Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

Identification of Night Eating Behaviour and Investigation into Its Characteristics in an Obese Population

Background Night Eating Syndrome (NES) was characterised in 2003 as comprising; morning anorexia, evening hyperphagia, night-time awakenings, consumption of high calorie snacks during awakenings and an absence of other eating disorders (ED). Method An identification study was conducted in a hospital–based UK obesity clinic with 81 individuals undertaking a diagnostic interview and completing a proposed screening tool. Full NES (n=7) and partial NES (n=24) individuals were combined into one Night Eating Behaviour (NEB) group (n=31) and compared to all other participants (n=50). NEB characteristics were identified through qualitative thematic analysis of interview data, based on techniques used by Grounded Theorists. NEB individuals (n=28) were compared with matched controls. In a separate prevalence study, night-eating, sleep quality and suspected Obstructive Sleep Apnoea (OSA) were estimated in 103 participants using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and a validated Night Eating Questionnaire. Correlational analysis was also performed. Results In the identification study, full NES was rare (9%). Comparison of the NEB and non-NEB group showed significant differences in mood (p=0.001), work status (p= 0.03), perceived lack of control over eating (p= 0.03) and variability in sleep duration (p25, 3.9% (n=4), based on a higher cut score of >30, poor sleep quality 74% (n= 76) and suspected OSA 32% (n= 33). A strong relationship (r = 0.55, p = < 0.001) between night-eating and poor sleep quality was found, with day-time sleepiness having no influence over this relationship. Conclusion Comparison of the study findings with new NES criteria (2010) shows poor differentiation between NES and morbid obesity. In obese populations, a shift of focus is proposed to an alternative ‘Impaired Sleep Syndrome’ of which night-eaters may be a sub-group, often with severe depression. Night-eaters also exhibit too many features of other ED for this relationship to be ignored

Chemotherapy-Response Monitoring of Breast Cancer Patients Using Quantitative Ultrasound-Based Intra-Tumour Heterogeneities

© 2017 The Author(s). Anti-cancer therapies including chemotherapy aim to induce tumour cell death. Cell death introduces alterations in cell morphology and tissue micro-structures that cause measurable changes in tissue echogenicity. This study investigated the effectiveness of quantitative ultrasound (QUS) parametric imaging to characterize intra-tumour heterogeneity and monitor the pathological response of breast cancer to chemotherapy in a large cohort of patients (n = 100). Results demonstrated that QUS imaging can non-invasively monitor pathological response and outcome of breast cancer patients to chemotherapy early following treatment initiation. Specifically, QUS biomarkers quantifying spatial heterogeneities in size, concentration and spacing of acoustic scatterers could predict treatment responses of patients with cross-validated accuracies of 82 ± 0.7%, 86 ± 0.7% and 85 ± 0.9% and areas under the receiver operating characteristic (ROC) curve of 0.75 ± 0.1, 0.80 ± 0.1 and 0.89 ± 0.1 at 1, 4 and 8 weeks after the start of treatment, respectively. The patients classified as responders and non-responders using QUS biomarkers demonstrated significantly different survivals, in good agreement with clinical and pathological endpoints. The results form a basis for using early predictive information on survival-linked patient response to facilitate adapting standard anti-cancer treatments on an individual patient basis

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Underwater Vocalizations as a Tool for Studying the Distribution and Relative Abundance of Wintering Pinnipeds in the High Arctic

Recordings of the underwater vocalizations of ringed seals, bearded seals and walruses were made in the High Arctic between late March and late June 1980 and 1981, to evaluate the potential for using sub-ice vocalizations to study the distribution and relative abundance of wintering pinnipeds. Most of the calls made by these three species are identified and an initial lexicon is presented. Ringed seal vocalizations were more frequent in late April than earlier in the season or in late June, whereas the highest vocalization rates recorded for bearded seals were in late June. Vocalization rates of all three species were indicative of their distribution and relative abundance in different areas and sea ice habitat types. We conclude that underwater vocalizations have the potential for giving more precise information on the relative abundance of wintering pinnipeds than techniques previously used. It may be possible, provided the necessary information on the vocal behaviour of these species is acquired, to use this technique for censusing.Key words: vocalizations, ringed seal, bearded seal, walrus, distributionMots cl&eacute;s: vocalisations, phoque annel&eacute;, phoque barbu, morse, distributio

Physical Activity Policy for Older Adults in the Northwest Territories, Canada: Gaps and Opportunities for Gains

In the Northwest Territories (NWT), Canada, the population of older adults is increasing, and this population reports much poorer health than other age cohorts. Given the number of benefits that physical activity (PA) can have for older adults, we analyzed policies concerning older adults and PA of both the NWT government and non-governmental organizations in the health, recreation, and sports sectors. Our findings indicate that although the majority of the organizations had no PA policies specific to older adults or Aboriginal older adults, some organizations completed all five stages of the policy cycle (agenda setting, policy formulation, decision making, implementation, and evaluation). Our analysis suggests that PA for older adults is not on the agenda for many organizations in the NWT and that often the policy process does not continue past the decision-making stage. To address the need for connections between all stages of the policy cycle, we suggest that organizations collaborate across multiple sectors and with older adults to develop a territory-wide, age-friendly rural and remote community strategy that is applicable to the NWT. Prioritizing age-friendly communities would, in turn, facilitate appropriate PA opportunities for older adults in the NWT and thus contribute to a healthier aging population.Dans les Territoires du Nord-Ouest (T.N.-O.), au Canada, la population de personnes âgées augmente, et la santé de ce segment de population est bien inférieure à celle des autres segments. Étant donné les bienfaits que peut comporter l’activité physique (AP) chez les personnes âgées, nous avons analysé les politiques concernant les personnes âgées et l’AP au sein des organismes gouvernementaux et non gouvernementaux des Territoires du Nord-Ouest en matière de santé, de loisirs et de sports. Nos constatations indiquent que même si la majorité des organismes n’étaient pas dotés de politiques d’AP visant particulièrement les personnes âgées ou les Autochtones âgés, certains organismes avaient déjà fait les cinq étapes du cycle stratégique (détermination de l’ordre du jour, formulation de politiques, prise de décisions, mise en oeuvre et évaluation). Notre analyse suggère que pour bien des organismes des T.N.-O., l’AP chez les personnes âgées ne figure pas au programme et que souvent, le processus d’élaboration de politiques ne se poursuit pas après l’étape de la prise de décisions. Afin de relier toutes les étapes du cycle, nous suggérons que les organismes des divers secteurs collaborent entre eux ainsi qu’avec les personnes âgées afin de parvenir à une stratégie qui correspond bien aux gens plus âgés des localités rurales et éloignées, à l’échelle des T.N.-O. En accordant une priorité à la création de collectivités qui tiennent compte des personnes âgées, on pourrait aboutir à des activités physiques convenant aux personnes âgées des T.N.-O., ce qui contribuerait à une population vieillissante en meilleure santé

Pattern of Local Recurrence After Conservative Surgery and Radiotherapy for Soft Tissue Sarcoma

Purpose: Over the past three decades our centre has adopted a policy of conservative surgery followed by adjuvant radicaldose radiotherapy for medium-and high-grade soft tissue sarcomas. For all cases of local recurrence following this treatment we aimed to define the spatial relationship between sites of recurrence and the positions of the phase 1 and 2 radiotherapy volumes

Summer distribution and movements of narwhals (Monodon monoceros) in Eclipse Sound and adjacent waters, North Baffin Island, N.W.T.

Each year from 1987 to 1991 and in 1993, 3-6 helicopter surveys were flown in August to study the distribution and movements of narwhals (Monodon monoceros) in their summering grounds in western Eclipse Sound, Milne Inlet, Koluktoo Bay and Tremblay Sound. Their summer distribution is influenced by ice cover. They prefer waters that while giving them shelter from the wind, are over deep bottoms. Narwhals associate with ice in Eclipse Sound, a large expanse of water, while it persists, but do not frequent Tremblay Sound, a narrow fjord, when it has ice cover. When Eclipse Sound is ice-free, narwhals frequent smaller water bodies. Favoured areas in the ice-free season have in common the characteristics of being steep-sided and deep. Narwhals associate in small groups, but these groups aggregate to form larger herds that generally move together. In the short term, movements and distribution are greatly affected by the near presence of killer whales (Orcinus orca), which narwhals seek to avoid