Treatment Of Primary Liver Cancer Research Articles

Network Pharmacology to Reveal the Mechanism of Fufang Banmao Capsule for Treating Unresectable Primary Liver Cancer and Clinical Data Validation.

Fufang Banmao capsule (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data. The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC. FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinical data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69. Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.

Efficacy and safety of B-ultrasound-guided radiofrequency ablation in the treatment of primary liver cancer: Systematic review and meta-analysis.

Primary liver cancer is one of the most lethal malignancies in the world. Traditional treatment methods have limitations in terms of efficacy and safety. Radiofrequency ablation (RFA) guided by B-ultrasound, as a minimally invasive treatment, has attracted increasing attention in the treatment of primary liver cancer in recent years. To study the efficacy and safety of RFA were compared with those of traditional surgery (TS) for treating small liver cancer. At least 2 people were required to search domestic and foreign public databases, including foreign databases such as EMBASE, PubMed and the Cochrane Library, and Chinese databases such as the China National Knowledge Infrastructure database, China Biomedical Literature database, Wanfang database and VIP database. Controlled trials of RFA vs conventional surgery for small liver cancer were retrieved from January 2008 to January 2023. They were screened and evaluated according to the quality evaluation criteria in the Cochrane Handbook of Systematic Reviews. The meta-analysis was performed using RevMan 5.3 software. A total of 10 studies were included in this study, including 1503 patients in the RFA group and 1657 patients in the surgery group. The results of the meta-analysis showed that there was no significant difference in 1-year overall survival between the two groups (P > 0.05), while the 3-year and 5-year overall survival rates and 1-year, 3-year and 5-year tumor-free survival rates in the surgery group were greater than those in the RFA group (P < 0.05). In terms of complications, the incidence of complications in the RFA group was lower than that in the surgery group (P < 0.05). In terms of long-term survival, TS is better than RFA for small liver cancer patients. However, RFA has fewer complications and is safer.

Epidemiology of malignant neoplasms. Role of locoregional methods of treatment of primary liver cancer

Epidemiology of malignant neoplasms. Role of locoregional methods of treatment of primary liver cancer

Laparoscopic ablation for liver malignancies: initial experience at a Scandinavian high volume HPB center

BackgroundAblation is an effective, parenchymal-sparing treatment for primary liver cancer and liver metastases. The purpose of this study was to report our initial experience with laparoscopic microwave ablation regarding postoperative complications, rate of conversions to open procedure, and technical efficacy.MethodsThis was a quality improvement project carried out at a tertiary care center in Denmark. Patients ≥ 18 years old with liver malignancies, not available for percutaneous ablation, and treated with ultrasound-guided laparoscopic ablation were included.ResultsFrom March 2023 to December 2023, 39 patients were referred for laparoscopic ablation after a multidisciplinary team conference. Of these, two procedures were converted to open procedures due to adhesion and tumor progression. Three patients rejected the sharing of medical information, two procedures were canceled and in one case the strategy was changed perioperatively. Therefore, 32 procedures in 31 patients were available for analysis. Complete ablation was evaluated after 1 month and was achieved in 100% of the procedures. None of the patients died, and no complications were reported in 21 cases (65.6%). Most patients with complications had a grade 1 complication based on the Clavien–Dindo classification, which among others included abdominal and shoulder pain, atrial fibrillation, and subcutaneous hematoma. Two patients had a complication grade 2 (wound infection and decompensated cirrhosis) and one had a grade 4b (sepsis due to pneumonia and urinary tract infection). The median Comprehensive Complication Index was 12.2 (interquartile range 8.7–24.2). Furthermore, univariable logistic regression showed that ≥ 2 tumors treated were associated with a higher risk of complications (odds ratio 6.37, 95% confidence interval [1.20;33.85], p-value = 0.0297).ConclusionUltrasound-guided laparoscopic microwave ablation of liver malignancies is feasible and safe with little risk for complications, a high technical efficacy, and a low rate of conversions to open procedures.

Development of cantharidin/baicalin co-delivery system based on mitochondrial targeting strategy for enhanced hepatocellular carcinoma therapy

Cantharidin (CTD) as a treatment for primary liver cancer are well known, and although structural alteration and nano-delivery are efficient in diminishing toxicity, its urinary and digestive toxicity has hindered its clinical application. Based on the synergistic effect of CTD and baicalin (BA) on proliferation inhibition of liver tumor cells, the highly expressed folic acid (FA) receptor of liver cancer cell membrane and the high negative membrane potential of tumor cell mitochondria, we synthesized CHEMS-FRFK and prepared a dual-ligand modified co-delivery liposomes (FA/FRFK-CTD/BA-Lips). Liposomes were spherical particles with uniform particle size, high encapsulation rate, good stability and no hemolysis. The results confirmed that FA/FRFK-CTD/BA-Lips had good targeting to mitochondria of tumor cells, and its target effect on mitochondria of HepG2 was better than that of Huh-7 cells. Compared with CTD, the cytotoxicity of liposomes on HepG2 is 7.0 times higher, while the cytotoxic effect on normal liver cells Thle-2 is 2.1 times lower. It may be related to increasing clathrin-mediated endocytosis, inhibiting tumor cell migration, arresting cell cycle in G1/G0 phase, and promoting mitochondria-mediated endogenous Bcl-2/Caspase 3 apoptosis pathway. Meanwhile, FA/FRFK-CTD/BA-Lips could alter the pharmacokinetic behavior of CTD and BA by increasing concentrations in vivo, slowing release and excretion, good anti-tumor with no obvious toxicity, and successfully delivered CTD/BA to liver tissue, tumor cells and mitochondria. Therefore, FA/FRFK-CTD/BA-Lips, as a delivery system targeting the mitochondria of liver cancer cells, has promising development potential, and could provide a new strategy for solving the problem of CTD toxicity and the treatment of hepatocellular carcinoma.

A Mendelian randomization analysis reveals the multifaceted role of the skin microbiota in liver cancer.

Hepatocellular carcinoma (HCC, or hepatic cancer, HC) and cholangiocarcinoma (CCA, or hepatic bile duct cancer, HBDC) are two major types of primary liver cancer (PLC). Previous studies have suggested that microbiota can either act as risk factors or preventive factors in PLC. However, no study has reported the relationship between skin microbiota and PLC. Therefore, we conducted a two-sample Mendelian randomization (MR) study to assess the causality between skin microbiota and PLC. Data from the genome-wide association study (GWAS) on skin microbiota were collected. The GWAS summary data of GCST90018803 (HBDC) and GCST90018858 (HC) were utilized in the discovery and verification phases, respectively. The inverse variance weighted (IVW) method was utilized as the principal method in our MR study. The MR-Egger intercept test, Cochran's Q-test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis were conducted to identify the heterogeneity and pleiotropy. The results showed that Veillonella (unc.) plays a protective role in HBDC, while the family Neisseriaceae has a positive association with HBDC risk. The class Betaproteobacteria, Veillonella (unc.), and the phylum Bacillota (Firmicutes) play a protective role in HC. Staphylococcus epidermidis, Corynebacterium (unc.), the family Neisseriaceae, and Pasteurellaceae sp. were associated with an increased risk of HC. This study provided new evidence regarding the association between skin microbiota and PLC, suggesting that skin microbiota plays a role in PLC progression. Skin microbiota could be a novel and effective way for PLC diagnosis and treatment.

Rare primary liver cancers: An EASL position paper.

In recent years, owing to advances in our understanding of hepatocarcinogenesis, rare primary liver cancers (PLCs), including combined hepatocellular-cholangiocarcinoma, fibrolamellar carcinoma, and hepatic epithelioid hemangioendothelioma have garnered increased attention. In this position paper, an international panel of experts representing oncology, hepatology, pathology, radiology, surgery, and molecular biology has summarised the available information and evidence on the pathogenesis, diagnosis, and treatment of rare PLCs. While clinical trials of systemic treatments are underway for some rare PLCs, it is evident that more research, involving national and international collaboration, is required.

Transcatheter Hepatic Artery Embolization Versus Hepatic Artery Perfusion Chemoembolization in the Interventional Treatment of Primary Hepatocellular Carcinoma: Clinical Effect Observation

Objective: To investigate the clinical effect of transcatheter hepatic artery embolization and hepatic artery perfusion chemoembolization on the interventional treatment of primary liver cancer. Methods: Eighty-two primary hepatocellular carcinoma patients who came to the outpatient clinic for treatment from August 2020 to November 2023 were selected as the study subjects. Based on the retrospective analysis, they were divided into 45 cases in the embolization group and 37 cases in the chemoembolization group according to the difference of treatment methods. The embolization group was treated with transcatheter hepatic artery embolization, and the chemoembolization group was treated with hepatic artery perfusion chemoembolization. The clinical efficacy, survival rate, survival quality score, serum tumor markers, and incidence of adverse reactions were observed in the two groups. Results: The clinical efficacy, survival quality score, and serum tumor markers of the chemoembolization group were higher than that of the embolization group, and the incidence of adverse reactions was lower than that of the embolization group, with statistically significant differences (P &lt; 0.05). The survival rate of the chemoembolization group was not statistically significant when compared with that of the embolization group (P &gt; 0.05). Conclusion: In the treatment of primary hepatocellular carcinoma, hepatic artery perfusion chemoembolization is better than transcatheter hepatic artery embolization, which can effectively improve the quality of patients’ survival and reduce the incidence of adverse reactions, and it is worth further popularized in the clinic.

Benefit-risk assessment of three oral Chinese patent medicines for activating blood and eliminating mass in treating primary liver cancer based on network Meta-analysis and multi-criteria decision analysis

Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer.

This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

Metabolomics research on treatment of primary liver cancer with Cortex Juglandis Mandshuricae on LC-MS/MS technology

Diethylnitrosamine (DEN) was applied to create the primary liver cancer (PLC) animal model. In the study, the normal group, model group, cyclophosphamide (CTX) group, Cortex Juglandis Mandshuricae (CJM) extract group, myricetin group and myricitrin group were divided. LC-MS/MS technology was applied to determine the metabolites of liver tissue samples from different locations (nodular and non-nodular parts of liver tissue) in each group of rats. Through metabolomics research, the connection and difference of anti-PLC induced by the CJM extract, myricetin and myricitrin was analyzed. The surface of the liver tissues of rats in the model group was rough, dimly colored, inelastic, on which there were scattered gray white cancer nodules and blood stasis points. The number of cancer nodules was significantly reduced, and the degree of cell malignancy was low, but there were some inflammatory cell infiltrations, necrosis area and karyokinesis in the CJM extract group, myricetin group, myricitrin group and CTX group. The result of metabolic research indicated that 45 potential biomarkers of the PLC were found, as gamma-aminoisobutyrate, taurochenodeoxycholate, xanthurenic acid, etc. There were 22 differential metabolites in the CTX group, 16 differential metabolites in the CJM extract group, 14 differential metabolites in the myricetin group, 14 differential metabolites in the myricitrin group.

Chinese expert consensus on composite ablation system for the treatment of primary liver cancer (2023 edition)

Chinese expert consensus on composite ablation system for the treatment of primary liver cancer (2023 edition)

Prediction of potential targets and toxicological insights of Astragalus in liver cancer based on network pharmacology: Integrating systems biology, drug interaction networks, and toxicological perspectives.

This study investigates Astragalus's efficacy as a novel therapeutic option for primary liver cancer (PLC), capitalizing on its anti-inflammatory and antiviral effects. We utilized network pharmacology to unveil Astragalus's potential targets against PLC, revealing significant gene expression alterations in treated samples-20 genes were up-regulated, and 20 were down-regulated compared to controls. Our analysis extended to single-cell resolution, where we processed scRNA-seq data to discern 15 unique cell clusters within the immune, malignant, and stromal compartments through advanced algorithms like UMAP and tSNE. To delve deeper into the functional implications of these gene expression changes, we conducted comprehensive gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, alongside Gene Set Variation Analysis, to elucidate the biological processes and pathways involved. Further, we constructed protein-protein interaction networks to visualize the intricate molecular interplay, highlighting the down-regulation of MT1E in PLC cells, a finding corroborated by quantitative polymerase chain reaction. Molecular docking studies affirmed the potent interaction between Astragalus's active compounds and MT proteins, underscoring a targeted therapeutic mechanism. Our investigation also encompassed a detailed cellular landscape analysis, identifying nine cell subgroups related to MT1 expression and specifying five cell subsets through the SingleR package. Advanced trajectory and cell-cell interaction analyses offered deeper insights into the dynamics of MT1-associated cellular subpopulations. This comprehensive methodology not only underpins Astragalus's promising role in PLC treatment but also advances our understanding of its molecular and cellular mechanisms, paving the way for targeted therapeutic strategies.

MiR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2

ABSTRACT Metabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography – mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC in vivo. Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment.

Traditional Chinese Medicine in post-resection liver cancer therapy: a meta-analysis of efficacy.

To systematically evaluate the efficacy of traditional Chinese medicine (TCM) in the comprehensive post-resection treatment of primary liver cancer. Clinical studies on TCM in the comprehensive treatment of primary liver cancer post-resection were retrieved from PubMed, Embase, Cochrane and Google Scholar databases. The search encompassed the period from the inception of each database up to June 28, 2024. Two independent reviewers conducted literature screening based on pre-established inclusion and exclusion criteria, performed data extraction, and evaluated the risk of bias and the methodological quality of the included studies. A meta-analysis was conducted utilizing Review Manager 5.3 software. A total of 12 studies involving 19,116 patients were included in this study. The meta-analysis revealed that TCM treatment following liver cancer resection significantly reduced the recurrence rate, mortality and incidence of adverse events (RR = 0.76, 95% CI 0.70-0.83, P < 0.00001; RR = 0.79, 95% CI 0.71-0.88, P < 0.0001; RR = 0.71, 95% CI 0.57-0.89, P = 0.003). Additionally, TCM notably increased the 1-, 3-, and 5-year overall survival rate (RR = 1.08, 95% CI 1.05-1.11, P < 0.00001; RR = 1.19, 95% CI 1.14-1.23, P < 0.00001; RR = 1.26, 95% CI 1.12-1.42, P < 0.0001), and extended the recurrence-free survival time and the 5-year overall survival time (HR = 0.72, 95% CI 0.65-0.81, P < 0.00001; HR = 0.73, 95% CI 0.61-0.87, P = 0.0004) in patients with primary liver cancer after resection. TCM has a beneficial impact on the comprehensive treatment of primary liver cancer post-resection. However, further validation through higher-quality clinical studies is warranted.

To Discuss the Pathogenesis and Treatment of Primary Liver Cancer Based on the Theory of “Qiyu”

To Discuss the Pathogenesis and Treatment of Primary Liver Cancer Based on the Theory of “Qiyu”

A history of the treatment of primary liver cancer.

A history of the treatment of primary liver cancer.

A clinical study of targeted immunotherapy combined with hepatic arterial chemoembolization in the treatment of liver injury associated with primary liver cancer

Objective: To investigate the conditions of occurrence and factors influencing liver injury caused by molecular targeted drugs and immune checkpoint inhibitors combined with hepatic arterial chemoembolization (TACE) in the treatment of primary liver cancer. Methods: 105 cases of primary liver cancer admitted to the Third Hospital of Hebei Medical University from January 2020 to June 2023 were selected. Patients liver biochemical indicators conditional changes before and after treatment with targeted drugs+TACE and targeted drugs+immune checkpoint inhibitors (ICIs)+TACE were analyzed. Liver injuries above grade 2 and its independent risk factors to predict and evaluate model accuracy were established. Independent samples t-test, analysis of variance, and rank sum test were used for comparison of measurement data between groups. Count data were compared with a χ(2) test between groups. Results: A total of 50 (47.62%) of the 105 cases developed liver injury during the treatment course, with 26 (52%) cases of first-grade liver injury, 16 (32%) cases of second-grade liver injury, 8 (16%) cases of third-grade liver injury, and none of fourth-grade liver injury. There was no statistically significant difference in the incidence of liver injury between the two groups of patients (χ(2)=1.299, P = 0.637). Multivariate logistic regression analysis showed that total bilirubin, prealbumin, and prothrombin activity were independent risk factors for the occurrence of liver injury. The total bilirubin-prealbumin-prothrombin activity (TAP) model was established. TAP diagnosis of grade 2 or higher liver injury had an area under the receiver characteristic curve of 0.935, sensitivity of 84.35%, and specificity of 92.31% at a cut-off value of 1.24, and significantly better diagnostic performance than albumin-bilirubin (ALBI) grade. Conclusion: The occurrence of severe liver injury is minimal and well tolerated in the targeted drug + TACE treatment group and targeted drug + ICIs + TACE treatment group. The TAP model can be used as a new method to assess the risk of liver injury above grade 2 in patients treated with targeted immunotherapy combined with TACE.

Patient-derived precision cut tissue slices from primary liver cancer as a potential platform for preclinical drug testing

The exploitation of anti-tumour immunity, harnessed through immunomodulatory therapies, has fundamentally changed the treatment of primary liver cancer (PLC). However, this has posed significant challenges in preclinical research. Novel immunologically relevant models for PLC are urgently required to improve the translation from bench to bedside and back, explore and predict effective combinatorial therapies, aid novel drug discovery and develop personalised treatment modalities. We used human precision-cut tissue slices (PCTS) derived from resected tumours to create a patient-specific immunocompetent disease model that captures the multifaceted and intricate heterogeneity of the tumour and the tumour microenvironment. Tissue architecture, tumour viability and treatment response to single agent and combination therapies were assessed longitudinally over 8 days of exvivo culture by histological analysis, detection of proliferation/cell death markers, ATP content via HPLC. Immune cell infiltrate was assessed using PCR and immunofluorescence. Checkpoint receptor expression was quantified via Quantigene RNA assay. After optimising the culture conditions, PCTS maintained the original tissue architecture, including tumour morphology, stroma and tumour-infiltrated leukocytes. Moreover, PCTS retained the tumour-specific immunophenotype over time, suggesting the utility of PCTS to investigate immunotherapeutic drug efficacy and identify non-responsiveness. Here we have characterised the PCTS model and demonstrated its effectiveness as a robust preclinical tool that will significantly support the development of successful (immuno)therapeutic strategies for PLC. Foundation for Liver Research, London.

Benefit-Risk Assessment of Chinese Medicine Injections for Primary Liver Cancer Based on Multi-criteria Decision Analysis.

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.