Regorafenib Enhances the Efficacy of Photodynamic Therapy in Hepatocellular carcinoma through MAPK Signaling Pathway Suppression DOI Creative Commons

Song Zhang,

Xiaohong Zhang, Yali Ren

et al.

Photodiagnosis and Photodynamic Therapy, Journal Year: 2024, Volume and Issue: 49, P. 104319 - 104319

Published: Aug. 23, 2024

Photodynamic therapy (PDT) is a promising and innovative approach for treating tumors. The synergistic effect of PDT chemotherapy can enhance the anti-tumor efficacy by leveraging their complementing benefits. In this study, we created lipid vesicles to deliver photosensitizer (chlorin e6, Ce6) Regorafenib into tumors purpose examining effectiveness mechanism Lipo-Ce6@Rego-PDT (LCR-P) on Hepatocellular carcinoma (HCC) both in vitro vivo. We found that cytotoxicity HCC caused LCR-P was significantly stronger than Lipo-Ce6-PDT (LC-P). Cellular ROS production group approximately higher LC-P group, inhibited phosphorylation JNK, ERK, P38 Furthermore, downregulated expression Bcl-2 upregulated Bax cleaved caspase-3 Compared with LC-P, increased cell apoptosis rate. body weight HE staining normal organs primarily indicated safety combined strategy. These results indicate combination Lipo-Ce6 efficiency exhibits good biosafety.

Language: Английский

Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents DOI Creative Commons
Ali Doostmohammadi,

Hossein Jooya,

Kimia Ghorbanian

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 15, 2024

Abstract Cancer is a major public health problem worldwide with more than an estimated 19.3 million new cases in 2020. The occurrence rises dramatically age, and the overall risk accumulation combined tendency for cellular repair mechanisms to be less effective older individuals. Conventional cancer treatments, such as radiotherapy, surgery, chemotherapy, have been used decades combat cancer. However, emergence of novel fields research has led exploration innovative treatment approaches focused on immunotherapy, epigenetic therapy, targeted multi-omics, also multi-target therapy. hypothesis was based that drugs designed act against individual targets cannot usually battle multigenic diseases like Multi-target therapies, either combination or sequential order, recommended acquired intrinsic resistance anti-cancer treatments. Several studies multi-targeting treatments due their advantages include; overcoming clonal heterogeneity, lower multi-drug (MDR), decreased drug toxicity, thereby side effects. In this study, we'll discuss about drugs, benefits improving recent advances field multi-targeted drugs. Also, we will study performed clinical trials using therapeutic agents treatment.

Language: Английский

Citations

40
Biomarker discovery in hepatocellular carcinoma (HCC) for personalized treatment and enhanced prognosis DOI

Baofa Yu,

Wenxue Ma

Cytokine & Growth Factor Reviews, Journal Year: 2024, Volume and Issue: 79, P. 29 - 38

Published: Aug. 24, 2024

Language: Английский

Citations

12
Unveiling the intratumoral microbiota within cancer landscapes DOI Creative Commons
Shusheng Che, Zhiyong Yan, Yugong Feng

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109893 - 109893

Published: May 3, 2024

Recent advances in cancer research have unveiled a significant yet previously underappreciated aspect of oncology: the presence and role intratumoral microbiota. These microbial residents, encompassing bacteria, fungi, viruses within tumor tissues, been found to exert considerable influence on development, progression, efficacy therapeutic interventions. This review aims synthesize these groundbreaking discoveries, providing an integrated overview identification, characterization, functional roles microbiota biology. We focus elucidating complex interactions between microorganisms microenvironment, highlighting their potential as novel biomarkers targets. The purpose this is offer comprehensive understanding dimension cancer, paving way for innovative approaches diagnosis treatment.

Language: Английский

Citations

10
Discovery of A Novel Series of Quinazoline–Thiazole Hybrids as Potential Antiproliferative and Anti-Angiogenic Agents DOI Creative Commons
Alexandru Șandor, Ionel Fizeșan,

Ioana Ionuţ

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 218 - 218

Published: Feb. 12, 2024

Considering the pivotal role of angiogenesis in solid tumor progression, we developed a novel series quinazoline–thiazole hybrids (SA01–SA07) as antiproliferative and anti-angiogenic agents. Four out seven compounds displayed superior activity (IC50 =1.83-4.24 µM) on HepG2 cells compared to sorafenib = 6.28 µM). The affinity towards VEGFR2 kinase domain was assessed through silico prediction by molecular docking, dynamics studies, MM-PBSA. high degree similarity regarding binding pose within active site VEGFR2, with different orientation 4-substituted-thiazole moieties allosteric pocket. Molecular MM-PBSA evaluations identified SA05 hybrid forming most stable complex sorafenib. impact vascular cell proliferation EA.hy926 cells. Six (SA01–SA05, SA07) anti-proliferative 0.79–5.85 6.62 toxicity evaluated BJ Further studies effect promising compounds, SA04 SA05, assessment EA.hy296 motility using wound healing assay ovo potential CAM sorafenib, led confirmation potential.

Language: Английский

Citations

7
The ADAM17 inhibitor ZLDI-8 sensitized hepatocellular carcinoma cells to sorafenib through Notch1-integrin β-talk DOI Creative Commons
Chang Xu, Xudong Gao,

Tianshu Ren

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107142 - 107142

Published: March 24, 2024

ZLDI-8 is an A disintegrin and metalloproteinase domain 17 (ADAM17) inhibitor that suppresses the shedding of Notch1 to intracellular (NICD). In previous studies, we found was able sensitize HCC sorafenib, but mechanism action remains unclear. The sensitizing effects were tested both in vitro vivo. EMT-related factors, sorafenib sensitivity-related proteins ECM-related gene expression assessed using immunohistochemistry, RTPCR Western blotting. Knockdown assays conducted determine relationship between Notch Integrin pathways. CoIP assays, nuclear cytoplasmic fractionation immunofluorescence colocalization applied explore interaction Appropriate statistical analysis methods used assess significance experimental results ensure scientific validity reliability design. We ECM- downregulated after treatment (P<0.05). significantly Integrinβ1 Integrinβ3 vivo (P<0.05), possibly through Foxc2-dependent regulation. Mechanistically, interfering with Integrin-linked kinase (ILK) NICD may downregulate targeted by thereby cells sorafenib. retroregulation Integrinβ ILK occur be result translocation complexus. Our study indicates blocking pathway affect crosstalk Integrinβ/ILK signaling pathways, thus providing a potential therapeutic strategy for HCC.

Language: Английский

Citations

7
Scaffold Hopping Method for Design and Development of Potential Allosteric AKT Inhibitors DOI
Alireza Poustforoosh

Molecular Biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

Language: Английский

Citations

7
Recent advancements in the small-molecule drugs for hepatocellular carcinoma (HCC): Structure-activity relationships, pharmacological activities, and the clinical trials DOI Open Access

Qichuan Deng,

Yü Huang, Jing Zeng

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117343 - 117343

Published: Aug. 24, 2024

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies in world and sixth leading cause cancer death worldwide, it urgent to find safe effective drugs for treatment. As an important therapeutic method, small-molecule are continually being updated achieve improved effects. The purpose this study was investigate structural effects various FDA-listed sorafenib, cabozantinib, lenvatinib, regorafenib on corresponding HCC targets possible optimization methods, explore mechanism identifying potential that offer better efficacy fewer side

Language: Английский

Citations

4
Identification of molecular subtypes based on PANoptosis-related genes and construction of a signature for predicting the prognosis and response to immunotherapy response in hepatocellular carcinoma DOI Creative Commons
Jinfeng Zhu, Qian Huang, Xingyu Peng

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 18, 2023

Previous studies have demonstrated that PANoptosis is strongly correlated with cancer immunity and progression. This study aimed to develop a PANoptosis-related signature (PANRS) explore its potential value in predicting the prognosis immunotherapy response of hepatocellular carcinoma (HCC).Based on expression genes, three molecular subtypes were identified. To construct signature, differentially expressed genes between different subjected multivariate least absolute shrinkage selection operator Cox regression analyses. The risk scores patients training set calculated using signature. classified into high-risk low-risk groups based median scores. predictive performance was evaluated Kaplan-Meier plotter, receiving operating characteristic curves, nomogram, calibration curve. results validated external datasets. Additionally, correlation immune landscape drug sensitivity examined. Furthermore, effect LPCAT1 knockdown HCC cell behavior verified vitro experiments.This developed PANRS. score obtained by PANRS an independent factor for exhibited good prognostic performance. nomogram constructed clinical information can accurately predicted survival probability HCC. Patients high tend generate immunosuppressive microenvironment. They also favorable immunotherapy, as evidenced tumor mutational burden, checkpoint gene expression, human leukocyte antigen low dysfunction exclusion enabled identification 15 chemotherapeutic agents, including sorafenib, levels, guiding treatment. upregulated lines. markedly decreased proliferation migration.PANRS predict consequently guide individualized

Language: Английский

Citations

11
Prognostic impact of primary versus secondary resistance to sorafenib in patients with HCC DOI Creative Commons
Lei Jin,

Hongyuan Dai,

Ya Zhang

et al.

Therapeutic Advances in Medical Oncology, Journal Year: 2025, Volume and Issue: 17

Published: Jan. 1, 2025

Background: Sorafenib is a first-line treatment option for patients with hepatocellular carcinoma (HCC). However, the impact of sorafenib resistance type on patient survival prediction and choice second-line regimen unknown. Objectives: This study aims to explore factors predicting in HCC receiving sorafenib, survival, optimal regimen. Design: was retrospective cohort study. Methods: We recruited all advanced who received from January 2019 2023 two medical centers China. They were divided into primary secondary groups according tumor progression within 3 months. Resistance outcome this The outcomes progression-free (PFS) overall (OS). Results: A total 424 met inclusion criteria, including 165 (38.9%) group 259 (61.1%) group. independent risk alpha-fetoprotein (AFP) > 400 ng/mL alanine aminotransferase (ALT) 40 U/L. Patients had significantly shorter median OS than those (9.0 months vs 23.0 months, p < 0.001). Compared tyrosine kinase inhibitor (TKI) monotherapy, use TKI plus PD-1 combination therapy as conferred longer PFS (6.0 10.0 0.001) (13.0 22.0 Conclusion: has high incidence short develop resistance. AFP ALT are influential resistance, it valuable these metrics guide sorafenib. As therapy, should be preferentially recommended.

Language: Английский

Citations

0
Drug resistance in TKI therapy for hepatocellular carcinoma: mechanisms and strategies DOI
Xue Jiang,

Xiaoying Ge,

Yueying Huang

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217472 - 217472

Published: Jan. 1, 2025

Language: Английский

Citations

0