Abstract:
:Cachexia, or wasting of skeletal muscle and fat, afflicts many patients with chronic diseases including cancer, organ failure, and AIDS. Muscle wasting reduces quality of life and decreases response to therapy. Cachexia is caused partly by elevated inflammatory cytokines, including interleukin-6 (IL-6). Others and we have shown that IL-6 alone is sufficient to induce cachexia both in vitro and in vivo. The mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor Selumetinib has been tested in clinical trials for various cancers. Moreover, Selumetinib has also been shown to inhibit the production of IL-6. In a retrospective analysis of a phase II clinical trial in advanced cholangiocarcinoma, patients treated with Selumetinib experienced significant gains in skeletal muscle vs. patients receiving standard therapy. However, the use of Selumetinib as a treatment for cachexia has yet to be investigated mechanistically. We sought to determine whether MEK inhibition could protect against cancer-induced cachexia in mice. In vitro, Selumetinib induced C2C12 myotube hypertrophy and nuclear accretion. Next we tested Selumetinib in the Lewis lung carcinoma (LLC) model of cancer cachexia. Treatment with Selumetinib reduced tumor mass and reduced circulating and tumor IL-6; however MEK inhibition did not preserve muscle mass. Similar wasting was seen in limb muscles of Selumetinib and vehicle-treated LLC mice, while greater fat and carcass weight loss was observed with Selumetinib treatment. As well, Selumetinib did not block wasting in C2C12 myotubes treated with LLC serum. Taken together, out results suggest that this MEK inhibitor is not protective in LLC cancer cachexia despite lowering IL-6 levels, and further that it might exacerbate tumor-induced weight loss. Differences from other studies might be disease, species or model-specific.
journal_name
Front Physioljournal_title
Frontiers in physiologyauthors
Au ED,Desai AP,Koniaris LG,Zimmers TAdoi
10.3389/fphys.2016.00682subject
Has Abstractpub_date
2017-01-18 00:00:00pages
682issn
1664-042Xjournal_volume
7pub_type
杂志文章abstract::Antibiotic resistance is a major issue in animal industries and antibiotic-free alternatives are needed to treat infectious diseases and improve performance of pigs. Plant extracts have been suggested as a potential solution. The present study was conducted to investigate the effects of Astragalus polysaccharides (Aps...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00418
更新日期:2019-04-12 00:00:00
abstract::Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. In addition to the widely studied dysregulated glucose metabolism to fuel tumor cell growth, accumulating evidences suggest that utiliz...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2015.00382
更新日期:2015-12-16 00:00:00
abstract::The extracellular tooth enamel matrix is a unique, protein-rich environment that provides the structural basis for the growth of long and parallel oriented enamel crystals. Here we have conducted a series of in vivo and in vitro studies to characterize the changes in matrix shape and organization that take place durin...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00790
更新日期:2017-10-17 00:00:00
abstract::Mucolipins (TRPML) are endosome/lysosome Ca2+ permeable channels belonging to the family of transient receptor potential channels. In mammals, there are three TRPML proteins, TRPML1, 2, and 3, encoded by MCOLN1-3 genes. Among these channels, TRPML1 is a reactive oxygen species sensor localized on the lysosomal membran...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2020.00251
更新日期:2020-03-24 00:00:00
abstract:UNLABELLED:Limitations of current methods: Normalization of resting energy expenditure (REE) for body composition using the 2-compartment model fat mass (FM), and fat-free mass (FFM) has inherent limitations for the interpretation of REE and may lead to erroneous conclusions when comparing people with a wide range of a...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2013.00047
更新日期:2013-03-25 00:00:00
abstract::Molar hypomineralisation (MH) is becoming globally recognised as a significant public health problem linked to childhood tooth decay. However, with causation and pathogenesis unclear after 100 years of investigation, better pathological understanding is needed if MH is to become preventable. Our studies have implicate...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.579015
更新日期:2020-09-30 00:00:00
abstract::Introduction: Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Little is known concerning the adaptive responses of BRS during acclimatization to high altitude at rest and during exercise. Methods: Twenty-one healthy sea-level residents were tested near sea lev...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00767
更新日期:2018-06-21 00:00:00
abstract::Sarcopenia is the age-related progressive loss of skeletal muscle mass and strength finally leading to poor physical performance. Impaired myogenesis contributes to the pathogenesis of sarcopenia, while mitochondrial dysfunctions are thought to play a primary role in skeletal muscle loss during aging. Here we studied ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.00897
更新日期:2019-07-10 00:00:00
abstract::Dental and periodontal tissue development is a complex process involving various cell-types. A finely orchestrated network of communications between these cells is implicated. During early development, communications between cells from the oral epithelium and the underlying mesenchyme govern the dental morphogenesis w...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2015.00319
更新日期:2015-11-05 00:00:00
abstract::Length-dependent activation of calcium-dependent myocardial force generation provides the basis for the Frank-Starling mechanism. To directly compare the effects of mutations associated with hypertrophic cardiomyopathy and dilated cardiomyopathy, the native troponin complex in skinned trabecular fibers of guinea pigs ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00516
更新日期:2020-06-03 00:00:00
abstract::Cryptochromes (CRYs) are flavoproteins that are sensitive to blue light, first identified in Arabidopsis and then in Drosophila and mice. They are evolutionarily conserved and play fundamental roles in the circadian clock of living organisms, enabling them to adapt to the daily 24-h cycles. The role of CRYs in circadi...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2020.00099
更新日期:2020-03-05 00:00:00
abstract::Exhaled breath carbon monoxide (eCO) is a candidate biomarker for non-invasive assessment of oxidative stress and respiratory diseases. Standard end-tidal CO analysis, however, cannot distinguish, whether eCO reflects endogenous CO production, lung diffusion properties or exogenous sources, and is unable to resolve a ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00927
更新日期:2018-07-30 00:00:00
abstract:Purpose:The aim of this study was to verify whether physiological components [vertical jumps (Squat Jump - SJ and Countermovement Jump - CMJ), eccentric utilization ratio (EUR) of vertical jumps, running economy (RE), metabolic cost (C MET ), first and second ventilatory th...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00979
更新日期:2020-08-05 00:00:00
abstract::Excessive alcohol consumption is associated with hepatic steatosis and dysregulation of the gut microbiota in patients with alcohol use disorder (AUD). However, how gut microbiota responds when patients stop drinking has not been well studied. In this study, we use shotgun metagenomic sequencing to elucidate the alter...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00370
更新日期:2020-04-24 00:00:00
abstract::[This corrects the article DOI: 10.3389/fphys.2019.00116.]. ...
journal_title:Frontiers in physiology
pub_type: 杂志文章,已发布勘误
doi:10.3389/fphys.2019.00669
更新日期:2019-05-28 00:00:00
abstract::Biological aging is an inevitable part of life that has intrigued individuals for millennia. The progressive decline in biological systems impacts cardiac function and increases vulnerability to stress contributing to morbidity and mortality in aged individuals. Yet, our understanding of the molecular, biochemical and...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00048
更新日期:2020-02-07 00:00:00
abstract::The transient receptor potential vanilloid member 1 (TRPV1) in the central nervous system may contribute to homeostatic plasticity by regulating intracellular Ca2+, which becomes unbalanced in age-related neurodegenerative diseases, including Alzheimer's and Huntington's. Glaucomatous optic neuropathy - the world's le...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00249
更新日期:2020-03-26 00:00:00
abstract::Untreated chronic hypertension causes left ventricular hypertrophy, which is related to the occurrence of atrial fibrillation. Dronedarone is an antiarrhythmic agent recently approved for atrial fibrillation. Our group previously demonstrated that dronedarone produced an early regression of left ventricular hypertroph...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2020.00967
更新日期:2020-08-26 00:00:00
abstract::To fully unravel the ixodid ticks' role as vectors of viral pathogens, their susceptibility to new control measures, and their ability to develop acaricide resistance, acclimatization of ticks under laboratory conditions is greatly needed. However, the unique and complicated feeding behavior of these ticks compared to...
journal_title:Frontiers in physiology
pub_type: 杂志文章,评审
doi:10.3389/fphys.2018.01728
更新日期:2018-12-04 00:00:00
abstract::Adipokinetic hormones (AKHs) are well known to mobilize lipids and carbohydrates for energy-consuming activities in insects. These neuropeptides exert their functions by interacting with AKH receptors (AKHRs) located on the plasma membrane of fat body cells, which regulates energy mobilization by stimulating lipolysis...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01904
更新日期:2019-01-08 00:00:00
abstract::Short bowel syndrome (SBS) is characterized by severe intestinal malabsorption following restrictive surgery. The objective of this study was to determine the functional contribution of SBS-microbiota after resection. It is well-known that SBS-microbiota displayed specific features with a prevalence of Lactobacillus, ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00224
更新日期:2017-04-19 00:00:00
abstract::Spodoptera exigua and S. litura are two sympatric species in China and many other countries. Both moths employ a multiple component sex pheromone blend, including a common component Z9,E12-14:OAc, and two specific components Z9-14:OH and Z11-16:OAc for S. exigua, and one specific component Z9,E11-14:OAc for S. litura....
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01256
更新日期:2019-09-27 00:00:00
abstract::The study was conducted to compare and evaluate effects of four different macro-algaes on growth, immune response, and intestinal microbiota of Litopenaeus vannamei. In the rearing trial 1, shrimp were fed five diets containing four sources of macro-algaes for 8 weeks, named D1 (without macro-algae), D2 (Porphyra hait...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01880
更新日期:2019-01-09 00:00:00
abstract::Acute liver failure (ALF) is characterized by a sudden and severe deterioration of liver function, typically mirrored by a marked increase of the international normalized ratio (INR) and hepatic encephalopathy (HE). Due to various possible causes hepatocytes get damaged via either apoptotic or necrotic pathways. Antic...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2012.00340
更新日期:2012-08-28 00:00:00
abstract::Astronauts exposed to microgravity face sensorimotor challenges affecting balance control when readapting to Earth's gravity upon return from spaceflight. Small amounts of electrical noise applied to the vestibular system have been shown to improve balance control during standing and walking under discordant sensory c...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.00301
更新日期:2018-03-29 00:00:00
abstract::Many disease fighting strategies have focused on the generation of NK cells, since they constitute the main immune barrier against cancer and intracellular pathogens such as viruses. Therefore, a predictive model for the development of NK cells would constitute a useful tool to test several hypotheses regarding the pr...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01029
更新日期:2018-08-02 00:00:00
abstract::The large amount of energy expended during flapping flight is associated with heat generated through the increased work of the flight muscles. This increased muscle work rate can manifest itself in core body temperature (Tb) increase of 1-2°C in birds during flight. Therefore, episodic body cooling may be mandatory in...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2017.00532
更新日期:2017-07-25 00:00:00
abstract::Denervation induces skeletal muscle atrophy, accompanied by complex biochemical and physiological changes, with potentially devastating outcomes even an increased mortality. Currently, however, there remains a paucity of effective strategies to treat skeletal muscle atrophy. Therefore, it is required to understand the...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01298
更新日期:2019-10-11 00:00:00
abstract::We tested the hypotheses that prior aerobic (Study 1) or anaerobic (Study 2) exercise attenuates the increase in renal vascular resistance (RVR) during sympathetic stimulation. Ten healthy young adults (5 females) participated in both Study 1 (aerobic exercise) and Study 2 (anaerobic exercise). In Study 1, subjects co...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2018.01928
更新日期:2019-01-10 00:00:00
abstract::The aim of this study was to examine the effects of Lactobacillus brevis on the microbial community and serum metabolome in colitis induced by dextran sulfate sodium (DSS). ICR mice were randomly distributed into three treatment groups: (i) L. brevis treatment alone (control), (ii) DSS administration alone, and (iii) ...
journal_title:Frontiers in physiology
pub_type: 杂志文章
doi:10.3389/fphys.2019.01152
更新日期:2019-09-18 00:00:00