STIMULI-RESPONSIVE SUPRAMOLECULAR HYDROGELS FOR PACLITAXEL DELIVERY: PROGRESS AND PROSPECTS

Aspects of Molecular Medicine, Год журнала: 2025, Номер 5, С. 100062 - 100062

Опубликована: Янв. 5, 2025

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STAT3 Signaling Pathway in Health and Disease

MedComm, Год журнала: 2025, Номер 6(4)

Опубликована: Март 30, 2025

ABSTRACT Signal transducer and activator of transcription 3 (STAT3) is a critical factor involved in multiple physiological pathological processes. While STAT3 plays an essential role homeostasis, its persistent activation has been implicated the pathogenesis various diseases, particularly cancer, bone‐related autoimmune disorders, inflammatory cardiovascular neurodegenerative conditions. The interleukin‐6/Janus kinase (JAK)/STAT3 signaling axis central to activation, influencing tumor microenvironment remodeling, angiogenesis, immune evasion, therapy resistance. Despite extensive research, precise mechanisms underlying dysregulated disease progression remain incompletely understood, no United States Food Drug Administration (USFDA)‐approved direct inhibitors currently exist. This review provides comprehensive evaluation STAT3's health disease, emphasizing involvement cancer stem cell maintenance, metastasis, inflammation, drug We systematically discuss therapeutic strategies, including JAK (tofacitinib, ruxolitinib), Src Homology 2 domain (S3I‐201, STATTIC), antisense oligonucleotides (AZD9150), nanomedicine‐based delivery systems, which enhance specificity bioavailability while reducing toxicity. By integrating molecular mechanisms, pathology, emerging interventions, this fills knowledge gap STAT3‐targeted therapy. Our insights into crosstalk, epigenetic regulation, resistance offer foundation for developing next‐generation with greater clinical efficacy translational potential.

Язык: Английский

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Habitat Radiomics Based on Dynamic Contrast‐Enhanced Magnetic Resonance Imaging for Assessing Axillary Lymph Node Burden in Clinical T1–T2 Stage Breast Cancer: A Multicenter and Interpretable Study

Journal of Magnetic Resonance Imaging, Год журнала: 2025, Номер unknown

Опубликована: Апрель 21, 2025

ABSTRACT Background Axillary lymph node burden(ALNB) is a critical factor in determining treatment strategies for clinical T 1 –T 2 (cT ) stage breast cancer. However, as ALNB assessment relies on invasive procedures, exploring non‐invasive methods essential. Purpose To develop and validate habitat radiomics model assessing cT cancer, incorporating radiogenomic data to improve interpretability. Study Type Retrospective. Population 468 patients with cancer from two institutions The Cancer Imaging Archive (TCIA) Genome Atlas (TCGA)‐Breast Invasive Carcinoma (BRCA) were included. cohort was divided into training ( n = 173), internal validation 58), external 130), TCGA‐BRCA sets 107). Patients categorized high nodal burden (HNB; > 3 positive nodes) non‐HNB (≤ groups. Field Strength/Sequence 1.5‐T MRI 3.0‐T MRI, three‐dimensional dynamic contrast‐enhanced T1‐weighted gradient‐echo sequences. Assessment Two logistic regression models developed using habitat‐based features. Model performance evaluated the AUC. SHapley Additive exPlanations (SHAP) analysis employed identify key Radiogenomic analysis, including gene set enrichment drug sensitivity assessments, conducted transcriptomic set. Statistical Tests Pearson correlation, Mann–Whitney U , genetic algorithm, regression, AUC delong test, SHAP analysis. A p ‐value < 0.05 considered statistically significant. Results Habitat outperformed Clinical (AUCs: 0.840–0.932 vs. 0.558–0.673). used rank feature importance, subregion showing highest average value. indicated upregulation of KEGG ribosome pathway HNB group identified differential profiles among risk Data Conclusion has potential assess assist radiologists axillary diagnosis, which may help reduce need unnecessary ALN dissection. Evidence Level: 3. Technical Efficacy: Stage 2.

Язык: Английский

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Discovery and biological evaluation of a novel and highly potent JAK2 inhibitor for the treatment of triple negative breast cancer

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2025, Номер 40(1)

Опубликована: Апрель 29, 2025

Janus kinase 2 (JAK2) is considered an attractive target for the treatment of triple-negative breast cancer (TNBC). Herein, we discovered six JAK2 inhibitors using structure-based virtual screening and molecular docking. Among them, JNN-5 was best compound. It indicated strong inhibitory effects on in nanomolar range (IC50 = 0.41 ± 0.03 nM), high selectivity over JAK1 JAK3 (selectivity index (SI) > 73.17). Moreover, dynamics (MD) simulation exhibited that bound with stability to JH1. Cellular assays revealed displayed antiproliferative activities TNBC cell lines (MDA-MB-468, MDA-MB-213, HCC70, MDA-MB-157). significantly reduced migration HUVECs dose-dependence. had a significant effect multidrug-resistant MDA-MB-231/ADR 0.37 0.02 μM). These data demonstrate may be highly effective selective antitumor compound TNBC.

Язык: Английский

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Deciphering the landscape of triple negative breast cancer from microenvironment dynamics and molecular insights to biomarker analysis and therapeutic modalities

Medicinal Research Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Abstract Triple negative breast cancer (TNBC) displays a notable challenge in clinical oncology due to its invasive nature which is attributed the absence of progesterone receptor (PR), estrogen (ER), and human epidermal growth factor (HER‐2). The heterogenous tumor microenvironment (TME) TNBC composed diverse constituents that intricately interact evade immune response facilitate progression metastasis. Based on molecular gene expression, classified into four subtypes: basal‐like (BL1 BL2), luminal androgen (LAR), immunomodulatory (IM), mesenchymal. an aggressive histological variant with adverse prognosis poor therapeutic response. lack most patients could be heterogeneity disease, highlighting need for more effective treatments reliable prognostic biomarkers. Targeting certain signaling pathways their components has emerged as promising strategy improving patient outcomes. In this review, we have summarized interactions among various dynamic TME discussed classification subtypes. Moreover, purpose review compile provide overview recent data about recently discovered novel biomarkers targeted therapeutics proven successful treating metastatic TNBC. emergence strategies such chemoimmunotherapy, chimeric antigen (CAR)‐T cells‐based immunotherapy, phytometabolites‐mediated natural therapy, photodynamic photothermal approaches made significant positive impact paved way interventions.

Язык: Английский

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Curcumin enhances ATG3-dependent autophagy and inhibits metastasis in cervical carcinoma

Cell Division, Год журнала: 2024, Номер 19(1)

Опубликована: Ноя. 28, 2024

Cervical carcinoma poses a significant health threat, with traditional treatments proving inadequate in advanced stages. Curcumin, bioactive compound derived from turmeric, exhibits notable anti-inflammatory, antioxidant, and antineoplastic properties, potentially modulating autophagy, metastasis cancer cells. This study examines curcumin's impact on autophagy cervical carcinoma, focusing its interaction autophagy-related gene 3 (ATG3). SiHa HeLa cell lines were treated curcumin, ATG3 knockdown (shATG3), their combination. Cell migration was evaluated via wound healing assays, while proliferation CCK-8 assays. LC3 expression assessed using immunofluorescence western blotting. Molecular docking simulations identified binding interactions key proteins. Curcumin shATG3 significantly inhibited both proliferation, synergistic effect observed when combined. enhanced, indicating increased autophagy. Docking studies revealed potential to MMP2, MMP9, TGF-β, ATG3, LC3, p62, suggesting modulation of these pathways. The combination curcumin also enhancing supporting the as therapeutic agent for carcinoma. Further clinical research is needed validate findings.

Язык: Английский

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Curcumin Enhances ATG3-Dependent Autophagy and Inhibits Metastasis in Cervical Carcinoma

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июль 25, 2024

Cervical carcinoma poses a significant health threat, with traditional treatments proving inadequate in advanced stages. Curcumin, bioactive compound derived from turmeric, exhibits notable anti-inflammatory, antioxidant, and antineoplastic properties, potentially modulating autophagy, metastasis cancer cells. This study examines curcumin's impact on autophagy cervical carcinoma, focusing its interaction autophagy-related gene 3 (ATG3). SiHa HeLa cell lines were treated curcumin, ATG3 knockdown (shATG3), their combination. Cell migration was evaluated via wound healing assays, LC3 expression assessed using immunofluorescence western blotting. Molecular docking simulations identified binding interactions key proteins. Curcumin shATG3 significantly inhibited migration, synergistic effect observed when combined. enhanced, indicating increased autophagy. Docking studies revealed potential to MMP2, MMP9, TGF-β, ATG3, LC3, p62, suggesting modulation of these pathways. The combination curcumin demonstrates inhibition enhancement supporting as therapeutic agent for carcinoma. Further clinical research is warranted confirm findings.

Язык: Английский

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Methionine restriction inhibits pancreatic cancer proliferation while suppressing JAK2/STAT3 pathway

Pancreatology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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