Activation of the phosphatidylinositol-3-kinase (PI3K) signaling cascade is increasingly recognized as a common feature of thyroid follicular neoplasms. Among the PI3K downstream effectors, the main kinase, directly responsible for the increased cell growth and proliferation, is called mammalian target of rapamycin (mTOR). This central kinase might be directly inhibited via rapamycin and its derivatives. The aim of the present study was to examine whether RAD001 (everolimus) can selectively suppress the proliferation of different anaplastic thyroid cancer (ATC) cells. Five different human ATC cell lines were exposed to different concentrations of RAD001. Importantly, we found a dose-dependent growth inhibition in two ATC cell lines at concentrations of 43.5 and 94.5 nM although not as intensive as within the RAD001 responding K562cell line. The other cell lines revealed a GI (50) between 168 to 234 nM. In parallel, quantitative PCR of PCNA displayed a reduced expression of PCNA within the responding cell lines, respectively. In summary, we found a good responding effect in a part of ATC cell lines, which may have a clinical impact.
Recent in vitro and in vivo studies have shown a potent inhibition of cytochrome P450 CYP3A4 through human immune deficiency virus (HIV) protease inhibitors (PIs). The PI ritonavir is described as the most potent compound within these CYP3A4 inhibitors. We present 2 cases who developed the sequelae of glucocorticoid excess following ritonavir therapy and inhalative glucocorticoid treatment: A 60-year-old HIV positive man developed the typical symptoms of Cushing's syndrome and a 52-year-old HIV positive man developed severe osteoporosis.
Adrenal masses are one of the most common tumors in humans. They are a very heterogenous group of diseases and include benign and malignant adrenocortical lesions, metastases, pheochromocytomas and other entities. Adrenal masses originating from steroidogenic or chromaffin cells may be silent or the source of subclinical or overt hormone excess, such as primary aldosteronism, hypercortisolism or symptomatic catecholamine excess. On the other hand, adrenal hyperplasia may be the result of excess ACTH secretion in steroid biosynthesis disorders with deficient glucocorticoid secretion, in glucocorticoid resistance, in Cushing's disease, or ectopic ACTH syndrome. Algorithms for endocrine testing, imaging studies and their combination are available for defining the tumor entity and for the characterization of the hormone excess syndromes. Recent developments in molecular biology have provided tools for testing for hereditary tumor syndromes associated with adrenal tumorigenesis and to establish strategies for further treatment and follow-up.
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