Systemic delivery of Salmonella typhimurium transformed with IDO shRNA enhances intratumoral vector colonization and suppresses tumor growth.

Generating antitumor responses through the inhibition of tumor-derived immune suppression represents a promising strategy in the development of cancer immunotherapeutics. Here, we present a strategy incorporating delivery of the bacterium Salmonella typhimurium (ST), naturally tropic for the hypoxic tumor environment, transformed with a small hairpin RNA (shRNA) plasmid against the immunosuppressive molecule indoleamine 2,3-dioxygenase 1 (shIDO). When systemically delivered into mice, shIDO silences host IDO expression and leads to massive intratumoral cell death that is associated with significant tumor infiltration by polymorphonuclear neutrophils (PMN).

Survivin the battle against immunosuppression.

Improving on the limited success of cancer immunotherapy requires new approaches to inhibit immunosuppressive pathways initiated by tumor cells to "escape" protective immunity. One unique approach utilizes Salmonella for systemic delivery of inhibitory RNA, targeting the immunosuppressive molecule Stat3, and a Survivin vaccine to suppress growth of aggressive murine tumors.

Number and phenotype of rheumatoid arthritis patients' CD4+CD25hi regulatory T cells are not affected by adalimumab or etanercept.

Objective: To analyse the therapeutic effects of etanercept (ETA) or adalimumab (ADA) on the numbers and phenotypes of CD4+CD25hi Tregs in RA patients.

Methods: RA patients received ADA (n = 28) or ETA (n = 20) and stable-dose MTX or LEF. Therapeutic responses were assessed with the 28-joint DAS (DAS-28) criteria after 12 weeks of treatment.

Enhancement of cancer vaccine therapy by systemic delivery of a tumor-targeting Salmonella-based STAT3 shRNA suppresses the growth of established melanoma tumors.

Cancer vaccine therapies have only achieved limited success when focusing on effector immunity with the goal of eliciting robust tumor-specific T-cell responses. More recently, there is an emerging understanding that effective immunity can only be achieved by coordinate disruption of tumor-derived immunosuppression. Toward that goal, we have developed a potent Salmonella-based vaccine expressing codon-optimized survivin (CO-SVN), referred to as 3342Max.

Characterization of the transcriptional signature of C/EBPbeta isoforms (LAP/LIP) in Hep3B cells: implication of LIP in pro-survival functions.

Background & Aims: C/EBPbeta is an important mediator of several cellular processes, such as differentiation, proliferation, and survival of hepatic cells. However, a complete catalog of the targets of C/EBPbeta or the mechanism by which this transcription factor regulates certain liver-dependent pathways has not been clearly determined. Two major natural isoforms of this transcription factor exist: the liver-enriched activating protein (LAP) and the liver-enriched inhibitory protein (LIP), a functional LAP antagonist.

Cutting edge: CD4-independent development of functional FoxP3+ regulatory T cells.

The CD4 coreceptor is mandatory for the differentiation and function of conventional MHC class II-restricted T cells, but little is known about its contribution in regulatory T cells (Tregs). We thus investigated the Treg compartment in mice lacking CD4. CD3+CD8-FoxP3+ cells were readily detected in the periphery of CD4(-/-) mice, where their percentages were even increased as compared with wild-type animals.

Expression and detection strategies for an scFv fragment retaining the same high affinity than Fab and whole antibody: Implications for therapeutic use in prion diseases.

Since antibodies currently constitute the most rapidly growing class of human therapeutics, the high-yield production of recombinant antibodies and antibody fragments is a real challenge. Using as model a monoclonal antibody directed against the human prion protein that we prepared previously and tested for its therapeutic value, we describe here experimental conditions allowing the production of large quantities (up to 35 mg/l of bacterial culture) of correctly refolded and totally functional single chain fragment variable (scFv). These quantities were sufficient to characterize the binding properties of this small recombinant fragment through in vitro and ex vivo approaches.

Hardiness, stress, and burnout among intensive care nurses.

The purposes of this study were to determine whether hardiness is a predictor of burnout and whether it can buffer the effect of stress on burnout. Thirty-one registered nurses who work in intensive care units completed the Hardiness test, the Nursing Stress scale, and the Tedium scale. Descriptive statistics, correlational statistics, t tests, analysis of variance, and hierarchical multiple regressions were used to analyze the data.

Use of morphine sulfate (MS Contin) in patients with burns: a pilot study.

Morphine sulfate (MS Contin), a proven analgesic in the treatment of cancer pain and chronic benign pain, seems to be a good analgesic for the treatment of burn pain. MS Contin is morphine sulfate incorporated in a wax cellulose matrix delivery system. This wax cellulose delivery system gives MS Contin its duration of action.