79 results on '"Epithelial growth factor"'
Search Results
2. Epithelial to mesenchymal transition in mammary gland tissue fibrosis and insights into drug therapeutics.
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Syed, Mudasir Ahmad, Bhat, Basharat, Wali, Abiza, Saleem, Afnan, Dar, Lateef Ahmad, Gugjoo, Mudasir Bashir, Bhat, Shakil, and Bhat, Sahar Saleem
- Subjects
EPITHELIAL-mesenchymal transition ,MAMMARY glands ,RECEPTOR for advanced glycation end products (RAGE) ,ADVANCED glycation end-products ,FIBROSIS ,EPITHELIAL cells - Abstract
Background. The epithelial-mesenchymal transition (EMT) is a multi-step morphogenetic process in which epithelial cells lose their epithelial properties and gain mesenchymal characteristics. The process of EMT has been shown to mediate mammary gland fibrosis. Understanding how mesenchymal cells emerge from an epithelial default state will aid in unravelling the mechanisms that control fibrosis and, ultimately, in identifying therapeutic targets to alleviate fibrosis. Methods. The effects of EGF and high glucose (HG) on EMT in mammary epithelial cells, MCF10A and GMECs, as well as their pathogenic role, were studied. In-silico analysis was used to find interacting partners and protein-chemical/drug molecule interactions. Results. On treatment with EGF and/or HG, qPCR analysis showed a significant increase in the gene expression of EMT markers and downstream signalling genes. The expression of these genes was reduced on treatment with EGF+HG combination in both cell lines. The protein expression of COL1A1 increased as compared to the control in cells treated with EGF or HG alone, but when the cells were treated with EGF and HG together, the protein expression of COL1A1 decreased. ROS levels and cell death increased in cells treated with EGF and HG alone, whereas cells treated with EGF and HG together showed a decrease in ROS production and apoptosis. In-silico analysis of protein-protein interactions suggest the possible role of MAPK1, actin alpha 2 (ACTA2), COL1A1, and NFKB1 in regulating TGFβ 1, ubiquitin C (UBC), specificity protein 1 (SP1) and E1A binding protein P300 (EP300). Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment suggests advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signalling pathway, relaxin signalling pathway and extra cellular matrix (ECM) receptor interactions underlying fibrosis mechanism. Conclusion. This study demonstrates that EGF and HG induce EMT in mammary epithelial cells and may also have a role in fibrosis. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Epithelial to mesenchymal transition in mammary gland tissue fibrosis and insights into drug therapeutics
- Author
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Mudasir Ahmad Syed, Basharat Bhat, Abiza Wali, Afnan Saleem, Lateef Ahmad Dar, Mudasir Bashir Gugjoo, Shakil Bhat, and Sahar Saleem Bhat
- Subjects
Epithelium-mesenchymal transition ,Fibrosis ,Goat mammary epithelial cells ,MCF10A ,Epithelial growth factor ,Drug targeting ,Medicine ,Biology (General) ,QH301-705.5 - Abstract
Background The epithelial-mesenchymal transition (EMT) is a multi-step morphogenetic process in which epithelial cells lose their epithelial properties and gain mesenchymal characteristics. The process of EMT has been shown to mediate mammary gland fibrosis. Understanding how mesenchymal cells emerge from an epithelial default state will aid in unravelling the mechanisms that control fibrosis and, ultimately, in identifying therapeutic targets to alleviate fibrosis. Methods The effects of EGF and high glucose (HG) on EMT in mammary epithelial cells, MCF10A and GMECs, as well as their pathogenic role, were studied. In-silico analysis was used to find interacting partners and protein-chemical/drug molecule interactions. Results On treatment with EGF and/or HG, qPCR analysis showed a significant increase in the gene expression of EMT markers and downstream signalling genes. The expression of these genes was reduced on treatment with EGF+HG combination in both cell lines. The protein expression of COL1A1 increased as compared to the control in cells treated with EGF or HG alone, but when the cells were treated with EGF and HG together, the protein expression of COL1A1 decreased. ROS levels and cell death increased in cells treated with EGF and HG alone, whereas cells treated with EGF and HG together showed a decrease in ROS production and apoptosis. In-silico analysis of protein-protein interactions suggest the possible role of MAPK1, actin alpha 2 (ACTA2), COL1A1, and NFκB1 in regulating TGFβ1, ubiquitin C (UBC), specificity protein 1 (SP1) and E1A binding protein P300 (EP300). Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment suggests advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signalling pathway, relaxin signalling pathway and extra cellular matrix (ECM) receptor interactions underlying fibrosis mechanism. Conclusion This study demonstrates that EGF and HG induce EMT in mammary epithelial cells and may also have a role in fibrosis.
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- 2023
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4. The effect of human recombinant epidermal growth factor in the treatment of diabetic foot ulcers
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Mehmet Kadir Bartın and Gokalp Okut
- Subjects
diabetic foot ulcers ,diabetes mellitus ,epithelial growth factor ,Medicine - Abstract
Objectives. Diabetic foot ulcer (DFU) is one of the most important and common complication of type 2 diabetes mellitus (T2DM). A new therapy, consisting of intralesional administration of human recombinant epidermal growth factor (hrEGF), has been suggested to accelerate wound healing and prevent amputations. The effect of hrEGF on DFU treatment was investigated in this study. Materials and Methods. 20 patients with DFU were included in this study, all of whom were receiving insulin treatment for T2DM. In addition, they received intralesional therapy with a dose of 75 μgr of hrEGF, three times a week. Results. In 18 patients, complete granulation response was achieved in approximately 3,3 weeks. There were 2 cases of recurrence at 6 months after EGF treatment. Between 6 and 12 doses of epidermal growth factor were used for this study. The most common side effects were tremor, chills, pain and burning at the site of administration. Conclusions. Our study shows that intralesional administration of hrEGF in T2DM can prevent amputations in DFU and also accelerate wound healing. Thus, intralesional application of hrEGF should be an option for standard care, as a second line of treatment (given its cost-effectiveness) when appropriate.
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- 2022
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5. Case Report: Could topical epidermal growth factor be considered a new therapy for skin injuries in premature infants?
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Cossovel F, Marrazzo F, Nider S, Traunero A, Dussi G, Travan L, Cirino M, and Zanon D
- Abstract
In this case report, we present the experience of a premature neonate born at 28 weeks of gestation who, following prolonged respiratory support, developed a pressure injury on the columella despite the implementation of all appropriate preventive techniques. This injury did not improve with standard therapies; therefore, it was necessary to apply a topical galenic therapy containing epidermal growth factor, resulting in complete healing of the lesion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cossovel, Marrazzo, Nider, Traunero, Dussi, Travan, Cirino and Zanon.)
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- 2024
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6. Heparin-Modified Amniotic Membrane Combined With Growth Factors for Promoting Corneal Wound Healing After Alkali Burn
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Xuan Zhao, Xin Zuo, Jing Zhong, Bowen Wang, Saiqun Li, Yichen Xiao, and Jin Yuan
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amniotic membrane ,heparin ,sustained release ,epithelial growth factor ,corneal alkali burns ,Biotechnology ,TP248.13-248.65 - Abstract
Ocular chemical burns are potentially blinding ocular injuries and require urgent management. Amniotic membrane (AM) transplantation is an effective surgical treatment, one of the reasons is because AM is a rich source of growth factors that can promote epithelialization and wound healing. However, growth factors will be gradually lost and insufficient after preparation process and long-time storage, leading to unsatisfactory therapeutic effects. Herein, we present a modified AM (AM-HEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro. The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37°C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo, compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing.
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- 2020
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7. Evaluation of a rat meibomian gland dysfunction model induced by closure of meibomian gland orifices
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Zi-Yi Dong, Ming Ying, Jie Zheng, Lan-Jun Hu, Jiang-Yan Xie, and Yi Ma
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1083 ,meibomian gland dysfunction ,animal model ,epithelial growth factor ,interleukin-6 ,interleukin-8 ,tumor necrosis factor-α ,Ki67 ,Ophthalmology ,RE1-994 - Abstract
AIM: To find a stable, inexpensive, and reliable method to produce a rat meibomian gland dysfunction (MGD) model. METHODS: We inserted slim guidewires into the meibomian gland orifices of twelve Brown Norway rats and fulgurized every guidewire to destroy part of the meibomian gland. We then observed the morphological changes in the eyelid margin, and compared the data of tear breakup time (TBUT), Schirmer I test, and the corneal fluorescence staining scores at different times (1, 2, 4, and 6wk). We observed pathological changes of the cornea, conjunctiva and meibomian gland, and we used real-time polymerase chain reaction to analyze epithelial growth factor (EGF), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and Ki67. RESULTS: In the fourth week, compared with the control group, the TBUT of the model group began to decreased (P0.05). The corneal dots were significantly increased in the fourth week when the fusion stain began to appear (P0.05). CONCLUSION: The MGD rat model, produced via electrocauterization of meibomian gland orifices, matched clinical manifestations and cytokine levels. Our research provides a new method of achieving an MGD animal model.
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- 2018
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8. Amphiregulin Antibody and Reduction of Axial Elongation in Experimental Myopia
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Wen Jun Jiang, Hui Xin Song, Shao Yu Li, Bin Guo, Jian Feng Wu, Guo Ping Li, Da Dong Guo, De Long Shi, Hong Sheng Bi, and Jost B. Jonas
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Amphiregulin ,Epithelial growth factor ,Experimental myopia ,Axial elongation ,Myopia ,Medicine ,Medicine (General) ,R5-920 - Abstract
To examine the mechanism of ocular axial elongation in myopia, guinea pigs (age: 2–3 weeks) which either underwent unilateral or bilateral lens-induced myopization (group 1) or which were primarily myopic at baseline (group 2) received unilateral intraocular injections of amphiregulin antibody (doses: 5, 10, or 15 μg) three times in intervals of 9 days. A third group of emmetropic guinea pigs got intraocular unilateral injections of amphiregulin (doses: 0.25, 0.50 or 1.00 ng, respectively). In each group, the contralateral eyes received intraocular injections of Ringer's solution. In intra-animal inter-eye comparison and intra-eye follow-up comparison in groups 1 and 2, the study eyes as compared to the contralateral eyes showed a dose-dependent reduction in axial elongation. In group 3, study eyes and control eyes did not differ significantly in axial elongation. Immunohistochemistry revealed amphiregulin labelling at the retinal pigment epithelium in eyes with lens-induced myopization and Ringer's solution injection, but not in eyes with amphiregulin antibody injection. Intraocular injections of amphiregulin-antibody led to a reduction of lens-induced axial myopic elongation and of the physiological eye enlargement in young guinea pigs. In contrast, intraocularly injected amphiregulin in a dose of ≤1 ng did not show a significant effect. Amphiregulin may be one of several essential molecular factors for axial elongation.
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- 2017
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9. Nimotuzumab
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Tridente, Giuseppe and Tridente, Giuseppe
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- 2014
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10. Cold atmospheric plasma, a new promising advanced treatment modality for oral cancer.
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Sarkar, Arpita, Pal, Dipankar, Das, Lopamoodra, Saha, Subrata, and Sarkar, Subir
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LOW temperature plasmas ,ORAL cancer ,REACTIVE nitrogen species ,MEDICAL sciences ,ATMOSPHERIC ionization - Abstract
Cold atmospheric plasma (CAP) comprises electrons, ions, protons and reactive species. It is generated by ionization of gas at atmospheric pressure. CAP has been widely used for various applications in the field of modern medical and dental science. Over the last few decades CAP has been applied for cancer treatment. Different mechanisms of CAP to reduce the cancer cells are: apoptosis, interfering cell cycle, phosphorylation of p53, making cancer cell surface rough, inhibition of epithelial growth factor receptors, damaging DNA and mitochondria. These effects are caused due to production of reactive oxygen species and reactive nitrogen species. Various reactive species of nitrogen and oxygen are mostly involved to decrease the tumour size and increase survival rate. The effect of CAP on cancer cell is time dependent. A comprehensive review on the CAP treatment for oral cancer has been reported in the present article. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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11. phosphatidylinositol-4,5-bisphosphate 4-phosphatase 3.1.3.78
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Schomburg, Dietmar, Schomburg, Ida, Schomburg, Dietmar, editor, and Schomburg, Ida, editor
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- 2013
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12. Understanding Hypoxic Environments: Biomaterials Approaches to Neural Stabilization and Regeneration after Ischemia
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Leach, Jennie B., Powell, Elizabeth M., Gefen, Amit, editor, and Roy, Krishnendu, editor
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- 2010
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13. Pulmonary Organogenesis and Developmental Abnormalities
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Allen, Timothy Craig, Cagle, Philip T., Cagle, Philip T., editor, Zander, Dani S., editor, Popper, Helmut H., editor, Jagirdar, Jaishree, editor, Haque, Abida K., editor, and Barrios, Roberto, editor
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- 2008
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14. Limited Neural Differentiation of Retinal Pigment Epithelium
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Wakusawa, Ryosuke, Abe, Toshiaki, Saigo, Yoko, Tamai, Makoto, Back, Nathan, editor, Cohen, Irun R., editor, Kritchevsky, David, editor, Lajtha, Abel, editor, Paoletti, Rodolfo, editor, Hollyfield, Joe G., editor, Anderson, Robert E., editor, and LaVail, Matthew M., editor
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- 2006
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15. Responses of the SVZ to Demyelinating Diseases
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Nait-Oumesmar, B., Decker, L., Picard-Riera, N., Evercooren, A. Baron-Van, and Levison, Steven W., editor
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- 2006
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16. Effect of epithelial growth factor on matrix metalloproteinase-2 and E-cadherin/β-catenin expression in an in situ model of tumorigenesis.
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Navarini, Natalia Festugatto, De Araújo, Vera Cavalcanti, Sperandio, Marcelo, Napimoga, Marcelo Henrique, Teixeira, Lucas Novaes, De Araújo, Ney Soares, and Martinez, Elizabeth Ferreira
- Subjects
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MATRIX metalloproteinases , *GROWTH factors , *CADHERINS , *CATENIN genetics , *CARCINOGENESIS , *GENETICS , *THERAPEUTICS - Abstract
The aim of the present study was to analyze the in vitro effect of various doses of epidermal growth factor (EGF; 5 and 10 ng/ml) on matrix metalloproteinase-2 (MMP-2) secretion and E-cadherin/β-catenin expression by co-cultured cells that mimic an in situ carcinoma ex-pleomorphic adenoma, where benign myoepithelial cells from a pleomorphic adenoma surround malignant epithelial cells. EGF was supplemented in various doses and the effects were evaluated following four days of cell culture. ELISA was performed to determine MMP-2 secretion levels. Gene expression for E-cadherin and β-catenin was analyzed using quantitative polymerase chain reaction. The results revealed that E-cadherin expression decreased when the cells were supplemented with 5 ng/ml EGF. ELISA results indicated that MMP-2 secretion increased when EGF was supplemented at concentrations of 5 and 10 ng/ml. The present findings demonstrated that EGF may be involved in the epithelial-mesenchymal transition process via altering the E-cadherin/β-catenin complex and increasing MMP-2 secretion, which may then favor the dissolution of the basement membrane to the benefit of malignant cell clusters, contributing to the development of an invasive phenotype in this in vitro model of tumorigenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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17. A novel treatment approach for retinoblastoma by targeting epithelial growth factor receptor expression with a shRNA lentiviral system.
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Yong Chai, Juhua Xiao, Yunyan Du, Zhipeng Luo, Jun Lei, Shouhua Zhang, and Kai Huang
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- *
RETINOBLASTOMA , *ENDOTHELIAL growth factors , *DISEASE progression , *RNA , *CANCER cell proliferation , *THERAPEUTICS - Abstract
Objective(s): Non-invasive treatment options for retinoblastoma (RB), the most common malignant eye tumor among children, are lacking. Epithelial growth factor receptor (EGFR) accelerates cell proliferation, survival, and invasion of many tumors including RB. However, RB treatment by targeting EGFR has not yet been researched. In the current study, we investigated the effect of EGFR downregulation on RB progression using shRNA lentiviral vectors. Materials and Methods: EGFR expression in Weri-Rb-1 cells was down-regulated by EGFR shRNA-bearing lentiviral vectors. Cell death, proliferation, cell cycle as well as invasion after EGFR down-regulation were determined. Further signaling pathway analysis was done by Western blot. Results: Our results revealed that EGFR shRNA could specifically down-regulate EGFR expression and down-regulation of this protein promoted cell death. Further analysis on cell cycle demonstrated that EGFR down-regulation also suppressed cell proliferation by arresting cells at G1 phase. Invasion analysis showed that EGFR down-regulation suppressed cell invasion and was correlated with alteration in the expression of matrix metalloproteinases 2 and 9. Further signaling pathway analysis revealed that EGFR down-regulation mediated RB progression was through PI3K/AKT/mTOR signaling pathway. Conclusion: Our study revealed that EGFR down-regulation, through the PI3K/AKT/mTOR signaling pathway, could inhibit RB progression by promoting cell death while suppressing cell proliferation and invasion. The findings of our study indicated that down-regulation of EGFR using shRNA lentiviral vectors may offer a novel non-invasive treatment for RB. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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18. Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.
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Mapuskar KA, Vasquez Martinez G, Pulliam CF, Petronek MS, Steinbach EJ, Monga V, Furqan M, Jetton JG, Saunders DP, Pearce A, Davidson S, Pitre L, Dunlap NE, Fairbanks R, Lee CM, Mott SL, Bodeker KL, Cl H, Buatti JM, Anderson CM, Beardsley RA, Holmlund JT, Zepeda-Orozco D, Spitz DR, and Allen BG
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- Humans, Benchmarking, Cisplatin adverse effects, Iron metabolism, Kidney metabolism, Retrospective Studies, Squamous Cell Carcinoma of Head and Neck drug therapy, Squamous Cell Carcinoma of Head and Neck metabolism, Squamous Cell Carcinoma of Head and Neck pathology, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms metabolism, Renal Insufficiency, Chronic chemically induced, Renal Insufficiency, Chronic drug therapy
- Abstract
Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery., Competing Interests: Declaration of competing interest Drs. Spitz and Allen acknowledge support for their laboratory efforts from a sponsored research agreement from Galera Therapeutics, Inc. Dr. Beardsley is an employee of and owns stock in, Galera Therapeutics, Inc. Dr. Holmlund owns stock in Galera Therapeutics, Inc. No potential conflicts of interest were disclosed by the other authors., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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19. Wound Healing: Physiology, Clinical Progress, Growth Factors, and the Secret of the Fetus
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Efron, David T., Witte, Maria B., Barbul, Adrian, Baue, Arthur E., editor, Faist, Eugen, editor, and Fry, Donald E., editor
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- 2000
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20. Signal Transduction by the Receptor Tyrosine Kinase Ret
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van Weering, D. H. J., Bos, J. L., Schlag, P. M., editor, Senn, H.-J., editor, Diehl, V., editor, Parkin, D. M., editor, Rajewsky, M. F., editor, Rubens, R., editor, Wannenmacher, M., editor, Schwab, Manfred, editor, Rabes, Hartmut M., editor, Munk, Klaus, editor, and Hofschneider, Hans Peter, editor
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- 1998
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21. Fusion Toxins
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Foss, F. M., Burg, Günter, editor, and Dummer, Reinhard G., editor
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- 1997
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22. Calcium Signals in Cell Proliferation, Differentiation, and Death
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Whitfield, James F., Foà, Piero P., editor, and Walsh, Mary F., editor
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- 1994
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23. Measurements in wound healing with observations on the effects of topical agents on full thickness dermal incised wounds.
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Theunissen, D., Seymour, B., Forder, M., Cox, S.G., and Rode, H.
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BURN patients , *WOUND healing , *DRUG efficacy , *SULFADIAZINE , *GROWTH factors , *THERAPEUTICS - Abstract
Introduction: A multitude of topical wound treatments are used today. Although it is well established that the micro-environment of healing wounds can be altered to improve healing, it is difficult to measure the subtle differences in outcome where therapies are compared.Method: We compared wound healing properties between four different topical agents in surgically incised wounds in a pig model. The four topical agents, 5% Povidone-Iodine cream, 1% Silver-Sulphadiazine, 2% Mupirocin, and 1% Silver-Sulphadiazine plus 1mg/100g recombinant-human epithelial growth factor (EGF) were randomly assigned to four test animals each. Test agents were compared to each other and to untreated controls. We investigated existing and new methodologies of measurement of wound healing: clinical and histological visual scoring systems, immuno-histochemistry, and computerized image analysis of the wounds on days 3, 7, and 28.Results: All agents were found to have improved healing rates with better cellular architecture. Healing was faster, histological appearance resembled normal architecture sooner, clinical appearance improved, mitotic activity was stimulated and more collagen was deposited in comparison to the wounds with no agents. EGF-treated wounds showed an increased rate of epithelisation, but the rate of healing did not correlate well with evaluation of cosmetic outcome.Conclusion: Topical agents improve all aspects of wound healing. The addition of a human recombinant EGF to Silver-Sulphadiazine increases epithelial growth and amounts of collagen in the regenerating wounds at day 7. [ABSTRACT FROM AUTHOR]- Published
- 2016
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24. Steroid modulation of the expression of growth factors and oncogenes in breast cancer
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McCarty, K. S., Jr., McCarty, K. S., Sr., McGuire, William L., editor, Lippman, Marc E., editor, and Dickson, Robert B., editor
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- 1991
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25. Mesenchymal stem cells protect podocytes from apoptosis induced by high glucose via secretion of epithelial growth factor.
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Diangeng Li, Nan Wang, Li Zhang, Zhu Hanyu, Bai Xueyuan, Bo Fu, Cui Shaoyuan, Weiguang Zhang, Sun Xuefeng, Rongshan Li, and Xiangmei Chen
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- *
APOPTOSIS , *GLUCOSE , *EPITHELIAL cells , *DIABETIC nephropathies , *MESENCHYMAL stem cells , *CONFOCAL fluorescence microscopy - Abstract
Introduction: The apoptosis and subsequent injury of podocytes plays a pathogenic role in diabetic nephropathy (DN). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and reducing cellular injury. Our previous study found that MSCs could protect kidneys from diabetes-induced injury without obvious engraftment. So we evaluated the effects of human adipose-derived MSCs (hAd-MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms. Methods: We used flow cytometry, Western blot and confocal fluorescence microscopy to study podocytic apoptosis and injury induced by HG at 24 hours, 48 hours, and 72 hours in the presence or absence of MSC-conditioned medium (CM). An antibody-based cytokine array was used to identify the mediating factor, which was verified by adding the neutralizing antibody (NtAb) to block its function or adding the recombinant cytokine to the medium to induce its function. Results: hAd-MSC-CM reduced podocytic apoptosis in a dose-dependent manner, decreased the expression of podocytic cleaved caspase-3, and prevented the reduced expression and maintained the normal arrangement of podocytic synaptopodin and nephrin. However, human embryonic lung cell (Wi38)-CM failed to ameliorate podocytic apoptosis or injury. Twelve cytokines with concentration ratios (MSC-CM/Wi38-CM) >10-fold were identified. Epithelial growth factor (EGF) was singled out for its known ability to prevent apoptosis. Recombinant human EGF (rhEGF) prevented podocytic apoptosis and injury similarly to hAd-MSC-CM but, upon blockade of EGF, the beneficial effect of hAd-MSC-CM decreased dramatically. Conclusions: hAd-MSCs prevent podocytic apoptosis and injury induced by HG, mainly through secreting soluble EG. [ABSTRACT FROM AUTHOR]
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- 2013
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26. NHERF-1 regulation of EGF and neurotensin signalling in HT-29 epithelial cells
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Kruger, Wade A., Monteith, Gregory R., and Poronnik, Philip
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- *
NEUROTENSIN , *EPIDERMAL growth factor receptors , *GENE expression , *EPITHELIAL cells , *CELLULAR signal transduction , *SCAFFOLD proteins - Abstract
Abstract: Neurotensin receptors (NT-R) and the epidermal growth factor receptors (EGF-R) are commonly overexpressed in many epithelial origin tumours. In addition to their role as mitogenic mediators through specific cell signalling, recent studies indicate that the activity/expression of scaffold proteins responsible for the assembly and coordination of the signalling complexes may also have central roles in epithelial transformation. In particular, the “epithelial” PSD-95/Dlg/Zo-1 (PDZ) scaffold/adapter protein, Na+/H+ exchanger regulatory factor isoform one (NHERF-1), has been identified as a potential regulator of cellular transformation. NHERF-1 is a known regulator of EGF-R function and plays numerous roles in G-protein-coupled receptor signalling. Because of the synergistic signalling between these two potent mitogens, we investigated a potential role for NHERF-1 in the molecular mechanism linking the aberrant proliferative phenotype initiated by some G-Protein-coupled receptor activators in the colon adenocarcinoma HT-29 cell line. Knockdown (80%) of endogenous NHERF-1 leads to significant reduction in proliferation rate; an effect that could not be recovered by exogenous application of either NT or EGF. Inhibition of the EGF-R with AG1487 also inhibited proliferation and this effect could not be recovered with NT. Knockdown of NHERF-1 significantly altered the expression of the EGF-R, and almost completely abolished the NT-mediated increases in intracellular free Ca2+. Knockdown of NHERF-1 also attenuated UTP-mediated purinergic Ca2+ signalling. Taken together, these data suggest that NHERF-1 plays a more central role in cell proliferation by modulating Gq-mediated signalling pathways. [Copyright &y& Elsevier]
- Published
- 2013
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27. Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration.
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Jonas, Jost B., Tao, Yong, Neumaier, Michael, and Findeisen, Peter
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- *
OPHTHALMOLOGY , *CYTOKINES , *RETINAL degeneration , *CATARACT surgery , *ANTIVIRAL agents , *OPTICAL coherence tomography , *CHEMILUMINESCENCE immunoassay - Abstract
. Purpose: To measure the concentration of cytokines in the aqueous humour of eyes with exudative age-related macular degeneration (AMD). Methods: The clinical interventional study included a study group of 18 patients with exudative AMD and a control group of 20 patients undergoing routine cataract surgery. Age did not vary significantly (p = 0.36) between study group (80.8 ± 6.4 years) and control group (77.0 ± 9.9 years), nor did gender (p = 0.75). During the interventions, aqueous humour samples were obtained, in which the concentration of cytokines was measured using a solid-phase chemiluminescence immunoassay. Macular thickness was measured by optical coherence tomography (OCT). Results: In the study group as compared to the control group, significantly higher concentrations were measured for epithelial growth factor (EGF) (p = 0.017), human growth factor (HGF) (p = 0.048), intercellular adhesion molecule-1 (ICAM1) (p = 0.028), interleukin 12p40 (IL12p40) (p = 0.009), interleukin 1a2 (IL1a2) (p = 0.01), interleukin 3 (IL3) (p = 0.02), interleukin 6 (IL6) (p = 0.006), interleukin 8 (IL8) (p = 0.02), monocyte chemoattractant protein-1 (MCP-1) (p = 0.048), monokine induced by interferon gamma (MIG) (p = 0.016), matrix metalloproteinase 9 (MMP9) (p = 0.004) and plasminogen activator inhibitor 1 (PAI1) (p = 0.006). Macular thickness was significantly associated with the concentrations of EGF (p = 0.001), HGF (p = 0.02), ICAM1 (p = 0.001), interleukin 12p40 (p = 0.006), IL 1a2 (p = 0.002), MIG (p = 0.001), MMP9 (p < 0.001) and PAI1 (p = 0.01). Interleukin 6 and MCP-1 showed significant associations with the height of retinal pigment epithelium detachment. Conclusions: Numerous cytokines are associated with the presence and the amount of exudative AMD. [ABSTRACT FROM AUTHOR]
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- 2012
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28. Bradykinin inhibits high glucose- and growth factor-induced collagen synthesis in mesangial cells through the B2-kinin receptor.
- Author
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Blaes, Nelly, Pécher, Christiane, Mehrenberger, Marion, Cellier, Eric, Praddaude, Françoise, Chevalier, Jacques, Tack, Ivan, Couture, Réjean, and Girolami, Jean-Pierre
- Abstract
Mesangial matrix expansion is an early lesion leading to glomeruloclerosis and chronic renal diseases. A beneficial effect is achieved with angiotensin I-converting enzyme inhibitors (ACEI), which also favor bradykinin (BK) B2 receptor (B2R) activation. To define the underlying mechanism, we hypothesized that B2R activation could be a negative regulator of collagen synthesis in mesangial cells (MC). We investigated the effect of BK on collagen synthesis and signaling in MC. Inflammation was evaluated by intercellular adhesion molecule-1 (ICAM-1) expression. BK inhibited collagen I and IV synthesis stimulated by high glucose, epithelial growth factor (EGF), and transforming growth factor-β (TGF-β) but did not alter ICAM-1. Inhibition of collagen synthesis was B2R but not B1R mediated. PKC or phosphatidylinositol 3-kinase (PI3K) inhibitors mimicked the BK effect. B2R activation inhibited TGF-β- and EGF-induced Erk1/2, Smad2/3, Akt S473, and EGFR phosphorylation. A phosphatase inhibitor prevented BK effects. The in vivo impact of B2R on mesangial matrix expansion was assessed in streptozotocin-diabetic rodents. Deletion of B2R increased mesangial matrix expansion and albuminuria in diabetic mice. In diabetic rats, matrix expansion and albuminuria were prevented by ACEI but not by ACEI and B2R antagonist cotreatment. Consistently, the lowered BK content of diabetic glomeruli was restored by ACEI. In conclusion, deficient B2R activation aggravated mesangial matrix expansion in diabetic rodents whereas B2R activation reduced MC collagen synthesis by a mechanism targeting Erk1/2 and Akt, common pathways activated by EGF and TGF-β. Taken together, the data support the hypothesis of an antifibrosing effect of B2R activation. [ABSTRACT FROM AUTHOR]
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- 2012
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29. EGF/TGFβ1 co-stimulation of oral squamous cell carcinoma cells causes an epithelial-mesenchymal transition cell phenotype expressing laminin 332.
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Richter, Petra, Umbreit, Claudia, Franz, Marcus, Berndt, Angela, Grimm, Susanne, Uecker, Andrea, Böhmer, Frank D., Kosmehl, Hartwig, and Berndt, Alexander
- Subjects
- *
EPIDERMAL growth factor , *TRANSFORMING growth factors-beta , *SQUAMOUS cell carcinoma , *MESSENGER RNA , *CELL culture , *CELL adhesion , *COLLAGEN , *PHENOTYPES , *GENE expression - Abstract
J Oral Pathol Med (2011) : 46-54 Epithelial-mesenchymal transition (EMT) is suggested to be crucial for the development of an invasive and metastatic carcinoma cell phenotype. Therefore, the definition of this phenotype is of great clinical interest. We recently evidenced vimentin positive cells in oral squamous cell carcinoma (OSCC) invasive front expressing laminin γ2 chain mRNA implicating an EMT origin of these cells. To further elucidate the nature of these cells, we have investigated the relation between EMT criteria and laminin-332 expression in a cell culture model of transforming growth factor beta-1 (TGFβ1)/epithelial growth factor (EGF) long time co-stimulation. We demonstrate that in contrast to TGFβ1 or EGF alone, co-stimulation induces phenotype transition in OSCC cells which fulfils the criteria of EMT in terms of vimentin up-regulation and E-cadherin down-regulation on protein level as well as cell scattering. Furthermore, cells displayed a strongly enhanced invasiveness and adhesion to type I-IV collagens. Phenotype transition is accompanied by an enhanced expression of laminin-332, especially of its γ2 chain. We further analyse the expression of extracellular matrix related genes by RT-PCR profiling. With respect to strongly enhanced proteins, data confirm the EMT phenotype of co-stimulated OSCC cells and expression of laminin-332. Furthermore, alpha catenin, collagen type 16, the integrin α7 and β1 chains, and MMP11 are suggested as candidates with potential role in EMT in OSCC. In summary we are able to show that EMT in OSCC is mediated by multiple growth factors and is accompanied by laminin γ2 chain up-regulation evidencing the existence of an intermediate Vim/Ln332 EMT phenotype as seen in situ. [ABSTRACT FROM AUTHOR]
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- 2011
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30. Heat-stress-induced damage to porcine small intestinal epithelium associated with downregulation of epithelial growth factor signaling.
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Liu, F., Yin, J., Du, M., Yan, P., Xu, J., Zhu, X., and Yu, J.
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- *
PHYSIOLOGICAL effects of heat , *SWINE , *EPITHELIUM , *INTESTINAL mucosa , *GROWTH factors , *DUODENUM , *JEJUNUM , *ANIMAL nutrition , *ANIMAL science - Abstract
Extreme heat during certain clays of the summer renders pigs susceptible to severe heat stress, which negatively affects their growth performance. We hypothesized that such heat stress impaired the small intestinal mucosa, a site responsible for nutrient absorption. To simulate heat stress, Chinese experimental mini-pigs were treated with 5 h of continual 40°C temperature each clay for 10 d in succession. Pigs were killed at 1, 3, 6 and 10 d after treatment, and small intestinal epithelia were sampled for histochemical examination and biochemical analyses. The duodenum and jejunum were seriously damaged within 3 d of initiation of treatment. Subsequent study of the process of jejunum recovery showed that the initiation of recovery started within 6 d following heat stress. Such damage was associated with the downregulation of epithelial growth factor signaling. In conclusion, heat stress induced short-term damage to the epithehum of porcine intestine. Because the intestinal epitheliumn is crucial for nutrient uptake, such damage should partially account for the impairment of growth performance of pigs under heat stress. [ABSTRACT FROM AUTHOR]
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- 2009
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31. Modulation of the inflammatory response and apoptosis using epidermal growth factor and hepatocyte growth factor in a liver injury model: a potential approach to the management and treatment of cholestatic liver disease.
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Thatch, Keith A., Schwartz, Marshall Z., Yoo, Edward Y., Mendelson, Kim G., and Duke, Duane S.
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LIVER injuries ,HEPATOCYTE growth factor ,LIVER failure ,APOPTOSIS ,LIVER diseases ,EPIDERMAL growth factor ,LABORATORY rats ,ANIMAL models in research - Abstract
Abstract: Background/Purpose: The major side effect of total parenteral nutrition is liver injury leading to liver failure. This study was designed to assess specific growth factors in modulating the hepatic response in an ANIT-induced liver-injury model. Methods: Sprague-Dawley rats were divided into four groups: control (n = 5), liver-injury control (α-naphtylisocyocyanate [ANIT], 100 mg/kg, n = 8), ANIT + epidermal growth factor (EGF, 150 μg/kg per day, n = 10), and ANIT + hepatocyte growth factor (HGF, 250 μg/kg per day, n = 9). Rats were given intraperitoneal injections of saline (control) or ANIT and implantation of an osmotic mini-pump for 7 days of continuous intravenous saline (liver injury control), EGF, or HGF. Seven and 14 days later, liver biopsies were obtained and evaluated for interleukin (IL)–6 and tumor necrosis factor α expression by immunofluorescent staining, and for apoptosis, by the terminal transferase dUTP nick end labeling (TUNEL) technique. All animals were euthanized at 14 days. Results: Epidermal growth factor (P < .025) and HGF (P < .001) groups induced less IL-6 expression at day 14 compared to liver-injury controls. In addition, the interval decrease in IL-6 expression between days 7 and 14 was greater in EGF (P < .001) and HGF (P < .001) groups compared to liver-injury controls. At day 14, HGF also demonstrated decreased tumor necrosis factor α expression (P < .005). Apoptotic activity was significantly less for the EGF (P < .011) and HGF (P < .0012) groups. Conclusion: Epidermal growth factor and HGF modulated the hepatic inflammatory response and apoptotic index in this established liver-injury model and may diminish or prevent liver damage in patients with total parenteral nutrition–induced liver injury. [Copyright &y& Elsevier]
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- 2008
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32. Novel advances in pancreatic cancer treatment.
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Vulfovich, Michel and Rocha-Lima, Caio
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PANCREATIC cancer treatment ,CANCER treatment ,DRUGS ,DRUG therapy ,CLINICAL trials - Abstract
Little progress has been made on the treatment of advanced pancreatic cancer. Gemcitabine has been an acceptable standard for more than a decade. The benefit of single-agent gemcitabine in advanced and metastatic pancreatic cancer is small. Adding other chemotherapy agents to gemcitabine has not resulted in meaningful improvement in survival. The randomized trials studying the addition of molecular targeting agents (cetuximab, bevacizumab, farnesyl transferase inhibitors and metalloproteinase inhibitors) to gemcitabine compared with gemcitabine alone have been disappointing. A small gain in median survival by adding erlotinib to gemcitabine has recently been reported. We herein review novel agents in pancreatic cancer that may change the current nihilistic approach in the management of this challenging disease. [ABSTRACT FROM AUTHOR]
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- 2008
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33. Role of CCN2/CTGF in the proliferation of Mastomys enterochromaffin-like cells and gastric carcinoid development.
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Kidd, M., Modlin, I. M., Eick, G. N., Camp, R. L., and Mane, S. M.
- Subjects
- *
STOMACH cancer , *CARCINOID , *CELL proliferation , *MITOGENS , *GASTROINTESTINAL hormones - Abstract
Mastomys enterochromaffin-like (ECL) cell proliferation is initially gastrin driven, but once neoplasia develops, cells become gastrin autonomous. We hypothesized that CCN2 (CTGF), a mitogenic growth factor, may regulate ECL cell proliferation. A Mastomys GeneChip database was examined (dCHIP) to identify CCN2 expression levels. CCN2 in normal and tumor ECL cell preparations obtained using FACS (100 nM acridine orange) was examined by real-time PCR. CCN2 protein was identified in mucosal and ECL cell preparations by immunohistochemistry. Short-term cultured cells were stimulated with either CCN2 or CCN2 + EGF, and proliferation was measured (MIT assay). The ERK1/2 inhibitor PD-98059 (0.1-100 µM) was assessed in terms of CCN2 (1 ng/ml)-mediated proliferation and ERK 1/2 phosphorylation. CCN2 transcript and protein was then examined in clinical gastric carcinoids. The ccn2 transcript was upregulated in tumor samples compared with the normal mucosa (+2.36-fold, P < 0.01). PCR demonstrated that ccn2 was not expressed in FACS-prepared (>98% pure) normal ECL cells but was elevated in tumor ECL cell fractions (41.3 ± 10.7-fold). Immunostaining of the Mastomys gastric mucosa and FACS preparations confirmed that CCN2 protein was present in ECL tumors but not in normal EGL cells. Neither CCN2 nor CCN2 + EGF stimulated normal ECL cell proliferation. CCN2 stimulated tumor proliferation (EC50 ~0.01 ng/ml); EGF significantly augmented (P < 0.01) CCN2-induced tumor cell proliferation (EC50 = 20 pg/ml). PD-98059 inhibited CCN2-induced proliferation (-12 ± 3%, P < 0.05) and ERK1/2 phosphorylation (-34 ± 5%, P <0.05) in tumor cells. In clinical samples, both CCN2 transcript and protein were elevated in gastrin-autonomous carcinoids (P < 0.02) compared with the normal mucosa. In conclusion, CCN2 may be a proliferative regulator of Mastomys ECL neoplastic proliferation once these cells become autonomous of gastrin regulation. Identification of CCN2 in gastric carcinoid tissue may be useful both as an indicator of ECL cell transformation and may define gastrin autonomy, a criteria of gastric carcinoid malignancy. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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34. Growth factor- and heparin-dependent regulation of constitutive and agonist-mediated human endothelial barrier function.
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Moy, Alan B., Blackwell, Ken, Wu, Mack H., and Granger, Harris J.
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EPIDERMAL growth factor , *HEPARIN , *GROWTH factors , *THROMBIN , *BLOOD coagulation factors - Abstract
We report functional differences in constitutive and agonist-mediated endothelial barrier function between cultured primary and Clonetics human umbilical vein endothelial cells (pHUVEC and cHUVEC) grown in soluble growth factors and heparin. Basal transendothelial resistance (TER) was much lower in pHUVEC than in cHUVEC grown in medium supplemented with growth factors, such as basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and human epithelial growth factor (EGF), and heparin. On the basis of a numerical model of TER, the increased basal TER in cHUVEC was due to effects on cell-matrix adhesion and membrane capacitance. Heparin and bFGF increased constitutive TER in cultured pHUVEC, and heparin mediated additional increases in constitutive TER in pHUVEC supplemented with bFGF. EGF attenuated bFGF-mediated increases in TER. On the basis of the numerical model, in contrast to cHUVEC, heparin and bFGF augmented TER through effects on cell-cell adhesion and membrane capacitance in pHUVEC. Thrombin mediated quantitatively greater amplitude and a more sustained decline in TER in cultured cHUVEC than pHUVEC. Thrombin-mediated barrier dysfunction was attenuated in pHUVEC conditioned in EGF in the presence or absence of heparin. Thrombin-mediated barrier dysfunction was also attenuated when monolayers were exposed to low concentrations of heparin and further attenuated in the presence of bFGF. cAMP stimulation mediated differential attenuation of thrombin-mediated barrier dysfunction between pHUVEC and cHUVEC. VEGF displayed differential effects in TER in serum-free medium. Taken together, these data demonstrate marked differential regulation of constitutive and agonist-mediated endothelial barrier function in response to mitogens and heparin stimulation. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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35. EGF stimulates glioblastoma metastasis by induction of matrix metalloproteinase-9 in an EGFR-dependent mechanism
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Hong Shu, Duo Chen, Xing-Chen Chen, Guan Junhong, and Xiangtai Wei
- Subjects
0301 basic medicine ,signal transducer and activator of transcription 3/5 ,medicine.medical_specialty ,Metastasis ,03 medical and health sciences ,Transactivation ,0302 clinical medicine ,Growth factor receptor ,Epidermal growth factor ,matrix metalloproteinase-9 ,Internal medicine ,medicine ,Protein kinase B ,PI3K/AKT/mTOR pathway ,STAT5 ,epithelial growth factor ,biology ,business.industry ,glioblastoma ,medicine.disease ,030104 developmental biology ,Endocrinology ,Oncology ,030220 oncology & carcinogenesis ,epithelial growth factor receptor ,biology.protein ,STAT protein ,Cancer research ,business ,Research Paper - Abstract
// Xing-Chen Chen 1 , Xiang-Tai Wei 1 , Jun-Hong Guan 1 , Hong Shu 1 and Duo Chen 1 1 Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, P. R. China Correspondence to: Duo Chen, email: chend@sj-hospital.org Keywords: glioblastoma, epithelial growth factor, epithelial growth factor receptor, signal transducer and activator of transcription 3/5, matrix metalloproteinase-9 Received: February 20, 2017 Accepted: June 30, 2017 Published: July 27, 2017 ABSTRACT Epidermal growth factor (EGF) and EGF receptor (EGFR) play prominent roles in the metastasis of glioblastoma (GBM). However, the molecular mechanisms for the function of EGF and EGFR in GBM metastasis have not been elucidated. Herein, we demonstrate that coactivation of EGF and EGFR drives tumor metastasis in a matrix metalloproteinase-9 (MMP-9)–dependent manner. Expression levels of EGF, EGFR, and MMP-9 were substantially upregulated in the GBM and edema zones of patients, compared with those of paired unaffected participants. Secretion of EGF and MMP-9 was reduced in the cerebrospinal fluid (CSF) after removing GBM for 2 weeks by operation. To the mechanism, MMP-9 was upregulated by activating EGF and EGFR via PI3K/AKT- and ERK1/2-dependent pathways. Moreover, signal transducer and activator of transcription (STAT) 3 and STAT5 mediated the activation of NF-κB by PI3K/AKT and ERK1/2 pathways. This resulted in transactivation of MMP-9 in GBM. Finally, MMP-9 induction facilitated abnormal proliferation, migration, and invasion of cells, which contributed to GBM metastasis.
- Published
- 2017
36. Chronic exposure to EGF affects trafficking and function of ENaC channel in cystic fibrosis cells
- Author
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Cao, Lishuang, Owsianik, Grzegorz, Becq, Frédéric, and Nilius, Bernd
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- *
AMILORIDE , *CYSTIC fibrosis , *CELLS , *GENETIC disorders - Abstract
Abstract: Using the whole-cell patch-clamp technique, we identified an amiloride (AMI)-sensitive Na+ current in cystic fibrosis cells, JME/CF15, growing in standard medium. The reversal potential of this current depended on Na+ concentrations and the cation selectivity was much higher for Na+ than for K+, indicating that the current is through ENaC channels. In contrast, cells from EGF-containing medium lacked AMI-sensitive Na+ currents. In permeabilized cells growing in EGF-containing medium, αENaC was mainly detected in a perinuclear region, while in cells from standard medium it was distributed over the cell body. Western-blot analysis showed that in standard medium cells expressed fast-migrating EndoH-insensitive and slow-migrating EndoH-sensitive αENaC fractions, while in cells growing in the presence of EGF, αENaC was only detected as the fast-migrating EndoH-insensitive fraction. Long-term incubation of cells with EGF resulted in an increased basal Ca2+ level, [Ca2+]i. A similar increase of [Ca2+]i was also observed in the presence of 2μM thapsigargin, resulting in inhibition of ENaC function. Thus, in JME/CF15 cells inhibition of the ENaC function by chronic incubation with EGF is a Ca2+-mediated process that affects trafficking and surface expression of ENaC channels. [Copyright &y& Elsevier]
- Published
- 2005
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37. Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells.
- Author
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Sauvant, C., Hesse, D., Holzinger, H., Evans, K.K., Dantzler, W.H., and Gekle, M.
- Subjects
- *
GROWTH factors , *EPITHELIAL cells , *BIOLOGICAL transport , *CELL lines , *LABORATORY animals , *CELLULAR signal transduction - Abstract
We recently showed that, in a proximal tubule cell line (opossum kidney cells), epithelial growth factor (EGF) stimulates basolateral organic anion transport (OAT) via ERK1/2, arachidonic acid, phospholipase A2, and generation of prostaglandins. PGE2 binds the prostanoid receptor and, thus, activates adenylate cyclase and PKA, which stimulate basolateral organic anion uptake. In the present study, we investigated whether this regulatory cascade is also true 1) for ex vivo conditions in isolated renal proximal (S2) tubules from rabbit and 2) in a human renal epithelial cell line stably expressing human OAT1 (IHKE-hOAT1). EGF activated ERK1/2 in S2 tubules and IHKE-hOAT1, and, in both cases, inhibition of ERK activation (by U-0126) abolished this stimulation. In S2 tubules and IHKE-hOAT1, EGF led to an increase of organic anion uptake, which again was inhibited by U-0126. PGE2 stimulated basolateral organic anion uptake in rabbit S2 tubules and IHKEhOAT1. EGF- and PGE2-mediated stimulation of organic anion uptake was abolished by inhibition of PKA in rabbit S2 tubules and IHKE-hOAT1, respectively. We conclude that 1) stimulation of basolateral organic anion uptake by EGF or PGE2 is a widespread (if not general) regulatory mechanism, 2) the signal transduction pathway involved seems to be general, 3) stimulation of basolateral organic anion uptake by EGF or PGE2 is also present under ex vivo conditions and, thus, is not a cell culture artifact, 4) activation of OAT1 is sufficient to explain the stimulatory effects of EGF and PGE2 in opossum kidney cells and rabbit S2 segments, and 5) stimulation of basolateral OAT1 by EGF or PGE2 is also important in humans and, thus, may have clinical implications. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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38. Differential expression and upregulation of interleukin-1α, interleukin-1β and interleukin-6 by freshly isolated human small intestinal epithelial cells.
- Author
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Madrigal-Estebas, Laura, Doherty, Derek G., O'Donoghue, Diarmuid P., Feighery, Conleth, and O'Farrelly, Cliona
- Subjects
- *
INTERLEUKIN-1 , *INTERLEUKIN-6 , *EPITHELIAL cells - Abstract
Background: Small intestinal epithelial cells (SIEC) may contribute to local immune regulation. Aim: To examine production of interleukin (IL)-1α , IL-1β and IL-6 by freshly isolated human SIEC. Methods: IL-1α and IL-1β mRNA in epithelial layers (EL) prepared from small intestine and in intestinal epithelial cell (EC) lines were examined by reverse transcription-polymerase chain reaction. IL-1α, IL-1β and IL-6 protein expression by SIEC was examined by flow cytometry before and after activation with lipopolysaccharide and epithelial growth factor. Results: IL-1α and IL-1β mRNA was detected in EL and EC lines. Background expression of IL-1α and IL-1β protein by SIEC was observed, which did not increase even following activation. IL-6 protein was expressed by SIEC, in a proportion that increased in two out of three samples following activation. Conclusions: IL-6 expression and the presence of IL-1α and IL-1β mRNA suggest a role for SIEC in the regulation of local inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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39. DOES L-ARGININE INDUCE INTESTINAL ADAPTATION BY EPITHELIAL GROWTH FACTOR?
- Author
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Camli, Alparslan, Barlas, Meral, and Yagmurlu, Aydin
- Subjects
- *
ARGININE , *AMINO acids , *GROWTH factors , *CYTOKINES , *BLOOD plasma , *ANTHROPOMETRY - Abstract
To evaluate whether L-Arginine has an effect on endogenous epidermal growth factor secretion and intestinal adaptation in massive small bowel resection an experimental study was performed.Fourteen albino Wistar rats weighing 250−300 g were used for the study. After performing 50% small bowel resection and anastomosis the rats were randomly divided into two groups. The first group received 500 mg/kg/day of L-Arginine intraperitoneally for 14 days just after the surgical procedure. The control group received isotonic saline instead. Body weight measurement was preformed daily. At the end of the second postoperative week all rats underwent relaparotomy. Small bowel was resected for histopathological examination. Levels of epidermal growth factor were measured by enzyme-linked immunosorbent assay in serum, saliva, and urine at the end of second postoperative week in both groups.The weight gain was higher in the L-Arginine treated group (P < 0.05). Serum, saliva and urinary epidermal growth factor levels were significantly higher at the end of the second week compared to the control group (P < 0.05). The villus height was higher on histopathological examination in L-Arginine treated group compared to the control group (P < 0.05).L-Arginine resulted in a better intestinal adaptation after massive bowel resection. The high levels of epidermal growth factor in body fluids of L-Arginine treated rats could be the explanation for this effect. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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40. Heparin-Modified Amniotic Membrane Combined With Growth Factors for Promoting Corneal Wound Healing After Alkali Burn.
- Author
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Zhao X, Zuo X, Zhong J, Wang B, Li S, Xiao Y, and Yuan J
- Abstract
Ocular chemical burns are potentially blinding ocular injuries and require urgent management. Amniotic membrane (AM) transplantation is an effective surgical treatment, one of the reasons is because AM is a rich source of growth factors that can promote epithelialization and wound healing. However, growth factors will be gradually lost and insufficient after preparation process and long-time storage, leading to unsatisfactory therapeutic effects. Herein, we present a modified AM (AM-HEP) for the supplement and sustained release of growth factor by surface grafting heparin for treatment of ocular chemical burns. Heparin grafting rate and stability, microstructure, physical property, and sustained release of epithelial growth factor (EGF) of AM-HEP were characterized. Biocompatibility and ability to promote corneal epithelial cell growth and migration were evaluated and compared with a biological amnion, which is available on the market in vitro . The therapeutic effects of AM-HEP combined with EGF (AM-HEP@EGF) in vivo had been evaluated in a model of mouse corneal alkali burn. The results indicated that heparin was introduced into AM and maintain stability over 3 weeks at 37°C. The modification process of AM-HEP did not affect microstructure and physical property after comparing with non-modified AM. EGF could be combined quickly and effectively with AM-HEP; the sustained release could last for more than 14 days. AM-HEP@EGF could significantly promote corneal epithelial cell growth and migration, compared with non-modified AM and control group. Faster corneal epithelialization was observed with the transplantation of AM-HEP@EGF in vivo , compared with the untreated control group. The corneas in the AM-HEP@EGF group have less inflammation and were more transparent than those in the control group. The results from in vitro and in vivo experiments demonstrated that AM-HEP@EGF could significantly enhance the therapeutic effects. Taken together, AM-HEP@EGF is exhibited to be a potent clinical application in corneal alkali burns through accelerating corneal epithelial wound healing., (Copyright © 2020 Zhao, Zuo, Zhong, Wang, Li, Xiao and Yuan.)
- Published
- 2020
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41. The Role of Intracellular pH in Hormone Action
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Moore, R. D. and Gilles, Raymond, editor
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- 1985
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42. Hormones and Oncogenes in Human Breast Cancer
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Bates, Susan E., Lippman, Marc E., Spelsberg, T. C., editor, and Kumar, R., editor
- Published
- 1987
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43. Enthalpy- versus Entropy-Driven Molecular Recognition in the Era of Biologics.
- Author
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Varese M, Guardiola S, García J, and Giralt E
- Subjects
- Antibodies immunology, Antigens immunology, Models, Molecular, Protein Domains, Small Molecule Libraries metabolism, Small Molecule Libraries pharmacology, Entropy
- Abstract
Our laboratory has recently identified two nanobodies (small antibodies produced by camelids)-Nb1 and Nb6-that bind efficiently to epithelial growth factor (EGF) and inhibit its ability to activate its receptor (EGFR). Because of the relevance of the EGF/EGFR axis as a target in oncology, these new nanobodies have promising therapeutic potential. This article, however, is focused on another feature of these nanobodies: their distinct thermodynamic signatures. Nb1 binds to EGF through an entropy-driven mechanism whereas Nb6 binds to this factor under enthalpic control. We discuss the advantages and disadvantages of each mechanism in the contexts of traditional medical chemistry (small-molecule drugs) and also of biological drugs. In this latter case, the implications in terms of selectivity are far from being clearly established and further experimental data are required. Their monomeric natures, high stability, and ease of recombinant production make nanobodies ideally suited for thermodynamic studies. Moreover, nanobodies, thanks to their simpler structures in comparison with conventional antibodies, might provide better understanding of the structural basis of the thermodynamic parameters of antigen recognition., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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44. Mutated genes in pancreatic cancer
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He, Song-bing and Li, De-chun
- Published
- 2010
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45. Induction of Differentiation in Human Solid Tumor Cells by Anti-Tumor Agents in Serum Depleted Medium
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Rey, A., Cupissol, D., Ursule, E., Serrou, B., Fischer, G., editor, and Wieser, R. J., editor
- Published
- 1983
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46. The Role of Zinc on the Trophic Growth Factors, Nerve Growth Factor and Gustin
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Henkin, R. I., Law, J. S., Nelson, N. R., Hurley, Lucille S., editor, Keen, Carl L., editor, Lönnerdal, Bo, editor, and Rucker, Robert B., editor
- Published
- 1988
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47. Under the right conditions: protecting podocytes from diabetes-induced damage
- Author
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Imran Ali and Derek P. Brazil
- Subjects
medicine.medical_specialty ,Time Factors ,Synaptophysin ,Medicine (miscellaneous) ,Podocyte ,Apoptosis ,Injury ,Diabetic nephropathy ,Biology ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Epithelial growth factor ,Mice ,Epidermal growth factor ,Internal medicine ,Diabetes mellitus ,Conditioned medium ,medicine ,Animals ,Humans ,Cells, Cultured ,Epidermal Growth Factor ,Caspase 3 ,Podocytes ,Research ,Mesenchymal stem cell ,Membrane Proteins ,Cell Biology ,medicine.disease ,Antibodies, Neutralizing ,Recombinant Proteins ,medicine.anatomical_structure ,Endocrinology ,Glucose ,Adipose Tissue ,Culture Media, Conditioned ,Commentary ,Cancer research ,Cytokines ,Molecular Medicine ,Mesenchymal stem cells ,Stem cell - Abstract
Introduction The apoptosis and subsequent injury of podocytes plays a pathogenic role in diabetic nephropathy (DN). Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and reducing cellular injury. Our previous study found that MSCs could protect kidneys from diabetes-induced injury without obvious engraftment. So we evaluated the effects of human adipose-derived MSCs (hAd-MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms. Methods We used flow cytometry, Western blot and confocal fluorescence microscopy to study podocytic apoptosis and injury induced by HG at 24 hours, 48 hours, and 72 hours in the presence or absence of MSC-conditioned medium (CM). An antibody-based cytokine array was used to identify the mediating factor, which was verified by adding the neutralizing antibody (NtAb) to block its function or adding the recombinant cytokine to the medium to induce its function. Results hAd-MSC-CM reduced podocytic apoptosis in a dose-dependent manner, decreased the expression of podocytic cleaved caspase-3, and prevented the reduced expression and maintained the normal arrangement of podocytic synaptopodin and nephrin. However, human embryonic lung cell (Wi38)-CM failed to ameliorate podocytic apoptosis or injury. Twelve cytokines with concentration ratios (MSC-CM/Wi38-CM) >10-fold were identified. Epithelial growth factor (EGF) was singled out for its known ability to prevent apoptosis. Recombinant human EGF (rhEGF) prevented podocytic apoptosis and injury similarly to hAd-MSC-CM but, upon blockade of EGF, the beneficial effect of hAd-MSC-CM decreased dramatically. Conclusions hAd-MSCs prevent podocytic apoptosis and injury induced by HG, mainly through secreting soluble EG.
- Published
- 2013
48. Isolation and determination of potentially probiotic species
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Žaper, Josip, Rakić, Anita, Jukić, Mila, Listešc, Eddy, Burčul, Franko, and Garssen, Johan
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Probiotic species ,Epithelial Growth Factor ,Pancreatins ,Antibiotics - Abstract
Functional food is getting right place in biotechnology, where it should be primarily for physiological needs, such as the prophylaxis among patients (basal metabolism), stimulation for sportsmen (working metabolism), perinatal diet, adolescent diet and gerontological diet. Namely, any gender and age requires a special nutrient ratio, which is determined by specific physiology. In this regard the probiotics, as well as adequate prebiotics are of specific interest. Without essential vitamins (B-complex) intestinal microflora of our organism becomes prone to diseases, avitaminosis, and difficulties in amilozide digestion. It has been proven that besides vitamins our microflora also performs nutrient (prebiotics) fermentation and excretes antibiotics (symbiotics, bacteriocines), which are evolutionary analogs of hormones in eumetazoas. They are oligopeptides by structure. Correct excretion of exohormones of pancreas, as well as taking ad libido prebiotic, that endosymbiotic microflora, as well as its antibiotics (hormones, symbiotics) can be of significant assistance to liver physiology as well as to overall homeostasis of organism.
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- 2011
49. Evaluation of a rat meibomian gland dysfunction model induced by closure of meibomian gland orifices.
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Dong ZY, Ying M, Zheng J, Hu LJ, Xie JY, and Ma Y
- Abstract
Aim: To find a stable, inexpensive, and reliable method to produce a rat meibomian gland dysfunction (MGD) model., Methods: We inserted slim guidewires into the meibomian gland orifices of twelve Brown Norway rats and fulgurized every guidewire to destroy part of the meibomian gland. We then observed the morphological changes in the eyelid margin, and compared the data of tear breakup time (TBUT), Schirmer I test, and the corneal fluorescence staining scores at different times (1, 2, 4, and 6wk). We observed pathological changes of the cornea, conjunctiva and meibomian gland, and we used real-time polymerase chain reaction to analyze epithelial growth factor (EGF), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and Ki67., Results: In the fourth week, compared with the control group, the TBUT of the model group began to decreased ( P <0.05). The tear secretion remained stable ( P >0.05). The corneal dots were significantly increased in the fourth week when the fusion stain began to appear ( P <0.05). In the fourth week, partial meibomian gland openings had hoary secretions blocked, orifices were expanded, and there was a partial convex deformation. In the sixth week, the tissue section showed that the number of conjunctival goblet cells was decreased, epithelial cells were irregular, the epithelium was detached and rough, and meibomian glands were lost. The expressions of EGF, IL-6, IL-8, and TNF-α in corneal, conjunctival, and meibomian tissues were highly increased ( P <0.05), but no statistical difference was found in the expression of Ki67 in corneal and conjunctival tissues ( P >0.05)., Conclusion: The MGD rat model, produced via electrocauterization of meibomian gland orifices, matched clinical manifestations and cytokine levels. Our research provides a new method of achieving an MGD animal model.
- Published
- 2018
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50. Exquisite antitumour response to trastuzumab in a patient with no evidence of Ras-Raf-MAPK and PI3K-Akt pathways activation.
- Abstract
We report on the case of a patient with a diagnosis of a HER2-overexpressing metastatic breast cancer which was refractory to a combination of a Raf kinase inhibitor and docetaxel, but highly sensitive to trastuzumab, a HER2-targeted monoclonal antibody. Interestingly, there was no evidence of Ras-Raf-MAPK or PI3K-Akt pathways activation., Case Reports, Journal Article, info:eu-repo/semantics/published
- Published
- 2004
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