Therapeutic outcome of cyclic VAD (vincristine, doxorubicin and dexamethasone) therapy in primary systemic AL amyloidosis patients

ArticleINTERNAL MEDICINE. 47(17):1517-1522(2008)journal articl

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.Comment: 45 pages 5 figure

Surgical removal of amyloid-laden lymph nodes: a possible therapeutic approach in a primary systemic AL amyloidosis patient with focal lymphadenopathy

We report a patient with primary systemic AL amyloidosis who suffered from remarkable bilateral cervical lymphadenopathy. Intensive chemotherapies, including two cycles of high-dose melphalan with autologous peripheral blood stem cell transplantation, were insufficiently effective for both the lymphadenopathy and amyloidogenic IgG lambda lambda-type M-protein in serum, but the patient showed complete haematological remission after extensive surgical removal of enlarged lymph nodes that had massive depositions of lambda lambda-type immunoglobulin light chain-derived amyloid. Lymphadenectomy may be a possible therapeutic approach with regard to both cosmetic and haematological aspects in primary systemic AL amyloidosis patients with focal lymphadenopathy.ArticleAMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS. 18(2):79-82 (2011)journal articl

Radiation hardness studies of a 130 nm Silicon Germanium BiCMOS technology with a dedicated ASIC

We present the radiation hardness studies on the bipolar devices of the 130 nm 8WL Silicon Germanium (SiGe) BiCMOS technology from IBM. This technology has been proposed as one of the candidates for the Front-End (FE) readout chip of the upgraded Inner Detector (ID) and the Liquid Argon Calorimeter (LAr) of the ATLAS Upgrade experiment. After neutron irradiations, devices remain at acceptable performances at the maximum radiation levels expected in the Si tracker and LAr calorimeter