Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 17, 2023

Abstract Having a hypoxic microenvironment is common and salient feature of most solid tumors. Hypoxia has profound effect on the biological behavior malignant phenotype cancer cells, mediates effects chemotherapy, radiotherapy, immunotherapy through complex mechanisms, closely associated with poor prognosis in various patients. Accumulating studies have demonstrated that normalization tumor vasculature, nanoparticle carriers biocarriers can effectively increase oxygen concentration microenvironment, improve drug delivery efficacy radiotherapy. They also infiltration innate adaptive anti-tumor immune cells to enhance immunotherapy. Furthermore, drugs targeting key genes hypoxia, including hypoxia tracers, hypoxia-activated prodrugs, hypoxia-inducible factors downstream targets, be used for visualization quantitative analysis antitumor activity. However, relationship between an area research requires further exploration. Here, we investigated potential development cancer, changes signaling pathways occur adapt environments, mechanisms hypoxia-induced tolerance, chemotherapeutic enhanced radiation as well insights applications therapy.

Language: Английский

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Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in which the airways narrow or collapse during sleep, causing obstructive apnea. The prevalence of OSAS continues to rise worldwide, particularly middle-aged and elderly individuals. mechanism upper airway incompletely understood but associated with several factors, including obesity, craniofacial changes, altered muscle function airway, pharyngeal neuropathy, fluid shifts neck. main characteristics are recurrent pauses respiration, lead intermittent hypoxia (IH) hypercapnia, accompanied by blood oxygen desaturation arousal sharply increases risk diseases. This paper first briefly describes epidemiology, incidence, pathophysiological mechanisms OSAS. Next, alterations relevant signaling pathways induced IH systematically reviewed discussed. For example, can induce gut microbiota (GM) dysbiosis, impair intestinal barrier, alter metabolites. These ultimately secondary oxidative stress, systemic inflammation, sympathetic activation. We then summarize effects on disease pathogenesis, cardiocerebrovascular disorders, neurological metabolic diseases, cancer, reproductive COVID-19. Finally, different therapeutic strategies for caused causes proposed. Multidisciplinary approaches shared decision-making necessary successful treatment future, more randomized controlled trials needed further evaluation define what treatments best specific patients.

Language: Английский

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Magnesium Gradient‐Based Hierarchical Scaffold for Dual‐Lineage Regeneration of Osteochondral Defect

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(43)

Published: July 2, 2023

Abstract Osteochondral regeneration remains a great challenge due to the limited self‐healing ability and complexity of its hierarchical structure composition. Mg 2+ hypoxia are two effective modulators in boosting chondrogenesis. To this end, double‐layered scaffold (D) consisting hydrogel layer on porous cryogel is fabricated mimic osteochondral tissue. An gradient incorporated into with hypoxia‐mimicking deferoxamine (DFO) embedded (D‐Mg‐DFO), which remarkably augments dual‐lineage both cartilage subchondral bone. The higher supplementation from upper hydrogel, associated situation small pore size, exhibits promotive effects chondrogenic differentiation. lower bottom cryogel, interconnected macroporous structure, achieves multiple contributions stem cell migration bone marrow cavity, matrix mineralization, osteogenesis. Furthermore, rabbits’ trochlea defects established evaluate regenerative outcome. Compared control scaffolds containing only or DFO, D‐Mg‐DFO presents best effect under synergistic contribution factors. Overall, work provides new design toward an repair defect.

Language: Английский

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Stimuli-responsive polysaccharide-based smart hydrogels for diabetic wound healing: Design aspects, preparation methods and regulatory perspectives

Carbohydrate Polymers, Journal Year: 2023, Volume and Issue: 324, P. 121537 - 121537

Published: Nov. 2, 2023

Language: Английский

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Diagnostic and prognostic value of triglyceride glucose index: a comprehensive evaluation of meta-analysis

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 23, 2024

The present umbrella review aims to collate and summarize the findings from previous meta-analyses on Triglyceride Glucose (TyG) Index, providing insights clinicians, researchers, policymakers regarding usefulness of this biomarker in various clinical settings. A comprehensive search was conducted PubMed, Scopus, Web Science up April 14, 2024, without language restrictions. AMSTAR2 checklist assessed methodological quality included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. total 32 studies finally included. results revealed significant associations between TyG index health outcomes. For kidney outcomes, a high significantly associated with an increased risk contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82–2.77) chronic disease (CKD) (RR 1.46, 1.32–1.63). High type 2 diabetes mellitus (T2DM) 3.53, 2.74–4.54), gestational (GDM) 2.41, 1.48–3.91), diabetic retinopathy (DR) 2.34, 1.31–4.19). Regarding metabolic diseases, higher patients obstructive sleep apnea (OSA) (SMD 0.86, 0.57–1.15), syndrome (MD 0.83, 0.74–0.93), non-alcoholic fatty liver (NAFLD) 2.36, 1.88–2.97) compared those these conditions. In cerebrovascular dementia 1.14, 1.12–1.16), cognitive impairment 2.31, 1.38–3.86), ischemic stroke 1.37, 1.22–1.54). cardiovascular showed heart failure (HF) (HR 1.21, 1.12–1.30), atrial fibrillation (AF) 1.22, 0.57–1.87), hypertension (HTN) 1.52, 1.25–1.85). is promising for screening predicting medical conditions, particularly related insulin resistance disorders. However, heterogeneity suggest need further high-quality research confirm refine utility index.

Language: Английский

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Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 30, 2024

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One the main transcription factors activated by hypoxia hypoxia-inducible factor (HIF), which regulates expression genes involved in various aspects tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, cell migration. This can negatively impact patient outcomes inducing therapeutic resistance. The importance clearly demonstrated continued research into finding clinically relevant biomarkers, hypoxia-targeting therapies. problems lack applicable methods detection, standardisation. Additionally, lot detecting do not take consideration complexity hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% are hypoxic. ECM important component TME, developed both cancer associated fibroblasts (CAFs) cells. However, it distinguish different roles develop biomarkers novel compounds. Fibronectin (FN), collagen (COL) hyaluronic acid (HA) components that create fibres. These fibres crosslinked specific enzymes lysyl oxidase (LOX) stiffness induces fibrosis. partially regulated HIFs. review highlights understanding role current data shows contradictory results on also indicates needed identifying CAF subtypes exact roles; with some showing pro-tumorigenic capacity others having anti-tumorigenic roles. has made difficult fully elucidate CAFs within TME. clear an area requires unravelling strategies target have resulted worsened prognosis. cells discussed been modulating environment. Which led development immunotherapies PD-L1. hypoxia-induced changes confer resistance conventional therapies, such chemotherapy, radiotherapy, immunotherapy. summarizes knowledge TME its implications for therapy It discusses potential prognostic predictive indictors treatment response, well challenges opportunities targeting clinical trials.

Language: Английский

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ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: March 14, 2024

At least 40% of human cancers are associated with aberrant ERK pathway activity (ERKp). Inhibitors targeting various effectors within the ERKp have been developed and explored for over two decades. Conversely, a substantial body evidence suggests that both normal cells and, notably to greater extent, cancer exhibit susceptibility hyperactivation ERKp. However, this vulnerability remains relatively unexplored. In review, we reexamine on selective lethality highly elevated in varying backgrounds. We synthesize insights proposed harnessing ERK-associated therapeutical approaches contextualize these established pharmacological cancer-targeting models. Moreover, compile intriguing preclinical findings agonism diverse Lastly, present conceptual framework target discovery regarding agonism, emphasizing utilization mutual exclusivity among oncogenes develop novel targeted therapies precision oncology.

Language: Английский

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Oxidative Stress and Age-Related Tumors

Antioxidants, Journal Year: 2024, Volume and Issue: 13(9), P. 1109 - 1109

Published: Sept. 13, 2024

Oxidative stress is the result of imbalance between reactive oxygen and nitrogen species (RONS), which are produced by several endogenous exogenous processes, antioxidant defenses consisting molecules that protect biological systems from free radical toxicity. a major factor in aging process, contributing to accumulation cellular damage over time. biomolecules, leads DNA alterations, lipid peroxidation, protein oxidation, mitochondrial dysfunction resulting senescence, immune system tissue dysfunctions, increased susceptibility age-related pathologies, such as inflammatory disorders, cardiovascular neurodegenerative diseases, diabetes, cancer. stress-driven mutations, or methylation histone modification, alter gene expression, key determinants tumor initiation, angiogenesis, metastasis, therapy resistance. Accumulation genetic epigenetic damage, oxidative contributes, eventually unrestrained cell proliferation, inhibition differentiation, evasion death, providing favorable conditions for tumorigenesis. Colorectal, breast, lung, prostate, skin cancers most frequent aging-associated malignancies, implicated their pathogenesis behavior. Our aim shed light on molecular mechanisms link stress, aging, cancers, highlighting impact both RONS antioxidants, provided diet exercise, immunity, development an antitumor response. The dual role ROS physiological regulators signaling responsible well its use anti-tumor therapeutic purposes, will also be discussed. Managing crucial promoting healthy reducing risk tumors.

Language: Английский

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Factors Influencing Venous Remodeling in the Development of Varicose Veins of the Lower Limbs

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1560 - 1560

Published: Jan. 26, 2024

One of the early symptoms chronic venous disease (CVD) is varicose veins (VV) lower limbs. There are many etiological environmental factors influencing development insufficiency (CVI), although genetic and family history play a key role. All these induce changes in hemodynamic system limbs leading to blood stasis, hypoxia, inflammation, oxidative stress, proteolytic activity matrix metalloproteinases (MMPs), microcirculation and, consequently, remodeling wall. The aim this review present current knowledge on CVD, including pathophysiology mechanisms related vein wall remodeling. Particular emphasis has been placed describing role inflammation stress involvement extracellular hemoglobin as pathogenetic VV. Additionally, active substances used treatment VV were discussed.

Language: Английский

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Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

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