Elevated MRP4/ABCC4 expression is found in malignant compared to benign prostate tissue while lower MRP4/ABCC4 expression is seen after AA. Furthermore, MRP4/ABCC4 is upregulated by androgen and downregulated by anti-androgen treatment in vitro potentially through an indirect mode of action. These data strongly suggest that MRP4/ABCC4 is an androgen-regulated gene important in the progression to PC and may be a potential drug target.

SYNOPSISPatients who are being treated with warfarin may sometimes be prescribed or buy antiplatelet drugs, such as aspirin. As warfarin and antiplatelet drugs increase the risk of bleeding, their combination can put patients at risk of a major haemorrhage. This risk may be further increased by the patient's age and other illnesses. A thorough history is therefore important in assessing the risk of haemorrhage. Patients need to be informed of the risk and should be encouraged to have their international normalised ratio checked regularly.

Multiple myeloma (MM) remains incurable despite high-dose chemotherapy, autologous stem cell transplants and novel agents. Even with the improved survival of MM patients treated with novel agents, including bortezomib (Bz), the therapeutic options in relapsed/refractory MM remain limited. The majority of MM patients eventually develop resistance to Bz, although the mechanisms of the resistance are poorly understood. Methods: Lysosomal associated membrane protein 2A (LAMP2A) mRNA and protein expression levels were assessed in ex vivo patient samples and a Bz-resistant MM cell line model by in real-rime PCR, western blotting and immunohistochemistry. In vitro modelling of chaperone-mediated autophagy (CMA) activity in response to ER stress were assessed by western blotting and confocal microscopy. The effects of CMA inhibition on MM cell viability and Bz sensitivity in MM cells were assessed by Annexin V/7AAD apoptosis assays using flow cytometry. Results: In this study, there is evidence that CMA, a chaperone-mediated protein degradation pathway, is upregulated in Bz-resistant MM and the inhibition of CMA sensitises resistant cells to Bz. The protein levels of LAMP2A, the rate-limiting factor of the CMA pathway, are significantly increased in MM patients resistant to Bz and within our Bz-resistant cell line model. Bz-resistant cell lines also possessed higher basal CMA activity than the Bz-sensitive parent cell line. In MM cell lines, CMA activity was upregulated in response to ER stress induced by Bz. The inhibition of CMA sensitises Bz-resistant cells to Bz and the combination of CMA inhibition and Bz in vitro had a more cytotoxic effect on myeloma cells than Bz alone. Conclusion: In summary, the upregulation of CMA is a potential mechanism of resistance to Bz and a novel target to overcome Bz-resistant MM.

Summary. We describe a large Syrian±Lebanese family who clinically manifest X-linked thrombocytopenia (XLT). To date, five family members have undergone splenectomy with rapid and sustained normalization of their platelet numbers. Genomic analysis demonstrated that affected men in this cohort had the missense C168T (Thr45Met) mutation in exon 2 of the Wiskott±Aldrich Syndrome protein (WASp) gene. Exon 2 is the commonest site for mutations associated with XLT and mild forms of WAS, and the C168T missense mutation is the most frequent. Detection of this mutation by restriction enzyme digestion provides an efficient screening test for prompt identification and for assessment of female carrier status.

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