Multicenter phase I/II study of chemoradiotherapy with high-dose CDDP for head and neck squamous cell carcinoma in Japan

Recent data indicated that concurrent chemoradiotherapy (CCRT) using high dose cisplatin (CDDP) is the most useful treatment for advanced head and neck squamous cell carcinoma (SCC). Regarding the dose of CDDP, 100mg/m2 is most recommended in Western countries. However, in terms of a balance of efficacy and adverse events, appropriate dose of cytotoxic drugs such as CDDP may be different among the different ethnic groups. In this multicenter phase I/II study, we aimed to identify the optimal dose of CDDP in CCRT for patients with advanced head and neck SCC in the Japanese.

http://ift.tt/2IDWZAP

Severe immunodeficiency associated with acute lymphoblastic leukemia and its treatment

Immunodeficiency can be associated with acute lymphoblastic leukemia (ALL) in various ways. ALL can be a feature of various primary immunodeficiencies including, but not limited, to X-linked agammaglobulinemia, chromosomal breakage disorders such as ataxia telangiectasia, and GATA2 haploinsufficiency.1–4 ALL also can be secondary to an infection such as human immunodeficiency virus. A congenital leukemia such as ALL can lead to abnormal newborn screening results for severe combined immunodeficiency.

http://ift.tt/2GaGfDf

Lysine Deacetylases and Regulated Glycolysis in Macrophages

Publication date: Available online 19 March 2018
Source:Trends in Immunology
Author(s): Melanie R. Shakespear, Abishek Iyer, Catherine Youting Cheng, Kaustav Das Gupta, Amit Singhal, David P. Fairlie, Matthew J. Sweet
Regulated cellular metabolism has emerged as a fundamental process controlling macrophage functions, but there is still much to uncover about the precise signaling mechanisms involved. Lysine acetylation regulates the activity, stability, and/or localization of metabolic enzymes, as well as inflammatory responses, in macrophages. Two protein families, the classical zinc-dependent histone deacetylases (HDACs) and the NAD-dependent HDACs (sirtuins, SIRTs), mediate lysine deacetylation. We describe here mechanisms by which classical HDACs and SIRTs directly regulate specific glycolytic enzymes, as well as evidence that links these protein deacetylases to the regulation of glycolysis-related genes. In these contexts, we discuss HDACs and SIRTs as key control points for regulating immunometabolism and inflammatory outputs from macrophages.



http://ift.tt/2FV9jex

“That’s enough now!”: A prospective study of the effects of maternal control on children’s snack intake

Publication date: 1 July 2018
Source:Appetite, Volume 126
Author(s): Samantha B. Boots, Marika Tiggemann, Nadia Corsini
The aim of this study was to investigate maternal feeding strategies as prospective predictors of young children's snack intake. Participants were 252 mothers of children aged 3–11 years old who completed questionnaire measures of parent feeding strategies (Restriction and Covert Control) and reported on their child's healthy and unhealthy snack intake at two time points separated by three years. Longitudinal regression models showed no prediction of healthy snack food intake. However, Time 1 parental restrictive feeding predicted greater unhealthy snack intake at Time 2, while Time 1 covert feeding strategies predicted lower unhealthy snack intake at Time 2. Structural equation modeling showed that these associations were independent of known covariates that influence children's snack intake (child and parent weight, education level and SES). The results provide longitudinal evidence for the negative impact of restrictive parent feeding strategies on children's snack intake and highlight the importance of dissuading parents from using this type of feeding control. Instead, parents should be encouraged to use more covert feeding strategies that are associated with less unhealthy snack intake over the longer term.



http://ift.tt/2FPLQzm

NKG2D-MICA Interaction: A Paradigm Shift in Innate Recognition [PILLARS OF IMMUNOLOGY]

http://ift.tt/2G7MFTy

Blockade of Host {beta}2-Adrenergic Receptor Enhances Graft-versus-Tumor Effect through Modulating APCs [TRANSPLANTATION]

Allogeneic hematopoietic cell transplantation is a potential curative therapy for hematologic malignancies. Host APCs are pivotal to the desired graft-versus-tumor (GVT) effect. Recent studies have shown that β2-adrenergic receptor (β2AR) signaling can have an important impact on immune cell function, including dendritic cells (DCs). In this article, we demonstrate that pretreatment of host mice with a β2AR blocker significantly increases the GVT effect of donor CD8⁺ T cells by decreasing tumor burden without increasing graft-versus-host disease. β2AR-deficient host mice have significantly increased effector memory and central memory CD8⁺ T cells and improved reconstitution of T cells, including CD4⁺Foxp3⁺ regulatory T cells. Notably, β2AR deficiency induces increased CD11c⁺ DC development. Also, β2AR-deficient bone marrow–derived DCs induce higher CD8⁺ T cell proliferation and improved tumor killing in vitro. Metabolic profiling shows that β2AR deficiency renders DCs more immunogenic through upregulation of mTOR activity and reduction of STAT3 phosphorylation. Altogether, these findings demonstrate an important role for host β2AR signaling in suppressing T cell reconstitution and GVT activity.

http://ift.tt/2FLEaxX

Pillars Article: Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA. Science. 1999. 285: 727-729 [PILLARS OF IMMUNOLOGY]

http://ift.tt/2HMYYSt