• 제목/요약/키워드: Human trials

검색결과 399건 처리시간 0.021초

Multiple Effects of a Novel Epothilone Analog on Cellular Processes and Signaling Pathways Regulated by Rac1 GTPase in the Human Breast Cancer Cells

  • Zhang, Hong;An, Fan;Tang, Li;Qiu, Rongguo
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권2호
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    • pp.109-120
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    • 2014
  • The epothilones are a class of microtubule inhibitors that exhibit a strong antitumor activity. UTD2 is a novel epothilone analog generated by genetic manipulation of the polyketide biosynthetic gene cluster. This study investigated the effects of UTD2 on the actin cytoskeleton and its critical regulators, and the signaling pathways which are essential for cell motility, growth and survival in MCF-7 breast cancer cells. Results showed that UTD2 inhibited the cellular functions of actin cytoskeleton, such as wound-closure, migration and invasion, as well as adhesion. Our study further demonstrated that UTD2 suppressed Rac1 GTPase activation and reduced the activity of PAK1, which is a downstream effector of Rac1, while the activity of Cdc42 was not affected. Additionally, the phosphorylation of p38 and ERK were significantly inhibited, but the phosphorylation of JNK remained the same after UTD2 treatment. Moreover, UTD2 inhibited the activity and mRNA expression of MMP-2, which plays a key role in cell motility. UTD2 also reduced the phosphorylation of Akt, which is an important signaling kinase regulating the cell survival through Rac1. Furthermore, UTD2 interrupted the synergy between Rac1 and Raf in focus formation assays. Taken together, these results indicated that UTD2 exerted multiple effects on the actin cytoskeleton and signaling pathways associated with Rac1. This study provided novel insights into the molecular mechanism of the antineoplastic and antimetastatic activities of epothilones. Our findings also suggest that the signaling pathways regulated by Rac1 may be evaluated as biomarkers for the response to therapy in clinical trials of epothilones.

Efficiency Evaluation of Nozawa-Style Black Light Trap for Control of Anopheline Mosquitoes

  • Lee, Hee-Il;Seo, Bo-Youl;Shin, E-Hyun;Burkett, Douglas A.;Lee, Jong-Koo;Shin, Young-Hack
    • Parasites, Hosts and Diseases
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    • 제47권2호
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    • pp.159-165
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    • 2009
  • House-residual spraying and insecticide-treated bed nets have achieved some success in controlling anthropophilic and endophagic vectors. However, these methods have relatively low efficacy in Korea because Anopheles sinensis, the primary malaria vector, is highly zoophilic and exophilic. So, we focused our vector control efforts within livestock enclosures using ultraviolet black light traps as a mechanical control measure. We found that black light traps captured significantly more mosquitoes at 2 and 2.5 m above the ground (P<0.05). We also evaluated the effectiveness of trap spacing within the livestock enclosure. In general, traps spaced between 4 and 7m apart captured mosquitoes more efficiently than those spaced closer together (P>0.05). Based on these findings, we concluded that each black light trap in the livestock enclosures killed 7,586 female mosquitoes per trap per night during the peak mosquito season (July-August). In May-August 2003, additional concurrent field trials were conducted in Ganghwa county. We got 74.9% reduction (P<0.05) of An. sinensis in human dwellings and 61.5% reduction (P>0.05) in the livestock enclosures. The black light trap operation in the livestock enclosures proved to be an effective control method and should be incorporated into existing control strategies in developed countries.

Haplotype Analysis and Single Nucleotide Polymorphism Frequency of Organic Cation Transporter Gene (OCT1 and 2) in Korean Subjects

  • Kim, Se-Mi;Lee, Sang-No;Yoon, Hwa;Kang, Hyun-Ah;Cho, Hea-Young;Lee, Il-Kwon;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • 제39권5호
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    • pp.345-351
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    • 2009
  • Organic cation transporters (OCTs) are important for absorption, elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is located in a cluster on chromosome 6 and OCTs are in major organs such as intestine, liver, kidney, brain and placenta. Therefore, expression levels and function of OCTs directly affect plasma levels and intracellular concentrations of drugs and thereby determine therapeutic response. The aim of this study was to investigate the frequency of the SNPs on OCT1 (C181T and C1022T) and OCT2 (G808T) to analyze haplotype frequency in healthy Korean population. Human subjects have been genotyped for OCT1 (C181T for 195 subjects and C1022T for 825 subjects), using polymerase chain reaction-based diagnostic tests (RFLP). And for OCT2 (G808T), a total of 861 subjects have been genotyped, using pyrosequencing method. Haplotype was statistically inferred using an algorithm based on the expectation-maximization (EM). OCT1 C181T genotyping showed 100% homozygous wild-type (C/C). OCT1 C1022T genotyping showed wild-type (C/C), heterozygous (C/T) and homozygous mutant-type (T/T) and each accounted for 72.1, 24.5 and 3.4%, respectively. OCT2 G808T genotyping results also showed homozygous wild-type (G/G), heterozygous (G/T) and homozygous mutant-type (T/T) and each took 81.8, 17.9 and 0.3%, respectively. Based on these genotype data, haplotype analysis between OCT1 C181T and OCT1 C1022T has proceeded. The result has revealed that linkage disequilibrium between alleles is not obvious (P=0.0122).

미래 지식정보시대의 새로운 디자인 패러다임 구조파악과 교육프로그램 전략 및 커리큘럼 개발에 관한 연구 (The Development of Strategy for Educational Program and Curriculum Based on Understanding New Design Paradigm of Future Knowledge-Information Age)

  • 민경우;이순종;이건표
    • 디자인학연구
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    • 제15권1호
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    • pp.399-406
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    • 2002
  • 21세기에 들어서면서 디자인이 변해가고 있다는 많은 담론적 이야기는 행해지고 있지만 아직 체계적으로 그 새로운 디자인 패러다임의 실체규명을 이루고 이를 근간으로 한 디자인 교육 프로그램의 전략 제시는 연구가 부족한 실정이다. 이에 본 연구는 문화적 관점에서 디자인 패러다임의 구조 변화를 규명하고 이에 맞는 새로운 지식 정보사회의 디자인 교육프로그램의 기본 전략을 개발하고 제시하는 것을 그 연구 목적으로 한다. 우선 문화적 관점에서 디자인을 이해하여 이의 기본 구조를 밝혔다. 문화는 가장 구체적인 '인공물', 그리고 '가치'와 가장 추상적이고 관념적인 '잠재의식' 등의 구조로 형성되어 있으며 이는 상호 순환적인 관계에 있음이 밝혀졌다. 이는 곧 디자인 속성의 기본 구조인 '기능', '심미성', '상징성' 등의 구조와도 부합되는 것으로 이는 곧 디자인 패러다임의 변천에 따른 디자인 방법의 변천을 살펴 볼 수 있는 기본 프레임웍의 기능을 수행하게 된다. 이를 통하여 디자인 패러다임의 변천을 살펴보고 정보지식사회의 디자인 교육 요건의 특성이 파악되었다 이들 특성으로는 '인간중심', '상황의존적', '사용자 참여적', '비촉각적', 등으로 파악되었으며 이를 중심으로 한 새로운 디자인 프로그램의 전략 모형이 제시되었다.

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이종이식된 인체 편평상피세포암에 대한 종양괴사인자의 방사선감작효과에 대한 연구 (The Radiation Sensitizer Effect of $TNF-{\alpha}$ on Heterotransplanted Human Squamous Cell Carcinoma)

  • 정필상;김한균;윤형근
    • 대한두경부종양학회지
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    • 제14권2호
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    • pp.151-155
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    • 1998
  • Background and Objectives: Numerous studies were conducted to develop radiosensitizers to increase antitumor effect and decrease systemic toxicity of ionizing radiation. In current study, the authors tested the synergistic effect of mutant $TNF-{\alpha}(M_3S)$ with radiation therapy on heterotransplanted hypoparyngeal squamous cell carcinoma. Materials and Method: SNU-1041 cell line was heterotransplanted to nude mice. When the tumors grew up to $70mm^3$ or more, the animals were randomly placed into 4 groups(n=10/group). Group I : 0.1ml of normal saline injected intraperitoneally once a day for 5 days. Group II : 10ug of $TNF-{\alpha}$ injected intraperitoneally once a day for 5 days. Group III : a single radiation dose of 10 Gy per animal delivered. Group IV : single radiation dose of 10 Gy was delivered 1 hour after intraperitoneal injection of $TNF-{\alpha}$ 10 ug. Results: Four weeks after treatment, group IV showed the least tumor growth during the 4 weeks follow up and the relative tumor growth rate(RTG) of each groups after 4 weeks were 31, 5.8, 10, and 3.2 respectively(p<0.05). Conclusion: These study suggests that pretreatment with $TNF-{\alpha}$ can significantly enhance the effects of radiation therapy and further studies may be needed for clinical trials of combination treatment of $TNF-{\alpha}$ and radiation.

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버섯 전후면과 꼭지부 상태의 자동 인식 (Automatic Recognition of the Front/Back Sides and Stalk States for Mushrooms(Lentinus Edodes L.))

  • 황헌;이충호
    • Journal of Biosystems Engineering
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    • 제19권2호
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    • pp.124-137
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    • 1994
  • Visual features of a mushroom(Lentinus Edodes, L.) are critical in grading and sorting as most agricultural products are. Because of its complex and various visual features, grading and sorting of mushrooms have been done manually by the human expert. To realize the automatic handling and grading of mushrooms in real time, the computer vision system should be utilized and the efficient and robust processing of the camera captured visual information be provided. Since visual features of a mushroom are distributed over the front and back sides, recognizing sides and states of the stalk including the stalk orientation from the captured image is a prime process in the automatic task processing. In this paper, the efficient and robust recognition process identifying the front and back side and the state of the stalk was developed and its performance was compared with other recognition trials. First, recognition was tried based on the rule set up with some experimental heuristics using the quantitative features such as geometry and texture extracted from the segmented mushroom image. And the neural net based learning recognition was done without extracting quantitative features. For network inputs the segmented binary image obtained from the combined type automatic thresholding was tested first. And then the gray valued raw camera image was directly utilized. The state of the stalk seriously affects the measured size of the mushroom cap. When its effect is serious, the stalk should be excluded in mushroom cap sizing. In this paper, the stalk removal process followed by the boundary regeneration of the cap image was also presented. The neural net based gray valued raw image processing showed the successful results for our recognition task. The developed technology through this research may open the new way of the quality inspection and sorting especially for the agricultural products whose visual features are fuzzy and not uniquely defined.

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호르몬 처리에 의한 범가자미, Verasper variegatus 의 성숙과 배란유도 (Effectof of Hormonal Treatment of Induced Maturation and Ovulation in the Spotted Halibut, Verapser variegatus)

  • 백혜자;김윤;안철민;조기채;명정인;이남주
    • 한국양식학회지
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    • 제13권1호
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    • pp.47-53
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    • 2000
  • 사육수조내 자연산란이 이루어지지 않는 범가자미 암컷을 대상으로 호르몬 처리에 의안 인위적 성숙.배란 유도 실험이 이루어졌다. 산란시기에 범가자미 체중 kg당 HCG 265~678 IU, 17${\alpha}$ 20${\beta}$ OHP 0.5~1.0${\mu}$g 농도의 복강주사와 LHRHa 63~81 ${\mu}$g의 펠렛을 투여한 결과, HCG농도 약 300 IU가 범가자미의 최정성숙과 배란유도에 효과적인 것으로 나타났다. 17${\alpga}$ 20${\beta}$ OHP와 대조군에서는 난의 성숙이 거의 진행되지 않았으며, LHRHa 펠렛 실험군에서도 난의 최종성숙과 배란이 일어나지 않았다. 따라서 범가자미 암컷의 경우 현재 많이 사용되고 있는 LHRHa 펠렛 투여보다도 저농도의 HCG (dir 300 IU/kg 체중)o 주사가 난의 최종성숙과 배란에 더 효과적인 것으로 나타났다.

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제조에 대한 문헌고찰(文獻考察) (Literature Investigation of Jejo)

  • 조남경;김종덕
    • 사상체질의학회지
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    • 제19권2호
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    • pp.11-21
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    • 2007
  • 1. Objectives The object of this thesis is to find the basis on why Jejo was assigned as a Taeumin medicine, and to understand Taeumin edema. 2. Methods ${\ulcorner}$Dongyisusebowon${\lrcorner}$ 'Shinchukbon', 'Gabobon', 'Chobonkwun', other related Sasang Constitutional Medicine(SCM) books, herbal medicine books such as ${\ulcorner}$Bonchokangmok${\lrcorner}$, and etc. were compared and researched. 3. Results & Conclusions (1) In Sasang Constitutional Medicine, edema is seen as a critical condition. The first cause of edema in Taeumin is fatigue, a condition where the flow of Qi and Fluid Qi is stagnated. Secondly, edema is caused as Taeeumin is mentally stressed(勞心焦思) and he/she is unable to accomplish his/her plans over many trials or as when they find pleasure in striving for greed. When Lungs which is Incline & Small Viscera(偏小之臟) in Taeumin decreases, it diminishes Real Count of Longevity(命脈實數) which leads to edema formation. (2) Perspective of Human Nature & Character(心性學) and Regimen(養生法) became included gradually in the treatment methods and prescription of edema in Taeumin as ${\ulcorner}$Dongyisusebowon${\lrcorner}$ was revised over time. The revisions also lead to more diversity in prescriptions. (3) Jejo didn't appear In ${\ulcorner}$Dongyisusebowon${\lrcorner}$ 'Chobonkwun' and 'Gabobon'. It was first presented in 'Shinchukbon' as a medicine to treat edema in Taeumin. (4) Jejo have effects of easing clumps. Also it has a strong radiating ability(發散力) which induces perspiration to treat diseases. Finally Jejo is used to remove Takki(濁氣) by utilizing powerful Exhale Gathering Qi contained in it.

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뇌졸중 환자에서 상지 회복을 위해 컴퓨터-인간 연동을 이용한 가상현실 기반 훈련 프로그램 (Virtual Reality-based Training Program Using Computer-human Interface for Recovery of Upper Extremity Use in Stroke Patients)

  • 이경희;황기철
    • 디지털융복합연구
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    • 제14권1호
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    • pp.285-290
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    • 2016
  • 본 연구는 뇌졸중 환자의 상지 재활에 사용되는 컴퓨터-인간 연동을 이용한 가상현실 기반 훈련 프로그램 중재의 효과를 알아보고자 하였다. 2015년 2월까지 Medline 데이터베이스에서 뇌졸중 환자의 상지 재활을 위한 가상 현실 중재를 다루는 무작위 대조군 임상 연구들을 검색하였다. PEDro 스케일이 연구의 질을 사정하기 위해 사용되었다. 선정된 8개의 연구가 분석되어졌다. PEDro 스케일은 5 부터 8/10까지 다양했다. 모든 연구들은 가상현실 기반 훈련 그룹에서 상지 기능 회복에 유의한 결과를 보였다. 본 연구는 뇌졸중 환자의 상지 회복을 위해 사용되는 가상 현실 기반 훈련 프로그램의 적용이 다양하고 예측할 수 없는 실행으로 구성된 과제 지향적이고 점진적인 학습을 제공함을 통해 특히 배움에 효과가 있음을 보여주었다. 본 연구에서는 가상현실 훈련 프로그램을 뇌졸중 환자의 상지 기능 재활에 탁월한 학습 효과를 기대할 수 있으며 과제-지향과 등급화된 학습을 제공하는데 효과적이다.

ROLE OF REACTIVE OXYGEN SPECIES IN MALE INFERTILITY

  • Sharma, Rakesh K.;Agarwal, Ashok
    • 대한생식의학회:학술대회논문집
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    • 대한불임학회 2000년도 제39차 춘계 학술대회
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    • pp.13-28
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    • 2000
  • Human spermatozoa exhibit a capacity to generate ROS and initiate peroxidation of the unsaturated fatty acids in the sperm plasma membrane, which plays a key role in the etiology of male infertility. The short half-life and limited diffusion of these molecules is consistent with their physiologic role in key biological events such as acrosome reaction and hyperactivation. The intrinsic reactivity of these metabolites in peroxidative damage induced by ROS, particularly $H_2O_2$ and the superoxide anion, has been proposed as a major cause of defective sperm function in cases of male infertility. The number of antioxidants known to attack different stages of peroxidative damage is growing, and it will be of interest to compare alpha-tocopherol and ascorbic acid with these for their therapeutic potential in vitro and in vivo. Both spermatozoa and leukocytes generate ROS, although leukocytes produce much higher levels. The clinical significance of leukocyte presence in semen is controversial. Seminal plasma confers some protection against ROS damage because it contains enzymes that scavenge ROS, such as catalase and superoxide dismutase. A variety of defense mechanisms comprising a number of antioxidants can be employed to reduce or overcome oxidative stress caused by excessive ROS. Determination of male infertility etiology is important, as it will help us develop effective therapies to overcome excessive ROS generation. ROS can have both beneficial and detrimental effects on the spermatozoa and the balancing between the amounts of ROS produced and the amounts scavenged at any moment will determine whether a given sperm function will be promoted or jeopardized. Accurate assessment of ROS levels and, subsequently, OS is Vital, as this will help clinicians both elucidate the fertility status and identify the subgroups of patients that respond or do not respond to these therapeutic strategies. The overt commercial claims of antioxidant benefits and supplements for fertility purposes must be cautiously looked into, until proper multicentered clinical trials are studied. From the current data it appears that no Single adjuvant will be able to enhance the fertilizing capacity of sperm in infertile men, and a combination of the possible strategies that are not toxic at the dosage used would be a feasible approach.

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