A Case Report: Pseudoangiomatous Stromal Hyperplasia Tumor Presenting as a Palpable Mass.

We report a case of woman with a palpable lump on her left breast. On mammography, a huge mass located between the inner and the outer inferior breast quadrants of the left breast was found. The ultrasound examination realized later revealed a heterogeneous mass with smooth and lobulated borders. An MRI was also performed, showing an oval mass with heterogeneous areas of enhancement. Finally, a core biopsy under sonographic guidance revealed a pseudoangiomatous stromal hyperplasia of the breast.

Profound differences in the transport of steroids by two mouse P-glycoproteins.

There are two mouse P-glycoproteins that convey multidrug resistance, mdr1 (mdr1b) and mdr3 (mdr1a), by serving as drug efflux transporters. These proteins each exhibit tissue-specific expression. There is relatively high expression of the mdr1 gene in the adrenals, the site of glucocorticoid and mineralocorticoid hormone synthesis. We previously demonstrated that mdr1 gene expression in murine thymoma cells correlated well with a decrease in their ability to accumulate the glucocorticoid dexamethasone and their increased resistance to glucocorticoid-induced apoptosis. Additional evidence is presented that supports the proposition that the mdr1 P-glycoprotein can transport glucocorticoids. Specifically, introduction and expression of the mouse mdr1 gene in the human HEK 293T cell line conveys a multidrug resistance phenotype that includes a reduced capacity to accumulate dexamethasone. Moreover, isolation of additional mdr1-expressing mouse lymphoid cells, without using steroids in the selection, confirms the linkage between multidrug resistance conveyed by the mdr1 P-glycoprotein and resistance to dexamethasone. In contrast, two newly isolated lymphoid lines, selectively expressing the mdr3 gene, were not found to have increased dexamethasone resistance or the capacity to accumulate significantly lower levels of hormone. The results support the concept that the mdr1 and mdr3 P-glycoproteins may serve alternative roles in the transport of endogenous substances such as steroids.

Identification of P-glycoprotein mutations causing a loss of steroid recognition and transport.

P-glycoproteins transport a wide variety of hydrophobic compounds out of cells. While the diversity of transported molecules suggests a mechanism involving broad specificity, there is evidence of significant discrimination within given classes of molecules. One example of this behavior is transport of corticosteroids by the murine mdr1 P-glycoprotein. The presence of hydroxyl groups, associated with specific steroid carbon atoms, regulates the ability of corticosteroids to be transported. This specificity is demonstrated here by experiments measuring the ability of steroids to inhibit drug transport. The results indicate that a keto oxygen associated with the 3- and 20-carbon atoms, as well as a 17-carbon hydroxyl group, each acts to enhance steroidal P-glycoprotein inhibitory activity. Moreover, inhibitory steroids can be used for directed selection of variant cells, expressing mutated P-glycoproteins with a severely impaired ability to transport dexamethasone. The five mutations, reported here, are located within transmembrane domains 4-6, proximal to the cytoplasmic interface. The altered P-glycoproteins exhibit reduced capacity to be inhibited by specific steroids, suggesting decreased capacity to bind these molecules avidly. Studies comparing the relative inhibitory activity of a series of steroids indicate that these mutations alter recognition of the 17alpha-hydroxyl group and the 20-keto oxygen atom.