Morphologic Detection of Multiple Steroid Binding Sites in Breast Cancer by Histochemistry and By Immunocytochemistry with Monoclonal Antireceptor Antibody
P. Pertschuk Louis, Lee Sin Hang in Localization of Putative Steroid Receptors, 2018
There is general agreement that a valid histologic method for detection of steroid receptors in human breast cancer would be a valuable clinical tool. Furthermore, by permitting determinations of tumor cell steroid binding heterogeneity and allowing for evaluation of the potential contribution of nonma-lignant tissue elements to the total steroid binding capacity of a specimen, a histologic procedure would be an important adjunct to conventional biochemical receptor assays. Of significantly greater importance than conformity with biochemical data both from a practical viewpoint as well as in helping to shed some light upon the nature of the binding revealed by histologic assays is their level of agreement with the clinical hormone responsiveness of breast cancer patients. The exact nature and significance of the binding sites revealed by histochemical assays remain unclear. Possibilities that some of the discrepancies which appear to exist may be due to artifacts in biochemical as well as in histochemical analytical methods should be explored.
Histochemical Sex Steroid Hormone Receptor Assay and Treatment of Breast Cancer in Chinese Patients
P. Pertschuk Louis, Lee Sin Hang in Localization of Putative Steroid Receptors, 2018
As one of the most common malignancies in women, the incidence of breast cancer in China is only second to that of carcinoma of the uterine cervix. With the development of methods of hormone receptor assay and their clinical application, most practicing oncologists have classified breast cancers into two categories. They are the steroid hormone receptor (HR) positive and the steroid hormone receptor-negative; and the hormone receptor status of the tumor is regarded as an important parameter in assessment of the patient's condition, the planning of treatment protocol, and the prediction of response to endocrine therapy. The cancer cells that fluoresced as intensely as or more than the benign ductal epithelial cells were considered sex steroid receptor positive. The HR-rich cancers, as defined by our criteria, have a higher rate of response to endocrine therapy than the HR-poor tumors, and an HR-rich tumor generally indicates a longer survival rate for the patient.
Critical Issues in the Evaluation of Histochemical and Biochemical Methods for Steroid Receptor Analysis
P. Pertschuk Louis, Lee Sin Hang in Localization of Putative Steroid Receptors, 2018
The presence of sex steroid receptors in human carcinomas was first convincingly shown by Jensen and co-workers. Steroid binding proteins present in the blood have various affinities and binding capacities for sex steroids. The various histochemical techniques reported are discussed and compared to what is known regarding the capacity of these procedures to adequately evaluate estrogen receptor (ER) in situ or otherwise. Although the number of grading systems used by authors studying correlation of histologic and nuclear tumor grades with ER status makes comparisons difficult, a definite trend towards a higher incidence of ER positivity in well-differentiated carcinomas as compared to poorly differentiated tumors exists. The availability of well-documented specific biochemical assays for steroid receptors diminishes the importance of trying to predict receptor content utilizing histologic parameters of questionable predictive value. Several investigators have used immunocytochemical methods with antibody directed against the sex steroid in attempts to localize ER on frozen sections or in fresh tumor cells.
Sebaceous gland receptors
Published in Dermato-Endocrinology, 2009
Receptors are proteins, embedded in a cell or cytoplasmic membrane, to which a mobile signaling molecule may attach. Receptor ligands may be peptides (such as neurotransmitters), hormones, pharmaceutical drugs and/or a toxins, whereas “binding” ordinarily initiates a cellular response. Human sebocytes are biologically and metabolically very active cells and consequently express numerous receptors. Three of 4 groups of peptide/neurotransmitter receptors, the so-called serpentine receptor group are present (corticotropin-releasing hormone receptors 1 and 2, melanocortin-1 and 5 receptors, μ-opiate receptors, VPAC receptors, cannabinoid receptors 1 and 2, vascular endothelial growth factor receptor and histamine 1 receptor). The single-transmembrane domain receptors are represented by the insulin-like growth factor-I receptor and the third group, which does not possess intrinsic tyrosine kinase activity, by the growth factor receptor. Nuclear receptors expressed in sebocytes are grouped into two major subtypes. From the steroid receptor family, the androgen receptor and the progesterone receptor are expressed. The thyroid receptor family includes the estrogen receptors (α and β isotypes), the retinoic acid receptors (isotypes α and γ) and retinoid X receptors (isotypes α, β, γ), the vitamin D receptor, the peroxisome proliferator-activated receptors (isotypes α, δ and γ) and the liver X receptors (α and β isotypes). The vanilloid receptor belongs to the transient ion channels and is expressed in differentiating human sebocytes. Further sebocyte receptors, which may influence their function are fibroblast growth factor receptor 2, epidermal growth factor receptor, c-MET, CD14, Toll-like receptor 2, Toll-like receptor 4 and Toll-like receptor 6. Receptor-ligand interactions control sebocyte proliferation, differentiation and lipid synthesis. However, not every ligand that binds to a sebocyte receptor also activates it, such ligands are receptor antagonists and inverse agonists.
Investigation on the Potential Role of the AH Receptor Nuclear Translocator Protein in Vitamin D Receptor Action
Published in Journal of Receptor Research, 1993
Suzanne Reisz-Porszasz, Herminio Reyes, Hector F. Deluca, Jean M. Prahl, Oliver Hankinson
The Ah receptor nuclear translocator protein (ARNT) is required for binding of the Ah (dioxin) receptor to the xenobiotic responsive element (XRE), and is a structural component of the XRE-binding form of the Ah receptor. The vitamin D receptor requires an accessory protein for binding to the vitamin D responsive element (VDRE) in the osteocalcin gene. Since the vitamin D receptor has similarities to the Ah receptor, we investigated whether ARNT is also required for vitamin D receptor activity. Two lines of evidence demonstrate that ARNT is not required for vitamin D receptor activity, and therefore does not correspond to the vitamin D receptor accessory protein: i) Antibodies to ARNT have no effect on binding of the vitamin D receptor to the VDRE. ii) c4, a mutant of Hepa-1 cells that is defective in ARNT activity, and in which binding of the Ah receptor to the XRE does not occur, possesses a vitamin D receptor with full activity for binding the VDRE.
Non-peptidic δ opioid receptor agonists and antagonists (2000 – 2012)
Published in Expert Opinion on Therapeutic Patents, 2013
Hideaki Fujii, Toshihiro Takahashi, Hiroshi Nagase
Introduction: The δ opioid receptor mediates various pharmacological effects such as antinociceptive and antidepressant effects, whereas it does not appear to induce μ opioid-like side effects such as dependence, respiratory depression and constipation. Therefore, the δ opioid receptor is a promising drug target. Areas covered: This review covers literature and patents concerning non-peptidic δ opioid receptor agonists, antagonists, modulators and ligands from 2000 to 2012. Pharmacological effects induced by δ receptor agonists or antagonists are also discussed. Expert opinion: Potential therapeutic effects by δ receptor agonists are antinociceptive, antidepressant, anxiolytic, cardioprotective and neuroprotective effects. Among them, anxiolytic effects are of particular interest because the anxiolytic effects by a δ receptor agonist have been observed in humans. Although non-peptidic δ receptor agonists were reported to show convulsive effects via the δ opioid receptor, some δ receptor agonists are known to produce no convulsive behaviors. Therefore, it may be possible to eliminate convulsion induced by a δ receptor agonist. Many δ receptor antagonists were also reported but there is little new information about pharmacological effects by a δ receptor antagonist. Although detailed results were not revealed, two δ receptor antagonists with μ receptor agonistic or antagonistic properties are in the late stages of the clinical trial.
Related Knowledge Centers
- Cell Membrane
- Cell Nucleus
- Cell Surface Receptor
- Pharmacology
- Cytoplasm
- Cell