Identification and characterization of Nanobodies targeting the EphA4 receptor Neurobiology

The ephrin receptor A4 (EphA4) is one of the receptors in the ephrin system that plays a pivotal role in a variety of cell-cell interactions, mostly studied during development. In addition, EphA4 has been found to play a role in cancer biology as well as in the pathogenesis of several neurological disorders such as stroke, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease. Pharmacological blocking of EphA4 has been suggested to be a therapeutic strategy for these disorders. Therefore, the aim of our study was to generate potent and selective Nanobodies against the ligand-binding domain of the human EphA4 receptor. We identified two Nanobodies, Nb 39 and Nb 53, that bind EphA4 with affinities in the nanomolar range. These Nanobodies were most selective for EphA4, with residual binding to EphA7 only. Using Alphascreen technology, we found that both Nanobodies displaced all known EphA4-binding ephrins from the receptor. Furthermore, Nb 39 and Nb 53 inhibited ephrin-induced phosphorylation of the EphA4 protein in a cell-based assay. Finally, in a cortical neuron primary culture, both Nanobodies were able to inhibit endogenous EphA4-mediated growth-cone collapse induced by ephrin-B3. Our results demonstrate the potential of Nanobodies to target the ligand-binding domain of EphA4. These Nanobodies may deserve further evaluation as potential therapeutics in disorders in which EphA4-mediated signaling plays a role.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Methods and Resources Source Type: research

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Conclusions: We conclude that the downregulation of OCSC markers may signal a reduction in OCSC population following MMP20/DSPP silencing in OSCC cells, while also increasing their sensitivity to cisplatin. Thus, our findings suggest a potential role for DSPP and MMP20 in sustaining OCSC population in OSCCs, possibly, through mechanism(s) that alter OCSC sensitivity to treatment with chemotherapeutic agents such as cisplatin. PMID: 30002682 [PubMed - in process]
Source: Cellular and Molecular Biology Letters - Category: Biochemistry Authors: Tags: Cell Mol Biol Lett Source Type: research
Authors: Jacob JE, Cherian A, Gopakumar K, Iype T, Yohannan DG, Divya KP Abstract Chaotic analysis is a relatively novel area in the study of physiological signals. Chaotic features of electroencephalogram have been analyzed in various disease states like epilepsy, Alzheimer's disease, sleep disorders, and depression. All these diseases have primary involvement of the brain. Our study examines the chaotic parameters in metabolic encephalopathy, where the brain functions are involved secondary to a metabolic disturbance. Our analysis clearly showed significant lower values for chaotic parameters, correlation dimensi...
Source: Neurology Research International - Category: Neurology Tags: Neurol Res Int Source Type: research
Authors: Liu F, Li C, Zhu J, Ren L, Qi X Abstract BACKGROUND AND AIM: ABO blood type is an invariant factor. There is a link between ABO blood type and some malignancies, such as gastric, pancreatic, and skin cancer. The role of ABO blood type in the pathogenesis of hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to explore the relationship between ABO blood type and risk of HCC. METHODS: Literature search was conducted among the PubMed, EMBASE, and Cochrane Library databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Seven papers were ...
Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
Publication date: September 2018Source: Clinica Chimica Acta, Volume 484Author(s): Yuejin Li, Weiwei Wang, Zheliang Liu, Yuan Jiang, Jinping Lu, Haitao Xie, Faqing TangAbstractBackgroundAnterior Gradient (AGR) 2 concentration increases in the serum of tumor patients, and their diagnostic and prognostic significances were evaluated in some tumors. The previous works showed that AGR2 high express in nasopharyngeal carcinoma (NPC) biopsy tissues. However, whether AGR2 serves as a diagnostic and prognostic marker for NPC remains unclear.Methods42 healthy volunteers, 34 breast cancer patients and 124 NPC patients were enrolled ...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
Authors: Kapałczyńska M, Kolenda T, Przybyła W, Zajączkowska M, Teresiak A, Filas V, Ibbs M, Bliźniak R, Łuczewski Ł, Lamperska K Abstract Cell culture is a widely used in vitro tool for improving our understanding of cell biology, tissue morphology, and mechanisms of diseases, drug action, protein production and the development of tissue engineering. Most research regarding cancer biology is based on experiments using two-dimensional (2D) cell cultures in vitro. However, 2D cultures have many limitations, such as the disturbance of interactions between the cellular and extracellular environments, changes in...
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Conclusions: Our data indicated that colorectal cancer patients undergoing emergency surgery showed an advanced stage. The emergency patients had a higher rate of mortality than elective cases. PMID: 30002700 [PubMed]
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Conclusions: These results imply that the up-regulation of UCA1 and MALAT1 lncRNAs in ESCC tissues can impact the degree of tumor progression and is predictive of postoperative survival. Therefore, the expression levels of these lncRNAs can be used as measurement indexes to determine the prognosis of ESCC patients. PMID: 30002691 [PubMed]
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Conclusions: Taken together, this work demonstrated that miR-181b might have the ability to overcome chemo resistance of small cell lung cancer cells, and restoration of this miRNA may represent a potential therapeutic strategy for improving chemo sensitivity in small cell lung cancer. PMID: 30002690 [PubMed]
Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
Publication date: Available online 14 July 2018Source: Artificial Intelligence in MedicineAuthor(s): Aaron N. Richter, Taghi M. KhoshgoftaarAbstractAdvancements are constantly being made in oncology, improving prevention and treatment of cancers. To help reduce the impact and deadliness of cancers, they must be detected early. Additionally, there is a risk of cancers recurring after potentially curative treatments are performed. Predictive models can be built using historical patient data to model the characteristics of patients that developed cancer or relapsed. These models can then be deployed into clinical settings to ...
Source: Artificial Intelligence in Medicine - Category: Bioinformatics Source Type: research
ConclusionsBy highlighting the conserved structural and functional domains of LDH from two entirely different species, this study has graded potential inhibitory molecules on the basis of their binding affinities so that they can be applied for in vivo anticancer studies.
Source: Electronic Journal of Biotechnology - Category: Biotechnology Source Type: research
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