Tumor Cytobiology of IGF-1R In Breast Tumor Activation and Propagation; And the Role of Celecoxib in Its Inhibition DOI
Maher M. Akl, Amr Ahmed

Published: April 30, 2024

The Insulin-like Growth Factor 1 Receptor (IGF-1R) stands as a central orchestrator in cellular signaling, governing pivotal processes encompassing growth, proliferation, and differentiation. Its aberrant activation is intricately intertwined with the pathogenesis progression of breast cancer, heterogeneous disease presenting formidable clinical challenges. Amidst burgeoning landscape therapeutic interventions, Celecoxib, nonsteroidal anti-inflammatory drug (NSAID), has emerged promising candidate for targeting dysregulated IGF-1R pathway. This review delineates intricate molecular mechanisms underlying Celecoxib's modulation pathway, elucidating its pharmacokinetic properties implications cancer management. Celecoxib exerts inhibitory effects on through multifaceted interactions, impeding receptor downstream signaling cascades tumor proliferation metastasis. Furthermore, it regulates expression at both transcriptional translational levels, exerting nuanced control over responses. Moreover, impact transcends mere inhibition, potentiates pro-apoptotic pathways disrupts tumor-permissive microenvironments. A understanding profile imperative, considering sustained targeted inhibition potential synergistic combinatorial regimens cancer. comprehensive elucidation underscores paramount importance deciphering interplay heralding novel avenues precision medicine tailored interventions management

Language: Английский

Glycolipid Metabolic Disorders, Metainflammation, Oxidative Stress, and Cardiovascular Diseases: Unraveling Pathways DOI Creative Commons

Enzo Pereira de Lima,

Renato Cesar Moretti,

Karina Torres Pomini

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(7), P. 519 - 519

Published: July 12, 2024

Glycolipid metabolic disorders (GLMDs) are various resulting from dysregulation in glycolipid levels, consequently leading to an increased risk of obesity, diabetes, liver dysfunction, neuromuscular complications, and cardiorenal vascular diseases (CRVDs). In patients with GLMDs, excess caloric intake a lack physical activity may contribute oxidative stress (OxS) systemic inflammation. This study aimed review the connection between GLMD, OxS, metainflammation, onset CRVD. GLMD is due causing dysfunction synthesis, breakdown, absorption glucose lipids body, excessive ectopic accumulation these molecules. mainly neuroendocrine dysregulation, insulin resistance, metainflammation. many inflammatory markers defense cells play vital role related tissues organs, such as blood vessels, pancreatic islets, liver, muscle, kidneys, adipocytes, promoting lesions that affect interconnected organs through their signaling pathways. Advanced glycation end products, ATP-binding cassette transporter 1, Glucagon-like peptide-1, Toll-like receptor-4, sphingosine-1-phosphate (S1P) crucial since they glucolipid metabolism. The consequences this system organ damage morbidity mortality.

Language: Английский

Citations

25
Regulation of bone homeostasis: signaling pathways and therapeutic targets DOI Creative Commons

Zebin Wu,

Wenming Li,

Kunlong Jiang

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: July 24, 2024

As a highly dynamic tissue, bone is continuously rebuilt throughout life. Both formation by osteoblasts and resorption osteoclasts constitute reconstruction homeostasis. The equilibrium of homeostasis governed many complicated signaling pathways that weave together to form an intricate network. These coordinate the meticulous processes resorption, ensuring structural integrity vitality skeletal system. Dysregulation homeostatic regulatory network contributes development progression diseases. Significantly, imbalanced further disrupts triggers cascade reaction exacerbates disease engenders deleterious cycle. Here, we summarize influence on homeostasis, elucidating interplay crosstalk among them. Additionally, review mechanisms underpinning imbalances across diverse landscapes, highlighting current prospective therapeutic targets clinical drugs. We hope this will contribute holistic understanding molecular sustaining which are promising research shed light targeted

Language: Английский

Citations

9
Inflammatory signaling in NASH driven by hepatocyte mitochondrial dysfunctions DOI Creative Commons
Melissa Myint, Francesca Oppedisano, Valeria De Giorgi

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 26, 2023

Abstract Liver steatosis, inflammation, and variable degrees of fibrosis are the pathological manifestations nonalcoholic steatohepatitis (NASH), an aggressive presentation most prevalent chronic liver disease in Western world known as fatty (NAFL). Mitochondrial hepatocyte dysfunction is a primary event that triggers affecting Kupffer hepatic stellate cell behaviour. Here, we consider role impaired mitochondrial function caused by lipotoxicity during oxidative stress hepatocytes. Dysfunction phosphorylation ROS production cause release damage-associated molecular patterns from dying hepatocytes, leading to activation innate immunity trans-differentiation cells, thereby driving NASH.

Language: Английский

Citations

22
Metabolites and Immune Response in Tumor Microenvironments DOI Open Access
Salvatore Cortellino, Valter D. Longo

Cancers, Journal Year: 2023, Volume and Issue: 15(15), P. 3898 - 3898

Published: July 31, 2023

The remodeled cancer cell metabolism affects the tumor microenvironment and promotes an immunosuppressive state by changing levels of macro- micronutrients releasing hormones cytokines that recruit immune cells. Novel dietary interventions such as amino acid restriction periodic fasting mimicking diets can prevent or dampen formation acting systemically on release growth factors, inhibiting proinflammatory cytokines, remodeling vasculature extracellular matrix. Here, we discuss latest research effects these therapeutic immunometabolism response future scenarios pertaining to how could contribute therapy.

Language: Английский

Citations

19
AGEs and RAGE: metabolic and molecular signatures of the glycation-inflammation axis in malignant or metastatic cancers DOI Creative Commons
Gowri Palanissami, Solomon F.D. Paul

Exploration of Targeted Anti-tumor Therapy, Journal Year: 2023, Volume and Issue: unknown, P. 812 - 849

Published: Sept. 28, 2023

From attributing mutations to cancers with the advent of cutting-edge genetic technology in recent decades, re-searching age-old theory intrinsic metabolic shift (Warburg’s glycolysis), quest for a precise panacea mainly metastatic cancers, remains incessant. This review delineates advanced glycation end product (AGE)-receptor AGE (RAGE) pathway driven intricate oncogenic cues, budding from (glycolytic) reliance tumour cells, branching into emergence malignancies. Strong AGE-RAGE concomitance metastasis, chemo-resistance and cancer resurgence adversely incite disease progression patient mortality. At conjunction are “glycolytically” generated AGEs AGE-activated RAGE, instigating aberrant molecular pathways, culminating aggressive as by-products insurgence, modify metabolome, epigenome microbiome, besides coercing inter-, intra- extra-cellular micro-milieu conducive events like epithelial-mesenchymal transition (EMT). synergistically elicit ATP surge surplus energy, autophagy apoptotic evasion chemo-resistance, insulin-like growth factor 1 (IGF-1) meta-inflammation angiogenesis, high mobility group box-1 (HMGB1) immune tolerance, S100 proteins p53 protein attenuation suppression. pronouncedly reported invasive forms breast, prostate, colon pancreatic higher patients than healthy counterparts, stage localized phase. Hence, investigation person-specific presence AGEs, soluble RAGE can be advocated impending bio-markers diagnostic, prognostic therapeutic purposes, predict risk diabetes, obesity, syndrome well general population, monitor prognosis metastasis cancer, reckon complications survivors. Furthermore, clinical reports exogenous (dietary) endogenous (internally formed) patients, contemporary trials involving axis underlined theranostic implications.

Language: Английский

Citations

16
Development of Receptor for Advanced Glycation End Products (RAGE) ligands through target directed dynamic combinatorial chemistry: a novel class of possible antagonists DOI Creative Commons
Anca‐Elena Dascălu, Christophe Furman, Isabelle Landrieu

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(20)

Published: Feb. 7, 2024

Abstract RAGE is a transmembrane receptor of immunoglobulin family that can bind various endogenous and exogenous ligands, initiating the inflammatory downstream signaling pathways, including inflammaging. Therefore, represents an attractive drug target for age‐related diseases. For development small‐molecule antagonists, we employed protein‐templated dynamic combinatorial chemistry (ptDCC) using RAGE′s VC1 domain as template, first application this approach in context RAGE. The affinities DCC hits were validated microscale thermophoresis. Subsequent screening against AGE2 (glyceraldehyde‐modified AGE)‐sRAGE (solubleRAGE) (AGE2‐BSA/sRAGE) interaction ELISA tests led to identification antagonists with micromolar potency. Our findings not only demonstrate successful ptDCC on but also highlight its potential address pressing need alternative strategies area research has experienced slowdown recent years.

Language: Английский

Citations

5
Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies DOI
Yasaman Naeimzadeh, Amir Tajbakhsh,

Mahnaz Nemati

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 978, P. 176803 - 176803

Published: June 29, 2024

Language: Английский

Citations

5
Development of a microarray microfluidic chip mass spectrometry platform based on UV curable 3D hepatocellular sphere bio-ink for rapid screening inhibitors of advanced glycosylation end products from natural compounds DOI

Wang Hechen,

Xie Yanqiao,

Liu Longchan

et al.

Biosensors and Bioelectronics, Journal Year: 2025, Volume and Issue: unknown, P. 117499 - 117499

Published: April 1, 2025

Language: Английский

Citations

0
The Ephrin tyrosine kinase a3 (EphA3) is a novel mediator of RAGE-prompted motility of breast cancer cells DOI Creative Commons
Marianna Talia, Francesca Cirillo,

Asia Spinelli

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: July 12, 2023

The receptor for advanced glycation-end products (RAGE) and its ligands have been implicated in obesity associated inflammatory processes as well metabolic alterations like diabetes. In addition, RAGE-mediated signaling has reported to contribute the metastatic progression of breast cancer (BC), although mechanistic insights are still required. Here, we provide novel findings regarding transcriptomic landscape molecular events through which RAGE may prompt aggressive features estrogen (ER)-positive BC. MCF7 T47D BC cells stably overexpressing human were used a model system evaluate important changes cell protrusions, migration, invasion colony formation both vitro scanning electron microscopy, clonogenic, migration assays vivo zebrafish xenografts experiments. whole transcriptome RAGE-overexpressing was screened by high-throughput RNA sequencing. Thereafter, Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analyses allowed prediction potential functions differentially expressed genes (DEGs). Flow cytometry, real time-PCR, chromatin immunoprecipitation, immunofluorescence western blot performed investigate network involved regulation target gene namely EphA3. clinical significance EphA3 explored TCGA cohort patients survivALL package, whereas pro-migratory role ascertained cancer-associated fibroblasts (CAFs). Statistical analysis t-tests. RNA-seq GSEA revealed that overexpression leads motility-related signature ER-positive cells. Accordingly, found exhibit long filopodia-like membrane protrusions an enhanced dissemination potential, determined diverse experimental assays. Mechanistically, established first time act physical mediator CAFs motility homotypic heterotypic interactions. Our data demonstrate up-regulation migratory ability Noteworthy, our suggest be considered facilitating scattering from primary tumor mass. Overall, current results useful more comprehensive therapeutic approaches BC, particularly obese diabetic characterized high levels.

Language: Английский

Citations

9
Quantitative Assessment of Intracellular Effectors and Cellular Response in RAGE Activation DOI Open Access

Vinitha Deepu,

Vikrant Rai,

Devendra K Agrawal

et al.

Archives of Internal Medicine Research, Journal Year: 2024, Volume and Issue: 07(02)

Published: Jan. 1, 2024

The review delves into the methods for quantitative assessment of intracellular effectors and cellular response Receptor Advanced Glycation End products (RAGE), a vital transmembrane receptor involved in range physiological pathological processes. RAGE bind to (AGEs) other ligands, which turn activate diverse downstream signaling pathways that impact responses such as inflammation, oxidative stress, immune reactions. article discusses activated by followed differential activation across various diseases. This will ultimately guide researchers developing targeted effective interventions diseases associated with activation. Further, we have discussed how PCR, western blotting, microscopic examination molecules can be leveraged monitor, diagnose, explore involving proteins unique post-translational modifications. underscores pressing need advancements molecular approaches disease detection management RAGE.

Language: Английский

Citations

3