Three Strategies in Engineering Nanomedicines for Tumor Microenvironment‐Enabled Phototherapy

Small, Journal Year: 2023, Volume and Issue: 19(37)

Published: May 24, 2023

Canonical phototherapeutics have several limitations, including a lack of tumor selectivity, nondiscriminatory phototoxicity, and hypoxia aggravation. The microenvironment (TME) is characterized by hypoxia, acidic pH, high levels H2 O2 , GSH, proteases. To overcome the shortcomings canonical phototherapy achieve optimal theranostic effects with minimal side effects, unique TME characteristics are employed in development phototherapeutic nanomedicines. In this review, effectiveness three strategies for developing advanced based on various examined. first strategy involves targeted delivery to tumors assistance TME-induced nanoparticle disassembly or surface modification. second near-infrared absorption increase-induced activation triggered factors. third enhancing therapeutic efficacy ameliorating TME. functionalities, working principles, significance applications highlighted. Finally, possible challenges future perspectives further discussed.

Language: Английский

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Metabolism pathway-based subtyping in endometrial cancer: An integrated study by multi-omics analysis and machine learning algorithms

Molecular Therapy — Nucleic Acids, Journal Year: 2024, Volume and Issue: 35(2), P. 102155 - 102155

Published: Feb. 16, 2024

Endometrial cancer (EC), the second most common malignancy in female reproductive system, has garnered increasing attention for its genomic heterogeneity, but understanding of metabolic characteristics is still poor. We explored dysfunctions EC through a comprehensive multi-omics analysis (RNA-seq datasets from The Cancer Genome Atlas [TCGA], Cell Line Encyclopedia [CCLE], and GEO datasets; Clinical Proteomic Tumor Analysis Consortium [CPTAC] proteomics; CCLE metabolomics) to develop useful molecular targets precision therapy. Unsupervised consensus clustering was performed categorize patients into three metabolism-pathway-based subgroups (MPSs). These MPS had distinct clinical prognoses, transcriptomic alterations, immune microenvironment landscape, unique patterns chemotherapy sensitivity. Moreover, MPS2 subgroup better response immunotherapy. Finally, machine learning algorithms (LASSO, random forest, stepwise multivariate Cox regression) were used developing prognostic metagene signature based on molecules. Thus, 13-hub gene-based classifier constructed predict patients' subtypes, offering more accessible practical approach. This metabolism-based classification system can enhance predictions guide strategies immunotherapy metabolism-targeted therapy EC.

Language: Английский

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Targeting of mitochondrial fission through natural flavanones elicits anti-myeloma activity

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 27, 2024

Abstract Background Mitochondrial alterations, often dependent on unbalanced mitochondrial dynamics, feature in the pathobiology of human cancers, including multiple myeloma (MM). Flavanones are natural flavonoids endowed with targeting activities. Herein, we investigated capability Hesperetin (Hes) and Naringenin (Nar), two aglycones Hesperidin Naringin flavanone glycosides, to selectively target Drp1, a pivotal regulator prompting anti-MM activity. Methods Molecular docking analyses were performed crystallographic structure Dynamin-1-like protein (Drp1), using Hes Nar molecular structures. Cell viability apoptosis assessed MM cell lines, or co-culture systems primary bone marrow stromal cells, Titer Glo Annexin V-7AAD staining, respectively; clonogenicity was determined methylcellulose colony assays. Transcriptomic carried out Ion AmpliSeq™ platform; mRNA expression levels by quantitative RT-PCR western blotting, respectively. architecture transmission electron microscopy. Real time measurement oxygen consumption high resolution respirometry living cells. In vivo anti-tumor activity evaluated NOD-SCID mice subcutaneously engrafted Results found accommodate within GTPase binding site inhibit Drp1 activity, leading hyperfused mitochondria reduced OXPHOS. vitro, viability, even presence patient-derived triggering ER stress apoptosis. Interestingly, rewired metabolism through down-regulation master transcriptional activators (SREBF-1, c-MYC) lipogenesis genes. An extract Tacle, Citrus variety rich Naringin, capable recapitulate phenotypic perturbations each flavanone, vivo. Conclusion proliferation, rewire induce cells via antagonism fission driver Drp1. These results provide framework for development therapeutics aberrant dependencies.

Language: Английский

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Novel Molecular Targets in Endometrial Cancer: Mechanisms and Perspectives for Therapy

Biologics, Journal Year: 2024, Volume and Issue: Volume 18, P. 79 - 93

Published: March 1, 2024

Abstract: Endometrial cancer (EC) has a high epidemiological impact with incidence and mortality rising worldwide. In recent years, the integration of pathologic molecular classification provided relevant information to understand heterogeneity in biology EC, which led evolution management patients. Currently, therapeutic breakthroughs have been made advanced EC improve oncologic outcomes, efforts include patient reported outcomes. Precision personalized medicine are under way exploring different combination approaches target cross-talk pathways, cell microenvironment, metabolic vulnerabilities drug delivery. Yet, collaborative needed face challenges practice by refining selection, ideal biomarker identification, de-escalation therapies according emerging genomic features EC. Keywords: endometrial cancer, targeted therapy, targets, precision

Language: Английский

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Exploring the Role of Hypoxia and HIF-1α in the Intersection of Type 2 Diabetes Mellitus and Endometrial Cancer

Current Oncology, Journal Year: 2025, Volume and Issue: 32(2), P. 106 - 106

Published: Feb. 13, 2025

Diabetes and Cancer are the most complex chronic diseases, accounting for significant global mortality morbidity. The association between Type 2 DM (T2DM) endometrial cancer (EC) is multifaced, sharing numerous risk factors, including insulin resistance, obesity, hypoxia, oxidative stress. Hypoxia plays a vital role in T2DM pathogenesis by altering level pancreatic β-cell failure through an imbalance antioxidant enzymes cellular levels, while inflammation contributes to EC malignancy. HIF-1α potent transcription factor involved modulating responses hypoxia within disease environment. Targeting signaling cascade, major metabolic regulator may contribute advanced therapeutic advances. This review focuses on EC, especially focusing HIF pathways. These intersect with key pathways pathology, such as signaling, PI3K/AKT, mTOR pathway, MUC1/HIF-1α hormonal imbalance. Understanding this relationship paves way future researchers develop HIF-1α-targeted therapies that could lead novel combination treat these comorbid conditions.

Language: Английский

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Endometrial Cancer Is Associated with Altered Metabolism and Composition of Fatty Acids

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3322 - 3322

Published: April 2, 2025

Endometrial cancer (EC) is a complex gynecologic malignancy that requires deeper understanding of its molecular basis to improve therapeutic strategies. In this study, we investigated the role fatty acid (FA) reprogramming in progression EC. We analyzed FA profiles identify stage-specific changes and gene expression key enzymes involved synthesis, desaturation, elongation, transport, oxidation at different stages Our results show EC tissues have lower levels saturated branched-chain FA, higher very long-chain n-3 polyunsaturated (PUFA), monounsaturated with exception myristoleic acid. The differences n-6 PUFA were inconsistent. Gene analysis revealed upregulation controlling de novo including ACACA, FASN, SCD1, ELOVL1. contrast, genes related transport cell β-oxidation was downregulated. some metabolism upregulated, while others These demonstrate lipid suggest potential targets for novel interventions

Language: Английский

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Biobanking and gynecologic oncology - Special considerations, challenges and opportunities

European Journal of Surgical Oncology, Journal Year: 2025, Volume and Issue: unknown, P. 109713 - 109713

Published: April 1, 2025

Language: Английский

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Diagnosis Test Accuracy of Artificial Intelligence for Endometrial Cancer: Systematic Review and Meta-Analysis

Journal of Medical Internet Research, Journal Year: 2025, Volume and Issue: 27, P. e66530 - e66530

Published: April 18, 2025

Background Endometrial cancer is one of the most common gynecological tumors, and early screening diagnosis are crucial for its treatment. Research on application artificial intelligence (AI) in endometrial increasing, but there currently no comprehensive meta-analysis to evaluate diagnostic accuracy AI cancer. Objective This paper presents a systematic review AI-based screening, which needed clarify provide evidence technology Methods A search was conducted across PubMed, Embase, Cochrane Library, Web Science, Scopus databases include studies published English, evaluated performance screening. total 2 independent reviewers screened titles abstracts, quality selected assessed using Quality Assessment Diagnostic Accuracy Studies—2 (QUADAS-2) tool. The certainty test Grading Recommendations Assessment, Development, Evaluation (GRADE) system. Results 13 were included, hierarchical summary receiver operating characteristic model used showed that overall sensitivity 86% (95% CI 79%-90%) specificity 92% 87%-95%). Subgroup analysis revealed similar results type, study region, publication year, low. Conclusions can effectively detect patients with cancer, large-scale population future further Trial Registration PROSPERO CRD42024519835; https://www.crd.york.ac.uk/PROSPERO/view/CRD42024519835

Language: Английский

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Glucose metabolism reprogramming in gynecologic malignant tumors

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(9), P. 2627 - 2645

Published: Jan. 1, 2024

The incidence and mortality of gynecological tumors are progressively increasing due to factors such as obesity, viral infection, unhealthy habits, well social economic pressures.Consequently, it has emerged a significant threat women's health.Numerous studies have revealed the remarkable metabolic activity tumor cells in glycolysis its ability influence malignant biological behavior through specific mechanisms.Therefore, is crucial for patients gynecologists comprehend role glycolytic proteins, regulatory molecules, signaling pathways tumorigenesis, progression, treatment.This article aims review correlation between abnormal glucose metabolism gynecologic including cervical cancer (CC), endometrial carcinoma (EC), ovarian (OC).The findings from this research will provide valuable scientific insights early screening, timely diagnosis treatment interventions while also aiding prevention recurrence among individuals with tumors.

Language: Английский

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Glycometabolism and lipid metabolism related genes predict the prognosis of endometrial carcinoma and their effects on tumor cells

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 8, 2024

Glycometabolism and lipid metabolism are critical in cancer metabolic reprogramming. The primary aim of this study was to develop a prognostic model incorporating glycometabolism metabolism-related genes (GLRGs) for accurate prognosis assessment patients with endometrial carcinoma (EC).

Language: Английский

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