A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia‐inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors. © 2015 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Strategies for success: a toolbox of coping strategies used by breastfeeding women

Aims. The purpose of this paper is to present the findings of two qualitative studies which identified strategies used by breastfeeding women to assist them to continue breastfeeding. Background. While breastfeeding initiation rates are high in Australia, the majority of women wean before the recommended time. The identification of interventions which may increase breastfeeding duration is therefore a research priority. Design. The Against All Odds study used a case‐controlled design to investigate the characteristics of women who continued to breastfeed in the face of extraordinary difficulties. Phase One of the I Think I Can study employed the Nominal Group Technique to investigate the views of subject matter experts regarding which psychological factors may influence the duration of breastfeeding. Method. Against All Odds study participants (n = 40) undertook a one‐ to two‐hour interview and the transcribed data were analysed using thematic analysis. Stratified purposeful sampling was employed in the I Think I Can study (n = 21), with participants assigned group membership according to their most recent breastfeeding experience. A fourth group was composed of experienced breastfeeding clinicians. The nominal group technique was used to generate group data and segments of the discussion were audiotaped and transcribed for thematic analysis. Results. Participants in both the studies raised strategies used to assist them in their efforts to cope with the challenges of breastfeeding and early motherhood. These strategies included increasing breastfeeding knowledge, staying relaxed and ‘looking after yourself’, the use of positive self‐talk, challenging unhelpful beliefs, problem solving, goal setting and the practice of mindfulness. Conclusions. Employment of these simple behavioural and cognitive strategies may assist women to cope with the pressures inherent in the experience of early mothering, thereby increasing the duration of breastfeeding. Relevance to clinical practice. These results may represent a ‘tool box’ of coping strategies which can be provided to women for use in the postnatal period.     

The immune system as a physiological indicator of marginal copper status?

Cu appears to have many important functional roles in the body that apparently relate, among others, to the maintenance of immune function, bone health and haemostasis. Some have suggested a role for long-term marginal Cu deficiency in the aetiology of a number of degenerative diseases. Accurate diagnosis of marginal Cu deficiency, however, has remained elusive despite an increased understanding of the biochemistry of Cu and its physiological roles in the body. Traditional markers of Cu status, such as serum Cu and caeruloplasmin protein concentrations are insensitive to subtle changes in Cu status. Cu-containing enzymes, such as Cu-Zn-superoxide dismutase, cytochrome c oxidase and diamine oxidase, may be more reliable but evidence to date is not conclusive. Development of markers sensitive to marginal Cu status is essential before conclusions can be drawn concerning the risks of long-term intake of suboptimal dietary Cu. As Cu appears to be essential for maintenance of immune function, activities of specific immunological markers, altered in Cu deficiency, offer alternatives. This review evaluates a selection of immunological markers that could be considered potentially sensitive markers of marginal Cu status. The indices of immune function reviewed are neutrophil function, interleukin 2 production, blastogenic response to mitogens and lymphocyte subset phenotyping.     

The Trauma Recovery and Empowerment Model (TREM): conceptual and practical issues in a group intervention for women

This article describes the Trauma Recovery and Empowerment Model (TREM), a manualized group intervention designed for women trauma survivors with severe mental disorders, and discusses key issues in its conceptualization and implementation. TREM recognizes the complexity of long-term adaptation to trauma and addresses a range of difficulties common among survivors of sexual and physical abuse. Focusing primarily on the development of specific recovery skills and current functioning, TREM utilizes techniques shown to be effective in trauma recovery services. The group's content and structure are also informed by the role of gender in the ways women experience and cope with trauma.     

Hypoglycemic events and glycosylated hemoglobin values in patients with type 2 diabetes mellitus newly initiated on insulin glargine or premixed insulin combination products.

PURPOSE: Rates of hypoglycemic events and their associated costs were compared among patients with type 2 diabetes mellitus newly initiated on insulin glargine or a premixed insulin fixed-combination product. METHODS: Patients newly initiated on insulin glargine or premixed insulin fixed-combination products (including pen delivery systems) between June 1, 2001, and February 29, 2004, were identified using an administrative claims database. Hypoglycemic events were identified from International Classification of Diseases, 9th Revision, Clinical Modification codes. Multivariate analyses were performed. RESULTS: A total of 2315 patients met the inclusion criteria. Of those, 1212 received insulin glargine and 1103 received a premixed fixed-combination insulin product. The mean +/- S.D. treatment duration was 13.7 +/- 8.1 months. Patients treated with premixed insulin had a higher hypoglycemic event rate than glargine patients (13.8 versus 7.0/100 patients/year; p = 0.027), which yielded a number needed to treat of 15 patients. The mean cost per hypoglycemic event was $1049 (95% confidence interval, $426-1672). The mean annual cost of all insulin use was $46 more for the insulin glargine cohort than for those who received premixed insulin ($534 versus $488, respectively) (p < 0.05). Mean postindex insulin use was higher in patients receiving premixed insulin than in those treated with insulin glargine (48.1 versus 43.8 units per day) (p < 0.05). CONCLUSION: Patients with type 2 diabetes mellitus who were newly initiated on insulin glargine had a lower rate of hypoglycemic events compared with patients newly initiated on a premixed fixed-combination insulin product. Treatment of 15 patients with insulin glargine instead of premixed insulin for one year would avoid one hypoglycemic event per year.     

Contingent reinforcement for reduced breath carbon monoxide levels: Target-specific effects on cigarette smoking

This study determined the effects on smoking behavior of providing contingent reinforcement for nonsmoking versus reduced smoking afternoon breath carbon monoxide (CO) target levels. Twenty-eight hired chronic smoker volunteers were randomly assigned to one of three experimental conditions during a 10-day intervention: (a) 8 ppm target CO, $5 per day incentive (n = 11); (b) 16 ppm target CO, $4 per day incentive (n = 8); or (c) 8 ppm target CO, no incentive (n = 9). Both payment groups showed significantly lower CO levels and greater amounts of daytime smoking reduction than the no-pay group. A specific effect of CO target was also seen; 45% of subjects in the 8 ppm group compared with 0% of subjects in the 16 ppm target and no-pay groups produced average afternoon CO levels of 8.5 ppm or lower during the intervention. Average levels of CO and smoking reduction did not differ for the two paid groups, however, because some subjects in the 8 ppm group failed to reduce CO sufficiently to contact the reinforcer. Contingent reinforcement based on expired air CO levels can exercise powerful and precise (target-specific) control over smoking behavior, but there may be individual differences in ability to meet reinforcement contingencies if difficult targets are introduced abruptly.     

Long-term breast cancer survivors' use of complementary therapies: perceived impact on recovery and prevention of recurrence

OBJECTIVE: Many cancer survivors use some form of complementary therapy (CT); this is particularly true for women with breast cancer. The majority of reports on CT use in women with breast cancer have focused on CT use during cancer treatment or within a year or two of treatment completion. The purpose of this study was to evaluate longer-term breast cancer survivors' (average, 8.7 years) frequency of CT use and their beliefs about the role of CT in cancer recovery and the prevention of cancer recurrence, as well as the relationship of CT use with current life satisfaction. METHODS: A mail survey was completed by 608 breast cancer survivors a minimum of 2 years after their most recent cancer diagnosis. Participants were contacted through the American Cancer Society Reach to Recovery program in Florida. The self-report questionnaire inquired about the use of various CTs, beliefs about CT, current life satisfaction, demographic characteristics, and cancer treatment history. RESULTS: Most of the respondents were older than 50, were Caucasian, were married, had attended or completed college, and were at least 5 years after breast cancer treatment. The most commonly used CTs included exercise, vitamins, prayer/spiritual practice, support groups, humor, self-help books, and relaxation. These survivors used CT therapies because they wanted to play a more active role in their cancer recovery, to manage stress, and to maintain hope. A majority of them reported that they used CT to reduce the risk of cancer recurrence. Use of CT was not correlated with life satisfaction. CONCLUSIONS: Most of the breast cancer survivors in this study had used some form of CT since the time of their most recent cancer diagnosis and believed that such therapies could be of significant benefit, despite a lack of correlation between CT use and current life satisfaction. Many believed that use of CT may prevent cancer recurrence. It is important, therefore, to investigate the efficacy of various CTs among longer-term cancer survivors, especially with regard to their potential in preventing cancer recurrence.