Selective killing of Burkitt's lymphoma cells by mBAFF-targeted delivery of PinX1

Increased expression of BAFF (B cell-activating factor belonging to the TNF family) and its receptors has been identified in numerous B-cell malignancies. A soluble human BAFF mutant (mBAFF), binding to BAFF receptors but failing to activate B-lymphocyte proliferation, may function as a competitive inhibitor of BAFF and may serve as a novel ligand for targeted therapy of BAFF receptor-positive malignancies. Pin2/TRF1-interacting protein X1 (PinX1), a nucleolar protein, potently inhibits telomerase activity and affects tumorigenicity. In this study, we generated novel recombinant proteins containing mBAFF, a polyarginine tract 9R and PinX1 (or its C/N terminal), to target lymphoma cells. The fusion proteins PinX1/C–G4S–9R–G4S–mBAFF and PinX1/C–9R–mBAFF specifically bind and internalize into BAFF receptor-positive cells, and subsequently induce growth inhibition and apoptosis. The selective cytotoxicity of the fusion proteins is a BAFF receptor-mediated process and depends on mBAFF, PinX1/C and 9R. Moreover, the fusion proteins specifically kill BAFF receptor-expressing Burkitt's lymphoma (BL) cells by inhibiting telomerase activity and the consequent shortening of telomeres. Therapeutic experiments using PinX1C–G4S–9R–G4S–mBAFF in severe combined immunodeficient (SCID) mice implanted with Raji cells showed significantly prolonged survival times, indicating the in vivo antitumor activity of the fusion protein. These results suggest the potential of PinX1/C–G4S–9R–G4S–mBAFF in targeted therapy of BL

Uterine leiomyosarcoma and pyometra in a dog

A seven-year-old entire female, mixed-breed dog, weighing 19 kg, was presented with a 2-day history of abdominal distension, reduced appetite and general dullness. Abdominal palpation revealed a large mass. Radiography showed a large mass occupying the left mid-abdominal area and convoluted loops of tubular fluid opacity occupying the right mid-abdominal area. Ultrasonography revealed a large heterogeneous mass with an anechoic area and some hyperechoic foci, indicative of calcification, in the mid-abdominal area. Furthermore, hypoechoic areas were found in the middle and caudal abdominal area and were presumed to be the fluid-filled uterine horns. At laparotomy, a 10 center dot 5x14 center dot 5-cm firm mass was found in the uterine body, while the uterine horns were filled with a thick red-brownish exudate; ovariohysterectomy was subsequently performed. A diagnosis of uterine leiomyosarcoma associated with pyometra was established by histopathology and immunohistochemistry