical absorbance capacity assay (ORAC) were measured. Mann-Whitney U test, Kruskal-Wallis test were used for statistical analysis. Results: Lipid peroxide levels in the venous plasma of group B and C were significantly higher than those of group A (group B: 4.59±0.30, group C: 5.40±0.22 vs. group A: 3.90±0.26 nmol/mg protein, P<0.05). Lipid peroxide levels in the venous plasma of group C were significantly higher than those of group B (P<0.05). Protein carbonyl levels in the venous plasma of group C were significantly higher than those of group A (group C: 5.68±0.42 vs. group A: 5.43±0.41 nmol/mg protein, P<0.05). There was no significant difference of protein carbonyl levels in the venous plasma between group A and B. ORAC levels in the venous plasma of group B and C were significantly lower than those of group A (group B: 117.90±0.48, group C: 111.68±1.23 vs. group A: 119.14±1.12 mM/mL, P<0.05). ORAC levels in the venous plasma of group C were significantly lower than those of group B (P<0.05). Conclusion: In the blood of the women with preterm premature rupture of membranes, the lipid peroxidation was increased and the antioxidant capacity was decreased compared to women with normal pregnancy and preterm labor with intact membranes. These results suggest that oxidative stress was increased in preterm premature rupture of membranes.

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        Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells

        Lee,,Yoon-Jin,Bae,,Jin-Ho,Kim,,Soo-A,Kim,,Sung-Ho,Woo,,Kee-Min,Nam,,Hae-Seon,Cho,,Moon-Kyun,Lee,,Sang-Han Korean Society for Molecular and Cellular Biology 2017 Molecules and cells Vol.40 No.8

        The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

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