Hepatocellar Carcinoma Research Articles

Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients with Chronic Hepatitis B or C Infection

Abstract Background Hpatocellular carcinoma HCC is now the sixth most common cause of cancer worldwide. The second leading cause of cancer death after lung cancer in men is HCC. The most frequently used screening tests for HCC patients are hepatic ultrasound (US) with or without assessment of alpha-fetoprotein, but the diagnostic value of AFP is recently challenged due to its low sensitivity and specificity. So the aim of this study was to evaluate the role of mac 2 as a diagnostic marker in HCC Egyptian patients. Objective This study will assess the role of Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection. Patients and Methods This study had been carried out on 70 subjects, age range more than 18 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain Shams university hospitals from august 2022 to june 2023, after informed consent were taken from the patients Results This study was carried out on 70 participants divided into 2 group: 35 patient post viral cirrhotic patients with Hepatocellular Carcinoma, 35 patient post viral cirrhotic patients without hepatocellar Carcinoma selected from Ain Shams university hospitals, after informed consent were taken from the patients. Subjects were divided as follow: Group A (Hcc): 35 patients with Hepatocellular carcinoma, More than 18 years. Group B (Cirrhotic): 35 patients with liver cirrhosis without Hepatocellular carcinoma, age more than 18 years Conclusion We concluded from this study that: Serum Mac2 level was significantly higher in patients with HCC regardless of other characteristics as presence of combined conditions as DM and HTN or Viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. MAC 2 is more sensitive than AFP in differentiation between HCC and cirrhoitic patients but AFP is more specific. Using of mac 2 will improve the diagnostic field and can help in early detection of HCC in surveillance programs Together with AFP.

RETRACTED ARTICLE: Hepatic stellate cell mediates transcription of TNFSF14 in hepatocellular carcinoma cells via H2S/CSE-JNK/JunB signaling pathway

Hepatic stellate cells (HSC) and hydrogen sulfide (H2S) both play important roles in the development of hepatocellar carcinoma (HCC). Whereas, in the microenvironment of HCC, whether HSC participate in regulating the biological process of HCC cells by releasing H2S remains elusive. In vitro, Flow cytometry (FCM), CCK-8, RNA-sequencing, Western blotting, RT-qPCR, immunofluorescence and ChIP assays were carried out in the HCC cells to investigate the effect of H2S on biological functions and JNK/JunB-TNFSF14 signaling pathway. Specimens from HCC patients were analyzed by RT-qPCR and Western blotting assays for evaluating the expression of TNFSF14 and CSE. Statistical analysis was used to analyze the correlation between TNFSF14 expression and clinical data of HCC patients. Based on the FCM and CCK-8 results, we found the LX-2 cells were able to induce HCC cells apoptosis through releasing H2S. RNA-sequencing, RT-qPCR, and Western blotting results showed that TNFSF14 gene was upregulated in both LX-2 and NaHS group. NaHS treated in HCC cells led to JNK/JunB signaling pathway activating and greater binding of p-JunB to its responsive elements on TNFSF14 promoter. Impairment of TNFSF14 induction alleviated LX-2 and NaHS induced apoptosis of HepG2 and PLC/PRF/5 cells. Furthermore, TNFSF14 expression in HCC tissues was lower than the adjacent tissue. HCC patients with low expression of TNFSF14 had higher malignant degree and poor prognosis. In summary, demonstration of the involvement of HSC-derived H2S in JNK/JunB mediated expression of TNFSF14 gene strongly indicates H2S palys an important role in the regulation of HCC apoptosis.

Increased Estimated Tumour Size to Total Liver Volume Ratio is Associated with Worse Survival in Resectable Hepatocellular Carcinoma

Introduction: Tumour diameter is a known prognostic factor for hepatocellar carcinoma but does not fully reflect tumour burden. In this study we aim to explore the relationship between the estimated tumour volume to total liver volume ratio and overall survival. Method: Patients who were diagnosed of hepatocellular carcinoma with computer tomography (CT) liver volumetry performed during the period of November 2009 to November 2019 were included. Patients underwent hepatic resection were included. Estimated tumour volume (ETV) was defined as 2/3 x π x (largest tumour diameter/2)³ TLV was determined by CT volumetry. Statistical analysis with prospectively collected data was performed. Results: 143 patients was included in the study. The median ETV was 220.9cm3 (0.9—4188.8cm3). The median TLV was 1379.2cm3 (541.6—136524.0) and ETV:TLV ranges 0.0007—7.7341. The hazard ratio was 1.138 for diameter of largest tumour (p< 0.001) and was 1.540 for ETV:TLV (p< 0.001). The optimal cut-off value of ETV:TLV was 0.065 by the ROC curve. Survival analysis showed that patients with ETV:TLV < 0.065 had significantly better 5-year overall survival than those with ETV:TLV >/=0.065 (84.7% vs 45.3%; p< 0.001). 5-year disease free survival was also better in patients with ETV:TLV < 0.065 (50.7% vs 20.5%; p< 0.001). Conclusion: An increase in ETV:TLV to over 0.065 is associated with worse survival outcomes. This can be used as a prognostic tool in the management of HCC.

Imatinib and GNF-5 Exhibit an Inhibitory Effect on Growth of Hepatocellar Carcinoma Cells by Downregulating S-phase Kinase-associated Protein 2.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is one of the leading causes of cancer-related deaths worldwide. Imatinib and GNF-5 are breakpoint cluster region-Abelson murine leukemia tyrosine kinase inhibitors which have been approved for the treatment of chronic myeloid leukemia and various solid tumors. However, the effect and underlying mechanisms of imatinib and GNF-5 in HCC remain poorly defined. In this study, we investigated the anticancer activity and underlying mechanisms of imatinib and GNF-5 in HepG2 human hepatocarcinoma cells. Cell proliferation and anchorage-independent colony formation assays were done to evaluate the effects of imatinib and GNF-5 on the growth of HepG2 cells. The cell cycle was assessed by flow cytometry and verified by immunoblot analysis. Gene overexpression and knockdown assays were conducted to evaluate the function of S-phase kinase-associated protein 2 (Skp2). Imatinib and GNF-5 significantly inhibited the growth of HepG2 cells. Imatinib and GNF-5 induced G0/G1 phase cell cycle arrest by downregulating Skp2 and upregulating p27 and p21. Overexpression of Skp2 reduced the effect of imatinib and GNF-5 on HepG2 cells. Knockdown of Skp2 suppressed the proliferation and induced G0/G1 phase arrest. Furthermore, knockdown of Skp2 enhanced the effect of imatinib and GNF-5 on growth of HepG2 cells. In conclusion, imatinib and GNF-5 effectively suppress HepG2 cell growth by inhibiting Skp2 expression. Skp2 promotes the cell proliferation and reverse G0/G1 phase cell cycle arrest and it represents a potential therapeutic target for HCC treatment.

989P Effects of combination therapy using lenvatinib and anti-pd-1 antibody on liver function in patients with advanced hepatocellar carcinoma

989P Effects of combination therapy using lenvatinib and anti-pd-1 antibody on liver function in patients with advanced hepatocellar carcinoma

Comparison of Survival Rates Based on Recommended Treatment Algorithms of BCLC or HKLC Staging Systems for Hepatocellar Carcinoma Patients

Comparison of Survival Rates Based on Recommended Treatment Algorithms of BCLC or HKLC Staging Systems for Hepatocellar Carcinoma Patients

Colon perforation during sorafenib therapy for advanced hepatocelluar carcinoma. A case report.

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.

Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis

Chemo-resistance is a serious obstacle for successful treatment of cancer. Apigenin, a dietary flavonoid, has been reported as an anticancer drug in various malignant cancers. This study aimed to investigate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM. We observed that apigenin significantly enhanced doxorubicin sensitivity, induced miR-520b expression and inhibited ATG7-dependent autophagy in BEL-7402/ADM cells. In addition, we also showed that miR-520b mimics increased doxorubicin sensitivity and inhibited ATG7-dependent autophagy. Meanwhile, we indicated that ATG7 was a potential target of miR-520b. Furthermore, APG inhibited the growth of hepatocellar carcinoma xenografts in nude mice by up-regulating miR-520b and inhibiting ATG7. Our finding provides evidence that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-520b/ATG7 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma.

Antiproliferative Activity of Phenylpropanoids Isolated from Lagotis brevituba Maxim.

The aim of the present study was to evaluate the antiproliferative effect of phenylpropanoids isolated from the n-BuOH-soluble fraction of an ethanolic extract of Lagotis brevituba Maxim. The phenylpropanoids were identified as echinacoside, lagotioside, glucopyranosyl(1-6)martynoside, plantamoside, and verbascoside. Three of the compounds, lagotioside, glucopyranosyl(1-6)martynoside, and plantamoside, were isolated from L. brevituba for the first time. The antiproliferative activity of the isolates was evaluated in human gastric carcinoma (MGC-803), human colorectal carcinoma (HCT116), human hepatocellar carcinoma (HepG2), and human lung cancer (HCT116) cells using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Plantamoside showed promising activity against MGC-803 cells, with a half maximal inhibitory concentration value of 37.09μM. The mechanism of the pro-apoptosis effect of plantamoside was then evaluated in MGC-803 cells. Changes in cell morphology, including disorganization of the architecture of actin microfilaments and formation of apoptotic bodies, together with cell cycle arrest in G2/M phases, were observed after treatment of plantamoside. The antiproliferative and pro-apoptotic effects were associated with a decrease in the ratio of Bcl-2/Bax and reduced mitochondrial membrane potential, which was accompanied by the release of reactive oxygen species and Ca2+ into the cytoplasm. Taken together, the results indicated that plantamoside promotes apoptosis via a mitochondria-dependent mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

Simultaneous inhibition of growth and metastasis of hepatocellular carcinoma by co-delivery of ursolic acid and sorafenib using lactobionic acid modified and pH-sensitive chitosan-conjugated mesoporous silica nanocomplex

Co-delivery multiple drugs using nanocarriers has been recognized as a promising strategy for cancer treatment to enhance therapeutic efficacy. In this study, a pH sensitive mesoporous silica nanoparticles (MSN) based controlled release nanoparticles for co-delivery of sorafenib (SO), a multi-tyrosine kinase inhibitor, and ursolic acid (UA), a sensitive agent for SO, was developed, which was decorated with pH sensitive chitosan (CS) and lactobionic acid (LA) targeting to asialoglycoprotein receptor (ASGPR) over-expressing hepatocellar carcinoma cells (denoted as USMNs-CL). The nanocomplex enhanced bioavailability of hydrophobic drugs, efficient tumor cell targeting and exhibited pH-responsive function and sustained release profile. USMNs-CL showed synergistic cytotoxicity and could attenuate the adhesion, migration of ASGPR over-expressing liver cancer SMMC-7721cells at non-toxic concentrations. Moreover, the complex nanoparticles significantly increased the cellular apoptosis and down-regulated the expression of EGFR and VEGFR2 proteins related with cell proliferation and tumor angiogenesis. Invivo, compared with UA or SO alone, the nanocomplex significantly reduced the tumor burden in hepatocellular carcinoma (HCC) H22 tumor-bearing mice model and inhibited the lung metastasis in the H22 lung metastasis models. Overall, co-delivery of UA and SO by MSN-CS-LA nanocarriers could provide a promising strategy for HCC combinational therapy, especially for the HCC metastasis chemoprevention.

Expression of epithelial cell adhesion molecule associated with elevated ductular reactions in hepatocellar carcinoma

To evaluate the prognostic significance of the epithelial cell adhesion molecule (EpCAM) expression in HCC, the relationship between EpCAM with ductular reactions and other clinical features. From 2001 to 2003, 106 HCC patients who underwent curative resection in Eastern Hepatobiliary Hospital were enrolled. The expression of EpCAM in tumoral tissues and ductular reactions in paired non-tumoral tissues was assessed by immunohistochemistry. EpCAM was evaluated with prognosis, ductular reactions and other clinical variables. HCC expressing high level of EpCAM showed more aggressively than usual progressed HCC. High EpCAM expression was associated with poor overall survival and recurrence free survival. (P=0.0005, 0.0019, respectively). A close association was found between tumoral EpCAM expression and peritumoral ductular reactions. Patients with high level of ductular reactions tended to have higher EpCAM expression than those with low level (P=0.016). HCC stratification by EpCAM may reflect different prognosis. EpCAM expression correlated with ductular reactions may be a result of unregulated activation and differentiation blockage of progenitor cells.

Generation of liver-specific TGF-α and c-Myc-overexpressing fibroblasts for future creation of a liver cancer porcine model.

Liver cancer is one of the most serious life-threatening diseases in the world. Although the rodent model of hepatocellar carcinoma (HCC) is commonly used, it is limited when considering preclinical applications, including transarterial chemoembolization. The pig is a more appropriate model for applying preclinical procedures as it has similar anatomical and physiological characteristics to humans. In the current study, transgenic fibroblasts were generated that overexpressed two proto-oncogenes specifically in hepatocytes. Porcine TGF-α and c-myc genes were isolated and these were linked with the porcine albumin promoter, which has exhibited selective activity in liver cells. Targeting vectors were introduced into the porcine fibroblasts using a liposome-mediated delivery system and the transgenic cell line was screened with 3 weeks of G-418 treatment. Selected vector‑positive colonies were further confirmed with polymerase chain reaction-based genotyping. Thus, the transgenic cell lines created in the current study should induce liver cancer in pig models following somatic cell nuclear transfer.

Clinical study on the sensitivity test guided hepato-arterial/portal-vein chemotherapy in patients with unresectable hepatocellar carcinoma

Purpose: Approximately 20 % of tumors have the opportunity to be resected in patients with hepatocellar carcinoma (HCC) and their prognoses were acceptable. For the unrespectable HCC, however, the outcomes were rather poor because the specialty of the tumor blood supply and the tumor was insensitive to the chemotherapy drug. The objective of this study was to find sensitive drugs for individual patients and determine the safety and antitumor activity of hepatic intra-arterial and portal vein infusion chemotherapy. Methods : A total of 120 patients with the mean patient age of 56 years and with unresectable HCC were randomly divided into experimental group and control group. The experiment group was infused through an intra-arterial and portal vein catheter 3 different drugs were chosen by the results of drug sensitive test, whereas the control group was treated for TACE. The changes in tumor-size and AFP, two-step operation rate, survival rate, and complications were observed in these patients. Results: The tumor size reduced in 28(47.6 %) cases, stabilized in 14(23.3 %) cases, and progressed in 18(30 %) cases in experimental group as measured by CT or MRI after six chemotherapy cycles, whereas the corresponding data was 17(28.5 %) cases, 7(11.5 %) cases and 36(60 %) cases in the control group (P &lt; 0.05). The AFP was declined in 51 cases in experimental group and in 30 cases in control group (P &lt; 0.05). In the experimental group, the median follow-up time was 21 months; the overall survival rates (OS) of 6 months, 12 months, and 18 months were 86 %, 72 %, and 65 %, respectively. In the control group, the median follow-up time was 16 months; the OS rates of 6 months and 12 months were 58 % and 40 %, respectively. Six patients in the experimental group and 3 patients in the control group had two-step operation. There was no severe incidence of complications in both groups. In the experimental group, 2 (3 %) patients had wound infection, 8 cases had the chemotherapy relative diarrhea, and 18 (30 %) cases had grade Ⅰ or Ⅱ bone marrow suppression. In the control group, the chemotherapy relative diarrhea were 15 (25 %) cases and grade Ⅰ or Ⅱ bone marrow suppression were 33 (55 %) cases. Conclusion : The artery and portal vein pump transfusion chemotherapy guided by drug sensitive test was efficient for HCC treatment. The patients can get longer OS and lower complication incidence. -------------------------------------------------------- Cite this article as: Wu D, Wei S, Luo C, Wu X, Feng Y, Zhang F, Nie L, Xia X. Clinical study on the sensitivity test guided hepato-arterial/portal -vein chemotherapy in patients with unresectable hepatocellar carci-noma. Int J Cancer Ther Oncol 2014; 2(2):02029. DOI: 10.14319/ijcto.0202.9

Fatal Tumor Lysis Syndrome Following Sorafenib Treatment

Sorafenib is one of the few approved treatments for advanced hepatocellar carcinoma. It is an oral multi-targeted tyrosine kinase inhibitor. It could be associated with a wide variety of adverse effects. However tumor lysis syndrome was reported in 2 cases only following sorafenib treatment. Here we report a fatal case of tumor lysis syndrome 3 weeks following sorafenib treatment in a patient with advanced hepatitis B virus-related hepatocellular carcinoma. We suggest using preventing measures for TLS prior to initiation of such treatment. J Med Cases. 2013;4(4):269-270 doi: https://doi.org/10.4021/jmc1049w

Association Between Insulin-like Growth Factor-2 Expression and Prognosis after Transcatheter Arterial Chemoembolization and Octreotide in Patients with Hepatocellar Carcinoma

To investigate the association between the change of IGF-2 level in serum after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) progression, especially in relation to metastasis. IGF-2 in serum was measured by quantitative sandwich enzyme-linked immunosorbent assay before, 3 days and 4 weeks after TACE in 60 patients with HCC. The occurrence of HCC metastasis was also evaluated, 3 months after TACE. (1) The average serum level of IGF-2 in the 60 patients with HCC was 136.5 ± 87.3 pg/ml; (2) A tendency for increase was observed with heterogenous uptake of octreotide and portal vein thrombosis. Metastatic foci were found in 37/38 patients in the group with IGF-2 increasing (97.0%), in contrast to 3/22 (13.6%) patients with IGF-2 decrease. The increase of IGF-2 level in serum appears to be associated with the occurrence of metastatic HCC after TACE and chemotherapy.

Colon Perforation during Sorafenib Therapy for Advanced Hepatocelluar Carcinoma. A Case Report

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.

The efficacy and safety of transcatheter arterial chemoembolization combined with Endostar for primary hepatocellar carcinoma

Objective:To investigate the efficacy and safety of combined therapy of transcatheter arterial chemoembolization with Endostar for primary hepatocellular carcinoma.Methods:Fifty patients with hepatocellar carcinoma were given the combined therapy of transcatheter arterial chemoembolization with Endostar.The adverse reaction and short-term efficacy were evaluated after the combined therapy to evaluate the safety and efficacy of the combined therapy.Results:After the 50 patients with hepatocellar carcinoma received the combined therapy of transcatheter arterial chemoembolization with Endostar,the mainly observed adverse effects were Ⅰ to Ⅱ degree neutropenia and elevation in hepatic enzymes.No severe adverse effects were observed in our study.The results of short-term efficacy showed that among the 50 patients with hepatocellular carcinoma 3 had partial response(PR),40 had stable disease(SD),and 7 had progressive disease(PD).Disease control rate(DCR) was 86.0%.Conclusion:Transcatheter arterial chemoembolization combined with Endostar was safe and effective in the treatment of primary hepatocellular carcinoma.

Distinct effect of Chrysanthemum indicum Linné extracts on isoproterenol-induced growth of human hepatocellular carcinoma cells

Chrysanthemum indicum Linné (Asteraceae) is a common Chinese herbal medicine that has been traditionally used for the treatment of inflammation, hypertension and neoplastic diseases in China. However, the mechanism that account for the inhibitory activity of Chrysanthemum indicum Linné against cancer cells is poorly understood. We investigated the effect of Chrysanthemum indicum Linné extracts (CILE) on isoproterenol (ISO) induced growth of human hepatocellar carcinoma (HCC) cells in correlation with the intracellular activity of MAPK/ERK1/2. We found that CILE was effective in attenuating the mitogenic effect of ISO on both HepG2 and MHCC97H cells. The inhibitory effect of CILE was mediated by inhibiting the ISO-induced activation of MAPK/ERK1/2 via beta2-AR in tumor cells. Our findings will be helpful in understanding the anticancer mechanism of CILE.

A case-control study on relationship between attack of primary hepatocellar carcinoma and psychological factors

目的 探讨心理因素对原发性肝癌的影响规律.方法 对温州地区180例原发性肝癌进行1:1配对病例对照研究.结果 通过条件Logistic模型分析,发现强迫、抑郁、敌对、焦虑与肝癌的发生存在显著相关.其OR值分别为3.216、5.799、4.036.结论 强迫、抑郁、焦虑是温州地区原发性肝癌危险因素。

A case of hepatocellar carcinoma associated with mixed connective tissue disease

A case of hepatocellar carcinoma associated with mixed connective tissue disease