Epithelial Growth Factor Receptor Expression Research Articles

Comparison of EGFR (Epithelial Growth Factor Receptor) expression as a protein marker in Oral Erosive & Reticular Lichen Planus and Oral Epithelial Dysplasia

Comparison of EGFR (Epithelial Growth Factor Receptor) expression as a protein marker in Oral Erosive & Reticular Lichen Planus and Oral Epithelial Dysplasia

Sushi domain-containing protein 4 binds to epithelial growth factor receptor and initiates autophagy in an EGFR phosphorylation independent manner

BackgroundSushi domain-containing protein 4 (SUSD4) is a recently discovered protein with unknown cellular functions. We previously revealed that SUSD4 can act as complement inhibitor and as a potential tumor suppressor.MethodsIn a syngeneic mouse model of breast cancer, tumors expressing SUSD4 had a smaller volume compared with the corresponding mock control tumors. Additionally, data from three different expression databases and online analysis tools confirm that for breast cancer patients, high mRNA expression of SUSD4 in the tumor tissue correlates with a better prognosis. In vitro experiments utilized triple-negative breast cancer cell lines (BT-20 and MDA-MB-468) stably expressing SUSD4. Moreover, we established a cell line based on BT-20 in which the gene for EGFR was knocked out with the CRISPR-Cas9 method.ResultsWe discovered that the Epithelial Growth Factor Receptor (EGFR) interacts with SUSD4. Furthermore, triple-negative breast cancer cell lines stably expressing SUSD4 had higher autophagic flux. The initiation of autophagy required the expression of EGFR but not phosphorylation of the receptor. Expression of SUSD4 in the breast cancer cells led to activation of the tumor suppressor LKB1 and consequently to the activation of AMPKα1. Finally, autophagy was initiated after stimulation of the ULK1, Atg14 and Beclin-1 axis in SUSD4 expressing cells.ConclusionsIn this study we provide novel insight into the molecular mechanism of action whereby SUSD4 acts as an EGFR inhibitor without affecting the phosphorylation of the receptor and may potentially influence the recycling of EGFR to the plasma membrane.

Mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) expression in different breast cancer subtypes and their clinical significance.

Increasing evidence has shown that mammaglobin, GATA-binding protein 3 (GATA3), and epithelial growth factor receptor (EGFR) have unique clinical implications for breast cancer subtyping and classification, as well as for breast cancer targeted therapy. It is particularly important to clarify the correlation between their expression and different molecular breast carcinoma subtypes to better understand the molecular basis of the subtypes and to identify effective therapeutic targets for the disease. This study aimed to evaluate mammaglobin, GATA3, and EGFR expression in different breast cancer subtypes, as well as their clinical significance. Subjects of the study included 228 patients with breast cancer at The First Affiliated Hospital of University of Science and Technology of China. They were divided into triple negative (TN), Luminal A, Luminal B, and HER-2 positive (HER-2.P) breast cancer groups based on molecular classification. Immunohistochemical methods were used to detect mammaglobin, GATA3, and EGFR expression in cases of different molecular subtypes before determining the correlation between protein expression and subtype. Mammaglobin and GATA3 expression levels were found to significantly vary with respect to histopathological grade, lymph node status, and molecular subtype; EGFR expression was significantly correlated with breast cancer histopathological grade and molecular subtype. For breast cancer, the expression levels of mammaglobin and GATA3, as well as mammaglobin and EGFR, were significantly correlated. In addition, there was a significantly negative correlation between the expression levels of GATA3 and EGFR in breast cancer tissue samples, especially in HER-2.P samples. These findings provide a theoretical basis for assessing breast cancer clinical prognosis based on the cancer subtype, and hence, have significant practical value.

α-MSH ameliorates corneal surface dysfunction in scopolamine-induced dry eye rats and human corneal epithelial cells via enhancing EGFR expression

Dry eye (DE) is a chronic, multifactorial ocular surface disease associated with visual disturbance, tear film instability, hyperosmolarity, ocular surface inflammation and damage. Effective intervention is necessary to control this disease. In this study we topically applied α-melanocyte stimulating hormone (α-MSH) on the ocular surface of scopolamine-induced DE rats and found that it promoted tear secretion, reduced tear breakup time and fluorescein sodium staining and increased the number of conjunctival goblet cells. To investigate the mechanism, protein array was conducted, which showed that α-MSH exerted its effects via epithelial growth factor receptor (EGFR) in the JAK-STAT signaling pathway. Furthermore, in vitro experiments showed that α-MSH protected human corneal epithelial cells (hCECs) by maintaining their migration ability and viability and decreasing apoptosis. However, blockade of EGFR abolished these protective effects. Moreover, α-MSH decreased the level of autophagy in benzalkonium chloride (BAC)-stressed hCECs via EGFR. These results demonstrated that α-MSH ameliorated lesions and restored ocular surface functions by upregulating EGFR expression.

Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment.

Simple SummaryOur findings indicated that the EGF-EGFR pathway was highly activated in very young patients with recurrent or metastatic NPC. High EGFR expression in patients with metastatic NPC resulted in poor clinical outcomes. To examine whether the EGFR pathway serves as a therapeutic target for NPC, NPC patient-derived xenograft (PDX) and NPC cell lines were treated with EGFR inhibitors (EGFRi) and a cell cycle blocker. Either EGFRi or cell cycle blocker treatment alone could reduce NPC cell growth and PDX tumor growth. Furthermore, combination treatment exerted an additive suppression effect on PDX tumor growth. This study provides promising evidence that EGFRi used in combination with a cell cycle blocker may be used to treat patients with NPC.Background: Nasopharyngeal carcinoma (NPC) involves host genetics, environmental and viral factors. In clinical observations, patients of young and old ages were found to have higher recurrence and metastatic rates. Methods: Cytokine array was employed to screen druggable target(s). The candidate target(s) were confirmed through patient-derived xenografts (PDXs) and a new EBV-positive cell line, NPC-B13. Results: Overexpression of epithelial growth factor (EGF) and EGF receptor (EGFR) was detected in young patients than in older patients. The growth of NPC PDX tumors and cell lines was inhibited by EGFR inhibitors (EGFRi) cetuximab and afatinib when used separately or in combination with the cell cycle blocker palbociclib. Western blot analysis of these drug-treated PDXs demonstrated that the blockade of the EGF signaling pathway was associated with a decrease in the p-EGFR level and reduction in PDX tumor size. RNA sequencing results of PDX tumors elucidated that cell cycle-related pathways were suppressed in response to drug treatments. High EGFR expression (IHC score ≥ grade 3) was correlated with poor survival in metastatic patients (p = 0.008). Conclusions: Our results provide encouraging preliminary data related to the combination treatment of EGFRi and palbociclib in patients with NPC.

Immunohistochemical characterisation and histopathology of astrocytic neoplasms at a tertiary Nigerian hospital.

To describe histological features and pattern of expression of selected markers including epithelial growth factor receptor (EGFR), mutant p53 and mutant isocitrate dehydrogenase-1 (IDH-1R132H) among astrocytic neoplasms at the University College Hospital, Ibadan, Nigeria. A retrospective cross-sectional study involving histologically diagnosed Central Nervous System (CNS) neoplasms between January 2004 and December 2015. Haematoxylin and Eosin Slides of 81 cases of astrocytomas were retrieved, re-cut and reviewed. Ethical clearance was obtained from the ethical board of the hospital. Immunohistochemistry using the Biotin-Streptavidin system was performed with IDH-1 R132H, p53 and EGFR mouse monoclonal antibodies (MOABs) specific against all the cases of astrocytomas under review. All cases were graded and classified using the World Health Organisation (WHO) Classification of Central Nervous System tumours (2016). Membranous and cytoplasmic staining of EGFR and IDH-1R132H mouse monoclonal antibodies, respectively, were regarded as positive while nuclear staining of p53 mouse monoclonal antibody was regarded as positive. The data obtained were analysed with the level of statistical significance set at P<.05. Males constituted a majority of cases, 50 (61.7%). Male-Female ratio was 1.6:1. Mean age was 30.6years. Tumours were of a higher WHO grade with increasing age, albeit glioblastoma cases tended to present at younger ages. The higher WHO grades were more likely to be located supratentorially. Glioblastomas accounted for most of the diagnosis 39 (48.1%), followed by pilocytic astrocytomas at 23 (28.4%). There was a low positive cytoplasmic expression of IDH-1 with only three (3.7%) being positive, eight (9.9%) showed a positive nuclear expression for mutant p53 while 17 (21%) showed membranous positivity for EGFR expression. There are similar epidemiological trends between our cohort of patients and as described in most instances worldwide. Optimal stratification for astrocytomas can be achieved using a combination of IDH-1/EGFR immunohistochemistry.

Impaired airway epithelial cell wound-healing capacity is associated with airway remodelling following RSV infection in severe preschool wheeze.

Respiratory syncytial virus (RSV) causes exacerbations of asthma and preschool wheeze (PSW). However, the anti-viral and repair responses of the bronchial epithelium in children with severe therapy-resistant asthma (STRA) and PSW are poorly understood. Children with STRA (age 12 [6-16] years), PSW (age 2 [1-5] years) and non-asthmatic controls (age 7 [2-14] years) underwent bronchoscopy with endobronchial brushings and biopsies. Anti-viral, wound injury responses were quantified in biopsies and primary bronchial epithelial cells (PBECs) in response to RSV, poly(I:C), house dust mite (HDM) or IL-33 using RT-qPCR, Luminex and live cell imaging. Collagen deposition and tissue expression of epithelial growth factor receptor (EGFR), IL-33 and receptor ST2 were investigated in bronchial biopsies. PBECs from STRA and PSW had increased TLR3 gene expression and increased secretion of anti-viral and pro-inflammatory cytokines (IFN-γ, IL-6 and IL-13) in response to RSV compared to controls. Exposure of PBECs to concomitant TLR3 agonist poly(I:C) and HDM resulted in a significant reduction in epithelial cell proliferation in PSW compared to controls. Wound-healing was also impaired in PSW compared to controls at baseline and following IL-33 stimulation. In addition, tissue EGFR expression was significantly reduced in PSW and correlated with collagen deposition in endobronchial biopsies. Despite increased anti-viral responses, preschool children with severe wheeze had impaired airway epithelial proliferative responses following damage. This might be connected to the low expression of EGFR in PSW which may affect epithelial function and contribute to asthma pathogenesis.

THE RELATION OF EBNA-1 AND EGFR EXPRESSION SCREENING FROM ADVANCED STAGE UNDIFFERENTIATED NASOPHARYNGEAL CANCER

Introduction:&#x0D; Nasopharyngeal carcinoma (NPC) is a lymphoepithelial malignancy of the nasopharynx, one of the etiologies is the infection of Epstein–Barr virus in undifferentiated type of nasopharyngeal carcinoma. The Epstein-Barr virus Nucleus Antigen-1 (EBNA-1) is Epstein–Barr virus-encoded proteins as regulatory virus transcription. Epithelial Growth Factor Receptor (EGFR) consist of a single polypeptide chain of amino acid, ErbB members, tyrosine kinase receptor, a transmembrane glycoprotein encoded by gen location in the short arms of a chromosome and overexpression in epithelial tumors. EGFR plays a central role in signal transduction pathways which regulate key cellular functions in epithelial malignancies. and may also present in NPC.&#x0D; Objective:&#x0D; To investigate this relation of expression patterns of EBNA-1 and EGFR in a histological type of undifferentiated nasopharyngeal carcinoma.&#x0D; Method:&#x0D; Observational, analytical study with a cross-sectional method of 34 formalin-fixed within inclusion criteria are EBNA-1 and positive staining of EGFR expression (30 patients) and exclusion criteria of negative staining of EGFR (4 patients). All biopsy samples work with paraffin embedded and resulted in hematoxylin-eosin undifferentiated histological types of the advanced stage in nasopharyngeal carcinoma. EBNA-1 and EGFR expression used immunohistochemistry staining.&#x0D; Result:&#x0D; EBNA-1 and EGFR expression level were detection and correlated with the advanced stadium of nasopharyngeal undifferentiated carcinoma.&#x0D; Conclusion: &#x0D; EBNA-1 is significantly related to EGFR expression in the advanced stadium of undifferentiated nasopharyngeal carcinoma. Overexpression of EGFR is mostly found in advanced NPC but not in all ages. Male is dominated and overall age below 55 years old. Screening of EGFR with immunohistochemistry is highly considered before anti-EGFR treatment

Effect of hypoxia on epithelial growth factor receptor expression and cell apoptosis of breast cancer and cervical cancer xenografts in nude mice

Objective To observe the effect of hypoxia on the expression of epithelial growth factor receptor (EGFR) and cell apoptosis of breast and cervical cancer xenografts in nude mouse models. Methods The nude mouse models with MCF-7 and HeLa xenografts were established. The degree of hypoxia and EGFR expression were observed by confocal microscopy. The influence of EGFR expression on cell apoptosis under hypoxia was observed by TUNEL assay. Results EGFR expression was either up-regulated or down-regulated in the MCF-7 and HeLa cells with high degree of hypoxia. Furthermore, the degree of apoptosis was reduced in tumor tissues with high EGFR expression compared with that in those with low expression of EGFR. Conclusion The hypoxia in MCF-7 and HeLa cells exerts heterogeneous effect on EGFR expression. Under hypoxic conditions, EGFR expression is negatively correlated with cell apoptosis. Key words: Xenografts in nude mice; Breast cancer cell line; Cervical cancer cell line; Hypoxia; Epithelial growth factor receptor

Research of expression and correlation of ADAM8 and EGFR in the osteosarcoma tissue

Objective: To lay a foundation for the research on the targeted therapy of osteosarcoma or the regulatory mechanism of the occurrence and development of osteosarcoma by studying the expression of a disintegrin and metalloproteinase domain-containing protein 8 (ADAM8) and epithelial growth factor receptor (EGFR) in osteosarcoma.Methods: Osteosarcoma tissues, osteochondroma tissues, osteoarthritis tissues and normal bone tissues were selected and included in this research. By use of tissue chips and immunohistochemistry, the expression levels of ADAM8 and EGFR in the previously-mentioned tissues were observed and compared. Spearman’s rank correlation test was used to analyze the correlation of ADAM8 and EGFR and their relationship with clinicopathological factors in these cases.Results: The positive expression levels of ADAM8 in osteosarcoma tissues, osteochondroma tissues, osteoarthritis tissues and normal bone tissues were 80.95%, 36.36%, 62.86% and 24.14% respectively, the difference was of statistical significance (p &lt; .05); the positive expression levels of EGFR in osteosarcoma tissues, osteochondroma tissues, osteoarthritis tissues and normal bone tissues were 66.67%, 9.09%, 40.00% and 4.76% respectively, the difference was of statistical significance (p &lt; .05); Spearman’s rank correlation test showed that ADAM8 was positively correlated with EGFR (r = .379, p &lt; .05).Conclusions: Both ADAM8 and EGFR have a much higher expression in osteosarcoma tissues, and the combined detection of two indexes can be considered as a new method in the clinical diagnosis of osteosarcoma.

Ecto-5'-nucleotidase (CD73) is a potential target of hepatocellular carcinoma.

High expression of ecto-5'-nucleotidase (CD73) has been reported in a number of epithelium origin malignancies. Here, we hypothesize that CD73 promotes hepatocellular carcinoma (HCC) growth and metastasis and that the effect is mediated by epithelial growth factor receptor (EGFR). HCC cells with different malignancies and Tissue microarrays of the tumor and peritumoral liver tissues from 30 independent patients were used to examine CD73 and EGFR expression. Then, MTT and Ki67 detection, together with cell adhesion, invasion, and migration assays were used to evaluate the effects of CD73 on cell growth and metastasis. The expression of EGFR in HCC cells was also tested after suppressing or overexpressing CD73. Lastly, tumor tissues from nude mice, which had been injected subcutaneously with HCC cells, were transplanted subcutaneously into CD73-/- and wild-type (WT) C57 mice. CD73 expression was higher in HCC cells with greater metastatic potentials and tumor tissues compared with low metastatic cells and peritumor tissues. CD73 and EGFR were coexpressed and positively correlated in tumor and peritumor liver tissues in HCC tissue microarrays. Up-regulationof CD73 by plasmid transfection or by pharmacological agents promoted EGFR expression in HCC cells, whereas suppression of CD73 inhibited these effects. The growth of transplanted tumor tissues was dramatically slower in CD73-/- mice than in WT type mice in the in vivo experiments. CD73 promotes HCC growth and metastasis and upregulated the expression of EGFR in HCC. Thus, CD73 and EGFR are potential targets in the treatment of HCC.

Immunohistochemical Characterization and Subclassification of Triple Negative Breast Cancer of Egyptian Female Patients

AbstractBackground: Triple negative breast cancer is representing a heterogeneous group of breast cancer. Many trials were carried out for its subclassification by different markers. This classification also could help in new treatment modalities.Aim of Study: To investigate and identify additional possible prognostic markers that can help in subclassification of triple negative breast cancer.Patients and Methods: This retrospective study included 59 women with triple negative breast cancer referred to NCI, Cairo University, Egypt. Clinical data were collected. Immu-nohistochemical analyses were performed for the assessment of CK5/6, Epithelial growth factor receptor (EGFR), and Claudin 4. All cases were followed-up with a median follow-up time 40.5 months (range: 8-67).Results: Among the studied cases (71.2%) were positive to CK5/6, (45.8%) were positive to EGFR, (89.8%) represented Claudin4 high. Expression of CK5/6 revealed a significant relationship with tumor size. Expression of EGFR revealed a significant relationship with stage of the tumor. Most of cases of Claudin 4 high represented high grade, high stage and node positivity, but not reached the significant level. There is significant relationship found between grade and DFS, as well as OS with grade, stage, occurrence of metastasis and node positivity.Conclusion: Triple negative breast cancer is a heteroge-neous molecular type of breast cancer. Basal markers such as CK5/6 and EGFR are used for identification of basal subgroup of TNBC. This subclassification of triple negative breast cancer helps in categorization of patients who are candidate for targeted therapy, such as tyrosine kinase inhibitors (TKIs) in cases positive for EGFR. Expression of Claudin 4 also helps in classification of triple negative breast cancer, and selection of cases that could be targeted by monoclonal antibodies.

Interaction between epidermal growth factor receptor and interleukin-6 receptor in NSCLC progression.

Even though the interaction between epithelial growth factor receptor (EGFR) and interleukin-6 receptor (IL-6R) has been found in many tumors, there is a lack of relevant in-depth study of lung cancer. The following study investigates the interaction of EGFR and IL-6R in lung cancer. In the current study, EGFR, IL-6, and glycoprotein 130 (GP130) were highly expressed in non-small cell lung cancer (NSCLC) tissue samples and were associated with clinicopathological features and poor prognosis of patients with NSCLC. Furthermore, the effect of EGF and IL-6 on biological behavior of lung cancer cells (cell proliferation, invasion, cycle, and apoptosis) and the expression of EGFR, GP130, p-protein kinase B (p-AKT), and p-p44/42 mitogen-activated protein kinase (p-p44/42 MAPK) was significantly stronger compared with other treatment groups (all P < 0.05). These results suggest that EGFR and IL-6R have synergistic effects on NSCLC progression. This could help to solve the problem of EGFR inhibitors in the treatment of lung cancer resistance and improve the efficacy of current treatment for lung cancer through a combination of EGFR and IL-6R signaling pathways.

Association between EGFR mutation and expression of BRCA1 and RAP80 in non-small cell lung cancer.

Association between the epithelial growth factor receptor (EGFR) mutation and the expression of breast cancer 1 (BRCA1) and receptor-associated protein 80 (RAP80) in non-small cell lung cancer (NSCLC) was studied. From September 2014 to September 2016, 51 patients with NSCLC who were hospitalized in Department of Thoracic Surgery in The Affiliated Jiangyin Hospital of Southeast University Medical College and underwent biopsy or operation were selected. The pathological changes of lung tissue were detected by hematoxylin and eosin histopathological staining. The fluorescent expression of BRCA1 and RAP80 protein in the two groups was determined by immunofluorescence staining. Reverse transcriptase polymerase chain reaction method and western blot analysis were used to detect BRCA1 and RAP80 mRNA and protein expression. Then the EGFR gene mutation was detected and analyzed. The results show that non-small cell lung cancer has an association with smoking. Compared with the control, the lung tissue structure of the NSCLC group was damaged. The protein fluorescence expression of BRCA1 and RAP80 in non-small cell lung cancer group was significantly increased. The expression of BRCA1 and RAP80 mRNA and protein in NSCLC group was significantly increased. The difference in expression of BRCA1 and RAP80 in the control and the non-small cell lung cancer group was statistically significant (P<0.05). EGFR gene mutations detected 14 of the 51 patients with genetic mutations. Non-small cell lung cancer and smoking have certain relevance, and BRCA1 and RAP80 expression in the development and progression of NSCLC has a close relationship. EGFR mutation in non-small cell lung cancer significantly related to the mutation of EGFR and BRCA1 and RAP80 gene expression plays an important role in the diagnosis and treatment of NSCLC.

Inhibitory effect of interfering the phosphorylation of epithelial growth factor receptor on breast cancer cell xenografts in nude mice

Objective To investigate the effect of interfering phosphorylation of epithelial growth factor receptor (EGFR) on breast cancer cell xenografts in nude mice. Methods Breast cancer cell MDA-MB-231 xenograft model was established in nude mice and treated with adenovirus Ad5-hSulf1. The effect of hSulf-1 gene was examined on the inhibition of EGFR phosphorylation and xenograft growth. Results The recombinant adenovirus Ad5-hSulf1 expressed hSulf-1 factor and inhibited tumor growth. There was an obvious difference in tumor volume between Ad5-hSulf1 group (670.83±65.02) mm3 and blank control group (1 815.33±214.43) mm3 (P=0.000). The expression of hSulf-1 did not affect total EGFR expression but decreased p-EGFR expression level. Conclusion The expression of hSulf-1 can inhibit the EGFR phosphorylation and then inhibit the breast cancer xenograft growth. Key words: Breast cancer; Signal pathway; Epithelial growth factor receptor; Phosphorylation; Model, animal

Immunoexpression of progesterone receptor, epithelial growth factor receptor and galectin-3 in uterine smooth muscle tumors

Uterine smooth muscle tumors constitute a spectrum of neoplasms. Diagnosis of leiomyomas (LMs) is usually straight forwards; however, atypical leiomyomas (ALMs) and smooth muscle tumors of uncertain malignant potential (STUMPs) have overlapping features and need to be distinguished from leiomyosarcoma. To evaluate progesterone receptor (PR), epithelial growth factor receptor (EGF-R), and galectin-3 expression in LMs, ALMs, STUMPs, and leiomyosarcomas and to assess their possible role in differentiating those tumors. Immunoexpression of EGF-R, PR, and galectin-3 were studied in 44 cases of uterine smooth muscle tumors through retrospective study. Studied cases included 20 LM, 9 ALM, 5 STUMP, and 10 leiomyosarcomas. A semiquantitative score was used to evaluate immunohistochemical staining. EGF-R overexpression was detected in leiomyosarcomas while a lack of or reduced EGF-R expression was observed in the nonsarcomatous group (LMs, ALMs, and STUMPs) with a highly significant difference. On the contrary, there was weak or negative PR staining in leiomyosarcomas compared to intense PR expression in the nonsarcomatous group with a highly significant difference. Meanwhile, galectin-3 was downregulated in leiomyosarcomas compared to the nonsarcomatous group with a significant difference. Correlation analysis revealed negative correlation between EGF-R and PR expression with significant statistical results while correlation of galectin-3 with EGF-R and PR showed insignificant statistical results. Immunoexpression of EGF-R, PR, and galectin-3 could help differentiate challenging cases of uterine smooth muscle tumors. Further studies are recommended to investigate interactions between EGF-R, PR, and galectin-3 and to plan new therapeutic strategies.

ZBTB20 regulates EGFR expression and hepatocyte proliferation in mouse liver regeneration

Liver has a unique regenerative capacity, however, its regulatory mechanism is not fully defined. We have established the zinc-finger protein ZBTB20 as a key transcriptional repressor for alpha-fetoprotein (AFP) gene in liver. As a marker of hepatic differentiation, AFP expression is closely associated with hepatocyte proliferation. Unexpectedly, here we showed that ZBTB20 acts as a positive regulator of hepatic replication and is required for efficient liver regeneration. The mice specifically lacking ZBTB20 in hepatocytes exhibited a remarkable defect in liver regeneration after partial hepatectomy, which was characterized by impaired hepatocyte proliferation along with delayed cyclin D1 induction and diminished AKT activation. Furthermore, we found that epithelial growth factor receptor (EGFR) expression was dramatically reduced in the liver in the absence of ZBTB20, thereby substantially attenuating the activation of EGFR signaling pathway in regenerating liver. Adenovirus-mediated EGFR overexpression in ZBTB20-deficient hepatocytes could largely restore AKT activation in response to EGFR ligands in vitro, as well as hepatocyte replication in liver regeneration. Furthermore, ZBTB20 overexpression could significantly restore hepatic EGFR expression and cell proliferation after hepatectomy in ZBTB20-deficient liver. Taken together, our data point to ZBTB20 as a critical regulator of EGFR expression and hepatocyte proliferation in mouse liver regeneration, and may serve as a potential therapeutic target in clinical settings of liver regeneration.

EGFR Immunoexpression in Malignant Serous and Mucinous Ovarian Tumors.

The epithelial growth factor receptor (EGFR) is involved in various stages of cancer growth such as tumor initiation, angiogenesis and metastasis, being an attractive target for oncogenic therapy. The present study aims to evaluate the EGFR expression in 54 cases of serous and mucinous ovarian borderline tumors and carcinomas. EGFR expression was present in more than half of the investigated tumors, more frequently in carcinomas than in borderline tumors, especially in the serous type. The highest values of the final staining score (FSS) were observed only in serous carcinomas in the advanced stages of the disease. As a result of frequent expression of EGFR in ovarian tumors, it is necessary to monitor EGFR inhibitors for ovarian cancer therapy, but probably after establishing more rigorous selection and stratification criteria for patients.

Adnectin-Based Design of Chimeric Antigen Receptor for T Cell Engineering

Although chimeric antigen receptor (CAR)-engineered Tcell therapy has achieved encouraging clinical trial results for treating hematological cancers, further optimization can likely expand this therapeutic success to more patients and other cancer types. Most CAR constructs used in clinical trials incorporate single chain variable fragment (scFv) as the extracellular antigen recognition domain. The immunogenicity ofnonhuman scFv could cause host rejection against CAR Tcells and compromise their persistence and efficacy. The limited availability of scFvs and slow discovery of new monoclonal antibodies also limit the development of novel CAR constructs. Adnectin, a class of affinity molecules derived from the tenth type III domain of human fibronectin, can be an alternative to scFv as an antigen-binding moiety in the design of CAR molecules. We constructed adnectin-based CARs targeting epithelial growth factor receptor (EGFR) and found that compared to scFv-based CAR, Tcells engineered with adnectin-based CARs exhibited equivalent cell-killing activity against target H292 lung cancer cells invitro and had comparable antitumor efficacy in xenograft tumor-bearing mice invivo. In addition, with optimal affinity tuning, adnectin-based CAR showed higher selectivity on target cells with high EGFR expression than on those with low expression. This new design of adnectin CARs can potentially facilitate the development of Tcell immunotherapy for cancer and other diseases.

Exploration of Dynamic Elastic Modulus Changes on Glioblastoma Cell Populations with Aberrant EGFR Expression as a Potential Therapeutic Intervention Using a Tunable Hyaluronic Acid Hydrogel Platform.

Glioblastoma (GBM) is one of most aggressive forms of brain cancer, with a median survival time of 14.6 months following diagnosis. This low survival rate could in part be attributed to the lack of model systems of this type of cancer that faithfully recapitulate the tumor architecture and microenvironment seen in vivo in humans. Therapeutic studies would provide results that could be translated to the clinic efficiently. Here, we assess the role of the tumor microenvironment physical parameters on the tumor, and its potential use as a biomarker using a hyaluronic acid hydrogel system capable of elastic modulus tuning and dynamic elastic moduli changes. Experiments were conducted to assess the sensitivity of glioblastoma cell populations with different mutations to varying elastic moduli. Cells with aberrant epithelial growth factor receptor (EGFR) expression have a predilection for a stiffer environment, sensing these parameters through focal adhesion kinase (FAK). Importantly, the inhibition of FAK or EGFR generally resulted in reversed elastic modulus preference. Lastly, we explore the concept of therapeutically targeting the elastic modulus and dynamically reducing it via chemical or enzymatic degradation, both showing the capability to reduce or stunt proliferation rates of these GBM populations.