The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol

Background: People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied.Methods/design: A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels.Discussion: This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible.Trial registration: Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235. © 2012 Dhillon et al.; licensee BioMed Central Ltd

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

Novel Colicin F-Y of Yersinia frederiksenii Inhibits Pathogenic Yersinia Strains via YiuR-Mediated Reception, TonB Import, and Cell Membrane Pore Formation

A novel colicin type, designated colicin F-Y, was found to be encoded and produced by the strain Yersinia frederiksenii Y27601. Colicin F-Y was active against both pathogenic and nonpathogenic strains of the genus Yersinia. Plasmid YF27601 (5,574 bp) of Y. frederiksenii Y27601 was completely sequenced. The colicin F-Y activity gene (cfyA) and the colicin F-Y immunity gene (cfyI) were identified. The deduced amino acid sequence of colicin F-Y was very similar in its C-terminal pore-forming domain to colicin Ib (69% identity in the last 178 amino acid residues), indicating pore forming as its lethal mode of action. Transposon mutagenesis of the colicin F-Y-susceptible strain Yersinia kristensenii Y276 revealed the yiuR gene (ykris001_4440), which encodes the YiuR outer membrane protein with unknown function, as the colicin F-Y receptor molecule. Introduction of the yiuR gene into the colicin F-Y-resistant strain Y. kristensenii Y104 restored its susceptibility to colicin F-Y. In contrast, the colicin F-Y-resistant strain Escherichia coli TOP10F' acquired susceptibility to colicin F-Y only when both the yiuR and tonB genes from Y. kristensenii Y276 were introduced. Similarities between colicins F-Y and Ib, similarities between the Cir and YiuR receptors, and the detected partial cross-immunity of colicin F-Y and colicin Ib producers suggest a common evolutionary origin of the colicin F-Y-YiuR and colicin Ib-Cir systems

Weight Gain Is Associated with Medial Contact Site of Subthalamic Stimulation in Parkinson's Disease

The aim of our study was to assess changes in body-weight in relation to active electrode contact position in the subthalamic nucleus. Regular body weight measurements were done in 20 patients with advanced Parkinson's disease within a period of 18 months after implantation. T1-weighted (1.5T) magnetic resonance images were used to determine electrode position in the subthalamic nucleus and the Unified Parkinson's disease rating scale (UPDRS-III) was used for motor assessment. The distance of the contacts from the wall of the third ventricle in the mediolateral direction inversely correlated with weight gain (r = −0.55, p<0.01) and with neurostimulation-related motor condition expressed as the contralateral hemi-body UPDRS-III (r = −0.42, p<0.01). Patients with at least one contact within 9.3 mm of the wall experienced significantly greater weight gain (9.4±(SD)4.4 kg, N = 11) than those with both contacts located laterally (3.9±2.7 kg, N = 9) (p<0.001). The position of the active contact is critical not only for motor outcome but is also associated with weight gain, suggesting a regional effect of subthalamic stimulation on adjacent structures involved in the central regulation of energy balance, food intake or reward

Transcriptional Regulation of the Beta-Synuclein 5′-Promoter Metal Response Element by Metal Transcription Factor-1

The progression of many human neurodegenerative disorders is associated with an accumulation of alpha-synuclein. Alpha-synuclein belongs to the homologous synuclein family, which includes beta-synuclein. It has been proposed that beta-synuclein may be a natural regulator of alpha-synuclein. Therefore controlling beta-synuclein expression may control the accumulation of alpha-synuclein and ultimately prevent disease progression. The regulation of synucleins is poorly understood. We investigated the transcriptional regulation of beta-synuclein, with the aim of identifying molecules that differentially control beta-synuclein expression levels. To investigate transcriptional regulation of beta-synuclein, we used reporter gene assays and bioinformatics. We identified a region −1.1/−0.6 kb upstream of the beta-synuclein translational start site to be a key regulatory region of beta-synuclein 5′-promoter activity in human dopaminergic cells (SH-SY5Y). Within this key promoter region we identified a metal response element pertaining to a putative Metal Transcription Factor-1 (MTF-1) binding site. We demonstrated that MTF-1 binds to this 5′-promoter region using EMSA analysis. Moreover, we showed that MTF-1 differentially regulates beta-synuclein promoter binding site, as well as beta-synuclein mRNA and protein expression. This effect of MTF-1 on expression was found to be specific to beta-synuclein when compared to alpha-synuclein. Understanding the regulation of synucleins and how they interact may point to molecular targets that could be manipulated for therapeutic benefit. In this study we showed that MTF-1 differentially controls the expression of beta-synuclein when compared to its homolog alpha-synuclein. This could potentially provide a novel targets or pathways for therapeutic intervention and/or treatment of synucleinopathies

'Pragmatic randomized controlled trial of individually prescribed exercise versus usual care in a heterogeneous cancer survivor population': A feasibility study PEACH Trial: Prescribed exercise after chemotherapy

<p>Abstract</p> <p>Background</p> <p>Many cancer survivors suffer a range of physical and psychological symptoms which may persist for months or years after cessation of treatment. Despite the known benefits of exercise and its potential to address many of the adverse effects of treatment, the role of exercise as well as optimum duration, frequency, and intensity in this population has yet to be fully elucidated. Many cancer rehabilitation programmes presented in the literature are very long and have tight eligibility criteria which make them non-applicable to the majority of cancer survivors. This paper presents the protocol of a novel 8-week intervention which aims to increase fitness, and address other physical symptoms in a heterogeneous cancer survivor population.</p> <p>Methods/design</p> <p>The aim is to recruit 64 cancer survivors 2-6 months after completion of chemotherapy, usually adjuvant, with curative intent. Subjects will be recruited through oncology clinics in a single institution and randomised to usual care or an exercise intervention. The exercise intervention consists of two specifically tailored supervised moderate intensity aerobic exercise sessions weekly over 8-weeks. All participants will be assessed at baseline (0 weeks), at the end of the intervention (8 weeks), and at 3-month follow-up. The primary outcome measure is fitness, and secondary patient-related outcome measures include fatigue, quality of life, and morphological outcomes. A further secondary outcome is process evaluation including adherence to and compliance with the exercise program.</p> <p>Discussion</p> <p>This study will provide valuable information about the physical outcomes of this 8-week supervised aerobic programme. Additionally, process information and economic evaluation will inform the feasibility of implementing this program in a heterogeneous population post cessation of chemotherapy.</p> <p>Trial Registration</p> <p>NCT01030887</p