Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis

BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

Multiparameter magnetic resonance imaging-based radiomics model for the prediction of rectal cancer metachronous liver metastasis

BACKGROUND The liver,as the main target organ for hematogenous metastasis of colorectal cancer,early and accurate prediction of liver metastasis is crucial for the diagnosis and treatment of patients.Herein,this study aims to investigate the application value of a combined machine learning(ML)based model based on the multiparameter magnetic resonance imaging for prediction of rectal metachronous liver metastasis(MLM).AIM To investigate the efficacy of radiomics based on multiparametric magnetic resonance imaging images of preoperative first diagnosed rectal cancer in predicting MLM from rectal cancer.METHODS We retrospectively analyzed 301 patients with rectal cancer confirmed by surgical pathology at Jingzhou Central Hospital from January 2017 to December 2023.All participants were randomly assigned to the training or validation queue in a 7:3 ratio.We first apply generalized linear regression model(GLRM)and random forest model(RFM)algorithm to construct an MLM prediction model in the training queue,and evaluate the discriminative power of the MLM prediction model using area under curve(AUC)and decision curve analysis(DCA).Then,the robustness and generalizability of the MLM prediction model were evaluated based on the internal validation set between the validation queue groups.RESULTS Among the 301 patients included in the study,16.28%were ultimately diagnosed with MLM through pathological examination.Multivariate analysis showed that carcinoembryonic antigen,and magnetic resonance imaging radiomics were independent predictors of MLM.Then,the GLRM prediction model was developed with a comprehensive nomogram to achieve satisfactory differentiation.The prediction performance of GLRM in the training and validation queue was 0.765[95%confidence interval(CI):0.710-0.820]and 0.767(95%CI:0.712-0.822),respectively.Compared with GLRM,RFM achieved superior performance with AUC of 0.919(95%CI:0.868-0.970)and 0.901(95%CI:0.850-0.952)in the training and validation queue,respectively.The DCA indicated that the predictive ability and net profit of clinical RFM were improved.CONCLUSION By combining multiparameter magnetic resonance imaging with the effectiveness and robustness of ML-based predictive models,the proposed clinical RFM can serve as an insight tool for preoperative assessment of MLM risk stratification and provide important information for individual diagnosis and treatment of rectal cancer patients.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Unraveling the therapeutic potential of Calculus Bovis in liver cancer:A novel step for targeted cancer treatment

Hepatocellular carcinoma is one of the leading causes of cancer-related deaths globally,and effective treatments are urgently needed.The present study aimed to investigate the inhibitory effect of Calculus Bovis(CB)on liver cancer and the underlying mechanisms.CB inhibited M2 tumor-associated macrophage polarization and modulated the Wnt/β-catenin signaling pathway,thereby suppressing the proliferation of liver cancer cells.The inhibitory effect on liver cancer growth was confirmed by both in vivo and in vitro experiments(detailed by Huang et al).The present study provides a theoretical basis for the application of CB for the treatment of liver cancer,providing new avenues for liver cancer treatment.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Current landscape of preoperative neoadjuvant therapies for initial resectable colorectal cancer liver metastasis

Colorectal cancer liver metastasis(CRLM)presents a clinical challenge,and optimizing treatment strategies is crucial for improving patient outcomes.Surgical resection,a key element in achieving prolonged survival,is often linked to a heightened risk of recurrence.Acknowledging the potential benefits of preoperative neoadjuvant chemotherapy in managing resectable liver metastases,this approach has gained attention for its role in tumor downsizing,assessing biological behavior,and reducing the risk of postoperative recurrence.However,the use of neoadjuvant chemotherapy in initially resectable CRLM sparks ongoing debates.The balance between tumor reduction and the risk of hepatic injury,coupled with concerns about delaying surgery,necessitates a nuanced approach.This article explores recent research insights and draws upon the practical experiences at our center to address critical issues regarding considerations for initially resectable cases.Examining the criteria for patient selection and the judicious choice of neoadjuvant regimens are pivotal areas of discussion.Striking the right balance between maximizing treatment efficacy and minimizing adverse effects is imperative.The dynamic landscape of precision medicine is also reflected in the evolving role of gene testing,such as RAS/BRAF and PIK3CA,in tailoring neoadjuvant regimens.Furthermore,the review emphasizes the need for a multidisciplinary approach to navigate the comp-lexities of CRLM.Integrating technical expertise and biological insights is crucial in refining neoadjuvant strategies.The management of progression following neoadjuvant chemotherapy requires a tailored approach,acknowledging the diverse biological behaviors that may emerge.In conclusion,this review aims to provide a comprehensive perspective on the considerations,challenges,and advancements in the use of neoadjuvant chemotherapy for initially resectable CRLM.By combining evidencebased insights with practical experiences,we aspire to contribute to the ongoing discourse on refining treatment paradigms for improved outcomes in patients with CRLM.

Identification of an immune-related gene signature for predicting prognosis and immunotherapy efficacy in liver cancer via cell-cell communication

BACKGROUND Liver cancer is one of the deadliest malignant tumors worldwide.Immunotherapy has provided hope to patients with advanced liver cancer,but only a small fraction of patients benefit from this treatment due to individual differences.Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies,thereby improving patient survival rates.Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer,the impact of cell-cell interactions in the tumor microenvir-onment has not been adequately considered.AIM To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy.METHODS Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways.Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells.The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features,and a least absolute shrinkage and selection operator(LASSO)regression model was constructed to screen for diagnostic-related features.Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model.Finally,3 genes(stathmin 1,cofilin 1,and C-C chemokine ligand 5)significantly associated with survival were identified and used to construct an immune-related gene signature.RESULTS The immune-related gene signature composed of stathmin 1,cofilin 1,and C-C chemokine ligand 5 was identified through cell-cell communication.The effectiveness of the identified gene signature was validated based on experi-mental results of predictive immunotherapy response,tumor mutation burden analysis,immune cell infiltration analysis,survival analysis,and expression analysis.CONCLUSION The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment,providing insights for personalized treatment strategies.

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

BACKGROUND 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.AIM To investigate the clinical efficacy and safety of Gamma Knife®combined with TACE and immune-targeted therapy in the treatment of primary liver cancer.METHODS 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.RESULTS 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.CONCLUSION 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.

Small particle drug-eluting beads-transarterial chemoembolization combined with targeted therapy in the clinical treatment of unresectable liver cancer

BACKGROUND Liver cancer is a highly malignant tumor with significant clinical impact.Chemotherapy alone often yields suboptimal outcomes in both the short and long term,characterized by high rates of local recurrence and distant metastasis,leading to a poor long-term prognosis.AIM To evaluate the clinical efficacy of small particle drug-eluting beads-transarterial chemoembolization(DEB-TACE)combined with targeted therapy for the treatment of unresectable liver cancer.METHODS We analyzed clinical data from 74 patients with unresectable liver cancer admitted between January 2019 and December 2020.Based on the different treatment regimens administered,patients were divided into the control(36 patients receiving sorafenib alone)and joint(38 patients receiving small particle DEB-TACE combined with sorafenib)groups.We compared liver function indicators[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),albumin(ALB)]and serum tumor markers[alpha fetoprotein(AFP)]before and after treatment in both groups.Short-term efficacy measures[complete response(CR),partial response,progression disease,stable disease,objective response rate(ORR),and disease control rate(DCR)]were assessed post-treatment.Long-term follow-up evaluated median overall survival(OS),progression-free survival(PFS),and adverse reaction rates between the two groups.RESULTS One month post-treatment,the joint group demonstrated significantly higher rates of CR,ORR,and DCR compared to the control group(P<0.05).Three days after treatment,the joint group showed elevated levels of ALT,AST,and TBIL but reduced levels of ALB and AFP compared to the control group(P<0.05).The median OS was 18 months for the control group and 25 months for the joint group,while the median PFS was 15 months for the control group and 22 months for the joint group,with significant differences observed(log-rank:χ2=7.824,6.861,respectively;P=0.005,0.009,respectively).The incidence of adverse reactions was not significantly different between the groups(P>0.05).CONCLUSION The combination of small particle DEB-TACE and sorafenib significantly improves both short-and long-term outcomes in the treatment of unresectable liver cancer while preserving liver function.

Uninvolved liver dose prediction in stereotactic body radiation therapy for liver cancer based on the neural network method

BACKGROUND The quality of a radiotherapy plan often depends on the knowledge and expertise of the plan designers.AIM To predict the uninvolved liver dose in stereotactic body radiotherapy(SBRT)for liver cancer using a neural network-based method.METHODS A total of 114 SBRT plans for liver cancer were used to test the neural network method.Sub-organs of the uninvolved liver were automatically generated.Correlations between the volume of each sub-organ,uninvolved liver dose,and neural network prediction model were established using MATLAB.Of the cases,70%were selected as the training set,15%as the validation set,and 15%as the test set.The regression R-value and mean square error(MSE)were used to evaluate the model.RESULTS The volume of the uninvolved liver was related to the volume of the corresponding sub-organs.For all sets of Rvalues of the prediction model,except for D_(n0)which was 0.7513,all R-values of D_(n10)-D_(n100)and D_(nmean)were>0.8.The MSE of the prediction model was also low.CONCLUSION We developed a neural network-based method to predict the uninvolved liver dose in SBRT for liver cancer.It is simple and easy to use and warrants further promotion and application.

Immunotherapy for gastric cancer and liver metastasis: Is it time to bid farewell

Patients with metastatic gastric cancer have a grim prognosis.Palliative che-motherapy offers a limited survival improvement,but recent advancements in immunotherapy have sparked hope.However,the effectiveness of immunothe-rapy in patients with liver metastases remains debated.This article reviews a recent study by Liu et al and evaluates conflicting evidence on the impact of liver metastases on response to immunotherapy in metastatic gastric cancer.While some studies suggest no significant difference in treatment response based on liver involvement,others report varied response rates.The present study,a re-trospective analysis of 48 patients by Liu et al,examines this issue and concludes that immunotherapy is less effective in patients with liver metastases.Despite methodological limitations and a small sample size,the study contributes to the ongoing discourse.The nuanced response to immunotherapy in certain patients underscores the importance of understanding the tumor microenvironment,immune cell infiltration,and the expression of immune checkpoints.Rather than dismissing immunotherapy for patients with gastric cancer and liver metastases,a shift towards personalized treatment strategies and a more profound under-standing of tumor-specific biomarkers is essential.By unraveling the molecular intricacies of individual cases,clinicians may tailor more effective and customized treatments,offering a glimmer of hope for this challenging patient group.

Pembrolizumab in patients with gastric cancer and liver metastases: A paradigm shift in immunotherapy

In this editorial,we explore the impact of immunotherapy and its safety in pa-tients with advanced gastric cancer(GC)and liver involvement.GC,a formidable adversary in the oncology landscape,presents its most challenging battlefront when it reaches stage IV,often characterized by liver metastases.The prognosis for patients at this advanced stage is daunting,with systemic chemotherapy tra-ditionally offering a median overall survival slightly over a year.However,the landscape of treatment is evolving,with new strategies and therapies offering a glimmer of hope.

Role of immunotherapy in gastric cancer with liver metastasis

Gastric cancer continues to be a significant issue for public health,marked by its widespread occurrence and high mortality rates,even as the incidence of the disease shows a declining trend.The liver is the primary site for metastatic spread,with the peritoneum,lungs,and bones also being common targets.With the advent of biologic treatments and the introduction of immunotherapy for patients with metastatic conditions,the options to treat metastatic gastric cancer have expanded.This diversified therapeutic approach is designed to enhance patient quality of life and prolong survival,showcasing the progress in treatment modalities for individuals with gastric cancer and liver metastases.

Inhibition of M2 tumor-associated macrophages polarization by modulating the Wnt/β-catenin pathway as a possible liver cancer therapy method

The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver cancer.Huang et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin pathway.The interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular docking.It is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of neoplasms.It is assumed that M2 TAM promote proliferation and migration of tumor cells.Attempts to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological diseases.Undoubtedly,the work of the Chinese authors deserves attention and further development.

Immunotherapy in gastric cancer with liver metastasis:Challenges and opportunities

In this editorial,we review the article by Liu et al published in the World Journal of Gastrointestinal Surgery investigating the efficacy and safety of immunotherapy in patients with gastric cancer(GC)and liver metastasis.GC,the fifth most com-monly diagnosed malignancy worldwide,presents a significant challenge due to its multifactorial etiology and a grim prognosis for unresectable or recurrent cases.The advent of immune checkpoint inhibitors(ICIs)has revolutionized oncology;yet liver metastasis has been associated with reduced response rates,progression-free survival,and overall survival in various malignancies.The Che-ckMate-649 and KEYNOTE-859 trials demonstrated promising results with ICIs in advanced GC,particularly in patients with liver metastasis.However,a meta-analysis of liver metastatic solid tumors revealed worse outcomes with ICIs,high-lighting the need for further investigation.While combined therapies,including ICIs with local treatments,show promise in improving outcomes,the nuanced landscape of ICIs in liver metastatic GC necessitates continued research for robust conclusions.The current contradictions in the literature underscore the impor-tance of cautious interpretation and the exploration of tailored approaches to enhance clinical efficacy in this challenging patient population.

Primary liver cancer organoids and their application to research and therapy

Primary liver cancer is a leading cause of death worldwide. To create advanced treatments for primary liver cancer, studies have utilized models such as 2D cell culture and in vivo animal models. Recent developments in cancer organoids have created the possibility for 3D in vitro cultures that recapitulates the cancer cell structure and operation as well as the tumor microenvironment (TME) . However, before organoids can be directly translated to clinical use, tissue processing and culture medium must be standardized with unified protocols to decrease variability in results. Herein, we present the wide variety of published methodologies used to derive liver cancer organoids from patient tumor tissues. Additionally, we summarize validation methodologies for organoids in terms of marker expression levels with immunohistochemistry as well as the presence of mutations and variants through RNA-sequencing. Primary liver cancer organoids have exciting applications allowing for faster drug testing at a larger scale. Primary liver cancer organoids also assisit in uncovering new mechanisms. Through the coculture of different immune cells and cancer organoids, organoids are now better able to recapitulate the liver cancer TME. In addition, it further aids in the investigation of drug development and drug resistance. Lastly, we posit that the usage of liver cancer organoids in animal models provides researchers a methodology to overcome the current limitations of culture systems.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Prevention of metastasis to liver by using 5-FU intraperitoneal chemotherapy in nude mice inoculated with human colonic cancer cells

AIMS Using a new approach of regional adjuvant chemotherapy to prevent cancer cells hepatic metasta- sis after radical surgery of large bowel cancer. METHODS A model of liver with metastasis of hu- man colonic cancer (HCC) cells in nude mice was used to observe the effect in prevention of metastasis of HCC cells inoculated via spleen applied with early postoper- ative intraperitoneal (IP) chemotherapy using large dose of 5-FU. RESULTS The incidence of metastasis to liver was decreased by 40%,the mean number of metastatic liv- er nodules in each animal was reduced by 50.89% and the mean survival times of each animal was prolonged by 48.21% by using 5-FU 40 mg/NS 40 ml/kg IP for two consecutive days as compared with the controls. CONCLUSIONS IP is a new and more effective re- gional adjuvant chemotheraputic approach in the pre- vention of liver metastasis HCC cells after radical surgery of large bowel cancer.

Calculus bovis inhibits M2 tumor-associated macrophage polarization via Wnt/β-catenin pathway modulation to suppress liver cancer

BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.