Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 7, 2020

The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, analysis cancer patients within pre- post-therapeutic period is required to identify several types cells, which carry a risk for disease progression subsequent relapse. Cancer stem cells (CSCs) are subpopulation tumor that can drive initiation cause relapses. At time point initiation, CSCs originate from either differentiated or adult tissue resident cells. Due their importance, characterize have been identified correlated prognosis. However, shown display high plasticity, changes phenotypic functional appearance. Such induced by chemo- radiotherapeutics as well senescent alterations microenvironment. Induction senescence causes shrinkage modulating an anti-tumorigenic environment undergo growth arrest immune attracted. Besides these positive effects after therapy, also negative displayed post-therapeutically. These unfavorable directly promote stemness CSC plasticity phenotypes, activating pathways non-CSCs, promoting escape activation pathways. end, all lead relapse metastasis. This review provides overview most frequently used markers implementation focussing on deadliest solid (lung, stomach, liver, breast colorectal cancers) hematological (acute myeloid leukemia, chronic leukemia) cancers. Furthermore, it gives examples how might be influenced therapeutics, such radiotherapy, It points out, crucial monitor residual CSCs, pro-tumorigenic senescence-associated secretory phenotype follow-up using specific biomarkers. As future perspective, targeted immune-mediated strategy chimeric antigen receptor based approaches removal remaining chemotherapy-resistant personalized therapeutic approach discussed.

Language: Английский

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A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 16, 2022

Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment bone biopsies from two aged human cohorts. We further demonstrate reductions SenMayo following genetic clearance of cells mice adipose tissue humans pharmacological clearance. next use to identify hematopoietic or mesenchymal at single level murine marrow/bone scRNA-seq data. Thus, identifies across tissues species with high fidelity. Using this panel, are able characterize key intercellular signaling pathways. also represents potentially clinically applicable panel for monitoring burden aging other conditions as well studies senolytic drugs.

Language: Английский

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Role of p53 in the Regulation of Cellular Senescence

Biomolecules, Journal Year: 2020, Volume and Issue: 10(3), P. 420 - 420

Published: March 8, 2020

The p53 transcription factor plays a critical role in cellular responses to stress. Its activation response DNA damage leads cell growth arrest, allowing for repair, or directs senescence apoptosis, thereby maintaining genome integrity. Senescence is permanent cell-cycle arrest that has crucial aging, and it also represents robust physiological antitumor response, which counteracts oncogenic insults. In addition, senescent cells can negatively impact the surrounding tissue microenvironment neighboring by secreting pro-inflammatory cytokines, ultimately triggering dysfunction and/or unfavorable outcomes. This review focuses on characteristics of recent advances contribution senescence. Moreover, we discuss p53-mediated regulation several pathophysiological microenvironments could be associated with its development.

Language: Английский

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Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration

Cells, Journal Year: 2020, Volume and Issue: 9(5), P. 1157 - 1157

Published: May 7, 2020

Exosomes are nano-sized vesicles that serve as mediators for cell-to-cell communication. With their unique nucleic acids, proteins, and lipids cargo compositions reflect the characteristics of producer cells, exosomes can be utilized cell-free therapeutics. Among derived from various cellular origins, mesenchymal stem cell-derived (MSC-exosomes) have gained great attention due to immunomodulatory regenerative functions. Indeed, many studies shown anti-inflammatory, anti-aging wound healing effects MSC-exosomes in vitro vivo models. In addition, recent advances field exosome biology enabled development specific guidelines quality control methods, which will ultimately lead clinical application exosomes. This review highlights investigate therapeutic potential relevant mode actions skin diseases, well measures required exosome-derived

Language: Английский

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All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases

F1000Research, Journal Year: 2020, Volume and Issue: 9, P. 69 - 69

Published: Jan. 31, 2020

Improved hygiene leading to reduced exposure microorganisms has been implicated as one possible cause for the recent “epidemic” of chronic inflammatory diseases (CIDs) in industrialized countries. That is essence hypothesis that argues rising incidence CIDs may be, at least part, result lifestyle and environmental changes have made us too “clean” our own good, so causing microbiota. Apart from genetic makeup triggers, inappropriate increase intestinal permeability (which be influenced by composition gut microbiota), a “hyper-belligerent” immune system responsible tolerance–immune response balance, microbiome its epigenetic influence on host genomic expression identified three additional elements CIDs. During past decade, growing number publications focused human genetics, microbiome, proteomics, suggesting loss mucosal barrier function, particularly gastrointestinal tract, substantially affect antigen trafficking, ultimately influencing close bidirectional interaction between system. This cross-talk highly influential shaping function shifting predisposition clinical outcome. observation led re-visitation causes epidemics, key pathogenic role permeability. Pre-clinical studies shown zonulin family, group proteins modulating permeability, variety CIDs, including autoimmune, infective, metabolic, tumoral diseases. These data offer novel therapeutic targets which pathway their pathogenesis.

Language: Английский

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Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 659 - 659

Published: Feb. 19, 2023

Doxorubicin (DOX) constitutes the major constituent of anti-cancer treatment regimens currently in clinical use. However, precise mechanisms DOX’s action are not fully understood. Emerging evidence points to pleiotropic anticancer activity DOX, including its contribution DNA damage, reactive oxygen species (ROS) production, apoptosis, senescence, autophagy, ferroptosis, and pyroptosis induction, as well immunomodulatory role. This review aims collect information on DOX influence anti-tumor immune response, providing a rationale behind importance modern cancer therapy.

Language: Английский

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Mitochondria dysfunction and metabolic reprogramming as drivers of idiopathic pulmonary fibrosis

Redox Biology, Journal Year: 2020, Volume and Issue: 33, P. 101509 - 101509

Published: March 19, 2020

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. It characterized by deposition extracellular matrix proteins, like collagen and fibronectin in the interstitium leading to respiratory failure. Our understanding pathobiology underlying IPF still incomplete; however, it accepted that aging major risk factor while growing evidence suggests mitochondria plays an important role initiation progression fibrosis. Mitochondria dysfunction metabolic reprogramming had been identified different cells (alveolar epithelial cells, fibroblasts, macrophages) promoting low resilience increasing susceptibility activation profibrotic responses. Here we summarize changes mitochondrial numbers, biogenesis, turnover associated adaptations promote disrepair lung. Finally, highlight new possible therapeutic approaches focused on ameliorate dysfunction.

Language: Английский

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Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Particle and Fibre Toxicology, Journal Year: 2020, Volume and Issue: 17(1)

Published: July 25, 2020

Air pollution is killing close to 5 million people a year, and harming billions more. levels remain extremely high in many parts of the world, air pollution-associated premature deaths have been reported for urbanized areas, particularly linked presence airborne nano-sized ultrafine particles.To date, most research studies did focus on adverse effects human cardiovascular respiratory systems. Although skin direct contact with pollutants, their damaging are still under investigation. Epidemiological data suggested correlation between exposure pollutants aggravation symptoms chronic immunological diseases. In this study, systematic literature review was conducted understand current knowledge particulate matter skin. It aims at providing deeper understanding interactions further assess potential risks health.Particulate shown induce barrier dysfunction provoke formation reactive oxygen species through indirect mechanisms, leading oxidative stress induced activation inflammatory cascade Moreover, positive extrinsic aging atopic eczema relative risk increasing exposure.

Language: Английский

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Dietary Anti-Aging Polyphenols and Potential Mechanisms

Antioxidants, Journal Year: 2021, Volume and Issue: 10(2), P. 283 - 283

Published: Feb. 13, 2021

For years, the consumption of a diet rich in fruits and vegetables has been considered healthy, increasing longevity, decreasing morbidities. With assistance basic research investigating potential mechanisms, it become clear that beneficial effects plant-based foods are mainly due to large amount bioactive phenolic compounds contained. Indeed, substantial dietary intervention studies humans have supported supplementation polyphenols various health-promoting effects, especially elderly population. In vitro examinations on anti-aging mechanisms widely performed, using different types natural synthetic compounds. The aim this review is critically evaluate experimental evidence demonstrating aging-related diseases. We highlight polyphenols, including antioxidant signaling, preventing cellular senescence, targeting microRNA, influencing NO bioavailability, promoting mitochondrial function. While trends utilizing disorders getting growing attention, we suggest exploration combination multiple or polyphenol-rich foods, as would be more physiologically relevant daily life.

Language: Английский

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Brain Energy Metabolism: Astrocytes in Neurodegenerative Diseases

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 29(1), P. 24 - 36

Published: Oct. 3, 2022

Abstract Astrocytes are the most abundant cells in brain. They have many important functions central nervous system (CNS), including maintenance of glutamate and ion homeostasis, elimination oxidative stress, energy storage glycogen, tissue repair, regulating synaptic activity by releasing neurotransmitters, participating formation. special highly ramified structure. Their branches contact with synapses neurons inwardly, fine structure wrapping synapses; their feet blood vessels brain parenchyma outward, almost whole The adjacent astrocytes rarely overlap communicate each other through gap junction channels. ideal location enables them to sense weak changes surroundings provide structural basis for supply neurons. Neurons closely coupled units metabolism consume a lot ATPs process neurotransmission. metabolic substrates neurons, maintain high neuron, facilitate information transmission This article reviews characteristics glucose metabolism, lipid amino acid astrocytes. interactions between microglia were also detailed discussed. Finally, we classified analyzed role disorder occurrence development neurodegenerative diseases.

Language: Английский

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