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Sample records for characterizing hcv-related hepatocellular

  1. Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

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    Buonaguro Luigi

    2009-10-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is a major cause of hepatocellular carcinoma (HCC worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls. Methods Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001. Results Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart. Conclusion In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection

  2. Low-dose intermittent interferon-alpha therapy for HCV-related liver cirrhosis after curative treatment of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the efficacy of low-dose intermittent interferon (JFN) therapy in patients with hepatitis C virus (HCV)-related compensated cirrhosis who had received curative treatment for primary hepatocellular carcinoma (NCC).METHODS: We performed a prospective case controlled study. Sixteen patients received 3 MIU of natural IFN-alpha intramuscularly 3 times weekly for at least 48 wk (IFN group). They were compared with 16 matched historical controls (non-JFN group).RESULTS: The cumulative rate of first recurrence of HCC was not significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 68.6% vs 80% at 1-and 3-year, P=0.157, respectively).The cumulative rate of second recurrence was not also significantly different between the IFN group and the non-IFN group (0% vs 6.7% and 35.9% vs 67% at 1-and 3-year, P=0.056, respectively). Although the difference in the Child-Pugh classification score between the groups at initial treatment of HCC was not significant, the score was significantly worse at the time of data analysis in the non-IFN group than IFN group (7.19±1.42 vs 5.81±0.75, P=0.0008). The cumulative rate of deviation from objects of any treatment for recurrent HCC was also higher in the non-IFN group than IFN group (6.7% and 27% vs 0 and 0% at 1- and 3-year, P=0.048, respectively).CONCLUSION: Low-dose intermittent IFN-alpha therapy for patients with HCV-related compensated cirrhosis after curative HCC treatment was effective by making patients tolerant to medical or surgical treatment for recurrent HCC in the later period of observation.

  3. Interferon plus ribavirin and interferon alone in preventing hepatocellular carcinoma:A prospective study on patients with HCV related cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Francesco Azzaroli; Antonio Colecchia; Constance Mwangemi; Davide Festi; Enrico Roda; Massimo Derenzini; Giuseppe Mazzella; Esterita Accogli; Giovanni Nigro; Davide Trerè; Silvia Giovanelli; Anna Miracolo; Francesca Lodato; Marco Montagnani; Mariarosa Tamé

    2004-01-01

    AIM: To determine the role of interferon (IFN) with or without ribavirin in preventing or delaying hepatocellular carcinoma (HCC) development in patients with hepatitis C virus (HCV)related cirrhosis. Data on the preventive effect of IFN plus ribavirin treatment are lacking.METHODS: A total of 101 patients (62 males and 39 females,mean age 55.1±1.4 years) with histologically proven HCV related liver cirrhosis plus compatible biochemistry and ultrasonography were enrolled in the study. Biochemistry and ultrasonography were performed every 6 mo. Ultrasound guided liver biopsy was performed on all detected focal lesions. Follow-up lasted for 5 years. Cellular proliferation,evaluated by measuring Ag-NOR proteins in hepatocytes nuclei, was expressed as AgNOR-Proliferative index (AgNOR-PI) (cut-off = 2.5). Forty-one patients (27 males,14 females) were only followed up after the end of an yearly treatment with IFN-alpha2b (old treatment control group = OTCG). Sixty naive patients were stratified according to sex and AgNOR-PI and then randomized in two groups:30 were treated with IFN-alpha2b + ribavirin (treatment group = TG), the remaining were not treated (control group = CG). Nonresponders (NR) or relapsers in the TG received further IFN/ribavirin treatments after a 6 mo of withdrawal.RESULTS: AgNOR-PI was significantly lowered by IFN (P<0.001). HCC incidence was higher in patients with AgNOR-PI>2.5 (26% vs3%, P<0.01). Two NR in the OTCG,none in the TG and 9 patients in the CG developed HCC during follow-up. The Kaplan-Mayer survival curves showed statistically significant differences both between OTCG and CG (P<0.004) and between TG and CG (P<0.003).CONCLUSION: IFN/ribavirin treatment associated with retreatment courses of NR seems to produce the best results in terms of HCC prevention. AgNOR-PI is a useful marker of possible HCC development.

  4. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

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    Simon, Elana P.; Freije, Catherine A.; Farber, Benjamin A.; Lalazar, Gadi; Darcy, David G.; Honeyman, Joshua N.; Chiaroni-Clarke, Rachel; Dill, Brian D.; Molina, Henrik; Umesh K Bhanot; La Quaglia, Michael P.; Rosenberg, Brad R.; Simon, Sanford M.

    2015-01-01

    Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare pediatric liver cancer. A deletion of ∼400 kb in one copy of chromosome 19 results in a chimeric protein, an activated protein kinase A. No other deletions, amplifications, mutations, or structural variants were found. This strongly implicates the chimera as the driving mutation. This paper examines gene expression in FLHCC. The results establish FLHCC as a single disease distinct from other cancers, including hepatocellular carcinoma. ...

  5. Cryoglobulinemia in elderly patients with HCV-related chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Francesco; Giuseppe; Foschi; Anna; Chiara; Dall’Aglio; Arianna; Lanzi; Giorgio; Marano; Sara; Savini; Pietro; Andreone; Mauro; Bernardi; Giuseppe; Francesco; Stefanini

    2010-01-01

    Hepatitis C virus(HCV) infection affects about 3% of the world’s population and often leads to chronic liver disease.In some industrialized countries,HCV prevalence increases with age,but the optimal management of older patients has not been accurately defined.HCV infection can also lead to lymphoproliferative disorders,the most common being mixed cryoglobulinemia(MC),and also for this condition that frequently affects elderly patients,the optimal therapeutic strategy is still debated.We report the case of a 77-year-old Caucasian woman with HCV-related chronic hepatitis and cutaneous manifestations consisting of urticaria and pruritus related to MC resistant to antihistamines.The patient underwent a treatment with interferon and ribavirin.Such a treatment led to early biochemical and virological response associated with the resolution of cryoglobulinemia and cutaneous symptoms.After the end of treatment,HCV replication relapsed,but cryoglobulinemia and cutaneous symptoms did not recur.In the absence of definite treatment guidelines in this particular context,our experience suggests that the presence of symptoms related to HCV-infection that deeply affect patient quality of life warrants antiviral therapy even beyond the age limits that currently exclude patients from treatment.

  6. HCV-related liver cancer in people with haemophilia

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    Meijer, K.; Haagsma, E. B.

    2012-01-01

    . The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long-term sequelae, one of which is liver cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC).

  7. Hepatitis C Virus and Hepatocellular Carcinoma

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    Masao Omata

    2013-01-01

    Full Text Available Hepatitis C virus (HCV, a hepatotropic virus, is a single stranded-positive RNA virus of ~9,600 nt. length belonging to the Flaviviridae family. HCV infection causes acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC. It has been reported that HCV-coding proteins interact with host-cell factors that are involved in cell cycle regulation, transcriptional regulation, cell proliferation and apoptosis. Severe inflammation and advanced liver fibrosis in the liver background are also associated with the incidence of HCV-related HCC. In this review, we discuss the mechanism of hepatocarcinogenesis in HCV-related liver diseases.

  8. PPARs and HCV-Related Hepatocarcinoma: A Mitochondrial Point of View

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    Francesca Agriesti

    2012-01-01

    Full Text Available Hepatitis-C-virus-related infective diseases are worldwide spread pathologies affecting primarily liver. The infection is often asymptomatic, but when chronically persisting can lead to liver scarring and ultimately to cirrhosis, which is generally apparent after decades. In some cases, cirrhosis will progress to develop liver failure, liver cancer, or life-threatening esophageal and gastric varices. HCV-infected cells undergo profound metabolic dysregulation whose mechanisms are yet not well understood. An emerging feature in the pathogenesis of the HCV-related disease is the setting of a pro-oxidative condition caused by dysfunctions of mitochondria which proved to be targets of viral proteins. This causes deregulation of mitochondria-dependent catabolic pathway including fatty acid oxidation. Nuclear receptors and their ligands are fundamental regulators of the liver metabolic homeostasis, which are disrupted following HCV infection. In this contest, specific attention has been focused on the peroxisome proliferator activated receptors given their role in controlling liver lipid metabolism and the availability of specific pharmacological drugs of potential therapeutic utilization. However, the reported role of PPARs in HCV infection provides conflicting results likely due to different species-specific contests. In this paper we summarize the current knowledge on this issue and offer a reconciling model based on mitochondria-related features.

  9. Treatment of Patients With HCV Related Cirrhosis: Many Rewards With Very Few Risks

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    Alessio Aghemo

    2012-06-01

    Full Text Available Antiviral treatment of chronic hepatitis C virus (HCV is aimed at the persistent eradication of the virus, the so-called sustained virological response (SVR, with the aim ultimately being to prevent the development of liver-related complications and improve patients’ survival. Patients with HCV-related compensated cirrhosis are the group most likely to benefit from viral clearance, as several retrospective studies have shown liver complications rates to be positively modified by the achievement of a SVR. Whether these benefits rely on viral clearance or on the histological improvements seen following successful interferon (IFn-based therapies has recently been a matter for debate, as studies have shown cirrhosis to regress in some patients with a SVR. Whatever the mechanisms, cirrhosis has the uncanny ability to be both a dominant indication for therapy, as well as one of the strongest baseline factors associated with reduced efficacy of any IFn-based regimen. This has led to the development of alternative treatment strategies, such as low dose pegylated IFn (PegIFn monotherapy, that unfortunately has proven to be of limited efficacy. For this reason regimens able to clear the virus without relying on the broad antiviral effect of IFN are eagerly awaited.

  10. Potential of G-CSF supplementation to counter the neutrophil effects of standard PEG-IFNα plus ribavirin combination therapy for treating HCV-related cirrhosis

    Institute of Scientific and Technical Information of China (English)

    孙素梅

    2013-01-01

    Objective To investigate the effects of the granulocyte colony stimulating factor (G-CSF) with pegylated interferon alpha (PEC-IFNα) plus ribavirin (RBV) and PEG-IFNαreduction in the treatment of the compensatory hepatitis C virus (HCV) -related cirrhosis.Methods Fourty-eight patients with compensatory HCV-related

  11. Immune signatures in human PBMCs of idiotypic vaccine for HCV-related lymphoproliferative disorders

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    Romagnoli Luca

    2010-02-01

    Full Text Available Abstract Hepatitis C virus (HCV is one of the major risk factors for chronic hepatitis, which may progress to cirrhosis and hepatocellular carcinoma, as well as for type II mixed cryoglobulinemia (MC, which may further evolve into an overt B-cell non-Hodgkin's lymphoma (NHL. It has been previously shown that B-cell receptor (BCR repertoire, expressed by clonal B-cells involved in type II MC as well as in HCV-associated NHL, is constrained to a limited number of variable heavy (VH- and light (VL-chain genes. Among these, the VK3-20 light chain idiotype has been selected as a possible target for passive as well as active immunization strategy. In the present study, we describe the results of a multiparametric analysis of the innate and early adaptive immune response after ex vivo stimulation of human immune cells with the VK3-20 protein. This objective has been pursued by implementing high-throughput technologies such as multiparameter flow cytometry and multiplex analysis of cytokines and chemokines.

  12. Liver Stiffness Measurement by Fibroscan Predicts the Presence and Size of Esophageal Varices in Egyptian Patients with HCV Related Liver Cirrhosis

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    Saad, Yasmin; Said, Mohamed; Idris, Mohamed O.; Rabee, Ayman; Zakaria, Salama

    2013-01-01

    Background and Aim: Liver stiffness measured by transient elastgraphy correlates with Hepatic vein pressure gradient, liver Stiffness value of 21 kpa predicts significant portal hypertension. Aim is to predict esophageal varices presence by fibroscan and possible grading by degree of liver stiffness in HCV related cirrhotic patients.

  13. Establishment and characterization of 7 novel hepatocellular carcinoma cell lines from patient-derived tumor xenografts.

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    Hong Xin

    Full Text Available Hepatocellular carcinoma (HCC is a common cancer with poor prognosis worldwide and the molecular mechanism is not well understood. This study aimed to establish a collection of human HCC cell lines from patient-derived xenograft (PDX models. From the 20 surgical HCC sample collections, 7 tumors were successfully developed in immunodeficient mice and further established 7 novel HCC cell lines (LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, LIXC012 and CPL0903 by primary culture. The characterization of cell lines was defined by morphology, growth kinetics, cell cycle, chromosome analysis, short tandem repeat (STR analysis, molecular profile, and tumorigenicity. Additionally, response to clinical chemotherapeutics was validated both in vitro and in vivo. STR analysis indicated that all cell lines were unique cells different from known cell lines and free of contamination by bacteria or mycoplasma. The other findings were quite heterogeneous between individual lines. Chromosome aberration could be found in all cell lines. Alpha-fetoprotein was overexpressed only in 3 out of 7 cell lines. 4 cell lines expressed high level of vimentin. Ki67 was strongly stained in all cell lines. mRNA level of retinoic acid induced protein 3 (RAI3 was decreased in all cell lines. The 7 novel cell lines showed variable sensitivity to 8 tested compounds. LIXC011 and CPL0903 possessed multiple drug resistance property. Sorafenib inhibited xenograft tumor growth of LIXC006, but not of LIXC012. Our results indicated that the 7 novel cell lines with low passage maintaining their clinical and pathological characters could be good tools for further exploring the molecular mechanism of HCC and anti-cancer drug screening.

  14. Establishment and Characterization of 7 Novel Hepatocellular Carcinoma Cell Lines from Patient-Derived Tumor Xenografts

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    Hu, Gang; Xie, Fubo; Ouyang, Kedong; Tang, Xuzhen; Wang, Minjun; Wen, Danyi; Zhu, Yizhun; Qin, Xiaoran

    2014-01-01

    Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis worldwide and the molecular mechanism is not well understood. This study aimed to establish a collection of human HCC cell lines from patient-derived xenograft (PDX) models. From the 20 surgical HCC sample collections, 7 tumors were successfully developed in immunodeficient mice and further established 7 novel HCC cell lines (LIXC002, LIXC003, LIXC004, LIXC006, LIXC011, LIXC012 and CPL0903) by primary culture. The characterization of cell lines was defined by morphology, growth kinetics, cell cycle, chromosome analysis, short tandem repeat (STR) analysis, molecular profile, and tumorigenicity. Additionally, response to clinical chemotherapeutics was validated both in vitro and in vivo. STR analysis indicated that all cell lines were unique cells different from known cell lines and free of contamination by bacteria or mycoplasma. The other findings were quite heterogeneous between individual lines. Chromosome aberration could be found in all cell lines. Alpha-fetoprotein was overexpressed only in 3 out of 7 cell lines. 4 cell lines expressed high level of vimentin. Ki67 was strongly stained in all cell lines. mRNA level of retinoic acid induced protein 3 (RAI3) was decreased in all cell lines. The 7 novel cell lines showed variable sensitivity to 8 tested compounds. LIXC011 and CPL0903 possessed multiple drug resistance property. Sorafenib inhibited xenograft tumor growth of LIXC006, but not of LIXC012. Our results indicated that the 7 novel cell lines with low passage maintaining their clinical and pathological characters could be good tools for further exploring the molecular mechanism of HCC and anti-cancer drug screening. PMID:24416385

  15. Characterization of hepatocellular carcinoma (HCC) lesions using a novel CT-based volume perfusion (VPCT) technique

    International Nuclear Information System (INIS)

    Highlights: • Quantification of perfusion with VPCT has great potential for functional imaging. • We present our preliminary results of perfusion parameters (Blood Flow, Blood Volume and kk-trans) of hepatocellular carcinoma (HCC) in terms of using VPCT and two different calculation methods, compare their results and look for correlation between tumor arterialization and lesion size. • VPCT can measure tumor volume perfusion non-invasively and enables quantification of the degree of HCC arterialization. Results are dependent on the technique used with best inter-method correlation for Blood Flow. • Tumor arterialization did not proved size-dependent. - Abstract: Objective: To characterize hepatocellular carcinoma (HCC) in terms of perfusion parameters using volume perfusion CT (VPCT) and two different calculation methods, compare their results, look for interobserver agreement of measurements and correlation between tumor arterialization and lesion size. Material and methods: This study was part of a prospective monitoring study in patients with HCC undergoing TACE, which was approved by the local Institutional Review Board. 79 HCC-patients (mean age, 64.7) with liver cirrhosis were enrolled. VPCT was performed for 40 s covering the involved liver (80 kV, 100/120 mAs) using 64 mm × 0.6 mm collimation, 26 consecutive volume measurements, 50 mL iodinated contrast IV and 5 mL/s flow rate. Mean/maximum blood flow (BF; ml/100 mL/min), blood volume (BV) and k-trans were determined both with the maximum slope + Patlak vs. deconvolution method. Additionally, the portal venous liver perfusion (PVP), the arterial liver perfusion (ALP) and the hepatic perfusion index (HPI) were determined for each tumor including size measurements. Interobserver agreement for all perfusion parameters was calculated using intraclass correlation coefficients (ICC). Results: The max. slope + Patlak method yielded: BFmean/max = 37.8/57 mL/100 g-tissue/′, BVmean/max = 9.8/11.1 mL/100 g

  16. Characterization of Hepatocellular Carcinoma Related Genes and Metabolites in Human Nonalcoholic Fatty Liver Disease

    Czech Academy of Sciences Publication Activity Database

    Clarke, D. J.; Novák, Petr; Lake, A.D.; Shipkova, P.; Aranibar, N.; Robertson, D.; Severson, P.L.; Reily, M.D.; Futscher, B. W.; Lehman-McKeeman, L.D.; Cherrington, N.J.

    2014-01-01

    Roč. 59, č. 2 (2014), s. 365-374. ISSN 0163-2116 Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : nonalcoholic fatty liver disease * nonalcoholic steatohepatitis * hepatocellular carcinoma * metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.613, year: 2014

  17. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells

    International Nuclear Information System (INIS)

    The CD133 antigen, identified as a hematopoietic stem cell marker, appears in various human embryonic epithelia including the neural tube, gut, and kidney. We herein investigated whether CD133+ cells isolated from human hepatocellular carcinoma cell lines possess cancer stem/progenitor cell-like properties. Among the three cell lines studied, the CD133 antigen was found to be expressed only on the surface of Huh-7 cells. CD133+ cells from Huh-7 performed a higher in vitro proliferative potential and lower mRNA expressions of mature hepatocyte markers, glutamine synthetase and cytochrome P450 3A4, than CD133- population of Huh-7 cells. When either CD133+ or CD133- cells were subcutaneously injected into SCID mice, CD133+ cells formed tumors, whereas CD133- cells induced either a very small number of tumors or none at all. Taken together, the identification of CD133+ cells could thus be a potentially powerful tool to investigate the tumorigenic process in the hepatoma system and to also develop effective therapies targeted against hepatocellular carcinoma

  18. Characterization of the oncogenic function of centromere protein F in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yongdong; Liu, Lulu; Zeng, Tingting; Zhu, Ying-Hui [State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou (China); Li, Jiangchao [Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou (China); Chen, Leilei [Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong (China); Li, Yan; Yuan, Yun-Fei [State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou (China); Ma, Stephanie, E-mail: stefma@hku.hk [Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong (China); State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong (China); Guan, Xin-Yuan, E-mail: xyguan@hkucc.hku.hk [State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou (China); Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong (China); State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong (China)

    2013-07-12

    Highlights: •Overexpression of CENPF is frequently detected in HCC. •Upregulation of CENPF serves as an independent prognosis factor in HCC patients. •CENPF functions as an oncogene in HCC by promoting cell G2/M transition. -- Abstract: Centromere protein F (CENPF) is an essential nuclear protein associated with the centromere-kinetochore complex and plays a critical role in chromosome segregation during mitosis. Up-regulation of CENPF expression has previously been detected in several solid tumors. In this study, we aim to study the expression and functional role of CENPF in hepatocellular carcinoma (HCC). We found CENPF was frequently overexpressed in HCC as compared with non-tumor tissue. Up-regulated CENPF expression in HCC was positively correlated with serum AFP, venous invasion, advanced differentiation stage and a shorter overall survival. Cox regression analysis found that overexpression of CENPF was an independent prognosis factor in HCC. Functional studies found that silencing CENPF could decrease the ability of the cells to proliferate, form colonies and induce tumor formation in nude mice. Silencing CENPF also resulted in the cell cycle arrest at G2/M checkpoint by down-regulating cell cycle proteins cdc2 and cyclin B1. Our data suggest that CENPF is frequently overexpressed in HCC and plays a critical role in driving HCC tumorigenesis.

  19. Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

    Science.gov (United States)

    Saito, Takafumi; Sugimoto, Masahiro; Okumoto, Kazuo; Haga, Hiroaki; Katsumi, Tomohiro; Mizuno, Kei; Nishina, Taketo; Sato, Sonoko; Igarashi, Kaori; Maki, Hiroko; Tomita, Masaru; Ueno, Yoshiyuki; Soga, Tomoyoshi

    2016-01-01

    AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis. METHODS: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively. RESULTS: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001). CONCLUSION: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.

  20. Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells.

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    Jiao Liu

    Full Text Available BACKGROUND: The Hepatitis C virus (HCV core protein has been implicated as a potential oncogene or a cofactor in HCV-related hepatocellular carcinoma (HCC, but the underlying mechanisms are unknown. Overactivation of the Wnt/β-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/β-catenin activation remains to be further characterized. Therefore, we attempted to determine whether HCV core protein plays an important role in regulating Wnt/β-catenin signaling in HCC cells. METHODOLOGY: Wnt/β-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expression were examined by Western blot, immunofluorescence staining, RT-qPCR, and reporter assay. PRINCIPAL FINDINGS: HCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes β-catenin levels in hepatoma cell line Huh7 through inactivation of GSK-3β, which contributes to the up-regulation of downstream target genes, such as c-Myc, cyclin D1, WISP2 and CTGF. Also, core protein increases cell proliferation rate and promotes Wnt3A-induced tumor growth in the xenograft tumor model of human HCC. CONCLUSIONS/SIGNIFICANCE: HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis.

  1. Liver resection for hemoperitoneum caused by spontaneous rupture of unrecognized hepatocellular carcinoma.

    Science.gov (United States)

    Casciaro, G E; Spaziani, E; Costantino, A; Ceci, F; Di Grazia, C; Martellucci, A; Pecchia, M; Cipriani, B; De Angelis, F; Corelli, S; Napoleoni, A; Stefanelli, F; Salvadori, C; Parisella, M; Nicodemi, S; Stagnitti, F

    2012-01-01

    Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although its spontaneous rupture is rare in Western countries, it constitutes a surgical emergency and is associated with high mortality. There is a lack of consensus as to the best approach and what parameters to use in choosing it. The three main approaches are conservative, endovascular and resection - the treatment of choice for acute abdominal bleeding. We report a case of hemoperitoneum following the spontaneous rupture of an unrecognized HCV-related HCC in a patient with no history of liver disease. The patient was successfully treated by emergency surgery, with resection of two segments of the left liver. PMID:22958803

  2. Promoter methylation of CDKN2A and lack of p16 expression characterize patients with hepatocellular carcinoma

    International Nuclear Information System (INIS)

    The product of CDKN2A, p16 is an essential regulator of the cell cycle controlling the entry into the S-phase. Herein, we evaluated CDKN2A promoter methylation and p16 protein expression for the differentiation of hepatocellular carcinoma (HCC) from other liver tumors. Tumor and corresponding non-tumor liver tissue samples were obtained from 85 patients with liver tumors. CDKN2A promoter methylation was studied using MethyLight technique and methylation-specific PCR (MSP). In the MethyLight analysis, samples with ≥ 4% of PMR (percentage of methylated reference) were regarded as hypermethylated. p16 expression was evaluated by immunohistochemistry in tissue sections (n = 148) obtained from 81 patients using an immunoreactivity score (IRS) ranging from 0 (no expression) to 6 (strong expression). Hypermethylation of the CDKN2A promoter was found in 23 HCCs (69.7%; mean PMR = 42.34 ± 27.8%), six (20.7%; mean PMR = 31.85 ± 18%) liver metastases and in the extralesional tissue of only one patient. Using MSP, 32% of the non-tumor (n = 85), 70% of the HCCs, 40% of the CCCs and 24% of the liver metastases were hypermethylated. Correspondingly, nuclear p16 expression was found immunohistochemically in five (10.9%, mean IRS = 0.5) HCCs, 23 (92%; mean IRS = 4.9) metastases and only occasionally in hepatocytes of non-lesional liver tissues (mean IRS = 1.2). The difference of CDKN2A-methylation and p16 protein expression between HCCs and liver metastases was statistically significant (p < 0.01, respectively). Promoter methylation of CDKN2A gene and lack of p16 expression characterize patients with HCC

  3. Hepatocellular calcification

    DEFF Research Database (Denmark)

    Ladefoged, Claus; Frifelt, J J

    1987-01-01

    Autopsy of a twenty year old girl dying from complications of renal and cardiac failure demonstrated severe hepatocellular calcification, a rare finding. The pathogenesis is thought to be a combination of dystrophic calcification caused by severe centrilobular necrosis and metastatic calcification...

  4. Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development.

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    Christian M Lange

    Full Text Available BACKGROUND: Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV-related hepatocellular carcinoma (HCC. METHODOLOGY/PRINCIPAL FINDINGS: Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3 serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657, GC (rs2282679, and DHCR7 (rs7944926, rs12785878 genotypes and 25(OHD3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs that are associated with reduced 25(OHD3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99-1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12-2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13-1.78] for DHCR7; ORs for risk genotypes. In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP was observed, suggesting a specific influence of the genetic determinants of 25(OHD3 serum levels on hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.

  5. AS30D Model of Hepatocellular Carcinoma: Tumorigenicity and Preliminary Characterization by Imaging, Histopathology, and Immunohistochemistry

    International Nuclear Information System (INIS)

    This study was designed to determine the tumorigenicity of the AS30D HCC cell line following orthotopic injection into rat liver and preliminarily characterize the tumor model by both magnetic resonance imaging (MRI) and ultrasound (US) as well as histopathology and immunohistochemistry.MaterialsAS30D cell line in vitro proliferation was assessed by using MTT assay. Female rats (N = 5) underwent injection of the AS30D cell line into one site in the liver. Rats subsequently underwent MR imaging at days 7 and 14 to assess tumor establishment and volume. One rat underwent US of the liver at day 7. Rats were euthanized at day 7 or 14 and livers were subjected to gross, histopathologic (H and E), and immunohistochemical (CD31) analysis to assess for tumor growth and neovascularization. AS30D cell line demonstrated an in vitro doubling time of 33.2 ± 5.3 h. MR imaging demonstrated hyperintense T2-weighted and hypointense T1-weighted lesions with tumor induction in five of five and three of three sites at days 7 and 14, respectively. The mean (SD) tumor volume was 126.1 ± 36.2 mm3 at day 7 (N = 5). US of the liver demonstrated a well-circumscribed, hypoechoic mass and comparison of tumor dimensions agreed well with MRI. Analysis of H and E- and CD31-stained sections demonstrated moderate-high grade epithelial tumors with minimal tumor necrosis and evidence of diffuse intratumoral and peritumoral neovascularization by day 7. AS30D HCC cell line is tumorigenic following orthotopic injection into rat liver and can be used to generate an early vascularizing, slower-growing rat HCC tumor model.

  6. Beneifcial effect of reifned red palm oil on lipid peroxidation and monocyte tissue factor in HCV-related liver disease:a randomized controlled study

    Institute of Scientific and Technical Information of China (English)

    Roberto Catanzaro; Nicola Zerbinati; Umberto Solimene; Massimiliano Marcellino; Dheeraj Mohania; Angelo Italia; Antonio Ayala; Francesco Marotta

    2016-01-01

    BACKGROUND: A large amount of endotoxin can be detected in the peripheral venous blood of patients with liver cirrhosis, contributing to the pathogenesis of hepatotoxicity because of its role in oxidative stress. The present study aimed to test the effect of the supplementation with red palm oil (RPO), which is a natural oil obtained from oil palm fruit (Elaeis guineensis) rich in natural fat-soluble tocopherols, tocotrienols and carot-enoids, on lipid peroxidation and endotoxemia with plasma endotoxin-inactivating capacity, proinlfammatory cytokines proifle, and monocyte tissue factor in patients with chronic liver disease. METHODS: The study group consisted of sixty patients (34 males and 26 females; mean age 62 years, range 54-75) with Child A/B, genotype 1 HCV-related cirrhosis without a history of ethanol consumption, randomly enrolled into an 8-week oral daily treatment with either vitamin E or RPO. All patients had undergone an upper gastrointestinal endoscopy 8 months before, and 13 out of them showed esophageal varices. RESULTS: Both treatments signiifcantly decreased erythro-cyte malondialdehyde and urinary isoprostane output, only RPO signiifcantly affected macrophage-colony stimulating fac-tor and monocyte tissue factor. Liver ultrasound imaging did not show any change. CONCLUSIONS: RPO beneifcially modulates oxidative stress and, not least, downregulates macrophage/monocyte inlfam-matory parameters. RPO can be safely advised as a valuable nutritional implementation tool in the management of chron-ic liver diseases.

  7. Differential association of STAT3 and HK-II expression in hepatitis B virus- and hepatitis C virus-related hepatocellular carcinoma.

    Science.gov (United States)

    Li, Man; Wang, Weihua; Jin, Rui; Zhang, Tieying; Li, Na; Han, Qunying; Wei, Ping; Liu, Zhengwen

    2016-09-01

    STAT3 and hexokinase II (HK-II) are involved in viral infection and carcinogenesis of various cancers including hepatocellular carcinoma (HCC). The roles of STAT3 and HK-II in hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related HCC remain largely unclear. This study examined STAT3 and HK-II expression in HBV- and HCV-related HCC, HBV-related liver fibrosis, and normal control liver by using tissue microarray and immunohistochemical method. Results showed that STAT3 expression in HBV-related HCC, HCV-related HCC, and HBV-related liver fibrosis was significantly higher than in control liver (P < 0.001, P = 0.016, and P = 0.005, respectively) and had no significant differences between these three diseased liver tissues. The HK-II expression in HBV-related HCC was significantly higher than that in HCV-related HCC, HBV-related liver fibrosis, and control liver (P = 0.007, P = 0.029, and P = 0.008, respectively) but had no significant elevation in and no significant differences between HCV-related HCC, HBV-related liver fibrosis, and control liver. The HK-II expression was significantly correlated to STAT3 expression in HBV-related HCC (P = 0.022), but no correlation was observed in HCV-related HCC, HBV-related liver fibrosis, and control liver. In conclusion, STAT3 expression is upregulated in both HBV- and HCV-related HCC, while HK-II is predominantly upregulated and correlated to STAT3 in HBV-related HCC. These differential expression and association may suggest the distinct roles of STAT3 and HK-II in hepatocarcinogenesis of HBV and HCV infection. Studies are needed to confirm the relationship of STAT3 and HK-II and to examine the underlying mechanisms. J. Med. Virol. 88:1552-1559, 2016. © 2016 Wiley Periodicals, Inc. PMID:26889748

  8. Serum manganese superoxide dismutase and thioredoxin are potential prognostic markers for hepatitis C virus-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tsutomu Tamai; Akihiro Moriuchi; Makoto Oketani; Akio Ido; Hirohito Tsubouchi; Hirofumi Uto; Yoichiro Takami; Kouhei Oda; Akiko Saishoji; Masashi Hashiguchi; Kotaro Kumagai; Takeshi Kure; Seiichi Mawatari

    2011-01-01

    AIM: To evaluate the clinical significance of oxidative stress markers in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).METHODS: Sixty-four consecutive patients who were admitted to Kagoshima University Medical and Dental Hospital were enrolled in this retrospective study. All patients had chronic liver disease (CLD) due to infection with HCV. Thirty patients with HCV-related HCC, 34 with HCV-related CLD without HCC (non-HCC), and 20 healthy volunteers (HVs) were enrolled. Possible associations between serum manganese superoxide dismutase (MnSOD) and thioredoxin (TRX) levels and clinical parameters or patient prognosis were analyzed over a mean follow-up period of 31.7 mo.RESULTS: The serum MnSOD levels were significantly higher in patients with HCV-related HCC than in patients without HCC (P = 0.03) or HVs (P < 0.001). Similarly,serum TRX levels were also significantly higher in patients with HCV-related HCC than in patients without HCC (P = 0.04) or HVs (P < 0.01). However, serum levels of MnSOD and TRX were not correlated in patients with HCC. Among patients with HCC, the overall survival rate (OSR) was lower in patients with MnSOD levels ≥ 110 ng/mL than in patients with levels < 110 ng/mL (P = 0.01), and the OSR tended to be lower in patients with TRX levels < 80 ng/mL (P = 0.05). In addition,patient prognosis with HCC was poorest with serum MnSOD levels ≥ 110 ng/mL and serum TRX levels < 80 ng/mL. Furthermore, a multivariate analysis using a Cox proportional hazard model and serum levels of five factors (MnSOD, prothrombin time, serum albumin, serum α-fetoprotein (AFP), and serum des-γ-carboxy prothrombin) revealed that MnSOD levels ≥ 110 ng/mL (risk ratio: 4.12, 95% confidential interval: 1.22-13.88, P = 0.02) and AFP levels ≥ 40 ng/mL (risk ratio: 6.75; 95% confidential interval: 1.70-26.85, P < 0.01) were independent risk factors associated with a poor patient prognosis.CONCLUSION: Serum MnSOD and TRX levels are

  9. Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma.

    Science.gov (United States)

    Giannitrapani, Lydia; Soresi, Maurizio; Balasus, Daniele; Licata, Anna; Montalto, Giuseppe

    2013-04-28

    Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC. PMID:23674845

  10. Identification of Driver Genes in Hepatocellular Carcinoma by Exome Sequencing

    OpenAIRE

    Sean P Cleary; Jeck, William R.; Zhao, Xiaobei; Chen, Kui; Selitsky, Sara R.; Savich, Gleb L.; Tan, Ting-Xu; Wu, Michael C.; Getz, Gad; Lawrence, Michael S.; Joel S Parker; Li, Jinyu; Powers, Scott; Kim, Hyeja; Fischer, Sandra

    2013-01-01

    Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma. As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in hepatocellular carcinoma. We performed whole exome sequencing on 87 hepatocellular carcinomas and matched normal adjacent tissues to anaverage coverage of 59x. The overall mutation rate was rough...

  11. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy for...... the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by...... hepatocellular carcinoma. Randomised clinical trials with low-risk of bias may help in defining the role of cryotherapy in the treatment of hepatocellular carcinoma....

  12. Hepatocellular carcinoma.

    Science.gov (United States)

    Llovet, Josep M; Zucman-Rossi, Jessica; Pikarsky, Eli; Sangro, Bruno; Schwartz, Myron; Sherman, Morris; Gores, Gregory

    2016-01-01

    Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies - resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches. PMID:27158749

  13. Hepatocellular carcinoma.

    Science.gov (United States)

    Edwards, J T; Macdonald, G A

    2000-05-01

    The incidence of hepatocellular carcinoma (HCC) appears to be declining in Taiwan and potentially in other high-prevalence areas as a consequence of vaccination for hepatitis B virus (HBV). However, there is evidence that the incidence of HCC is increasing in North America and Europe. This appears to be related to the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. There is also growing evidence to support an increase in the risk of HCC in patients with HCV who are coinfected with occult HBV (patients who have lost HBV surface antigen but still have detectable HBV DNA either in blood or liver). Occult HBV infection in patients with HCV may be more common than previously thought, and HCC that occurs in this setting appears to have a worse prognosis. There is continuing interest in the effect of interferon therapy on the incidence of HCC in patients with HCV. Several studies from Japan have shown a benefit in patients without cirrhosis, although there are a number of potentially confounding variables that may partly explain these results. Prospective randomized studies are needed to investigate this important question. The molecular biology of HCC and the events of malignant transformation in the liver continue to be areas of intense study. Recently, there has been considerable interest in telomeres, the repeat units on the ends of chromosomes, and the enzyme that maintains these, telomerase. Telomeres shorten with each cell division and can be used to determine the number of divisions a cell has undergone. Eventually they reach a critical length, with further loss resulting in cellular senescence. Telomerase restores telomere length and may help malignant cells escape senescence. Nearly all HCCs have telomerase activity and assessments of telomeres and telomerase may be clinically useful. PMID:17023886

  14. Inflammatory pseudotumor of the liver occurring during the course of hepatitis C virus-related hepatocellular carcinoma treatment: A case report

    Science.gov (United States)

    Honmyo, Naruhiko; Kobayashi, Tsuyoshi; Tashiro, Hirotaka; Ishiyama, Kohei; Ide, Kentaro; Tahara, Hiroyuki; Ohira, Masahiro; Kuroda, Shintaro; Arihiro, Koji; Ohdan, Hideki

    2016-01-01

    Introduction Inflammatory pseudotumor (IPT) of the liver is a rare and benign disease that has a good prognosis. It is often difficult to distinguish IPT from hepatic malignancies, such as hepatocellular carcinoma (HCC), because specific clinical symptoms are absent and the diseases’ radiological findings can be similar. IPT is particularly difficult to distinguish from HCC in livers with hepatitis C virus (HCV)-related cirrhosis. We report a case of IPT of the liver that mimicked HCV-related HCC recurrence. Presentation of case A 78-year-old asymptomatic Japanese man who had undergone hepatectomy for HCV-related HCCs (moderately differentiated type) in segments 7 and 5 four and a half years previously was referred to our hospital for treatment of a 30-mm enhanced tumor in segment 5 (a typical HCC pattern). The tumor was identified via abdominal dynamic computed tomography (CT) and CT with hepatic arteriography and arterial portography. Thereafter, liver segmentectomy 5 was performed, and the histopathological diagnosis was a 10-mm IPT of the liver. After 1.5 years, magnetic resonance imaging revealed two new enhanced lesions in segment 8, which showed the typical pattern of HCC. Because these lesions grew in size for 3 months, liver segmentectomy 8 was performed for HCC recurrence. Histopathological examination showed that both lesions were HCCs. Conclusion HCV-related HCC has a high rate of multicentric recurrence. Our experience suggests that, when a hepatic lesion is suspected to be HCC, surgical resection should be considered for curative treatment and to rule out malignancy, even if the lesion may be an IPT. PMID:26826935

  15. Postoperative therapy options for hepatocellular carcinoma.

    Science.gov (United States)

    Zhong, Jian-Hong; Ma, Liang; Li, Le-Qun

    2014-06-01

    Hepatocellular carcinoma (HCC) is associated with poor prognosis and often recurs even after curative hepatic resection (HR) or radiofrequency ablation (RFA). In fact, recurrence is the most frequent cause of postoperative death in patients with HCC; it can arise through intrahepatic metastasis by the primary tumor or through the emergence of de novo tumors. Even though studies have examined numerous adjuvant therapies and chemotherapies for their ability to prevent recurrence, no consensus recommendations exist about their clinical application. To gain a comprehensive picture of clinical options, we identified 39 randomized controlled trials, involving 4113 participants, which explore the efficacy of adjuvant or chemotherapies to prevent HCC recurrence after potentially curative HR or RFA. The available evidence suggests a significant improvement in recurrence-free survival and overall survival when transarterial chemoembolization is used for patients who are at high risk for recurrence, lamivudine for patients with hepatitis B virus (HBV)-related HCC (>500 copies of HBV DNA/ml), and interferon-α for patients with hepatitis C virus (HCV)-infected HCC. In contrast, available evidence does not definitively establish clinical benefits of interferon-β for patients with HCV-related HCC, interferon-α for patients with HBV-related HCC, or any of the following therapies for patients with HCC: iodine-125 brachytherapy, autologous tumor vaccination, adoptive immunotherapy, or therapy involving acyclic retinoid, vitamin K2 analog, iodine-131-labeled lipiodol, sorafenib, heparanase inhibitor PI-88, or capecitabine. Though the findings of our review should be interpreted with caution because of clinical heterogeneity and small sample size in the included trials, they highlight gaps in the evidence base, and therefore, may guide future research. PMID:24716523

  16. Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Shunzhen Zheng

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is the third most common cause of cancer related mortality worldwide. 9-Nitrocamptothecin (9NC is a potent topoisomerase-I inhibitor with strong anticancer effect. To increase the solubility and stability, we synthesized a novel 9NC loaded liposomes (9NC-LP via incorporating 9NC into liposomes. In the present study, we determined the effects of 9NC and 9NC-LP on in vitro and in vivo, and the underlying mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: We first analyzed the characteristics of 9NC-LP. Then we compared the effects of 9NC and 9NC-LP on the proliferation and apoptosis of HepG2, Bel-7402, Hep3B and L02 cells in vitro. We also investigated their anticancer properties in nude mice bearing HCC xenograft in vivo. 9NC-LP has a uniform size (around 190 nm and zeta potential (∼-11 mV, and exhibited a steady sustained-release pattern profile in vitro. Both 9NC and 9NC-LP could cause cell cycle arrest and apoptosis in a dose-dependent and p53-dependent manner. However, this effect was not ubiquitous in all cell lines. Exposure to 9NC-LP led to increased expression of p53, p21, p27, Bax, caspase-3, caspase-8, caspase-9 and apoptosis-inducing factor, mitochondrion-associated 1 and decreased expression of Bcl-2, cyclin E, cyclin A, Cdk2 and cyclin D1. Furthermore, 9NC-LP exhibited a more potent antiproliferative effect and less side effects in vivo. Western blot analysis of the xenograft tumors in nude mice showed similar changes in protein expression in vivo. CONCLUSIONS/SIGNIFICANCE: In conclusion, 9NC and 9NC-LP can inhibit HCC growth via cell cycle arrest and induction of apoptosis. 9NC-LP has a more potent anti-tumor effect and fewer side effects in vivo, which means it is a promising reagent for cancer therapy via intravenous administration.

  17. Natural history of hepatitis-related hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    David Yiu-Kuen But, Ching-Lung Lai, Man-Fung Yuen

    2008-03-01

    Full Text Available Hepatocellular carcinoma (HCC is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus (HBV vaccination programs, better food hygiene, increased global hepatitis C virus (HCV prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV-related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways: chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein (AFP are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients’ survival and match best treatment option.

  18. Natural history of hepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    David Yiu-Kuen But; Ching-Lung Lai; Man-Fung Yuen

    2008-01-01

    Hepatocellular carcinoma (HCC) is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus (HBV) vaccination programs, better food hygiene, increased global hepatitis C virus (HCV) prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV-related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways: chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein (AFP) are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients' survival and match best treatment option.

  19. The Impact of Transarterial Therapy in Hepatitis C Related Hepatocellular Carcinoma on Long Term Outcomes after Liver Transplantation

    Science.gov (United States)

    Cabrera, Roniel; Dhanasekaran, Renu; Caridi, James; Clark, Virgina; Morelli, Giuseppe; Soldevila-Pico, Consuelo; Magglioca, Joseph; Nelson, David; Firpi, Roberto Jose

    2011-01-01

    Objectives To evaluate the impact for long term outcomes of transarterial embolization (TAE) therapy in patients with HCV-related hepatocellular carcinoma (HCC) on the waiting list for liver transplantation (LT). Methods We retrospectively evaluated the post-LT patients with HCV-related HCC who received TAE intervention (n=33) and those who had no treatment (n=47) while on the waiting list to determine long term outcomes. Results Over a ten year period, of the 424 patients transplanted with HCV, 80 patients had HCC with a tumor burden within Milan criteria. For the entire study cohort the mean duration of post-LT follow-up was 3.5 yrs; mean time on transplant waiting list was 120 days; and median post-LT survival was 8.9 yrs. The survival rates at 1, 3, 5 and 10 yrs were 82%, 70%, 55% and 35%, respectively. From the study cohort, 33 patients received TAE and 47 patients did not while on the waiting list. The two groups were well matched, except, that the intervention subjects received post-LT interferon more often and had a shorter time on the waiting list (56.2 days) when compared to the no treatment group (164.6 days, ptransplant. PMID:21552101

  20. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  1. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  2. Hepatitis C Virus Protein Interaction Network Analysis Based on Hepatocellular Carcinoma.

    Science.gov (United States)

    Han, Yuewen; Niu, Jun; Wang, Dong; Li, Yuanyuan

    2016-01-01

    Epidemiological studies have validated the association between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). An increasing number of studies show that protein-protein interactions (PPIs) between HCV proteins and host proteins play a vital role in infection and mediate HCC progression. In this work, we collected all published interaction between HCV and human proteins, which include 455 unique human proteins participating in 524 HCV-human interactions. Then, we construct the HCV-human and HCV-HCC protein interaction networks, which display the biological knowledge regarding the mechanism of HCV pathogenesis, particularly with respect to pathogenesis of HCC. Through in-depth analysis of the HCV-HCC interaction network, we found that interactors are enriched in the JAK/STAT, p53, MAPK, TNF, Wnt, and cell cycle pathways. Using a random walk with restart algorithm, we predicted the importance of each protein in the HCV-HCC network and found that AKT1 may play a key role in the HCC progression. Moreover, we found that NS5A promotes HCC cells proliferation and metastasis by activating AKT/GSK3β/β-catenin pathway. This work provides a basis for a detailed map tracking new cellular interactions of HCV and identifying potential targets for HCV-related hepatocellular carcinoma treatment. PMID:27115606

  3. Hepatitis C Virus Protein Interaction Network Analysis Based on Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yuewen Han

    Full Text Available Epidemiological studies have validated the association between hepatitis C virus (HCV infection and hepatocellular carcinoma (HCC. An increasing number of studies show that protein-protein interactions (PPIs between HCV proteins and host proteins play a vital role in infection and mediate HCC progression. In this work, we collected all published interaction between HCV and human proteins, which include 455 unique human proteins participating in 524 HCV-human interactions. Then, we construct the HCV-human and HCV-HCC protein interaction networks, which display the biological knowledge regarding the mechanism of HCV pathogenesis, particularly with respect to pathogenesis of HCC. Through in-depth analysis of the HCV-HCC interaction network, we found that interactors are enriched in the JAK/STAT, p53, MAPK, TNF, Wnt, and cell cycle pathways. Using a random walk with restart algorithm, we predicted the importance of each protein in the HCV-HCC network and found that AKT1 may play a key role in the HCC progression. Moreover, we found that NS5A promotes HCC cells proliferation and metastasis by activating AKT/GSK3β/β-catenin pathway. This work provides a basis for a detailed map tracking new cellular interactions of HCV and identifying potential targets for HCV-related hepatocellular carcinoma treatment.

  4. 基因1型慢性丙型肝炎代偿期肝硬化患者抗病毒治疗后的长期随访研究%Long-term follow-up study of genotype 1 patients with HCV-related compensated cirrhosis treated with pegylated interferon alpha-2a and ribavirin

    Institute of Scientific and Technical Information of China (English)

    张曹庚; 项晓刚; 刘柯慧; 曹竹君; 谢青; 王晖

    2016-01-01

    hepatitis C virus (HCV) genotype 1 patients with compensated cirrhosis .Methods In our parallel retrospective cohort study ,HCV genotype 1 patients with HCV related compensated cirrhosis received PR therapy and symptomatic treatment with colony‐stimulating factors (CSF) .And the patients undertook a long‐term follow‐up for 5 years .The efficacy and recurrence rate of antiviral therapy were evaluated .Transient elastography (TE) was used in liver stiffness measurement ( LSM ) . The occurrences of clinical events , including hepatic encephalopathy , ascites , gastrointestinal bleeding ,hepatocellular carcinoma (HCC) and death ,was compared between sustained virological response (SVR) group and non‐sustained virological response (NSVR) group .Results Fifty‐four HCV genotype 1 patients with HCV related compensated cirrhosis completed the PR therapy , and 34 (64 .81% ) achieved SVR . Fourteen among 23 patients(65 .22% ) achieved SVR after the first antiviral therapy ,so did 9/14 (64 .29% ) patients after the second ,8/13 (76 .92% ) after the third ,2/3 (66 .67% ) after the forth and 1/1 (100% ) after the fifth .Only one case relapsed at 6 weeks after achievement of SVR .During the antiviral treatment period ,LSM improved to varying degrees ,which showed a significant statistical difference in SVR groups (P= 0 .0004) .During the long‐term follow‐up ,the LSM of SVR group showed a further decline and kept at a low level .However ,there was no improvement of LSM in NSVR group .During the follow‐up for 60 months on average ,there were 3 cases developing HCC in NSVR group ,while 0 in SVR group .Incidence of clinical events ,such as ascites [P=0 .0168 ,RR= 0 .2353 (95% CI 0 .0390‐1 .422)] and HCC [P=0 .0391 ,RR= 0 . 0000] ,between the two groups showed significant difference .Conclusion PR therapy can effectively restrain virus replication for HCV genotype 1 patients with HCV related compensated cirrhosis .Combination therapy with CSF can improve treatment compliance

  5. Effect and safety of interferon for hepatocellular carcinoma: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Liping Zhuang

    Full Text Available BACKGROUND: The effect of interferon(IFN in the management of hepatocellular carcinoma (HCC remains controversial, and no clear recommendations have been proposed. OBJECTIVES: To evaluate the effect and safety of IFN for HCC. METHODS: PubMed, OvidSP, and Cochrane Library were searched from their establishment date until August 30, 2012. Studies that met the inclusion criteria were systematically evaluated and then subjected to meta-analysis. RESULTS: Thirteen randomized control trials (RCTs involving 1344 patients were eligible for this study. When IFN was used as an adjuvant therapy for HCC patients after curative therapy, the meta-analysis showed that IFN reduced the 1-, 2-, 3-, 4-, and 5-year recurrence rates. Subgroup analysis showed that IFN reduced the 2-, 3-, 4-, and 5-year recurrence rates of hepatitis C viral (HCV-related HCC. The effect of IFN for on hepatitis B virus(HBV-related HCC patients could not be determined because of isufficient data. After surgical resection, adjuvant IFN therapy reduced the 4- and 5- recurrence rates. All studies reported that IFN could not improve the overall survival of HCV-realated HCC patients after curative therapies. Only one study showed that IFN was associated with better overall survival in HCC patients after curative therapy and subgroup of HCC patients after surgical resection. Thus, meta-analysis was not performed. Different treatment options were used as control to study the effect of IFN for intermediate and advanced HCC patients, thus meta-analysis was not appropriate. All included studies, except for one, reported that IFN treatment was well tolerated. CONCLUSIONS: After curative therapies, adjuvant IFN reduced the recurrence of HCC. IFN did not improve the survival of HCV-related HCC patients after curative therapy. Whether IFN is effective for intermediate and advanced HCC patients could not be determined because of insufficient data. The toxicity of IFN was acceptable.

  6. Hepatitis C virus suppresses Hepatocyte Nuclear Factor 4 alpha, a key regulator of hepatocellular carcinoma.

    Science.gov (United States)

    Vallianou, Ioanna; Dafou, Dimitra; Vassilaki, Niki; Mavromara, Penelope; Hadzopoulou-Cladaras, Margarita

    2016-09-01

    Hepatitis C Virus (HCV) infection presents with a disturbed lipid profile and can evolve to hepatic steatosis and hepatocellular carcinoma (HCC). Hepatocyte Nuclear Factor 4 alpha (HNF4α) is the most abundant transcription factor in the liver, a key regulator of hepatic lipid metabolism and a critical determinant of Epithelial to Mesenchymal Transition and hepatic development. We have previously shown that transient inhibition of HNF4α initiates transformation of immortalized hepatocytes through a feedback loop consisting of miR-24, IL6 receptor (IL6R), STAT3, miR-124 and miR-629, suggesting a central role of HNF4α in HCC. However, the role of HNF4α in Hepatitis C Virus (HCV)-related hepatocarcinoma has not been evaluated and remains controversial. In this study, we provide strong evidence suggesting that HCV downregulates HNF4α expression at both transcriptional and translational levels. The observed decrease of HNF4α expression correlated with the downregulation of its downstream targets, HNF1α and MTP. Ectopic overexpression of HCV proteins also exhibited an inhibitory effect on HNF4α levels. The inhibition of HNF4α expression by HCV appeared to be mediated at transcriptional level as HCV proteins suppressed HNF4α gene promoter activity. HCV also up-regulated IL6R, activated STAT3 protein phosphorylation and altered the expression of acute phase genes. Furthermore, as HCV triggered the loss of HNF4α a consequent change of miR-24, miR-629 or miR-124 was observed. Our findings demonstrated that HCV-related HCC could be mediated through HNF4α-microRNA deregulation implying a possible role of HNF4α in HCV hepatocarcinogenesis. HCV inhibition of HNF4α could be sustained to promote HCC. PMID:27477312

  7. HCV-Related Nervous System Disorders

    OpenAIRE

    Salvatore Monaco; Sergio Ferrari; Alberto Gajofatto; Gianluigi Zanusso; Sara Mariotto

    2012-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a wide spectrum of extrahepatic manifestations, affecting different organ systems. Neurological complications occur in a large number of patients and range from peripheral neuropathy to cognitive impairment. Pathogenetic mechanisms responsible for nervous system dysfunction are mainly related to the upregulation of the host immune response with production of autoantibodies, immune complexes, and cryoglobulins. Alternative mecha...

  8. A New Sampling Method for Spleen Stiffness Measurement Based on Quantitative Acoustic Radiation Force Impulse Elastography for Noninvasive Assessment of Esophageal Varices in Newly Diagnosed HCV-Related Cirrhosis

    Directory of Open Access Journals (Sweden)

    Leonardo Rizzo

    2014-01-01

    Full Text Available In our study, we evaluated the feasibility of a new sampling method for splenic stiffness (SS measurement by Quantitative Acoustic Radiation Force Impulse Elastography (Virtual Touch Tissue Quantification (VTTQ.We measured SS in 54 patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV, 27 with Chronic Hepatitis C (CHC F1–F3, and 63 healthy controls. VTTQ-SS was significantly higher among cirrhotic patients with EV (3.37 m/s in comparison with controls (2.19 m/s, P<0.001, CHC patients (2.37 m/s, P<0.001, and cirrhotic patients without EV (2.7 m/s, P<0.001. Moreover, VTTQ-SS was significantly higher among cirrhotic patients without EV in comparison with both controls (P<0.001 and CHC patients (P<0.01. The optimal VTTQ-SS cut-off value for predicting EV was 3.1 m/s (AUROC = 0.96, sensitivity 96.4%, specificity 88.5%, positive predictive value 90%, negative predictive value 96%, positive likelihood ratio 8.36, and negative likelihood ratio 0.04. In conclusion, VTTQ-SS is a promising noninvasive and reliable diagnostic tool to screen cirrhotic patients for EV and reduce the need for upper gastrointestinal endoscopy. By using our cut-off value of 3.1 m/s, we would avoid endoscopy in around 45% of cirrhotic subjects, with significant time and cost savings.

  9. Tumor suppressor and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Juliette Martin; Jean-Frangois Dufour

    2008-01-01

    A few signaling pathways are driving the growth of hepatocellular carcinoma. Each of these pathways possesses negative regulators. These enzymes, which normally suppress unchecked cell proliferation, are circumvented in the oncogenic process, either the over-activity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective. The loss of several key tumor suppressors has been described in hepatocellular carcinoma. Here, we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.

  10. Biomarkers for hepatocellular carcinoma.

    Science.gov (United States)

    Behne, Tara; Copur, M Sitki

    2012-01-01

    The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains challenging. Increased understanding of cancer biology and technological advances have enabled identification of a multitude of pathological, genetic, and molecular events that drive hepatocarcinogenesis leading to discovery of numerous potential biomarkers in this disease. They are currently being aggressively evaluated to establish their value in early diagnosis, optimization of therapy, reducing the emergence of new tumors, and preventing the recurrence after surgical resection or liver transplantation. These markers not only help in prediction of prognosis or recurrence but may also assist in deciding appropriate modality of therapy and may represent novel potential targets for therapeutic interventions. In this paper, a summary of most relevant available data from published papers reporting various tissue and serum biomarkers involved in hepatocellular carcinoma was presented. PMID:22655201

  11. Immunology of hepatocellular carcinoma

    OpenAIRE

    Sachdeva, Meenakshi; Chawla, Yogesh K.; Arora, Sunil K

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can ...

  12. Prevention of hepatocellular carcinoma.

    Science.gov (United States)

    Kew, Michael C

    2010-01-01

    Because of its frequency and grave prognosis, preventing hepatocellular carcinoma is an urgent priority. Prevention should be possible because environmental carcinogens-chronic hepatitis B and C virus infections, dietary exposure to aflatoxins, and iron overload-cause the great majority of these tumors. Chronic hepatitis B virus infection accounts for 55% of global hepatocellular carcinomas and 80% of those in the high-incidence Asia Pacific and sub-Saharan African regions. In these regions the infection that becomes chronic is predominantly acquired very early in life. A safe and effective vaccine against this virus is available and its universal inclusion in the immunization of infants has already resulted in a marked reduction of chronic infection and a 70% decrease in the occurrence of hepatocellular carcinoma in those immunized. Chronic hepatitis C virus infection is the major cause of hepatocellular carcinoma in industrialized countries. The infection is mainly acquired in adulthood and, until a vaccine becomes available, prevention will consist mainly of identifying, counselling, and treating chronically infected individuals, preventing spread of the virus by the use of safe injection practices (particularly in intravenous drug abusers), and screening all donated blood for the presence of the virus. 4.5 billion of the world.s population are exposed to dietary aflatoxins. Prevention involves treating susceptible crops to prevent fungal contamination, and handling the foodstuffs in such a way as to prevent contamination during storage. Iron overload in hereditary hemochromatosis can be prevented by repeated venesection and in African dietary iron overload by fermenting the home-brewed beer in iron-free containers. PMID:20526004

  13. Serum transforming growth factor beta 1 in hepatitis c virus related chronic liver disease and hepatocellular carcinoma patients

    International Nuclear Information System (INIS)

    hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the most frequent human malignant neoplasms. it is estimated to cause more than a quarter of a million deaths each year throughout the world. the aim of the present work was to assess the value of serum level of TGF-betal in patients with HCV related CLD and its level in patients with HCC and to evaluate its sensitivity and specificity in comparison to AFP in early diagnosis of HCC. the study was performed on two groups of egyptian patients, from the tropical medicine department and outpatient,s clinic for early detection of hepatocellular carcinoma (HCC), Ain Shams university hospitals; croup 1 consisted of forty patients with chronic liver disease, their ages ranged between 85 and 35 years (mean 51.8+ 9.2 years) included 23 male patients (57.5%) and 17 female patients (42.5%), group 11 consisted of forty patients with HCC, their age ranged between 72 and 42 years (mean 54.0+ 7.5 years) included 30 male patients (75%) and 10 female patients (25%)

  14. MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

    Science.gov (United States)

    Fiorino, Sirio; Bacchi-Reggiani, Maria Letizia; Visani, Michela; Acquaviva, Giorgia; Fornelli, Adele; Masetti, Michele; Tura, Andrea; Grizzi, Fabio; Zanello, Matteo; Mastrangelo, Laura; Lombardi, Raffaele; Di Tommaso, Luca; Bondi, Arrigo; Sabbatani, Sergio; Domanico, Andrea; Fabbri, Carlo; Leandri, Paolo; Pession, Annalisa; Jovine, Elio; de Biase, Dario

    2016-04-21

    Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "microRNAs", "miRNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis. PMID:27099435

  15. Viral hepatitis and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of 131I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs

  16. Current update on combined hepatocellular-cholangiocarcinoma.

    Science.gov (United States)

    Maximin, Suresh; Ganeshan, Dhakshina Moorthy; Shanbhogue, Alampady K; Dighe, Manjiri K; Yeh, Matthew M; Kolokythas, Orpheus; Bhargava, Puneet; Lalwani, Neeraj

    2014-01-01

    Combined hepatocellular-cholangiocarcinoma is a rare but unique primary hepatic tumor with characteristic histology and tumor biology. Recent development in genetics and molecular biology support the fact that combined hepatocellular-cholangiocarcinoma is closely linked with cholangiocarcinoma, rather than hepatocellular carcinoma. Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management. PMID:26937426

  17. Surveillance for Hepatocellular Carcinoma

    OpenAIRE

    Ramachandran, Jeyamani

    2014-01-01

    Hepatocellular carcinoma (HCC) is a dreaded complication of cirrhosis as it is the commonest cause of mortality in these patients. The last few years have seen a dramatic improvement in the management of this tumor as nearly 50–70% of selected patients with early HCC survive for a median period of up to 5 years after liver transplantation, resection or local ablation. Surveillance has been found to be an effective tool to detect early tumors and expand the applicability of these curative trea...

  18. The impact of viral hepatitis-related hepatocellular carcinoma to post-transplant outcomes.

    Science.gov (United States)

    Younossi, Z M; Stepanova, M; Saab, S; Ahmed, A; Lam, B; Srishord, M; Venkatesan, C; Wai, H; Henry, L

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common complication of HCV infection leading to liver transplantation. We evaluated the impact of aetiology of liver disease on patient and graft survival following liver transplantation for HCC. From the Scientific Registry of Transplant Recipients (2002-2011), all adults who underwent liver transplantation for HCC were retrospectively included. Aetiology of liver disease was grouped into HCV, HBV, HCV-HBV co-infection and nonviral liver disease. Of 8,733 liver transplant recipients with HCC, 5507 had HCV, 631 had HBV, 163 were co-infected, and 2432 had nonviral causes of liver disease. In follow-up (48 ± 32 months), 8.2% had graft failure and 29.5% died. The mean rates of graft failure were 9.5%, 4.7%, 6.1% and 6.4% in HCV, HBV, HCV-HBV co-infection and nonviral liver disease, respectively (P failure (adjusted hazard ratio = 1.84 (1.46-2.33), P < 0.0001) and mortality (1.35 (1.21-1.50), P < 0.0001) in multivariate analysis. Patients with HCV-related HCC are at higher risk of adverse post-transplant outcomes. These patients should be considered for preemptive interferon-free antiviral therapy prior to or immediately following liver transplantation. PMID:26289820

  19. Assessment of the Selenoprotein M (SELM over-expression on human hepatocellular carcinoma tissues by immunohistochemistry

    Directory of Open Access Journals (Sweden)

    E. Guerriero

    2014-10-01

    Full Text Available Selenium is an essential trace mineral of fundamental importance to human healthy and exerts its biological function through selenoproteins. In particular, Selenoprotein M (SELM is located in the endoplasmic reticulum and contains the common redox motif of cysteine-X-X-selenocysteine type. It attracts great attention due to its high expression in brain and its potential roles as antioxidant, neuroprotective, and cytosolic calcium regulator. Recently, our group found SELM over-expression  in human hepatocellular carcinoma (HCC cell lines. In this report some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV-related cirrhosis and HCC were immunohistochemically stained and SELM expression scoring was evaluated. Our results evidence for the first time an increase of SELM expression in HCC liver tissues, and its gradual expression raise associated with an increased malignancy grade. Therefore, we propose to use i SELM as putative marker for HCC as well as ii simple immunohistochemistry technique to distinguish between the different grades of malignancy. 

  20. Body mass index is associated with age-at-onset of HCVinfected hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Takumi Akiyama; Toshihiko Mizuta; Seiji Kawazoe; Yuichiro Eguchi; Yasunori Kawaguchi; Hirokazu Takahashi; Iwata Ozaki; Kazuma Fujimoto

    2011-01-01

    AIM:To identify factors associated with the age at onset of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).METHODS:Five hundred and fifty-six consecutive patients positive for HCV antibody and treatmentna(i)ve HCC diagnosed between 1995 and 2004 were analyzed.Patients were classified into three groups according to age at HCC onset: 60 years old were lower and mean BMI values of female patients 25 kg/m2 [hazard ratio (HR),1.8,P = 0.045],excessive alcohol consumption (HR,2.5,P = 0.024),male sex (HR,3.6,P = 0.002),and GGT levels > 50 IU/L (HR,2.4,P = 0.014) were independently associated with HCC onset in patients < 60 years.Low ALT level was the only factor associated with HCC onset in patients aged ≥ 80 years.CONCLUSION:Increased BMI is associated with increased risk for early HCC development in HCV-infected patients.Achieving recommended BMI and reducing alcohol intake could help prevent hepatic carcinogenesis.

  1. GPX4 and GPX7 over-expression in human hepatocellular carcinoma tissues

    Directory of Open Access Journals (Sweden)

    E. Guerriero

    2015-12-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. The selenium is an essential trace mineral implicated as a key factor in the early stage of cancer and exerts its biological function through the selenoproteins. In the last years our group has been studying the involvement of some selenoproteins in HCC. However, no many data are reported in literature about the correlation between HCC and the glutathione peroxidases (GPXs, both selenium and non selenium-containing GPXs. In this paper we have evaluated the GPX4 and GPX7 expression in some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV-related cirrhosis and HCC by immunohistochemistry and RT-qPCR analysis. Our results evidenced that i GPX4 and GPX7 had a statistically significant over-expression in HCC tissues compared to cirrhotic counterparts used as non tumor tissues, and ii their expression was higher in grade III HCC tissues with respect to grade I-II samples. Therefore, we propose to use GPX4 and GPX7 as possible markers for improving HCC diagnosis/prognosis.

  2. GPX4 and GPX7 Over-Expression in Human Hepatocellular Carcinoma Tissues

    Science.gov (United States)

    Guerriero, E.; Capone, F.; Accardo, M.; Sorice, A.; Costantini, M.; Colonna, G.; Castello, G.

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. The selenium is an essential trace mineral implicated as a key factor in the early stage of cancer and exerts its biological function through the selenoproteins. In the last years our group has been studying the involvement of some selenoproteins in HCC. However, no many data are reported in literature about the correlation between HCC and the glutathione peroxidases (GPXs), both selenium and non selenium-containing GPXs. In this paper we have evaluated the GPX4 and GPX7 expression in some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV)-related cirrhosis and HCC by immunohistochemistry and RT-qPCR analysis. Our results evidenced that i) GPX4 and GPX7 had a statistically significant over-expression in HCC tissues compared to cirrhotic counterparts used as non tumor tissues, and ii) their expression was higher in grade III HCC tissues with respect to grade I-II samples. Therefore, we propose to use GPX4 and GPX7 as possible markers for improving HCC diagnosis/prognosis. PMID:26708178

  3. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Fumio, E-mail: fnomura@faculty.chiba-u.jp [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Kazuyuki; Miura, Toshihide [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Tomonaga, Takeshi [Laboratory of Proteome Research, National Institute of Biomedical Innovation, Ibaraki (Japan); Yoshitomi, Hideyuki [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Imazeki, Fumio [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Takizawa, Hirotaka [Kashiwado Clinic in Port-Square of the Kashiwado Memorial Foundation, Chiba (Japan); Mogushi, Kaoru [Information Center for Medical Sciences, Tokyo Dental and Medical University, Tokyo (Japan); Miyazaki, Masaru [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Yokosuka, Osamu [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Overexpression of Ku86 in human liver cancer was shown by immunohistochemistry. Black-Right-Pointing-Pointer Serum anti-Ku86 was significantly elevated in early hepatocellular carcinoma. Black-Right-Pointing-Pointer Anti-Ku86 may be more sensitive than the conventional markers for early detection. Black-Right-Pointing-Pointer Serum anti-Ku86 significantly decreased after surgical resection of liver tumors. Black-Right-Pointing-Pointer Elevation of serum anti-Ku86 in other non-liver solid tumors was minimal. -- Abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detection of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41 {+-} 0.28 vs. 0.18 {+-} 0.08 Abs at 450 nm, P < 0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60.7% of

  4. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Highlights: ► Overexpression of Ku86 in human liver cancer was shown by immunohistochemistry. ► Serum anti-Ku86 was significantly elevated in early hepatocellular carcinoma. ► Anti-Ku86 may be more sensitive than the conventional markers for early detection. ► Serum anti-Ku86 significantly decreased after surgical resection of liver tumors. ► Elevation of serum anti-Ku86 in other non-liver solid tumors was minimal. -- Abstract: Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is one of the most common cancers worldwide and the third most common cause of cancer-related death. Imaging studies including ultrasound and computed tomography are recommended for early detection of HCC, but they are operator dependent, costly and involve radiation. Therefore, there is a need for simple and sensitive serum markers for the early detection of hepatocellular carcinoma (HCC). In our recent proteomic studies, a number of proteins overexpressed in HCC tissues were identified. We thought if the serum autoantibodies to these overexpressed proteins were detectable in HCC patients. Of these proteins, we focused on Ku86, a nuclear protein involved in multiple biological processes and aimed to assess the diagnostic value of serum anti-Ku86 in the early detection of HCC. Serum samples were obtained prior to treatment from 58 consecutive patients with early or relatively early hepatitis C virus (HCV)-related HCC and 137 patients with HCV-related liver cirrhosis without evidence of HCC. Enzyme immunoassays were used to measure serum levels of autoantibodies. Serum levels of anti-Ku86 antibodies were significantly elevated in HCC patients compared to those in liver cirrhosis patients (0.41 ± 0.28 vs. 0.18 ± 0.08 Abs at 450 nm, P < 0001). Setting the cut-off level to give 90% specificity, anti-Ku86 was positive in 60.7% of stage I solitary tumor <2 cm in diameter, whereas the sensitivities of alpha-fetoprotein (AFP) and protein induced by vitamin K

  5. Current update on combined hepatocellular-cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Suresh Maximin

    2014-01-01

    Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management.

  6. Immunology of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancyof the liver, advancing from a damaged, cirrhoticliver to HCC. Globally, HCC is the sixth most prevalentcancer and the third-most prevalent reason for neoplasticdisease-related deaths. A diverse array ofinfiltrating immunocytes regulates the developmentand progression of HCC, as is the case in many othercancers. An understanding of the various immunecomponents during HCC becomes necessary so thatnovel therapeutic strategies can be designed to combatthe disease. A dysregulated immune system (includingchanges in the number and/or function of immunecells, cytokine levels, and the expression of inhibitoryreceptors or their ligands) plays a key role in thedevelopment of HCC. Alterations in either the innateor adaptive arm of the immune system and cross-talkbetween them make the immune system tolerant totumors, leading to disease progression. In this review,we have discussed the status and roles of variousimmune effector cells (e.g. , dendritic cells, natural killercells, macrophages, and T cells), their cytokine profile,and the chemokine-receptor axis in promoting orimpeding HCC.

  7. Rapid long-lasting biochemical and radiological response to sorafenib in a case of advanced hepatocellular carcinoma.

    Science.gov (United States)

    Gerardi, Assunta Maria Teresa; Stoppino, Luca Pio; Liso, Arcangelo; Macarini, Luca; Landriscina, Matteo

    2013-03-01

    The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard of care for advanced stages of this disease. However, in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib. PMID:23426789

  8. Rapid long-lasting biochemical and radiological response to sorafenib in a case of advanced hepatocellular carcinoma

    Science.gov (United States)

    GERARDI, ASSUNTA MARIA TERESA; STOPPINO, LUCA PIO; LISO, ARCANGELO; MACARINI, LUCA; LANDRISCINA, MATTEO

    2013-01-01

    The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard of care for advanced stages of this disease. However, in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib. PMID:23426789

  9. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  10. Non-surgical management of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Most of patients with hepatocellular carcinoma (HCC) cannot benefit from surgical therapies. Among non-surgical options, only radiofrequency can challenge surgery for small size tumours. Conformal radiotherapy is likely highly efficient on solitary tumours, but controlled studies are warranted to conclude. Other options are purely palliative. Trans-arterial hepatic chemo-embolization is the goal-standard for multifocal hepatocellular carcinoma and Sorafenib for hepatocellular carcinoma with portal vein invasion, leading to modest but significant benefit on survival rates. Yttrium-90 radio-embolization is under evaluation through controlled studies, and could be of major interest for multifocal hepatocellular carcinoma with or without portal venous invasion. (authors)

  11. DNA methylation in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Iris Tischoff; Andrea Tannapfel

    2008-01-01

    As for many other tumors, development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes (TSG). In the last decades, in addition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes by promoter hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. In HCC, aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation.

  12. Clinical guideline SEOM: hepatocellular carcinoma

    OpenAIRE

    Sastre, J.; Díaz-Beveridge, R.; García-Foncillas, J; Guardeño, R.; C. López; Pazo, R.; Rodriguez-Salas, N.; Salgado, M; Salud, A; Feliu, J

    2015-01-01

    Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A–B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Acc...

  13. Transarterial embolization of metastatic mediastinal hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chia-Chang Chen

    2013-01-01

    Full Text Available This paper introduces an innovative treatment for extra-hepatic metastasis of hepatocellular carcinoma. A 71-year-old patient had a stable liver condition following treatment for hepatocellular carcinoma, but later developed symptomatic mediastinal metastasis. This rapidly growing mediastinal mass induced symptoms including cough and hoarseness. Serial sessions of transarterial embolization (TAE successfully controlled this mediastinal mass with limited side effects. The patient’s survival time since the initial diagnosis of the mediastinal hepatocellular carcinoma was 32 mo, significantly longer than the 12 mo mean survival period of patients with similar diagnoses: metastatic hepatocellular carcinoma and a liver condition with a Child-Pugh class A score. Currently, oral sorafenib is the treatment of choice for metastatic hepatocellular carcinoma. Recent studies indicate that locoregional treatment of extra-hepatic metastasis of hepatocellular carcinomas might also significantly improve the prognosis in patients with their primary hepatic lesions under control. Many effective locoregional therapies for extrahepatic metastasis, including radiation and surgical resection, may provide palliative effects for hepatocellular carcinoma-associated mediastinal metastasis. This case report demonstrates that TAE of metastatic mediastinal hepatocellular carcinoma provided this patient with tumor control and increased survival time. This finding is important as it can potentially provide an alternative treatment option for patients with similar symptoms and diagnoses.

  14. Retrospective Evaluation of Patients with Hepatocellular Carcinoma: Single-Center Experience

    Directory of Open Access Journals (Sweden)

    Tuncer Temel1

    2015-03-01

    Full Text Available Objective: Primary liver cancer is one of the most common and lethal type of tumors in the world. Hepatocellular forms compose about 80% of all primary liver tumors. Our aim is to evaluate the patients with hepatocellular carcinoma admitted to our clinic retrospectively. Methods: First we identified viral hepatitis serology and whether antiviral treatment was administered before the diagnosis and the period until the development of hepatocellular carcinoma for each case with hepatocellular carcinoma. Child-Pugh stage in cirrhotic cases, the stage of viral hepatitis in non-cirrhotic cases, and the treatment method suggested for hepatocellular carcinoma and the average life expectancy (for the patients whose life expectancy is known were evaluated. Alpha-feto protein levels and computerized tomography, ultrasound, magnetic resonance imaging findings were evaluated retrospectively. Correlation between alpha-feto protein levels and tumor numbers were evaluated statistically. Results: Total of 69 patients were evaluated. The median age at presentation was 62.8 (ranging from 25 to 80 years. Median (overall survival OS was 7.0 (ranging from 0 to 145 months in all patients. 18 patients (41.9% were Child-Pugh Class A, 12 (27.9% patients were Child-Pugh Class B and 13 (30.2% patients were Child-Pugh Class C. It was found that patients with severely high alpha-feto protein levels (>200 ng/ml, have 4 fold risk of multiple liver masses (OR: 4.05, 95% CI: 1.22-13.42. For the characterization of a liver mass as hepatocellular carcinoma, the diagnostic effectiveness of computerized tomography was 54.3%, and that of magnetic resonance imaging was 55.8%. Conclusion: As a result the patients with hepatocellular carcinoma can be diagnosed with combination of laboratory findings and imaging techniques. Alpha-feto protein levels are important for follow up of such patients and identifying the multiple mass presences.

  15. Clinical Aspects of Hepatocellular Carcinoma

    OpenAIRE

    Verhoef, Cornelis

    2008-01-01

    textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer mortality1. Despite the high numbers of patients diagnosed worldwide (the estimated number of people is 0.5 million cases per year), HCC continue to pose challenging clinical problems. The assessment of the tumor and treatment options needs a multi-disciplinary approach in which the surgeon plays a central role. The aim of this thesis is to update on the incidence,...

  16. Transhemangioma Ablation of Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  17. Transhemangioma Ablation of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

    2012-12-15

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  18. Non-Invasive Radiofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mustafa Raoof

    2011-01-01

    Full Text Available Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed.

  19. Surgical Treatment for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmad A Madkhali

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC is an epithelial tumor derived from hepatocytes; it accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related deaths. HCC treatment is a multidisciplinary and a multimodal task, with surgery in the form of liver resection and liver transplantation (LT representing the only potentially curative modality. However, there are variable opinions and discussions about applying these surgical options and using other supporting treatments. This article is a narrative review that includes articles published from 1984 to 2013 located by searching scientific databases such as PubMed, SCOPUS, and Elsevier, with the main keyword of hepatocellular carcinoma in addition to other keywords such as liver transplantation, liver resection, transarterial chemoembolization, portal vein embolization, bridging therapy, and downstaging. In this review, we focus mainly on the surgical treatment options offered for HCC, in order to illustrate the current relevant data available in the literature to help in applying these surgical options and to use other supporting treatment modalities when appropriate.

  20. Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment

    OpenAIRE

    Dafina Janevska; Viktorija Chaloska-Ivanova; Vlado Janevski

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue. This article provides a...

  1. Contemporary management of fibrolamellar hepatocellular carcinoma

    OpenAIRE

    Tefera Kassahun, Woubet

    2016-01-01

    Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant liver tumor which is thought to be a variant of conventional hepatocellular carcinoma (HCC). It accounts for a small proportion of HCC cases and occurs in a distinctly different group of patients which are young and usually not in the setting of chronic liver disease. The diagnosis of FL-HCC requires the integration of clinical information, imaging studies, and histology. In terms of the treatment options, the only potentially cur...

  2. Acute hepatic porphyria and hepatocellular carcinoma.

    OpenAIRE

    Kauppinen, R.; Mustajoki, P

    1988-01-01

    In this study we examined the case histories of 163 living and 82 deceased adult Finnish patients with acute hepatic porphyria. There were 184 patients with acute intermittent porphyria and 61 patients with variegate porphyria. Among the 124 of the 163 living patients, who were traced 1984-1985, no hepatocellular carcinoma was found. Among the 82 deceased patients the cause of death was porphyria in 29 (36%), cardiovascular disease in 23 (29%) and hepatocellular carcinoma in 7 (9%). Of the 7 ...

  3. Treatment of alcohol use disorder patients affected by liver cirrhosis and/or hepatocellular carcinoma awaiting liver transplantation.

    Science.gov (United States)

    Testino, Gianni; Leone, Silvia; Borro, Paolo

    2016-08-01

    Alcohol is one of the top three priority areas for public health worldwide. Alcohol is the second leading cause of liver disease, and 45-60% of cirrhosis deaths are alcohol related. In the United States it represents 30% of liver transplants and in Europe 50%. Twenty to 40% of cases of steatosis evolve into steatohepatitis, and l8-20% directly into liver cirrhosis; 20-40% of cases of steatohepatitis evolve into cirrhosis and 4-5% into hepatocellular carcinoma. This cascade of events takes 5 to 40 years. The temporal variability is related to the genetic pattern of the subject and the presence of associated risk factors. Thirty to 40% of patients with alcoholic liver disease (ALD) suffer from HCV, and 70% of HCV patients have a history of risky / harmful alcohol consumption. A severe clinical condition is certainly the overlap of acute alcoholic hepatitis (AAH) with a framework of HCV-related chronic hepatitis: acute chronic liver failure (ACLF). In the case of decompensated cirrhosis, severe AAH or ACLF non responder to medical therapy the indication, in selected patients, is certainly liver transplantation (LT). ALD treatment is important, but not very effective if abstention is not reached. In case of liver disease related or correlated to LT such as decompensated cirrhosis, severe AAH or ACLF the possibility of anticraving therapy is restricted to metadoxine and baclofen. In all alcohol use disorder patients with ALD psycho-social therapy and attendance at SHG groups it is mandatory, even in post-transplant period. PMID:27148681

  4. Alcoholic cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Stickel, Felix

    2015-01-01

    Hepatocellular carcinoma shows a rising incidence worldwide, and the largest burden of disease in Western countries derives from patients with alcoholic liver disease (ALD) and cirrhosis, the latter being the premier premalignant factor for HCC. The present chapter addresses key issues including the epidemiology of alcohol-associated HCC, and its link to other coexisting non-alcoholic liver diseases, and additional host and environmental risk factors including the underlying genetics. Also discussed are molecular mechanisms of alcohol-associated liver cancer evolution involving the mediators of alcohol toxicity and carcinogenicity, acetaldehyde and reactive oxygen species, as well as the recently described mutagenic adducts which these mediators form with DNA. Specifically, interference of alcohol with retinoids and cofactors of transmethylation processes are outlined. Information presented in this chapter illustrates that the development of HCC in the context of ALD is multifaceted and suggests several molecular targets for prevention and markers for the screening of risk groups. PMID:25427904

  5. Hepatocellular carcinoma and industrial epidemics

    Institute of Scientific and Technical Information of China (English)

    Alain Braillon; Gérard Dubois

    2011-01-01

    Worldwide, the burden of the non viral causes of hepatocellular carcinoma (HCC) is usually underestimated. Clearly industrial goods, tobacco, alcohol and processed foods are the agents of new epidemics in modern times which far outscore the burden of infectious agents on morbidity and mortality. Smoking, a dose-related contributing factor for HCC, receives too little attention in clinical practice. In France, tobacco, hepatitis B and C virus and alcohol are the main risk factors for HCC mortality (33%, 31% and 26%, respectively). In developing countries, where tobacco consumption is dramatically increasing, this epidemic may soon surpass hepatitis B. Obesity and diabetes are the contributing factors too. The role of industrial processed foods in the increase of the prevalence of obesity and diabetes cannot be ignored.

  6. The Applicability of a Human Immunohistochemical Panel to Mouse Models of Hepatocellular Neoplasia.

    Science.gov (United States)

    Salleng, Kenneth J; Revetta, Frank L; Deane, Natasha G; Washington, M Kay

    2015-10-01

    Various immunohistochemical panels are used as aids to distinguish between primary hepatocellular malignancies and metastatic tumors and between benign lesions and carcinomas. We compared the immunohistochemical spectrum of hepatocellular lesions in mice with that of human hepatocellular carcinoma (HCC). Specifically, we compared the staining parameters of 128 murine foci of cellular alteration (FCA) and tumors (adenoma and HCC) from archival tissue blocks of 3 transgenic mouse models (LFABP-cyclin D1, Alb1-TGFβ1, and LFABP-cyclin D1 × Alb1-TGFβ1) with those of archival human HCC (n = 5). Antibodies were chosen according to their published performance and characterization in human hepatocellular tumor diagnosis and included: arginase 1 (Arg1), β-catenin, glutamine synthetase (GS), glypican 3, hepatocyte paraffin 1 (HepPar1), and cytokeratin 19 (CK19). GS was the single best immunostain for identifying hepatocellular tumors in mice, with 100% positive staining. Data showed a trend toward loss of normal function (staining) with Arg1, with a higher percentage of positive staining in FCA than in adenomas and HCC. All FCA lacked murine β-catenin nuclear translocation, which was present in 2 of the 7 adenomas and 22 of the 96 HCC tested. HepPar1 staining was lower than anticipated, except in trabecular HCC (16 of 22 samples were positive). Glyp3 stained very lightly, and only scattered CK19-positive cells were noted (4 of 44 cases of mouse trabecular HCC). Thus, GS appears to be the most useful marker for identifying neoplasia in the transgenic mouse models we tested and should be included in immunohistochemistry assessing hepatocellular neoplasia development. PMID:26473343

  7. Early detection of hepatocellular carcinoma co-occurring with hepatitis C virus infection: A mathematical model

    Science.gov (United States)

    Zekri, Abdel-Rahman Nabawy; Youssef, Amira Salah El-Din; Bakr, Yasser Mabrouk; Gabr, Reham Mohamed; Ahmed, Ola Sayed; Elberry, Mostafa Hamed; Mayla, Ahmed Mahmoud; Abouelhoda, Mohamed; Bahnassy, Abeer A

    2016-01-01

    AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP). METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups. RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10-4) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status. CONCLUSION: Our

  8. Viral Genotypes and Associated Risk Factors of Hepatocellular Carcinoma in India

    International Nuclear Information System (INIS)

    This study aims to investigate the etiological relationship among hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol as risk factors in a cohort of hepatocellular carcinoma (HCC) patients from India. The clinical and biochemical profiles and tumor characteristics in the HCC cases were also evaluated. A total of 357 consecutive cases of HCC fulfilling the diagnostic criteria from the Barcelona–2000 EASL conference were included in the study. The blood samples were evaluated for serological evidence of HBV and HCV infection, viral load, and genotypes using serological tests, reverse transcription-polymerase chain reaction, and restriction fragment length polymorphism. The male/female ratio for the HCC cases was 5.87:1. Majority of the HCC patients (33.9%) were 50 to 59 years of age, with a mean age of 4±13.23 years. More than half the cases (60.8%) had underlying cirrhosis at presentation. Among the HCC patients, 68.9% were HBV related, 21.3% were HCV related, 18.8% were alcoholic, and 18.2% were of cryptogenic origin. The presence of any marker positive for HBV increased the risk for developing HCC by almost 27 times [OR: 27.33; (12.87–60.0)]. An increased risk of 10.6 times was observed for HCC development for cases positive for any HCV marker [OR: 10.55; (3.13–42.73)]. Heavy alcohol consumption along with HCV RNA positivity in cirrhotic patients was found to be a risk for developing HCC by 3 folds [OR: 3.17; (0.37–70.71)]. Patients of chronic HBV infection followed by chronic HCV infection were at higher risk of developing HCC in India. Chronic alcohol consumption was found to be a risk factor in cirrhotic cases only when it was associated with HCV RNA positivity. Most of the patients had a large tumor size (>5 cm) with multiple liver nodules, indicating an advanced stage of the disease thus making curative therapies difficult

  9. Contrast enhanced ultrasound of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kazushi Numata, Wen Luo, Manabu Morimoto, Masaaki Kondo, Yosuke Kunishi, Tomohiko Sasaki, Akito Nozaki, Katsuaki Tanaka

    2010-02-01

    Full Text Available Sonazoid (Daiichi Sankyo, Tokyo, Japan, a second-generation of a lipid-stabilized suspension of a perfluorobutane gas microbubble contrast agent, has been used clinically in patients with liver tumors and for harmonic gray-scale ultrasonography (US in Japan since January 2007. Sonazoid-enhanced US has two phases of contrast enhancement: vascular and late. In the late phase of Sonazoid-enhanced US, we scanned the whole liver using this modality at a low mechanical index (MI without destroying the microbubbles, and this method allows detection of small viable hepatocellular carcinoma (HCC lesions which cannot be detected by conventional US as perfusion defects in the late phase. Re-injection of Sonazoid into an HCC lesion which previously showed a perfusion defect in the late phase is useful for confirming blood flow into the defects. High MI intermittent imaging at 2 frames per second in the late phase is also helpful in differentiation between necrosis and viable hypervascular HCC lesions. Sonazoid-enhanced US by the coded harmonic angio mode at a high MI not only allows clear observation of tumor vessels and tumor enhancement, but also permits automatic scanning with Sonazoid-enhanced three dimensional (3D US. Fusion images combining US with contrast-enhanced CT or contrast-enhanced MRI have made it easy to detect typical or atypical HCC lesions. By these methods, Sonazoid-enhanced US can characterize liver tumors, grade HCC lesions histologically, recognize HCC dedifferentiation, evaluate the efficacy of ablation therapy or transcatheter arterial embolization, and guide ablation therapy for unresectable HCC. This article reviews the current developments and applications of Sonazoid-enhanced US and Sonazoid-enhanced 3D US for diagnosing and treating hepatic lesions, especially HCC.

  10. Treatment Approaches for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Khaldoun Almhanna

    2007-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide, and it is responsible for up to one million deaths annually. Although multiple risk factors for HCC have been identifi ed, and despite preventive measures, the incidence of HCC continues to rise to epidemiologic proportions in the United States. In general, tumor resection and orthotopic liver transplantation are the treatment with the best outcome; however, HCC is generally diagnosed late in its course when patients are not eligible for curative treatment options. HCC is a relatively Chemo-refractory tumor secondary to heterogeneity of the tumor and the high rate of multidrug resistant gene expression. There are no standard treatments for HCC, multiple palliative treatment modalities have been used for patients with unresectable disease. None of these modalities have shown any superiority; and the retrospective nature of these available data has confounded any reasonable conclusions. Different institutions use different treatment schema dependent on the center expertise. Sorafenib, a tyrosine kinase inhibitor, has recently demonstrated a survival advantage in metastatic HCC, and if approved by the FDA, might become the standard of care. In this article we will review the rationale behind the currently available treatment options for HCC.

  11. Interventional treatments for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yong-Song Guan; Yuan Liu

    2006-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20%of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive interventional managements including local ablation and transarterial chemoembolization (TACE). In this paper, we review the interventional treatments of HCC. DATA SOURCES:A literature search of PubMed database was conducted and research articles were reviewed. RESULTS: Percutaneous ethanol injection (PEI) is usually applied to small HCC for a complete necrosis. Radiofrequency ablation, an alternative to PEI, also causes tumor necrosis and needs fewer times of ablation. Other methods such as acetic acid injection, laser, microwave, etc have enriched local ablation for HCC. High intensity focus ultrasound (HIFU) is thought to be promising. TACE, another common modality, can improve the survival rate of patients with HCC. The newly developed embolic agents and adjuvant rAd-p53 gene therapy are well reported. CONCLUSIONS:Surgically-noneligible HCC can be treated with interventional procedures. Each method has its advantages and disadvantages. However, it is still pressing to develop ablative methods as well as new embolic agents for a better prognosis of HCC.

  12. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs;

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case of...... synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  13. Histological and Immunohistochemical Revision of Hepatocellular Adenomas: A Learning Experience

    Directory of Open Access Journals (Sweden)

    S. Fonseca

    2013-01-01

    Full Text Available Light has been shed on the genotype/phenotype correlation in hepatocellular adenoma (HCA recognizing HNF1α-inactivated HCA (H-HCA, inflammatory HCA (IHCA, and β-catenin-activated HCA (b-HCA. We reviewed retrospectively our surgical HCA series to learn how to recognize the different subtypes histopathologically and how to interpret adequately their immunohistochemical staining. From January 1992 to January 2012, 37 patients underwent surgical resection for HCA in our institution. Nine had H-HCA (25% characterized by steatosis and loss of L-FABP expression; 20 had IHCA (55.5% showing CRP and/or SAA expression, sinusoidal dilatation, and variable inflammation; and 1 patient had both H-HCA and IHCA. In 5 patients (14%, b-HCA with GS and β-catenin nuclear positivity was diagnosed, two already with hepatocellular carcinoma. Two cases (5.5% remained unclassified. One of the b-HCA showed also the H-HCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/HNF1α-inactivated HCA, another b-HCA exhibited the IHCA histological and immunohistochemical characteristics suggesting a subgroup of β-catenin-activated/inflammatory HCA. Interestingly, three patients had underlying vascular abnormalities. Using the recently published criteria enabled us to classify histopathologically our retrospective HCA surgical series with accurate recognition of b-HCA for which we confirm the higher risk of malignant transformation. We also underlined the association between HCA and vascular abnormalities.

  14. Histone deacetylase inhibitors for treatment of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Danila CORADINI; Annalisa SPERANZA

    2005-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in the world.Surgical resection has been considered the optimal treatment approach, but only a small proportion of patients are suitable candidates for surgery, and the relapse rate is high. Approaches to prevent recurrence, including chemoemboliza-tion before and adjuvant therapy after surgery, have proven to have a limited benefit;liver transplantation is successful in treating limited-stage HCC because only a minority of patients qualify for transplantation. Therefore, new therapeutic strategies are urgently needed. Because in addition to the classical genetic mechanisms of deletion or inactivating point mutations, epigenetic alterations, such as hyperacetylation of the chromatin-associated histones (responsible for gene silencing), are believed to be involved in the development and progression of HCC, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In particular, pre-clinical results obtained using HA-But, an HDAC inhibitor in which butyric acid residues are esterified to a hyaluronic acid backbone and characterized by a high affinity for the membrane receptor CD44, indicated that this class of compounds may represent a promising approach for hepatocellular carcinoma treatment.

  15. Primary hepatic tumors with myxoid change: morphologically unique hepatic adenomas and hepatocellular carcinomas.

    Science.gov (United States)

    Salaria, Safia N; Graham, Rondell P; Aishima, Shinichi; Mounajjed, Taofic; Yeh, Matthew M; Torbenson, Michael S

    2015-03-01

    Mucin production in primary liver neoplasms is typically interpreted as evidence for biliary differentiation. However, we have observed benign and malignant liver tumors that have abundant extracellular myxoid/mucinous material, yet have only evidence of hepatocellular differentiation. To further characterize these unusual findings, 9 cases were identified and further studied. Four cases were hepatic adenomas, whereas 5 were hepatocellular carcinomas. Extracellular myxoid/mucinous material was diffuse in 7 cases and patchy in 2 cases. The extracellular myxoid/mucinous material was typically weakly mucicarmine positive (N=6) and Alcian blue positive (N=8). All tumors were well differentiated, and none had evidence for biliary differentiation by morphology or immunohistochemistry. The hepatic adenomas arose in nondiabetic and nonobese patients. Both the hepatic adenomas and the hepatocellular carcinomas were strongly and diffusely HepPar1 positive, CK19 negative, and showed loss of LFABP protein expression. These findings indicate that extracellular myxoid/mucinous material in isolation should not be interpreted as cholangiocarcinoma. Furthermore, the unique morphology, the clinical characteristics, and the immunophenotype results suggest that myxoid hepatic adenomas and hepatocellular carcinoma may be unique tumor variants. PMID:25602798

  16. Hepatocellular Carcinoma: Risk Factors, Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Dafina Janevska

    2015-10-01

    Full Text Available Hepatocellular carcinoma (HCC is the most often primary cancer of the liver and is one if the leading cause of cancer-related death worldwide. The incidence of HCC has geographic distribution with the highest levels in countries with developing economies. Patients with hepatocellular carcinoma have poor prognosis despite the achievements in surgery techniques and other therapeutic procedures and it is a reason why continuous attention should be paid to this issue. This article provides an overview of this disease based on an extensive review of relevant literature. The article summarizes the current risk factors, diagnosis, staging and the management of HCC.

  17. Synchronous Fibrolamellar Hepatocellular Carcinoma and Auricular Myxoma

    Science.gov (United States)

    González-Cantú, Yessica M.; Rodriguez-Padilla, Cristina; Tena-Suck, Martha Lilia; García de la Fuente, Alberto; Mejía-Bañuelos, Rosa María; Díaz Mendoza, Raymundo; Quintanilla-Garza, Samuel; Batisda-Acuña, Yolaester

    2015-01-01

    Synchronic occurrence of benign and malignant tumors is extremely rare. Fibrolamellar hepatocellular carcinoma represents 1% to 2% of all hepatocarcinomas, while myxomas represent about half of all the cases of primary tumors of the heart. We present the case of a 53-year-old woman with a left atrial myxoma that was surgically removed. Several weeks later, the patient returned to the hospital with abdominal pain. CT scan showed a mass in the left lobe of the liver that was resected and diagnosed as fibrolamellar hepatocellular carcinoma. As of this writing, the patient is healthy. PMID:26509093

  18. Hepatocellular carcinoma: epidemiology and risk factors

    Directory of Open Access Journals (Sweden)

    Kew MC

    2014-08-01

    Full Text Available Michael C Kew Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa Abstract: Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron

  19. Microwave ablation of hepatocellular carcinoma.

    Science.gov (United States)

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-11-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  20. New advances in hepatocellular carcinoma

    Science.gov (United States)

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  1. New advances in hepatocellular carcinoma.

    Science.gov (United States)

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  2. Microwave ablation of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Although surgical resection is still the optimal treatmentoption for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgicaltreatment alternative, thanks to their minimalinvasiveness, excellent tolerability and safety profile,proven efficacy in local disease control, virtuallyunlimited repeatability and cost-effectiveness. Differentenergy sources are currently employed in clinics asphysical agents for percutaneous or intra-surgicalthermal ablation of HCC nodules. Among them, radiofrequency(RF) currents are the most used, whilemicrowave ablations (MWA) are becoming increasinglypopular. Starting from the 90s', RF ablation (RFA) rapidlybecame the standard of care in ablation, especially inthe treatment of small HCC nodules; however, RFAexhibits substantial performance limitations in thetreatment of large lesions and/or tumors located nearmajor heat sinks. MWA, first introduced in the FarEastern clinical practice in the 80s', showing promisingresults but also severe limitations in the controllabilityof the emitted field and in the high amount of poweremployed for the ablation of large tumors, resultingin a poor coagulative performance and a relativelyhigh complication rate, nowadays shows better resultsboth in terms of treatment controllability and of overallcoagulative performance, thanks to the improvementof technology. In this review we provide an extensiveand detailed overview of the key physical and technicalaspects of MWA and of the currently available systems,and we want to discuss the most relevant published dataon MWA treatments of HCC nodules in regard to clinicalresults and to the type and rate of complications, both inabsolute terms and in comparison with RFA.

  3. Newer markers for hepatocellular carcinoma.

    Science.gov (United States)

    Marrero, Jorge A; Lok, Anna S F

    2004-11-01

    The incidence of hepatocellular carcinoma (HCC) is increasing worldwide; the overall survival of patients with HCC is grim because most patients are diagnosed late, when curative treatment is not possible. Cirrhosis is the strongest risk factor for the development of HCC. HCC surveillance with alpha-fetoprotein (AFP) and ultrasonography has been recommended for persons with cirrhosis. However, AFP level is insensitive for the early detection of HCC, and ultrasonography is expensive and operator dependent. Clearly, there is a need for novel strategies for the early detection of HCC. The ideal biomarker assay for HCC would be sensitive, specific, noninvasive, reproducible, inexpensive, and acceptable to patients. The Early Detection Research Network of the National Cancer Institute has proposed 5 phases for biomarker validation: preclinical exploratory studies, clinical assay development for disease, retrospective longitudinal study to detect preclinical disease, prospective screening study, and cancer control studies. Several biomarkers, such as des-gamma carboxyprothrombin, lens culinaris agglutinin-reactive AFP, human hepatocyte growth factor, and insulin-like growth factor-1, are promising, but none of these markers has been validated for clinical use. Limitations of the current literature include inadequate sample size, heterogeneity in biomarker assay methods and result reporting, limited analysis of demographics and cause of liver disease as covariates in the expression of these markers, and a scarcity of longitudinal studies evaluating the ability of biomarkers to detect preclinical disease. There is an urgent need for novel biomarkers for the detection of early HCC; the National Cancer Institute proposal provides a framework for future validation studies. PMID:15508074

  4. Decreased Aquaporin Expression Leads to Increased Resistance to Apoptosis in Hepatocellular Carcinoma

    OpenAIRE

    Jablonski, Elizabeth M.; Mattocks, M. Adrian; Sokolov, Eugene; Koniaris, Leonidas G.; Hughes, Francis M; Fausto, Nelson; Pierce, Robert H.; Mckillop, Iain H.

    2006-01-01

    Cells undergoing apoptosis are characterized by decreased cell size due to changes in intracellular ion concentration and rapid, aquaporin (AQP)-dependent water movement out of the cell, events required for the activation of pro-apoptotic enzymes. The current study demonstrates AQP 8 and 9 expression is significantly decreased in hepatocellular carcinoma (HCC) versus normal liver. Isolation of hepatic tumor cells (H4IIE) and hepatocytes confirmed a lack of water movement across the H4IIE cell...

  5. Genotype phenotype classification of hepatocellular adenoma

    Institute of Scientific and Technical Information of China (English)

    Paulette Bioulac-Sage; Jean Frédéric Blanc; Sandra Rebouissou; Charles Balabaud; Jessica Zucman-Rossi

    2007-01-01

    Studies that compare tumor genotype with phenotype have provided the basis of a new histological/molecular classification of hepatocellular adenomas. Based on two molecular criteria (presence of a TCF1/HNF1α or β-catenin mutation), and an additional histological criterion (presence or absence of an inflammatory infiltrate), subgroups of hepatocellular adenoma can be defined and distinguished from focal nodular hyperplasia. Analysis of 96 hepatocellular adenomas performed by a French collaborative network showed that they can be divided into four broad subgroups: the first one is defined by the presence of mutations in TCF1 gene inactivating the hepatocyte nuclear factor 1 (HNF1α); the second by the presence of β-catenin activating mutations; the category without mutations of HNF1α or β-catenin is further divided into 2 subgroups depending on the presence or absence of inflammation. Therefore, the approach to the diagnosis of problematic benign hepatocytic nodules may be entering a new era directed by new molecular information. It is hoped that immunohistological tools will improve significantly diagnosis of liver biopsy in our ability to distinguish hepatocellular adenoma from focal nodular hyperplasia (FNH), and to delineate clinically meaningful entities within each group to define the best clinical management. The optimal care of patients with a liver nodule will benefit from the recent knowledge coming from molecular biology and the combined expertise of hepatologists, pathologists, radiologists, and surgeons.

  6. Radioembolisation for treatment of pediatric hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Transarterial radioembolisation with yttrium-90 (TARE-Y90), a catheter-directed therapy, has been used extensively in adults to treat primary and secondary hepatic malignancies. To our knowledge, the use of this palliative technique has not been described in children. We present two children with unresectable hepatocellular carcinoma (HCC) treated with TARE-Y90. (orig.)

  7. Radioembolisation for treatment of pediatric hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, Clifford Matthew; Kukreja, Kamlesh [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Geller, James I. [Cincinnati Children' s Hospital Medical Center, Department of Hematology/Oncology, Cincinnati, OH (United States); Schatzman, Carmen; Ristagno, Ross [University of Cincinnati, UC Health, Department of Radiology, Division of Interventional Radiology, Cincinnati, OH (United States)

    2013-07-15

    Transarterial radioembolisation with yttrium-90 (TARE-Y90), a catheter-directed therapy, has been used extensively in adults to treat primary and secondary hepatic malignancies. To our knowledge, the use of this palliative technique has not been described in children. We present two children with unresectable hepatocellular carcinoma (HCC) treated with TARE-Y90. (orig.)

  8. Expression of liver fatty acid binding protein in hepatocellular carcinoma.

    Science.gov (United States)

    Cho, Soo-Jin; Ferrell, Linda D; Gill, Ryan M

    2016-04-01

    Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down-regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors. PMID:26997447

  9. File list: Unc.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: His.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: His.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Unc.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: His.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: Unc.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: His.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 Histone Liver Carcinoma, Hepatocellula...r http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

  16. File list: Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 Unclassified Liver Carcinoma, Hepatocellula...r http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  17. Hepatocellular carcinoma: a clinico pathological study

    International Nuclear Information System (INIS)

    To describe the clinico-pathological and radiological profile of hepatocellular carcinoma. All consecutive patients suspected of having hepatocellular carcinoma (HCC), were admitted and included in this study. Diagnosis of HCC was established by clinical, biochemical, ultrasonographic and histopathologic findings. Patients with primary carcinoma elsewhere in the body, metastatic in the liver, fibrolamellar carcinoma and benign tumours were excluded from the study. At ultrasonography, the details of tumour size and number, portal vein thrombosis and presence of ascites were recorded. Patients were staged according to Okuda staging system. Results were described in mean and percentage values. There were 82 patients with hepatocellular carcinoma including 58 males and 24 females, with male to female ratio of 2.8:1. The mean age of patients was 56.24 +- 13.65 years. Right hypochondrial pain was the main symptom in 52 (63.4%) patients. The duration of symptoms varied from 1 month to 2 years. Tumour size was larger than 50% of liver size in 42 (51.2%) with portal vein thrombosis in 10 (12.19%). Anti HCV was positive in 44 (53.7%), HBsAg in 26 (31.7%) and both were found positive in 2 (2.44%) patients. Ten patients (12.2/%) found negative both for anti-HCV and HBsAg. According to Okuda staging system 18 patients had stage 1, 50 had stage 2 and 14 had stage 3 hepatocellular carcinoma. The mean age of presentation of hepatocellular carcinoma was younger as compared to western countries with potentially large non-resectable lesions. Chronic hepatitis C and B was found to be the major known factors. Patients with chronic hepatitis C and B should undergo vigorous HCC surveillance to detect early, potentially respectable HCC. (author)

  18. Interventional Radionuclide Therapy of Hepatocellular Carcinoma:Assessment of Intratumoral Retention of HPMA Copolymers

    Institute of Scientific and Technical Information of China (English)

    YUAN Jian-chao; MIAO Cheng-ping; ZENG Xian-wu; GUO Hong-yun; WANG Xiao-qi; LIAO Shi-qi; XIE Xiao-li

    2013-01-01

    To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma,poly(HPMA)-APMA-DTPA[HPMA=N-(2-hydroxypropyl) methacrylamide; APMA=N-(3-aminopropyl)methacrylamide; DTPA=diethylenetriaminepentaacetic acid] was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N'-azobis(isobutyronitrile) as the initiator.The copolymers were characterized with nuclear magnetic resonance(NMR) spectroscopy and gel permeation chromatography(GPC,Mn=2.2×104,Mw/Mn=1.38).Subsequently,poly(HPMA)-APMA-DTPA was conjugated with 99mTc radionuclide.Prolonged retention of poly(HPMA)-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography(SPECT-CT) at 1,2,4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice.DTPA-99mTC was also synthesized and characterized for comparison.The data suggest that the poly(HPMA)-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.

  19. Hepatocellular carcinoma in the Malaysian Orang Asli.

    Science.gov (United States)

    Sumithran, E; Prathap, K

    1976-05-01

    Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people. PMID:177187

  20. Tumoral pulmonary emboli from angioinvasive hepatocellular carcinoma.

    Science.gov (United States)

    Clark, Toshimasa; Maximin, Suresh; Shriki, Jabi; Bhargava, Puneet

    2014-01-01

    Tumoral pulmonary emboli from hepatocellular carcinoma (HCC) have rarely been described, although invasion of the portal and hepatic venous systems is a well-known complication. HCC originating in a noncirrhotic liver in the absence of chronic hepatitis B infection is also uncommon. We present a case of a patient with chronic hepatitis C infection without hepatic cirrhosis who developed angioinvasive HCC with intracardiac extension and tumoral pulmonary emboli. Differential considerations, including combined HCC-cholangiocarcinoma, other hepatic mesenchymal tumors, and metastasis, are discussed. Owing to poor prognosis, no resection was attempted. Autopsy was performed because of the unusual clinical presentation, and immunohistochemistry of the hepatic tumor, the intracardiac extension, and the pulmonary emboli were concordant with hepatocellular origin. Even though definitive diagnosis may not affect patient outcome, it is important for radiologists and clinicians to be aware that angioinvasive HCC may arise in the absence of cirrhosis. PMID:24948215

  1. Combined hepatocellular cholangiocarcinoma: Controversies to be addressed

    Science.gov (United States)

    Wang, An-Qiang; Zheng, Yong-Chang; Du, Juan; Zhu, Cheng-Pei; Huang, Han-Chun; Wang, Shan-Shan; Wu, Liang-Cai; Wan, Xue-Shuai; Zhang, Hao-Hai; Miao, Ruo-Yu; Sang, Xin-Ting; Zhao, Hai-Tao

    2016-01-01

    Combined hepatocellular cholangiocarcinoma (CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions. PMID:27182157

  2. Primary hepatocellular carcinoma in extrahepatic bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Seok Tae; Ham, Soo Youn; Park, Cheol Min; Kim, Jung Hyuk; Cha, In Ho; Chung, Kyoo Byung; Suh, Woon Hyuck; Lee, Chang Hong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    1991-03-15

    Obstructive jaundice due to hepatocellular carcinoma in an extrahepatic bile duct, without a mass lesion in the liver parenchyma, is extremely rare. We experienced two cases of primary hepatocellular carcinoma arising from an extrahepatic bile duct: one in a 53-year-old man whose {alpha} -fetoprotein value was 800 ng/ml, and another in a 39-year-old woman, in whom the mass lesion was found to be attached to an extrahepatic bile duct. These tumors had a well-marginated sausage-like shape on CT and US, and the contrast media passed freely along their margins on both PTC and ERCP. Recurrences of these tumors were observed in the extrahepatic bile duct 6 and 2 months after surgery, respectively.

  3. Radiotherapy for metastatic fibrolamellar hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Justin G. Peacock

    2013-07-01

    Full Text Available Fibrolamellar hepatocellular carcinoma (FLHCC is a rare variant of hepatocellular carcinoma (HCC that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.

  4. Welcome to Journal of Hepatocellular Carcinoma

    OpenAIRE

    Kaseb AO

    2015-01-01

    Ahmed O Kaseb Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Hepatocellular carcinoma (HCC) develops as a consequence of underlying chronic liver disease, most commonly cirrhosis. Therefore, HCC management draws on the expertise of a wide range of medical specialists. Currently, novel therapeutic modalities for HCC are investigated within the framework of a multidisciplinary approach. Therefore, there is a critical...

  5. Targeting cancer stem cells in hepatocellular carcinoma

    OpenAIRE

    MISHRA, LOPA

    2014-01-01

    Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC) is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the fun...

  6. Welcome to Journal of Hepatocellular Carcinoma

    OpenAIRE

    Kaseb AO

    2015-01-01

    Ahmed O Kaseb Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Hepatocellular carcinoma (HCC) develops as a consequence of underlying chronic liver disease, most commonly cirrhosis. Therefore, HCC management draws on the expertise of a wide range of medical specialists. Currently, novel therapeutic modalities for HCC are investigated within the framework of a multidisciplinary approach. Therefore, there is a critical nee...

  7. Imaging appearance of treated hepatocellular carcinoma.

    OpenAIRE

    Agnello, F; SALVAGGIO, G; G. Cabibbo(); Maida, M; Lagalla, R.; Midiri, M; Brancatelli, G

    2013-01-01

    Surgical resection and imaging guided treatments play a crucial role in the management of hepatocellular carcinoma (HCC). Although the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and has a key role in HCC decision-making process. However, radiological assessment of HCC treatment efficacy is often controversial. There are few doubts on the evaluation of surgical resection; in fact, all known tumor sites should be removed....

  8. Aflatoxins, hepatocellular carcinoma and public health

    OpenAIRE

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide, primarily affecting populations in the developing countries. Aflatoxin, a food contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a known human carcinogen that has been shown to be a causative agent in the pathogenesis of HCC. Aflatoxin can affect a wide range of food commodities including corns, oilseeds, spices, and tree nuts as well as milk, meat, and dried fruit. Many ...

  9. Prevention of hepatocellular carcinoma by immunization*

    OpenAIRE

    1983-01-01

    The evidence for an association between the carrier state of hepatitis B virus infection and hepatocellular carcinoma (liver cell cancer) is now sufficiently strong to justify the use of a vaccine against this infection as a means of preventing this cancer. Effective vaccines are available and have been tested in feasibility studies, and their use in field trials to test their effectiveness against the long-term risk of developing this cancer is now possible. At the present time, only limited...

  10. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

    International Nuclear Information System (INIS)

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  11. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-04-15

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  12. Fat in the liver: diagnosis and characterization

    International Nuclear Information System (INIS)

    The purpose of this article is to provide an update on imaging techniques useful for detection and characterization of fat in the liver. Imaging findings of liver steatosis, both diffuse steatosis and focal fatty change, as well as focal fatty sparing, are presented. In addition, we will review computed tomography (CT) and magnetic resonance (MR) findings of focal liver lesions with fatty metamorphosis, including hepatocellular carcinoma, hepatocellular adenoma, focal nodular hyperplasia, angiomyolipoma, lipoma, and metastases. (orig.)

  13. Fat in the liver: diagnosis and characterization

    Energy Technology Data Exchange (ETDEWEB)

    Valls, Carlos [Hospital Universitari de Bellvitge, Department of Radiology, Barcelona (Spain); Hopital Beaujon, Department of Radiology, Clichy (France); Iannacconne, Ricardo [Hopital Beaujon, Department of Radiology, Clichy (France); Ospedale la Sapienza, Department of Radiology, Roma (Italy); Alba, Esther [Hospital Universitari de Bellvitge, Department of Radiology, Barcelona (Spain); Murakami, Takamichi; Hori, Masatoshi [Osaka University Graduate School of Medicine, Department of Radiology, Osaka (Japan); Passariello, Roberto [Ospedale la Sapienza, Department of Radiology, Roma (Italy); Vilgrain, Valerie [Hopital Beaujon, Department of Radiology, Clichy (France)

    2006-10-15

    The purpose of this article is to provide an update on imaging techniques useful for detection and characterization of fat in the liver. Imaging findings of liver steatosis, both diffuse steatosis and focal fatty change, as well as focal fatty sparing, are presented. In addition, we will review computed tomography (CT) and magnetic resonance (MR) findings of focal liver lesions with fatty metamorphosis, including hepatocellular carcinoma, hepatocellular adenoma, focal nodular hyperplasia, angiomyolipoma, lipoma, and metastases. (orig.)

  14. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due to...

  15. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Oliveri, Roberto S; Wetterslev, Jørn; Gluud, Christian

    2011-01-01

    Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.......Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC....

  16. Hypertrophic osteopathy associated with hepatocellular carcinoma in a dog

    OpenAIRE

    Randall, Victoria D.; Souza, Carlos; Vanderhart, Daniel; Boston, Sarah

    2015-01-01

    A 9-year-old spayed female dog diagnosed with hepatocellular carcinoma and hypertrophic osteopathy was negative for additional lesions on computed tomography of the thorax and abdomen. Resection of the affected liver lobe resulted in resolution of clinical signs. This is the first case of hypertrophic osteopathy secondary to hepatocellular carcinoma.

  17. Clinical trials of antiangiogenic therapy for hepatocellular carcinoma.

    Science.gov (United States)

    Taketomi, Akinobu

    2016-04-01

    Angiogenesis is a promising therapeutic target to inhibit tumor growth. This review summarizes data from clinical trials of antiangiogenic agents in hepatocellular carcinoma. A systematic search of PubMed was performed to identify clinical trials of specific antiangiogenic agents in hepatocellular carcinoma treatment, particularly phase III trials involving treatment guidelines for advanced hepatocellular carcinoma. Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma. Two large-scale, randomized phase III trials using sorafenib involving patients with unresectable HCC showed a significant survival benefit compared with placebo control groups. However, subsequent phase III trials of antiangiogenic agents in hepatocellular carcinoma have failed to improve survival compared with standard treatment protocols using sorafenib. The efficacy of antiangiogenic agents in combination with other drugs, transarterial chemoembolization, and surgical resection is currently being investigated. Future research is expected to optimize antiangiogenic therapies in combination with standard treatment with sorafenib. PMID:26899258

  18. NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma.

    Science.gov (United States)

    Wilson, C L; Jurk, D; Fullard, N; Banks, P; Page, A; Luli, S; Elsharkawy, A M; Gieling, R G; Chakraborty, J Bagchi; Fox, C; Richardson, C; Callaghan, K; Blair, G E; Fox, N; Lagnado, A; Passos, J F; Moore, A J; Smith, G R; Tiniakos, D G; Mann, J; Oakley, F; Mann, D A

    2015-01-01

    Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1(S340A/S340A)mice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC. PMID:25879839

  19. Telomere shortening correlates with increasing aneuploidy of chromosome 8 in human hepatocellular carcinoma.

    Science.gov (United States)

    Plentz, Ruben R; Schlegelberger, Brigitte; Flemming, Peer; Gebel, Michael; Kreipe, Hans; Manns, Michael P; Rudolph, K Lenhard; Wilkens, Ludwig

    2005-09-01

    Chromosomal instability (CIN) leads to an increase in aneuploidy and chromosomal aberrations in human hepatocellular carcinoma (HCC). Telomere shortening appears as one mechanism fostering the development of CIN. Whether telomere shortening correlates to specific genetic changes that characterize a certain type of cancer has yet to be established. In our recent study, we combined on a cellular level the analysis of hepatocellular telomere fluorescent intensity (TFI) and copy number of chromosome 8-one of the hallmark chromosomal alterations in hepatocellular carcinoma (HCC). We investigated 15 cytological fine-needle biopsies of aneuploid HCC and 5 touch prints of cadaver livers without cancer. Hepatocyte-specific TFI and the measurement of centromere-specific probe for chromosome 8 were both performed by quantitative fluorescence in situ hybridization (qFISH) or FISH. Combined analysis of both methods (coFISH) allowed measurement of telomere length and chromosome 8 copy number on a single cell level. We observed that telomere shortening correlates significantly with increasing copy number of chromosome 8 in HCC on the cellular level. Above the level of 5 copies of chromosome 8 per nucleus, no further shortening of telomeres was found, indicating that telomeres had reached a critically short length at this stage of aneuploidy. In conclusion, our study gives direct evidence that telomere shortening is linked to a specific genetic alteration characteristic for human HCC. PMID:16116624

  20. NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma

    Science.gov (United States)

    Wilson, C. L.; Jurk, D.; Fullard, N.; Banks, P.; Page, A.; Luli, S.; Elsharkawy, A. M.; Gieling, R. G.; Chakraborty, J. Bagchi; Fox, C.; Richardson, C.; Callaghan, K.; Blair, G. E.; Fox, N.; Lagnado, A.; Passos, J. F.; Moore, A. J.; Smith, G. R.; Tiniakos, D. G.; Mann, J.; Oakley, F.; Mann, D. A.

    2015-04-01

    Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1S340A/S340Amice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.

  1. Quantitative detection of common deletion of mitochondrial DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Shao; Hong-Yi Gao; Yu-Hong Li; Yu Zhang; You-Yong Lu; Yi-Xin Zeng

    2004-01-01

    AIM: To study the deletion of mitochondiral DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia and its significance in the development of cancer.METHODS: Deleted mtDNA (CD-mtDNA) and wild type mtDNA (WT-mtDNA) were quantitatively analyzed by using real-time PCR in 27 hepatocellular carcinomas (HCC)and corresponding noncancerous liver tissues and 27hepatocellular nodular hyperplasiae (HNH).RESULTS: A novel CD (4 981 bp) was detected in 85%(23/27) and 83%(22/27) of HCC and HNH tumor tissues,respectively, which were significantly higher than that in paired noncancerous liver tissues (57%, 15/27) (P<0.05).The CD/WT-mtDNA ratio in HCC tumors was 0.00092(median, interquartile range, 0.0001202-0.00105), which was significantly higher than that in paired noncancerous liver tissues (median, 0.000, quartile range, 0-0) (P=0.002,Mann-Whitney Test), and was 25 of times of that in HNH tissues (median, 0.0000374, quartile range, 0-0.0004225)(P=0.002, Mann-Whitney test).CONCLUSION: CD-mtDNA mutation plays an important role in the development and progression of HCC.

  2. Involvement of DNA Damage Response Pathways in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Sheau-Fang Yang

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC has been known as one of the most lethal human malignancies, due to the difficulty of early detection, chemoresistance, and radioresistance, and is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. Its development has been closely associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Genetic alterations and genomic instability, probably resulted from unrepaired DNA lesions, are increasingly recognized as a common feature of human HCC. Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known as the DNA damage response (DDR, is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. It has been demonstrated that various HCC-associated risk factors are able to promote DNA damages, formation of DNA adducts, and chromosomal aberrations. Hence, alterations in the DDR pathways may accumulate these lesions to trigger hepatocarcinogenesis and also to facilitate advanced HCC progression. This review collects some of the most known information about the link between HCC-associated risk factors and DDR pathways in HCC. Hopefully, the review will remind the researchers and clinicians of further characterizing and validating the roles of these DDR pathways in HCC.

  3. Pedunculated hepatocellular carcinoma and splenic metastasis

    Institute of Scientific and Technical Information of China (English)

    Mao-Lin Yan; Yao-Dong Wang; Zhi-De Lai; Yi-Feng Tian; Hong-Biao Chen; Fu-Nan Qiu; Song-Qiang Zhou

    2009-01-01

    Only a few cases of pedunculated hepatocellular carcinoma (P-HCC) have been reported in the literature. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes,kidney, bone marrow and adrenals. Metastasis to spleen is mostly via hematogenous metastasis, direct metastasis to spleen was very rare. We report a case of P-HCC presenting as a left upper abdominal lesions which involved the spleen that was actually a P-HCC with splenic metastasis. This case is unique as P-HCC directly involved the spleen which is not via hematogenous metastasis.

  4. [Hepatocellular carcinoma and vitamin K2].

    Science.gov (United States)

    Mizuta, Toshihiko; Ozaki, Iwata

    2015-11-01

    Despite recent progress in diagnosis and therapy, hepatocellular carcinoma(HCC)remains among the cancers with the poorest prognoses. Vitamin Ks(VKs)have been shown to suppress the growth of HCC cells. Long-term administration of VK2 has established its clinical safety, but it does not appear to exhibit marked anti-tumor effects when administered alone. For more effective use of VK2 against HCC, co-administration of VK2 with other proven anticancer agents or development of a new VK preparation with a modified side-chain should be investigated in the future. PMID:26503869

  5. Non-viral causes of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Wojciech; Blonski; David; S; Kotlyar; Kimberly; A; Forde

    2010-01-01

    Hepatocellular carcinoma(HCC) is the most common primary liver malignancy and represents an international public health concern as one of the most deadly cancers worldwide.The main etiology of HCC is chronic infection with hepatitis B and hepatitis C viruses.However,there are other important factors that contribute to the international burden of HCC.Among these are obesity,diabetes,non-alcoholic steatohepatitis and dietary exposures.Emerging evidence suggests that the etiology of many cases of HCC is in fac...

  6. Epigenetics of hepatocellular carcinoma: a new horizon

    Institute of Scientific and Technical Information of China (English)

    LIU Wei-ren; SHI Ying-hong; PENG Yuan-fei; FAN Jia

    2012-01-01

    Epigenetic changes refer to stable alterations in gene expression with no underlying modifications in the genetic sequence itself.It has become clear that not only gene variations but also epigenetic modifications may contribute to varied diseases,including cancer.This review will provide an overview of how epigenetic factors,including genomic DNA methylation,histone modifications,and miRNA regulation,contribute to hepatocellular carcinoma (HCC) dissemination,invasion,and metastasis.Additionally,the reversal of dysregulated epigenetic changes has emerged as a potential strategy for the treatment of HCC,and we will summarize the latest epigenetic therapies for HCC.

  7. Innovative surgical approaches for hepatocellular carcinoma.

    Science.gov (United States)

    Memeo, Riccardo; de'Angelis, Nicola; de Blasi, Vito; Cherkaoui, Zineb; Brunetti, Oronzo; Longo, Vito; Piardi, Tullio; Sommacale, Daniele; Marescaux, Jacques; Mutter, Didier; Pessaux, Patrick

    2016-05-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, with an increasing diffusion in Europe and the United States. The management of such a cancer is continuously progressing and the objective of this paper is to evaluate innovation in the surgical treatment of HCC. In this review, we will analyze the modern concept of preoperative management, the role of laparoscopic and robotic surgery, the intrao-perative use of three dimensional models and augme-nted reality, as well as the potential application of fluore-scence. PMID:27168871

  8. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.

  9. Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Chun-Hsiang; Wey, Keh-Cherng; Mo, Lein-Ray; Chang, Kuo-Kwan; Lin, Ruey-Chang; Kuo, Jen-Juan

    2015-01-01

    curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy. PMID:25987009

  10. Primary hepatocellular carcinoma and metabolic syndrome:An update

    Institute of Scientific and Technical Information of China (English)

    Rubayat; Rahman; Ghassan; M; Hammoud; Ashraf; A; Al-mashhrawi; Khulood; T; Ahmed; Jamal; A; Ibdah

    2013-01-01

    Hepatocellular carcinoma(HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis.This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia,and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes,and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing.Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome,both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.

  11. Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma

    OpenAIRE

    Cabrera, Roniel; Ararat, Miguel; Xu, Yiling; Brusko, Todd; Wasserfall, Clive; Atkinson, Mark A.; Chang, Lung Ji; Liu, Chen; Nelson, David R.

    2012-01-01

    Hepatocellular carcinoma (HCC) is a difficult to treat cancer characterized by poor tumor immunity with only one approved systemic drug, sorafenib. If novel combination treatments are to be developed with immunological agents, the effects of sorafenib on tumor immunity are important to understand. In this study, we investigate the impact of sorafenib on the CD4+CD25− effector T cells (Teff) and CD4+CD25+ regulatory T cells (Tregs) from patients with HCC. We isolated Teff and Treg from periphe...

  12. Mitochondrial damage and cholesterol storage in human hepatocellular carcinoma cells with silencing of UBIAD1 gene expression

    OpenAIRE

    Morales, Carlos R.; Grigoryeva, Lubov S.; Xuefang Pan; Luigi Bruno; Gilles Hickson; Michael H. Ngo; McMaster, Christopher R.; Samuels, Mark E.; Pshezhetsky, Alexey V

    2014-01-01

    Heterozygous mutations in the UBIAD1 gene cause Schnyder corneal dystrophy characterized by abnormal cholesterol and phospholipid deposits in the cornea. Ubiad1 protein was recently identified as Golgi prenyltransferase responsible for biosynthesis of vitamin K2 and CoQ10, a key protein in the mitochondrial electron transport chain. Our study shows that silencing UBIAD1 in cultured human hepatocellular carcinoma cells causes dramatic morphological changes and cholesterol storage in the mitoch...

  13. Sorafenib and radiotherapy association for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Conformal radiotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC), producing local control rates above 90% within the radiation beam. However, survival after radiotherapy remains limited by the high frequency of intra- and extra-hepatic recurrences, which occurs in 40-50 and 20-30% of cases, respectively. Sorafenib (BAY43-9006, Nexavar; Bayer, West Haven, CT) is a small molecule inhibitor that demonstrated potent activity to target v-raf murine sarcoma oncogene homologue B1 (BRAF) and VEGFR tyrosine kinases. Sorafenib is the only drug that demonstrated effectiveness to increase overall survival in advanced or metastatic hepatocellular carcinoma. The rationale to combine radiotherapy with sorafenib is the following: (1) targeting RAS-RAF-MAPK and VEGFR signaling pathways, which are specifically activated after exposure to radiation, and responsible for radio-resistance phenomenon; (2) enhancing the oxygen effect through normalization of the surviving tumor vasculature; and (3) synchronization of the cell cycle. Sorafenib and radiotherapy represent complementary strategies, as radiotherapy may be useful to prolong the effect of sorafenib through control of the macroscopic disease, when sorafenib may target latent microscopic disease. Sorafenib and radiotherapy associations are thus based on a relevant biological and clinical rationale and are being evaluated in ongoing phase I-II trials. (authors)

  14. Overexpression of engulfment and cell motility 1 promotes cell invasion and migration of hepatocellular carcinoma

    OpenAIRE

    JIANG, JIARUI; Liu, Guoqing; Miao, Xiongying; HUA, SONGWEN; ZHONG, DEWU

    2011-01-01

    Engulfment and cell motility 1 (Elmo1) has been linked to the invasive phenotype of glioma cells. The use of Elmo1 inhibitors is currently being evaluated in hepato-cellular carcinoma (HCC), but the molecular mechanisms of their therapeutic effect have yet to be determined. Elmo1 expression in HCC tissue samples from 131 cases and in 5 HCC cell lines was determined by immunohistochemistry, quantitative RT-PCR and Western blotting. To functionally characterize Elmo1 in HCC, Elmo1 expression in...

  15. Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

    Science.gov (United States)

    2015-12-01

    Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

  16. Intratumoral sampling variability in hepatocellular carcinoma: A case report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The differential diagnosis between hepatocellular carcinoma (HCC) and regenerative liver nodules and other primary liver tumors may be very difficult,particularly when performed on liver biopsies. Difficulties in histological typing may be often minimized by immunohistochemistry. Among the numerous markers proposed, CK18, Hep Par1 and glypican 3 (GPC3) are considered the most useful in HCC diagnosis. Here we report a case of HCC in a 72-year-old male with HBV-related chronic liver disease, characterized by a marked morphological and immunohistochemical intratumoral variability. In this case, tumor grading ranged from areas extremely well differentiated, similar to regenerative nodule, to undifferentiated regions, with large atypical multinucleated cells. While almost all sub nodules were immunostained by Hep Par 1, immunoreactivity for glypican 3 and for Ck18 was patchy, with negative tumor region adjacent to the highly immunoreactive areas. Our case stresses the relevance of sampling variability in the diagnosis of HCC, and indicates that caution should be taken in grading an HCC and in the interpretation of immunohistochemical stains when only small core biopsies from liver nodules are available.

  17. Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Susumu Imoto; Taisuke Nakajima; Kenji Ando; Keiji Mita; Katsumi Fukuda; Ryo Nishikawa; Yu-ichiro Koma; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2009-01-01

    We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

  18. Integrating subpathway analysis to identify candidate agents for hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jiye; Li, Mi; Wang, Yun; Liu, Xiaoping

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second most common cause of cancer-associated death worldwide, characterized by a high invasiveness and resistance to normal anticancer treatments. The need to develop new therapeutic agents for HCC is urgent. Here, we developed a bioinformatics method to identify potential novel drugs for HCC by integrating HCC-related and drug-affected subpathways. By using the RNA-seq data from the TCGA (The Cancer Genome Atlas) database, we first identified 1,763 differentially expressed genes between HCC and normal samples. Next, we identified 104 significant HCC-related subpathways. We also identified the subpathways associated with small molecular drugs in the CMap database. Finally, by integrating HCC-related and drug-affected subpathways, we identified 40 novel small molecular drugs capable of targeting these HCC-involved subpathways. In addition to previously reported agents (ie, calmidazolium), our method also identified potentially novel agents for targeting HCC. We experimentally verified that one of these novel agents, prenylamine, induced HCC cell apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, an acridine orange/ethidium bromide stain, and electron microscopy. In addition, we found that prenylamine not only affected several classic apoptosis-related proteins, including Bax, Bcl-2, and cytochrome c, but also increased caspase-3 activity. These candidate small molecular drugs identified by us may provide insights into novel therapeutic approaches for HCC. PMID:27022281

  19. Hepatitis B and alcohol affect survival of hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Linda L. Wong; Whitney M. Limm; Naoky Tsai; Richard Severino

    2005-01-01

    AIM: In the USA, Hawaii has the highest incidence of hepatocellular carcinoma (HCC) and a diverse population.It is an ideal place to characterize HCC in the context of ethnicity/risk factors.METHODS: A total of 262 cases of HCC (1992-2003) were retrospectively reviewed for demographics, ethnicity, birthplace, viral hepatitis, alcohol use, diabetes, smoking and risk factors for viral hepatitis such as intravenous drug abuse (IVDA), transfusions, tattoos and vertical transmission. Tumor stage, Child's class, Cancer of the Liver Italian Program (CLIP) score, α-fetoprotein level, treatment and survival were recorded.RESULTS: Gender, age, viral hepatitis, alcohol, IVDA, and diabetes differed significantly in Asians, non-Asians and Pacific Islanders. There were also specific differences within Asian subgroups. Alpha-fetoprotein, smoking, transfusions, stage and resectability did not differ between groups. Asians were more likely to have hepatitis B, while non-Asians were more likely to have hepatitis C. Factors that decreased survival included hepatitis B, alcohol, elevated alpha-fetoprotein, CLIP >2 and increased Child's class. When Asians were combined with Pacific Islanders, median survival (1.52 years vs 3.54 years), 1- and 3-year survival was significantly worse than those for non-Asians. After Cox regression analysis for hepatitis B and alcohol, there was no difference in survival by ethnicity.CONCLUSION: Various ethnicities have different risk factors for HCC. Hepatitis B, alcohol, and α-fetoprotein are more important factors for survival than ethnicity.

  20. Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD.

    Science.gov (United States)

    Reeves, Helen L; Zaki, Marco Y W; Day, Christopher P

    2016-05-01

    Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. Rather than falling as a result of prevention and treatments for viral hepatitis, an increase is evident in developed nations consequent to the rising prevalence of obesity and type 2 diabetes mellitus (T2DM)-the two major risk factors for nonalcoholic fatty liver disease (NAFLD). The majority of patients with HCC complicating these conditions present with advanced disease as the tools for surveillance are inadequate, and the "at-risk" population is not well characterized. This review will summarize the epidemiological evidence linking obesity, T2DM, and NAFLD with HCC, what is known about the pathogenic mechanisms involved, as well as their relevance for clinicians managing patients at risk. There will also be an overview of the "unmet needs" surrounding this topic, with suggestions for the direction translational research should take in order to prevent progression of NAFLD to HCC, to improve early detection of HCC in those with NAFLD, as well as to improve outcomes for those affected. PMID:26921078

  1. Trends in the development of MET inhibitors for hepatocellular carcinoma.

    Science.gov (United States)

    Okuma, Hitomi S; Kondo, Shunsuke

    2016-05-01

    Hepatocellular carcinoma is the third most common cause of cancer-related deaths worldwide. The multikinase inhibitor sorafenib has improved survival and is now considered the standard of care; however, the benefits are still disappointing, and thus, new effective treatments are required. In human hepatocellular carcinoma, MET, which is encoded by the HGFR gene, is activated by amplification, overexpression or mutation, and it has recently emerged as a possible therapeutic target in various tumors including hepatocellular carcinoma. In fact, some drugs targeting the HGF/MET axis are currently under investigation in clinical trials. Here, we review the role of MET and trends in the development of MET inhibitors for hepatocellular carcinoma. PMID:26984595

  2. BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

    Directory of Open Access Journals (Sweden)

    A. Kh. Bekyashev

    2012-01-01

    Full Text Available Hepatocellular carcinoma ranks 5th in prevalence and 3rd in cancer mortality worldwide. The prognosis of this disease is very poor: the 5-year survival rate was not more than 3–5%. Metastases generally occur in the lung, in the lymph nodes of the abdomen, chest, and neck, in the vertebrae, kidneys, and adrenals. The cases of brain metastasis from hepatocellular cancer are very rare. Overall, the prognosis is very poor for patients with brain metastases from hepatocellular carcinoma. Nevertheless, solitary brain metastases and good hepatic function are favorable survival criteria; thus, the treatment of this group of patients may lead to their better survival. The paper describes a clinical case of brain metastasis from hepatocellular carcinoma in a patient receiving the combination treatment involving neurosurgical treatment and targeted therapy. 

  3. Percutaneous local therapies for hepatocellular carcinoma impair gastric function

    Institute of Scientific and Technical Information of China (English)

    Fumihiko Kinekawa; Shigeki Kuriyama; Kazuya Matsuda; Tsutomu Masaki; Kazutaka Kurokohchi; Hirohito Yoneyama; Hideyuki Inoue; Hirohide Kurata; Yoshihito Uchida; Seishiro Watanabe

    2006-01-01

    @@ TO THE EDITOR Percutaneous local therapies, such as percutaneous ethanol injection (PEI), microwave coagulation and radiofrequency ablation (RFA), are frequently used worldwide for the treatment of hepatocellular carcinoma (HCC) because of their high effectiveness.

  4. Pictures of focal nodular hyperplasia and hepatocellular adenomas

    Institute of Scientific and Technical Information of China (English)

    Christine; Sempoux; Charles; Balabaud; Paulette; Bioulac-Sage

    2014-01-01

    This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.

  5. Targeting hepatocellular carcinoma with aptamer-functionalized PLGA/PLA-PEG nanoparticles

    Science.gov (United States)

    Weigum, Shannon E.; Sutton, Melissa; Barnes, Eugenia; Miller, Sarah; Betancourt, Tania

    2014-08-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, particularly in regions where chronic Hepatitis B and C infections are common. Nanoparticle assemblies that incorporate high-affinity aptamers which specifically bind malignant hepatocellular carcinoma cells could be useful for targeted drug delivery or enhancing contrast with existing ablation therapies. The in vitro interactions of a tumor-specific aptamer, TLS11a, were characterized in a hepatoma cell line via live-cell fluorescence imaging, SDS-PAGE and Western Blotting techniques. Cell surface binding of the aptamer-AlexaFluor®546 conjugate was found to occur within 20 minutes of initial exposure, followed by internalization and localization to late endosomes or lysosomes using a pH-sensitive LysoSensor™ Green dye and confocal microscopy. Aptamer-functionalized polymer nanoparticles containing poly(lactic-co-glycolic acid) (PLGA) and poly(lactide)-b-poly(ethylene glycol) (PLA-PEG) were then prepared by nanoprecipitation and passively loaded with the chemotherapeutic agent, doxorubicin, yielding spherical nanoparticles approximately 50 nm in diameter. Targeted drug delivery and cytotoxicity was assessed using live/dead fluorescent dyes and a MTT colorimetric viability assay with elevated levels of cell death found in cultures treated with either the aptamer-coated and uncoated polymer nanoparticles. Identification and characterization of the cell surface protein epitope(s) recognized by the TLS11a aptamer are ongoing along with nanoparticle optimization, but these preliminary studies support continued investigation of this aptamer and functionalized nanoparticle conjugates for targeted labeling and drug delivery within malignant hepatocellular carcinomas.

  6. Revisiting the pathology of resected benign hepatocellular nodules using new immunohistochemical markers.

    Science.gov (United States)

    Bioulac-Sage, Paulette; Cubel, Gaelle; Balabaud, Charles; Zucman-Rossi, Jessica

    2011-02-01

    In this review, the authors focus on the use of immunohistochemistry to characterize the different types and subtypes of benign hepatocellular nodules. They describe the classical and currently accepted features leading to the easy and formal diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). In addition, they report some atypical features and difficulties in the interpretation of section staining analyses, which represent important parameters for pathologists. A significant contribution of molecular biology to the characterization of FNH has been to reclassify some cases of FNH as inflammatory HCA. Furthermore, the pattern of overexpression of glutamine synthetase (GS), a target gene of β-catenin has been successfully used to identify FNH by immunohistochemistry. Molecular approaches have demonstrated that HCA is a heterogeneous entity. Genotype classification of HCA has allowed the identification of three subtypes: HNF1A-mutated HCA (H-HCA) in 35% of cases, β-catenin-mutated HCA (b-HCA) in 10%, and inflammatory HCA (IHCA) in 55%. Following molecular data, the diagnosis of H-HCA relies on the lack of liver fatty acid binding protein (LFABP) immunostaining. The diagnosis of b-HCA is straightforward when GS is strongly and diffusely expressed by lesional hepatocytes, and is accompanied by nuclear β-catenin immunoreactivity. In IHCA, serum amyloid protein and C- reactive protein are strongly and usually diffusely expressed by tumoral hepatocytes with a sharp limit with the surrounding nontumoral liver. IHCA can also be β-catenin activated (10%). Due to the strong association of b-HCA with hepatocellular carcinoma transformation, the identification of this HCA subtype is extremely important. PMID:21344354

  7. Liver Resection after Downstaging Hepatocellular Carcinoma with Sorafenib

    OpenAIRE

    L. Barbier; Muscari, F.; Le Guellec, S.; Pariente, A; Otal, P.; Suc, B.

    2011-01-01

    Background. Sorafenib is a molecular-targeted therapy used in palliative treatment of advanced hepatocellular carcinoma in Child A patients. Aims. To address the question of sorafenib as neoadjuvant treatment. Methods. We describe the cases of 2 patients who had surgery after sorafenib. Results. The patients had a large hepatocellular carcinoma in the right liver with venous neoplastic thrombi (1 in the right portal branch, 1 in the right hepatic vein). After 9 months of sorafenib, reassessme...

  8. State-of-the-art ultrasonography of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Over the last few decades sonographic techniques have progressed remarkably. Recent advances in ultrasonography include harmonics, real-time spatial compound imaging, adaptive image processing, 3D power Doppler imaging and contrast-enhanced gray-scale harmonic ultrasonography. These advances have had positive effects on the diagnosis of hepatocellular carcinomas and on the evaluation of their responses to therapy. In this article, we review recent sonographic advances for the diagnosis and treatment of hepatocellular carcinomas and its typical imaging features

  9. BIOCHEMICAL NUTRITIONAL PROFILE OF LIVER CIRRHOSIS PATIENTS WITH HEPATOCELLULAR CARCINOMA

    Directory of Open Access Journals (Sweden)

    Gabriela Zanatta PORT

    2014-03-01

    Full Text Available Context Liver cirrhosis patients with hepatocellular carcinoma present nutritional alterations and metabolic disorders that negatively impact the prognosis. Objective The objective is to identify alterations in the metabolism of macro and micronutrients among liver cirrhosis patients with and without hepatocellular carcinoma and their relation to the Child-Turcote-Pugh score and Barcelona Clinic Liver Cancer staging. Methods Analytical transversal study, with 31 hepatocellular carcinoma patients and 48 liver cirrhosis patients. Laboratorial exams were carried out. The existence of an association between the biochemical parameters and the disease severity as well as the presence of hepatocellular carcinoma was assessed. Results The metabolic-nutritional profile of liver cirrhosis patients caused by the hepatitis C virus and hepatocellular carcinoma showed alterations, specifically the lipid (total cholesterol, HDL and triglycerides, protein (albumin, creatinine and uric acid, iron (transferrin, iron and ferritin saturation, hematocrit and hemoglobin, zinc and B12 vitamin profiles. There is a relation between nutritional biochemical markers and the Child-Turcote-Pugh, as well as Barcelona Clinic Liver Cancer staging. Conclusions Considering the existence of alterations in the metabolism of nutrients in liver cirrhosis patients with and without hepatocellular carcinoma, and also that conventional nutritional assessment methods present limitations for this population, the biochemical laboratorial exams are valid to complement the diagnosis of the nutritional state in a quick and practical manner.

  10. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Bagi, Cedo M., E-mail: cedo.bagi@pfizer.com; Andresen, Catharine J. [Global Science & Technology, PGRD, Pfizer Inc, Groton, CT 06340 (United States)

    2010-07-07

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.

  11. Combined interventional therapies of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Qian; Gan-Sheng Feng; Thomas Vogl

    2003-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonmalignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades,the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone,and play more important roles in treating unresectable HCC.

  12. Stem cell research in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chengyi SUN; Shi ZUO

    2008-01-01

    The traditional view that adult human liver tumors, mainly hepatocellular carcinoma (HCC), arise from mature cell types has been challenged in recent dec-ades. The results of several studies suggest that HCC can be derived from liver stem cells. There are four levels of cells in the liver stem cell lineage: hepatocytes, hepatic stem cells/oval cells, bone marrow stem cells and hepato-pancreas stem cells. However, whether HCC is resulted from the differentiation block of stem cells and, moreover, which liver stem cell lineage is the source cell of hepatocarcinogenesis remain controversial. In this review, we focus on the current status of liver stem cell research and their roles in carcinogenesis of HCC, in order to explore new approaches for stem cell therapy of HCC.

  13. Combined hepatocellular-cholangiocarcinoma: a case report.

    Science.gov (United States)

    Toh, C H; Cheung, Y C; Ng, S H; Lin, C Y; Chan, S C; Ng, K K

    2004-12-01

    Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare primary liver tumour. We report a carrier of both HBV and HCV presenting with intermittent abdominal pain, fever, chillness and elevated á-fetoprotein (AFP) of 1197 ng/ml. Computed tomography showed an irregular hypodense mass in the left lateral segment of the liver with vague contrast enhancement and multiple regional lymphadenopathy. Hepatic angiogram showed that the mass was hypovascular and the left portal vein was occluded with a tapered end. Percutaneous ultrasound-guided core needle biopsy of the liver yielded HCC-CC. We suggest that HCC-CC should be considered in hypovascular liver tumours with striking elevation of serum AFP and multiple regional lymphadenopathy. PMID:15646418

  14. Montelukast induced acute hepatocellular liver injury

    Directory of Open Access Journals (Sweden)

    Harugeri A

    2009-01-01

    Full Text Available A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast induced hepatocellular liver injury. Liver tests began to improve and returned to normal 55 days after drug cessation. Causality of this adverse drug reaction by the Council for International Organizations of Medical Sciences or Roussel Uclaf Causality Assessment Method (CIOMS or RUCAM and Naranjo′s algorithm was ′probable′. Liver tests should be monitored in patients receiving montelukast and any early signs of liver injury should be investigated with a high index of suspicion for drug induced liver injury.

  15. Models of Hepatocellular Carcinoma and Biomarker Strategy

    International Nuclear Information System (INIS)

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients

  16. Focal nodular hyperplasia and hepatocellular adenoma

    International Nuclear Information System (INIS)

    Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are liver lesions of hepatocellular origin. The FNH is a commonly occurring hepatic lesion whereas HCA is very rare. Non-invasive differentiation between HCA subtypes and atypical FNH may pose a diagnostic challenge as both entities predominantly occur in middle-aged female patients. The conventional imaging modalities include ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI). Distinguishing FNH from HCA is of great importance clinically as FNH is considered to be a benign lesion and needs no further management. In contrast HCA is considered to be a borderline tumor due to the risk of hemorrhage, growth and even malignant transformation and requires individualized management. The abovementioned radiological procedures usually enable an accurate and certain diagnosis of a typical FNH to be achieved. In cases of atypical FNH, particularly in patients with a clinical history of malignancy, these imaging modalities are insufficient to establish a clear diagnosis. In this scenario, the use of modern hepatobiliary contrast-enhanced MRI will enable a differentiation between FNH and metastasis with a high sensitivity and specificity. Furthermore, it allows a differentiation of FNH from 90 % of adenoma subtypes. This article describes the histopathological and radiological features of these lesions and explains the advantages and limitations of various imaging modalities used for the diagnosis and differentiation of these entities. The new classification of HCAs according to phenotype and genotype and their imaging features, as well as different enhancement patterns, are described. The correlation between HCA subtypes and their individual management are also discussed. (orig.)

  17. Hepatocellular adenoma: what is new in 2008.

    Science.gov (United States)

    Bioulac-Sage, Paulette; Laumonier, Hervé; Laurent, Christophe; Zucman-Rossi, Jessica; Balabaud, Charles

    2008-09-01

    Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1alpha (HNF1alpha) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1alpha-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1alpha germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating beta-catenin mutation was found in 10% of HCA. These beta-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress beta-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express beta-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1alpha-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of

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  1. Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients.

    Science.gov (United States)

    Motawi, Tarek K; Shaker, Olfat G; El-Maraghy, Shohda A; Senousy, Mahmoud A

    2015-01-01

    Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis

  2. Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients.

    Directory of Open Access Journals (Sweden)

    Tarek K Motawi

    Full Text Available Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4 subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3 to cirrhosis (F4 to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a with high diagnostic accuracy for HCC (AUC = 0.946. The microRNA panel also discriminated HCC from controls (AUC = 0.949, CLD (AUC = 0.945, and F3-F4 (AUC = 0.955. Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver

  3. Role of Percutaneous Microwave Ablation in Treatment of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed Tharwat Sayed *, Sahar M El Fiky*,

    2014-07-01

    Full Text Available Introduction: Hepatocellular carcinoma (HCC is one of the most common malignancies worldwide with an annual occurrence of one million new cases. An etiologic association between HBV infection and the development of HCC has been established. Hepatitis C virus is also proving an important predisposing factor for this malignancy, the use of minimally invasive Percutaneous ablative technique (e.g. Radiofrequency (RF and Microwave ablation (MW has gained great momentum and because of the drawbacks of RF ablation, several groups have successfully proved the efficacious nature of Microwave ablation in the treatment of hepatocellular carcinoma. Aim of the Work: The aim of this work is to highlight the role, the principles and the applications of percutaneous Microwave Ablation in Hepatocellular carcinoma. Methods: The studied group included 30 patients (25 men and 5 women with hepatocellular carcinoma. All patients underwent microwave ablation for the hepatocellular carcinoma. Results: The results of the procedures will be assessed as regarding sizeand enhancement of the lesion (s on triphasic CT abdomen before the procedure and at the follow up at one month as well as the Alpha fetoprotein levels. Conclusion: MWA technique represents a safe, fast and efficacious way to perform hepatic ablation in patients with HCC. Initial results are encouraging; however, longer follow-up is needed for further classification of our results.

  4. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features.

    Science.gov (United States)

    Lessel, Davor; Vaz, Bruno; Halder, Swagata; Lockhart, Paul J; Marinovic-Terzic, Ivana; Lopez-Mosqueda, Jaime; Philipp, Melanie; Sim, Joe C H; Smith, Katherine R; Oehler, Judith; Cabrera, Elisa; Freire, Raimundo; Pope, Kate; Nahid, Amsha; Norris, Fiona; Leventer, Richard J; Delatycki, Martin B; Barbi, Gotthold; von Ameln, Simon; Högel, Josef; Degoricija, Marina; Fertig, Regina; Burkhalter, Martin D; Hofmann, Kay; Thiele, Holger; Altmüller, Janine; Nürnberg, Gudrun; Nürnberg, Peter; Bahlo, Melanie; Martin, George M; Aalfs, Cora M; Oshima, Junko; Terzic, Janos; Amor, David J; Dikic, Ivan; Ramadan, Kristijan; Kubisch, Christian

    2014-11-01

    Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families. All three patients are affected by a new segmental progeroid syndrome characterized by genomic instability and susceptibility toward early onset hepatocellular carcinoma. SPRTN was recently proposed to have a function in translesional DNA synthesis and the prevention of mutagenesis. Our in vivo and in vitro characterization of identified mutations has uncovered an essential role for SPRTN in the prevention of DNA replication stress during general DNA replication and in replication-related G2/M-checkpoint regulation. In addition to demonstrating the pathogenicity of identified SPRTN mutations, our findings provide a molecular explanation of how SPRTN dysfunction causes accelerated aging and susceptibility toward carcinoma. PMID:25261934

  5. Acute myeloid leukemia masquerading as hepatocellular carcinoma.

    Science.gov (United States)

    Abu-Zeinah, Ghaith F; Weisman, Paul; Ganesh, Karuna; Katz, Seth S; Dogan, Ahmet; Abou-Alfa, Ghassan K; Stein, Eytan M; Jarnagin, William; Mauro, Michael J; Harding, James J

    2016-06-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient's liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  6. Aflatoxins, hepatocellular carcinoma and public health

    Directory of Open Access Journals (Sweden)

    Arvin Magnussen

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer deaths worldwide, primarily affecting populations in the developing countries. Aflatoxin, a food contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a known human carcinogen that has been shown to be a causative agent in the pathogenesis of HCC. Aflatoxin can affect a wide range of food commodities including corns, oilseeds, spices, and tree nuts as well as milk, meat, and dried fruit. Many factors affect the growth of Aspergillus fungi and the level of aflatoxin contamination in food. Drought stress is one of the factors that increase susceptibility of plants to Aspergillus and thus aflatoxin contamination. A recent drought is thought to be responsible for finding of trace amounts of aflatoxin in some of the corn harvested in the United States. Although it’s too soon to know whether aflatoxin will be a significant problem, since United States is the world’s largest corn producer and exporter, this has raised alarm bells. Strict regulations and testing of finished foods and feeds in the United States should prevent a major health scare, and prevent human exposure to deleterious levels of aflatoxin. Unfortunately, such regulations and testing are not in place in many countries. The purpose of this editorial is to summarize the current knowledge on association of aflatoxin and HCC, encourage future research and draw attention to this global public health issue.

  7. Cancer-associated fibroblasts in hepatocellular carcinoma.

    Science.gov (United States)

    Kubo, Norio; Araki, Kenichiro; Kuwano, Hiroyuki; Shirabe, Ken

    2016-08-14

    The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAFtargeted therapy may be effective for suppression not only of fibrosis but also cancer progression. PMID:27570421

  8. Diabetes mellitus and metformin in hepatocellular carcinoma

    Science.gov (United States)

    Fujita, Koji; Iwama, Hisakazu; Miyoshi, Hisaaki; Tani, Joji; Oura, Kyoko; Tadokoro, Tomoko; Sakamoto, Teppei; Nomura, Takako; Morishita, Asahiro; Yoneyama, Hirohito; Masaki, Tsutomu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. Diabetes mellitus, a risk factor for cancer, is also globally endemic. The clinical link between these two diseases has been the subject of investigation for a century, and diabetes mellitus has been established as a risk factor for HCC. Accordingly, metformin, a first-line oral anti-diabetic, was first proposed as a candidate anti-cancer agent in 2005 in a cohort study in Scotland. Several subsequent large cohort studies and randomized controlled trials have not demonstrated significant efficacy for metformin in suppressing HCC incidence and mortality in diabetic patients; however, two recent randomized controlled trials have reported positive data for the tumor-preventive potential of metformin in non-diabetic subjects. The search for biological links between cancer and diabetes has revealed intracellular pathways that are shared by cancer and diabetes. The signal transduction mechanisms by which metformin suppresses carcinogenesis in cell lines or xenograft tissues and improves chemoresistance in cancer stem cells have also been elucidated. This review addresses the clinical and biological links between HCC and diabetes mellitus and the anti-cancer activity of metformin in clinical studies and basic experiments. PMID:27468203

  9. Mast cells and human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fabio Grizzi; Barbara Franceschini; Maurizio Chiriva-Internati; Young Liu; Paul L. Hermonat; Nicola Dioguardi

    2003-01-01

    AIM: To investigate the density of mast cells (MCs) in human hepatocellular carcinoma (HCC), and to determine whether the MCs density has any correlations with histopathological grading, staging or some baseline patient characteristics.METHODS: Tissue sections of 22 primary HCCs were histochemically stained with toluidine blue, in order to be able to quantify the MCs in and around the neoplasm using a computer-assisted image analysis system. HCC was staged and graded by two independent pathologists. To identify the sinusoidal capillarisation of each specimen 3μm thick sections were histochemically stained with sirius red, and semi-quantitatively evaluated by two independent observers. The data were statistically analysed using Spearman′s correlation and Student′s t-test when appropriate.RESULTS: MCs density did not correlate with the age or sex of the patients, the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, or the stage or grade of the HCC. No significant differences were found between the MCs density of the patients with and without hepatitis C virus infection, but they were significantly higher in the specimens showing marked sinusoidal capillarisation.CONCLUSION: The lack of any significant correlation between MCs density and the stage or grade of the neoplastic lesions suggests that there is no causal relationship between MCs recruitment and HCC. However, as capillarisation proceeds concurrently with arterial blood supply during hepatocarcinogenesis, MCs may be considered of primary importance in the transition from sinusoidal to capillary-type endothelial cells and the HCC growth.

  10. Liver resection for intermediate hepatocellular carcinoma.

    Science.gov (United States)

    Yi, Peng-Sheng; Zhang, Ming; Zhao, Ji-Tong; Xu, Ming-Qing

    2016-05-18

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC. PMID:27190577

  11. [Inspection of guidelines for hepatocellular carcinoma].

    Science.gov (United States)

    Arii, Shigeki

    2010-04-01

    An evidence-based clinical guideline for diagnosing and treating hepatocellular carcinoma patients was published in 2005, based on 7,118 original English papers(published between 1966-2002)and edited by the executive members of the Liver Cancer Study Group of Japan (Chief Editor, Professor M. Makuuchi, MD). These were composed of 58 clinical questions which covered prevention, surveillance, diagnosis, surgery, transplantation, chemotherapy, radiotherapy, chemoembolization and ablation therapy. The surveys investigating the validity and usefulness of this guideline revealed that it is well worked out and considered useful by medical practitioners. This guideline changed the therapeutic strategy of 20% of the experts. However, 43% of experts and 30% of non experts believed that this guideline restricted their medical discretion. Moreover, the percentage of medical practitioners who felt that medical malpractice suits would increase exceeded those who did not. A revised 2009 version was published based on the evaluation of 2,950 original papers (published between 2002-2007). Major revisions were not made, but clinical questions and scientific statements were updated. However, this version of the guideline does not provide clear recommendations in about 40% of the clinical questions because of lack of evidence. The guideline must be utilized based on an appropriate understanding of medical science and medical practice, and not on dogmatism. PMID:20414014

  12. Comprehensive sequential interventional therapy for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Liang; FAN Wei-jun; HUANG Jin-hua; LI Chuan-xing; ZHAO Ming; WANG Li-gang; TANG Tian

    2009-01-01

    Background Since the 1980s, various approaches to interventional therapy have been developed, with the development and achievement of medical imaging technology. This study aimed to evaluate the effectiveness of comprehensive sequential interventional therapy especially personal therapeutic plan in 53 radical cure patients with hepatocellular carcinoma (HCC).Methods From January 2003 to January 2005, a total of 203 patients with HCC received sequential interventional treatment in our hospital. Fifty-three patients achieved radical cure outcomes. Those patients were treated with transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or high intensity focused ultrasound (HIFU), sequentially and in combination depending on their clinical and pathological features. PET-CT was used to evaluate, assess, and guide treatment.Results Based on the imaging and serological data, all the patients had a personal therapeutic plan. The longest follow-up time was 24 months, the shortest was 6 months, and mean survival time was 16.5 months.Conclusion Comprehensive sequential interventional therapy especially personal therapeutic plan for HCC play roles in interventional treatment of HCC in middle or advanced stage.

  13. Survivin in survival of hepatocellular carcinoma.

    Science.gov (United States)

    Su, Changqing

    2016-09-01

    Survivin is an anti-apoptotic protein belonging to the inhibitor of apoptosis protein (IAP) family. It is involved in the regulation of important physiological and pathological processes in cells and functions to inhibit cell apoptosis and promote cell proliferation. Normally and terminally differentiated tissues are nearly negative for survivin. In contrast, survivin is highly expressed in most human tumor tissues, including hepatocellular carcinoma (HCC). The abnormal overexpression of survivin is closely related to the malignant biological behaviors of tumors. During the development and progression of HCC, the high level of survivin expression promotes cancer cell proliferation, inhibits cancer cell apoptosis, induces tumor stromal angiogenesis, reduces the sensitivity of cancer cells to radiotherapy and chemotherapy, and ultimately affects the prognosis of patients with HCC. Survivin expression is regulated by a large number of factors. The latest discovery indicated that the transcription factor octamer-binding transcription factor 4 (OCT4) enhances the expression of survivin though cyclin D1 (CCND1), which, in part, accounts for tumor cell proliferation, recurrence and metastasis. Survivin plays key roles in HCC, which renders it an ideal target for the treatment of HCC. The present article reviews the research progress on the relationship between survivin and HCC and on the HCC treatment strategies targeting survivin. PMID:26118774

  14. Management of recurrent hepatocellular carcinoma afterliver transplant

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the leading cause ofdeaths in patients with hepatitis B or C, and its incidencehas increased considerably over the past decade and is stillon the rise. Liver transplantation (LT) provides the bestchance of cure for patients with HCC and liver cirrhosis.With the implementation of the MELD exception systemfor patients with HCC waitlisted for LT, the number ofrecipients of LT is increasing, so is the number of patientswho have recurrence of HCC after LT. Treatments forintrahepatic recurrence after transplantation and afterother kinds of surgery are more or less the same, butlong-term cure of posttransplant recurrence is rarelyseen as it is a "systemic" disease. Nonetheless, surgicalresection has been shown to be effective in prolongingpatient survival despite the technical difficulty in resectinggraft livers. Besides surgical resection, different kindsof treatment are also in use, including transarterialchemoembolization, radiofrequency ablation, highintensityfocused ultrasound ablation, and stereotacticbody radiation therapy. Targeted therapy and modulationof immunosuppressants are also adopted to treat thedeadly disease.

  15. Prevention of hepatocellular carcinoma: Focusing onantioxidant therapy

    Institute of Scientific and Technical Information of China (English)

    Koji Miyanishi; Toshifumi Hoki; Shingo Tanaka; Junji Kato

    2015-01-01

    Oxidative stress has been investigated in the context ofalcoholic liver injury for many years and shown to be acausal factor of chronic hepatitis C (CHC), nonalcoholicsteatohepatitis (NASH), drug-induced liver injury, Wilson's disease, and hemochromatosis. In CHC, it has beendemonstrated that oxidative stress plays an importantrole in hepatocarcinogenesis. In cases with persistenthepatitis due to failure of hepatitis C virus eradication,or chronic liver disease, such as NASH, the treatment ofwhich remains unestablished, it is important to reduceserum alanine aminotransferase levels and prevent liverfibrosis and development of hepatocellular carcinoma.This also suggests the importance of antioxidanttherapy. Among treatment options where it would beexpected that anti-inflammatory activity plays a rolein their confirmed efficacy for chronic hepatitis, irondepletion therapy, glycyrrhizin, ursodeoxycholic acid,Sho-Saiko-To, and vitamin E can all be consideredantioxidant therapies. To date, however, the ability ofthese treatments to prevent cancer has been confirmedonly in CHC. Nevertheless, anti-inflammatory and antifibroticeffects have been demonstrated in other liverdiseases and these therapies may potentially be effectivefor cancer prevention.

  16. Acute myeloid leukemia masquerading as hepatocellular carcinoma

    Science.gov (United States)

    Abu-Zeinah, Ghaith F.; Weisman, Paul; Ganesh, Karuna; Katz, Seth S.; Dogan, Ahmet; Abou-Alfa, Ghassan K.; Stein, Eytan M.; Jarnagin, William; Mauro, Michael J.

    2016-01-01

    Hepatocellular carcinoma (HCC) is often diagnosed on the basis of high quality imaging without a biopsy in the cirrhotic liver. This is a case of a 64-year-old Caucasian man with no history of liver disease or cirrhosis that presented with fatigue, weight loss, and abdominal distension and was found to have a large, isolated liver mass with arterial enhancement and portal venous washout on triple-phase computed tomography (CT) suspicious for HCC. The patient was initially referred for a surgical evaluation. Meanwhile, he developed fevers, pancytopenia, and worsening back pain, and a subsequent spinal MRI revealed a heterogeneous bone marrow signal suspicious for metastatic disease. A bone marrow biopsy that followed was diffusely necrotic. A core biopsy of the patient’s liver mass was then performed and was diagnostic of acute monocytic-monoblastic leukemia. Findings from peripheral flow cytometry and a repeat bone marrow biopsy were also consistent with this diagnosis, and induction chemotherapy with cytarabine and idarubicin was initiated. This case describes a rare presentation of myeloid sarcoma (MS) as an isolated, hypervascular liver mass that mimics HCC in its radiographic appearance. Due to the broad differential for a liver mass, a confirmatory biopsy should routinely be considered prior to surgical intervention. PMID:27284485

  17. Repeated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A

  18. Management of hepatocellular carcinoma in the elderly

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Mean age of hepatocellular carcinoma (HCC) patients hasbeen progressively increasing over the last decades andageing of these patients is becoming a real challenge inevery day clinical practice. Unfortunately, internationalguidelines on HCC management do not address thisproblem exhaustively and do not provide any specific recommendation. We carried out a literature search inMEDLINE database for studies reporting on epidemiology,clinical characteristics and treatment outcome of HCCin elderly patients. Available data seem to indicatethat in elderly patients the outcome of HCC is mostlyinfluenced by liver function and tumor stage rather thanby age and the latter should not influence treatmentallocation. Age is not a risk for resection and olderpatients with resectable HCC and good liver functioncould gain benefit from surgery. Mild comorbiditiesdo not seem a contraindication for surgery in agedpatients. Conversely, major resection in elderly, evenwhen performed in experienced high-volume centres,should be avoided. Both percutaneous ablation andtransarterial chemoembolization are not contraindicatedin aged patients and safety profile of these proceduresis acceptable. Sorafenib is a viable option for advancedHCC in elderly provided that a careful evaluation ofconcomitant comorbidities, particularly cardiovascularones, is taken into account. Available data seem tosuggest that in either elderly and younger, treatment isa main predictor of outcome. Consequently, a nihilisticattitude of physicians towards under- or no-treatment ofaged patients should not be longer justified.

  19. In Utero Hepatocellular Transplantation in Rats

    Directory of Open Access Journals (Sweden)

    Emma Muñoz-Sáez

    2013-01-01

    Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

  20. Hepatocellular carcinoma and cholangiocarcinoma: an update.

    Science.gov (United States)

    Yazici, Cemal; Niemeyer, David J; Iannitti, David A; Russo, Mark W

    2014-01-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer worldwide and is rising in incidence. Ultrasound is the preferred modality for screening high-risk patients for HCC because it detects clinically significant nodules, widespread availability and lower cost. HCC does not require a biopsy for diagnosis if specific imaging criteria are fulfilled. Transarterial chemoembolization (TACE) is the most common modality used to treat HCC followed by ablation. Cholangiocarcinoma (CCA) is increasing in incidence and the second most common primary malignancy of the liver. There is no effective screening strategy for CCA although magnetic resonance imaging and carbohydrate antigen 19-9 (CA 19-9) are commonly used without proven benefit. Therapy for CCA is challenging and resection, when possible, is the mainstay of therapy. Gemcitabine in combination with cisplatin or biologics may offer a modest survival benefit. Liver transplantation for CCA is associated with reasonable survival in select cases. Molecular diagnostics offer the potential to develop personalized approaches in the management of HCC and CCA. PMID:24245910

  1. Treatment of hepatocellular carcinoma: beyond international guidelines.

    Science.gov (United States)

    Sangiovanni, Angelo; Colombo, Massimo

    2016-01-01

    Treatment of hepatocellular carcinoma (HCC) is guided by the tumour stage. The Barcelona clinical liver cancer (BCLC) score endorsed by the European Society of the Liver EASL divides patients into five prognostic categories, each with a distinct treatment indication. Hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in accurately selected patients with very early (BCLC 0) and early stage (BCLC A) tumours providing a survival rate of between 50 and 75% at year five. In patients with a large tumour burden such as those with intermediate stage BCLC B, repeated treatments with transarterial chemoembolization (TACE) are advocated with clinical benefits (from 16 to 22 months). Survival may also improve in patients who are in poor condition or who do not respond to TACE and those with an advanced HCC (BCLC C), following oral therapy with the multikinase inhibitor, sorafenib. However, most recommendations are based on uncontrolled studies and expert opinions rather than well-designed controlled trials, and up to one-third of patients do not fit recommendations because of advanced age, the presence of significant comorbidities or a strategic location of the nodule. For these patients, treatment of HCC beyond guidelines is often advocated. PMID:26725909

  2. Diagnosis and treatment of hepatocellular carcinoma: Anupdate

    Institute of Scientific and Technical Information of China (English)

    Javier Tejeda-Maldonado; Ignacio García-Juárez; Jonathan Aguirre-Valadez; Adrián González-Aguirre; Mario Vilatobá-Chapa; Alejandra Armengol-Alonso; Francisco Escobar-Penagos; Aldo Torre; Juan Francisco Sánchez-ávila; Diego Luis Carrillo-Pérez

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the mostcommon malignancies leading to high mortality ratesin the general population; in cirrhotic patients, it isthe primary cause of death. The diagnosis is usuallydelayed in spite of at-risk population screening recommendations,i.e., patients infected with hepatitis B or Cvirus. Hepatocarcinogenesis hinges on a great numberof genetic and molecular abnormalities that lead totumor angiogenesis and foster their disseminationpotential. The diagnosis is mainly based on imagingstudies such as computed tomography and magneticresonance, in which lesions present a characteristicclassical pattern of early arterial enhancement followedby contrast medium "washout" in late venous phase.On occasion, when imaging studies are not conclusive,biopsy of the lesion must be performed to establish thediagnosis. The Barcelona Clinic Liver Cancer stagingmethod is the most frequently used worldwide andrecommended by the international guidelines of HCCmanagement. Currently available treatments includetumor resection, liver transplant, sorafenib and locoregionaltherapies (alcoholization, radiofrequencyablation, chemoembolization). The prognosis of hepatocarcinomais determined according to the lesion's stageand in cirrhotic patients, on residual liver function.Curative treatments, such as liver transplant, aresought in patients diagnosed in early stages; patients inmore advanced stages, were not greatly benefitted bychemotherapy in terms of survival until the advent oftarget molecules such as sorafenib.

  3. Tumor vaccine against recurrence of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bao-Gang Peng; Li-Jiang Liang; Qiang He; Ming Kuang; Jia-Ming Lia; Ming-De Lu; Jie-Fu Huang

    2005-01-01

    AIM: To investigate the effects of autologous tumor vaccine on recurrence of hepatocellular carcinoma (HCC).METHODS: Sixty patients with HCC who had undergone curative resection, were randomly divided into HCC vaccine group and control group. Three vaccinations at 2-wk intervals were performed after curative hepatic resection. Delayedtype- hypersensitivity (DTH) test was performed before and after vaccination. Primary endpoints were the time of recurrence.RESULTS: Four patients in control group and 6 patients in HCC vaccine group were withdrawn from the study. The vaccine containing human autologous HCC fragments showed no essential adverse effect in a phase Ⅱ clinical trial and 17 of 24 patients developed a DTH response against the fragments. Three of 17 DTH-positive response patients and 5 of 7 DTH- negative response patients had recurrences after curative resection. After the operation,1-, 2- and 3-year recurrence rates of HCC vaccine groupwere 16.7%, 29.2% and 33.3%, respectively. But, 1-, 2- and3-year recurrence rates of the control group were 30.8%,53.8% and 61.5%, respectively. The time before the first recurrence in the vaccinated patients was significantly longer than that in the control patients (P<0.05).CONCLUSION: Autologous tumor vaccine is of promise in decreasing recurrence of human HCC.

  4. Spontaneous rupture of hepatocellular carcinoma in children

    Directory of Open Access Journals (Sweden)

    Nejmeddine Affes

    2010-01-01

    Full Text Available Spontaneous rupture of hepatocellular carcinoma (HCC with intraperitoneal haemorrhage is a life-threatening complication with a high mortality rate. The mechanism of spontaneous rupture of HCC is unknown. It may be related to venous congestion, haemorrhage, central necrosis, or trauma. Patients with ruptured tumours confirmed on computerised tomography (CT scan underwent immediate cardiovascular resuscitation. Depending on the stage of the tumour as seen on the CT scan and the condition of the patient, stoppage of bleeding was accomplished by transcutaneous hepatic artery embolisation, selective hepatic artery ligation, or hepatic resection. Only clinically stable, small tumours were resected as an emergency procedure. We report the case of a 12-year-old child admitted with acute right upper quadrant abdominal pain and signs of hypovolaemia. Ultrasonography revealed free peritoneal fluid and left liver haematoma was suspected. CT scan showed a tumour on the left side of the liver and free peritoneal fluid. Emergency laparotomy revealed haemoperitoneum and a 5-cm diameter left liver tumour which was ulcerated and haemorrhagic. The tumour was completely resected. Histopathological examination confirmed a diagnosis of rupture of differentiated HCC.

  5. CT findings of exophytic hepatocellular carcinoma

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    Lee, Sang Jin; Cho, June Sik; Kim, Hyung Lyul; Lee, Chung Keun; Kim, Dae Hong; Rhee, Byung Chull [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

    1993-11-15

    We retrospectively evaluated the characteristic computed tomographic(CT) findings in nine patients with exohepatic hepatocellular carcinoma(HCC) pathologically prove by surgery(n=2) or percutaneous needle biopsy(n=7). The CT findings of exphepatic HCC were correlated with clinical findings and compared with those of usual HCC. Lesions were in the left lobe(n=7) and right lobe(n=2) of the liver. All lesions showed a well-marginated hypodense mass with capsular enhancement on enhanced CT scan. The patterns of capsular enhancement were complete in five and partial in four case. The portal vein thrombosis was seen only in one case. There was no difference between exohepatic HCC and usual HCC in clinical findings such as increased {alpha}-fetoprotein({alpha}-FP), positive hepatitis B surface antigen(HBsAg), and underlying liver cirrhosis. In conclusion, the CT findings of exohepatic HCC were a well-defined hyperdense mass with complete or partial capsular enhancement and these findings may be useful in differentiation from the tumors of adjacent organs.

  6. Hepatocellular carcinoma: a systems biology perspective

    Directory of Open Access Journals (Sweden)

    Lorenza Alice D'alessandro

    2013-02-01

    Full Text Available Hepatocellular carcinomas (HCC have different etiology and heterogenic genomic alterations lead to high complexity. The molecular features of HCC have largely been studied by gene expression and proteome profiling focusing on the correlations between the expression of specific markers and clinical data. Integration of the increasing amounts of data in databases has facilitated the link of genomic and proteomic profiles of HCC to disease state and clinical outcome. Despite the current knowledge, specific molecular markers remain to be identified and new strategies are required to establish novel targeted therapies. In the last years, mathematical models reconstructing gene and protein networks based on experimental data of HCC have been developed providing powerful tools to predict candidate interactions and potential targets for therapy. Furthermore, the combination of dynamic and logical mathematical models with quantitative data allows detailed mechanistic insights into system properties. To address effects at the organ level, mathematical models reconstructing the three-dimensional organization of liver lobules were developed. In the future, integration of different modeling approaches capturing the effects at the cellular up to the organ level is required to address the complex properties of HCC and to enable the discovery of new targets for HCC prevention or treatment.

  7. Laser Ablation for Small Hepatocellular Carcinoma

    Science.gov (United States)

    Pacella, Claudio Maurizio; Francica, Giampiero; Di Costanzo, Giovanni Giuseppe

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is increasingly detected at small size (liver transplantation, or percutaneous ablation have been proposed. When surgical options are precluded, image-guided tumor ablation is recommended as the most appropriate therapeutic choice in terms of tumor local control, safety, and improvement in survival. Laser ablation (LA) represents one of currently available loco-ablative techniques: light is delivered via flexible quartz fibers of diameter from 300 to 600 μm inserted into tumor lesion through either fine needles (21g Chiba needles) or large-bore catheters. The thermal destruction of tissue is achieved through conversion of absorbed light (usually infrared) into heat. A range of different imaging modalities have been used to guide percutaneous laser ablation, but ultrasound and magnetic resonance imaging are most widely employed, according to local experience and resource availability. Available clinical data suggest that LA is highly effective in terms of tumoricidal capability with an excellent safety profile; the best results in terms of long-term survival are obtained in early HCC so that LA can be proposed not only in unresectable cases but, not differently from radiofrequency ablation, also as the first-line treatment. PMID:22191028

  8. EPIDEMIOLOGY, ETIOPATHOLOGY AND DIAGNOSTIC OF HEPATOCELLULAR CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. Vlad

    2011-02-01

    Full Text Available Hepatocellular Carcinoma (HCC is among the most common of solid human malignancies, with an annual incidence of 100.000 new cases. The worldwide distribution of HCC is not uniform, the highest rates are found in Southeast Asia and Sub-Saharian Africa. The HCC imcidence in Romania varies between 4-10 cases to 100.000 inhabitants per year. HCC is more likely to develop in men than in women, the sex ratio being approximately 8:1 in high-incidence areas. Chronic hepatitis B virus and C virus have been implicated as important etiologic factors in the development of HCC, being responsable for 80% of the cases. The most of the carcinomas are developped on the cirrhotic liver. A number of other risk factors also are involved in HCC: diabetes mellitus, obesity, chronic ethilism, oral contraceptives, smoking and dietary intake of aphlatoxines. HCC is usually diagnosed at a late stage. The clinical presentation are not typical, suggesting only the basic liver pathology. Ultrasounds, CT- scan and MRI confirm the presence of a mass in the liver. Alfa-fetoprotein (AFP, alfa-fetoprotein L3 fraction and des-gammacarboxiprotrombina (also known as PIVKA II test are considered as serological markers for HCC. The indication of screening is for the patients with liver cirrhosis or chronic hepatitis B and/ or C virus. The level of AFP and liver ultrasounds are mandatory to be done as screening tests to every 6 months to the risk patients.

  9. Senescence and immortality in hepatocellular carcinoma.

    Science.gov (United States)

    Ozturk, Mehmet; Arslan-Ergul, Ayca; Bagislar, Sevgi; Senturk, Serif; Yuzugullu, Haluk

    2009-12-01

    Cellular senescence is a process leading to terminal growth arrest with characteristic morphological features. This process is mediated by telomere-dependent, oncogene-induced and ROS-induced pathways, but persistent DNA damage is the most common cause. Senescence arrest is mediated by p16(INK4a)- and p21(Cip1)-dependent pathways both leading to retinoblastoma protein (pRb) activation. p53 plays a relay role between DNA damage sensing and p21(Cip1) activation. pRb arrests the cell cycle by recruiting proliferation genes to facultative heterochromatin for permanent silencing. Replicative senescence that occurs in hepatocytes in culture and in liver cirrhosis is associated with lack of telomerase activity and results in telomere shortening. Hepatocellular carcinoma (HCC) cells display inactivating mutations of p53 and epigenetic silencing of p16(INK4a). Moreover, they re-express telomerase reverse transcriptase required for telomere maintenance. Thus, senescence bypass and cellular immortality is likely to contribute significantly to HCC development. Oncogene-induced senescence in premalignant lesions and reversible immortality of cancer cells including HCC offer new potentials for tumor prevention and treatment. PMID:19070423

  10.  Pigmented hepatocellular adenoma with β-catenin activation: case report and literature review.

    Science.gov (United States)

    Coelho, Rosa; Gonçalves, Regina; Carneiro, Fátima; Fernandes, Margarida; Lopes, Joanne; Guimarães, Susana; Macedo, Guilherme

    2016-01-01

     Hepatocellular adenomas (HCAs) are benign liver tumors recently characterized into 4 different types according to genetic, pathological and clinical features. The prognosis is not well established yet and malignant transformation has been recently associated with β-catenin activation. We aimed to describe a case of a pigmented HCA with β-catenin nuclear expression and inflammatory features and to review the cases of pigmented HCAs in the literature. We report a case of a young female patient without contraceptive use, with a liver tumor diagnosis. Liver biopsy revealed diffuse expression of β-catenin and a partial hepatic resection was performed. The histologic analysis revealed a hepatocellular tumor composed of uniform trabeculae of hepatocytes and solid areas, the later with a significant amount of black pigment highlighted by Masson-Fontana stain. Immunohistochemistry showed co-expression of C-reactive protein and serum amyloid A in the tumor. Literature review revealed that pigmented HCAs, previously reported as dark adenomas, are rare tumors. In HCAs, the presence of β-catenin activation should be searched for due to the higher risk of malignant transformation in hepatocarcinoma. We describe a pigmented HCA with β-catenin nuclear expression and inflammatory features being the fifth case reported so far. PMID:27236161

  11. Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea. The clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio. Cryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology. Cryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted

  12. Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online

    Directory of Open Access Journals (Sweden)

    Chen Chang-Han

    2007-02-01

    Full Text Available Abstract Background The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. Results Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO http://ehco.iis.sinica.edu.tw, to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25% from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. Conclusion This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment.

  13. Hemodynamic characteristics of early stage hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hemodynamic characteristics were studied by using in vivo vascular imaging techniques in 17 resected early stage hepatocellular carcinoma (e-HCC) by comparing them with 49 resected advanced HCCs (ad-HCC) less than 3 cm in diameter. In this study, e-HCC was defined as the nodule being uniformly composed of well-differentiated HCC or adenomatous hyperplastic nodule containing well-differentiated HCC foci within the nodule. In vivo vascular imaging techniques are as follows; US angiography with intraarterial CO2 microbubbles were performed to assess the tumor arterial vascularity, and CT during arterial portography (CTAP) was performed to assess the portal perfusion within the nodule. Of 17 e-HCC nodules 5 were hypervascular, 5 were isovascular, 4 were hypovascular, and 3 were vascular spot in hypovascular pattern in contrast to 49 ad-HCC nodules, 43 of which were hypervascular and 6 were isovascular. Of 14 e-HCCs, 9 nodules showed perfusion defect and 5 did not on CTAP, whereas all 37 ad-HCCs on which CTAP was performed, showed perfusion defect. Forty-one percent (7/17) of e-HCC showed fatty metamorphosis in contrast to 8% (4/49) of ad-HCC. In conclusion, hemodynamic characteristics of e-HCC are summarized as follows. (1) Arterial tumor neovascularization is relatively low. (2) Portal perfusion is present in some of e-HCC cases. (3) Hypoperfusion state both from arterial and portal supply is present in some of e-HCC cases. (4) Vascular spot in hypovascular pattern is characteristic arterial pattern in AH containing HCC foci. (5) Fatty metamorphosis may be related with hypoperfusion state of the nodule in e-HCC. (author)

  14. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  15. Angiogenesis in liver cirrhosis and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Amarapurkar Anjali

    2008-07-01

    Full Text Available Background: Angiogenesis has been well documented in hepatocellular carcinoma (HCC. As liver cirrhosis is considered preneoplastic condition, the aim of this study was to evaluate the process of angiogenesis using CD 34 as an endothelial cell marker in normal liver, cirrhosis and HCC. Materials and Methods: A total of 111 cases were included in this study, which consisted of 30 cases each of normal liver and cirrhosis that were all autopsy cases. Twenty-one cases of HCC included 10 autopsy specimens, nine surgically resected specimens and two liver biopsies. Remaining were 30 cases of metastasis to the liver, which included 20 autopsy specimens, one surgically resected specimen and nine liver biopsies. The patients were between the age range from 17 to 80 years with 70 males and 11 females. Paraffin-embedded liver sections of all these cases were stained routinely by hematoxylin-eosin stain, while immunohistochemistry for CD 34 was performed for expression of endothelial cells. The positivity of CD 34 staining was evaluated by counting in 10 high-power field, grading was done from 0 to 4 and compared between normal liver, cirrhosis and HCC and metastasis. Results: CD 34 was positive in 16/30 (53.3% cases of cirrhosis, 18/21 (85% cases of HCC and 26 (86.6% of metastasis to the liver. None of the normal liver showed any positivity. Grade 3 to 4 positivity was seen in 4/16 (25% and 13/18 (72% cases of cirrhosis and HCC, respectively. Amongst these, 10 were moderately differentiated, one well differentiated and rest two were fibrolamellar and sarcomatoid variants of HCC. Conclusion: Over expression of endothelial cell marker CD 34 with gradual progression was found from normal liver to cirrhosis to HCC and metastasis. Understanding of this process of angiogenesis might help in the design of efficient and safe antiangiogenic therapy for these liver disorders.

  16. Stereotactic Body Radiotherapy for Primary Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Andolino, David L., E-mail: dandolin@iupui.edu [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN (United States); Johnson, Cynthia S. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN (United States); Maluccio, Mary [Department of Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Kwo, Paul [Department of Medicine, Indiana University School of Medicine, Indianapolis, IN (United States); Tector, A. Joseph [Department of Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Zook, Jennifer; Johnstone, Peter A.S.; Cardenes, Higinia R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN (United States)

    2011-11-15

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). Methods and Materials: From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. Results: The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no {>=}Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. Conclusions: SBRT is a safe, effective, noninvasive option for patients with HCC {<=}6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant.

  17. C/EBPα Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma through Inhibiting EGFR/β-Catenin Signaling Mediated EMT

    OpenAIRE

    Huan, Hongbo; Wen, Xudong; Chen, Xuejiao; Wu, Lili; Liu, Weihui; Habib, Nagy A.; Bie, Ping; Xia, Feng

    2016-01-01

    Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPα. Intravenous injection of C/EBPα-sa...

  18. A Case of Sphenoid Sinus Metastasis in Hepatocellular Carcinoma.

    Science.gov (United States)

    Lee, Tae Hoon; Rangan, Vikram; Khallafi, Hicham

    2016-06-01

    Sphenoid sinus metastasis from hepatocellular carcinoma (HCC) has been reported only rarely. We present a case of solitary sphenoid sinus metastasis of a 2.7 × 2.3 cm single HCC lesion. (Hepatology 2016;63:2050-2053). PMID:26928869

  19. Hepatocellular carcinoma: perfusion quantification with dynamic contrast-enhanced MRI

    NARCIS (Netherlands)

    Taouli, B.; Johnson, R.S.; Hajdu, C.H.; Oei, M.T.H.; Merad, M.; Yee, H.; Rusinek, H.

    2013-01-01

    The objective of our study was to report our initial experience with dynamic contrast-enhanced MRI (DCE-MRI) for perfusion quantification of hepatocellular carcinoma (HCC) and surrounding liver.DCE-MRI of the liver was prospectively performed on 31 patients with HCC (male-female ratio, 26:5; mean ag

  20. Loss of fragile histidine triad protein in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Xin Song; Yuan-Yuan Nin; Ya-Li Lu; Xiang-Hong Li

    2003-01-01

    AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers,but little is known about its expression in human hepatocellular carcinogenesis and evolution.METHODS: Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression.RESULTS: All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83(65.0 %) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue werehighly significant (P=0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P=0.219); (b) in tumors with higher clinical stage Ⅲ and ⅣV (91.3 %, P=0.000), compared with tumors with lower stage Ⅰ and Ⅱ (27.6 %); and (c) in cancers with bigger tumor size (>50 mm) (75.0 %, P=0.017), compared withsmaller tumor size (≤ 50 mm). CONCLUSION: FHIT inactivation seems to be both an earlyand a later event, associated with carcinogenesis andprogression to more aggressive hepatocellular carcinomas.Thus, evaluation of Fhit expression by immunohistochemistryin hepatocellular carcinoma may provide important diagnosticand prognostic information in clinical application.

  1. High immunosuppressive burden in advanced hepatocellular carcinoma patients

    OpenAIRE

    Lugade, Amit A.; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2013-01-01

    The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

  2. The glucagon test in obstructive and hepatocellular jaundice

    OpenAIRE

    Berstock, David A.; Wood, John R.; Williams, Roger,

    1982-01-01

    The plasma glucose response to an intravenous bolus of glucagon was examined in patients with obstructive jaundice, hepatocellular jaundice and in healthy volunteers. Plasma glucose levels were determined before and at 15, 30 and 45 min after glucagon. The glucose response to glucagon differed markedly in the two patient groups with significantly higher plasma glucose values in the obstructive jaundice group.

  3. Mechanisms and signiifcance of lipoprotein(a) in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Ning Xu; Xue-Guang Zhang

    2009-01-01

    BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid proifles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords "hepatocellular carcinoma" and "lipoprotein(a)". The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apo-lipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolismin vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein(a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display signiifcant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.

  4. The Correlation between Gene Polymorphism and Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    The association of gene polymorphism and susceptibility to hepatocellular carcinoma (HCC) has been widely studied in recent years. Gene mutations are closely related to HCC. Understanding and measuring the gene mutations are useful to reduce the incidence of HCC and improve its prognosis.

  5. Peanut butter consumption and hepatocellular carcinoma in Sudan

    NARCIS (Netherlands)

    El Hadi Omer, R.

    2001-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with 80% of cases occurring in developing countries in sub-Saharan regions in Africa, South-East Asia and China. The cancer is highly fatal and survival is generally less than 1 year from diagnosis. Clinical records suggest

  6. Identification of T-Cell Factor-4 isoforms that contribute to the malignant phenotype of hepatocellular carcinoma cells

    OpenAIRE

    Tsedensodnom, Orkhontuya; Koga, Hironori; Rosenberg, Stephen A.; Nambotin, Sarah B.; Carroll, John J.; Wands, Jack R.; Kim, Miran

    2011-01-01

    The Wnt/β-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). Downstream signaling events involving the Wnt/β-catenin cascade occur through T-cell factor (TCF) proteins. The human TCF-4 gene is composed of 17 exons with multiple alternative splicing sites. However, the role of different TCF-4 isoforms in the pathogenesis of HCC is unknown. The purpose of this study was to identify and characterize TCF-4 isoforms in HCC. We identified 14 novel TCF-4 isoforms fr...

  7. Mitochondrial damage and cholesterol storage in human hepatocellular carcinoma cells with silencing of UBIAD1 gene expression

    Directory of Open Access Journals (Sweden)

    Carlos R. Morales

    2014-01-01

    Full Text Available Heterozygous mutations in the UBIAD1 gene cause Schnyder corneal dystrophy characterized by abnormal cholesterol and phospholipid deposits in the cornea. Ubiad1 protein was recently identified as Golgi prenyltransferase responsible for biosynthesis of vitamin K2 and CoQ10, a key protein in the mitochondrial electron transport chain. Our study shows that silencing UBIAD1 in cultured human hepatocellular carcinoma cells causes dramatic morphological changes and cholesterol storage in the mitochondria, emphasizing an important role of UBIAD1 in mitochondrial function.

  8. Risk Analysis of Hepatocellular Carcinoma in Northeast China

    Institute of Scientific and Technical Information of China (English)

    Zhi-fang Jia; Meng Su; Miao He; Zhi-hua Yin; Wei Wu; Xue-lian Li; Peng Guan; Bao-sen Zhou

    2009-01-01

    Objective: It is known that chronic hepatitis B virus (HBV) infection is a main risk factor for hepatocellular carcinoma (HCC). To assess the effect of HBV infection and its interaction with other factors on the risk for HCC, a hospital-based case-control study was carried out in Northeast China. Methods: A total of 384 cases with hepatocellular carcinoma and 432 controls without evidence of liver diseases were enrolled in the study. Blood samples were collected to detect the serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and questionnaires about lifestyle and family tumor history were performed in all subjects. Results: The total infection rate of HBV in hepatocellular carcinoma cases was 70.8% and 10.0% in non-liver disease controls. There was a statistically significant difference (P<0.0001) between cases and controls (OR= 22.0; 95%CI:15.0-32.3). Interaction analysis indicated that in HBV chronic carriers with HCV infection or alcohol consumption or family HCC history, the risk for HCC increased (OR=41.1, 95%CI: 20.2-83.9, OR=125.0, 95%CI: 66.5-235.2; OR=56.9, 95%CI: 27.2-119.3 respectively). In addition, hepatitis B history, HCV infection, hepatic cirrhosis and family history of HCC were also potential HCC independent risk factors. Conclusion: We confirmed that HBV is a chief risk factor for hepatocellular carcinoma and accounts for 67.7% of all hepatocellular carcinoma in Northeast China. HCV infection, alcohol intake and family history could enhance the risk for HCC in chronic HBV carriers.

  9. Overexpression of engulfment and cell motility 1 promotes cell invasion and migration of hepatocellular carcinoma.

    Science.gov (United States)

    Jiang, Jiarui; Liu, Guoqing; Miao, Xiongying; Hua, Songwen; Zhong, Dewu

    2011-05-01

    Engulfment and cell motility 1 (Elmo1) has been linked to the invasive phenotype of glioma cells. The use of Elmo1 inhibitors is currently being evaluated in hepato-cellular carcinoma (HCC), but the molecular mechanisms of their therapeutic effect have yet to be determined. Elmo1 expression in HCC tissue samples from 131 cases and in 5 HCC cell lines was determined by immunohistochemistry, quantitative RT-PCR and Western blotting. To functionally characterize Elmo1 in HCC, Elmo1 expression in the HCCLM3 cell line was blocked by siRNA. Cell migration was measured by wound healing and transwell migration assays in vitro. Elmo1 overexpression was significantly correlated with cell invasion and the poor prognosis of HCC. Elmo1-siRNA-treated HCCLM3 cells demonstrated a reduction in cell migration. The present study demonstrated for the first time that the suppression of Elmo1 expression inhibits cell invasion in HCC. PMID:22977532

  10. Screening for hepatocellular carcinoma by Egyptian physicians

    Institute of Scientific and Technical Information of China (English)

    Sahar; M; Hassany; Ehab; F; Abdou; Moustafa; Mohamed; El; Taher; Afaf; Adel; Abdeltwab; Hubert; E; Blum

    2015-01-01

    AIM: To assess the practice of Egyptian physicians in screening patients for hepatocellular carcinoma(HCC). METHODS: The study included 154 physicians from all over Egypt caring for patients at risk for HCC. The study was based on a questionnaire with 20 items. Each questionnaire consisted of two parts:(1) personal information regarding the physician(name, age, specialty and type of health care setting); and(2) professional experience in the care of patients at risk for HCC development(screening, knowledge about the cause and natural course of liver diseases and HCC risk). RESULTS: Sixty-eight percent of doctors with an MD degree, 48% of doctors with a master degree or a diploma and 40% of doctors with a Bachelor of Medicine, Bachelor of Surgery certificate considered the hepatitis C virus(HCV) genotype as risk factor for HCC development(P < 0.05). Ninety percent of physicians specialized in tropical medicine, internal medicine or gastroenterology and 67% of physicians in other specialties advise patients to undergo screening for HCV and hepatitis B virus infection as well as liver cirrhosis(P < 0.05). Eighty-six percent of doctors in University Hospitals and 69% of Ministry of Health(MOH) doctors consider HCV infection as the leading cause of HCC in Egypt(P < 0.05). Seventy-two percent of doctors with an MD degree, 55% of doctors with a master degree or a diploma, 56% of doctors with an MBBCH certificate, 74% of doctors in University Hospitals and 46% of MOH hospital doctors consider abdominal ultrasonography as the most important investigation in HCC screening(P < 0.05). Sixty-five percent of physicians in tropical medicine, internal medicine or gastroenterology and 37% of physicians in other specialties recommend as HCC screening interval of 3 mo(P < 0.05). Seventy-one percent of doctors with an MD degree, 50% of doctors with a master degree or diploma and 60% of doctors with an MBBCH certificate follow the same recommendation.CONCLUSION: In Egypt, physicians

  11. The prognostic molecular markers in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin; Zhao-You Tang

    2002-01-01

    The prognosis of hepatocellular carcinoma (HCC) stillremains dismal, although many advances in its clinicalstudy have been made. It is important for tumor control toidentity the factors that predispose patients to death. Withnew discoveries in cancer biology, the pathological andbiological prognostic factors of HCC have been studied quiteextensively. Analyzing molecular markers (biomarkers) withprognostic significance is a complementary method. A largenumber of molecular factors have been shown to associatewith the invasiveness of HCC, and have potential prognosticsignificance. One important aspect is the analysis ofmolecular markers for the cellular malignancy phenotypeThese include alterations in DNA ploidy, cellularproliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, andCSE1L/CAS protein), nuclear morphology, the p53 geneand its related molecule MDM2, other cell cycle regulators(cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenesand their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members ), apoptosisrelated factors (Fas and FasL), as well as telomeraseactivity. Another important aspect is the analysis ofmolecular markers involved in the process of cancerinvasion and metastasis. Adhesion molecules (E-cadherin,catenins, serum intercellular adhesion molecule-1, CD44variants), proteinases involved in the clegradation ofextracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAl), aswell as other molecules have been regarded as biomarkersfor the malignant phenotype of HCC, and are related toprognosis and therapeutic outcomes. Tumor angiogenesisis critical to both the growth and metastasis of cancersincluding HCC, and has drawn much attention in recentyears. Many angiogenesis-related markers, such as vascularendothelial growth factor (VEGF), basic fibroblast growthfactor (bFGF), platelet-derived endothelial cell growth factor( PD-ECGF ), thrombospondin ( TSP ), angiogenin,pleiotrophin, and endostatin (ES) levels, as well asinratumor

  12. Chromosome instability in human hepatocellular carcinoma depends on p53 status and aflatoxin exposure.

    Science.gov (United States)

    Pineau, Pascal; Marchio, Agnès; Battiston, Carlo; Cordina, Emilie; Russo, Alessandro; Terris, Benoît; Qin, Lun-Xiu; Turlin, Bruno; Tang, Zhao-You; Mazzaferro, Vincenzo; Dejean, Anne

    2008-05-31

    Hepatocellular carcinoma (HCC) is a heterogeneous disease triggered by various risk factors and frequently characterized by chromosome instability. This instability is considered to be caused primarily by Hepatitis B virus (HBV), although aflatoxin B1 (AFB1), a potent fungal mutagen is also suspected to influence chromosomal repair. We studied 90 HCCs from Italy, the country with the highest incidence of hepatocellular carcinoma in Europe, 81 samples from France and 52 specimens from Shanghai, in a region where intake of AFB1 via the diet is known to be high. All 223 tumours were characterized for 15 different genomic targets, including allelic loss at 13 chromosome arms and mutations of beta-catenin and p53 genes. Despite disparity in risk-factor distribution, Italian and French cases did not significantly differ for 14 of the 15 targets tested. beta-Catenin and p53 displayed moderate and similar mutation rates (18-29% of cases) in European series. By contrast, tumours from Shanghai were significantly different, with a lower mutation rate for beta-catenin (4% vs. 26%, p<0.0003) and a higher mutation rate for p53 (48% vs. 22%, p<0.0001) when compared with tumours of European origin. The Arg249Ser mutation, hallmark of exposure to AFB1, represented half of the changes in p53 in Shanghai. Furthermore, when stratified for the presence of HBV or p53 mutations, chromosome instability was always higher in Chinese than in European patients. This difference was particularly strong in p53-wildtype tumours (fractional allelic loss, 29.4% vs. 16.7%, p<0.0001). We suggest that AFB1-associated mutagenesis represents a plausible cause for the higher chromosome instability observed in Chinese HCCs, when compared with European primary liver carcinomas. PMID:18467159

  13. Immunosupression in liver transplant for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Juan Carlos Restrepo Restrepo

    2007-02-01

    Full Text Available

    The hepatocellular carcinoma (HCC has turned into a frequent indication for liver transplant. The reports of different series indicate that it represents at least 12% of all liver transplants in Europe. But what kind of inmunosuppression is better in these patients is an unanswered question. Our intension with this review is to give basic information to define which would be the best immunosuppression alternative. There is enough information on the relationship between immunosuppression and cancer, as it is seen in states of primary immunodeficiency or infection with the Human Immunodeficiency virus (HIV. The immune system offers a state of permanent guard to avoid the arousal of neoplasic diseases in immunocompetent patients and from this point of view it has been seen that in immunosuppressed patients there is an association with this condition and the development of lymphoproliferative disorders, which can range from reversible diseases (polyclonal proliferation of B type lymphocytes to the development of a lymphoma and other types of tumors, like the ones observed in skin, genital region or oropharynx. Colon tumors and breast tumors have not been associated with immunosuppression. Immunosuppressive medication takes part in a different manner in the development of tumors, it has been said that steroids that are associated with some tumors, especially those regarding skin, paradoxically have a protective role in the development of lymph tissue tumors.

    It has been said about Azathioprine and Mycophenolate mofetil (MMF that its immunosuppressive effect is an antiproliferative type of immunosuppression, inhibiting the synthesis of purinic nucleotides, especially in lymphocytes. Azathioprine has been involved in the development of hepatic tumors, especially in the era previous

  14. Lipid-AuNPs@PDA nanohybrid for MRI/CT imaging and photothermal therapy of hepatocellular carcinoma.

    Science.gov (United States)

    Zeng, Yongyi; Zhang, Da; Wu, Ming; Liu, Ying; Zhang, Xiang; Li, Ling; Li, Zheng; Han, Xiao; Wei, Xueyong; Liu, Xiaolong

    2014-08-27

    Multifunctional theranostic nanoparticles represent an emerging agent with the potential to offer extremely sensitive diagnosis and targeted cancer therapy. Herein, we report the synthesis and characterization of a multifunctional theranostic agent (referred to as LA-LAPNHs) for targeted magnetic resonance imaging/computed X-ray tomography (MRI/CT) dual-mode imaging and photothermal therapy of hepatocellular carcinoma. The LA-LAPNHs were characterized as having a core-shell structure with the gold nanoparticles (AuNPs)@polydopamine (PDA) as the inner core, the indocyanine green (ICG), which is electrostatically absorbed onto the surface of PDA, as the photothermal therapeutic agent, and the lipids modified with gadolinium-1,4,7,10-tetraacetic acid and lactobionic acid (LA), which is self-assembled on the outer surface as the shell. The LA-LAPNHs could be selectively internalized into the hepatocellular cell line (HepG2 cells) but not into HeLa cells due to the specific recognition ability of LA to asialoglycoprotein receptor. Additionally, the dual-mode imaging ability of the LA-LAPNH aqueous solution was confirmed by enhanced MR and CT imaging showing a shorter T1 relaxation time and a higher Hounsfield unit value, respectively. In addition, the LA-LAPNHs showed significant photothermal cytotoxicity against liver cancer cells with near-infrared irradiation due to their strong absorbance in the region between 700 and 850 nm. In summary, this study demonstrates that LA-LAPNHs may be a promising candidate for targeted MR/CT dual-mode imaging and photothermal therapy of hepatocellular carcinoma. PMID:25090604

  15. Sorafenib-Induced Interstitial Pneumonitis in a Patient with Hepatocellular Carcinoma: A Case Report

    OpenAIRE

    Myung, Hyung-Joon; Jeong, Sook-Hyang; Kim, Jin-Wook; Kim, Hee-Sup; Jang, Je-Hyuck; Yoon, Ho Il; Kim, Jae-Sung

    2010-01-01

    Sorafenib is an oral multikinase inhibitor that has shown a survival benefit in patients with advanced hepatocellular carcinoma, and is considered to be generally safe. We treated a patient with interstitial lung disease that was associated with sorafenib therapy for the treatment of advanced hepatocellular carcinoma. A 74-year-old man with hepatitis-C-virus-related hepatocellular carcinoma was treated with sorafenib. After 8 days of sorafenib administration, he received radiation therapy for...

  16. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells

    OpenAIRE

    Yafei Zhang; Bicheng Zhang; Anran Zhang; Yong Zhao; Jie Zhao; Jian Liu; Jianfei Gao; Dianchun Fang; Zhiguo Rao

    2012-01-01

    OBJECTIVE: Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. METHODS: Flow cytome...

  17. Fas antigen expression and its relationship with apoptosis in human hepatocellular carcinoma and noncancerous tissues.

    OpenAIRE

    K. Higaki; Yano, H.; Kojiro, M.

    1996-01-01

    Apoptosis, a programmed cell death, can be observed in the tissues of viral or autoimmune hepatitis and of hepatocellular carcinoma. Fas antigen (Fas) was proposed as a protein that triggers apoptosis. To elucidate the relationship between Fas expression and its location in hepatocellular carcinoma cells, we histochemically examined Fas expression by using 25 hepatocellular carcinoma tissues and their corresponding noncancerous tissues, which were surgically obtained from the same patients. I...

  18. Application of Proteomics to the Study of Hepatocellular Carcinoma and Some Related Diseases

    Institute of Scientific and Technical Information of China (English)

    Yueguo Li; Xin Geng; Weiming Zhang

    2005-01-01

    Hepatocellular carcinoma is a malignant tumor causing one of the highest death rates in the world. Viral hepatitis, hepatic fibrosis and hepatocirrhosis etc. Are some of the most important causes of hepatocellular carcinoma. With the advent of the post-genomic age, studying carcinoma and some related diseases using the developing technology of proteomics has become a major focus of researchers. This article is a review of the application of proteomics to study hepatocellular carcinoma and some related diseases.

  19. NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma

    OpenAIRE

    Wilson, CL; Jurk, D.; Fullard, N.; Banks, P.; Page, A.; Luli, S.; Elsharkawy, AM; Gieling, RG; Chakraborty, JB; Fox, C; Richardson, C.; Callaghan, K.; Blair, GE; Fox, N; Lagnado, A.

    2015-01-01

    Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dime...

  20. FTIR microspectroscopy defines early drug resistant human hepatocellular carcinoma (HepG2) cells.

    Science.gov (United States)

    Junhom, Cholpajsorn; Weerapreeyakul, Natthida; Tanthanuch, Waraporn; Thumanu, Kanjana

    2016-01-01

    Characterization and identification of cancer cell, chemotherapy, resistance is important for both routine cancer therapy and trouble-shooting the medication treatment regimen. Present techniques for characterizing cancer cell resistance require multiple methods and steps, which are time-consuming and expensive. We present a protocol for simple sample handling, rapid detection, and spectral characterization of early resistant hepatocellular carcinoma (HepG2) cells, using Fourier transform infrared microspectroscopy (FTIR). Studies on alteration of the biochemical properties in a resistant HepG2 cell were evaluated-viz., increase efflux proteins (MRP-1 and P-gp) activity, total GSH content, anti-apoptotic (Bcl2) expression, and reduction of pro-apoptotic (Bax) proteins. Principle component analysis (PCA) was used to discriminate resistant HepG2 cells from parental HepG2 cells. Three important FTIR spectral regions were evaluated for reproducibility and discrimination ability-viz., lipid (3,000-2,800 cm(-1)), protein (1,700-1,500 cm(-1)) and carbohydrate and nucleic acid (1,300-900 cm(-1)). These 3 spectral regions can be used as spectroscopic biomarkers for differentiation of early or low resistance. This work presents a novel concept for high-throughput, FTIR spectroscopic discrimination of early resistance; thus enabling identification and characterization of cancer cell resistance. PMID:26708618

  1. Non-surgical management of hepatocellular carcinoma; Prise en charge non chirurgicale du carcinome hepatocellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Merle, P. [Service d' hepato-gastroenterologie, hopital de l' Hotel-Dieu, 69 - Lyon (France); Inserm U871 -Oncogenese hepatique et hepatites virales-, 69 - Lyon (France); IFR62 Lyon-Est, universite Lyon 1, 69 - Lyon (France); Mornex, F. [Departement de radiotherapie-oncologie, centre hospitalier Lyon-Sud, 69 - Pierre-Benite (France)

    2010-10-15

    Most of patients with hepatocellular carcinoma (HCC) cannot benefit from surgical therapies. Among non-surgical options, only radiofrequency can challenge surgery for small size tumours. Conformal radiotherapy is likely highly efficient on solitary tumours, but controlled studies are warranted to conclude. Other options are purely palliative. Trans-arterial hepatic chemo-embolization is the goal-standard for multifocal hepatocellular carcinoma and Sorafenib for hepatocellular carcinoma with portal vein invasion, leading to modest but significant benefit on survival rates. Yttrium-90 radio-embolization is under evaluation through controlled studies, and could be of major interest for multifocal hepatocellular carcinoma with or without portal venous invasion. (authors)

  2. Liver transplantation for hepatocellular carcinoma in Uruguay

    International Nuclear Information System (INIS)

    Full text:introduction and objectives: Hepatocellular carcinoma (HCC)is the 6th neoplasia in frequency and the 1st cause of death in cirrhotic patients. Today it is one of the main indications for transplantation liver in early stages. The stated goal is to describe our experience in transplant HCC liver by defining epidemiology, imaging, pathological (A P)and variables of prognostic relevance. Methods: A descriptive, observational and retrospective cirrhotic patients with HCC in tracking National Transplant Program Liver of Uruguay in the period 16/06/2009-28/09/2012. For the diagnosis and staging us criteria rely on Barcelona Clinic Liver Cancer (BCLC)and Milan. Results: Epidemiology: 16 patients were evaluated for transplantation for HCC, and there were 2 cases of incidental diagnosis post-transplant (N = 18). 17 were men. The mean age was 57 years. 15 were detected under surveillance program. The most prevalent etiologies were alcohol- and HCV infection. Diagnosis and Staging: All patients underwent three-phase CT, MRI required 9. 10 had single lesion, 6 had 2 or 3 lesions and 2 cases were diagnosed by image. 11 patients met Milan criteria. The average value of alpha-fetoprotein (AFP)was 225 ng / ml, only in 4 cases was greater than 50 ng / ml. Staging according BCLC: 13 were A, 2 B, 2 C and 1 D. entry to list and transplant: The patient with stage D did not enter. 2 are under evaluation. 13 entered list of which 1 is currently listed, 3 out of list, by progression, 2nd neoplasia and death sepsis. Finally, 9 patients were transplanted for HCC (18 % of the indications for transplantation). The average wait time listed was 45 (0-128)days. Of the 11 patients transplanted with HCC die in block, 1 for sepsis and another relapse. The remaining 8 have not recurred and are alive to date with normal AFP. A P findings, prognostic markers: In 3 had single lesion, 5 had 2 or 3 lesions, and 3 > 3 lesions. Six were within Milan criteria. the total tumor size was > 10 cm in 3

  3. Clinical and laboratory features of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Andrés Cárdenas

    2007-02-01

    Full Text Available

    The clinical presentation of hepatocellular carcinoma (HCC differs between patients in developing countries (African and Chinese populations from those in industrialized countries. In industrialized countries, HCC co-exists with symptomatic cirrhosis in 80% of cases and clinical manifestations are usually related to those of the underlying disease. On the other hand, patients from developing countries have HCC and cirrhosis in approximately 40% of cases. Underlying cirrhosis in many cases is not advanced and does not produce any symptoms or associated symptoms are masked by those of the tumor (right upper quadrant pain, mass in the upper abdomen, weight loss and weakness. In a subset of patients, there are no clinical manifestations as HCC may occur in the context of hepatitis B infection without cirrhosis.

    Clinical Manifestations

    In Western countries, nearly 35% percent of patients with HCC are asymptomatic. Some of the most common clinical manifestations include: abdominal pain (53-58% of patients, especially in epigastrium or right upper quadrant, abdominal mass (30%, weight loss, malaise, anorexia, cachexia, jaundice or fever.

    Physical Exam

    Physical findings vary with the stage of disease. The patient may exhibit slight or moderate wasting when first seen. In patients with cirrhosis, typical stigmata of chronic liver disease may be present. In advanced stages of HCC the liver may be enlarged and there is significant tenderness. An arterial bruit may be heard over the liver

  4. Inflammatory pseudotumor of the liver occurring during the course of hepatitis C virus-related hepatocellular carcinoma treatment: A case report

    Directory of Open Access Journals (Sweden)

    Naruhiko Honmyo

    2016-01-01

    Conclusion: HCV-related HCC has a high rate of multicentric recurrence. Our experience suggests that, when a hepatic lesion is suspected to be HCC, surgical resection should be considered for curative treatment and to rule out malignancy, even if the lesion may be an IPT.

  5. Chronic hepatitis C presenting with a diagnosis of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Hallager, Sofie; Weis, Nina

    2014-01-01

    Chronic hepatitis C (CHC) affects around 16,000 individuals in Denmark of whom about 50% are diagnosed. In the presence of CHC and cirrhosis the annual risk of hepatocellular carcinoma (HCC) is 1-5%. We report on two patients who presented with disseminated HCC at the time of CHC diagnosis. At the...... time of diagnosis only non-curative treatment was available. An earlier diagnosis of CHC could potentially have led to a cure and prevention of HCC....

  6. Surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus

    OpenAIRE

    Jia, Weidong

    2015-01-01

    Portal vein tumor thrombus (PVTT) is one of the important biological characteristics of hepatocellular carcinoma (HCC), and also a serious complication and a metastatic mode. Surgical treatment is still the most effective therapy for HCC with PVTT. This article describes the history and present situation of surgical treatment of HCC with PVTT, the anatomical basis for PVTT formation, classification of PVTT, indications for surgery, selection of surgical approaches, and evaluation of the surgi...

  7. Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

    OpenAIRE

    Miyahara, Koji; Nouso, Kazuhiro; Yamamoto,Kazuhide

    2014-01-01

    The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conven...

  8. Intraperitoneal seeding from hepatocellular carcinoma following percutaneous ethanol ablation therapy.

    Science.gov (United States)

    Kurl, S; Farin, P; Rytkonen, H; Soimakallio, S

    1997-01-01

    We present a case of intraperitoneal seeding in a 36-year-old woman with a large primary hepatocellular carcinoma located superfically in the left lobe of the otherwise normal liver. The patient was treated with percutaneous ethanol ablation therapy. Eight months after the treatment computed tomography and ultrasonography (US) revealed an intraperitoneal seeding that was confirmed with US-guided percutaneous biopsy. PMID:9107646

  9. FXR induces SOCS3 and suppresses hepatocellular carcinoma

    OpenAIRE

    Guo, Fei; Xu, Zhizhen; Zhang, Yan; Jiang, Peng; Huang, Gang; Chen, Shan; Lyu, Xilin; Zheng, Ping; Zhao, Xin; Zeng, Yijun; Wang, Shuguang; He, Fengtian

    2015-01-01

    Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in the liver carcinogenesis mainly by inhibiting signal transducer and activator of transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in liver, has an important role in protecting against hepatocellular carcinoma (HCC). However, it is unclear whether the tumor suppressive activity of FXR involves the regulation of SOCS3. In the present study, we found that activation of FXR by its specific...

  10. Proteomics for the early diagnosis and treatment of hepatocellular carcinoma

    OpenAIRE

    Autor OJS

    2007-01-01

    The incidence of primary cancer has been increasing globally and now-a-days it constitutes the 5th most frequent cancer of humans representing around 5% of all cancers worldwide. Chronic HBV infection assumes greater significance because of its reported association with cirrhosis, and more ominously hepatocellular carcinoma or HCC. Hepatitis B infection constitutes a major global problem with nearl...

  11. Decreased PCSK9 expression in human hepatocellular carcinoma

    OpenAIRE

    Bhat, Mamatha; Skill, Nicolas; Marcus, Victoria; Deschenes, Marc; Tan, Xianming; Bouteaud, Jeanne; Negi, Sarita; Awan, Zuhier; Aikin, Reid; Kwan, Janet; Amre, Ramila; Tabaries, Sebastien; Hassanain, Mazen; Seidah, Nabil G.; Maluccio, Mary

    2015-01-01

    Background The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. Methods Thirty-nine...

  12. Type IV collagen-degrading enzyme activity in hepatocellular carcinoma.

    OpenAIRE

    Nakatsukasa,Harushige

    1986-01-01

    Type IV collagen-degrading enzyme activity was measured in liver homogenate obtained from 10 patients with hepatocellular carcinomas. Type IV collagen, the enzyme substrate, was extracted from human placenta with pepsin digestion, and labeled with [1-14C] acetic anhydride. The homogenate was preincubated with p-aminophenylmercuric acetate to activate the latent form of the enzyme, and then the enzyme activity was measured at pH 7.5 by adding a substrate mixture. Referring to previous reports,...

  13. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

    OpenAIRE

    Chen-Yi Liao; Ching-Chang Lee; Chi-chang Tsai; Chao-Wen Hsueh; Chih-Chiang Wang; I-Hung Chen; Ming-Kai Tsai; Mei-Yu Liu; An-Tie Hsieh; Kuan-Jen Su; Hau-Ming Wu; Shih-Chung Huang; Yi-Chen Wang; Chien-Yao Wang; Shu-Fang Huang

    2015-01-01

    We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, ...

  14. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2{+-}7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non

  15. Controversies in imaging of hepatocellular carcinoma: multidetector CT (MDCT)

    OpenAIRE

    Silverman, Paul M.; Szklaruk, Janio

    2005-01-01

    Primary hepatocellular carcinoma (HCC) is a significant tumor worldwide and represents the most common primary hepatic neoplasm. Staging criteria are important for appreciation of timely work up of these neoplasms in contradiction with surgical colleagues. This article demonstrates the appearance of HCC on multiphasic, multidetector CT (MDCT) and relates these findings to current staging criteria. The variable appearance on different planes of contrast is critical to appreciate in staging thi...

  16. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    OpenAIRE

    Yu Hong; Jiang Long; Hai Li; Shuhong Chen; Qiqi Liu; Bei Zhang; Xiaomin He; Yan Wang; Hongyi Li; Yimei Li; Tao Zhang; Chenzhen Lu; Hao Yan; Minli Zhang; Qing Li

    2015-01-01

    Background: Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods: Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing pro...

  17. Immune repertoire: A potential biomarker and therapeutic for hepatocellular carcinoma.

    Science.gov (United States)

    Han, Yingxin; Li, Hongmei; Guan, Yanfang; Huang, Jian

    2016-09-01

    The immune repertoire (IR) refers to the sum of B cells and T cells with functional diversity in the circulatory system of one individual at any given time. Immune cells, which reside within microenvironments and are responsible for protecting the human body, include T cells, B cells, macrophages, and dendritic cells. These dedicated immune cells have a characteristic structure and function. T and B cells are the main lymphocytes and are responsible for cellular immunity and humoral immunity, respectively. The T cell receptor (TCR) and B cell receptor (BCR) are composed of multiple peptide chains with antigen specificity. The amino acid composition and sequence order are more diverse in the complementarity-determining regions (including CDR1, CDR2 and CDR3) of each peptide chain, allowing a vast library of TCRs and BCRs. IR research is becoming increasingly focused on the study of CDR3 diversity. Deep profiling of CDR3s using high-throughput sequencing is a powerful approach for elucidating the composition and distribution of the CDR3s in a given sample, with in-depth information at the sequence level. Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. To identify novel biomarkers for diagnosis and drug targets for therapeutic interventions, several groups attempted to describe immune repertoire characteristics of the liver in the physiological environment or/and pathological conditions. This paper reviews the recent progress in IR research on human diseases, including hepatocellular carcinoma, attempting to depict the relationships between hepatocellular carcinogenesis and the IR, and discusses the possibility of IR as a potential biomarker and therapeutic for hepatocellular carcinoma. PMID:26188280

  18. Gamma Knife Surgery for Brain Metastasis from Hepatocellular Carcinoma

    OpenAIRE

    Qingsheng Xu; Pan Wu; Yiping Feng; Ke Ye; Ying Tong; Yongqing Zhou

    2014-01-01

    OBJECTIVES: The authors evaluated the results of Gamma knife surgery (GKS) for the treatment of metastatic brain tumors from hepatocellular carcinoma (HCC). METHODS AND RESULTS: The authors conducted a retrospective review of the clinical characteristics and treatment outcomes in 14 patients with metastatic brain tumors from HCC who underwent GKS. Twelve (85.7%) patients were male. The mean age of the patients was 53±12 years. There were totally 22 brain metastases in 14 patients and 8 patien...

  19. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

    OpenAIRE

    Wachsmann, Jason; PENG, FANGYU

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many ...

  20. Laser ablation of hepatocellular carcinoma-A review

    OpenAIRE

    Gough-Palmer, Antony Lawrence; Gedroyc, Wladyslaw Michal Witold

    2008-01-01

    A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma (HCC) in the last decade. Laser ablation (LA) and radiofrequency ablation (RFA) are the two most widely used of these. This article provides an up to date overview of the role of laser ablation in the local treatment of HCC. General principles, technique, image guidance and patient selection are discussed. A review of published data on treatment efficacy, long term ...

  1. Hepatitis B virus infection and the risk of hepatocellular carcinoma

    OpenAIRE

    2011-01-01

    Epidemiological studies have provided overwhelming evidence for a causal role of chronic hepatitis B virus (HBV) infection in the development of hepatocellular carcinoma (HCC). However, the pathogenesis of HBV infection and carcinogenesis of HBV-associated HCC are still elusive. This review will summarize the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. The role of HBV in tumor formation appears to be complex, and may involve both direct and indirect mecha...

  2. Non-Coding RNAs as Therapeutic Targets in Hepatocellular Cancer

    OpenAIRE

    Braconi, Chiara; Patel, Tushar

    2012-01-01

    Hepatocellular carcinoma (HCC) is a common malignancy that affects a large number of patients worldwide, with an increasing incidence in the United States and Europe. The therapies that are currently available for patients with inoperable HCC have limited benefits. Although molecular targeted therapies against selected cell signaling pathways have shown some promising results, their impact has been minimal. There is a need to identify and explore other targets for the development of novel the...

  3. Noncoding RNA as therapeutic targets for Hepatocellular Carcinoma

    OpenAIRE

    George, Joseph; Patel, Tushar

    2015-01-01

    Recent studies have suggested that non-coding RNAs (ncRNAs) contribute to the pathogenesis and progression of hepatocellular carcinoma (HCC). These RNA genes may be involved in various pathobiological processes such as cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. Aberrant expression of ncRNA resulting from deregulated epigenetic, transcriptional or post-transcriptional activity has been described in several studies. ncRNAs comprise of a highly diverse group of transc...

  4. Molecular therapy for the treatment of hepatocellular carcinoma

    OpenAIRE

    Greten, T.F.; Korangy, F; Manns, M P; Malek, N. P.

    2008-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Conventional cytotoxic chemotherapy has failed to show a substantial benefit for patients with HCC. Recently, a number of new drugs targeting molecular mechanisms involved in liver cell transformation have entered into clinical trials and led to encouraging results. In this review we summarise this data and point to a number of new compounds, which are currently being tested and can potentially broaden our therapeutic a...

  5. Right ventricular exclusion for hepatocellular carcinoma metastatic to the heart

    Directory of Open Access Journals (Sweden)

    Fan Shou-Zen

    2010-10-01

    Full Text Available Abstract We used for the first time a right ventricular exclusion procedure for the treatment of hepatocellular carcinoma metastatic to the right ventricle. Our case report shows that this surgical option can be effective as rescue therapy for right ventricular outflow tract obstruction secondary to myocardial metastasis in critically ill patients. Most notably, this technique can prevent inadvertent dislodgement of tumor cells.

  6. Contemporary Strategies in the Management of Hepatocellular Carcinoma

    OpenAIRE

    Shirin Elizabeth Khorsandi; Nigel Heaton

    2012-01-01

    Liver transplantation is the treatment of choice for selected patients with hepatocellular carcinoma (HCC) on a background of chronic liver disease. Liver resection or locoregional ablative therapies may be indicated for patients with preserved synthetic function without significant portal hypertension. Milan criteria were introduced to select suitable patients for liver transplant with low risk of tumor recurrence and 5-year survival in excess of 70%. Currently the incidence of HCC is climbi...

  7. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    OpenAIRE

    Ryuichi Kita; Toru Kimura; Hiroki Nishikawa; Yukio Osaki

    2012-01-01

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of ...

  8. Post liver transplantation lymphoproliferative disorder mimics recurrence of hepatocellular carcinoma

    OpenAIRE

    Poovorawan, Kittiyod; Linlawan, Sittikorn; Wisedopas, Naruemon; Komolmit, Piyawat

    2013-01-01

    We report a case of Epstein-Barr virus (EBV)-related postliver transplantation lymphoproliferative disorder (PTLD) in a patient with post liver transplant which initially presented in a CT scan image mimicking recurrence of hepatocellular carcinoma. Histopathology showed atypical plasma cell-like infiltration, and immunohistochemistry confirmed diagnosis of EBV-associated diffuse large B-cell lymphoma. Typical imaging from dynamic phases contrast CT scan might not accurately diagnose recurren...

  9. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    OpenAIRE

    Aleksandra Niedzwiecki; Tatiana Kalinovsky; Roomi, Nusrath W.; M. Waheed Roomi; Matthias Rath

    2012-01-01

    The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the e...

  10. Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

    OpenAIRE

    Miyake, Toru; Hoshino, Seiichiro; Yoshida, Yoichiro; AISU, NAOYA; Tanimura, Syu; Hisano, Satoshi; Kuno, Nobuaki; Sohda, Tetsuro; Sakisaka, Shotaro; Yamashita, Yuichi

    2012-01-01

    Ectopic hepatocellular carcinoma (HCC) is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomo...

  11. Association of lipid peroxidation with hepatocellular injury in preterm infants

    OpenAIRE

    Weinberger, Barry; Watorek, Kazimierz; Strauss, Richard; Witz, Gisela; Hiatt, Mark; Hegyi, Thomas

    2002-01-01

    Introduction We wished to determine whether cholestasis induced by total parenteral nutrition (TPN) in preterm newborn infants is associated with increased oxidative stress secondary to increased reactive oxygen intermediates. We hypothesized that elevated urinary thiobarbituric-acid-reacting substances (TBARS), a marker of oxidative stress, would be associated with hepatocellular injury as measured by serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. Materials and met...

  12. The significance of Brf1 overexpression in human hepatocellular carcinoma

    OpenAIRE

    Zhong, Qian; Xi, Shaoyan; Liang, Jianzhong; Shi, Ganggang; Huang, Yi; Zhang, Yanmei; Levy, Daniel; Zhong, Shuping

    2015-01-01

    Brf1 (TFIIB-related factor 1) plays a crucial role in cell transformation and tumorigenesis. However, the significance of Brf1 expression in human HCC (hepatocellular carcinoma) cases remains to be addressed. In this study, biopsies of human HCC, liver tumor samples of mice and cell lines of normal and tumor liver were utilized to determine the alteration of Brf1 expression using cytological and molecular biological approaches. Brf1 expression is increased in human HCC cases, which is correla...

  13. Hepatocellular Carcinoma Presenting with Obstructive Jaundice during Pregnancy

    OpenAIRE

    Huan-wei Chen; Feng-jie Wang; Jie-yuan Li; Eric C. H. Lai; Wan Yee Lau

    2014-01-01

    Introduction. Both hepatocellular carcinoma (HCC) presenting during pregnancy and HCC presenting with obstructive jaundice due to a tumor cast in the biliary tract are very rare. The management of these patients remains challenging. Presentation of Case. A 23-year-old lady presented with obstructive jaundice at 38 weeks of gestation. Investigations showed HCC with a biliary tumor thrombus. She received percutaneous transhepatic biliary drainage (PTBD) and caesarean section. Right hepatectomy,...

  14. A case report of hepatocellular carcinoma in common hepatic duct

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chi Sung; Park, In Ae; Choi, Sang Woon; Chung, Jung Kee [YongDeungPo City Hospital, Seoul (Korea, Republic of)

    1989-08-15

    We experienced a rare case of intraductal (common hepatic duct) hepatocellular carcinoma. Review of the literature disclosed 30 cases or less in which common duct involvement was a predominant clinical feature. Well demarcated, ovoid filling defect mass in CHD without parenchymal tumor mass was noted in ultrasound, PTC and CT study. The liver was cirrhotic, but {alpha}-fetoprotein level was normal. Differential diagnosis especially with Klatskin tumor is important and thought to be possible.

  15. Mycotoxins are conventional and novel risk biomarkers for hepatocellular carcinoma

    OpenAIRE

    2013-01-01

    Hepatocellular carcinoma (HCC) is a common malignant disease with poor prognosis. To improve the clinical outcome, early diagnosis of HCC arising from nonviral agents and hepatitis virus is important. Among several etiological factors, mycotoxins defined as carcinogens by the International Agency for Research in Cancer might be one of the critical risk factors for nonviral HCC. Aflatoxin B1 is the most well-known carcinogenic mycotoxin for HCC, but the role of the other types of mycotoxin rem...

  16. Radiofrequency Ablation of Hepatocellular Carcinoma: Pros and Cons

    OpenAIRE

    Rhim, Hyunchul; Lim, Hyo K.

    2010-01-01

    Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excelle...

  17. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    OpenAIRE

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic r...

  18. Current status of radiofrequency ablation of hepatocellular carcinoma

    OpenAIRE

    Rhim, Hyunchul; Lim, Hyo K.; Choi, Dongil

    2010-01-01

    Loco-regional treatments for hepatocellular carcinoma (HCC) are important alternatives to curative transplantation or resection. Among them, radiofrequency ablation (RFA) is accepted as the most popular technique showing excellent local tumor control and acceptable morbidity. The current role of RFA is well documented in the evidence-based practice guidelines of European Association of Study of Liver, American Association of Study of the Liver Disease and Japanese academic societies. Several ...

  19. Simultaneous Resection of Disseminated Hepatocellular Carcinoma and Colon Cancer

    OpenAIRE

    Haga, Yuki; Chiba, Tetsuhiro; Ohira, Gaku; Kanai, Fumihiko; Yokota, Hajime; Motoyama, Tenyu; Ogasawara, Sadahisa; Suzuki, Eiichiro; Ooka, Yoshihiko; Tawada, Akinobu; Miyauchi, Hideaki; Matubara, Hisahiro; Yokosuka, Osamu

    2013-01-01

    A 75-year-old woman with abdominal pain and vomiting was admitted to our hospital. Colonoscopy showed an advanced colon cancer that encompassed the entire circumference of the descending colon's lumen. The patient was diagnosed with occlusive ileus associated with the colon cancer. She had been watched for liver cirrhosis due to the hepatitis C virus and received radiofrequency ablation therapy for hepatocellular carcinoma (HCC) 6 years previously. Although she exhibited a gradual increase in...

  20. Hepatitis C Virus Serologic and Virologic Tests and Clinical Diagnosis of HCV-Related Liver Disease

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available The use of serological and virological tests has become essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Virological tools include serological assays for anti-HCV antibody detection and serological determination of the HCV genotype, and molecular assays that detect and quantify HCV RNA and determine the HCV genotype. Anti-HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. Only patients with detectable HCV RNA should be considered for pegylated interferon alfa and ribavirin therapy and the HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.

  1. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    Directory of Open Access Journals (Sweden)

    Behl Susanne

    2008-03-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

  2. The Effect of Twist Expression on Angiogenesis in Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gangmin Xi; Lin Zhang; Zhongli Zhan; Lihua Zhang; Xiyin Wei; Yi Yang; Yurong Shi; Fei Zhang; Ruifang Niu

    2006-01-01

    OBJECTIVE Hepatocellular carcinoma (HCC) is a hypervascular tumor for which angiogenesis plays an important role in its progression. The aim of this study was to investigate the expression of TWIST and VEGF and determine their roles in angiogenesis of HCC.METHODS Expression Twist and VEGF mRNA was determined by realtime RT-PCR in 30 pairs of hepatocellular carcinoma and matched noncancerous tissues. Immunohistochemistry was carried out to analyze the protein expression of Twist and VEGF in 40 hepatocellular carcinoma cases. Staining of endothelial cells for CD34 was used to evaluate the microvessel density (MVD).RESULTS We found that the HCC specimens showing positive Twist expression in tumor cells had a higher microvessel density than those without Twist expression. Furthermore, we found that overexpression of the Twist protein positively correlated with up-regulation of VEGF in the HCC tissues (r=0.479, P=0.002).CONCLUSION Our results demonstrate that Twist may play an important role in the angiogenesis of HCC and a high-level of Twist expression may be related to the malignant potential of tumor cells.

  3. Histopathological image analysis of chemical-induced hepatocellular hypertrophy in mice.

    Science.gov (United States)

    Asaoka, Yoshiji; Togashi, Yuko; Mutsuga, Mayu; Imura, Naoko; Miyoshi, Tomoya; Miyamoto, Yohei

    2016-04-01

    Chemical-induced hepatocellular hypertrophy is frequently observed in rodents, and is mostly caused by the induction of phase I and phase II drug metabolic enzymes and peroxisomal lipid metabolic enzymes. Liver weight is a sensitive and commonly used marker for detecting hepatocellular hypertrophy, but is also increased by a number of other factors. Histopathological observations subjectively detect changes such as hepatocellular hypertrophy based on the size of a hepatocyte. Therefore, quantitative microscopic observations are required to evaluate histopathological alterations objectively. In the present study, we developed a novel quantitative method for an image analysis of hepatocellular hypertrophy using liver sections stained with hematoxylin and eosin, and demonstrated its usefulness for evaluating hepatocellular hypertrophy induced by phenobarbital (a phase I and phase II enzyme inducer) and clofibrate (a peroxisomal enzyme inducer) in mice. The algorithm of this imaging analysis was designed to recognize an individual hepatocyte through a combination of pixel-based and object-based analyses. Hepatocellular nuclei and the surrounding non-hepatocellular cells were recognized by the pixel-based analysis, while the areas of the recognized hepatocellular nuclei were then expanded until they ran against their expanding neighboring hepatocytes and surrounding non-hepatocellular cells by the object-based analysis. The expanded area of each hepatocellular nucleus was regarded as the size of an individual hepatocyte. The results of this imaging analysis showed that changes in the sizes of hepatocytes corresponded with histopathological observations in phenobarbital and clofibrate-treated mice, and revealed a correlation between hepatocyte size and liver weight. In conclusion, our novel image analysis method is very useful for quantitative evaluations of chemical-induced hepatocellular hypertrophy. PMID:26776450

  4. Histological features of early hepatocellular carcinomas and their developmental process: for daily practical clinical application: Hepatocellular carcinoma

    OpenAIRE

    Kondo, Fukuo

    2008-01-01

    Based on clinical and pathological experience, indistinct margin-type hepatocellular carcinomas (HCCs) were considered to be typical early-stage HCCs with good prognosis. For histological diagnosis, the assessment of stromal invasion (tumor invasion into portal tracts and fibrous septa) is very important. In differentiating stromal invasion from pseudoinvasion (benign hepatic tissue in the fibrous stroma), the following 5 items are useful: (1) macroscopic or panoramic views of the histologica...

  5. Re-188 Lipiodol therapy of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Full text: Hepatocellular carcinoma (HCC) is a malignant epithelial tumour arising from parenchymatous liver cells. It is one of the world's most common malignancies, causing almost one million deaths annually. About 315,000 new cases of HCC are reported per year which constitutes 5.6% of all cancers among males and 2.7% of all cancers among females. Control strategies to prevent occurrence of HCC are sub-optimal; this is evident by the rising incidence of HCC even in developed nations like the USA, where the prevalence of the disease is one of the lowest in the world. Currently, patients with HCC have an extremely poor prognosis with a five year survival rate of less than 5% . However, morbidity and mortality in such patients are not determined by the presence of HCC alone, but are also influenced by the activity of the underlying liver disease, as well as the functional status of the liver. The stage of the tumor (size, number, vascular invasion, extra hepatic spread) has been consistently documented to be an important determinant of the natural course of the disease. These factors are major variables that influence various therapeutic strategies directed against this tumor in recent times. Therefore, therapy in HCC needs to be optimized depending upon the above mentioned influences on the final outcome of the disease. Various forms of therapy such as surgical resection, orthotopic liver transplantation (OLT), percutaneous injection to induce coagulative necrosis of the tumor using agents like ethanol, acetic acid, hot saline, microwave and laser have been considered as radical treatment of HCC, aiming at curing the disease. The understanding of pathology, pathogenesis, natural course and risk factors of HCC during the last three decades has resulted in the development of multiple therapeutic approaches with promising yet varying results. Most patients with hepatoma from the developing countries at the time of their presentation to the doctor fall into the

  6. Hepatitis infections, aflatoxin and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Pierre Hainaut

    2007-02-01

    Full Text Available

    The incidence rates of hepatocellular carcinoma (HCC show large geographic variations, globally reflecting the prevalence of two main aetiologic factors, hepatitis B (HBV and/or C (HCV virus infection and exposure to high levels of aflatoxin in the diet (Chen et al. 1997. The highest incidence rates are observed in regions where most of the population is exposed to both factors, such as in parts of eastern Asia and in sub-Saharan Africa (Parkin et al. 2001. These high incidences are consistent with the fact that HBV chronicity and exposure to aflatoxin have a multiplicative effect of risk for HCC. Depending on aetiology and geographic area, mutations in TP53 show striking differences in prevalence and pattern. In Europe and the US, where alcohol is a major risk factor in addition to viral infections, mutations occur in about 25% of HCC and show as much diversity in their type and codon position as in most other epithelial cancers. However, in high incidence areas such as Mozambique, Senegal, The Gambia (Africa and Qidong county (China, TP53 is mutated in over 50% of the cases and the vast majority of these mutations are a single missense, hotspot mutation at codon 249, AGG to AGT, resulting in the substitution of arginine into serine (249ser. This mutation is uncommon in regions where aflatoxin is not present at significant levels in the diet. In areas of intermediate exposure to aflatoxin, as for example in Thailand, the prevalence of the 249ser mutation is intermediate between high- and low-incidence areas. Thus, there is a dose-dependent relationship between exposure to aflatoxin, incidence of HCC and prevalence of 249ser mutation. Aflatoxins are toxic and carcinogenic metabolites produced by several varieties of molds, mainly Aspergillus flavus and Aspergillus parasiticum. These molds contaminate a wide range of traditional agricultural products in countries

  7. Primary study of leptin and human hepatocellular carcinoma in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing Zhou; Wei Lei; Lei Shen; He-Sheng Luo; Zhi-Xiang Shen

    2008-01-01

    AIM: To investigate the expression level and effects of leptin in human hepatocellular carcinoma cells in vitro and to explore the correlation between them.METHODS: Human hepatocellular carcinoma cell line HepG2 was cultured in vitro, and (the expression level)mRNA of leptin and leptin receptors in HepG2 were assessed using reverse transcription polymerase chain reaction (RT-PCR). Effects of different concentrations of leptin (50 ng/mL, 100 ng/mL, 200 ng/mL) on HepG2 were detected with colorimetric assay by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) after incubation periods of 24 h, 48 h,and 72 h. Flow cytometry was performed to assess cell cycle progression of different concentrations of leptin as stated above after each 24 h incubation period.RESULTS: mRNA of leptin and leptin receptors (including short and long isoforms) were expressed in HepG2.The 72 h incubation of leptin at different concentrations (50 ng/mL, 100 ng/mL, 200 ng/mL) promoted proliferation of HepG2 in a concentration- and timedependent manner. The experimental group shows significant statistical differences when compared to the controlled group which contained 0 ng/mL of leptin. As the concentration of leptin increases, significant fewer cells were detected in G0-G1 phase and more cells in S and G2-M phases.CONCLUSION: Leptin and leptin receptor are simultaneously expressed in human hepatocellular carcinoma cell line HepG2. Addition of leptin (O ng/mL200 ng/mL) in 72 h periods indicated there is a concentration- and time-dependent correlation in the stimulation of HepG2 cell proliferation. The effect of proliferation by leptin is due to promotion of DNA synthesis and enhancement of mitotic activity. The relationship between leptin and human hepatocellular carcinoma cells might indicate that adipokine could be associated with the progression of human hepatocellular carcinoma.

  8. Hepatocellular Carcinoma: Review of Epidemiology, Screening, Imaging Diagnosis, Response Assessment, and Treatment.

    Science.gov (United States)

    Clark, Toshimasa; Maximin, Suresh; Meier, Jeffrey; Pokharel, Sajal; Bhargava, Puneet

    2015-01-01

    Hepatocellular carcinoma is a common malignancy for which prevention, screening, diagnosis, treatment, and surveillance demand a multidisciplinary approach. Knowledge of the underlying pathophysiology as well as advances in clinical management should be employed by radiologists to effectively communicate with hepatologists, surgeons, and oncologists. In this review article, we present recent developments in the clinical management of hepatocellular carcinoma. PMID:25979220

  9. Benign hepatocellular nodules : What have we learned using the patho-molecular classification

    NARCIS (Netherlands)

    Sempoux, Christine; Chang, Charissa; Gouw, Annette; Chiche, Laurence; Zucman-Rossi, Jessica; Balabaud, Charles; Bioulac-Sage, Paulette

    2013-01-01

    Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors that develop most frequently in females and in non-cirrhotic livers. HCA are prone to bleed and to transform into hepatocellutar carcinoma (HCC). Four major subgroups of HCA have been thus far identifie

  10. INVESTIGATION OF THE THERAPEUTIC EFFECT OF EXPRESSION OF TRAIL IN VIVO ON MOUSE HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张桂梅; 薛胜利; 张慧; 黎培员; 李东; 冯作化

    2003-01-01

    Objective: To construct an eukaryotic expressing plasmid of mouse TRAIL (mTRAIL), and investigate its ability to induce the apoptosis of hepatocellular carcinoma cells in vitro and in vivo, its inhibitory effect on the growth of hepatocellular carcinoma, and its synergism with pCH510, an eukaryotic expressing plasmid of recombinant human FN polypeptide. Methods: The eukaryotic expressing plasmid of mTRAIL was constructed by RT-PCR and DNA recombination techniques. Gene transfection was performed in vitro and in vivo. The apoptosis rate of hepatocellular carcinoma cells was measured by Flow Cytometry. The apoptosis of hepatocellular carcinoma cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) and histochemistry techniques. The inhibitory effect of gene transfection on solid tumor was observed in mice. Results: The cDNA of mTRAIL was amplified by RT-PCR from the RNA of mouse spleen cells, and cloned into the eukaryotic expressing vector pcDNA3.1. The recombinant plasmid was designated as pX1. The BHK cells transfected with plasmid pX1 could attack H22 hepatocellular carcinoma cells and induce the apoptosis of them. The transfection of plasmid pX1 through injection into mouse muscles could inhibit the growth of hepatocellular carcinoma by inducing the apoptosis of tumor cells. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth. Conclusion: Plamid pX1 could be expressed in cells and in vivo in mouse. The expression of pX1 in vivo and in vitro could induce the apoptosis of hepatocellular carcinoma cells and inhibit the growth of hepatocellular carcinoma. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth.

  11. COMPARATIVE STUDY ON LIVER TRANSPLANTATION WITH AND WITHOUT HEPATOCELLULAR CARCINOMA WITH CIRRHOSIS: ANALYSIS OF MELD, WAITING TIME AND SURVIVAL

    Science.gov (United States)

    de FREITAS, Alexandre Coutinho Teixeira; SHIGUIHARA, Rafael Shinmi; MONTEIRO, Ruan Teles; PAZETO, Thiago Linck; COELHO, Júlio Cezar Uili

    2016-01-01

    Background : Liver transplantation is the usual treatment for hepatocellular carcinoma. Aim: To analyze the MELD score, waiting time and three month and one year survival for liver transplantation in cirrhotic patients affected by hepatocellular carcinoma or not. Methods : This was a retrospective, observational and analytical study of 93 patients submitted to liver transplantation. Results : There were 28 hepatocellular carcinoma and 65 non-hepatocellular carcinoma patients with no differences related to age and sex distribution. The main causes of cirrhosis on hepatocellular carcinoma were hepatitis C virus (57.1%) and hepatitis B virus (28.5%), more frequent than non-hepatocellular carcinoma patients, which presented 27.7% and 4.6% respectively. The physiological and exception MELD score on hepatocellular carcinoma were 11.9 and 22.3 points. On non-hepatocellular carcinoma, it was 19.4 points, higher than the physiological MELD and lower than the exception MELD on hepatocellular carcinoma. The waiting time for transplantation was 96.2 days for neoplasia, shorter than the waiting time for non-neoplasia patients, which was 165.6 days. Three month and one year survival were 85.7% and 78.6% for neoplasia patients, similar to non-neoplasia, which were 77% and 75.4%. Conclusion: Hepatocellular carcinoma patients presented lower physiological MELD score, higher exception MELD score and shorter waiting time for transplantation when compared to non-hepatocellular carcinoma patients. Three month and one year survival were the same between the groups. PMID:27120734

  12. Twist expression promotes migration and invasion in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate cancer metastasis. It is known to induce epithelial-mesenchymal transition (EMT). In this study, we evaluated the expression of twist and its effect on cell migration in hepatocellular carcinoma (HCC). We examined twist expression using immunohistochemistry in 20 tissue samples of hepatocellular carcinoma, and assessed twist expression in HCC cell lines by RT-PCR and Western blot analysis. Ectopic twist expression was created by introducing a twist construct in the twist-negative HCC cell lines. Endogenous twist expression was blocked by twist siRNA in the twist-positive HCC cell lines. We studied EMT related markers, E-cadherin, Vimentin, and N-cadherin by Western blot analysis. Cell proliferation was measured by MTT assay, and cell migration was measured by in vitro wound healing assay. We used immunofluorescent vinculin staining to visualize focal adhesion. We detected strong and intermediate twist expression in 7 of 20 tumor samples, and no significant twist expression was found in the tumor-free resection margins. In addition, we detected twist expression in HLE, HLF, and SK-Hep1 cells, but not in PLC/RPF/5, HepG2, and Huh7 cells. Ectopic twist-expressing cells demonstrated enhanced cell motility, but twist expression did not affect cell proliferation. Twist expression induced epithelial-mesenchymal transition together with related morphologic changes. Focal adhesion contact was reduced significantly in ectopic twist-expressing cells. Twist-siRNA-treated HLE, HLF, and SK-Hep1 cells demonstrated a reduction in cell migration by 50, 40 and 18%, respectively. Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition

  13. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria

    Science.gov (United States)

    Xu, Xiao; Lu, Di; Ling, Qi; Wei, Xuyong; Wu, Jian; Zhou, Lin; Yan, Sheng; Wu, Liming; Geng, Lei; Ke, Qinghong; Gao, Feng; Tu, Zhenhua; Wang, Weilin; Zhang, Min; Shen, Yan; Xie, Haiyang; Jiang, Wenshi; Wang, Haibo; Zheng, Shusen

    2016-01-01

    Objective Liver transplantation is an optimal radical therapy for selected patients with hepatocellular carcinoma. The stringent organ allocation system driven by the Milan criteria has been challenged by alternative sets of expanded criteria. Careful analysis is needed to prove that the Milan criteria can be expanded safely and effectively. Design This study collectively reviewed 6012 patients of hepatocellular carcinoma from the China Liver Transplant Registry. Expanded criteria were evaluated to characterise an optimised expansion with acceptable outcomes beyond the Milan criteria. Results Compared with the Milan criteria, Valencia, University of California, San Francisco, University Clinic of Navarra and Hangzhou criteria provided an expansion of 12.4%, 16.3%, 19.6%, and 51.5%, respectively. The post-transplant survivals of patients fulfilling the expanded criteria were comparable to that of the Milan criteria. The analysis of net reclassification improvement and area under the receiver operating characteristic curves showed an excellent efficiency in recurrence prediction for the expanded criteria compared with the Milan criteria. In patients exceeding Milan but fulfilling the Hangzhou criteria (N=1352), α-fetoprotein (AFP) >100 ng/mL and tumour burden>8 cm were the only two independent prognostic factors (p8 cm but AFP≤100 ng/mL) and type B (tumour burden >8 cm but AFP between 100 and 400 ng/mL). Type A showed significantly higher 5-year tumour-free survival rates compared with type B (p<0.001). Conclusions The Milan criteria can be expanded safely and effectively. The prognostic stratification system based on the Hangzhou criteria serves as a hierarchy of transplant candidates for hepatocellular carcinoma. PMID:25804634

  14. Dynamic localization of hepatocellular transporters in health and disease

    Institute of Scientific and Technical Information of China (English)

    Marcelo G Roma; Fernando A Crocenzi; Aldo D Mottino

    2008-01-01

    Vesicle-based trafficking of hepatocellular transporters involves delivery of the newly-synthesized carriers from the rough endoplasmic reticulum to either the plasma membrane domain or to an endosomal, submembrane compartment, followed by exocytic targeting to the plasma membrane. Once delivered to the plasma membrane, the transporters usually undergo recycling between the plasma membrane and the endosomal compartment, which usually serves as a reservoir of pre-existing transporters available on demand. The balance between exocytic targeting and endocytic internalization from/to this recycling compartment is therefore a chief determinant of the overall capability of the liver epithelium to secrete bile and to detoxify endo and xenobiotics. Hence, it is a highly regulated process. Impaired regulation of this balance may lead to abnormal localization of these transporters, which results in bile secretory failure due to endocytic internalization of key transporters involved in bile formation. This occurs in several experimental models of hepatocellular cholestasis, and in most human cholestatic liver diseases. This review describes the molecular bases involved in the biology of the dynamic localization of hepatocellular transporters and its regulation, with a focus on the involvement of signaling pathways in this process. Their alterations in different experimental models of cholestasis and in human cholestatic liver disease are reviewed. In addition, the causes explaining the pathological condition (e.g. disorganization of actin or actin-transporter linkers) and the mediators involved (e.g. activation of cholestatic signaling transduction pathways) are also discussed. Finally, several experimental therapeutic approaches based upon the administration of compounds known to stimulate exocytic insertion of canalicular transporters (e.g. cAMP, tauroursodeoxycholate) are described.

  15. Octreotide inhibits proliferation and induces apoptosis of hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Hai-lin LIU; Li HUO; Lei WANG

    2004-01-01

    AIM: To study the effect of octreotide on cell proliferation and apoptosis in different hepatocellular carcinoma (HCC) cells and hepatocytes. METHODS: The proliferation of HCC cells (HepG2, SMMC-7721) and hepatocytes (L-02) was determined by MTT assay. Apoptosis was detected either by fluorescent staining, transmission electron microscopy or flow cytometry. The content of AFP in the supernatant of cultured HCC cells was determined by electrochemiluminescence immunoassay. The expression of SSTR subtypes was identified by RT-PCR.RESULTS: The proliferation of HCC cells and L-02 cells was inhibited significantly by octreotide (0.25, 0.5, 1.0,2.0 and 4.0 mg/L). However, the apoptosis of HCC cells markedly increased in a concentration-dependent manner.Both the apoptosis index and the percentage of apoptotic cells in L-02 cells were significantly lower than those of HepG2 and SMMC-7721 cells. The content of AFP in the supematant of cultured HepG2 cells treated with octreotide was also statistically reduced. Furthermore, SSTR2 and SSTR4 were positive in both the hepatocellular carcinoma cells and in the L-02 cells. SSTR3 was only expressed in the two heptatocellular carcinoma cells, and SSTR5 was found in the SMMC-7721 cells. No SSTR1 was detected either in HCC cells or L-02 cells. CONCLUSIONS:Apoptosis induction is a major mechanism of octreotide inhibition on hepatocellular cells. SSTR3 is expressed in the HCC cells, but not in the L-02 cells, which suggests a molecular basis for the HCC-selective effects of octreotide.

  16. Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

    LENUS (Irish Health Repository)

    O'Donnell, D H

    2012-02-01

    Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

  17. Laser ablation of hepatocellular carcinoma-A review

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma (HCC) in the last decade. Laser ablation (LA) and radiofrequency ablation (RFA) are the two most widely used of these. This article provides an up to date overview of the role of laser ablation in the local treatment of HCC. General principles, technique, image guidance and patient selection are discussed. A review of published data on treatment efficacy, long term outcome and complication rates of laser ablation is included and comparison with RFA made. The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed.

  18. Current role of ultrasound for the management of hepatocellular carcinoma

    OpenAIRE

    Maruyama, Hitoshi; Yoshikawa, Masaharu; Yokosuka, Osamu

    2008-01-01

    Hepatocellular carcinoma (HCC) has a decisive influence on the prognosis of cirrhotic patients. Although α-fetoprotein (AFP) is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound (US) plays a major role among them, because it provides real-time and non-invasive observation by a sim...

  19. Irreversible Electroporation in the Treatment of Hepatocellular Carcinoma.

    Science.gov (United States)

    Lencioni, Riccardo; Crocetti, Laura; Narayanan, Govindarajan

    2015-09-01

    Irreversible electroporation (IRE) is a new nonthermal ablation modality that can be used to treat primary and metastatic lesions in the liver. This article describes the way IRE works, reviews safety and efficacy data, and presents strategies and recommendations for its use in everyday practice. In a series of liver lesions of various histologies, initial success was 100%; local recurrence rates were greater in larger lesions. In another series of hepatocellular carcinoma only, there was a 79% complete response rate overall and 93% in lesions less than 3 cm. Safety is comparable with those of other ablation modalities. IRE has advantages over other ablation modalities with comparable success rates. PMID:26365542

  20. CT diagnosis of abdominal lymph node metastases in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, T.; Nakamura, H.; Choi, S.; Morimoto, K.; Kawamoto, S.; Hori, S.; Tokunaga, K.; Yoskioka, H.; Kuroda, C.

    1985-08-01

    CT scanning is useful for diagnosing abdominal lymph node metastasis. Using this technique, histologically confirmed abdominal lymph node metastases were detected in nine of 49 patients (33 autopsy cases and 16 laparotomy cases) with hepatocellular carcinoma (hepatoma). Among the 49 patients, three had periportal (6.1%), six peripancreatic (12.2.%) and six para-aortic adenopathies (12.2%). Two of the patients had adenopathy at all three sites. Retrospectively, CT detected two periportal, four peripancreatic and all six para-aortic adenopathies. Most of the hepatomas with adenopathy showed infiltrative growth; tumour thrombosis of the portal vein was a common complication.

  1. CT diagnosis of abdominal lymph node metastases in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    CT scanning is useful for diagnosing abdominal lymph node metastasis. Using this technique, histologically confirmed abdominal lymph node metastases were detected in nine of 49 patients (33 autopsy cases and 16 laparotomy cases) with hepatocellular carcinoma (hepatoma). Among the 49 patients, three had periportal (6.1%), six peripancreatic (12.2.%) and six para-aortic adenopathies (12.2%). Two of the patients had adenopathy at all three sites. Retrospectively, CT detected two periportal, four peripancreatic and all six para-aortic adenopathies. Most of the hepatomas with adenopathy showed infiltrative growth; tumour thrombosis of the portal vein was a common complication. (orig.)

  2. Impact of PIVKA-II in diagnosis of hepatocellular carcinoma

    OpenAIRE

    Zakhary, Nadia I.; Khodeer, Sherif M.; Hanan E. Shafik; Camelia A. Abdel Malak

    2013-01-01

    Liver cancer grows silently with mild or no symptoms until advanced. In the absence of an effective treatment for advanced stage of hepatic cancer hope lies in early detection, and screening for high-risk population. Among Egyptians viral hepatitis is the most common risk factor for hepatocellular carcinoma (HCC). The current work was designed to determine the level of prothrombin induced by vitamin K absence-II (PIVKA-II) in sera of patients suffering from HCC and hepatitis C virus (HCV) pat...

  3. Recurrence of hepatocellular carcinoma with rapid growth after spontaneous regression

    OpenAIRE

    Nakajima, Tomoki; Moriguchi, Michihisa; Watanabe, Tadashi; Noda, Masao; Fuji, Nobuaki; Minami, Masahito; Itoh, Yoshito; Okanoue, Takeshi

    2004-01-01

    We report an 80-year-old man who presented with sponta- neous regression of hepatocellular carcinoma (HCC). He complained of sudden right flank pain and low-grade fever. The level of protein induced by vitamin K antagonist (PIVKA)-II was 1137 mAU/mL. A computed tomography scan in November 2000 demonstrated a low-density mass located in liver S4 with marginal enhancement and a cystic mass of 68 mm × 55 mm in liver S6, with slightly high density content and without marginal enhancement. Angiogr...

  4. Abdominal lymph node metastases of hepatocellular carcinoma diagnosed by computed tomography and angiography

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hironobu; Oi, Hiromichi (Osaka Univ. (Japan). Research Inst. for Microbial Diseases); Tanaka, Takeshi; Sai, Soomi; Hori, Shinichi

    1984-04-01

    CT scans of 164 patients with hepatocellular carcinoma were studied, and abdominal lymph node metastases were detected in 13 cases. Most of these lymph node metastases occured in periportal, peripancreatic and paraaortic lymph nodes. Ten instances of each these metastases were identified by CT. Six of the patients had metastases in all three sites. In 9 of 13 cases, lymph node metastases were demonstrated by angiography and various degrees of contrast material stain were seen. Lymph node metastasis of hepatocellular carcinoma is apt to be hypervascular. Most of hepatocellular carcinoma with lymph node metastasis showed infiltrative growth, and tumor thrombosis in the portal vein was commonly complicated.

  5. Hepatitis B virus infection and the risk of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ya-Jun Tan

    2011-01-01

    Epidemiological studies have provided overwhelming evidence for a causal role of chronic hepatitis B virus (HBV) infection in the development of hepatocellular carcinoma (HCC). However, the pathogenesis of HBV infection and carcinogenesis of HBV-associated HCC are still elusive. This review will summarize the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. The role of HBV in tumor formation appears to be complex, and may involve both direct and indirect mechanisms. Integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion, and it has been shown to enhance the host chromosomal instability, leading to large inverted duplications, deletions and chromosomal translocations. It has been shown that the rate of chromosomal alterations is increased significantly in HBV-related tumors. Prolonged expression of the viral regulatory HBV x protein may contribute to regulating cellular transcription, protein degradation, proliferation, and apoptotic signaling pathways, and it plays a critical role in the development of hepatocellular carcinoma.

  6. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

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    Chantragan Srisomsap

    2010-01-01

    Full Text Available Cholangiocarcinoma (CCA and hepatocellular carcinoma (HCC occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1 and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2, laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.

  7. Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma. METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300.RESULTS:The replicative multiples in Hep3B and HepG after 48 h of CNHK300 proliferation were 40625and 65326 fold, respectively, similar to that of wtAd5..However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ.CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI),but could not affect growth of normal cells even at a high MOI.CONCLUSION:CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5),but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

  8. Hepatocellular carcinoma: a retrospective analysis of 118 cases

    International Nuclear Information System (INIS)

    Objective: This study aimed at documenting the spectrum of clinico pathological variations in hepatocellular carcinoma (HCC). Design: It was a retrospective study. Place and duration of Study: This study was conducted at the Institute of Nuclear Medicine and Oncology (INMOL) Hospital, Lahore from March 1997 to December 2000. Patients and Methods: The profiles of 118 patients with a biopsy proven hepatocellular carcinoma were analyzed in this period. The data collected was age, sex, clinical presentation and laboratory investigations including liver function tests, alpha fetoprotein and hepatitis profile. Results: Weight loss, jaundice and right upper quadrant abdominal pain were the main presenting symptoms. Out of 118 patients, alpha fetoprotein values were raised in 63(53.38%) patients 106 (89.83%) patients were found to have or have had HBV infections, and 92 (77.96%) patients were anti-HCV positive. Eighty-three (70.33%) patients were cirrhotic. History of alcohol abuse was bound in three patients. Conclusion: The common association of HCC with cirrhosis and hepatitis B and C suggests that vaccination against HBV on nationwide basis can decrease prevalence of this malignancy. There is a need to generate public awareness regarding the transmission of these viruses. Early diagnosis and intervention is also important to the successful management of HCC. (author)

  9. Intergrin gene expression profiles of human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lian-Xin Liu; Hong-Chi Jiang; Zhi-Hua Liu; Jing Zhou; Wei-Hui Zhang; An-Long Zhu; Xiu-Qin Wang; Min Wu

    2002-01-01

    AIM: To investigate gene expression profiles of intergringenes in hepatocellular carcinoma (HCC) through theusage of Atlas Human Cancer Array membranes, semi-quantitative reverse transcription polymerase chainreaction (RT-PCR) and Northern blot.METHODS: Hybridization of cDNA array membrane wasperformed with α 32P-labeled cDNA probes synthesizedfrom RNA isolated from hepatocellular carcinoma andadjacent non-cirrhotic liver. AtlasImage, which is asoftware specific to array, was used to analyze theresult. RT-PCR of 24 pairs specimen and Northern blotof 4 pairs specimen were used to confirm the expressionpattern of some intergrin genes identified by Atlasarrays hybridization.RESULTS: Among 588 genes spotted in membrane, 17genes were related to intergrin. Four genes were up-regulated, such as intergrin alpha8, beta1, beta7 andbeta8 in HCC. Whereas there were no genes down-regulated in HCC. RT-PCR and Northern blot analysisof intergrin beta1 gene gave results consistent withcDNA array findings.CONCLUSION: Investigation of these intergrin genesshould help to disclose the molecular mechanism of thecell adhesion, invasive and metastasis of HCC. A fewgenes are reported to have changed in HCC for the firsttime. The quick and high-throughout method of profilinggene expression by cDNA array provides us overviewof key factors that may involved in HCC, and may findthe clue of the study of HCC metastasis and moleculartargets of anti-metastasis therapy. The preciserelationship between the altered genes and HCC is amatter of further investigation.

  10. Recent insights on risk factors of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Nabil Mohie Abdel-Hamid

    2009-10-01

    Full Text Available Hepatocellular carcinoma (HCC is a disease prevalent in many populations worldwide. It initiates many economic and health problems in management modalities and leads to increasing mortality rates. Worldwide, trials have attempted to discover specific early markers for detection and prediction of the disease, hoping to set a more precise strategy for liver cancer prevention. Unfortunately, many economic, cultural and disciplinary levels contribute to confounding preventive strategies. Many risk factors contribute to predisposition to HCC, which can present individually or simultaneously. Previous articles discussed many risk factors for hepatocellular carcinogenesis; however, most of them didn't consider collectively the most recent data relating to causes. In this article, the pathogenesis and risk factors of HCC are discussed. Most of the intermediary steps of HCC involve molecular and transcriptional events leading to hepatocyte malignant transformation. These steps are mainly triggered by hepatitis B, C or transfusion-transmitted virus, either alone, or with other factors. Diabetes seems to be a major contributing risk factor. Schistosomiasis, a blood infestation, mostly affects Nile basin inhabitants leading to bladder, renal and hepatic cancers. Alcoholism, food and water pollutants and some drugs can also lead to HCC. Additionally, some hereditary diseases, as hemochromatosis, α -1-antitrypsin deficiency and tyrosinaemia are known to lead to the development of HCC, if not well managed.

  11. Clonal Origin of Hepatocellular Carcinoma and Recurrence After Liver Transplantation.

    Science.gov (United States)

    Wang, Zhenglu; Gong, Weihua; Shou, Dawei; Zhang, Luzhou; Gu, Xiangqian; Wang, Yuliang; Teng, Dahong; Zheng, Hong

    2016-01-01

    BACKGROUND This study aimed to determine whether patterns of tumor clonal origin in pluri-nodular hepatocellular carcinoma (PNHC) could serve as an indicator of tumor recurrence following liver transplantation. MATERIAL AND METHODS Tumor tissue samples from 60 PNHC patients who underwent liver transplantation were examined. The diagnosis of patients conformed to the University of California San Francisco (UCSF) standards for pluri-nodular hepatocellular carcinoma. We performed loss of heterozygosity tests at multiple microsatellite sites to determine the clonal origins of the tumors. Clinical information, pathological data, preoperative serum alpha-feto protein (AFP) and postoperative follow-ups were obtained and correlations between the clonal origin of the tumor, tumor-free survival, pathological characteristics, and AFP levels in serum were studied. RESULTS A total of 165 tumor nodules were collected. Tumor clonal origins were identified as intrahepatic metastasis (IM; 41.67%), multicentric occurrence (MO; 55%) or unidentified (3.33%). Three-year tumor-free survival for the IM group was 48% compared to 75.76% in the MO group (pAFP concentration for these groups was 226.80 μg/L (2.78-3000 μg/L) and 24.59 μg/L (1.16-531. 30 μg/L; pAFP levels, the risk of recurrence can be established in advance. PMID:27487734

  12. Spontaneous regression of a large hepatocellular carcinoma: case report

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    Alqutub, Adel

    2011-01-01

    Full Text Available The prognosis of untreated advanced hepatocellular carcinoma (HCC is grim with a median survival of less than 6 months. Spontaneous regression of HCC has been defined as the disappearance of the hepatic lesions in the absence of any specific therapy. The spontaneous regression of a very large HCC is very rare and limited data is available in the English literature. We describe spontaneous regression of hepatocellular carcinoma in a 65-year-old male who presented to our clinic with vague abdominal pain and weight loss of two months duration. He was found to have multiple hepatic lesions with elevation of serum alpha-fetoprotein (AFP level to 6,500 µg/L (normal <20 µg/L. Computed tomography revealed advanced HCC replacing almost 80% of the right hepatic lobe. Without any intervention the patient showed gradual improvement over a period of few months. Follow-up CT scan revealed disappearance of hepatic lesions with progressive decline of AFP levels to normal. Various mechanisms have been postulated to explain this rare phenomenon, but the exact mechanism remains a mystery.

  13. Hepatocellular apoptosis after hepatectomy in obstructive jaundice in rats

    Institute of Scientific and Technical Information of China (English)

    DeS-heng Wang; Ke-Feng Dou; Kai-Zong Li; Zhi-Qing Gao; Zhen-Shun Song; Zheng-Cai Liu

    2003-01-01

    AIM: To investigate the hepatocellular apoptosis after hepatectomy in obstructive jaundice and biliary decompression rats.METHODS: After bile duct ligation for 7 days, rats were randomly divided into OB group in which the rats undervvent 70 % hepatectorny, OB-CD group in which the rats underwent hepatectorny accompanied by choledochoduodenostomy, CDHx group in which the rats underwent choledochoduodenostomy and then received 70 % hepatectomy on the fifth day after biliary decompression. The control group (Hx group) only underwent hepatectorny.RESULTS: The level of total serum bilirubin and serum enzymes was significantly lower in CD-Hx group than in OB-CD and OB groups on day 1, 3 and 5 after hepatectorny. The apeptotic index was significantly lower in CD-Hx group than in OB-CD and OB groups on day 3 and 5. The oligonucleosomal DNA fragments and Caspase-3 activity were also lower in CD-Hx group than in OB-CD and OB groups 3 days after hepatectorny,without differences between CD-Hx and Hx groups.CONCLUSION. Hepatocellular apoptosis plays vital roles in jaundice rats, and biliary decompression is more effective in treatment of patients with severe jaundice before operation.

  14. Modeling and Analyzing Gene Co-Expression in Hepatocellular Carcinoma Using Actor-Semiotic Networks and Centrality Signatures

    Directory of Open Access Journals (Sweden)

    David C.Y. Fung

    2008-01-01

    Full Text Available Primary hepatocellular carcinoma (HCC is currently the fifth most common malignancy and the third most common cause of cancer mortality worldwide. Because of its high prevalence in developing nations, there have been numerous efforts made in the molecular characterization of primary HCC. However, a better understanding into the pathology of HCC required software-assisted network modeling and analysis. In this paper, the author presented his first attempt in exploring the biological implication of gene co-expression in HCC using actor-semiotic network modeling and analysis. The network was first constructed by integrating inter-actor relationships, e.g. gene co-expression, microRNA-to-gene, and protein interactions, with semiotic relationships, e.g. gene-to-Gene Ontology Process. Topological features that are highly discriminative of the HCC phenotype were identified by visual inspection. Finally, the author devised a graph signature- based analysis method to supplement the network exploration.

  15. OCT4 increases BIRC5 and CCND1 expression and promotes cancer progression in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    OCT4 and BIRC5 are preferentially expressed in human cancer cells and mediate cancer cell survival and tumor maintenance. However, the molecular mechanism that regulates OCT4 and BIRC5 expression is not well characterized. By manipulating OCT4 and BIRC5 expression in hepatocellular carcinoma (HCC) cell lines, the regulatory mechanism of OCT4 on BIRC5 and CCND1 were investigated. Increasing or decreasing OCT4 expression could enhance or suppress BIRC5 expression, respectively, by regulating the activity of BIRC5 promoter. Because there is no binding site for OCT4 within BIRC5 promoter, the effect of OCT4 on BIRC5 promoter is indirect. An octamer motif for OCT4 in the CCND1 promoter has directly and partly participated in the regulation of CCND1 promoter activity, suggesting that OCT4 also could upregulated the expression of CCND1. Co-suppression of OCT4 and BIRC5 induced cancer cell apoptosis and cell cycle arrest, thereby efficiently inhibiting the proliferative activity of cancer cells and suppressing the growth of HCC xenogrfts in nude mice. OCT4 can upregulate BIRC5 and CCND1 expression by increasing their promoter activity. These factors collusively promotes HCC cell proliferation, and co-suppression of OCT4 and BIRC5 is potentially beneficial for HCC treatment

  16. Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

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    Sonja M. Kessler

    2014-04-01

    Full Text Available Non-alcoholic steatohepatitis (NASH represents a risk factor for the development of hepatocellular carcinoma (HCC and is characterized by quantitative and qualitative changes in hepatic lipids. Since elongation of fatty acids from C16 to C18 has recently been reported to promote both hepatic lipid accumulation and inflammation we aimed to investigate whether a frequently used mouse NASH model reflects this clinically relevant feature and whether C16 to C18 elongation can be observed in HCC development. Feeding mice a methionine and choline deficient diet to model NASH not only increased total hepatic fatty acids and cholesterol, but also distinctly elevated the C18/C16 ratio, which was not changed in a model of simple steatosis (ob/ob mice. Depletion of Kupffer cells abrogated both quantitative and qualitative methionine-and-choline deficient (MCD-induced alterations in hepatic lipids. Interestingly, mimicking inflammatory events in early hepatocarcinogenesis by diethylnitrosamine-induced carcinogenesis (48 h increased hepatic lipids and the C18/C16 ratio. Analyses of human liver samples from patients with NASH or NASH-related HCC showed an elevated expression of the elongase ELOVL6, which is responsible for the elongation of C16 fatty acids. Taken together, our findings suggest a detrimental role of an altered fatty acid pattern in the progression of NASH-related liver disease.

  17. Novel Tumor-associated Antigen of Hepatocellular Carcinoma Defined by Monoclonal Antibody E4-65

    Institute of Scientific and Technical Information of China (English)

    Ke ZOU; Jihang JU; Hong XIE

    2007-01-01

    A monoclonal antibody, E4-65, produced by immunizing mice with SMMC-7721 cells, a human hepatocellular carcinoma (HCC) cell line, was used to identify and characterize an unreported HCC-associated antigen. Indirect immunofluorescence studies showed that E4-65 antibody reacted with five out of eight HCC cell lines, but not with 10 non-HCC tumor cell lines or a normal liver cell line. Using immunohistochemical examination, E4-65 antigen was detected on the cell membranes and in the cytoplasm of human liver tumor tissues, but was not found in most other tumors, or normal adult or fetal tissues, except for a weakly positive reaction in tissues of the digestive system. Western blot analysis showed that E4-65 antibody bound to a 45 kDa protein in the human HCC cell line and tissue lysates. Enzyme treatment and lectin blotting did not detect the carbohydrate chain in E4-65 antigen. This HCC-associated protein represents a potentially useful target for diagnoses and immunotherapy of human HCC.

  18. Progress and Prospects of Long Noncoding RNAs (lncRNAs in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen Li

    2015-05-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional “noise” to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC.

  19. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI.

    Science.gov (United States)

    Joo, Ijin; Lee, Jeong Min

    2016-02-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  20. CT Appearance of Hepatocellular Carcinoma after Locoregional Treatments: A Comprehensive Review.

    Science.gov (United States)

    Marin, Daniel; Cappabianca, Salvatore; Serra, Nicola; Sica, Assunta; Lassandro, Francesco; D'Angelo, Roberto; La Porta, Michelearcangelo; Fiore, Francesco; Somma, Francesco

    2015-01-01

    Hepatocellular carcinoma (HCC) is a major health problem worldwide, affecting more than 600,000 new patients per year. Curative treatments are available in a small percentage of patients, while most of them present in stages requiring locoregional treatments such as thermoablation, transarterial chemoembolization, and/or radioembolization. These therapies result in specific imaging features that the general radiologist has to be aware of in order to assess the response to treatment and to correctly manage the follow-up of treated patients. Multiphasic helical computed tomography has become a popular imaging modality for detecting hypervascular tumors and characterizing liver lesions. On this basis, many staging and diagnostic systems have been proposed for evaluating response to all different existing strategies. Radiofrequencies and microwaves generate thermoablation of tumors, and transarterial chemoembolization exploits the double effect of the locoregional administration of drugs and embolizing particles. Eventually radioembolization uses a beta-emitting isotope to induce necrosis. Therefore, the aim of this comprehensive review is to analyze and compare CT imaging appearance of HCC after various locoregional treatments, with regard to specific indications for all possible procedures. PMID:26798332

  1. Review of dynamic contrast-enhanced ultrasound guidance in ablation therapy for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yasunori Minami; Masatoshi Kudo

    2011-01-01

    Local ablative techniques-percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation (RFA)-have been developed to treat unresectable hepatocellular carcinoma (HCC). The success rate of percutaneous ablation therapy for HCC depends on correct targeting of the tumor via an imaging technique. However, probe insertion often is not completely accurate for small HCC nodules, which are poorly defined on conventional B-mode ultrasound (US) alone. Thus, multiple sessions of ablation therapy are frequently required in difficult cases. By means of two breakthroughs in US technology, harmonic imaging and the development of second-generation contrast agents, dynamic contrast-enhanced harmonic US imaging with an intravenous contrast agent can depict tumor vascularity sensitively and accurately, and is able to evaluate small hypervascular HCCs even when B-mode US cannot adequately characterize the tumors. Therefore, dynamic contrast-enhanced US can facilitate RFA electrode placement in hypervascular HCC, which is poorly depicted by B-mode US. The use of dynamic contrast-enhanced US guidance in ablation therapy for liver cancer is an efficient approach. Here, we present an overview of the current status of dynamic contrast-enhanced US-guided ablation therapy, and summarize the current indications and outcomes of reported clinical use in comparison with that of other modalities.

  2. Progress and Prospects of Long Noncoding RNAs (lncRNAs) in Hepatocellular Carcinoma.

    Science.gov (United States)

    Li, Chen; Chen, Jing; Zhang, Kai; Feng, Bing; Wang, Rui; Chen, Longbang

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional "noise" to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC. PMID:25968300

  3. Identification of tumor-initiating cells in a canine hepatocellular carcinoma cell line.

    Science.gov (United States)

    Michishita, Masaki; Ezaki, Shiori; Ogihara, Kikumi; Naya, Yuko; Azakami, Daigo; Nakagawa, Takayuki; Sasaki, Nobuo; Arai, Toshiro; Shida, Takuo; Takahashi, Kimimasa

    2014-04-01

    Tumor-initiating cells (TICs) or cancer stem cells (CSCs), a small subset of tumor cells, are involved in tumor initiation, progression, recurrence and metastasis. In human hepatocellular carcinoma (HCC), TICs are enriched with cell surface markers and have the ability to self-renew and differentiate tumors at a high frequency. We established a canine HCC cell line, HCC930599, and analyzed it for stem and progenitor cell marker expression using flow cytometry. HCC930599 showed high CD44 and CD29, moderate CD90, and low CD133, CD34, CD24, CD117, and CD13 expression. CD90(+)CD44(+) and CD90(-)CD44(+) cells were characterized using the in vitro sphere assay and an in vivo transplant model. CD90(+)CD44(+) cells acquired enhanced self-renewal capacity, proliferative activity and tumourigenicity compared with CD90(-)CD44(+) cells, suggesting that TICs exist in the HCC930599 cell line and that CD90 is a marker for enriched TICs. Understanding TIC characteristics may help elucidate hepatic carcinogenesis and HCC therapy development. PMID:24534130

  4. Hepatitis B and Hepatitis C Infection Biomarkers and TP53 Mutations in Hepatocellular Carcinomas from Colombia

    Directory of Open Access Journals (Sweden)

    Maria-Cristina Navas

    2011-01-01

    Full Text Available Hepatocellular Carcinoma (HCC is a leading cause of cancer-related death worldwide. Globally, the most important HCC risk factors are Hepatitis B Virus (HBV and/or Hepatitis C Virus (HCV, chronic alcoholism, and dietary exposure to aflatoxins. We have described the epidemiological pattern of 202 HCC samples obtained from Colombian patients. Additionally we investigated HBV/HCV infections and TP53 mutations in 49 of these HCC cases. HBV biomarkers were detected in 58.1% of the cases; HBV genotypes F and D were characterized in three of the samples. The HCV biomarker was detected in 37% of the samples while HBV/HCV coinfection was found in 19.2%. Among TP53 mutations, 10.5% occur at the common aflatoxin mutation hotspot, codon 249. No data regarding chronic alcoholism was available from the cases. In conclusion, in this first study of HCC and biomarkers in a Colombian population, the main HCC risk factor was HBV infection.

  5. Alpha-fetoprotein expression is a potential prognostic marker in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dénes G(o)r(o)g; János Reg(o)ly-Mérei; Sándor Paku; László Kopper; Péter Nagy

    2005-01-01

    AIM: To characterize the alpha-fetoprotein (AFP) positive and negative hepatocellular carcinoma (HCC) samples.METHODS: Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the following antigens: AFP, β-catenin, p53, CD44, MSH-2,MLH-1, and HNF-4. The tumors were divided into two groups based on the AFP expression. The immunophenotypic data and important clinical parameters were studied between the two groups.RESULTS: Twenty-one of the thirty-seven examined HCCs were AFP positive. Seven with nuclear p53 staining were AFP positive, while seven tumors with nuclear β-catenin staining were AFP negative. CD44 staining and high histological tumor grade were more frequent among the AFP-positive HCCs. The other immunophenotypical and dinical parameters did not show statistically significant difference in their distribution between the AFP positive and negative samples.CONCLUSION: AFP expression in HCC correlates with unfavorable prognostic factors, while nuclear β-catenin positivity is more common among the AFP-negative liver tumors. This observation supports the microarray data onin vivo human tumors.

  6. Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

    Science.gov (United States)

    Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

    2016-07-21

    Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

  7. Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Caecilia HC Sukowati, Natalia Rosso, Lory S Crocè, Claudio Tiribelli

    2010-03-01

    Full Text Available Hepatocellular carcinoma (HCC is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.

  8. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway.

    Science.gov (United States)

    Cardin, Romilda; Piciocchi, Marika; Bortolami, Marina; Kotsafti, Andromachi; Barzon, Luisa; Lavezzo, Enrico; Sinigaglia, Alessandro; Rodriguez-Castro, Kryssia Isabel; Rugge, Massimo; Farinati, Fabio

    2014-03-28

    The histo-pathologic and molecular mechanisms leading to initiation and progression of hepatocellular carcinoma (HCC) are still ill-defined; however, there is increasing evidence that the gradual accumulation of mutations, genetic and epigenetic changes which occur in preneoplastic hepatocytes results in the development of dysplastic foci, nodules, and finally, overt HCC. As well as many other neoplasias, liver cancer is considered an "inflammatory cancer", arising from a context of inflammation, and characterized by inflammation-related mechanisms that favor tumor cell survival, proliferation, and invasion. Molecular mechanisms that link inflammation and neoplasia have been widely investigated, and it has been well established that inflammatory cells recruited at these sites with ongoing inflammatory activity release chemokines that enhance the production of reactive oxygen species. The latter, in turn, probably have a major pathogenic role in the continuum starting from hepatitis followed by chronic inflammation, and ultimately leading to cancer. The relationship amongst chronic liver injury, free radical production, and development of HCC is explored in the present review, particularly in the light of the complex network that involves oxidative DNA damage, cytokine synthesis, telomere dysfunction, and microRNA regulation. PMID:24696595

  9. Sorafenib Combined With Transarterial Chemoembolization in Treating HBV-infected Patients With Intermediate Hepatocellular Carcinoma

    Science.gov (United States)

    2012-04-24

    PHENYTOIN/SORAFENIB [VA Drug Interaction]; Liver Neoplasms; Carcinoma, Hepatocellular; Digestive System Neoplasms; Neoplasms by Site; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; DOXORUBICIN/TRASTUZUMAB [VA Drug Interaction]; HBV

  10. Expression and survival prediction of microRNA-155 in hepatocellular carcinoma after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    韩中博

    2013-01-01

    Objective To explore the expression of microRNA-155in hepatocellular carcinoma(HCC)and its contribution to recurrence and prognosis of HCC after liver transplantation(LT).Methods The expression levels

  11. Expression and survival prediction of microRNA-155 in hepatocellular carcinoma after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    韩中博

    2013-01-01

    Objective To explore the expression of microRNA-155in hepatocellular carcinoma(HCC)and its contribution to recurrence and prognosis of HCC after liver transplantation(LT).Methods The expression levels of

  12. Polysaccharide from Lentinus edodes combined with oxaliplatin possesses the synergy and attenuation effect in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yu; Li, Qiang; Wang, Junfeng; Cheng, Fang; Huang, Xiao; Cheng, Yao; Wang, Kaiping

    2016-07-28

    Despite the great progress in the treatment of hepatocellular carcinoma, combination chemotherapy is still the main choice of treatment for patients with unresectable metastatic or recurrent hepatocellular cancer. Lentinan, which has been used as an immunomodulator in the treatment of cancer, possesses anti-tumor activities. However, the mechanisms by which Lentinan inhibits hepatocellular carcinoma remain unknown. Our study showed that Lentinan has a significantly synergistic anti-tumor effect with oxaliplatin against HepG2 cells in vitro and in H22 tumor-bearing mice through the mitochondria pathway and for the inhibition of NF-κB, Stat3 and survivin signaling. Moreover, Lentinan moderated side effects induced by oxaliplatin. These findings suggested that Lentinan may be an ideal agent for the combination therapy of oxaliplatin against hepatocellular carcinoma. PMID:27130669

  13. Diagnostic value for extrahepatic metastases of hepatocellular carcinoma in positron emission tomography/computed tomography scan

    OpenAIRE

    2012-01-01

    AIM: To evaluated the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan in diagnosis of hepatocellular carcinoma (HCC) and extrahepatic metastases.

  14. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    OpenAIRE

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    The safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced hepatocellular carcinoma were assessed. Bevacizumab was active and well tolerated. The clinical value of circulating endothelial cells and interleukin-6 and -8 warrants further investigation.

  15. Effects of Ginkgo biloba extract on cell proliferation and cytotoxicity in human hepatocellular carcinoma cells

    OpenAIRE

    Chao, Jane CJ; Chu, Chia Chou

    2004-01-01

    AIM: To study the effect of Ginkgo biloba extract (EGb 761) containing 22%-27% flavonoids (ginkgo-flavone glycosides) and 5%-7% terpenoids (ginkgolides and bilobalides) on cell proliferation and cytotoxicity in human hepatocellular carcinoma (HCC) cells.

  16. Growth arrest and apoptosis of human hepatocellular carcinoma cells induced by hexamethylene bisacetamide

    OpenAIRE

    Ouyang, Gao-Liang; Cai, Qiu-Feng; Min LIU; Chen, Rui-Chuan; Huang, Zhi; Jiang, Rui-Sheng; Chen, Fu; Hong, Shui-Gen; Bao, Shi-Deng

    2004-01-01

    AIM: To investigate the cellular effects of hybrid polar compound hexamethylene bisacetamide (HMBA) on the growth and apoptosis of human hepatocellular carcinoma cells and to provide the molecular mechanism for potential application of HMBA in the treatment of liver cancer.

  17. Imaging of hepatocellular carcinoma recurrence post liver resection: a pictorial essay

    International Nuclear Information System (INIS)

    This pictorial essay presents and discusses the imaging findings of patients with hepatocellular carcinoma recurrence post liver resection. A broad range of recurrence patterns is reviewed including intrahepatic and extrahepatic recurrences.

  18. Multidetector CT in evaluating blood supply of hepatocellular carcinoma after transcatheter arterial chemoembolization

    OpenAIRE

    Guan, Yong-Song; Zheng, Xiao-Hua; Zhou, Xiang-Ping; Huang, Juan; Sun, Long; Chen, Xian; Li, Xiao; He, Qing

    2004-01-01

    AIM: To assess the value of multidetector-row computed tomography (MDCT) in choosing retreatment methods of hepatocellular carcinoma (HCC) through evaluating the blood supply of low-density area of HCC after transcatheter arterial chemoembolization (TACE).

  19. Screening and analysis of hepatocellular carcinomaassociated antigens and their encoding genes

    Institute of Scientific and Technical Information of China (English)

    SHI Yongyu; WANG Hongcheng; LI Yan; PANG Xuewen; SUN Wensheng; CHEN Weifeng

    2003-01-01

    Identification of hepatocellular carcinoma- associated tumor antigens is necessary and pivotal for specific immunotherapy in hepatocellular carcinoma (HCC) patients. In the present study, HCC cDNAs are constructed into ZAP cDNA expression library and screened by sera of patients with HCC. The positive clones are DNA sequenced and analyzed by bioinformatics. Thirty-one genes of hepatocellular carcinoma-associated tumor antigens are identified, of which 1 is unknown and 30 are known. The proteins encoded by these known genes can be classified into 8 categories: constitutive molecules of hepatocytes, RNA transcription and splicing-associated molecules, protein metabolism-associated molecules, energy synthesis-associated molecules, signal transduction molecules, cell adhesion molecules, immunosuppressive molecules, and proteins with unknown function. Among these genes, CAGE is a cancer-testis (CT) antigen. It is concluded that identification of hepatocellular carcinoma-associated tumor antigens provides potential targets for immunotherapy of HCC patients and facilitates explanation of carcinogenesis of HCC.

  20. Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advancedstage hepatocellular carcinoma.METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B,n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups.RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT):533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine:66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01)and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L,P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroidmaintenance group.CONCLUSION: Early steroid withdrawal was safe after liver transprantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an

  1. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    International Nuclear Information System (INIS)

    Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Median survival was 11.5 months (95% CI 7.9–15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition to response to thymostimulin

  2. Lactosylated liposomes for targeted delivery of doxorubicin to hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zhou X

    2012-10-01

    Full Text Available Xiaoju Zhou,1,2,* Mengzi Zhang,2,* Bryant Yung,2 Hong Li,2 Chenguang Zhou,2 L James Lee,3,4 Robert J Lee2,41State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan, People’s Republic of China; 2Division of Pharmaceutics, 3Department of Chemical and Biomolecular Engineering, 4NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA*These authors contributed equally to this workBackground: N-lactosyl-dioleoylphosphatidylethanolamine (Lac-DOPE was synthesized and evaluated as a liver-specific targeting ligand via asialoglycoprotein receptors for liposomal delivery of doxorubicin.Methods: Lactosylated liposomes encapsulating calcein (Lac-L-calcein or doxorubicin (Lac-L-DOX composed of egg phosphatidylcholine, cholesterol, monomethoxy polyethylene glycol 2000-distearoyl phosphatidylethanolamine, and Lac-DOPE at 50:35:5:10 (mol/mol were prepared by polycarbonate membrane extrusion and evaluated in human hepatocellular carcinoma HepG2 cells. Cellular uptake of Lac-L-calcein was monitored by confocal microscopy and by flow cytometry. The cytotoxicity of Lac-L-DOX was evaluated by MTT assay. The pharmacokinetic properties of Lac-L-DOX were studied in normal mice, and its biodistribution and antitumor activity were studied in nude mice with HepG2 xenografts.Results: The size of Lac-L-DOX was less than 100 nm and the liposomes demonstrated excellent colloidal stability. In vitro uptake of Lac-L-calcein by HepG2 cells was four times greater than that of non-targeted L-calcein. In the presence of 20 mM lactose, the uptake of Lac-L-calcein was inhibited, suggesting that asialoglycoprotein receptors mediated the observed cellular uptake. Lac-L-DOX exhibited enhanced in vivo cytotoxicity compared with the nontargeted liposomal doxorubicin (L

  3. A case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma

    OpenAIRE

    Tsuji, Kunihiro; Takemura, Kenichi; Minami, Keisuke; Teramoto, Ryota; Nakashima, Keisuke; Yamada, Shinya; Doyama, Hisashi; Oiwake, Hisanori; Hasatani, Kenkou

    2013-01-01

    We report on a case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. A 70-year-old man was admitted to our hospital with fatigue, myalgia and an elevated creatine phosphokinase level. He was diagnosed as rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. After discontinuation of sorafenib, his fatigue and myalgia resolved and his creatine phosphokinase level returned to normal. Rhabdomyolysis related to sorafenib treatme...

  4. EFFECT OF DARUHARIDRA AND PUNARNAVA IN HEPATOCELLULAR JAUNDICE: A CLINICAL STUDY

    OpenAIRE

    Ram Bhuwal; Pandey Hari Shankar; Dwivedi Kamal Nayan

    2011-01-01

    A clinical study was done on twenty patients of hepatocellular Jaundice. Ghanasatva (water soluble solid) of Daruharidra (Berberis aristata DC.)(Root and Stem) and leave juice of Punarnava (Boerhavia diffusa Linn.) was given to patients after their enrollment in study. Signs and symptoms of hepatocellular jaundice as yellow colour of eyes, nails, urine and loss of appetite, weakness, nausea, vomiting, fever, epigastric discomfort as well as biochemical assessment was done as GBP, S. bilirubin...

  5. Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas

    OpenAIRE

    Shin, Jin Ho; Kim, Chong Jai; Jeon, Eun Jeong; Sung, Chang Ohk; Shin, Hwa Jeong; Choi, Jene; Yu, Eunsil

    2015-01-01

    Background: C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined...

  6. Hepatocellular carcinoma and the penetrance of HFE C282Y mutations: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Lonsdale Ray

    2005-06-01

    Full Text Available Abstract Background Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFE C282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma is uncertain. We have carried out a cross-sectional study to determine the proportion of diagnosed hepatocellular carcinoma patients who are homozygous for the HFE C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia. Methods Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for HFE C282Y mutations; the data produced were compared with the frequency of HFE mutations in a large sample of the local population. Data were also retrieved from the East Anglian Cancer Intelligence Unit to determine the annual incidence of hepatocellular carcinoma; and from appropriate life tables. Results Eight out of 144 of the cases were homozygous for the HFE C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male HFE C282Y homozygotes were more likely to be diagnosed with hepatocellular carcinoma (odds ratio [OR] = 14, 95% confidence interval [CI] = 5–37. For this population, we estimate that the penetrance of the HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females. Conclusion In this population, we found that only a very small proportion of homozygotes for the HFE C282Y mutation developed hepatocellular carcinoma. However, individuals with this genotype have a significantly increased risk of this rare disease relative to those who do not carry the mutations.

  7. Study of hepatocellular function in the murine model following hepatic artery selective clamping

    OpenAIRE

    Tralhão, JG; Abrantes, AM; Gonçalves, AC; Hoti, E.; Laranjo, M; Martins, R.; Oliveiros, B.; Cardoso, D; Sarmento-Ribeiro, AB; Botelho, MF; Castro e Sousa, F

    2013-01-01

    PURPOSE: To investigate the impact of selective hepatic artery clamping (SHAC) in hepatocellular function. METHODS: Three groups of Wistar male rats were subjected to SHAC ischemia period of 60min: Group A continuous SHAC were subjected to SHAC ischemia period of 60min, Group B intermittent SHAC of 30min with 5min of reperfusion and Group C intermittent SHAC of 15min with 5min of reperfusion. Animals without SHAC were included-Group D. To evaluate hepatocellular function blood marker...

  8. Lung metastasis of fatty hepatocellular carcinoma after liver transplant: a case report.

    Science.gov (United States)

    Tepeoğlu, Merih; Özdemir, B Handan; Ok Atılgan, Alev; Akdur, Aydıncan; Haberal, Mehmet

    2014-03-01

    Hepatocellular carcinoma with prominent fatty change is rare, and to date only a few cases have been reported. In this article, we present a 57-yearold woman who underwent a liver transplant for hepatocellular carcinoma. Ten months after liver transplant, she presented with a persistent cough. Computed tomography of the chest was performed, revealing a solid lung mass that measured 1 × 0.9 cm in the right inferior lobe. Right inferior lobectomy was performed, and the final diagnosis was noted as hepatocellular carcinoma with prominent fatty change. Fatty change was extensive in the tumor; therefore, lipoid pneumonia was the first condition that was considered in the differential diagnosis during examination of the lobectomy material. For the differential diagnosis, the immunohistochemistry panel was studied to show the hepatocellular nature of the tumor. Although metastasis of hepatocellular carcinoma to the lungs is expected, hepatocellular carcinoma with prominent fatty change can cause diagnostic difficulties, such as lipoid pneumonia, especially in small lung biopsies. PMID:24635803

  9. A case of primary clear cell hepatocellular carcinoma in a non-cirrhotic liver: an immunohistochemical and ultrastructural study

    OpenAIRE

    Erica Fan Clayton; Emma Elizabeth Furth; Amy Ziober; Theodore Xu; Yuan Yao; Pil Gyu Hwang; Zhanyong Bing

    2012-01-01

    The clear cell variant of hepatocellular carcinoma is a rare entity, occurring at a frequency of less than 10% of hepatocellular carcinoma, with a female prevalence and usually associated with hepatitis C and cirrhosis. We reported a case of primary clear cell hepatocellular carcinoma occurring in a non-cirrhotic liver without history of hepatitis. Our examination included gross pathology, histopathology, immunohistochemistry, special stains, and electron microscopy evaluation. The tumor was ...

  10. Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma

    OpenAIRE

    Sabokrouh, Abdolreza; Vaisi-raygani, Asad; Goodarzi, Mohammad Taghi; Shohreh KHATAMI*; Taghizadeh-jahed, Massoud; Shahabadi, Nahid; Lakpour, Niknam; Shakiba, Yadollah

    2015-01-01

    Background: High expression of telomerase and Bcl-2 are reported in hepatocellular carcinoma. Some anticancer drugs show their effects through reduction of these factors. In this study, it was aimed to investigate the effects of a new synthetic compound, platinum azidothymidine, on inhibition of telomerase and Bcl-2 expression in hepatocellular carcinoma compared to azidothymidine. Methods: To study the effects of Pt-AZT on hepatocellular carcinoma and compare its effects with AZT in inhibiti...

  11. Contemporary Strategies in the Management of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Shirin Elizabeth Khorsandi

    2012-01-01

    Full Text Available Liver transplantation is the treatment of choice for selected patients with hepatocellular carcinoma (HCC on a background of chronic liver disease. Liver resection or locoregional ablative therapies may be indicated for patients with preserved synthetic function without significant portal hypertension. Milan criteria were introduced to select suitable patients for liver transplant with low risk of tumor recurrence and 5-year survival in excess of 70%. Currently the incidence of HCC is climbing rapidly and in a current climate of organ shortage has led to the re-evaluation of locoregional therapies and resectional surgery to manage the case load. The introduction of biological therapies has had a new dimension to care, adding to the complexities of multidisciplinary team working in the management of HCC. The aim of this paper is to give a brief overview of present day management strategies and decision making.

  12. Systemic therapy for hepatocellular carcinoma (HCC): from bench to bedside

    International Nuclear Information System (INIS)

    Primary liver cancer is the fifth most common cancer worldwide and the third most common cause of cancer mortality. For patients with early resectable disease, surgical resection or transplantation is considered a potentially curative modality for hepatocellular carcinoma (HCC); on the other hand, for patients with unresectable or metastatic disease, treatment is essentially palliative and prior to the approval of sorafenib, there was no globally approved systemic treatment for patients presenting with unresectable or metastatic HCC. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit in a large phase III trial. Thus, novel systemic approaches represent a high unmet medical need in advanced HCC. In this review article, we will try to take a journey through the history of systemic therapeutic options for HCC passing through the current standard options and exploring the potential new systemic options for this disease.

  13. Surgical treatment of hepatocellular carcinoma with severe intratumoral arterioportal shunt

    Directory of Open Access Journals (Sweden)

    Hiromichi Ishii, Teruhisa Sonoyama, Shingo Nakashima, Hiroyuki Nagata, Atsushi Shiozaki, Yoshiaki Kuriu, Hisashi Ikoma, Masayoshi Nakanishi, Daisuke Ichikawa, Hitoshi Fujiwara, Kazuma Okamoto, Toshiya Ochiai, Yukihito Kokuba, Chohei Sakakura, Eigo Otsuji

    2010-07-01

    Full Text Available We report a case of hepatocellular carcinoma (HCC that caused a severe arterioportal shunt (APS. A 49-year-old man was admitted to hospital due to esophagogastric variceal hemorrhage and HCC, and underwent endoscopic variceal ligation (EVL and endoscopic injection sclerotherapy (EIS. He was then referred to our hospital. Abdominal computed tomography revealed a low-density lesion in the posterior segment of the liver and an intratumoral APS, which caused portal hypertension. Although the patient underwent EVL, EIS, Hassab’s operation, and transcatheter arterial embolization for APS, he vomited blood due to rupture of esophagogastric varices. Right hepatectomy was performed for the treatment of HCC and APS, although the indocyanine green retention value at 15 min after intravenous injection was poor (30%. The patient’s postoperative course was uneventful. Eventually, APS disappeared and the esophagogastric varices improved.

  14. Proteomics for the early diagnosis and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Autor OJS

    2007-02-01

    Full Text Available

    The incidence of primary cancer has been increasing globally and now-a-days it constitutes the 5th most frequent cancer of humans representing around 5% of all cancers worldwide. Chronic HBV infection assumes greater significance because of its reported association with cirrhosis, and more ominously hepatocellular carcinoma or HCC. Hepatitis B infection constitutes a major global problem with nearly 400 million infected individuals. It contributes to a significant degree of morbidity on account of the associated chronicity that develops in 5-10% of infected adults and more than 90% of infected neonates. Globally, around one million people suffering from HBVrelated chronic heptatitis and HCC die per year. Despite the availability of an effective prophylactic vaccine against hepatitis B for over 20 years, effective treatment of the chronic disease and associated HCC remains elusive. Therefore, identification of the cellular mediators and effectors of HCC is an important medical objective for developing new diagnostic tools and therapeutic strategies against it. Molecular biomarkers hold great promise for refining our ability to establish early diagnosis and prognosis for HCC, and to predict response to therapy. Proteomics is a rapidly expanding discipline that is expected to change the way in which disease can be diagnosed, treated and monitored in the near future. The proteomic analysis of serum and tumors should allow accurate prediction of what is happening at the protein level in a cancer cell or a body fluid proteome. It is the hope that, by deciphering the alterations in serum and liver proteome, biomarkers and patterns of biomarkers will be found that should be helpful in improving early detection, diagnosis and treatment monitoring of HCC. In the last few years, HCC has been extensively investigated using different proteomic approaches on HCC cell lines

  15. Radioembolization for hepatocellular carcinoma using TheraSphere®

    Directory of Open Access Journals (Sweden)

    Safiyya Mohamed Ali

    2011-01-01

    Full Text Available Background/Aim: Hepatocellular carcinoma (HCC is the most common primary malignancy of the liver. Radioembolization with yttrium-90 (Y90 microspheres is a new concept in radiation therapy for HCC. This review focuses on the indications, efficacy, side effects, and future direction of Y90 therapy, using TheraSphere® , in HCC patients. Results: Comprehensive literature reviews have described the clinical and scientific evidence of Y90 therapy. The Radioembolization Brachytherapy Oncology Consortium has concluded that there is sufficient evidence to support the safe and effective use of this locoregional therapy in HCC patients, including those with portal vein thrombosis. Conclusions: There are currently no randomized clinical trials done on TheraSphere® and none of the studies so far have shown a survival benefit. Thus, although it represents a very promising therapy with excellent initial results, it cannot be fully recommended yet, till well-designed, large, randomized clinical studies are conducted showing survival benefits.

  16. Regression of hepatocellular carcinoma during vitamin K administration

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Nouso; Nobuaki Okano; Masahiro Nakagawa; Motowo Mizuno; Yasuyuki Araki; Yasushi Shiratori; Shuji Uematsu; Kunihiro Shiraga; Ryoichi Okamoto; Ryo Harada; Shoko Takayama; Wakako Kawai; Shigeru Kimura; Toru Ueki

    2005-01-01

    An 85-year-old man with HCV infection and diabetes mellitus was diagnosed as having hepatocellular carcinoma (HCC, 13 cm in diameter) based on high serum alpha-fetoprotein (AFP),AFP-L3,and des-γ-carboxy prothrombin levels as well as typical enhancement pattern on contrast-enhanced CT. The patient did not receive any interventional treatments because of advanced age and the advanced stage of HCC.He chose to take vitamin K,which was reported to suppress the growth of HCC in vitro. Three months after starting vitamin K, all three tumor markers were normalized and HCC was markedly regressed, showing no enhancement in the early arterial phase on CT. Here we present the report describing the regression of HCC during the administration of vitamin K.

  17. Hepatocellular carcinoma: transcriptome diversity regulated by RNA editing.

    Science.gov (United States)

    Li, Yan; Chen, Leilei; Chan, Tim Hon Man; Guan, Xin-Yuan

    2013-08-01

    Hepatocellular carcinoma (HCC) can be envisioned as a prolonged multi-stage process accumulating genetic and epigenetic changes. In the past years, DNA alterations lent us important clues to the comprehension of molecular pathways involved in HCC. However, as an increasing number of RNAs were identified to be subject to A-to-I modifications, it has become apparent that RNA editing might be the causal basis of various human diseases. Recent evidence has strengthened this notion by correlating hyper-edited AZIN1 (antizyme inhibitor 1) protein with HCC onset and the mechanisms that regulate cell transformation. As we continue to demystify it, RNA editing astonishes us with its diverse substrates, esoteric functions, elaborate machinery and complex interaction with HBV/HCV viral infection. In this review, we examine the contribution of A-to-I RNA editing to caner onset/progression and explore its potential implications for cancer treatment advances. PMID:23748106

  18. Clear cell hepatocellular carcinoma: Back to the basics for diagnosis

    Directory of Open Access Journals (Sweden)

    Puja Sakhuja

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a common cancer world-wide with a higher incidence in Asia. Clear cell variant of HCC (CCHCC has a frequency ranging from 0.4% to 37%. The presence of 90-100% clear cells is rare. In the present case, a 35-year-old female patient presented with fever and a large abdominal mass in the right hypochondrium. Histology of the tumor revealed >95% clear cells and after taking multiple sections from different areas of tumor only few scattered cells with eosinophilic cytoplasm were found. Immunohistochemistry with Hep Par 1, Glypican 3 and polyclonal carcinoembryonic antigen were negative as were all other markers for metastatic clear cell tumors. Histological diagnosis was based on routine H and E sections showing a histological pattern of architecture with thickened trabeculae. We describe a rare case of CCHCC with >95% clear cells and no immunoreactivity in tumor cells in a non-cirrhotic liver.

  19. Radiotherapy for multiple brain metastases from hepatocellular carcinomas

    Institute of Scientific and Technical Information of China (English)

    Nobuyuki Toshikuni; Kazuhiko Morii; Michinori Yamamoto

    2007-01-01

    A 78-year-old man with liver cirrhosis was found to have multiple hepatocellular carcinomas (HCCs)and underwent 3 sessions of transcatheter arterial chemoembolization. Fourteen months after diagnosis,the patient presented with left hemiparesis. Contrastenhanced magnetic resonance imaging showed multiple metastases with ring-shaped enhancement in the cerebrum and cerebellum. There were no metastases to other organs. The metastatic lesions almost completely disappeared after whole-brain radiotherapy with a total dose of 50 Gy. Neurologic symptoms decreased,and the patient's quality of life improved. The patient underwent 2 more sessions of transcatheter arterial chemoembolization. Twelve months after the diagnosis of brain metastasis, the patient remains alive. The present case indicates that radiotherapy can improve quality of life and prolong survival in some patients with brain metastases from HCCs.

  20. Diagnostic value of alpha-fetoprotein for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma (HCC) variously occupies the fifth or sixth position as the most frequent neoplasia worldwide. The present work used alphafetoprotein (AFP) determinations on the ultra-micro analytical system (SUMA) as a tumoral marker in 189 cirrhotic patients evaluated at the Center for Medical and Surgical Research between January 1999 and September 2005. The principal factors associated to increases in AFP were HCC and viral cirrhosis. In all, 22 patients (11.64%) suffered from HCC, with viral cirrhosis caused mainly by hepatitis C virus infections as the most important etiological factor. AFP as a tumoral marker displayed a sensitivity of 68.18% and a specificity of 92.17%, which increased to 86.36 and 100% respectively when combined with abdominal sonography. It is concluded that AFP is valuable for the diagnosis of HCC

  1. Recent advances in the prevention of hepatocellular carcinoma recurrence.

    Science.gov (United States)

    Lu, Li-Chun; Cheng, Ann-Lii; Poon, Ronnie T P

    2014-11-01

    Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Early-stage HCC can be curatively treated, but the recurrence rate remains high. To date, adjuvant treatments have not proven effective in preventing HCC recurrence after curative treatment. Although early studies explored the potential of vitamin K2, retinoid, chemotherapy, and recently, sorafenib, none of the studies reported successful outcomes. Several new lines of evidence have emerged to support the use of novel antiviral agents for preventing the recurrence of virus-related HCC after curative treatment. In this review, the authors provide a thorough overview of the various adjuvant treatments that have been attempted or are being considered for trial. PMID:25369304

  2. Relationship between microvessel density and telomerase activity in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Piao; Min He; Yang Shi; Tong-Yu Tang

    2004-01-01

    AIM: To study the relationship between microvessel density (MVD), telomerase activity and biological characteristics in hepatocellular carcinoma (HCC).METHODS: S-P immunohistochemical method and telomeric repeat amplification protocol (TRAP) were respectively used to analyze the MVD and telomerase activity in 58 HCC and adjacent normal tissues.RESULTS: The MVD in HCC with metastasis, lower differentiation or without intact capsule was significantly higher than that in HCC with intact capsule, higher differentiation, or without metastasis. While MVD had no relationship with tumor size, hepatic virus infection and other clinical factors. Telomerase activity was related to differentiation degree, but not to tumor size or histological grade. MVD in HCC with telomerase activity was higher than that in HCC without telomerase activity.CONCLUSION: MVD and telomerase activity may serve as diagnostic criteria of HCC in earlier stage. Meanwhile,there may be a cooperative effect between MVD and telomerase on the growth and metastasis of HCC.

  3. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

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    Chen-Yi Liao

    2015-01-01

    Full Text Available We would like to highlight the application of natural products to hepatocellular carcinoma (HCC. We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

  4. Malignant fibrous histiocytoma presenting as hemoperitoneum mimicking hepatocellular carcinoma rupture

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Malignant fibrous histiocytoma (MFH) is a pleomorphic mesenchynal sarcoma. It is uncommonly arises primarily from the intra-peritoneal cavity. Primary peritoneal MFH with tumor bleeding and rupture is rare. We describe the imaging features of a 70-year-old patient presenting with ruptured hemorrhagic peritoneal MFH at subhepatic area, accompanied by massive hemoperitoneum,mimicking a ruptured pedunculated hepatocellular carcinoma. Computed tomography (CT) revealed a large heterogeneous enhanced subhepatic mass with adjacent liver, gallbladder and colon invasion. Tumor hemorrhage and rupture complicated with peritoneal seeding and massive bloody ascites were also detected.Angiography showed a hypervascular tumor fed by enlarged right hepatic arteries, cystic artery and omental branches of gastroepiploic artery. The patient underwent laparotomy for tumor resection, but the tumor recurred one month after operation. To our knowledge, the CT appearance of ruptured intraperitoneal MFH complicated by hemoperitoneum has not been previously described.

  5. Usefulness of intraoperative sonography in the management of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Intraoperative sonography was performed on 74 tumor nodules in 61 patients with hepatocellular carcinoma to evaluate the detectability of the tumors as compared with conventional sonography. CT, angiography and Lipiodol-CT. Detection rates of tumor nodules were 84% on sonography, 90% on CT scans, 89% on angiography, 100% on Lipiodol-CT and intraoperative sonography. In operating field, tumors were invisible in 27 of 74 cases (36%) and nonpalpable in 20 of 74 cases (27%). In 30 tumors less than 2 cm in diameter, invisible tumors were 56% and nonpalpable tumors were 53% Our results suggest that intraoperative sonography is the final diagnostic imaging procedure before surgery and in cases of invisible and nonpalpable tumors in operating field, this procedure is mandatory to improve surgical results

  6. Hormonal control of the metabolic machinery of hepatocellular carcinoma

    Science.gov (United States)

    Wong, Carmen Chak-Lui; Wong, Chun-Ming

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide. It is an aggressive cancer with low cure rate, frequent metastasis, and highly resistant to conventional chemotherapies. Better knowledge regarding the molecular and metabolic alterations in HCC will be instrumental to the development of novel therapeutic interventions against HCC. In the August 2015 issue of Hepatology, Nie et al. reports an important molecular pathway that contributes to the Warburg Effect in HCC. They have beautifully demonstrated that the loss of a component of a hormonal system, the mineralocorticoid receptor (MR), reprogrammed the metabolic machinery of HCC cells to aerobic glycolysis through the miR-338-3p-PKL/R axis. The implication could be that in addition to drugs that directly target the metabolic enzymes in cancer cells, more translational efforts could be focused on the development of drugs that involve the activation of the MR-aldosterone system or other hormonal systems to target the Warburg effect.

  7. Development of MicroRNA Therapeutics for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Rajagopal N. Aravalli

    2013-03-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common form of liver cancer and is the third leading cause of cancer-related deaths worldwide. Treatment options for HCC are very limited, as it is often diagnosed at a late stage. Recent studies have demonstrated that microRNAs (miRNAs, a class of non-coding RNAs, are aberrantly expressed in HCC. Some of these were shown to be functionally involved in carcinogenesis and tumor progression, suggesting that miRNAs can serve as novel molecular targets for HCC therapy. Several promising studies have recently demonstrated the therapeutic potential of miRNAs in animal models and in reducing the viral load in hepatitis C patients. In this review, these advances and strategies for modulating miRNAs for in vivo therapeutic delivery and replacement therapy are discussed.

  8. SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma.

    Science.gov (United States)

    Navarro-Imaz, Hiart; Rueda, Yuri; Fresnedo, Olatz

    2016-09-01

    SND1 is a multifunctional protein participating, among others, in gene transcription and mRNA metabolism. SND1 is overexpressed in cancer cells and promotes viability and tumourigenicity of hepatocellular carcinoma cells. This study shows that cholesterol synthesis is increased in SND1-overexpressing hepatoma cells. Neither newly synthesised nor extracellularly supplied cholesterol are able to suppress this increase; however, inhibition of cholesterol esterification reverted the activated state of sterol-regulatory element-binding protein 2 (SREBP2) and cholesterogenesis. These results highlight SND1 as a potential regulator of cellular cholesterol distribution and homeostasis in hepatoma cells, and support the rationale for the therapeutic use of molecules that influence cholesterol management when SND1 is overexpressed. PMID:27238764

  9. Y-90 microshperes in the treatment of unresectable hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Al-Kalbani Abdullah

    2008-01-01

    Full Text Available A small percentage of patients with hepatocellular carcinoma (HCC are candidates for curative treatment in form of resection or transplantation. There are different treatment options for unresectable HCC-like local ablative therapies and recently systemic therapy with Sorafenib. All of these have variable response rate and had been proven to improve survival. In the last few years, there is a growing interest in TheraSphere radioembolization. It consists of yttrium90 (Y-90 embedded into nonbiodegradable glass microspheres. It is selectively administered by intraarterial hepatic injection giving high doses of radiation to the tumor and sparing the liver parenchyma. It has been shown to improve survival and used as a bridge to transplantation and to downstage tumors for resection. Therasphere seems to have favorable safety profile and has been used in patients with portal vein thrombosis with successful outcome.

  10. Herbal Medicine and Hepatocellular Carcinoma: Applications and Challenges

    Directory of Open Access Journals (Sweden)

    Yan Li

    2011-01-01

    Full Text Available Use of herbal medicine in the treatment of liver cancer has a long tradition. The compounds derived from the herb and herbal composites are of considerable interest among oncologists. In the past, certain herbal compounds and herbal composite formulas have been studied through in vitro and in vivo as an anti-hepatocellular carcinoma (HCC agent, enhancing our knowledge about their biologic functions and targets. However there is a significant distinction between the herbal medicine and the herbal production even though both are the plant-based remedies used in the practice. In this article, for the sake of clarity, the effective herbal compounds and herbal composite formulas against HCC are discussed, with emphasizing the basic conceptions of herbal medicine in order to have a better understanding of the prevention and treatment of HCC by herbal active compounds and herbal composite formulas.

  11. Hepatocellular carcinoma in elderly patients: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Brunot A

    2016-06-01

    Full Text Available Angélique Brunot, Samuel Le Sourd, Marc Pracht, Julien Edeline Department of Medical Oncology, Centre Eugene Marquis, Rennes, FranceAbstract: Hepatocellular carcinoma (HCC is the second most common cause of death by cancer in the world. Due to the delayed HCC development in hepatitis C carriers and nonalcoholic fatty liver disease, the incidence of HCC in the elderly is increasing and is becoming a global health issue. Elderly patients with HCC should be assessed through proper oncologic approach, namely, screening tools for frailty (Geriatric-8 or Vulnerable Elders Survey-13 and comprehensive geriatric assessment. This review of the literature supports the same treatment options for elderly patients as for younger patients, in elderly patients selected as fit following proper oncogeriatric assessment. Unfit patients should be managed through a multidisciplinary team involving both oncological and geriatrician professionals. Specific studies and recommendations for HCC in the elderly should be encouraged.Keywords: liver cancer, treatment, surgery, geriatric evaluation, sorafenib

  12. Hepatocellular Carcinoma Radiation Therapy: Review of Evidence and Future Opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Klein, Jonathan [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada); Dawson, Laura A., E-mail: laura.dawson@rmp.uhn.on.ca [Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario (Canada)

    2013-09-01

    Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Curative therapy is not an option for most patients, often because of underlying liver disease. Experience in radiation therapy (RT) for HCC is rapidly increasing. Conformal RT can deliver tumoricidal doses to focal HCC with low rates of toxicity and sustained local control in HCC unsuitable for other locoregional treatments. Stereotactic body RT and particle therapy have been used with long-term control in early HCC or as a bridge to liver transplant. RT has also been effective in treating HCC with portal venous thrombosis. Patients with impaired liver function and extensive disease are at increased risk of toxicity and recurrence. More research on how to combine RT with other standard and novel therapies is warranted. Randomized trials are also needed before RT will be generally accepted as a treatment option for HCC. This review discusses the current state of the literature and opportunities for future research.

  13. Chemoembolization for recurrent hepatocellular carcinoma after liver transplantation

    International Nuclear Information System (INIS)

    Objective: To evaluate the interventional chemoembolization in treating unresectable recurrent hepatocellular carcinoma (HCC) after liver transplantation. Methods: Twelve patients with unresectable recurrent HCC underwent one or more cycles (mean 2.25 cycles) of transarteria] chemoembolization (TACE) after liver transplantation. The results were evaluated by follow-up CT scans and were classified into four grades. The survival rate was calculated by using Kaplan-Meier survival curve. Results: No severe complications developed during follow-up period. Of the total twelve patients, targeted tumor showed a reduction in size by 30% in 7 (58.3%) after TACE. However, intrahepatic recurrence or extrahepatic metastasis occurred in 11 patients (91.3%). Conclusion: Our data obtained from this study indicates that TACE treatment seems to produce an effective tumor response for targeted recurrent HCC after liver transplantation. (authors)

  14. MRI Features of Hepatocellular Carcinoma Related to Biologic Behavior

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Eun-Suk [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720 (Korea, Republic of); Choi, Jin-Young [Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-11-01

    Imaging studies including magnetic resonance imaging (MRI) play a crucial role in the diagnosis and staging of hepatocellular carcinoma (HCC). Several recent studies reveal a large number of MRI features related to the prognosis of HCC. In this review, we discuss various MRI features of HCC and their implications for the diagnosis and prognosis as imaging biomarkers. As a whole, the favorable MRI findings of HCC are small size, encapsulation, intralesional fat, high apparent diffusion coefficient (ADC) value, and smooth margins or hyperintensity on the hepatobiliary phase of gadoxetic acid-enhanced MRI. Unfavorable findings include large size, multifocality, low ADC value, non-smooth margins or hypointensity on hepatobiliary phase images. MRI findings are potential imaging biomarkers in patients with HCC.

  15. [Telomere length and telomerase activity in hepatocellular carcinoma].

    Science.gov (United States)

    Nakashio, R; Kitamoto, M; Nakanishi, T; Takaishi, H; Takahashi, S; Kajiyama, G

    1998-05-01

    Telomerase activity and terminal restriction fragment (TRF) length were examined in hepatocellular carcinoma (HCC). Telomerase activity was assayed by telomeric repeat amplification protocol (TRAP) connected with an internal telomerase assay standard (ITAS). The incidence of strong telomerase activity (highly variable level compared with the activity of non-cancerous liver tissue) was 79% in well, 84% in moderately, and 100% in poorly differentiated HCC, while 0% in non-cancerous liver tissues. The incidence of TRF length alteration (reduction or elongation) was 53% in HCC. The incidence of TRF alteration was significantly higher in HCC exceeding 3 cm in diameter, moderately or poorly differentiated in histology. Telomerase activity was not associated with TRF length alteration in HCC. In conclusion, strong telomerase activity and TRF length alteration increased with HCC tumor progressions. PMID:9613130

  16. Telomerase activity and telomere length in human hepatocellular carcinoma.

    Science.gov (United States)

    Huang, G T; Lee, H S; Chen, C H; Chiou, L L; Lin, Y W; Lee, C Z; Chen, D S; Sheu, J C

    1998-11-01

    Telomerase activity is activated and telomere length altered in various types of cancers, including hepatocellular carcinoma (HCC). A total of 39 HCC tissues and the corresponding non-tumour livers were analysed and correlated with clinical parameters. Telomere length was determined by terminal restriction fragment assay, and telomerase activity was assayed by telomeric repeat amplification protocol. Telomerase activity was positive in 24 of the 39 tumour tissues (1.15-285.13 total product generated (TPG) units) and in six of the 39 non-tumour liver tissues (1.05-1.73 TPG units). In the 28 cases analysed for telomere length, telomere length was shortened in 11 cases, lengthened in six cases, and unaltered in 11 cases compared with non-tumour tissues. Neither telomere length nor telomerase activity was correlated to any clinical parameters. PMID:10023320

  17. Metastatic hepatocellular carcinoma of the external auditory canal

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC.He presented to our department with a three-month history of increasing left otalgia, and hearing loss with recent fresh aural bleeding. Histopathologic examination indicated that the tumor was secondary to HCC. Although external irradiation was not effective, the tumor was treated with surgical debulking and high dose rate 192 Ir remote afterloading system (RALS) for postoperative intracavitary irradiation. A review of the literature revealed only five other cases of HCC metastasis to the temporal bone, all of which mainly metastasteed in the internal acoustic meatus. The present case is the first report of HCC metastasis to the EAC.

  18. Remarkable Anticancer Activity of Teucrium polium on Hepatocellular Carcinogenic Rats

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    Ariyo Movahedi

    2014-01-01

    Full Text Available The term cancer has been concomitant with despair, agony, and dreadful death. Like many other diseases, herbal therapy has been used to prevent or suppress cancer. The present study investigated the capability of the decoction of Teucrium polium L. from Lamiaceae family to protect liver cells against hepatocellular carcinoma in carcinogenesis-induced animal model. After 28 weeks of treatment with decoction of Teucrium polium L., serum biochemical markers including ALT, AST, AFP, GGT, ALP, HCY, TNF-α, α2MG, and CBG have been regulated auspiciously. Total antioxidant status also has been increased intensely. Liver lesion score in treated group was lessened and glucocorticoid activity has been intensified significantly. In conclusion, Teucrium polium L. decoction might inhibit or suppress liver cancer development.

  19. Liver transplantation for hepatocellular carcinoma:an update

    Institute of Scientific and Technical Information of China (English)

    Ali Zarrinpar; Fady Kaldas; RonaldW Busuttil

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with multiple etiologies, high incidence, and high mortality. The standard surgical management for patients with HCC consists of locoregional ablation, surgical resection, or liver transplantation, depending on the background state of the liver. Eighty percent of patients initially presenting with HCC are unresectable, either due to the extent of tumor or the level of underlying hepatic dysfunction. While in patients with no evidence of cirrhosis and good hepatic function resection has been the surgical treatment of choice, it is contraindicated in patients with moderate to severe cirrhosis. Liver transplantation is the optimal surgical treatment. DATA  SOURCES: PubMed search of recent articles (from January 2000 to March 2011) was performed looking for relevant articles about hepatocellular carcinoma and its treatment. Additional articles were identified by evaluating references from selected articles. RESULTS: Here we review criteria for transplantation, the types, indications, and role of locoregional therapy in treating the cancer and in downstaging for possible later transplantation. We also summarize the contribution of immunosuppression and adjuvant chemotherapy in the management and prevention of HCC recurrence. Finally we discuss recent advances in imaging, tumor biology, and genomics as we delineate the remaining challenges for the diagnosis and treatment of this disease. CONCLUSIONS: Much can be improved in the diagnosis and treatment of HCC. A great challenge will be to improve patient selection to criteria based on tumor biology. Another will be to incorporate systemic agents post-operatively in patients at high risk for recurrence, paying close attention to efficacy and safety. The future direction of the effort in treating HCC will be to stimulate prospective trials, develop molecular imaging of lymphovascular invasion, to improve recipient selection, and to investigate

  20. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2012-03-01

    Full Text Available The incidence of hepatocellular carcinoma (HCC, once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs that degrade the extracellular matrix (ECM have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay, MMPs secretion (by gelatinase zymography, cell invasion (through Matrigel and induction of apoptosis (by live green caspase. In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and

  1. Hepatocellular carcinoma: natural history, current management, and emerging tools

    Directory of Open Access Journals (Sweden)

    Tinkle CL

    2012-07-01

    Full Text Available Christopher L Tinkle, Daphne Haas-KoganDepartment of Radiation Oncology, University of California, San Francisco, CA, USAAbstract: Hepatocellular carcinoma (HCC is the most common primary liver tumor and represents the third-leading cause of cancer-related death in the world. The incidence of HCC continues to increase worldwide, with a unique geographic, age, and sex distribution. The most important risk factor associated with HCC is liver cirrhosis, with the majority of cases caused by chronic infection with hepatitis B (HBV and C (HCV viruses and alcohol abuse, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary prevention in the form of HBV vaccination has led to a significant decrease in HBV-related HCC, and initiation of antiviral therapy appears to reduce the incidence of HCC in patients with chronic HBV or HCV infection. Additionally, the use of ultrasonography enables the early detection of small liver tumors and forms the backbone of recommended surveillance programs for patients at high risk for the development of HCC. Cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, represent further noninvasive techniques that are increasingly employed to diagnose HCC in patients with cirrhosis. The mainstay of potentially curative therapy includes surgery – either resection or liver transplantation. However, most patients are ineligible for surgery, because of either advanced disease or underlying liver dysfunction, and are managed with locoregional and/or systemic therapies. Randomized controlled trials have demonstrated a survival benefit with both local therapies, either ablation or embolization, and systemic therapy in the form of the multikinase inhibitor sorafenib. Despite this, median survival remains poor and recurrence rates significant. Further advances in our understanding of the molecular pathogenesis of HCC hold promise in improving the

  2. Progressive telomere shortening and telomerase reactivation during hepatocellular carcinogenesis.

    Science.gov (United States)

    Miura, N; Horikawa, I; Nishimoto, A; Ohmura, H; Ito, H; Hirohashi, S; Shay, J W; Oshimura, M

    1997-01-01

    Telomeres shorten progressively with age in normal somatic cells in culture and in vivo. The maintenance of telomere length is assumed to be an obligatory step in the progression and immortalization of most human tumor cells. To understand the role of telomere dynamics in the development of hepatocellular carcinoma (HCC), we examined the length of terminal restriction fragment (TRF), as an indicator for telomere length, in HCC and surrounding tissues with chronic active hepatitis (CAH) or liver cirrhosis (LC). The study was performed in 12 hepatitis C virus (HCV) antibody-positive, 12 hepatitis B virus (HBV) antigen-positive tissues, and 4 tissue samples from virus-negative patients with HCC. The peak TRFs in all 3 types of HCC were significantly shorter than those of the surrounding tissues (i.e., LC or CAH). TRFs examined in one patient with atypical adenomatous hyperplasia (AAH) also was shortened. Thus, progressive TRF shortening occurs from normal to CAH to LC to HCC(AAH). Telomerase, an enzyme that adds repeated telomere sequences onto the chromosome ends and stabilizes telomere length in immortal cells, also was examined in tissues and detected in high levels almost exclusively in HCCs. Interestingly, the intensity of telomerase activity in the AAH case was similar to that of HCC. In addition, the telomerase activity of biopsy samples with a fine 21-gauge needle also was examined in 10 HCCs, 2 adenomatous hyperplasias (AHs), 2 LCs, and 2 CAHs. We found strong telomerase activity in all the HCCs and surprisingly in the 2 cases that were pathologically diagnosed as AH. Thus, the findings strongly suggest that persistent cell proliferation or rapid cell turnover through damage of hepatic cells result in a process of multistep hepatocellular carcinogenesis. Thus, progressive shortening of telomeres and the activation of telomerase may be a useful marker for the early detection of malignant progression in liver disease. PMID:9062581

  3. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression

  4. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Roomi, M. Waheed; Roomi, Nusrath W.; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra, E-mail: a.niedz@drrath.com; Rath, Matthias [Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050 (United States)

    2012-03-23

    The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression

  5. Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-α deficiency

    Directory of Open Access Journals (Sweden)

    Roberta Resaz

    2014-09-01

    Full Text Available Glycogen storage disease type 1a (GSD-1a is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α, and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs. A globally G6Pase-α-deficient (G6pc−/− mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc−/− mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc−/− mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc−/− mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10–20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC. In conclusion, LS‑G6pc−/− mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.

  6. Lactobionic acid-modified dendrimer-entrapped gold nanoparticles for targeted computed tomography imaging of human hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Hui; Wang, Han; Xu, Yanhong; Guo, Rui; Wen, Shihui; Huang, Yunpeng; Liu, Weina; Shen, Mingwu; Zhao, Jinglong; Zhang, Guixiang; Shi, Xiangyang

    2014-05-14

    Development of novel nanomaterial-based contrast agents for targeted computed tomography (CT) imaging of tumors still remains a great challenge. Here we describe a novel approach to fabricating lactobionic acid (LA)-modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 pre-modified with fluorescein isothiocyanate and poly(ethylene glycol)-linked LA were employed as templates to form Au nanoparticles. The remaining dendrimer terminal amines were subjected to an acetylation reaction to form LA-Au DENPs. The prepared LA-Au DENPs were characterized via different methods. Our results reveal that the multifunctional Au DENPs with a Au core size of 2.7 nm have good stability under different pH (5-8) and temperature (4-50 °C) conditions and in different aqueous media, and are noncytotoxic to normal cells but cytotoxic to the targeted hepatocarcinoma cells in the given concentration range. In vitro flow cytometry data show that the LA-Au DENPs can be specifically uptaken by a model hepatocarcinoma cell line overexpressing asialoglycoprotein receptors through an active receptor-mediated targeting pathway. Importantly, the LA-Au DENPs can be used as a highly effective nanoprobe for specific CT imaging of hepatocarcinoma cells in vitro and the xenoplanted tumor model in vivo. The developed LA-Au DENPs with X-ray attenuation property greater than clinically employed iodine-based CT contrast agents hold a great promise to be used as a nanoprobe for targeted CT imaging of human hepatocellular carcinoma. PMID:24712914

  7. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells

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    Yafei Zhang

    2012-09-01

    Full Text Available OBJECTIVE: Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. METHODS: Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects. RESULTS: Assays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice. CONCLUSIONS: Our results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new

  8. Imaging characteristics of hepatocellular adenoma compared with pathologic findings

    International Nuclear Information System (INIS)

    Objective: To retrospectively compare CT and MR features of hepatocellular adenoma with pathologic findings. Methods: Twelve patients with histopathologically proved hepatocellular adenoma were classified on the basis of pathologic and genotype phenotype findings into four groups: steatotic type, cytological abnormality type, telangiectatic adenoma with inflammatory infiltrates type and atypical adenoma type. The CT and MR features of each type were reviewed retrospectively compared with the pathological results. Results: In this retrospective study, 12 patients were examined with CT (8 patients) and MR (8 patients). Among 12 patients, 4 patients showed a steatotic type. One patient showed hypo-density on the non-enhanced CT and 3 patients demonstrated hypo-density on all phases of the post-contrast scans. Two lesions showed iso-intense signal on the in-phase T1WI with signal dropout on the out-of-phase T1WI, and hypo-intense signal on the T2WI with fat suppression sequences. One lesion demonstrated moderate hypointense signal on all phases of the post-contrast MRI scans. Two patients with the telangiectatic adenoma inflammatory infiltrates type were found. One patient showed hypo-density on the non-enhanced CT scans and hyper-density on all phases of the post-contrast CT scans. One patient demonstrated iso-intense signal and the other hypo-intense signal on the T1WI, and both displayed moderate hyper-intense signal on the T2WI with fat suppression sequences and hyper-intense signal with gradual enhancement on all phases of post-contrast MR scans. There were 3 patients with a cytological abnormality type. One patient appeared hypo-density and 1 patient showed uniform iso-density on non-enhanced CT scans. All patients who had undergone contrast-enhanced CT scans were found to have hyper-density on the hepatic arterial-dominant phase and became slightly lower on the portal venous phase. On the delay phase the density reduced further. One mass showed iso

  9. Emerging role of Hpo signaling and YAP in hepatocellular carcinoma

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    Valero V III

    2015-06-01

    Full Text Available Vicente Valero III,1 Timothy M Pawlik,1 Robert A Anders21Department of Surgery, Division of Surgical Oncology, 2Department of Pathology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: Hepatocellular carcinoma (HCC is the sixth most common cancer and the third most common cause of cancer-related mortality worldwide. Due to the poor prognosis and limited therapeutic options, there is great interest in further understanding better the molecular underpinnings and potential molecular targets associated with HCC. The Hippo (Hpo signaling pathway and YAP, its principal downstream effector, represent an innovative area of research in HCC. Pioneered in Drosophila melanogaster, the Hpo cascade controls tissue homeostasis including organ size, cell proliferation, apoptosis, as well as cell-cycle regulation and differentiation. This conserved kinase cascade in mammals depends on central control by the tumor suppressor mammalian sterile 20-like kinase 1/2 (Mst1/2. The Mst1/2 commences the downstream kinase cascade, ultimately activating the oncoprotein YAP and allowing its physical association with downstream targets to enhance the gene expression signatures that are involved in proliferation and survival. Alterations in YAP expression and defective regulation of other key Hpo pathway members, such as Mst1/2, Salvador, neurofibromatosis and Mer (Nf2/mer, large tumor suppressor homolog 1/2 (Lats1/2, and Mps one binder kinase activator-like 1A and 1B (Mob1 drive carcinogenesis in animal models. The dysregulation of the Hpo pathway – resulting in an unchecked activation of YAP – culminates in the development of a broad range of human tumor types, including HCC. The abrogation of Mst1/2-mediated YAP phosphorylation permits YAP entry into the nucleus in murine models and functions similarly in human HCCs. Chemoresistance mechanisms displayed by HCC tumors occur in a YAP-dependent manner. The HCC specimens

  10. Leptin signaling molecular actions and drug target in hepatocellular carcinoma

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    Jiang N

    2014-11-01

    Full Text Available Nan Jiang,1,* Rongtong Sun,2,* Qing Sun3 1Shandong University School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Weihai Municipal Hospital, Weihai, Shandong Province, People’s Republic of China; 3Department of Pathology, QianFoShan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC, are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both

  11. Effect of PTPRD rs2279776 gene and interaction with hepatitis B virus mutations on the risk of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    邓阳

    2014-01-01

    Objective To investigate the effect of rs2279776 at the PTPRD and its interactions on hepatitis B virus(HBV)mutations as well as related risk on hepatocellular carcinoma(HCC).Methods A total of 3023 individ-uals,including 1012 healthy controls,990 HCC-free HBV-infected subjects,and 1021 HBV-caused hepatocellular carcinoma patients(HCC)

  12. TACE combined with contrast-enhanced sonography guided RFA in treating massive primary hepatocellular carcinomas: a clinical therapeutic evaluation

    Institute of Scientific and Technical Information of China (English)

    许帅

    2014-01-01

    Objective To evaluate the effect of transcatheter arterial chemoembolization(TACE)combined with contrast-enhanced sonography guided radiofrequency ablation(RFA)in treating massive primary hepatocellular carcinomas.Methods Forty-eight patients with massive primary hepatocellular carcinoma were treated with TACE combined with contrast-enhanced sonography guided RFA.The clinical data of these patients,collected in our

  13. Hepatocellular carcinoma surveillance rates in commercially insured patients with noncirrhotic chronic hepatitis B.

    Science.gov (United States)

    Goldberg, D S; Valderrama, A; Kamalakar, R; Sansgiry, S S; Babajanyan, S; Lewis, J D

    2015-09-01

    American association for the study of liver diseases (AASLD) and European Association for the Study of the Liver (EASL) guidelines recommend biannual hepatocellular carcinoma (HCC) screening for noncirrhotic patients with chronic hepatitis B infection (HBV), yet there are no data estimating surveillance rates or factors associated with surveillance. We performed a retrospective cohort study of US patients using the Truven Health Analytics databases from 2006 to 2010 and identified patients with noncirrhotic chronic HBV. Surveillance patterns were characterized using categorical and continuous outcomes, with the continuous measure of the proportion of time 'up to date' with surveillance (PUTDS), with the 6-month interval following each ultrasound categorized as 'up to date'. During a median follow-up of 26.0 (IQR: 16.2-40.0) months among 4576 noncirrhotic patients with chronic HBV (median age: 44 years, IQR: 36-52), only 306 (6.7%) had complete surveillance (one ultrasound every 6-month interval), 2727 (59.6%) incomplete (≥1 ultrasound) and 1543 (33.7%) none. The mean PUTDS was 0.34 ± 0.29, and the median was 0.32 (IQR: 0.03-0.52). In multinomial logistic regression models, patients diagnosed by a nongastroenterologist were significantly less likely to have complete surveillance (P HIV (P regression models, nongastroenterologist provider, health insurance subtype, HBV/HIV coinfection, rural status and metabolic syndrome were independently associated with decreased surveillance. Patients with HIV had an absolute decrease in the PUTDS of 0.24, while patients in less populated rural areas had an absolute decrease of 0.10. HCC surveillance rates in noncirrhotic patients with chronic HBV in the United States are poor and lower than reported rates of HCC surveillance in cirrhotic patients. PMID:25581816

  14. Adult mouse model of early hepatocellular carcinoma promoted by alcoholic liver disease

    Science.gov (United States)

    Ambade, Aditya; Satishchandran, Abhishek; Gyongyosi, Benedek; Lowe, Patrick; Szabo, Gyongyi

    2016-01-01

    AIM: To establish a mouse model of alcohol-driven hepatocellular carcinoma (HCC) that develops in livers with alcoholic liver disease (ALD). METHODS: Adult C57BL/6 male mice received multiple doses of chemical carcinogen diethyl nitrosamine (DEN) followed by 7 wk of 4% Lieber-DeCarli diet. Serum alanine aminotransferase (ALT), alpha fetoprotein (AFP) and liver Cyp2e1 were assessed. Expression of F4/80, CD68 for macrophages and Ly6G, MPO, E-selectin for neutrophils was measured. Macrophage polarization was determined by IL-1β/iNOS (M1) and Arg-1/IL-10/CD163/CD206 (M2) expression. Liver steatosis and fibrosis were measured by oil-red-O and Sirius red staining respectively. HCC development was monitored by magnetic resonance imaging, confirmed by histology. Cellular proliferation was assessed by proliferating cell nuclear antigen (PCNA). RESULTS: Alcohol-DEN mice showed higher ALTs than pair fed-DEN mice throughout the alcohol feeding without weight gain. Alcohol feeding resulted in increased ALT, liver steatosis and inflammation compared to pair-fed controls. Alcohol-DEN mice had reduced steatosis and increased fibrosis indicating advanced liver disease. Molecular characterization showed highest levels of both neutrophil and macrophage markers in alcohol-DEN livers. Importantly, M2 macrophages were predominantly higher in alcohol-DEN livers. Magnetic resonance imaging revealed increased numbers of intrahepatic cysts and liver histology confirmed the presence of early HCC in alcohol-DEN mice compared to all other groups. This correlated with increased serum alpha-fetoprotein, a marker of HCC, in alcohol-DEN mice. PCNA immunostaining revealed significantly increased hepatocyte proliferation in livers from alcohol-DEN compared to pair fed-DEN or alcohol-fed mice. CONCLUSION: We describe a new 12-wk HCC model in adult mice that develops in livers with alcoholic hepatitis and defines ALD as co-factor in HCC. PMID:27122661

  15. Clinical and pathological features and surgical treatment of Budd-Chiari syndrome-associated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Ya-dong; XUE Huan-zhou; ZHANG Xiao; XU Zong-quan; JIANG Qing-feng; SHEN Quan; YU Miao

    2013-01-01

    Background Budd-Chiari syndrome (BCS) is characterized by liver sinusoidal congestion,ischemic liver cell damage,and liver portal hypertension caused by hepatic venous outflow constriction.The aim of this research was to investigate the clinicopathological features of BCS-associated hepatocellular carcinoma (HCC) and explore its surgical treatment and prognosis.Methods Clinical data from 38 patients with BCS-associated HCC who were surgically treated in our hospital from July 1998 to August 2010 were retrospectively analyzed.The clinicopathological features and prognosis of patients with BCS-associated HCC and surgical treatment for BCS-associated HCC were investigated.Results Compared to the patients with hepatitis B virus (HBV)-associated HCC,the patients with BCS-associated HCC showed a female predominance,and had significantly higher cirrhosis rate,higher incidence of solitary tumors,lower incidence of infiltrative growth,higher proportion of marginal or exogenous growth,lower rate of portal vein invasion,and higher degree of differentiation.Median survival was longer in patients with BCS-associated HCC (76 months) than in those with HBV associated HCC (38 months).Of 38 patients with BCS-associated HCC,22 patients who received combined surgery mainly by liver resection plus cavoatrial shunts exhibited hepatic venous outflow constriction relief,while the other 16 patients only underwent liver resection.The combined surgery group had significantly longer survival and lower incidences of post-operative lethal complications (P <0.05).Multivariate analysis showed that relief of hepatic venous outflow obstruction was a protective factor for survival of patients with BCS-associated HCC,whereas portal vein invasion was a risk factor.Conclusions BCS-associated HCC has a more favorable biological behavior and prognosis than HBV-associated HCC.For patients with BCS-associated HCC,tumor resection accompanied with relief of hepatic venous outflow obstruction can reduce

  16. An inducible hepatocellular carcinoma model for preclinical evaluation of antiangiogenic therapy in adult mice.

    Science.gov (United States)

    Runge, Anja; Hu, Junhao; Wieland, Matthias; Bergeest, Jan-Philip; Mogler, Carolin; Neumann, André; Géraud, Cyrill; Arnold, Bernd; Rohr, Karl; Komljenovic, Dorde; Schirmacher, Peter; Goerdt, Sergij; Augustin, Hellmut G

    2014-08-01

    The limited availability of experimental tumor models that faithfully mimic the progression of human tumors and their response to therapy remains a major bottleneck to the clinical translation and application of novel therapeutic principles. To address this challenge in hepatocellular carcinoma (HCC), one of the deadliest and most common cancers in the world, we developed and validated an inducible model of hepatocarcinogenesis in adult mice. Tumorigenesis was triggered by intravenous adenoviral delivery of Cre recombinase in transgenic mice expressing the hepatocyte-specific albumin promoter, a loxP-flanked stop cassette, and the SV40 large T-antigen (iAST). Cre recombinase-mediated excision of the stop cassette led to a transient viral hepatitis and resulted in multinodular tumorigenesis within 5 to 8 weeks. Tumor nodules with histologic characteristics of human HCC established a functional vasculature by cooption, remodeling, and angiogenic expansion of the preexisting sinusoidal liver vasculature with increasing signs of vascular immaturity during tumor progression. Treatment of mice with sorafenib rapidly resulted in the induction of vascular regression, inhibition of tumor growth, and enhanced overall survival. Vascular regression was characterized by loss of endothelial cells leaving behind avascular type IV collagen-positive empty sleeves with remaining pericytes. Sorafenib treatment led to transcriptional changes of Igf1, Id1, and cMet over time, which may reflect the emergence of potential escape mechanisms. Taken together, our results established the iAST model of inducible hepatocarcinogenesis as a robust and versatile preclinical model to study HCC progression and validate novel therapies. PMID:24906623

  17. Factors Associated with Outcomes and Response to Therapy in Patients with Infiltrative Hepatocellular Carcinoma

    Science.gov (United States)

    Mehta, Neil; Fidelman, Nicholas; Sarkar, Monika; Yao, Francis Y.

    2014-01-01

    Background & Aims Infiltrative hepatocellular carcinoma (iHCC) is characterized by its indistinct borders and lack of a typical pattern of contrast enhancement. There are few published data on iHCC. We assessed outcomes, effects of treatment, and prognostic factors in a large cohort of patients with iHCC. Methods We analyzed data from 155 patients (median age 60 years; 79% male; median level of α-fetoprotein [AFP] 347 ng/mL; median model for end-stage liver disease score [MELD] 13) with iHCC, based on contrast-enhanced computed tomography or magnetic resonance imaging, from 2002 to 2010 at the University of California, San Francisco Medical Center. All imaging study results were independently reviewed by 2 investigators. Results Most of the patients had tumors of Barcelona Clinic Liver Cancer stage C (70%) or D (22%). The median maximum tumor diameter was 11.3 cm; 41% of lesions were hypovascular, 82% had macrovascular invasion, and 52% had extra-hepatic metastases. Median survival was 4.0 months, and rates of survival at 6 and 12 months were 30% and 10%, respectively. On multivariate analysis, predictors of 6-month mortality were Child-Pugh class B or C cirrhosis; lack of tumor-directed therapy with chemoembolization (TACE), radiofrequency ablation, or sorafenib; AFP level >1000 ng/mL; female sex; MELD score; and maximum tumor diameter. The percentages of patients surviving 6 and 12 months were 17% and 2% for those that received no therapy (n=109), 73% and 36% for those that received sorafenib (n=11), and 45% and 17% for those that that received TACE (n=18) (all P values TACE or sorafenib appears to prolong survival and requires further investigation. PMID:23333661

  18. Fenretinide-induced apoptosis of Huh-7 hepatocellular carcinoma is retinoic acid receptor β dependent

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    Wan Yu-Jui

    2007-12-01

    Full Text Available Abstract Background Retinoids are used to treat several types of cancer; however, their effects on liver cancer have not been fully characterized. To investigate the therapeutic potential of retinoids on hepatocellular carcinoma (HCC, the present study evaluates the apoptotic effect of a panel of natural and synthetic retinoids in three human HCC cell lines as well as explores the underlying mechanisms. Methods Apoptosis was determined by caspase-3 cleavage using western blot, DNA double-strand breaks using TUNEL assay, and phosphatidylserine translocation using flow cytometry analysis. Gene expression of nuclear receptors was assessed by real-time PCR. Transactivation assay and chromatin immunoprecipitation (ChIP were conducted to evaluate the activation of RXRα/RARβ pathway by fenretinide. Knockdown of RARβ mRNA expression was achieved by siRNA transfection. Results Our data revealed that fenretinide effectively induces apoptosis in Huh-7 and Hep3B cells. Gene expression analysis of nuclear receptors revealed that the basal and inducibility of retinoic acid receptor β (RARβ expression positively correlate with the susceptibility of HCC cells to fenretinide treatment. Furthermore, fenretinide transactivates the RXRα/RARβ-mediated pathway and directly increases the transcriptional activity of RARβ. Knockdown of RARβ mRNA expression significantly impairs fenretinide-induced apoptosis in Huh-7 cells. Conclusion Our findings reveal that endogenous expression of retinoids receptor RARβ gene determines the susceptibility of HCC cells to fenretinide-induced apoptosis. Our results also demonstrate fenretinide directly activates RARβ and induces apoptosis in Huh-7 cells in a RARβ-dependent manner. These findings suggest a novel role of RARβ as a tumor suppressor by mediating the signals of certain chemotherapeutic agents.

  19. Recent progress in radiofrequency ablation therapy for hepatocellular carcinoma.

    Science.gov (United States)

    Ikeda, Kenji; Osaki, Yukio; Nakanishi, Hiroyuki; Nasu, Akihiro; Kawamura, Yusuke; Jyoko, Koji; Sano, Takatomo; Sunagozaka, Hajime; Uchino, Koji; Minami, Yasunori; Saito, Yu; Nagai, Kazumasa; Inokuchi, Ryosuke; Kokubu, Shigehiro; Kudo, Masatoshi

    2014-01-01

    In order to attain better ablation and more effective management of hepatocellular carcinoma (HCC), new approaches and devices in radiofrequency ablation (RFA) therapy were presented and discussed in a workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan. A novel bipolar RFA apparatus was introduced in Japan in January 2013. Hundreds of subjects with HCC were treated with multipolar RFA with varied devices and plans. Among these, no-touch ablation was one of the most useful procedures in the treatment of HCC with the apparatus. In RFA therapy, a few assisting devices and techniques were applied for convenience and improvement of the thermal ablation procedure. Contrast-enhanced ultrasonography and three-dimensional fusion imaging technique using volume data of CT or MRI could improve exact targeting and shorten the treatment time for RFA procedures under ultrasonographic guidance. A more complicated method using a workstation was also reported as being helpful in planning the ablated shape and volume in multineedle RFA. The effective use of sedatives and antianalgesics as well as a novel microwave apparatus with a cooled-tip electrode was also discussed. PMID:25427736

  20. Clinical studies of hepatocellular carcinoma with liver cirrhosis and ascites.

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    Yuasa,Shiro

    1984-06-01

    Full Text Available A comparison was made of the clinical findings of 59 patients with liver cirrhosis (LC accompanied with hepatocellular carcinoma (HCC (of which 35 had ascites and 24 did not at the time of admission and 164 patients with LC, but without HCC (of which 39 had ascites and 125 did not. HCC patients were older and more often had hepatomegaly, vascular spider and pleural effusion than LC patients. Ascites was more frequently observed in HCC than in LC patients when the serum albumin level and the indocyanine green disappearance rate were relatively well maintained and when peripheral edema was absent. There was no difference in the ascitic protein concentration between LC and HCC patients. Malignant cells were detected in ascites only in 14% of the HCC patients. These facts indicate the presence of ascites-inducing factors in HCC patients which have no direct relation to serum colloid osmotic pressure and effective hepatic blood flow. Almost all of the HCC patients with ascites (96% died with ascites, whereas 54% of the LC patients with ascites recovered from the ascitic condition.

  1. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    International Nuclear Information System (INIS)

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer

  2. Transarterial radioembolization for hepatocellular carcinoma: An update and perspectives.

    Science.gov (United States)

    Sacco, Rodolfo; Mismas, Valeria; Marceglia, Sara; Romano, Antonio; Giacomelli, Luca; Bertini, Marco; Federici, Graziana; Metrangolo, Salvatore; Parisi, Giuseppe; Tumino, Emanuele; Bresci, Giampaolo; Corti, Ambra; Tredici, Manuel; Piccinno, Michele; Giorgi, Luigi; Bartolozzi, Carlo; Bargellini, Irene

    2015-06-01

    In the last decade trans-arterial radioembolization has given promising results in the treatment of patients with intermediate or advanced stage hepatocellular carcinoma (HCC), both in terms of disease control and tolerability profile. This technique consists of the selective intra-arterial administration of microspheres loaded with a radioactive compound (usually Yttrium(90)), and exerts its therapeutic effect through the radiation carried by these microspheres. A careful and meticulous selection of patients is crucial before performing the radioembolization to correctly perform the procedure and reduce the incidence of complications. Radioembolization is a technically complex and expensive technique, which has only recently entered clinical practice and is supported by scant results from phase III clinical trials. Nevertheless, it may represent a valid alternative to transarterial chemoembolization (TACE) in the treatment of intermediate-stage HCC patients, as shown by a comparative retrospective assessment that reported a longer time to progression, but not of overall survival, and a more favorable safety profile for radioembolization. In addition, this treatment has reported a higher percentage of tumor shrinkage, if compared to TACE, for pre-transplant downsizing and it represents a promising therapeutic option in patients with large extent of disease and insufficient residual liver volume who are not immediately eligible for surgery. Radioembolization might also be a suitable companion to sorafenib in advanced HCC or it can be used as a potential alternative to this treatment in patients who are not responding or do not tolerate sorafenib. PMID:26074690

  3. FXR induces SOCS3 and suppresses hepatocellular carcinoma.

    Science.gov (United States)

    Guo, Fei; Xu, Zhizhen; Zhang, Yan; Jiang, Peng; Huang, Gang; Chen, Shan; Lyu, Xilin; Zheng, Ping; Zhao, Xin; Zeng, Yijun; Wang, Shuguang; He, Fengtian

    2015-10-27

    Suppressor of cytokine signaling 3 (SOCS3) is regarded as a vital repressor in the liver carcinogenesis mainly by inhibiting signal transducer and activator of transcription 3 (STAT3) activity. Farnesoid X Receptor (FXR), highly expressed in liver, has an important role in protecting against hepatocellular carcinoma (HCC). However, it is unclear whether the tumor suppressive activity of FXR involves the regulation of SOCS3. In the present study, we found that activation of FXR by its specific agonist GW4064 in HCC cells inhibited cell growth, induced cell cycle arrest at G1 phase, elevated p21 expression and repressed STAT3 activity. The above anti-tumor effects of FXR were dramatically alleviated by knockdown of SOCS3 with siRNA. Reporter assay revealed that FXR activation enhanced the transcriptional activity of SOCS3 promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay displayed that FXR directly bound to IR9 DNA motif within SOCS3 promoter region. The in vivo study in nude mice showed that treatment with FXR ligand GW4064 could decelerate the growth of HCC xenografts, up-regulate SOCS3 and p21 expression and inhibit STAT3 phosphorylation in the xenografts. These results suggest that induction of SOCS3 may be a novel mechanism by which FXR exerts its anti-HCC effects, and the FXR-SOCS3 signaling may serve as a new potential target for the prevention/treatment of HCC. PMID:26416445

  4. Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria.

    Science.gov (United States)

    Elshamy, Mohammed; Aucejo, Federico; Menon, K V Narayanan; Eghtesad, Bijan

    2016-07-28

    Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria (MC) (single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy (LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCC-LT criteria models and pre-LT treatment strategies are required. PMID:27478537

  5. Differentiating Hepatocellular Carcinoma from Hepatitis C Using Metabolite Profiling

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    Siwei Wei

    2012-10-01

    Full Text Available Hepatocellular carcinoma (HCC accounts for most liver cancer cases worldwide. Contraction of the hepatitis C virus (HCV is considered a major risk factor for liver cancer. In order to identify the risk of cancer, metabolic profiling of serum samples from patients with HCC (n=40 and HCV (n=22 was performed by 1H nuclear magnetic resonance spectroscopy. Multivariate statistical analysis showed a distinct separation of the two patient cohorts, indicating a distinct metabolic difference between HCC and HCV patient groups based on signals from lipids and other individual metabolites. Univariate analysis showed that three metabolites (choline, valine and creatinine were significantly altered in HCC. A PLS-DA model based on these three metabolites showed a sensitivity of 80%, specificity of 71% and an area under the receiver operating curve of 0.83, outperforming the clinical marker alpha-fetoprotein (AFP. The robustness of the model was tested using Monte-Carlo cross validation (MCCV. This study showed that metabolite profiling could provide an alternative approach for HCC screening in HCV patients, many of whom have high risk for developing liver cancer.

  6. Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New

    Science.gov (United States)

    Faloppi, Luca; Bianconi, Maristella; Memeo, Riccardo; Casadei Gardini, Andrea; Giampieri, Riccardo; Bittoni, Alessandro; Andrikou, Kalliopi; Del Prete, Michela; Cascinu, Stefano; Scartozzi, Mario

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease. PMID:27314036

  7. Small hepatocellular carcinomas in chronic liver disease: Detection with SPECT

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    Kudo, M.; Hirasa, M.; Takakuwa, H.; Ibuki, Y.; Fujimi, K.; Miyamura, M.; Tomita, S.; Komori, H.; Todo, A.; Kitaura, Y.

    1986-06-01

    Single-photon emission computed tomography (SPECT) performed using a rotating gamma camera was compared with ..cap alpha../sub 1/-fetoprotein (AFP) assay, conventional liver scintigraphy, ultrasound (US) imaging, computed tomography (CT), and selective celiac angiography in 40 patients with a total of 50 small hepatocellular carcinomas (HCCs;<5 cm). The detection rates of US and CT were determined on an initial screening study and on a second, more precisely focused study. The detection rate of small HCCs by the various modalities was as follows: AFP, 13%; liver scintigraphy, 36%; SPECT, 72%; initial screening US, 80%; second, more precise US studies, 94%; initial screening CT, 64%; second, more precise CT study, 82%; angiography, 88%. Although SPECT was inferior to the initial screening US examination in detecting HCCs less than 2 cm in size, its sensitivity was identical to that of the initial screening US study for detecting HCCs of 2-5 cm. The combination of SPECT and US was an excellent method for the early detection of HCCs, yielding a detection rate of 94%.

  8. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

  9. Radiation therapy for abdominal lymph node metastasis from hepatocellular carcinoma

    International Nuclear Information System (INIS)

    We report the results of radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma (HCC). From 1998 to 2004, 45 cases were treated with radiotherapy (RT), with a dose between 30 and 55 Gy. The radiation response, overall survival, prognostic factors, and complications were evaluated. Thirty-nine cases were able to be evaluated for response: 10 cases showed complete response; 21 cases showed a partial response; and 8 cases showed stable disease. The overall response rate was 79.5%. The response rate was 87.5% for patients receiving ≥40 Gy10 (biologically effective dose, α/β=10) and 42.9% for patients receiving 10 (P=0.02). The median survival time was 10 months for responders and 6 months for nonresponders (P=0.01). The absence of other concurrent distant metastasis and controllable primary HCC were significant prognostic factors. RT induced gastric or duodenal ulcer development in nine patients. All of these patients had received more than 50 Gy10, and these complications were not detected among patients receiving 10 (0% vs 37.5%, P10 to 50 Gy10 might be the optimal RT dose. (author)

  10. Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization

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    Elias Björnson

    2015-12-01

    Full Text Available Hepatocellular carcinoma (HCC is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1 in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC.

  11. Spinal cord compression secondary to bone metastases from hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dinesh Chandra Doval; Komal Bhatia; Ashok Kumar Vaid; Keechelat Pavithran; Jai Bhagwan Sharma; Digant Hazarika; Amarnath Jena

    2006-01-01

    Bone metastases are rare in primary hepatocellular carcinoma (HCC). Spinal cord compression (SCC) due to bone metastases occur commonly in patients with lung and breast carcinomas, and metastatic HCC is an unusual cause of SCC. Spinal cord compression is an oncologic emergency and treatment delays can lead to irreversible consequences. Thus, the awareness that SCC could be a potential complication of bone metastases due to HCC is of significance in initiation of early treatment that can improve the quality of life and survival of the patients, if diagnosed earlier. This paper describes four cases of primary HCC with varied manifestations of SCC due to bone metastases. The first patient presented primarily with the symptoms of bone pains corresponding to the bone metastases sites rather than symptoms of associated hepatic pathology and eventually developed SCC. The second patient, diagnosed as having HCC, developed extradural SCC leading to paraplegia during the course of illness, for which he underwent emergency laminectomy with posterior fixation. The third patient developed SCC soon after the primary diagnosis and had to undergo emergency laminectomy. Post laminectomy he had good neurological recovery. The Fourth patient presented primarily with radicular pains rather than frank paraplegia as the first manifestation of SCC.

  12. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus

    Institute of Scientific and Technical Information of China (English)

    Masami Minagawa; Masatoshi Makuuchi

    2006-01-01

    The prognosis of patients with hepatocellular carcinoma (HCC)accompanied by portal vein tumor thrombus (PVTT) is generally poor if left untreated: a median survival time of 2.7-4.0 mo has been reported. Furthermore, while transcatheter arterial chemoembolization (TACE) has been shown to be safe in selected patients, the median survival time with this treatment is still only 3.8-9.5 mo. Systemic single-agent chemotherapy for HCC with PVTT has failed to improve the prognosis, and the response rates have been less than 20%. While regional chemotherapy with low-dose cisplatin and 5-fluorouracil or interferon and 5-fluorouracil via hepatic arterial infusion has increased the response rate, the median survival time has not exceeded 12 (range 4.5-11.8) mo.Combined treatment consisting of radiation for PVTT and TACE for liver tumor has achieved a high response rate, but the median survival rates have still been only 3.8-10.7 mo. With hepatic resection as monotherapy,the 5-year survival rate and median survival time were reportedly 4%-28.5% and 6-14 mo. The most promising results were reported for combined treatments consisting of hepatectomy and TACE, chemotherapy, or internal radiation. The reported 5-year survival rates and median survival times were 42% and 31 mo for TACE followed by hepatectomy; 36.3% and 22.1 mo for hepatectomy followed by hepatic arterial infusion chemotherapy; and 56% for chemotherapy or internal radiation followed by hepatectomy.

  13. Prevention of hepatocellular carcinoma in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Conrado; M; Fernández-Rodríguez; María; Luisa; Gutiérrez-García

    2014-01-01

    Patients with chronic hepatitis B are at significant risk for hepatocellular carcinoma(HCC). Globally,over half a million people each year are diagnosed with HCC,with marked geographical variations. Despite overwhelming evidence for a causal role of hepatitis B virus(HBV) infection in the development of HCC and a well-established relationship between high baseline hepatitis B viral load and cumulative risk of HCC,the molecular basis for this association has not been fully elucidated. In addition,a beneficial role for antiviral therapy in preventing the development of HCC has been difficult to establish. This review examines the biological and molecular mechanisms of HBV-related hepatocarcinogenesis,recent results on the effect of modern nucleos(t)ides on the rate of HCC development in high risk HBV cohorts and the potential mechanisms by which long-term antiviral therapy with potent inhibitors of HBV replication might reduce the risk of HCC in patients with chronic hepatitis B. Although evidence from randomized controlled trials shows the favourable effects of antiviral agentsin achieving profound and durable suppression of HBV DNA levels while improving liver function and histology,robust evidence of other long-term clinical outcomes,such as prevention of HCC,are limited.

  14. [Needle tract seeding of hepatocellular carcinoma after liver transplantation].

    Science.gov (United States)

    Mrzljak, Anna; Kardum-Skelin, Ika; Blasković, Darko; Skegro, Dinko; Jadrijević, Stipislav; Colić-Cvrlje, Vesna

    2011-09-01

    Ultrasound guided fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) are effective methods for the diagnosis of focal hepatic lesions. In case of neoplastic lesions, however, this may be followed by the seeding of malignant cells along the needle tract. We report a case of subcutaneous needle tract seeding of hepatocellular carcinoma (HCC) 25 months after liver transplantation. A 57-year-old man with compensated hepatitis-B-related liver cirrhosis was diagnosed with HCC by CNB, and the lesion was resected. Ten months after the procedure, FNAC of a small hepatic lesion confirmed tumor recurrence. The patient was successfully transplanted and 25 months later, a subcutaneous tumor appeared on the abdominal wall over the previous site of puncture without further dissemination of the disease. Total resection of the lesion confirmed HCC. It remains undetermined whether the seeding appeared after FNAC or CNB. After 18-month follow-up the patient was uneventful. The objectives of this report are to present clinical aspects and outcome of HCC needle tract seeding in a transplanted patient, discussing the problems and pitfalls of diagnostic workup and management of HCC. PMID:23126051

  15. Diagnostic value of α-fetoprotein in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    In the world the hepatocellular carcinoma (HCC) is the fifth to sixth most common malignancy. An increase in its incidence is looming in Cuba as a result of the population aging and the increase of morbi-mortality due to liver cirrhosis (CH). α-fetoprotein (AFP) by SUMA®, was used in this work as a tumor marker technique in 189 Cirrhotic patients evaluated at the CIMEQ, between January 1999 and September 2005. The main factors associated with an elevation of AFP were HCC, viral cirrhosis, and the age of 50 years or more. Presented CHC 22 (11.64%) patients, who had an average age of 55 years and the predominant sex was male (86,36%). The most important cause associated with this malignant disease was viral CH, mainly the virus of hepatitis C. This tumor marker showed a sensitivity and specificity of 68.18% and 92.17%, respectively. When combined with abdominal ultrasound was increase 86.36% sensitivity and 100% specificity. Elevated AFP levels associated with tumor prognosis factors. It can be concluded that the AFP had value in the diagnosis of HCC. This work is the first of its kind carried out in Cuba, and allows the design of a workable strategy for the research, monitoring and prognosis of HCC, having a wide network of laboratories SUMA®,, with a low cost per each determination. (author)

  16. Improving clinical trial design for hepatocellular carcinoma treatments

    Directory of Open Access Journals (Sweden)

    Garrett Hisatake

    2011-12-01

    Full Text Available Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.

  17. Current role of ultrasound for the management of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hitoshi Maruyama; Masaharu Yoshikawa; Osamu Yokosuka

    2008-01-01

    Hepatocellular carcinoma (HCC) has a decisive influence on the prognosis of cirrhotic patients. Although a-fetoprotein (AFP) is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound (US) plays a major role among them, because it provides real-time and non-invasive observation by a simple and easy technique. In addition, US-guided needle puncture methods are frequently required for the diagnosis and/or treatment process of HCC. The development of digital technology has led to the detection of blood flow by color Doppler US, and the sensitivity for detecting tumor vascularity has shown remarkable improvement with the introduction of microbubble contrast agents. Moreover, near realtime 3-dimensional US images are now available. As for the treatment of HCC, high intensity focused ultrasound (HIFU) was developed as a novel technology that provides transcutaneous ablation effect without needle puncture. These advancements in the US field have led to rapid progress in HCC management, and continuing advances are expected. This article reviews the current application of US for HCC in clinical practice.

  18. Adrenal metastasis as first presentation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zacharakis Evangelos

    2005-07-01

    Full Text Available Abstract Background Metastases from hepatocellular carcinoma (HCC can be found in the lung and adrenal gland. We report case of a patient who presented with adrenal metastasis as the first clinical manifestation of HCC. Case presentation A patient was referred for surgical treatment for a tumor in retro-peritoneal space. The computerized tomography (CT scan revealed a mass originating from the left adrenal gland. The patient underwent left adrenalectomy and the exploration of abdominal cavity did not reveal any other palpable lesions. Histologically, the resected lesion was a poorly differentiated metastatic tumor from HCC. Seven months later patient was readmitted complaining of cachexia, icterus, and significant weight loss. CT scan revealed hyperdense lesions of the liver Conclusion HCC may have atypical presentations like in present case. Fine needle aspiration/tru-cut® biopsy might be useful in the investigation of an accidentally discovered adrenal mass regardless of the size and can lead to the detection of a primary tumor.

  19. Carbon dioxide digital subtraction angiography manifestations of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    LU Wei; LI Yan-hao; HE Xiao-feng; CHEN Yong; ZENG Qing-le; XU Xiao-li

    2002-01-01

    Objective: To investigate the imaging features and clinical significance of carbon dioxide digital subtraction angiography (CO2-DSA) in the diagnosis and treatment of hepatocellular carcinoma (HCC).Methods: Both CO2-DSA and conventional DSA were performed in all 47 patients with HCC, and the angiographic manifestations of CO2-DSA were compared with those of conventional DSA in the same patients.Results: Peripheral arterial and capillary imaging by CO2-DSA was inferior to that by conventional DSA, although blood pools were well visualized with CO2. Improved visualization of arterioportal shunting (APS)was obtained with CO2-DSA compared with that by conventional angiography. APS was observed in 33 cases by CO2-DSA and in 12 cases by conventional angiography (P<0. 001). Retrograde visualization of the portal vein (PV) trunk and its large branches was demonstrated in 16 cases by CO2-DSA and in 1 case by conventional DSA (P<0. 001). The manifestation of lipiodol retention in the tumors was consistent with CO2-DSA images after TAE in 38 cases, and with those of conventional DSA in 23 cases (P<0. 01). Conclusion: CO2-DSA was superior to conventional DSA in the detection of APS and retrograde visualization of PV system,and the former can provide usefulness information for the treatment planning (chemoembolization) and patient prognosis. Demonstration of APS by CO2-DSA may suggest the presence of intrahepatic metastases.

  20. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    Science.gov (United States)

    Hong, Yu; Long, Jiang; Li, Hai; Chen, Shuhong; Liu, Qiqi; Zhang, Bei; He, Xiaomin; Wang, Yan; Li, Hongyi; Li, Yimei; Zhang, Tao; Lu, Chenzhen; Yan, Hao; Zhang, Minli; Li, Qing; Cao, Bangwei; Bai, Zhigang; Wang, Jin; Zhang, Zhongtao; Zhu, Shengtao; Zheng, Jiasheng; Ou, Xiaojuan; Ma, Hong; Jia, Jidong; You, Hong; Wang, Shengqi; Huang, Jian

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. Findings Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. Interpretation Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID:26137588

  1. Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

    Directory of Open Access Journals (Sweden)

    Toru Miyake

    2012-09-01

    Full Text Available Ectopic hepatocellular carcinoma (HCC is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomography revealed multiple nodular lesions in the abdominal cavity with ascites without a possible primary tumor. Exploratory laparoscopy was performed, which revealed bloody ascites and multiple brown nodular tumors measuring approximately 10 mm in size that were disseminated on the perineum and mesentery. A postoperative PET-CT scan was performed but it did not reveal any evidence of a tumor in the liver. The tumors resected from the peritoneum were diagnosed as HCC. The present case of HCC was thought to have possibly developed from ectopic liver on the peritoneum or mesentery.

  2. Simultaneous Resection of Disseminated Hepatocellular Carcinoma and Colon Cancer

    Directory of Open Access Journals (Sweden)

    Yuki Haga

    2013-01-01

    Full Text Available A 75-year-old woman with abdominal pain and vomiting was admitted to our hospital. Colonoscopy showed an advanced colon cancer that encompassed the entire circumference of the descending colon’s lumen. The patient was diagnosed with occlusive ileus associated with the colon cancer. She had been watched for liver cirrhosis due to the hepatitis C virus and received radiofrequency ablation therapy for hepatocellular carcinoma (HCC 6 years previously. Although she exhibited a gradual increase in serum levels of α-fetoprotein and PIVKA-II starting 2 years before admission, no tumors were detected in the liver by abdominal ultrasonography and computed tomography. On admission, contrast-enhanced computed tomography revealed not only the colon cancer but also a tumor adjacent to the cecum. Both tumors were successfully removed by surgery and a pathological analysis revealed that the cecum tumor was poorly-differentiated HCC. The serum levels of α-fetoprotein and PIVKA-II declined markedly after the operation and no masses considered as peritoneal metastasis have been detected to date. This is the first report of the simultaneous resection of disseminated HCC and colon cancer.

  3. Significant biomarkers for the management of hepatocellular carcinoma.

    Science.gov (United States)

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru

    2015-06-01

    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC. PMID:25855582

  4. Non-coding RNAs as therapeutic targets in hepatocellular cancer.

    Science.gov (United States)

    Braconi, Chiara; Patel, Tushar

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common malignancy that affects a large number of patients worldwide, with an increasing incidence in the United States and Europe. The therapies that are currently available for patients with inoperable HCC have limited benefits. Although molecular targeted therapies against selected cell signaling pathways have shown some promising results, their impact has been minimal. There is a need to identify and explore other targets for the development of novel therapeutics. Several non-protein coding RNAs (ncRNA) have recently been implicated in hepatocarcinogenesis and tumor progression. These ncRNA genes represent promising targets for cancer. However, therapeutic targeting of ncRNA genes has not been employed for HCC. The use of antisense oligonucleotides and viral vector delivery approaches have been shown to be feasible approaches to modulate ncRNA expression. HCC is an optimal cancer to evaluate novel RNA based therapeutic approaches because of the potential of effective delivery and uptake of therapeutic agents to the liver. In this review, we discuss selected ncRNA that could function as potential targets in HCC treatment and outline approaches to target ncRNA expression. Future challenges include the need to achieve site-specific targeting with acceptable safety and efficacy. PMID:22873215

  5. Computational hepatocellular carcinoma tumor grading based on cell nuclei classification.

    Science.gov (United States)

    Atupelage, Chamidu; Nagahashi, Hiroshi; Kimura, Fumikazu; Yamaguchi, Masahiro; Tokiya, Abe; Hashiguchi, Akinori; Sakamoto, Michiie

    2014-10-01

    Hepatocellular carcinoma (HCC) is the most common histological type of primary liver cancer. HCC is graded according to the malignancy of the tissues. It is important to diagnose low-grade HCC tumors because these tissues have good prognosis. Image interpretation-based computer-aided diagnosis (CAD) systems have been developed to automate the HCC grading process. Generally, the HCC grade is determined by the characteristics of liver cell nuclei. Therefore, it is preferable that CAD systems utilize only liver cell nuclei for HCC grading. This paper proposes an automated HCC diagnosing method. In particular, it defines a pipeline-path that excludes nonliver cell nuclei in two consequent pipeline-modules and utilizes the liver cell nuclear features for HCC grading. The significance of excluding the nonliver cell nuclei for HCC grading is experimentally evaluated. Four categories of liver cell nuclear features were utilized for classifying the HCC tumors. Results indicated that nuclear texture is the dominant feature for HCC grading and others contribute to increase the classification accuracy. The proposed method was employed to classify a set of regions of interest selected from HCC whole slide images into five classes and resulted in a 95.97% correct classification rate. PMID:26158066

  6. Induction of hepatocellular carcinoma by in vivo gene targeting

    Science.gov (United States)

    Wang, Pei-Rong; Xu, Mei; Toffanin, Sara; Li, Yi; Llovet, Josep M.; Russell, David W.

    2012-01-01

    The distinct phenotypic and prognostic subclasses of human hepatocellular carcinoma (HCC) are difficult to reproduce in animal experiments. Here we have used in vivo gene targeting to insert an enhancer-promoter element at an imprinted chromosome 12 locus in mice, thereby converting ∼1 in 20,000 normal hepatocytes into a focus of HCC with a single genetic modification. A 300-kb chromosomal domain containing multiple mRNAs, snoRNAs, and microRNAs was activated surrounding the integration site. An identical domain was activated at the syntenic locus in a specific molecular subclass of spontaneous human HCCs with a similar histological phenotype, which was associated with partial loss of DNA methylation. These findings demonstrate the accuracy of in vivo gene targeting in modeling human cancer and suggest future applications in studying various tumors in diverse animal species. In addition, similar insertion events produced by randomly integrating vectors could be a concern for liver-directed human gene therapy. PMID:22733778

  7. Hyperproliferative Hepatocellular Alterations after Intraportal Transplantation of Thyroid Follicles

    Science.gov (United States)

    Dombrowski, Frank; Klotz, Luisa; Hacker, Hans Jörg; Li, Yanhua; Klingmüller, Dietrich; Brix, Klaudia; Herzog, Volker; Bannasch, Peter

    2000-01-01

    The thyroid hormone 3,5,3′-triiodo-l-thyronine (T3) is a strong direct hepatocyte mitogen in vivo. The effects of T3 resemble those of peroxisome proliferators, which are known to induce hepatocellular tumors in rats. With the aim of studying long-term local effects of thyroid hormones on liver parenchyma, small pieces of thyroid tissue were transplanted via the portal veins into the livers of thyroidectomized male Lewis rats. At 1 week, 3 weeks, 3 months, and 18 months after transplantation, the transplants were found to proliferate, to synthesize thyroglobulin, and to release thyroxine and T3. At 3 and 18 months after transplantation, the hepatocytes of the liver acini downstream of the transplanted follicles showed an increase in cytoplasmic basophilia, a loss of glycogen, an enlargement and hyperchromasia of their nuclei, and a strong increase in cell turnover compared with unaltered liver acini. The altered hepatocytes exhibited an increase in the activities of glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, malic enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, cytochrome-c-oxidase, and acid phosphatase; the activities of glycogen synthase and glycogen phosphorylase were strongly decreased. The hepatocytic alterations downstream of the transplanted follicles could be explained by effects of T3. On the other hand, they resembled alterations characteristic of amphophilic preneoplastic liver foci observed in different models of hepatocarcinogenesis. PMID:10623658

  8. Update in management of hepatocellular carcinoma in Eastern population.

    Science.gov (United States)

    Chu, Kevin Ka Wan; Cheung, Tan To

    2015-06-18

    Hepatocellular carcinoma (HCC) is one of the commonest malignant tumours in the East. Although the management of HCC in the West is mainly based on the Barcelona Clinic for Liver Cancer staging, it is considered too conservative by Asian countries where the number of HCC patients is huge. Scientific and clinical advances were made in aspects of diagnosis, staging, and treatment of HCC. HCC is well known to be associated with cirrhosis and the treatment of HCC must take into account the presence and stage of chronic liver disease. The major treatment modalities of HCC include: (1) surgical resection; (2) liver transplantation; (3) local ablation therapy; (4) transarterial locoregional treatment; and (5) systemic treatment. Among these, resection, liver transplantation and ablation therapy for small HCC are considered as curative treatment. Portal vein embolisation and the associating liver partition with portal vein ligation for staged hepatectomy may reduce dropout in patients with marginally resectable disease but the midterm and long-term results are still to be confirmed. Patient selection for the best treatment modality is the key to success of treatment of HCC. The purpose of current review is to provide a description of the current advances in diagnosis, staging, pre-operative liver function assessment and treatment options for patients with HCC in the east. PMID:26085915

  9. National Cancer Centre Singapore Consensus Guidelines for Hepatocellular Carcinoma.

    Science.gov (United States)

    Chow, Pierce K H; Choo, Su Pin; Ng, David C E; Lo, Richard H G; Wang, Michael L C; Toh, Han Chong; Tai, David W M; Goh, Brian K P; Wong, Jen San; Tay, Kiang Hiong; Goh, Anthony S W; Yan, Sean X; Loke, Kelvin S H; Thang, Sue Ping; Gogna, Apoorva; Too, Chow Wei; Irani, Farah Gillian; Leong, Sum; Lim, Kiat Hon; Thng, Choon Hua

    2016-04-01

    Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26(th) September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data. PMID:27386428

  10. Update in management of hepatocellular carcinoma inEastern population

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the commonestmalignant tumours in the East. Although themanagement of HCC in the West is mainly basedon the Barcelona Clinic for Liver Cancer staging, it isconsidered too conservative by Asian countries wherethe number of HCC patients is huge. Scientific andclinical advances were made in aspects of diagnosis,staging, and treatment of HCC. HCC is well known to be associated with cirrhosis and the treatment of HCC musttake into account the presence and stage of chronicliver disease. The major treatment modalities of HCCinclude: (1) surgical resection; (2) liver transplantation;(3) local ablation therapy; (4) transarterial locoregionaltreatment; and (5) systemic treatment. Among these,resection, liver transplantation and ablation therapy forsmall HCC are considered as curative treatment. Portalvein embolisation and the associating liver partitionwith portal vein ligation for staged hepatectomy mayreduce dropout in patients with marginally resectabledisease but the midterm and long-term results are stillto be confirmed. Patient selection for the best treatmentmodality is the key to success of treatment of HCC. Thepurpose of current review is to provide a descriptionof the current advances in diagnosis, staging, preoperativeliver function assessment and treatmentoptions for patients with HCC in the east.

  11. Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis.

    Science.gov (United States)

    Xu, Xinsen; Zhou, Yanyan; Miao, Runchen; Chen, Wei; Qu, Kai; Pang, Qing; Liu, Chang

    2016-06-01

    We performed weighted gene coexpression network analysis (WGCNA) to gain insights into the molecular aspects of hepatocellular carcinoma (HCC). Raw microarray datasets (including 488 samples) were downloaded from the Gene Expression Omnibus (GEO) website. Data were normalized using the RMA algorithm. We utilized the WGCNA to identify the coexpressed genes (modules) after non-specific filtering. Correlation and survival analyses were conducted using the modules, and gene ontology (GO) enrichment was applied to explore the possible mechanisms. Eight distinct modules were identified by the WGCNA. Pink and red modules were associated with liver function, whereas turquoise and black modules were inversely correlated with tumor staging. Poor outcomes were found in the low expression group in the turquoise module and in the high expression group in the red module. In addition, GO enrichment analysis suggested that inflammation, immune, virus-related, and interferon-mediated pathways were enriched in the turquoise module. Several potential biomarkers, such as cyclin-dependent kinase 1 (CDK1), topoisomerase 2α (TOP2A), and serpin peptidase inhibitor clade C (antithrombin) member 1 (SERPINC1), were also identified. In conclusion, gene signatures identified from the genome-based assays could contribute to HCC stratification. WGCNA was able to identify significant groups of genes associated with cancer prognosis. PMID:27052251

  12. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  13. Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    You-xin Ji; Lei Sun; Zong-chun Zhang; Zhong-fa Zhang; Ke-tao Lan; Ke-ke Nie; Chuan-xin Geng; Shi-chao Liu; Ling Zhang; Xing-jun Zhuang; Xiao Zou

    2014-01-01

    Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

  14. Treatment of hepatocellular carcinoma: A single-center experience

    International Nuclear Information System (INIS)

    Purpose. The comparative efficacy of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) was investigated. Methods. Two hundred and sixty consecutive patients were retrospectively analyzed: 156 had received between one and six chemoembolization sessions at 3-month intervals, 33 had had PEI, and the remaining 71 patients refused any treatment. The follow-up ranged from 3 to 36 months. Survival rates were statistically analyzed by life-table analysis. Results. Patients' survival was affected by the number of nodules and by the Child's and Okuda's classes; no relationship was found between survival rates and the histologic grade or vascular supply of the tumor. In the case of a single lesion of Okuda's class I, TACE was more effective than PEI. In multifocal HCC, TACE was better than no treatment in Okuda's class I and Child's class A. Conclusion. We suggest TACE as the treatment of choice in Child A or Okuda I patients with multifocal HCCs; it seems of little help in Child B-C or Okuda II-III patients

  15. Transarterial Chemoembolization (TACE) in hepatocellular carcinoma: Technique, indication and results

    International Nuclear Information System (INIS)

    To present current data on technique, indications and results of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). The principle of TACE is the intra-arterial injection of chemotherapeutic drug combinations like doxorubicin, cisplatin and mitomycin into the hepatic artery, followed by lipiodol injection, Gelfoam for vessel occlusion and degradable microspheres. The side effects and complications after TACE range from fever, upper abdominal pain and vomiting to acute or chronic liver cell failure. The palliative effect in unresectable HCC using TACE allows local tumor control in 15 to 60% of cases and 5-year survival rates ranging from 8 - 43%. The potentially curative treatment option allows local tumor control from 18 - 63%. The neoadjuvant treatment option of TACE in combination with other treatment options like percutaneous ethanol injection (PEI) or radiofrequency ablation (RFA) reach local tumor control rates between 80 - 96%. The bridging effect of TACE before liver transplantation reaches 5-year survival rates from 59 - 93%. The symptomatic therapy option of TACE is used to counteract pain directly caused by HCC and acute/subacute bleeding in the HCC. The local tumor response reaches up to 88% and the bleeding control is from 83 to 100%. (orig.)

  16. Platelets contribute to growth and metastasis in hepatocellular carcinoma.

    Science.gov (United States)

    Bihari, Chhagan; Rastogi, Archana; Shasthry, Saggere Muralikrishna; Bajpai, Meenu; Bhadoria, Ajeet Singh; Rajesh, S; Mukund, Amar; Kumar, Anupam; Sarin, Shiv K

    2016-09-01

    To determine the association of platelets with hepatocellular carcinoma (HCC) growth and its metastasis. We examined platelets, laboratory, and radiological data of consecutive 420 HCC and 1008 cirrhosis cases. Follow-up information of platelet count in cirrhosis to HCC, pre- to post-therapy, and post-therapy to HCC outcome was analyzed. Cytokine profiling was performed in HCC and cirrhosis (n = 10 each). On the basis of imaging, HCC was divided into six subgroups. Cytosmears of HCC were assessed for platelet clustering around tumor cells. An in vitro Matrigel invasion assay was performed on human HCC cell lines using graded concentration of platelets. Baseline platelet numbers and platelet/lymphocyte ratios (PLRs) were significantly higher (p AFP, PIVKAII, platelets, and PLR increase (p AFP (p < 0.001) associated with distant metastasis. Platelet clustering seen in 75.7% of HCC group 3, 45% in group 2, and 12.5% in group 1 cases (p < 0.001). Invaded cells in Matrigel assay positively correlated with platelet concentration. Platelets can contribute to the development, growth, invasion, and metastasis of HCC. Rising platelet count after HCC therapy is indicative of incomplete response or recurrence. PMID:27457354

  17. Risk factors for residual tumor after resection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hong Chen; Bo-Heng Zhang; Yin Xin; Zheng-Gang Ren; Jia Fan; Shuang-Jian Qiu; Jian Zhou

    2011-01-01

    AIM: To identify the clinicopathological risk factors correlated with residual tumor in hepatocellular carcinoma (HCC) patients after resection.METHODS: From January 2001 to April 2007, 766 HCC patients who had undergone resection were included in this research.Lipiodol angiography was performed within 2 mo after surgery and followed by post-Lipiodol computed tomography (CT) 4 wk later for all 766 patients to monitor tumor in the remnant liver.Tumor detected within the first 3-mo postoperative period was defined as residual tumor.Patients were divided into 2 groups: disease or disease-free within the first 3 mo after surgery.Risk factors for residual tumor were investigated among various clinicopathological variables.RESULTS: A total of 63 (8.22%) patients were found to have residual tumor after surgery.Three independent factors associated with residual tumor were identified by multivariate analysis: preoperative serum α -fetoprotein (AFP) level [odds ratio (OR) = 1.68 (95% confidence interval (CI): 1.20-2.36)], tumor size [OR = 1.73 (95% CI: 1.29-2.31)] and microvascular invasion [OR = 1.91 (95% CI: 1.12-3.24)].CONCLUSION: Residual tumor is related to AFP level, tumor size and microvascular invasion.Patients at high risk should undergo closer follow-up and could be candidates for multimodality therapy.

  18. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  19. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Hiroki, E-mail: h-nishikawa@osaka-med.jrc.or.jp; Osaki, Yukio; Kita, Ryuichi; Kimura, Toru [Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027 (Japan)

    2012-02-21

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  20. Transcatheter Arterial Chemoembolization Based on Hepatic Hemodynamics for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Satoru Murata

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the sixth most common cancer and the third leading cause of cancer-related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation can improve survival in HCC patients diagnosed at an early stage and offer potential long-term curative effects. Patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE, and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced-stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced-stage HCC.

  1. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Directory of Open Access Journals (Sweden)

    Ryuichi Kita

    2012-02-01

    Full Text Available Transcatheter methods such as transcatheter arterial chemoembolization (TACE and hepatic arterial infusion chemotherapy (HAIC have an important role in the treatment for advanced hepatocellular carcinoma (HCC. Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  2. Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria

    Science.gov (United States)

    Elshamy, Mohammed; Aucejo, Federico; Menon, K V Narayanan; Eghtesad, Bijan

    2016-01-01

    Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria (MC) (single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy (LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCC-LT criteria models and pre-LT treatment strategies are required.

  3. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region.

    Science.gov (United States)

    Zhu, Ran Xu; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man-Fung

    2016-05-23

    Hepatocellular carcinoma (HCC) is the predominant primary liver cancer in many countries and is the third most common cause of cancer-related death in the Asia-Pacific region. The incidence of HCC is higher in men and in those over 40 years old. In the Asia-Pacific region, chronic hepatitis B virus and hepatitis C virus infections are the main etiological agents; in particular, chronic hepatitis B infection (CHB) is still the major cause in all Asia-Pacific countries except for Japan. Over the past two decades, the incidence of HCC has remained stable in countries in the region except for Singapore and Hong Kong, where the incidence for both sexes is currently decreasing. Chronic hepatitis C infection (CHC) is an important cause of HCC in Japan, representing 70% of HCCs. Over the past several decades, the prevalence of CHC has been increasing in many Asia-Pacific countries, including Australia, New Zealand, and India. Despite advancements in treatment, HCC is still an important health problem because of the associated substantial mortality. An effective surveillance program could offer early diagnosis and hence better treatment options. Antiviral treatment for both CHB and CHC is effective in reducing the incidence of HCC. PMID:27114433

  4. Present and future possibilities for early diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Piotr Stefaniuk, Janusz Cianciara, Alicja Wiercinska-Drapalo

    2010-01-01

    Full Text Available Hepatocellular carcinoma (HCC represents the fifth most common cancer in the world, and the third most frequent oncological cause of death. The incidence of HCC is on the increase. HCC typically develops in patients with chronic liver diseases, and cirrhosis, usually with viral etiology, is the strongest predisposing factor. Nowadays HCC diagnosis is a multistage process including clinical, laboratory, imaging and pathological examinations. The prognosis of HCC is mostly poor, because of detection at an advanced, non-resectable stage. Potentially curative treatment (surgery is limited and really possible only for cases with small HCC malignancies. For this reason, more effective surveillance strategies should be used to screen for early occurrence of HCC targeted to the population at risk. So far, the generally accepted serological marker is α-fetoprotein (AFP. Its diagnostic accuracy is unsatisfactory and questionable because of low sensitivity, therefore there is a strong demand by clinicians for new HCC-specific biomarkers. In this review, we will focus on other biomarkers that seem to improve HCC diagnosis, such as AFP-L3, des-γ-carboxyprothrombin, α-l-fucosidase, γ-glutamyl transferase, glypican-3, squamous cell carcinoma antigen, a new generation of immunoglobulin M-immunocomplexes, and very promising gene-expression profiling.

  5. Bioinformatics analysis of metastasis-related proteins in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Pei-Ming Song; Yang Zhang; Yu-Fei He; Hui-Min Bao; Jian-Hua Luo; Yin-Kun Liu; Peng-Yuan Yang; Xian Chen

    2008-01-01

    AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomark-er candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools.METHODS: Metastasis-related proteins were determined by stable isotope labeling and MS analysis and analyzed with bioinformatics resources, including Phobius, Kyoto encyclopedia of genes and genomes (KEGG), online mendelian inheritance in man (OHIH) and human protein reference database (HPRD).RESULTS: All the metastasis-related proteins were linked to 83 pathways in KEGG, including MAPK and p53 signal pathways. Protein-protein interaction network showed that all the metastasis-related proteins were categorized into 19 function groups, including cell cycle, apoptosis and signal transcluction. OMIM analysis linked these proteins to 186 OMIM entries.CONCLUSION: Metastasis-related proteins provide HCC cells with biological advantages in cell proliferation, migration and angiogenesis, and facilitate metastasis of HCC cells. The bird's eye view can reveal a global charac-teristic of metastasis-related proteins and many differen-tially expressed proteins can be identified as candidates for diagnosis and treatment of HCC.

  6. The effect of LOXL2 in hepatocellular carcinoma.

    Science.gov (United States)

    Wu, Linghong; Zhang, Yuan; Zhu, Ying; Cong, Qingwei; Xiang, Yan; Fu, Linlin

    2016-09-01

    Lysyl oxidase-like 2 (LOXL2) is key in the hepatocellular carcinoma (HCC) tumor microenvironment and metastatic niche formation. However, its effect on proliferation and clinical parameters in HCC require further elucidation. The present study aimed to investigate LOXL2 expression in HCC from in vitro and clinical aspects. The present study constructed LOXL2‑small interfering RNA with a lentiviral vector, investigated the effect of LOXL2 on proliferation using HCC cell lines via a series of assays, including reverse transcription‑quantitative polymerase chain reaction, cell counting, colony formation, assessment of cell cycle and apoptosis using flow cytometry, MTT and BrdU. Furthermore, 80 tissue samples from HCC patients at The First Affiliated Hospital of Dalian Medical University (Dalian, China) from 2007 to 2010. Immunohistochemical staining was used to clinically verify LOXL2 expression. The results of the present study demonstrate that LOXL2 silencing decreased cell numbers, proliferation, colony formations and cell growth, induced cell cycle arrest and increased apoptosis. Clinically, expression levels of LOXL2 was markedly increased in matched adjacent non‑tumor tissue (ANT) samples compared with levels in tumor tissue (TT) samples, and this gradually increased with higher histological grade and more advanced TNM classification in the matched ANT and TT samples. LOXL2 was determined to promote proliferation of HCC and demonstrated to be highly expressed in HCC ANT samples compared with TT samples. PMID:27430160

  7. Pure laparoscopic hepatectomy for hepatocellular carcinoma with chronic liver disease

    Directory of Open Access Journals (Sweden)

    Zenichi Morise

    2013-01-01

    Full Text Available Pure laparoscopic hepatectomy is a less invasive procedure than conventional open hepatectomy for the resection of hepatic lesions. Increases in experiences with the technique, in combination with advances in technology, have promoted the popularity of pure laparoscopic hepatectomy. However, indications for usage and potential contraindications of the procedure remain unresolved. The characteristics and specific advantages of the procedure, especially for hepatocellular carcinoma (HCC patients with chronic liver diseases, are reviewed and discussed in this paper. For cirrhotic patients with liver tumors, pure laparoscopic hepatectomy minimizes destruction of the collateral blood and lymphatic flow from laparotomy and mobilization, and mesenchymal injury from compression. Therefore, pure laparoscopic hepatectomy has the specific advantage of minimal postoperative ascites production that leads to lowering the risk of disturbance in water or electrolyte balance and hypoproteinemia. It minimizes complications that routinely trigger postoperative serious liver failure. Under adequate patient positioning and port arrangement, the partial resection of the liver in the area of subphrenic space, peri-inferior vena cava area or next to the attachment of retro-peritoneum is facilitated in pure laparoscopic surgery by providing good vision and manipulation in the small operative field. Furthermore, the features of reduced post-operative adhesion, good vision, and manipulation within the small area between the adhesions make this procedure safer in the context of repeat hepatectomy procedures. These improved features are especially advantageous for patients with liver cirrhosis and multicentric and/or metachronous HCCs.

  8. Ruptured hepatocellular carcinoma following chemoembolization:a western experience

    Institute of Scientific and Technical Information of China (English)

    Narendra Battula; Parthi Srinivasan; Mansoor Madanur; Srinivas Prabhu Chava; Oliver Priest; Mohamed Rela; Nigel Heaton

    2007-01-01

    BACKGROUND:Transcatheter arterial chemoembolization (TACE) is a recommended ifrst line therapy for unresectable hepatocellular carcinoma (HCC). Serious complications such as neutropenic sepsis and hepatic decompensation are well known, but rupture of HCC following TACE is a rare and potentially fatal complication. The aim of this study was to identify the incidence of ruptured HCC following TACE and the associated risk factors. METHODS:A retrospective analysis was performed using our liver database with key words "chemoembolization","ruptured HCC" covering the patients who received chemoembolization from January 1995 to December 2005. There were no exclusions. RESULTS:A total of 294 patients received chemoemboliza-tion in 530 sessions during the 10-year period. Of these, 2 ruptured following treatment (incidence 0.68%). The mean age was 65 years and the interval between the treatment and rupture was 2 and 24 days. The common factors were male sex, large tumor size (range 11-13 cm), and exophytic tumor growth. One patient died 2 days after rupture with hepatic decompensation while the second is alive after a 6-month follow up without tumor recurrence. CONCLUSIONS:Ruptured HCC following TACE is a rare but serious complication. Large tumor size, male sex, and exophytic growth of tumor may be predisposing factors for rupture.

  9. Management strategies for hepatocellular carcinoma: old certainties and new realities.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Tarquini, Roberto; Valoriani, Alice; Oben, Jude; Vinciguerra, Manlio; Marra, Fabio

    2016-08-01

    Hepatocellular carcinoma (HCC) is a highly prevalent disease ranking among the ten most common cancers worldwide with increasing trend of incidence in most developed countries. The great healthcare costs and economic burden of HCC dictate proper preventive interventions as well as surveillance and screening programs to decrease disease incidence and allow early diagnosis. HCC treatment outcomes are affected by several variables, including liver function, patient's performance status, and tumor stage. In line with the Barcelona Clinic Liver Cancer (BCLC) staging curative treatments, such as surgery or radio-frequency ablation, are indicated in early-stage HCC (BCLC-A), and the noncurative treatments are indicated in intermediate and advanced stages of HCC (BCLC-B, C). Transarterial chemoembolization (TACE) represents the treatment of choice for intermediate-stage HCC with Child-Pugh A cirrhosis, and the long-term survival after liver transplantation is inferior to that of early-stage HCCs. In advanced-stage HCC or when complete necrosis is not achieved or early recurrence after TACE develops, individualized treatments such as systemic treatment or combined radiation therapy are indicated. The increasing knowledge of the genomic landscape of HCC and the development of molecular-targeted therapies is heading toward expanding the armamentarium for HCC management. PMID:26077653

  10. Hormonal control of the metabolic machinery of hepatocellular carcinoma.

    Science.gov (United States)

    Wong, Carmen Chak-Lui; Wong, Chun-Ming; Ng, Irene Oi-Lin

    2016-06-01

    Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide. It is an aggressive cancer with low cure rate, frequent metastasis, and highly resistant to conventional chemotherapies. Better knowledge regarding the molecular and metabolic alterations in HCC will be instrumental to the development of novel therapeutic interventions against HCC. In the August 2015 issue of Hepatology, Nie et al. reports an important molecular pathway that contributes to the Warburg Effect in HCC. They have beautifully demonstrated that the loss of a component of a hormonal system, the mineralocorticoid receptor (MR), reprogrammed the metabolic machinery of HCC cells to aerobic glycolysis through the miR-338-3p-PKL/R axis. The implication could be that in addition to drugs that directly target the metabolic enzymes in cancer cells, more translational efforts could be focused on the development of drugs that involve the activation of the MR-aldosterone system or other hormonal systems to target the Warburg effect. PMID:27275458

  11. Genome-wide DNA methylation analysis in hepatocellular carcinoma.

    Science.gov (United States)

    Yamada, Nobuhisa; Yasui, Kohichiroh; Dohi, Osamu; Gen, Yasuyuki; Tomie, Akira; Kitaichi, Tomoko; Iwai, Naoto; Mitsuyoshi, Hironori; Sumida, Yoshio; Moriguchi, Michihisa; Yamaguchi, Kanji; Nishikawa, Taichiro; Umemura, Atsushi; Naito, Yuji; Tanaka, Shinji; Arii, Shigeki; Itoh, Yoshito

    2016-04-01

    Epigenetic changes as well as genetic changes are mechanisms of tumorigenesis. We aimed to identify novel genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). We screened for genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in primary HCC (the discovery set). The microarray analysis revealed that there were 2,670 CpG sites that significantly differed in regards to the methylation level between the tumor and non-tumor liver tissues; 875 were significantly hypermethylated and 1,795 were significantly hypomethylated in the HCC tumors compared to the non‑tumor tissues. Further analyses using methylation-specific PCR, combined with expression analysis, in the validation set of primary HCC showed that, in addition to three known tumor-suppressor genes (APC, CDKN2A, and GSTP1), eight genes (AKR1B1, GRASP, MAP9, NXPE3, RSPH9, SPINT2, STEAP4, and ZNF154) were significantly hypermethylated and downregulated in the HCC tumors compared to the non-tumor liver tissues. Our results suggest that epigenetic silencing of these genes may be associated with HCC. PMID:26883180

  12. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Directory of Open Access Journals (Sweden)

    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

  13. Promising Urinary Protein Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Moemen AK Abdalla, Yousef Haj-Ahmad

    2012-01-01

    Full Text Available Hepatocellular Carcinoma is a major healthcare problem, representing the third most common cause of cancer-related mortality worldwide. There are 130 million Hepatitis C virus infected patients worldwide who are at a high-risk for developing Hepatocellular Carcinoma. Due to the fact that reliable parameters and/or tools for the early detection of Hepatocellular Carcinoma among high-risk individuals are severely lacking, Hepatocellular Carcinoma patients are always diagnosed at a late stage where surgical solutions or effective treatment are not possible. Urine was collected from 106 Hepatitis C infected patients patients, 32 of whom had already developed Hepatocellular Carcinoma and 74 patients who were diagnosed as Hepatocellular Carcinoma -free at the time of initial sample collection. In addition to these patients, urine samples were also collected from 12 healthy control individuals. Total urinary proteins were isolated from the urine samples and LC-MS/MS was used to identify potential protein HCC biomarker candidates. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant over-expression of three proteins: DJ-1, Chromatin Assembly Factor-1 (CAF-1 and Heat Shock Protein 60 (HSP60, was a characteristic event among Hepatocellular Carcinoma - post Hepatitis C virus infected patients. As a single-based Hepatocellular Carcinoma biomarker, CAF-1 over-expression identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 90%, sensitivity of 66% and with an overall diagnostic accuracy of 78%. Moreover, the CAF-1/HSP60 tandem identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 92%, sensitivity of 61% and with an overall diagnostic accuracy of 77%.

  14. Promising Urinary Protein Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients.

    Science.gov (United States)

    Abdalla, Moemen Ak; Haj-Ahmad, Yousef

    2012-01-01

    Hepatocellular Carcinoma is a major healthcare problem, representing the third most common cause of cancer-related mortality worldwide. There are 130 million Hepatitis C virus infected patients worldwide who are at a high-risk for developing Hepatocellular Carcinoma. Due to the fact that reliable parameters and/or tools for the early detection of Hepatocellular Carcinoma among high-risk individuals are severely lacking, Hepatocellular Carcinoma patients are always diagnosed at a late stage where surgical solutions or effective treatment are not possible. Urine was collected from 106 Hepatitis C infected patients patients, 32 of whom had already developed Hepatocellular Carcinoma and 74 patients who were diagnosed as Hepatocellular Carcinoma -free at the time of initial sample collection. In addition to these patients, urine samples were also collected from 12 healthy control individuals. Total urinary proteins were isolated from the urine samples and LC-MS/MS was used to identify potential protein HCC biomarker candidates. This was followed by validating relative expression levels of proteins present in urine among all the patients using quantitative real time-PCR. This approach revealed that significant over-expression of three proteins: DJ-1, Chromatin Assembly Factor-1 (CAF-1) and Heat Shock Protein 60 (HSP60), was a characteristic event among Hepatocellular Carcinoma - post Hepatitis C virus infected patients. As a single-based Hepatocellular Carcinoma biomarker, CAF-1 over-expression identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 90%, sensitivity of 66% and with an overall diagnostic accuracy of 78%. Moreover, the CAF-1/HSP60 tandem identified Hepatocellular Carcinoma among Hepatitis C virus infected patients with a specificity of 92%, sensitivity of 61% and with an overall diagnostic accuracy of 77%. PMID:23074380

  15. Trans-arterial chemo-embolization and conformal radiotherapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma is a poor prognosis tumour. The potential curative therapeutic options are ortho-topic liver transplantation, surgical resection and radiofrequency ablation. Unfortunately, only a minority of patients (around 20%) are eligible for these techniques. Thus, patients can benefit from palliative options, such as trans-arterial chemo-embolization (TACE) or sorafenib that bring only modest benefit on survival. Conformal radiotherapy allows delivering high dose radiation within a precise tumour volume while sparing the surrounding liver parenchyma. As employed in mono-therapy, conformal radiotherapy is highly efficient for small size hepatocellular carcinoma (< 5 cm). Above 5 cm, its efficacy is more limited but its association with TACE gives spectacular rates of complete responses. Controlled phase 2 or 3 trials are urgently warranted to define its indications in the therapeutic algorithm of hepatocellular carcinoma. (authors)

  16. Treatment of portal vein tumor thrombosis in patients with hepatocellular carcinoma by TACE

    International Nuclear Information System (INIS)

    Objective: To evaluate the therapeutic effect of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma with tumor thrombosis of portal vein. Methods: One hundred and six patients of hepatocellular carcinoma with tumor thrombosis of portal vein under treatment of TACE were observed before and after the procedure. Results: After TACE tumor size reduced >50% in 23 patients, <50% in 25, no significant change in 44. The size of tumor enlarged in 12. The disappearance of portal vein tumor thrombosis accessed in 14, with reduction in 39, and no significant change in 51. Two patients died within thrombosis accessed in 14, with reduction in 39, and no significant change in 51. Two patients died within on week. Conclusion: TACE provides good therapeutic effect on hepatocellular carcinoma with tumor thrombosis of portal vein. (authors)

  17. Radioembolisation and portal vein embolization before resection of large hepatocellular carcinoma.

    Science.gov (United States)

    Bouazza, Fikri; Poncelet, Arthur; Garcia, Camilo Alejandro; Delatte, Philippe; Engelhom, Jean Luc; Gomez Galdon, Maria; Deleporte, Amélie; Hendlisz, Alain; Vanderlinden, Bruno; Flamen, Patrick; Donckier, Vincent

    2015-08-28

    Resectability of hepatocellular carcinoma in patients with chronic liver disease is dramatically limited by the need to preserve sufficient remnant liver in order to avoid postoperative liver insufficiency. Preoperative treatments aimed at downsizing the tumor and promoting hypertrophy of the future remnant liver may improve resectability and reduce operative morbidity. Here we report the case of a patient with a large hepatocellular carcinoma arising from chronic liver disease. Preoperative treatment, including tumor downsizing with transarterial radioembolization and induction of future remnant liver hypertrophy with right portal vein embolization, resulted in a 53% reduction in tumor volume and compensatory hypertrophy in the contralateral liver. The patient subsequently underwent extended right hepatectomy with no postoperative signs of liver decompensation. Pathological examination demonstrated a margin-free resection and major tumor response. This new therapeutic sequence, combining efficient tumor targeting and subsequent portal vein embolization, could improve the feasibility and safety of major liver resection for hepatocellular carcinoma in patients with liver injury. PMID:26327775

  18. Fibrolamellar Hepatocellular Carcinoma Presenting as Obstructive Jaundice: Uncommon Presentation of a Rare Entity

    International Nuclear Information System (INIS)

    Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor, significantly different from generic hepatocellular carcinoma with distinct demographics, risk factors, imaging features, histopathology and prognosis. Unlike conventional hepatocellular carcinoma, it presents in young individuals with no preexisting hepatitis or cirrhosis and does not cause elevation of serum alpha feto proteins in most cases. This paper presents a case report of this rare tumor in a young female with an unusual clinical manifestation of obstructive jaundice (which has not been reported so far) along with a review of its imaging and pathological features, with treatment options. Fibrolamellar HCC is a rare variant of classic HCC with different epidemiology, risk factors, clinical manifestations, radiological, pathological and prognostic features. Therefore, it is important to be familiar with the entity for its early diagnosis and management

  19. Pre-diagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations

    DEFF Research Database (Denmark)

    Fedirko, Veronika; Duarte-Salles, Talita; Bamia, Christina;

    2014-01-01

    size or smoking status. Conclusion: In this prospective study on Western European populations, serum levels of 25(OH)D were inversely associated with risk of hepatocellular carcinoma. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest......-hydroxyvitamin D [25(OH)D] serum levels and risk of hepatocellular carcinoma in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by...... age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRR) of hepatocellular carcinoma associated with continuous (per 10 nmol/L) or...

  20. Genetic and epigenetic alterations in hepatitis B virus-associated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yongjun; Tian; Jing-hsiung; James; Ou

    2015-01-01

    Hepatitis B virus(HBV) is a major cause of hepatocellular carcinoma(HCC). Its chronic infection can lead to chronic liver inflammation and the accumulation of genetic alterations to result in the oncogenic transformation of hepatocytes. HBV can also sensitize hepatocytes to oncogenic transformation by causing genetic and epigenetic changes of the host chromosomes. HBV DNA can insert into host chromosomes and recent large-scale whole-genome sequencing studies revealed recurrent HBV DNA integrations sites that may play important roles in the initiation of hepatocellular carcinogenesis. HBV can also cause epigenetic changes by altering the methylation status of cellular DNA, the post-translational modification of histones, and the expression of micro RNAs. These changes can also lead to the eventual hepatocellular transformation. These recent findings on the genetic and epigenetic alterations of the host chromosomes induced by HBV opened a new avenue for the development of novel diagnosis and treatments for HBV-induced HCC.

  1. Screening for the early diagnosis of hepatocellular carcinoma: A cost-effectiveness analysis

    International Nuclear Information System (INIS)

    The authors investigated the cost-effectiveness of a screening program for the early diagnosis and treatment of hepatocellular carcinoma (HCC) in liver cirrhosis patients. An hepatocellular carcinoma screening program in liver cirrhosis patients should be carried out when the hepatocellular carcinoma makes a major cause of death and considering that: 1) the diagnosis techniques should be highly sensitive and specific; 2) the overall cost of the screening program should not be too high; 3) patient survival should be improved. Screening all liver cirrhosis patients is a questionable approach because it is very expensive and its benefit in terms of patient survival is poor. More targeted screening programs with definite risk factors should be tested for cost-effectiveness

  2. EFFECT OF DARUHARIDRA AND PUNARNAVA IN HEPATOCELLULAR JAUNDICE: A CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Ram Bhuwal

    2011-05-01

    Full Text Available A clinical study was done on twenty patients of hepatocellular Jaundice. Ghanasatva (water soluble solid of Daruharidra (Berberis aristata DC.(Root and Stem and leave juice of Punarnava (Boerhavia diffusa Linn. was given to patients after their enrollment in study. Signs and symptoms of hepatocellular jaundice as yellow colour of eyes, nails, urine and loss of appetite, weakness, nausea, vomiting, fever, epigastric discomfort as well as biochemical assessment was done as GBP, S. bilirubin, S. alkaline phosphate, SGOT, SGPT & HBsAg etc. were recorded before and after treatment. Self control method was adopted in this study, patients of haemolytic and obstructive jaundice and jaundice due to carcinoma of liver, GB, pancreas etc. were excluded from the study. Assessment suggests improvement in patients suffering from hepatocellular jaundice after three months of treatment.

  3. Role of diffusion-weighted imaging, apparent diffusion coefficient and correlation with hepatobiliary phase findings in the differentiation of hepatocellular carcinoma from dysplastic nodules in cirrhotic liver

    International Nuclear Information System (INIS)

    To investigate the utility of diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and the correlation with hepatobiliary phase (delayed phase imaging, DPI) findings in the differentiation of cirrhotic hepatocellular nodules. Forty-three patients with 53 pathology-proven nodules (29 hepatocellular carcinomas (HCCs), 13 high-grade (HGDNs) and 11 low-grade dysplastic nodules (LGDNs); mean size 2.17 cm, range 1-4 cm), who underwent liver MRI with DWI and DPI sequences, were retrospectively reviewed. Lesions were classified as hypointense, isointense, or hyperintense relative to the adjacent liver parenchyma. ADC of each nodule, of the surrounding parenchyma, and lesion-to-liver ratio were calculated. Hyperintensity versus iso/hypointensity on DWI, hypointensity versus iso/hyperintensity on DPI, and the mean lesion-to-liver ratio showed a statistically significant difference both between HCCs versus DNs and between ''HCCs + HGDNs'' versus LGDNs (p < 0.05); sensitivity, specificity, and accuracy for the diagnosis of ''HCCs + HGDNs'' were 96.8 %, 100 %, 97.4 % respectively when combining hyperintensity on DWI and hypointensity on DPI, and 90.9 %, 81.0 %, 83.6 % respectively when lesion-to-liver ratio was <0.95. Hyperintensity on DWI, especially in association with hypointensity on DPI, and low lesion-to-liver ratios should raise the suspicion of HCC, or at least of HGDN, thus helping the characterization of atypically enhancing lesions. (orig.)

  4. Biogenic-production of SnO2 nanoparticles and its cytotoxic effect against hepatocellular carcinoma cell line (HepG2).

    Science.gov (United States)

    Roopan, Selvaraj Mohana; Kumar, Subramanian Hari Subbish; Madhumitha, Gunabalan; Suthindhiran, Krishnamurthy

    2015-02-01

    In this paper, we have established for the first time, the terrific efficiency of aqueous extract of agricultural waste dried peel of sugar apple (Annona squamosa) in the rapid synthesis of stable SnO2 nanoparticles. In topical years, the deployment of secondary metabolites from plant extract has emerged as a novel technology for the synthesis of various nanoparticles. In this paper, we have studied the potential of SnO2 nanoparticles assembly using agricultural waste source for the first time. The synthesized nanoparticles were characterized and confirmed as SnO2 nanoparticles by using UV-visible spectroscopy, XRD, and TEM analysis. The motivation of this study was to examine cytotoxicity study of SnO2 nanoparticles against hepatocellular carcinoma cell line (HepG2). SnO2 nanoparticles inhibited the cell proliferation in a dose- and time-dependent manner with an IC50 value of 148 μg/mL. The treated cells showed an altered morphology with increasing concentrations of SnO2 nanoparticles. Our result shows that the SnO2 nanoparticles exhibit moderate cytotoxicity towards the hepatocellular carcinoma (HepG2) at tested concentrations. PMID:25410804

  5. Role of diffusion-weighted imaging, apparent diffusion coefficient and correlation with hepatobiliary phase findings in the differentiation of hepatocellular carcinoma from dysplastic nodules in cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Inchingolo, Riccardo; De Gaetano, Anna Maria; Curione, Davide; Ciresa, Marzia; Bonomo, Lorenzo [Catholic University of the Sacred Heart, Department of Bioimaging and Radiological Sciences, Institute of Radiology, ' ' Agostino Gemelli' ' Hospital, Rome (Italy); Miele, Luca; Pompili, Maurizio [Catholic University of the Sacred Heart, Department of Internal Medicine, ' ' Agostino Gemelli' ' Hospital, Rome (Italy); Vecchio, Fabio Maria [Catholic University of the Sacred Heart, Department of Anatomo-Pathology, ' ' Agostino Gemelli' ' Hospital, Rome (Italy); Giuliante, Felice [Catholic University of the Sacred Heart, Department of Surgery, ' ' Agostino Gemelli' ' Hospital, Rome (Italy)

    2015-04-01

    To investigate the utility of diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and the correlation with hepatobiliary phase (delayed phase imaging, DPI) findings in the differentiation of cirrhotic hepatocellular nodules. Forty-three patients with 53 pathology-proven nodules (29 hepatocellular carcinomas (HCCs), 13 high-grade (HGDNs) and 11 low-grade dysplastic nodules (LGDNs); mean size 2.17 cm, range 1-4 cm), who underwent liver MRI with DWI and DPI sequences, were retrospectively reviewed. Lesions were classified as hypointense, isointense, or hyperintense relative to the adjacent liver parenchyma. ADC of each nodule, of the surrounding parenchyma, and lesion-to-liver ratio were calculated. Hyperintensity versus iso/hypointensity on DWI, hypointensity versus iso/hyperintensity on DPI, and the mean lesion-to-liver ratio showed a statistically significant difference both between HCCs versus DNs and between ''HCCs + HGDNs'' versus LGDNs (p < 0.05); sensitivity, specificity, and accuracy for the diagnosis of ''HCCs + HGDNs'' were 96.8 %, 100 %, 97.4 % respectively when combining hyperintensity on DWI and hypointensity on DPI, and 90.9 %, 81.0 %, 83.6 % respectively when lesion-to-liver ratio was <0.95. Hyperintensity on DWI, especially in association with hypointensity on DPI, and low lesion-to-liver ratios should raise the suspicion of HCC, or at least of HGDN, thus helping the characterization of atypically enhancing lesions. (orig.)

  6. Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kenichi Hakamada; Norihisa Kimura; Takuya Miura; Hajime Morohashi; Keinosuke Ishido; Masaki Nara; Yoshikazu Toyoki; Shunji Narumi; Mutsuo Sasaki

    2008-01-01

    AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma.METHODS:Among 142 consecutive patients with known DCP levels,who underwent hepatectomy because of hepatocellular carcinoma,85 patients met the criteria for small hepatocellular carcinoma,i.e.one≤5 cm sized single tumor or no more than three≤3 cm sized tumors.RESULTS:The overall survival rate of the 142 patients was 92.1% for 1 year,69.6% for 3 years,and 56.9% for 5 years.Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP≥400mAU/mL (P = 0.02) were independent prognostic factors.In the group of patients who met the criteria for small hepatocellular carcinoma,DCP≥400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005).In patients who did not meet the criteria,the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01).In 75% of patients with small hepatocellular carcinoma and high DCP levels,recurrence occurred extrahepatically.CONCLUSION:For small hepatocellular carcinoma,a high preoperative DCP level appears indicative for tumor recurrence.Because many patients with a high preoperative DCP level develop extrahepatic recurrence,it is necessary to screen the whole body.

  7. A new cluster-based oversampling method for improving survival prediction of hepatocellular carcinoma patients.

    Science.gov (United States)

    Santos, Miriam Seoane; Abreu, Pedro Henriques; García-Laencina, Pedro J; Simão, Adélia; Carvalho, Armando

    2015-12-01

    Liver cancer is the sixth most frequently diagnosed cancer and, particularly, Hepatocellular Carcinoma (HCC) represents more than 90% of primary liver cancers. Clinicians assess each patient's treatment on the basis of evidence-based medicine, which may not always apply to a specific patient, given the biological variability among individuals. Over the years, and for the particular case of Hepatocellular Carcinoma, some research studies have been developing strategies for assisting clinicians in decision making, using computational methods (e.g. machine learning techniques) to extract knowledge from the clinical data. However, these studies have some limitations that have not yet been addressed: some do not focus entirely on Hepatocellular Carcinoma patients, others have strict application boundaries, and none considers the heterogeneity between patients nor the presence of missing data, a common drawback in healthcare contexts. In this work, a real complex Hepatocellular Carcinoma database composed of heterogeneous clinical features is studied. We propose a new cluster-based oversampling approach robust to small and imbalanced datasets, which accounts for the heterogeneity of patients with Hepatocellular Carcinoma. The preprocessing procedures of this work are based on data imputation considering appropriate distance metrics for both heterogeneous and missing data (HEOM) and clustering studies to assess the underlying patient groups in the studied dataset (K-means). The final approach is applied in order to diminish the impact of underlying patient profiles with reduced sizes on survival prediction. It is based on K-means clustering and the SMOTE algorithm to build a representative dataset and use it as training example for different machine learning procedures (logistic regression and neural networks). The results are evaluated in terms of survival prediction and compared across baseline approaches that do not consider clustering and/or oversampling using the

  8. Identification of T-cell factor-4 isoforms that contribute to the malignant phenotype of hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    The Wnt/β-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). Downstream signaling events involving the Wnt/β-catenin cascade occur through T-cell factor (TCF) proteins. The human TCF-4 gene is composed of 17 exons with multiple alternative splicing sites. However, the role of different TCF-4 isoforms in the pathogenesis of HCC is unknown. The purpose of this study was to identify and characterize TCF-4 isoforms in HCC. We identified 14 novel TCF-4 isoforms from four HCC cell lines. Functional analysis following transfection and expression in HCC cells revealed distinct effects on the phenotype. The TCF-4J isoform expression produced striking features of malignant transformation characterized by high cell proliferation rate, migration and colony formation even though its transcriptional activity was low. In contrast, the TCF-4K isoform displayed low TCF transcriptional activity; cell proliferation rate and colony formation were reduced as well. Interestingly, TCF-4J and TCF-4K differed by only five amino acids (the SxxSS motif). Thus, these studies suggest that conserved splicing motifs may have a major influence on the transcriptional activity and functional properties of TCF-4 isoforms and alter the characteristics of the malignant phenotype.

  9. Identification of T-cell factor-4 isoforms that contribute to the malignant phenotype of hepatocellular carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tsedensodnom, Orkhontuya [Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI (United States); Department of Molecular Biology Cell Biology and Biochemistry, The Warren Alpert Medical School of Brown University, Providence, RI (United States); Koga, Hironori; Rosenberg, Stephen A.; Nambotin, Sarah B.; Carroll, John J.; Wands, Jack R. [Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI (United States); Kim, Miran, E-mail: Miran_Kim@brown.edu [Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI (United States)

    2011-04-15

    The Wnt/{beta}-catenin signaling pathway is frequently activated in hepatocellular carcinoma (HCC). Downstream signaling events involving the Wnt/{beta}-catenin cascade occur through T-cell factor (TCF) proteins. The human TCF-4 gene is composed of 17 exons with multiple alternative splicing sites. However, the role of different TCF-4 isoforms in the pathogenesis of HCC is unknown. The purpose of this study was to identify and characterize TCF-4 isoforms in HCC. We identified 14 novel TCF-4 isoforms from four HCC cell lines. Functional analysis following transfection and expression in HCC cells revealed distinct effects on the phenotype. The TCF-4J isoform expression produced striking features of malignant transformation characterized by high cell proliferation rate, migration and colony formation even though its transcriptional activity was low. In contrast, the TCF-4K isoform displayed low TCF transcriptional activity; cell proliferation rate and colony formation were reduced as well. Interestingly, TCF-4J and TCF-4K differed by only five amino acids (the SxxSS motif). Thus, these studies suggest that conserved splicing motifs may have a major influence on the transcriptional activity and functional properties of TCF-4 isoforms and alter the characteristics of the malignant phenotype.

  10. Hypoxia-induced enhancement of cell invasiveness in SMMC7721 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To explore the effects of hypoxia(1% O2)on the ability of cell invasiveness and expression of KAI1/CD82 in SMMC7721 hepatocellular carcinoma cells.Methods SMMC7721 hepatocellular carcinoma cells were cultured by hypoxia(1% O2)in vitro,and the ability of cell invasiveness was analyzed by cell invasion assay.Immunohistochemistry staining technique was used to evaluate the protein expression of KAI1/CD82.Results Cell invasion assay revealed that hypoxia enhanced the ability of invasiveness of hepatoc...

  11. Major liver resection for hepatocellular carcinoma in the morbidly obese: A proposed strategy to improve outcome

    Directory of Open Access Journals (Sweden)

    Ozaki Claire F

    2008-09-01

    Full Text Available Abstract Background Morbid obesity strongly predicts morbidity and mortality in surgical patients. However, obesity's impact on outcome after major liver resection is unknown. Case presentation We describe the management of a large hepatocellular carcinoma in a morbidly obese patient (body mass index >50 kg/m2. Additionally, we propose a strategy for reducing postoperative complications and improving outcome after major liver resection. Conclusion To our knowledge, this is the first report of major liver resection in a morbidly obese patient with hepatocellular carcinoma. The approach we used could make this operation nearly as safe in obese patients as it is in their normal-weight counterparts.

  12. Multimodality imaging of fat-containing adrenal metastasis from hepatocellular carcinoma.

    Science.gov (United States)

    Tariq, Umar; Poder, Liina; Carlson, David; Courtier, Jesse; Joe, Bonnie N; Coakley, Fergus V

    2012-06-01

    A biopsy-proven fat-containing metastasis to the adrenal gland in a patient with hepatocellular carcinoma demonstrated low density on nonenhanced CT, heterogeneity on contrast-enhanced CT, and marked signal loss on opposed-phase gradient-echo MRI, mimicking an adrenal adenoma. However, the mass was not present on older studies and showed increased FDG uptake on PET. The possibility of a fat-containing metastasis should be considered for an apparent adrenal adenoma in a patient with a primary hepatocellular carcinoma. PMID:22614216

  13. Atypical presentation of hepatocellular carcinoma: a mass on the left thoracic wall

    International Nuclear Information System (INIS)

    Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely. We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region. Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified

  14. Advanced Hepatocellular Carcinoma with Subtotal Occlusion of the Inferior Vena Cava and a Right Atrial Mass

    Directory of Open Access Journals (Sweden)

    Christian Steinberg

    2013-01-01

    Full Text Available Hepatocellular carcinoma usually metastasizes to regional lymph nodes, lung, and bones but can rarely invade the inferior vena cava with intravascular extension to the right atrium. We present the case of a 75-year-old man who was admitted for generalized oedema and was found to have advanced HCC with invasion of the inferior vena cava and endovascular extension to the right atrium. In contrast to the great majority of hepatocellular carcinoma, which usually develops on the basis of liver cirrhosis due to identifiable risk factors, none of those factors were present in our patient.

  15. Expression of PTPeta in human hepatocellular carcinoma tissue and SMMC7721 cells and its significance

    OpenAIRE

    Xu, Xiao-Bing; Zhang, Xiao-Hua; Yang, Miao-Fang; Min-li LI; Zhu, Ren-Min

    2012-01-01

    Objective To investigate the expression of protein tyrosine phosphatase eta (PTPeta) in hepatocellular carcinoma tissue and SMMC-7721 cells, and observe the effects of SMMC7721 cell density on PTPeta expression. Methods  Immunohistochemistry method was used to detect the protein expression of PTPeta in hepatocellular carcinoma tissues and SMMC-7721 cells. RT-PCR was employed to detect the mRNA expression of PTPeta in different growth density of SMMC-7721 cells (1×103, 5×103, 1×104, 5×104/cm2)...

  16. Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized w...

  17. Role of Mitochondrial Translocation of Telomerase in Hepatocellular Carcinoma Cells with Multidrug Resistance

    OpenAIRE

    Ling, Xianlong; Wen, Lei; Zhou, Yuan

    2012-01-01

    Multidrug resistance (MDR) is a major obstacle of cancer chemotherapy. This study aimed to investigate the role of mitochondrial translocation of telomerase (hTERT) in MDR of human hepatocellular carcinoma (HCC) cells. In this study, three HCC cell lines (SK-Hep1/CDDP1 cells, SK-Hep1/CDDP2 cells and SK-Hep1/CDDP3 cells) with differential resistance index (RI) to cisplatin (CDDP) were induced by pulse treatment of SK-Hep1 (human hepatocellular cell line) with CDDP in vitro. The RI of SK-Hep1/C...

  18. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  19. Value of postoperative radiotherapy for centrally located hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Objective: To assess the effects of postoperative radiotherapy on the prognosis and recurrent patterns of centrally located hepatocellular carcinoma (HCC). Methods: From July 2007 to December 2011, 116 patients with centrally located HCC (resection margin < 1 cm) were treated by surgery, and 33 of them received postoperative radiotherapy. The prognosis and recurrent patterns were compared between the postoperative radiotherapy (PORT) group and surgery alone (SA) group. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS); the log-rank test was used for univariate analysis, and the Cox regression model was used for multivariate prognostic analysis. Results: The 1-, 3-, and 5-year sample sizes were 104, 89 and 83, respectively. The 1-, 3-, and 5-year DFS rates for PORT group were 82%, 64%, and 49%, respectively, versus 63%, 52%, and 22% for SA group (P=0.038); the 1-, 3-, and 5-year OS rates for PORT group were 97%, 89%, and 68%, respectively, versus 87%, 68%, and 46% for SA group (P=0.009). The numbers of patients with surgical margin recurrence, single recurrence beyond the margin, and diffuse recurrence in PORT group were 0, 11, and 2, respectively, versus 8, 11, and 18 in SA group (P=0.011); the numbers of patients with early recurrence (within 18 months after surgery) and late recurrence (at least 18 months after surgery) in PORT group were 6 and 7, respectively, versus 36 and 7 in SA group (P=0.016). Conclusions: Postoperative radiotherapy is safe and can significantly improve prognosis in patients with centrally located HCC. (authors)

  20. Biomarkers for hepatocellular carcinoma: diagnostic and therapeutic utility

    Directory of Open Access Journals (Sweden)

    Ferrín G

    2015-04-01

    Full Text Available Gustavo Ferrín,1,2 Patricia Aguilar-Melero,1 Manuel Rodríguez-Perálvarez,1,2 José Luis Montero-Álvarez,1,2 Manuel de la Mata1,2 1Liver Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain; 2Centro de Investigación Biomédica en Red (CIBER, Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain Abstract: Because of the high prevalence and associated-mortality of hepatocellular carcinoma (HCC, early diagnosis of the disease is vital for patient survival. In this regard, tumor size is one of the two main prognostic factors for surgical resection, which constitutes the only curative treatment for HCC along with liver transplantation. However, techniques for HCC surveillance and diagnosis that are currently used in clinical practice have certain limitations that may be inherent to the tumor development. Thus, it is important to continue efforts in the search for biomarkers that increase diagnostic accuracy for HCC. In this review, we focus on different biological sources of candidate biomarkers for HCC diagnosis. Although those biomarkers identified from biological samples obtained by noninvasive methods have greater diagnostic value, we have also considered those obtained from liver tissue because of their potential therapeutic value. To date, sorafenib is the only US Food and Drug Administration-approved antineoplastic for HCC. However, this therapeutic agent shows very low tumor response rates and frequently causes acquired resistance in HCC patients. We discuss the use of HCC biomarkers as therapeutic targets themselves, or as targets to increase sensitivity to sorafenib treatment. Keywords: diagnosis, sorafenib, therapy