• 제목/요약/키워드: proliferation, migration

검색결과 587건 처리시간 0.029초

Metallothinein 1E Enhances Glioma Invasion through Modulation Matrix Metalloproteinases-2 and 9 in U87MG Mouse Brain Tumor Model

  • Hur, Hyuk;Ryu, Hyang-Hwa;Li, Chun-Hao;Kim, In Young;Jang, Woo-Youl;Jung, Shin
    • Journal of Korean Neurosurgical Society
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    • 제59권6호
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    • pp.551-558
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    • 2016
  • Malignant glioma cells invading surrounding normal brain are inoperable and resistant to radio- and chemotherapy, and eventually lead to tumor regrowth. Identification of genes related to motility is important for understanding the molecular biological behavior of invasive gliomas. According to our previous studies, Metallothionein 1E (MT1E) was identified to enhance migration of human malignant glioma cells. The purpose of this study was to confirm that MT1E could modulate glioma invasion in vivo. Firstly we established 2 cell lines; MTS23, overexpressed by MT1E complementary DNA construct and pV12 as control. The expression of matrix metalloproteinases (MMP)-2, -9 and a disintegrin and metalloproteinase 17 were increased in MTS23 compared with pV12. Furthermore it was confirmed that MT1E could modulate MMPs secretion and translocation of NFkB p50 and B-cell lymphoma-3 through small interfering ribonucleic acid knocked U87MG cells. Then MTS23 and pV12 were injected into intracranial region of 5 week old male nude mouse. After 4 weeks, for brain tissues of these two groups, histological analysis, and immunohistochemical stain of MMP-2, 9 and Nestin were performed. As results, the group injected with MTS23 showed irregular margin and tumor cells infiltrating the surrounding normal brain, while that of pV12 (control) had round and clear margin. And regrowth of tumor cells in MTS23 group was observed in another site apart from tumor cell inoculation. MT1E could enhance tumor proliferation and invasion of malignant glioma through regulation of activation and expression of MMPs.

Epstein-Barr Virus-infected Akata Cells Are Sensitive to Histone Deacetylase Inhibitor TSA-provoked Apoptosis

  • Kook, Sung-Ho;Son, Young-Ok;Han, Seong-Kyu;Lee, Hyung-Soon;Kim, Beom-Tae;Jang, Yong-Suk;Choi, Ki-Choon;Lee, Keun-Soo;Kim, So-Soon;Lim, Ji-Young;Jeon, Young-Mi;Kim, Jong-Ghee;Lee, Jeong-Chae
    • BMB Reports
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    • 제38권6호
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    • pp.755-762
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    • 2005
  • Epstein-Barr virus (EBV) infects more than 90% of the world's population and has a potential oncogenic nature. A histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), has shown potential ability in cancer chemoprevention and treatment, but its effect on EBV-infected Akata cells has not been examined. This study investigated the effect of TSA on the proliferation and apoptosis of the cells. TSA inhibited cell growth and induced cytotoxicity in the EBV infected Akata cells. TSA treatment sensitively induced apoptosis in the cell, which was demonstrated by the increased number of positively stained cells in the TUNEL assay, the migration of many cells to the sub-$G_0/G_1$ phase in flow cytometric analysis, and the ladder formation of genomic DNA. Western blot analysis showed that caspase-dependent pathways are involved in the TSA-induced apoptosis of EBV-infected Akata cells. Overall, this study shows that EBV-infected B lymphomas are quite sensitive to TSA-provoked apoptosis.

G protein-coupled receptors in stem cell maintenance and somatic reprogramming to pluripotent or cancer stem cells

  • Choi, Hye Yeon;Saha, Subbroto Kumar;Kim, Kyeongseok;Kim, Sangsu;Yang, Gwang-Mo;Kim, BongWoo;Kim, Jin-Hoi;Cho, Ssang-Goo
    • BMB Reports
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    • 제48권2호
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    • pp.68-80
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    • 2015
  • G protein-coupled receptors (GPCRs) are a large class of transmembrane receptors categorized into five distinct families: rhodopsin, secretin, adhesion, glutamate, and frizzled. They bind and regulate 80% of all hormones and account for 20-50% of the pharmaceuticals currently on the market. Hundreds of GPCRs integrate and coordinate the functions of individual cells, mediating signaling between various organs. GPCRs are crucial players in tumor progression, adipogenesis, and inflammation. Several studies have also confirmed their central roles in embryonic development and stem cell maintenance. Recently, GPCRs have emerged as key players in the regulation of cell survival, proliferation, migration, and self-renewal in pluripotent (PSCs) and cancer stem cells (CSCs). Our study and other reports have revealed that the expression of many GPCRs is modulated during the generation of induced PSCs (iPSCs) or CSCs as well as during CSC sphere formation. These GPCRs may have crucial roles in the regulation of self-renewal and other biological properties of iPSCs and CSCs. This review addresses the current understanding of the role of GPCRs in stem cell maintenance and somatic reprogramming to PSCs or CSCs.

인체 섬유아세포 및 케라티노사이트에 대한 지방줄기세포 분비물의 세포생물학적 기능 (Cell Biological Function of Secretome of Adipose-Derived Stem Cells on Human Dermal Fibroblasts and Keratinocytes)

  • 이재설;이종환
    • 한국미생물·생명공학회지
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    • 제40권2호
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    • pp.117-127
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    • 2012
  • 피부재생에 대한 지방줄기세포 배양상등액(ADSC-CM)의 효능에 대한 연구를 진행하였다. ADSC-CM이 피부재생에 기여하는 기작은 명확하지 못하지만, ADSC-CM은 다양한 분비물을 포함하고 있고 따라서 피부트러블 처리를 위한 훌륭한 재료이다. 저 산소 상태에서 생산된 ADSC-CM, 즉 advanced adipose-derived stem cell protein extract (AAPE)는 피부재생에 보다 좋은 재료이다. 본 연구는 피부 재생에 결정적 역할을 하는 인체 primary 세포인 섬유아세포(HDF)와 케라티노사이트(HK)를 이용하여 AAPE의 효능을 검증하였다. 0.32 ${\mu}g/ml$ AAPE에서 콜라겐 합성이 관찰 되었으며 AAPE는 stress fiber 형성을 강화하였다. DNA microarray 결과에서는 세포증식, 세포이동, 세포부착, 상처반응에 관여하는 133개의 유전자 발현이 조절되는 것을 알았다. Antibody array를 통해 CD54, FGF-2, GM-CSF, IL-4, IL-6, VEGF, TGF-${\beta}2$, TGF-${\beta}3$, MMP-1, MMP-10, 그리고 MMP-19와 같은 MMP, 성장인자, 사이토카인등 25개의 알려진 단백질이 포함되어 있다는 것을 알았다. 따라서, AAPE는 HK의 세포생물학적 기능을 활성화 할 수 있다고 사료되며 HDF에서는 콜라겐 합성을 유도하였다. 이러한 결과는 AAPE가 피부재생에 임상적 적용이 가능하리라는 것을 의미한다.

구연산과 테트라싸이클린으로 처리한 치근면에서 rhBMP-2가 치주인대섬유아세포와 골아세포의 활성에 미치는 영향 (Effect of Citric Acid and Tetracycline HCl Root Conditioning on rhBMP-2 on Human Periodontal Ligament Fibroblast and Osteoblast cell)

  • 심정민;한수부;설양조;이용무;김경화;계승범;최상묵;정종평
    • Journal of Periodontal and Implant Science
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    • 제31권1호
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    • pp.21-41
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    • 2001
  • The goal of Periodontal treatment is predictable periodontal regeneration. But until now, many products including GTR materials and growth factors are beyond of complete regeneration. BMP can induce ectopic bone formation when implanted into sites such as rat muscle and can greatly enhance healing of bony defects when applied exogenously. BMP can promote periodontal regeneration by their ability to stimulate new bone and new cementum formation. But little is known about optimal conditions required for the application. Root conditioning is used for bioacive root change so altered root surface provides a substrate that promotes chemotaxis, migration and attachment of peridontal cells encouraging connective attachment to the denuded root surface. The aim of this study is to investigate whether the acid conditioning change effect of rhBMP-2 on human periodontal ligament cell and osteoblast cell line. 288 periodontally involved root dentin slices are divided into 6 groups, each 48, 1)control, 2)treated with BMP, 3)treated with citric acid 4)treated with citric acid+BMP 5)treated with tetracycline 6)treated with TC+BMP. Each group was devided half, so 12 root dentin slices were seeded with periodontal ligament cells and 12 were seeded with osteoblasts. At day 2 and 7, cell number, protein assay, ALP activitiy was measured. To investigate morphology of cultured cells, SEM was employed. Statistical analysis was performed with SPSS 8.0 either t-test or ANOVA test. The results are ; Protein assay and cell number was slightly decreased in CA+BMP group compared to Ca group but it was not statistically significant and ALP activity was much more increased in CA+BMP group compared to CA group so there was no statistically significance between BMP and CA+BMP group and statistically significant compared to control group. Cell number and protein assay was slightly increased in TC group and ALP activity was much less the BMP group and CA group. Cell number and protein and ALP activity was not much increased in TC+BMP group. TC group and TC+BMP group showed cell morphology change in SEM. This results suggested that application of root surface with citric acid before BMP treatment might give better result in periodontal regeneration.

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Minipig에서 외과적으로 형성한 일벽성 치주 결손부에 이식한 macroporous biphasic calcium phosphate ($MBCP^{(R)}$)와 fluorohydroxyapatite($Algipore^{(R)}$)의 조직학적 평가 (Histologic evaluation of macroporous biphasic calcium phosphate($MBCP^{(R)}$) and flouorohydrxyapatite($Algipore^{(R)}$) in surgically created 1-wall periodontal intrabony defects of minipigs)

  • 이중석;채경준;정의원;김창성;조규성;채중규;김종관;최성호
    • Journal of Periodontal and Implant Science
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    • 제37권1호
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    • pp.125-136
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    • 2007
  • Periodontal regenerative therapy and tissue engineering on defects destructed by severe periodontitis need maintaining of space, which provides the environment for cell migration, proliferation and differentiation. Application of bone grafts may offer this environment in periodontal defects. This study evaluated bone graft materials, $MBCP^{(R)}$ and $Algipore^{(R)}$ , in surgically created i-wall periodontal intrabony defects of minipigs by histological analysis. Critical sized($4mm{\times}4mm$), one wall periodontal intrabony defects were surgically produced at the proximal aspect of mandibular premolars in either right and left jaw quadrants in four minipigs. The control group was treated with debridement alone, and experimental group was treated with debridement and $MBCP^{(R)}$ and $Algipore^{(R)}$ application. The healing processes were histologically observed after 8 weeks and the results were as follows. 1. In the control group, limited new bone formation was observed. 2. In MBCP group, more new bone formation was observed compared to other groups. 3. Histologically, dispersed mixture of new bone, biomaterial particles and connective tissue were shown and osteoblasts, osteoclasts and new vessels were present in this area. 4. Defects with Algipore showed limited new bone formation and biomaterial particles capsulated by connective tissue. 5. Histologically, lots of osteoclasts were observed around the biomaterial but relatively small numbers of osteblasts were shown. Within the limitation to this study protocol, $MBCP^{(R)}$ application in 1-wall intrabony defect enhanced new bone formation rather than $Algipore^{(R)}$ application.

특발성 치은 섬유종증에 의한 상악 측절치의 변위 (DISPLACEMENT OF MAXILLARY LATERAL INCISOR CAUSED BY IDIOPATHIC GINGIVAL FIBROMATOSIS)

  • 정지숙;박호원;이주현;서현우;이석근
    • 대한소아치과학회지
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    • 제38권3호
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    • pp.296-302
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    • 2011
  • 특발성 치은 섬유종증은 드물게 나타나는 질환으로 외과적 제거 후에도 쉽게 재발될 수 있다. 이 질환은 보통 전반적인 양상으로 양측성으로 나타나고, 때때로 국소적인 양상으로 편측성으로 나타나기도 하며, 국소적인 양상일 경우 보통 상악구치 부나상악 결절 부위에 나타난다. 이 질환으로 인해 치아 변위, 부정 교합, 저작, 발음, 심미적인 문제 등이 발생할 수 있다. 5세 남아가 상악 우측 유측절치 부위의 치은 비대를 주소로 내원하였고, 9세경에 재내원 시 상악 우측 측절치의 심한 변위가 관찰되었다. 본 환아는 이 질환에 연관된 어떠한 의과적 병력 및 가족력이 없었으며, 임상적, 조직병리학적 검사 결과 특발성 치은 섬유종증으로 진단되었다. 교정적인 방법으로 변위된 치아를 재배열시키기 위해 상악 우측 중절치와변위된상악 우측 측절치 부위의 과증식된섬유성 조직을 외과적으로 제거하였다. 이 질환의 유전적 특성을 알기 위해 제거된 조직을 간단한 면역조직화학 배열법을 사용해 평가하였다. 평가 결과 병소 조직의 각질세포, 섬유모세포, 내피세포, 대식세포 내에 CTGF, HSP-70, MMP-1, PCNA, CMG2, TNF-${\alpha}$의 증가된 발현이 관찰되었다. 따라서 치은 섬유종증은 치은 조직의 섬유 상피성 증식과 염증 반응에 의한 CTGF, HSP-70, MMP-1, PCNA, CMG2, TNF-${\alpha}$의 수반하는 과발현에 의해 발생되었다.

Antimutagenic Effects of Ginsenoside Rb$_1$, Rg$_1$ in the CHO-K1 Cells by Benzo[a]pyrene with Chromosomal Aberration Test and Comet Assay

  • Kim, Jong-Kyu;Kim, Soo-Jin;Rim, Kyung-Taek;Cho, Hae-Won;Kim, Hyeon-Yeong;Yang, Jeong-Sun
    • Molecular & Cellular Toxicology
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    • 제5권2호
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    • pp.126-132
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    • 2009
  • The usage and types of chemicals are advancing, specializing, large-scaled increasing, and new chemical exposed workers are concerning to occupational disease. The generation of reactive oxygen in the body from carcinogen, mutation and DNA damage in cancer is protected by natural antioxidants (phytochemicals) with antimutagenic effect. There were many reports of ginsenoside Rb$_1$, Rg$_1$ grievances of the genetic mutation to suppress the effect confirm the genetic toxicity test with chromosomal aberration test and the Comet (SCGE) assay confirmed the suppression effect occurring chromosomal DNA damage. We had wanted to evaluate the compatibility and sensitivity between the chromosomal aberration (CA) test and the Comet assay. We used the CA test and Comet assay to evaluate the anti-genotoxicity of ginsenoside Rb$_1$ and Rg$_1$, in CHO-K1 (Chinese hamster ovary fibroblast) cell in vitro, composed negative control (solvent), positive control (benzo[a]pyrene), test group (carcinogen+variety concentration of ginsenoside) group. The positive control was benzo[a]pyrene (50 $\mu$M), well-known carcinogen, and the negative control was the 1 % DMSO solvent. The test group was a variety concentration of ginsenoside Rb$_1$, Rg$_1$ with 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10%. In chromo-somal aberration test, we measured the number of cells with abnormally structured chromosome. In Comet assay, the Olive tail moment (OTM) and Tail length (TL) values were measured. The ratio of cell proliferation was increased 8.3% in 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1%, 10% Rb$_1$ treated groups, and increased 10.4% in 10$^{-10}$%, 10$^{-8}$%, 10$^{-6}$%, 10$^{-4}$%, 10$^{-2}$%, 1% Rg$_1$ treated groups. In the CA test, the number of chromosomal aberration was decreased all the Rb$_1$ and Rg$_1$ treated groups. In the Comet assay, the OTM values were decreased in all the Rb$_1$ and Rg$_1$ treated groups. To evaluate the compatibility between CA and Comet assay, we compared the reducing ratio of chromosomal abnormalities with its OTM values, it was identified the antimutagenicity of ginsenoside, but it was more sensitive the CA test than the Comet assay. Ginsenoside Rb$_1$ and Rg$_1$ significantly decrease the number of cells with chromosomal aberration, and decrease the extent of DNA migration. Therefore, ginsenoside Rb$_1$, Rg$_1$ are thought as an antioxidant phytochemicals to protect mutagenicity. The in vitro Comet assay seems to be less sensitive than the in vitro chromosomal aberration test.

Proteomic Analysis and the Antimetastatic Effect of N-(4methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-Induced Apoptosis in Human Melanoma SK-MEL-28 cells

  • Choi Su-La;Choi Yun-Sil;Kim Young-Kwan;Sung Nack-Do;Kho Chang-Won;Park Byong-Chul;Kim Eun-Mi;Lee Jung-Hyung;Kim Kyung-Mee;Kim Min-Yung;Myung Pyung-Keun
    • Archives of Pharmacal Research
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    • 제29권3호
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    • pp.224-234
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    • 2006
  • We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

Gintonin absorption in intestinal model systems

  • Lee, Byung-Hwan;Choi, Sun-Hye;Kim, Hyeon-Joong;Park, Sang-Deuk;Rhim, Hyewhon;Kim, Hyoung-Chun;Hwang, Sung-Hee;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • 제42권1호
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    • pp.35-41
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    • 2018
  • Background: Recently, we identified a novel ginseng-derived lysophosphatidic acid receptor ligand, called gintonin. We showed that gintonin induces $[Ca^{2+}]i$ transient-mediated morphological changes, proliferation, and migration in cells expressing lysophosphatidic acid receptors and that oral administration of gintonin exhibits anti-Alzheimer disease effects in model mice. However, little is known about the intestinal absorption of gintonin. The aim of this study was to investigate gintonin absorption using two model systems. Methods: Gintonin membrane permeation was examined using a parallel artificial membrane permeation assay, and gintonin absorption was evaluated in a mouse everted intestinal sac model. Results: The parallel artificial membrane permeation assay showed that gintonin could permeate an artificial membrane in a dose-dependent manner. In the everted sac model, gintonin absorption increased with incubation time (from 0 min to 60 min), followed by a decrease in absorption. Gintonin absorption into everted sacs was also dose dependent, with a nonlinear correlation between gintonin absorption and concentration at 0.1-3 mg/mL and saturation at 3-5 mg/mL. Gintonin absorption was inhibited by the Rho kinase inhibitor Y-27632 and the sodiumeglucose transporter inhibitor phloridzin. Moreover, lipid extraction with methanol also attenuated gintonin absorption, suggesting the importance of the lipid portion of gintonin in absorption. This result shows that gintonin might be absorbed through passive diffusion, paracellular, and active transport pathways. Conclusion: The present study shows that gintonin could be absorbed in the intestine through transcellular and paracellular diffusion, and active transport. In addition, the lipid component of gintonin might play a key role in its intestinal absorption.