Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

T-cell inhibitors: a bench-to-bedside review.

ABSTRACT: Allergic contact dermatitis is the quintessential example of a delayed-in-time and T-cell-mediated immune response. In the last decade, many of the molecular events required to initiate (or block) such a response have been uncovered. Textbook and journal reviews have emphasized the costimulatory requirements, with less focus on the coinhibitory signals that are of equal importance in understanding this central event of adaptive immunity. To fill this gap, we offer a compendium of discoveries characterizing the ligand-receptor pairs inhibiting T-cell activation and of selected illnesses and therapeutic applications that illuminate their role in health and disease.

SUBMITTER: Das S

PROVIDER: S-EPMC3485635 | biostudies-literature | 2012 Sep-Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

T-cell inhibitors: a bench-to-bedside review.

Das Shinjita S Ariizumi Kiyoshi K Cruz Ponciano D PD

Dermatitis : contact, atopic, occupational, drug 20120901 5

Allergic contact dermatitis is the quintessential example of a delayed-in-time and T-cell-mediated immune response. In the last decade, many of the molecular events required to initiate (or block) such a response have been uncovered. Textbook and journal reviews have emphasized the costimulatory requirements, with less focus on the coinhibitory signals that are of equal importance in understanding this central event of adaptive immunity. To fill this gap, we offer a compendium of discoveries cha ...[more]

PMID: 23010825

Similar Datasets

MEK and the inhibitors: from bench to bedside.

Project description:Four distinct MAP kinase signaling pathways involving 7 MEK enzymes have been identified. MEK1 and MEK2 are the prototype members of MEK family proteins. Several MEK inhibitors are in clinical trials. Trametinib is being evaluated by FDA for the treatment of metastatic melanoma with BRAF V600 mutation. Selumetinib has been studied in combination with docetaxel in phase II randomized trial in previously treated patients with advanced lung cancer. Selumetinib group had better response rate and progression-free survival. This review also summarized new MEK inhibitors in clinical development, including pimasertib, refametinib, PD-0325901, TAK733, MEK162 (ARRY 438162), RO5126766, WX-554, RO4987655 (CH4987655), GDC-0973 (XL518), and AZD8330.

| S-EPMC3626705 | biostudies-literature

RTK Inhibitors in Melanoma: From Bench to Bedside.

Project description:MAPK (mitogen activated protein kinase) and PI3K/AKT (Phosphatidylinositol-3-Kinase and Protein Kinase B) pathways play a key role in melanoma progression and metastasis that are regulated by receptor tyrosine kinases (RTKs). Although RTKs are mutated in a small percentage of melanomas, several receptors were found up regulated/altered in various stages of melanoma initiation, progression, or metastasis. Targeting RTKs remains a significant challenge in melanoma, due to their variable expression across different melanoma stages of progression and among melanoma subtypes that consequently affect response to treatment and disease progression. In this review, we discuss in details the activation mechanism of several key RTKs: type III: c-KIT (mast/stem cell growth factor receptor); type I: EGFR (Epidermal growth factor receptor); type VIII: HGFR (hepatocyte growth factor receptor); type V: VEGFR (Vascular endothelial growth factor), structure variants, the function of their structural domains, and their alteration and its association with melanoma initiation and progression. Furthermore, several RTK inhibitors targeting the same receptor were tested alone or in combination with other therapies, yielding variable responses among different melanoma groups. Here, we classified RTK inhibitors by families and summarized all tested drugs in melanoma indicating the rationale behind the use of these drugs in each melanoma subgroups from preclinical studies to clinical trials with a specific focus on their purpose of treatment, resulted effect, and outcomes.

| S-EPMC8038208 | biostudies-literature

B-Raf and the inhibitors: from bench to bedside.

Project description:The B-Raf protein is a key signaling molecule in the mitogen activated protein kinase (MAPK) signaling pathway and has been implicated in the pathogenesis of a variety of cancers. An important V600E mutation has been identified and can cause constitutive B-Raf activation. Recent studies have evaluated a variety of small molecule inhibitors targeting B-Raf, including PLX4032/vemurafenib, dabrafenib, LGX818, GDC0879, XL281, ARQ736, PLX3603 (RO5212054), and RAF265. Therapeutic resistance has been identified and various mechanisms described. This review also discussed the current understanding of B-Raf signaling mechanism, methods of mutation detection, treatment strategies as well as potential methods of overcoming therapeutic resistance.

| S-EPMC3646677 | biostudies-literature

Molecular Diagnostics in Sepsis: from Bedside to Bench

Project description:Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. Keywords: genomics, diagnosis, microarray, calprotectin

2006-08-29 | GSE5663 | GEO

Research in Sickle Cell Disease: From Bedside to Bench to Bedside.

Project description:Sickle cell disease (SCD) is an exemplar of bidirectional translational research, starting with a remarkable astute observation of the abnormally shaped red blood cells that motivated decades of bench research that have now translated into new drugs and genetic therapies. Introduction of hydroxyurea (HU) therapy, the only SCD-modifying treatment for >30 years and now standard care, was initiated through another clinical observation by a pediatrician. While the clinical efficacy of HU is primarily due to its fetal hemoglobin (HbF) induction, the exact mechanism of how it increases HbF remains not fully understood. Unraveling of the molecular mechanism of how HU increases HbF has provided insights on the development of new HbF-reactivating agents in the pipeline. HU has other salutary effects, reduction of cellular adhesion to the vascular endothelium and inflammation, and dissecting these mechanisms has informed bench-both cellular and animal-research for development of the 3 recently approved agents: endari, voxelotor, and crizanlizumab; truly, a bidirectional bench to bedside translation. Decades of research to understand the mechanisms of fetal to adult hemoglobin have also culminated in promising anti-sickling genetic therapies and the first-in-human studies of reactivating an endogenous (γ-globin) gene HBG utilizing innovative genomic approaches.

| S-EPMC8171370 | biostudies-literature

Natural Product Inspired N-Terminal Hsp90 Inhibitors: From Bench to Bedside?

Project description:The 90 kDa heat shock proteins (Hsp90) are responsible for the conformational maturation of nascent polypeptides and the rematuration of denatured proteins. Proteins dependent upon Hsp90 are associated with all six hallmarks of cancer. Upon Hsp90 inhibition, protein substrates are degraded via the ubiquitin-proteasome pathway. Consequentially, inhibition of Hsp90 offers a therapeutic opportunity for the treatment of cancer. Natural product inhibitors of Hsp90 have been identified in vitro, which have served as leads for the development of more efficacious inhibitors and analogs that have entered clinical trials. This review highlights the development of natural product analogs, as well as the development of clinically important inhibitors that arose from natural products.

| S-EPMC4659773 | biostudies-literature

Natural Killer Cell Immunotherapy: From Bench to Bedside.

Project description:The potential of natural killer (NK) cells to target numerous malignancies in vitro has been well documented; however, only limited success has been seen in the clinic. Although NK cells prove non-toxic and safe regardless of the cell numbers injected, there is often little persistence and expansion observed in a patient, which is vital for mounting an effective cellular response. NK cells can be isolated directly from peripheral blood, umbilical cord blood, or bone marrow, expanded in vitro using cytokines or differentiated in vitro from hematopoietic stem cells. Drugs that support NK cell function such as lenalidomide and bortezomib have also been studied in the clinic, however, the optimum combination, which can vary among different malignancies, is yet to be identified. NK cell proliferation, persistence, and function can further be improved by various activation techniques such as priming and cytokine addition though whether stimulation pre- or post-injection is more favorable is another obstacle to be tackled. Here, we review the various methods of obtaining and activating NK cells for use in the clinic while considering the ideal product and drug complement for the most successful cellular therapy.

| S-EPMC4453475 | biostudies-literature

Bench-to-bedside review: Association of genetic variation with sepsis.

Project description:Susceptibility and response to infectious disease is, in part, heritable. Initial attempts to identify the causal genetic polymorphisms have not been entirely successful because of the complexity of the genetic, epigenetic, and environmental factors that influence susceptibility and response to infectious disease and because of flaws in study design. Potential associations between clinical outcome from sepsis and many inflammatory cytokine gene polymorphisms, innate immunity pathway gene polymorphisms, and coagulation cascade polymorphisms have been observed. Confirmation in large, well conducted, multicenter studies is required to confirm current findings and to make them clinically applicable. Unbiased investigation of all genes in the human genome is an emerging approach. New, economical, high-throughput technologies may make this possible. It is now feasible to genotype thousands of tag single nucleotide polymorphisms across the genome in thousands of patients, thus addressing the issues of small sample size and bias in selecting candidate polymorphisms and genes for genetic association studies. By performing genome-wide association studies, genome-wide scans of nonsynonymous single nucleotide polymorphisms, and testing for differential allelic expression and copy number polymorphisms, we may yet be able to tease out the complex influence of genetic variation on susceptibility and response to infectious disease.

| S-EPMC2689454 | biostudies-literature

The Role of mTOR Inhibitors in Hematologic Disease: From Bench to Bedside.

Project description:The mTOR pathway plays a central role in many cellular processes, such as cellular growth, protein synthesis, glucose, and lipid metabolism. Aberrant regulation of mTOR is a hallmark of many cancers, including hematological malignancies. mTOR inhibitors, such as Rapamycin and Rapamycin analogs (Rapalogs), have become a promising class of agents to treat malignant blood diseases-either alone or in combination with other treatment regimens. This review highlights experimental evidence underlying the molecular mechanisms of mTOR inhibitors and summarizes their evolving role in the treatment of hematologic disease, including leukemia, lymphoma, myeloma, immune hemocytopenia, and graft-versus-host disease (GVHD). Based on data presented in this review, we believe that mTOR inhibitors are becoming a trusted therapeutic in the clinical hematologist's toolbelt and should be considered more routinely in combination therapy for the management of hematologic disease.

| S-EPMC7821787 | biostudies-literature

The development of PARP inhibitors in ovarian cancer: from bench to bedside.

Project description:The nuclear enzyme poly (ADP-ribose) polymerase (PARP) represents an important novel target in the treatment of ovarian cancer. This article charts over 50 years of research from the discovery of the first PARP enzyme in 1963, to the approval and licensing in 2015 of the first PARP inhibitor, olaparib (Lynparza), in the treatment of BRCA-mutated ovarian cancer.

| S-EPMC4816267 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data