• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권2호
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• pp.97-108
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• 2011

Cancer stem cells have stem cell-like features, such as the ability for self-renewal and differentiation but show unlimited growth because they have the lost normal regulation of cell growth. Cancer stem cells and normal stem cells have similar features. They show high motility, diversity of progeny, robust proliferative potential, association with blood vessels, immature expression profiles, nestin expression, epidermal growth factor (EGF)-receptor expression, phosphatase and tensin homolog (PTEN) expression, hedgehog pathway activity, telomerase activity, and Wnt pathway activity. On the other hand, with cancer cells, some of these signaling pathways are abnormally modified. In 1875, Cohnheim suggested the concept of cancer stem cells. Recently, evidence for the existence of cancer stem cells was identified. In 1994, the cancer stem cells' specific cell surface marker for leukemia was identified. Since then, other specific cell surface markers for cancer stem cells in solid tumors (e.g. breast and colon cancer) have been identified. In oral cancer, studies on cancer stem cells have been performed mainly with squamous cell carcinomas. Oral cancer specific cell surface markers, which are genes strongly expressed in oral cancer and cancer stem cell specific side populations, have been identified. Cancer stem cells are resistant to radiotherapy and chemotherapy. Therefore, to eliminate malignant tumors efficiently and reduce the recurrence rate, therapy targeting cancer stem cells needs to be performed. Currently, studies targeting the cancer stem cells' specific signaling pathways, telomerase and tumor vasculatures are being done.

• Journal of Korean Neurosurgical Society
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• 제62권2호
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• pp.153-165
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• 2019

Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• 대한한방내과학회지
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• 제37권1호
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• pp.65-76
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• 2016

Objectives: The purpose of this study was to identify the inhibitory effects of Hwangheuk-san (HHS), a Korean multi-herb formula comprising four medicinal herbs, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, using the human bladder cancer 5637 cell line.Methods: Cell viability, motility, and invasion were assessed by 3-(4,5-dimethyl-2 thiazolyl)-2,5-diphnyl-2H-tetrazolium bromide (MTT), wound healing migration, and Transwell assays, respectively. Gene expression was detected by Western blot analysis. In addition, the activities of matrix metalloproteinases (MMPs) and the values for transepithelial electrical resistance (TER) were analyzed using a Gelatinase Activity Assay Kit and an Epithelial Tissue Voltohmmeter, respectively.Results: Our data indicated that within the concentration range that was not cytotoxic, HHS effectively inhibited the cell motility and invasiveness of 5637 cells. HHS markedly decreased the expression and activity of MMP-2 and MMP-9, which was associated with unregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2. Further investigation revealed that phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT was decreased in HHS-treated 5637 cells, and a PI3K/AKT inhibitor synergistically reduced the inhibition of migration and invasion and also inactivated MMP-2 and MMP-9. Moreover, HHS increased the tightening of tight junctions (TJs), which was demonstrated by an increase in the TER, and reduced the expression the levels of claudin family members (claudin-3 and -4), which are major components involved in the tightening of TJs.Conclusions: The present findings demonstrated that HHS attenuated the migration and invasion of bladder cancer 5637 cells by modulating the activity of the PI3K/Akt signaling pathway and also through TJ tightening.

• BMB Reports
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• 제45권8호
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• pp.427-432
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• 2012

Primary cilia, single hair-like appendage on the surface of the most mammalian cells, were once considered to be vestigial cellular organelles for a past century because of their tiny structure and unknown function. Although they lack ancestral motility function of cilia or flagella, they share common ground with multiciliated motile cilia and flagella on internal structure such as microtubule based nine outer doublets nucleated from the base of mother centrioles called basal body. Making cilia, ciliogenesis, in cells depends on the cell cycle stage due to reuse of centrioles for cell division forming mitotic spindle pole (M phase) and assembling cilia from basal body (starting G1 phase and maintaining most of interphase). Ciliary assembly required two conflicting processes such as assembly and disassembly and balance between these two processes determines the length of cilia. Both process required highly conserved transport system to supply needed substance to grow tip of cilia and bring ciliary turnover product back to the base of cilia using motor protein, kinesin and dynein, and transport protein complex, IFT particles. Disruption of ciliary structure or function causes multiple human disorder called ciliopathies affecting disease of diverse ciliated tissues ranging from eye, kidney, respiratory tract and brain. Recent explosion of research on the primary cilia and their involvement on animal development and disease attracts scientific interest on how extensively the function of cilia related to specific cell physiology and signaling pathway. In this review, I introduce general features of primary cilia and recent progress in understanding of the ciliary length control and signaling pathways transduced through primary cilia in vertebrates.

• BMB Reports
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• 제51권9호
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• pp.425-426
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• 2018

As highly conserved signaling cascades of multicellular organisms, Wnt and Hippo pathways control a wide range of cellular activities, including cell adhesion, fate determination, cell cycle, motility, polarity, and metabolism. Dysregulation of those pathways are implicated in many human diseases, including cancer. Similarly to ${\beta}-catenin$ in the Wnt pathway, the YAP transcription co-activator is a major player in Hippo. Although the intracellular dynamics of YAP are well-known to largely depend on phosphorylation by LATS and AMPK kinases, the molecular effector of YAP cytosolic translocation remains unidentified. Recently, we reported that the Dishevelled (DVL), a key scaffolding protein between canonical and non-canonical Wnt pathway, is responsible for nuclear export of phosphorylated YAP. The DVL is also required for YAP intracellular trafficking induced by E-cadherin, ${\alpha}-catenin$, or metabolic stress. Note that the p53/LATS2 and LKB1/AMPK tumor suppressor axes, commonly inactivated in human cancer, govern the reciprocal inhibition between DVL and YAP. Conversely, loss of the tumor suppressor allows co-activation of YAP and Wnt independent of epithelial polarity or contact inhibition in human cancer. These observations provide novel mechanistic insight into (1) a tight molecular connection merging the Wnt and Hippo pathways, and (2) the importance of tumor suppressor contexts with respect to controlled proliferation and epithelial polarity regulated by cell adhesion.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.565-570
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• 2015

Breast and colorectal cancers rank high in Iran as causes of mortality. Most of the current treatments are expensive and non-specific. The potential anticancer properties of common home gecko, Cyrtopodion scabrum, were investigated in this study. The effects of C. scabrum extract on proliferation, viability and migration of the colorectal cancer (SW-742), breast cancer (MCF-7) and normal (MSC) cell lines were investigated using MTT and in vitro wound healing assay. $IC_{50}$ values calculated for the extract were $559{\pm}28.9{\mu}g/mL$ for MCF-7 and $339{\pm}11.3{\mu}g/mL$ for SW-742. No toxic effects on the normal control cells were observed. MCF-7 and SW-742 cell growth was inhibited by 32.6% and 62%, under optimum conditions, compared to the untreated control cells. The extract also decreased the motility and migration ability of both cancer cell lines, with no significant effects on the normal control cells. Data suggest C. scabrum extract as a useful natural resource for targeting cancer cells specifically.

• Journal of Korean Biological Nursing Science
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• 제7권1호
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• pp.47-56
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• 2005

nm23-H1 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. However, its role with respect to the invasive behavior of central nervous system tumors has scarcely been addressed Because cell motility and invasion plays an essential role in metastatic dissemination, we have studied whether motile human glioma cell(U87MG) transfected with nm23-H1 complementary DNA have any alterations in their ability to migrate and invade. There was no significant changes in the shape and size of the cells following nm23-H1 transfection. The role of nm23-H1 in glioma migration and invasion have been evaluated by in vitro simple scratch technique and brain slice invasion model Basal migration ability of nm23-H1 transfectants cell(U87MG-pEGFP-nm23) were lesser than U87MG. Accordingly, U87MG-pEGFP-nm23 didn't migrate away apparently from the tumors implanted site comparing U87MG in brain slice invasion model. These results suggest that nm23-H1 may play an important role in suppressing the human glioma migration and invasion.

• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5391-5396
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• 2013

Aim: To investigate the role of Golgi phosphoprotein 3 (GOLPH3) in tumour growth and metastasis of esophageal squamous cancer. Methods: A lentiviral shRNA-vector was utilized to stably knockdown GOLPH3 in Eca-109 esophageal squamous cancer cells. mRNA transcription and protein expression of GOLPH3 were examined by real-time quantitative PCR and Western blotting, respectively. Cell proliferation activity was assessed by MTT assay and invasion and migration potentials by matrigel invasion and transwell motility assays. Results: Stable knockdown in the GOLPH3 cell line was established. PD-A gene expression was significantly suppressed by lentivirus-mediated RNAi, which resulted in reducing the capacity for cell proliferation, migration, invasion and adhesion in vitro. In vivo, GOLPH3 depletion resulted in inhibition of tumour growth, with stable decrease in the expression of GOLPH3 in tumor xenografts. Conclusions: Our findings suggest that lentivirus mediated silencing of the GOLPH3 gene has a significant anti-tumour effect on esophageal squamous cancer in vitro and in vivo. In addition, the results indicate that GOLPH3 might be an effective molecular target for gene therapy in esophageal squamous cancer.

• Journal of Microbiology and Biotechnology
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• 제14권2호
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• pp.379-384
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• 2004

Fibroblast growth factor-2 (FGF-2) is known to modulate numerous cellular functions in various cell types, including cell proliferation, differentiation, survival, adhesion, migration, and motility, and also in processes such as wound healing, angiogenesis, and vasculogenesis. FGF-2 regulates the expression of several molecules thought to mediate critical steps during angiogenesis. This study examines the mechanisms underlying FGF-2-induced cell migration, using human umbilical vein endothelial cells (HUVECs). FGF-2 induced the nondirectional and directional migration of endothelial cells, which are inhibited by MMPs and plasmin inhibitors, and induced the secretion of matrix metalloproteinase-3 (MMP3) and MMP-9, but not MMP-l and MMP-2. FGF-2 also induced the secretion of the tissue inhibitor of metalloproteinase-l (TIMP-I), but not of TIMP- 2. Also, the pan-PKC inhibitor inhibited FGF-2-induced MMP-9 secretion. It is, therefore, suggested that FGF-2 induces the migration of cultured endothelial cells by means of increased MMPs and plasmin secretion. Furthermore, FGF-2 may increase MMP-9 secretion by activating the PKC pathway.

• 한국가시화정보학회지
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• 제16권2호
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• pp.38-44
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• 2018

Cellular jamming phenomenon, defined as a kinetic arrest, is a commonly observed event in dense cell aggregates in epithelial tissues. Cells lose their motility when the density of the cell population becomes too high. Yet, not much is known about how the jamming occurs and how it influences individual cells in the population. In this study, we investigated the mechanisms during the formation of the jammed state by visualizing various dynamic components such as velocity, traction, and intercellular stress. The visualized properties exhibited interrelated features in similar time domains that can be categorized into specific stages, namely migrating, transitional and steady state. During the migrating stage, cells generated spatially correlated tractions and migrations at the collective migration step and lost these properties becoming a transitional stage. These stepwise analyses presented correlative components which are expected to adjust for explaining the detailed mechanisms of cellular jamming.