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Irreversible electroporation (IRE) employs high-voltage electrical pulses for non-thermal image-guided tumor ablation in solid organs. The pulses disrupt the membrane potential of all cells within the ablation zone causing loss of tumour cell homeostasis resulting in death. IRE has the advantage of sparing extracellular matrix structures and thereby preserving the anatomical integrity of blood vessels, bile ducts, and ureters. This trait distinguishes IRE from more commonly used thermal ablation techniques like microwave- and radiofrequency ablation. Several prospective phase-1 and -2 studies demonstrated the safety and efficacy of IRE for the treatment of central liver, locally advanced pancreatic, and local prostate tumours. In addition, IRE induces a systemic immune response. When this immune effect can be amplified by combinatory treatment with immunotherapeutic drugs its synergy might form a bridge between local and systemic therapies with the potential to develop into a fundamentally new approach to cancer treatment.
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Cell Signal
September 2025
School of Forensic Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, People's Republic of China.
Triple-negative breast cancer (TNBC) presents a formidable therapeutic challenge due to its aggressive behavior, molecular heterogeneity, and lack of actionable targets. This study identifies activation-induced cytidine deaminase (AID) as a pivotal epigenetic driver reprogramming the tumor microenvironment (TME) via non-canonical regulation of NOTCH signaling. Mechanistically, AID recruits histone acetyltransferase 1 (HAT1) to form a chromatin-remodeling complex that binds the JAG1 promoter region (-1.
View Article and Find Full Text PDFJ Invest Dermatol
September 2025
Departamento de Biología Molecular, Instituto Universitario de Biología Molecular IUBM-UAM and Centro de Biología Molecular Severo Ochoa (UAM-CSIC), 28049 Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain; CIBER de Enfermedades Cardiovasculares, ISCIII (CIBERCV
Tightly regulated cell-cell and cell-niche intercommunications via intertwined signaling networks are involved in maintaining normal hair follicle (HF) homeostasis, cycling and cell fate determination. However, knowledge of specific mechanisms by which hair loss takes place under pathological situations is needed. Using a keratinocyte-specific knockout mouse model, we uncover that the G-protein-coupled receptor kinase 2 (GRK2) signaling node plays a key role in HF homeostasis.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Xianyang, China. Electronic address:
Pancreatic adenocarcinoma (PAAD) lacks effective therapies due to complex macromolecular signaling networks. Here, we identified the natural compound Trienomycin A (TA) as a potent binder and degrader of the key signaling adaptor protein Insulin Receptor Substrate 1 (IRS1), disrupting its macromolecular assembly in insulin-like growth pathways. Through integrated biochemical, cellular, and in vivo analyses, we demonstrated that TA directly bound the phosphotyrosine-binding (PTB) domain of IRS1, inducing proteasomal degradation of this critical macromolecular hub mediated by the E3 ubiquitin ligase FBXW8.
View Article and Find Full Text PDFJ Control Release
September 2025
School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, Guangdong, China; Dongguan Liaobu Hospital, Dongguan 523400, Guangdong, China. Electronic address:
Fluorine-19 magnetic resonance imaging (F MRI) offers distinct advantages, including background-free signal detection, quantitative analysis, and deep tissue penetration. However, its application is currently limited by challenges associated with existing F MRI contrast agents, such as short transverse relaxation times (T), limited imaging sensitivity, and suboptimal biocompatibility. To overcome these limitations, a glutathione (GSH)-responsive triblock copolymer (PB7), featuring self-immolative characteristics, has been developed.
View Article and Find Full Text PDFMed Oncol
September 2025
Department of Biotechnology, Institute of Engineering and Management, University of Engineering and Management, Kolkata, Kolkata, India.
Oligomeric proanthocyanidins (OPCs), condensed tannins found plentiful in grape seeds and berries, have higher bioavailability and therapeutic benefits due to their low degree of polymerization. Recent evidence places OPCs as effective modulators of cancer stem cell (CSC) plasticity and tumor growth. Mechanistically, OPCs orchestrate multi-pathway inhibition by destabilizing Wnt/β-catenin, Notch, PI3K/Akt/mTOR, JAK/STAT3, and Hedgehog pathways, triggering β-catenin degradation, silencing stemness regulators (OCT4, NANOG, SOX2), and stimulating tumor-suppressive microRNAs (miR-200, miR-34a).
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