Role of the Hedgehog signaling pathway in hepatocellular carcinoma and its tumor microenvironment / 临床肝胆病杂志

The Hedgehog （Hh） signaling pathway plays an important role in the development and progression of hepatocellular carcinoma and its tumor microenvironment， and abnormal activation of Hh signal can accelerate the growth of tumor. The crosstalk between the Hh signaling pathway and TME is closely associated with tumor growth and the formation of inhibitory tumor microenvironment. Evidence shows that inhibition of Hh signal plays an important role in inhibiting the growth of hepatocellular carcinoma. This article reviews the current research status of the role， mechanism， and potential therapeutic significance of abnormal activation of Hh signal in hepatocellular carcinoma and its tumor microenvironment， so as to provide new ideas for the treatment of hepatocellular carcinoma.

Advances in the application of microspheres and nanoparticles in transcatheter arterial chemoembolization for the treatment of hepatocellular carcinoma / 临床肝胆病杂志

In recent years， transcatheter arterial chemoembolization （TACE） has emerged as a common treatment modality for the treatment of hepatocellular carcinoma （HCC）. However， with the ongoing development of embolic agent techniques， the new advances in microspheres and nanoparticles have brought new hope for improving the efficacy and safety of TACE. This article reviews the latest advances and applications of microspheres and nanoparticles in TACE for HCC. First， this article introduces the background of TACE as a therapeutic approach and the emergence of microsphere and nanoparticle techniques， and then it describes the application of various types of microspheres and nanoparticles in TACE and discusses the requisite attributes of an ideal embolic agents. The article focuses on the advances in material science and engineering， as well as the clinical efficacy of drug-eluting microspheres and nanoparticles versus conventional TACE. Furthermore， it discusses the importance of radiological examination in TACE and summarizes the research advances in the radiopaque and magnetic resonance-visible embolic agents. This article also explores the future development directions and challenges of TACE. It also points out the combination of microspheres and nanoparticles with other treatment modalities， the application of personalized and precision medicine in TACE， and the potential regimen of TACE in clinical translation， and meanwhile， it raises the issues of ethics and regulation that need to be further discussed. It is believed that microspheres and nanoparticles have a potential effect in TACE， which provides a theoretical basis and technical support for innovating HCC treatment regimens and improving the prognosis of patients through TACE interventions.

Efficacy and safety of transcatheter arterial chemoembolization combined with targeted therapy and immunotherapy in treatment of patients with stage Ⅱ‍b/Ⅲ‍a hepatocellular carcinoma based on China Liver Cancer Staging / 临床肝胆病杂志

ObjectiveTo evaluate the efficacy and safety of first-line transcatheter arterial chemoembolization （TACE） combined with targeted therapy and immunotherapy in the treatment of patients with stage Ⅱb/Ⅲa hepatocellular carcinoma （HCC） based on China Liver Cancer Staging （CNLC）. MethodsA total of 198 patients who received first-line TACE combined with targeted therapy and immunotherapy or received TACE alone from January 2015 to December 2022 in the First Affiliated Hospital of Soochow University were enrolled in this study， and after propensity score matching， there were 50 patients in combination group and 50 patients in TACE group. The Kaplan-Meier method was used to calculate median overall survival （mOS） and median progression-free survival （mPFS）. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate objective response rate （ORR） and disease control rate （DCR）， and Common Terminology Criteria for Adverse Events v5.0 was used to evaluate adverse events. The chi-square test was used for comparison of categorical data between two groups； the t-test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate survival time and calculate 95% confidence interval （CI）， and the Log-rank test was used for comparison of mOS and mPFS between two groups. ResultsThe combination group had an mOS of 30.1 months （95%CI： 21.9‍ ‍—‍ ‍38.3）， and the TACE group had an mOS of 14.5 months （95%CI： 11.0 ‍—‍‍ ‍18.0）， with a significant difference between the two groups （χ2=17.8， P<0.001）； the combination group had an mPFS of 10.3 months （95%CI： 8.8‍ ‍—‍ ‍11.8）， and the TACE group had an mPFS of 7.1 months （95%CI： 5.8‍ — ‍8.4）， with a significant difference between the two groups （χ2=10.4， P<0.001）. There were significant differences between the combination group and the TACE group in ORR （84% vs 58%， P<0.05） and DCR （94% vs 80%， P<0.05）. There was no significant difference between the combination group and the TACE group in the incidence rate of adverse events （24% vs 16%， P=0.317）， and no adverse event-related deaths were observed in either group. ConclusionCompared with TACE alone， TACE combined with targeted therapy and immunotherapy has a better efficacy in the treatment of patients with CNLC stage Ⅱb/Ⅲa HCC， without increasing the incidence rate of severe adverse events.

Efficacy and safety of cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody in treatment of unresectable hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis. ResultsThe median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）. ConclusionFor patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.

Role of NOD-like receptor protein 3 inflammasome in the development and progression of hepatocellular carcinoma / 临床肝胆病杂志

In recent years， NOD-like receptor protein 3 （NLRP3） inflammasome in tumors has become a research hotspot， especially in melanoma， colorectal cancer， lung cancer， and breast cancer， and more and more evidence has shown that inflammation plays a role in the development， progression， angiogenesis， and invasion of cancer. Hepatocellular carcinoma （HCC） is the most common type of primary liver cancer， and there are still controversies over the role of NLRP3 inflammasome in the development and progression of HCC. Therefore， this article reviews the potential impact of NLRP3 inflammasome in the progression of HCC and its mechanism of action in anticancer therapy， and it is believed that NLRP3 inflammasome can be used as an effective therapeutic target for HCC patients.

Research advances in second-line therapies for hepatocellular carcinoma after resistance to targeted therapy combined with immunotherapy / 临床肝胆病杂志

In recent years， clinical studies on targeted therapy and immunotherapy for advanced hepatocellular carcinoma used alone or in combination have provided abundant evidence on efficacy and safety for the selection of first-line therapies. However， no consensus has been reached on the selection of second-line therapies in various clinical guidelines for hepatocellular carcinoma， which is caused by the fact that existing evidence is limited to the options after failure of sorafenib and that there is still a lack of high-level evidence for new first-line therapies such as second-line therapies after resistance to targeted therapy and immunotherapy for hepatocellular carcinoma. This article reviews the results of current clinical trials and summarizes the studies on second-line therapies for hepatocellular carcinoma after resistance to first-line targeted therapy and immunotherapy for hepatocellular carcinoma based on the different mechanisms of action of drugs， as well as the research advances in recent years. For hepatocellular carcinoma patients with resistance to first-line targeted therapy and immunotherapy， targeted combination therapy and dual-immune therapy are expected to improve treatment outcome and survival， and more prospective clinical studies are needed in the future to provide effective and safe treatment regimens for hepatocellular carcinoma patients with resistance to targeted therapy and immunotherapy.

Effect of kinesin family member 15 on the proliferation of hepatocellular carcinoma cells and its mechanism of action / 临床肝胆病杂志

ObjectiveTo investigate the effect of kinesin family member 15 （KIF15） on the proliferation of hepatocellular carcinoma （HCC） cells and its mechanism of action. MethodsTCGA and GEPIA datasets were analyzed to determine the expression of KIF15 in HCC and its effect on tumor stage and survival. Quantitative real-time PCR and Western blot were used to measure the expression level of KIF15 in human-derived HCC cell lines （HepG2， Hep3B， MHCC-97H， and LM3） and human normal liver cell line L02 cultured in vitro， and Hep3B and HepG2 were selected for subsequent studies. CCK-8 assay， plate colony formation assay， and EdU staining were performed for Hep3B cells transfected with shRNA-NC or shRNA-KIF15 and HepG2 cells transfected with LV-vector or LV-KIF15 to evaluate the viability and proliferative capacity of these cells. GSEA was used to analyze the potential signaling pathways associated with KIF15 in HCC， and Western blot was used for detection. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe analysis of TCGA and GEPIA datasets showed that in HCC patients， the expression of KIF15 in HCC tissue was significantly higher than that in normal tissue， and the HCC patients with high KIF15 expression tended to have a poorer prognosis. Compared with sh-NC-Hep3B， sh3-Hep3B showed significant reductions in the mRNA and protein levels of KIF15 （P<0.05）， cell viability， clone formation number， and EdU positive rate （all P<0.05）. Compared with vector-HepG2， LV-KIF15-HepG2 showed significant increases in the mRNA and protein levels of KIF15 （P<0.05）， cell viability， clone formation number， and EdU positive rate （all P<0.05）. Subcutaneous tumor assay showed that compared with sh-NC-Hep3B， sh3-Hep3B showed reductions in tumor volume and tumor weight， as well as a significant reduction in the immunohistochemical score of Ki67 and a significant increase in the immunohistochemical score of TUNEL （P<0.05）. GSEA analysis showed that the PI3K/AKT/mTOR pathway was positively correlated with KIF15 in HCC （NES=1.59， P<0.001）. Western blot showed that LY294002 could inhibit the PI3K/AKT/mTOR pathway upregulated in LV-KIF15-HepG2， and compared with LV-KIF15-HepG2， LY294002+LV-KIF15-HepG2 showed significant reductions in cell viability， clone formation number， and EdU positive rate （all P<0.05）. ConclusionKIF15 enhances the viability and proliferative capacity of HCC cells by upregulating the PI3K/AKT/mTOR signaling pathway.

Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

Current status and prospects of transarterial chemoembolization and its combined regimens in the treatment of hepatocellular carcinoma / 临床肝胆病杂志

Transarterial chemoembolization （TACE） is currently the primary treatment method for advanced liver cancer. This article elaborates on the current status of application of TACE in hepatocellular carcinoma from the aspects of existing techniques， patient selection， and efficacy assessment and summarizes the research advances and prospects of TACE combined with local treatment and systemic therapy， so as to provide new ideas for clinical practice and experimental studies.

Radiological characteristics of hepatocellular carcinoma that achieved complete response after chemoembolization with drug-eluting beads for liver transplantation planning

ABSTRACT Objective To describe the radiological characteristics of hepatocellular carcinoma (HCC) lesions that achieved a complete response following drug-eluting bead transarterial chemoembolization (DEB-TACE) preceding liver transplantation. Methods This single-center case-control study enrolled patients with hepatocellular carcinoma who underwent neoadjuvant DEB-TACE therapy, were followed up with contrast-enhanced magnetic resonance imaging or computed tomography, and were successively evaluated according to the modified Response Evaluation Criteria in Solid Tumors. The HCCs were divided into two groups based on their diameter (Group A: ≤3cm; Group B: 3cm). Viability was assessed using the Kaplan-Meier method according to tumor size categories. The relationship between tumor variables was analyzed using bivariate Cox regression. Results Three-hundred and twenty-eight patients with 667 hepatocellular carcinomas who underwent their first DEB-TACE session were enrolled. A total of 105 hepatocellular carcinomas in 59 patients exhibited complete response after the initial DEB-TACE session and were divided into Group A (92 HCCs) and Group B (13 HCCs). The diameter in Group A decreased significantly compared to the pre-procedure size until the second assessment (p<0.001), with no subsequent reduction in diameter, despite maintaining a complete response. In Group B, the reduction in diameter remained significant compared with the initial value until the sixth imaging evaluation (p=0.014). The average reduction was 45.1% for Group B and a maximum of 14.9% in Group A. Conclusion HCCs >3cm exhibited a greater reduction in size and a longer time to recurrence. HCCs ≤3cm had a shorter relapse time. The recurrence rates were similar. These findings may aid in planning for liver transplantation.

Hepatosplenic schistosomiasis-associated chronic portal vein thrombosis: risk factor for hepatocellular carcinoma? / Esquistossomose hepatosplênica associada à trombose crônica da veia porta: fator de risco para o carcinoma hepatocelular?

ABSTRACT BACKGROUND: Hepatosplenic schistosomiasis is an endemic disease prevalent in tropical countries and is associated with a high incidence of portal vein thrombosis. Inflammatory changes caused by both parasitic infection and portal thrombosis can lead to the development of chronic liver disease with potential carcinogenesis. AIMS: To assess the incidence of portal vein thrombosis and hepatocellular carcinoma in patients with schistosomiasis during long-term follow-up. METHODS: A retrospective study was conducted involving patients with schistosomiasis followed up at our institution between 1990 and 2021. RESULTS: A total of 126 patients with schistosomiasis were evaluated in the study. The mean follow-up time was 16 years (range 5-31). Of the total, 73 (57.9%) patients presented portal vein thrombosis during follow-up. Six (8.1%) of them were diagnosed with hepatocellular carcinoma, all with portal vein thrombosis diagnosed more than ten years before. CONCLUSIONS: The incidence of hepatocellular carcinoma in patients with schistosomiasis and chronic portal vein thrombosis highlights the importance of a systematic long-term follow-up in this group of patients.

RESUMO RACIONAL: A esquistossomose hepatoesplênica é uma doença endêmica prevalente em países tropicais e está associada a uma alta incidência de trombose da veia porta. Alterações inflamatórias causadas tanto pela infecção parasitária quanto pela trombose portal podem levar ao desenvolvimento de doença hepática crônica com potencial carcinogênico. OBJETIVOS: Avaliar a incidência de trombose da veia porta e carcinoma hepatocelular em pacientes com esquistossomose durante um seguimento de longo prazo. MÉTODOS: Foi realizado estudo retrospectivo envolvendo pacientes com esquistossomose acompanhados em nossa instituição entre 1990 e 2021. RESULTADOS: Um total de 126 pacientes com esquistossomose foram avaliados no estudo. O tempo médio de acompanhamento foi de 16 anos (variando de 5 a 31). Do total, 73 (57,9%) pacientes apresentaram trombose da veia porta durante o seguimento e seis (8,1%) deles foram diagnosticados com carcinoma hepatocelular, todos com trombose da veia porta diagnosticada há mais de 10 anos. CONCLUSÕES: A incidência de carcinoma hepatocelular em pacientes com esquistossomose e trombose da veia porta crônica destaca a importância de um acompanhamento sistemático de longo prazo nesse grupo de pacientes.

ZNF460 Mediates STAT3 Phosphorylation to Promote Progression of Hepatocellular Carcinoma by Activating ZDHHC7 Transcription / 胃肠病学

Background: ZNF460 is a member of the zinc finger protein family transcription factors, and is involved in the regulation of a variety of cellular functions. It has been demonstrated to be closely related to digestive system cancers. Aims: To analyze the expression level of ZNF460 in hepatocellular carcinoma (HCC), and explore the effect and potential mechanisms of ZNF460 on tumor cell proliferation. Methods: Immunohistochemical staining was used to determine the expression level of ZNF460 in tissue microarray of 76 HCC and paired adjacent tissues, and the correlation between ZNF460 expression and TNM staging was analyzed. The effect of ZNF460 on HCC cell proliferation was evaluated by CCK‑ 8 and colony formation assays. Genes positively related to ZNF460 expression in HCC were screened through LinkedOmics database, and the KEGG and GSEA pathway enrichment analyses were performed; the possible downstream molecules of ZNF460 were explored and verified by overexpression or knockdown of ZNF460 in HCC cells combined with luciferase reporter assay and other experiments. Results: ZNF460 was highly expressed in HCC and was positively correlated with TNM staging. ZNF460 promoted the proliferation of HCC cells, and the underlying mechanism might be associated with the transcriptional activation of ZDHHC7, the coding gene of palmitoyl transferase DHHC7 and the subsequent STAT3 palmitoylation and phosphorylation. Conclusions: ZNF460 is highly expressed in HCC and promotes cell proliferation and tumor progression via STAT3 activation. It might be a promising molecular marker and therapeutic target for HCC.

From viral hepatitis to hepatocellular carcinoma: The role of exosomal microRNAs / 临床肝胆病杂志

Exosomes are nano-sized phospholipid bilayer vesicles containing abundant and complex biomolecules, such as DNA, mRNAs, microRNAs (miRNAs), lipids, and proteins. Exosomes can be secreted and ingested by most types of cells to transfer information through intercellular transport. After uptake by recipient cells, exosomes release bioactive substances to regulate the biological processes of recipient cells, such as promoting tumor growth and metastasis. Changes of exosomes and their contents are associated with a variety of diseases. In recent years, the role of exosomal miRNAs in the development and progression of hepatocellular carcinoma (HCC) caused by viral hepatitis has attracted wide attention, and exosomal miRNAs from different sources play different roles in this process. This article briefly reviews the research on the role of exosomal miRNAs in the development and progression of viral hepatitis-related HCC and proposes that exosomal miRNAs may be the targets for immunotherapy for HCC microenvironment.

Biological connotation of "phlegm-turbidity" theory in hepatocellular carcinoma microenvironment based on abnormal lipid metabolism / 临床肝胆病杂志

There is still a lack of effective strategies for the prevention and treatment of liver cancer, and a deep understanding of its pathogenesis may help to develop new treatment methods. Due to the abnormal changes of lipid metabolism in the development and progression of liver cancer, such process is closely associated with the "phlegm-turbidity" theory in traditional Chinese medicine (TCM). Starting from the changes of lipid metabolism in hepatocellular carcinoma microenvironment, this article discusses the association of the abnormal changes of lipid metabolism in tumor cells and immune cells with the "phlegm-turbidity" theory and the clinical efficacy of phlegm-eliminating therapies in clinical practice. Since the "phlegm-turbidity" theory in TCM plays an important role in the pathogenesis and pathological changes of liver cancer, the analysis of its theoretical connotation helps to clarify pathological mechanism, thereby providing a theoretical basis for the role of TCM in the prevention and treatment of liver cancer.

Mechanism of action of N7-methylguanosine in hepatocellular carcinoma / 临床肝胆病杂志

N7-methylguanosine （m7G） is one of the most popular RNA modifications at present and has attracted wide attention from researchers in China and globally. By influencing the metabolism of various RNA molecules （including messenger RNA， ribosomal RNA， microRNA， and transfer RNA）， m7G modification actively participates in many biological processes such as cell proliferation， differentiation， and apoptosis. More and more evidence has shown that m7G plays a key role in the development of cancer， and abnormal m7G levels are closely associated with the development and progression of cancer by regulating the expression of multiple oncogenes and tumor suppressor genes. Hepatocellular carcinoma is the most common gastrointestinal tumor in China， and current treatment methods tend to have an unsatisfactory therapeutic effect. At present， the potential molecular mechanism of m7G modification in hepatocellular carcinoma remains unclear. This article reviews the potential mechanism of action of m7G modification in hepatocellular carcinoma and the m7G-related diagnosis and treatment strategies.

Role of HBV DNA polymerase in mediating the immune escape of tumor cells in HBV-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo determine whether HBV DNA polymerase is associated with T-cell failure and thus mediates the immune escape of HBV-related hepatocellular carcinoma （HCC） tumor cells， and to investigate the specific molecular mechanisms. MethodsLiver cancer cell lines Huh7 and HepG2 stably transfected with HBV DNA polymerase expression plasmid with Flag （Flag-HBV-P） and intercellular adhesion molecule-1 （ICAM1） were co-cultured with Jurkat cells， and MTT assay， qRT-PCR， and ELISA were used to measure Jurkat cell proliferation， activation （CD69 expression）， and secretion of the cytokine IFN-γ. RNA-seq was used to screen for differentially expressed immune-associated molecules between stably transfected cell lines and control cells， and mRNA half-life and protein half-life assays were used to determine the specific levels of the immune-associated molecules that were affected by HBV DNA polymerase. Related websites were used to predict the transcription factors that may bind to the promoter region of this immune-associated molecule， Western blot was used to verify the effect of transcription factors on the immune-associated molecule， and rescue experiment was used to determine whether HBV DNA polymerase affects the expression level of the immune-associated molecule through this transcription factor. The independent-samples t test was used for comparison between two groups. ResultsThe experimental group had significant reductions in Jurkat cell proliferation， activation， and cytokine secretion compared with the control group （all P<0.01）. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had significant reductions in the mRNA and protein expression levels of ICAM1 （all P<0.01）. Website prediction identified the ICAM1 promoter and preliminarily highlighted NFKB1， RELA， and STAT3. Compared with the control group， the experimental group （Huh7 and HepG2 cell lines） had a significant reduction in the protein expression level of p65 （all P<0.01）. After p65 overexpression， there was a significant increase in the protein expression level of ICAM1， and after the expression of p65 was reduced， there was a significant reduction in the protein expression level of ICAM1 （all P<0.01）. In the rescue experiment， there was no significant difference in the protein expression level of ICAM1 between the control group and the experimental group after p65 overexpression （all P>0.05）. After the overexpression of ICAM1， there were no significant differences in the proliferation， activation， and cytokine secretion of Jurkat cells between the control group and the experimental group （Huh7 and HepG2 cell lines） （all P>0.05）. ConclusionHBV DNA polymerase downregulates the level of ICAM1 to mediate HCC immune escape by inhibiting the expression of p65 in NF-κB.

Research advances in tumor-associated macrophages in hepatocellular carcinoma microenvironment / 临床肝胆病杂志

Since there is a lack of obvious clinical symptoms in the early stage of hepatocellular carcinoma (HCC), most patients have progressed to the advanced stage at the time of confirmed diagnosis. There are limited treatment options for HCC patients who miss the opportunity for surgery, so it is of great importance to find new therapeutic targets. Tumor-associated macrophages (TAMs) are a group of macrophages existing in the tumor immune microenvironment and affect the malignant behaviors of HCC cells and the state of immune escape within the tumor. This article introduces the origin and classification of TAM, summarizes the role and mechanism of TAMs in vascular proliferation, invasion and metastasis, formation and maintenance of stemness, and anti-tumor immunity in HCC, and briefly describes the current research advances in therapeutic targets for TAM, and it is pointed out that targeting TAM may be a promising direction for clinical treatment.

Role of macrophage polarization and its crosstalk with neighboring cells in hepatocellular carcinoma / 临床肝胆病杂志

Inflammation is closely associated with the development of cancer. Tumor-associated macrophages (TAM) actively participate in tumor-related inflammation and promote tumor growth and metastasis, while under certain conditions, TAM also show cytotoxicity and tumor killing activity and thus inhibit the progression of cancer. Crosstalk between TAM and neighboring cells is closely associated with the progression of hepatocellular carcinoma (HCC) and drug resistance during treatment. This article summarizes the role of macrophages in HCC and the crosstalk between macrophages and other cells, so as to provide new strategies for the clinical diagnosis and treatment of HCC.

Research advances in immunotherapy for hepatocellular carcinoma / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) has an insidious onset, and most patients are in the advanced stage when attending the hospital and thus lose the opportunity for radical surgical resection, which results in the poor prognosis of patients. With the development of clinical treatment, the treatment of advanced HCC has gradually transitioned from the relatively single and limited treatment options in the past to the new model of comprehensive treatment. In recent years, immunotherapy, represented by immune checkpoint inhibitors (ICIs), has become widely used in clinical practice. At present, a number of clinical studies have been conducted for immunotherapy combined with local and targeted antitumor therapy, and in particular, ICIs combined with targeted therapy have become a research hotspot in the field of HCC treatment. This article reviews the research advances in immunotherapy for the treatment of HCC.