Glutathione (GSH) is the most abundant antioxidant found in living organisms and has multiple functions, most of which maintain cellular redox homeostasis. GSH preserves sufficient levels of cysteine ...and detoxifies xenobiotics while also conferring therapeutic resistance to cancer cells. However, GSH metabolism plays both beneficial and pathogenic roles in a variety of malignancies. It is crucial to the removal and detoxification of carcinogens, and alterations in this pathway can have a profound effect on cell survival. Excess GSH promotes tumor progression, where elevated levels correlate with increased metastasis. In this review, we discuss recent studies that focus on deciphering the role of GSH in tumor initiation and progression as well as mechanisms underlying how GSH imparts treatment resistance to growing cancers. Targeting GSH synthesis/utilization therefore represents a potential means of rendering tumor cells more susceptible to different treatment options such as chemotherapy and radiotherapy.
Résumé
La pochite est une inflammation non spécifique du réservoir confectionné après coloproctectomie avec anastomose iléoanale pour rectocolite hémorragique ou polypose adénomateuse familiale. Le ...diagnostic est porté sur des critères cliniques, endoscopiques et histologiques. On distingue la forme aiguë traitée par antibiothérapie sur des données empiriques et la forme chronique persistant au-delà de quatre semaines malgré les antibiotiques. Cette forme concerne 15 % des patients. Son traitement est mal codifié, empirique, en raison de la faiblesse en nombre et en qualité des études. Les antibiotiques, les corticoïdes, puis les biothérapies (essentiellement les anti-TNF) peuvent être prescrits pour traiter la pochite chronique.
Molecular oxygen (O
) sustains intracellular bioenergetics and is consumed by numerous biochemical reactions, making it essential for most species on Earth. Accordingly, decreased oxygen ...concentration (hypoxia) is a major stressor that generally subverts life of aerobic species and is a prominent feature of pathological states encountered in bacterial infection, inflammation, wounds, cardiovascular defects and cancer. Therefore, key adaptive mechanisms to cope with hypoxia have evolved in mammals. Systemically, these adaptations include increased ventilation, cardiac output, blood vessel growth and circulating red blood cell numbers. On a cellular level, ATP-consuming reactions are suppressed, and metabolism is altered until oxygen homeostasis is restored. A critical question is how mammalian cells sense oxygen levels to coordinate diverse biological outputs during hypoxia. The best-studied mechanism of response to hypoxia involves hypoxia inducible factors (HIFs), which are stabilized by low oxygen availability and control the expression of a multitude of genes, including those involved in cell survival, angiogenesis, glycolysis and invasion/metastasis. Importantly, changes in oxygen can also be sensed via other stress pathways as well as changes in metabolite levels and the generation of reactive oxygen species by mitochondria. Collectively, this leads to cellular adaptations of protein synthesis, energy metabolism, mitochondrial respiration, lipid and carbon metabolism as well as nutrient acquisition. These mechanisms are integral inputs into fine-tuning the responses to hypoxic stress.
The tumor microenvironment Anderson, Nicole M.; Simon, M. Celeste
Current biology,
08/2020, Letnik:
30, Številka:
16
Journal Article
Recenzirano
Odprti dostop
A tumor is not simply a group of cancer cells, but rather a heterogeneous collection of infiltrating and resident host cells, secreted factors and extracellular matrix. Tumor cells stimulate ...significant molecular, cellular and physical changes within their host tissues to support tumor growth and progression. An emerging tumor microenvironment is a complex and continuously evolving entity. The composition of the tumor microenvironment varies between tumor types, but hallmark features include immune cells, stromal cells, blood vessels, and extracellular matrix. It is believed that the “tumor microenvironment is not just a silent bystander, but rather an active promoter of cancer progression” (Truffi et al., 2020). Early in tumor growth, a dynamic and reciprocal relationship develops between cancer cells and components of the tumor microenvironment that supports cancer cell survival, local invasion and metastatic dissemination. To overcome a hypoxic and acidic microenvironment, the tumor microenvironment coordinates a program that promotes angiogenesis to restore oxygen and nutrient supply and remove metabolic waste. Tumors become infiltrated with diverse adaptive and innate immune cells that can perform both pro- and anti- tumorigenic functions (Figure 1). An expanding literature on the tumor microenvironment has identified new targets within it for therapeutic intervention.
The tumor microenvironment is a complex entity. Here, Anderson and Simon introduce this complex collection of cells, metabolites and extracellular matrix, and the role it plays in cancer progression.
Microfluidic devices offer the potential to automate a wide variety of chemical and biological operations that are applicable for diagnostic and therapeutic operations with higher efficiency as well ...as higher repeatability and reproducibility. Polymer based microfluidic devices offer particular advantages including those of cost and biocompatibility. Here, we describe direct and replication approaches for manufacturing of polymer microfluidic devices. Replications approaches require fabrication of mould or master and we describe different methods of mould manufacture, including mechanical (micro-cutting; ultrasonic machining), energy-assisted methods (electrodischarge machining, micro-electrochemical machining, laser ablation, electron beam machining, focused ion beam (FIB) machining), traditional micro-electromechanical systems (MEMS) processes, as well as mould fabrication approaches for curved surfaces. The approaches for microfluidic device fabrications are described in terms of low volume production (casting, lamination, laser ablation, 3D printing) and high-volume production (hot embossing, injection moulding, and film or sheet operations).
Protein is an essential macronutrient and a key structural component of many foods. The nutritional and technological properties of food protein ingredients depend on their source, extraction and ...purification, modification during food manufacture, and interactions with other food components. In addition to covering these elements, this review seeks to highlight underappreciated aspects of protein environmental sustainability and explores the potential of cultured meat and insect-derived proteins.
Résumé
Rationnel
Les données sur le sur-risque de lymphome chez les patients traités par thiopurine pour maladie inflammatoire chronique intestinale sont controversées. Nous avons établi ce risque ...dans une étude de cohorte observationnelle prospective.
Méthode
19 486 patients avec maladie inflammatoire chronique intestinale, dont 11,759 (60,3%) maladies de Crohn et 7727 (39,7%) rectocolites hémorragiques ou colites indéterminées ont été inclus dans une cohorte nationale française par 680 gastro-entérologues qui renseignaient en détail le traitement immunosuppresseur, les cas de cancer et les décès durant toute la période de suivi. Le risque de lymphome était évalué en fonction de l’exposition aux thiopurines. Le suivi médian était de 35 mois (IQR 29–40).
Résultats
A l’inclusion, 5 867 (30,1%) patients recevaient une thiopurine, 2 809 (14,4%) avaient arrêté un traitement par thiopurine et 10 810 (55,5%) n’avaient jamais reçu de thiopurine. 23 lymphomes de novo ont été diagnostiqués : il s’agissait d’un cas de maladie de Hodgkin, et 22 cas de lymphomes non Hodgkininens. Le taux d’incidence de lymphome était de 0,90 (95% CI 0,50–1,49) pour 1 000 patients-année chez ceux ayant une thiopurine, 0,20/1000 (0,02–0,72) patients-année chez ceux ayant arrêté les thiopurines, et 0,26/1000 (0,10–0,57) patients-année chez ceux n’ayant jamais reçu de thiopurine (p=0,0054). Le risque relatif en analyse multivariée de lymphome était de 5,28 (2,01–13,9, p=0,0007) entre les patients ayant un traitement par thiopurine et ceux n’ayant jamais reçu de thiopurine. La plupart des cas survenus sous thiopurines partageaient les caractéristiques des lymphomes post-transplantation.
Interprétation
Les patients qui reçoivent des thiopurines pour maladie inflammatoire chronique intestinale ont un risque accru de lymphome.
Solid tumors reside in harsh tumor microenvironments (TMEs) together with various stromal cell types. During tumor progression and metastasis, both tumor and stromal cells undergo rapid metabolic ...adaptations. Tumor cells metabolically coordinate or compete with their “neighbors” to maintain biosynthetic and bioenergetic demands while escaping immunosurveillance or therapeutic interventions. Here, we provide an update on metabolic communication between tumor cells and heterogeneous stromal components in primary and metastatic TMEs and discuss emerging strategies to target metabolic communications for improved cancer treatments.
Growing solid tumors consist of malignant cancer cells and heterogeneous stromal cell components. This Review from Simon and Li provides an updated overview of metabolic communication between tumor cells and stromal cells in primary and metastatic tumor microenvironments and discusses emerging strategies to target metabolic interactions for improved cancer therapies.
Vascular disease remains the leading cause of death and disability, the etiology of which often involves atherosclerosis. The current treatment of atherosclerosis by pharmacotherapy has limited ...therapeutic efficacy. Here we report a biomimetic drug delivery system derived from macrophage membrane coated ROS-responsive nanoparticles (NPs). The macrophage membrane not only avoids the clearance of NPs from the reticuloendothelial system, but also leads NPs to the inflammatory tissues, where the ROS-responsiveness of NPs enables specific payload release. Moreover, the macrophage membrane sequesters proinflammatory cytokines to suppress local inflammation. The synergistic effects of pharmacotherapy and inflammatory cytokines sequestration from such a biomimetic drug delivery system lead to improved therapeutic efficacy in atherosclerosis. Comparison to macrophage internalized with ROS-responsive NPs, as a live-cell based drug delivery system for treatment of atherosclerosis, suggests that cell membrane coated drug delivery approach is likely more suitable for dealing with an inflammatory disease than the live-cell approach.
PDF
