Liver Cancer Patients Research Articles

Study on the Clinical Use of a Respiratory Navigator Combined with Breath-Hold for MRI- Guided Liver SBRT

Respiratory movement strongly affects the accuracy of stereotactic body radiation therapy (SBRT) of liver malignancies treated without the use of a respiratory gating system. This study investigates the feasibility and advantages of using a respiratory navigator-guided combined with patient breath-hold for liver SBRT in an adaptive magnetic-resonance guided workflow. Clinical datasets of 10 liver cancer patients treated with 1.5T MR-Linac with respiratory navigator-guided SBRT combined with patient breath-hold were retrospectively analyzed. All patients underwent simulation CT with and without contrast, and 4D-CT and 3D-T2w MRI without contrast. Patients received a prescription dose ranging from 36 to 50 Gy in 5 to 8 fractions and followed the adapt to shape (ATS) workflow including contours adjustment and a subsequent MR-based synthetic CT (sCT) calculation on the online MRI acquired. The reference treatment plan was optimized on the expiratory phase of the 4D-CT, and during the online session the contours and the adapted plans were performed using the 3D-T2w navigator MRI of the patient's end-expiratory signal; 2D-T2w real-time monitoring MRI was also used as support for the contour's definition. The radiation therapist instructed the patients to hold their breath at the end of the breathing cycle for the time of the beam on. A total of 59 fractions were analyzed. For each fraction the dosimetric parameters of the target and normal liver of the adaptive and reference plans were compared; particularly the volume, the conformity index (CI) and gradient index (GI) for the target, and V5, V10 and Dmean for the normal liver. T-student statistical analysis was performed; a p-value less than 0.05 was considered statistically significant. In the free breathing state, the 3D-T2w navigator MRI images enable a clear visualization of the tumor and its boundaries. The average target CI of the adaptive and reference plans is not significantly different (p = 0.448), while the GI is significantly higher (p = 0.043). Normal liver V10 and Dmean are lower and V5 is slightly increased, but without statistical differences. The mean values and standard deviation of the dosimetric parameters of the reference and adapted plans are shown in the Table below. The use of a respiratory navigator combined with the breath-hold for MRI- guided liver SBRT allows clear visualization of the tumor, ensures the accuracy of the delivered dose and may be considered an alternative when the respiratory gating system is not available during MRgART sessions.

Clinical significance of serum oxidative stress and serum uric acid levels before surgery for hepatitis B-related liver cancer.

The incidence and mortality of liver cancer are among the highest of all malignant tumors in China. The high recurrence rate after conventional hepatectomy is worrying. There is a lack of effective prognostic indicators for liver cancer. To explore the clinical significance of preoperative serum oxidative stress and serum uric acid (UA) levels in hepatitis B-related liver cancer. The medical records of 110 hepatitis B-related liver cancer patients who underwent hepatectomy in Gansu Provincial Hospital were retrospectively analyzed. Recurrence in patients within 3 years after surgery was determined. The logistic regression model and Pearson or Spearman correlation were used to analyze the correlation between oxidative stress level and UA, and the recurrence of hepatitis B-related liver cancer. Compared with the non-recurrence group, the levels of superoxide dismutase (SOD) and glutathione (GSH) in the recurrence group were lower and the levels of malondialdehyde (MDA) and UA were higher (all P < 0.05). UA, SOD, MDA, and GSH were risk factors for postoperative recurrence in hepatitis B-related liver cancer patients (P < 0.05). UA was positively correlated with MDA (r = 0.395, P < 0.001) and negatively correlated with GSH (r = -0.204, P = 0.032). The area under the receiver operating characteristic curve (AUC) of SOD, MDA, GSH, and UA in predicting the prognosis was 0.276, 0.910, 0.199, and 0.784, respectively (all P < 0.001). The preoperative serum SOD, GSH, MDA, and UA levels had significant predictive effects on postoperative recurrence of hepatitis B-related liver cancer.

The influence of adjunctive traditional Chinese medicine therapy on survival in primary liver cancer: a real-world study based on electronic medical records.

Background: Traditional Chinese medicine (TCM) effectively improves the survival rate and quality of life of primary liver cancer patients, but high-level evidence is lacking. Patients and methods: Patients were selected from 5 tertiary hospitals in Henan Province, China. Two thousand sixty-seven patients with primary liver cancer were included in the study. The electronic medical records (EMRs) of the patients were collected. Patients who received adjunctive TCM treatment and underwent treatment cumulative time for more than 1 month were classified as the TCM intervention cohort. Patients who did not receive adjunctive TCM treatment or underwent treatment cumulative time for less than 1 month were classified as the non-TCM intervention cohort. The main outcome indicators were the survival rate and overall survival time. The propensity score inverse probability weighting method was used to balance the differences between the groups. Results: The primary cohort comprised 2,067 patients, including 462 patients who received adjunctive TCM treatment and 1,605 patients who did not receive adjunctive TCM treatment. The results of the Kaplan‒Meier survival curve indicated that the survival rate and median survival time of the exposure group before and after propensity score weighting were greater than those of the control group (p < 0.0001). Univariate Cox regression analysis after propensity score weighting showed that adjunctive TCM treatment was an independent protective factor for survival [regression coefficient = -0.215, hazard ratio (HR) = 0.8066, 95% confidence interval (CI) (0.6609-0.9844)]. Conclusion: Adjuvant treatment with TCM has a protective effect on the prognosis of patients with primary liver cancer; it can reduce the mortality and prolong the survival time.

Comparing Predicted Toxicities between Hypofractionated Proton and Photon Radiotherapy of Liver Cancer Patients with Different Adaptive Schemes.

With the availability of MRI linacs, online adaptive intensity modulated radiotherapy (IMRT) has become a treatment option for liver cancer patients, often combined with hypofractionation. Intensity modulated proton therapy (IMPT) has the potential to reduce the dose to healthy tissue, but it is particularly sensitive to changes in the beam path and might therefore benefit from online adaptation. This study compares the normal tissue complication probabilities (NTCPs) for liver and duodenal toxicity for adaptive and non-adaptive IMRT and IMPT treatments of liver cancer patients. Adaptive and non-adaptive IMRT and IMPT plans were optimized to 50 Gy (RBE = 1.1 for IMPT) in five fractions for 10 liver cancer patients, using the original MRI linac images and physician-drawn structures. Three liver NTCP models were used to predict radiation-induced liver disease, an increase in albumin-bilirubin level, and a Child-Pugh score increase of more than 2. Additionally, three duodenal NTCP models were used to predict gastric bleeding, gastrointestinal (GI) toxicity with grades >3, and duodenal toxicity grades 2-4. NTCPs were calculated for adaptive and non-adaptive IMRT and IMPT treatments. In general, IMRT showed higher NTCP values than IMPT and the differences were often significant. However, the differences between adaptive and non-adaptive treatment schemes were not significant, indicating that the NTCP benefit of adaptive treatment regimens is expected to be smaller than the expected difference between IMRT and IMPT.

System analysis based on the lysosome-related genes identifies HPS4 as a novel therapy target for liver hepatocellular carcinoma.

Liver cancer is a leading cause of cancer-related deaths worldwide. Lysosomal dysfunction is implicated in cancer progression; however, prognostic prediction models based on lysosome-related genes (LRGs) are lacking in liver cancer. This study aimed to establish an LRG-based model to improve prognosis prediction and explore potential therapeutic targets in liver cancer. Expression profiles of 61 LRGs were analyzed in The Cancer Genome Atlas liver cancer cohorts. There were 14 LRGs identified, and their association with clinical outcomes was evaluated. Unsupervised clustering, Cox regression, and functional assays were performed. Patients were classified into high-risk and low-risk subgroups based on the 14 LRGs. The high-risk group had significantly worse overall survival. Aberrant immune infiltration and checkpoint expression were observed in the high-risk group. Furthermore, HPS4 was identified as an independent prognostic indicator. Knockdown of HPS4 suppressed liver cancer cell proliferation and induced apoptosis. This study developed an LRG-based prognostic model to improve risk stratification in liver cancer. The potential value of HPS4 as a therapeutic target and biomarker was demonstrated. Regulation of HPS4 may offer novel strategies for precision treatment in liver cancer patients.

Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase.

Hepatocellular carcinoma (HCC) is a frequently diagnosed malignancy with a high mortality rate. Cisplatin (CDDP) is a widely applied anti-cancer drug. However, a large population of liver cancer patients developed CDDP resistance. The polypyrimidine tract binding protein (PTBP1) is an RNA-binding protein involving in progressions of diverse cancers. Here we report PTBP1 was significantly upregulated in liver tumors and cell lines. Silencing PTBP1 effectively sensitized HCC cells to CDDP. From the established CDDP-resistant HCC cell line (HepG2 CDDP Res), we observed that CDDP-resistant cells were more sensitive to CDDP under low glutamine supply compared with that in HCC parental cells. CDDP-resistant HCC cells displayed elevated glutamine metabolism rate. Consistently, PTBP1 promotes glutamine uptake and the glutamine metabolism key enzyme, glutaminase (GLS) expression. Bioinformatics analysis predicted that the 3'-UTR of GLS mRNA contained PTBP1 binding motifs which were further validated by RNA immunoprecipitation and RNA pull-down assays. PTBP1 associated with GLS 3'-UTR to stabilize GLS mRNA in HCC cells. Finally, we demonstrated that the PTBP1-promoted CDDP resistance of HCC cells was through modulating the GLS-glutamine metabolism axis. Summarily, our findings uncovered a PTBP1-mediated CDDP resistance pathway in HCC, suggesting that PTBP1 is a promisingly therapeutic target to overcome chemoresistance of HCC.

Tumor-associated endothelial cell prognostic risk model and tumor immune environment modulation in liver cancer based on single-cell and bulk RNA sequencing: Experimental verification

BackgroundTo build a prognostic and immunotherapeutic response prediction model for liver cancer based on marker genes of tumor-associated endothelial cell (TEC). MethodSingle cell sequencing data from Gene Expression Omnibus (GEO) liver cancer patients were utilized to identify TEC subpopulations. Models were built from transcriptomic and clinical data of TCGA liver cancer patients. The GSE76427 and ICGC databases were used as independent validation sets. Time-dependent receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used to verify the ability of the model to predict survival. XCELL, TIMER, QUANTISEQ, CIBERSORT, CIBERSORT-ABS, and ssGSEA were applied to evaluate tumor immune cell infiltration. The TIDE score was used to predict the effect of immunotherapy. Immune blockade checkpoint gene, tumor mutational load and GSVA enrichment analyses were further explored. The expression levels of candidate genes were measured and validated by real-time PCR between liver cancer tissues and adjacent nontumor liver tissues. ResultsEighty-seven genes were identified as marker genes for TECs. IGFBP3, RHOC, S100A16, FSCN1, and CLEC3B were included in the constructed prognostic model. Time-dependent ROC curve values were higher than 0.700 in both the model and validation groups. The low risk group exhibited high immune cell infiltration and function than the higher risk group. The TIDE score indicated that the low-risk group benefited more from immunotherapy than the high-risk group. The risk score and multiple immune blockade checkpoint genes and immune-related pathways were strongly correlated. ConclusionNovel signatures of TEC marker genes showed a powerful ability to predict prognosis and immunotherapy response in patients with liver cancer.

Association of Phosphorylated Pyruvate Dehydrogenase with Pyruvate Kinase M2 Promotes PKM2 Stability in Response to Insulin.

Insulin is a crucial signalling molecule that primarily functions to reduce blood glucose levels through cellular uptake of glucose. In addition to its role in glucose homeostasis, insulin has been shown to regulate cell proliferation. Specifically, insulin enhances the phosphorylation of pyruvate dehydrogenase E1α (PDHA1) at the Ser293 residue and promotes the proliferation of HepG2 hepatocellular carcinoma cells. Furthermore, we previously observed that p-Ser293 PDHA1 bound with pyruvate kinase M2 (PKM2) as confirmed by coimmunoprecipitation. In this study, we used an in silico analysis to predict the structural conformation of the two binding proteins. However, the function of the protein complex remained unclear. To investigate further, we treated cells with si-PDHA1 and si-PKM2, which led to a reduction in PKM2 and p-Ser293 PDHA1 levels, respectively. Additionally, we found that the PDHA S293A dephospho-mimic reduced PKM2 levels and its associated enzyme activity. Treatment with MG132 and leupeptin impeded the PDHA1 S293A-mediated PKM2 reduction. These results suggest that the association between p-PDHA1 and PKM2 promotes their stability and protects them from protein degradation. Of interest, we observed that p-PDHA1 and PKM2 were localized in the nucleus in liver cancer patients. Under insulin stimulation, the knockdown of both PDHA1 and PKM2 led to a reduction in the expression of common genes, including KDMB1. These findings suggest that p-PDHA1 and PKM2 play a regulatory role in these proteins' expression and induce tumorigenesis in response to insulin.

Nrf2 Regulates the Expression of CYP2D6 by Inhibiting the Activity of Krüppel-Like Factor 9 (KLF9).

The aim of the present study is to gain insight into the biology of Parkinson's disease (PD) and cancer to drive translational advances enabling more effective prevention and/or potential treatments. The expression of Cytochrome P450 2D6 (CYP2D6) is correlated with various diseases such as PD and cancer; therefore, exploring its regulatory mechanism at transcriptional levels is of interest. NF-E2-related factor 2 (Nrf2) has been known to be responsible for regulating phase II and phase III drug-metabolizing genes. The objectives of this study are to investigate the transcriptional regulation of CYP2D6 by Nrf2 and to analyze its role in PD and cancer. Nrf2 was transiently expressed in human hepatoma Hep3B cells, and the expression of CYP2D6 was examined by RT-qPCR. The promoter activity of CYP2D6 and the DNA binding of Nrf2 were examined by luciferase and ChIP assay, respectively. We then investigated the expression and correlation of Nrf2 and CYP2D6 in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. In the present study, we demonstrated that Nrf2 down-regulated CYP2D6 mRNA expression in hepatoma Hep3B cells. Mechanistically, Nrf2 binds to the antioxidant responsive element (ARE) in the proximity of krüppel- like factor 9 (KLF9)-binding site within the -550/+51 of CYP2D6 promoter. The inhibition and activation of Nrf2 enhanced and suppressed KLF9 effects on CYP2D6 expression, respectively. The expression levels of Nrf2 and CYP2D6 were upregulated and downregulated in the PD patient GEO datasets compared to the healthy control tissues, and Nrf2 was negatively correlated with CYP2D6. In liver cancer patients, decreased CYP2D6 levels were apparent and associated with a lower probability of survival. Our work revealed the inhibitory role of Nrf2 in regulating CYP2D6 expression. Moreover, Nrf2- dependent regulation of CYP2D6 can be used as a prognostic factor and therapeutic strategy in PD and liver cancer.

A Four Amino Acid Metabolism-Associated Genes (AMGs) Signature for Predicting Overall Survival Outcomes and Immunotherapeutic Efficacy in Hepatocellular Carcinoma.

Metabolites are important indicators of cancer and mutations in genes involved in amino acid metabolism may influence tumorigenesis. Immunotherapy is an effective cancer treatment option; however, its relationship with amino acid metabolism has not been reported. In this study, RNA-seq data for 371 liver cancer patients were acquired from TCGA and used as the training set. Data for 231 liver cancer patients were obtained from ICGC and used as the validation set to establish a gene signature for predicting liver cancer overall survival outcomes and immunotherapeutic responses. Four reliable groups based on 132 amino acid metabolism-related DEGs were obtained by consistent clustering of 371 HCC patients and a four-gene signature for prediction of liver cancer survival outcomes was developed. Our data show that in different clinical groups, the overall survival outcomes in the high-risk group were markedly low relative to the low-risk group. Univariate and multivariate analyses revealed that the characteristics of the 4-gene signature were independent prognostic factors for liver cancer. The ROC curve revealed that the risk characteristic is an efficient predictor for 1-, 2-, and 3-year HCC survival outcomes. The GSVA and KEGG pathway analyses revealed that high-risk score tumors were associated with all aspects of the degree of malignancy in liver cancer. There were more mutant genes and greater immune infiltrations in the high-risk groups. Assessment of the three immunotherapeutic cohorts established that low-risk score patients significantly benefited from immunotherapy. Then, we established a prognostic nomogram based on the TCGA cohort. In conclusion, the 4-gene signature is a reliable diagnostic marker and predictor for immunotherapeutic efficacy.

Progress of Photodynamic Therapy in Hepatocellular Carcinoma Using Nano/Microtechnology

This article aims to examine the research advancements in photodynamic therapy (PDT) for hepatocellular carcinoma (HCC) utilizing nano/microtechnology. The objective is to provide valuable insights for disease prevention and control in patients with liver cancer (LC). LC is a prevalent form of cancer that inflicts significant suffering on patients. Early treatment plays a crucial role in improving the prognosis and enhancing the quality of life (QoL) for LC patients. While PDT has proven effective in treating surface and intracerebral tumors, studies focusing on intra-abdominal tumors, particularly liver tumors, are limited. Hence, it is essential to comprehend the clinical value and therapeutic outcomes of PDT for LC, particularly in the context of nano/microtechnology. With rapid advancements in nanotechnology, its integration into the medical field has grown extensively. By leveraging nanotechnology, the analysis of PDT’s effects on HCC yields significant clinical value. This article reviews the clinical diagnostic methods and therapeutic approaches for LC, emphasizes the impact of PDT on clinical outcomes for LC patients, and analyzes the progress of PDT applied to HCC under the framework of nano/microtechnology. The findings aim to offer valuable references for the clinical treatment of LC patients.

Outcomes of Liver Cancer Patients Undergoing Elective Surgery after Recovering from Mild SARS-CoV-2 Omicron Infection: A Retrospective Cohort Study.

With the emergence of new virus variants, limited data are available on the impact of SARS-CoV-2 Omicron infection on surgery outcomes in cancer patients who have been widely vaccinated. This study aimed to determine whether undergoing hepatectomy poses a higher risk of postoperative complications for liver cancer patients who have had mild Omicron infection before surgery. A propensity-matched cohort study was conducted at a tertiary liver center from 8 October 2022 to 13 January 2023. In total, 238 liver cancer patients who underwent hepatectomy were included, with 57 (23.9%) recovering from preoperative SARS-CoV-2 Omicron infection and 190 (79.8%) receiving COVID-19 vaccination. Pre- and post-matching, there was no significant difference in the occurrence of postoperative outcomes between preoperative COVID-19 recovered patients and COVID-19 negative patients. Multivariate logistic regression showed that the COVID-19 status was not associated with postoperative major pulmonary and cardiac complications. However, preexisting comorbidities (odds ratio [OR], 4.645; 95% confidence interval [CI], 1.295-16.667), laparotomy (OR, 10.572; 95% CI, 1.220-91.585), and COVID-19 unvaccinated (OR, 5.408; 95% CI, 1.489-19.633) had increased odds of major complications related to SARS-CoV-2 infection. In conclusion, liver cancer patients who have recovered from preoperative COVID-19 do not face an increased risk of postoperative complications.

Pre- and post-operative comprehensive nursing care versus conventional nursing care: An evaluation of quality of life, postoperative pain, adverse effects, and treatment satisfaction of patients who underwent surgeries and interventional therapies for liver cancer.

Interventional therapies including chemotherapies and radiotherapies are the most preferred treatment for liver cancer. However, these therapies have adverse effects. Therefore, careful care is required to relieve these adverse effects. The objectives of this study were to evaluate the quality of life, pain, anxiety, depression, adverse effects, and satisfaction of patients with liver cancer who received pre- and post-operative comprehensive nursing care against those of patients who received conventional nursing care. Patients with liver cancer who underwent surgeries and interventional therapies for liver cancer received pre- and post-operative comprehensive nursing care (CMN cohort, n = 105) or conventional nursing care (CNN cohort, n = 135), or did not receive any kind of nursing care (NNC cohort, n = 175). Before the non-treatment intervention(s) (BL), none of the patients had absent post-operative pain, all patients had mild or moderate anxiety and depression, and patients had ≤70 overall quality of life score. In the NNC cohort, a few of the patients reported being completely dissatisfied with overall personal satisfaction, and anxiety, depression, and overall the quality of life of patients were clinically worse during the follow-up period generally after completion of all doses of chemo radiotherapies (EL) as compared to BL. Hospital stays due to surgery, visual analog scale (VAS) score, Zung Self-rating Anxiety Scale score, the Self-rating Depression Scale score, and rehospitalization due to any reason(s) in follow-up were fewer and overall quality of life score and overall personal satisfaction score were higher for patients of the CMN cohort than those of patients at BL and those of patients of the CNN and the NNC cohorts at EL (P < .05 for all). Fever, bleeding, urinary retention, gastrointestinal disturbance, and hepatic and renal impairments reported in patients of the NNC cohort. Fever, bleeding, and urinary retention reported in patients of the CNN cohort (P < .05 for all). Nursing non-treatment intervention(s) is necessary for liver cancer patients after surgery, in the follow-up, and between 2 doses of chemoradiotherapies. Pre- and post-operative comprehensive nursing care relieves postoperative pain, psychological burden and improves quality of life in the follow-up period in patients who underwent surgeries and interventional therapies for liver cancer (Level of Evidence: IV; Technical Efficacy: Stage 5).

Analysis of the Effects of the WeChat Health Management Platform on the Self-Care Ability and Quality of Life of Patients with Liver Cancer Undergoing Interventional Therapy

Background: With the popularity of WeChat, Internet-based nursing approaches are gradually being applied to disease care, as they can better meet nursing requirements. Objectives: To explore the impact of the WeChat health management platform on the self-care ability and quality of life of patients with liver cancer undergoing interventional therapy Methods: A total of 82 patients with liver cancer who underwent interventional therapy were selected from January 2020 to January 2021 and randomly divided into the observation (n = 41) and control (n = 41) groups. The control group received routine nursing measures, while the observation group received the new nursing mode based on the WeChat health management platform. The WeChat health management platform can help patients develop health education plans, remind them of follow-up appointments, promote knowledge about nursing measures for liver cancer interventional therapies, provide feedback on medication use to doctors, and strengthen doctor–patient communication. The self-care ability and quality of life of the two groups of patients were compared before and after the intervention. Results: After the intervention, the Hamilton Anxiety Scale (HAMA) and Hamilton Rating Scale for Depression (HAMD) scores were lower in the patients of the observation group than those in the control group, indicating an improvement in the adverse moods and quality of life of patients in the observation group. Also, the psychological, physical, and social functions and overall health scores of patients in the observation group were higher than those in the control group (all P-values &lt; 0.05). Conclusions: The WeChat health management platform could improve the self-care ability of liver cancer patients undergoing interventional therapy and their mood and quality of life, which is worthy of clinical reference.

Examining the Mechanisms of Huachansu Injection on Liver Cancer through Integrated Bioinformatics Analysis.

The objective of this study is to explore the potential anti-liver cancer mechanism of Huachansu injection through integrated bioinformatics analysis. Active ingredients of Huachansu injection (extraction of toad skin) were obtained, and their potential drug targets were predicted via SwissTargetPrediction database. Liver cancer disease targets were identified from the GEO (Gene Expression Omnibus) dataset and four public databases. Then Protein-Protein Interaction (PPI) network of toad skin was constructed. GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed subsequently. Finally, molecular docking was performed using Auto Dock Vina. In the search for therapeutic targets, twenty active components of toad skin were screened for further study, five hundred and sixty-eight targets of components were identified. In the search for disease targets, three thousand two hundred and twenty-seven genes were identified after removal of duplicated genes, one hundred and fifty-nine genes were up-regulated in liver cancer samples while two hundred and seventy-eight were down-regulated in liver cancer patients. After predicting the therapeutic targets of the components, the results were cross-checked with the disease targets, thirteen up-regulated targets and ten down-regulated targets were obtained. Finally, in the results of molecular docking, seven targets (CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK) were potential up-regulated targets, three targets (SHBG, SRD5A2, NR1I2) were potential down-regulated targets, all of which have the best binding energy and molecular interactions. CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, and TTK could be potential upregulated target proteins of Huachansu injection for treating liver cancer. The mechanism of Huachansu injection in the treatment of liver cancer through these up-regulated targets is related to cell cycle, cellular senescence, viral carcinogenesis, p53 signaling pathway. SHBG, SRD5A2, and NR1I2 could be potential down-regulated target proteins of Huachansu injection in treating liver cancer.

The feasibility and safety of the brachial artery approach in the treatment of hepatic artery infusion chemotherapy: a retrospective study.

Compared to hepatic artery infusion chemotherapy (HAIC) treatment through the femoral artery (TFA), the brachial artery (TBA) is more flexible and easier for patients to accept. However, the feasibility of TBA has not been studied yet. This study aims to evaluate the feasibility and safety of HAIC via the TBA. We retrospectively reviewed the medical records of 63 patients with primary liver cancer who were treated with HAIC via TBA. In this study, a total of 163 HAIC procedures were performed via the left brachial artery pathway, and each patient underwent an average of 2.59 procedures. One patient received 5 treatments, 18 patients received 4 treatments, 15 patients received 3 treatments, 12 patients received 2 treatments, and 17 patients received 1 treatment. The main evaluation indicators were the technical success rate and complication rate. The main technical success rate was 99.4% (162/163). No patient required conversion to the femoral artery (TFA) access. All the complications were minor and occurred in 11 patients (6.75%). Subcutaneous ecchymosis occurred in 3 (1.84%) patients, arterial thrombosis in 2 patients (1.23%), and catheter displacement in 6 patients (3.68%). No serious complications occurred. TBA pathway is feasible and safe for HAIC treatment of liver cancer patients. More research is needed in the future to confirm whether TBA is superior to other pathways.

The integration of machine learning and multi-omics analysis provides a powerful approach to screen aging-related genes and predict prognosis and immunotherapy efficacy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with high incidence and mortality rates. Aging-related genes are closely related to the occurrence and development of cancer. Therefore, it is of great significance to evaluate the prognosis of HCC patients by constructing a model based on aging-related genes. Non-negative matrix factorization (NMF) clustering analysis was used to cluster the samples. The correlation between the risk score and immune cells, immune checkpoints, and Mismatch Repair (MMR) was evaluated through Spearman correlation test. Real Time Quantitative PCR (RT-qPCR) and immunohistochemistry were used to validate the expression levels of key genes in tissue and cells for the constructed model. By performing NMF clustering, we were able to effectively group the liver cancer samples into two distinct clusters. Considering the potential correlation between aging-related genes and the prognosis of liver cancer patients, we used aging-related genes to construct a prognostic model. Spearman correlation analysis showed that the model risk score was closely related to MMR and immune checkpoint expression. Drug sensitivity analysis also provided guidance for the clinical use of chemotherapy drugs. RT-qPCR showed that TFDP1, NDRG1, and FXR1 were expressed at higher levels in different liver cancer cell lines compared to normal liver cells. In summary, we have developed an aging-related model to predict the prognosis of hepatocellular carcinoma and guide clinical drug treatment for different patients.

Upregulation of Parkinson's disease-associated protein alpha-synuclein suppresses tumorigenesis via interaction with mGluR5 and gamma-synuclein in liver cancer

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer, indicating that PD-associated proteins may mediate the development of cancer. Here, we investigated a potential role of PD-associated protein α-synuclein in regulating liver cancer progression in vivo and in vitro. We found the negative correlation of α-synuclein with metabotropic glutamate receptor 5 (mGluR5) and γ-synuclein by analyzing the data from The Cancer Genome Atlas database, liver cancer patients and hepatoma cells with overexpressed α-synuclein. Moreover, upregulated α-synuclein suppressed the growth, migration, and invasion. α-synuclein was found to associate with mGluR5 and γ-synuclein, and the truncated N-terminal of α-synuclein was essential for the interaction. Furthermore, overexpressed α-synuclein exerted the inhibitory effect on hepatoma cells through the degradation of mGluR5 and γ-synuclein via α-synuclein-dependent autophagy-lysosomal pathway (ALP). Consistently, in vivo experiments with rotenone-induced rat model of PD also confirmed that, upregulated α-synuclein in liver cancer tissues through targeting on mGluR5/α-synuclein/γ-synuclein complex inhibited tumorigenesis involving in ALP-dependent degradation of mGluR5 and γ-synuclein. These findings give an insight into an important role of PD-associated protein α-synuclein accompanied by the complex of mGluR5/α-synuclein/γ-synuclein in distant communications between PD and liver cancer, and provide a new strategy in therapeutics for the treatment of liver cancer.

Nestin Expression and the Survival of Patients With Digestive Tract Cancers: A Systematic Review and Meta-Analysis.

Several cancers have been associated with poor prognoses based on nestin, a confirmed marker of cancer stem cells. However, there is conflicting evidence regarding the prognostic value of tumor nestin expression in patients with digestive tract cancers. An investigation of the association between nestin and survival in patients with digestive tract cancers was performed in this meta-analysis. Meta-analyses were conducted using PubMed, Embase, and Web of Science databases to search for cohort studies. We analyzed the data using a random-effects model that incorporates differences between studies. The pooled analysis showed a negative association between nestin expression and overall survival (hazard ratio: 1.38, 95% CI: 1.11 to 1.72, P = .004, I2 = 68%) and disease-free survival (hazard ratio: 1.48, 95% CI: 1.12 to 1.96, P = .005, I2 = 56%). Subgroup analysis showed that nestin expression was associated with poorer overall survival in gastric cancer (hazard ratio: 1.46, P < .001) and liver cancer (hazard ratio: 2.05, P < .001) patients, but not in colorectal cancer (hazard ratio: 1.03, P = .89) or pancreatic cancer (hazard ratio: 0.96, P = .80) patients. Further subgroup analysis showed a consistent association between nestin expression and poor overall survival in Asian and non-Asian studies, and in studies with univariate and multivariate regression models. To sum up, the presence of high nestin expression in digestive tract cancer patients is associated with poorer survival, particularly in patients with gastric and liver cancers.

Progress of PD-1/PD-L1 signaling in immune response to liver transplantation for hepatocellular carcinoma.

Primary liver cancer is one of the most common malignant tumors in China. The vast majority of primary liver cancer are hepatocellular carcinoma. Due to its high incidence and mortality from HCC, HCC has always been a feared type of cancer. Liver transplantation, as one of the important means to treat advanced liver cancer, has brought new hope to patients. However, as patients have been in a state of immunosuppression after liver transplantation, these patients face new problems of HCC recurrence and metastasis. A increasing number of studies have proved that blocking the PD-1/PD-L1 signaling pathway and restoring the immune killing inhibition of T cells can produce better therapeutic effects on tumors and chronic infectious diseases. As a promising treatment in the field of tumor immunotherapy, PD-1/PD-L1 inhibitors have achieved important results in liver cancer patients, but their application in liver transplantation patients is still highly controversial. This paper will introduce the mechanism of action of PD-1/PD-L1 signaling pathway and the current basic and clinical studies of PD-1/PD-L1 signaling pathway associated with immune response in HCC transplantation.