To identify novel non-invasive biomarkers for improved detection, risk assessment and prognostic evaluation of cancer, expression profiles of circulating microRNAs are currently under evaluation. ...Circulating microRNAs are highly promising candidates in this context, as they present some key characteristics for cancer biomarkers: they are tissue-specific with reproducible expression and consistency among individuals from the same species, they are potentially derived directly from the tumour and therefore might correlate with tumour progression and recurrence, and they are bound to proteins or contained in subcellular particles, such as microvesicles or exosomes, making them highly stable and resistant to degradation. The present review highlights the origin of circulating microRNAs, their stability in blood samples, and techniques to isolate exosomal microRNAs, and then addresses the current evidence supporting potential clinical applications of circulating miRNAs for diagnostic and prognostic purposes.
SUMMARY
Esophageal cancer is a serious malignancy often treated with multimodal interventions and complex surgical resection. As treatment moves to centers of excellence with emphasis on enhanced ...recovery approaches, the role of the physiotherapist has expanded. The aim of this review is to discuss the rationale behind both the evolving prehabilitative role of the physiotherapist and more established postoperative interventions for patients with esophageal cancer. While a weak association between preoperative cardiopulmonary fitness and post-esophagectomy outcome is reported, cardiotoxicity during neoadjuvant chemotherapy and/or radiotherapy may heighten postoperative risk. Preliminary studies suggest that prehabilitative inspiratory muscle training may improve postoperative outcome. Weight and muscle loss are a recognized sequelae of esophageal cancer and the functional consequences of this should be assessed. Postoperative physiotherapy priorities include effective airway clearance and early mobilization. The benefits of respiratory physiotherapy post-esophagectomy are described by a small number of studies, however, practice increasingly recognizes the importance of early mobilization as a key component of postoperative recovery. The benefits of exercise training in patients with contraindications to mobilization remain to be explored. While there is a strong basis for tailored physiotherapy interventions in the management of patients with esophageal cancer, this review highlights the need for studies to inform prehabilitative and postoperative interventions.
Purpose
Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with ...skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC.
Methods
Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function).
Results
Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years,
n
= 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic
n
= 2) to post-treatment (pre-sarcopenic
n
= 5, severely sarcopenic
n
= 1).
Conclusions
Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.
Successful treatment of gonorrhoea is the mainstay of public health control. Cefixime and ceftriaxone, highly active third generation cephalosporins, are today the recommended first-line agents in ...most countries and azithromycin is a second-line agent. However, there is increasing evidence of decreasing susceptibility and emergence of therapeutic failures. In this report two cases of clinical failure to cefixime are described, one of which additionally shows failure to azithromycin and selection of a less susceptible strain during treatment.
Abstract Objectives To examine the energy expenditure and heart rate response while playing active video games, and the effect of gaming experience on energy expenditure. Design Cross-sectional ...study. Participants and interventions Twenty-eight healthy participants (18 male, age 19 to 27 years) played either Wii Sports Boxing, Tennis and Baseball, or Wii Sports Boxing and Wii Fit Free Jogging. Main outcome measures Percentage maximal heart rate (%HRmax) and metabolic equivalents (METs) were measured during 15 minutes of rest and during each game. Results Mean %HRmax and METs while playing each of the four games were as follows: Wii Fit Free Jogging 71% standard deviation (SD) 13%, 5.9 (SD 1.8); Wii Sports Boxing 58% (SD 13%), 3.2 (SD 1.1); Wii Sports Baseball 42% (SD 6%), 2.0 (SD 0.5); and Wii Sports Tennis 42% (SD 7%), 2.0 (SD 0.4). Subjects with gaming experience achieved a lower heart rate playing Wii Sports Tennis compared with subjects without gaming experience. Conclusions Wii Sports Boxing, Tennis and Baseball are light-intensity activities, and Wii Fit Free Jogging is a moderate-intensity activity. Experience of gaming may affect the exercise intensity of games requiring controller skill.
AIM:To investigate expression of microRNA(miRNA)and potential targets in chemotherapy resistant esoph-ageal cancer cell lines.METHODS:An in-vitro model of acquired chemotherapy resistance in ...esophageal adeno-(EAC)and squamous cell carcinoma(ESCC)cells was used,and microRNA expression profiles for cisplatin or 5-fluorouracil(5-FU)resistant variants vs chemotherapy sensitive controls were compared using microarray and quantitative real-time polymerase chain reaction(PCR).The expression of chemotherapy-relevant genes potentially targeted by the dysregulated microRNAs in the chemotherapy resistant variants was also evaluated.RESULTS:Chemotherapy resistant sublines were found to have specific miRNA signatures,and these miRNA signatures were different for the cisplatin vs 5-FU resistant cells from the same tumor cell line,and also for EAC vs ESCC cells with resistance to the same specific chemotherapy agent.Amongst others,miR-27b-3p,miR-193b-3p,miR-192-5p,miR-378 a-3p,miR-125a-5p and miR-18a-3p were dysregulated,consistent with negative posttranscriptional control of KRAS,TYMS,ABCC3,CBL-B and ERBB2 expression via these miRNAs.CONCLUSION:The current study supports the hypothesis that microRNA expression has an impact on chemotherapy resistance in esophageal cancer.
SUMMARY
Reduced physical functioning is common following resections for esophageal cancer; however, objective data on physical performance outcomes in this cohort are rare. The aim of this study was ...to assess the physical performance and health related quality of life (HRQOL) of disease free survivors and compare findings in a case matched noncancer control group. Twenty-five males (mean (±SD) aged 63 (±6) years) who were over 6 months postesophagectomy and disease-free were compared with 25 controls (60 ± 6 years). Physical functioning was assessed through hand grip strength (dynamometry), exercise capacity (incremental shuttle walk test), physical activity levels (RT3 accelerometer), and body composition (bio-electrical impedance analysis). Health-related quality of life was measured using the EORTC QLQ-C30 questionnaire. Esophageal cancer survivors demonstrated significantly lower fitness (P < 0.001) and time spent in moderate (P < 0.001) and vigorous (P < 0.001) intensity physical activity compared with controls. Global health status and quality of life were similar in both groups (P = 0.245); however, physical and role functioning domains were lower in the cancer survivors (P < 0.001, and P = 0.001, respectively). These data show that disease-free survivors of curative esophageal cancer treatment demonstrate a significant compromise in physical functioning compared with controls, thus highlighting the multiple, complex rehabilitative needs of this cohort.
The factors and mechanisms involved in vacuolar transport in plants, and in particular those directing vesicles to their target endomembrane compartment, remain largely unknown. To identify ...components of the vacuolar trafficking machinery, we searched for Arabidopsis modified transport to the vacuole (mtv) mutants that abnormally secrete the synthetic vacuolar cargo VAC2. We report here on the identification of 17 mtv mutations, corresponding to mutant alleles of MTV2/VSR4, MTV3/PTEN2A MTV7/EREL1, MTV8/ARFC1, MTV9/PUF2, MTV10/VPS3, MTV11/VPS15, MTV12/GRV2, MTV14/GFS10, MTV15/BET11, MTV16/VPS51, MTV17/VPS54, and MTV18/VSR1. Eight of the MTV proteins localize at the interface between the trans-Golgi network (TGN) and the multivesicular bodies (MVBs), supporting that the trafficking step between these compartments is essential for segregating vacuolar proteins from those destined for secretion. Importantly, the GARP tethering complex subunits MTV16/VPS51 and MTV17/VPS54 were found at endoplasmic reticulum (ER)- and microtubule-associated compartments (EMACs). Moreover, MTV16/VPS51 interacts with the motor domain of kinesins, suggesting that, in addition to tethering vesicles, the GARP complex may regulate the motors that transport them. Our findings unveil a previously uncharacterized compartment of the plant vacuolar trafficking pathway and support a role for microtubules and kinesins in GARP-dependent transport of soluble vacuolar cargo in plants.
The Origin of Phragmoplast Asymmetry Smertenko, Andrei P.; Piette, Bernard; Hussey, Patrick J.
CB/Current biology,
11/2011, Letnik:
21, Številka:
22
Journal Article
Recenzirano
Odprti dostop
The phragmoplast coordinates cytokinesis in plants 1. It directs vesicles to the midzone, the site where they coalesce to form the new cell plate. Failure in phragmoplast function results in aborted ...or incomplete cytokinesis leading to embryo lethality, morphological defects, or multinucleate cells 2, 3. The asymmetry of vesicular traffic is regulated by microtubules 1, 4, 5, 6, and the current model suggests that this asymmetry is established and maintained through treadmilling of parallel microtubules. However, we have analyzed the behavior of microtubules in the phragmoplast using live-cell imaging coupled with mathematical modeling and dynamic simulations and report that microtubules initiate randomly in the phragmoplast and that the majority exhibit dynamic instability with higher turnover rates nearer to the midzone. The directional transport of vesicles is possible because the majority of the microtubules polymerize toward the midzone. Here, we propose the first inclusive model where microtubule dynamics and phragmoplast asymmetry are consistent with the localization and activity of proteins known to regulate microtubule assembly and disassembly.
► Live-cell imaging reveals that MT treadmilling does not drive phragmoplast morphology ► Mathematical modeling reveals that phragmoplast MTs are undergoing dynamic instability
Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are ...required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC.
Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature.
A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone.
We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.
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