Ask about this productRelated genes to: NOTCH1 antibody
- Gene:
- NOTCH1 NIH gene
- Name:
- notch receptor 1
- Previous symbol:
- TAN1
- Synonyms:
- -
- Chromosome:
- 9q34.3
- Locus Type:
- gene with protein product
- Date approved:
- 1992-02-13
- Date modifiied:
- 2019-04-23
Related products to: NOTCH1 antibody
Related articles to: NOTCH1 antibody
- Vulvar squamous cell carcinoma (VSCC) comprises biologically distinct subtypes with divergent molecular profiles and clinical behaviors. In this study, we performed comprehensive genomic profiling of 48 primary VSCCs, integrating mutational and copy number data with HPV status and clinicopathological parameters. Tumors were stratified into HPV-associated (HPVA), HPV-independent (HPVI), and a third proposed subgroup characterized by HPV negativity and wild-type TP53 status. Overall, 650 somatic mutations were identified, with TP53, TERT promoter, NOTCH1, PIK3CA, and CDKN2A being the most frequently altered genes. HPVA VSCCs exhibited a higher mutational burden and enrichment of PIK3CA, NOTCH1, and MLL2 mutations, consistent with APOBEC-driven mutagenesis. HPVI VSCCs showed frequent TP53, TERTp, and CDKN2A mutations, along with an age-related mutational signature. Copy number alterations were more common in HPVI tumors, with recurrent amplifications in CCND1, FGF3/4/19, and CDK pathway genes. Six VSCCs lacked both HPV association and TP53 mutations, supporting the existence of a third molecular subtype, with frequent TERTp mutations and limited additional alterations. No significant survival differences were observed between subtypes, although nodal status remained prognostically relevant. These findings refine the molecular taxonomy of VSCC, support the recognition of a third genomic subgroup, and highlight subtype-specific therapeutic targets. - Source: PubMed
Publication date: 2026/05/11
Choschzick MHoesli LStergiou CRüschoff J H - Stem cells from the apical papilla (SCAPs) are dental mesenchymal stem cells known for their high proliferative and multilineage potential. However, prolonged in vitro expansion may alter their phenotype due to microenvironmental stress. This exploratory study aimed to investigate whether prolonged high-density culture with restricted medium renewal is associated with morphological, protein-level, and transcriptional changes indicative of partial mesenchymal-epithelial transition (MET) in SCAPs. Donor-derived SCAPs were cultured under standard or prolonged high-density conditions. Morphological assessment was conducted using phase-contrast microscopy, protein expression was evaluated through immunofluorescence, and gene expression was analyzed using a Human epithelial-mesenchymal transition (EMT) reverse-transcription quantitative polymerase chain reaction (RT-qPCR) array. Prolonged culture resulted in a transition from spindle-shaped mesenchymal cells to compact epithelial-like clusters. This morphological change was accompanied by the upregulation of epithelial-associated genes, such as cadherin 1 (CDH1) and keratin 14 (KRT14), alongside the downregulation of extracellular matrix (ECM) and adhesion-related genes, including collagen type I alpha 2 chain (COL1A2), collagen type V alpha 2 chain (COL5A2), fibronectin 1 (FN1), and several integrins. Key regulators associated with EMT, including snail family transcriptional repressor 1 (SNAI1), snail family transcriptional repressor 3 (SNAI3), zinc finger E-box-binding homeobox 1 (ZEB1), notch receptor 1 (NOTCH1), and epidermal growth factor receptor (EGFR), were downregulated. In contrast, bone morphogenetic proteins 2 (BMP2) and 7 (BMP7), transforming growth factor beta 2 (TGFB2), matrix metalloproteinases 2 (MMP2) and 3 (MMP3), and secreted phosphoprotein 1 (SPP1) were upregulated. Immunofluorescence further demonstrated the expression of enamel-associated proteins, including amelogenin and ameloblastin, in long-term cultures. In conclusion, prolonged high-density culture with limited medium renewal was associated with coordinated epithelial-like phenotypic and transcriptional changes in SCAPs, suggesting the potential for partial mesenchymal-epithelial plasticity and emphasizing the sensitivity of dental stem cells to the culture microenvironment during in vitro expansion. - Source: PubMed
Publication date: 2026/05/11
Kercheva KameliyaMiteva MarinaKalenderova SilviaMitev VanyoMihaylova ZornitsaIshkitiev NikolayDimitrova Violeta S - F-box and WD repeat domain-containing 7 () encodes the substrate-recognition subunit of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complex, where it regulates proteasome-mediated degradation of key cell cycle and developmental proteins. The aim of this review is to provide a comprehensive overview of the currently available evidence on the clinical and molecular features of -related neurodevelopmental disorder (NDD). While somatic mutations in are well-established drivers of human tumors, germline variants have only recently been linked to a distinctive neurological disorder. Reported germline variants include missense, frameshift, splice-site, and larger structural variants, with the majority clustering in the WD40 domain and disrupting substrate recognition. Functional studies confirm impaired degradation of critical regulators such as cyclin E, MYC, and NOTCH1. Clinically, affected individuals present with early developmental delay, hypotonia, and impaired language acquisition, frequently accompanied by structural brain anomalies, craniofacial dysmorphisms, and variable growth abnormalities. Additional manifestations include congenital anomalies and broad gastrointestinal involvement. Wilms tumor (WT) has been reported in a few individuals carrying germline or constitutional mosaic variants, with evidence of a second somatic hit documented in tumor tissue, supporting a rare but biologically plausible role of this gene in determining WT predisposition. - Source: PubMed
Publication date: 2026/05/08
Savasta SComisi F FFiumicelli EDell'Isola G BDi Pasquale GMangano G DZagaroli LSalpietro VVerrotti A - Microglia are key regulators of neuroinflammation and neuronal survival after ischemic stroke. Emerging single-cell, transcriptomic, and metabolic studies show that ischemia induces rapid microglial reprogramming toward pro-inflammatory states that exacerbate neuronal death, oxidative stress, blood-brain barrier (BBB) disruption, and white-matter injury. Multiple pathways, including TLR4/NF-κB, NLRP3 inflammasome activation, Notch1-JAK/STAT signaling, epigenetic modulators such as HDAC3 and METTL14, and metabolic shifts involving AMPK/mTOR/HIF1α, collectively shape post-stroke microglial polarization. High-altitude hypoxia elicits similar inflammatory responses, activating microglia through RAGE-MAPK/NFκB signaling, CX3CL1/CX3CR1-dependent synaptic pruning, mitochondrial dysfunction, and lactate-mediated chromatin changes, highlighting hypoxia as a convergent driver of neuroinflammation. Modulating microglial activity, therefore, represents a promising therapeutic strategy. A wide range of natural compounds (e.g., curcumin, acteoside, astagaloside IV, artemisinin), synthetic agents (e.g., DBZ, resolvin D1), and cellular/molecular cellular interventions (e.g., rhFGF21, S100A9 inhibition, RBM3 induction) have shown efficacy in reducing inflammation, preserving BBB integrity, improving mitochondrial function, and promoting M2-like reparative phenotypes in preclinical models. Advances in understanding microglial subtypes, including CH25H, OASL, CD11c, and antioxidant Prdx1-enriched populations, further highlight their dynamic roles across injury and repair. This review presents current insights into microglial signalling, epigenetic and metabolic regulation, and therapeutic targeting in ischemic stroke, integrating parallel insights from high-altitude hypoxia. Together, these prospectives illuminate microglia as crucial mediators of neurovascular injury and recovery, and highlight opportunities for translating microglia-directed therapies into clinical interventions. - Source: PubMed
Publication date: 2026/05/06
Khan ShafaSultan ArmiyaSadik MohdAshraf Mohammad Zahid - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by marked molecular heterogeneity and limited targeted therapeutic options. Its incidence is rising in many low- and middle-income countries, where genetic profiling of affected patients remains largely unexplored despite evident clinical disparities. This study aimed to characterize, for the first time in a Tunisian cohort, the spectrum of germline and somatic mutations in TNBC patients and to assess their potential impact on therapeutic response. Targeted next-generation sequencing (NGS) of hotspot regions across 50 cancer-related genes was performed in twelve patients using the AmpliSeq for Illumina Cancer Hotspot Panel v2, applied to both tumor tissues and matched adjacent non-tumoral tissues. Bioinformatics analysis revealed recurrent germline variants present in all samples, notably in TP53 (rs1042522), CSF1R (rs2066933), FGFR3 (rs7688609), RET (rs1800861), KDR (rs7692791), and PDGFRA (rs1873778). In tumor tissues, 32 deleterious somatic variants were detected across 20 oncogenes, with TP53 emerging as the most frequently mutated gene (58%). Distinct mutational patterns were observed in relation to treatment response. Notably, the co-occurrence of AKT1 (rs121434592) and TP53 (rs876660754) was observed in a patient with treatment resistance, whereas an in-frame deletion in NOTCH1 (p.Val1578del) was uniquely detected in patients who subsequently experienced disease recurrence. These findings provide the first comprehensive characterization of germline and somatic alterations in Tunisian TNBC patients, representing a North African cohort. They reveal the heterogeneity of mutation patterns linked to treatment response, and emphasize the importance of genomic profiling into clinical practice and guide personalized therapeutic strategies. - Source: PubMed
Publication date: 2026/04/22
Mehri AsmaLaaribi Ahmed BalighJbir IchrafChelbi EmnaChelly BeyaChaabane AbirNechi SalwaOuzari Hadda-Imen