Carlsenmcdougall7309

BACKGROUND Older adults have the highest sedentary time across all age groups, and only a small portion is meeting the minimum recommendations for weekly physical activity. Little research to date has looked at how changes in one of these behaviours influences the other. AIM To assess changes in 24-h movement behaviours (sedentary time, light intensity physical activity (LPA), moderate-vigorous PA (MVPA) and sleep) over three consecutive days, following acute bouts of exercise of varying intensity in older adults. METHODS Participants (n = 28, 69.7 ± 6.5 years) completed a maximal exercise test and the following exercise protocols in random order moderate continuous exercise (MOD), high-intensity interval exercise (HI) and sprint interval exercise (SPRT). A thigh-worn device (ActivPAL™) was used to measure movement behaviours at baseline and the 3 days following each exercise session. RESULTS Repeated measures analysis of variance indicated that compared to baseline, participants decreased MVPA in the 3 days following all exercise sessions and decreased LPA following HI and SPRT (p  less then  0.05). Over half of the sample had clinically meaningful increases in sedentary time (30 min/day) in the days following exercise participation. DISCUSSION Older adults who compensate for exercise participation by reducing physical activity and increasing sedentary time in subsequent days may require behavioural counseling to ensure that incidental and recreational physical activities are not reduced. BIBF 1120 clinical trial CONCLUSION It appears that older adults compensate for acute exercise by decreasing MVPA and LPA, and increasing sedentary time in the days following exercise. Future research is needed to determine whether compensation persists with regular engagement.Experimental tumor modeling has long supported the discovery of fundamental mechanisms of tumorigenesis and tumor progression, as well as provided platforms for the development of novel therapies. Still, the attrition rates observed today in clinical translation could be, in part, mitigated by more accurate recapitulation of environmental cues in research and preclinical models. The increasing understanding of the decisive role that tumor microenvironmental cues play in the outcome of drug response urges its integration in preclinical tumor models. In this chapter we review recent developments concerning in vitro and ex vivo approaches.The zebrafish larvae have emerged as a powerful model for studying tumorigenesis in vivo, with remarkable conservation with mammals in genetics, molecular and cell biology. Zebrafish tumor models bear the significant advantages of optical clarity in comparison to that in the mammalian models, allowing noninvasive investigation of the tumor cell and its microenvironment at single-cell resolution. Here we review recent progressions in the field of zebrafish models of solid tumor diseases in two main categories the genetically engineered tumor models in which all cells in the tumor microenvironment are zebrafish cells, and xenograft tumor models in which the tumor microenvironment is composed of zebrafish cells and cells from other species. link2 Notably, the zebrafish patient-derived xenograft (zPDX) models can be used for personalized drug assessment on primary tumor biopsies, including the pancreatic cancer. For the future studies, a series of high throughput drug screenings on the library of transgenic zebrafish models of solid tumor are expected to provide systematic database of oncogenic mutation, cell-of-origin, and leading compounds; and the humanization of zebrafish in genetics and cellular composition will make it more practical hosts for zPDX modeling. link3 Together, zebrafish tumor model systems are unique and convenient in vivo platforms, with great potential to serve as valuable tools for cancer researches.This chapter provides a brief overview of the methods to study and modulate the metabolic phenotype of the tumor microenvironment, including own research work to demonstrate the impact that metabolic shifts in the host have on cancer. Firstly, we briefly discuss the relevance of using animal models to address this topic, and also the importance of acknowledging that animals have diverse metabolic phenotypes according to species, and even with strain, age or sex. We also present original data to highlight the impact that changes in metabolic phenotype of the microenvironment have on tumor progression. Using an acute leukemia mouse xenograft model and high-fat diet we show that a shift in the host metabolic phenotype, induced by high-fat feeding, significantly impacts on tumor progression. The mechanism through which this occurs involves a direct effect of the increased levels of circulating lipoproteins in both tumor and non-neoplastic cells.Cancers are complex tissues composed by genetically altered cancer cells and stromal elements such as inflammatory/immune cells, fibroblasts, endothelial cells and pericytes, neuronal cells, and a non-cellular component, the extracellular matrix. The complex network of interactions and crosstalk established between cancer cells and the supportig cellular and non-cellular components of the microenvironment are of extreme importance for tumor initiation and progression, strongly impacting the course and the outcome of the disease. Therefore, a better understanding of the tumorigenic processes implies the combined study of the cancer cell and the biologic, chemical and mechanic constituents of the tumor microenvironment, as their concerted action plays a major role in the carcinogenic pathway and is a key determinant of the efficacy of anti-cancer treatments. The use of animal models (e.g. Mouse, Zebrafish and Drosophila) to study cancer has greatly impacted our understanding of the processes governing initiation, progression and metastasis and allowed the discovery and pre-clinical validation of novel cancer treatments as it allows to recreate tumor development in a more pathophysiologic environment.Altered metabolism is one of the key hallmarks of cancer. The development of sensitive, reproducible and robust bioanalytical tools such as Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry techniques offers numerous opportunities for cancer metabolism research, and provides additional and exciting avenues in cancer diagnosis, prognosis and for the development of more effective and personalized treatments. In this chapter, we introduce the current state of the art of metabolomics and metabolic phenotyping approaches in cancer research and clinical diagnostics.Ovarian cancer is a silent cancer which rate survival mainly relays in early stage detection. The discovery of reliable ovarian cancer biomarkers plays a crucial role in the disease management and strongly impact in patient's prognosis and survival. Although having many limitations CA125 is a classical ovarian cancer biomarker, but current research using proteomic or metabolomic methodologies struggles to find alternative biomarkers, using non-invasive our relatively non-invasive sources such as urine, serum, plasma, tissue, ascites or exosomes. Metabolism and metabolites are key players in cancer biology and its importance in biomarkers discovery cannot be neglected. In this chapter we overview the state of art and the challenges facing the use and discovery of biomarkers and focus on ovarian cancer early detection.Hydrogen sulfide (H2S), while historically perceived merely as a toxicant, has progressively emerged as a key regulator of numerous processes in mammalian physiology, exerting its signaling function essentially through interaction with and/or modification of proteins, targeting mainly cysteine residues and metal centers. As a gaseous signaling molecule that freely diffuses across aqueous and hydrophobic biological milieu, it has been designated the third 'gasotransmitter' in mammalian physiology. H2S is synthesized and detoxified by specialized endogenous enzymes that operate under a tight regulation, ensuring homeostatic levels of this otherwise toxic molecule. Indeed, imbalances in H2S levels associated with dysfunctional H2S metabolism have been growingly correlated with various human pathologies, from cardiovascular and neurodegenerative diseases to cancer. Several cancer cell lines and specimens have been shown to naturally overexpress one or more of the H2S-synthesizing enzymes. The resulting increased H2S levels have been proposed to promote cancer development through the regulation of various cancer-related processes, which led to the interest in pharmacological targeting of H2S metabolism. Herein are summarized some of the key observations that place H2S metabolism and signaling pathways at the forefront of the cellular mechanisms that support the establishment and development of a tumor within its complex and challenging microenvironment. Special emphasis is given to the mechanisms whereby H2S helps shaping cancer cell bioenergetic metabolism and affords resistance and adaptive mechanisms to hypoxia.Lung cancer is the leading cause of cancer-related deaths worldwide in both men and women. Conventional chemotherapy has failed to provide long-term benefits for many patients and in the past decade, important advances were made to understand the underlying molecular/genetic mechanisms of lung cancer, allowing the unfolding of several other pathological entities. Considering these molecular subtypes, and the appearance of promising targeted therapies, an effective personalized control of the disease has emerged, nonetheless benefiting a small proportion of patients. Although immunotherapy has also appeared as a new hope, it is still not accessible to the majority of patients with lung cancer.The metabolism of energy and biomass is the basis of cellular survival. This is true for normal cells under physiological conditions and it is also true for pathophysiologically altered cells, such as cancer cells. Thus, knowledge of the metabolic remodelling that occurs in cancer cells in the sense of, on one hand, surviving in the microenvironment of the organ in which the tumour develops and, on the other hand, escaping from drugs conditioned microenvironment, is essential to understand the disease and to develop new therapeutic approaches.Despite all the progresses developed in prevention and new treatment approaches, cancer is the second leading cause of death worldwide, being chemoresistance a pivotal barrier in cancer management. Cancer cells present several mechanisms of drug resistance/tolerance and recently, growing evidence have been supporting a role of metabolism reprograming per se as a driver of chemoresistance. In fact, cancer cells display several adaptive mechanisms that allow the emergency of chemoresistance, revealing cancer as a disease that adapts and evolve along with the treatment. Therefore, clinical protocols that take into account the adaptive potential of cancer cells should be more effective than the current traditional standard protocols on the fighting against cancer.In here, some of the recent findings on the role of metabolism reprograming in cancer chemoresistance emergence will be discussed, as the potential evolutionary strategies that could unable these adaptations, hence allowing to prevent the emergency of treatment resistance, changing cancer outcome.