The role of CDK4/6 inhibitors in breast cancer

Oral inhibitors of CDK4/6 have been shown to increase response rates and prolong disease control when combined with endocrine therapy in hormone-responsive (HR+) HER2-negative advanced breast cancer. Palbociclib, ribociclib and abemaciclib are all approved in combination with non-steroidal aromatase inhibitors in first-line therapy for post-menopausal women, with a 40–45% improvement in progression-free survival seen with the addition of any of these CDK4/6 inhibitors. Additional approved indications, including first- and second-line combination therapy for pre-menopausal women, combination with fulvestrant and use as monotherapy, vary with each agent and are reviewed fully in the subsequent texts. These agents also differ in their toxicity profiles and monitoring requirements, and prescribers should be aware of the individual requirements for each agent. Current clinical trials are investigating the expanded use of these agents in other breast cancer subtypes, such as HER2-positive and triple-negative breast cancer, as well as in the adjuvant and neoadjuvant treatments of early breast cancer. Resistance to CDK4/6 inhibition can occur through multiple mechanisms. Rational combinations with other therapies, such as PI3K inhibitors, HER2-directed therapies and immunotherapy, are being explored

Cancer-related fatigue and self-care agency: A multicentre survey of patients receiving chemotherapy

Aims and objectives: To measure cancer-related fatigue (CRF), self-care agency (SCA) and fatigue self-care strategies, and to explore the relationship between CRF and SCA. Background: Cancer-related fatigue has been consistently rated as the most elusive, common and severe of symptoms that patients with cancer undergoing chemotherapy experience. Despite its frequency and severity, CRF is poorly managed. A renewed focus on supporting self-care among patients with cancer has been found to reduce symptom burden, empower patients and improve patient satisfaction. Understanding the link between self-care agency (i.e. capability and willingness to self-care) and CRF levels will help practitioners to better support individuals on the cancer journey. Design: A descriptive, correlational survey design was employed. Methods: Patients (n = 362) undergoing chemotherapy with a primary diagnosis of breast, colorectal, Hodgkin's and non-Hodgkin's lymphoma cancers were recruited from four oncology centres in one city in the South of Ireland. Participants completed the Piper Fatigue Scale-Revised, Appraisal of Self-care Agency Scale and a researcher-developed Fatigue Self-Care Survey. Multivariate logistic regression was used to examine the relationship between CRF and self-care agency using a dichotomous dependent variable score of four as the cut-off between those deemed to be fatigued (≥4) and those not fatigued (<4). As recommended by the EQUATOR Network, the STROBE checklist of items for cross-sectional studies is used to report the study. Results: The incidence of CRF was high with 75% of participants scoring clinically relevant CRF. Higher SCA (OR = 0.96, 95% CI = 0.93–0.99, p = .011) was associated with decreased odds of developing CRF. Having non-Hodgkin's lymphoma (OR = 3.02, 95% CI = 1.29–7.07, p = .011) was associated with increased odds of developing CRF. Conclusions: Patient's undergoing chemotherapy experience significant fatigue. Higher capability for self-care is associated with lower fatigue. The promotion of SCA and self-care strategies can impact on CRF. Relevance to clinical practice: Understanding the link between self-care abilities and fatigue can lead to more individualised and tailored approaches to CRF

High extinction ratio robust evanescent PM fibre coupler

Dominic F. Murphy and Conleth D. Husseyhttp://www.tyndall.ie/hosted/photonicsireland2009/index.htm

Neurofilament expression in human T lymphocytes

peer-reviewedThe expression of intermediate filaments in normal cells is mainly determined by their embryonal developmental origin. Flow cytometry using monoclonal antibody RT97 demonstrated that neurofilament was detectable in the human HuT 78 T-cell line and on resting T lymphocytes. Expression was greatly increased on lymphocytes activated for 3 days with phorbol ester. Western blotting confirmed the presence of the 200,000 MW form of neurofilament in T lymphocytes. Stimulation of peripheral blood T cells with phorbol myristate acetate (PMA) or with anti-CD3 monoclonal antibodies resulted in a marked increase in detection of phosphorylated neurofilament on Western blotting. Stimulation of HuT 78 cells with anti-LFA-1 resulted in redistribution of neurofilament from a perinuclear spheroid core into dendritic processes. These data indicate that T cells activated through the T-cell receptor associated complex express an intermediate filament usually associated with neurally derived cells. The finding that neurofilament expression and organization are regulated by T-cell surface molecules suggests a role for this intermediate filament in T-cell function