• 대한구순구개열학회지
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• 제4권1호
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• pp.13-26
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• 2001

Cleft lip and/or palate is the congenital orofacial malformation most commonly occurred in humans, The disease is multifactorial and is probably caused by genetic and/or environmental factors, So, there are many problems in research concerning etiology and in treatment of the disease, Even the most practiced and sophisticated methods of surgical repair are necessarily followed by scar contraction and fibrosis, which result in skeletal defects, dental abnormalities, cosmetic disfigurement, and speech impairment, As a result, Fetal surgery can be considered but practiced rarely when the deformity is not fatal to life, And treatment of cleft palate is performed in the form of medicine projection into uterus in animal experiments, Many studies show that growth factor and its receptor emerge from the developing palate; and the epidermal growth factor receptors have a important role in craniofacial development and in palatal fusion, The palatal morphogenesis of the avine is different from the mammal's; it takes the form of physiologic cleft palate, Recently, cleft palate fusion experiment was performed when the avine were in the period of palate formation through the exogenous TGF-β3 addition, and it showed that the exogenous TGF-β3 makes fusion of divided palate through certain process when cleft palate is occurred in palatal formation, In this study, I had the conformation of the fusion of cleft palate through the addition of TGF-β in case of chicken embryo, and observed the effect of TGF-β in EGF receptor distribution, And the following is the results of this study, 1. In case of the TGF-βl and β3 addition group, there was the decrease of EGFR(Epidermal Growth Factor Receptor) immunoreactivity in mesenchymal cells beneath the medial edge epithelium and also in epithelial mesenchymal interface which is between medial edge epithelium and nasal septum in 72 hours, 2, The immunoreactivity of the control group resembles that of normal chicken embryo palate in development, 3. In the view through fluorescence confocal microscopy, there was confluence in TGF-β3 addition group, This shows that the confluence induced by exogenous TGF-β3 is related to EGFR expression in palate of chicken embryo, which is a physiologic cleft palate model.

• 대한의생명과학회지
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• 제11권2호
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• pp.175-183
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• 2005

The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

• 대한임상검사과학회지
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• 제39권3호
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• pp.217-222
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• 2007

In the last 5 years the Epidermal Growth Factor Receptor (EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefits in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Also the targeting of the epithelial growth factor receptor (EGFR) kinase domain using the closely related inhibitors gefitinib and erlotinib has generally been ineffective against solid tumors, many of which over express the receptor. We found that there were some differential expressions according to primary antibodies of the EGFR protein which being used as one of the histological tumor markers for non-small cell lung cancer (NSCLC). We also found that there are some differential expressions according to antibodies, the pH of the antigen retrieval (AR) buffer solutions and kinds of enzymes. There were some differential expressions according to the secondary antibodies and the detection systems. We analyzed the correlations between the immunohistochemical expressions of the EGFR protein and the gene mutations of the EGFR. The differences between automatic stainers and manual staining methods were also evaluated.

• 한국동물생명공학회지
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• 제35권4호
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• pp.297-306
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• 2020

The aims of the present study were to confirm that regulation of the PA and environment via TGF-β regulation of sperm by Percoll-separated in porcine uterine epithelial cells. And, it was performed to identify the cytokines (TGF-β1, 2 and 3, TGF-β receptor1 and 2; interleukin, IL-6, IL-8) and PA-related genes (urokinase-PA, uPA; tissue-PA, tPA; PA inhibitor, PAI; uPA-receptor, uPAR) by spermatozoa. The experiment used porcine uterus epithelial cells (pUECs) and uterine tissue epithelial cells, Boar sperm were separated by discontinuous Percoll density gradient (45/90%), and tissues were co-incubated with spermatozoa, followed by real-time PCR. PA activity was measured of sperm by discontinuous Percoll density gradient (45/90%) for 24 hours. To measure viability and acrosome damage of sperm double stained propidium iodide (PI) and SYBR-14 or FITC-PNA were used. In results, binding ratio of Percoll-separated sperm was found no differences, but sperms isolated from 90% Percoll layer reduced PA activity (p < 0.05). when co-cultured sperm selected Percoll in porcine uterus tissues epithelial cells, 90% layer sperm increased TGF-β R1, contrastively tPA and PAI-1 in comparison with control (p < 0.05). 45% sperm was decreased the expression of uPA (p < 0.05). TGF-β decreased PA activity in the supernatant collected from pUECs (p < 0.05). Especially, The group including uPA, PAI-1 were induce sperm intact, while it was reduced in sperm damage when compared to control (p < 0.05). Also, there was no significant difference group of tPA and tPA+I in the dead sperm and acrosome damage compared to control. The expression of tPA and PAI showed a common response. Percoll-separated spermatozoa in 90% layer reduced tPA and IL-related gene mRNA expression. Thus, Percoll-sparated sperm in 90% layer show that it can suppress inflammation through increased expression of TGF-β and downregulation of PA and IL in epithelial cells compared to 45% layer Percoll.

• Journal of Acupuncture Research
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• 제31권2호
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• pp.87-98
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• 2014

Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

• BMB Reports
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• 제45권12호
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• pp.719-723
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• 2012

A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ~30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권3호
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• pp.245-249
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• 2008

Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids and has a potent mitogenic activity that stimulates proliferation of various normal and neoplastic cells through the interaction with its specific receptor(epidermal growth factor receptor, EGFR). Pleomorphic adenoma is the most common salivary benign tumor and histologically, it contains the epithelial cell, the myo-epithelial cell and mesenchymal ingredient, which is various aspect. Adenoid cystic carcinoma is an infiltrative malignant salivary gland tumor with three different histological patterns: cribriform, tubular or solid. The tumor cell structure composed of modified myoepithelial cell, and basaloid cell. In this study, we used an immunohistochemical technique to investigate the expression of EGF in 6 specimens of adenoid cystic carcinoma and 10 specimens of pleomorphic adenoma taken from patients treated at Dept. of Oral and Maxillofacial Surgery, Dankook University. The results were as follows. 1. In pleomorphic adenoma, ductal structure and scattered spindle cells in hyalinized stroma, disclosing myxoid stroma and hyalin, cartilage formation were observed. Immunohistologically, weak EGF expression in ductal structure and negative in stromal area were observed. 2. Cribriform type of adenoid cystic carcinoma showed numerous pseudocyst surrounded by dark small neoplastic cells in the back-ground of fibrous connective tissue and moderate EGF expression of dark cells adjacent to pseudo lumen in cribriform pattern, while weak expression in other most cells. 3. Tubular type of adenoid cystic carcinoma showed numerous ductal pattern surrounded by two layered neoplastic cells in the back-ground of fibrous connective tissue and strong EGF expression in luminal cells of ductal structure, while weak expression in outer cells. From the results obtained, we suggest that EGF is mainly biosynthesized in cells forming duct like structures of tubulo-ductal type or cribriform adenoid cystic carcinoma and it may play a role, as a cell mitogen in adenoid cystic carcinoma growth.

• Journal of Chest Surgery
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• 제50권3호
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• pp.153-162
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• 2017

Background: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. Methods: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. Results: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. Conclusion: C HIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.

• International Journal of Oral Biology
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• 제39권2호
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• pp.107-114
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• 2014

Taste is an important sense in survival and growth of animals. The growth and maintenance of taste buds, the receptor organs of taste sense, are under the regulation of various neurotrophic factors. But the distribution aspect of neurotrophic factors and their receptors in distinct taste cell types are not clearly known. The present research was designed to characterize mRNA expression pattern of neurotrophic factors and their receptors in distinct type of taste cells. In male 45-60 day-old Sprague-Dawley rats, epithelial tissues with and without circumvallate and folliate papillaes were dissected and homogenized, and mRNA expressions for neurotrophic factors and their receptors were determined by RT-PCR. The mRNA expressions of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), receptor tyrosine kinase B (TrkB), exclusion of nerve growth factor (NGF), neurotrophin-4/5 (NT4/5), receptor tyrosine kinase A (TrkA), receptor tyrosine kinase C (TrkC), and p75NGFR were observed in some population of taste cell. In support of this result and to characterize which types of taste cells express NT3, BDNF, or TrkB, we examined mRNA expressions of NT3, BDNF, or TrkB in the $PLC{\beta}2$ (a marker of Type II cell)-and/or SNAP25 (a marker of Type III cell)-positive taste cells by a single taste cell RT-PCR and found that the ratio of positively stained cell numbers were 17.4, 6.5, 84.1, 70.3, and 1.4 % for $PLC{\beta}2$, SNAP25, NT3, BDNF, and TrkB, respectively. In addition, all of $PLC{\beta}2$-and SNAP25-positive taste cells expressed NT3 mRNA, except for one taste bud cell. The ratios of NT3 mRNA expressions were 100% and 91.7% in the SNAP25-and $PLC{\beta}2$-positive taste cells, respectively. However, two TrkB-positive taste cells co-expressed neither $PLC{\beta}2$ nor SNAP 25. The results suggest that the most of type II or type III cells express BDNF and NT3 mRNA, but the expression is shown to be less in type I taste cells.

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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• pp.197-207
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• 2024

The potential of tivozanib as a treatment for oral squamous cell carcinoma (OSCC) was explored in this study. We investigated the effects of tivozanib on OSCC using the Ca9-22 and CAL27 cell lines. OSCC is a highly prevalent cancer type with a significant risk of lymphatic metastasis and recurrence, which necessitates the development of innovative treatment approaches. Tivozanib, a vascular endothelial growth factor receptor inhibitor, has shown efficacy in inhibiting neovascularization in various cancer types but has not been thoroughly studied in OSCC. Our comprehensive assessment revealed that tivozanib effectively inhibited OSCC cells. This was accompanied by the suppression of Bcl-2, a reduction in matrix metalloproteinase levels, and the induction of intrinsic pathway-mediated apoptosis. Furthermore, tivozanib contributed to epithelial-to-mesenchymal transition (EMT) inhibition by increasing E-cadherin levels while decreasing N-cadherin levels. These findings highlight the substantial anticancer potential of tivozanib in OSCC and thus its promise as a therapeutic option. Beyond reducing cell viability and inducing apoptosis, the capacity of tivozanib to inhibit EMT and modulate key proteins presents the possibility of a paradigm shift in OSCC treatment.