Search results for " metabolism"
showing 10 items of 4843 documents
Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy
2017
The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogramming also plays a significant role in suppressing the immune attack on the tumor cells and in resis…
Potential of induced metabolic bioluminescence imaging to uncover metabolic effects of antiangiogenic therapy in tumors
2016
Tumor heterogeneity at the genetic level has been illustrated by a multitude of studies on the genomics of cancer, but whether tumors can be heterogeneous at the metabolic level is an issue which has been less systematically investigated so far. A burning related question is whether the metabolic features of tumors can change either following natural tumor progression (i.e. in primary tumors versus metastasis) or therapeutic interventions. In this regard, recent findings by independent teams indicate that anti-angiogenic drugs cause metabolic perturbations in tumors as well as metabolic adaptations associated with increased malignancy. Induced metabolic bioluminescence imaging (imBI) is an …
Betulinic acid induces a novel cell death pathway that depends on cardiolipin modification
2016
Cancer is associated with strong changes in lipid metabolism. For instance, normal cells take up fatty acids (FAs) from the circulation, while tumour cells generate their own and become dependent on de novo FA synthesis, which could provide a vulnerability to target tumour cells. Betulinic acid (BetA) is a natural compound that selectively kills tumour cells through an ill-defined mechanism that is independent of BAX and BAK, but depends on mitochondrial permeability transition-pore opening. Here we unravel this pathway and show that BetA inhibits the activity of steroyl-CoA-desaturase (SCD-1). This enzyme is overexpressed in tumour cells and critically important for cells that utilize de n…
Targeting Immune Modulators in Glioma While Avoiding Autoimmune Conditions
2021
Simple Summary Glioblastoma multiforme is a futile disease usually leading to the patient’s death within one year post-diagnosis; therefore, novel treatment options are desperately needed. In this regard, activation of the inert immune system has moved into focus in recent years. Malignant brain tumors, as well as autoimmune diseases, elicit aberrant immune responses. In this way, glioma escapes the host’s immune system and, thus, activation of the immune response in order to reduce tumor tolerance can serve as an alternative treatment option. Immune checkpoint modulators in combination with traditional therapies have gained attention in both glioma and autoimmune diseases. In this review, …
Platelet-Derived GARP Induces Peripheral Regulatory T Cells—Potential Impact on T Cell Suppression in Patients with Melanoma-Associated Thrombocytosis
2020
Platelets have been recently described as an important component of the innate and adaptive immunity through their interaction with immune cells. However, information on the platelet&ndash
Crude oil exposures reveal roles for intracellular calcium cycling in haddock craniofacial and cardiac development.
2016
AbstractRecent studies have shown that crude oil exposure affects cardiac development in fish by disrupting excitation-contraction (EC) coupling. We previously found that eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets, potentially leading to more profound toxic effects from uptake of polycyclic aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil (0.7–7 μg/L ∑PAH), here we exposed a broader range of developmental stages over both short and prolonged durations. We quantified effects on cardiac function and morphogenesis, characterized novel craniofacial defects, and examined the expression of genes encoding potential targets underly…
Homozygous Resistance to Thyroid Hormone β: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?
2017
Resistance to thyroid hormone β (RTHβ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTHβ, with additional characteri…
Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients
2017
In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary…
MYC Induces a Hybrid Energetics Program Early in Cell Reprogramming
2018
Summary Cell reprogramming is thought to be associated with a full metabolic switch from an oxidative- to a glycolytic-based metabolism. However, neither the dynamics nor the factors controlling this metabolic switch are fully understood. By using cellular, biochemical, protein array, metabolomic, and respirometry analyses, we found that c-MYC establishes a robust bivalent energetics program early in cell reprogramming. Cells prone to undergo reprogramming exhibit high mitochondrial membrane potential and display a hybrid metabolism. We conclude that MYC proteins orchestrate a rewiring of somatic cell metabolism early in cell reprogramming, whereby somatic cells acquire the phenotypic plast…
Deregulated miRNAs in bone health: Epigenetic roles in osteoporosis.
2019
MicroRNA (miRNA) has shown to enhance or inhibit cell proliferation, differentiation and activity of different cell types in bone tissue. The discovery of miRNA actions and their targets has helped to identify them as novel regulations actors in bone. Various studies have shown that miRNA deregulation mediates the progression of bone-related pathologies, such as osteoporosis. The present review intends to give an exhaustive overview of miRNAs with experimentally validated targets involved in bone homeostasis and highlight their possible role in osteoporosis development. Moreover, the review analyzes miRNAs identified in clinical trials and involved in osteoporosis.