P1, N=200, Not yet recruiting, University of Virginia | Phase classification: P1/2 --> P1 | Initiation date: Jul 2024 --> Jan 2025

P4, N=364, Completed, Astellas Pharma Europe Ltd. | Phase classification: P3b/4 --> P4

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.

P2, N=72, Not yet recruiting, Guangdong Raynovent Biotech Co., Ltd

P3, N=120, Not yet recruiting, Huashan Hospital

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.

P4, N=308, Completed, VA Office of Research and Development | Active, not recruiting --> Completed

P4, N=880, Recruiting, VA Office of Research and Development | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

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

P=N/A, N=280, Not yet recruiting, Albert Einstein College of Medicine

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

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.

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.

P=N/A, N=300, Not yet recruiting, Assistance Publique - Hôpitaux de Paris

P4, N=308, Active, not recruiting, VA Office of Research and Development | Recruiting --> Active, not recruiting | N=549 --> 308

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.

P1/2, N=28, Active, not recruiting, Antonio Calles Blanco | Trial completion date: Feb 2024 --> Mar 2025

P3, N=1266, Recruiting, Queen Mary University of London | Not yet recruiting --> Recruiting

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.

P2, N=60, Recruiting, Children's Hospital of Philadelphia | N=30 --> 60

P2, N=0, Withdrawn, AdventHealth | N=36 --> 0 | Recruiting --> Withdrawn

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.

P3, N=100, Not yet recruiting, Taipei Medical University WanFang Hospital

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.

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.

P2, N=9, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P=N/A, N=100, Recruiting, Region Skane | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jun 2024 --> Dec 2026

P2/3, N=1800, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre

P2/3, N=26, Completed, University of Liverpool | Active, not recruiting --> Completed

P3, N=180, Not yet recruiting, Luye Pharma Group Ltd.

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.

P3, N=100, Recruiting, Rush University Medical Center

Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels...Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR. .

P1, N=16, Recruiting, University of Zurich | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Jul 2024 --> Oct 2024

P2, N=30, Recruiting, UNC Lineberger Comprehensive Cancer Center | Trial completion date: Jul 2026 --> Dec 2027 | Trial primary completion date: Jul 2024 --> Dec 2025

Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.

We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes.

P3, N=1266, Not yet recruiting, Queen Mary University of London | Initiation date: Mar 2024 --> Jul 2024 | Trial primary completion date: Mar 2026 --> Jul 2026

Significant upregulation of Bax (2.96-fold) and caspase-3 (3.46-fold) while Bcl-2 was downregulated by 2-fold. Findings established a preclinical rationale for the combination of silibinin and vinblastine. This combination produces synergistic effects in MDA-MB-231 cells by altering pro- and anti-apoptotic genes, which may reduce the toxicity and side effects of vinblastine.