Introduction to the CEA Family: Structure, Function and Secretion

1992 ◽  
Vol 7 (3) ◽  
pp. 132-136 ◽  
Author(s):  
S. Von Kleist
Keyword(s):  
Tumor Immunology ◽  
Great Promise ◽  
Target Antigen ◽  
Large Gene Family ◽  
Large Gene ◽  
Human Carcinomas ◽  
Radio Isotopes ◽  
Immunoglobulin Supergene Family ◽  
Supergene Family

Due to the phenomenal progress in the field of tumor immunology that took place during the last twenty years, we dispose today of highly specific and sensitive techniques and reagents like monoclonal antibodies (MAbs). In this context the discovery in human carcinomas of tumor-associated antigens, such as CEA, was of primary importance, especially since the latter was found to have clinical relevance as a tumor marker. Based on animal models, a new in vivo technology for the detection of tumors and metastases was developed in recent years, that uses anti-CEA MAbs, or fragments of them, coupled to radio-isotopes. This technique, called radioimmunodetection (RAID), also paved the way for immunotherapeutic procedures, where again CEA served as the target-antigen. This new technique holds great promise, provided the epitope-specificity of the MAbs is well-controlled: it has been shown that CEA belongs to a large gene-family of at least 22 members, which can be subdivided into two subgroups (i.e., the CEA- and the PSG-subgroup) and which in turn belongs to the immunoglobulin-supergene family. Great structural similarities render the distinction of the various cross-reactive molecules by immunological means rather difficult.

Iodine-Induced Expression of Immunoglobulin Supergene Family in Normal Human Thyroid Tissue in vivo

1996 ◽  
pp. 32-35
Author(s):  
Petra-Maria Schumm-Draeger ◽  
Hans-Peter Fortmeyer ◽  
Hubertus Johannes Christoph Wenisch ◽  
Claudia Müller ◽  
Klaus Henning Usadel
Keyword(s):  
Thyroid Tissue ◽  
Human Thyroid ◽  
Induced Expression ◽  
Human Thyroid Tissue ◽  
Normal Human ◽  
Immunoglobulin Supergene Family ◽  
Supergene Family

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

scholarly journals High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhou Fang ◽  
Junjian Chen ◽  
Ye Zhu ◽  
Guansong Hu ◽  
Haoqian Xin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Rational Design ◽  
Click Reaction ◽  
Reaction Times ◽  
Great Promise ◽  
Biomaterial Surfaces

AbstractPeptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.

scholarly journals Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds

1993 ◽  
Vol 122 (4) ◽  
pp. 951-960 ◽  
Author(s):  
H Zhou ◽  
A Fuks ◽  
G Alcaraz ◽  
TJ Bolling ◽  
CP Stanners
Keyword(s):  
Carcinoembryonic Antigen ◽  
Cell Aggregation ◽  
Intercellular Adhesion ◽  
Cell Surface Expression ◽  
Adhesive Properties ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Internal Repeat ◽  
Immunoglobulin Supergene Family ◽  
Supergene Family

Both carcinoembryonic antigen (CEA) and neural cell adhesion molecule (NCAM) belong to the immunoglobulin supergene family and have been demonstrated to function as homotypic Ca(++)-independent intercellular adhesion molecules. CEA and NCAM cannot associate heterotypically indicating that they have different binding specificities. To define the domains of CEA involved in homotypic interaction, hybrid cDNAs consisting of various domains from CEA and NCAM were constructed and were transfected into a CHO-derived cell line; stable transfectant clones showing cell surface expression of CEA/NCAM chimeric-proteins were assessed for their adhesive properties by homotypic and heterotypic aggregation assays. The results indicate that all five of the Ig(C)-like domains of NCAM are required for intercellular adhesion while the COOH-terminal domain containing the fibronectin-like repeats is dispensable. The results also show that adhesion mediated by CEA involves binding between the Ig(V)-like amino-terminal domain and one of the Ig(C)-like internal repeat domains: thus while transfectants expressing constructs containing either the N domain or the internal domains alone were incapable of homotypic adhesion, they formed heterotypic aggregates when mixed. Furthermore, peptides consisting of both the N domain and the third internal repeat domain of CEA blocked CEA-mediated cell aggregation, thus providing direct evidence for the involvement of the two domains in adhesion. We therefore propose a novel model for interactions between immunoglobulin supergene family members in which especially strong binding is effected by double reciprocal interactions between the V-like domains and C-like domains of antiparallel CEA molecules on apposing cell surfaces.

Abstract 129: Embryonic Stem Cell Derived Exosomes Revive Endogenous Repair Mechanisms In Failing Heart

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mohsin Khan ◽  
Suresh K Verma ◽  
Alexander R Mackie ◽  
Erin Vaughan ◽  
Srikanth Garikipati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Great Promise ◽  
Target Cells ◽  
Free System ◽  
Teratoma Formation

Rationale: Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to ethical concerns, lack of autologous donors and teratoma formation. Recently, it has been observed that beneficial effects of stem cells are mediated by exosomes secreted out under various physiological conditions. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective: Determine the effect of ESC derived exosomes for cardiac repair and modulation of CPCs functions in the heart following myocardial infarction. Methods and Results: Exosomes were isolated from murine ESCs (mES Ex) or embryonic fibroblasts (MEFs) by ultracentrifugation and verified by Flotillin-1 immunoblot analysis. Induction of pluripotent markers, survival and in vitro tube formation was enhanced in target cells receiving ESC exosomes indicating therapeutic potential of mES Ex. mES Ex administration resulted in enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex mediated considerable enhancement of cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 4 weeks after mES Ex transfer. miRNA Array analysis of ESC and MEF exosomes revealed significantly high expression of miR290-295 cluster in the ESC exosomes compared to MEF exosomes. The underlying beneficial effect of mES Ex was tied to delivery of ESC miR-294 to the heart and in particular CPCs thereby promoting CPC survival and proliferation as analyzed by FACS based cell death analysis and CyQuant assay respectively. Interestingly, enhanced G1/S transition was observed in CPCs treated with miR-294 in conjunction with significant reduction of G1 phase. Conclusion: In conclusion, mES Ex provide a novel cell free system for cardiac regeneration with the ability to modulate both cardiomyocyte and CPC based repair programs in the heart thereby avoiding the risk of teratoma formation associated with ESCs.

scholarly journals Implementation of a dynamic intestinal gut-on-a-chip barrier model for transport studies of lipophilic dioxin congeners

RSC Advances ◽  
2018 ◽  
Vol 8 (57) ◽  
pp. 32440-32453 ◽  
Author(s):  
Kornphimol Kulthong ◽  
Loes Duivenvoorde ◽  
Barbara Z. Mizera ◽  
Deborah Rijkers ◽  
Guillaume ten Dam ◽  
...  
Keyword(s):  
Great Promise ◽  
Transport Studies ◽  
Functional Complexity ◽  
Organ On A Chip ◽  
Barrier Model

Novel microfluidic technologies allow the manufacture ofin vitroorgan-on-a-chip systems that hold great promise to adequately recapitulate the biophysical and functional complexity of organs foundin vivo.

Identification of critical antigen-specific mechanisms in the development of immune thrombocytopenic purpura in mice

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2520-2527 ◽  
Author(s):  
Bernhard Nieswandt ◽  
Wolfgang Bergmeier ◽  
Kirsten Rackebrandt ◽  
J. Engelbert Gessner ◽  
Hubert Zirngibl
Keyword(s):  
Platelet Activating Factor ◽  
Target Antigen ◽  
Transient Effects ◽  
Platelet Destruction ◽  
Spontaneous Bleeding ◽  
Antiplatelet Antibodies ◽  
Systemic Reactions ◽  
Linear Epitopes ◽  
Immunoglobulin G Subclass

Abstract The pathogenic effects of antiplatelet antibodies were investigated in mice. Monoclonal antibodies (mAbs) of different immunoglobulin G subclass directed against mouse GPIIbIIIa, GPIIIa, GPIbα, GPIb-IX, GPV, and CD31 were generated and characterized biochemically. MAbs against GPIb-IX, GPV, CD31, and linear epitopes on GPIIIa had mild and transient effects on platelet counts and induced no spontaneous bleeding. Anti-GPIbα mAbs induced profound irreversible thrombocytopenia (< 3% of normal) by Fc-independent mechanisms but only had minor effects on hematocrits. In contrast, injection of intact mAbs, but not F(ab)2 fragments, against conformational epitopes on GPIIbIIIa, induced irreversible thrombocytopenia, acute systemic reactions, hypothermia, decreased hematocrits, and a paradoxical loss of surface GPIIbIIIa on platelets in vivo, the latter suggesting the formation of platelet-derived microparticles. Blockage of platelet-activating factor receptors inhibited the acute reactions, but not thrombocytopenia, loss of GPIIbIIIa, and decreases in hematocrits. Repeated injections of low doses of anti-GPIIbIIIa antibodies resulted in profound thrombocytopenia and bleeding, whereas no acute systemic reactions were observed. These data strongly suggest that the identity of the target antigen recognized by antiplatelet antibodies determines the mechanisms of platelet destruction and the severity of bleeding in mice, the latter depending on previously unrecognized anti-GPIIbIIIa-specific inflammatory mechanisms.

scholarly journals Overview of DNA Self-Assembling: Progresses in Biomedical Applications

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 268 ◽  
Author(s):  
Andreia Jorge ◽  
Ramon Eritja
Keyword(s):  
Programming Languages ◽  
Biomedical Applications ◽  
Great Promise ◽  
Dna Nanostructures ◽  
Modular Assembly ◽  
Molecular Programming ◽  
Self Assembling ◽  
Theranostic Agents ◽  
Assembly Principles

Molecular self-assembling is ubiquitous in nature providing structural and functional machinery for the cells. In recent decades, material science has been inspired by the nature’s assembly principles to create artificially higher-order structures customized with therapeutic and targeting molecules, organic and inorganic fluorescent probes that have opened new perspectives for biomedical applications. Among these novel man-made materials, DNA nanostructures hold great promise for the modular assembly of biocompatible molecules at the nanoscale of multiple shapes and sizes, designed via molecular programming languages. Herein, we summarize the recent advances made in the designing of DNA nanostructures with special emphasis on their application in biomedical research as imaging and diagnostic platforms, drug, gene, and protein vehicles, as well as theranostic agents that are meant to operate in-cell and in-vivo.

scholarly journals Ultrasound-Mediated Local Drug and Gene Delivery Using Nanocarriers

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Qiu-Lan Zhou ◽  
Zhi-Yi Chen ◽  
Yi-Xiang Wang ◽  
Feng Yang ◽  
Yan Lin ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Research Progress ◽  
Great Promise ◽  
Blood Capillary ◽  
Tumor Tissues ◽  
Ultrasound Molecular Imaging ◽  
Pass Through ◽  
Capillary Walls

With the development of nanotechnology, nanocarriers have been increasingly used for curative drug/gene delivery. Various nanocarriers are being introduced and assessed, such as polymer nanoparticles, liposomes, and micelles. As a novel theranostic system, nanocarriers hold great promise for ultrasound molecular imaging, targeted drug/gene delivery, and therapy. Nanocarriers, with the properties of smaller particle size, and long circulation time, would be advantageous in diagnostic and therapeutic applications. Nanocarriers can pass through blood capillary walls and cell membrane walls to deliver drugs. The mechanisms of interaction between ultrasound and nanocarriers are not clearly understood, which may be related to cavitation, mechanical effects, thermal effects, and so forth. These effects may induce transient membrane permeabilization (sonoporation) on a single cell level, cell death, and disruption of tissue structure, ensuring noninvasive, targeted, and efficient drug/gene delivery and therapy. The system has been used in various tissues and organs (in vitro or in vivo), including tumor tissues, kidney, cardiac, skeletal muscle, and vascular smooth muscle. In this review, we explore the research progress and application of ultrasound-mediated local drug/gene delivery with nanocarriers.

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