Mary Adams

Bio: Mary Adams is an academic researcher from King's College London. The author has contributed to research in topics: Lenalidomide & Antibody-dependent cell-mediated cytotoxicity. The author has an hindex of 14, co-authored 36 publications receiving 1280 citations. Previous affiliations of Mary Adams include University of Kent & Guy's and St Thomas' NHS Foundation Trust.

Lenalidomide Enhances Natural Killer Cell and Monocyte-Mediated Antibody-Dependent Cellular Cytotoxicity of Rituximab-Treated CD20+ Tumor Cells

Abstract: Purpose: Lenalidomide has significant activity in myelodysplastic syndromes, multiple myeloma, and non-Hodgkin9s lymphoma (NHL). In previous studies, natural killer (NK) cell expansion by lenalidomide was shown to enhance the cytotoxic effect of rituximab. This study assessed the ability of lenalidomide to enhance antibody-dependent cellular cytotoxicity (ADCC) in rituximab-treated NHL cell lines and primary tumor cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) in vitro . Experimental Design: An in vitro ADCC system was used to assess the ability of lenalidomide to enhance human NK cell and monocyte function in response to rituximab. Results: Lenalidomide directly enhanced IFN-γ production via Fc-γ receptor-mediated signaling in response to IgG. It was also a potent enhancer of NK cell-mediated and monocyte-mediated tumor cell ADCC for a variety of rituximab-treated NHL cell lines in vitro , an effect that was dependent on the presence of antibody and either interleukin-2 or interleukin-12. Lenalidomide also enhanced the ability of NK cells to kill primary tumor cells derived from three patients with B-CLL who have been treated previously with fludarabine plus cyclophosphamide. Enhanced NK cell ADCC was associated with enhanced granzyme B and Fas ligand expression and could be inhibited by a granzyme B inhibitor and partially inhibited by antibody to FasL. Enhanced NK cell Fc-γ receptor signaling is associated with enhanced phosphorylated extracellular signal-related kinase levels leading to enhanced effector function. Conclusions: These findings suggest that lenalidomide has the potential to enhance the rituximab-induced killing of NHL cell lines and primary B-cell chronic lymphocytic leukemia cells via a NK cell-mediated and monocyte-mediated ADCC mechanism in vitro , providing a strong rationale for the combination of lenalidomide with IgG1 antibodies to target tumor-specific antigens in patients with cancer.

Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis.

Abstract: Background and purpose: Apremilast is an orally administered phosphodiesterase-4 inhibitor, currently in phase 2 clinical studies of psoriasis and other chronic inflammatory diseases. The inhibitory effects of apremilast on pro-inflammatory responses of human primary peripheral blood mononuclear cells (PBMC), polymorphonuclear cells, natural killer (NK) cells and epidermal keratinocytes were explored in vitro, and in a preclinical model of psoriasis.

'Poppets and parcels': the links between staff experience of work and acutely ill older peoples' experience of hospital care

Abstract: Background. Few empirical studies have directly examined the relationship between staff experiences of providing healthcare and patient experience. Present concerns over the care of older people in UK acute hospitals – and the reported attitudes of staff in such settings – highlight an important area of study. Aims and objectives. To examine the links between staff experience of work and patient experience of care in a ‘Medicine for Older People’ (MfOP) service in England. Methods. A mixed methods case study undertaken over 8 months incorporating a 149-item staff survey (66/192 – 34% response rate), a 48-item patient survey (26/111 – 23%), 18 staff interviews, 18 patient and carer interviews and 41 hours of non-participant observation. Results. Variation in patient experience is significantly influenced by staff work experiences. A high-demand/low-control work environment, poor staffing, ward leadership and co-worker relationships can each add to the inherent difficulties staff face when caring for acutely ill older people. Staff seek to alleviate the impact of such difficulties by finding personal satisfaction from caring for ‘the poppets’; those patients they enjoy caring for and for whom they feel able to ‘make a difference’. Other patients – noting dehumanising aspects of their care – felt like ‘parcels’. Patients are aware of being seen by staff as ‘difficult’ or ‘demanding’ and seek to manage their relationships with nursing staff accordingly. Conclusions. The work experiences of staff in a MfOP service impacted directly on patient care experience. Poor ward and patient care climates often lead staff to seek job satisfaction through caring for ‘poppets’, leaving less favoured – and often more complex patients – to receive less personalised care. Implications for practice. Investment in staff well-being and ward climate is essential for the consistent delivery of high-quality care for older people in acute settings.

Barriers and opportunities for enhancing patient recruitment and retention in clinical research: findings from an interview study in an NHS academic health science centre.

Abstract: In the UK, the recruitment of patients into clinical research is a national health research and development policy priority. There has been limited investigation of how national level factors operate as barriers or facilitators to recruitment work, particularly from the perspective of staff undertaking patient recruitment work. The aim of this study is to identify and examine staff views of the key organisational barriers and facilitators to patient recruitment work in one clinical research group located in an NHS Academic Health Science Centre. A qualitative study utilizing in-depth, one-to-one semi-structured interviews with 11 purposively selected staff with particular responsibilities to recruit and retain patients as clinical research subjects. Thematic analysis classified interview data by recurring themes, concepts, and emergent categories for the purposes of establishing explanatory accounts. The findings highlight four key factors that staff perceived to be most significant for the successful recruitment and retention of patients in research and identify how staff located these factors within patients, studies, the research centre, the trust, and beyond the trust. Firstly, competition for research participants at an organisational and national level was perceived to undermine recruitment success. Secondly, the tension between clinical and clinical research workloads was seen to interrupt patient recruitment into studies, despite national funding arrangements to manage excess treatment costs. Thirdly, staff perceived an imbalance between personal patient burden and benefit. Ethical committee regulation, designed to protect patients, was perceived by some staff to detract from clarification and systematisation of incentivisation strategies. Finally, the structure and relationships within clinical research teams, in particular the low tacit status of recruitment skills, was seen as influential. The results of this case-study, conducted in an exemplary NHS academic research centre, highlight current systematic challenges to patient recruitment and retention in clinical studies more generally as seen from the perspective of staff at the 'sharp end’ of recruiting. Staff experience is that, beyond individual clinical research design and protocol factors, wider organisational and extra-organisational norms, structures, and processes operate as significant facilitators or hindrances in the recruitment of patients as research subjects.

Lenalidomide enhances antibody-dependent cellular cytotoxicity of solid tumor cells in vitro: influence of host immune and tumor markers

Abstract: We evaluated the effect of combining lenalidomide with therapeutic antibodies on antibody-dependant cell-mediated cytotoxicity (ADCC) of solid tumor cells, and the requirement for expression of natural killer (NK) cell-activating receptors and their solid tumor surface ligands. Twenty-three human tumor cell lines (colon, breast, lung, head and neck, ovary, and bone sarcoma) were analyzed. NK effector cells were isolated from healthy donors, pre-treated with and without lenalidomide, and incubated with antibody-coated tumor cells to determine ADCC. In blocking experiments, NK cells were pre-incubated with anti-DNAM-1 or anti-NKG2D antibodies, and target colorectal cells were pre-incubated with anti-CD155 (PVR), anti-MIC-A/B, or anti-ULBP 3 antibodies. Differences between groups were assessed using unpaired and paired Student’s t test and one-way ANOVA. Lenalidomide enhanced NK cell-mediated ADCC of trastuzumab- and cetuximab-coated tumor cells. Activity against colorectal cancer cells was dependent on target antigen expression, but independent of KRAS status and FcγRIIIa genotype. The extent of ADCC and its enhancement by lenalidomide correlated with NK cell expression of NKG2D and DNAM-1, and tumor cell expression of PVR and MIC-A. Blocking of NKG2D and, to a lesser extent, DNAM-1 inhibited ADCC. Anti-MIC-A/B monoclonal antibody blocked natural cytotoxicity, but not ADCC. Lenalidomide enhances the ability of IgG1-isotype antibodies to mediate ADCC of solid tumor cells, the extent of which is largely dependent on NKG2D–NKG2D ligand interactions, but appears to be independent of MIC-A/B. This provides a rationale for exploratory clinical studies and an assessment of potential biomarkers predictive of clinical benefit.

Research Methods in Health. Investigating health and health services

Abstract: This new edition of Ann Bowling's well-known and highly respected text has been thoroughly revised and updated to reflect key methodological developments in health research. It is a comprehensive, easy to read, guide to the range of methods used to study and evaluate health and health services. It describes the concepts and methods used by the main disciplines involved in health research, including: demography, epidemiology, health economics, psychology and sociology.The research methods described cover the assessment of health needs, morbidity and mortality trends and rates, costing health services, sampling for survey research, cross-sectional and longitudinal survey design, experimental methods and techniques of group assignment, questionnaire design, interviewing techniques, coding and analysis of quantitative data, methods and analysis of qualitative observational studies, and types of unstructured interviewing. With new material on topics such as cluster randomization, utility analyses, patients' preferences, and perception of risk, the text is aimed at students and researchers of health and health services. It has also been designed for health professionals and policy makers who have responsibility for applying research findings in practice, and who need to know how to judge the value of that research.

Targeting natural killer cells in cancer immunotherapy

Abstract: Alteration in the expression of cell-surface proteins is a common consequence of malignant transformation. Natural killer (NK) cells use an array of germline-encoded activating and inhibitory receptors that scan for altered protein-expression patterns, but tumor evasion of detection by the immune system is now recognized as one of the hallmarks of cancer. NK cells display rapid and potent immunity to metastasis or hematological cancers, and major efforts are now being undertaken to fully exploit NK cell anti-tumor properties in the clinic. Diverse approaches encompass the development of large-scale NK cell-expansion protocols for adoptive transfer, the establishment of a microenvironment favorable to NK cell activity, the redirection of NK cell activity against tumor cells and the release of inhibitory signals that limit NK cell function. In this Review we detail recent advances in NK cell-based immunotherapies and discuss the advantages and limitations of these strategies.

Psoriasis Pathogenesis and Treatment.

Abstract: Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.