scholarly journals The Role of epigenetic modifications of DNA and histones in the treatment of oncohematological diseases

2021 ◽  
Vol 66 (2) ◽  
pp. 263-279
Author(s):  
D. V. Karpenko ◽  
N. A. Petinati ◽  
N. J. Drize ◽  
A. E. Bigildeev
Keyword(s):  
Clinical Trial ◽  
Cytosine Methylation ◽  
Current Knowledge ◽  
Hypomethylating Agents ◽  
Epigenetic Change ◽  
Therapeutic Approaches ◽  
Enzymatic Machinery ◽  
Key Pathways ◽  
Dna Cytosine Methylation

Introduction. Current knowledge of tumour biology attests a dual genetic and epigenetic nature of cancer cell abnormalities. Tumour epigenetics research provided insights into the key pathways mediating oncogenesis and facilitated novel epigenetic therapies.Aim — an overview of intricate involvement of epigenetic change in haematological morbidity and current therapeutic approaches to target the related mechanisms.Main findings. We review the best known epigenetic marks in tumour cells, e.g. DNA cytosine methylation, methylation and acetylation of histone proteins, the underlying enzymatic machinery and its role in oncogenesis. The epigenetic profile-changing drugs are described, including DNA hypomethylating agents, histone deacetylase and methylase inhibitors. A particular focus is made on substances currently approved in haematological therapy or undergoing clinical trial phases for future clinical availability.

scholarly journals Regulatory T Cell-Enhancing Therapies to Treat Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 723
Author(s):  
Hafid Ait-Oufella ◽  
Jean-Rémi Lavillegrand ◽  
Alain Tedgui
Keyword(s):  
T Cell ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Therapeutic Approaches ◽  
Coronary Patients ◽  
Cell Subpopulations ◽  
Atherosclerotic Process ◽  
T Cell Subpopulations ◽  
Disease Analysis

Experimental studies have provided strong evidence that chronic inflammation triggered by the sub-endothelial accumulation of cholesterol-rich lipoproteins in arteries is essential in the initiation and progression of atherosclerosis. Recent clinical trials highlighting the efficacy of anti-inflammatory therapies in coronary patients have confirmed that this is also true in humans Monocytes/macrophages are central cells in the atherosclerotic process, but adaptive immunity, through B and T lymphocytes, as well as dendritic cells, also modulates the progression of the disease. Analysis of the role of different T cell subpopulations in murine models of atherosclerosis identified effector Th1 cells as proatherogenic, whereas regulatory T cells (Tregs) have been shown to protect against atherosclerosis. For these reasons, better understanding of how Tregs influence the atherosclerotic process is believed to provide novel Treg-targeted therapies to combat atherosclerosis. This review article summarizes current knowledge about the role of Tregs in atherosclerosis and discusses ways to enhance their function as novel immunomodulatory therapeutic approaches against cardiovascular disease.

scholarly journals The Gut Ecosystem: A Critical Player in Stroke

2020 ◽  
Author(s):  
Rosa Delgado Jiménez ◽  
Corinne Benakis
Keyword(s):  
Current Knowledge ◽  
Critical Factor ◽  
Intestinal Microbiome ◽  
Brain Disorders ◽  
Therapeutic Approaches ◽  
Health And Disease ◽  
Brain Stroke ◽  
The Brain ◽  
Improve Patient

AbstractThe intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

scholarly journals Role of PD-L1 in Gut Mucosa Tolerance and Chronic Inflammation

2020 ◽  
Vol 21 (23) ◽  
pp. 9165
Author(s):  
Marina Chulkina ◽  
Ellen J. Beswick ◽  
Irina V. Pinchuk
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
The Body ◽  
Regulatory Cells ◽  
Gi Tract ◽  
Therapeutic Approaches ◽  
Gut Mucosa ◽  
Mucosal Homeostasis ◽  
Gi Mucosa

The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this review, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches.

scholarly journals The Role of Conventionally Fractionated Radiotherapy and Stereotactic Radiotherapy in the Treatment of Carcinoid Tumors and Large-Cell Neuroendocrine Cancer of the Lung

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 177
Author(s):  
Mateusz Bilski ◽  
Paulina Mertowska ◽  
Sebastian Mertowski ◽  
Marcin Sawicki ◽  
Anna Hymos ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Case Reports ◽  
Peptide Receptor Radionuclide Therapy ◽  
Large Cell ◽  
Surgical Removal ◽  
Therapeutic Approaches ◽  
Conventional Radiotherapy ◽  
Fractionated Radiotherapy ◽  
Choice Of Treatment

The occurrence of neuroendocrine tumors among the diagnosed neoplasms is extremely rare and is associated with difficulties in undertaking effective therapy due to the histopathological differentiation of individual subtypes and the scarce clinical data and recommendations found in the literature. The choice of treatment largely depends not only on its type, but also on the location and production of excess hormones by the tumor itself. Common therapeutic approaches include surgical removal of the tumor, the use of chemotherapy, targeted drug therapy, peptide receptor radionuclide therapy, and the use of radiation therapy. This article reviews the current knowledge on the classification and application of radiotherapy in the treatment of lung NETs. Case reports were presented in which treatment with conventional radiotherapy, radical and palliative radiochemotherapy, as well as stereotactic fractionated radiotherapy in the treatment of typical (TC) and atypical (AT) lung carcinoids and large cell neuroendocrine carcinoma (LCNC) were used. We hope that the solutions presented in the literature will allow many radiation oncologists to make the best, often personalized decisions about the therapeutic qualifications of patients.

scholarly journals Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils—The Current Knowledge, Pharmacological Modulation and Future Prospects

2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Gierlikowska ◽  
Albert Stachura ◽  
Wojciech Gierlikowski ◽  
Urszula Demkow
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Innate Immune ◽  
Therapeutic Approaches ◽  
Effector Functions ◽  
Pharmacological Modulation ◽  
Synthetic Drugs ◽  
Extracellular Traps

Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.

scholarly journals Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression

2018 ◽  
Vol 8 (1) ◽  
pp. 26 ◽  
Author(s):  
Alice Conigliaro ◽  
Carla Cicchini
Keyword(s):  
Tumor Progression ◽  
Intercellular Communication ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Cell Communication ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Dna And Rna

Growing evidence points to exosomes as key mediators of cell–cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated intercellular communication in tumor-niche establishment, migration, invasion, and metastasis processes. This body of evidence suggests the relevance of taking into account exosome-mediated signaling and its multifaceted aspects to develop innovative anti-tumoral therapeutic approaches.

scholarly journals The Evolving Role of Gut Microbiota in the Management of Irritable Bowel Syndrome: An Overview of the Current Knowledge

2020 ◽  
Vol 9 (3) ◽  
pp. 685 ◽  
Author(s):  
Amir Mari ◽  
Fadi Abu Baker ◽  
Mahmud Mahamid ◽  
Wisam Sbeit ◽  
Tawfik Khoury
Keyword(s):  
Irritable Bowel Syndrome ◽  
Current Knowledge ◽  
Gastrointestinal Disorder ◽  
Economic Effects ◽  
Therapeutic Approaches ◽  
High Prevalence ◽  
Attractive Option ◽  
Irritable Bowel ◽  
Substantial Morbidity

The intestinal microbiota is one of the most rapidly evolving areas in biology and medicine. Extensive research in the last decade has escalated our understanding of the role of the microbiota in the pathogenesis of several intestinal and extra-intestinal disorders. Marked by high prevalence, substantial morbidity, and enormous costs, irritable bowel syndrome (IBS) is an important chronic gastrointestinal disorder that is widely encountered by gastroenterologists. Despite advances in our understanding of its pathophysiology, curative interventions have yet to be discovered, and therapeutic approaches remain symptom-driven. Recently, accumulating evidence has enlightened the possible impact of an imbalanced gut microbiome in the pathogenesis of IBS. In fact, several studies have documented altered microbiota in patients, while others have shown that IBS severity was associated with a distinct microbiota signature. These findings may pave the way for the use of microbiota manipulation strategies as an attractive option for IBS management, and may have an essential role in efforts to reduce the societal and economic effects of this ever-growing disorder. In this review, we have outlined the results of the latest research on the association between microbiota and IBS and their implications for the clinical management of affected patients.

scholarly journals Glioma Stem Cells: Signaling, Microenvironment, and Therapy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Brandon D. Liebelt ◽  
Takashi Shingu ◽  
Xin Zhou ◽  
Jiangong Ren ◽  
Seul A. Shin ◽  
...  
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Primary Brain Tumor ◽  
Tumor Formation ◽  
Therapeutic Approaches ◽  
Microenvironmental Factors ◽  
Xenograft Models ◽  
And Function ◽  
Vascular Formation

Glioblastoma remains the most common and devastating primary brain tumor despite maximal therapy with surgery, chemotherapy, and radiation. The glioma stem cell (GSC) subpopulation has been identified in glioblastoma and likely plays a key role in resistance of these tumors to conventional therapies as well as recurrent disease. GSCs are capable of self-renewal and differentiation; glioblastoma-derived GSCs are capable ofde novotumor formation when implanted in xenograft models. Further, GSCs possess unique surface markers, modulate characteristic signaling pathways to promote tumorigenesis, and play key roles in glioma vascular formation. These features, in addition to microenvironmental factors, present possible targets for specifically directing therapy against the GSC population within glioblastoma. In this review, the authors summarize the current knowledge of GSC biology and function and the role of GSCs in new vascular formation within glioblastoma and discuss potential therapeutic approaches to target GSCs.

Endogenous Neural Progenitor Cells as Therapeutic Target After Spinal Cord Injury

Physiology ◽  
2008 ◽  
Vol 23 (5) ◽  
pp. 296-304 ◽  
Author(s):  
Franz-Josef Obermair ◽  
Aileen Schröter ◽  
Michaela Thallmair
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Current Knowledge ◽  
Neural Progenitor ◽  
Injured Spinal Cord ◽  
Therapeutic Approaches ◽  
Cord Injury

Growing knowledge about the role of neural progenitor cells supports the hope that stem cell-based therapeutic approaches aimed at restoring function in the lesioned central nervous system can be established. Possible therapies for promoting recovery after spinal cord injury include stimulating the formation of neurons and glial cells by endogenous progenitor cells. This article reviews the current knowledge about the nature of adult progenitor cells in the intact and injured spinal cord and summarizes possibilities and limitations of cellular replacement strategies based on manipulations of endogenous spinal cord progenitor cells and their environment.

scholarly journals Role of Extracellular Matrix in Gastrointestinal Cancer-Associated Angiogenesis

2020 ◽  
Vol 21 (10) ◽  
pp. 3686 ◽  
Author(s):  
Eva Andreuzzi ◽  
Alessandra Capuano ◽  
Evelina Poletto ◽  
Eliana Pivetta ◽  
Albina Fejza ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cancer Progression ◽  
Cell Function ◽  
Current Knowledge ◽  
Tumor Development ◽  
Therapy Response ◽  
Therapeutic Approaches ◽  
Endothelial Cell Function ◽  
New Therapeutic Approaches

Gastrointestinal tumors are responsible for more cancer-related fatalities than any other type of tumors, and colorectal and gastric malignancies account for a large part of these diseases. Thus, there is an urgent need to develop new therapeutic approaches to improve the patients’ outcome and the tumor microenvironment is a promising arena for the development of such treatments. In fact, the nature of the microenvironment in the different gastrointestinal tracts may significantly influence not only tumor development but also the therapy response. In particular, an important microenvironmental component and a potential therapeutic target is the vasculature. In this context, the extracellular matrix is a key component exerting an active effect in all the hallmarks of cancer, including angiogenesis. Here, we summarized the current knowledge on the role of extracellular matrix in affecting endothelial cell function and intratumoral vascularization in the context of colorectal and gastric cancer. The extracellular matrix acts both directly on endothelial cells and indirectly through its remodeling and the consequent release of growth factors. We envision that a deeper understanding of the role of extracellular matrix and of its remodeling during cancer progression is of chief importance for the development of new, more efficacious, targeted therapies.

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