scholarly journals Circulating cell-free mtDNA content is associated with outcome of HCC patients receiving TACE combined with traditional Chinese medicine treatment

Author(s):  
Guanlin Zhou ◽  
Ying Li ◽  
Shicheng Li ◽  
Hongxia Liu ◽  
Fei Xu ◽  
...  

Abstract Objectives: Hepatocellular carcinoma (HCC) accounts for 70%-85% of liver cancer, and about 85% of HCC are hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) in china. Most patients are already in the middle or late stages of the disease at the time of diagnosis, trans-hepatic arterial chemoembolization (TACE) combine with traditional Chinese medicine (TCM) have been reported as an effective treatment, and effective prognostic molecular markers are helpful to predict therapeutic efficacy. In this study, we aim to explore whether circulating cell-free mitochondrial DNA (ccf-mtDNA) content is associated with the outcome for HCC patients receiving TACE combine with TCM treatment. Method: Retrospective analysis was conducted in a cohort with 141 HBV-HCC patients. Univariate and multivariate analysis was conducted with Cox proportional risk regression model to explore the correlation between ccf-mtDNA content and patient prognosis. Kaplan-Meier method was used to draw the survival curve of ccf-mtDNA content and the survival prognosis of patients. Results: (1) high content of serum ccf-mtDNA is an independent risk factor for the prognosis of HBV-HCC patients treated with TACE combined with TCM adjuvant therapy (HR=4.010, 95%IC=1.252-12.844, P = 0.019). (2) K-M survival analysis showed that patients with high ccf-mtDNA content had poor prognosis (Log Rank P=0.027). Conclusions: Our findings suggest that ccf-mtDNA is a potential novel non-invasive biomarker for prognosis of HCC patients receiving TACE combine with TCM treatment.

2021 ◽  
Vol 11 ◽  
Author(s):  
Wentao Jia ◽  
Shufang Liang ◽  
Binbin Cheng ◽  
Changquan Ling

Invasion and metastasis are the main reasons for the high mortality of liver cancer, which involve the interaction of tumor stromal cells and malignant cells. Cancer-associated fibroblasts (CAFs) are one of the major constituents of tumor stromal cells affecting tumor growth, invasion, and metastasis. The heterogeneous properties and sources of CAFs make both tumor-supporting and tumor-suppression effects possible. The mechanisms for CAFs in supporting hepatocellular carcinoma (HCC) progression can be categorized into upregulated aggressiveness and stemness, transformed metabolism toward glycolysis and glutamine reductive carboxylation, polarized tumor immunity toward immune escape of HCC cells, and increased angiogenesis. The tumor-suppressive effect of fibroblasts highlights the functional heterogenicity of CAF populations and provides new insights into tumor–stromal interplay mechanisms. In this review, we introduced several key inflammatory signaling pathways in the transformation of CAFs from normal stromal cells and the heterogeneous biofunctions of activated CAFs. In view of the pleiotropic regulation properties of traditional Chinese medicine (TCM) and heterogeneous effects of CAFs, we also introduced the application and values of TCM in the treatment of HCC through targeting CAFs.


2016 ◽  
Vol 16 (4) ◽  
pp. 597-604 ◽  
Author(s):  
Chen Jianxin ◽  
Xu Qingxia ◽  
Wang Junhui ◽  
Zheng Qinhong

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Although surgery is known as the most promising radical treatment, a high recurrent or metastatic rate after surgery has limited its clinical efficacy. Sorafenib, a target agent, has seemed to be the only option for metastatic HCC patients to date, but none of clinical trials showed it could prolong the overall survival (OS) of advanced HCC to 1 year. How to prolong the OS and improve cure rate of HCC patients is still beset with difficulties. This report presents a rare case of recurrent HCC patient with complete regression of target lesion with 2 years of Chinese herbal treatment. A 64-year-old Chinese man with hepatitis B virus–associated chronic hepatitis presented HCC has been clinically diagnosed tumor relapse and omentum metastasis with computed tomography and α-fetoprotein blood test 4 months after surgery. It was decided the patient would receive traditional Chinese medicine treatment because of poor prognosis. After approximately 2 years of treatment, recurrent hepatic tumor and omentum metastasis have been found in complete regression. The patient remains alive over 31 months after relapse.


2021 ◽  
Vol 12 ◽  
Author(s):  
Guanlin Zhou ◽  
Ying Li ◽  
Shicheng Li ◽  
Hongxia Liu ◽  
Fei Xu ◽  
...  

Hepatocellular carcinoma (HCC) accounts for 70–85% of liver cancer, and about 85% of HCC are hepatitis B virus-related (HBV-HCC) in China. Transarterial chemoembolization (TACE) combined with traditional Chinese medicine (TCM) has been reported as an effective treatment. Potential biomarkers to stratify patients who may benefit from this treatment are needed. In this study, we aimed to evaluate whether circulating cell-free mitochondrial DNA (ccf-mtDNA) content was associated with the outcome of HCC patients, especially of those who received the combination treatment of TACE and TCM. Univariate and multivariate Cox analyses were conducted to evaluate the association between ccf-mtDNA content and the overall survival of HBV-HCC patients. Kaplan–Meier analysis was used to compare the survival differences between patients with low and high ccf-mtDNA content. In a hospital-based cohort with 141 HBV-HCC patients, there was no statistically significant association between the ccf-mtDNA content and the overall survival of HBV-HCC patients in the univariate analysis, but a borderline significant association was found in the multivariate analyses. In a subcohort of 50 HBV-HCC patients who received TACE and TCM treatment, high ccfDNA content conferred an increased death risk with a hazard ratio of 4.01 (95% confidence interval: 1.25–12.84, p = 0.019) in the multivariate analysis. Kaplan–Meier survival analysis also showed that patients with high ccf-mtDNA content had unfavorable survival (log rank p = 0.097). Our findings suggest that ccf-mtDNA content is a potential non-invasive prognostic biomarker in HCC patients receiving TACE and TCM treatment.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052093128
Author(s):  
Qiuwei Li ◽  
Liying Guo ◽  
Li Wang ◽  
Jing Miao ◽  
Huantian Cui ◽  
...  

Objective To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation. Methods Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52 ± 2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples. Results Microflora of gold juice exhibited considerable changes following “ancient method” processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, Bacteroides, and Prevotella 9. Conclusions This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10745
Author(s):  
Qin Zhang ◽  
Zhangying Feng ◽  
Mengxi Gao ◽  
Liru Guo

Background SiNiSan (SNS) is an ancient traditional Chinese medicine (TCM) used to treat liver and spleen deficiencies. We studied the unique advantages of using SNS to treat hepatocellular carcinoma (HCC) with multiple components and targets to determine its potential mechanism of action. Methods The active compounds from the individual herbs in the SNS formula and their targets were mined from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). HCC-associated targets were collected from the TCGA and GEO databases and samples were collected from patients with stage III hepatocellular carcinoma. A compound-disease target network was constructed, visualized, and analyzed using Cytoscape software. We built a protein-protein interaction (PPI) network using the String database. We enriched and analyzed key targets using GSEA, GO, and KEGG in order to explore their functions. Autodock software was used to simulate the process of SNS molecules acting on HCC targets. Results A total of 113 candidate compounds were taken from SNS, and 64 of the same targets were chosen from HCC and SNS. The predominant targets genes were PTGS2, ESR1, CHEK1, CCNA2, NOS2 and AR; kaempferol and quercetin from SNS were the principal ingredients in HCC treatment. The compounds may work against HCC due to a cellular response to steroid hormones and histone phosphorylation. The P53 signaling pathway was significantly enriched in the gene set GSEA enrichment analysis and differential gene KEGG enrichment analysis. Conclusions Our results showed that the SNS component has a large number of stage III HCC targets. Among the targets, the sex hormone receptors, the AR and ESR1 genes, are the core targets of SNS component and the most active proteins in the PPI network. In addition, quercetin, which has the most targets, can act on the main targets (BAX, CDK1, CCNB1, SERPINE1, CHEK2, and IGFBP3) of the P53 pathway to treat HCC.


2021 ◽  
Author(s):  
Qing-Juan Wu ◽  
Wen-Liang Lv ◽  
Juan-Mei Li ◽  
Ting-Ting Zhang ◽  
Wen-Hui Zhou ◽  
...  

Abstract Introduction: Hepatitis B-related compensated liver cirrhosis is related to higher risk of hepatocellular carcinoma, anti-viral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aim to test the integrative medicine (chinese medicine plus anti-riral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis B-related compensated liver cirrhosis.Methods and Analysis: This is a multicentre randomised controlled trial, total 5 hospitals and 802 patients will involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction(YQSHD) group (n=401) or the placebo group (n=401). The YQSHD group receives YQSHD granule with Entecavir(ETV), the placebo group receives YQSHD placebo with ETV. Treatment period will last for 52 weeks, and follow-up period for 52±2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. Objective of this trial is “the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%”.Ethics and dissemination:The protocol has been approved by the Medical Ethics Committee of Guang’anmen Hospital, China (No.2019-006-KY), and the other centres in the trial will not begin recruiting until local ethical approval has been obtained.Trial final results will be disseminated via publication. Trial registration: ChiCTR1900021532, this protocol was registered in the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/searchproj.aspx) on February 26th, 2019.


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