NOTCH1 expression

Mechanistically, DUSP6 dephosphorylates phospho-Y2116, which in turn reduces NTM ubiquitination, leading to increased NTM stability and transcriptional activity. As a result, the expression of Notch1-targeted proliferation genes is increased to promote tumour cell growth.

NOTCH1 was conducive to cancer-associated fibroblasts (CAFs) immune infiltration, while the metastatic process was more dependent on the differentiation and angiogenesis function of NOTCH1. Accordingly, the heterogeneity of NOTCH1 in immune infiltration was extensively analyzed in this study based on the pan-cancer study, which can contribute to the formulation of specific immunotherapy strategies.

We report on the design of hypoxia-induced dual-stage acting dendrimeric nanoparticles (NPs) for selective delivery of two chemotherapeutic model drugs doxorubicin (DOX) and tirapazamin (TPZ) for deepened drug delivery into hypoxic tumors in vitro...Importantly, hypoxia-responsive disintegration and hypoxia-induced activation of HAP drug were synergized to promote deep and homogenous HAP distribution in whole microtumor regions to efficiently eliminate residual tumor cells. Our results indicate the safety and high therapeutic potential of PAP system for targeted drug delivery of chemotherapeutics in particular HAPs which show maximum anti-cancer activity against hypoxic solid tumors.

In conclusion, GXYLT2 may be related to the pathogenesis of GC, and its abnormal expression could be associated with epithelial-mesenchymal transition. Consequently, GXYLT2 may be considered a promising prognostic marker in the context of GC.

To counteract monotherapy-induced tumor relapse, we assessed GSI-paclitaxel and dasatinib-paclitaxel combination treatments in NOTCH inhibitor-sensitive and -resistant TNBC xenotransplants, respectively. These distinct preventive combinations and second-line treatment option dependent on NOTCH1 and SOX2 expression in TNBC are able to induce tumor growth control and reduce metastatic burden.

On the basis of these results, it is reasonably speculated that targeting ANXA1 would provide an effective approach for treatment of AML. In support of this new therapeutic paradigm, provided proof-of-concept data by antagonizing ANXA1 using NICD inhibitory peptides.

Taken together, the present study finds that Cep possesses excellent anti-metastasis of HCC, wherein the GRP78 could be directly bound and activated by Cep, leading to ER stress and Notch1 blockage. This study reveals for the first time the effect, critical target, and mechanism of the Cep-mediated anti-cancer effect, providing novel insights into the molecular target therapy by phytomedicine.

Rescue assays indicated that repressed SCLC cell growth caused by MACC1-AS1 knockdown could be reserved by miR-579-3p repression or NOTCH1 overexpression. In brief, lncRNA MACC1-AS1 boosted SCLC cell growth via sequestering miR-579-3p and mediating NOTCH1-pathway.

Consistent with this, pharmacological inhibition of c-Jun with SP600125 reduced GGCT and inhibited GSC proliferation...These results indicate that GGCT, whose expression is promoted by c-Jun, plays an important role in the proliferation and tumorigenic potential of GSCs, and that the phenotype caused by its knockdown is contributed by a decrease in Notch1. Thus, GGCT may represent a novel therapeutic target for attacking GSCs.

Our data indicated that miR-184 expression is increased in myeloma plasma cells. Down-regulation of miR-184 promotes MM cell apoptosis and inhibits proliferation and colony formation by regulating Notch1 expression.

The Notch1 signaling pathway participates in the pathogenesis of AM possibly by regulating the proliferation, migration, invasion and glycolysis of endometrial cells.

In human NOTCH1-dependent leukemias, high expression levels of BCAT1 may predispose to worse prognosis. Therapeutically, BCAT1 inhibition specifically synergized with etoposide to eliminate tumors in patient-derived xenograft models suggesting that BCAT1 inhibitors may have a part to play in salvage protocols for refractory T-ALL.

Our results suggest inhibition of SUV39H1 may affect angiogenesis by regulating Notch1 expression. This study provides a foundation for SUV39H1 as a potential therapeutic target for OSCC.

It also could significantly increase the co-expression of MVH/Jagged1, MVH/Hes1, and MVH/Notch1 proteins(P<0.01 or P<0.001). It suggested that TG play the role of γ-secretagorease inhibitors by downregulating the OGSC markers including MVH and Oct4 and Notch signaling pathway molecules such as Notch1, Hes1, and Jagged1, participate in the OGSC pathway, and mediate reproductive toxicity caused by the Notch signaling pathway.

Intriguingly, inhibiting mTOR pathway at the initial stages of monocyte differentiation to LC-like, fosters the pathognomonic LCH program highly increasing CD207 levels, together with NOTCH1 induction. We define here that AXLhigh could also be taken as a strong pathognomonic marker for LCH, and the release of Langerin and NOTCH1 expression depends on the inhibition of the mTOR pathway.

TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.

In addition, miR-15a, miR-181, and miR-146 were decreased and miR-155 had increased expression in most samples. The activation of the NOTCH pathway in vitro increases the susceptibility of primary CLL cells to apoptosis despite high BCL2 expression.

These results suggest that FA protects against glucose deprivation. These effects were associated with AMPK activation, a critical metabolic mediator in nutrient consumption and availability that activates the Notch-1 pathway.

It can also improve the abnormal DLBCL microenvironment in which immune escape occurs, and inhibit immune escape. This study provides a new therapeutic idea for the exploration of individualized precision therapy for patients with malignant lymphoma.

Our study demonstrates that in patients with breast AdCC, overexpression of NOTCH1 ≥20% is associated with larger tumour size and aggressive clinical outcomes. Importantly, NOTCH1 inhibitors may have potential therapeutic effect in patients with breast AdCC.

Moreover, gene expression of caspase 3, caspase 9, Notch 1, cyclin D1, NF-кB, IL-6, and VEGF was significantly more effective with PCSeNPs than similar doses of free extract. The PCSeNPs mediated their promising anti-cancerous action by enhancing apoptosis and mitigating inflammation, which manifested in promoting the total survival rate and the tumor volume decrease.

Encouraged by its efficacy, it was further investigated for its antitumor activity and mechanism of action, using sorafenib as a reference standard...It also downregulated Notch1 protein expression and decreased TGF-β1 production. Molecular docking simulations suggest that 8e binds as a promising type II kinase inhibitor in the target kinases interacting with the key regions in their kinase domain.

Ferroptosis inducers may serve as potential candidates for novel molecular therapy against AML and T-ALL.

After cerebral ischemia, APS can alleviate symptoms of secondary damage to the VPN, which may be attributed to the suppression of the Notch1/NFκB pathway.

NOTCH1 mediates the activation of microglia in the L5-S2 spinal cord, leading to the secretion of inflammatory factors and enhanced electrical excitability of neurons, which is related to persistent and refractory chronic prostatitis-related pain.

A NOTCH-TBC1D15 inhibitor was found to inhibit NOTCH-dependent pathways and exhibited potent therapeutic effects in PDX mouse models. This unique targeting of the NOTCH-TBC1D15 interaction not only normalized the perinuclear localization of mitochondria but also promoted potent cytotoxic effects against TICs to eradicate patient-derived xenografts through NOTCH-dependent pathways.

Resveratrol may play a role in anti T-ALL by inhibiting Notch1 signaling pathway in mice.

In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.

Analysis of one patient still alive from the first group, diagnosed with mTNBC in 2019, showed a complete metabolic response (CMR) after a composite approach implicating first-line mCHT followed by second-line epirubicin and third-line nab-paclitaxel, and was chosen for subsequent molecular characterization. Additionally, we found changes in the expression of oncogenes, such as MYC and AKT, along with their respective proteins. Overall, our data suggest that a first-line treatment with mCHT followed by MTD might be effective by negatively regulating stemness traits usually associated with the emergence of drug resistance.

Acute PM2.5 exposure can activate Notch1-GATA3 pathway in asthma bronchial epithelial cells model, which might be involved in PM2.5-induced asthma exacerbation. miR-139-5p has a potential protective role of inhibiting PM2.5-induced asthma airway inflammation by targeting Notch1.

Expression of NOTCH1, ID1, and LST1 genes showed a significant increase at the HCC tumor border. Targeting these genes can be considered as a useful therapeutic strategy to prevent distant metastasis in HCC patients.

The co-treatment of TNBC cells with doxorubicin (Doxo) and CNC was also investigated...The observed effects of CNC may reflect the possible anti-cancer activities of CNC in both types of TNBC. However, cell type and CNC dose should be considered.

These findings illuminate the novel role of FBXO8 as a prognostic and therapeutic target across different molecular subtypes of breast cancer. Finally, through the utilization of virtual screening and Molecular Dynamics simulations, we successfully identified two FDA-approved medications, Ledipasvir and Paritaprevir, that demonstrated robust binding capabilities and interactions with FBXO8.

Yougui Wan can inhibit the inflammatory response in IDD rats, reduce the degradation of extracellular matrix, reduce apoptosis in nucleus pulposus cells, and alleviate intervertebral disk degeneration. The mechanism may be related to the regulation of the Notch signaling pathway.

The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.

These data show that Prox1 decreased RB cell proliferation and drug resistance by targeting Notch1, implying that Prox1 could be a potential therapeutic target for RB.

Intriguingly, low-dose OMP-52 M51 strongly facilitated the capacity of ferroptosis inducer erastin to trigger ferroptotic cell death, revealing that OMP-52 M51 could improve the sensitivity of ACC cells to ferroptosis. In vivo, OMP-52 M51 administration suppressed tumor growth and induced ferroptosis in the constructed ACC xenograft mouse model. Collectively, our findings demonstrated that NOTCH1 inhibition by OMP-52 M51 represses the proliferation and epithelial-mesenchymal transition (EMT) in ACCs, and promotes ferroptosis, revealing the potential therapeutical application of OMP-52 M51 in ACC.

Lipid nanoparticles targeting YTHDF1 significantly enhanced the efficacy of lenvatinib and sorafenib in HCC in vivo. Taken together, YTHDF1 drives HCC stemness and drug resistance through a YTHDF1-m6A-NOTCH1 epitranscriptomic axis, and YTHDF1 is a potential therapeutic target for treating HCC.

This study stands as the pioneer in examining the role of DACT3 in glioma progression and comprehensively elucidating its molecular mechanisms in glioma development. Therefore, our results suggest that DACT3 holds promise as both a prognostic factor and a potential biomarker for guiding treatment strategies in glioma patients (Graphical Abstract).

Our data confirmed a reduced CD20 expression in CLL patients with NOTCH1 and SF3B1 mutations. In addition, an approach was proposed to identify high-risk CLL patients for prediction of such mutations: previously untreated CLL patients at advanced Binet - Rai stages (BII, CIII, CIV) with a reduced number of double-positive CD20+CD5+ cells in peripheral blood and/or low iMFI of CD20+ cells.

Lenvatinib regulated resistance and stemness in organoids via the Notch pathway.

In summary, the regulatory effects of Rg5 on the Notch1 signaling pathway play a crucial role in modulating hepatic lipid metabolism and preventing hepatocyte apoptosis, thereby impeding the progression of NASH. These findings highlight the potential of Rg5 as a promising natural product for interventions targeting NASH.