Clonal Abundance of Tumor-Specific CD4(+) T Cells Potentiates Efficacy and Alters Susceptibility to Exhaustion.

Current approaches to cancer immunotherapy aim to engage the natural T cell response against tumors. One limitation is the elimination of self-antigen-specific T cells from the immune repertoire. Using a system in which precursor frequency can be manipulated in a murine melanoma model, we demonstrated that the clonal abundance of CD4(+) T cells specific for self-tumor antigen positively correlated with antitumor efficacy.

The New Era of Cancer Immunotherapy: Manipulating T-Cell Activity to Overcome Malignancy.

Using the immune system to control cancer has been investigated for over a century. Yet it is only over the last several years that therapeutic agents acting directly on the immune system have demonstrated improved overall survival for cancer patients in phase III clinical trials. Furthermore, it appears that some patients treated with such agents have been cured of metastatic cancer.

Influences on human papillomavirus (HPV)-related information needs among women having HPV tests for follow-up of abnormal cervical cytology.

Objectives: Testing for human papillomavirus (HPV) infection has recently been introduced into cervical screening programmes. We investigated (1) barriers to accessing and absorbing information and (2) factors that influence information needs among women undergoing HPV tests.

Methods: In-depth interviews were conducted with 27 women who had HPV tests performed in a colposcopy clinic as part of follow-up of low-grade abnormal cytology or post-treatment for cervical intraepithelial neoplasia (CIN).

Motivators for women to attend cervical screening: the influential role of GPs.

Background: Participation in organized cervical cancer screening has declined recently. While research has focussed on barriers to screening participation, less attention has been paid to what motivates women to attend. Moreover, little is known about health care provider/practitioner-level barriers and facilitators to participation.

Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice.

Immunotherapy for cancer using antibodies to enhance T-cell function has been successful in recent clinical trials. Many molecules that improve activation and effector function of T cells have been investigated as potential new targets for immunomodulatory antibodies, including the tumor necrosis factor receptor superfamily members GITR and OX40. Antibodies engaging GITR or OX40 result in significant tumor protection in preclinical models.

Preoperative enoxaparin versus postoperative semuloparin thromboprophylaxis in major abdominal surgery: a randomized controlled trial.

Objective: To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery.

Background: Venous thromboembolism is an important complication following major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity.

'It's a can of worms': understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework.

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention.

Modulation of GITR for cancer immunotherapy.

Modulation of co-inhibitory and co-stimulatory receptors of the immune system has become a promising new approach for immunotherapy of cancer. With the recent FDA approval of CTLA-4 blockade serving as an important proof of principal, many new targets are now being translated into the clinic. Preclinical research has demonstrated that targeting glucocorticoid-induced tumor necrosis factor (TNF) receptor related gene (GITR), a member of TNF receptor superfamily, by agonist antibodies or natural ligand, can serve as an effective anti-tumor therapy.

Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicentre, placebo-controlled trial.

Background: Blockade of the endocannabinoid receptor reduces obesity and improves metabolic abnormalities such as triglycerides, HDL cholesterol, and fasting blood glucose. We assessed whether rimonabant would improve major vascular event-free survival.

Methods: This double-blind, placebo-controlled trial was undertaken in 974 hospitals in 42 countries.

Gene expression profiling of monocyte-derived macrophages following infection with Mycobacterium avium subspecies avium and Mycobacterium avium subspecies paratuberculosis.

Mycobacterium avium subspecies paratuberculosis (MAP) and Mycobacterium avium subspecies avium (MAA) represent two closely related intracellular bacteria with vastly different associated pathologies. MAA can cause severe respiratory infections in immune compromised humans but is nonpathogenic in ruminants and is more readily controlled by the bovine immune system than MAP. MAP causes a fatal wasting syndrome in ruminants, typified by granulomatous enteritis localized in the small intestine.