Macrophage Polarization States in the Tumor Microenvironment

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(13), P. 6995 - 6995

Published: June 29, 2021

The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly deemed tumor-associated (TAMs), contributors to many pro-tumorigenic outcomes cancer through angiogenic and lymphangiogenic regulation, immune suppression, hypoxia induction, cell proliferation, metastasis. microenvironment (TME) can influence recruitment polarization, giving way these outcomes. Investigating TME-induced polarization is critical for further understanding of TAM-related pro-tumor potential development new therapeutic approaches. This review explores the current promoting

Language: Английский

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Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: June 28, 2022

Abstract Cancer is one of the leading causes death worldwide, and factors responsible for its progression need to be elucidated. Exosomes are structures with an average size 100 nm that can transport proteins, lipids, nucleic acids. This review focuses on role exosomes in cancer therapy. We discuss how able modulate components tumor microenvironment influence proliferation migration rates cells. also highlight that, depending their cargo, suppress or promote cell enhance reduce response radio- chemo-therapies. In addition, we describe trigger chronic inflammation lead immune evasion by focusing ability transfer non-coding RNAs between cells other molecular signaling pathways such as PTEN PI3K/Akt cancer. Subsequently, use carriers anti-tumor agents genetic tools control progression. then tumor-derived carcinogenesis. Finally, devote a section study diagnostic prognostic clinical courses important treatment patients. provides comprehensive understanding therapy, therapeutic value remodeling microenvironment. Graphical

Language: Английский

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Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Dec. 24, 2020

Abstract On 12 March 2020, the outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by World Health Organization. As 4 August more than 18 million confirmed infections had been reported globally. Most patients have mild symptoms, but some develop respiratory failure which is leading cause death among COVID-19 patients. Endothelial cells with high levels angiotensin-converting enzyme 2 expression are major participants and regulators inflammatory reactions coagulation. Accumulating evidence suggests that endothelial activation dysfunction participate in pathogenesis altering integrity vessel barrier, promoting pro-coagulative state, inducing inflammation, even mediating leukocyte infiltration. This review describes proposed cellular molecular mechanisms during emphasizing principal mediators therapeutic implications.

Language: Английский

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COVID-19-associated vasculitis and vasculopathy

Journal of Thrombosis and Thrombolysis, Journal Year: 2020, Volume and Issue: 50(3), P. 499 - 511

Published: July 22, 2020

The COVID-19 pandemic now totaling 13,000,000 cases and over 571,000 deaths has continued to teach the medical, scientific lay communities about viral infectious disease in modern era. Among many lessons learned for medical community is potential transmissibility host infectivity of SARS–CoV-2 virus. Moreover, it become clear that virus can affect any organ including circulatory system, directly via either tissue tropism or indirectly stemming from inflammatory responses form innate immunity, leukocyte debris such as cell-free DNA histones RNA particles. following review considers COVID-19-associated vasculitis vasculopathy a defining feature virus-induced systemic with acute, subacute chronic health implications.

Language: Английский

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Incomplete response to Anti-VEGF therapy in neovascular AMD: Exploring disease mechanisms and therapeutic opportunities

Progress in Retinal and Eye Research, Journal Year: 2020, Volume and Issue: 82, P. 100906 - 100906

Published: Oct. 3, 2020

Language: Английский

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Combining microenvironment normalization strategies to improve cancer immunotherapy

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(7), P. 3728 - 3737

Published: Feb. 3, 2020

Advances in immunotherapy have revolutionized the treatment of multiple cancers. Unfortunately, tumors usually impaired blood perfusion, which limits delivery therapeutics and cytotoxic immune cells to also results hypoxia-a hallmark abnormal tumor microenvironment (TME)-that causes immunosuppression. We proposed that normalization TME using antiangiogenic drugs and/or mechanotherapeutics can overcome these challenges. Recently, with checkpoint blockers was shown effectively induce vascular some types cancer. Although therapeutic approaches been used combination preclinical clinical studies, their combined effects on are not fully understood. To identify strategies for improved immunotherapy, we developed a mathematical framework incorporates complex interactions among various cancer cells, stroma, angiogenic molecules, vasculature. Model predictions were compared data from five previously reported experimental studies. found low doses improve when two treatments administered sequentially, but high less efficacious because excessive vessel pruning hypoxia. Stroma further increase efficacy benefit is additive normalization. conclude functionality dictates thus increased perfusion should be investigated as predictive biomarker response immunotherapy.

Language: Английский

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Exosomes in Angiogenesis and Anti-angiogenic Therapy in Cancers

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(16), P. 5840 - 5840

Published: Aug. 14, 2020

Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes involved in angiogenesis cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. promote suppressing expression of factor-inhibiting hypoxia-inducible 1 (HIF-1). Uptake tumor-derived exosomes (TEX) normal cells activates angiogenic signaling pathways stimulates vessel formation. TEX-driven cross-talk mesenchymal stem (MSCs) with immune blocks their anti-tumor activity. Effective inhibition tumor may arrest progression. Bevacizumab, a VEGF-specific antibody, was first antiangiogenic agent to enter clinic. The most important clinical problem associated therapy using VEGF- or VEFGR-targeting agents drug resistance. Combined strategies based on inhibitors immunotherapy effectively enhances therapies various cancers, but effective treatment requires further research.

Language: Английский

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Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

Frontiers in Aging Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: April 14, 2020

Pericytes are unique, multi-functional mural cells localized at the abluminal side of perivascular space in microvessels. Originally discovered nineteenth century, pericytes had drawn less attention until decades ago mainly due to lack specific markers. Recently, however, a growing body evidence has revealed that play various important roles: development and maintenance blood-brain barrier (BBB), regulation neurovascular system (e.g., vascular stability, vessel formation, cerebral blood flow, etc.), trafficking inflammatory cells, clearance toxic waste products from brain, acquisition stem cell-like properties. In unit, perform these functions through coordinated crosstalk with neighboring including endothelial, glial, neuronal cells. Dysfunction contribute wide variety diseases lead cognitive impairments such as small disease (SVD), acute stroke, Alzheimer’s (AD), other neurological disorders. For instance, SVDs, pericyte degeneration leads microvessel instability demyelination while constriction after ischemia causes no-reflow phenomenon brain capillaries. AD, which shares some common risk factors dementia, reduction coverage subsequent microvascular observed association white matter attenuation impaired cognition. Pericyte loss BBB-breakdown, stagnates amyloid β leakage neurotoxic molecules into parenchyma. this review, we first summarize characteristics pericytes, their roles central nervous system. Then, focus on how dysfunctional pathogenesis impairment ‘small vessel’ ‘large diseases, well AD. Finally, discuss therapeutic implications for disorders by targeting pericytes.

Language: Английский

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Molecular insight of regorafenib treatment for colorectal cancer

Cancer Treatment Reviews, Journal Year: 2019, Volume and Issue: 81, P. 101912 - 101912

Published: Oct. 28, 2019

Language: Английский

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Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 25, 2022

Angiogenesis is a vital process for the growth and dissemination of solid cancers. Numerous molecular pathways are known to drive angiogenic switch in cancer cells promoting new blood vessels increased incidence distant metastasis. Several angiogenesis inhibitors clinically available treatment different types advanced These mostly belong monoclonal antibodies or small-molecule tyrosine kinase targeting classical vascular endothelial factor (VEGF) its receptors. Nevertheless, breast one example tumors that had constantly failed respond terms improved survival outcomes patients. Accordingly, it paramount importance assess mechanisms driving signaling explore suitable drug targets can be further investigated preclinical clinical settings. This review summarizes current evidence effect anti-angiogenic drugs treatment. Further, major associated with intrinsic acquired resistance anti-VEGF therapy discussed. The also describes from studies on novel non-VEGF several approaches normalization tumor vasculature by pericytes, utilization microRNAs extracellular tumor-associate vesicles, using immunotherapeutic drugs, nanotechnology.

Language: Английский

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