Nevertheless, repression of EMT and Wnt pathway progression by Silibinin was perceived from the gene expression studies. Overall, the current study highlights the tweaking of intricate signaling crosstalk between glycolysis and the Wnt pathway in TNBC cells through inhibiting ENO1 and GLUT4.
14 hours ago
Journal
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ENO1 (Enolase 1) • SLC2A4 (Solute Carrier Family 2 Member 4)
Interestingly, our study shows that lurbinectedin treatment upregulates MHC-I/II genes and CD8 in SCLC clinical samples. We provide mechanistic insights into the effect of lurbinectedin on STING-mediated multimodal immune activation and demonstrate that lurbinectedin treatment represents a promising therapeutic strategy to potentiate the efficacy of immunotherapy in SCLC.
8 days ago
Journal
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CD8 (cluster of differentiation 8) • STING (stimulator of interferon response cGAMP interactor 1)
The patient was diagnosed as having stage IV HER2-positive breast cancer, which was treated with a regimen of trastuzumab (8 mg/kg), pertuzumab (first dose: 840 mg; second dose onward: 420 mg) and docetaxel (75 mg/m2) every 3 weeks. After 4 months of chemotherapy, the patient received complete remission. In conclusion, concomitant use of rifampicin and clarithromycin may increase the blood concentration of docetaxel.
9 days ago
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
Its therapeutic efficacy was comparable to, if not better than, that of Silibinin when administered at a dose of 400 mg/kg. EEIB showed significant therapeutic effects on alcohol-induced liver injury in mice, and its mechanism of action was related to the SIRT1-AMPK, nuclear factor-kappa B (NF-κB), and Nrf2 signaling pathways, in which sesquiterpenes may be the potential active ingredients.
P2/3, N=1800, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre | Initiation date: Oct 2024 --> Feb 2025
The results of molecular dynamics indicated that Silibinin could stably bind to PI3Kδ. Silibinin was a structurally novel 3,5,7-trihydroxychroman-4-one PI3Kδ inhibitor, providing valuable information for the subsequent discovery of PI3Kδ inhibitors.
Overall, silibinin treatment reduced the expression of p-p65NF-κB, COX-2, and p-p38 in response to ASD exposure, while increasing HO-1 expression both in vitro and in vivo. These findings suggest that silibinin mitigates pulmonary inflammation caused by ASD exposure by reducing inflammatory signaling and oxidative stress, indicating its potential as a therapeutic agent for ASD-induced pulmonary inflammation.
Collectively, our findings reveal, for the first time, that LINC01116 enhances Pol I transcription by scaffolding essential transcription factors to the ribosomal DNA promoter, thereby driving oncogenic activities in LUAD. We propose the c-Myc-LINC01116-Pol I axis as a critical oncogenic pathway and a potential therapeutic target for modulating Pol I transcription in LUAD.
P2/3, N=3400, Recruiting, Centers for Disease Control and Prevention | Trial completion date: Dec 2028 --> Dec 2029 | Trial primary completion date: Dec 2028 --> Dec 2029
3 months ago
Trial completion date • Trial primary completion date
P1/2, N=70, Not yet recruiting, University of California, San Francisco | Trial completion date: Jul 2027 --> Oct 2027 | Initiation date: Jul 2024 --> Oct 2024 | Trial primary completion date: Jan 2026 --> May 2026
3 months ago
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.
This increase correlates with a failure of the nuclear exosome and BRCA1, both of which are involved in nascent RNA degradation, to localise to active promoters. Our data suggest that MYCN and TFIIIC exert an censoring function in early transcription that limits promoter accumulation of inactive RNAPII and facilitates promoter-proximal degradation of nascent RNA.
4 months ago
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
This induction was attenuated upon PXR activation in hPXR-LX2 cells by treatment with the destabilization domain-stabilizing chemical Shield-1 and the human PXR ligand rifampicin...Reporter assays with the POSTN promoter showed that PXR inhibited the NF-κB-mediated transcription of POSTN. Consequently, PXR activation in HSCs is expected to inhibit transdifferentiation by downregulating POSTN expression, thereby suppressing EMT of liver cancer cells.
4 months ago
Journal
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TGFB1 (Transforming Growth Factor Beta 1) • COL1A1 (Collagen Type I Alpha 1 Chain) • POSTN (Periostin)
The expression patterns of all HNF4A-AS1 transcripts were further investigated in liver cell growth from human embryonic stem cells to matured hepatocyte-like cells, HepaRG differentiation, and exposure to rifampicin treatment...Significance Statement This study explores the alternative transcripts of HNF4A-AS1, showing how their expression changes in different biological conditions, from various liver diseases to the growth and differentiation of hepatocytes, and drug metabolism. The generated knowledge is essential for understanding the independent roles of different transcripts from the same lncRNA in different liver diseases and drug metabolism situations.
4 months ago
Journal
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CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) • HNF1A (HNF1 Homeobox A)
Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin...HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.
This study helped clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in dual induction of apoptosis and necroptosis. In particular, necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL. Our work provided an experimental basis for the research on cell death induced by SiL and revealed its possible applications for improving the management of lung cancer.
The outcomes of this study indicate the high potential of PEGylated niosomal nanoparticles for encapsulation and delivery of silibinin to cancer cells, with no negative effects on normal cells.
5 months ago
Preclinical • Journal • IO biomarker
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CCND1 (Cyclin D1) • BAX (BCL2-associated X protein)
Taken together, the data shows that (1) lurbinectedin combined with ipilimumab and nivolumab is a safe regimen with a MTD of 3.2 mg/m2 for lurbinectedin and (2) there were no serious treatment related adverse events reported. The phase II part of the study is currently open for previously untreated patient enrollment.
Interestingly, silibinin protected PBMCs against the U-87-induced suppression. Altogether, these results proposed the immunomodulatory potential of silibinin on T cells of PBMCs, as well as its partially protective effects on PBMCs against the suppression induced by U-87 MG cells.