Hepatitis B virus X protein targets Bcl-2 proteins to increase intracellular calcium, required for virus replication and cell death induction.
AuthorsGeng X, Huang C, Qin Y, McCombs JE, Yuan Q, Harry BL, Palmer AE, Xia NS, Xue D,
JournalProc Natl Acad Sci U S A
PubMed ID23091012
'Infection with the hepatitis B virus (HBV) promotes the development of hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) and is a leading cause of morbidity and mortality worldwide. HBV X protein (HBx) is an important effector for HBV pathogenesis, but its cellular targets and acting mechanisms remain elusive. We show here ... More
Live attenuated lentivirus infection elicits polyfunctional simian immunodeficiency virus Gag-specific CD8+ T cells with reduced apoptotic susceptibility in rhesus macaques that control virus replication after challenge with pathogenic SIVmac239.
AuthorsGenescà M, Rourke T, Li J, Bost K, Chohan B, McChesney MB, Miller CJ,
JournalJ Immunol
PubMed ID17878372
'HIV-specific CD8+ T cells that secrete multiple cytokines in response to Ag stimulation are associated with the control of virus replication during chronic HIV infection. To determine whether the presence of polyfunctional CD8+ T cell responses distinguishes protected and unprotected monkeys in a live attenuated lentivirus model, SIV Gag peptide-specific ... More
A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction.
AuthorsZemans RL, Briones N, Young SK, Malcolm KC, Refaeli Y, Downey GP, Worthen GS,
JournalJ Immunol Methods
PubMed ID19010330
'Neutrophils are a critical component of the innate immune response to invading microbial pathogens. However, an excessive and/or prolonged neutrophil response can result in tissue injury that is thought to underlie the pathogenesis of various inflammatory diseases. The development of novel therapeutic strategies for inflammatory diseases depends on an improved ... More
Modified vaccinia virus Ankara-based vaccine vectors induce apoptosis in dendritic cells draining from the skin via both the extrinsic and intrinsic caspase pathways, preventing efficient antigen presentation.
'Dendritic cells (DC) are potent antigen-presenting cells and central to the induction of immune responses following infection or vaccination. The collection of DC migrating from peripheral tissues by cannulation of the afferent lymphatic vessels provides DC which can be used directly ex vivo without extensive in vitro manipulations. We have ... More
The phosphatidylinositol-3-kinase inhibitor NVP-BKM120 overcomes resistance signals derived from microenvironment by regulating the Akt/FoxO3a/Bim axis in chronic lymphocytic leukemia cells.
AuthorsRosich L, Saborit-Villarroya I, López-Guerra M, Xargay-Torrent S, Montraveta A, Aymerich M, Villamor N, Campo E, Pérez-Galán P, Roué G, Colomer D,
Journal
PubMed ID23850807
Phosphatidylinositol-3-kinase pathway is constitutively activated in chronic lymphocytic leukemia mainly due to microenvironment signals, including stromal cell interaction and CXCR4 and B-cell receptor activation. Because of the importance of phosphatidylinositol-3-kinase signaling in chronic lymphocytic leukemia, we investigated the activity of the NVP-BKM120, an orally available pan class I phosphatidylinositol-3-kinase inhibitor. ... More
Nitroreductase, a near-infrared reporter platform for in vivo time-domain optical imaging of metastatic cancer.
AuthorsMcCormack E, Silden E, West RM, Pavlin T, Micklem DR, Lorens JB, Haug BE, Cooper ME, Gjertsen BT,
JournalCancer Res
PubMed ID23233739
The ability to visualize reporter gene expression in vivo has revolutionized all facets of biologic investigation and none more so than imaging applications in oncology. Near-infrared reporter gene imaging may facilitate more accurate evaluation of chemotherapeutic response in preclinical models of orthotopic and metastatic cancers. We report the development of ... More
Drug resistance to inhibitors of the human double minute-2 E3 ligase is mediated by point mutations of p53, but can be overcome with the p53 targeting agent RITA.
The human double minute (HDM)-2 E3 ubiquitin ligase plays a key role in p53 turnover and has been validated preclinically as a target in multiple myeloma (MM) and mantle cell lymphoma (MCL). HDM-2 inhibitors are entering clinical trials, and we therefore sought to understand potential mechanisms of resistance in lymphoid ... More
Contact-dependent interference with invariant NKT cell activation by herpes simplex virus-infected cells.
AuthorsBosnjak L, Sahlström P, Paquin-Proulx D, Leeansyah E, Moll M, Sandberg JK,
JournalJ Immunol
PubMed ID22581860
Invariant CD1d-restricted NKT (iNKT) cells play important roles in generating protective immune responses against infections. In this study, we have investigated the role of human iNKT cells in HSV-1 infection and their interaction with epidermal keratinocytes. These cells express CD1d and are the primary target of the virus. Keratinocytes loaded ... More
Stroma-dependent apoptosis in clonal hematopoietic precursors correlates with expression of PYCARD.
The role of the marrow microenvironment in the pathophysiology of myelodysplastic syndromes (MDSs) remains controversial. Using stromal/hematopoietic cell cocultures, we investigated the effects of stroma-derived signals on apoptosis sensitivity in hematopoietic precursors. The leukemia-derived cell line KG1a is resistant to proapoptotic ligands. However, when cocultured with the human stromal cell ... More