• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.320-323
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• 2011

We conducted this study to investigate whether berberine signifi cantly affects MUC5AC mucin gene expression and mucin production induced by epidermal growth factor (EGF), phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) from human airway epithelial cells. Confl uent NCI-H292 cells were pretreated with varying concentrations of berberine for 30 min and then stimulated with EGF, PMA or TNF-${\alpha}$ for 24 h. MUC5AC mucin gene expression and mucin production were measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Berberine was found to inhibit the expression of MUC5AC mucin gene induced by EGF, PMA or TNF-${\alpha}$. Berberine also inhibited the production of MUC5AC mucin protein stimulated by the same inducers. This result suggests that berberine can regulate the expression of mucin gene and production of mucin protein, by directly acting on human airway epithelial cells.

• Clinical and Experimental Reproductive Medicine
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• v.48 no.4
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• pp.303-310
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• 2021

Decorin (DCN) is a proteoglycan belonging to the small leucine-rich proteoglycan family. It is composed of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate. DCN is a structural component of connective tissues that can bind to type I collagen. It plays a role in the assembly of the extracellular matrix (ECM), and it is related to fibrillogenesis. It can interact with fibronectin, thrombospondin, complement component C1, transforming growth factor (TGF), and epidermal growth factor receptor. Normal DCN expression regulates a wide range of cellular processes, including proliferation, migration, apoptosis, and autophagy, through interactions with various molecules. However, its aberrant expression is associated with oocyte maturation, oocyte quality, and poor extravillous trophoblast invasion of the uterus, which underlies the occurrence of preeclampsia and intrauterine growth restriction. Spatiotemporal hormonal control of successful pregnancy should regulate the concentration and activity of specific proteins such as proteoglycan participating in the ECM remodeling of trophoblastic and uterine cells in fetal membranes and uterus. At the human feto-maternal interface, TGF-β and DCN play crucial roles in the regulation of trophoblast invasion of the uterus. This review summarizes the role of the proteoglycan DCN as an important and multifunctional molecule in the physiological regulation of oocyte maturation and trophoblast migration. This review also shows that recombinant DCN proteins might be useful for substantiating diverse functions in both animal and in vitro models of oogenesis and implantation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.25 no.1
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• pp.107-119
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• 1999

3 Kinds of PEG-hEGF conjugate, PEG5-hEGF, PEG5-hEGF, PEG10-hEGF, were synthesized. Major fractions containing 2 chains of PEG were separated by preparative GPC. Molecular weight was estimated by GPC-MALLS, TOF-Mass and SDS-PAGE, and the data were well corresponding to calculated one. The cell proliferation effect of the conjugates was evaluated, Indicating that the conjugate bound to longer chain PEG exhibits lower activity. Selective modification of hEGF and activity preservation of PEG-hEGF conjugate are undergoing.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.109-114
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• 2016

In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and trafficking of tumor necrosis factor-alpha (TNF-${\alpha}$) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarified that the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease. Thus, this review focuses on our understanding of iRhoms and the involved mechanisms in the cellular processes.

• Journal of Korean Neurosurgical Society
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• v.63 no.2
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• pp.163-170
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• 2020

Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.

• Radiation Oncology Journal
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• v.32 no.3
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• pp.156-162
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• 2014

Purpose: This study was designed to evaluate the efficacy and safety of topically applied recombinant human epidermal growth factor (rhEGF) for the prevention of radiation-induced dermatitis in cancer patients. Materials and Methods: From December 2010 to April 2012, a total of 1,172 cancer patients who received radiotherapy (RT) of more than 50 Gy were prospectively enrolled and treated with EGF-based cream. An acute skin reaction classified according to the Radiation Therapy Oncology Group 6-point rating scale was the primary end point and we also assessed the occurrence of edema, dry skin, or pruritus. Results: The percentage of radiation dermatitis with maximum grade 0 and grade 1 was 19% and 58% at the time of 50 Gy, and it became 29% and 47% after completion of planned RT. This increment was observed only in breast cancer patients (from 18%/62% to 32%/49%). Adverse events related to the EGF-based cream developed in 49 patients (4%) with mild erythema the most common. Skin toxicity grade >2 was observed in 5% of the patients. Edema, dry skin, and pruritus grade ${\geq}3$ developed in 9%, 9%, and 1% of the patients, respectively. Conclusion: Prophylactic use of an EGF-based cream is effective in preventing radiation dermatitis with tolerable toxicity. Further studies comparing EGF cream with other topical agents may be necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6221-6225
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• 2012

Background: To determine the frequency of HER-2 overexpression in colorectal cancer (CRC) patients, and to explore the relationship between clinicopathological prognostic factors and their effects on survival, based on immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) analysis. Materials and Methods: The study included 80 patients with a histologically proven diagnosis of CRC that received adjuvant FOLFOX-4 chemotherapy at our department between March 2006 and September 2010. Patient data were analyzed retrospectively. Results: The median follow-up period and age of the patients were 24 months and 59 years, respectively. In immunohistochemical staining, 3+ staining was found in 2 patients (2.5%) while 2+ was in 13 (16%). FISH for HER-2 was performed for all of these 15 patients; samples which were 3+ showed positivity but the ones with 2+ were negative. There was no significant correlation between HER-2 expression and age, gender, tumor localization, histological subtype, grade, lymphovascular and perineural invasion, or pTN stage (P>0.05), even when the patients with HER-2 overexpression were analyzed separately. There was also no significant relationship between progression-free survival (PFS) and overall survival (OS), and HER-2 expression, gender, tumor localization, obstruction-perforation, bleeding, histological type, grade, lymphovascular and perineural invasion, or pT staging (P>0.05); however, there was a significant relationship between lymph node involvement, and PFS and OS (P<0.05). Conclusions: Evaluation of HER-2 overexpression in a more comprehensive, multi-center, prospective trial with standardized methods will be an appropriate approach.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3053-3059
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• 2012

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases that plays important roles in all processes of cell development. Their overexpression is related to many cancers, including examples in the breast, ovaries and stomach. Anticancer therapies targeting the HER2 receptor have shown promise, and monoclonal antibodies against subdomains II and IV of the HER2 extra-cellular domain (ECD), Pertuzumab and Herceptin, are currently used in treatments for some types of breast cancers. Since anti HER2 antibodies targeting distinct epitopes have different biological effects on cancer cells; in this research linear and conformational B cell epitopes of HER2 ECD, subdomain III, were identified by bioinformatics analyses using a combination of linear B cell epitope prediction web servers such as ABCpred, BCPREDs, Bepired, Bcepred and Elliprro. Then, Discotope, CBtope and SUPERFICIAL software tools were employed for conformational B cell epitope prediction. In contrast to previously reported epitopes of HER2 ECD we predicted conformational B cell epitopes $P1_C$: 378-393 (PESFDGDPASNTAPLQ) and $P2_C$: 500-510 (PEDECVGEGLA) by the integrated strategy and P4: PESFDGD-X-TAPLQ; P5: PESFDGDP X TAPLQ; P6: ESFDGDP X NTAPLQP; P7: PESFDGDP-X-NTAPLQ; P8: ESFDG-XX-TAPLQPEQL and P9: ESFDGDP-X-NTAPLQP by SUPERFICIAL software. These epitopes could be further used as peptide antigens to actively immune mice for development of new monoclonal antibodies and peptide cancer vaccines that target different epitopes or structural domains of HER2 ECD.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.16-21
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• 2011

HER-2 (Human Epidermal Growth Factor Receptor-2) is a protein giving higher aggressiveness in human breast cancers. Trastuzumab is a monoclonal antibody that targets HER-2 and is known to extend survival across all stages of HER2-positive breast cancer. In this study, we attempted to development of a quantitative ELISA (Enzyme-Linked ImmunoSorbent Assay) for evaluating anti HER-2 antibodies using human HER-2 recombinant proteins to support antibody producing processes and pharmacokinetic studies. We established direct or indirect ELISA method for the trastuzumab-like protein combined human recombinant HER-2. The ELISA method will prove to be great value in quantitating anti-HER-2 antibodies levels for developing anticancer antibodies.

• BMB Reports
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• v.51 no.3
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• pp.119-125
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• 2018

The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis of YAP expressions can facilitate the identification of patients who respond better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted inhibitors. The prominence of YAP for those aspects of cancer biology denotes that these factors are ideal targets for the development of anti-cancer medications. Therefore, our report strongly indicates that the YAP is of potential prognostic utility and druggability in various human cancers.