• Title/Summary/Keyword: mesenchymal

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Early Growth Response Protein-1 Involves in Transforming Growth factor-β1 Induced Epithelial-Mesenchymal Transition and Inhibits Migration of Non-Small-Cell Lung Cancer Cells

  • Shan, Li-Na;Song, Yong-Gui;Su, Dan;Liu, Ya-Li;Shi, Xian-Bao;Lu, Si-Jing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.4137-4142
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    • 2015
  • The zinc finger transcription factor EGR 1 has a role in controlling synaptic plasticity, wound repair, female reproductive capacity, inflammation, growth control, apoptosis and tumor progression. Recent studies mainly focused on its role in growth control and apoptosis, however, little is known about its role in epithelial-mesenchymal transition (EMT). Here, we aim to explore whether EGR 1 is involved in TGF-${\beta}1$-induced EMT in non-smallcell lung cancer cells. Transforming growth factor (TGF)-${\beta}1$ was utilized to induce EMT in this study. Western blotting, RT-PCR, and transwell chambers were used to identify phenotype changes. Western blotting was also used to observe changes of the expression of EGR 1. The lentivirus-mediated EGR 1 vector was used to increase EGR 1 expression. We investigated the change of migration to evaluate the effect of EGR 1 on non-small-cell lung cancer cells migration by transwell chambers. After stimulating with TGF-${\beta}1$, almost all A549 cells and Luca 1 cells (Non-small-cell lung cancer primary cells) changed to mesenchymal phenotype and acquired more migration capabilities. These cells also had lower EGR 1 protein expression. Overexpression of EGR 1 gene with EGR 1 vector could decrease tumor cell migration capabilities significantly after adding TGF-${\beta}1$. These data s howed an important role of EGR 1 in the EMT of non-small-cell lung cancer cells, as well as migration.

Mesenchymal Chondrosarcoma - 3 Cases Report - (간엽성 연골육종 - 3례 보고 -)

  • Gu, Mi-Jin;Bae, Young-Kyong;Choi, Joon-Hyuk;Kim, Mi-Jin;Choi, Won-Hee;Shin, Duk-Seop;Suh, Jang-Soo
    • Journal of Yeungnam Medical Science
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    • v.17 no.1
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    • pp.87-92
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    • 2000
  • Mesenchymal chondrosarcoma is a rare malignant tumor of skeletal and extraskeletal origin, and which shows aggressive local behavior as well as a high metastatic potential. We report 3 cases of mesenchymal chondrosarcoma. Two cases were male and one was female. Their ages ranged from 25 to 32 years(mean: 28 years). Tissue was obtained by wide excision in two patients. and by incisional biopsy in one. The mass was located in the rib(case 1), orbital floor(case 2), and abdominal wall(case 3). Roentgenographically, the tumor resembles ordinary chondrosarcoma, showing osteolytic and obstructive appearance with stippled calcification. Grossly, the tumor was lobulating, solid fish-fleshy like mass with calcification and ossification. Histologically, the tumor shows characteristic bimorphic pattern composed of islands of well differentiated hyaline cartilage admixed with a cellular area of undifferentiated small cells. The small cells usually displayed a hemangiopericytoid or an alveolar pattern.

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EFFECTS OF bFGF AND PDGF-BB ON OSTEOBLAST DIFFERENTIATION OF BONE MARROW-DERIVED MESENCHYMAL STEM CELL IN RAT (bFGF, PDGF-BB가 백서 골수기원 간엽 줄기세포의 조직골세포 분화에 미치는 영향에 관한 연구)

  • Song, Gin-Ah;Choi, Jin-Young
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.32 no.6
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    • pp.495-505
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    • 2006
  • In this study we evaluate the effects of bFGF-BB and PDGF on in vitro proliferation, differentiation and mineralization of mesenchymal stem cells (MSCs) from rat. MSCs were prepared from the bone marrow of 6 or 7-week-old male rats with a technique previously described by Maniatopoulos et al. in 1988. Lineage differentiation to osteogenesis, chondrogenesis and adipogenesis were performed. At first, we characterized the cultured cell on passage 1, 3, 5, 7 with immunocytochemical staining using CD29, 44, 34, 45, ${\alpha}$-SMA and type I collagen. And to study the effects of bFGF and PDGF-BB on proliferation, differentiation and mineralization, we seeded the expanded cell at a density of 6 $6{\times}10^3\;cells/cm^2$ to 100-mm dish for evaluation of cell proliferation and MTT assay was carried out on day 2, 4, 7, 9. We also resuspended the cells with same density $(6{\times}10^3\;cells/cm^2)$ to 24 well plates for subculture. On the following day, the attached cells were exposed to 2.5ng/ml bFGF and/or 25ng/ml PDGF-BB daily during 5 days. The osteocalcin (OC) level was assessed and mineral contents were evaluated with alizarin red S staining on subculture day 2, 7, 14, 21. We identified the mesenchymal stem cell from the bone marrow derived cells of rat through their successful multi-differentiation and stable display of its phenotype. And bFGF and PDGF-BB showed the effect that inhibited osteoblastic differentiation and mineralization mildly in above concentration at in vitro culture. This study was supported by grant 04-2004-0120 from the Seoul National University Hospital Research Fund.

Tumorigenesis Study of Canine Adipose Derived-mesenchymal Stem Cell (개 지방세포 유래의 중간엽 줄기세포의 종양형성시험)

  • Lee, Eun-Sun;Kwon, Eun-A;Park, Jeong-Ran;Kang, Byung-Chul;Kang, Kyung-Sun;Cho, Myung-Haing
    • Toxicological Research
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    • v.23 no.3
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    • pp.271-278
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    • 2007
  • Several recent studies demonstrated the potential of bioengineering using stem cells in regenerative medicine. Adult mesenchymal stem cells (MSCs) have the pluripotency to differentiate into cells of mesodermal origin, i.e., bone, cartilage, adipose, and muscle cells; they, therefore, have many potential clinical applications. On the other hand, stem cells possess a self-renewal capability similar to cancer cells. For safety evaluation of MSCs, in this study, we tested tumorigenecity of canine adipose derived mesenchymal stem cells (cAD-MSCs) using Balb/c-nu mice. In this study, there were no changes in mortality, clinical signs, body weights and biochemical parameters of all animals treated. In addition, there were no significant changes between control and treated groups in autopsy findings. These results indicate that cAD-MSC has no tumorigenic potential under the condition in this study.

Efficient In Vitro Labeling Rabbit Bone Marrow-Derived Mesenchymal Stem Cells with SPIO and Differentiating into Neural-Like Cells

  • Zhang, Ruiping;Li, Jing;Li, Jianding;Xie, Jun
    • Molecules and Cells
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    • v.37 no.9
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    • pp.650-655
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    • 2014
  • Mesenchymal stem cells (MSCs) can differentiate into neural cells to treat nervous system diseases. Magnetic resonance is an ideal means for cell tracking through labeling cells with superparamagnetic iron oxide (SPIO). However, no studies have described the neural differentiation ability of SPIO-labeled MSCs, which is the foundation for cell therapy and cell tracking in vivo. Our results showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) labeled in vitro with SPIO can be induced into neural-like cells without affecting the viability and labeling efficiency. The cellular uptake of SPIO was maintained after labeled BM-MSCs differentiated into neural-like cells, which were the basis for transplanted cells that can be dynamically and non-invasively tracked in vivo by MRI. Moreover, the SPIO-labeled induced neural-like cells showed neural cell morphology and expressed related markers such as NSE, MAP-2. Furthermore, whole-cell patch clamp recording demonstrated that these neural-like cells exhibited electrophysiological properties of neurons. More importantly, there was no significant difference in the cellular viability and $[Ca^{2+}]_i$ between the induced labeled and unlabeled neural-like cells. In this study, we show for the first time that SPIO-labeled MSCs retained their differentiation capacity and could differentiate into neural-like cells with high cell viability and a good cellular state in vitro.

Gene Profiles in a Smoke-Induced COPD Mouse Lung Model Following Treatment with Mesenchymal Stem Cells

  • Kim, You-Sun;Kokturk, Nurdan;Kim, Ji-Young;Lee, Sei Won;Lim, Jaeyun;Choi, Soo Jin;Oh, Wonil;Oh, Yeon-Mok
    • Molecules and Cells
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    • v.39 no.10
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    • pp.728-733
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    • 2016
  • Mesenchymal stem cells (MSCs) effectively reduce airway inflammation and regenerate the alveolus in cigarette- and elastase-induced chronic obstructive pulmonary disease (COPD) animal models. The effects of stem cells are thought to be paracrine and immune-modulatory because very few stem cells remain in the lung one day after their systemic injection, which has been demonstrated previously. In this report, we analyzed the gene expression profiles to compare mouse lungs with chronic exposure to cigarette smoke with non-exposed lungs. Gene expression profiling was also conducted in a mouse lung tissue with chronic exposure to cigarette smoke following the systemic injection of human cord blood-derived mesenchymal stem cells (hCB-MSCs). Globally, 834 genes were differentially expressed after systemic injection of hCB-MSCs. Seven and 21 genes, respectively, were up-and downregulated on days 1, 4, and 14 after HCB-MSC injection. The Hbb and Hba, genes with oxygen transport and antioxidant functions, were increased on days 1 and 14. A serine protease inhibitor was also increased at a similar time point after injection of hCB-MSCs. Gene Ontology analysis indicated that the levels of genes related to immune responses, metabolic processes, and blood vessel development were altered, indicating host responses after hCB-MSC injection. These gene expression changes suggest that MSCs induce a regeneration mechanism against COPD induced by cigarette smoke. These analyses provide basic data for understanding the regeneration mechanisms promoted by hCB-MSCs in cigarette smoke-induced COPD.

Characterization and Differentiation of Synovial Fluid Derived Mesenchymal Stem Cells from Dog (개 관절 윤활액 유래 중간엽 줄기세포의 특성과 분화능 분석)

  • Lee, Jeong-Hyeon;Lee, Sung-Lim
    • Journal of Embryo Transfer
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    • v.27 no.3
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    • pp.175-181
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    • 2012
  • The synovial tissues are a valuable MSCs source for cartilage tissue engineering because these cells are easily obtainable by the intra-articular biopsy during diagnosis. In this study, we isolated and characterized the canine MSCs derived from synovial fluid of female and male donors. Synovial fluid was flushed with saline solution from pre and post-puberty male (cM1-sMSC and cM2-sMSC) and female (cF1-sMSC and cF2-sMSC) dogs, and cells were isolated and cultured in advanced-DMEM (A-DMEM) supplemented with 10% FBS in a humidified 5% $CO_2$ atmosphere at $38.5^{\circ}C$. The cells were evaluated for the expression of the early transcriptional factors, such as Oct3/4, Nanog and Sox2 by RT-PCR. The cells were induced under conditions conductive for adipogenic, osteogenic, and chondrogenic lineages, then evaluated by specific staining (Oil red O, von Kossa, and Alcian Blue staining, respectively) and analyzed for lineage specific markers by RT-PCR. All cell types were positive for alkaline phosphatase (AP) activity and early transcriptional factors (Oct3/4 and Sox2) were also positively detected. However, Nanog were not positively detected in all cells. Further, these MSCs were observed to differentiate into mesenchymal lineages, such as adipocytes (Oil red O staining), osteocytes (von Kossa staining), and chondrocytes (Alcian Blue staining) by cell specific staining. Lineage-specific genes (osteocyte; osteonectin and Runx2, adipocytes; PRAR-${\gamma}2$, FABP and LEP, and chondrocytes; collagen type-2 and Sox9) were also detected in all cells. In this study, we successfully established synovial fluid derived mesenchymal stem cells from female and male dogs, and determined their basic biological properties and differentiation ability. These results suggested that synovial fluid is a valuable stem cell source for cartilage regeneration therapy, and it is easily accessible from osteoarthritic knee.

A Case of Mesenchymal Hamartoma Associated with Biliary Atresia (담도 폐쇄증 환아에서 우연히 발견된 간엽 과오종 1례)

  • Choi, Kyung-Dan;Seo, Jeong-Kee;Shin, Eon-Woo;Ko, Jae-Sung;Kim, Woo-Sun;Park, Young-Su;Kang, Kyung-Hoon;Chi, Je-Geun
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.4 no.1
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    • pp.113-119
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    • 2001
  • Mesenchymal hamartoma is an uncommon benign tumor usually found in childhood, especially during the first two years of life. The tumor consists of a solid component and multiple cyst. Without treatment, these lesions can grow to an enormous size. We experienced a case of mesenchymal hamartoma which was found incidentally, in a 8 month old girl who had ascending cholangitis after Kasai operation due to biliary atresia. On abdominal ultrasonography and CT, there was a well-defined homogeneous small echogenic mass in the right lobe of the liver with cirrhosis. Five months later, she underwent liver transplantation. Gross picture of the resected liver showed a dark greenish pigmented solid mass in the right lobe of the cirrhotic liver. Microscopic findings showed reactive mesenchyma and epithelial overgrowth.

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Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells

  • Do, Nam Yong;Shin, Hyun-Jae;Lee, Ji-Eun
    • Nutrition Research and Practice
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    • v.11 no.2
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    • pp.83-89
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    • 2017
  • BACKGROUND/OBJECTIVES: Epithelial-mesenchymal transition (EMT) is involved in not only cancer development and metastasis but also non-cancerous conditions. Hypoxia is one of the proposed critical factors contributing to formation of chronic rhinosinusitis or nasal polyposis. Wheatgrass (Triticum aestivum) has antioxidant, anti-aging, and anti-inflammatory effects. In this study, we analyzed whether wheatgrass has an inhibitory effect on the EMT process in airway epithelial cells. MATERIALS/METHODS: A549 human lung adenocarcinoma cells were incubated in hypoxic conditions ($CO_2$ 5%/$O_2$ 1%) for 24 h in the presence of different concentrations of wheatgrass extract (50, 75, 100, and $150{\mu}g/mL$) and changes in expression of epithelial or mesenchymal markers were evaluated by immunoblotting and immunofluorescence. Accordingly, associated EMT-related transcriptional factors, Snail and Smad, were also evaluated. RESULTS: Hypoxia increased expression of N-cadherin and reduced expression of E-cadherin. Mechanistically, E-cadherin levels were recovered during hypoxia by silencing hypoxia inducible factor (HIF)-$1{\alpha}$ or administering wheatgrass extract. Wheatgrass inhibited the hypoxia-mediated EMT by reducing the expression of phosphorylated Smad3 (pSmad3) and Snail. It suppressed the hypoxia-mediated EMT processes of airway epithelial cells via HIF-$1{\alpha}$ and the pSmad3 signaling pathway. CONCLUSION: These results suggest that wheatgrass has potential as a therapeutic or supplementary agent for HIF-1-related diseases.

Background Cytologic Features of Metastatic Carcinomas in the Liver in Fine Needle Aspiration Cytology - Analysis of 20 Cases - (간의 전이성 상피암 20예의 세침 천자 흡인시 배경 병변의 세포학적 소견)

  • Myong, Na-Hye;Koh, Jae-Soo;Ha, Chang-Won;Cho, Kyung-Ja;Jang, Ja-June
    • The Korean Journal of Cytopathology
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    • v.2 no.2
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    • pp.90-97
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    • 1991
  • Liver is generally known as an organ which is most commonly involved by the metastic tumors. According to the tendency of using fine needle aspiration in the diagnosis of hepatic tumors, the differentital diagnosis between hepatocellular carcinoma and metastatic carcinoma frequently has been a main issue in the poorly differentitated cases, especially to the pathologists of Korea, an endemic area of hepatocellular carcinoma. Until now the problem has been usually solved by the comparison of cytologic characteristics of their tumor cells but not by background cytologic features which rarely have been studied. We observed the background cytologic features helpful for the differential diagnosis through the analysis of 20 cases who had confirmed primary cancer and were diagnosed as metastatic carcinomas in the liver by fine needle aspiration cytology. Twenty cases included 9 adenocarcinomas, 7 spuamous cell carcinomas, 1 small cell carcinoma, 1 carcinoid, 1 adenoid cystic carcinoma, and 1 renal cell cacinoma. Analysis of background cytologic features revealed that 77% of adenocacinoma cases showed benign mesenchymal components and hepatocytes and spuamous cell carcinoma cases disclosed benign mesenchymal tissue (71%) and necrosis (57%), Remaining cases showed variable combinations of benign mesenchymal component, necrosis, hepatocytes, and bile duct epithelial cells. No case revealed atypical hepatocytic naked nuclei, a useful cytologic finding of hepatocellular carcinoma. In summary, the background cytologic features more commonly observed in metastatic carcinomas than in the hepatocellular carcinoma were benign mesenchymal components, hepatocytes, necrosis, and bile duct epithelium. The endothelial cells and hepatocytic naked nuclei, two relatively specific findings of hepatocellular carcinoma were not observed except for renal ceil carcinoma. Above background cytologic features are thought to be helpful for the differential diagnosis between the hepatocellular carcinoma and various metastatic carcinomas in the poorly differentiated cases.

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