• 제목/요약/키워드: cell type specific

검색결과 666건 처리시간 0.032초

폐의 분화와 폐암에서 SRC-3와 TTF-I의 역할 (Roles of Steroid Receptor Coactivator-3 and TTF-1 in Lung Development and Lung Cancer)

  • 곽인석
    • 생명과학회지
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    • 제25권12호
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    • pp.1439-1444
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    • 2015
  • Steroid Receptor Coactivator (SRC)는 스테로이드 수용체 전사 활성화 단백질로, 이중에서 SRC-3는 많은 종류의 종양과 관련하여 연구되었다. 그러나 현재 배아에서의 폐의 분화와 폐암 진행과정에서 SRC-3의 기능적 역할에 대한 연구는 제한적이다. 본 연구는 SRC-3가 생쥐 배아의 폐 분화과정에서 기관지와 폐포의 분화에 중요한 역할을 함을 보여준다. 높은 레벨의 SRC-3 유전자 발현이 클라라 세포와 type II 세포에서 배아발달 말기 시기인 E17.5 - E18.5에서 관찰되었으며, 성체 생쥐의 폐에서도 클라라 세포와 type II 세포에서 SRC-3 유전자 발현이 관찰되었다. SRC-3의 폐암에서의 역할을 연구하기 위하여 클라라 세포 특이적 폐암 생쥐 모델을 이용하여 관찰한 결과, SRC-3 잡종 생쥐의 폐와 클라라 세포 특이적 종양 생쥐의 폐에서 TTF-1 유전자와 SRC-3 유전자는 공동 발현되었다. 위 모델에서 TTF-1 유전자 발현은 클라라 세포 유래 종양부위와 다발성 선암 영역에서 선명하게 관찰되었지만, SRC-3 유전자 발현은 다발성 선암 부위에서는 관찰되지 않았다. 이 결과로 SRC-3가 폐암 진행과정 중 침윤성에는 중요한 역할을 수행하지 않음을 확인하였다. SRC-3와 TTF-1의 폐암에서 역할을 클라라 세포 특이적 암 세포주인 mtCC 세포를 사용하여 transient transfection 분석한 결과, TTF-1는 클라라 세포 특이적 단백질인 CCSP 유전자 발현을 현저하게 활성화하였으나, SRC-3는 CCSP 유전자 발현의 활성화에 중요하게 관여하지 않음을 확인하였다. 이 결과는 SRC-3가 폐암 진행에 필수적인 역할을 수행하는 단백질이 아님을 제시한다. 결론적으로, SRC-3는 생쥐 배아와 성체 생쥐에서 기관지와 폐포의 분화에 중요한 역할을 수행하지만, 클라라 세포 유래의 폐암 진행 과정에서는 SRC-3는 중요한 역할을 수행하지 않는다.

Calcium Signaling of Dioleoyl Phosphatidic Acid via Endogenous LPA Receptors: A Study Using HCT116 and HT29 Human Colon Cancer Cell Lines

  • Chang, Young-Ja;Kim, Hyo-Lim;Sacket, Santosh J.;Kim, Kye-Ok;Han, Mi-Jin;Jo, Ji-Yeong;Im, Dong-Soon
    • Biomolecules & Therapeutics
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    • 제15권3호
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    • pp.150-155
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    • 2007
  • In the present study, we have tested the effect of dioleoyl phosphatidic acid (PA) on intracellular $Ca_{2+}$ concentration ($[Ca^{2+}]_{i}$) in two human colon cancer cell lines (HCT116 and HT29). PA and lysophosphatidic acid (LPA), a bioactive lysolipid, increased $[Ca^{2+}]_{i}$ in both HCT116 and HT29 cell lines. Increases of $[Ca^{2+}]_{i}$ by PA and LPA were more robust in HCT116 cells than in HT29 cells. A specific inhibitor of phospholipase C (U73122), however, was not inhibitory to the cell responses. Pertussis toxin, a specific inhibitor of $G_{i/o}$ type G proteins, however, had an inhibitory effect on the responses except for an LPA-induced one in HT29 cells. Ruthenium red, an inhibitor of the ryanodine receptor, was not inhibitory on the responses, however, 2-APB, a specific inhibitor of inositol 1,4,5-trisphosphate receptor, completely inhibited both lipid-induced $Ca^{2+}$ increases in both cell types. Furthermore, by using Ki16425 and VPC32183, two structurally dissimilar specific antagonists for $LPA_{1}/LPA_{3}$ receptors, an involvement of endogenous LPA receptors in the $Ca^{2+}$ responses was observed. Ki16425 completely inhibited the responses but the susceptibility to VPC32183 was different to PA and LPA in the two cell types. Expression levels of five LPA receptors in the HCT116 and HT29 cells were also assessed. Our data support the notion that PA could increase $[Ca^{2+}]_{i}$ in human colon cancer cells, probably via endogenous LPA receptors, G proteins and $IP_{3}$ receptors, thereby suggesting a role of PA as an intercellular lipid mediator.

향장기성 두경부 편평세포암종의 미세잔존암 모델에서 GM-CSF 유전자를 이입시킨 제한복제성 헤르페스바이러스 벡터를 이용한 종양백신의 유전자 치료 (Gene Therapy Using GM-CSF Gene Transferred by a Defective Infectious Single-cycle Herpes Virus in Micro-residual Organotropic Head and Neck Squamous Cell Cancer Model)

  • 김세헌;최은창;김한수;장정현;김지훈;김광문
    • 대한두경부종양학회지
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    • 제19권1호
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    • pp.25-33
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    • 2003
  • Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

Disease-specific pluripotent stem cells

  • Kang, Hoon-Chul
    • Clinical and Experimental Pediatrics
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    • 제53권8호
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    • pp.786-789
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    • 2010
  • Induced pluripotent stem (iPS) cells are generated by epigenetic reprogramming of somatic cells through the exogenous expression of transcription factors. Recently, the generation of iPS cells from patients with a variety of genetic diseases was found to likely have a major impact on regenerative medicine, because these cells self-renew indefinitely in culture while retaining the capacity to differentiate into any cell type in the body, thereby enabling disease investigation and drug development. This review focuses on the current state of iPS cell technology and discusses the potential applications of these cells for disease modeling; drug discovery; and eventually, cell replacement therapy.

Prophylactic and Therapeutic Applications of Genetic Materials Carrying Viral Apoptotic Function

  • Yang Joo-Sung
    • 한국미생물학회:학술대회논문집
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    • 한국미생물학회 2002년도 추계학술대회
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    • pp.118-120
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    • 2002
  • Genetic materials including DNA plasmid are effective delivery vehicle to express interesting gene efficiently and safely not to generate replication competent virus. Moreover, it has advantages to design a better vector and to simplify manufacturing and storage condition. To understand a possible pathogenic mechanism by a flavivirus, West Nile virus (WNV), WNV genome sequence was aligned to other pathogenic viral genome. Interestingly, WNV capsid (Cp) amino acid sequence has some homology to HIV-l Vpr protein. These proteins induce apoptosis in human cell lines as well as in vivo and cell cycle arrest. Therefore, DNA plasmid carrying apoptosis-inducing and cell cycle arresting viral proteins including a HIV-1 Vpr and a WNV Cp protein can be useful for anti-cancer therapeutic applications. This WNV Cp protein is an early expressed protein which can be a reasonable target antigen (Ag) for vaccine design. Immunization of a DNA construct encoding WNV Cp protein induces a strong Ag-specific humoral and Th1-type immune responses in animal. Therefore, DNA plasmid encoding apoptotic viral proteins can be useful tool for therapeutic and prophylactic applications.

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Spinning Detonation 파의 3차원 수치 해석 (Three-Dimensional Numerical Analysis of Spinning Detonation Wave)

  • 조덕래;최정열;원수희
    • 한국연소학회:학술대회논문집
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    • 한국연소학회 2006년도 제32회 KOSCO SYMPOSIUM 논문집
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    • pp.205-212
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    • 2006
  • Three-dimensional numerical study was carried out for the investigation of the detonation wave structures propagating in tubes. Fluid dynamics equations and conservation equation of reaction progress variable were analyzed by a MUSCL-type TVD scheme and four stage Runge-Kutta time integration. Chemical reaction was modeled by using a simplified one-step irreversible kinetics model. The variable gas properties between unburned and burned states were considered by using variable specific heat ratio formulation. The unsteady computational results in three-dimension show the detailed mechanisms of rectangular and diagonal mode of detonation wave instabilities resulting same cell length but different cell width in smoked-foil record. The results for the small reaction constant shows the spinning mode of three-dimensional detonation wave dynamics, which was rarely observed in the previous numerical simulation of the detonation waves.

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Heterosigma akasiwo의 핵형분석을 통한 생활사 연구를 위한 DAPI이용 기법

  • 이주연;한명수
    • 한국환경생물학회:학술대회논문집
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    • 한국환경생물학회 2003년도 학술대회
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    • pp.121-124
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    • 2003
  • The goals of this study is to elucidate life cycle and to detect genetic differences within a single species of Heterosigma akashiwo. To elucidate life cycle of H. akashiwo, have to study of benthic stage and vegetative cell. So we studied identification of H. akashiwo cyst. The relative contents of DNA in nuclei were determined in Heterosigma akashiwo. Different stages of the life history were obtained from culture and natural sediments, and examined by microfluorometry after staining with the DNA-specific fluorochrome 4'-6-dianudubi-2-phenylindole(DAPI). Large cells mainly in exponensial stage, while small cell, pre-encystment cells(\ulcorner\ulcorner), showed in the end of the late growth stage. Type of DNA content showed the different with growth stage. Usually the small cell has the high level of IOD.

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Human Induced Pluripotent Stem Cells : Clinical Significance and Applications in Neurologic Diseases

  • Chang, Eun-Ah;Jin, Sung-Won;Nam, Myung-Hyun;Kim, Sang-Dae
    • Journal of Korean Neurosurgical Society
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    • 제62권5호
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    • pp.493-501
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    • 2019
  • The generation of human induced pluripotent stem cells (iPSCs) from somatic cells using gene transfer opens new areas for precision medicine with personalized cell therapy and encourages the discovery of essential platforms for targeted drug development. iPSCs retain the genome of the donor, may regenerate indefinitely, and undergo differentiation into virtually any cell type of interest using a range of published protocols. There has been enormous interest among researchers regarding the application of iPSC technology to regenerative medicine and human disease modeling, in particular, modeling of neurologic diseases using patient-specific iPSCs. For instance, Parkinson's disease, Alzheimer's disease, and spinal cord injuries may be treated with iPSC therapy or replacement tissues obtained from iPSCs. In this review, we discuss the work so far on generation and characterization of iPSCs and focus on recent advances in the use of human iPSCs in clinical setting.

Characterization of Korean Cattle Keratin IV Gene

  • Kim, D.Y.;Yu, S.L.;Sang, B.C.;Yu, D.Y.
    • Asian-Australasian Journal of Animal Sciences
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    • 제16권7호
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    • pp.1055-1059
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    • 2003
  • Keratins, the constituents of epithelial intermediate filaments, are precisely regulated in a tissue and development specific manner. There are two types of keratin in bovine. The type I is acidic keratin and the type II is neutral/basic keratin. 1.5 kb of 5' flanking sequence of Korean cattle Keratin IV gene, type II keratin (59 kDa), was cloned and sequenced. A symmetrical motif AApuCCAAA are located in a defined region upstream of the TATA box. Proximal SP1, AP1, E-box and CACC elements as the major determinants of transcription are identified. When it was compared to the bovine sequence from -600 bp to ATG upstream, the homology was 97% in nucleotide sequence. Several A and T sequences, located in the promoter region, are deleted in the Korean cattle. An expression vector consisted of Korean cattle Keratin IV gene promoter/SV40 large T antigen was transfected to HaCaT cell (Epithelial keratinocyte). The transformed HaCaT cells showed active proliferation when treated with PDGF (Platelet-derived growth factor) in 0.3% soft agar compared to control cells. These results indicate that Korean cattle Keratin IVgene promoter can be used as a promoter for transfection into epithelial cell.

Work Function Modification of Indium Tin Oxide Thin Films Sputtered on Silicon Substrate

  • Oh, Gyujin;Kim, Eun Kyu
    • 한국진공학회:학술대회논문집
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    • 한국진공학회 2014년도 제46회 동계 정기학술대회 초록집
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    • pp.351.2-351.2
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    • 2014
  • Indium tin oxide (ITO) has a lot of variations of its properties because it is basically in an amorphous state. Therefore, the differences in composition ratio of ITO can result in alteration of electrical properties. Normally, ITO is considered as transparent conductive oxide (TCO), possessing excellent properties for the optical and electrical devices. Quantitatively, TCO has transparency over 80 percent within the range of 380nm to 780nm, which is visible light although its specific resistance is less than $10-3{\Omega}/cm$. Thus, the solar cell is the best example for which ITO has perfectly matching profile. In addition, when ITO is used as transparent conductive electrode, this material essentially has to have a proper work function with contact materials. For instance, heterojunction with intrinsic thin layer (HIT) solar cell could have both front ITO and backside ITO. Because each side of ITO films has different type of contact materials, p-type amorphous silicon and n-type amorphous silicon, work function of ITO has to be modified to transport carrier with low built-in potential and Schottky barrier, and approximately requires variation from 3 eV to 5 eV. In this study, we examine the change of work function for different sputtering conditions using ultraviolet photoelectron spectroscopy (UPS). Structure of ITO films was investigated by spectroscopic ellipsometry (SE) and scanning electron microscopy (SEM). Optical transmittance of the films was evaluated by using an ultraviolet-visible (UV-Vis) spectrophotometer

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