Volatile anaesthesia and peri-operative outcomes related to cancer: a feasibility and pilot study for a large randomised control trial.

Published data suggest that the type of general anaesthesia used during surgical resection for cancer may impact on patient long-term outcome. However, robust prospective clinical evidence is essential to guide a change in clinical practice. We explored the feasibility of conducting a randomised controlled trial to investigate the impact of total intravenous anaesthesia with propofol vs. inhalational volatile anaesthesia on postoperative outcomes of patients undergoing major cancer surgery. We undertook a randomised, double-blind feasibility and pilot study of propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia during cancer resection surgery at three tertiary hospitals in Australia and the USA. Patients were randomly allocated to receive propofol total intravenous anaesthesia or volatile-based maintenance anaesthesia. Primary outcomes for this study were successful recruitment to the study and successful delivery of the assigned anaesthetic treatment as per randomisation arm. Of the 217 eligible patients approached, 146 were recruited, a recruitment rate of 67.3% (95%CI 60.6-73.5%). One hundred and forty-five patients adhered to the randomised treatment arm, 99.3% (95%CI 96.2-100%). Intra-operative patient characteristics and postoperative complications were comparable between the two intervention groups. This feasibility and pilot study supports the viability of the protocol for a large, randomised controlled trial to investigate the effect of anaesthesia technique on postoperative cancer outcomes. The volatile anaesthesia and peri-operative outcomes related to cancer (VAPOR-C) study that is planned to follow this feasibility study is an international, multicentre trial with the aim of providing evidence-based guidelines for the anaesthetic management of patients undergoing major cancer surgery.

Social regulation of the lymph node transcriptome in rhesus macaques (Macaca mulatta).

Previous research has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type I interferon anti-viral genes in circulating blood cells. However, the impact of social conditions on lymphoid tissue gene regulation remains largely unexplored. This project assessed how social instability in adult male rhesus macaques (N=10, 5 in unstable, and 5 in stable social conditions) might regulate gene expression within secondary lymphoid tissue (lymph nodes; LN). Unstable social conditions down-regulated axillary LN expression of genes involved in Type I interferon anti-viral responses. Transcript origin analyses implicated monocytes and B cells as cellular mediators of these effects, and promoter-based bioinformatics analyses indicated reduced activity of AP-1, NF-κB, IRF, and CREB transcription factors within the axillary LN microenvironment. Although the current study is limited in sample size, these results suggest that social influences on immune cell gene regulation extend beyond the circulating leukocyte pool to alter generalized transcriptome profiles in secondary lymphoid tissue, and they do so in a regulatory program that resembles the pattern of antiviral inhibition previously observed in circulating leukocytes.

Genes involved in breast cancer metastasis to bone.

Metastasis to bone occurs frequently in advanced breast cancer and is accompanied by debilitating skeletal complications. Current treatments are palliative and new therapies that specifically prevent the spread of breast cancer to bone are urgently required. While our understanding of interactions between breast cancer cells and bone cells has greatly improved, we still know little about the molecular determinants that regulate specific homing of breast cancer cells to the bone. In this review, we focus on genes that have been implicated in migration and adhesion of breast cancer cells to bone, as well as genes that promote tumor cell proliferation in the bone microenvironment. In addition, the review discusses new technologies, including better animal models, that will further assist with the identification of the molecular determinants of bone metastasis and will guide the development of new therapies.

The role of CD45 and CD45-associated molecules in T cell activation.

CD45 (lymphocyte common antigen) is a receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes, and which plays a crucial role in the function of these cells. On T cells the extracellular domain of CD45 is expressed in several different isoforms, and the particular isoform(s) expressed depends on the particular subpopulation of cell, their state of maturation, and whether or not they have previously been exposed to antigen. It has been established that the expression of CD45 is essential for the activation of T cells via the TCR, and that different CD45 isoforms display a different ability to support T cell activation. Although the tyrosine phosphatase activity of the intracellular region of CD45 has been shown to be crucial for supporting signal transduction from the TCR, the nature of the ligands for the different isoforms of CD45 have been elusive. Moreover, the precise mechanism by which potential ligands may regulate CD45 function is unclear. Interestingly, in T cells CD45 has been shown to associate with numerous molecules, both membrane associated and intracellular; these include components of the TCR-CD3 complex and CD4/CD8. In addition, CD45 is reported to associate with several intracellular protein tyrosine kinases including p56lck and p59fyn of the src family, and ZAP-70 of the Syk family, and with numerous proteins of 29-34 kDa. These CD45-associated molecules may play an important role in regulating CD45 tyrosine phosphatase activity and function. However, although the role of some of the CD45-associated molecules (e.g. CD45-AP and LPAP) has become better understood in recent years, the role of others still remains obscure. This review aims to summarize recent findings on the role of CD45 and CD45-associated molecules in T cell activation, and to highlight issues that seem relevant to ongoing research in this area.