APRIL is overexpressed in cancer: link with tumor progression

<p>Abstract</p> <p>Background</p> <p>BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.</p> <p>Methods</p> <p>We compared the expression of <it>BAFF, APRIL, TACI and BAFF-R </it>gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.</p> <p>Results</p> <p>We found significant overexpression of <it>TACI </it>in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, <it>BAFF and APRIL </it>are overexpressed in many cancers and we show that <it>APRIL </it>expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.</p> <p>Conclusion</p> <p>Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.</p

Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.

Parenteral delivery of long-Acting glucagon-like peptide-1 (GLP-1) mimetics has received much attention as a therapeutic option for diabetes. However, cell therapy-based GLP-1 treatments may provide a more physiological regulation of blood glucose. The present study assessed the effects of chronic GLP-1 delivery by cell therapy, using the GLP-1-secreting GLUTag cell line, in normoglycemic and streptozotocin-induced diabetic mice. GLUTag cell aggregates were transplanted into the subscapular region of mice. Over 30 days, cellular transplantation gave rise to encapsulated and well-vascularized growths, which contained immunoreactive GLP-1. Cell implantation was well tolerated and had no appreciable metabolic effects in normal mice. However, transplantation significantly (P<0.001) countered excessive food and fluid intake in diabetic mice and maintained normal body weight. Circulating glucose (P<0.01) and glucagon (P<0.05) were significantly reduced and plasma insulin and GLP-1 dramatically increased. This was associated with significantly (P<0.01) improved glucose tolerance in diabetic mice. Histological examination of the pancreata of these mice revealed elevations (P<0.001) in islet and β-cell area, with reduced (P<0.001) -cell area. Increased β-cell mass reflected the enhanced proliferation relative to apoptosis. These studies emphasize the potential of chronic GLP-1 delivery by cell therapy as a potential therapeutic option for diabetes

Case Report Mycobacterium haemophilum Masquerading as Leprosy in a Renal Transplant Patient

Opportunistic infections following immunosuppression in solid organ transplant (SOT) patients are common complications with the skin being a common sight of infection. Nontuberculous mycobacteria (NTM) are rare but potential causes of skin infection in SOT patients. We present a case of an adult male immunosuppressed following renal transplantation who presented with an asymptomatic rash for several months. The patient&apos;s skin eruption consisted of erythematous papules and plaques coalescing into an annular formation. After failure of the initial empiric therapy, a punch biopsy was performed that demonstrated nerve involvement suspicious for Mycobacterium leprae. However, culture of the biopsy specimen grew acid-fast bacilli that were subsequently identified as M. haemophilum. His rash improved after a prolonged course of clarithromycin and ciprofloxacin. Both organisms are potential causes of opportunistic skin infections and can be difficult to distinguish with similar predilection for skin and other biochemical and genetic similarities. Ultimately they can be distinguished with culture as M. haemophilum will grow in culture and M. leprae will not. This case was unique due to nerve involvement on biopsy which is classically seen on biopsies of leprosy