Systemic use of non‐biologic corticosteroids in orofacial diseases

Systemic non‐biologic agents have long been in clinical use in medicine – often with considerable efficacy, albeit with some adverse effects – as with all medications. With the advent of biologic agents, all of which currently are restricted to systemic use, there is a growing need to ensure which agents have the better therapeutic ratio. The non‐biologic agents (NBAs) include a range of agents, most especially the corticosteroids (corticosteroids). This study reviews the corticosteroids in systemic use in management of orofacial mucocutaneous diseases; subsequent studies discuss corticosteroid‐sparing agents used in the management of orofacial diseases, such as calcineurin inhibitors used to produce immunosuppression; purine synthetase inhibitors; and cytotoxic and other immunomodulatory agents.     

Marker Systems Based on MicroRNA Gene Methylation for the Diagnosis of Stage I-II Breast Cancer

Bulletin of Experimental Biology and Medicine - Groups of microRNA genes, methylation of which is associated with the initial (I-II) stages of breast cancer, are determined, and new markers and...     

Regulation of high-affinity IgE receptor-mediated mast cell activation by murine low-affinity IgG receptors.

Allergic symptoms result from the release of granular and lipidic mediators and of cytokines by inflammatory cells. The whole process is initiated by the aggregation of mast cell and basophil high-affinity IgE receptors (Fc epsilon RI) by IgE and antigen. We report here that IgE-induced release of mediator and cytokine can be inhibited by cross-linking Fc epsilon RI to low-affinity IgG receptors (Fc gamma RII) which are constitutively expressed on mast cells and basophils. Using a model of stable transfectants in RBL-2H3 cells expressing endogeneous rat Fc epsilon RI and recombinant murine Fc gamma RII, we showed that inhibition requires that Fc epsilon RI be crosslinked to Fc gamma RII by the same multivalent ligand. Inhibition of cross-linked receptors left non-cross-linked Fc epsilon RI capable of triggering mediator release and was reversible upon disengagement. Both isoforms of wild-type Fc gamma RII were equally capable of inhibiting Fc epsilon RI-mediated mast cell activation provided they had an intact intracytoplasmic domain. Our results demonstrate that mast cell secretory responses triggered by high-affinity receptors for IgE may be controlled by low-affinity receptors for IgG. This regulation of Fc epsilon RI-mediated mast cell activation is of potential interest in mast cell physiology and in allergic pathology.     

Bone‐induced c‐kit expression in prostate cancer: A driver of intraosseous tumor growth

Loss of BRCA2 function stimulates prostate cancer (PCa) cell invasion and is associated with more aggressive and metastatic tumors in PCa patients. Concurrently, the receptor tyrosine kinase c‐kit is highly expressed in skeletal metastases of PCa patients and induced in PCa cells placed into the bone microenvironment in experimental models. However, the precise requirement of c‐kit for intraosseous growth of PCa and its relation to BRCA2 expression remain unexplored. Here, we show that c‐kit expression promotes migration and invasion of PCa cells. Alongside, we found that c‐kit expression in PCa cells parallels BRCA2 downregulation. Gene rescue experiments with human BRCA2 transgene in c‐kit‐transfected PCa cells resulted in reduction of c‐kit protein expression and migration and invasion, suggesting a functional significance of BRCA2 downregulation by c‐kit. The inverse association between c‐kit and BRCA2 gene expressions in PCa cells was confirmed using laser capture microdissection in experimental intraosseous tumors and bone metastases of PCa patients. Inhibition of bone‐induced c‐kit expression in PCa cells transduced with lentiviral short hairpin RNA reduced intraosseous tumor incidence and growth. Overall, our results provide evidence of a novel pathway that links bone‐induced c‐kit expression in PCa cells to BRCA2 downregulation and supports bone metastasis.