The development of novel microspheres for the combination of sonodynamic therapy (SDT) with transarterial embolization (TAE) therapy to amplify their efficacy has received increasing attention. Herein, a novel strategy for encapsulating sonosensitizers (e.g., oxygen-deficient manganese tungstate (MnWOX) nanodots) with gelatin microspheres was proposed. The obtained MnWOX-encapsulated microspheres (abbr. Mn-GMSs) facilitated efficient sonodynamic-embolization-metalloimmune therapy via the immune effects of metal ions on orthotopic liver cancer tumor after transarterial embolization (TAE). Due to the strong cavitation effect caused by the porous structure, Mn-GMSs exhibited a greater reactive oxygen species (ROS) generation rate than the free MnWOX nanodots under US irradiation. Efficient SDT revealed robust cell-killing effects and triggered strong immunogenic cell death (ICD). Moreover, the Mn ions released from the bioactive Mn-GMSs further stimulated the dendritic cells (DCs) maturation and triggered the activation of the cGAS/STING pathway to enhance the immunological effect. Thus, Mn-GMSs achieved significant SDT therapeutic outcomes in H22 tumors in mice, and the combination of the Mn-GMSs triggered SDT with programmed cell death ligand 1 (PD-L1) antibodies could further enhance therapeutic outcomes. The Mn-GMSs exhibited high ROS generation efficacy under US irradiation, significant immune activation, good efficacy in combination with immune checkpoint inhibitor, and great potential for artery embolization-assisted drug delivery, thus enabling effective destruction of liver tumors in rats and rabbits. Therefore, this work provides a strategy for applying SDT in deep tumors and highlights a promising sonodynamic-embolization therapy for combating liver cancers.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a pressing need for effective biomarkers and therapeutic targets. Despite the clinical use of alpha-fetoprotein (AFP) as a diagnostic biomarker, its limitations in sensitivity and specificity necessitate the identification of novel markers. In this study, we investigated the role of Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in HCC prognosis and its potential as a therapeutic target. Utilizing spatial transcriptomics and single-cell RNA sequencing (scRNA-seq), we dissected the cellular composition of PRKDC in HCC tissue samples, revealing its high expression in malignant cell subpopulations and its association with the tumor immune microenvironment. Through clinical signature analysis, we observed widespread PRKDC expression in HCC tissues, particularly in immune cells, highlighting its link to immune cell infiltration. Further analyses confirmed high PRKDC expression in malignant cells and its inhibitory effect on immune cell infiltration. Copy number variation (CNV) analysis revealed significant genomic instability, with PRKDC exhibiting both amplifications and deletions across chromosomal regions, underscoring its role in tumorigenesis. Functional overexpression of PRKDC in HCC cell lines enhanced cell proliferation, migration, and altered cell cycle dynamics, with a notable increase in the G2/S phase. Taken together, we first to integrate spatial transcriptomics and single-cell transcriptomics and bulk RNA-seq to reveal that PRKDC is a reliable prognostic biomarker and a potential therapeutic target. High PRKDC expression is associated with shorter survival times and an abnormal tumor microenvironment, highlighting its impact on immune cell infiltration and HCC prognosis. Targeting PRKDC could selectively inhibit its expression in tumor cells, providing new strategies for HCC treatment.

Hepatocellular carcinoma (HCC) is among the most aggressive and lethal human tumors. Many functional studies have demonstrated the role of non-coding RNAs (ncRNA), particularly microRNAs (miRNA), in the regulation of hepatocarcinogenesis driving pathways. MiR-125a-5p (miR-125a) has been consistently reported as an oncosuppressive miRNA, as demonstrated in vivo and in vitro. However, its HCC relevant targets and molecular mechanisms are still largely unknown. Here, a genome-wide perspective of the whole miR-125a targetome has been achieved. In particular, two different HCC cell lines were subjected to a miRNA boosting by mimic transfections, and consequently many genes were de-regulated, as observed by a transcriptomic approach. The merging of down-regulated genes with results from bioinformatic predictive tools yielded a number of candidate direct targets that were further experimentally validated by luciferase-based reporter assays. Different novel targets were found, in particular ARID3A, CCNJ, LIPA, NR6A1, and NUP210, oncogenes in various tumors and here also related to HCC through miR-125a regulation. The RNA interactions investigated in this work could pave the way to piece together the RNA regulatory networks governed by the miRNA impacting on hepatocarcinogenesis, and be exploited in the future for identifying novel biomarkers and therapeutic targets in HCC.

For patients with hepatocellular carcinoma (HCC), stereotactic body radiation therapy (SBRT) has emerged as a locoregional treatment. Our purpose was to report outcomes in patients with HCC with Child-Pugh A (CP A) versus Child-Pugh B or C (CP B/C) liver dysfunction treated with SBRT.

A retrospective analysis of 80 patients with HCC, with a total of 94 tumors treated with SBRT, was conducted at a single institution. Outcomes were compared between patients with CP A (n = 51) and CP B/C (n = 29) liver dysfunction. Outcomes of interest included local control, overall survival (OS), and toxicity.

Median tumor size was 3.2 cm. There were 59 tumors included in the CP A cohort and 35 tumors in the CP B/C cohort. Median radiation dose was 50 Gy in 5 fractions for the CP A cohort and 40 Gy in 5 fractions for the CP B/C cohort. The rates of pathologic complete response were similar between the 2 groups at 63% for the CP A group and 61% for the CP B/C group. The estimated 1-year local control rates were similar between the 2 groups at 93% for the CP A group and 91% for the CP B/C group (P = .59). The 1-year OS for the CP A group was 85%, whereas the 1-year OS for the CP B/C group was 61% (P = .19). There was a 5.9% rate of grade 3+ toxicity in the CP A group and a 20.7% rate of grade 3+ toxicity in the CPB/C group.

Our findings suggest that SBRT is feasible and effective in patients with both CP A and CP B/C liver dysfunction with similar rates of local control and pathologic complete response despite lower radiation doses in the CP B/C cohort. In patients with more advanced CP B/C cirrhosis, toxicities were higher and must be weighed against possible treatment benefits. Further studies characterizing the optimal role of SBRT in patients with advanced cirrhosis are warranted.

Hepatocellular carcinoma (HCC) continues to pose a global health concern, necessitating the exploration of innovative therapeutic approaches. In the recent decade, targeting tumor stroma consisting of extracellular matrix (ECM), immune cells, vascular system, hypoxia, and also suppressive mechanisms in HCC has attracted interest in repressing tumor growth and metastasis. Phytochemicals have attained considerable attention because of their manifold biological effects and high capacity for anticancer activities. These chemical agents have shown the capability to modulate different cells and secretions within the stroma of malignancies. In recent years, the development of nanoformulations has further enhanced the therapeutic potential of phytochemicals by improving their solubility, bioavailability, and targeted delivery to tumor tissues. This review aims to provide an encyclopedic overview of the potential of phytochemicals and their nanoformulations as promising therapeutic strategies for targeting HCC. The review initially highlights the broad array of phytochemicals exhibiting potent anticancer properties, including flavonoids, alkaloids, terpenoids, and phenolic compounds, among others. Then, the nanoformulations and modification of these agents will be reviewed. Finally, we will review the latest experiments that have examined the modulation of HCC using adjuvant phytochemicals and their nanoformulations.

Background: Hepatocellular carcinoma (HCC) is a prevalent liver cancer with poor prognosis, often linked to hepatitis B (HBV) and C (HCV) infections. This meta-analysis evaluates the efficacy of immunotherapy in HCC, particularly in cases arising from viral hepatitis. Methods: In adherence to PRISMA Statement 2020 guidelines, the immunotherapeutic outcomes comprised objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Data were analyzed from randomized controlled trials up to April 2024 using the fixed-effects models in R (V.4.3.3.) and RevMan (Cochrane). Results: This study included 9 trials with 5316 patients. The ORR was slightly higher in the viral group at 27.93% compared to 24.07% in the non-viral group, though this difference was not significant (p = 0.15). Viral HCC patients exhibited a median PFS of 7.3 months (IQR: 6.2-8.4) compared to 5.8 months (IQR: 5.48-6.13) in non-viral patients, a significant improvement (p = 0.005). Similarly, median OS was longer in the viral group at 16.8 months (IQR: 12.99-20.61) versus 15.2 months (IQR: 13.25-17.15) for non-viral HCC, which was also significant (p < 0.0001). The median OS for viral HCC was 16.8 months (IQR: 14.11-19.49 months), with HBV patients experiencing slightly higher survival at 17.15 months (IQR: 14.3-20 months) compared to 16.8 months (IQR: 12.99-20.61 months) for HCV patients; this difference was not statistically significant (p = 0.89). Conclusions: Immunotherapy shows potential in treating HCC, with significantly better outcomes in viral HCC, particularly HBV-associated cases. The heterogeneity highlights the need for personalized treatment approaches based on the viral background of HCC patients. Further research should aim to optimize these therapies to improve survival rates.

Ferroptosis, a recently elucidated style of regulated cell death, has emerged as a significant area of investigation in cancer biology. Natural active compounds that have anti-cancer effects are promising candidates for cancer prevention. Iberverin, a natural compound derived from Brassica oleracea var. capitata, has been shown to exert anti-tumor activities in some cancers. However, its role in hepatocellular carcinoma (HCC) cells and the molecular mechanisms are still poorly understood. In this study, we proved that iberverin can induce intracellular reactive oxygen species (ROS) generation to inhibit cell proliferation and initiate ferroptotic cell death in HCC cells, which can be eradicated by the ferroptosis inhibitor ferrostatin-1 (Fer-1) or deferoxamine mesylate (DFO) and ROS scavenger (GSH or NAC). Mechanistically, iberverin treatment can simultaneously downregulate SLC7A11 mRNA level and degrade GPX4 through the ubiquitination pathway, leading to lipid peroxidation and ferroptotic cell death in HCC cells. Significantly, a low dose of iberverin can remarkably increase the sensitivity of HCC cells to ferroptosis induced by canonical ferroptosis inducers RSL3 and imidazole ketone erastin (IKE). This study uncovers a critical function of iberverin in preventing HCC through ferroptosis and provides a promising strategy for HCC treatment either via iberverin alone or in combination with canonical ferroptosis inducers in the future.

Hepatocellular carcinoma (HCC) is usually diagnosed in patients at the age of > 45 years. We aimed to determine the prognosis of patients with HCC at the age of 30-44 years compared with that of patients at a more senior age.

Based on the Sun Yat-sen University Cancer Center database, a total of 1745 patients with HCC were retrospectively enrolled and were assigned to three age groups (30-44, 45-59, and 60-70 years). The primary endpoint was overall survival. Among baseline characteristics, five variables including sex, serum albumin level, total bilirubin level, the maximum tumor diameter, and the number of tumor nodules were adjusted using propensity score matching.

Patients aged 30-44 years presented a worse overall survival, a greater number of HCC nodules, a greater maximum tumor diameter, and higher serum alpha-fetoprotein (AFP) concentration than those aged 45-59 years in a crude analysis (p < 0.05). Using propensity score matching, the difference in overall survival between the two cohorts was canceled (p > 0.05).

The prognosis of patients with HCC at age 30-44 years was equal to that of patients aged 45-59 years.

Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global health challenge due to its high mortality rate. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) are the two main types of primary liver cancer (PLC), each with its own set of complexities. Secondary or metastatic liver cancer is more common than PLC. It is frequently observed in malignancies such as colorectal, pancreatic, melanoma, lung, and breast cancer. Liver cancer is often diagnosed at an advanced stage, making it difficult to treat. This highlights the need for focused research on early detection and effective treatment strategies. This review explores the epidemiology, risk factors, and diagnostic techniques for HCC. The development of HCC involves various risk factors, including chronic liver diseases, hepatitis B and C infections, alcohol consumption, obesity, smoking, and genetic predispositions. Various invasive and non-invasive diagnostic techniques, such as biopsy, liquid biopsy, and imaging modalities like ultrasonography, computed tomography scans (CT scans), magnetic resonance imaging (MRI), and positron emission tomography (PET) scans, are utilized for HCC detection and monitoring. Advances in imaging technology and biomarker research have led to more accurate and sensitive methods for early HCC detection. We also reviewed advanced research on emerging techniques, including next-generation sequencing, metabolomics, epigenetic biomarkers, and microbiome analysis, which show great potential for advancing early diagnosis and personalized treatment strategies. This literature review provides insights into the current state of liver cancer diagnosis and promising future advancements. Ongoing research and innovation in these areas are essential for improving early diagnosis and reducing the global burden of liver cancer.

The liver plays a crucrial role in detoxification, metabolism, and nutrient storage. Because liver cancer ranks among the top three leading causes of death globally, there is an urgent need for developing treatment strategies for liver cancer. Although traditional approaches such as radiation, chemotherapy, surgical removal, and transplantation are widely practiced, the number of patients with liver cancer continues to increase rapidly each year. Some novel therapeutics for liver cancer have been studied for many years. In the past decade, oncolytic therapy has emerged, in which viruses selectively infect and destroy cancer cells while sparing normal cells. However, oncolytic virotherapy for liver cancer remains relatively obscure due to the aggressive nature of the disease and the limited effectiveness of treatment. To keep pace with the latest developments in oncolytic tumor therapy for liver cancer, this review summarizes basic science studies and clinical trials conducted within 5 years, focusing on the efficacy and safety profiles of the five most commonly used oncolytic viruses: herpes simplex virus, adenovirus, influenza virus, vaccinia virus, and coxsackievirus.

Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound C-3 from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription. Optimization led to the identification of a potent and covalent inhibitor CV-4-26 that exhibited great antitumor activity in HCC and HB cell lines in vitro, xenografted human HCC, and murine HB in vivo. These outcomes signify the potential of a highly promising therapeutic candidate for addressing a subset of HCC and HB cancers. In the cases of current treatment challenges due to high upregulation of YAP-TEAD activity, these findings offer a targeted alternative for more effective interventions against liver cancer.

Conventional cancer therapies can have significant adverse effects as they are not targeted to cancer cells and may damage healthy cells. Single-stranded oligonucleotides assembled in a particular architecture, known as aptamers, enable them to attach selectively to target areas. Usually, they are created by Systematic Evolution of Ligand by Exponential enrichment (SELEX), and they go through a rigorous pharmacological revision process to change their therapeutic half-life, affinity, and specificity. They could thus offer a viable substitute for antibodies in the targeted cancer treatment market. Although aptamers can be a better choice in some situations, antibodies are still appropriate for many other uses. The technique of delivering aptamers is simple and reasonable, and the time needed to manufacture them is relatively brief. Aptamers do not require animals or an immune response to be produced, in contrast to antibodies. When used as a medication, aptamers can directly suppress tumor cells. As an alternative, they can be included in systems for targeted drug delivery that administer medications specifically to tumor cells while reducing toxicity to healthy cells. The most recent and cutting-edge methods for treating gastrointestinal (GI) tract cancer with aptamers will be covered in this review, with a focus on targeted therapy as a means of conquering resistance to traditional medicines.

Hepatocellular carcinoma (HCC) has emerged as a major contributor to the worldwide cancer burden. Improved methods are needed for early cancer detection and image-guided surgery. Peptides have small dimensions that can overcome delivery challenges to achieve high tumor concentrations and deep penetration. We used phage display methods to biopan against the extra-cellular domain of the purified EpCAM protein, and used IRDye800 as a near-infrared (NIR) fluorophore. The 12-mer sequence HPDMFTRTHSHN was identified, and specific binding to EpCAM was validated with HCC cells in vitro. A binding affinity of kd = 67 nM and onset of k = 0.136 min-1 (7.35 min) were determined. Serum stability was measured with a half-life of T1/2 = 2.6 h. NIR fluorescence images showed peak uptake in vivo by human HCC patient-derived xenograft (PDX) tumors at 1.5 h post-injection. Also, the peptide was able to bind to foci of local and distant metastases in liver and lung. Peptide biodistribution showed high uptake in tumor versus other organs. No signs of acute toxicity were detected during animal necropsy. Immunofluorescence staining of human liver showed specific binding to HCC compared with cirrhosis, adenoma, and normal specimens.

Hepatocellular carcinoma (HCC) is a common critical type of hepatic cancer worldwide. Recent guidelines have considered ablative therapeutic approaches as the primary option for managing early-stage surgically untreatable HCC. Among these therapies, radiofrequency ablation (RFA) and microwave ablation (MWA) have attained a significant role due to their efficacy and theoretical advantages. This review aims to compare and analyze the efficacy and safety of two common modalities, i.e., MWA and RFA, in the management of HCC. The literature search included PubMed, Cochrane Central Register of Controlled Trials, Medline, and Ovid for articles published until 2024. The outcomes included the local tumor progression (LTP), complete ablation (CA), the overall survival (OS) rate, or major complications. A meta-analysis was performed using Review Manager 5.3. The systematic review included six randomized controlled trials, including 826 patients. The findings revealed that MWA resulted in lower LTP and higher CA rates compared to RFA. However, the effect of complications was higher in the MWA therapy group. Despite that, the differences between all parameters were not significant. Statistical significance was not evident in the OS rates between the two modalities. Three studies found comparable survival rates between the two modalities, while one study reported similar local tumor recurrence-free survival rates between the two approaches. Both techniques appear to be effective and safe for the management of liver tumors, providing clinicians with valuable options for personalized patient care. Further high-quality research is needed to confirm these findings and guide clinical decision-making.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Small extracellular vesicles (sEVs) are bilayer lipid membrane vesicles containing RNA that exhibit promising diagnostic and prognostic potential as cancer biomarkers.

To establish a miRNA panel from peripheral blood for use as a noninvasive biomarker for the diagnosis of HCC.

sEVs obtained from plasma were profiled using high-throughput sequencing. The identified differential miRNA expression patterns were subsequently validated using quantitative real-time polymerase chain reaction analysis.

The random forest method identified ten distinct miRNAs distinguishing HCC plasma from non-HCC plasma. During validation, miR-140-3p (p = 0.0001) and miR-3200-3p (p = 0.0017) exhibited significant downregulation. Enrichment analysis uncovered a notable correlation between the target genes of these miRNAs and cancer development. Utilizing logistic regression, we developed a diagnostic model incorporating these validated miRNAs. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) of 0.951, with a sensitivity of 90.1% and specificity of 87.8%.

These aberrantly expressed miRNAs delivered by sEVs potentially contribute to HCC pathology and may serve as diagnostic biomarkers for HCC.

One of the most prevalent types of cancer worldwide today is gastric intestinal (GI) tumors. To guarantee their lives, people with a developed GI require palliative care. This covers the application of targeted medicines in addition to chemotherapy treatments including cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed. Because of the evidence of drug resistance emerging in poor patient outcomes and prognoses, determining the exact process of medication resistance is motivated. Besides, it is noteworthy that exosomes and noncoding RNAs, like microRNAs and long non-coding RNAs (lncRNAs), produced from tumor cells are implicated in both GI medication resistance and the carcinogenesis and development of GI disease. Biochemical events related to the cell cycle, differentiation of cells, growth, and pluripotency, in addition to gene transcription, splicing, and epigenetics, are all regulated by noncoding RNAs (ncRNAs). Therefore, it should come as a wonder that several ncRNAs have been connected in recent years to drug susceptibility and resistance as well as tumorigenesis. Additionally, through communicating directly with medications, altering the transcriptome of tumor cells, and affecting the immune system, exosomes may govern treatment resistance. Because of this, exosomal lncRNAs often act as a competitive endogenous RNA (ceRNA) of miRNAs to carry out its role in modifying drug resistance. In light of this, we provide an overview of the roles and processes of ncRNA-enriched exosomes in GI medication resistance.

To evaluate the benefit-risk of 3 commonly used Chinese medicine injections, Aidi Injection (ADI), Cinobufagin Injection (CINI) and Compound Kushen Injection (CKI), in the treatment of primary liver cancer (PLC), so as to provide a reference for clinical decision-making.

Randomized controlled trials (RCTs) of ADI, CINI and CKI in the treatment of PLC published in the databases of China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, SinoMed, PubMed, Cochrane Library, and Web of Science were retrieved from January 2020 to October 2022. The data of benefit and risk indicators were combined to obtain the effect value. The multi-criteria decision analysis (MCDA) model was applied to build the decision tree. The benefit value, risk value and benefit risk value of the 3 injections in PLC treatment were calculated. Monte Carlo simulation was carried out to calculate the 95% confidence interval and probability of differences among the 3 injections, so as to optimize the evaluation results.

A total of 71 RCTs were included. The benefit values of ADI, CINI and CKI combined with transcatheter arterial chemoembolization (TACE) were 42, 38 and 36, respectively. The risk values were 42, 25 and 37, respectively. The benefit risk values were 42, 31 and 37, respectively. The benefit risk differences of ADI vs. CINI, ADI vs. CKI, and CKI vs. CINI were 11 (-0.86, 17.75), 5 (-5.01, 11.09), and 6 (-1.87, 12.63), respectively. The probability that ADI superior to CINI, ADI superior to CKI, and CKI superior to CINI was 96.26%, 77.27%, and 92.62%, respectively.

Based on the results of MCDA model, CINI combined with TACE has the greatest risk in the treatment of the PLC. Considering the efficacy and safety, the possible priority of the 3 Chinese medicine injections combined with TACE in the treatment of PLC is ADI, CKI and CINI.

Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep-G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF-κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p-AKT, PI3K, mTOR, NF-κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF-κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.

Cancer is a fatal disease that severely affects humans. Designing new anticancer strategies and understanding the mechanism of action of anticancer agents is imperative.

In this study, we evaluated the utility of metformin and D-limonene, alone or in combination, as potential anticancer therapeutics using the human liver and breast cancer cell lines HepG2 and MCF-7.

An integrated systems pharmacology approach is presented for illustrating the molecular interactions between metformin and D-limonene.

We applied a systems-based analysis to introduce a drug-target-pathway network that clarifies different mechanisms of treatment. The combination treatment of metformin and D-limonene induced apoptosis in both cell lines compared with single drug treatments, as indicated by flow cytometric and gene expression analysis.

The mRNA expression of Bax and P53 genes were significantly upregulated while Bcl-2, iNOS, and Cox-2 were significantly downregulated in all treatment groups compared with normal cells. The percentages of late apoptotic HepG2 and MCF-7 cells were higher in all treatment groups, particularly in the combination treatment group. Calculations for the combination index (CI) revealed a synergistic effect between both drugs for HepG2 cells (CI = 0.14) and MCF-7 cells (CI = 0.22).

Our data show that metformin, D-limonene, and their combinations exerted significant antitumor effects on the cancer cell lines by inducing apoptosis and modulating the expression of apoptotic genes.

The combined treatment of transcatheter arterial chemoembolization (TACE) and apatinib had beneficial effects on the survival of patients with advanced hepatocellular carcinoma (HCC), but the efficacy of this regimen is still controversial and needs further investigation.

The clinical records of advanced HCC patients between May 2015 and December 2016 were collected from our hospital. They were categorized into the TACE monotherapy group and the combination of TACE and apatinib group. After propensity score matching (PSM) analysis, the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and occurrence of adverse events were compared between the two treatments.

There were 115 HCC patients included in the study. Among them, 53 received TACE monotherapy and 62 were treated with TACE plus apatinib. After PSM analysis, 50 pairs of patients were compared. The DCR of the TACE group was significantly lower than that of the combination of TACE and apatinib group (35 [70%] versus 45 [90%], P < 0.05). The ORR of the TACE group was also significantly lower than that of the combination of TACE and apatinib group (22 [44%] versus 34 [68%], P < 0.05). Patients who received the combined treatment of TACE and apatinib had longer PFS compared with those in the TACE monotherapy group ( P < 0.001). Moreover, hypertension, hand-foot syndrome, and albuminuria were more common in the combination of TACE and apatinib group ( P < 0.05), although all adverse events were well tolerated.

The combined treatment of TACE and apatinib showed beneficial effects on tumor response, survival outcomes, and tolerance to treatment, which may be used as a routine regimen for advanced HCC patients.

Apoptosis and autophagy have been shown to act cooperatively and antagonistically in self-elimination process. On the one side, apoptosis and autophagy can act as partners to induce cell death in a coordinated or cooperative manner; on the flip side, autophagy acts as an antagonist to block apoptotic cell death by promoting cell survival. Our previous research indicated that trillin could induce apoptosis of PLC/PRF/5 cells, but the effects of trillin on autophagy as well as its functional relationship to apoptosis have not been elucidated. Here, the running study aims to investigate the function and molecular mechanism of trillin on autophagy with hepatocellular carcinoma (HCC) cells. The objective of this study is to investigate the molecular mechanism of trillin on autophagy in HCC cells. Protein levels of autophagy markers beclin1, LC3B, and p62 were detected by western blotting. 6-Hydroxyflavone and stattic were used to test the role of trillin regulation of autophagy via serine threonine kinase (AKT)/extracellular-regulated protein kinases (ERK) 1/2/mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Flow cytometry was used to detect caspase 3 activity and apoptosis in PLC/PRF/5 cells treated with trillin for 24 h with or without rapamycin, stattic, and 6-hydroxyflavone. The protein level of autophagy marker beclin1 was decreased, whilst the protein level of p62 was significantly increased by trillin treatment, indicating trillin treatment led to inhibition of autophagy in HCC cells. Trillin treatment could reduce the protein levels of p-AKT and p-ERK1/2, but enhance the protein levels of mTOR and p-mTOR, suggesting that trillin could inhibit AKT/ERK rather than mTOR. The AKT/ERK activator 6-hydroxyflavone could reverse the loss of AKT and ERK1/2 phosphorylation induced by trillin, implying that trillin impairs autophagy through activated mTOR rather than AKT/ERK. STAT3 and p-STAT3 were significantly upregulated by the trillin treatment with an increase in dose from 0 to 50 μM, suggesting that autophagy inhibition is mediated by trillin via activation of STAT3 signaling. The STAT3 inhibitor stattic significantly reversed the increased STAT3 phosphorylation at tyrosine 705 induced by trillin. The mTOR signaling inhibitor rapamycin reversed the trillin-induced mTOR phosphorylation enhancement but exerted no effects on total mTOR levels, suggesting trillin treatment led to inhibition of autophagy in HCC cells through activating mTOR/STAT3 pathway. Furthermore, caspase 3 activities and the total rate of apoptosis were increased by trillin treatment, which was reversed by rapamycin, stattic, and 6-hydroxyflavone, proving that trillin promotes apoptosis via activation of mTOR/STAT3 signaling. Trillin induced autophagy inhibition and promoted apoptosis in PLC/PRF/5 cells via the activation of mTOR/STAT3 signaling. Trillin has the potential to be a viable therapeutic option for HCC treatment.

HuaChanSu is active water extracts from the skin of Bufo bufo gargarizans Cantor. It has been already used to treat clinical cancers including HCC (Hepatocellular carcinoma, HCC), however, the molecular mechanisms under HuaChanSu's anti-cancer effects remain unclear. PPP (Pentose phosphate pathway, PPP), the major source of ribose and NADPH (Nicotinamide adenine dinucleotide phosphate, NADPH), is always over-activated and particularly critical for tumor cells growth. In this study, firstly, we illustrate that HuaChanSu restrains the growth of human hepatoma cells. More importantly, we demonstrate that the expression of G6PD (Glucose-6-phosphate dehydrogenase, G6PD), the first rate-limiting enzyme of the PPP, is restrained in human hepatoma cells after treatment with HuaChanSu. Additionally, our results show that G6PD enzyme activity and dimer formation are inhibited by HuaChanSu. Furthermore, we find that HuaChanSu could inhibit NADPH production and nucleotide level. In addition, we identify that expression of PLK1 (Polo-like kinase 1, PLK1) is also reduced in response to HuaChanSu, and knockdown of PLK1 restrains enzyme activity and dimer formation of G6PD, but has no effect on G6PD protein level. Subsequently, we demonstrate that inhibition of G6PD could restrain the proliferation of tumor cells and enhance the inhibitory effect of HuaChanSu on cell proliferation of human hepatoma cells. In conclusion, for the first time, our study reveals that HuaChanSu interferes with PPP via suppression of G6PD expression and enzyme activity to restrain growth of tumor cells, and these results provide a novel insight for the anti-hepatoma mechanisms of HuaChanSu and promote the innovation of the research model of TCM. Moreover, the development of drugs targeting abnormal tumor metabolism is currently a hot topic, our works provide theoretical support for further drug development from HuaChanSu, meanwhile, the revelation of the new molecular mechanism also provides a new perspective for the study of the pathogenesis of liver cancer.

HuaChanSu suppresses expression of G6PD, the first rate-limiting enzyme of the PPP, restrains G6PD enzyme activity and dimer formation via inhibition of PLK1, knockdown of G6PD could impair the growth of human hepatoma cells and increase the blocking effect of HuaChanSu on cell proliferation of cancer cells. In addition, HuaChanSu restrains NADPH production and nucleotide level, implying the suppression of PPP flux. Our study suggests that HuaChanSu interferes with PPP via G6PD inhibition to exert anti-hepatoma effects.

Primary hepatic carcinoma (PHC) has an insidious onset and is usually diagnosed in the middle and late stages. Although transcatheter arterial chemoembolization (TACE) is the preferred option for treating middle- and advanced-stage PHC, it has limited efficacy in killing tumor cells and poor long-term efficacy. TACE plus percutaneous microwave coagulation therapy (PMCT) is more effective than interventional therapy alone and can improve survival time. However, there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC.

To investigate the effect of PMCT + TACE on serum tumor markers and the prognosis of middle-late PHC.

This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People's Hospital between March 2018 and February 2021. Patients were divided into a single group (treated with TACE, n = 75) and a combined group (treated with TACE + PMCT, n = 75). Before and after treatment, the clinical efficacy and serum tumor marker levels [carbohydrate antigen 19-9 (CA19-9), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA)] of both groups were observed. The 1-year survival rates and prognostic factors of the two groups were analyzed.

The combined group had 21 and 35 cases of complete remission (CR) and partial remission (PR), respectively. The single group had 13 and 25 cases of CR and PR, respectively. After 4 wk of treatment, the serum CA19-9, CEA, and AFP levels in the single and combined groups decreased, with the decrease in the combined group being more significant (P < 0.05). The 1-year survival rate of the combined group (80.00%) was higher than that of the single group (60.00%) (P < 0.05). The average survival time within 1 year in the combined group was 299.38 ± 61.13 d, longer than that in the single group (214.41 ± 72.97 d, P < 0.05). COX analysis revealed that tumor diameter, tumor number, and the treatment method were prognostic factors for patients with middle-late PHC (P < 0.05).

TACE + PMCT is effective in treating patients with mid-late PHC. It reduces the levels of tumor markers, prolongs survival, and improves prognosis.

Hepatitis, a global public health concern, presents a significant burden on healthcare systems worldwide. Particularly, hepatitis B and C are viral infections that can lead to severe liver damage, cirrhosis, and even hepatocellular carcinoma (HCC). The urgency to combat these diseases has driven researchers to explore existing small-molecule drugs as potential therapeutics. This comprehensive review provides a systematic overview of synthetic routes to key antiviral agents used to manage hepatitis. Furthermore, it elucidates the mechanisms of action of these drugs, shedding light on their interference with viral replication and liver disease progression. The review also discusses the clinical applications of these drugs, including their use in combination therapies and various patient populations. By evaluating the synthetic pathways and clinical utility of these drugs, this review not only consolidates current knowledge but also highlights potential future directions for research and drug development in the fight against hepatitis, ultimately contributing to improved patient outcomes and reduced global disease burden.

Hepatocellular carcinoma (HCC) is the seventh most highly prevalent malignant tumor globally and the second most common cause of mortality. HCC develops with complex pathways that occur through multistage biological processes. Non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, alcoholic liver disease, autoimmune hepatitis, hepatitis B, and hepatitis C are the causative etiologies of HCC. HCC develops as a result of epigenetic changes, protein-coding gene mutations, and altered signaling pathways. Biomarkers and potential therapeutic targets for HCC open up new possibilities for treating the disease. Immune checkpoint inhibitors are included in the treatment options in combination with molecular targeted therapy.

Regardless of etiology, hepatocarcinogenesis is frequently preceded by a distinctive sequence of chronic necroinflammation, compensatory hepatic regeneration, development of hepatic fibrosis, and ultimately cirrhosis. The liver being central immunomodulators, closely maintains immunotolerance. Any dysregulation in this management of immunotolerance is a hallmark of chronic hepatic disease and hepatocellular carcinoma (HCC). Apart from other malignancies, hepatocellular carcinoma accounts for 90% of liver cancers. Several emerging evidences have recognized diet as lifestyle associated risk factor in HCC development. However, natural compounds have the potential to fight hepatoma aggressiveness via inhibition of cellular proliferation and modulation of oncogenic pathways. This review aimed to identify the several plant-based foods for their protective role in HCC prevention by understating the molecular mechanisms involved in inhibition of progression and proliferation of cancer. Information from relevant publications in which several plant-based foods demonstrated protective potential against HCC has been integrated as well as evaluated. For data integration, Science direct, Google scholar, and Scopus websites were used. Nutrition-based approaches in the deterrence of several cancers offer a substantial benefit to currently used medical therapies and should be implemented more often as an adjunct to first-line medical therapy. Furthermore, the inclusion of these plant-based foods (vegetables, fruits, herbs, and spices) may improve general health and decline cancer incidence.

Unawareness of hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation. This study evaluated the risk of HBV unawareness and its relationship with HCC severity. This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients with HBV unawareness and awareness with and without surveillance. Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at the time of HCC diagnosis. Patients with HBV unawareness were significantly younger and had poorer liver function than those with HBV awareness. Patients with HBV unawareness also had a significantly higher rate of detectable HBV DNA and an advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients with HBV unawareness and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated that HBV awareness with periodic surveillance was associated with early stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past 10 years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness. HBV unawareness and lack of regular surveillance correlated with advanced HCC at presentation. Efforts to improve HBV education, disease awareness, and HCC surveillance are needed.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The survival rate after hepatectomy as the first line of treatment for HCC depends on various factors. This study evaluated the association of the ABO blood group and Rh with overall survival (OS) and Recurrence-free survival (RFS) rate after hepatectomy.

This multicenter retrospective cohort study reviewed the medical files of 639 HCC patients who underwent hepatectomy from 2010 to 2022 in three medical centers affiliated with the Iran University of Medical Sciences. Patient data, including demographic, clinical, tumor characteristics, and post-surgery outcomes, were collected by referring to the patient's medical profiles. The Cox proportional hazard investigated the relationship between ABO blood group type and OS and RFS rate after hepatectomy.

The five-year OS and RFS rates were 25.4% and 18.7%, respectively. The five-year OS (Lok rank:40.89, P:0.001) and RFS rate in patients with blood type A were significantly lower than in non-A patients. (Lok rank:10.8, P:0.001) The multivariate Cox analysis showed that blood type A, age < 45 years, tumor size > 5 cm, Poor tumor differentiation, presence of metastasis, The number of involved lymph nodes ≤ 2, and serum Alpha-Fetoprotein)AFP( level ≥ 400 were significantly related to the decreased survival rate of HCC patients after hepatectomy (P < 0.05) There was no significant association between Rh with OS and RFS (P > 0.05).

Blood group type A, compared to non-A, can be associated with decreased OS and RFS rates in patients with HCC after hepatectomy.

Currently, many challenges are associated with hepatocellular carcinoma (HCC) as the failure of early diagnosis, and the lack of effective therapy. This study aimed to investigate the possible role of tuftelin 1 (TUFT 1) in the early diagnosis of HCC and evaluate the potential contribution of the TUFT 1/Ca+2 /phosphinositol 3 kinase (PI3K) pathway in dantrolene sodium (Dan) therapeutic outcomes. The study was performed on two sets of rats, the staging (30 rats) and treatment sets (80 rats). HCC was induced by a single dose of diethylnitrosamine (DENA). The hepatic content of TUFT 1 protein was assayed via western blot and immunohistochemistry (IHC), while PI3K, vascular endothelial growth factor (VEGF), Cyclin D1, and matrix-metalloproteinase-9 (MMP-9) contents were assessed using enzyme-linked immunosorbent assay. Hepatic and serum calcium were measured colorimetrically. Furthermore, the nuclear proliferation marker, (Ki-67), (Kiel [Ki] where the antibody was produced in the University Department of Pathology and the original clone number is 67)-expression was assessed by IHC. TUFT 1/Ca+2 /PI3K signaling pathway was progressively activated in the 3 studied stages of HCC with subsequent upregulation of angiogenesis, cell cycle, and metastasis. More interestingly, Dan led to TUFT 1/Ca+2 /PI3K pathway disruption by diminution of the hepatic contents of TUFT 1, calcium, PI3K, VEGF, Cyclin D1, and MMP-9 in a dose-dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC. Moreover, Dan exerted an antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2 /PI3K pathway.

A large-scale multicenter study validated aldo-keto reductase 1B10 (AKR1B10) as a new serum marker of hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic value of serum AKR1B10 in HCC.

273 naïve HCC patients enrolled for serum AKR1B10 tests were followed up for 2 years. Survival and clinical data were collected. Kaplan-Meier survival analysis and log-rank tests were used to estimate correlation of patient survival with serum AKR1B10. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of serum AKR1B10 level independently or in combination with other clinicopathological factors. α-fetoprotein (AFP) was analyzed in parallel for comparison.

Serum AKR1B10 associated with tumor stage (p = 0.012), size (p = 0.004), primary tumor number (p = 0.019), and Child-Pugh classification (p = 0.003). HCC patients with a high level of serum AKR1B10 (≥ 267.9 pg/ml) had median survival (MS) of 25 months (95% confidence interval [CI] 20.788-29.212) vs. MS of 34 months (CI 28.911-39.089) in patients with normal serum AKR1B10 (p < 0.001). Univariate and multivariate COX regression analyses showed that serum AKR1B10 level was an unfavorable prognostic marker of HCC independently (HR 1.830, 95% CI 1.312-2.552; p < 0.001) or in combination with other clinical factors (HR 1.883, 95% CI 1.264-2.806; p = 0.002), such as TNM stage, tumor size and portal invasion. In the same cohort of HCC patients, AFP exhibited prognostic value at a cut-off of 400 ng/ml, but not at 20 ng/ml and 200 ng/ml.

Serum AKR1B10 is a new prognostic marker of HCC, better than AFP.

Biannual Ultrasound showed insufficient sensitivity in detecting small or early-stage hepatocellular carcinoma (HCC). Abbreviated magnetic resonance imaging (A-MRI) protocols with fewer sequences demonstrated higher HCC detection sensitivity than ultrasound with acceptable cost and examination time.

To compare the diagnostic performance of gadoxetic acid-enhanced A-MRI with a full sequence MRI (F-MRI) protocol for small HCC (≤2 cm) in cirrhotic or hepatitis B virus-infected high-risk patients.

Two hundred and four consecutive patients with 166 pathologically confirmed small HCC who underwent preoperative gadoxetic acid-enhanced MRI were retrospectively included. A-MRI set comprised T1-weighted hepatobiliary phase imaging, T2-weighted imaging, diffusion-weighted imaging and apparent diffusion coefficient mapping. Two independent radiologists blinded to clinical data assessed the A-MRI set and F-MRI set. Per-patient HCC and per-lesion HCC diagnostic performance were compared.

Per-patient HCC detection sensitivity of A-MRI set was 93.8% and 91.2% for observer 1 and observer 2, and, for the F-MRI set, the per-patient HCC detection sensitivity was 96.6% and 95.2%, respectively. There was no significant difference in per-patient sensitivity, specificity and per-lesion HCC detection sensitivity between the two imaging sets for both readers. (P = 0.06-0.25) The A-MRI set showed higher sensitivity on HCC without arterial phase hyperenhancement, and the F-MRI set demonstrated with higher sensitivity on HCC with arterial phase hyperenhancement (P < 0.05).

A-MRI using diagnostic criteria including hypointensity on hepatobiliary phase plus mild to moderate hyperintensity on T2-weighted imaging or restricted diffusion demonstrated comparable sensitivity and specificity for small HCC compared to the F-MRI protocol in high-risk patients.

Circadian rhythms play a central role in maintaining metabolic homeostasis and orchestrating inter-organ crosstalk. Research evidence indicates that disruption to rhythms, which occurs through shift work, chronic sleep disruption, molecular clock polymorphisms, or the consumption of alcohol or high-fat diets, can influence inflammatory status and disrupt timing between the brain and periphery or between the body and the external environment. Within the liver and gut, circadian rhythms direct the timing of glucose and lipid homeostasis, bile acid and xenobiotic metabolism, and nutrient absorption, making these systems particularly susceptible to the effects of disrupted rhythms. In this review, the impacts of circadian disruption will be discussed with emphasis on inflammatory conditions affecting the liver and gut, and the potential for chronotherapy for these conditions will be explored.

Hepatocellular carcinoma (HCC), ranks as the third most prevalent malignancy contributing to cancer-related death on a global scale. Hepatocellular carcinoma is known to be the fifth most frequently diagnosed malignancy of the males while among females, it is ranked as the seventh most common malignancy. The study was conducted to detect the sensitivity of primary HCC using 18F-flourodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan.

This prospective study was conducted to identify the primary HCC in a sample size of 51 patients, in whom FDG PET-CT scan was performed between May 2022 and December 2022.

Among the cohort of 51 patients, primary HCC was detected on FDG PET-CT in 43 individuals representing true-positive cases. Conversely, FDG PET-CT was unable to detect HCC in 8 cases, representing false-negative. Out of 51 patients, 74.5% of HCC cases exhibited multifocal pattern. The maximum standardized uptake value (SUV max) of the primary malignant site ranged from 1.9 to 16.1, with a mean of 3.7 ± 2.8. The FDG PET-CT revealed abnormal sites of the uptake outside liver in 23 individuals. The research confirmed the tumor recurrence in four previously treated patients. In the conducted investigation, FDG PET-CT showed 84.3% sensitivity for the diagnosis of HCC.

The study demonstrates that FDG PET-CT is a viable option for the detection of HCC. The sensitivity of FDG PET-CT in our population is comparable and in agreement with international data for diagnosis of HCC thereby favoring its reproducibility among geographical and ethnic groups. However, owing to the reduced ability of FDG PET-CT scan to identify well-differentiated/low-grade HCC, the routine use of FDG PET-CT scan may not be considered in cases requiring evaluation of primary disease only.

Arshad K, Hanan SD, Younis MN, et al. Detection of Primary Hepatocellular Carcinoma on 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography. Euroasian J Hepato-Gastroenterol 2023;13(2):66-72.

The role of hepatectomy for hepatocellular carcinoma (HCC) with multifocality or intrahepatic vascular involvement remains ill-defined. Our objective was to evaluate benefits of surgical resection for patients with these high-risk features.

The National Cancer Database was used to identify HCC patients with vascular involvement and/or multifocality (T2/T3, N-/M-) from 2011 to 2015. Propensity score matching (k-nearest neighbors, no replacement, 1:1) grouped patients by treatment: surgical resection versus non-surgical modalities. Groups were matched using patient, clinical, and liver-specific characteristics. Median overall survival (OS) was calculated using Kaplan-Meier, and adjusted analyses were performed using shared frailty models.

14,557 patients met inclusion criteria, including 1892 (9.4%) treated with surgical resection. Median cohort OS was 20.5 months. After adjustment, surgical resection was associated with survival advantage compared to non-surgical treatment (37.8 versus 15.7 months, log-rank P < .001; adjusted hazard ratio 0.49, 95% confidence interval, 0.45-0.54). Patients with minimal comorbidity, unifocal disease, and age <54 had highest probability of survival one year post-surgery.

Surgical resection is associated with a survival advantage in HCC with multifocality and/or intrahepatic vascular involvement. The presence of these features should not contraindicate consideration of hepatectomy in suitable surgical candidates.

Treatment with antiangiogenic tyrosine kinase inhibitors (TKIs) has shown longer overall survival (OS) and progression-free survival (PFS) than with placebo in patients with advanced hepatocellular carcinoma (HCC) who have previously received systemic therapy. Unfortunately, TKIs are associated with some rare adverse events such as tracheoesophageal fistula formation (TEF). The common risk factors for TEF formation include radiation therapy, prior instrumentation of the esophagus/airway, surgery, and esophagitis. We present a case of a 64-year-old man with a history of HCC who developed TEF after three months of treatment with cabozantinib. Patients experiencing these events require prompt termination of the antiangiogenic TKI. Urgent intervention should be pursued to prevent respiratory failure. Clinicians should be aware of the potential adverse effects of antiangiogenic TKIs, especially in high-risk patients.

The mechanism of hepatocellular carcinoma (HCC) development induced by liver fibrosis is obscure. The objective of this study is to establish miRNAs from exosomes associated with liver fibrosis, and to identify potential biomarkers for the prediction of personalized clinical management effectiveness in HCC. Our research focused on miRNAs from exosomes and mRNA from liver fibrosis, which we found in the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) evaluated miRNAs from exosomes associated with liver fibrosis, and Wilcoxon analysis assessed differentially expressed mRNAs (DEGs) across liver fibrosis/normal tissues. Following that, DEGs were assessed through gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, based on the screened targeted genes, including SAMD12 and CADM2, we further elucidated their correlation in HCC patients from the BEST database. The Kaplan-Meier Plotter platform was applied to evaluate the prognostic values of miRNA in HCC. In vitro and vivo experiments validated our findings. Six miRNAs associated with liver fibrosis were evaluated in our investigation. In-depth research presented exosome-derived miR-106a-5p, SAMD12 and CADM2 could exert valuable predictive implications for HCC treatment and illness assessment. Serum miR-106a-5p derived from liver fibrosis was decreased compared with healthy individuals. SAMD12 and CADM2 were diminished in liver cancer cell lines, and their knockdown of them exacerbated the proliferation capacities of liver cells in vitro. Exosome-derived miRNA of liver fibrosis modulated tumorigenesis by targeting SAMD12 and CADM2 in HCC.

Hepatocellular carcinoma is the third most common cause of cancer-related death according to the International Agency for Research on Cancer. Dihydroartemisinin (DHA), an antimalarial drug, has been reported to exhibit anticancer activity but with a short half-life. We synthesized a series of bile acid-dihydroartemisinin hybrids to improve its stability and anticancer activity and demonstrated that an ursodeoxycholic-DHA (UDC-DHA) hybrid was 10-fold more potent than DHA against HepG2 hepatocellular carcinoma cells. The objectives of this study were to evaluate the anticancer activity and investigate the molecular mechanisms of UDCMe-Z-DHA, a hybrid of ursodeoxycholic acid methyl ester and DHA via a triazole linkage. We found that UDCMe-Z-DHA was even more potent than UDC-DHA in HepG2 cells with IC₅₀ of 1 μM. Time course experiments and stability in medium determined by cell viability assay as well as HPLC-MS/MS analysis revealed that UDCMe-Z-DHA was more stable than DHA, which in part accounted for the increased anticancer activity. Mechanistic studies revealed that UDCMe-Z-DHA caused G0/G1 arrest and induced reactive oxygen species (ROS), mitochondrial membrane potential loss and autophagy, which may in turn lead to apoptosis. Compared to DHA, UDCMe-Z-DHA displayed much lower cytotoxicity toward normal cells. Thus, UDCMe-Z-DHA may be a potential drug candidate for hepatocellular carcinoma.

Clearance of hepatitis B surface antigen (HBsAg) is an ideal therapeutic goal for patients with chronic hepatitis B virus (HBV) infection. Haematopoietic stem cell transplantation (HSCT) is the most effective therapy for a variety of haematological diseases. For patients with chronic HBV infection who received allo-HSCT, recipient hepatitis B serological status might change after allo-HSCT; however, data on the loss of HBsAg following allo-HSCT are relatively rare. We first reviewed patients with chronic HBV infection who received allo-HSCT in our centre from 2010 to 2020, and 125 patients were included in our study. A total of 62 patients (49.6%) with chronic HBV infection achieved HBsAg loss after allo-HSCT. Positivity for HBeAb and HBsAb in donors as well as no cytomegalovirus (CMV) infection were identified as independent risk factors for HBsAg loss after allo-HSCT. A predictive model including positivity for HBeAb and HBsAb in donors and no CMV infection was subsequently developed and performed well with effective discrimination and calibration. In addition, patients could benefit when this model is used in the clinic, as revealed via decision-curve analysis (DCA). However, multicentre prospective studies are required for validation.

Long noncoding RNAs (lncRNAs) have been reported to be involved in the development and progression of various human malignancies. However, the role of lncRNA CASC2 in hepatocellular carcinoma (HCC) remains mostly unknown. The aim of this study was to investigate the potential roles and underlying mechanisms of CASC2 in HCC progression. We found that CASC2 expressions were downregulated in HCC tissue samples and cell lines. The clinical assays revealed that lower levels of CASC2 were associated with the TNM stage, lymph node metastasis, and a poorer prognosis specific to HCC patients. Overexpression of CASC2 inhibited the proliferating, migratory, and invasion capacity of HCC cells. Bioinformatics analysis and the luciferase reporter assay revealed that CASC2 worked as a molecular sponge for miR-155. And CASC2 could upregulate SOCS1 expression by inhibiting miR-155 expression in HCC cells. Furthermore, SOCS1 inhibition partially inverses the suppression effect of cell proliferation, migration, and invasion regulated by CASC2 in Huh7 and HepG2 cells. Taken together, our findings identified CASC2 as a tumor suppressor to inhibit HCC development by regulating the miR-155/SOCS1 axis, and CASC2 might be a potential therapeutic target of HCC for future clinical treatment.