Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

[The involvement of galectin-1 in implantation and pregnancy maintenance at the maternal-fetal interface].

Abstract: As a member of galectins family, galectin-1(Gal-1)is widely expressed in tissues and cells, and participates in a variety of physiological and pathological processes, such as cell adhesion, proliferation, apoptosis and inflammatory reaction. Recently, it has been found that Gal-1 is highly expressed at the maternal-fetal interface and plays important roles in trophoblast cell proliferation, differentiation and invasion, endometrial receptivity, placental angiogenesis and maternal-fetal immune tolerance. In this review, we outline the expression of Gal-1 at the maternal-fetal interface and the involvement of Gal-1 in embryo implantation and pregnancy maintenance, to provide novel insights for the early diagnosis, prognostic assessment and treatment of early pregnancy loss and pregnancy-related diseases.

Immune Reactions: Headlines, Overviews, Tables and Graphics

Abstract: 1 Cytokines, Growth Factors, Chemokines and their receptors.- 1.1 Overview.- 1.1.1 Cytokines in Hematopoiesis.- 1.1.2 Classification of Growth Factors.- 1.1.3 Receptors for Cytokines.- 1.1.4 Receptors for Growth Factors.- 1.1.5 Characteristics of Chemokines.- 1.1.6 Neutrophil-Activating Peptides.- 1.2 Characteristics of Mediators, Receptors.- 1.2.1 SCF, IL-1, IL-1 RA.- 1.2.2. IL-2.- 1.2.3 IL-3, IL-4, IL-5, IL-6.- 1.2.4 LIF, IL-7, IL-8.- 1.2.5 IL-10, IL-11, IL-12, IL-13.- 1.2.6 GM-CSF, G-CSF, M-CSF, Erythropoietin, Thrombopoietin, IFN Gamma.- 1.2.7 IGF, TNF, TGF, PDGF, EGF, FGF.- 1.2.8 Oncostatin, CNTF.- 1.2.9 Approaches to Inhibit the Biological Effect of Growth Factors.- 2 Cell-Adhesion Molecules.- 2.1 Overview.- 2.1.1 Classification.- 2.1.2 Function.- 2.2 Characteristics.- 2.2.1 Immunoglobulin Gene Superfamily Type.- 2.2.2 Integrin Type.- 2.2.3 Cell Distribution.- 2.2.4 Binding Partners.- 2.2.5 Modulation of Expression and Function.- 2.2.6 Structure and Function of CD44.- 2.2.7 Structure and Function of Cadherins.- 3 Antigen Presentation.- 3.1 Overview.- 3.2 Details.- 3.2.1 Dendritic Cells.- 3.2.2 Antigen-Binding Molecules.- 3.2.3 MHC Genes.- 3.2.4 Regulation of MHC Gene Expression.- 3.2.5 Loading of Antigen-Presenting Molecules.- 3.2.6 Antigen Presentation by B-Cells.- 3.2.7 Expression of MHC Molecules.- 3.2.8 Modulation of Expression of MHC Molecules.- 4 Differentiation of T-Cells.- 4.1 Overview.- 4.2 Details.- 4.2.1 T-Cell Development.- 4.2.2 The T-Cell Receptor.- 4.2.3 The CD4 Molecule.- 4.2.4 The CD8 Molecule.- 4.2.5 Activation of T-Cells by Antigen-Presenting Cells.- 4.2.6 Signal Transduction After Activation of the TCR Complex.- 4.2.7 Activation of T Cells.- 4.2.8 Activation of Memory T-Cells.- 4.2.9 Pharmacological Intervention of T-Cell Activation.- 5 Superantigens.- 5.1 Overview.- 5.1.1 Comparison Between Conventional Antigens and Superantigens.- 5.1.2 Function.- 5.2 Details.- 5.2.1 Foreign Superantigens.- 5.2.2 Self-Superantigens of Mouse Mammary Tumor Virus (MMTV).- 6 Differentiation of B-Cells.- 6.1 Overview.- 6.2 Details.- 6.2.1 B-Cell Development.- 6.2.2 The B-Cell Receptor.- 6.2.3 Transcriptional Control of Ig Heavy- and Ig Light-Chain Genes.- 7 Antibody Formation.- 7.1 Overview.- 7.2 Details.- 7.2.1 VDJ Recombination.- 7.2.2 Cooperation of B-Cells with T Cells.- 7.2.3 B-Cell Differentiation in Lymph Nodes.- 7.2.4 Main Cytokines Involved in Differentiation to Plasma Cells.- 8 Fc Receptors and Antibody Interaction.- 8.1 Overview.- 8.2 Details.- 8.2.1 Properties of Murine Fc Receptors.- 8.2.2 Human Fc Receptors.- 8.2.3. Modulation by Cytokines.- 8.2.4 Release of Immunoglobulin Binding Proteins (IBFs) and Its Modulation.- 8.2.5 Blockage of Antibody Production.- 9 Generation of the IgA Response.- 9.1 Overview.- 9.2 Details.- 9.2.1 Properties of Secretory and Serum IgA.- 9.2.2 Circulation and Metabolization of IgA.- 9.2.3 Enteral IgA Response.- 9.2.4 Secretory Immunoglobulin A (sIgA) in Tears.- 10 Complement Activation and Inhibition.- 10.1 Overview.- 10.1.1 Classification.- 10.1.2 Activation.- 10.1.3 Blockage of Comlement Mediated Lysis by Nucleated Cells.- 10.2 Details.- 10.2.1 Function of Complement Inhibitors.- 10.2.2 Activity of Complement Split Products on Cells.- 10.2.3 Complement Receptors.- 10.2.4 Interactions Between Complement Components and Platelets.- 10.2.5 Resistance of Nucleated Cells (NC) to Lysis by Membrane Attacking Complex (MAC) of Complement.- 10.2.6 Activation of Nucleated Cells by Membrane Attacking Complex.- 10.2.7 Diseases Associated with Inherited or Acquired Deficiency of Complement Components.- 10.2.8 Approaches for Immunotherapy with Regulators of Complement Activation.- 11 Cell-Mediated Cytotoxicity.- 11.1 Overview.- 11.2 Details.- 11.2.1 Cytotoxicity by T-Lymphocytes.- 11.2.2 Cellular Cytotoxicity via Mechanisms Not Involving Recognition of Antigens Presented by MHC-1.- 12 Immune-Mediated Inflammatory Reaction.- 12.1 Overview.- 12.1.1 Cascades of the Inflammatory Response.- 12.1.2 Central Role of the Hageman Factor.- 12.1.3 Complexity of Interactions (Cells, Cytokines, Mediators).- 12.2 Details.- 12.2.1 Activation and Action of Kinins.- 12.2.2 Biological Action of Mediators of the Arachidonic Acid Pathway.- 12.2.3 Diseases Associated with Prominent Neutrophil Infiltrates.- 12.2.4 Metabolic Changes Induced by Cytokines.- 12.2.5 Putative Mechanism of the Delayed-Type Hypersensitivity Reaction.- 12.2.6 Approaches for the Therapy of Inflammatory Reactions.- 13 Interactions with Endothelial Cells.- 13.1 Overview.- 13.1,1 Granulocytes and Endothelial Cells.- 13.1.2 Lymphocytes and Endothelial Cells.- 13.2 Details.- 13.2.1 Activation of Endothelial Cells.- 13.2.2 Endothelium-Derived Relaxing Factors (EDRF).- 13.2.3 Endothelium-Derived Contracting Factors (EDCF).- 13.2.4 Immunological Aspects of Artheriosclerosis.- 14 Involvement of the Clotting System and Platelets.- 14.1 Overview.- 14.2 Details.- 14.2.1 Inhibition of Coagulation in Normal Epithelium.- 14.2.2 Effect of Growth Factors and Cytokines on Plasminogen Activator Secretion.- 14.2.3 Activation and Aggregation of Platelets.- 14.2.4 Role of Transforming Growth Factor-?.- 14.2.5 Arachidonic Acid Metabolism in Platelets.- 14.2.6 Inhibitors of Platelet Aggregation.- 14.2.7 Modulation of Platelet Aggregation In Vivo.- 14.2.8 Cytokines that Stimulate Megakaryocytopoiesis.- 15 Enzymatic Degradation of Extracellular Matrix.- 15.1 Overview.- 15.1.1 Destruction of Extracellular Matrix.- 15.1.2 Interaction of Proteases.- 15.2 Details.- 15.2.1 Matrix Metalloproteinases (MMP).- 15.2.2 Cellular Proteases.- 15.2.3 Modulation of Secretion of Cellular Proteases.- 16 Angiogenesis.- 16.1 Overview.- 16.2 Details.- 16.2.1 Angiogenic or Mitogenic Peptides.- 16.2.2 Vascular Endothelial Growth Factor.- 16.2.3 Balance Between uPA/PAT 1 and FGF/TGF-?.- 16.2.4 Inhibitors of Angiogenesis.- 17 Systemic Inflammatory Reaction Syndrome.- 17.1 Overview.- 17.2 Details.- 17.2.1 Pathophysiological Pathways.- 17.2.2 Role of LBS Binding Protein.- 17.2.3 Role of Complement and Neutrophils.- 17.2.4 Approaches to Influencing SIRS.- 18 Immune Complex Mediated Diseases.- 18.1 Overview.- 18.2 Details.- 18.2.1 Conformational Change of Antibody.- 18.2.2 Effector Function of Immunoglobulins.- 18.2.3 Size of Immune Complexes.- 18.2.4 Inhibition/Solubilization of IC by Complement.- 18.2.5 Elimination of IC.- 18.2.6 IC Diseases Associated with Changes in the Expression of CR-1, CR-2, CR-3, C-IA (INH).- 18.2.7 Approaches for Therapy of IC Diseases.- 19 Allergic Diseases.- 19.1 Overview.- 19.2 Details.- 19.2.1 Modulation of IgE Secretion by Cytokines.- 19.2.2 Allergic Inflammation.- 19.2.3 Role of Langerhans Cells.- 19.2.4 Role of Fc? RII (CD23).- 19.2.5 Histamine-Releasing Factors (HRF).- 19.2.6 Treatment of Allergic Diseases.- 20 Autoimmune Diseases.- 20.1 Overview.- 20.1.1 Reasons for Autoimmune Reactions.- 20.1.2 Autoantibodies in Normal Persons.- 20.1.3 Role of B-Cells and T-Helper Cells in Autoimmune Diseases.- 20.2 Details.- 20.2.1 Specificity of Human Autoantibodies.- 20.2.2 Relationship to Exposure to Xenobiotics.- 20.2.3 Approaches to Treat Autoimmune Diseases.- 21 Immune Suppression.- 21.1 Overview.- 21.1.1 Therapeutic Activity and Toxicity of Immune Suppressives.- 21.1.2 Mode of Action of Immune Suppressive Drugs.- 21.2 Details.- 21.2.1 Mode of Action of Specific Agents.- 21.2.2 Monoclonal Antibodies.- 22 Immune Reaction in Neoplasia.- 22.1 Overview.- 22.2 Details.- 22.2.1 Human Tumor Antigens Detected by Immune Response.- 22.2.2 Viruses Associated with Cancer.- 22.2.3 Vaccines for Prophylaxis of Virus-Induced Tumors.- 22.2.4 Tumors and Infiltrating Macrophages.- 22.2.5 Tumors and Infiltrating Lymphocytes.- 22.2.6 Tumor Therapy with Cytokines.- 22.2.7 Active Specific Therapy with "Tumor Vaccines".- 22.2.8 Mechanisms by Which Tumor Cells Become "Immune Resistant".- 22.2.9 Tumor Therapy with Antibody Preparations.- 22.2.10 Targeting of Drugs with Monoclonal Antibodies to Malignant Cells.- 22.2.11 Reasons for the Limited Success of Antibodies.- 22.2.12 Pharmacokinetic Parameters for Antibodies.- 22.2.13 Antibody-Dependent Enzyme-Mediated Prodrug Therapy.- 22.2.14 Antibody Engineering.- 23 CNS and Immune Reactions.- 23.1 Overview.- 23.2 Details.- 23.2.1 Modulation of the Immune System by Neuropeptides.- 23.2.2 IL-1 as a "Neuropeptide".- 23.2.3 Cytokines and Cytokine Receptors expressed by Cells of the CNS and Endocrine Organs.- 23.2.4 Communication of the CNS with the Immune System.- 23.2.5 Modulation of the Endocrine System by Immune Mediators.- 23.2.6 Hormonal Influence on Antibodies in Mucosal tissues.- 23.2.7 Immune Response and Epilepsy.- 24 Genetic Background of Apoptosis and Malignant Lymphocyte Growth.- 24.1 Apoptosis and Malignant Lymphocyte Growth.- 24.2 Mechanisms of Tumorigenesis.- 25 Somatic Gene Therapy.- 25.1 Overview.- 25.1.1 Opportunities and Risks.- 25.1.2 Preconditions.- 25.1.3 Methods.- 25.2 Details.- 25.2.1 Viral Transfer of Genes.- 25.2.2 Liposomal Transfer of Genes.- 25.2.3 Receptor Mediated Transfer of Genes.- 25.2.4 Experimental Therapeutic Approaches.- 25.2.5 Immunization with Polynucleotides.- 26 CD Terminology.- References.

A New Approach to Inhibit Prototypic Galectins

Abstract: Given the critical role of galectins in cancer and other diseases, considerable efforts have been deployed towards the development of carbohydrate-based inhibitors that limit the binding of galectins to glycosylated residues on cell surface receptors. However, despite decades of research, progress in this field has not met expectations. In this article, we discuss the rationale justifying the development of a new class of galectin-specific peptide inhibitors that disrupt the formation of a prototypic galectin and its protumorigenic functions. These dimer interfering peptides (DIPs) represent an interesting alternative—and possibly a complementary avenue—to neutralize galectin-mediated protumoral functions. If validated, the approach could broaden the classes of galectin inhibitors that can be readily generated against other prototypic galectins, and possibly all other galectin subtypes. A. The Need for New Galectin Inhibitors Members of the galectin family exert essential functions by interacting with a large diversity of binding partners, both outside and inside cells. Following their release outside cells, either passively from dead cells or actively via non-classical secretion pathways, extracellular galectins bind glycosylated growth receptors on the surface of normal and cancer cells to control their signaling threshold. These interactions are primarily mediated by a highlyconserved glycan binding site (GBS) located on the surface of each carbohydrate recognition domain (CRD) that form galectin dimers or oligomers (Fig. 1A–B). However, under stress or pathological conditions, the expression level of galectins is often significantly increased and leads to misregulated functions. For example, increased expression of intracellular galectins in cancer cells may lead to altered cell growth, sensitivity to chemotherapeutic agents, and/or increased invasive behavior (1). Outside the cell, galectins bind to glycosylated receptors on the surface of immune cells to control the fate of effector and regulatory lymphoid and myeloid cell populations (2). Such properties enable galectins to induce apoptosis of cancer-killing T cells or to induce a tolerogenic state in tumor-associated macrophages (3). Thus, galectins represent a significant obstacle to successful cancer immunotherapy. Considerable efforts are therefore being deployed to modulate their activities. Until now, most efforts have focused on carbohydrate-based inhibitors aimed at disrupting GBS-dependent intracellular signals triggered upon binding of galectins to cell surface glycoreceptors. Often, these inhibitors are high molecular weight, naturally occurring or chemically-modified plant polysaccharides with significant structural complexity, or small mono/disaccharides that block binding of extracellular galectins to cell surface glycoreceptors (4, 5). These include modified citrus pectin (MCP) or GCS-100. In some cases, the effectiveness of this approach in neutralizing the galectin-mediated immune suppression has been demonstrated using in vivo preclinical studies. For example, intratumoral injection of thiodigalactoside (TDG) increases the infiltration of cancer-killing immune cells (6, 7). However, the effectiveness of plant oligosaccharides and other galectin carbohydrate-based inhibitors in restoring cancer-killing activity of immune cells, such as the synthetic glycoamine analog lactulosyl-L-Leu, remains to be established. Until now, studies on the anti-tumoral efficacy of these compounds have mostly focused on their ability to inhibit the survival of human cancer cells or their resistance to drug-induced apoptosis (8–10). Moreover, these carbohydrate-based inhibitors often have a relatively low binding affinity for galectins and the assumption that many of these drugs are true selective CRD inhibitors has recently been challenged (11). Based on the hypothesis that galectin ligand binding avidity is increased during clustering of glycoreceptors, several investigators have thus developed synthetic glycopolymers/glycodendrimers that target the GBS of galectins (12–15). Yet, the greatest challenge using GBS inhibitors (GBSIs) is to achieve high selectivity to minimize off-target effects, especially considering the striking structural and GBS similarity between all human galectin CRDs (Fig. 1C). The use of (glyco) peptides identified following screening of libraries is an interesting avenue that is being explored to identify GBSIs with better selectivity for galectin-1 and -3 (16). High selectivity is a critical issue because carbohydrate-based inhibitors with limited selectivity may also have limited efficacy given the proand anti-tumoral functions of galectins and the relatively wide repertoire of galectins expressed in tumor tissues. We and others MINIREVIEW doi: 10.4052/tigg.1730.1SE (Article for special issue on Galectins)

Galectins and galectin-mediated autophagy regulation: new insights into targeted cancer therapy

Abstract: Galectins are animal lectins with specific affinity for galactosides via the conserved carbohydrate recognition domains. Increasing studies recently have identified critical roles of galectin family members in tumor progression. Abnormal expression of galectins contributes to the proliferation, metastasis, epithelial-mesenchymal transformation (EMT), immunosuppression, radio-resistance and chemoresistance in various cancers, which has attracted cumulative clinical interest in galectin-based cancer treatment. Galectin family members have been reported to participate in autophagy regulation under physiological conditions and in non-tumoral diseases, and implication of galectins in multiple processes of carcinogenesis also involves regulation of autophagy, however, the relationship between galectins, autophagy and cancer remains largely unclear. In this review, we introduce the structure and function of galectins at the molecular level, summarize their engagements in autophagy and cancer progression, and also highlight the regulation of autophagy by galectins in cancer as well as the therapeutic potentials of galectin and autophagy-based strategies. Elaborating on the mechanism of galectin-regulated autophagy in cancers will accelerate the exploitation of galectins-autophagy targeted therapies in treatment for cancer.

The role of galectins-1, 3, 7, 8 and 9 as potential diagnostic and therapeutic markers in ovarian cancer

Abstract: The incidence of ovarian cancer is increasing, particularly throughout the highly developed countries, while this cancer type remains a major diagnostic and therapeutic challenge. The currently poorly recognized lectins called galectins have various roles in interactions occurring in the tumor microenvironment. Galectins are involved in tumor-associated processes, including the promotion of growth, adhesion, angiogenesis and survival of tumor cells. Results of research studies performed so far point to a complex role of galectins-1, 3, −7, −8 and −9 in carcinogenesis of ovarian cancer and elucidation of the mechanisms may contribute to novel forms of therapies targeting the proteins. In particular, it appears important to recognize the reasons for changes in expression of galectins. Galectins also appear to be a useful diagnostic and prognostic tool to evaluate tumor progression or the efficacy of therapies in patients with ovarian cancer, which requires further study.