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Dendritic Cells for Active Anti-cancer Immunotherapy: Targeting Activation Pathways Through Genetic Modification.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tumour immunotherapy has become a treatment modality for cancer, harnessing the immune system to recognize and eradicate tumour cells specifically. It is based on the expression of tumour associated antigens (TAA) by the tumour cells and aims at the induction of TAA-specific effector T cell responses, whilst overruling various mechanisms that can hamper the anti-tumour immune response, e.g. regulatory T cells (Treg). (Re-) activation of effector T cells requires the completion of a carefully orchestrated series of specific steps. Particularly important is the provision of TAA presentation and strong stimulatory signals...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - October 29, 2009 Category: Endocrinology Authors: Breckpot K, Escors D Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Future Developments in Osteoporosis Therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Anti-resorptives that prevent osteoclasts from resorbing bone are the mainstay of treatment for osteoporosis, while parathyroid hormone is the only agent available that stimulates osteoblasts to form bone. Advances in knowledge about metabolic pathways in bone cell biology have identified specific points of intervention whereby formation and function of osteoclasts and osteoblasts can be inhibited or stimulated. The next generation of therapies for osteoporosis may include molecules that antagonize integrin or inhibit Src tyrosine kinase, vacuolar H+-ATPase, chloride channel or cathepsin K, thus preventing osteoclasts ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - October 29, 2009 Category: Endocrinology Authors: Ng KW Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Interleukin-24: A Molecule with Potential Anti-Cancer Activity and a Cytokine in Search of a Function.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The gene encoding Melanoma-differentiation antigen-7 (MDA-7) was discovered more than 10 years ago. Its potential anti-cancer activity was surmised because its expression is inversely correlated with the cell proliferation status. Indeed adenoviral delivery of this gene proved to be efficient in killing several cancer cell lines and great strides have been made concerning its molecular ways of action. Later it was shown that mda7 encoded a secreted cytokine which belongs to the IL-10, class-II family of cytokines. We recently found that this molecule exerted apoptotic activity on stimulating but not on resting lymphocy...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 17, 2009 Category: Endocrinology Authors: Dalloul A, Sainz-Perez A Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Differential Conservation of Nucleotides and Conservation/Mutation Correlations Between Nucleotides, with Special Reference to CXC 1 and 4 and FP Receptors Involved in Immune Regulation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We examined six groups of coding mRNA sequences: chemokine CXC 1 and 4 and formyl peptide receptors; a group comprising different receptors of the rhodopsin-like superfamily, together with some viral sequences which share significant homologies with these receptors; a group of viral sequences with homologies with the rhodopsin-like receptors; a group of solute carriers. In all the experimental groups the second nucleotide of the triplet was the most conserved and a significant positive correlation existed between conservation/mutation indexes of the two first nucleotides. Similar conservation/mutation patterns could be of ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Panaro MA, Lisi S, Acquafredda A, Cianciulli A, Mitolo CI, Saccia M, Mitolo V Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Human Exposure to Endocrine Disruptors and Breast Milk.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Endocrine system is one of the most sensitive communication networks of the human body which influences all aspects of human health and well-being, including reproductive potential, cognitive functions, thyroid and metabolism, digestion and hormonal balance. In recent years basic laboratory research has been focused on the potential relationship between environmental contaminants and cellular endocrine function. Environmental contaminants are ubiquitous in the environment, alter endocrine physiology and produce endocrine disruption without acting as classic toxicants. These endocrine disruptors (EDCs) are lipophilic an...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Stefanidou M, Maravelias C, Spiliopoulou C Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

TNF alpha Inhibition as Treatment Modality for Certain Rheumatologic and Gastrointestinal Diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
With the development of biologicals that specifically target tumor necrosis factor (TNF)alpha, our therapeutic approach to inflammatory diseases has dramatically changed. There are currently three anti-TNFalpha drugs available: etanercept, infliximab, and adalimumab. Etanercept is a recombinant fusion protein that can be used alone or in combination with other medications for conditions such as rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, psoriasis, and ankylosing spondylitis. Infliximab, a chimeric humanized monoclonal antibody and adalimumab, a fully human monoclonal antibody are approved...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Wiedmann MW, Mössner J, Baerwald C, Pierer M Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Role of Iodine, Selenium and Other Micronutrients in Thyroid Function and Disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. Nowadays about 800 million people are affected by iodine deficiency disorders that include goiter, hypothyroidism, mental retardation, and a wide spectrum of other growth and developmental abnormalities. Iodine supplementation, under form of iodized salt and iodized vegetable oil, produced dramatic improvements in many areas, even though iodine deficiency is still a pro...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Triggiani V, Tafaro E, Giagulli VA, Sabbà C, Resta F, Licchelli B, Guastamacchia E Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Immunomodulatory and Anti-Inflammatory Activities of Statins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The statins are a group of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase that are used extensively in medical practice because of their ability to reduce cardiovascular mortality and stroke. Although this protective activity was initially ascribed to the inhibition of cholesterol biosynthesis in the liver, clinical trials and basic research studies indicate that, beyond their cholesterol-lowering activity, statins might affect the function of different cell types in extrahepatic tissues. Here we will review the different mechanisms by which the statins exert their immunomodulatory and anti-inflammatory ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Mira E, Mañes S Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Genetic Alterations in Differentiated Thyroid Cancers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article provides a detailed review of the altered cell proliferation pathway activations found in thyroid carcinogenesis. The molecular targets that may be disrupted by therapeutic agents during the abnormal proliferation are also summarized. PMID: 19594419 [PubMed - as supplied by publisher] (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Salehian B, Liu Z Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Factors Modulating Fibrates Response: Therapeutic Implications and Alternative Strategies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews the mechanism of action and the functional roles of fibrates, emphasizing the factors modulating their capacity to activate PPARalpha and affecting their effectiveness. These factors may possibly explain the findings obtained in animal studies and clinical trials with fibrates which showed either untoward effects and/or inefficient hypolipidemic action of PPARalpha activation. We also discuss briefly the natural and synthetic agonists of PPARalphawhich are currently being developed and supposedly display greater effectiveness and fewer adverse effects than fibrates. PMID: 19594420 [PubMed - as supp...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Panadero MI, González MC, Herrera E, Bocos C Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Synergistic Activation of Leukocytes by Bacterial Chemoattractants: Potential Drug Targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Accumulating evidence demonstrates that bacterial chemoattractants not only attract leukocytes (chemotaxis) but also contribute directly to inflammation by activation of leukocytes to produce a variety of pro-inflammatory cytokines. Recent studies have shown that mixtures of the bacterial chemoattractant fMLP (N-formyl-Met-Leu-Phe) and other bacterial products/components such as LPS (lipopolysaccharide) behave synergistically in activating leukocytes. These results suggest that inflammatory responses are induced by multiple inducers that operate synergistically through multiple signaling pathways. This synergy is likel...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Chen LY, Pan ZK Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

A Current Update on the Use of Alpha Lipoic Acid in the Management of Type 2 Diabetes Mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type 2 Diabetes Mellitus (T2DM) which is characterised by insulin resistance, is closely linked to the triad of glucolipotoxicity, inflammation and oxidative stress. Increased adiposity, leading to increased free fatty acids (FFAs), contributes to insulin resistance by disrupting the signal transduction pathway of insulin mediated glucose disposal, and causes impaired insulin secretion. Hyperglycaemia and dyslipidaemia driven oxidative stress resulting from enhanced free-radical formation and/or defects in antioxidant defence is implicated in the pathogenesis of diabetic neuropathy (DN). This and other inflammatory pat...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - July 16, 2009 Category: Endocrinology Authors: Poh Z Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Retinoids as critical modulators of immune functions: new therapeutic perspectives for old compounds.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Retinoids are vitamin A derivatives that critically regulate several physiological and pathological processes, including immune functions and cancer development. These biological response modifiers exert their pleiotropic effects through the interaction with nuclear receptors, defined as retinoic acid receptors (RARs) and retinoid X receptors (RXRs). These ligand-activated nuclear receptors induce the transcription of target genes by binding to responsive elements in the promoter regions. RARs and RXRs are also capable to interact with other nuclear receptors, thus expanding their spectrum of action on gene expression....
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Montrone M, Martorelli D, Rosato A, Dolcetti R Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

T-lymphocytes: a target for stimulatory and inhibitory effects of zinc ions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The trace element zinc is a crucial cofactor for many proteins involved in cellular processes like differentiation, proliferation and apoptosis. Zinc homeostasis is tightly regulated and disturbance of this homeostasis due to genetic defects, zinc deficiency, or supplementation influences the development and the progression of various infectious and autoimmune diseases. The immune system is strongly impaired during zinc deficiency, predominantly the cell-mediated response by T-lymphocytes. During zinc deprivation T-lymphocyte development, polarization into effector cells, and function are impaired. This leads to reduce...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Hönscheid A, Rink L, Haase H Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

The AKT axis as a therapeutic target in autoimmune diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autoimmunity affects a substantial fraction of our population. In patients with autoimmune disease, the immune system recognizes self-tissues as foreign. Common autoimmune diseases include rheumatoid arthritis, diabetes mellitus, lupus and multiple sclerosis. Though different target organs may be affected in different autoimmune diseases, aberrations in adaptive or innate immunity underlie all of these diseases. Abnormal functioning, differentiation and/or activation of T-cells, B-cells and myeloid cells have been documented in various autoimmune diseases. More recent studies have also detailed anomalous activation of ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Wu T, Mohan C Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Targeting indoleamine 2,3-dioxygenase (IDO) to counteract tumour-induced immune dysfunction: from biochemistry to clinical development.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The enzyme indoleamine 2,3-dioxygenase (IDO) regulates immune responses through the capacity to degrade the essential amino acid tryptophan into kynurenine and other downstream metabolites that suppress effector T-cell function and favour the differentiation of regulatory T cells. Considerable experimental evidence indicates that IDO can be expressed by dendritic cells, by tumour cells or by surrounding stromal cells, either within proximity of the tumour or at distal sites. Recent advances in the biochemistry of IDO and in our understanding of the biological relevance of IDO-mediated tryptophan consumption to the esta...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Rutella S, Bonanno G, De Cristofaro R Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Impact of IL-17 on cells of the monocyte lineage in health and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Discovered in 1993, IL-17 has been the focus of intensive research during the last decade, in particular because of its neutrophil-accumulating capacity in several mammalian organs. We now know that the IL-17 family includes as a minimum 6 members, of whom at least IL-17A and IL-17F can be produced by T cells. Thus, IL-17 is positioned at the interface of acquired and innate immunity and constitutes a link between T cell activity and the accumulation of neutrophils locally in organs. Interestingly, there is now accumulating evidence that IL-17 has effects on myeloid cells other than neutrophils as well, namely on cells...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Sergejeva S, Lindén A Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Dissecting insulin signaling pathways: individualised therapeutic targets for diagnosis and treatment of insulin resistant states.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Life expectancy in the developed world is increasing, but this comes with a simultaneous explosion in 'age-related' as well as 'lifestyle-related' diseases, resulting in a decline in quality of life. Three such diseases are Type 2 diabetes mellitus (T2DM), Polycystic Ovarian Syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD), which all share a common reduced cellular response to the hormone insulin (termed insulin resistance). In T2DM, insulin resistance is clearly a contributing factor to disease progression, and is associated with obesity, the single greatest risk factor for all three conditions. Current r...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Woods YL, Petrie JR, Sutherland C Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Inflammatory bowel disease and celiac disease: overlaps in the pathology and genetics, and their potential drug targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe the details and overlaps in the pathomechanism and genetics of inflammatory bowel disease and celiac disease, and discuss potential drug targets for intervention. PMID: 19519468 [PubMed - in process] (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - May 31, 2009 Category: Endocrinology Authors: Festen EA, Szperl AM, Weersma RK, Wijmenga C, Wapenaar MC Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Various non-injectable delivery systems for the treatment of diabetes mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Diabetes mellitus (diabetes) is suffered by more than 180 million people and is responsible for approximately 2.9 million deaths each year. This mortality rate is expected to increase by 50 % in the next decade. Due to the inconvenience of the traditional treatment of diabetes by subcutaneous administration of insulin injection, various attempts are made in the production, purification, formulation and methods of delivery of insulin. However, despite advances in recent years, these attempts have met with limited success. Various alternative routes such as rectal, ocular, nasal, pulmonary and oral have been exploited. T...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Yadav N, Morris G, Harding SE, Ang S, Adams GG Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Interferon-Beta therapy monitoring in multiple sclerosis patients.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Interferon-beta (IFN-beta) therapy has a central place in the management of multiple sclerosis (MS). The three recombinant IFN-beta preparations currently available have shown benefit on activity measures (relapses and active lesions apparent on magnetic resonance imaging), while therapy advantages on progression measures (disability and total lesion burden) are less consistent. Moreover, IFN-beta is effective only in a percentage of patients, since in many of them neutralizing anti-IFN-beta antibodies develop after 6-18 months of treatment, leading to loss of drug bioactivity. Comparative data across studies made with...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Sottini A, Capra R, Serana F, Chiarini M, Caimi L, Imberti L Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Cardiovascular physiology of androgens and androgen testosterone therapy in postmenopausal women.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Women before menopause are at relatively lower risk of cardiovascular disease (CVD) compared with age-matched men and after menopause this gender advantage disappears. Androgen has been known to be an independent factor contributing to the higher male susceptibility to CVD, through adverse effects on lipids, blood pressure, and glucose metabolism. High androgen levels also contribute to CVD development in women with polycystic ovary syndrome as well as androgen abusing athletes and body builders. On the other hand, decline in androgen levels, as a result of ageing in men, is associated with hypertension, diabetes and a...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Ling S, Komesaroff PA, Sudhir K Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

p38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Type 2 diabetes is associated with insulin resistance, endothelial dysfunction and accelerated atherosclerotic diseases. Though underlying mechanisms remain to be unraveled, p38 mitogen-activated protein kinase (MAPK) appears to play important roles in their pathogenesis. As a member of the MAPK family, it regulates the activities of many transcription factors and proteins/enzymes and thus has a wide-spectrum of biological effects. Patients with insulin resistance and/or type 2 diabetes have high levels of plasma free fatty acids, inflammatory cytokines, and/or glucose, and over-activation of the cardiovascular renin-a...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Liu Z, Cao W Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Mutation, selection and the amino Acid hydropathic character: a study on receptor genes involved in immune and non-immune functions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In some mRNA sequences, namely those of formyl peptide receptors and chemokine CXC receptors 4, it has been observed that the second nucleotide (nt) of the coding triplets is significantly more highly conserved than the first nt and the correlation between the conservation indexes of the first two nt is positive and significantly higher than the "basic" correlation usually found between adjacent nt. A theoretical analysis demonstrated that random mutations in the first nt preserve hydrophobicity in 73 % of triplets coding for hydrophobic amino acids (aa) and hydrophilicity in 77 % of triplets coding for hydrophilic aa,...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Panaro MA, Sisto M, Mitolo CI, Cianciulli A, Mitolo V Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Glucans as biological response modifiers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
beta-D-glucans belong to a group of natural, physiologically active compounds, generally called biological response modifiers. Glucans represent highly conserved structural components of cell walls in yeast, fungi, or seaweed. Despite long history of research, the exact mechanisms of glucan action remain unsolved. The present review starts with the history of glucans. Next, the detailed information about the possible glucan sources is followed by a description of the mechanisms of action. Physiological functions of glucan suggest the possible use of glucans not only as non-specific immunomodulator, but also as its poss...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Novak M, Vetvicka V Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

A Novel Approach to Anticancer Therapies: Peroxisome Proliferator Activator-Receptor-gamma as a New Target Therapy in the Treatment of Human Urological Cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we examined the expression of PPAR-gamma in human urological cancer (including renal cell carcinoma, bladder tumor, prostate cancer and testicular cancer) by RT-PCR and immunohistochemistry, and we also examined the effect of PPAR-gamma ligand in these cells by MTT assay, flow cytometry and hoechest staining. PPAR-gamma expression was significantly more extensive and intense in malignant tissues than in normal tissues. PPAR-gamma ligand induced the reduction of malignant cell viability through early apoptosis. These results demonstrated that generated PPAR-gamma in urological cancer cells may play an importa...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Matsuyama M, Yoshimura R Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Targeting histone deacetylases for the treatment of immune, endocrine & metabolic disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Targeting histone deacetylases for the treatment of immune, endocrine & metabolic disorders. Endocr Metab Immune Disord Drug Targets. 2009 Mar;9(1):84-107 Authors: Lawless MW, Norris S, O'Byrne KJ, Gray SG The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Lawless MW, Norris S, O'Byrne KJ, Gray SG Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Methodologic issues in the validation of putative biomarkers and surrogate endpoints in treatment evaluation for systemic lupus erythematosus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No new drugs have been approved for the treatment of systemic lupus erythematosus (SLE) by the Food and Drug Administration for the last 30 years. One barrier has been the lack of validated biomarkers and surrogate endpoints. Validation of SLE biomarkers in the past have been methodologically flawed. We put forth a conceptual framework and five critical criterion for validating putative biomarkers and bio-surrogates in this heterogeneous multi-system disease with protean manifestations. Using the example of a putative biomarker for end-stage lupus nephritis, we performed computer simulations for planning a biomarker bi...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 1, 2009 Category: Endocrinology Authors: Liang MH, Simard JF, Costenbader K, Dore BT, Ward M, Fortin PR, Illei GG, Manzi S, Mittleman B, Buyon J, Gupta S, Abrahamowicz M Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

The Protective Function of Human C-reactive Protein in Mouse Models of Streptococcus pneumoniae Infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Human C-reactive protein (CRP), injected intravenously into mice or produced inside mice by a human transgene, protects mice from death following administration of lethal numbers of Streptococcus pneumoniae. The protective effect of CRP is due to reduction in the concentration of bacteria in the blood. The exact mechanism of CRP-dependent killing of pneumococci and the partners of CRP in this process are yet to be defined. The current efforts to determine the mechanism of action of CRP in mice are directed by four known in vitro functions of CRP: 1. the ability of pneumococcal C-polysaccharide-complexed CRP to activate...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Agrawal A, Suresh MV, Singh SK, Ferguson DA Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Further LDL Cholesterol Lowering Through Targeting PCSK9 for Coronary Artery Disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that belongs to the proprotein convertase family. PCSK9 is synthesized as a zymogen and its prodomain is cleaved by its own catalytic activity. The cleaved prodomain forms a protein complex with the rest of the PCSK9 carboxyl terminus within the endoplasmic reticulum and is secreted. Secreted PCSK9 has been shown to be able to reduce low-density lipoprotein receptor (LDLR) levels in vitro and in vivo. Thus PCSK9 has emerged as an important player modulating LDLR levels and plasma LDL cholesterol. Furthermore, PCSK9 deficiency leads to significan...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Cao G, Qian YW, Kowala MC, Konrad RJ Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

The adenosine a2b receptor: its role in inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Investigations into the role of the adenosine A2b receptor have been enigmatic due to the lack of good selective high affinity agonists and antagonists. Over the last few years several new antagonist compounds, based either on a xanthine or pyrrolpyrimidine (polyheterocyclic) structure have been designed and these have been used to localise A2b receptors in different tissues and to determine their function. Recently, animals harbouring either a loss or an over-expression of the A2b receptor have been created and these suggest an anti-inflammatory role for the receptor. In this short review, we describe how the A2b rece...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Ham J, Rees DA Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Emerging Roles for the CD36 Scavenger Receptor as a Potential Therapeutic Target for Corneal Neovascularization.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present evidence that CD36 contributes significantly to the maintenance of corneal avascularity wherein its deficiency leads to age-related corneal NV. Data further reveal that activation of CD36 substantially attenuates and induces regression of inflammatory corneal NV via concerted inhibition of VEGFA, c-Jun N terminal kinase-1, and c-Jun. In parallel studies, we demonstrate that hypoxia, a fundamental stimulus of NV, markedly elevates CD36 corneal expression in a hypoxia-inducible factor-1 and reactive oxygen species dependent manner. Collectively, our findings unveil interesting avenues for future research on the in...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Mwaikambo BR, Yang C, Ong H, Chemtob S, Hardy P Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

SRC as a therapeutic target in breast cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Src kinase plays a key role in multiple signalling pathways regulating diverse cell functions from proliferation and survival to invasion and angiogenesis. In breast cancer, both Src protein levels and kinase activity are frequently elevated and its important role in these oncogenic processes make it a potential target for therapeutic intervention. Importantly, recent evidence has revealed a role for Src in mediating anti-hormone action and in acquired endocrine resistance. A number of small molecule inhibitors of Src kinase have been developed with preclinical data demonstrating their effectiveness at suppressing brea...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Morgan L, Nicholson RI, Hiscox S Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

The role of negative costimulators during parasitic infections.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Activation of T lymphocytes through TCR signalling takes place within the context of numerous other cell surface proteins. To prevent unnecessary activation of T cells the immune system has developed an intricate balance between positive and negative costimulatory signals. Positive costimulatory signals determine whether antigen recognition by T cells leads to full activation or to anergy/death. In contrast, the expression of negative costimulatory molecules by T cells such as cytotoxic T lymphocyte antigen 4 (CTLA-4) mediates the regulation of an immune response and thus plays a pivotal role in the maintenance of peri...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Lepenies B, Jacobs T Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Roles of retinoic Acid in induction of immunity and immune tolerance.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
It has long been recognized that vitamin A and its metabolites have immune-regulatory roles but the mechanism has been unclear. Recently, there has been a significant progress in elucidating the functions of retinoic acid in regulation of immune cell development. Retinoic acid (all-trans and 9-cis retinoic acid) is produced from the cells of the intestine such as dendritic cells and provides an intestine-specific environmental cue to differentiating immune cells. When T cells and B cells are activated in the intestine and associated-lymphoid tissues, gut homing receptors are induced on the cells in a retinoic acid and ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Kim CH Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Future targets for immune therapy in colitis?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Crohn's disease and Ulcerative Colitis, collectively termed inflammatory bowel disease (IBD), are chronic inflammatory disorders of the bowel. It is generally accepted that the pathology associated with IBD is characterized by a hyper-reactive immune response in the gut wall directed against the commensal intestinal bacterial flora, and that the CD4+ T cells dominate the adaptive immune response. Chemokines are small proteins involved in the guidance of migration of immune cells during normal homeostasis and inflammation. Chemokines have been shown to play a central role in recruiting inflammatory cells to the inflamed...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Kristensen NN, Claesson MH Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Does Non-Alcoholic Fatty Liver Disease (NAFLD) Increase Cardiovascular Risk?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Non alcoholic fatty liver disease (NAFLD) is defined as fat accumulation exceeding 5% to 10% by the weight of the liver, in the absence of other causes of steatosis. NAFLD is strongly associated with metabolic diseases, such as metabolic syndrome. At present, insulin resistance, elevated concentrations of free fatty acids and oxidants, and an imbalance between different cytokines have been identified as the common pathophysiological elements underlying both NAFLD and metabolic syndrome. Emerging evidence also considers NAFLD as the hepatic manifestation of metabolic syndrome and supports a possible direct role of fat l...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Montecucco F, Mach F Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Tissue Factor Modulation by Angiotensin II: A Clue to a Better Understanding of the Cardiovascular Effects of Renin-Angiotensin System Blockade?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Systemic hypertension, a pathological process to which the renin-angiotensin system contributes importantly, is characterized by a thrombophilic diathesis and an increased risk for acute ischemic coronary events. That apparently contradictory profile might, to some extent, relate to the modulating properties of Angiotensin II, the effector arm of the renin angiotensin system, on tissue factor expression, the physiologic initiator of blood coagulation and a basic mechanism in the pathogenesis of acute thrombosis. In fact, monocytes and macrophages within the atherosclerotic plaque as well as inflamed vascular endothelia...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - December 1, 2008 Category: Endocrinology Authors: Celi A, Del Fiorentino A, Cianchetti S, Pedrinelli R Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Celiac disease: pathogenesis and novel therapeutic strategies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Celiac disease is a digestive disease, considered as an autoimmune disorder, that damages the small intestine and interferes with absorption of nutrients. Individuals affected by celiac disease cannot tolerate a protein called gluten, present in wheat, rye, and barley, but also in other common products such as stamp and envelope adhesive, medicines, and vitamins. Celiac disease is a genetic condition that is triggered-or becomes active for the first time-after surgery, pregnancy, childbirth, viral infection, or severe emotional stress. Symptoms may occur in the digestive system, or in other parts of the body. Diagnosis...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Baldassarre M, Laneve AM, Grosso R, Laforgia N Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Cannabinoids as therapeutic agents for ablating neuroinflammatory disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cannabinoids have been reported to alter the activities of immune cells in vitro and in vivo. These compounds may serve as ideal agents for adjunct treatment of pathological processes that have a neuroinflammatory component. As highly lipophilic molecules, they readily access the brain. Furthermore, they have relatively low toxicity and can be engineered to selectively target cannabinoid receptors. To date, two cannabinoid receptors have been identified, characterized and designated CB(1) and CB(2). CB(1) appears to be constitutively expressed within the CNS while CB(2) apparently is induced during inflammation. The in...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Cabral GA, Griffin-Thomas L Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Genome study of kidney disease in the age of post genome-sequencing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The genome-based study of human disease has been developing rapidly with the completion of the human genome project and the remarkable progress of technology. The genetic variation information associated with disease will certainly enable us to discover potential drug targets and to develop personalized medicine. Chronic kidney disease (CKD) is now recognized as a public health problem because its prevalence is increasing all over the world. No treatment can reverse the progression of CKD to end-stage renal disease (ESRD), which requires enormous medical resources. Moreover, CKD is known to be a strong risk factor for ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Doi K, Okamoto K, Tokunaga K, Fujita T, Noiri E Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Harnessing CD36 to Rein in Inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Maintaining health requires a dynamic balance between the influence of pro-inflammatory and anti-inflammatory mediators. While inflammation serves an important protective role against infection, unrestrained inflammation is acutely lethal and unresolved inflammation contributes to a broad range of chronic disorders. Immunotherapy with cytokines themselves or cytokine antagonists faces strict limitations due to efficacy, safety and cost. More successful treatment of the pro-inflammatory component of chronic disorders may emerge from strategies designed to reset the balance between pro and anti-inflammatory cytokines thr...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Parsons MS, Barrett L, Little C, Grant MD Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Allosteric modulators of the human calcium-sensing receptor: structures, sites of action, and therapeutic potentials.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The human extracellular Ca(2+)-sensing receptor (CaR) plays a key role in the regulation of serum calcium and parathyroid hormone. This large dimeric receptor consists of domains with topologically distinctive orthosteric and allosteric sites. Positive allosteric modulators of the CaR, which increase CaR activation and thereby decrease secretion of parathyroid hormone, are potential for the treatment of primary and secondary hyperparathyroidism. Conversely, negative allosteric modulators of the CaR, which decrease the receptor activation and thereby stimulate endogenous parathyroid hormone secretion, are potential for ...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Hu J Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Trends in metabolic syndrome and gene networks in human and rodent models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metabolic syndrome (MetS) can be considered a pheno-physiological cluster of metabolically interrelated risk factors for diabetes mellitus and cardiovascular disease. MetS has emerged as a result of complex interactions among environmental stresses and MetS gene networks and their products. In this review we summarize trends in MetS definitions, their associated controversies and possibilities for their refinement. The National Cholesterol Education Program MetS definition with its improvements by the American Heart Association and NHLBI Conference has the potential to become the primary clinical definition of MetS. Fo...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Kraja AT, Province MA, Huang P, Jarvis JP, Rice T, Cheverud JM, Rao DC Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Bone morphogenetic protein-smad pathway as drug targets for osteoporosis and cancer therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily. Engaging of BMPs to BMP receptors on the cell surface leads to activation of the receptor kinase activity, which phosphorylates Smad1/5/8. Smad1, 5, or 8, with Smad4, forms a complex, which is translocated to the nucleus, where it binds to the consensus DNA sequence to regulate the transcription of BMP target genes. BMP-Smad signaling regulates stem cell renewal, cell proliferation, differentiation, migration, and apoptosis, and controls embryo development and postnatal tissue homoeostasis. Both human and mouse genetic studies have demonstrated...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Li B Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Critical role of the endocannabinoid system in the regulation of food intake and energy metabolism, with phylogenetic, developmental, and pathophysiological implications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The endocannabinoid system (ECS) consists of two receptors (CB(1) and CB(2)), several endogenous ligands (primarily anandamide and 2-AG), and over a dozen ligand-metabolizing enzymes. The ECS has deep phylogenetic roots and regulates many aspects of embryological development and homeostasis, including neuroprotection and neural plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and the focus of this review: hunger, feeding, and metabolism. The ECS controls energy balance and lipid metabolism centrally (in the hypothalamus and mesolimbic pathways) and peripherally (in adipocy...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - September 1, 2008 Category: Endocrinology Authors: Viveros MP, de Fonseca FR, Bermudez-Silva FJ, McPartland JM Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Efficacy of dietary supplementation with botanicals on carbohydrate metabolism in humans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Botanical products are widely used in nutritional supplementation for promotion of health or prevention of diseases. With the high prevalence of obesity and type 2 diabetes, abnormalities in carbohydrate metabolism are common in the general population and obtaining glycemic control is important in reducing the complications of diabetes. If shown to be effective, botanical products have a unique position in potentially aiding the general public in regard to obesity and diabetes. They can be obtained "over-the-counter" and may have less side effects compared to many synthetic drugs. Although most of the popular botanical...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - June 1, 2008 Category: Endocrinology Authors: Cefalu WT, Ye J, Wang ZQ Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Botanical treatments for diabetes and obesity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 18537693 [PubMed - in process] (Source: Endocrine, Metabolic and Immune Disorders Drug Targets)
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - June 1, 2008 Category: Endocrinology Authors: Ye J Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Mechanisms underlying beneficial health effects of tea catechins to improve insulin resistance and endothelial dysfunction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Tea is a popular beverage with a number of putative beneficial health effects. A recent large epidemiological study in Japan demonstrates that increased tea consumption is associated with decreased cardiovascular mortality (but not cancer mortality) in a dose-dependent manner. The polyphenol epigallocatechin-3-gallate (EGCG) is the most abundant tea catechin. Beneficial effects of EGCG therapy have been reported in a number of human and animal studies. Emerging evidence suggests that EGCG may improve endothelial function, hypertension, coronary heart disease, obesity, insulin resistance, as well as glucose and lipid me...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - June 1, 2008 Category: Endocrinology Authors: Kim JA Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals

Moderate wine consumption in the prevention of metabolic syndrome and its related medical complications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The metabolic syndrome (MetS) encompasses a constellation of cardio-metabolic abnormalities associated with a high risk of developing type 2 diabetes and cardiovascular disease (CVD), the top killer in the ageing population. Recent studies have demonstrated multiple beneficial effects of moderate wine consumption in the protection against development of the MetS and its related medical complications. The association of moderate wine consumption with lower incidence of the MetS and atherosclerotic heart disease has been repeatedly documented in numerous epidemiological studies on diverse ethnic groups. In addition to th...
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - June 1, 2008 Category: Endocrinology Authors: Liu L, Wang Y, Lam KS, Xu A Tags: Endocr Metab Immune Disord Drug Targets Source Type: journals