Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P<0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P<0.05). EPA (18.2±3.2 pg/ml) and combination (18.4±3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9±1.4 pg/ml, P≤0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P≤0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P≤0.05). Activity of total SOD was higher in the oxypurinol group (32.2±1.5 U/ml) compared to control (27.0±1.3 U/ml, P<0.01), GPx activity was lower in the EPA group (8.76±2.0 U/ml) compared to control (14.0±1.9 U/ml, P<0.05), and catalase activity was lower in the combination group (14.4±2.8 U/ml) compared to control (20.9±2.0 U/ml, P<0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.

A strain-promoted alkyne-azide cycloaddition (SPAAC) reaction of a novel EpCAM aptamer-fluorescent conjugate for imaging of cancer cells

For the first time, a novel EpCAM aptamer (SYL3C)-DIBO-AF594 fluorescent conjugate was synthesised by bioorthogonal chemistry utilizing a strain promoted alkyne-azide cycloaddition (copper free click) reaction (SPAAC). The ligation efficiency of SPAAC was improved by freeze-thaw cycles. The obtained conjugate showed target specific binding and aided in the imaging of various EpCAM positive cancer cell lines like MCF7, MDAMB453, Weri-RB1 and PC3.

Machine-learning prediction of cancer survival: a retrospective study using electronic administrative records and a cancer registry

Using the prediction of cancer outcome as a model, we have tested the hypothesis that through analysing routinely collected digital data contained in an electronic administrative record (EAR), using machine-learning techniques, we could enhance conventional methods in predicting clinical outcomes.

Nucleic acid aptamer-guided cancer therapeutics and diagnostics: the next generation of cancer medicine

Conventional anticancer therapies, such as chemo- and/or radio-therapy are often unable to completely eradicate cancers due to abnormal tumor microenvironment, as well as increased drug/radiation resistance. More effective therapeutic strategies for overcoming these obstacles are urgently in demand. Aptamers, as chemical antibodies that bind to targets with high affinity and specificity, are a promising new and novel agent for both cancer diagnostic and therapeutic applications. Aptamer-based cancer cell targeting facilitates the development of active targeting in which aptamer-mediated drug delivery could provide promising anticancer outcomes. This review is to update the current progress of aptamer-based cancer diagnosis and aptamer-mediated active targeting for cancer therapy in vivo, exploring the potential of this novel form of targeted cancer therapy.

Development of a conceptual model of cancer caregiver health literacy.

Caregivers play a vital role in caring for people diagnosed with cancer. However, little is understood about caregivers' capacity to find, understand, appraise and use information to improve health outcomes. The study aimed to develop a conceptual model that describes the elements of cancer caregiver health literacy. Six concept mapping workshops were conducted with 13 caregivers, 13 people with cancer and 11 healthcare providers/policymakers. An iterative, mixed methods approach was used to analyse and synthesise workshop data and to generate the conceptual model. Six major themes and 17 subthemes were identified from 279 statements generated by participants during concept mapping workshops. Major themes included: access to information, understanding of information, relationship with healthcare providers, relationship with the care recipient, managing challenges of caregiving and support systems. The study extends conceptualisations of health literacy by identifying factors specific to caregiving within the cancer context. The findings demonstrate that caregiver health literacy is multidimensional, includes a broad range of individual and interpersonal elements, and is influenced by broader healthcare system and community factors. These results provide guidance for the development of: caregiver health literacy measurement tools; strategies for improving health service delivery, and; interventions to improve caregiver health literacy.

Chemosensory science in the context of cancer treatment: implications for patient care

Introduction: This collaborative commentary brings together both clinical and sensory science perspectives in an effort to explain the mechanisms of cancer treatment and the ensuing implications for the sensorium. Strategy: This paper makes the distinction between food hedonics and true chemosensory effects in the cancer context and describes the adverse effects cancer and its treatment have on the eating and drinking experience, including gastronomic, nutritional and emotional implications. Results from a prospective breast cancer cohort study, conducted by an interdisciplinary team of nurses, medical oncologists, dietitians and sensory science researchers shed new light on specific sensory symptomatology associated with chemotherapy treatment and the implications this has for informing reliable pre-treatment patient education. Findings: Two conceptual models are posed as frameworks for better understanding the determinants and consequences of altered eating and drinking experiences during chemotherapy, as well as the link between patient-reported symptoms and chemosensory or hedonic disturbances. Discussion: Application of evidence of cancer treatment and its sensory effects in the patient treatment context continues to be a challenge for cancer clinicians, especially where standardised testing of taste and smell function are not able to be practically administered. Conclusions: Recommendations are made for further research and practice pursuits to underpin improved food enjoyment and dietary quality throughout the cancer trajectory. Clinician education of sensory science is also encouraged.

Comparison of anthropometric measures as predictors of cancer incidence: a pooled collaborative analysis of 11 Australian cohorts

Obesity is a risk factor for cancer. However, it is not known if general adiposity, as measured by body mass index (BMI) or central adiposity [e.g., waist circumference (WC)] have stronger associations with cancer, or which anthropometric measure best predicts cancer risk. We included 79,458 men and women from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on anthropometry [BMI, WC, Hip Circumference (HC), WHR, waist to height ratio (WtHR), A Body Shape Index (ABSI)], linked to the Australian Cancer Database. Cox proportional hazards models assessed the association between each anthropometric marker, per standard deviation and the risk of overall, colorectal, post-menopausal (PM) breast, prostate and obesity-related cancers. We assessed the discriminative ability of models using Harrell's c-statistic. All anthropometric markers were associated with overall, colorectal and obesity-related cancers. BMI, WC and HC were associated with PM breast cancer and no significant associations were seen for prostate cancer. Strongest associations were observed for WC across all outcomes, excluding PM breast cancer for which HC was strongest. WC had greater discrimination compared to BMI for overall and colorectal cancer in men and women with c-statistics ranging from 0.70 to 0.71. We show all anthropometric measures are associated with the overall, colorectal, PM breast and obesity-related cancer in men and women, but not prostate cancer. WC discriminated marginally better than BMI. However, all anthropometric measures were similarly moderately predictive of cancer risk. We do not recommend one anthropometric marker over another for assessing an individuals' risk of cancer.

Understanding toxicities and complications of cancer treatment: a data mining approach

Cancer remains a major challenge in modern medicine. Increasing prevalence of cancer, particularly in developing countries, demands better understanding of the effectiveness and adverse consequences of different cancer treatment regimes in real patient population. Current understanding of cancer treatment toxicities is often derived from either “clean” patient cohorts or coarse population statistics. It is difficult to get up-to-date and local assessment of treatment toxicities for specific cancer centres. In this paper, we applied an Apriori-based method for discovering toxicity progression patterns in the form of temporal association rules. Our experiments show the effectiveness of the proposed method in discovering major toxicity patterns in comparison with the pairwise association analysis. Our method is applicable for most cancer centres with even rudimentary electronic medical records and has the potential to provide real-time surveillance and quality assurance in cancer care.