Epidermal Growth
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2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Zhou ◽  
An-qi Jin ◽  
Shi-chong Zhou ◽  
Jia-wei Li ◽  
Wen-xiang Zhi ◽  
...  

Abstract Background Human epidermal growth factor receptor2+ subtype breast cancer has a high degree of malignancy and a poor prognosis. The aim of this study is to develop a prediction model for the human epidermal growth factor receptor2+ subtype (non-luminal) of breast cancer based on the clinical and ultrasound features related with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor2. Methods We collected clinical data and reviewed preoperative ultrasound images of enrolled breast cancers from September 2017 to August 2020. We divided the data into in three groups as follows. Group I: estrogen receptor ± , Group II: progesterone receptor ± and Group III: human epidermal growth factor receptor2 ± . Univariate and multivariate logistic regression analyses were used to analyze the clinical and ultrasound features related with biomarkers among these groups. A model to predict human epidermal growth factor receptor2+ subtype was then developed based on the results of multivariate regression analyses, and the efficacy was evaluated using the area under receiver operating characteristic curve, accuracy, sensitivity, specificity. Results The human epidermal growth factor receptor2+ subtype accounted for 138 cases (11.8%) in the training set and 51 cases (10.1%) in the test set. In the multivariate regression analysis, age ≤ 50 years was an independent predictor of progesterone receptor + (p = 0.007), and posterior enhancement was a negative predictor of progesterone receptor + (p = 0.013) in Group II; palpable axillary lymph node, round, irregular shape and calcifications were independent predictors of the positivity for human epidermal growth factor receptor-2 in Group III (p = 0.001, p = 0.007, p = 0.010, p < 0.001, respectively). In Group I, shape was the only factor related to estrogen receptor status in the univariate analysis (p < 0.05). The area under receiver operating characteristic curve, accuracy, sensitivity, specificity of the model to predict human epidermal growth factor receptor2+ subtype breast cancer was 0.697, 60.14%, 72.46%, 58.49% and 0.725, 72.06%, 64.71%, 72.89% in the training and test sets, respectively. Conclusions Our study established a model to predict the human epidermal growth factor receptor2-positive subtype with moderate performance. And the results demonstrated that clinical and ultrasound features were significantly associated with biomarkers.


2021 ◽  
Vol 9 (4) ◽  
pp. 86-93
Author(s):  
Tamiris Fazza Kelmer ◽  
◽  
Mario Jorge Sobreira da Silva ◽  
Maely Peçanha Favero Retto ◽  
◽  
...  

Introdução: O câncer de mama apresenta alta taxa de incidência no Brasil e no mundo e estima-se que cerca de 20% dos casos sejam classifcados como Human Epidermal Growth Fator Receptor – tipo 2-positivo (HER2-positivo). Para tratamento desse tipo de câncer é indicado o uso de terapia-alvo, utilizando medicamentos biológicos, dentre eles, trastuzumabe. Por ser um medicamento considerado de alto custo, a entrada de seus biossimilares no mercado pode promover redução de custos aos serviços de saúde. Objetivo: Analisar os estudos clínicos de fase III de trastuzumabe biossimilares aprovados no Brasil até o ano de 2020. Método: Foi realizada uma revisão de escopo com estudos clínicos utilizados para o registro dos medicamentos biossimilares trastuzumabe no âmbito da Agência Nacional de Vigilância Sanitária (Anvisa). Os dados foram analisados quanto: i) aos protocolos de tratamento envolvidos nos estudos; ii) aos desfechos e características das populações investigadas; iii) ao perfl de segurança dos medicamentos biossimilares. Resultados: Foram selecionados, analisados e comparados seis estudos. Os estudos foram realizados com protocolos de tratamento, objetivos e medicamentos diferentes. A taxa de resposta completa foi o desfecho primário analisado na maioria dos estudos, seguido da resposta patológica completa. Em relação à população, os estudos envolveram a análise da população com intenção de tratar e/ou os pacientes que completaram o tratamento. Em todos os estudos, o perfl de segurança dos medicamentos biossimilares foi semelhante ao do medicamento de referência. Conclusões: Os estudos analisados foram capazes de demonstrar similaridade entre biossimilares e o medicamento de referência em relação.à efcácia e à segurança, porém apresentaram diferenças em relação à metodologia utilizada, população e desfechos analisados.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yongjian Huang ◽  
Jana Ognjenovic ◽  
Deepti Karandur ◽  
Kate Miller ◽  
Alan Merk ◽  
...  

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-α with similar affinity, but generates different signals from these ligands. To address the mechanistic basis of this phenomenon, we have carried out cryo-EM analyses of human EGFR bound to EGF and TGF-α. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-α. The two extreme states of this ensemble represent distinct ligand-bound quaternary structures in which the membrane-proximal tips of the extracellular module are either juxtaposed or separated. EGF and TGF-α differ in their ability to maintain the conformation with the membrane-proximal tips of the extracellular module separated, and this conformation is stabilized preferentially by an oncogenic EGFR mutation. Close proximity of the transmembrane helices at the junction with the extracellular module has been associated previously with increased EGFR activity. Our results show how EGFR can couple the binding of different ligands to differential modulation of this proximity, thereby suggesting a molecular mechanism for the generation of ligand-sensitive differential outputs in this receptor family.


Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1909
Author(s):  
Min Jeong Kim ◽  
Su Jeong Ha ◽  
Bo Ram So ◽  
Chang-Kil Kim ◽  
Kyung-Min Kim ◽  
...  

The skin acts as the primary defense organ that protects the body from the external environment. Skin cancer is one of the most common cancers in the world. Skin carcinogenesis is usually caused by cell degeneration due to exposure to ultraviolet (UV) radiation, which causes changes in various signaling networks, disrupting the homeostasis of single skin cells. In this review, we summarize the roles of nicotinamide adenine dinucleotide phosphate oxidase (NOX) and epidermal growth factor receptor (EGFR) in UV-induced skin carcinogenesis. Furthermore, we describe the crosstalk that exists between NOX, EGFR, and protein tyrosine phosphatase κ and its oncogenic downstream signaling pathways. Chemoprevention is the use of chemical compounds to recover the healthy status of the skin or delay cancer development. Current evidence from in vitro and in vivo studies on chemopreventive phytochemicals that target NOX, EGFR, or both, as major regulators of skin carcinogenesis will also be discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppe Scalabrino

Recent findings showing that epidermal growth factor (EGF) is significantly decreased in the cerebrospinal fluid (CSF) and spinal cord (SC) of living or deceased multiple sclerosis (MS) patients, and that its repeated administration to rodents with chemically- or virally-induced demyelination of the central nervous system (CNS) or experimental allergic encephalomyelitis (EAE) prevents demyelination and inflammatory reactions in the CNS, have led to a critical reassessment of the MS pathogenesis, partly because EGF is considered to have little or no role in immunology. EGF is the only myelinotrophic factor that has been tested in the CSF and spinal cord of MS patients, and it has been shown there is a good correspondence between liquid and tissue levels. This review: (a) briefly summarises the positive EGF effects on neural stem cells, oligodendrocyte cell lineage, and astrocytes in order to explain, at least in part, the biological basis of the myelin loss and remyelination failure in MS; and (b) after a short analysis of the evolution of the principle of cause-effect in the history of Western philosophy, highlights the lack of any experimental immune-, toxin-, or virus-mediated model that precisely reproduces the histopathological features and “clinical” symptoms of MS, thus underlining the inapplicability of Claude Bernard's crucial sequence of “observation, hypothesis, and hypothesis testing.” This is followed by a discussion of most of the putative non-immunologically-linked points of MS pathogenesis (abnormalities in myelinotrophic factor CSF levels, oligodendrocytes (ODCs), astrocytes, extracellular matrix, and epigenetics) on the basis of Popper's falsification principle, and the suggestion that autoimmunity and phologosis reactions (surely the most devasting consequences of the disease) are probably the last links in a chain of events that trigger the reactions. As it is likely that there is a lack of other myelinotrophic growth factors because myelinogenesis is controlled by various CNS and extra-CNS growth factors and other molecules within and outside ODCs, further studies are needed to investigate the role of non-immunological molecules at the time of the onset of the disease. In the words of Galilei, the human mind should be prepared to understand what nature has created.


2021 ◽  
Vol 22 (22) ◽  
pp. 12579
Author(s):  
Paul Kwangho Kwon ◽  
Sung Wook Kim ◽  
Ranjit De ◽  
Sung Woo Jeong ◽  
Kyong-Tai Kim

Although proliferation of keratinocytes, a major type of skin cells, is a key factor in maintaining the function of skin, their ability to proliferate tends to diminish with age. To solve such a problem, researchers in medical and skin cosmetic fields have tried to utilize epidermal growth factor (EGF), but achieved limited success. Therefore, a small natural compound that can mimic the activity of EGF is highly desired in both medical and cosmetic fields. Here, using the modified biosensor system, we observed that natural small-compound isoprocurcumenol, which is a terpenoid molecule derived from turmeric, can activate EGFR signaling. It increased the phosphorylation of ERK and AKT, and upregulated the expression of genes related to cell growth and proliferation, such as c-myc, c-jun, c-fos, and egr-1. In addition, isoprocurcumenol induced the proliferation of keratinocytes in both physical and UVB-induced cellular damage, indicative of its function in skin regeneration. These findings reveal that EGF-like isoprocurcumenol promotes the proliferation of keratinocytes and further suggest its potential as an ingredient for medical and cosmetics use.


2021 ◽  
Vol 23 (11) ◽  
pp. 603-611
Author(s):  
Dr. Maitham Mohammed AL-Khateeb ◽  
◽  
Dr. Ahmed Rabee Abid ◽  
Dr.Arkan Karrem Abd ◽  
◽  
...  

Back ground: Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death in women. HER2 is a transmembrane receptor with tyrosine kinase. It belongs to a family of four receptors (EGFR/HER1, HER2, HER3, HER4) that are involved in regulating cell growth, survival and differentiation. Structural studies revealed that HER2 is always in an active conformation and ready to interact with the ligand-activated HER receptors, before the advent of HER2-directed therapies, this increased level of HER2 was associated with high recurrence rates and increased mortality in patients with node-positive and node-negative disease. Aim of study: To calculate the incidence of human epidermal growth factor receptor 2 positive results in addition to its relation to estrogen receptor and progesterone receptor results in breast cancer cases in AL-Yarmouk teaching hospital and compare our results to regional and international results. Patients and Methods: Analysis of a prospectively collected clinical database was performed. We included 40 patients who had mastectomy for stage one to stage three breast cancer cases, from October 2018 to October 2019, where by complete receptor information were done. Fluorescence in Situ Hybridization test had been requested. The corresponding H&E-stained slides from all cases were reviewed. Unstained tissue sections containing tumor, as well as adjacent normal breast parenchyma when possible and corresponding to those used for the Fluorescence In Situ Hybridization test were selected from each case for immunohistochemical staining, comparison with regional and international results was done. Results: Total number of cases collected was 40 cases of breast cancer; they were investigated for human epidermal growth factor receptors 2 in addition to estrogen and progesterone receptors. Age of the patients ranged from 30 to 69 years (mean, 49.27 years). HER2/ neu positive cases were (8) (20%) of cases, and negative cases were (32) (80%), in addition to a statically significant relation to ER and PR receptor results. Conclusion: The incidence of human epidermal growth factor receptors 2 positive at AL-Yarmouk teaching hospital was 20%, estrogen receptors \ progesterone receptors positive was (57.5%) and the relation between these receptors was statistically significant.


2021 ◽  
Vol 23 (11) ◽  
pp. 603-611
Author(s):  
Dr. Maitham Mohammed AL-Khateeb ◽  
◽  
Dr. Ahmed Rabee Abid ◽  
Dr.Arkan Karrem Abd ◽  
◽  
...  

Back ground: Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death in women. HER2 is a transmembrane receptor with tyrosine kinase. It belongs to a family of four receptors (EGFR/HER1, HER2, HER3, HER4) that are involved in regulating cell growth, survival and differentiation. Structural studies revealed that HER2 is always in an active conformation and ready to interact with the ligand-activated HER receptors, before the advent of HER2-directed therapies, this increased level of HER2 was associated with high recurrence rates and increased mortality in patients with node-positive and node-negative disease. Aim of study: To calculate the incidence of human epidermal growth factor receptor 2 positive results in addition to its relation to estrogen receptor and progesterone receptor results in breast cancer cases in AL-Yarmouk teaching hospital and compare our results to regional and international results. Patients and Methods: Analysis of a prospectively collected clinical database was performed. We included 40 patients who had mastectomy for stage one to stage three breast cancer cases, from October 2018 to October 2019, where by complete receptor information were done. Fluorescence in Situ Hybridization test had been requested. The corresponding H&E-stained slides from all cases were reviewed. Unstained tissue sections containing tumor, as well as adjacent normal breast parenchyma when possible and corresponding to those used for the Fluorescence In Situ Hybridization test were selected from each case for immunohistochemical staining, comparison with regional and international results was done. Results: Total number of cases collected was 40 cases of breast cancer; they were investigated for human epidermal growth factor receptors 2 in addition to estrogen and progesterone receptors. Age of the patients ranged from 30 to 69 years (mean, 49.27 years). HER2/ neu positive cases were (8) (20%) of cases, and negative cases were (32) (80%), in addition to a statically significant relation to ER and PR receptor results. Conclusion: The incidence of human epidermal growth factor receptors 2 positive at AL-Yarmouk teaching hospital was 20%, estrogen receptors \ progesterone receptors positive was (57.5%) and the relation between these receptors was statistically significant.


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