Don M Benson

..These findings suggest that IPH2101 is safe and tolerable at doses that achieve full inhibitory KIR saturation, and this approach warrants further development in MM. This trial was registered at www.clinicaltrials.gov as #NCT00552396...

..A novel small molecular STAT3 inhibitor, FLLL32 was specifically designed from dietary agent, curcumin to inhibit constitutive STAT3 signaling in multiple myeloma, glioblastoma, liver cancer, and colorectal cancer cells...

..These mechanistic, preclinical data support the use of a combination of IPH2101 and lenalidomide in a phase 2 trial for MM...

..BCV and HDM confer similar long-term outcomes with similar toxicity profiles as conditioning regimens prior to autologous stem cell transplant in patients with MM...

..Our data extrapolate on prior work and expand on ongoing controversies about optimal induction regimens for patients with MM planned for subsequent HDC/SCT and optimal sequencing of therapies...

..These findings suggest potentially novel roles for sFLC in patients with MM with an intact M protein receiving novel agent-based induction strategies followed by HDC/SCT...

..Day 100 and overall non-relapse mortality rate was 12.5% and 25%, respectively. Allogeneic HSCT appears feasible in patients with transformed FL and is associated with acceptable treatment-related mortality and low relapse rates...

..A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered...

..At a median follow-up of 38 months, 3-yr progression-free survival following autologous HSCT was 40%. The 3-yr overall survival was 52%. The cumulative incidence of relapse and non-relapse mortality rate was 41% and 25%, respectively...

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..We hypothesized this lead compound would specifically inhibit the STAT3 signaling pathway to induce apoptosis in melanoma cells...

..Furthermore, LLL12 significantly blocked tumor growth of MM cells in mouse model. Our results indicate that LLL12 blocks constitutive STAT3 and IL-6 induced STAT3 signaling and may be a potential therapeutic agent for MM...

..These data show that although curcumin can induce apoptosis of melanoma cells, it can also adversely affect the responsiveness of immune effector cells to clinically relevant cytokines that possess antitumor properties...

..Given the outcomes seen here in the setting of PD, such patients should proceed with transplant only in the setting of investigational therapy...

..The preclinical combination of lenalidomide with the mTOR inhibitor CCI-779 has displayed synergy in vitro and represents a novel combination in MM...

..To determine the safety, toxicity, and immune modulation of this combination of cytokines in vivo, we conducted a first-in-man phase I study...

..We describe the clinical presentation and diagnostic and therapeutic approach to these cases, highlighting the successful preoperative use of imatinib mesylate (Gleevec) followed by prostatectomy...

..The present review summarizes the current understanding of the NK cell versus MM effect and characterizes therapeutic interventions that exert anti-MM efficacy via NK cell function against the disease...

..Thus, IL-15 signaling and NKp46 may be useful targets in the treatment of patients with T-LGL or NKT leukemia...

..The data suggest that the ability of NE to regulate the expression of VEGF is not limited to solid epithelial tumors and suggests a possible regulatory role of catecholamine stress hormones in MM progression...

..These studies reveal an effective method to detect ERK activation in immune cells and demonstrate that IL-2 activates ERK in a subset of NK cells and monocytes but not T cells...

..The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells...

..These findings provide strong support for further clinical development of XmAb5574 as both a monotherapy and in combination with lenalidomide for the therapy of CLL and related CD19(+) B-cell malignancies...

..The results suggest that these miRNAs are positive regulators of p53 and that their downregulation plays a key role in MM development...

..Thus, Hlx expression in activated NK cells temporally controls and limits the monokine-induced production of IFN-gamma, in part through the targeted depletion of STAT4...

..Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-gamma production...

..Collectively, our data suggest that CD94 is an Ag that can be used to identify functionally distinct NK cell subsets in mice and could also be relevant to late-stage mouse NK cell development...

..CONCLUSIONS: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL...