Intestinal Akkermansia muciniphila complements the efficacy of PD1 therapy in MAFLD-related hepatocellular carcinoma.

Immune checkpoint inhibitors are not effective for metabolic dysfunction-associated fatty liver disease (MAFLD)-hepatocellular carcinoma (HCC) patients, and identifying the key gut microbiota that contributes to immune resistance in these patients is crucial. Analysis using 16S rRNA sequencing reveals a decrease in Akkermansia muciniphila (Akk) during MAFLD-promoted HCC development. Administration of Akk ameliorates liver steatosis and effectively attenuates the tumor growth in orthotopic MAFLD-HCC mouse models.

Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma.

Increasing evidence has demonstrated that drug resistance can be acquired in cancer cells by kinase rewiring, which is an obstacle for efficient cancer therapy. However, it is technically challenging to measure the expression of protein kinases on large scale due to their dynamic range in human proteome. We employ a lysine-targeted sulfonyl fluoride probe, named XO44, which binds to 133 endogenous kinases in intact lenvatinib-resistant hepatocellular carcinoma (HCC) cells.

Global trajectory and future prospects of metronomic chemotherapy research: A scientometric analysis (2000-2022).

This scientometric study aimed to provide a first comprehensive overview of the global research landscape of Metronomic Chemotherapy (MC) from 2000 to 2022 using a data-driven approach to identify key trends, collaborations, and potential opportunities. This study highlights the increasing prevalence of MC, with annual outputs increasing substantially over the same timeframe. The United States contributed the most to MC research, followed by Italy and China, while there was a lack of collaborative research efforts between countries and organizations.

Clathrin light chain A-enriched small extracellular vesicles remodel microvascular niche to induce hepatocellular carcinoma metastasis.

Small extracellular vesicles (sEVs) play a key role in exchanging cargoes between cells in tumour microenvironment. This study aimed to elucidate the functions and mechanisms of hepatocellular carcinoma (HCC) derived sEV-clathrin light chain A (CLTA) in remodelling microvascular niche. CLTA level in the circulating sEVs of HCC patients was analysed by enzyme-linked immunosorbent assay (ELISA).

An autophagy-inducing stapled peptide induces mitochondria dysfunction and triggers autotic cell death in triple-negative breast cancer.

Autophagy is a lysosome-dependent bulk degradation process essential for cell viability but excessive autophagy leads to a unique form of cell death termed autosis. Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with notable defect in its autophagy process. In previous studies, we developed stapled peptides that specifically targeted the essential autophagy protein Beclin 1 to induce autophagy and promote endolysosomal trafficking.

Protocol to track the biosynthesis of cholesterol in cultured HCC cells using C compound-specific stable isotopic tracers.

Cholesterol biosynthesis supports proliferation and drives resistance to tyrosine kinase inhibitor (TKI) therapy in hepatocellular carcinoma (HCC). Here, we present a protocol for using stable isotopic tracers to track the biosynthesis of cholesterol in cultured HCC cells. We describe steps for cell preparation, incubation, separation, and homogenization.

Identifying potential pharmacological targets and molecular pathways of Meliae cortex for COVID-19 therapy.

Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, has contributed to a significant increase in mortality. Proinflammatory cytokine-mediated cytokine release syndrome (CRS) contributes significantly to COVID-19. Meliae cortex has been reported for its several ethnomedical applications in the Chinese Pharmacopoeia.

Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and Cholangiocarcinoma.

Primary liver cancer (PLC) includes hepatocellular carcinoma and intrahepatic cholangiocarcinoma and is the sixth most common cancer worldwide with poor prognosis. PLC is characterized by an abundant stromal reaction in which cancer-associated fibroblasts (CAFs) are one of the major stromal components. Solid evidence has demonstrated the crucial role of CAFs in tumor progression, and CAF abundance is often correlated with poor clinical outcomes.

SCYL3, as a novel binding partner and regulator of ROCK2, promotes hepatocellular carcinoma progression.

Background & Aims: SCY1-like pseudokinase 3 (SCYL3) was identified as a binding partner of ezrin, implicating it in metastasis. However, the clinical relevance and functional role of SCYL3 in cancer remain uncharacterized. In this study, we aimed to elucidate the role of SCYL3 in the progression of hepatocellular carcinoma (HCC).

Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide due to its high rates of tumor recurrence and metastasis. Aberrant Wnt/β-catenin signaling has been shown to play a significant role in HCC development, progression and clinical impact on tumor behavior. Accumulating evidence has revealed the critical involvement of Wnt/β-catenin signaling in driving cancer stemness and metabolic reprogramming, which are regarded as emerging cancer hallmarks.

A special issue of Essays in Biochemistry on cancer stem cells.

Cancer stem cells (CSCs) are subpopulation of cells within the tumor bulk, which leads to tumor recurrence and therapeutic resistance. Identification of specific CSC targets for detection and efficient cancer therapy are the major hurdles in this research field. In this decade, basic researchers and clinicians made every effort to overcome these challenges to target CSCs using different approaches.

Network pharmacology and molecular docking-based investigations of Kochiae Fructus's active phytomolecules, molecular targets, and pathways in treating COVID-19.

COVID-19 disease is caused by SARS-CoV-2. Hyper-inflammation mediated by proinflammatory cytokines is humans' primary etiology of SARS-CoV-2 infection. Kochiae Fructus is widely used in China as traditional Chinese medicine (TCM) to treat inflammatory diseases.

Investigations of nitazoxanide molecular targets and pathways for the treatment of hepatocellular carcinoma using network pharmacology and molecular docking.

Nitazoxanide has been investigated for colorectal cancer and breast cancer. However, its molecular targets and pathways have not yet been explored for hepatocellular carcinoma (HCC) treatment. Utilizing a network pharmacology approach, nitazoxanide's potential targets and molecular pathways for HCC treatment were investigated.

Caspase-3-Induced Activation of SREBP2 Drives Drug Resistance via Promotion of Cholesterol Biosynthesis in Hepatocellular Carcinoma.

Unlabelled: Accumulating evidence has demonstrated that drug resistance can be acquired in cancer through the repopulation of tumors by cancer stem cell (CSC) expansion. Here, we investigated mechanisms driving resistance and CSC repopulation in hepatocellular carcinoma (HCC) as a cancer model using two drug-resistant, patient-derived tumor xenografts that mimicked the development of acquired resistance to sorafenib or lenvatinib treatment observed in patients with HCC. RNA sequencing analysis revealed that cholesterol biosynthesis was most commonly enriched in the drug-resistant xenografts.

Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of in Treating Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignancy with a high mortality rate globally. For thousands of years, has been used to treat human ailments and is regarded as a veritable treasure trove for drug discovery. This study has investigated the key active phytochemicals and molecular mechanisms of implicated in curing HCC.

Targeting protein kinases in cancer stem cells.

Cancer stem cells (CSCs) are subpopulations of cancer cells within the tumor bulk that have emerged as an attractive therapeutic target for cancer therapy. Accumulating evidence has shown the critical involvement of protein kinase signaling pathways in driving tumor development, cancer relapse, metastasis, and therapeutic resistance. Given that protein kinases are druggable targets for cancer therapy, tremendous efforts are being made to target CSCs with kinase inhibitors.

Histone chaperone FACT complex coordinates with HIF to mediate an expeditious transcription program to adapt to poorly oxygenated cancers.

Cancer cells adapt to hypoxia through HIFs (hypoxia-inducible factors), which initiate the transcription of numerous genes for cancer cell survival in the hypoxia microenvironment. In this study, we find that the FACT (facilitates chromatin transcription) complex works cooperatively with HIFs to facilitate the expeditious expression of HIF targets for hypoxia adaptation. Knockout (KO) of the FACT complex abolishes HIF-mediated transcription by impeding transcription elongation in hypoxic cancer cells.

Preclinical mouse models of hepatocellular carcinoma: An overview and update.

Hepatocellular carcinoma (HCC) is by far the most common histological subtype of primary liver cancer. HCC often originates from chronic liver injuries and inflammation, subsequently leading to fibrosis and cirrhosis. Preclinical animal models, especially mice, are viewed as valuable and reliable tools for investigating the molecular processes involved in hepatocarcinogenesis and facilitating the evaluations of the efficacy of novel therapies for HCC.

Patient pIgR-enriched extracellular vesicles drive cancer stemness, tumorigenesis and metastasis in hepatocellular carcinoma.

Background & Aims: Extracellular vesicles (EVs) play a pivotal role in connecting tumor cells with their local and distant microenvironments. Herein, we aimed to understand the role (on a molecular basis) patient-derived EVs play in modulating cancer stemness and tumorigenesis in the context of hepatocellular carcinoma (HCC).

Methods: EVs from patient sera were isolated, quantified and characterized.