• Title/Summary/Keyword: epidermal Growth factor

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Tilianin Inhibits MUC5AC Expression Mediated Via Down-Regulation of EGFR-MEK-ERK-Sp1 Signaling Pathway in NCI-H292 Human Airway Cells

  • Song, Won-Yong;Song, Yong-Seok;Ryu, Hyung Won;Oh, Sei-Ryang;Hong, JinTae;Yoon, Do-Young
    • Journal of Microbiology and Biotechnology
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    • v.27 no.1
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    • pp.49-56
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    • 2017
  • In the human airway, mucus exists to protect the respiratory system as a primary barrier of the innate immune system. However, hyperexpressed mucus limits airflow, resulting in a decrease of lung function. Among more than 20 mucin family members, MUC5AC and MUC5B are major glycoproteins in human airway mucus. The epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression. Even though there are some drugs for treating mucus hypersecretion, no drug has proven effects on humans. We found that the flavonoid tilianin regulated MUC5AC expression and also inhibited Sp1 phosphorylation. In this study, we investigated how tilianin would modulate EGFR signaling and regulate mucin production. In conclusion, tilianin inhibited MUC5AC expression mediated via modulating the EGFR-MEK-ERK-Sp1 signaling pathway in NCI-H292 human airway epithelial cells. This study may provide the basis for the novel treatment of mucus hypersecretion.

Lack of Prognostic Value of Human Epidermal Growth Factor- Like Receptor 2 Status in Inflammatory Breast Cancer (IBC): a Meta-analysis

  • Li, Xiu-Juan;Zha, Quan-Bin;Xu, Xin-Yu;Xia, Lei;Zhang, Zhe;Ren, Zhao-Jun;Tang, Jin-Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9615-9619
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    • 2014
  • Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer which is more likely to be her-2/neu amplified. While the her-2/neu status has been utilised to predict prognosis, the published data are inconsistent. The present meta-analysis was conducted to determine whether the her-2/neu status predicts outcomes. Papers were selected from the PubMed database based on defined inclusion and exclusion criteria. Parameters such as total patients, follow-up time and outcome statistics (i.e. overall survival (OS), relapse-free survival (RFS) were collected. The analysis included 6 studies with 2,838 IBC patients. The summary hazards ratio (HR) estimating the association of OS with HER-2-positive disease was 0.96 (95% confidence interval (95%CI: 0.85-1.10)), with similar findings for RFS (HR=0.81, 95%CI: 0.61-1.09). No obvious statistical heterogeneity was detected. This meta-analysis suggests that HER-2-positive status is not an independent adverse prognostic factor for survival among IBC patient cases.

Objective Quantitation of EGFR Protein Levels using Quantitative Dot Blot Method for the Prognosis of Gastric Cancer Patients

  • Xin, Lei;Tang, Fangrong;Song, Bo;Yang, Maozhou;Zhang, Jiandi
    • Journal of Gastric Cancer
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    • v.21 no.4
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    • pp.335-351
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    • 2021
  • Purpose: An underlying factor for the failure of several clinical trials of anti-epidermal growth factor receptor (EGFR) therapies is the lack of an effective method to identify patients who overexpress EGFR protein. The quantitative dot blot method (QDB) was used to measure EGFR protein levels objectively, absolutely, and quantitatively. Its feasibility was evaluated for the prognosis of overall survival (OS) of patients with gastric cancer. Materials and Methods: Slices of 2×5 ㎛ from formalin-fixed paraffin-embedded gastric cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for the Kaplan-Meier OS analysis. Results: EGFR protein levels ranged from 0 to 772.6 pmol/g (n=246) for all gastric cancer patients. A poor correlation was observed between quantitated EGFR levels and immunohistochemistry scores with ρ=0.024 and P=0.717 in Spearman's correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric cancer patients only through absolute quantitation, with a hazard ratio of 1.92 (95% confidence interval, 1.05-3.53; P=0.034) in multivariate Cox regression OS analysis. A cutoff of 208 pmol/g was proposed to stratify patients with a 3-year survival probability of 44% for patients with EGFR levels above the cutoff versus 68% for those below the cutoff based on Kaplan-Meier OS analysis (log rank test, P=0.002). Conclusions: A QDB-based assay was developed for gastric cancer specimens to measure EGFR protein levels absolutely, quantitatively, and objectively. This assay should facilitate clinical trials aimed at evaluation of anti-EGFR therapies retrospectively and prospectively for gastric cancer.

[6]-Gingerol Inhibits Phorbol Ester-Induce d Expression of Cyclooxygenase-2 in Mouse Skin: p38 MAPK and p65/RelA as Possible Molecular Targets

  • Kim, Sue-Ok;Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.05a
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    • pp.95.1-95
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    • 2003
  • Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

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Understanding EGFR Signaling in Breast Cancer and Breast Cancer Stem Cells: Overexpression and Therapeutic Implications

  • Alanazi, Ibrahim O;Khan, Zahid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.445-453
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    • 2016
  • Epidermal growth factor receptors (EGFRs/HERs) and downstream signaling pathways have been implicated in the pathogenesis of several malignancies including breast cancer and its resistance to treatment with chemotherapeutic drugs. Consequently, several monoclonal antibodies as well as small molecule inhibitors targeting these pathways have emerged as therapeutic tools in the recent past. However, studies have shown that utilizing these molecules in combination with chemotherapy has yielded only limited success. This review describes the current understanding of EGFRs/HERs and associated signaling pathways in relation to development of breast cancer and responses to various cancer treatments in the hope of pointing to improved prevention, diagnosis and treatment. Also, we review the role of breast cancer stem cells (BCSCs) in disease and the potential to target these cells.

An Integrated Process for the Separation and Purification of Biologically Active Proteins from Human Urine (인뇨로부터 유용단백질의 통합 분리정제 공정)

  • 김기용;정광회문흥모
    • KSBB Journal
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    • v.8 no.3
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    • pp.287-294
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    • 1993
  • For the purpose of combining the purification processes for several biologically active proteins form human urine, an efficient integrated fractionation procedure has been investigated. The procedure was started by concentration with ultrafiltration and pH precipitation followed by a selectable combination of chromatography on gel filtration, adsorption, ion exchanger, affinity, and reverse phase column. By this process, the purified urokinase, epidermal growth factor and albumin migrated as a single band on SDS-polyacrylamide gel electrophoresis and were fully active. The recoveries of these purified proteins were 48%, 17%, and 46%, respectively.

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Relationships of Concentrations of Endocrine Factors at Antemortem and Postmortem Periods to Carcass Weight and Backfat Thickness in Pigs

  • Yun, J.S.;Seo, D.S.;Rhee, M.S.;Oh, S.;Kim, B.C.;Ko, Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.16 no.3
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    • pp.335-341
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    • 2003
  • Carcass weight and backfat thickness are two of important elements in determining the carcass trait in pigs and are studied on animal genetics, nutrition, and endocrinology. Growth factors stimulate or inhibit the proliferation and differentiation of various cells. In particular, insulin-like growth factors (IGFs), transforming growth factor (TGF)-$\beta$, and epidermal growth factor (EGF) are involved in the growth and maintenance of muscle. Also, dehydroepiandrosterone-sulfate (DHEA-S) and cortisol are known to be related to the obesity and subcutaneous fat depth in pigs. Therefore, this study was performed to relate growth factors (IGFs, TGF-${\beta}1$, and EGF) and hormones (cortisol and DHEA-S) concentrations at antemortem and postmortem periods to carcass traits including carcass weight and backfat thickness. Blood and m. Longissimus were collected in pigs at antemortem (30 days before slaughter) and postmortem periods. After slaughtered, carcass weight and backfat thickness were measured. Growth factors and hormones in serum and m. Longissimus were measured by radioimmunoassay or enzyme-linked imuunosorbent assay. Before antemortem period, serum IGF-I and -II concentrations were positively correlated with the carcass weight and backfat thickness in gilts, and the concentrations of TGF- ${\beta}1$ and cortisol in barrows show the correlation with only carcass weight. Also, the positive correlations of muscular IGFs and TGF-${\beta}1$ at postmortem 45 min with the carcass weight and backfat thickness were detected. Consequently, these results suggest that the serum and muscular endocrine factors are involved in the carcass weight and backfat thickness in pigs.

Experimental Studies on the Expression of Hair Growth Related Factors after Acupuncture & Moxibustion Therapy (침구요법(鍼灸療法)에 의한 발모관련 인자들의 발현에 대한 실험적 연구)

  • Kim, Ho-Il;Kim, Cheong-Moo;Lee, Chang-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.4
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    • pp.674-682
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    • 2011
  • The present study was undertaken to investigate the effect of acupuncture & moxibustion therapy on the hair follicle growth of skin 5 days and 10 days by macroscopic, microscopic and immunohistochemical methods. The results were as follows : Macroscopic hair follicle growth of plum-blossom needle treated group and strong moxibustion treated group was more increase than that of control group. Microscopic hair follicle growth of plum-blossom needle treated group and strong moxibustion treated group was hair growing cycle, anagen phase VI and that of control group and weak moxibustion treated group was hair growing cycle, anagen phase IV. Immunohistochemical observations on the expression of various growth factors, enzyme and receptor in hair follicle cycle after local treatment of acupuncture & moxibustion therapy are as follows: Expression of fibroblast growth factor was more intense in epidermis in plum-blossom needle treated group, epidermis and secondary hair germ cells in strong moxibustion treated group than control group. Expression of epidermal growth factor was more intense in epidermis in all experimental groups, and secondary hair germ cells in moxibustion treated group than control group. Expression of c-kit receptor was more intense in epidermis, secondary hair germ cells, outer root sheath in all experimental groups than control group. Expression of protein kinase C-${\alpha}$ was more intense in epidermis, secondary hair germ cells, outer root sheath in all experimental groups than control group. Expression of vascular endothelial growth factor was more intense in epidermis, bulge, secondary hair germ cells, outer root sheath in plum-blossom needle treated group and strong moxibustion treated group than control group. We concluded that acupuncture & moxibustion therapy related to the expression of various growth factors, enzymes and receptor on the hair growth cycle for hair growth.