Human aldehyde oxidase‐1 (AOX1) is a cytosolic molybdo‐flavoenzyme of importance in drug metabolism and toxicity. However, it is not known how the expression of this gene is transcriptionally regulated. Estrogen receptor (ER), which is a nuclear receptor, plays important roles in physiological functions and is implicated in hormonal cancers, but it also regulates the expression of hepatic drug‐metabolizing enzymes. Conflicting microarray data show that AOX1 expression was increased or decreased in breast cancer compared to healthy tissues. We investigated whether ER agonists regulate AOX1 gene expression in a human cell culture model. As analyzed by real‐time polymerase chain reaction assays, MCF‐7 human breast adenocarcinoma cells expressed AOX1 and the basal AOX1 level varied with different types of fetal bovine serum (FBS). 17β‐Estradiol decreased AOX1 mRNA level in ER‐positive MCF‐7 cells, and this decrease was greatest in cells cultured in 10% charcoal‐stripped FBS. Time‐course experiments indicated that 17β‐estradiol decreased AOX1 expression in a time‐dependent manner with a maximum effect occurring after 72 h treatment. Non‐toxic concentrations (as assessed by a cell viability assay) of endogenous estrogens (estrone, 17β‐estradiol, estriol, and estetrol), synthetic estrogens (ethinylestradiol), and phytoestrogens (daidzein and genistein) decreased the expression of AOX1 (by 40–76%) and other known 17β‐estradiol‐regulated genes (SMAD3 and HBP1) and induced known ER‐regulated genes (GREB1 and TFF1) in MCF‐7 cells. Concentration‐response experiment indicated that estrone, 17β‐estradiol, estriol, and estetrol decreased AOX1 expression with EC50 value of 22.5 pM, 1.4 pM, 9.1 pM, and 513.9 pM, respectively, which are physiologically‐relevant concentrations in humans, suggesting that physiological levels of estrogens suppress AOX1 expression. By comparison, ethinylestradiol, daidzein, and genistein decreased AOX1 level with EC50 value of 1.3 pM, 94.6 nM, and 19.4 nM, respectively, which are clinically‐relevant concentrations after administration of the drug or phytoestrogen supplements. The EC50 values for AOX1 suppression and ERα activation by the agonists were well‐correlated. Non‐toxic concentrations of fulvestrant, a ER antagonist, negated both AOX1 suppression and TFF1 induction by estrogens, indicating that ER regulates AOX1 gene. ERα was the major ER isoform expressed in MCF‐7 cells, whereas ERβ was low or negligible, indicating that AOX1 suppression by ER agonists occurred via ERα, but not ERβ, activation in MCF‐7 cells. Suppression of AOX1 by estrogens did not occur in ER‐negative HepG2 human hepatocellular carcinoma cells. In conclusion, ethinylestradiol and 17β‐estradiol are the most potent AOX1 suppressors, followed by estriol, estrone, estetrol, genistein, and daidzein, and the suppression of AOX1 occurs by ERα activation. This is the first study showing hormonal regulation of AOX1 expression and provide insights into potential drug‐chemical interactions. Our findings also imply that interindividual...
Renal angiomyolipomas (AMLs), formerly known as PEComas (tumors showing perivascular epithelioid cell differentiation) are common benign renal masses composed of a varying ratio of fat, blood vessels, and smooth muscles. They are largely asymptomatic and diagnosed incidentally on imaging.The adipose tissue content is the factor that gives AMLs their characteristic appearance on imaging and makes them easily identifiable. However, the fat-poor or fat-invisible varieties, which are difficult to differentiate radiologically from renal cell carcinomas (RCCs), present a diagnostic challenge. It is thus essential to establish the diagnosis and identify the atypical and hereditary cases as they require more intense surveillance and management due to their potential for malignant transformation.Multiple management options are available, ranging from conservative approach to embolization and to the more radical option of nephrectomy. While the indications for intervention are relatively clear and aimed at a rather small cohort, the protocol for follow-up of the remainder of the cohort forming the majority of cases is not well established. The surveillance and discharge policies therefore vary between institutions and even between individual practitioners. We have reviewed the literature to establish an optimum management pathway focusing on the typical AMLs.
Inguinoscrotal bladder hernias are still a rare finding in clinical practice. The present report describes the case of a patient who presented with minimal symptoms and was found to have an inguinoscrotal bladder hernia that was confirmed on CT. The CT findings include very clear and interesting images, and the case is discussed further.
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