T-regulatory cell modulation: the future of cancer immunotherapy?

T-regulatory cells suppress anti-tumour immunity in cancer patients and in murine tumour models. Furthermore, their activity is likely to have an effect on the effectiveness of immunotherapeutic treatments for cancer. Here we describe the current status of developing clinical strategies for modulating Treg activity in cancer patients

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

Clinical and laboratory experience of vorinostat (suberoylanilide hydroxamic acid) in the treatment of cutaneous T-cell lymphoma

The most common cutaneous T-cell lymphomas (CTCLs) – mycosis fungoides (MF) and Sézary Syndrome – are characterised by the presence of clonally expanded, skin-homing helper-memory T cells exhibiting abnormal apoptotic control mechanisms. Epigenetic modulation of genes that induce apoptosis and differentiation of malignant T cells may therefore represent an attractive new strategy for targeted therapy for T-cell lymphomas. In vitro studies show that vorinostat (suberoylanilide hydroxamic acid or SAHA), an oral inhibitor of class I and II histone deacetylases, induces selective apoptosis of malignant CTCL cell lines and peripheral blood lymphocytes from CTCL patients at clinically achievable doses. In a Phase IIa clinical trial, vorinostat therapy achieved a meaningful partial response (>50% reduction in disease burden) in eight out of 33 (24%) patients with heavily pretreated, advanced refractory CTCL. The most common major toxicities of oral vorinostat therapy were fatigue and gastrointestinal symptoms (diarrhoea, altered taste, nausea, and dehydration from not eating). Thrombocytopenia was dose limiting in patients receiving oral vorinostat at the higher dose induction levels of 300 mg twice daily for 14 days. These studies suggest that vorinostat represents a promising new agent in the treatment of CTCL patients. Additional studies are underway to define the exact mechanism (s) of by which vorinostat induces selective apoptosis in CTCL cells and to further evaluate the antitumour efficacy of vorinostat in a Phase IIb study in CTCL patients

Developing the Questionnaire

AbstractThis chapter outlines the essential topics for developing and testing a questionnaire for a discrete choice experiment survey. It addresses issues such as the description of the environmental good, pretesting of the survey, incentive compatibility, consequentiality or mitigation of hypothetical bias. For the latter, cheap talk scripts, opt-out reminders or an oath script are discussed. Moreover, the use of instructional choice sets, the identification of protest responses and strategic bidders are considered. Finally, issues related to the payment vehicle and the cost vector design are the subject of this section

Supplementation of Indigenous Lactobacillus Bacteria in Live Prey and as Water Additive to Larviculture of Portunus pelagicus (Linnaeus, 1758)

Abstract: Experimental trials were conducted to demarcate the effects of indigenous Lactobacillus probiotics as bioencapsulated in live prey (rotifers Brachionus plicatilis and Artemia franciscana) and water additives together on the survival of blue swimming crab, Portunus pelagicus larvae. Three LAB probiotics L. plantarum, L. salivarius and L. rhamnosus at final concentration 1x10 7 cfu/mL were bioencapsulated in live prey added daily and same allowance was added to culture water on day 1, 3, 5, 7, 9, 11, 13 as a single isolates to treatments A, B, C and multi isolates to D with no probiotic added to control tanks. Bacteria were successfully accumulated in both rotifers and Artemia within two hours of incubation. Total viable count of bacteria in Artemia observed lower at sampling days in inoculated tanks compared to those at time of incubation, contrary it increased in controls and no Vibrio was determined in Artemia in LAB mixture isolate inoculated samples on the day 13. Highest LAB bacteria 4.10×10 3 was determined in Artemia on day 11 in those inoculated with mixture of LAB isolates. At the end of the trials, larvae treated with a mixture of LAB probiotics did produce significantly highest survival 13.83±0.76% over other LAB treatments. As a single isolate L. plantarum did produce survival 13.50±1.32% compared with those treated with L. salivarius and L. rhamnosus and those without probiotics (control). There was no statistical significance (p>0.05) in the survival of larvae in any treatment. Results indicate that LAB probiotics could be used to enhance survival of P. pelagicus larvae