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Objective: To investigate the expression profile of potential therapeutic biomarkers in plasma cell myeloma (PCM) by multicolor flow cytometry analysis.Methods: Bone marrow (BM) specimens were collected consecutively and analyzed using a routine PCM panel (CD38/CD138/CD45/CD19/CD20/CD28/CD56/CD117, cyto-kappa/lambda). The specimens were further assessed for CD30, CD44, CD49d, CD70, CD105, and CD184 expression in cases containing a substantial number of neoplastic plasma cells.Results: Totally, 101 patient BM samples were assessed, including 58 men and 43 women, with a median age of 64 years (34-89). Twenty-nine patients had newly diagnosed/untreated PCM, 40 had persistent/residual disease undergoing various therapies and 32 had relapsed disease. CD49d was expressed brightly and uniformly in all 45 patients tested. Expression of CD44 and CD184 was more variable with a median percentage of 77% (1-100) and 65% (5-100) respectively. Using an arbitrary 20% cutoff, CD44 was positive in 74 (73%) and CD184 in 92 (91%) cases with a mean fluorescence intensity ratio of 42.8 and 21.4. A higher CD44 expression was observed in patients with recurrent/persistent disease (P 5 0.028). Additionally, both CD44 (P 5 0.002) and CD184 (P 5 0.026) showed higher expressions in CD117-positive cases, but there was no correlation with cytogenetic groups. The CD30, CD70, and CD105 were expressed very infrequently in PCM, with a median expression of 0.2%, 0.2%, and 0.4% respectively.Conclusions: CD49d, CD44, and CD184, are highly expressed in PCM. CD49d expression is bright and uniform, whereas CD44 and CD184 are more heterogeneous. In contrast, surface CD30, CD70, and CD105 are infrequent. These data provide useful preclinical information for the design of potential novel targeted therapies in PCM patients. Despite of recent advances (1,2), plasma cell myeloma (PCM) remains an incurable disease and new approaches that induce long-term tumor regression and improve disease outcome are needed. Immunotherapy that targets tumor-associated antigens (TAAs) has been shown to be an effective treatment approach in cancer therapy, particularly for diseases re-emerging after therapy, and a number of new agents have been developed. Brentuximab vedotin, a monoclonal antibody (mAb)-monomethyauristatin E conjugate that targets CD30, was recently approved by the Federal Drug Administration for use in patients with re-

BackgroundLipocalin-2 (LCN2) is an indicator of the severity of lupus nephritis (LN) and plays a pivotal role in immune responses, but it is not known if its effect on LN pathogenesis derives from regulating the immune imbalance of T lymphocyte subsets.MethodsThe expression of LCN2 in T cells and kidneys was assessed in renal biopsies from patients with LN. We investigated the relationship between LCN2 levels and development of LN and systemic illness by injecting anti-LCN2 antibodies into MRL/lpr mice and analyzing pristane-treated LCN2−/− mice.ResultsLCN2 is highly expressed in CD4+ T cells and in renal tissues, and is associated with severe renal damage in patients with LN and in mice with experimental lupus. LCN2 promotes IFN-γ overexpression in CD4+ T cells through the IL-12/STAT4 pathway in an autocrine or paracrine manner. Both neutralization of LCN2 in MRL/lpr mice and genetic depletion of LCN2 in pristane-induced lupus mice greatly ameliorate nephritis. The frequency and number of splenic and renal Th1 cells decrease in proportion to LN disease activity. Conversely, administration of LCN2 exacerbates the disease with significantly higher renal activity scores and increased numbers of Th1 cells.ConclusionsLCN2 plays a crucial role in Th1 cell differentiation, and may present a potential therapeutic target for LN.

The ignition phenomena of 2,5-dimethylfuran (DMF), 2-methylfuran (MF), and furan are systematically investigated. Ignition delay times are measured over the temperature range of 1150–2010 K and pressures of 1.2, 4, and 16 bar for lean, stoichiometric, and rich DMF/Ar/O2 mixtures. For comparison, similar measurements for stoichiometric MF/O2/Ar and furan/O2/Ar are also conducted. Through a multi-regression analysis, the measured ignition delay times of DMF are fitted empirically in an Arrhenius-like form as a function of experimental parameters. It is observed that, when the fuel concentration, pressure, temperature, and equivalence ratio are kept constant, furan has the longest ignition delay times, while the reactivity of DMF and MF strongly depends upon the temperature. The experimental ignition delay times are compared to model predictions of Somers et al. and Liu et al. Both models could give qualitative agreement with DMF and MF ignition data, while the model of Somers et al. provides better quantitative agreement. Modifications have been made to the model of Somers et al. to agree better with present ignition delay times and other sets of furan data. Further reaction pathway and sensitivity analysis are carried out to understand their combustion kinetics.