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  1. Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma

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    Nguyen, Thuy B; Roncalli, Massimo; Tommaso, Luca Di; Kakar, Sanjay

    2017-01-01

    Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P = 0.4), and pathologically atypical cases (100%, P = 0.5), but significantly higher compared with clinically atypical cases (43%. P = 0.03) and none of typical adenomas (P hepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P = 0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P = 0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in the distinction of typical adenoma from atypical hepatocellular neoplasms. Glypican-3

  2. Combined use of heat-shock protein 70 and glutamine synthetase is useful in the distinction of typical hepatocellular adenoma from atypical hepatocellular neoplasms and well-differentiated hepatocellular carcinoma.

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    Nguyen, Thuy B; Roncalli, Massimo; Di Tommaso, Luca; Kakar, Sanjay

    2016-03-01

    Well-differentiated hepatocellular carcinoma can mimic high-grade dysplastic nodule in cirrhotic liver and hepatocellular adenoma in non-cirrhotic liver. This study evaluates the efficacy of combined use of heat-shock protein 70 (HSP70), glutamine synthetase (GS) and glypican-3 in this setting. Immunohistochemistry for these three markers was done in 17 typical hepatocellular adenoma, 15 high-grade dysplastic nodules, 20 atypical hepatocellular neoplasms (14 clinically atypical and 6 pathologically atypical), 14 very well-differentiated hepatocellular carcinoma, and 43 well-differentiated hepatocellular carcinoma. All three markers were negative in typical adenomas. HSP70 was positive in 10, 71, and 67% of atypical neoplasms, very well-differentiated and well-differentiated HCC, respectively, while GS was positive in 60, 50, and 60% of atypical neoplasms, very well-differentiated and well-differentiated hepatocellular carcinoma, respectively. Glypican-3 was negative in all atypical neoplasms and very well-differentiated hepatocellular carcinoma, and was positive in 27% of well-differentiated hepatocellular carcinoma. Positive staining with at least one marker (HSP70 and/or GS) was seen in 85% of very well-differentiated hepatocellular carcinoma, which was similar to well-differentiated hepatocellular carcinoma (78%, P=0.4), and pathologically atypical cases (100%, P=0.5), but significantly higher compared with clinically atypical cases (43%. P=0.03) and none of typical adenomas (Phepatocellular carcinoma compared with atypical neoplasms (45 vs 10%, P=0.004). Both these markers were also more often expressed in very well-differentiated hepatocellular carcinoma compared with atypical cases (38 vs 10%, P=0.06). In conclusion, the combined use of GS and HSP70 can be useful in the diagnosis of very well-differentiated hepatocellular carcinoma. These stains can also help in the distinction of typical adenoma from atypical hepatocellular neoplasms. Glypican-3 has low

  3. 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.

  4. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues

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    Li, Ning; Long, Yunzhu; Fan, Xuegong; Liu, Hongbo; Li, Cui; Chen, Lizhang; Wang, Zhiming

    2009-01-01

    Abstract Background Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Methods Eighteen cases of HBV-re...

  5. Liver cancer - hepatocellular carcinoma

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    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 ...

  6. Well-differentiated hepatocellular carcinoma in a ring-tailed lemur (Lemur catta).

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    Nemeth, N M; Blas-Machado, U; Cazzini, P; Oguni, J; Camus, M S; Dockery, K K; Butler, A M

    2013-02-01

    A 16-year-old male ring-tailed lemur (Lemur catta) was presented with severe cachexia and an abdominal mass. The encapsulated, multilobular mass replaced the right medial lobe of the liver and compressed the adjacent gall bladder. Multiple haemorrhages and necrotic foci were found within the mass. Microscopically, neoplastic cells formed cords of moderately pleomorphic, polygonal cells with mild to moderate anaplasia. Immunohistochemical markers used for diagnosis of hepatocellular carcinomas in man were used to characterize the neoplastic cells, which expressed hepatocyte-specific antigen, but not glypican-3 or polyclonal carcinoembryonic antigen. Gross, microscopical and immunohistochemical features of the tumour were most consistent with a well-differentiated hepatocellular carcinoma. Although this tumour is common among prosimians, to the authors' knowledge this is the first documented case in a ring-tailed lemur. Hepatocellular carcinomas have been associated with hepatitis virus infections and excessive hepatic iron in man; however, no association was established between this tumour and viral infection or hepatic iron storage disease in the present case. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. [Effects of differentially expressed proteins in hepatocellular carcinoma cell treated by different telomerase inhibitors].

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    Wei, Xiao; Zhang, Zhiyong; He, Min; Wang, Xia; Zheng, Weiwei

    2010-03-01

    To detect differentially expressed proteins in hepatocellular carcinoma cell line SMMC-7721 treated separately by eight telomerase inhibitors including antisense oligodeoxynuclectide of human telomerase RNA (hTR-ASODN), sense oligodeoxynuclectide of hTR (hTR-SODN), ASODN of human telomerase reverse transcriptase (hTERT-ASODN), SODN of hTERT (hTERT-SODN), epigallocatechin gallate (EGCG), 3'-azido-3'-deoxythymidine (AZT), all trans-retinoic acid (ATRA) and adriamycin (ADM) using surface enhanced laser desorption/ionization time of flight-mass spectrom (SELDI-TOF-MS) technology. SELDI-TOF-MS technology and weak cation exchanger (WCX-2) protein chip were used to detect differentially expressed secretory and cytoplasmic proteins of SMMC-7721 cell treated separately by eight telomerase inhibitors. The control group was hepatocellular carcinoma SMMC-7721 cell without any disposal. The results of WCX-2 protein chip showed that the secretory and cytoplasmic proteins were differentially expressed in SMMC-7721 cell treated separately by eight telomerase inhibitors. But some proteins were down-regulated or up-regulated together in all experimental groups. The molecular weight of these differential proteins were all less than 10,000 Da. Differentially expressed and common changes of proteins in SMMC-7721 cell treated separately by eight telomerase inhibitors would associate with telomerase activity.

  8. [Cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma].

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    Fan, Bing-Lin; Zhu, Wu-Ling; Zou, Guo-Lin; Luo, Guo-Sheng; Xu, Chun-Lei; Zhao, Wei-Xing

    2004-03-01

    Abnormal expression of genes is related to development and progression of hepatocellular carcinoma (HCC); however, the detailed mechanism is unclear yet because the known genetic information is not sufficient at present. This study was to explore cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma. The suppression subtractive hybridization was used to obtain subtracted cDNA products of HCC, then the products were cloned by T/A method. The differential expression of gene in HCC was identified by DNA sequencing analysis, Northern blot analysis, rapid amplification of cDNA end (RACE), and reverse transcription polymerase chain reaction (RT-PCR). Firstly, a cDNA fragment of 787 nucleotides was screened from the subtracted cDNA clones, and it was further discovered that the expression of the cDNA fragment was higher significantly in human hepatocellular carcinoma cell strains of SMMC-7721 and HepG2 than in normal hepatocytes by Northern blot analysis. The RACE was carried out and the gene of 1 597 bp containing polyA in 3'end was obtained, which has an entire open reading frame encoding 437 amino acids. Homology analysis showed that this was a gene encoding human FGG. RT-PCR analysis of FGG showed that the amplification of cancerous tissues, especially in metastasis of HCC, was raised as compared to that of adjacent non-cancerous tissues. Overexpression of FGG was discovered in SMMC-7721 and HepG2 cells. The up-regulation of FGG may be associated with the pathogenesis of HCC.

  9. Hepatocellular carcinoma and lifestyles.

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    Saran, Uttara; Humar, Bostjan; Kolly, Philippe; Dufour, Jean-François

    2016-01-01

    The majority of hepatocellular carcinoma occurs over pre-existing chronic liver diseases that share cirrhosis as an endpoint. In the last decade, a strong association between lifestyle and hepatocellular carcinoma has become evident. Abundance of energy-rich food and sedentary lifestyles have caused metabolic conditions such as obesity and diabetes mellitus to become global epidemics. Obesity and diabetes mellitus are both tightly linked to non-alcoholic fatty liver disease and also increase hepatocellular carcinoma risk independent of cirrhosis. Emerging data suggest that physical activity not only counteracts obesity, diabetes mellitus and non-alcoholic fatty liver disease, but also reduces cancer risk. Physical activity exerts significant anticancer effects in the absence of metabolic disorders. Here, we present a systematic review on lifestyles and hepatocellular carcinoma. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  10. Cryotherapy for hepatocellular carcinoma

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    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...... national and topic-specific databases, bibliographies, conference abstracts, journals, and grey literature. Furthermore, we reviewed the reference lists and contacted the principal authors of the identified studies. SELECTION CRITERIA: Randomised clinical trials (irrespective of language or publication...

  11. Distinct MDCT imaging features to differential diagnosis of hepatic paragonimiasis and small hepatocellular carcinoma.

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    Zhang, Sheng; Xie, Si-Ming; Chen, Yong-Hua; Liu, Xu-Bao; Mai, Gang

    2017-06-06

    We used multi-row detector computed tomography (MDCT) to identify the distinguishing characteristics of hepatic paragonimiasis and small hepatocellular carcinoma lesions. We analyzed a cohort of 60 patients, of which 26 had hepatic paragonimiasis and 34 with a small (≤ 3cm) hepatocellular carcinoma. MDCT detected 65 lesions that were retrospectively reviewed and analyzed based on their imaging features. Both groups showed distinct MDCT imaging features that could contribute to an accurate diagnosis. In the paragonimiasis group, 75% (21/28) lesions were located in the hepatic subcapsular region, whereas only 10.8% (4/37) of lesions in the hepatocellular carcinoma group were subcapsular. Most hepatic paragonimiasis lesions (57.1%; 16/28) also showed characteristic tubular or tunnel features that were not present in hepatocellular carcinomas. Further, 71.4% (20/28) paragonimiasis lesions were rim enhanced with irregular tract-like non-enhanced internal areas with a characteristic target loop, while 94.6% (35/37) of small hepatocellular carcinoma lesions showed homogenous enhancement in the arterial and venous phase. In addition, the period CT values for hepatic paragonimiasis were less than those of hepatic carcinomas (Pparagonimiasis from small hepatocellular carcinomas.

  12. Metabolic profiling of hepatitis B virus-related hepatocellular carcinoma with diverse differentiation grades.

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    Zhang, Lei; Huang, Ya; Lian, Mingjian; Fan, Zhijuan; Tian, Yaqiong; Wang, Yufan; Kang, Hua; Liu, Shuang; Liu, Shuye; Li, Tong; Shan, Zhongqiang

    2017-03-01

    The most effective diagnostic tool for the majority of hepatocellular carcinoma (HCC) patients is determining the differentiation grade of their tumors. However liver biopsies, which are currently the most effective way of determining tumor differentiation grade, have several limitations. The present study was designed to select serum characteristic metabolites that correlate with the differentiation grades of hepatitis B virus (HBV)-related HCC, and so could be used in the clinic as a non-invasive method of differentiating patients with different grades of HCC. A total of 58 patients with HBV-related HCC were included in the present study, and divided into three groups according to their tumor differentiation grade. A further 20 patients with HBV-related liver cirrhosis and 19 healthy volunteers were enrolled. Ultra-performance liquid chromatography-mass spectrometry was used to analyze endogenous metabolites. Multivariate statistical analysis was used to examine the data using MZmine 2.0 software. The 14 metabolites that were highly correlated with specific differentiation grades of HCC were then selected for additional study. Receiver operator characteristic curve analysis was used to evaluate their clinical value. In total, 5 metabolites were finally identified, including lysophosphatidylcholine (16:0), oleamide, monoglyceride (0:0/15:0/0:0), lysophosphatidylcholine (18:0) and lysophosphatidylcholine [22:5(7Z,10Z,13Z,16Z,19Z)]. All these metabolites exhibited an excellent ability to distinguish different types of HCC with various differentiation grades and the area under the curve of these metabolites was up to 0.942, showing promising clinical value.

  13. Hepatocellular carcinoma arising in adenoma: similar immunohistochemical and cytogenetic features in adenoma and hepatocellular carcinoma portions of the tumor

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    Paradis, Valerie; Pote, Nicolas; Jakate, Shriram; Ferrell, Linda D

    2016-01-01

    Well-differentiated hepatocellular carcinoma in non-cirrhotic liver can show morphological features similar to hepatocellular adenoma. In rare instances, hepatocellular carcinoma can arise in the setting of hepatocellular adenoma. This study compares the immunohistochemical and cytogenetic features of the hepatocellular adenoma-like and hepatocellular carcinoma portions of these tumors. Immunohistochemistry for β-catenin, glutamine synthetase, serum amyloid A protein, glypican-3, and heat-shock protein 70 was done in 11 cases of hepatocellular carcinoma arising in hepatocellular adenoma in non-cirrhotic liver. Tumors with nuclear β-catenin and/or diffuse glutamine synthetase were considered β-catenin activated. Fluorescence in situ hybridization (FISH) was done in nine cases for gains of chromosomes 1, 8 and MYC. There were seven men (33–75 years) and four women (29–65 years). Focal atypical morphological features were seen in hepatocellular adenoma-like areas in 7 (64%) cases. Hepatocellular adenoma-like areas showed features of inflammatory hepatocellular adenoma in 7 (64%) cases; 4 of these were also serum amyloid A-positive in the hepatocellular carcinoma portion. β-catenin activation, heat-shock protein 70 positivity, and chromosomal gains on FISH were seen in the hepatocellular adenoma portion in 55%, 40%, and 56% of cases, and 73%, 60%, and 78% of cases in the hepatocellular carcinoma portion, respectively. In conclusion, the hepatocellular adenoma-like portion of most cases of hepatocellular carcinoma arising in hepatocellular adenoma shows features typically seen in hepatocellular carcinoma such as focal morphological abnormalities, β-catenin activation, heat-shock protein 70 expression, and chromosomal gains. Hepatocellular adenoma-like areas in these tumors, especially in men and older women, may represent an extremely well-differentiated variant of hepatocellular carcinoma, whereas the morphologically recognizable hepatocellular carcinoma

  14. [Expression features of glypican-3 and its diagnostic and differential values in hepatocellular carcinoma].

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    Bian, Yin-zhu; Yao, Deng-fu; Zhang, Chong-guo; Li, Shan-shan; Wu, Wei; Dong, Zhi-zhen; Qiu, Li-wei; Yu, Dan-dan

    2011-04-01

    To investigate the expression features of glypican-3 (GPC-3) and its diagnostic and differential values in hepatocellular carcinoma (HCC). Rat hepatoma models were made and the dynamic expression features of GPC-3 protein and its gene were investigated by Western blotting and RT-PCR respectively. Liver specimens from 36 HCC patients were collected by self-control method and the expression and clinicopathological features of GPC-3 were analyzed by immunohistochemistry. Serum GPC-3 levels were quantitatively detected by ELISA and its efficiency for HCC diagnosis was evaluated in patients with liver diseases. The incidence of GPC-3 was 0% in control, 83.3% in degeneration, 100% in precancerosis and 100% in canceration during dynamic formation of rat hepatoma, respectively. The positive GPC-3 was brown granule- like staining localized in membrane and cytoplasm in human HCC. The GPC-3 positive rates were 80.6% in HCC, 41.7% in surrounding tissues and none in distal tissues (P differentiation grade or the number of tumor except of tumor size (Z = 2.941, P expression closely associated with HCC and might be useful for early diagnosis of HCC.

  15. Differential Expression of Sonic Hedgehog Protein in Human Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

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    Al-Bahrani, Redha; Nagamori, Seishi; Leng, Roger; Petryk, Anna; Sergi, Consolato

    2015-09-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CCA) are the two most common primary liver malignancies in adult patients. The molecular mechanisms underlying the pathogenesis of HCC and CCA are still poorly understood. Sonic hedgehog (SHH) signaling plays an essential role during mammalian development, i.e., promoting organ growth, tissue differentiation, and cell polarity. The upregulation of SHH has been observed during carcinogenesis, including colorectal carcinoma. Our aim was to investigate the expression pattern of SHH in HCC and CCA. We investigated 40 malignant tumors of the liver, including 21 HCC and 19 of intrahepatic CCA cases by immunohistochemistry (IHC) using a polyclonal antibody against SHH and Avidin-Biotin Complex method. We also investigated the co-localization of SHH and Bone morphogenetic protein 4 (BMP4) in CCA using indirect double IHC. Moreover, we examined whether SHH is expressed in two HCC cell lines HepG2 and HuH-7 and three CCA cell lines OZ, HuCCT1 and HuH28. We found that SHH was expressed in 15 out of 21 cases (71.4 %) of HCC and 100 % of CCA cases by immunohistochemistry. SHH expression showed a positive trend in liver tumors (HCC, CCA) with high grade (G2-G3). SHH localized to the epithelial cells, while BMP4 was expressed in the stromal cells in CCA by double IHC. However, both HCC and CCA cell lines showed SHH expression by Western blot analysis. In conclusion, SHH seems to be an interesting marker of de-differentiation in liver tumors and the simultaneous epithelial-mesenchymal expression may be an intriguing prompt to investigate cross-talks between SHH and BMP4.

  16. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

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    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased γ-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively

  17. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

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    Ionta, M. [Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas MG (Brazil); Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Rosa, M.C.; Almeida, R.B.; Freitas, V.M.; Rezende-Teixeira, P.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-05-25

    Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation [E-cadherin, connexin 26 (Cx26), and connexin 32 (Cx32)]. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

  18. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

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    M. Ionta

    2012-08-01

    Full Text Available Hepatocellular carcinoma (HCC is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM and cAMP (1 mM, an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β and liver differentiation (E-cadherin, connexin 26 (Cx26, and Cx32. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form expression while the expression of Cx43, Tyr216-GSK-3β (active form and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

  19. Differential combinatorial regulatory network analysis related to venous metastasis of hepatocellular carcinoma

    Science.gov (United States)

    2012-01-01

    Background Hepatocellular carcinoma (HCC) is one of the most fatal cancers in the world, and metastasis is a significant cause to the high mortality in patients with HCC. However, the molecular mechanism behind HCC metastasis is not fully understood. Study of regulatory networks may help investigate HCC metastasis in the way of systems biology profiling. Methods By utilizing both sequence information and parallel microRNA(miRNA) and mRNA expression data on the same cohort of HBV related HCC patients without or with venous metastasis, we constructed combinatorial regulatory networks of non-metastatic and metastatic HCC which contain transcription factor(TF) regulation and miRNA regulation. Differential regulation patterns, classifying marker modules, and key regulatory miRNAs were analyzed by comparing non-metastatic and metastatic networks. Results Globally TFs accounted for the main part of regulation while miRNAs for the minor part of regulation. However miRNAs displayed a more active role in the metastatic network than in the non-metastatic one. Seventeen differential regulatory modules discriminative of the metastatic status were identified as cumulative-module classifier, which could also distinguish survival time. MiR-16, miR-30a, Let-7e and miR-204 were identified as key miRNA regulators contributed to HCC metastasis. Conclusion In this work we demonstrated an integrative approach to conduct differential combinatorial regulatory network analysis in the specific context venous metastasis of HBV-HCC. Our results proposed possible transcriptional regulatory patterns underlying the different metastatic subgroups of HCC. The workflow in this study can be applied in similar context of cancer research and could also be extended to other clinical topics. PMID:23282077

  20. Dynamic expression patterns of differential proteins during early invasion of hepatocellular carcinoma.

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    Chen, Rong-Xin; Song, Hai-Yan; Dong, Yin-Ying; Hu, Chao; Zheng, Qiong-Dan; Xue, Tong-Chun; Liu, Xiao-Hui; Zhang, Yang; Chen, Jie; Ren, Zheng-Gang; Liu, Yin-Kun; Cui, Jie-Feng

    2014-01-01

    Tumor cell invasion into the surrounding matrix has been well documented as an early event of metastasis occurrence. However, the dynamic expression patterns of proteins during early invasion of hepatocellular carcinoma (HCC) are largely unknown. Using a three-dimensional HCC invasion culture model established previously, we investigated the dynamic expression patterns of identified proteins during early invasion of HCC. Highly metastatic MHCC97H cells and a liver tissue fragment were long-term co-cultured in a rotating wall vessel (RWV) bioreactor to simulate different pathological states of HCC invasion. The established spherical co-cultures were collected on days 0, 5, 10, and 15 for dynamic expression pattern analysis. Significantly different proteins among spheroids at different time points were screened and identified using quantitative proteomics of iTRAQ labeling coupled with LC-MS/MS. Dynamic expression patterns of differential proteins were further categorized by K-means clustering. The expression modes of several differentially expressed proteins were confirmed by Western blot and qRT-PCR. Time course analysis of invasion/metastasis gene expressions (MMP2, MMP7, MMP9, CD44, SPP1, CXCR4, CXCL12, and CDH1) showed remarkable, dynamic alterations during the invasion process of HCC. A total of 1,028 proteins were identified in spherical co-cultures collected at different time points by quantitative proteomics. Among these proteins, 529 common differential proteins related to HCC invasion were clustered into 25 types of expression patterns. Some proteins displayed significant dynamic alterations during the early invasion process of HCC, such as upregulation at the early invasion stage and downregulation at the late invasion stage (e.g., MAPRE1, PHB2, cathepsin D, etc.) or continuous upregulation during the entire invasion process (e.g., vitronectin, Met, clusterin, ICAM1, GSN, etc.). Dynamic expression patterns of candidate proteins during the early invasion

  1. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues

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    Li Cui

    2009-08-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC, a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC. Although hepatitis B virus (HBV has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Methods Eighteen cases of HBV-related HCC including 12 cases of LC-developed HCC and 6 cases of chronic hepatitis B (CHB-developed HCC were analyzed by two-dimensional electrophoresis (2-DE combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS, and the results were compared to those of paired adjacent non-tumorous liver tissues. Results A total of 17 differentially expressed proteins with diverse biological functions were identified. Among these, 10 proteins were up-regulated, whereas the other 7 proteins were down-regulated in cancerous tissues. Two proteins, c-Jun N-terminal kinase 2 and ADP/ATP carrier protein were found to be up-regulated only in CHB-developed HCC tissues. Insulin-like growth factor binding protein 2 and Rho-GTPase-activating protein 4 were down-regulated in LC-developed and CHB-developed HCC tissues, respectively. Although 11 out of these 17 proteins have been already described by previous studies, or are already known to be involved in hepatocarcinogenesis, this study revealed 6 new proteins differentially expressed in HBV-related HCC. Conclusion These findings elucidate that there are common features between CHB-developed HCC and LC-developed HCC. The identified proteins are valuable for studying the hepatocarcinogenesis, and may be potential diagnostic markers or therapeutic targets for HBV-related HCC.

  2. Proteomic analysis of differentially expressed proteins in hepatitis B virus-related hepatocellular carcinoma tissues.

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    Li, Ning; Long, Yunzhu; Fan, Xuegong; Liu, Hongbo; Li, Cui; Chen, Lizhang; Wang, Zhiming

    2009-08-28

    Hepatocellular carcinoma (HCC), a major cause of cancer death in China, is preceded by chronic hepatitis and liver cirrhosis (LC). Although hepatitis B virus (HBV) has been regarded as a clear etiology of human hepatocarcinogenesis, the mechanism is still needs to be further clarified. In this study, we used a proteomic approach to identify the differential expression protein profiles between HCC and the adjacent non-tumorous liver tissues. Eighteen cases of HBV-related HCC including 12 cases of LC-developed HCC and 6 cases of chronic hepatitis B (CHB)-developed HCC were analyzed by two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), and the results were compared to those of paired adjacent non-tumorous liver tissues. A total of 17 differentially expressed proteins with diverse biological functions were identified. Among these, 10 proteins were up-regulated, whereas the other 7 proteins were down-regulated in cancerous tissues. Two proteins, c-Jun N-terminal kinase 2 and ADP/ATP carrier protein were found to be up-regulated only in CHB-developed HCC tissues. Insulin-like growth factor binding protein 2 and Rho-GTPase-activating protein 4 were down-regulated in LC-developed and CHB-developed HCC tissues, respectively. Although 11 out of these 17 proteins have been already described by previous studies, or are already known to be involved in hepatocarcinogenesis, this study revealed 6 new proteins differentially expressed in HBV-related HCC. These findings elucidate that there are common features between CHB-developed HCC and LC-developed HCC. The identified proteins are valuable for studying the hepatocarcinogenesis, and may be potential diagnostic markers or therapeutic targets for HBV-related HCC.

  3. Characterization of novel monoclonal antibodies that target proteins differentially expressed in hepatocellular carcinoma : a proteomics approach

    OpenAIRE

    Öztaş, Emin

    2011-01-01

    Ankara : The Department of Molecular Biology and Genetics and the Institute of Engineering and Science of Bilkent University, 2011. Thesis (Ph. D.) -- Bilkent University, 2011. Includes bibliographical references leaves 85-91. Hepatocellular carcinoma (HCC) is the sixth common cancer in the world. Because of the late diagnosis of the disease, survival rates are still poor in the HCC patients. Surveillance strategies have to be developed in populations with high risk groups hav...

  4. Differential gene expression profiles of hepatocellular carcinomas associated or not with viral infection

    Directory of Open Access Journals (Sweden)

    M. Bellodi-Privato

    2009-12-01

    Full Text Available Chronic hepatitis B (HBV and C (HCV virus infections are the most important factors associated with hepatocellular carcinoma (HCC, but tumor prognosis remains poor due to the lack of diagnostic biomarkers. In order to identify novel diagnostic markers and therapeutic targets, the gene expression profile associated with viral and non-viral HCC was assessed in 9 tumor samples by oligo-microarrays. The differentially expressed genes were examined using a z-score and KEGG pathway for the search of ontological biological processes. We selected a non-redundant set of 15 genes with the lowest P value for clustering samples into three groups using the non-supervised algorithm k-means. Fisher’s linear discriminant analysis was then applied in an exhaustive search of trios of genes that could be used to build classifiers for class distinction. Different transcriptional levels of genes were identified in HCC of different etiologies and from different HCC samples. When comparing HBV-HCC vs HCV-HCC, HBV-HCC/HCV-HCC vs non-viral (NV-HCC, HBC-HCC vs NV-HCC, and HCV-HCC vs NV-HCC of the 58 non-redundant differentially expressed genes, only 6 genes (IKBKβ, CREBBP, WNT10B, PRDX6, ITGAV, and IFNAR1 were found to be associated with hepatic carcinogenesis. By combining trios, classifiers could be generated, which correctly classified 100% of the samples. This expression profiling may provide a useful tool for research into the pathophysiology of HCC. A detailed understanding of how these distinct genes are involved in molecular pathways is of fundamental importance to the development of effective HCC chemoprevention and treatment.

  5. PBK/TOPK in the differential diagnosis of cholangiocarcinoma from hepatocellular carcinoma and its involvement in prognosis of human cholangiocarcinoma.

    Science.gov (United States)

    He, Furong; Yan, Qingguo; Fan, Linni; Liu, Yixiong; Cui, Jihong; Wang, Juanhong; Wang, Lu; Wang, Yingmei; Wang, Zhe; Guo, Ying; Huang, Gaosheng

    2010-03-01

    The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients. Copyright 2010 Elsevier Inc. All rights reserved.

  6. Low SIRT3 expression correlates with poor differentiation and unfavorable prognosis in primary hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Chris Zhiyi Zhang

    Full Text Available SIRT3, a mitochondrial sirtuin belonging to nicotinamide adenine nucleotide (NAD dependent deacetylases, is implicated in metabolism, longevity and carcinogenesis. SIRT3 expression and its significance in hepatocellular carcinoma (HCC remain largely unclear. In this study, we demonstrated that SIRT3 expression in HCC tissue was much lower than that in paracarcinoma tissue, at both mRNA and protein levels. The cutoff value for low SIRT3 expression in HCC was defined according to receiver operating characteristic curve (ROC analysis. As disclosed by immunohistochemistry (IHC results, low SIRT3 expression was present in 67.3% (167/248 of HCC cases. Furthermore, low expression of SIRT3 was significantly correlated to differentiation (P = 0.013, clinical stage (P = 0.005, serum AFP level (P<0.01, tumor multiplicity (P = 0.026 and relapse (P = 0.028. Moreover, Kaplan-Meier analysis indicated that low SIRT3 expression associated with unfavorable overall survival (P<0.01 and recurrence-free survival (P = 0.004. The prognostic impact of SIRT3 was further confirmed by stratified survival analysis. Importantly, multivariate analysis revealed that low SIRT3 expression was an independent poor prognostic marker for overall survival (Hazard Ratio (HR 0.555, 95% confidence interval (95% CI 0.344-0.897, P = 0.016. Collectively, we conclude that SIRT3 is decreased in HCC and is a novel unfavorable marker for prognosis of patients with this fatal disease.

  7. Dynamic expression patterns of differential proteins during early invasion of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Rong-Xin Chen

    Full Text Available Tumor cell invasion into the surrounding matrix has been well documented as an early event of metastasis occurrence. However, the dynamic expression patterns of proteins during early invasion of hepatocellular carcinoma (HCC are largely unknown. Using a three-dimensional HCC invasion culture model established previously, we investigated the dynamic expression patterns of identified proteins during early invasion of HCC.Highly metastatic MHCC97H cells and a liver tissue fragment were long-term co-cultured in a rotating wall vessel (RWV bioreactor to simulate different pathological states of HCC invasion. The established spherical co-cultures were collected on days 0, 5, 10, and 15 for dynamic expression pattern analysis. Significantly different proteins among spheroids at different time points were screened and identified using quantitative proteomics of iTRAQ labeling coupled with LC-MS/MS. Dynamic expression patterns of differential proteins were further categorized by K-means clustering. The expression modes of several differentially expressed proteins were confirmed by Western blot and qRT-PCR.Time course analysis of invasion/metastasis gene expressions (MMP2, MMP7, MMP9, CD44, SPP1, CXCR4, CXCL12, and CDH1 showed remarkable, dynamic alterations during the invasion process of HCC. A total of 1,028 proteins were identified in spherical co-cultures collected at different time points by quantitative proteomics. Among these proteins, 529 common differential proteins related to HCC invasion were clustered into 25 types of expression patterns. Some proteins displayed significant dynamic alterations during the early invasion process of HCC, such as upregulation at the early invasion stage and downregulation at the late invasion stage (e.g., MAPRE1, PHB2, cathepsin D, etc. or continuous upregulation during the entire invasion process (e.g., vitronectin, Met, clusterin, ICAM1, GSN, etc..Dynamic expression patterns of candidate proteins during the

  8. Identifying the optimal gene and gene set in hepatocellular carcinoma based on differential expression and differential co-expression algorithm.

    Science.gov (United States)

    Dong, Li-Yang; Zhou, Wei-Zhong; Ni, Jun-Wei; Xiang, Wei; Hu, Wen-Hao; Yu, Chang; Li, Hai-Yan

    2017-02-01

    The objective of this study was to identify the optimal gene and gene set for hepatocellular carcinoma (HCC) utilizing differential expression and differential co-expression (DEDC) algorithm. The DEDC algorithm consisted of four parts: calculating differential expression (DE) by absolute t-value in t-statistics; computing differential co-expression (DC) based on Z-test; determining optimal thresholds on the basis of Chi-squared (χ2) maximization and the corresponding gene was the optimal gene; and evaluating functional relevance of genes categorized into different partitions to determine the optimal gene set with highest mean minimum functional information (FI) gain (Δ*G). The optimal thresholds divided genes into four partitions, high DE and high DC (HDE-HDC), high DE and low DC (HDE-LDC), low DE and high DC (LDE‑HDC), and low DE and low DC (LDE-LDC). In addition, the optimal gene was validated by conducting reverse transcription-polymerase chain reaction (RT-PCR) assay. The optimal threshold for DC and DE were 1.032 and 1.911, respectively. Using the optimal gene, the genes were divided into four partitions including: HDE-HDC (2,053 genes), HED-LDC (2,822 genes), LDE-HDC (2,622 genes), and LDE-LDC (6,169 genes). The optimal gene was microtubule‑associated protein RP/EB family member 1 (MAPRE1), and RT-PCR assay validated the significant difference between the HCC and normal state. The optimal gene set was nucleoside metabolic process (GO\\GO:0009116) with Δ*G = 18.681 and 24 HDE-HDC partitions in total. In conclusion, we successfully investigated the optimal gene, MAPRE1, and gene set, nucleoside metabolic process, which may be potential biomarkers for targeted therapy and provide significant insight for revealing the pathological mechanism underlying HCC.

  9. Histopathology of hepatocellular carcinoma.

    Science.gov (United States)

    Schlageter, Manuel; Terracciano, Luigi Maria; D'Angelo, Salvatore; Sorrentino, Paolo

    2014-11-21

    Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

  10. Differentiation of small hepatic hemangioma from small hepatocellular carcinoma: recently introduced spectral CT method.

    Science.gov (United States)

    Lv, Peijie; Lin, Xiao Zhu; Li, Jianying; Li, Weixia; Chen, Kemin

    2011-06-01

    To investigate the usefulness of computed tomographic (CT) spectral imaging parameters in differentiating small (≤3 cm) hepatic hemangioma (HH) from small hepatocellular carcinoma (HCC), with or without cirrhosis, during the late arterial phase (AP) and portal venous phase (PVP). This prospective study was institutional review board approved, and written informed consent was obtained from all patients. The authors examined 49 patients (39 men, 10 women; 65 lesions) with CT spectral imaging during the AP and the PVP. Twenty-one patients had HH; nine, HCC with cirrhosis; and 19, HCC without cirrhosis. Iodine concentrations were derived from iodine-based material-decomposition CT images and normalized to the iodine concentration in the aorta. The difference in iodine concentration between the AP and PVP (ie, iodine concentration difference [ICD]) and the lesion-to-normal parenchyma ratio (LNR) were calculated. Two readers qualitatively assessed lesion types on the basis of conventional CT characteristics. Sensitivity and specificity were compared between the qualitative and quantitative studies. The two-sample t test was performed to compare quantitative parameters between HH and HCC. Normalized iodine concentrations (NICs) and LNRs in patients with HH differed significantly from those in patients with HCC and cirrhosis and those in patients with HCC without cirrhosis: Mean NICs were 0.47 mg/mL ± 0.24 (standard deviation) versus 0.23 mg/mL ± 0.10 and 0.23 mg/mL ± 0.08, respectively, during the AP and 0.83 mg/mL ± 0.38 versus 0.47 mg/mL ± 0.86 and 0.52 mg/mL ± 0.11, respectively, during the PVP. Mean LNRs were 5.87 ± 3.36 versus 2.56 ± 1.10 and 2.29 ± 0.87, respectively, during the AP and 2.01 ± 1.33 versus 0.96 ± 0.16 and 0.93 ± 0.26, respectively, during the PVP. The mean ICD for the HH group (1.37 mg/mL ± 0.84) was significantly higher than the mean ICDs for the HCC-cirrhosis (0.33 mg/mL ± 0.29) (P NIC and LNR had higher sensitivity and specificity

  11. Differential expression of Rab27A/B correlates with clinical outcome in hepatocellular carcinoma.

    Science.gov (United States)

    Dong, Wei-Wei; Mou, Quan; Chen, Jian; Cui, Jian-Tao; Li, Wen-Mei; Xiao, Wen-Hua

    2012-04-21

    To investigate the association of Rab27A and Rab27B expression with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC). We used reverse transcription polymerase chain reaction (RT-PCR), real-time PCR, and Western blotting to detect Rab27A and Rab27B mRNA and protein expression in 5 human HCC lines and the immortalized hepatic HL-7702 cell line. We further examined 148 primary HCC samples matched with adjacent normal tissue and 80 non-HCC specimens by immunohistochemistry to evaluate the correlation of Rab27A and Rab27B expression with clinicopathological features and prognosis. Our data showed that Rab27A and Rab27B were differentially expressed in cell lines and primary HCC tumors. Rab27A mRNA and protein were detected in 67% (4/6) of human cell lines and 80% (4/5) of HCC cell lines, while Rab27B was found in 50% (3/6) of human lines and 40% (2/5) of HCC lines. Rab27A expression was higher in primary HCC (46.2%, 66/143) than in matched adjacent tissue (24.3%, 33/136, P expression and tumor tumor-node-metastasis (TNM) classification (P = 0.046 and P = 0.027, respectively), and between strong Rab27A expression and tumor differentiation grade (P = 0.008). Survival analyses revealed that patients with Rab27A(+) or Rab27B(+) tumors had significantly reduced overall survival compared with that of patients with Rab27A(-) or Rab27B(-) tumors (P = 0.015 and P = 0.005, respectively). Risk analyses revealed that Rab27B(+) and TNM III-IV were independent poor prognosis factors associated with a 3.36- and 3.37-fold higher relative risk of death, respectively. Rab27A and Rab27B expression were closely correlated with tumor progression and can be valuable prognostic indicators for HCC patients.

  12. Differential expression of anterior gradient protein 3 in intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

    Science.gov (United States)

    Brychtova, Veronika; Zampachova, Vita; Hrstka, Roman; Fabian, Pavel; Novak, Jiri; Hermanova, Marketa; Vojtesek, Borivoj

    2014-06-01

    Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer next to hepatocellular carcinoma (HCC). Despite the significant difference of the therapeutic strategy for both diseases, their histological appearance may be very similar. Thus the correct diagnosis is crucial for treatment choice but is often difficult to achieve. The aim of our study was to evaluate anterior gradient 3 (AGR3) as a new diagnostic marker helping to distinguish between ICC and HCC. AGR3 is a putative transmembrane protein implicated in breast, prostate and ovary tumorigenesis and belongs to the family of protein disulfide isomerases. Since there is little information on how AGR3 is expressed in normal and diseased tissues and what its exact function is, we analyzed its expression pattern in normal liver and tumor tissue of ICC and HCC. The immunohistochemical analysis in normal tissue revealed specific AGR3 expression in intrahepatic bile duct cholangiocytes which was not present in liver hepatocytes. Consequently we analyzed AGR3 expression in 74 representative samples of puncture biopsies, tissue excisions and resection specimens from which 48 samples were diagnosed as HCC and 26 as ICC. Our results showed AGR3 expression negative and weakly positive respectively in hepatocellular carcinomas compared to stronger AGR3 positivity in cholangiocellular carcinomas. AGR3 expression statistically significantly correlated to acid mucopolysaccharide expression and negatively correlated to glypican-3 expression. We conclude that according to receiver operating characteristics (ROC) analysis AGR3 expression is relatively specific for ICC and is potentially linked to mucosecretion, which may indicate potential implication in treatment resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Elevated alpha-fetoprotein: differential diagnosis - hepatocellular carcinoma and other disorders.

    Science.gov (United States)

    Wong, Robert J; Ahmed, Aijaz; Gish, Robert G

    2015-05-01

    The incidence of cirrhosis-related hepatocellular carcinoma (HCC) is rising. Curative surgical options are available; outcomes are acceptable with early diagnosis. Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) and des-gamma-carboxy prothrombin (DCP) are HCC risk markers. A high or increasing serum biomarker level can be predictive of the eventual development of HCC, large tumor size, advanced stage, extrahepatic metastases, portal vein thrombosis, and postoperative HCC recurrence. Based on FDA guidelines for HCC risk assessment, clinicians can consider using either the combination of AFP-L3 with DCP, or the combination of AFP-L3 with AFP and DCP. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. 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...

  15. Radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tokuuye, Koichi; Sumi, Minako; Kagami, Yoshikazu; Murayama, Shigeyuki [National Cancer Center Hospital, Tokyo (Japan). Radiation Oncology Div.; Kawashima, Mitsuhiko; Ikeda, Hiroshi [National Cancer Center Hospital East, Chiba (Japan). Radiation Div.; Ueno, Hideki; Okusaka, Takuji; Okada, Shuichi [National Cancer Center Hospital, Tokyo (Japan). Internal Medicine Div.

    2000-09-01

    Purpose: To retrospectively evaluate the effectiveness of radiotherapy with or without transarterial embolization (TAE) and/or percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma who were ineligible for surgery. Patients and Methods: From October 1984 to November 1997, 62 patients underwent radiotherapy receiving 50 to 70 Gy in 25 to 35 treatments with or without transarterial embolization and/or percutaneous ethanol injection and were followed for a median period of 8.6 months (1.5 to 92 months). Results: Overall median survival rates were 9.5 months. Significant prognostic factors were the extent of pretreatment liver function impairment, radiation field size and the existence of tumor thrombosis. Six-month and 1-year local control rates were 67 and 54%, respectively. Seven of the 8 patients who suffered from hepatic failure had poor pretreatment liver functions. Conclusion: Radiotherapy with or without transarterial embolization and/or percutaneous ethanol injection appears effective in controlling hepatocellular carcinoma and prolonged survival. Individualized treatment strategies are presented depending on the tumor presentation and the degree of liver function impairment. (orig.) [German] Hintergrund: Retrospektive Evaluierung der Wirksamkeit einer Bestrahlung mit oder ohne transarterielle Embolisation oder perkutaner Alkoholinjektion bei Patienten mit inoperablem hepatozellulaeren Karzinom. Patienten und Methodik: Von Oktober 1984 bis November 1997 wurden 62 Patienten mit einer Gesamtdosis von 50 bis 70 Gy in 25 bis 35 Fraktionen mit oder ohne transarterielle Embolisation oder perkutane Alkoholinjektion behandelt. Der mediane Follow-up betrug 8,6 Monate (1,5 bis 92 Monate). Ergebnisse: Das mediane Gesamtueberleben betrug 9,5 Monate. Signifikante prognostische Einflussfaktoren waren das Ausmass der praetherapeutischen Leberfunktionseinschraenkung, die Bestrahlungsfeldgroesse und das Vorhandensein von Tumorthrombosen. Nach sechs

  16. Hepatocellular carcinoma: a review

    Directory of Open Access Journals (Sweden)

    Balogh J

    2016-10-01

    Full Text Available Julius Balogh,1,2 David Victor III,1,3,4 Emad H Asham,1,2 Sherilyn Gordon Burroughs,1,2 Maha Boktour,1,2 Ashish Saharia,1,2 Xian Li,1,2 R Mark Ghobrial,1,2 Howard P Monsour Jr,1,3,4 1Sherrie and Alan Conover Center for Liver Disease and Transplantation, 2Division of Transplantation, Department of Surgery, 3Department of Gastroenterology and Transplant Hepatology, 4Department of Medicine, Houston Methodist Hospital, Houston, TX, USA Abstract: Hepatocellular carcinoma (HCC is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an

  17. Sarcoidosis-associated hepatocellular carcinoma.

    Science.gov (United States)

    Ogata, Sho; Horio, Takuya; Sugiura, Yoshiaki; Shimazaki, Hideyuki; Saito, Hiroki; Aiko, Satoshi; Nakanishi, Kuniaki; Kawai, Toshiaki

    2010-12-01

    Sarcoidosis is a systemic granulomatous inflammation of unknown etiology, and seems to involve the liver parenchyma in most cases. However, sarcoidosis-associated hepatocellular carcinoma is rare. We report here a case in which a hepatocellular carcinoma occurred within the liver, which was probably involved as a result of systemic sarcoidosis. A 57-year-old Japanese man had been followed up for 2 years because of diabetic nephropathy and sarcoidosis. On admission for pneumonia, imaging studies revealed an unexpected hepatic tumor. Histology revealed a hepatocellular carcinoma accompanied by T-lymphocytic infiltration and marked granulomatous inflammation, which was surrounding some tumor nodules. The background liver parenchyma exhibited a moderate degree of fibrosis with granulomatous inflammation. The patient had no other apparent liver disease such as viral hepatitis, steatohepatitis, or primary biliary cirrhosis. Therefore, in the present case, sarcoidosis may be considered the probable background etiology for hepatocarcinogenesis.

  18. Genetic heterogeneity of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Unsal, H.; Isselbacher, K.J. (Massachusetts General Hospital Cancer Center, Charlestown, MA (United States)); Yakicier, C.; Marcais, C.; Ozturk, M. (Institut National de la Sante et de la Recherche Medicale, Lyon (France)); Kew, M. (Univ. of Witwatersrand, Johannesburg (South Africa)); Volkmann, M. (Univ. of Heidelberg (Germany)); Zentgraf, H. (Deutsches Krebsforschungszentrum, Heidelberg (Germany))

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  19. Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma

    OpenAIRE

    Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

    2016-01-01

    Background : Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods : Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast micro...

  20. Epidemiology of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mimi C Yu

    2000-01-01

    Full Text Available Although rare in Canada and the United States, hepatocellular carcinoma (HCC ranks as the eighth most common cancer in the world. High-risk regions are East and Southeast Asia, and sub-Saharan Africa. Independent of race and geography, rates in men are at least two to three times those in women; this sex ratio is more pronounced in high-risk regions. Rates of HCC in the United States have increased by 70% over the past two decades. Registry data in Canada and Western Europe show similar trends. In contrast, the incidence of HCC in Singapore and Shanghai, China, both high-risk regions, has declined steadily over the past two decades. Among white and black Americans, there is an inverse relationship between social class status and HCC incidence. Chronic infection by the hepatitis B virus (HBV is by far the most important risk factor for HCC in humans. It is estimated that 80% of HCC worldwide is etiologically associated with HBV. In the United States, although the infection rate in the general population is low, HBV is estimated to account for one in four cases of HCC among non-Asians. Chronic infection by the hepatitis C virus is another important risk factor for HCC in the United States; however, this virus is believed to play a relatively minor role in the development of HCC in Africa and Asia. Dietary aflatoxin exposure is an important codeterminant of HCC risk in Africa and parts of Asia. In Canada and the United States, excessive alcohol intake, cigarette smoking and oral contraceptive use in women also are risk factors for HCC.

  1. Differential requirement for de novo lipogenesis in cholangiocarcinoma and hepatocellular carcinoma of mice and humans.

    Science.gov (United States)

    Li, Lei; Che, Li; Tharp, Kevin M; Park, Hyo-Min; Pilo, Maria G; Cao, Dan; Cigliano, Antonio; Latte, Gavinella; Xu, Zhong; Ribback, Silvia; Dombrowski, Frank; Evert, Matthias; Gores, Gregory J; Stahl, Andreas; Calvisi, Diego F; Chen, Xin

    2016-06-01

    Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty acid synthase (FASN) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-coenzyme A and malonyl-coenzyme A. Increased FASN expression has been reported in multiple tumor types, and inhibition of FASN expression has been shown to have tumor-suppressing activity. Intriguingly, we found that while FASN is up-regulated in human HCC samples, its expression is frequently low in human ICC specimens. Similar results were observed in mouse ICC models induced by different oncogenes. Ablating FASN in the mouse liver did not affect activated AKT and Notch (AKT/Notch intracellular domain 1) induced ICC formation in vivo. Furthermore, while both HCC and ICC lesions develop in mice following hydrodynamic injection of AKT and neuroblastoma Ras viral oncogene homolog oncogenes (AKT/Ras), deletion of FASN in AKT/Ras mice triggered the development almost exclusively of ICCs. In the absence of FASN, ICC cells might receive lipids for membrane synthesis through exogenous fatty acid uptake. In accordance with the latter hypothesis, ICC cells displayed high expression of fatty acid uptake-related proteins and robust long-chain fatty acid uptake. Our data demonstrate that FASN dependence is not a universal feature of liver tumors: while HCC development is highly dependent of FASN and its mediated lipogenesis, ICC tumorigenesis can be insensitive to FASN deprivation; our study supports novel therapeutic approaches to treat this pernicious tumor type with the inhibition of exogenous fatty acid uptake. (Hepatology 2016;63:1900-1913). © 2016 by the American Association for the Study of Liver Diseases.

  2. Differential expression of drug uptake and efflux transporters in Japanese patients with hepatocellular carcinoma.

    Science.gov (United States)

    Namisaki, Tadashi; Schaeffeler, Elke; Fukui, Hiroshi; Yoshiji, Hitoshi; Nakajima, Yoshiyuki; Fritz, Peter; Schwab, Matthias; Nies, Anne T

    2014-12-01

    Targeted chemotherapy for hepatocellular carcinoma (HCC) is impaired by intrinsic and/or acquired drug resistance. Because drugs used in HCC therapy (e.g., anthracyclines or the tyrosine kinase inhibitor sorafenib) are substrates of uptake and/or efflux transporters, variable expression of these transporters at the plasma membrane of tumor cells may contribute to drug resistance and subsequent clinical response. In this study, the variability of expression of uptake transporters [organic cation transporter (OCT) 1 and OCT3] and efflux transporters [multidrug resistance 1 (MDR1)/P-glycoprotein, multidrug resistance protein (MRP) 1, MRP2, and breast cancer resistance protein (BCRP)], selected for their implication in transporting drugs used in HCC therapy, was investigated. HCC and corresponding nontumor tissue samples were collected from 24 Japanese patients at the time of surgery. Protein expression was determined by immunohistochemistry. Expression data were correlated with clinicopathological characteristics and patients' outcome (median follow-up, 53 months). Generally, expression was highly variable among individual tumor samples. Yet median expression of OCT1, OCT3, and MDR1 in HCC was significantly lower (1.4-, 2.7-, and 2-fold, respectively) than in nontumor tissue, while expression of MRP2 persisted and BCRP showed a trend of increased levels in HCC. Patients with low BCRP expression had significantly shorter overall and recurrence-free survival times. Results suggest different expression patterns of drug transporters in HCC, which are associated only in part with clinicopathological characteristics. Detailed information on expression of drug transporters in HCC may be promising for individualization and optimization of drug therapy for liver cancer. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Hepatocellular carcinoma in Danish patients

    DEFF Research Database (Denmark)

    Stefansdottir, Jenna; Christensen, Erik; Schiødt, Frank Vinholt

    2017-01-01

    OBJECTIVE: Hepatocellular carcinoma (HCC) is a common cause of cancer, and most HCC patients have underlying cirrhosis. Retrospectively, we aimed to characterize patients with newly diagnosed HCC at a Danish hospital and to investigate survival and identify predictive factors for survival. METHODS...

  4. New Insights in Hepatocellular Carcinoma

    NARCIS (Netherlands)

    C.D.M. Witjes (Carlijn)

    2012-01-01

    textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC is one of the few cancers with well-defined major risk factors. Worldwide, in 80% of the cases HCC develops in cirrhotic livers, and cirrhosis is the

  5. Differential Proteomics Identification of HSP90 as Potential Serum Biomarker in Hepatocellular Carcinoma by Two-dimensional Electrophoresis and Mass Spectrometry

    OpenAIRE

    Sun, Yiyi; Zang, Zhihe; Xu, Xiaohong; Zhang, Zhonglin; Zhong, Ling; Zan, Wang; Zhao, Yan; Sun, Lin

    2010-01-01

    The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC) carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patie...

  6. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

    Science.gov (United States)

    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; Bhanot, Umesh K.; La Quaglia, Michael P.; Rosenberg, Brad R.; Simon, Sanford M.

    2015-01-01

    Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log2 fold change ≥1, false discovery rate ≤0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention. PMID:26489647

  7. Differential expression of OPN, VEGF-A, and HIF-1α and its clinical significance in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHENG Yan

    2013-01-01

    Full Text Available ObjectiveTo investigate the expression patterns of osteopontin (OPN, vascular endothelial growth factor-A (VEGF-A, and hypoxia-inducible factor-1α(HIF-1α in primary hepatocellular carcinoma (HCC and determine the clinical significance of this differential expression profile. MethodsImmunohistochemical staining of OPN, VEGF-A, and HIF-1α was carried out on primary HCC tissues from 90 patients, HCC-adjacent cirrhosis tissues from 20 of those patients, and normal liver tissues from 15 healthy controls. Correlations between expression levels and HCC clinicopathological characteristics were assessed by Spearman's correlation coefficient. ResultsThe majority of HCC tissues showed positive immunostaining for OPN (69/90, 76.67%, VEGF-A (64/90, 71.11%, and HIF-1α (66/90, 73.33%. OPN- and VEGF-A-positivity were significantly higher than the results from the cirrhosis tissues and normal tissues. HIF-1α-positivity was similar between the HCC and cirrhosis tissues, but both were significantly different from the normal tissues. The differential expressions of OPN, VEGF-A, and HIF-1α were significantly correlated with tumor thrombus, capsular integrity, tumor differentiation and stage, and metastasis (P<0.05. ConclusionHCC tissues overexpress OPN, VEGF-A, and HIF-1α and this differential profile may be related to HCC progression. Future investigations of this triad of factors may provide novel insights into the biological characteristics of HCC and reveal important targets of molecular therapy.

  8. Hepatocellular carcinoma in the adult Fontan patient.

    Science.gov (United States)

    Conroy, Michael R; Moe, Tabitha G

    2017-03-01

    In this study, we describe the case of a 36-year-old woman who was diagnosed with hepatocellular carcinoma on a background of Fontan procedure for tricuspid atresia. She had worsening heart failure in the months before presentation, and early investigations noted derangement in liver enzymes and hepatomegaly. Liver biopsy confirmed a hepatocellular carcinoma. Hepatocellular carcinoma is a rare but recognised consequence of cardiac cirrhosis in Fontan patients.

  9. Differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma on gadoxetic acid-enhanced liver MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rihyeon; Shin, Cheong-Il; Yoon, Jeong Hee; Joo, Ijin; Kim, Seong Ho; Hwang, Inpyeong [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Lee, Jeong Min; Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Seoul (Korea, Republic of); Lee, Eun Sun; Choi, Byung Ihn [Chung-Ang University Hospital, Department of Radiology, Seoul (Korea, Republic of)

    2016-06-15

    To determine the different imaging features of intrahepatic mass-forming cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study was institutional review board approved and the requirement for informed consent was waived. Patients who underwent gadoxetic acid-enhanced MRI with histologically confirmed IMCCs (n = 46) or HCCs (n = 58) were included. Imaging features of IMCCs and HCCs on gadoxetic acid-enhanced MRI including T2- and T1-weighted, diffusion weighted images, dynamic study and hepatobiliary phase (HBP) images were analyzed. Univariate and multivariate logistic regression analyses were performed to identify relevant differentiating features between IMCCs and HCCs. Multivariate analysis revealed heterogeneous T2 signal intensity and a hypointense rim on the HBP as suggestive findings of IMCCs and the wash-in and ''portal wash-out'' enhancement pattern as well as focal T1 high signal intensity foci as indicative of HCCs (all, p < 0.05). When we combined any three of the above four imaging features, we were able to diagnose IMCCs with 94 % (43/46) sensitivity and 86 % (50/58) specificity. Combined interpretation of enhancement characteristics including HBP images, morphologic features, and strict application of the ''portal wash-out'' pattern helped more accurate discrimination of IMCCs from HCCs. (orig.)

  10. New advances in hepatocellular carcinoma

    OpenAIRE

    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 conditi...

  11. Utility of R2* obtained from T2*-weighted imaging in differentiating hepatocellular carcinomas from cavernous hemangiomas of the liver.

    Directory of Open Access Journals (Sweden)

    Meiyu Sun

    Full Text Available PURPOSE: To evaluate the feasibility of applying R2* values to differentiate hepatocellular carcinomas (HCC from cavernous hemangiomas of the liver (CHL. MATERIALS AND METHODS: This retrospective study was approved by the participating Institutional Review Board and written informed consent for all subjects were obtained. Seventy-three patients with 79 pathologically identified HCCs and 65 patients with 91 clinically or pathologically identified CHLs were enrolled in this study. All subjects underwent a breath-hold multi-echo T2* weighted MR imaging on a 1.5 T clinical MR scanner. R2* values from HCC and CHL groups were compared using the Mann-Whitney non-parametric U test. A cut-off value of R2* was evaluated with receiver operator characteristic (ROC analysis. RESULTS: The mean R2* value was 23.32 ± 12.23 Hz (95% confidence interval [CI]: 20.58 Hz, 26.06 Hz for the HCC group, and 3.66 ± 2.37 Hz (95% CI: 3.17 Hz, 4.15 Hz for the CHL group. The mean R2* value for HCC was significantly higher than that of CHL (p<0.001. A threshold of 9.48 Hz for the minimum R2* value in the diagnosis of HCC resulted in a sensitivity of 96.20% (76 out of 79 patients, and a specificity of 97.80% (89 out of 91 patients. The positive predictive value (PPV, negative predictive value (NPV and diagnostic accuracy for HCC were 97.44% (76 out of 78 patients, 96.74% (89 out of 92 patients and 97.06% (165 out of 170 patients, respectively. The AUC for differentiation between these two groups was 0.994 (95% CI: 0.980, 1.000. CONCLUSIONS: R2* is a significant MRI biomarker to differentiate HCC from CHL with satisfying sensitivity and specificity.

  12. Gadoxetate disodium-enhanced MR imaging: Differentiation between early-enhancing non-tumorous lesions and hypervascular hepatocellular carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Goshima, Satoshi, E-mail: gossy@par.odn.ne.jp [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Kanematsu, Masayuki [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Department of Radiology Services, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Watanabe, Haruo; Kondo, Hiroshi; Mizuno, Nozomi; Kawada, Hiroshi [Department of Radiology, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1193 (Japan); Shiratori, Yoshimune [Department of Medical Informatics, Gifu University School of Medicine, Gifu (Japan); Onozuka, Minoru [Department of Physiology and Neuroscience, Kanagawa Dental College, Yokosuka (Japan); Moriyama, Noriyuki [Research Center for Cancer Prevention and Screening, National Cancer Center Hospital, Tsukiji (Japan); Bae, Kyongtae T. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2011-08-15

    Purpose: To retrospectively assess imaging features that help differentiate early-enhancing non-tumorous (EN) hepatic lesions from hepatocellular carcinomas (HCCs) on gadoxetate disodium-enhanced MR imaging. Materials and methods: Our institutional review board approved this retrospective study. We reviewed the studies of 158 patients (92 men and 65 women; age range: 29-91; mean age: 65.6 years) with chronic liver damage, who underwent gadoxetate disodium-enhanced MR imaging at 3T MR scanner. Hypervascular lesions identified during the hepatic artery phase were selected for a study cohort. The location, shape, size (maximum diameter and maximum area), and contrast enhancement signal intensity characteristics of the lesions were evaluated, then compared between the EN and HCC lesions. Results: A total of 65 EN lesions (range: 3-60 mm, mean: 13.6 {+-} 10.6 mm) from 35 patients and 33 HCCs (range: 9-61 mm, mean: 19.3 {+-} 12.6 mm) from 20 patients were identified. Lesions were more frequently round or oval in shape for HCCs (n = 29; 88%) than ENs (n = 26; 40%) (P < 0.01). Unexpectedly, some ENs (n = 12; 18%) showed hypointensity on hepatocyte-phase, and 6 (50%) of them were T2 hyperintense. For lesions smaller than 2 cm (9 ENs and 21 HCCs) on hepatic arterial-phase images, the mean area of hypointensity in hepatocyte-phase (54.2 {+-} 33.1 mm{sup 2}) was significantly smaller than those of the corresponding hyperintensity in hepatic arterial-phase (97.1 {+-} 42.0 mm{sup 2}) for EN lesions (P = 0.019), whereas no significant difference in area was found for HCCs. Conclusion: EN lesions may occasionally present with hypointensity during the hepatocyte-phase; presenting a diagnostic dilemma. In this situation, EN lesions may be differentiated from HCCs when a hypointense area in hepatocyte-phase is smaller than the corresponding hypervascular area in hepatic-arterial phase.

  13. Liver transplantation for Hepatocellular carcinoma: Predictors of ...

    African Journals Online (AJOL)

    DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT Subscription or Fee Access. Liver transplantation for Hepatocellular carcinoma: Predictors of recurrence in our study. HD Smith. Abstract. Hepatocellular carcinoma (HCC) is an aggressive malignancy mostly complicating some underlying liver pathology that ...

  14. Arginase-1 is a more sensitive marker than HepPar-1 and AFP in differential diagnosis of hepatocellular carcinoma from nonhepatocellular carcinoma.

    Science.gov (United States)

    Sang, Wei; Zhang, Wei; Cui, Wenli; Li, Xinxia; Abulajiang, Gulinar; Li, Qiaoxin

    2015-05-01

    Distinguishing hepatocellular carcinoma (HCC) from metastatic tumors is a challenging issue, especially in differential diagnosis between poorly differentiated HCC and metastasis tumors. Expression of Arg-1, HepPar-1, and α-fetoprotein (AFP) in 78 cases of HCC, 34 cases of metastatic tumors, and 228 cases of nonhepatocellular tumors of surgical specimens is measured by immunohistochemistry. Arg-1 immunoreactivity was detected in 75 of 78 (96.1 %) cases of HCC, whereas HepPar-1 and AFP immunoreactivity was detected in 63 of 78 (80.7 %) and 40 of 78 (51.3 %) cases of HCC, respectively. HepPar-1 and AFP expression was observed in three of 34 (8.8 %) cases and one of 34 (2.9 %) cases of metastatic tumors, respectively. In contrast, Arg-1 expression was absent in all 34 (0 %) cases of metastatic tumors. The sensitivity, specificity, positive predictive value, and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors and nonhepatocellular tumors are 96.1, 99.6, 98.7, and 98.8 % compared with 80.7, 92.0, 75.0, and 94.1 % for HepPar-1 and 51.3, 97.7, 87.0, and 87.1 % for AFP, respectively. Arg-1 is a more sensitive and better specific marker for HCC compared with HepPar-1 and AFP, indicating that Arg-1 can be easily applied in distinguishing HCC from metastatic tumors.

  15. Integrative and comparative genomics analysis of early hepatocellular carcinoma differentiated from liver regeneration in young and old

    Directory of Open Access Journals (Sweden)

    Ozand Pinar T

    2010-06-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is the third-leading cause of cancer-related deaths worldwide. It is often diagnosed at an advanced stage, and hence typically has a poor prognosis. To identify distinct molecular mechanisms for early HCC we developed a rat model of liver regeneration post-hepatectomy, as well as liver cells undergoing malignant transformation and compared them to normal liver using a microarray approach. Subsequently, we performed cross-species comparative analysis coupled with copy number alterations (CNA of independent early human HCC microarray studies to facilitate the identification of critical regulatory modules conserved across species. Results We identified 35 signature genes conserved across species, and shared among different types of early human HCCs. Over 70% of signature genes were cancer-related, and more than 50% of the conserved genes were mapped to human genomic CNA regions. Functional annotation revealed genes already implicated in HCC, as well as novel genes which were not previously reported in liver tumors. A subset of differentially expressed genes was validated using quantitative RT-PCR. Concordance was also confirmed for a significant number of genes and pathways in five independent validation microarray datasets. Our results indicated alterations in a number of cancer related pathways, including p53, p38 MAPK, ERK/MAPK, PI3K/AKT, and TGF-β signaling pathways, and potential critical regulatory role of MYC, ERBB2, HNF4A, and SMAD3 for early HCC transformation. Conclusions The integrative analysis of transcriptional deregulation, genomic CNA and comparative cross species analysis brings new insights into the molecular profile of early hepatoma formation. This approach may lead to robust biomarkers for the detection of early human HCC.

  16. Current management of hepatocellular carcinoma

    Science.gov (United States)

    Tabrizian, Parissa; Roayaie, Sasan; Schwartz, Myron E

    2014-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice. PMID:25132740

  17. [Systemic treatment for hepatocellular carcinoma].

    Science.gov (United States)

    Spangenberg, H C; Zuber-Jerger, I; Thimme, R; Blum, H E; Von Weizsäcker, F

    2003-11-01

    Hepatocellular carcinoma (HCC) is one of the most frequent malignancies worldwide. A variety of pharmacological strategies has been evaluated in the treatment of HCC: classical chemotherapy, tamoxifen, octreotide, thymostimulin, pravastatin, (131)I-lipiodol as well as transarterial chemoperfusion (TAC) and chemoembolisation (TACE). TACE monotherapy or TACE combined with pravastatin resulted in a survival benefit of selected HCC patients. New strategies such as immunotherapy, antiangiogenic agents or cyclooxygenase inhibitors are under clinical investigation and might play a role in future therapies for HCC. Efficient strategies for the primary prevention of HCC are available and promising concepts in the secondary prevention have been reported.

  18. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)

    1994-12-01

    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  19. Radiation-induced cholangitis with hepatocellular carcinoma.

    Science.gov (United States)

    Gorea, G; Demy, M; Tran Van Nhieu, J; Tigori, J; Aubé, C; Cherqui, D; Oberti, F; Caroli-Bosc, F-X; Calès, P

    2010-01-01

    There are no reports of hepatocellular carcinoma complicating postradiotherapy cholangitis. We report the case of a 45-year-old patient who had undergone upper abdominal radiotherapy for Hodgkin's disease, 21 years before, which was complicated years later by cholangitis with stricture of the common bile duct. Biliodigestive anastomosic surgery was scheduled due to recurrent angiocholitis, and hepatocellular carcinoma was discovered. The patient died from carcinoma some months later. Copyright 2009 Elsevier Masson SAS. All rights reserved.

  20. Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray.

    Science.gov (United States)

    Liu, Yuefang; Zhu, Xiaojing; Zhu, Jin; Liao, Shibing; Tang, Qi; Liu, Kaikun; Guan, Xiaohong; Zhang, Jianping; Feng, Zhenqing

    2007-10-01

    The genetic background of hepatocellular carcinoma (HCC) has yet to be completely understood. Here, we describe the application of suppression subtractive hybridization (SSH) coupled with cDNA microarray analysis for the isolation and identification of differential expression of genes in HCC. Twenty-six known genes were validated as up-regulated and 19 known genes as down-regulated in HCC. The known genes identified were found to have diverse functions. In addition to the overexpression of AFP, these genes (increased in the presence of HCC) are involved in many processes, such as transcription and protein biosynthesis (HNRPDL, PABPC1, POLR2K, SRP9, SNRPA, and six ribosomal protein genes including RPL8, RPL14, RPL41, RPS5, RPS17, RPS24), the metabolism of lipids and proteins (FADS1, ApoA-II, ApoM, FTL), cell proliferation (Syndecan-2, and Annexin A2), and signal transduction (LRRC28 and FMR1). Additionally, a glutathione-binding protein involved in the detoxification of methylglyoxal known as GLO1 and an enzyme which increases the formation of prostaglandin E(2) known as PLA2G10 were up-regulated in HCC. Among the underexpressed genes discovered in HCC, most were responsible for liver-synthesized proteins (fibrinogen, complement species, amyloid, albumin, haptoglobin, hemopexin and orosomucoid). The enzyme implicated in the biotransformation of CYP family members (LOC644587) was decreased. The genes coding enzymes ADH1C, ALDH6A1, ALDOB, Arginase and CES1 were also found. Additionally, we isolated a zinc transporter (Zip14) and a function-unknown gene named ZBTB11 (Zinc finger and BTB domain containing 11) which were underexpressed, and seven expression sequence tags deregulated in HCC without significant homology reported in the public database. Essentially, by using SSH combined with a cDNA microarray we have identified a number of genes associated with HCC, most of which have not been previously reported. Further characterization of these differentially expressed

  1. Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

    Directory of Open Access Journals (Sweden)

    Helma P. Cotrim

    2016-05-01

    Full Text Available OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul. The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3, in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in

  2. Differential expression of store-operated calcium- and proliferation-related genes in hepatocellular carcinoma cells following TRPC1 ion channel silencing.

    Science.gov (United States)

    Selli, Cigdem; Pearce, Dominic A; Sims, Andrew H; Tosun, Metiner

    2016-09-01

    TRPC1 and store-operated Ca(2+) (SOC) entry have previously been associated with hepatocellular carcinoma cell proliferation. The aim of the study was to determine genes and processes associated with TRPC1 down-regulation and the resulting increase of SOC entry and decrease in hepatocellular carcinoma cell proliferation. For this purpose, transcriptome analysis was performed to determine differentially expressed genes in TRPC1-silenced Huh7 cells. SOC entry- and proliferation-related genes correlated with TRPC1 down-regulation were also examined. Changes in SOC entry and cell proliferation were monitored in the TRPC1-silenced and parental cells and found to be significantly increased and decreased, respectively, in TRPC1-silenced cells. A total of 71 genes were significantly differentially expressed (40 up- and 31 down-regulated), including four mitogen-activated protein kinase (MAPK) signalling-associated genes. STIM1 levels were significantly up-regulated and negatively correlated with TRPC1 levels. In addition, expression of two cell cycle regulation genes, CDK11A/11B and URGCP, was observed to decrease, whereas ERBB3 and FGFR4, pro-survival genes, increased significantly in TRPC1-silenced cells. In conclusion, these results suggest reciprocal alterations in TRPC1 and STIM1 levels and a role for STIM1 in the regulation of SOC entry in TRPC1-silenced Huh7 cells. In addition to TRPC1, STIM1 may participate in Huh7 cell proliferation by regulating SOC entry. Alterations in MAPK signalling genes may be involved in diminished cell proliferation in TRPC1-silenced Huh7 cells. Similarly, changes in cell cycle regulating genes in TRPC1-silenced cells indicate possible cell cycle arrest along with compensatory up-regulation of ERBB3 growth factor receptor-amongst others-to maintain hepatocellular carcinoma cell proliferation.

  3. Differential proteomic analysis of cancer stem cell properties in hepatocellular carcinomas by isobaric tag labeling and mass spectrometry.

    Science.gov (United States)

    Ko, Ching-Huai; Cheng, Chieh-Fang; Lai, Chin-Pen; Tzu, Te-Hui; Chiu, Chih-Wei; Lin, Mei-Wei; Wu, Si-Yuan; Sun, Chung-Yuan; Tseng, Hsiang-Wen; Wang, Chun-Chung; Kuo, Zong-Keng; Wang, Ling-Mei; Chen, Sung-Fang

    2013-08-02

    Malignant tumors are relatively resistant to treatment due to their heterogeneous nature, drug resistance, and tendency for metastasis. Recent studies suggest that a subpopulation of cancer cells is responsible for the malignant outcomes. These cells are considered as cancer stem cells (CSC). Although a number of molecules have been identified in different cancer cells as markers for cancer stem cells, no promising markers are currently available for hepatocellular carcinoma cells. In this study, two clones of Hep3B cell lines were functionally characterized as control or CSC-like cells, based on properties including spheroid formation, drug resistance, and tumor initiation. Furthermore, their protein expression profiles were investigated by isobaric tags for relative and absolute quantitation (iTRAQ), and a total of 1,127 proteins were identified and quantified from the combined fractions; 50 proteins exhibited at least 2-fold differences between these two clones. These 50 proteins were analyzed by GeneGo and were found to be associated with liver neoplasms, hepatocellular carcinoma (HCC), and liver diseases. They were also components of metabolic pathways, immune responses, and cytoskeleton remodeling. Among these proteins, the expressions of S100P, S100A14, and vimentin were verified in several HCC cell lines, and their expressions were correlated with tumorigenicity in HCC cell lines. The functional significance of vimentin and S100A14 were also investigated and verified.

  4. Methylation in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    The development of HCC is a complex, multistep, multistage process. The molecular pathogenesis of HCC appears to involve multiple genetic aberrations in the molecular control of hepatocyte proliferation, differentiation and death and the maintenance of genomic integrity. This process is influenced by the cumulative activation and inactivation of oncogenes, tumor suppressor genes and other genes. p53, a tumor suppressor gene, is the most frequently mutated gene in human cancers. There is also a striking sequence specific binding and induction of mutations by AFB1 at codon 249 of p53 in HCC.

    Epigenetic alterations are also involved in cancer development and progression. Methylation of promoter CpG islands is associated with inhibition of transcriptional initiation and permanent silencing of downstream genes.

    It is now known that most important tumor suppressor genes are inactivated, not only by mutations and deletions but also by promoter methylation. Several studies indicated that p16, p15, RASSF1A, MGMT, and GSTP1 promoter hypermethylation are prevalent in HCC. In addition, geographic variation in the methylation status of tumor DNA indicates that environmental factors may influence the frequent and concordant degree of hypermethylation in multiple genes in HCC and that epigeneticenvironmental interactions may be involved in hepatocarcinogenesis. We have found significant relationships between promoter methylation and AFB1-DNA adducts confirming the impact of environmental exposures on gene methylation.

    DNA isolated from serum or plasma of cancer patients frequently contains the same genetic and

  5. Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis.

    Science.gov (United States)

    He, Ling; Zhang, Jianing; Jiang, Lili; Jin, Changgong; Zhao, Yongfu; Yang, Guang; Jia, Li

    2010-10-01

    Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cancers. In this study, the differential expressions of Axl were investigated in mouse hepatocarcinoma cell lines Hca-F and Hca-P, which have high- and low-metastatic potential to lymph nodes. Experimental inhibition of Axl by siRNA assessed further the metastatic potential of Axl. The results showed that down-regulation of Axl expression attenuated Hca-F cells proliferation, migration, and invasion in vitro, as well as inhibited metastasis to peripheral lymph nodes in vivo. Further analysis demonstrated that the addition of exogenous Gas6 mediated the migration and invasion of Hca-F cells both in vitro and in vivo through Axl. Furthermore, Gas6 stimulation of Axl in Hca-F cells resulted primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data suggest that Axl acts as a tumor lymphatic metastasis-associated gene, and may function partly through the regulation of Cyr61. © 2010 Wiley-Liss, Inc.

  6. Clinicopathological review of hepatocellular carcinoma in black ...

    African Journals Online (AJOL)

    Saharan Africa. The tumour runs a particularly fulminant course and is a major cause of deaths from cancer in the sub-continent. In most Black African patients, hepatocellular carcinoma presents clinically with typical symptoms and physical findings.

  7. Percutaneous cryoablation for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kyoung Doo Song

    2016-12-01

    Full Text Available Local ablation therapy is considered as a conventional treatment option for patients with early stage hepatocellular carcinoma (HCC. Although radiofrequency (RF ablation is widely used for HCC, the use of cryoablation has been increasing as newer and safer cryoablation systems have developed. The thermodynamic mechanism of freezing and thawing used in cryoablation is the Joule-Thomson effect. Cryoablation destroys tissue via direct tissue destruction and vascular-related injury. A few recent comparative studies have shown that percutaneous cryoablation for HCCs is comparable to percutaneous RF ablation in terms of long term therapeutic outcomes and complications. Cryoablation has several advantages over RF ablation such as well visualization of iceball, no causation of severe pain, and lack of severe damage to great vessels and gallbladder. It is important to know the advantages and disadvantages of cryoablation compared with RF ablation for improvement of therapeutic efficacy and safety.

  8. Glutathione treatment of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Ranek, L; Mantoni, M

    1992-01-01

    abnormal alfa-1-fetoprotein (AFP) returned to normal after GSH treatment. AFP remained normal throughout the treatment period in the other women. These observations indicate that GSH may have a sex-dependent effect on HCC. However, further studies involving more patients are required to pursue......This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH...... daily from the time of diagnosis. Two patients withdrew shortly after receiving GSH due to intolerable side-effects. Of the six eligible patients, two had mildly advanced tumors and four moderately advanced tumors. At 1-2-month intervals the liver was CT and ultra-sound scanned to assess the growth...

  9. An acute unusual presentation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zubin Dev Sharma

    2014-01-01

    Full Text Available Hepatocellular Carcinoma (HCC is a growing cause of mortality world over. The common risk factors include cirrhosis, viral infections, aflatoxin amongst others. Alpha Fetoprotein (AFP levels and Ultrasonography (USG are the preferred surveillance tools in early diagnosis of HCC. Here we present an unusual case of a young female with no known risk factors, no cirrhosis, no viral markers, and normal AFP levels who had a Acute hepatic failure eventually diagnosed as Primary Hepatocellular carcinoma.

  10. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients

    OpenAIRE

    Decaens, Thomas; Roudot-Thoraval, Françoise; Bresson-Hadni, Solange; Meyer, Carole; Gugenheim, Jean; Durand, Francois; Bernard, Pierre-Henri; Boillot, Olivier; Compagnon, Philippe; Calmus, Yvon; Hardwigsen, Jean; Ducerf, Christian; Pageaux, Georges Philippe; Dharancy, Sébastien; Chazouillères, Olivier

    2006-01-01

    AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT).

  11. 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.

    Science.gov (United States)

    Inchingolo, Riccardo; De Gaetano, Anna Maria; Curione, Davide; Ciresa, Marzia; Miele, Luca; Pompili, Maurizio; Vecchio, Fabio Maria; Giuliante, Felice; Bonomo, Lorenzo

    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 Correlation of DWI with DPI improves differential diagnosis of cirrhotic nodules. • Characterization of atypically enhancing lesions becomes more confident.

  12. Differential Proteomics Identification of HSP90 as Potential Serum Biomarker in Hepatocellular Carcinoma by Two-dimensional Electrophoresis and Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Yiyi Sun

    2010-03-01

    Full Text Available The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patients was confirmed using ELISA analysis. The observations suggest that HSP90 might be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of HCC. This work demonstrates that a comprehensive strategy of proteomic identification combined with further validation should be adopted in the field of cancer biomarker discovery.

  13. Surgical treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Laca, L; Dedinska, I; Miklusica, J; Janik, J; Palkoci, B; Pindura, M

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) in Europe and throughout the world is currently increasing. This is caused by an increase in the number of patients with alcoholic liver damage, metabolic syndrome, and by increasing incidence of hepatitis B and C.From January 1, 2004 to December 31, 2013, resection or radiofrequency ablation of the liver was done in 360 patients with benign lesions or malignant tumors of the liver. In 28 patients HCC was diagnosed and histologically confirmed (7.8 %). Seven patients had HCC associated with liver cirrhosis (25 %), and 21 patients were without histologically confirmed cirrhosis (75 %). R0 resection was done in 18 (64 %) patients.Surgical complications occurred in 6 (21 %) patients and reoperation due to tumor relapse or progression was done eight times in 6 (21 %) patients. One-year and five-year patients' survivals were 64 % and 10 %, repectively, and did not statistically differ from the survival of the whole set of patients with tumor diseases in the given time period. In the future it will be possible to improve the long-term survival of patients with HCC by using screening methods for presymptomatic diagnosis of HCC, precise preoperative diagnosis and efforts for R0 resection (Tab. 1, Fig. 4, Ref. 11).

  14. [Differential display of messenger RNA and identification of selenocysteine lyase gene in hepatocellular carcinoma cells transiently expressing hepatitis C virus core protein].

    Science.gov (United States)

    Yepes, Jesús Orlando; Luz Gunturiz, María; Henao, Luis Felipe; Navas, María Cristina; Balcázar, Norman; Gómez, Luis Alberto

    2006-06-01

    Hepatitis C virus is associated with diverse liver diseases including acute and chronic hepatitis, steatosis, cirrhosis and hepatocellular carcinoma. Several studies have explored viral mechanisms involved in the establishment of persistent infection and oncogenic Hepatitis C virus. Expression assays of Hepatitis C virus core protein suggest that this protein has transforming and carcinogenic properties with multifunctional activities in host cells. Characterization of expressed genes in cells expressing Core protein is important in order to identify candidate genes responsible for these pathogenic alterations. To compare and identify gene expression profiles in the human hepatocarcinoma derived cell line, HepG2, with transient expression of Hepatitis C virus Core protein. We have used comparative PCR-mediated differential display of mRNA from HepG2 hepatocarcinoma with and without transient expression of HCV Core protein or green fluorescent protein, previously obtained using the Semliki Forest Virus-based expression, through transduction of recombinant particles, rSFV-Core and rSFV-GFP, respectively. We observed differences in band intensities of mRNA in HepG2 cells transduced with rSFV-Core compared with those detected in cells without transduction, and transduced with rSFV-GFP. Cloning and sequencing of a gene fragment (258 bp) that was expressed differentially in HepG2 cells transduced with rSFV-Core, was identified as selenocystein lyase. The results confirm that HCV Core protein expressed in HepG2 is associated with specific changes in mRNA expression, including the gene for selenocystein lyase. This gene may be involved in the pathophysiology of hepatocellular carcinoma.

  15. Evaluating histologic differentiation of hepatitis B virus-related hepatocellular carcinoma using intravoxel incoherent motion and AFP levels alone and in combination.

    Science.gov (United States)

    Shan, Qungang; Chen, Jingbiao; Zhang, Tianhui; Yan, Ronghua; Wu, Jun; Shu, Yunhong; Kang, Zhuang; He, Bingjun; Zhang, Zhongping; Wang, Jin

    2017-08-01

    To evaluate histologic differentiation of hepatitis B virus (HBV)-related hepatocellular carcinomas (HCCs) using apparent diffusion coefficient (ADC) and intravoxel incoherent motion (IVIM)-derived metrics and to compare findings with alpha-fetoprotein (AFP) levels alone and in combination. One hundred and six chronic HBV-related HCC patients who underwent IVIM diffusion-weighted magnetic resonance imaging with eleven b values were enrolled. Mean ADC, diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) values were determined for all detected lesions. The metrics and AFP levels of different histologically differentiated groups were compared. Spearman's rank correlation was used to assess the statistical dependence among the histologically differentiated HCCs. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance of these metrics and AFP levels alone and in combination. ADC, D, and f values and AFP levels were significantly different among well-, moderately, and poorly differentiated HCCs. The four metrics were significantly correlated with histologic differentiation. The area under the ROC curve (AUC-ROC) of ADC, D, f, and AFP for diagnosing well-differentiated HCCs was 0.903, 0.84, 0.782, and 0.806, respectively, and the AUC-ROC of above metrics for diagnosing poorly differentiated HCCs was 0.787, 0.726, 0.624, and 0.633, respectively. The combination of ADC and AFP provided an AUC-ROC of 0.945 for well-differentiated HCC. However, this did not provide better performance for diagnosing poorly differentiated HCC. ADC, IVIM metrics, and AFP levels may be useful for evaluating histologic differentiation of HBV-related HCCs, and the combination of ADC and AFP provides better diagnostic performance for well-differentiated HCC.

  16. 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.)

  17. Welcome to Journal of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Kaseb AO

    2015-01-01

    Full Text Available 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 need for a dedicated journal for HCC with special emphasis on understanding pathogenesis, emerging diagnosis and treatment approaches, and translational research strategies.The new journal Journal of Hepatocellular Carcinoma strives to be the essential clinical guide for medical and surgical oncologists, hepatologists, interventional radiologists, and all physicians and researchers involved in the care of patients with HCC. Our journal is committed to building an intercontinental community of researchers and clinicians to encourage establishment of collaborations and development of improved strategies to advance the field and help our patients from a global prospective. HCC is a very heterogeneous disease with multiple risk factors and noted differences in natural history and treatment outcomes based on demographics, risk factors, and even geographic locations, as evident by the noted difference in the magnitude of effects and rate of adverse events based on recent clinical trials conducted on different continents using the same systemic or local therapy modality.1 Therefore, one of the ultimate goals of the journal is to advance our understanding of the biology and natural history of HCC given the differential outcome based on these variables.

  18. Current radiologic interventions in hepatocellular carcinoma.

    Science.gov (United States)

    Qasmi, Imran Masoud; Naeem, Tahir; Farrukh, Saeed; Mirza, Shakeel Ahmed; Khan, Muhammad Asad; Bhatti, Muhammad Asghar

    2006-09-01

    With the rising incidence of chronic liver disease caused by viral hepatitis, hepatocellular carcinoma is showing a corresponding rise worldwide. Surgery remains the mainstay of treatment, but patients unfit for surgery or liver transplantation form the bulk of those presenting with this disease. Palliative treatments are being used to treat those and radiological modalities form the mainstay of the treatment. Radiology plays a major role in the diagnosis, treatment and follow-up of hepatocellular carcinoma. Current radiological treatment modalities include percutaneous ethanol ablation, radiofrequency ablation and trans-arterial chemoembolization. This update highlights the recent advancements in the field and compares their relative merits and demerits.

  19. 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

  20. Mediterranean diet and hepatocellular carcinoma.

    Science.gov (United States)

    Turati, Federica; Trichopoulos, Dimitrios; Polesel, Jerry; Bravi, Francesca; Rossi, Marta; Talamini, Renato; Franceschi, Silvia; Montella, Maurizio; Trichopoulou, Antonia; La Vecchia, Carlo; Lagiou, Pagona

    2014-03-01

    Hepatocellular carcinoma (HCC) has a very poor prognosis and any effort to identify additional risk factors, besides those already established, would be important for the prevention of the disease. Data on the role of diet on HCC risk are still controversial. We have evaluated the association of adherence to the Mediterranean diet with HCC risk, as well as the interaction of this dietary pattern with chronic hepatitis infection, by combining two case-control studies undertaken in Italy and Greece, including overall 518 cases of HCC and 772 controls. Adherence to the traditional Mediterranean diet was assessed through the Mediterranean diet score (MDS), which ranges between 0 (lowest adherence) and 9 (highest adherence). Odds ratios (OR) for HCC were obtained through multiple logistic regression models, controlling for potentially confounding factors, including chronic infection with hepatitis B/C viruses. Compared to MDS of 0-3, the ORs for HCC were 0.66 (95% confidence interval (CI), 0.41-1.04) for MDS equal to 4 and 0.51 (95% CI, 0.34-0.75) for MDS ⩾ 5, with a significant trend (pMediterranean diet on HCC risk was disproportionally high among those chronically infected with hepatitis B and/or C viruses, with a suggestion of super-additive interaction, albeit statistically non-significant. Closer adherence to the Mediterranean diet appears to be protective against HCC. Our results also point to potential benefits from adhering to a Mediterranean dietary pattern for patients chronically infected with hepatitis viruses. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  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.

  2. Hepatitis C and hepatocellular carcinoma.

    Science.gov (United States)

    Fassio, Eduardo

    2010-01-01

    Chronic hepatitis C virus infection is a well-recognized risk factor for occurrence of hepatocellular carcinoma (HCC). In Europe, Oceania and America, chronic hepatitis C and alcoholic cirrhosis are the main risk factors for HCC. In Latin America, a few retrospective and one prospective study have also shown the predominant role played by hepatitis C in this setting. Furthermore, the incidence of HCC has been increasing in industrialized countries in the last decades; partially as a consequence of the increase in HCV-related cirrhosis (as the long-term sequel of the peak of infections occurring 2-4 decades ago). The main risk factor for HCC development in patients with hepatitis C is the presence of cirrhosis. Among patients with hepatitis C and cirrhosis, the annual incidence rate of HCC ranges between 1-8%, being higher in Japan (4-8%) intermediate in Italy (2-4%) and lower in USA (1.4%). Some studies have also found that HCC may be the first complication to develop and the more frequent cause of death in the compensated HCV-associated cirrhosis. Other risk factors for HCC occurrence are older age at infection, male gender, decreased platelet count, esophageal varices, presence of porphyria cutanea tarda, liver steatosis or diabetes, infection with genotype 1b, coinfection with hepatitis B virus or with HIV and chronic alcoholism. Many studies and also meta-analysis have reported that antiviral therapy based on interferon may reduce the incidence of HCC in chronic hepatitis C, especially in patients with sustained virologic response. Patients with HCV-related cirrhosis should undergo surveillance for HCC.

  3. Growth differentiation factor 15 is induced by hepatitis C virus infection and regulates hepatocellular carcinoma-related genes.

    Directory of Open Access Journals (Sweden)

    Youhui Si

    Full Text Available Liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC are commonly induced by chronic hepatitis C virus (HCV infection. We aimed to identify and characterize the involvement of previously screened cytokine GDF15 in HCV pathogenesis. We examined the GDF15 expression after HCV infection both in vitro and in vivo. Cultured JFH-1 HCV was used to determine the GDF15 function on virus propagation. GDF15 overexpression and RNA interference were employed to profile the GDF15-regulated genes, signaling pathways and cell biology phenotypes. The mRNA expression and protein secretion of GDF15 was dramatically increased in HCV-infected hepatoma cells, which maybe a host response to viral proteins or infection-induced cell stress. Patients infected with HCV had an average 15-fold higher blood GDF15 level than that of healthy volunteers. Three HCC individuals in the HCV cohort showed extremely high GDF15 concentrations. Transfection or exogenously supplied GDF15 enhanced HCV propagation, whereas knockdown of endogenous GDF15 resulted in inhibition of virus replication. Overexpressed GDF15 led to Akt activation and the phosphorylation of Akt downstream targeted GSK-3β and Raf. Several HCC-related molecules, such as E-cadherin, β-catenin, Cyclin A2/B1/D1, were up-regulated by GDF15 stimulation in vitro. Overexpression of GDF15 in hepatoma cells resulted in increased DNA synthesis, promoted cell proliferation, and importantly enhanced invasiveness of the cells. In conclusion, these results suggest that an elevated serum GDF15 level is a potential diagnostic marker for viral hepatitis, and GDF15 may contribute to HCV pathogenesis by altering the signaling and growth of host cells.

  4. Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

    Science.gov (United States)

    Xian, Zhi-Hong; Cong, Wen-Ming; Zhang, Shu-Hui; Wu, Meng-Chao

    2005-01-01

    AIM: To study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS: DNA isolated from tumors and corresponding noncancerous liver tissues of 56 HCC patients was amplified by random amplified polymorphic DNA (RAPD) with 10 random 10-mer arbitrary primers. The RAPD bands showing obvious differences in tumor tissue DNA corresponding to that of normal tissue were separated, purified, cloned and sequenced. DNA sequences were analyzed and compared with GenBank data. RESULTS: A total of 56 cases of HCC were demonstrated to have genetic alterations, which were detected by at least one primer. The detestability of genetic alterations ranged from 20% to 70% in each case, and 17.9% to 50% in each primer. Serum HBV infection, tumor size, histological grade, tumor capsule, as well as tumor intrahepatic metastasis, might be correlated with genetic alterations on certain primers. A band with a higher intensity of 480 bp or so amplified fragments in tumor DNA relative to normal DNA could be seen in 27 of 56 tumor samples using primer 4. Sequence analysis of these fragments showed 91% homology with Homo sapiens double homeobox protein DUX10 gene. CONCLUSION: Genetic alterations are a frequent event in HCC, and tumor related DNA fragments have been found in this study, which may be associated with hepatocarcin-ogenesis. RAPD is an effective method for the identification and analysis of genetic alterations in HCC, and may provide new information for further evaluating the molecular mechanism of hepatocarcinogenesis. PMID:15996039

  5. A rare case report: Carcinoma pancreas with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Vikas Yadav

    2014-01-01

    Full Text Available Synchronous double malignancies involving different organs are relatively rare and uncommon finding. We report an interesting case of double malignancy in which a patient exhibited synchronous two separate carcinomas, pancreatic and hepatocellular carcinoma (HCC. Patient was a 64-year-old male who presented primarily with symptoms pertaining to the biliary obstruction and ultrasound of abdomen revealing pancreatic head mass. HCC was detected incidentally during the investigations for carcinoma pancreas.

  6. Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ -MALDI-MS/MS.

    Science.gov (United States)

    He, X; Wang, Y; Zhang, W; Li, H; Luo, R; Zhou, Y; Liao, C Li M; Huang, H; Lv, X; Xie, Z; He, M

    2014-01-01

    Hepatocellular carcinoma(HCC) is serious condition associated with a high morbidity and mortality. Therefore is an urgent need to develop novel noninvasive techniques for early diagnosis, particularly for patients with AFP-negative [AFP(-)] HCC. In this study, iTRAQ-MALDI-MS/MS was used to identify differentially expressed proteins in AFP(-) HBV-related HCC compared with non-cancerous hepatitis B virus (HBV) and healthy controls subjects.Serum was obtained from 18 patients with AFP(-) HBV-related HCC, 18 matched patients with HBV without HCC and 18 healthy control subjects. High abundance proteins were removed from serum and the differentially expressed proteins from the three groups were screened out using iTRAQ-MALDI-MS/MS. The Gene Ontology (GO) function and the interaction networks of differentially expressed proteins were then analyzed. A total of 24 expressed differential proteins associated with AFP(-) HBV-related HCC were screened out, 15 proteins were up-regulated and 9 down-regulated. The most common molecular function of the 24 differentially expressed proteins was enzyme inhibition. Interaction network of the 24 differentially expressed proteins showed that 14 proteins (C5, KNG1, FN1, LRG1, HRG, SERPINC1, CRP, APOB, SAA1, APCS, C4BPA, CFI, CFB and GSN) were central to the functional network. The expression levels of the GSN protein were down-regulated in AFP(-) HBV-related HCC subjects compared with healthy controls and the HBV group (pproteins from the serum of AFP(-) HBV-related HCC appeared at the fulcrum of the functional network and were differentially expressed compare to HBV and healthy controls suggesting a possible association with HCC progression.

  7. Liver transplantation in patients with hepatocellular carcinoma

    NARCIS (Netherlands)

    Polak, Wojciech G.; Soyama, Akihiko; Slooff, Maarten J. H.

    2008-01-01

    Liver transplantation has a definitive place in the treatment of patients with hepatocellular carcinoma (HCC) in a cirrhotic liver. Patients with a tumor load within the Milan criteria have excellent survival comparable to survival in patients with benign indications. When tumor load exceeds the

  8. Hepatocellular Carcinoma - A synopsis of current developments ...

    African Journals Online (AJOL)

    This review highlights the burden associated with hepatocellular carcinoma and the progress made so far in the diagnosis, management, and treatment of the disease. It is based on a search of Medline, the Cochrane database of Systemic Reviews, and citation lists of relevant and current publications. Subject headings and ...

  9. Hepatocellular carcinoma in Jos, Nigeria | Echejoh | Nigerian ...

    African Journals Online (AJOL)

    Background: Hepatocellular carcinoma (HCC) is the most common abdominal malignancy, representing 80- 90% of primary liver malignancies around the world. There is a disturbing trend of increased incidence of HCC around the world. We therefore, determined the trend of HCC in Jos. Methods: A ten-year retrospective ...

  10. Liver transplantation for Hepatocellular carcinoma: Predictors of ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma (HCC) is an aggressive malignancy mostly complicating some underlying liver pathology that has lead to cirrhosis. Some of the epidemiological factors were summarized by the 54th AASLD meeting. South African Gastroenterology Journal Vol. 6 (3) 2008: pp. 6-12 ...

  11. Hepatocellular carcinoma in South Sudan: possible aetiologies ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma is one of the common malignancies in both the developed and developing worlds. This is most likely due to its wide variety of causes. The aetiologies vary from one part of the world to another determined by many factors ranging from geography, life style, availability of advanced medical care etc ...

  12. Hepatocellular carcinoma: risk groups, surveillance and outcome

    NARCIS (Netherlands)

    van Meer, S

    2016-01-01

    The burden of hepatocellular carcinoma (HCC) has changed in the past few decades. Although the majority of HCC cases develops in East Asia and Sub-Saharan Africa, HCC has become an increasing problem in Western countries such as the Netherlands. Surveillance for HCC is controversial because of

  13. Hepatocellular carcinoma in a young dog

    OpenAIRE

    Teshima, Takahiro; Matsumoto, Hirotaka; Shigihara, Kae; Sawada, Harumi; Michishita, Masaki; Takahashi, Kimimasa; Koyama, Hidekazu

    2013-01-01

    A 25-month-old Chihuahua dog with no clinical signs was evaluated for high serum liver enzymes. Ultrasonography and computed tomography revealed a mass in the left hepatic medial lobe. The histological diagnosis reached using resected tissues was hepatocellular carcinoma (HCC). To the authors’ knowledge, this is the youngest dog diagnosed with HCC.

  14. 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.)

  15. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2

    OpenAIRE

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNF?) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNF? on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNF? stimulus. We observed that HepG2 cell revealed a higher resistance to TNF?-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By usin...

  16. Capsule, septum, and T2 hyperintense foci for differentiation between large hepatocellular carcinoma (≥5 cm) and intrahepatic cholangiocarcinoma on gadoxetic acid MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jiyoung; Hong, Seong Sook; Kim, Hyun-joo [Soonchunhyang University College of Medicine, Department of Radiology, Seoul Hospital, Seoul (Korea, Republic of); Kim, Young Kon; Min, Ji Hye; Jeong, Woo Kyung [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Choi, Seo-Youn [Soonchunhyang University College of Medicine, Department of Radiology, Bucheon Hospital, Bucheon (Korea, Republic of); Ahn, Soohyun; Ahn, Hyeon Seon [Research Institute for Future Medicine, Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul (Korea, Republic of)

    2017-11-15

    To determine the added value of capsule, septum, and T2 hyperintense foci for differentiating large hepatocellular carcinoma (HCC; ≥ 5 cm) from intrahepatic cholangiocarcinoma (ICC) using gadoxetic acid MRI. The study included 116 patients (94 men, 22 women; mean age, 56.8 years) with surgically confirmed HCCs (n = 87, 5.0-18.0 cm) or ICCs (n = 29, 5.0-14.0 cm) who underwent gadoxetic acid MRI. Three observers independently reviewed MRIs in two sessions, examining enhancement patterns only and then adding capsule, septum, and T2 hyperintense foci. Reviewers used a five-point scale to score accuracy, sensitivity, and specificity. A significant increase was observed in accuracy when ancillary features (96.1-98.3%) were added compared to enhancement pattern only (83.6-88.4%; p ≤ 0.02). Sensitivity was significantly increased with combined reading (97.1-98.3%) compared to enhancement features only (81.6-88.5%; p ≤ 0.006) for two observers, with no difference in specificity (84.5-89.7% vs. 86.2-98.3%; p > 0.05). We found substantial to excellent interobserver agreement for ancillary features (0.598-0.976). Adding capsule, septum, and T2 hyperintense foci to enhancement patterns for gadoxetic acid MRI increased diagnostic performance for characterizing large HCC by differentiating it from ICC. (orig.)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

    Full Text Available His.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 Histone Liver Carcinoma, Hepatocellu...lar http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  2. Gd-EOB-DTPA-enhanced magnetic resonance imaging combined with T1 mapping predicts the degree of differentiation in hepatocellular carcinoma.

    Science.gov (United States)

    Peng, Zhenpeng; Jiang, Mengjie; Cai, Huasong; Chan, Tao; Dong, Zhi; Luo, Yanji; Li, Zi-Ping; Feng, Shi-Ting

    2016-08-12

    Variable degrees of differentiation in hepatocellular carcinoma(HCC)under Edmondson-Steiner grading system has been proven to be an independent prognostic indicator for HCC. Up till now, there has been no effective radiological method that can reveal the degree of differentiation in HCC before surgery. This paper aims to evaluate the use of Gd-EOB-DTPA-Enhanced Magnetic Resonance Imaging combined with T1 mapping for the diagnosis of HCC and assessing its degree of differentiation. Forty-four patients with 53 pathologically proven HCC had undergone Gd-EOB-DTPA enhanced MRI with T1 mapping before surgery. Out of the 53 lesions,13 were grade I, 27 were gradeII, and 13 were grade III. The T1 values of each lesion were measured before and at 20 min after Gd-EOB-DTPA administration (T1p and T1e). The absolute reduction in T1 value (T1d) and the percentage reduction (T1d %) were calculated. The one-way ANOVA and Pearson correlation were used for comparisons between the T1 mapping values. The T1d and T1d % of grade I, II and III of HCC was 660.5 ± 422.8ms、295.0 ± 99.6ms、276.2 ± 95.0ms and 54.0 ± 12.2 %、31.5 ± 6.9 %、27.7 ± 6.7 % respectively. The differences between grade Iand II, grade Iand III were statistically significant (p T1 mapping before and after Gd-EOB-DTPA administration can predict degree of differentiation in HCC.

  3. Differential Expression of Wnt Pathway Genes in Sporadic Hepatocellular Carcinomas Infected With Hepatitis B Virus Identified With OligoGE Arrays.

    Science.gov (United States)

    Lin, Xiaoyan; Wang, Qiangxiu; Cao, Zhixin; Geng, Ming; Cao, Yongcheng; Liu, Xiaohong

    2013-01-01

    Epidemiological evidence has clearly indicated that chronic infection with the hepatitis B virus (HBV) is the major risk factor for developing hepatocellular carcinoma (HCC). Nonetheless, the mechanisms by which HBV contributes to the pathogenesis of HCC have not been fully elucidated. Our aim was to characterize differential gene expression profiles related to the Wnt signaling pathway between primary tumor and adjacent normal tissues in HCC patients with concomitant HBVinfection . An oligoGEArray® (an oligonucleotide-based gene expression array platform) containing 126 Wnt signaling pathway-related genes was used to compare gene expressions between primary HCC and adjacent non-tumorous liver tissues from 10 patients with HCC. Selected differential genes were identified with real-time RT-PCR and immunohistochemistry (IHC). In particular, the protein of the differential gene DVL3 (disheveled, dsh homolog 3 [Drosophila]) was chosen to investigate whether it is up regulated in primary tumor correlated with the clinic pathological characteristics of HCC patients. For this purpose we examined 56 HCC tissue samples via IHC for the presence of DVL3 protein. Sixteen genes were identified with significant differential expression between HCC and adjacent non-tumorous liver tissue. These genes have been previously associated with the Frizzled signaling pathway, cell cycle, transcription, or protein degradation. All (100%) of the tumor samples results from 56 HCC patients tested were positive for DVL3 via IHC. Based on the intensity of DVL3 immunoreactivity, 25 (44.6%) and 31 (55.4%) of the patients were classified aslow and high-DVL3, respectively, which correlated with tumor stage (P = 0.029). This study clarified a number of Wnt pathway-related genes which are dysregulated in HBV-associated HCC. These genes may be contributedto the frequent activation of the Wnt signaling pathway. Our results promote the role of the Wnt signaling pathway in HBV-associated HCC.

  4. Rare Gingival Metastasis by Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Li-Jun Xue

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC uncommonly metastasizes to the gingiva, which always means a poor outcome. We reported a rare HCC case with multiple metastases to gingiva, lungs, and brain. A 60-year-old man was initially diagnosed as HCC with metastases to double lungs. He was subjected to a transarterial chemoembolization (TACE (5-fluorouracil, 750 mg and two cycles of intravenous chemotherapy (gemcitabine 1.8 g at days 1 and 8, oxaliplatin 200 mg at day 2, every 4 weeks. However, the volume of liver tumor still increased. A bean-size gingival nodule growing with occasional bleeding was also found. TACE (5-fluorouracil 750 mg, perarubicin 40 mg, cisplatin 20 mg was performed again and an oral sorafenib therapy (400 mg, twice per day was adopted. The disease maintained relatively stable for about 6 months until a second obvious progress. The gingival nodule was then palliatively excised and identified as a poorly differentiated metastatic HCC by histopathological examination. Best supportive treatments were made since the performance score was too bad. Finally, cerebral metastases occurred and the patient died of systemic failure. Upon review of previous reports, we discussed risk factors, clinical and pathological characteristics, treatments, and prognosis of gingival metastasis by HCC.

  5. Differential vascular endothelial growth factor A protein expression between small hepatocellular carcinoma and cirrhosis correlates with serum vascular endothelial growth factor A and alpha-fetoprotein.

    Science.gov (United States)

    Corradini, Stefano Ginanni; Morini, Sergio; Liguori, Francesca; Carotti, Simone; Muda, Andrea Onetti; Burza, Maria Antonella; Siciliano, Maria; Molinaro, Antonio; Cantafora, Alfredo; Blotta, Ida; Merli, Manuela; Berloco, Pasquale; Rossi, Massimo; Attili, Adolfo Francesco; Gaudio, Eugenio

    2009-01-01

    Drugs with antivascular endothelial growth factor A (anti-VEGF-A) action are under clinical evaluation with encouraging results in advanced hepatocellular carcinoma (HCC). The relative VEGF-A protein expression in non-advanced HCC and in the cirrhotic non-tumoral tissue in the same patient, a variable that could be important for treatment efficacy, has been investigated with conflicting results, only using the cirrhotic tissue surrounding the neoplasm (CS). We measured, for the first time, VEGF-A expression in non-advanced HCC and in the respective CS and cirrhotic tissue at a distance from the tumour (CD), in 24 patients who underwent liver transplantation. VEGF-A protein was more expressed (Pprotein expression in HCC was higher than in the corresponding CD in 83% of cases and AFP and serum VEGF-A corrected for the platelet count positively correlated with the differential VEGF-A protein expression between HCC and CD. Our data provide a rationale for clinical trials involving anti-VEGF-A treatments in patients with non-advanced HCC, and suggest that serum AFP and VEGF-A are variables to be taken into account in these studies.

  6. 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.

  7. 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.

  8. Clinical utility of imaging for evaluation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Murakami T

    2014-07-01

    Full Text Available Takamichi Murakami,1 Masakatsu Tsurusaki,1 Tomoko Hyodo,1 Yasuharu Imai2 1Department of Radiology, Kinki University Faculty of Medicine, 2Department of Hepatology and Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan Abstract: The hemodynamics of a hepatocellular nodule is the most important imaging parameter used to characterize various hepatocellular nodules in liver cirrhosis, because sequential changes occur in the feeding vessels and hemodynamic status during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular carcinoma (HCC are also usually based on vascular findings, eg, early arterial uptake followed by washout in the portal venous and equilibrium phases. Contrast-enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT, and dynamic magnetic resonance (MR imaging with gadopentetate dimeglumine (Gd-DTPA are useful for detecting hypervascular HCC on the basis of vascular criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA, a hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC. Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically differentiated HCC as hypointense relative to the liver parenchyma. 18F-fluorodeoxyglucose positron emission tomography imaging might not be suitable for the screening and detection of HCC, given its lower diagnostic performance. However, this technique plays an important role in determining whether HCC has spread beyond the liver. Keywords: hepatocellular carcinoma, evaluation, imaging, clinical utility

  9. Hepatitis C virus to hepatocellular carcinoma

    OpenAIRE

    Jahan Shah; Ashfaq Usman A; Qasim Muhammad; Khaliq Saba; Saleem Muhammad; Afzal Nadeem

    2012-01-01

    Abstract Hepatitis C virus causes acute and chronic hepatitis and can lead to permanent liver damage and hepatocellular carcinoma (HCC) in a significant number of patients via oxidative stress, insulin resistance (IR), fibrosis, liver cirrhosis and HCV induced steatosis. HCV induced steatosis and oxidative stress causes steato-hepatitis and these pathways lead to liver injury or HCC in chronic HCV infection. Steatosis and oxidative stress crosstalk play an important role in liver damage in HC...

  10. Slug promoted vasculogenic mimicry in hepatocellular carcinoma

    OpenAIRE

    Sun, Dan; Sun, Baocun; Liu, Tieju; Zhao, Xiulan; Che, Na; Gu, Qiang; Dong, Xueyi; Yao, Zhi; Li, Rui; Li, Jing; Chi, Jiadong; Sun, Ran

    2013-01-01

    Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumour cells to mimic the pattern of embryonic vasculogenic networks. Epithelial?mesenchymal transition (EMT) regulator slug have been implicated in the tumour invasion and metastasis of human hepatocellular carcinoma (HCC). However, the relationship between slug and VM formation is not clear. In the study, we demonstrated that slug expression was associated with EMT and cancer stem cell (CSCs) phenotype in HCC patients. ...

  11. Results of surgical treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Adriano Miziara Gonzalez

    2004-12-01

    Full Text Available Objective: To perform a retrospective review of 14 patientssubmitted to surgical treatment of hepatocellular carcinoma atthe Universidade Federal de Sao Paulo – UNIFESP. Methods:Review of data obtained from 14 patients with hepatocellularcarcinoma submitted to surgical resection in the Discipline ofSurgical Gastroenterology, at the Universidade Federal de SaoPaulo - Escola Paulista de Medicina, from June 1992 to September1998. Results: Three patients (21.4% were female and 11 (78.6%were male. Ten patients (71.4% had disease-related symptoms;76.8% were classified as Child-Pugh A. Alpha-fetoprotein levelswere analyzed in 13 patients and were elevated in 65.1%. Allpatients had abdominal ultrasound and computerized tomographyscans compatible with hepatocellular carcinoma. Surgicalresections varied from segmetectomy to trisegmentectomy.Bleeding was the most common intraoperative complication andcaused one death. The most frequent postoperative complicationwas ascitis, followed by pleural effusion, encephalopathy and biliaryfistula. Tumor recurrence rate was 61.5% at one year and wasrelated to tumors larger than 5 cm, tumor invasion and absence ofa capsule, suggesting late diagnosis. Mean disease-free survivalrate was 17 months and mean survival rate was 21 months.Conclusion: The patients with hepatocellular carcinoma submittedto surgical resection had a high recurrence rate in a one-yearfollow-up, probably due to large tumor size, vascular invasion andabsence of a capsule. The importance of an early diagnosis isemphasized.

  12. [A rare differential diagnosis of a somatoform autonomous disorder of the gastro-intestinal tract: the hepatocellular liver carcinoma in childhood].

    Science.gov (United States)

    Voll, Renate

    2008-07-01

    A severely ill 11-year-old boy came to the child psychiatric outpatient department of the Fachkrankenhaus Neckargemünd with the diagnosis of a somatoform disorder. Main symptoms included nausea, vomiting, abdominal pain and diarrhoea. He wished to be examined in order to enter the Stephen-Hawking-School for physically handicapped children in the town of Neckargemünd. Manual examination revealed a palpable mass in the right upper quadrant of the abdomen, which was imaged as a tumour of the liver. During the subsequent operation, a 500 ml hepatocellular carcinoma was found. The symptoms of the hepatocellular carcinoma, which rarely occurs in childhood, can perfectly mimic those of a somatoform disorder of the gastro-intestinal tract.

  13. Higher LPA2 and LPA6 mRNA Levels in Hepatocellular Carcinoma Are Associated with Poorer Differentiation, Microvascular Invasion and Earlier Recurrence with Higher Serum Autotaxin Levels.

    Directory of Open Access Journals (Sweden)

    Kenichiro Enooku

    Full Text Available Hepatocellular carcinoma (HCC commonly develops in patients with liver fibrosis; in these patients, the blood levels of lysophosphatidic acid (LPA and its generating enzyme autotaxin (ATX increase with the liver fibrosis stage. We aimed to examine the potential relevance of ATX and LPA in HCC. Fifty-eight HCC patients who underwent surgical treatment were consecutively enrolled in the study. Among the LPA receptors in HCC, higher LPA2 mRNA levels correlated with poorer differentiation, and higher LPA6 mRNA levels correlated with microvascular invasion, which suggested a higher malignant potential of HCC with increased LPA2 and LPA6 expression. In patients with primary HCC, neither LPA2 nor LPA6 mRNA levels were associated with recurrence. However, when serum ATX levels were combined for analysis as a surrogate for plasma LPA levels, the cumulative intra-hepatic recurrence rate was higher in patients in whom both serum ATX levels and LPA2 or LPA6 mRNA levels were higher than the median. However, the mRNA level of phosphatidic acid-selective phospholipase A1ɑ, another LPA-generating enzyme, in HCC patients was not associated with pathological findings or recurrence, even in combination with the expression of LPA receptors. Higher LPA2 mRNA levels were associated with poorer differentiation, and higher LPA6 levels were associated with microvascular invasion in HCC; both became a risk factor for recurrence after surgical treatment when combined with increased serum ATX levels. ATX and LPA receptors merit consideration as therapeutic targets of HCC.

  14. Diagnosis, staging and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    A.V.C. França

    2004-11-01

    Full Text Available Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies.

  15. Management dilemma of hepatocellular carcinoma in pregnancy: a ...

    African Journals Online (AJOL)

    There is paucity of evidence for best practice in hepatocellular carcinoma in pregnancy especially in the background of cirrhosis and decompensation. We present a 36 year old gravida 5 para 4 at 27 weeks gestation with hepatocellular carcinoma and main complaint of abdominal pain. She had chronic hepatitis B infection ...

  16. Hepatocellular carcinoma in glycogen storage disease type IV

    OpenAIRE

    de Moor, R A; Schweizer, J.; Van Hoek, B.; Wasser, M.; Vink, R.; Maaswinkel-Mooy, P.

    2000-01-01

    A 13 year old patient with juvenile type IV glycogen storage disease died of the complications of hepatocellular carcinoma. To our knowledge this is the first reported case of hepatocellular carcinoma in association with type IV glycogen storage disease.



  17. Orbital Metastasis of Hepatocellular Carcinoma: A Case Report ...

    African Journals Online (AJOL)

    Background: Hepatocellular carcinoma is one of the commonest malignancies in Nigeria, however metastasis to the orbit is a rare presentation. Objective: To present a rare case of orbital metastasis of hepatocellular carcinoma. Case Report: A 25-year-old man presented with a 3-month history of pain, progressive swelling ...

  18. Serum clusterin as a marker for diagnosing hepatocellular carcinoma

    African Journals Online (AJOL)

    Ragaa A. Ramadan

    2014-06-20

    Jun 20, 2014 ... Abstract Background: Approximately 80% of patients with hepatocellular carcinoma (HCC) are .... protein that is ubiquitously expressed and present in most .... G: group, CHC: chronic hepatitis-C virus infection related cirrhosis, HCC: hepatocellular carcinoma, AFP: alpha fetoprotein, CLU: clusterin. Z1: Z for ...

  19. 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....

  20. 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

  1. Type 2 Diabetes and Hepatocellular Carcinoma: Risk Factors and Pathogenesis.

    Science.gov (United States)

    Wainwright, P; Scorletti, E; Byrne, C D

    2017-04-01

    This review aims to assess the epidemiological evidence for a link between type 2 diabetes and hepatocellular carcinoma and to investigate possible pathophysiological mechanisms. The presence of type 2 diabetes significantly increases the risk of developing hepatocellular carcinoma, and treatment with metformin may be associated with a lower risk. Treatment with insulin and sulphonylureas may be associated with increased risk. The pathophysiology underlying development of hepatocellular carcinoma in this context is complex and is likely to involve increased proinflammatory mediators, oxidative stress, JNK-1 activation, increased IGF-1 activity, altered gut microbiota and immunomodulation. Hepatocellular carcinoma incidence is increasing and this is likely to be linked to the increasing incidence of type 2 diabetes, obesity and the metabolic syndrome. These conditions increase the risk of developing hepatocellular carcinoma, and a greater understanding of the underlying pathophysiology may help with the development of novel treatments.

  2. Impact of RGD Peptide Tethering to IL24/mda-7 (Melanoma Differentiation Associated Gene-7) on Apoptosis Induction in Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Bina, Samaneh; Shenavar, Fatemeh; Khodadad, Mahboobeh; Haghshenas, Mohammad Reza; Mortazavi, Mojtaba; Fattahi, Mohammad-Reza; Erfani, Nasrollah; Hosseini, Seyed Younes

    2015-01-01

    Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24), a unique tumor suppressor gene, has killing activity in a broad spectrum of cancer cells. Herein, plasmids producing mda-7 proteins fused to different RGD peptides (full RGD4C and shortened RGD, tRGD) were evaluated for apoptosis induction with a hepatocellular carcinoma cell line, Hep-G2. The study aim was to improve the apoptosis potency of mda-7 by tethering to RGD peptides. Three plasmids including mda-7, mda-7-RGD and mda-7-tRGD genes beside a control vector were transfected into Hep-G2 cells. After 72 hours incubation, cell viability was evaluated by MTT assay. In addition, the rate of apoptosis was analyzed by flow cytometry using PI/annexin staining. To detect early events in apoptosis, 18 hours after transfection, expression of the BAX gene was quantified by real time PCR. Modeling of proteins was also performed to extrapolate possible consequences of RGD modification on their structures and subsequent attachment to receptors. In MTT assays, while all mda-7 forms showed measurable inhibition of proliferation, unmodified mda-7 protein exhibited most significant effect compared to control plasmid (PRGD-fused mda-7 proteins. These findings were also supported by expression analysis of BAX gene (PRGD at the end of IL-24/Mda7 disrupt attachment to cognate receptor, IL-20R1/ IL-20R2. In conclusion, fusion of RGD4C and shortened RGD peptides to carboxyl terminal of mda7, not only reduce apoptosis property in vitro but also disrupt receptor attachment as demonstrated by protein modelling.

  3. Hepatocellular Carcinoma with Sarcomatoid Change without Anticancer Therapies

    Directory of Open Access Journals (Sweden)

    Naoki Yoshida

    2013-03-01

    Full Text Available Hepatocellular carcinoma (HCC with sarcomatoid change is a rare neoplasm of the liver, and recurrent therapies for HCC such as transcatheter arterial chemoembolization and percutaneous ablation therapy are presumed to promote sarcomatoid change. A 73-year-old man was admitted to our hospital diagnosed as having liver cancer originating from hepatitis C-related cirrhosis without any previous treatment for HCC. Ultrasonography showed that the tumor was hypoechoic, 3 cm in diameter, with unclear margins. Computed tomography demonstrated a low-density lesion with ring enhancement on delayed phase. Under a diagnosis of poorly differentiated HCC the patient underwent liver resection. Histologically, the tumor consisted of proliferation of spindle-shaped sarcomatoid carcinoma cells with unclear trabecular and pseudoglandular structures including a nodule of typical moderately differentiated HCC, which was observed to shift mutually in one region. Here, we report a case of sarcomatoid HCC with a review of the literature.

  4. Hepatitis C virus to hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jahan Shah

    2012-01-01

    Full Text Available Abstract Hepatitis C virus causes acute and chronic hepatitis and can lead to permanent liver damage and hepatocellular carcinoma (HCC in a significant number of patients via oxidative stress, insulin resistance (IR, fibrosis, liver cirrhosis and HCV induced steatosis. HCV induced steatosis and oxidative stress causes steato-hepatitis and these pathways lead to liver injury or HCC in chronic HCV infection. Steatosis and oxidative stress crosstalk play an important role in liver damage in HCV infection. This Review illustrates viral and host factors which induce Oxidative stress, steatosis and leads toward HCC. It also expresses Molecular cascade which leads oxidative stress and steatosis to HCC.

  5. Cellular prognostic markers in hepatocellular carcinoma.

    Science.gov (United States)

    Buonaguro, Luigi; Tagliamonte, Maria; Petrizzo, Annacarmen; Damiano, Elvira; Tornesello, Maria Lina; Buonaguro, Franco M

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the five big killers worldwide and is frequently associated with chronic hepatitis B and C virus (HBV and HCV) infections. Tumor microenvironment consists of a complex network of cells and factors that plays a key role in the tumor progression and prognosis. This is true also for HCC. Several studies have shown strikingly strong correlation between HCC clinical prognosis and intratumoral infiltration of cells affecting tumor growth, invasion, angiogenesis and metastasis. None of such cells is yet validated for routine diagnostic and prognostic assessment. The present review aims at providing a state-of-the-art of such studies.

  6. Chemoembolization and radioembolization for hepatocellular carcinoma.

    Science.gov (United States)

    Salem, Riad; Lewandowski, Robert J

    2013-06-01

    Hepatocellular carcinoma (HCC) continues to represent a major worldwide problem. Although treatments such as resection, transplantation, and ablation may provide a chance for a cure, these options are often precluded because of advanced disease presentation. Palliative treatments include transarterial embolization and systemic therapies. This review will summarize the state of the science for embolic therapies in HCC (conventional and drug-eluting chemoembolization, radioembolization) as well as discuss related topics including HCC staging, assessment of response, and ongoing clinical trials. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. Hepatitis C Virus and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    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. Research advances in Hedgehog signaling pathway in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LIU Jia

    2015-02-01

    Full Text Available Hedgehog (Hh signaling pathway is present in many animals and plays an important role in regulating embryonic development and differentiation. Aberrant activation of Hh signaling contributes to the pathogenesis of many malignancies. Recent studies have shown that dysregulated Hh signaling pathway participates in the tumorigenesis, tumor invasion, and metastasis of hepatocellular carcinoma (HCC. Investigation of the relationship between Hh signaling pathway and HCC will help elucidate the molecular mechanism of pathogenesis of HCC and provide a new insight into the development of novel anticancer therapy and therapeutic target.

  9. Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: A multicenter study of 412 patients

    Science.gov (United States)

    Decaens, Thomas; Roudot-Thoraval, Françoise; Bresson-Hadni, Solange; Meyer, Carole; Gugenheim, Jean; Durand, Francois; Bernard, Pierre-Henri; Boillot, Olivier; Compagnon, Philippe; Calmus, Yvon; Hardwigsen, Jean; Ducerf, Christian; Pageaux, Georges Philippe; Dharancy, Sébastien; Chazouillères, Olivier; Cherqui, Daniel; Duvoux, Christophe

    2006-01-01

    AIM: To assess pre-orthotopic liver transplantation (OLT) factors that could be evaluated pre-operatively or controlled post-operatively associated with hepatocellular carcinoma (HCC) recurrence and disease-free survival after liver transplantation (LT). METHODS: Four hundred and twelve patients transplanted for HCC between 1988 and 1998 in 14 French centers, who survived the postoperative period were studied. Kaplan Meier estimates were calculated for 24 variables potentially associated with recurrence of HCC. Uni- and multivariate analyses were conducted to identify independent predictors of recurrence. RESULTS: Overall 5-year disease-free survival was 57.1%. By univariate analysis, variables associated with disease-free survival were: presence of cirrhosis (P = 0.001), etiology of liver disease (P = 0.03), α fetoprotein level ( 2000; P 2N; P = 0.02), the number of nodules (1, 2-3 or ≥ 4; P = 0.02), maximal diameter of the largest nodule ( 5 cm; P 10 cm; P < 0.0001), bi-lobar location (P = 0.01), preoperative portal thrombosis (P < 0.0001), peri-operative treatment of the tumor (P = 0.002) and chemoembolization (P = 0.03), tumor differentiation (P = 0.01), initial type of calcineurin inhibitor (P = 0.003), the use of antilymphocyte antibodies (P = 0.02), rejection episodes (P = 0.003) and period of LT (P < 0.0001). By multivariate analysis, 6 variables were independently associated with HCC recurrence: maximal diameter of the largest nodule (P < 0.0001), time of LT (P < 0.0001), tumor differentiation (P < 0.0001), use of anti-lymphocyte antibody (ATG) or anti-CD3 antibody (OKT3) (P = 0.005), preoperative portal thrombosis (P = 0.06) and the number of nodules (P = 0.06). CONCLUSION: This study identifies immunosuppression, through the use of ATG or OKT3, as a predictive factor of tumor recurrence, and confirms the prognostic value of tumor differentiation. PMID:17143948

  10. Identification of a unique hepatocellular carcinoma line, Li-7, with CD13(+) cancer stem cells hierarchy and population change upon its differentiation during culture and effects of sorafenib.

    Science.gov (United States)

    Yamada, Takeshi; Abei, Masato; Danjoh, Inaho; Shirota, Ryoko; Yamashita, Taro; Hyodo, Ichinosuke; Nakamura, Yukio

    2015-04-11

    Cancer stem cell (CSC) research has highlighted the necessity of developing drugs targeting CSCs. We investigated a hepatocellular carcinoma (HCC) cell line that not only has CSC hierarchy but also shows phenotypic changes (population changes) upon differentiation of CSC during culture and can be used for screening drugs targeting CSC. Based on a hypothesis that the CSC proportion should decrease upon its differentiation into progenitors (population change), we tested HCC cell lines (HuH-7, Li-7, PLC/PRF/5, HLF, HLE) before and after 2 months culture for several markers (CD13, EpCAM, CD133, CD44, CD90, CD24, CD166). Tumorigenicity was tested using nude mice. To evaluate the CSC hierarchy, we investigated reconstructivity, proliferation, ALDH activity, spheroid formation, chemosensitivity and microarray analysis of the cell populations sorted by FACS. Only Li-7 cells showed a population change during culture: the proportion of CD13 positive cells decreased, while that of CD166 positive cells increased. The high tumorigenicity of the Li-7 was lost after the population change. CD13(+)/CD166(-) cells showed slow growth and reconstructed the bulk Li-7 populations composed of CD13(+)/CD166(-), CD13(-)/CD166(-) and CD13(-)/CD166(+) fractions, whereas CD13(-)/CD166(+) cells showed rapid growth but could not reproduce any other population. CD13(+)/CD166(-) cells showed high ALDH activity, spheroid forming ability and resistance to 5-fluorouracil. Microarray analysis demonstrated higher expression of stemness-related genes in CD166(-) than CD166(+) fraction. These results indicated a hierarchy in Li-7 cells, in which CD13(+)/CD166(-) and CD13(-)/CD166(+) cells serve as slow growing CSCs and rapid growing progenitors, respectively. Sorafenib selectively targeted the CD166(-) fraction, including CD13(+) CSCs, which exhibited higher mRNA expression for FGF3 and FGF4, candidate biomarkers for sorafenib. 5-fluorouracil followed by sorafenib inhibited the growth of bulk Li-7

  11. Serum protein biomarkers relevant to hepatocellular carcinoma and their detection.

    Science.gov (United States)

    Waidely, Eric; Al-Yuobi, Abdul-Rahman Obaid; Bashammakh, A S; El-Shahawi, Mohammad S; Leblanc, Roger M

    2016-01-07

    Hepatocellular carcinoma (HCC) is one of the most recurrent and lethal cancers worldwide. The low survival rate of this particular strain of carcinoma is largely due to the late stages at which it is diagnosed. Tumorigenesis of hepatocellular carcinoma is most frequently detected through ultrasonography, magnetic resonance imaging and computerized tomography scans, however, these methods are poor for detection of early tumor development. This review presents alternative hepatocellular carcinoma detection techniques through the use of protein and enzyme/isozyme biomarkers. The detection methods used to determine the serum levels of α-fetoprotein (AFP), glypican-3 (GPC3), Golgi protein 73 (GP73), α-L-fucosidase (AFU), des-γ-carboxyprothrombin (DCP), γ-glutamyl transferase (GGT) and squamous cell carcinoma antigen (SCCA) are presented and each marker's respective validity in the diagnosis of hepatocellular carcinoma is evaluated.

  12. Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target.

    Science.gov (United States)

    Ito, Hirotaka; Funahashi, Shin-ichi; Yamauchi, Naoko; Shibahara, Junji; Midorikawa, Yutaka; Kawai, Shigeto; Kinoshita, Yasuko; Watanabe, Akira; Hippo, Yoshitaka; Ohtomo, Toshihiko; Iwanari, Hiroko; Nakajima, Atsushi; Makuuchi, Masatoshi; Fukayama, Masashi; Hirata, Yuichi; Hamakubo, Takao; Kodama, Tatsuhiko; Tsuchiya, Masayuki; Aburatani, Hiroyuki

    2006-06-01

    Hepatocellular carcinoma is the most common primary malignancy of the liver and accounts for as many as one million deaths annually worldwide. The present study was done to identify new transmembrane molecules for antibody therapy in hepatocellular carcinoma. Gene expression profiles of pooled total RNA from three tissues each of moderately differentiated and poorly differentiated hepatocellular carcinoma were compared with those of normal liver, noncancerous liver tissue in hepatocellular carcinoma patients, 30 normal tissue samples, and five fetal tissue samples. Target genes up-regulated specifically in hepatocellular carcinoma were validated by immunohistochemical analysis and complement-dependent cytotoxicity assay using monoclonal antibodies generated against target molecules. The human homologue of the Drosophila Roundabout gene, axon guidance receptor homologue 1, ROBO1/DUTT1, a member of the immunoglobulin superfamily, was highly expressed in hepatocellular carcinoma, whereas it showed only a limited distribution in normal tissues. On immunohistochemical analysis using a newly generated anti-ROBO1 monoclonal antibody, positive signals were observed in 83 of 98 cases of hepatocellular carcinoma (84.7%). The mAb B2318C induced complement-dependent cytotoxicity in ROBO1-expressing cell lines and in the liver cancer cell line PLC/PRF/5. Strikingly, the ectodomain of ROBO1 was detected not only in the culture medium of liver cancer cell lines (PLC/PRF/5, HepG2, etc.) but also in sera from hepatocellular carcinoma patients (6 of 11). This is the first report that ROBO1 is overexpressed in hepatocellular carcinoma and shed into serum in humans. These observations suggest that ROBO1 is a potential new serologic marker for hepatocellular carcinoma and may represent a new therapeutic target.

  13. Role of SERPINB3 in hepatocellular carcinoma.

    Science.gov (United States)

    Pontisso, Patrizia

    2014-01-01

    SERPINB3 (formerly known as squamous cell carcinoma antigen-1 or SCCA1) is a member of the family of serine-protease inhibitors. SERPINB3 protects cells from oxidative stress conditions, but in chronic liver damage this serpin may lead to hepatocellular carcinoma through different strategies, including inhibition of apoptosis, induction of epithelial to mesenchymal transition and decrease of desmosomal junctions, cell proliferation and invasiveness. SERPINB3 may also contribute to tumor cell resistance to anti-neoplastic drugs through its binding to the respiratory Complex I, protecting cells from the pro-oxidant action of chemotherapeutic agents. Mechanisms of tumor growth promotion induced by SERPINB3 include the inhibition of intratumor infiltration of natural killer cells, up-regulation of Myc oncogene and the recent identification of this serpin as a Ras-responsive factor. In the liver SERPINB3 and SERPINBB4 isoforms (known as squamous cell carcinoma antigen or SCCA) are undetectable in normal hepatocytes, but their expression progressively increases in chronic liver diseases, dysplastic nodules and hepatocellular carcinoma. High SERPINB3 levels have been recently detected in HCC tissue of patients with early tumor recurrence after surgical resection. In serum SERPINB3/4 isoforms (or SCCA) are detectable bound to IgMs (SCCA-IgM) in the majority of HCV infected patients with HCC and in patients with cirrhosis their levels and/or the progressive increase have been found correlated to the risk of HCC development. Preliminary findings in patients with HCC revealed that SCCA-IgM was predictive of HCC prognosis, since low levels of this biomarker were able to identify HCC patients with long overall and progression-free survival.

  14. Proton irradiation for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Yasushi; Chiba, Shunya [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Tanaka, Naomi

    1999-02-01

    A curative effect of high dose proton irradiation for hepatoma was investigated. In cases of single nodular type HCC, radiation field was limited to tumor, and in cases of multi nodular type HCC, irradiation was also fractionated. An average dose of radiation was 4 Gy/time, average times were 16, and an average total dose was 72 Gy. Tumor size reduction rate at 6 months after proton irradiation (123 cases) was CR (17.9%), PR (52.0%), NC (29.3%) and PD (0.8%). And the reduction rate of tumor size in monotherapy cases was 100% (after 3 weeks), 96% (after 1 year) and 88% (after 2 years). The local control rate was 99.1% (after 1 year) and 91.4% (after 3-5 years). AFP value significantly decreased from 571.0{+-}1266.6 ng/ml before radiation to 145.4{+-}346.3 ng/ml after radiation (p<0.0005). The recurrence after radiation occurred more at outside of radiation field, significantly. Indication basis of proton irradiation was showed in this article. Because selective radiation is possible, the proton irradiation should be optimum therapy in specific carcinomas of deep organ. (K.H.)

  15. Hepatocellular carcinoma: epidemiology, biology, diagnosis, and therapies.

    Science.gov (United States)

    Gomes, Marcos António; Priolli, Denise Gonçalves; Tralhão, José Guilherme; Botelho, Maria Filomena

    2013-01-01

    Hepatocellular carcinoma is the fifth most common cancer in men and the seventh in women, as is diagnosed in more than half a million individuals worldwide every year. In Portugal, its incidence and mortality rates are low compared to other types of cancers. In Brazil, in the city of São Paulo, according to data released by the Brazilian Unified Health System (Sistema Único de Saúde - SUS), the incidence of primary liver cancer was 2.07/100,000 inhabitants. Although the vast majority of cases (85%) mainly affect developing countries, especially where infection by hepatitis B virus (HBV) is endemic, the incidence in developed countries is increasing. This pathology is associated with several risk factors, not only environmental but also genetic, generating an increasing interest in attaining a better understanding of this disease, which is still associated with very late diagnosis and poor prognosis. Of the available treatments, few patients benefit from their scanty advantages, increasingly stimulating research of new forms of treatment against this disease. This review aimed to briefly but fully identify risk factors, molecular and biochemical pathways, pathophysiology, diagnosis, and possible clinical approaches of hepatocellular carcinoma. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  16. Hepatocellular carcinoma: early-stage management challenges

    Directory of Open Access Journals (Sweden)

    Erstad DJ

    2017-06-01

    Full Text Available Derek J Erstad,1 Kenneth K Tanabe2–4 1Department of Surgery, Massachusetts General Hospital, 2Harvard Medical School, 3Division of Surgical Oncology, 4Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, Boston, MA, USA Abstract: Hepatocellular carcinoma (HCC is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. Keywords: hepatocellular carcinoma, hepatitis, surveillance, Barcelona clinic liver cancer, staging, cirrhosis, hepatectomy, hepatic resection, locoregional therapy, radiofrequency ablation, transarterial chemoembolization, liver transplantation

  17. Nanomedicines: a theranostic approach for hepatocellular carcinoma.

    Science.gov (United States)

    Usmani, Afreen; Mishra, Anuradha; Ahmad, Mohd

    2017-09-08

    The liver is an imperative organ of tremendous importance concerned with maintenance of metabolic functions and detoxification of exogenous and endogenous challenges like xenobiotics, viral infections and chronic alcoholism. Liver diseases particularly hepatitis B virus infections, liver cirrhosis and hepatocellular carcinoma continue to pose a significant health challenge worldwide due to the lack of therapeutic management options besides liver resection and transplantation. Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer mortality worldwide. HCC has a high mortality rate because of poor diagnosis. The majority of patients with liver cancer die within one year as a result of poor patient compliance. HCC is clinically treated by chemotherapy besides surgery. However, most anticancer drugs have high toxicity and low specificity, leading to systemic toxicity and severe side effects. To limit the severe side effects of cancer chemotherapy on normal tissues, tumor targeting drug delivery systems need to be explored, which provides the impetus to develop targeted therapies for achieving higher efficacy with minimal side effects. The nanostructures used as good drug carriers, possess advantages of good solubility including high drug encapsulation efficiency, high cellular uptake, further desirable pharmacokinetics and can preferentially accumulate at the tumor site through the enhanced permeability and retention (EPR) effect with the goal of minimizing toxic effects on healthy tissues while maintaining antitumor efficacy.

  18. Treatment options after sorafenib failure in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Dika, Imane El; Abou-Alfa, Ghassan K

    2017-12-01

    Second line therapy after failure of sorafenib continues to be under study. Prognosis of hepatocellular carcinoma is measured in months, with median overall survival reaching 10.7 months with sorafenib. Because of the modest net benefit sorafenib has contributed, and rising incidence of hepatocellular carcinoma in the world, continued efforts are ongoing to look for efficient upfront, second line, or combination therapies. Herein we review the most relevant to date published literature on treatment options beyond sorafenib, reported studies, ongoing investigational efforts, and possibilities for future studies in advanced hepatocellular carcinoma.

  19. Role of serum glypican-3 in the diagnosis and differentiation of small hepatocellular carcinoma from hepatitis-C virus cirrhosis

    Directory of Open Access Journals (Sweden)

    Eman A.E. Badr

    2014-09-01

    Conclusion: Serum GLP-3 levels are higher in HCC versus HCV cirrhosis, which can differentiate HCC from liver cirrhosis. Also, serum GLP-3 is highly sensitive and specific for detecting HCC. Moreover, GLP-3 is more sensitive than AFP for the detection of small HCC. Furthermore, a combination of both serum markers yielded an improved specificity and both sensitivity and specificity for the diagnosis of small and unicentric HCC, respectively.

  20. [A case of hepatocellular carcinoma complicated with Caroli's disease].

    Science.gov (United States)

    Ijima, Masashi; Shimoda, Ryuya; Katakai, Kenji; Seki, Asako; Oshimoto, Hirokazu; Masuda, Jun; Morinaga, Nobuhiro; Suzuki, Yutaka; Kakizaki, Satoru; Arai, Taido

    2010-09-01

    A 29-year-old man was admitted with right hypochondralgia and fever. Markedly dilated bile ducts were observed, mainly in the right lobe of the liver. Based on both the clinical findings and imaging, we diagnosed Caroli's disease and choledochal cyst complicated with cholangitis. Hepatocellular carcinoma (HCC) was also observed in segment 3, and the tumor measured 4cm in diameter. The patient was successfully treated with hepatectomy of the right lobe, partial hepatectomy of the left lateral lobe, and bile duct reconstruction. A histopathological examination revealed moderately differentiated HCC without any components of cholangiocellular carcinoma (CCC). Although Caroli's disease is complicated with CCC, a case of Caroli's disease complicated with HCC, as in the present case, is quite rare and therefore is considered to be worthy of reporting.

  1. Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi, China.

    Directory of Open Access Journals (Sweden)

    Lu-Nan Qi

    Full Text Available Both hepatitis B virus (HBV and aflatoxin B1 (AFB1 exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC. To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+/AFB1(+, HBV(+/AFB1(-, HBV(-/AFB1(+, HBV(-/AFB1(-. Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+/AFB1(+, HBV(+/AFB1(- and HBV(-/AFB1(+ groups compared to the HBV(-/AFB(- group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038 and was an unfavorable prognostic factor for tumor-free survival (P =0.045. A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8% of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+/AFB1(+ and HBV(-/AFB1(+ groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic effects

  2. Genome-wide and differential proteomic analysis of hepatitis B virus and aflatoxin B1 related hepatocellular carcinoma in Guangxi, China.

    Science.gov (United States)

    Qi, Lu-Nan; Li, Le-Qun; Chen, Yuan-Yuan; Chen, Zhao-Hong; Bai, Tao; Xiang, Bang-De; Qin, Xiao; Xiao, Kai-Yin; Peng, Min-Hao; Liu, Zhi-Ming; Liu, Tang-Wei; Qin, Xue; Li, Shan; Han, Ze-Guang; Mo, Zeng-Nan; Santella, Regina M; Winkler, Cheryl A; O'Brien, Stephen J; Peng, Tao

    2013-01-01

    Both hepatitis B virus (HBV) and aflatoxin B1 (AFB1) exposure can cause liver damage as well as increase the probability of hepatocellular carcinoma (HCC). To investigate the underlying genetic changes that may influence development of HCC associated with HBV infection and AFB1 exposure, HCC patients were subdivided into 4 groups depending upon HBV and AFB1 exposure status: (HBV(+)/AFB1(+), HBV(+)/AFB1(-), HBV(-)/AFB1(+), HBV(-)/AFB1(-)). Genetic abnormalities and protein expression profiles were analyzed by array-based comparative genomic hybridization and isobaric tagging for quantitation. A total of 573 chromosomal aberrations (CNAs) including 184 increased and 389 decreased were detected in our study population. Twenty-five recurrently altered regions (RARs; chromosomal alterations observed in ≥10 patients) in chromosomes were identified. Loss of 4q13.3-q35.2, 13q12.1-q21.2 and gain of 7q11.2-q35 were observed with a higher frequency in the HBV(+)/AFB1(+), HBV(+)/AFB1(-) and HBV(-)/AFB1(+) groups compared to the HBV(-)/AFB(-) group. Loss of 8p12-p23.2 was associated with high TNM stage tumors (P = 0.038) and was an unfavorable prognostic factor for tumor-free survival (P =0.045). A total of 133 differentially expressed proteins were identified in iTRAQ proteomics analysis, 69 (51.8%) of which mapped within identified RARs. The most common biological processes affected by HBV and AFB1 status in HCC tumorigenesis were detoxification and drug metabolism pathways, antigen processing and anti-apoptosis pathways. Expression of AKR1B10 was increased significantly in the HBV(+)/AFB1(+) and HBV(-)/AFB1(+) groups. A significant correlation between the expression of AKR1B10 mRNA and protein levels as well as AKR1B10 copy number was observered, which suggest that AKR1B10 may play a role in AFB1-related hepatocarcinogenesis. In summary, a number of genetic and gene expression alterations were found to be associated with HBV and AFB1- related HCC. The possible synergistic

  3. Giant Solitary Hepatocellular Carcinoma. A Case Report. | Asuquo ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, among indigenous inhabitants of Africa and it may present as solitary or multiple lesions often running a rapidly fatal course. Presented is a case of a 25 year female in apparent general good health with a giant solitary hepatocellular ...

  4. Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

    2011-01-01

    No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

  5. Hepatocellular carcinoma : Dutch guideline for surveillance, diagnosis and therapy

    NARCIS (Netherlands)

    Eskens, F. A. L. M.; van Erpecum, K. J.; de Jong, K. P.; van Delden, O. M.; Klumpen, H. J.; Verhoef, C.; Jansen, P. L. M.; van den Bosch, M. A. A. J.; Romero, A. Mendez; Verheij, J.; Bloemena, E.; de Man, R. A.

    Hepatocellular carcinoma (HCC) is rare in the Netherlands, even though the incidence has increased quite sharply in recent years. Standard treatment options consist of surgery, orthotopic liver transplantation, radiofrequency ablation, transarterial chemoembolisation (TACE) and systemic therapy with

  6. Introducing differential expression of human heat shock protein 27 in hepatocellular carcinoma: moving toward identification of cancer biomarker.

    Science.gov (United States)

    Khan, Rizma; Siddiqui, Nadir Naveed; Ul Haq, Ahtesham; Rahman, M Ataur

    2016-01-01

    Previously, it has to be acknowledged that overexpressed heat shock protein B27 (HSPB27) have been implicated in the etiology of wide range of human cancers. However, the molecular mechanism leading to the disease initiation to progression in liver cancer is still unknown. Present work was undertaken to investigate the differentially expressed HSPB27 in association with those damages that lead to liver cancer development. For the identification of liver cancer biomarker, samples were subjected to comparative proteomic analysis using two-dimensional gel electrophoresis (2-DE) and were further validated by Western blot and immunohistochemical analysis. After validation, in silico studies were applied to demonstrate the significantly induced phosphorylated and S-nitrosylated signals. The later included the interacting partner of HSPB27, i.e., mitogen-activated protein kinase-3 and 5 (MAPK3 and 5), ubiquitin C (UBC), v-akt murine thymoma viral oncogene homolog 1 (AKT1), mitogen-activated protein kinase 14 (MAPK14), and tumor protein p53 (TP53), which bestowed with critical capabilities, namely, apoptosis, cell cycling, stress activation, tumor suppression, cell survival, angiogenesis, proliferation, and stress resistance. Taking together, these results shed new light on the potential biomarker HSPB27 that overexpression of HSPB27 did lead to upregulation of their interacting partner that together demonstrate their possible role as a novel tumor progressive agent for the treatment of metastasis in liver cancer. HSPB27 is a promising diagnostic marker for liver cancer although further large-scale studies are required. Also, molecular profiling may help pave the road to the discovery of new therapies.

  7. 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

  8. [De novo lipogenesis: role in hepatocellular carcinoma].

    Science.gov (United States)

    Calvisi, D F

    2011-11-01

    Hepatocellular carcinoma (HCC) is one of the most frequent and lethal tumors worldwide. Thus, there is an urgent need to elucidate its molecular pathogenesis in order to develop novel diagnostic, preventive and therapeutic strategies for this deadly disease. Mounting evidence implies a pivotal role of proteins involved in lipid biosynthesis in the development and progression of human HCC. This review summarizes the data available on the pathogenetic relevance of lipogenic proteins in the growth of liver cancer cells, the mechanisms responsible for unrestrained lipid biosynthesis in HCC and the possible clinical implications arising from these discoveries. Altogether the data implicate the AKT-mTORC1-RPS6 signaling pathway as the main inducer of aberrant lipid synthesis in HCC and are indicative of therapeutic strategies aimed at inhibiting de novo lipogenesis for the treatment of human liver cancer.

  9. Gene signatures in hepatocellular carcinoma (HCC).

    Science.gov (United States)

    Andrisani, Ourania M; Studach, Leo; Merle, Philippe

    2011-02-01

    Primary hepatocellular carcinoma (HCC) is a significant human cancer globally, with poor prognosis. New and efficacious therapy strategies are needed as well as new biomarkers for early detection of at-risk patients. In this review, we discuss select microarray studies of human HCCs, and propose a gene signature that has promise for clinical/translational application. This gene signature combines the proliferation cluster of genes and the hepatic cancer initiating/stem cell gene cluster for identification of HCCs with poor prognosis. Evidence from cell-based assays identifies the existence of a mechanistic link between these two gene clusters, involving the proliferation cluster gene polo-like kinase 1 (PLK1). We propose that PLK1 is a promising therapy target for HCC. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Laparoscopic RFA with splenectomy for hepatocellular carcinoma.

    Science.gov (United States)

    Hu, Kunpeng; Lei, Purun; Yao, Zhicheng; Wang, Chenhu; Wang, Qingliang; Xu, Shilei; Xiong, Zhiyong; Huang, He; Xu, Ruiyun; Deng, Meihai; Liu, Bo

    2016-07-27

    The treatment of hepatocellular carcinoma (HCC) is complicated and challenging because of the frequent presence of cirrhosis. Therefore, we propose a novel surgical approach to minimize the invasiveness and risk in patients with HCC, hypersplenism, and esophagogastric varices. This was a retrospective study carried out in 25 patients with HCC and hypersplenism and who underwent simultaneous laparoscopic-guided radio-frequency ablation and laparoscopic splenectomy with endoscopic variceal ligation. Tumor size was restricted to a single nodule of splenectomy. Laparoscopic-guided radio-frequency ablation with laparoscopic splenectomy and endoscopic variceal ligation could be an available technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. This approach may help to minimize the surgical risks and results in a fast increase in platelet counts with an acceptable rate of complications.

  11. Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

    OpenAIRE

    Saif, Muhammad W; Iris Isufi; Jennifer Peccerillo; Syrigos, Kostas N.

    2011-01-01

    Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. La...

  12. Medical image of the week: hepatocellular carcinoma with pulmonary metastasis

    OpenAIRE

    Sobonya R; Geffre C; Hernandez N; Chaudhary S; Siddiqi TA

    2013-01-01

    A 58-year-old man with a history of hepatitis-C, liver cirrhosis and hepatocellular carcinoma treated with sorafenib and chemoembolization was admitted with septic shock due to spontaneous bacterial peritonitis with concomitant hemorrhage and acute renal failure. The patient did not respond to broad-spectrum antibiotics, aggressive care with multiple vasopressors and ventilatory support and died shortly after admission. An autopsy was performed revealing hepatocellular carcinoma with extens...

  13. Medical image of the week: hepatocellular carcinoma with pulmonary metastasis

    Directory of Open Access Journals (Sweden)

    Sobonya R

    2013-05-01

    Full Text Available A 58-year-old man with a history of hepatitis-C, liver cirrhosis and hepatocellular carcinoma treated with sorafenib and chemoembolization was admitted with septic shock due to spontaneous bacterial peritonitis with concomitant hemorrhage and acute renal failure. The patient did not respond to broad-spectrum antibiotics, aggressive care with multiple vasopressors and ventilatory support and died shortly after admission. An autopsy was performed revealing hepatocellular carcinoma with extensive intra-abdominal and thoracic metastasis.

  14. Oncofetal gene SALL4 in aggressive hepatocellular carcinoma.

    Science.gov (United States)

    Yong, Kol Jia; Gao, Chong; Lim, Joline S J; Yan, Benedict; Yang, Henry; Dimitrov, Todor; Kawasaki, Akira; Ong, Chee Wee; Wong, Kwong-Fai; Lee, Sanghoon; Ravikumar, Sharada; Srivastava, Supriya; Tian, Xi; Poon, Ronnie T; Fan, Sheung Tat; Luk, John M; Dan, Yock Young; Salto-Tellez, Manuel; Chai, Li; Tenen, Daniel G

    2013-06-13

    Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo. SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.).

  15. 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.

  16. Hepatocellular carcinoma in variegate porphyria: a case report and literature review.

    Science.gov (United States)

    Luvai, Ahai; Mbagaya, Wycliffe; Narayanan, Deepa; Degg, Tim; Toogood, Giles; Wyatt, Judith I; Swinson, Daniel; Hall, Claire J; Barth, Julian H

    2015-05-01

    Variegate porphyria is an autosomal dominant acute hepatic porphyria characterized by photosensitivity and acute neurovisceral attacks. Hepatocellular carcinoma has been described as a potential complication of variegate porphyria in case reports. We report a case of a 48-year-old woman who was diagnosed with hepatocellular carcinoma following a brief history of right upper quadrant pain which was preceded by a few months of blistering lesions in sun-exposed areas. She was biochemically diagnosed with variegate porphyria, and mutational analysis confirmed the presence of a heterozygous mutation in the protoporphyrinogen oxidase gene. Despite two hepatic resections, she developed pulmonary metastases. She responded remarkably well to Sorafenib and remains in remission 16 months after treatment. A review of the literature revealed that hepatocellular carcinoma in variegate porphyria has been described in at least eight cases. Retrospective and prospective cohort studies have suggested a plausible association between hepatocellular carcinoma and acute hepatic porphyrias. Hepatic porphyrias should be considered in the differential diagnoses of hepatocellular carcinoma of uncertain aetiology. Patients with known hepatic porphyrias may benefit from periodic monitoring for this complication. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Patterns of antigen expression in hepatoblastoma and hepatocellular carcinoma in childhood.

    Science.gov (United States)

    O'Brien, W J; Finlay, J L; Gilbert-Barness, E F

    1989-01-01

    Two hepatocellular carcinomas and six hepatoblastomas were examined for the presence of 13 antigens using immunoperoxidase, avidin-biotin, staining techniques. Primary antibodies were directed against alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), lysozyme (LYS), carcinoembryonic antigen (CEA), human chorionic gonadotropin (HCG), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE), epithelial membrane antigen (EMA), hepatitis B surface antigen (HbSA), lactoferrin (LF), desmin (DES), vimentin (VIM), and keratin (KER). Except for HbSA, the antigen staining pattern was unable to differentiate between hepatoblastoma and hepatocellular carcinoma. Both neoplasms where positive for AFP, AAT, CEA, EMA, and KER; however, neither stained for GFAP, NSE, LYS, LF, HCG, or DES. Vimentin was weakly positive in those hepatoblastomas where mesenchymal tissue was present in the tumor. Only the tissue adjacent to hepatocellular carcinomas stained positively for HbSA and correlated with the elevated serum levels of HbSA.

  18. Overexpression of squamous cell carcinoma antigen variants in hepatocellular carcinoma.

    Science.gov (United States)

    Pontisso, P; Calabrese, F; Benvegnù, L; Lise, M; Belluco, C; Ruvoletto, M G; Marino, M; Valente, M; Nitti, D; Gatta, A; Fassina, G

    2004-02-23

    Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and new tools for diagnostic and therapeutic purposes are ongoing. We have assessed whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in neoplastic cells of epithelial origin, is also expressed in liver cancer. Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs of different aetiology and in 20 normal livers. Proliferative activity was assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver tissue was available for SCCA cDNA amplification and sequencing. Squamous cell carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in none of the 20 controls. In the majority of the cases, the positive signal was found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable SCCA (scoreSCCA score >or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, PSCCA1 variant (G(351) to A) was identified in five cases, while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion, SCCA variants are overexpressed in HCC, independently of tumour aetiology. A novel SCCA1 variant has been identified in one third of liver tumours.

  19. Simulation of right atrial cardiac myxoma by silent hepatocellular carcinoma.

    Science.gov (United States)

    Giacalone, A; Suriani, A; Monga, G

    1996-12-01

    A clinically silent hepatocellular carcinoma presenting as a mixoma of the right atrium is described. Intra-atrial growth has been reported in advanced, clinically manifested cases of liver carcinomas in African and Japanese subjects, but very occasionally in Caucasian people. Our case further suggests that this occurrence should also be considered in Western Countries.

  20. Effect of smoking on survival of patients with hepatocellular carcinoma.

    Science.gov (United States)

    Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

    2017-11-01

    Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, P<.001) and remained independently predictive when adjusted for confounding variables. This study shows that smoking is an independent predictor of survival in hepatitis B virus/hepatitis C virus-infected patients with hepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Weis, Sebastian; Franke, Annegret; Mössner, Joachim

    2013-01-01

    Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol...

  2. Pediatric hepatocellular carcinoma: challenges and solutions

    Directory of Open Access Journals (Sweden)

    Schmid I

    2017-01-01

    Full Text Available Irene Schmid,1 Dietrich von Schweinitz,2 1Department of Pediatric Hematology and Oncology, 2Department of Pediatric Surgery, Dr. von Hauner Children`s Hospital, Ludwig-Maximilians-University, Munich, Germany Abstract: Hepatocellular carcinoma (HCC is a very rare entity in children, making it nearly impossible to orchestrate Phase II/III studies even as multinational cooperative trials. In contrast to adults, nearly 50% of the children have a response (α-fetoprotein decline and/or tumor shrinkage to chemotherapeutic agents such as cisplatin and doxorubicin (PLADO, demonstrating that HCC in childhood can be chemotherapy sensitive. As a result, the main treatment options in pediatric HCC focus on systemic drug therapies and resection as the central therapy. In nonmetastatic patients with complete resection upfront, the 5-year event-free survival and overall survival has reached 80%–90%. In almost all reported studies, children received adjuvant chemotherapy (mostly PLADO, but it has never been proven that postoperative chemotherapy is superior to observation. No data are available for the effects of sorafenib. The 3-year survival is <20% in children with unresectable HCC independent of the chemotherapy given preoperatively. Currently, PLADO in combination with sorafenib is recommended with the goal of achieving operability status. Alternatively, data are promising for the combination of sorafenib with gemcitabine and oxaliplatin. For children with nonresectable and nonmetastastic liver tumors, it has been shown that the Milan criteria regarding liver transplantation are not applicable – individual decisions have to be made. Transarterial chemoembolization could be offered to patients with chemotherapy-resistant liver tumors for palliative care or potentially to achieve surgical resectability, and therefore cure. Information about the feasibility or effects of new agents or approaches as discussed in adult HCC patients is not available for

  3. Solitary skull metastasis as initial manifestation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cho Jun

    2008-06-01

    Full Text Available Abstract Background A solitary skull metastasis from hepatocellular carcinoma (HCC prior to diagnosis of the primary tumor without liver dysfunction is a very rare event. Case presentation A 71-year-old male, without known liver disease, presented to our institution with a palpable occipital scalp mass. On brain magnetic resonance imaging (MRI, a highly enhanced and osteolytic skull tumor was observed. The histological diagnosis obtained from the percutaneous needle biopsy was a cranial metastasis from HCC. The metastatic tumor was removed via occipital craniectomy, and the two primary liver mass lesions were subsequently treated by transarterial chemoembolization. Conclusion An isolated skull metastasis may be the sole initial presentation of HCC. Early diagnosis is essential in order to treat the primary disease. A skull metastasis from HCC should be considered in the differential diagnosis in patients with subcutaneous scalp mass and osteolytic defects on X-ray.

  4. CYCLOOXYGENASE-2 AND HEPATOCELLULAR CARCINOMA: THE PROTEOMICS OF ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Jaya Gandhi

    2011-12-01

    Full Text Available Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. Chronic inflammation is recognised as a threat factor for cancer progression. Cyclooxygenase-2 is the major mediator of inflammation. Various studies on Cox-2 suggest its possible association with HCC differentiation. Sufficient genetic and pharmacologic evidences implicate its crucial role in neoplasia and it is also now clear that Cox-2 plays a crucial role in tumor progression. Cox-2 overexpression is associated with maintaining tumor microenvironment and has crucial implication for angiogenesis. Cox-2 operates in multifactorial fashion. Cox-2 selective inhibition has been reported as a successful tool in suppressing angiogenesis and metastasis. The pharmacological suppression of Cox-2 represents a bright future as a therapeutic tool for treatment of various malignancies. This review is an attempt to discuss the critical issue of overexpression of Cox-2 and its role in the development of HCC in particular and cancer in general.

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  1. File list: ALL.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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  2. Diagnostic and therapeutic management of hepatocellular carcinoma

    Science.gov (United States)

    Bellissimo, Francesco; Pinzone, Marilia Rita; Cacopardo, Bruno; Nunnari, Giuseppe

    2015-01-01

    Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines. PMID:26576088

  3. 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.

  4. 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.

  5. Update on Embolization Therapies for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kishore, Sirish; Friedman, Tamir; Madoff, David C

    2017-06-01

    The purpose of the review is to summarize the latest applications for embolotherapy in the management of patients with HCC according to BCLC stage. While traditionally reserved for patients with unresectable HCC and stage B disease, there is an important role for embolization therapies in earlier stage patients as an adjunct to ablation, bridging, or downstaging therapy, as a means to improve safety of resection, and potentially as an arterial ablative option in the case of radioembolization. Newer applications of radioembolization such as radiation segmentectomy have the potential to provide cure in localized unifocal disease, and transarterial chemoembolization-portal vein embolization and radiation lobectomy may provide a combination of treatment and future liver remnant hypertrophy for planned hepatic resection. There is also an increasing role for embolization in the treatment of stage C disease, and recent data suggest it can be used in combination with sorafenib with the potential for survival benefit over sorafenib alone, even in the case of portal vein tumor thrombus. Embolization therapies play an increasingly important role in patients with BCLC stage A-C hepatocellular carcinoma. While different therapies may be offered on a patient-specific basis, there are limited prospective RCT data to support superiority of one technique over another.

  6. Nonalcoholic fatty liver disease and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LI Liangping

    2016-03-01

    Full Text Available As the etiology of hepatocellular carcinoma (HCC has been changing, the incidence of HCC related to nonalcoholic fatty liver disease (NAFLD is gradually increasing in developed countries in Europe and America and some countries in Asia. This article introduces the close association between NAFLD and HCC, risk factors, clinicopathological features, and prevention and screening, and points out that although the incidence of NAFLD is not as high as that of hepatitis B- or hepatitis C-related HCC, there are a large absolute number of NAFLD patients, especially the high-risk patients with diabetes and obesity, or liver fibrosis/cirrhosis, due to a huge base number of NAFLD patients. NAFLD-related HCC is commonly seen in the elderly with various comorbidities and a poor prognosis. This article also points out that the prevention should focus on the effective treatment of NAFLD. The strict screening of high-risk population is the strategy for the diagnosis of early-stage HCC. At present, the sensitivity of alpha-fetoprotein is relatively low, and imaging examinations including computed tomography are the main screening methods; however, there are no measures for early warning of NAFLD-related HCC.

  7. Hepatocellular carcinoma: clinical frontiers and perspectives

    Science.gov (United States)

    Bruix, Jordi; Gores, Gregory J; Mazzaferro, Vincenzo

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies. PMID:24531850

  8. [Epidemiology and risk factors of hepatocellular carcinoma].

    Science.gov (United States)

    Budny, Agnieszka; Kozłowski, Piotr; Kamińska, Marzena; Jankiewicz, Małgorzata; Kolak, Agnieszka; Budny, Bożena; Budny, Witold; Niemunis-Sawicka, Joanna; Szczypiór, Grzegorz; Kurniawka, Bartosz; Burdan, Franciszek

    2017-09-29

    Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as α1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p.I148M of adiponutrin. HCC is usually detected incidentally, during ultrasound examination or during clinical diagnosis of liver failure. HCC can be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI), which is considered the most accurate diagnostic method. A core needle biopsy or the examination of the level of markers such as: alpha-fetoprotein (AFP), D-gamma-carboxy prothrombin (DCP), tumourassociated glycoprotein 72 (CA 72-4, TAG-72), are advised for a complete diagnostics.

  9. Laser Ablation for Small Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Claudio Maurizio Pacella

    2011-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignancies worldwide and is increasingly detected at small size (<5 cm owing to surveillance programmes in high-risk patients. For these cases, curative therapies such as resection, 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.

  10. Slug promoted vasculogenic mimicry in hepatocellular carcinoma.

    Science.gov (United States)

    Sun, Dan; Sun, Baocun; Liu, Tieju; Zhao, Xiulan; Che, Na; Gu, Qiang; Dong, Xueyi; Yao, Zhi; Li, Rui; Li, Jing; Chi, Jiadong; Sun, Ran

    2013-08-01

    Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumour cells to mimic the pattern of embryonic vasculogenic networks. Epithelial-mesenchymal transition (EMT) regulator slug have been implicated in the tumour invasion and metastasis of human hepatocellular carcinoma (HCC). However, the relationship between slug and VM formation is not clear. In the study, we demonstrated that slug expression was associated with EMT and cancer stem cell (CSCs) phenotype in HCC patients. Importantly, slug showed statistically correlation with VM formation. We consistently demonstrated that an overexpression of slug in HCC cells significantly increased CSCs subpopulation that was obvious by the increased clone forming efficiency in soft agar and by flowcytometry analysis. Meantime, the VM formation and VM mediator overexpression were also induced by slug induction. Finally, slug overexpression lead to the maintenance of CSCs phenotype and VM formation was demonstrated in vivo. Therefore, the results of this study indicate that slug induced the increase and maintenance of CSCs subpopulation and contributed to VM formation eventually. The related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  11. A Quantitative Proteomic Approach for Identification of Potential Biomarkers in Hepatocellular Carcinoma

    OpenAIRE

    Chaerkady, Raghothama; Harsha, H. C.; Nalli, Anuradha; Gucek, Marjan; Vivekanandan, Perumal; Akhtar, Javed; Cole, Robert N.; Simmers, Jessica; Schulick, Richard D.; Singh, Sujay; Torbenson, Michael; Pandey, Akhilesh; Thuluvath, Paul J.

    2008-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. In this study, our objective was to identify differentially regulated proteins in HCC through a quantitative proteomic approach using iTRAQ. More than 600 proteins were quantitated of which 59 proteins were overexpressed and 92 proteins were underexpressed in HCC as compared to adjacent normal tissue. Several differentially expressed proteins were not implicated previously in HCC. A subset of these proteins (six each fr...

  12. Nanomedicine in management of hepatocellular carcinoma: Challenges and opportunities.

    Science.gov (United States)

    Mohamed, Nourhan K; Hamad, Mostafa A; Hafez, Mohamed Z E; Wooley, Karen L; Elsabahy, Mahmoud

    2017-04-01

    Hepatocellular carcinoma is the second leading cause of cancer deaths worldwide. It is characterized by unique features that can be utilized for selective and targeted therapy, which aids in preserving healthy tissues from deteriorating effects of traditional chemotherapeutics. In this minireview, a brief overview of recent drug delivery attempts for the management of hepatocellular carcinoma with the aid of nanomedical structures is presented. The beneficial impact of nanomaterials in terms of prolonged retention in blood and target sites, controlled biodistribution and improved stability of the encapsulated payloads, will be described, together with the possibility of incorporating more than one cargo into the same nanostructure. Incorporation of stimuli-responsive components, decoration with targeting moieties and the use of molecularly targeted drugs for treatment of hepatocellular carcinoma are also highlighted. © 2016 UICC.

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

    Directory of Open Access Journals (Sweden)

    Wang J

    2016-03-01

    Full Text Available Jiye Wang,1 Mi Li,2 Yun Wang,3 Xiaoping Liu4 1The Criminal Science and Technology Department, Zhejiang Police College, Hangzhou, Zhejiang Province, 2Department of Nursing, Shandong College of Traditional Chinese Medicine College, Yantai, Shandong Province, 3Office Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, Shanxi Province, 4Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Shanghai, People’s Republic of China Abstract: 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

  14. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

    OpenAIRE

    Srisomsap, Chantragan; Sawangareetrakul, Phannee; Subhasitanont, Pantipa; Chokchaichamnankit, Daranee; Chiablaem, Khajeelak; Bhudhisawasdi, Vaharabhongsa; Wongkham, Sopit; Svasti, Jisnuson

    2009-01-01

    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...

  15. Dichlorodiphenyltrichloroethane (DDT) and risk of hepatocellular carcinoma

    Science.gov (United States)

    Persson, E. Christina; Graubard, Barry I.; Evans, Alison A.; London, W. Thomas; Weber, Jean-Philippe; LeBlanc, Alain; Chen, Gang; Lin, Wenyao; McGlynn, Katherine A.

    2014-01-01

    Dichlorodiphenyltrichloroethane (p,p’-DDT), an organochlorine pesticide known to have deleterious health effects in humans, has been linked to hepatocellular carcinoma (HCC) in rodents. A recent study has reported that p,p’-DDT and its most persistent metabolite, dichlorodiphenyldichloroethylene (p,p’-DDE), may also be associated with HCC in humans. To examine whether there is an association between p,p’-DDT and/or p,p’-DDE in a population at high-risk of developing HCC. A nested case-control study was conducted within the 83,794 person Haimen City Cohort in China. Sera and questionnaire data were collected from all participants between 1992 and 1993. The current study included 473 persons who developed HCC and 492 who did not, frequency matched on sex, age and area of residence. p,p’-DDT and p,p’-DDE levels were determined by mass spectrometry. Hepatitis B viral infection status (based on hepatitis B virus surface antigen; HBsAg) was also determined. Adjusting for age, sex, area of residence, HBsAg, family history of HCC, history of acute hepatitis, smoking, alcohol, occupation (farmers) and levels of p,p’-DDT or p,p’-DDE, odds ratios (OR) and 95% confidence intervals (CI) were calculated via unconditional logistic regression, p,p’-DDT and/or p,p’-DDE serum levels were significantly associated with sex, area of residence, occupation, alcohol consumption and cigarette smoking. Overall, the highest quintile of p,p’-DDT was associated with an increased risk of HCC, OR= 2.96 95% CI; 1.19–7.40. There were no statistically significant associations with p,p’-DDE. Overall, these results suggest that recent exposure to p,p’-DDT may increase risk of HCC. PMID:22290210

  16. Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

    Science.gov (United States)

    Ur Rahman, Zia; Hurairah, Abu

    2016-01-01

    Our objective was to study nonalcoholic fatty liver disease (NAFLD) as a relevant risk factor associated with hepatocellular carcinoma (HCC) in patients with and without cirrhosis. HCC is a common cancer worldwide that predominantly involves patients with hepatic cirrhosis. HCC has recently been linked to NAFLD, the hepatic manifestation of obesity and related metabolic disorders. This association is alarming due to the high prevalence of NAFLD globally, which may contribute to the rising incidence of HCC. A 31-year-old female with a history of dyslipidemia, hypertension, and diabetes mellitus presented with abdominal pain that persisted for six months. The pain was associated with gastrointestinal symptoms and weight loss. She was drug-free and a nonalcoholic and a nonsmoker. The physical examination was unremarkable. The abdominal exam showed a soft and non-tender abdomen, with no organomegaly or ascites. The laboratory evaluation was unremarkable. The imaging studies showed a hypodense lesion in the right hepatic lobe with strong arterial enhancement. Subsequently, the patient underwent a liver biopsy. The histopathology results were consistent with HCC. The patient underwent an uneventful segment VI liver resection and tumor-free margins were achieved. In our patient, NAFLD was designated as an independent etiology for HCC, without cirrhosis. Our patient recovered well and has been disease free for over a year. HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk of HCC. These results provide new targets for surveillance, prevention, early recognition, and effective treatment of HCC associated with NAFLD. PMID:27733959

  17. Liver failure after hepatocellular carcinoma surgery.

    Science.gov (United States)

    Motoyama, Hiroaki; Kobayashi, Akira; Yokoyama, Takahide; Shimizu, Akira; Furusawa, Norihiko; Sakai, Hiroshi; Kitagawa, Noriyuki; Ohkubo, Yohei; Tsukahara, Teruomi; Miyagawa, Shin-ichi

    2014-12-01

    The aim of this study was to construct a prediction model for posthepatectomy liver failure (PHLF), as defined by the International Study Group of Liver Surgery, and evaluate its accuracy in hepatocellular carcinoma (HCC) patients with cirrhosis or chronic hepatitis. A total of 277 consecutive hepatectomies for HCC between 2005 and 2013 were analyzed retrospectively. Multivariate logistic regression analysis was used to develop a predictive model for PHLF. The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were evaluated. The Hosmer-Lemeshow goodness-of-fit test was used to assess the model calibration. The constructed model was internally validated by k-fold cross-validation (k=5). PHLF developed in 12.6% of hepatectomies. Multivariate analysis identified the following variables as predictors of PHLF: elevated preoperative serum bilirubin level, elevated preoperative international normalized ratio, and intraoperative packed red blood cell transfusion. The predictive model allowed discrimination between patients who developed PHLF and those who did not, with a sensitivity of 82.9%, specificity of 72.3%, and AUROC curve of 0.81 (95% CI, 0.74 to 0.89). The Hosmer-Lemeshow test indicated a good fit (P=0.545). The AUROC curve of the developed model was significantly greater than that of the model for end-stage liver disease (MELD) score (P=0.014), suggesting that the former model is better at predicting the PHLF than the latter one. The developed model could be useful for predicting the occurrence of PHLF in HCC patients with underlying liver disease.

  18. Epidemiology of hepatocellular carcinoma in India.

    Science.gov (United States)

    Acharya, Subrat K

    2014-08-01

    Indian data on epidemiology of HCC is not available. Cancer is not a reportable disease in India and the cancer registries in India are mostly urban. National cancer registry program of the Indian Council of Medical Research (ICMR) has been recently expanded to include 21 population based and 6 hospital based cancer registries. The last published registry data by ICMR available in the cancer registry website (www.ncrpindia.org) was in 2008 which provides information on various cancers from 2006 to 2008. The other source of information was the report published by International Agency for Research on Cancer (WHO). According to these available data the age adjusted incidence rate of hepatocellular carcinoma (HCC) in India for men ranges from 0.7 to 7.5 and for women 0.2 to 2.2 per 100,000 population per year. The male:female ratio for HCC in India is 4:1. The age of presentation varies from 40 to 70 years. According to a study conducted by verbal autopsy in 1.1 million homes representing the whole country, the age standardized mortality rate for HCC in India for men is 6.8/100,000 and for women is 5.1/100,000. According to another study the incidence of HCC in cirrhotics in India is 1.6% per year. The unpublished data from various tertiary care centers suggest that the incidence of HCC is increasing in India. There is a need for a multi-centric HCC registry under the aegis of INASL.

  19. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Y.; Nakano, S.; Ibuka, K.; Hashizume, T.; Noguchi, A.; Sasaki, Y.; Imaoka, S.; Fujita, M.; Kawamoto, S.; Kasugai, H.

    1986-01-15

    For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma.

  20. Distinction between hemangioma of the liver and hepatocellular carcinoma: value of labeled RBC-SPECT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Kudo, M.; Ikekubo, K.; Yamamoto, K.; Ibuki, Y.; Hino, M.; Tomita, S.; Komori, H.; Orino, A.; Todo, A.

    1989-05-01

    The role of adding single-photon emission CT (SPECT) to /sup 99m/Tc-labeled RBC imaging of the liver was evaluated by specifically focusing on the differentiation between hepatic hemangioma and hepatocellular carcinoma. Planar RBC imaging followed by blood-pool SPECT scanning was performed in 77 patients with a total of 108 hemangiomas and in 29 patients with a total of 46 hepatocellular carcinomas. All lesions were smaller than 5 cm in diameter. Thirty-six (33%) of 108 hemangiomas were detected by planar delayed RBC imaging, whereas 63 (58%) were detected by the delayed RBC-SPECT scan. The smallest hemangioma shown by delayed RBC-SPECT scanning was 1.4 cm in diameter, compared with 1.7 cm by planar RBC scanning. When confined to nodules larger than 1.4 cm in diameter, 42% of hemangiomas (36/85) were detected by planar delayed RBC imaging, whereas 74% (63/85) were detected by delayed RBC-SPECT. Increase in sensitivity was noted in nodules 2.1-4.0 cm in diameter. No hepatocellular carcinomas were shown by delayed RBC planar or SPECT scans. We concluded that with the addition of SPECT, the sensitivity of delayed RBC scans in the detection of small hemangiomas is considerably improved. Delayed RBC-SPECT scanning can be used to distinguish hemangioma from hepatocellular carcinoma.

  1. Magnetic resonance imaging following treatment of advanced hepatocellular carcinoma with sorafenib

    Directory of Open Access Journals (Sweden)

    Joon-Il Choi

    2014-06-01

    Full Text Available Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.

  2. Inhibition of Regulatory Volume Decrease Enhances the Cytocidal Effect of Hypotonic Shock in Hepatocellular Carcinoma.

    Science.gov (United States)

    Kudou, Michihiro; Shiozaki, Atsushi; Kosuga, Toshiyuki; Ichikawa, Daisuke; Konishi, Hirotaka; Morimura, Ryo; Komatsu, Shuhei; Ikoma, Hisashi; Fujiwara, Hitoshi; Okamoto, Kazuma; Hosogi, Shigekuni; Nakahari, Takashi; Marunaka, Yoshinori; Otsuji, Eigo

    2016-01-01

    Background : Hypotonic shock induces cytocidal effects through cell rupture, and cancer therapy based on this mechanism has been clinically administered to hepatocellular carcinoma patients. We herein investigated the effectiveness of hypotonic shock combined with the inhibition of regulatory volume decrease as cancer therapy for hepatocellular carcinoma. Methods : Morphological changes in human hepatocellular carcinoma cell lines were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes under hypotonic shock with or without chloride, potassium, or water channel blockers were observed using a high-resolution flow cytometer. In order to investigate cytocidal effects, the number of surviving cells was compared after exposure to hypotonic solution with and without each channel blocker (re-incubation experiment). Results : Video recordings showed that cells exposed to distilled water rapidly swelled and then ruptured. Cell volume measurements revealed regulatory volume decrease under mild hypotonic shock, whereas severe hypotonic shock increased the number of broken fragments as a result of cell rupture. Moreover, regulatory volume decrease was inhibited in cells treated with each channel blocker. Re-incubation experiments showed the cytocidal effects of hypotonic shock in cells exposed to hypotonic solution, and additional treatments with each channel blocker enhanced these effects. Conclusion : The inhibition of regulatory volume decrease with chloride, potassium, or water channel blockers may enhance the cytocidal effects of hypotonic shock in hepatocellular carcinoma. Hypotonic shock combined with the inhibition of regulatory volume decrease was a more effective therapy than hypotonic shock alone.

  3. SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

    Science.gov (United States)

    Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

    2016-01-01

    Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos

  4. Mechanisms of pyruvate kinase M2 isoform inhibits cell motility in hepatocellular carcinoma cells.

    Science.gov (United States)

    Chen, Yan-Ling; Song, Jun-Jiao; Chen, Xiao-Chun; Xu, Wei; Zhi, Qiang; Liu, Yun-Peng; Xu, Hong-Zhi; Pan, Jin-Shui; Ren, Jian-Lin; Guleng, Bayasi

    2015-08-14

    To investigate biological mechanisms underlying pyruvate kinase M2 isoform (PKM2) regulation of cell migration and invasion in hepatocellular carcinoma cells. HepG2 and Huh-7 hepatocellular carcinoma cell lines were stably transfected and cultured in DMEM (HyClone, Logan, UT, United States). To investigate the effects of PKM2 on cellular proliferation, hepatocellular carcinoma cells were subjected to the Cell Counting Kit-8 (Dojindo, Kamimashiki-gun, Kumamoto, Japan). And investigate the effects of PKM2 on cell signal pathway related with migration and invasion, Western immunoblotting were used to find out the differential proteins. All the antibody used was purchaseed from Cell Signal Technology. In order to explore cell motility used Transwell invasion and wound healing assays. The transwell plate with 0.5 mg/mL collagen type I (BD Bioscience, San Jose, CA)-coated filters. The wound-healing assay was performed in 6-well plates. Total RNA was extracted using TRIzol reagent (Invitrogen, CA, United States) and then reverse transcription was conducted. Quantitative reverse transcription-polymerase chain reaction (PCR) analysis was performed with the ABI 7500 real-time PCR system (Applied Biosystems). We further use digital gene expression tag profiling and identification of differentially expressed genes. The cells seeded in four 96-well plates were measured OD450 by conducted Cell Counting Kit-8. From this conduction we observed that both HepG2 and Huh-7 hepatocellular carcinoma cells with silenced PKM2 turn on a proliferate inhibition; however, cell migration and invasion were enhanced compared with the control upon stimulation with epidermal growth factor (EGF). Our results indicate that the knockdown of PKM2 decreased the expression of E-cadherin and enhanced the activity of the EGF/EGFR signaling pathway, furthermore up-regulate the subsequent signal molecular the PLCγ1 and extracellular signal-regulated kinase 1/2 expression in the hepatocellular carcinoma

  5. Differential impact of risk factors for tumor recurrence in hepatitis B and hepatitis C virus-infected patients undergoing liver transplantation for hepatocellular carcinoma.

    Science.gov (United States)

    Krasnodębski, Maciej; Grąt, Michał; Masior, Łukasz; Patkowski, Waldemar; Krawczyk, Marek

    2015-02-02

    Hepatitis B (HBV) and C (HCV) virus infection are the 2 most important risk factors for the development of the hepatocellular carcinoma (HCC). The aim of this study was to assess the importance of the type of viral infection in evaluation of HCC recurrence risk after liver transplantation (LT). This retrospective study was based on 130 HCC patients undergoing LT. Patients were subdivided by HBV or HCV infection only or HBV and HCV co-infection (HBV-HCV). The primary outcome measure was recurrence-free survival (RFS) 5 years after transplantation. The 5-year RFS did not differ significantly according to HBV infection, HCV infection, or HBV-HCV co-infection in the entire study cohort (p=0.902) or among patients who fulfilled (p=0.454) or did not fulfill (p=0.999) the Milan criteria. Neither HCV (p=0.869) nor HBV (p=0.968) infection significantly affected 5-year RFS following adjustment for covariates. Higher lesion number (p=0.004), increased alpha-fetoprotein (p=0.017), microvascular invasion (p=0.004), and female donor sex (p=0.025) were significant risk factors for poor RFS in HBV patients; older recipient age (p=0.010) and increased total tumor volume (p=0.028) were significant risk factors in HCV patients. Although the viral infection type does not affect post-LT outcomes in HCC patients, the influence of other risk factors is markedly different in HBV- and HCV-related HCC.

  6. Pattern and chronological change of iodized oil retention in radiofrequency ablation-induced vascular injury area: differentiation from iodized oil retention in recurrent hepatocellular carcinoma on computed tomography.

    Science.gov (United States)

    Lee, Ji Young; Kim, Young-sun; Rhim, Hyunchul; Lim, Hyo K; Choi, Dongil; Lee, Won Jae

    2010-01-01

    The purpose of this study was to evaluate the pattern and the chronological change of iodized oil retention in a radiofrequency ablation (RFA)-induced vascular injury area as compared with that in recurrent hepatocellular carcinoma (HCC). Informed consents from all the patients and approval from the institutional review board were obtained. The computed tomographic scans of 226 patients who underwent both RFA and subsequent transcatheter arterial chemoembolization for recurrence were retrospectively reviewed. The RFA-induced vascular injury area that did not have HCC recurrence in it were examined and assessed whether iodized oil was retained after transcatheter arterial chemoembolization. We evaluated the incidence, the shape, and the duration of the iodized oil retention in the RFA-induced vascular injury area and compared them with those found in recurrent HCC from the same patient. The rate of misinterpretation was calculated. Of 59 RFA-induced vascular injury areas that were within the range of segmental embolization, 33 RFA-induced vascular injury areas (55.9%) in 31 patients retained iodized oil. The shapes of the iodized oil in the RFA-induced vascular injury area were diffuse-dense (n = 13), diffuse-faint (n = 8), nodular-dense (n = 8), or nodular-faint (n = 4). In 29 (93.5%) of 31 patients, at least one recurrent HCC retained iodized oil, and they were all nodular-dense in shape. The duration of the retention in RFA-induced vascular injury area (mean [SD], 3.3 [3.2] months) was significantly shorter than that in recurrent tumors (21.2 [12.5] months, P oil density in the RFA-induced vascular injury area was clinically misinterpreted as recurrent HCC. The RFA-induced vascular injury area frequently retains iodized oil, which could mimic recurrent HCC. However, we determined that iodized oil in the RFA-induced vascular injury area differs from that in HCC in variety in shape and shorter duration of retention.

  7. Reduced expression of TANGO in colon and hepatocellular carcinomas.

    Science.gov (United States)

    Arndt, Stephanie; Bosserhoff, Anja K

    2007-10-01

    The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.

  8. Meta-analysis of DNA methylation biomarkers in hepatocellular carcinoma

    OpenAIRE

    Zhang, Cheng; Li, Jinyun; Huang, Tao; Duan, Shiwei; Dai, Dongjun; Jiang, Danjie; Sui, Xinbing; Li, Da; Chen, Yidan; Ding, Fei; Huang, Changxin; Chen, Gongying; Wang, Kaifeng

    2016-01-01

    DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma t...

  9. MicroRNA-144 inhibits hepatocellular carcinoma cell proliferation ...

    Indian Academy of Sciences (India)

    MicroRNA 144 (miR-144), a small non-coding RNA, is frequently dysregulated in human several tumour progression,but its role and the underlying mechanisms in hepatocellular carcinoma (HCC) is poorly investigated. In thepresent study, the expression of miR-144 was firstly analysed in datasets derived from GSE21362 ...

  10. Infection of hepatitis C virus genotypes in hepatocellular carcinoma ...

    African Journals Online (AJOL)

    The aim of this retrospective study was to investigate the infection of hepatitis C virus (HCV) genotypes in hepatocellular carcinoma (HCC) patients from rural areas of Faisalabad region. Among 179 HCC subjects, men and women were 51 and 49%, respectively. All samples positive for HCV RNA by qualitative PCR were ...

  11. Sen Virus and Hepatocellular Carcinoma in Southern African Blacks ...

    African Journals Online (AJOL)

    SEN virus (SENV), or its variants (SENV-D and SENV-H), have been detected in the serum of patients with hepatocellular carcinoma (HCC), acute or chronic benign hepatic diseases, and healthy individuals in a number of countries. No information has hitherto been available in sub-Saharan African populations.

  12. Advanced Hepatocellular Carcinoma in 3 rd Trimester of Pregnancy ...

    African Journals Online (AJOL)

    Hepatocellular carcinoma is the commonest malignancy complicating chronic liver disease in the developing world. It could present with progressive right upper abdominal swelling and features of hepatic dysfunction. Pregnancy is associated with progressive abdominal distension and exerts increased physiological ...

  13. Non-bleeding Spontaneous Rupture of Hepatocellular Carcinoma ...

    African Journals Online (AJOL)

    Rupture of hepatocellular carcinoma (HCC) is not uncommon and most ruptured HCC present with hemoperitoneum and hemorrhagic shock. Management of ruptured HCC is different than non.ruptured one. Short. and long.term mortality increases following rupture of HCC with increasing chances of tumor dissemination.

  14. Liver resection for non-cirrhotic hepatocellular carcinoma in south ...

    African Journals Online (AJOL)

    Background. We describe the clinicopathologic features and outcome of South African patients who have undergone hepatic resection for hepatocellular carcinoma (HCC) arising in a non-cirrhotic liver. Methods. We utilised the prospective liver resection database in the Surgical Gastroenterology Unit at Groote Schuur ...

  15. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    OpenAIRE

    Mathonnet, Muriel; Descottes, Bernard; Valleix, Denis; Truffinet, Véronique; Labrousse, François; Denizot, Yves

    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).

  16. Peanut butter consumption and hepatocellular carcinoma in Sudan

    NARCIS (Netherlands)

    Hadi Omer, El 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

  17. Non‑bleeding Spontaneous Rupture of Hepatocellular Carcinoma

    African Journals Online (AJOL)

    Medical Education and Research, Ram Manohar Lohia Hospital, New Delhi, India. ABSTRACT. Rupture of hepatocellular carcinoma (HCC) is not .... A free application to browse and search the journal's content is now available for iPhone/iPad. The application provides “Table of Contents” of the latest issues, which are ...

  18. Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.

    Science.gov (United States)

    Yang, Chuang-Bo; Zhang, Shuang; Jia, Yong-Jun; Yu, Yong; Duan, Hai-Feng; Zhang, Xi-Rong; Ma, Guang-Ming; Ren, Chenglong; Yu, Nan

    2017-10-01

    To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RICAP-VP: [RICAP-VP=(ICAP-ICVP)/ICAP]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RICAP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all pSpectral CT provides additional quantitative parameters than conventional CT to improve the differentiation between small hepatocellular carcinoma with and without microvascular invasion. Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Viral pathogenesis of hepatocellular carcinoma in the United States.

    Science.gov (United States)

    Liang, T J; Jeffers, L J; Reddy, K R; De Medina, M; Parker, I T; Cheinquer, H; Idrovo, V; Rabassa, A; Schiff, E R

    1993-12-01

    Chronic hepatitis B virus infection is closely associated with the development of hepatocellular carcinoma, which is a major cause of cancer death worldwide. Recent studies have implicated hepatitis C virus infection as a major pathogenic agent of HBsAg-negative hepatocellular carcinoma. The significance of hepatitis C virus and hepatitis B virus infections in the occurrence of HBsAg-negative hepatocellular carcinoma has not been well established in the United States. We studied 91 HBsAg-negative American patients with hepatocellular carcinoma for evidence of hepatitis C virus or hepatitis B virus infection. These patients had no other predisposing factors to hepatocellular carcinoma. A sensitive polymerase chain reaction was employed to detect hepatitis C virus RNA and hepatitis B virus DNA in serum and liver. Three sets of hepatitis C virus and hepatitis B virus primers were used to optimize the detection of viral genomes. Hepatitis C virus antibodies were measured with second-generation immunoassays. Twenty-six (29%) of these patients carried low levels of hepatitis B virus DNA in either serum, liver/tumor tissue or both. On the basis of the results from serological and polymerase chain reaction analyses of serum and liver, we found that 53 of 91 patients (58%) exhibited evidence of hepatitis C virus infection. When data were combined, 14 patients (15%) had evidence of hepatitis B virus/hepatitis C virus coinfection, whereas 12 (13%) were infected with hepatitis B virus alone and 39 (43%) had hepatitis C virus only. Twenty-six (29%) had no markers of hepatitis B virus or hepatitis C virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Serotonin Activated Hepatic Stellate Cells Contribute to Sex Disparity in Hepatocellular Carcinoma

    OpenAIRE

    Yang, Qiqi; Yan, Chuan; Yin, Chunyue; Gong, Zhiyuan

    2017-01-01

    Background & Aims Hepatocellular carcinoma (HCC) occurs more frequently and aggressively in men than in women. Although sex hormones are believed to play a critical role in this disparity, the possible contribution of other factors largely is unknown. We aimed to investigate the role of serotonin on its contribution of sex discrepancy during HCC. Methods By using an inducible zebrafish HCC model through hepatocyte-specific transgenic kras V12 expression, differential rates of HCC in male and ...

  1. Successful Surgical Control of Peritoneal Dissemination of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Norio Yokoigawa

    2012-09-01

    Full Text Available Treatment for the peritoneal dissemination of hepatocellular carcinoma (HCC has not yet been established. We report a patient with HCC associated with disseminated intra-abdominal tumor. A 74-year-old man was admitted to our hospital. Computed tomography showed a 3 × 3 cm mass in the left hepatic lobe and a giant mass between the stomach and spleen. At laparotomy, the tumor was seen in the medial segment and evaginated to the diaphragm. There was a tumor between the stomach and spleen, confirmed as a 5 × 5 cm tumor evaginated from the left diaphragm, and a 7 × 7 cm tumor adhesive to the spleen. These two tumors were not continuous and were separated. Furthermore, we confirmed a 10 × 10 cm tumor in the pelvic cavity. We performed partial hepatectomy, resection of the tumor evaginated from the diaphragm, resection of the tumor of the spleen and tail of pancreas, and resection of the tumor in the pelvic cavity. Histopathologically, all resected tumors were confirmed to be well-differentiated HCC. HCC rarely disseminates intraperitoneally. It is considered that the peritoneal dissemination of HCC occurred from poorly differentiated or undifferentiated type. Then this report is a rare case. Although surgical treatment of peritoneal dissemination of HCC is not curative, surgery may improve survival and provide good quality of life in selected cases.

  2. Dynamic protein interaction modules in human hepatocellular carcinoma progression.

    Science.gov (United States)

    Yu, Hui; Lin, Chen-Ching; Li, Yuan-Yuan; Zhao, Zhongming

    2013-01-01

    Gene expression profiles have been frequently integrated with the human protein interactome to uncover functional modules under specific conditions like disease state. Beyond traditional differential expression analysis, differential co-expression analysis has emerged as a robust approach to reveal condition-specific network modules, with successful applications in a few human disease studies. Hepatocellular carcinoma (HCC), which is often interrelated with the Hepatitis C virus, typically develops through multiple stages. A comprehensive investigation of HCC progression-specific differential co-expression modules may advance our understanding of HCC's pathophysiological mechanisms. Compared with differentially expressed genes, differentially co-expressed genes were found more likely enriched with Hepatitis C virus binding proteins and cancer-mutated genes, and they were clustered more densely in the human reference protein interaction network. These observations indicated that a differential co-expression approach could outperform the standard differential expression network analysis in searching for disease-related modules. We then proposed a differential co-expression network approach to uncover network modules involved in HCC development. Specifically, we discovered subnetworks that enriched differentially co-expressed gene pairs in each HCC transition stage, and further resolved modules with coherent co-expression change patterns over all HCC developmental stages. Our identified network modules were enriched with HCC-related genes and implicated in cancer-related biological functions. In particular, APC and YWHAZ were highlighted as two most remarkable genes in the network modules, and their dynamic interaction partnership was resolved in HCC development. We demonstrated that integration of differential co-expression with the protein interactome could outperform the traditional differential expression approach in discovering network modules of human diseases

  3. Pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Yi-Tsung; Liu, Chia-Jen; Chen, Tzeng-Ji; Chen, Te-Li; Yeh, Yi-Chen; Wu, Hau-Shin; Tseng, Chih-Peng; Wang, Fu-Der; Tzeng, Cheng-Hwai; Fung, Chang-Phone

    2011-12-01

    Pyogenic liver abscess and hepatocellular carcinoma are common in Taiwan. We investigated the frequency of, risk factors for, and prognosis of pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma over a 12-year period in Taiwan. We extracted 32,454 patients with pyogenic liver abscess from a nationwide health registry in Taiwan during the period 1997-2008. The frequency of and risk factors for pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma were determined. The prognosis of these patients was compared with patients with hepatocellular carcinoma but without liver abscess. A total of 698 (2.15%) patients presented with liver abscess as the initial manifestation of underlying hepatocellular carcinoma during the 12-year period. Liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, and age ≥65 years were independent risk factors for liver abscess as the initial manifestation of underlying hepatocellular carcinoma. Furthermore, these patients had a lower 2-year survival rate than patients with hepatocellular carcinoma but without liver abscess (30% vs 37%; P=.004). The prognosis of patients who presented with pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma was poor. Physicians should not ignore the possibility of underlying hepatocellular carcinoma in patients with risk factors for the disease in regions with a high prevalence of both pyogenic liver abscess and hepatocellular carcinoma. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2.

    Science.gov (United States)

    Huang, Bee-Piao; Lin, Chun-Shiang; Wang, Chau-Jong; Kao, Shao-Hsuan

    2017-01-01

    Tumor necrosis factor alpha (TNFα) plays diverse roles in liver damage and hepatocarcinogenesis with its multipotent bioactivity. However, the influence of TNFα on protein expression of hepatocellular carcinoma (HCC) is incompletely understood. Therefore, we aimed to investigate the differential protein expression of HCC in response to TNFα stimulus. We observed that HepG2 cell revealed a higher resistance to TNFα-induced apoptosis as compared to the non-tumorigenic hepatocyte THLE-2. By using a label-free quantitative proteomic analysis, we found that 520 proteins were differentially expressed in the HepG2 cells exposed to TNFα, including 211 up-regulated and 309 down-regulated proteins. We further confirmed several proteins with significant expression change (TNFα/control ratio>2.0 or expressed proteins using Gene ontology and KEGG annotations, and the results implicated that TNFα might regulate ribosome, spliceosome, antigen processing and presentation, and energy metabolism in HepG2 cells. Moreover, we demonstrated that upregulation of heat shock protein 70 (HSP70) was involved in both the promoted migration and the inhibited apoptosis of HepG2 cells in response to TNFα. Collectively, these findings indicate that TNFα alters protein expression such as HSP70, which triggering specific molecular processes and signaling cascades that promote migration and inhibit apoptosis of HepG2 cells.

  5. Hepatocellular carcinoma (Letter to the editor)

    DEFF Research Database (Denmark)

    Békássy, Albert N.; Garwicz, Stanislaw; Jensen, O.A.

    1994-01-01

    Øjenpatologi, Alagill's syndrome, hepatic carcinoma, biliary atresia, histopathology, liver, child, liver cirrhosis, autopsy, eyes, AFP......Øjenpatologi, Alagill's syndrome, hepatic carcinoma, biliary atresia, histopathology, liver, child, liver cirrhosis, autopsy, eyes, AFP...

  6. 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

  7. 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

  8. Hepatocellular Carcinoma with Foamy Histiocyte-Like Appearance: A Deceptively Clear Cell Carcinoma Appearing Variant

    Directory of Open Access Journals (Sweden)

    Takuji Noro

    2010-08-01

    Full Text Available Hepatocellular carcinoma (HCC shows many pathological features, and it varies architecturally and cytologically. There have been many reports and discussions of the morphological features of HCC. A 63-year-old man was found to have a solitary tumor in liver segment 7 that was diagnosed as HCC. A partial resection of liver segment 7 was performed. Microscopically, the tumor lesion showed a moderately differentiated HCC. There was also a lesion with foamy histiocyte-like cells corresponding to the white lesion in the face of the cut tumor. Immunohistochemical staining showed that they were negative for CD68, S-100, vimentin, and HMB-45. The cytoplasm itself was negative on periodic acid Schiff (PAS and Sudan staining. Without immunohistological analysis, it is difficult to distinguish this HCC variant from clear cell carcinoma or metastases of renal cell carcinoma. It is important to recognize this type as a specific cytological variant of HCC that requires confirmation by immunohistochemistry. This report describes the case of a patient with a morphologically distinctive pattern of HCC with prominent cell cytoplasm that had a foamy histiocyte-like appearance. To the best of our knowledge, this is the first report of this HCC variant.

  9. Ultrasonography findings of thyroid metastasis in a patient with hepatocellular carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Ho; Park, Noh Hyuck; Lim, Jae Hoon; Park, Chan Sub; Seong, Su Ok; Kwon, Tae Jung [Myongji Hospital, Goyang (Korea, Republic of)

    2015-03-15

    Although the thyroid gland is one of the most vascular organs of the body, metastatic disease in the thyroid is encountered infrequently. However, at autopsy, the incidence rate of thyroid metastasis ranges from 1.25% to 24%. The primary sites are the kidney, lung, breast, and gastrointestinal tract. We report a rare case of a hepatocellular carcinoma metastatic to the thyroid gland. The patient had multiple palpable masses in the anterior and left lateral neck along the internal jugular chain on physical examination 9 months after the initial diagnosis of liver tumor. These masses were confirmed as metastasis from hepatocellular carcinoma by ultrasonography-guided 16-G core needle biopsy. We discuss the sonographic findings of thyroid metastasis and their use as an additional aid for differentiating between unknown primary tumor and thyroid metastasis.

  10. Inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma.

    Science.gov (United States)

    Han, Ke-Qi; He, Xue-Qun; Ma, Meng-Yu; Guo, Xiao-Dong; Zhang, Xue-Min; Chen, Jie; Han, Hui; Zhang, Wei-Wei; Zhu, Quan-Gang; Nian, Hua; Ma, Li-Jun

    2015-04-28

    To study the inflammatory microenvironment and expression of chemokines in hepatocellular carcinoma (HCC) in nude mice. CBRH-7919 HCC cells were injected into the subcutaneous region of nude mice. Beginning two weeks after the challenge, tumor growth was measured every week for six weeks. The stromal microenvironment and inflammatory cell infiltration was assessed by immunohistochemistry in paired tumor and adjacent peritumoral samples, and macrophage phenotype was assessed using double-stain immunohistochemistry incorporating expression of an intracellular enzyme. A chemokine PCR array, comprised of 98 genes, was used to screen differential gene expressions, which were validated by Western blotting. Additionally, expression of identified chemokines was knocked-down by RNA interference, and the effect on tumor growth was assessed. Inflammatory cell infiltrates are a key feature of adjacent peritumoral tissues with increased macrophage, neutrophil, and T cell (specifically helper and activated subsets) infiltration. Macrophages within adjacent peritumoral tissues express inducible nitric oxide synthase, suggestive of a proinflammatory phenotype. Fifty-one genes were identified in tumor tissues during the progression period, including 50 that were overexpressed (including CXCL1, CXCL2 and CXCL3) and three that were underexpressed (CXCR1, Ifg and Actb). RNA interference of CXCL1 in the CBRH-7919 cells decreased the growth of tumors in nude mice and inhibited expression of CXCL2, CXCL3 and interleukin-1β protein. These findings suggest that CXCL1 plays a critical role in tumor growth and may serve as a potential molecular target for use in HCC therapy.

  11. Effect of superoxide and inflammatory factor on aflatoxin B1 triggered hepatocellular carcinoma

    OpenAIRE

    Qin, Huimin; Li, Hongtao; Zhou, Xiaolin; Peng, Chen; Tan, Honghu; WANG, MINXIN

    2016-01-01

    Presently, there have been a lot of documents confirmed that aflatoxin B1 could promote the incident rate of hepato-cellular carcinoma, but the specific mechanism is not completely clear. Some evidences showed that it might relate to oxidative stress and inflammatory reaction. So the rat hepato-cellular carcinoma model was applied in this study for being discussed. Aflatoxin B1 was applied for inducing the rats to produce hepato-cellular carcinoma model to evaluate the expression of histopath...

  12. Cellular and stromal characteristics in the scirrhous hepatocellular carcinoma: comparison with hepatocellular carcinomas and intrahepatic cholangiocarcinomas.

    Science.gov (United States)

    Okamura, Nobuyoshi; Yoshida, Muneki; Shibuya, Akitaka; Sugiura, Hitoshi; Okayasu, Isao; Ohbu, Makoto

    2005-11-01

    Scirrhous hepatocellular carcinoma (SHCC) is a rare variation of HCC, for which characteristics of tumor cells and the fibrotic stroma have not been clarified in detail. The present study was therefore carried out to elucidate cytological features of tumor and stromal cells and components of the stromal extracellular matrix in 15 SHCC patients undergoing hepatectomy without preoperative transarterial embolization. Diagnosis was on the basis of a scirrhous histological pattern exceeding 50% of the tumor area. Expression of cytoplasmic and extracellular matrix proteins was compared among SHCC, HCC and intrahepatic cholangiocarcinoma (ICC) cases with immunohistochemical staining. The lesions could be histologically divided into radiating and sinusoidal types. Common stromal components of SHCC and ICC were collagen types I and III. There was no expression of laminin-5 in the stroma of SHCC, but it was present in almost all ICC cases. Tenascin-C expression was significantly lower in the SHCC cases and its distribution differed between SHCC and ICC. Matrix metalloproteinase-7 (MMP-7) expression was significantly higher in SHCC compared with HCC. Almost all stromal cells were alpha-smooth muscle actin-positive both in SHCC and ICC, whereas glial fibrillary acid protein (GFAP)-positive stromal cells were significantly more increased in ICC than in SHCC. SHCC clearly differed from HCC with respect to collagen types I, III and MMP-7 expression, and from ICC with regard to stromal components including laminin-5, tenascin-C and GFAP(+) stromal cells.

  13. Identification of Differential Protein Expression in Hepatocellular Carcinoma Induced Wistar Albino Rats by 2D Electrophoresis and MALDI-TOF-MS Analysis.

    Science.gov (United States)

    Vedarethinam, Vadanasundari; Dhanaraj, Karthik; Soundherrajan, Ilavenil; Sivanesan, Ravikumar

    2016-04-01

    Hepato cellular carcinoma (HCC) is a type of malignant tumor. To investigate the proteins in cancer molecular mechanism and its role in HCC, we have used proteomic tools such as 2DE and MALDI-TOF-MS. Our investigation ravels that, plasma α-fetoprotein and carcinoembryonic antigen levels were elevated in DEN induced rats and gradually decreased after the treatment with 1,3BPMU. 2DE and MALDI-TOF-MS tool offers to identify the up and down regulation of proteins in HCC. Proteomic study reveals that, five differentially expressed proteins were identified in DEN induced rats and 1,3BPMU treated rats i.e. three up regulated protein such as T kininogen, NDPKB, PRMT1 (DEN induced rats), RGS19 and PAF (1,3BPMU treated rats) in 3BPMU treated rats, activation of transcription of a single gene from multiple promoters provides flexibility in the controlled gene expression. The regulations of hepatocyte stimulating factor were slow down the proliferation of hepatic cell and uncontrolled hepatic cell growth and also molecular signals strongly argue for a patho-physiological role in liver metastasis to control the cell aggression. This indicates that, anti cancer property of 1,3BPMU can be used as potent anti cancer agent. The present study also shows the proteomic approach helps to elucidate the tumor maker as well as regulatory marker proteins in HCC.

  14. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

  15. Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy

    DEFF Research Database (Denmark)

    Ungureanu, Bogdan Silviu; Teodorescu, Cristian-Mihail; Săftoiu, Adrian

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results. In princ......Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results....... In principle, three different approaches can be used in the treatment of tumors with superparamagnetic iron oxide nanoparticles: magnetically induced hyperthermia, drug targeting and selective suppression of tumor growth. This review focuses on the use of iron oxide nanoparticles for the diagnosis...

  16. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances.

    Science.gov (United States)

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development.

  17. Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

    Science.gov (United States)

    Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

    2011-01-01

    Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

  18. Hepatocellular carcinoma: Implications for Asia-Pacific Oncology Nurses

    Directory of Open Access Journals (Sweden)

    Deborah A Boyle

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a prominent malignancy in the Asia-Pacific region. Despite considerable knowledge about it's scope and nature this malignancy remains incurable. This manuscript reviews the epidemiology of this cancer, its pathogenesis, risk factors, potential prevention, surveillance, treatment, and the oncology nurses' role relative to this malignancy. A literature search from the past decade was performed using the PubMed and CINAHL databases using the search terms “hepatocellular carcinoma,” “Asia,” and “nursing issues”. Themes such as etiology, prevention, treatment, and prognosis were included in this synthesis which has particular relevance to oncology nurses within the Asia-Pacific region.

  19. Simple Sugar Intake and Hepatocellular Carcinoma: Epidemiological and Mechanistic Insight

    Directory of Open Access Journals (Sweden)

    Juan Carlos Laguna

    2014-12-01

    Full Text Available Sugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved.

  20. Serological diagnosis of hepatocellular carcinoma: challenges and opportunities

    Directory of Open Access Journals (Sweden)

    LU Fengmin

    2017-07-01

    Full Text Available Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma. This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin. Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied. The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

  1. Combined approach for spontaneous rupture of hepatocellular carcinoma.

    Science.gov (United States)

    Rossetto, Anna; Adani, Gian Luigi; Risaliti, Andrea; Baccarani, Umberto; Bresadola, Vittorio; Lorenzin, Dario; Terrosu, Giovanni

    2010-01-27

    Ruptured hepatocellular carcinoma is a rare, emergency occurrence in western countries with high mortality risk. A number of hypotheses have been formulated in order to explain the precise mechanism that leads to hepatocellular carcinoma (HCC) rupture: sub-capsular location, dimensions, portal hypertension, tumour necrosis, local increase of venous pressure due to the outflow reduction caused by neoplastic invasion, and the presence of a previous vascular injury which might predispose to HCC rupture. There is still a debate in the literature concerning the best approach in cases of HCC rupture. Surgery is the first option for treatment of acute abdominal bleeding. However the advent of endovascular treatments widens the range of possible therapies for acute bleeding control and subsequent ablation purposes. We report a case of hemoperitoneum from spontaneous rupture of undiagnosed HCC, that was treated successfully by emergency surgical resection followed by transarterial chemo-embolization for local recurrence.

  2. Notch Inhibitor PF-03084014 Inhibits Hepatocellular Carcinoma Growth and Metastasis via Suppression of Cancer Stemness due to Reduced Activation of Notch1-Stat3.

    Science.gov (United States)

    Wu, Chuan Xing; Xu, Aimin; Zhang, Cathy C; Olson, Peter; Chen, Lin; Lee, Terence K; Cheung, Tan To; Lo, Chung Mau; Wang, Xiao Qi

    2017-08-01

    Aberrant activation of the Notch signaling pathway is implicated in many solid tumors, including hepatocellular carcinoma, indicating a potential use of Notch inhibitors for treatment. In this study, we investigated the antitumor and antimetastasis efficacy of the novel Notch inhibitor (γ-secretase inhibitor) PF-03084014 in hepatocellular carcinoma. Hepatocellular carcinoma spherical cells (stem-like cancer cells), a sphere-derived orthotopic tumor model and one patient-derived xenograft (PDX) model were used in our experiment. We demonstrated that PF-03084014 inhibited the self-renewal and proliferation of cancer stem cells. PF-03084014 reduced the hepatocellular carcinoma sphere-derived orthotopic tumor and blocked the hepatocellular carcinoma tumor liver to lung metastasis. We further tested the PF-03084014 in PDX models and confirmed the inhibition tumor growth effect. In addition, a low dose of PF-03084014 induced hepatocellular carcinoma sphere differentiation, resulting in chemosensitization. Antitumor activity was associated with PF-03084014-induced suppression of Notch1 activity, decreased Stat3 activation and phosphorylation of the Akt signaling pathway, and reduced epithelial-mesenchymal transition. These are the key contributors to the maintenance of cancer stemness and the promotion of cancer metastasis. Moreover, the Notch-Stat3 association was implicated in the clinical hepatocellular carcinoma prognosis. Collectively, PF-03084014 revealed antitumor and antimetastatic effects in hepatocellular carcinoma, providing evidence for the potential use of gamma-secretase inhibitors as a therapeutic option for the treatment of hepatocellular carcinoma. Mol Cancer Ther; 16(8); 1531-43. ©2017 AACR. ©2017 American Association for Cancer Research.

  3. Long-term survival in a case of hepatocellular carcinoma.

    OpenAIRE

    Shiota,Tetsuya; Watanabe,Akiharu; Mitani,Ken; Ito,Toshio; Tobe,Kazuo; Nagashima,Hideo

    1983-01-01

    A patient with an unresectable hepatocellular carcinoma (HCC) who survived without active treatment 3 years and 8 months after histological diagnosis is described. The size of the liver, which was already quite huge at the time of diagnosis, changed little during the entire clinical observation. However, 2 months before death, his condition deteriorated rapidly following gastrointestinal bleeding due to the direct invasion of the stomach by HCC. A critical reason for the unusually long-term s...

  4. Prognostic stratification of brain metastases from hepatocellular carcinoma.

    Science.gov (United States)

    Kim, Kyung Su; Kim, Kyubo; Chie, Eui Kyu; Kim, Yoon Jun; Yoon, Jung Hwan; Lee, Hyo-Suk; Ha, Sung W

    2014-10-01

    The aim of this study is to evaluate prognostic factors of brain metastases from hepatocellular carcinoma. Medical records of 95 patients who have been diagnosed of brain metastases from hepatocellular carcinoma between January 2000 and December 2011 were retrospectively reviewed. The median age at diagnosis of brain metastases is 56.1 years. Eighty-two patients were male. Median interval from diagnosis of hepatocellular carcinoma to brain metastases was 29.5 months. Eighty-eight patents had extracranial metastases, and the lung was the most frequent involved organ. Motor weakness was the most frequent presenting symptom (49.5%). Intracranial hemorrhage was present in 71 patients (74.7%). Brain metastases were treated with whole brain radiation therapy (WBRT) alone in 57 patients, radiosurgery alone in 18, surgery and WBRT in 6, surgery and radiosurgery in 3, surgery alone in 3, radiosurgery and WBRT in 2, and conservative management only in 6. Median overall survival was 3.0 months. Multivariate analysis showed ECOG performance status, Child-Pugh class, AFP level, number of brain lesions, and treatment modality were associated with survival (p < 0.05). When patients were stratified with four prognostic factors including ECOG performance status, Child-Pugh class, AFP level, and number of brain lesions, median survival time for patients with 0-1, 2, 3-4 risk factors were 5.8 months, 2.5 months and 0.6 months, respectively (p < 0.001). In conclusion, we can estimate the survival of patients by prognostic stratification, although overall prognosis of patients with brain metastases from hepatocellular carcinoma is poor.

  5. Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...... metabolism. These molecular subtypes are found in 582 Asian, but less so in 265 Caucasian patients. Thus, Asian ICC and HCC, while clinically treated as separate entities, share common molecular subtypes with similar actionable drivers to improve precision therapy....

  6. 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.

  7. Hepatocellular carcinoma in situs inversus totalis-a case report

    Directory of Open Access Journals (Sweden)

    Thuingaren Sareo

    2014-03-01

    Full Text Available A 43-year old male presented with persistent discomfort and pain upper abdomen (epigastrium more on left side associated with fever on and off, along with fatigue and loss of appetite for the last four months. Physical examination revealed mass on left hypochondrium extending to epigastrium with mild distension of the abdomen. Imaging studies of the patient showed dextrocardia on chest x-ray  postero-anterior (PA view, thoracic and abdominal CT scan showed situs inversus totalis with multiple SOL (space occupying lesion in right lobe of liver with largest measuring 8x6 cm2 in the 4th segment. USG-guided FNAC of the mass showed features of hepatocellular carcinoma. Thereupon, hepatocellular carcinoma in situs inversus totalis was diagosed to this patient and was clinically staged as T3aN0M0. He was given sorafenib 400 mg orally twice daily with an advice to come for regular assessment every 4 week.Keywords: hepatocellular carcinoma, situs inversus totalis, case report

  8. 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

  9. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

    Science.gov (United States)

    Li, Jun; Sung, Cecilia Ying Ju; Lee, Nikki; Ni, Yueqiong; Pihlajamäki, Jussi; Panagiotou, Gianni; El-Nezami, Hani

    2016-01-01

    The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment. PMID:26884164

  10. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Brian J. Peter

    2008-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

  11. Detection of hepatocellular carcinoma with multi-slice spiral CT by ...

    African Journals Online (AJOL)

    The purpose of the study is to evaluate the effect of iodine concentration of contrast material on detection of hepatocellular carcinoma with multi-slice spiral computed tomography (CT) by using double-arterial phase and portal venous phase enhanced scanning. Ninety-four (94) patients with hepatocellular carcinoma (HCC) ...

  12. Hypofractionated Stereotactic Radiotherapy after Transarterial Chemoembolisation Failure in an Unresectable Hepatocellular Carcinoma: A Case Presentation

    OpenAIRE

    Francesco Fiorica; Carlo Greco; Sergio Boccia; Sergio Sartori; Antonio Stefanelli; Francesco Cartei; Stefano Ursino

    2013-01-01

    Introduction. Transarterial chemoembolization is the first-line treatment in unresectable hepatocellular carcinoma. There is no standard treatment after transarterial chemoembolization failure. We report the case of a patient with advanced hepatocellular carcinoma who showed a complete response and a long cancer control with hypofractionated stereotactic radiotherapy after transarterial chemoembolization failure. Case Presentation. A 70-year-old Caucasian woman was treated with transarterial ...

  13. Primary hepatocellular carcinoma presenting as fulminant hepatic failure in a young woman.

    OpenAIRE

    Levy, L. J.; Swinburne, L. M.; Boulton, R. P.; Losowsky, M S

    1986-01-01

    A 29 year old Caucasian female, with no history of chronic liver disease, presented with fulminant hepatic failure, the cause of which was not established until post-mortem when it was found that she had a rare form of hepatocellular carcinoma. To our knowledge, this is the only detailed report of hepatocellular carcinoma presenting in this manner.

  14. Testosterone-receptor positive hepatocellular carcinoma in a 29-year old bodybuilder with a history of anabolic androgenic steroid abuse: a case report.

    Science.gov (United States)

    Solbach, Philipp; Potthoff, Andrej; Raatschen, Hans-Jürgen; Soudah, Bisharah; Lehmann, Ulrich; Schneider, Andrea; Gebel, Michael J; Manns, Michael P; Vogel, Arndt

    2015-05-20

    Continuous use of anabolic androgenic steroid in high-doses is associated with substantial health risks, including hepatocellular adenoma. Malignant transformation from hepatocellular adenoma to hepatocellular carcinoma after anabolic androgenic steroid abuse has been rarely reported. The morphological distinction of adenoma from well-differentiated hepatocellular carcinoma is challenging and requires elaborated imaging techniques and histology. We report about a 29-year old male professional bodybuilder who presented with mid-epigastric pain at the emergency unit. Ultrasound showed a severe hepatomegaly with multiple lesions. Contrast-enhanced ultrasound revealed a heterogeneous pattern with signs of hepatocellular carcinoma. CT scan of the abdomen confirmed multiple hypervascular lesions and central areas of necrosis without contrast enhancement. Subsequent diagnostics included fine needle aspiration (FNA) of suspicious lesions and mini-laparoscopy to establish the diagnosis of a β-catenin and testosterone-receptor positive hepatocellular carcinoma embedded in multiple adenomas. The patient was subsequently treated by liver transplantation and remains tumor-free 27 month after surgery. Hepatocellular carcinoma occurring in association with anabolic androgenic steroid abuse should sensitize physicians and especially professional bodybuilders for the harmful use of high doses of steroids.

  15. BLZF1 expression is of prognostic significance in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Run-Yue, E-mail: ry_huang@hotmail.com [Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510006 (China); Su, Shu-Guang [Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou (China); Wu, Dan-Chun [Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Fu, Jia [Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060 (China); Zeng, Xing, E-mail: zengxing-china@163.com [Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510006 (China)

    2015-11-20

    BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/β-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan–Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697–0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC. - Highlights: • BLZF1 expression was much lower in HCC tissues. • Low BLZF1 expression was associated with poor outcomes in a cohort of 634 HCC patients. • Multiple Cox regression analysis indicated nuclear BLZF1 as an independent predictor for overall survival.

  16. Pivotal Role of mTOR Signaling in Hepatocellular Carcinoma

    Science.gov (United States)

    Villanueva, Augusto; Chiang, Derek Y.; Newell, Pippa; Peix, Judit; Thung, Swan; Alsinet, Clara; Tovar, Victoria; Roayaie, Sasan; Minguez, Beatriz; Sole, Manel; Battiston, Carlo; van Laarhoven, Stijn; Fiel, Maria I; Di Feo, Analisa; Hoshida, Yujin; Yea, Steven; Toffanin, Sara; Ramos, Alex; Martignetti, John A.; Mazzaferro, Vincenzo; Bruix, Jordi; Waxman, Samuel; Schwartz, Myron; Meyerson, Matthew; Friedman, Scott L.; Llovet, Josep M.

    2008-01-01

    BACKGROUND The advent of targeted therapies in hepatocellular carcinoma (HCC) has underscored the importance of pathway characterization to identify novel molecular targets for treatment. Based on its role in cell growth and differentiation, we evaluated mTOR signaling activation in human HCC, as well as the anti-tumoral effect of a dual-level blockade of the mTOR pathway. METHODS The mTOR pathway was assessed using integrated data from mutation analysis (direct sequencing), DNA copy number changes (SNP-array), mRNA levels (qRT-PCR and gene expression microarray), and protein activation (immunostaining) in 351 human samples, including HCC (n=314), and non-tumoral tissue (n=37). Effects of dual blockade of mTOR signaling using a rapamycin analog (everolimus) and an EGFR/VEGFR inhibitor (AEE788) were evaluated in liver cancer cell lines, and in a tumor xenograft model. RESULTS Aberrant mTOR signaling (phosphorylated-RPS6) was present in half of the cases, associated with IGF pathway activation, EGF upregulation, and PTEN dysregulation. PTEN and PI3KCA-B mutations were rare events. Chromosomal gains in RICTOR (25% of patients) and positive pRPS6 staining correlated with recurrence. RICTOR-specific siRNA downregulation reduced tumor cell viability in vitro. Blockage of mTOR signaling with everolimus in vitro and in a xenograft model decelerated tumor growth and increased survival. This effect was enhanced in vivo after EGFR blockade. CONCLUSIONS MTOR signaling has a critical role in the pathogenesis of HCC, with evidence for the role of RICTOR in tumor oncogenesis. MTOR blockade with everolimus is effective in vivo. These findings establish a rationale for targeting mTOR pathway in clinical trials in HCC. PMID:18929564

  17. Transarterial chemoembolization for huge hepatocellular carcinoma with diameter over ten centimeters: a large cohort study.

    Science.gov (United States)

    Xue, Tongchun; Le, Fan; Chen, Rongxin; Xie, Xiaoying; Zhang, Lan; Ge, Ningling; Chen, Yi; Wang, Yanhong; Zhang, Boheng; Ye, Shenglong; Ren, Zhenggang

    2015-03-01

    Patients with huge hepatocellular carcinoma >10 cm in diameter represent a special subgroup for treatment. To date, there are few data and little consensus on treatment strategies for huge hepatocellular carcinoma. In this study, we summarized the effects and safety of transarterial chemoembolization for huge hepatocellular carcinoma. A retrospective study was performed based on a large cohort of patients (n = 511) with huge hepatocellular carcinoma who underwent serial transarterial chemoembolization between January 2008 to December 2011 and were followed up until March 2013. We found median survival time was 6.5 months. On multivariate analysis, Child-Pugh class (A versus B) (p failure (n = 6). In conclusion, transarterial chemoembolization is a safe and effective treatment for selected patients with huge hepatocellular carcinoma and is recommended as a component of combination therapy. In addition, patients with good liver function and low alpha-fetoprotein levels may acquire greater survival benefits from transarterial chemoembolization.

  18. Meta-analysis of DNA methylation biomarkers in hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Cheng; Li, Jinyun; Huang, Tao; Duan, Shiwei; Dai, Dongjun; Jiang, Danjie; Sui, Xinbing; Li, Da; Chen, Yidan; Ding, Fei; Huang, Changxin; Chen, Gongying; Wang, Kaifeng

    2016-12-06

    DNA methylation is an epigenetic mechanism in the pathogenesis of hepatocellular carcinoma (HCC). Here, we conducted a systematic meta-analysis to evaluate the contribution of DNA methylation to the risk of HCC. A total of 2109 publications were initially retrieved from PubMed, Web of Science, Cochrane Library, Embase, CNKI and Wanfang literature database. After a four-step filtration, we harvested 144 case-control articles in the meta-analysis. Our results revealed that 24 genes (carcinoma tissues vs adjacent tissues), 17 genes (carcinoma tissues vs normal tissues) and six genes (carcinoma serums vs normal serums) were significantly hypermethylated in HCC. Subgroup meta-analysis by geographical populations showed that six genes (carcinoma tissues vs adjacent tissues) and four genes (carcinoma tissues vs normal tissues) were significantly hypermethylated in HCC. Our meta-analysis identified the correlations between a number of aberrant methylated genes (p16, RASSF1A, GSTP1, p14, CDH1, APC, RUNX3, SOCS1, p15, MGMT, SFRP1, WIF1, PRDM2, DAPK1, RARβ, hMLH1, p73, DLC1, p53, SPINT2, OPCML and WT1) and HCC. Aberrant DNA methylation might become useful biomarkers for the prediction and diagnosis of HCC.

  19. 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.

  20. Twist expression promotes migration and invasion in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kobayashi Yoshiyuki

    2009-07-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition.

  1. Clostridium perfringens infection after transarterial chemoembolization for large hepatocellular carcinoma.

    Science.gov (United States)

    Li, Jing-Huan; Yao, Rong-Rong; Shen, Hu-Jia; Zhang, Lan; Xie, Xiao-Ying; Chen, Rong-Xin; Wang, Yan-Hong; Ren, Zheng-Gang

    2015-04-14

    We report an unusual case of Clostridium perfringens liver abscess formation after transcatheter arterial chemoembolization (TACE) for large hepatocellular carcinoma. Severe deterioration in liver and renal function accompanied with hemocytolysis was found on the 2(nd) day after TACE. Blood culture found Clostridium perfringens and abdominal computed tomography revealed a gas-containing abscess in the liver. Following antibiotics administration and support care, the infection was controlled and the liver and renal function turned normal. The 2(nd) TACE procedure was performed 1.5 mo later and no recurrent Clostridium perfringens infection was found.

  2. Abnormal Prothrombin (DES-γ-Carboxy Prothrombin) in Hepatocellular Carcinoma*

    OpenAIRE

    Nakao, A.; Virji, A; Iwaki, Y.; Carr, B; Iwatsuki, S.; Starzl, E.

    1991-01-01

    Des-γ-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist-II (PIVKA-II) was measured by an enzyme immunoassay (E-1023) using anti-DCP monoclonal antibody in 92 patients with various hepatobiliary diseases. Thirty-six of the 38 patients (94.7%) with hepatocellular carcinoma (HCC) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml, but only 18 of the 35 patients (51.4%) had AFP greater than 100 ng/ml (suspicious levels for HCC). There was no correlation ...

  3. Cervical Spinal Cord Compression: A Rare Presentation of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Puvanalingam Ayyadurai

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common primary malignancy of liver. Distant metastasis to various organs is well known. Skeletal metastasis is also reported to various locations. Vertebral metastasis has been reported mostly to thoracic spine. However, cervical spinal cord involvement leading to cord compression has been reported very rarely in literature. We present a case of 58-year-old male with liver cirrhosis presenting as neck pain. Further work-up revealed metastatic HCC to cervical spinal cord resulting in acute cord compression. Patient has been treated with neurosurgical intervention.

  4. 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.

  5. What's New in Transarterial Therapies for Hepatocellular Carcinoma?

    Science.gov (United States)

    May, Benjamin J; Murthy, Ravi; Madoff, David C

    2012-05-01

    Transarterial therapies play an important role in the treatment of hepatocellular carcinoma, both in a palliative setting and as an adjunct to surgery. These therapies exploit the dual blood supply of the liver to selectively target tumors via the hepatic artery, while sparing nontumorous liver. Currently available therapies include transarterial embolization; chemoembolization, with or without drug-eluting beads; and radioembolization. Transarterial techniques are also being used in the development of novel therapies. This article provides an outline of the technical and clinical applications of intraarterial therapies in the treatment of HCC and highlights pertinent future directions.

  6. Epigenetics in hepatocellular carcinoma: an update and future therapy perspectives.

    Science.gov (United States)

    Ma, Li; Chua, Mei-Sze; Andrisani, Ourania; So, Samuel

    2014-01-14

    Hepatocellular carcinoma (HCC), the predominant form of adult liver malignancies, is a global health concern. Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis. The deregulation of epigenetic mechanisms, which maintain heritable gene expression changes and chromatin organization, is implicated in the development of multiple cancers, including HCC. This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC, with an emphasis on HCC mediated by chronic hepatitis B virus infection. This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers, and highlights the future potential of similar therapies in the treatment of HCC.

  7. Research advances in regorafenib in treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    CHEN Weibo

    2017-12-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common malignant liver tumor, and there are limited systemic treatments for patients with advanced HCC. Regorafenib is an oral multi-kinase inhibitor, and phase III clinical trial has shown that regorafenib can significantly extend the median survival of patients with advanced HCC by 2.8 months, which makes it a second-line drug approved by FDA for the treatment of advanced HCC, just after sorafenib. This article reviews the basic and clinical research on regorafenib in the field of HCC.

  8. Known, new and emerging risk factors of hepatocellular carcinoma (review).

    Science.gov (United States)

    Trad, Dorra; Bibani, Norsaf; Sabbah, Meriam; Elloumi, Hela; Gargouri, Dalila; Ouakaa, Asma; Kharrat, Jamel

    2017-11-01

    Hepatocellular carcinoma (HCC) is the commonest primary cancer of the liver and is a leading cause of cancer-related death worldwide. And despite effective treatment of hepatitis B and C infection which is the prominent factor associated with HCC, the prevalence of this malignancy continues to rise probably due to other factors. So that, identifying risk factor of HCC is essential and effective surveillance programs are necessary in order to maximize patient outcomes. This article summarizes the known, new and emerging risk factors of HCC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Dancey, J; Astrup, L

    2003-01-01

    growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year (with possible extension for responders......Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits...

  10. Profiling of Hepatocellular Carcinoma Cell Cycle Regulating Genes Targeted by Calycosin

    OpenAIRE

    Zhang, Dongqing; Wang, Shufang; Zhu, Liguo; Tian, Yaping; Wang, Haibao; Zhuang, Yuan; Li, Yu; Wang, Deqing

    2013-01-01

    We cocultured calycosin with human hepatocellular carcinoma cell line (BEL-7402) to investigate the effect on cell proliferation. Calycosin can markedly block the cell growth in G1 phase (P < 0.01) on the IC50 concentration. There were seventeen genes involved in cell-cycle regulation showing differentially expressed in treated cells detected by gene chip. Eight genes were upregulated and nine genes were downregulated. Downregulated TFDP-1, CDKN2D, and SPK2 and upregulated CDC2 and CCNB1 migh...

  11. Etiopathogenesis of Differentiated Thyroid Carcinomas

    Directory of Open Access Journals (Sweden)

    Tanja Makazlieva

    2016-08-01

    Full Text Available INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database. DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies.

  12. A RARE CASE OF HEPATOCELLULAR CARCINOMA IN THE ARABIAN SAND CAT (FELIS MARGARITA HARRISONI).

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    Chege, Stephen M; Vissiennon, Théophile; Cavero, Tatiana; Kinne, Joerg; Toosy, Arshad

    2015-12-01

    Primary liver cancer is uncommon and is generally classified as hepatocellular carcinoma (HCC), bile duct carcinoma, neuroendocrine (or carcinoid) tumor, and mesenchymal tumor (sarcoma). Here we describe the gross and histopathology characteristics of a rare HCC in a captive Arabian sand cat (Felis margarita harrisoni) held at Al Ain Zoo, United Arab Emirates. The description of this case in the Arabian sand cat adds to the current knowledge of hepatocellular carcinoma in captive nondomestic felids.

  13. Spontaneous rupture of multifocal hepatocellular carcinoma: case report

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    Özen Ö

    2015-08-01

    Full Text Available Özkan Özen, Alptekin Tosun, Çiğdem Akgül Department of Radiology, Faculty of Medicine, Giresun University, Giresun, Turkey Abstract: Hemoperitoneum due to nontraumatic liver rupture is rare. The most common cause of nontraumatic rupture of the liver is hepatocellular carcinoma (HCC. The other causes of nontraumatic liver ruptures are peliosis hepatis, polyarteritis nodosa, systemic lupus erythematosus, preeclampsia, metastatic carcinoma, and other primary liver tumors. In this report, we present the computed tomography findings of spontaneous liver rupture in a 52-year-old male patient due to multifocal HCC, with the diagnosis proven by surgical specimen. Keywords: computed tomography, hemoperitoneum, liver, nontraumatic liver rupture

  14. Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

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    Chen, Zhi-Shui; He, Fan; Zeng, Fan-Jun; Jiang, Ji-Pin; Du, Dun-Feng; Liu, Bin

    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 advanced-stage 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 steroid-maintenance group. CONCLUSION: Early steroid withdrawal was safe after liver transplantation 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 increase

  15. Metformin confers risk reduction for developing hepatocellular carcinoma recurrence after liver resection.

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    Chan, Kun-Ming; Kuo, Chang-Fu; Hsu, Jun-Te; Chiou, Meng-Jiun; Wang, Yu-Chao; Wu, Tsung-Han; Lee, Chen-Fang; Wu, Ting-Jung; Chou, Hong-Shiue; Lee, Wei-Chen

    2017-03-01

    Hepatocellular carcinoma recurrence following liver resection remains a great concern. The study aims to examine the chemopreventive effect of metformin in patients undergoing liver resection for hepatocellular carcinoma from a population-based study. All patients registered as having hepatocellular carcinoma between January 1995 and December 2011 in a nationwide database were retrospectively analysed. Outcomes related to liver resection and the presence of diabetes mellitus were assessed. Prognosis in terms of the use of metformin was further explored, in which only patients in the long-term follow-up starting at 2 years were included for analysis. Patients with diabetes mellitus had a significantly poorer outcome than patients without diabetes mellitus. Among diabetes mellitus patients, metformin users had significantly better survival curves in both recurrence-free survival (Pmetformin use in hepatocellular carcinoma patients with diabetes mellitus was 0.65 (Pmetformin usage. Diabetes mellitus has an adverse effect on patients with hepatocellular carcinoma regardless of treatment modality. The use of metformin significantly reduces the risk of hepatocellular carcinoma recurrence and improves the overall outcome of patients after liver resection if patients survives the initial 2 years. Nonetheless, a prospective controlled study is recommended for validating the metformin use on preventing postoperative hepatocellular carcinoma recurrence. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

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    Takaki, Akinobu; Yamamoto, Kazuhide

    2015-05-08

    Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease (CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma.

  17. Nanosecond pulsed electric field ablation of hepatocellular carcinoma.

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    Beebe, Stephen J; Chen, Xinhua; Liu, Jie A; Schoenbach, Karl H

    2011-01-01

    Hepatocellular carcinoma often evades effective therapy and recurrences are frequent. Recently, nanosecond pulsed electric field (nsPEF) ablation using pulse power technology has emerged as a local-regional, non-thermal, and non-drug therapy for skin cancers. In the studies reported here we use nsPEFs to ablate murine, rat and human HCCs in vitro and an ectopic murine Hepa 1-6 HCC in vivo. Using pulses with 60 or 300 ns and electric fields as high as 60 kV/cm, murine Hepa 1-6, rat N1S1 and human HepG2 HCC are readily eliminated with changes in caspase-3 activity. Interestingly caspase activities increase in the mouse and human model and decrease in the rat model as electric field strengths are increased. In vivo, while sham treated control mice survived an average of 15 days after injection and before humane euthanasia, Hepa 1-6 tumors were eliminated for longer than 50 days with 3 treatments using one hundred pulses with 100 ns at 55 kV/cm. Survival was 40% in mice treated with 30 ns pulses at 55 kV/cm. This study demonstrates that nsPEF ablation is not limited to effectively treating skin cancers and provides a rationale for treating orthotopic hepatocellular carcinoma in pre-clinical applications and ultimately in clinical trials.

  18. Diabetes mellitus: a "true" independent risk factor for hepatocellular carcinoma?

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    Gao, Chun; Yao, Shu-Kun

    2009-10-01

    Diabetes mellitus (DM) is thought to be associated with an increased risk of hepatocellular carcinoma (HCC) in some published studies. However, can we draw the conclusion that DM is a "true" independent risk factor for HCC based on these references? MEDLINE and PubMed searches were conducted for published studies (between January 1966 and June 2009) to identify relevant articles using the keywords "diabetes", "insulin resistance" and "hepatocellular carcinoma", including "primary liver cancer". Because of the very limited number of relevant articles most were reviewed. This systematic review was conducted from 4 aspects: (1) the significant synergy between DM, hepatitis virus infection, and heavy alcohol consumption in HCC; (2) the role of DM independently in HCC cases while other identified risk factors were controlled or excluded; (3) obesity, DM, and nonalcoholic fatty liver disease in HCC patients; and (4) the impact of DM for the prognosis or surgical treatment in HCC patients with DM. No consensus has been reached among these studies and it is too early to draw the conclusion that DM is a "true" independent risk factor for HCC. DM can be regarded as a risk factor for HCC. However, whether DM itself directly predisposes to HCC or whether it is a "true" independent risk factor remains unclear. Related issues should be clarified by more research.

  19. Safety validation of decision trees for hepatocellular carcinoma.

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    Wang, Xian-Qiang; Liu, Zhe; Lv, Wen-Ping; Luo, Ying; Yang, Guang-Yun; Li, Chong-Hui; Meng, Xiang-Fei; Liu, Yang; Xu, Ke-Sen; Dong, Jia-Hong

    2015-08-21

    To evaluate a different decision tree for safe liver resection and verify its efficiency. A total of 2457 patients underwent hepatic resection between January 2004 and December 2010 at the Chinese PLA General Hospital, and 634 hepatocellular carcinoma (HCC) patients were eligible for the final analyses. Post-hepatectomy liver failure (PHLF) was identified by the association of prothrombin time 50 μmol/L (the "50-50" criteria), which were assessed at day 5 postoperatively or later. The Swiss-Clavien decision tree, Tokyo University-Makuuchi decision tree, and Chinese consensus decision tree were adopted to divide patients into two groups based on those decision trees in sequence, and the PHLF rates were recorded. The overall mortality and PHLF rate were 0.16% and 3.0%. A total of 19 patients experienced PHLF. The numbers of patients to whom the Swiss-Clavien, Tokyo University-Makuuchi, and Chinese consensus decision trees were applied were 581, 573, and 622, and the PHLF rates were 2.75%, 2.62%, and 2.73%, respectively. Significantly more cases satisfied the Chinese consensus decision tree than the Swiss-Clavien decision tree and Tokyo University-Makuuchi decision tree (P decision trees. The Chinese consensus decision tree expands the indications for hepatic resection for HCC patients and does not increase the PHLF rate compared to the Swiss-Clavien and Tokyo University-Makuuchi decision trees. It would be a safe and effective algorithm for hepatectomy in patients with hepatocellular carcinoma.

  20. Hepatocellular Carcinoma: Novel Molecular Targets in Carcinogenesis for Future Therapies

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    Gaetano Bertino

    2014-01-01

    Full Text Available Background. Hepatocellular carcinoma is one of the most common and lethal malignant tumors worldwide. Over the past 15 years, the incidence of HCC has more than doubled. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with HCC. A better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Materials and Methods. A search of the literature was made using cancer literature, the PubMed, Scopus, and Web of Science (WOS database for the following keywords: “hepatocellular carcinoma,” “molecular hepatocarcinogenesis,” “targeted therapy,” and “immunotherapy.” Discussion and Conclusion. Treatment decisions are complex and dependent upon tumor staging, presence of portal hypertension, and the underlying degree of liver dysfunction. The knowledge of molecular hepatocarcinogenesis broadened the horizon for patients with advanced HCC. During the last years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. In the future, new therapeutic options will be represented by a blend of immunotherapy-like vaccines and T-cell modulators, supplemented by molecularly targeted inhibitors of tumor signaling pathways.

  1. 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.

  2. 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.

  3. Computational grading of hepatocellular carcinoma using multifractal feature description.

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    Atupelage, Chamidu; Nagahashi, Hiroshi; Yamaguchi, Masahiro; Abe, Tokiya; Hashiguchi, Akinori; Sakamoto, Michiie

    2013-01-01

    Cancer grading has become an important topic in the field of image interpretation-based computer aided diagnosis systems. This paper proposes a novel feature descriptor to observe the characteristics of histopathological textures in a discriminative manner. The proposed feature descriptor utilizes fractal geometric analysis with four multifractal measures to construct an eight dimensional feature space. The proposed method employed a bag-of-feature-based classification model to discriminate a set of hepatocellular carcinoma images into five categories according to Edmondson and Steiner's grading system. Three feature selection methods were utilized to obtain the most discriminative features of codeword dictionary (codebook). Furthermore, we incorporated four other textural feature descriptors: Gabor-filters, LM-filters, local binary patterns, and Haralick, to obtain a benchmark of the accuracy of the classification. Two experiments were performed: (i) classifying non-neoplastic tissues and tumors and (ii) grading the hepatocellular carcinoma images into five classes. Experimental results indicated the significance of the multifractal features for describing the histopathological image texture because it outperformed other four feature descriptors. We graded a given ROI image by defining a threshold-based majority-voting rule and obtained an average correct classification rate around 95% for five classes classification. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Liver transplantation for intermediate hepatocellular carcinoma: An adaptive approach

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    Biolato, Marco; Marrone, Giuseppe; Miele, Luca; Gasbarrini, Antonio; Grieco, Antonio

    2017-01-01

    Hepatocellular carcinoma is becoming an increasing indication for liver transplantation, but selection and allocation of patients are challenging because of organ shortages. Conventional Milan criteria are the reference for the selection of patients worldwide, but many expanded criteria, like University of California San Francisco criteria and up-to-7 criteria, have demonstrated that survival and recurrence results are lower than those for restricted indications. Correct staging is crucial and should include surrogate markers of biological aggressiveness (α-fetoprotein, response to loco-regional treatments). Successful down-staging can select between patients with tumor burden initially beyond transplantation criteria those with a more favorable biology, provided a 3-mo stability in meeting the transplantation criteria. Allocation rules are constantly adjusted to minimize the imbalance between the priorities of candidates with and without hepatocellular carcinoma, and take into account local donor rate and waitlist dynamics. Recently, Mazzaferro et al proposed a benefit-oriented “adaptive approach”, in which the selection and allocation of patients are based on their response to non-transplantation treatments: low priority for transplantation in case of complete response, high priority in case of partial response or recurrence, and no listing in case of progression beyond transplantation criteria. PMID:28566879

  5. Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.

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    Yingjian Liang

    Full Text Available Diphenyl difluoroketone (EF24, a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.

  6. Distinct claudin expression profiles of hepatocellular carcinoma and metastatic colorectal and pancreatic carcinomas.

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    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-04-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 colorectal adenocarcinomas (CRLMs) and 15 pancreatic adenocarcinomas (PLMs) were studied together with paired surrounding non-tumorous liver samples and 5 normal liver samples. Strong claudin-3 and -7 immunohistochemical positivities were detected in CRLM samples, each with significantly stronger staining when compared with HCC and PLM groups. Claudin-1 protein was found highly expressed in CRLM, in contrast to lower expression in PLM and HCC. CRLMs and PLMs also were strongly positive for claudin-4, while being virtually undetectable in HCC. Claudin-2 showed strong positivity in non-tumorous liver tissue, whereas significantly weaker positivity was observed in all tumors. Differences in mRNA expression were mostly similar to those found by immunohistochemistry. In conclusion, HCC and both CRLM and PLM display distinct claudin expression profiles, which might provide better understanding of the pathobiology of these lesions and might be used for differential diagnosis.

  7. Extramammary Paget's Disease of the Scrotum Associated with Hepatocellular Carcinoma

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    Yu-Ching Li

    2009-10-01

    Full Text Available Extramammary Paget's disease (EMPD is a rare cutaneous carcinoma of epidermal origin. The diagnosis is frequently delayed, and the disease tends to be associated with an underlying adnexal or internal malignancy. There have been several reports of EMPD associated with carcinoma of the bladder, prostate, kidney, and colon. The association of hepato-cellular carcinoma (HCC with EMPD appears to be exceedingly rare; to our knowledge, it has been reported only once in the English literature. Herein, we report an unusual case of EMPD of the scrotum associated with HCC. EMPD was diagnosed 1 year after the appearance of an erythematous plaque, and HCC was noted 19 months after the diagnosis of EMPD. From our experience and literature review, in patients with nonspecific skin lesions that are unresponsive to conventional treatment, EMPD should be considered and skin biopsy performed. Long-term follow-up is needed to watch for the appearance of adnexal carcinoma or internal malignancy. [J Chin Med Assoc 2009;72(10:542–546

  8. Pelvic skeletal metastasis of hepatocellular carcinoma with sarcomatous change: a case report

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    Lin Wei-Hsin

    2010-05-01

    Full Text Available Abstract Sarcomatoid hepatocellular carcinoma (HCC is a very rare histologic variant of HCC. The characteristic of skeletal metastatic sarcomatoid hepatocellular carcinoma has never been reported. We reported a patient with sarcomatoid hepatocellular carcinoma pelvic metastasis who presented with huge pelvic metastasis that had relatively small osteolytic lesion centrally located accompanied by huge bipeduncular invasive expansile lesions into surrounding soft tissue. The lesion showed almost non-isotope uptake in 99mTc-methylene diphosphonate bone scintigraphy study. He underwent radiotherapy and tumor excision but the tumor rapidly recurred. In addition, serum α-fetoprotein level was never elevated beyond normal limit (

  9. [A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

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    Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

    2014-01-01

    Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  10. Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma.

    Science.gov (United States)

    Shih, Ying-Hsia; Peng, Cheng-Liang; Chiang, Ping-Fang; Lin, Wuu-Jyh; Luo, Tsai-Yueh; Shieh, Ming-Jium

    2015-01-01

    This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 ((188)Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of (188)Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (Pchemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma.

  11. Targeted disruption of fibrinogen like protein-1 accelerates hepatocellular carcinoma development

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    Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Bronson, Roderick T. [Department of Microbiology and Immunology, Harvard Medical School, Boston, MA 02115 (United States); Hornick, Jason L. [Department of Pathology, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Cohen, David E. [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Ukomadu, Chinweike, E-mail: cukomadu@partners.org [Division of Gastroenterology, Hepatology and Endoscopy, Department of Medicine. Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

    2015-09-18

    Fibrinogen like protein-1 (Fgl1) is a predominantly liver expressed protein that has been implicated as both a hepatoprotectant and a hepatocyte mitogen. Fgl1 expression is decreased in hepatocellular carcinoma (HCC) and its loss correlates with a poorly differentiated phenotype. To better elucidate the role of Fgl1 in hepatocarcinogenesis, we treated mice wild type or null for Fgl1 with diethyl nitrosamine and monitored for incidence of hepatocellular cancer. We find that mice lacking Fgl1 develop HCC at more than twice the rate of wild type mice. We show that hepatocellular cancers from Fgl1 null mice are molecularly distinct from those of the wild type mice. In tumors from Fgl1 null mice there is enhanced activation of Akt and downstream targets of the mammalian target of rapamycin (mTOR). In addition, there is paradoxical up regulation of putative hepatocellular cancer tumor suppressors; tripartite motif-containing protein 35 (Trim35) and tumor necrosis factor super family 10b (Tnfrsf10b). Taken together, these findings suggest that Fgl1 acts as a tumor suppressor in hepatocellular cancer through an Akt dependent mechanism and supports its role as a potential therapeutic target in HCC. - Highlights: • Fgl1 knockout mice (Fgl1KO) are more prone to carcinogen-induced liver cancer compared to wild type (WT) mates. • Tumors from the Fgl1KO are molecularly distinct with enhanced Akt and mTOR activity in comparison with Fgl1WT tumors. • Tumors from the Fgl1KO have enhanced expression of Trim35 and Tnfrsf10b, putative HCC tumor suppressors.

  12. Genetic Features of Aflatoxin-Associated Hepatocellular Carcinoma.

    Science.gov (United States)

    Zhang, Weilong; He, Huan; Zang, Mengya; Wu, Qifeng; Zhao, Hong; Lu, Ling-Ling; Ma, Peiqing; Zheng, Hongwei; Wang, Nengjin; Zhang, Ying; He, Siyuan; Chen, Xiaoyan; Wu, Zhiyuan; Wang, Xiaoyue; Cai, Jianqiang; Liu, Zhihua; Sun, Zongtang; Zeng, Yi-Xin; Qu, Chunfeng; Jiao, Yuchen

    2017-07-01

    Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC). However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure. We investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen. We obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China-a high-risk region for aflatoxin exposure (38.2% of food samples test positive for aflatoxin contamination). Somatic variants were identified using GATK Best Practices Pipeline. We validated part of the mutations from whole-genome sequencing and whole-exome sequencing by Sanger sequencing. We also analyzed genomes of 1072 HCCs, obtained from 5 datasets from China, the United States, France, and Japan. Mutations in 49 aflatoxin-associated HCCs and 1072 HCCs from other regions were analyzed using the Wellcome Trust Sanger Institute mutational signatures framework with non-negative matrix factorization. The mutation landscape and mutational signatures from the aflatoxin-associated HCC and HCC samples from general population were compared. We identified genetic features of aflatoxin-associated HCC, and used these to identify aflatoxin-associated HCCs in datasets from other regions. Tumor samples were analyzed by immunohistochemistry to determine microvessel density and levels of CD34 and CD274 (PD-L1). Aflatoxin-associated HCCs frequently contained C>A transversions, the sequence motif GCN, and strand bias. In addition to previously reported mutations in TP53, we found frequent mutations in the adhesion G protein-coupled receptor B1 gene (ADGRB1), which were associated with increased capillary density of tumor tissue. Aflatoxin-associated HCC tissues contained high-level potential mutation

  13. Clinical significance of CMTM4 expression in hepatocellular carcinoma

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    Bei CH

    2017-11-01

    Full Text Available Chunhua Bei,1,* Ying Zhang,1,* Riming Wei,1 Xiaonian Zhu,1 Zhigang Wang,1 Wen Zeng,2 Qiuyue Chen,3 Shengkui Tan1 1Department of Epidemiology and Statistics, School of Public Health, Guilin Medical University, 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, 3Department of Pathology, 181st Hospital of Chinese People’s Liberation Army, Guilin, People’s Republic of China *These authors contributed equally to this work Abstract: CMTM4 is the most conserved member of chemokine-like factor (CKLF-like MARVEL transmembrane domain-containing (CMTM family on chromosome 16q22.1, a locus that harbors a number of tumor-suppressor genes. In previous studies, CMTM4 was reported to be downregulated and exhibited tumor-suppressor activities by regulating cell growth and cell cycle in clear cell renal cell carcinoma. However, its roles in tumorigenesis of hepatocellular carcinoma (HCC remain poorly studied. This study first investigated the expression of CMTM4 in HCC, and then examined the association between the expression of CMTM4 with the clinicopathological features and prognosis of HCC patients. It was found that CMTM4 was downregulated in HCC tissues, compared with matched adjacent nontumor tissues, as detected by immunohistochemistry. In addition, Kaplan–Meier survival analysis showed that the negative expression of CMTM4 was associated with decreased overall survival rates in patients with HCC. The results of this study suggest CMTM4 plays a role as a tumor suppressor in HCC and CMTM4 negative expression is a risk factor for poor prognosis of HCC. Keywords: chemokine-like factor-like MARVEL transmembrane domain-containing 4, hepatocellular carcinoma, immunohistochemistry, prognosis

  14. Ezrin expression in the primary hepatocellular carcinoma patients and associated with clinical, pathological characteristics.

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    Pan, Debiao; Wang, Shi; Ye, Hailin; Xu, Shengqian; Ye, Guanxiong

    2016-12-01

    The aim of this study was to assess Ezrin expression in the primary hepatic carcinoma patients and associated with clinical, pathological characteristics. Fifty-one patients with primary hepatocellular carcinoma (PHC) with completed clinical data were retrospectively analyzed in this study. The Ezrin expression in PHC and normal control liver tissue was tested by immunohistochemical assay. The Ezrin expression and relationship with clinical characteristics were evaluated. The Ezrin positive rate were 66.7% and 15.7% with expression score of 3.21 ± 1.46 and 0.60 ± 1.10, respectively, in the cancer tissue and control tissue with statistical difference (P expression was associated with the metastasis status of the patients (P 0.05), gender (P > 0.05), differentiation (P > 0.05), and tumor diameter (P > 0.05). Ezrin protein is highly expressed in human PHC tissue which can be used for the prediction of metastasis disease.

  15. Metastatic hepatocellular carcinoma in the maxilla and mandible, an extremely rare presentation

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    Satya Ranjan Misra

    2015-01-01

    Full Text Available Malignancy is characterized by anaplasia, invasiveness, and metastasis. Primary oral squamous cell carcinoma is the most prevalent oral malignancy, but secondary malignancy from distant sites have also been reported. Hepatocellular carcinoma (HCC is a common primary liver malignancy that frequently metastasizes during the course of the disease, but < 1% of cases show oral involvement. Such secondary neoplasms do not have any pathognomonic clinical or radiologic findings, and therefore they pose a diagnostic challenge. Hence, in the differential diagnosis of malignant tumors of the oral cavity, it is essential to consider the occurrence of both primary as well as metastatic tumors despite the low incidence of the latter. A rare case of HCC metastasizing to both the maxilla and mandible is presented, in which the patient succumbed to the disease as a result of the delay in diagnosis.

  16. Effect of the HBV whole-X gene on the expression of hepatocellular carcinoma associated proteins.

    Science.gov (United States)

    Zhang, Yu; Liu, Hongli; Cui, Meiling; Liu, Jinfeng; Yi, Ruitian; Niu, Yinghua; Chen, Tianyan; Zhao, Yingren

    2016-06-01

    The hepatitis B virus (HBV) pre-X gene resides upstream of the HBV X gene, and together they form the HBV whole-X gene. Although it has been evident that the HBV whole-X protein is involved in the development of hepatocellular carcinoma, its biological role and molecular mechanism remain largely unknown. In this study, we subcloned the HBV whole-X gene and constructed a HBV whole-X expressing vector. After transfection of the HBV whole-X gene into HL-7702 cells, the profile of the differential cellular protein composition in the cells was analyzed by using two-dimensional electrophoresis coupled to matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The results showed that 18 major proteins were differentially expressed in the cells transfected with or without the HBV whole-X gene. The expression of these genes was further confirmed by reverse transcription-polymerase chain reaction and Western blot analysis. Our findings provide a new insight into the investigation of the pathological role that the HBV whole-X gene plays in the development of hepatocellular carcinoma and may lead to the design of novel strategies for the treatment of this disease. Copyright © 2014. Published by Elsevier B.V.

  17. Clinicopathological and prognostic significance of OCT4 in patients with hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liang CJ

    2017-12-01

    Full Text Available Chaojie Liang,* Yingchen Xu,* Hua Ge, Guangming Li, Jixiang Wu Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Background and aims: Octamer-binding transcription factor 4 (OCT4 has been implicated in the development of hepatocellular carcinoma (HCC, although the findings are controversial. We conducted a meta-analysis to assess the correlation between OCT4 and the clinicopathological characteristics and the prognostic value in HCC.Methods: An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and Chinese WanFang database. Correlations between OCT4 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios and hazard ratios with 95% CIs were calculated using STATA 14.2 software.Results: A total of 10 trials with 985 patients were included. Positive OCT4 expression was correlated with tumor size, tumor numbers, differentiation, and TNM stage. OCT4 expression was not correlated with gender, age, hepatitis B surface antigen, alfa-fetoprotein, liver cirrhosis, vascular invasion, or tumor encapsulation. OCT4 expression was associated with poor 3- and 5-year overall survival, and disease-free survival rate.Conclusion: OCT4 expression was associated with tumor size, tumor numbers, differentiation, and TNM stage in HCC. OCT4 may be a useful prognostic biomarker for HCC. Keywords: octamer-binding transcription factor 4, hepatocellular carcinoma, prognosis, meta-analysis

  18. Primary hepatocellular carcinoma in ectopic liver masquerading as left adrenal carcinoma: a rare occurrence

    Directory of Open Access Journals (Sweden)

    Shailendra Kumar

    2010-06-01

    Full Text Available We report a unique case of primary hepatocellular carcinoma in an ectopic liver rest in the left renal hilum masquerading as a left adrenal tumor. Adrenal tumors have been reported within adrenal rests inside the liver but hepatocellular carcinoma in ectopic liver rests in the adrenal area is an extremely rare entity. To the best of our knowledge, this is the first case report from the Indian subcontinent to describe this event in the English literature. Our patient, a sixty-year-old, non-diabetic, non-hypertensive male, presented with a history of left flank pain for the past six months. He was a chronic smoker and also consumed excessive amounts of alcohol. He had chronic obstructive pulmonary disease and was hepatitis B surface antigen positive. A contrast enhanced computer tomography scan of the abdomen showed an 8¥8¥8 cm, well-defined, heterogeneously enhancing mass with central necrosis, in the left suprarenal region. The provisional diagnosis of an adrenal tumor was made and open transperitoneal excision of the tumor along with two enlarged lymph nodes was done. Immunohistochemistry staining of the specimen revealed it to be a primary hepatocellular carcinoma. The patient died within six months of surgery owing to extensive metastases. We concluded that chronic hepatitis B infection and chronic and excessive alcohol consumption and/or chronic smoking may have been the predisposing factors for the occurrence of primary hepatocellular carcinoma in the liver rest in our patient. The prognosis appears to be poor despite surgical management.

  19. Distinct Claudin Expression Profiles of Hepatocellular Carcinoma and Metastatic Colorectal and Pancreatic Carcinomas

    OpenAIRE

    Holczbauer, Ágnes; Gyöngyösi, Benedek; Lotz, Gábor; Szijártó, Attila; Kupcsulik, Péter; Schaff, Zsuzsa; Kiss, András

    2013-01-01

    Tight junction proteins, including claudins, are often dysregulated during carcinogenesis and tumor progression. Moreover, the claudin expression pattern usually varies between different tumor entities. We aimed to investigate claudin expression profiles of primary and metastatic liver malignancies. We analyzed claudin-1, -2, -3, -4, and -7 expression by quantitative immunohistochemistry and real-time RT-PCR, respectively. Twenty hepatocellular carcinomas (HCCs) and liver metastases of 20 col...

  20. [Surgical treatment of hepatocellular carcinoma. Long term results].

    Science.gov (United States)

    Figueras, Juan; Ramos, Emilio; Ibáñez, Luis; Valls, Carles; Serrano, Teresa; Rafecas, Antonio; Casanovas, Teresa; Fabregat, Juan; Xiol, Xavier; Torras, Jaume; Baliellas, Carmen; Jaurrieta, Eduardo; Casais, Luis

    2002-03-30

    Surgical treatment for hepatocellular carcinoma remains controversial due to a lack of prospective randomized studies. Between January 1990 and December 2000, 121 liver transplantations (group 1) and 52 hepatectomies (group 2) were performed for hepatocellular carcinoma. Each surgical treatment was carried out depending on patients' and tumor's characteristics. Patients from group 1 had a more advanced tumoral grade, with higher involvement of two lobes (19 vs 4%; p = 0.015) and higher number of nodules (1.9 DE [2] vs 1.2 [0.6]; p = 0.001); yet the mean tumor size was lower (3 cm [1.5] vs 4.2 [3.2]; p = 0.006). Operative mortality (4% vs 2%; p = 0.66) and 5- and 10-years survival (68% and 42% vs 63% and 45%; p = 0.23) were similar between both groups. Nevertheless, 5- and 10-years recurrence rates (10.6% and 10.6% vs 50% and 65.5%; p < 0.0001) were more favourable in group 1. Prognostic factors of recurrence included microscopic vascular invasion (RR = 12.12; CI, 2.02-75.52) and alpha-fetoprotein levels higher than 300 ng/mL (RR = 7.12; 95% CI, 1.08-47.02) in group 1, and the pT3-4 stage (RR = 3.86; 95% CI, 1.06-14.03) in group 2. Mean time on waiting lists for liver transplantation was 3.06 (2.66) months and it has increased significantly in last years, especially among blood group 0 patients. However, this fact has not been associated with a worsening of survival rates (p = 0.98). After a good patient selection, either liver transplantation or hepatectomy achieve excellent long term survival rates in patients with hepatocellular carcinoma, though the former allows a better control of the tumoral disease. The increase of mean time on waiting lists for liver transplantation during the last years has not led to a worsening of survival results.

  1. Detection of hepatocellular carcinoma with multi-slice spiral CT by ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-06-07

    Jun 7, 2010 ... The purpose of the study is to evaluate the effect of iodine concentration of contrast material on detection of hepatocellular carcinoma with multi-slice spiral computed tomography (CT) by using double-arterial phase and portal venous phase enhanced scanning. Ninety-four (94) patients with hepatocellular ...

  2. A Rare Case of Mistaken Identity: Metastatic Hepatocellular Carcinoma to the Nose

    Directory of Open Access Journals (Sweden)

    GK Lee

    2010-06-01

    Full Text Available Hepatocellular carcinoma most often metastasizes to the lungs, abdominal lymph nodes, or bone. The identification of extrahepatic metastases of hepatocellular carcinoma to the sinonasal region has rarely been reported. We report a case of a 49 year-old man with a history of stage IV hepatocellular carcinoma presenting with two adjacent pigmented lesions on the tip of his nose. Initial pathological staining identified the lesion as a primary melanoma. However, upon further examination with the chemical markers CEA, CAM 5.2, and Keratin, it was determined that the lesions were consistent with hepatocellular carcinoma. This case highlights a potentially rare situation of mistaking a liver metastasis for a malignant melanoma.

  3. Single-domain monoclonal antibodies for the treatment of hepatocellular carcinoma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute seeks parties to license human monoclonal antibodies and immunoconjugates and co-develop, evaluate, and/or commercialize large-scale antibody production and hepatocellular carcinoma (HCC) xenograft mouse models.

  4. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Siddiqui, Maqsood A; Ali, Bahy A

    2013-01-01

    Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells. A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P hepatocellular carcinoma cells exposed to arsenic trioxide. The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.

  5. Computed tomography-guided transpulmonary radiofrequency ablation for hepatocellular carcinoma located in hepatic dome

    National Research Council Canada - National Science Library

    Mitsuo Toyoda Satoru Kakizaki Katsuhiko Horiuchi Kenji Katakai Naondo Sohara Ken Sato Hitoshi Takagi Masatomo Mori Takahito Nakajima

    2006-01-01

    ...) for hepatocellular carcinoma (HCC) located in the hepatic dome. METHODS: A total of seven patients with HCC comprising seven nodules located in the hepatic dome were treated from April 2004 to December 2004...

  6. Hemothorax caused by spontaneous rupture of hepatocellular carcinoma in the pleural cavity: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hin Hee; Ohm, Joon Young [Dept. of Radiology, Chungnam National University Hospital, Daejeon (Korea, Republic of); Kim, Song Soo; Kim, Jin Hwan [Dept. of Radiology, Chungnam National University School of Medicine, Daejeon(Korea, Republic of)

    2017-07-15

    Hemothorax resulting from ruptured hepatocellular carcinoma (HCC) is extremely rare and is generally caused by ruptured intrathoracic metastatic lesions. However, we report a rare case of hemothorax resulting from intrathoracic rupture of primary HCC.

  7. Survival, liver failure, and hepatocellular carcinoma in obesity-related cryptogenic cirrhosis

    National Research Council Canada - National Science Library

    Ratziu, Vlad; Bonyhay, Luminita; Di Martino, Vincent; Charlotte, Frederic; Cavallaro, Lucas; Sayegh-Tainturier, Marie-Hélène; Giral, Philippe; Grimaldi, André; Opolon, Pierre; Poynard, Thierry

    2002-01-01

    ...‐related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity...

  8. Fulminant hepatitis in a patient with hepatocellular carcinoma related to nonalcoholic steatohepatitis treated with sorafenib.

    Science.gov (United States)

    Brandi, Giovanni; De Lorenzo, Stefania; Di Girolamo, Stefania; Bellentani, Stefano; Saccoccio, Gioconda; Biasco, Guido

    2015-04-28

    We describe a case of acute liver failure in a patient with advanced hepatocellular carcinoma related to nonalcoholic steatohepatitis during sorafenib treatment. A 74-year-old man with diabetes mellitus and hypertension was diagnosed with hepatocellular carcinoma associated with fatty liver. Three weeks after sorafenib therapy, at Eastern Cooperative Oncology Group performance status 3, he developed jaundice, general weakness, flapping tremor, nausea, and anorexia. Sorafenib was stopped: laboratory tests showed a relevant elevation of transaminases suggesting diagnosis of acute hepatitis. During hospital admission, the patient died of liver failure. Sorafenib is the first successful target therapy effective for advanced hepatocellular carcinoma. The most common adverse events are fatigue, hand-foot skin reaction, skin rash/desquamation, diarrhea, and hypertension, whereas liver dysfunction is uncommon. To our knowledge, this is the first patient reported in the literature with hepatocellular carcinoma related to nonalcoholic steatohepatitis who died of rapid worsening of liver function during sorafenib treatment.

  9. ICG Clearance in Assessing Cirrhotic Patients with Hepatocellular Carcinoma for Major Hepatic Resection

    Directory of Open Access Journals (Sweden)

    Seigo Kitano

    1997-01-01

    Full Text Available Objective: To deWne the safety of major hepatectomy for hepatocellular carcinoma (HCC associated with cirrhosis and the selection criteria for surgery in terms of hospital mortality.

  10. Angiogenesis: From Chronic Liver Inflammation to Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Paloma Sanz-Cameno

    2010-01-01

    Full Text Available Recently, new information relating to the potential relevance of chronic hepatic inflammation to the development and progression of hepatocellular carcinoma (HCC has been generated. Persistent hepatocellular injury alters the homeostatic balance within the liver; deregulation of the expression of factors involved in wound healing may lead to the evolution of dysplastic lesions into transformed nodules. Progression of such nodules depends directly on the development and organization of a vascular network, which provides the nutritional and oxygen requirements to an expanding nodular mass. Angiogenic stimulation promotes intense structural and functional changes in liver architecture and physiology, in particular, it facilitates transformation of dysplasia to nodular lesions with carcinogenic potential. HCC depends on the growth and spreading of vessels throughout the tumor. Because these vascular phenomena correlate with disease progression and prognosis, therapeutic strategies are being developed that focus on precluding vascular expansion in these tumors. Accordingly, an in-depth study of factors that promote and support pathological angiogenesis in chronic hepatic diseases may provide insights into methods of preventing the development of HCC and/or stimulating the regression of established HCC.

  11. 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.

  12. New Insights into the Epigenetics of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Braira Wahid

    2017-01-01

    Full Text Available Hepatocellular Carcinoma (HCC is one of the most predominant malignancies with high fatality rate. This deadly cancer is rising at an alarming rate because it is quite resistant to radio- and chemotherapy. Different epigenetic mechanisms such as histone modifications, DNA methylation, chromatin remodeling, and expression of noncoding RNAs drive the cell proliferation, invasion, metastasis, initiation, progression, and development of HCC. These epigenetic alterations because of potential reversibility open way towards the development of biomarkers and therapeutics. The contribution of these epigenetic changes to HCC development has not been thoroughly explored yet. Further research on HCC epigenetics is necessary to better understand novel molecular-targeted HCC treatment and prevention. This review highlights latest research progress and current updates regarding epigenetics of HCC, biomarker discovery, and future preventive and therapeutic strategies to combat the increasing risk of HCC.

  13. Hepatogastric Fistula following Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Inderpreet Grover

    2014-10-01

    Full Text Available Hepatogastric fistula (HGF formation following transcatheter arterial chemoembolization (TACE leads to increased morbidity and mortality. A 51-year-old Caucasian male with chronic hepatitis B virus-associated cirrhosis and unresectable hepatocellular carcinoma (HCC presented to the Interventional Radiology Unit for TACE to achieve tumor necrosis. Following the procedure, the patient was admitted with symptoms of fever, epigastric and right upper quadrant pain secondary to the development of an abscess. The abscess was drained; however, an exceedingly rare HGF resulted that was favored to represent a direct invasion of HCC. HGF, the rare complication following TACE, leads to grave consequences and vigilant monitoring, for the development of this entity is recommended to reduce patient mortality. We present a case and literature review of HGF development following TACE for HCC.

  14. Imaging of hepatocellular carcinoma; Bildgebung des hepatozellulaeren Karzinoms

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    Lincke, Therese; Zech, Christoph [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Boll, Daniel

    2016-12-15

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Besides the improvement in diagnostics and therapy the quantity of new cases and fatalities per year are equal. The main risk factors for HCC developing are liver cirrhosis (causing 90% of HCCs), non-alcoholic fatty liver disease and chronic hepatitis B infection. Therefore, it is recommended to perform an ultrasound screening on patients at risk every 6 month to detect HCC-lesions early. HCC can be definitely diagnosed by imaging techniques using contrast agent such as contrast-enhanced-ultrasound (CEUS), contrast-enhanced-MRI (CE-MRI) and contrast-enhanced-CT (CE-CT). MRI has several advantages compared to the other modalities due to the multi-parametric approach and a higher sensitivity for tumor detection.

  15. Virus-induced hepatocellular carcinoma with special emphasis on HBV.

    Science.gov (United States)

    Wang, Ming; Xi, Dong; Ning, Qin

    2017-03-01

    Hepatocellular carcinoma (HCC) is a common malignant tumor with high lethality, and the hepatitis B virus (HBV) is a chief cause. HBV can accelerate HCC via multiple mechanisms. First, HBV induces immune reactions that lead to repeated hepatic inflammation, fibrosis and a deficient immune microenvironment. Subsequently, HBV can modify host genes near the insertion point through DNA integration to cause host cell genome instability and to generate carcinogenic fusion proteins. Additionally, HBV expresses diverse active proteins, especially HBx and HBs, which have a range of transactivation functions such as regulation of apoptosis, interference with intracellular signaling pathways, and alteration of epigenetics. Currently, primary prevention measures for HBV-induced HCC focus on vaccination and antiviral treatment. Here, we report the epidemiology, the molecular mechanism and the progress in therapeutic strategies for controlling HBV-induced HCC.

  16. Hepatocellular carcinoma in elderly patients: challenges and solutions.

    Science.gov (United States)

    Brunot, Angélique; Le Sourd, Samuel; Pracht, Marc; Edeline, Julien

    2016-01-01

    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.

  17. Research advances in cellular immunotherapy for primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHANG Ye

    2014-09-01

    Full Text Available The present therapy for primary hepatocellular carcinoma (HCC consists of surgery as well as local radiotherapy and chemotherapy. However, the majority of patients are susceptible to recurrence after comprehensive treatment, and the overall treatment outcome is not ideal due to the lack of effective drugs and strategies. Increasing evidence has demonstrated that the immune system is closely related to the development, progression, metastasis, and recurrence of HCC. Thus, immune therapy, especially cellular immunotherapy, could regulate immune function and induce specific antitumor immunity to achieve the goal of controlling HCC and reducing its recurrence and metastasis, which has become an essential part in the comprehensive treatment of HCC. The findings in preclinical and clinical studies on cellular immunotherapy for HCC data are reviewed, and the current problems are discussed.

  18. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Santangelo

    2017-01-01

    Full Text Available Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA from donor to recipient cells. Notably, tumor-derived exosomes (TDEs appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC, the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  19. Research progress in c-Met and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  20. Prebiotics: A Novel Approach to Treat Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Naz Fatima

    2017-01-01

    Full Text Available Hepatocellular carcinoma is one of the fatal malignancies and is considered as the third leading cause of death. Mutations, genetic modifications, dietary aflatoxins, or impairments in the regulation of oncogenic pathways may bring about liver cancer. An effective barrier against hepatotoxins is offered by gut-liver axis as a change in gut permeability and expanded translocation of lipopolysaccharides triggers the activation of Toll-like receptors which stimulate the process of hepatocarcinogenesis. Prebiotics, nondigestible oligosaccharides, have a pivotal role to play when it comes to inducing an antitumor effect. A healthy gut flora balance is imperative to downregulation of inflammatory cytokines and reducing lipopolysaccharides induced endotoxemia, thus inducing the antitumor effect.

  1. Small Bowel Metastasis of Hepatocellular Carcinoma Detected by Capsule Endoscopy

    Directory of Open Access Journals (Sweden)

    A. Igawa

    2013-11-01

    Full Text Available We report a rare case of metastasis of hepatocellular carcinoma (HCC to the small bowel that presented as a pedunculated epithelial polyp. A 60-year-old man with liver cirrhosis type B was treated for HCC (stage IVb at our hospital. He had been admitted for melena and anemia. Capsule endoscopy was performed in this patient with obscure gastrointestinal bleeding. It showed a polypoid lesion with bleeding in the ileum. Double-balloon endoscopy was performed. The lesion was determined to be a pedunculated polyp in the ileum. Histological examination of biopsy specimens showed tumor cells resembling HCC. We performed endoscopic mucosal resection for the lesion by double-balloon endoscopy to prevent bleeding from the tumor. The patient had no melena or anemia and his condition improved after endoscopic mucosal resection. However, he died of liver failure 2 months later.

  2. Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Young Mi Hong

    2016-06-01

    Full Text Available The bone is a common site for metastasis in hepatocellular carcinoma (HCC. However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin. Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.

  3. Vitamin D and K signaling pathways in hepatocellular carcinoma.

    Science.gov (United States)

    Louka, Manal L; Fawzy, Ahmed M; Naiem, Abdelrahman M; Elseknedy, Mustafa F; Abdelhalim, Ahmed E; Abdelghany, Mohamed A

    2017-09-20

    Hepatocellular carcinoma (HCC) is a primary liver malignancy, and is now the six most common in between malignancies. Early diagnosis of HCC with prompt treatment increases the opportunity of patients to survive. With the advances in understanding the molecular biology of HCC, new therapeutic strategies to treat HCC have emerged. There is a growing consensus that vitamins are important for the control of various cancers. Biochemical evidence clearly indicates that HCC cells are responsive to the inhibitory effect of vitamin D, vitamin D analogues and vitamin K. In this review, we summarize the mechanisms used by vitamin D and K to influence the development of HCC and the latest development of vitamin analogues for potential HCC therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. The Role of Bridging Therapy in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Roberto Galuppo

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common primary malignancy of the liver accounting for 7% of all cancers worldwide. Most cases of HCC develop within an established background of chronic liver disease. For that reason, liver resection is only possible in selected patients. Liver transplantation has become the treatment of choice in patients with HCC, end-stage liver disease, and significant portal hypertension. Shortage of organ donors has resulted in overall increase of waiting list time with increased risk of dropout due to tumor progression. Neoadjuvant therapies have emerged as an alternative to control tumor growth in patients while waiting. The aim of this study is to review the literature on the role of bridging therapy and downstaging prior to liver transplantation in patients with HCC. We are also presenting our single-center experience of 96 patients undergoing transplantation for HCC with and without bridging therapy.

  5. Application of proteomics in study of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Jiangang

    2014-09-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most fatal malignant tumors worldwide. As an important part of cutting-edge research fields, proteomics has been widely used in the studies of related diseases and has currently become a crucial experimental approach to research on HCC. Significantly expressed proteins can be identified as potential biomarkers for early diagnosis and targets for therapeutic drugs for HCC. Moreover, they can be used for prediction of the recurrence and prognosis of HCC, as well as for investigation of pathogenesis of the disease. The proteomic results from worldwide clinical studies of HCC are summarized, and it is suggested that the clinical application of results of basic research on HCC proteomics will bring great benefit to the diagnosis and treatment of HCC.

  6. Application of local ablative therapies for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHU Xiaoli

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a common malignant tumor in the world, and surgical resection and liver transplantation are two radical treatment modalities, but only 10%-20% of all patients can receive such treatments. In recent years, local therapies including radiofrequency ablation, microwave ablation, cryoablation, and the irreversible electroporation ablation which appeared recently have gradually become the alternative therapies for the patients who are unable to undergo surgery. In addition to local tumor growth control and improvement in survival outcomes, the ablation technology also helps to downgrade tumor for secondary resection. This article focuses on the research progress in radiofrequency ablation alone and in combination with other therapies in the treatment of HCC, compares radiofrequency ablation with other local ablative therapies, and briefly introduces the application of intelligent navigation technology in adjuvant ablation. With the development of medical imaging and progress in related fields, the ablation technology will be widely applied in clinical practice in the future.

  7. Thalidomide induces complete remission of advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Hung Chien

    2014-06-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most prevalent human cancers in the world, but its prognosis is extremely poor. HCC is considered a hypervascular tumor. Thalidomide, which has been known to inhibit growth factor-induced neovascularization, is a convenient alternative to target therapy such as sorafenib. We report a 65-year-old male patient with alcoholic liver cirrhosis that was diagnosed having multiple HCCs during surveillance. The patient was assessed as inoperable and unsuited for transhepatic arterial chemoembolization or systemic chemotherapy. After discussing the therapeutic alternatives, he decided to receive low-dose thalidomide (100 mg daily therapy. Fortunately, follow-up liver biochemical tests, serum α-fetoprotein level, and dynamic computed tomography showed complete remission of the HCCs 4.5 months after thalidomide treatment and this was documented for more than 22 months without evidence of tumor recurrence.

  8. Clinical Development of c-MET Inhibition in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Joycelyn J. X. Lee

    2015-10-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the leading causes of cancer death. In patients with advanced or unresectable HCC, there are few treatment options. Conventional chemotherapy has limited benefits. Sorafenib, a multi-kinase inhibitor, improves survival, but options for patients intolerant of or progressing on sorafenib are limited. There has been much interest in recent years in molecular therapeutic targets and drug development for HCC. One of the more promising molecular targets in HCC is the cellular-mesenchymal-epithelial transition (c-MET factor receptor. Encouraging phase II data on two c-MET inhibitors, tivantinib and cabozantinib, has led to phase III trials. This review describes the c-MET/hepatocyte growth factor (HGF signalling pathway and its relevance to HCC, and discusses the preclinical and clinical trial data for inhibitors of this pathway in HCC.

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

    Science.gov (United States)

    Matsuda, Yasunobu; Wakai, Toshifumi; Kubota, Masayuki; Osawa, Mami; Sanpei, Ayumi; Fujimaki, Shun

    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 remains unclear. Several studies have reported that a chromatographic separation technique based on high-performance liquid chromatography can successfully detect the concentration of mycotoxins in plasma. In this article, we review recent studies of mycotoxin, and discuss its possible significance as a biomarker of HCC. PMID:23674865

  10. A case of spontaneous regression of hepatocellular carcinoma after ultrasound guided liver biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Jeong Hyun [Dept. of Radiology, Dong A University Hospital, Dong A University College of Medicine, Busan (Korea, Republic of)

    2014-10-15

    Spontaneous regression of hepatocellular carcinoma after liver biopsy has not been reported in the English literature. Herein, we present a case of partial spontaneous regression of hepatocellular carcinoma after ultrasound guided liver biopsy in a 64-year-old female. During 28 months, the tumor, which had been shrinking, showed no interval change. However, after 28 months, tumor showed regrowth, which led to a segmentectomy.

  11. High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.

    Science.gov (United States)

    Pu, Meng; Wang, Jianlin; Huang, Qike; Zhao, Ge; Xia, Congcong; Shang, Runze; Zhang, Zhuochao; Bian, Zhenyuan; Yang, Xishegn; Tao, Kaishan

    2017-07-01

    Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor-metastasis-node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.

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

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    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.

  13. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

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    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

  14. 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

  15. Mexican consensus on the diagnosis and management of hepatocellular carcinoma.

    Science.gov (United States)

    González Huezo, María Sarai; Sánchez Ávila, Juan Francisco

    2014-01-01

    There has been an increase in the incidence of hepatocellular carcinoma (HCC) worldwide and information on this disease is limited in Mexico. To analyze the available evidence on the diagnosis and treatment of HCC in the Mexican population. The Mexican Association of Hepatology organized a meeting that 24 medical specialists interested in HCC attended. An electronic database search was carried out to identify documents published from 2000 with the keywords «Hepatocellular carcinoma» and «Mexico», «epidemiology», «diagnosis», and «treatment». The incidence of HCC in Mexico has increased over the last few decades. The mean age of disease presentation is in patients from 60 to 70 years old, and the man:woman ratio appears to be equal. HCC is frequently associated with underlying hepatopathy and the primary cause reported in our country is chronic hepatitis C virus) infection. Surveillance is recommended for high-risk groups in Child-Pugh stages A and B, and for those in stage C if the patient is on a waiting list or regarded as a candidate for liver transplantation. HCC should be evaluated by a multidisciplinary team of experts in the field. HCC is a neoplasia that is on the rise in Mexico, with epidemiologic characteristics similar to those of other populations. Diagnosis and treatment should be individualized in accordance with these Consensus guidelines. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

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

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    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

  17. An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations.

    Science.gov (United States)

    Bertani, Stéphane; Pineau, Pascal; Loli, Sebastian; Moura, Julien; Zimic, Mirko; Deharo, Eric; Ruiz, Eloy

    2013-01-01

    In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country. A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin. Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics. The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

  18. Expression of Fra-1 in human hepatocellular carcinoma and its prognostic significance.

    Science.gov (United States)

    Gao, Xiao-Qiang; Ge, Yong-Sheng; Shu, Qing-Hua; Ma, Hua-Xing

    2017-06-01

    This study aimed to explore the clinical significance and prognostic value of Fra-1 in hepatocellular carcinoma patients after curative resection. Fra-1 expression was investigated using a combination of techniques: immunohistochemistry for 66 samples of hepatocellular carcinoma and quantitative real-time polymerase chain reaction and western blotting assays for 19 matched hepatocellular carcinoma specimens. Fra-1 was present in 38 of 66 (57.6%) tumor tissues, with intense staining in the nuclei. There was also positive staining in 14 of 66 (21.2%) adjacent peritumoral tissues, with weak staining in the cytoplasm. Quantitative real-time polymerase chain reaction and western blotting assays confirmed higher expression of Fra-1 messenger RNA and Fra-1 protein in tumor tissues than adjacent non-tumor tissues for 19 hepatocellular carcinoma samples (p expression of Fra-1 was significantly related to vascular invasion and serum alpha-fetoprotein. Kaplan-Meier survival analysis found that overexpressed Fra-1 was correlated with poor overall survival and disease-free survival. Multivariate analysis identified Fra-1 as an independent prognostic factor. Fra-1 may be involved in the progress of hepatocellular carcinoma and could be a promising molecular candidate in the diagnosis and treatment of hepatocellular carcinoma.

  19. Antiangiogenic activity of vitexicarpine in experimentally induced hepatocellular carcinoma: Impact on vascular endothelial growth factor pathway.

    Science.gov (United States)

    Hassoun, Shimaa M; Abdel-Rahman, Noha; Eladl, Entsar I; El-Shishtawy, Mamdouh M

    2017-06-01

    Angiogenesis plays important roles in progression of hepatocellular carcinoma. The antiangiogenic mechanisms of vitexicarpine are not fully defined. Therefore, we conducted the following study to evaluate the antiangiogenic mechanism and antitumor activity of vitexicarpine in vivo model of hepatocellular carcinoma through modulation of vascular endothelial growth factor signaling pathway. Hepatocellular carcinoma was induced in Sprague Dawley rats by thioacetamide. Hepatocellular carcinoma was assessed by measuring serum alpha-fetoprotein and investigating liver sections stained with hematoxylin/eosin. Hepatocellular carcinoma rats were injected with vitexicarpine (150 mg/kg) for 2 weeks. Hepatic vascular endothelial growth factor was measured by enzyme-linked immunosorbent assay. Protein and expression of hepatic phospho-Ser473-AKT (p-AKT) and phospho-Tyr419-Src (p-Src) were determined. The apoptotic pathway was evaluated by assessment of protein expression of caspase-3. Vitexicarpine increased rats' survival time and decreased serum alpha-fetoprotein as well as it ameliorated fibrosis and massive hepatic tissue breakdown. It attenuated hepatocellular carcinoma-induced protein and gene expression of vascular endothelial growth factor, p-AKT, p-Src, and caspase-3. In conclusion, this study suggests that vitexicarpine possesses both antiangiogenic and antitumor activities through inhibition of vascular endothelial growth factor, p-AKT/AKT, and p-Src with subsequent inhibition of apoptotic pathway.

  20. A Peculiar Mutation Spectrum Emerging from Young Peruvian Patients with Hepatocellular Carcinoma

    Science.gov (United States)

    Marchio, Agnès; Bertani, Stéphane; Rojas Rojas, Teresa; Doimi, Franco; Terris, Benoît; Deharo, Eric; Dejean, Anne; Ruiz, Eloy; Pineau, Pascal

    2014-01-01

    Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms. PMID:25502816

  1. Long non-coding RNA TRPM2-AS as a potential biomarker for hepatocellular carcinoma.

    Science.gov (United States)

    Xu, C; Huang, Q; Zhang, C; Xu, W; Xu, G; Zhao, X; Liu, X; Du, Y

    2017-10-28

    There is increasing evidence that long non-coding RNAs are involved in hepatocellular carcinoma (HCC) tumorigenesis. The expression level of TRPM2-AS in HCC and its clinical association remain poorly defined. qRT-PCR was performed to detect the expression of TRPM2-AS in 108 HCC patients. The correlations between TRPM2-AS expression and clinicopathological factors and prognosis were evaluated. The inference of TRPM2-AS to the proliferation and apoptosis of HCC cells was detected. The aim of our study was to explore the expression of TRPM2-AS in hepatocellular carcinoma (HCC) and the relation with prognosis and clinical features. The expression of TRPM2-AS was higher in most HCC tissues and was significantly correlated with tumor size, AJCC stage, tumor differentiation, and the prognosis of HCC patients. Interfering TRPM2-AS expression using siRNA significantly inhibited cell proliferation and promoted cell apoptosis in two HCC cell lines. Long non-coding RNA TRPM2-AS is upregulated in HCC and represents a new biomarker for HCC and the inhibition of TRPM2-AS promotes apoptosis in HCC cells in vitro.

  2. Transcatheter arterial chemoembolization in patients with hepatocellular carcinoma and coexisting hepatic cavernous hemangioma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ran-Chou [Taipei City Hospital Renai Branch, Department of Radiology, Taipei (Taiwan); Taipei Medical University, Department of Radiology, School of Medicine, Taipei (Taiwan); Lii, Jiunn-Ming; Chen, Wei-Tsung; Tu, Hsing-Yang; Chiang, Liang-Chung [Taipei City Hospital Renai Branch, Department of Radiology, Taipei (Taiwan)

    2006-06-15

    We investigated the consequence of repeated transcatheter arterial chemoembolization (TACE) for coexisting small hepatic hemangioma in the treatment of patients with hepatocellular carcinomas and describe the imaging features of embolized hemangioma on the follow-up Lipiodol CT and MR. Six of 431 patients with biopsy-confirmed hepatocellular carcinomas, who underwent TACE, also had seven small hepatic cavernous hemangiomas (0.8{proportional_to}2.3 cm) in the same area of embolization. All six patients underwent repeated TACE All lesions were evaluated with CT and/or MR for the post-treatment follow-up. The outcomes and imaging features of these embolized hemangiomas were reviewed for the change of tumor size, Lipiodol deposition, enhancing pattern as well as embolization complications. Six of the seven hemangiomas did not depict changes in the size or enhancement pattern without being ablated. One hemangioma showed a decrease in size, but still persisted after TACE. All of the hemangiomas showed Lipiodol deposition for 2{proportional_to}15 months, in which five hemangiomas depicted irregular rim patterns. There is no complication caused by the procedures. The differentiation of small hepatic hemangiomas from viable HCC is important in the post-TACE follow-up to avoid unnecessary repeated embolization. (orig.)

  3. Profiling of Hepatocellular Carcinoma Cell Cycle Regulating Genes Targeted by Calycosin

    Directory of Open Access Journals (Sweden)

    Dongqing Zhang

    2013-01-01

    Full Text Available We cocultured calycosin with human hepatocellular carcinoma cell line (BEL-7402 to investigate the effect on cell proliferation. Calycosin can markedly block the cell growth in G1 phase (P<0.01 on the IC50 concentration. There were seventeen genes involved in cell-cycle regulation showing differentially expressed in treated cells detected by gene chip. Eight genes were upregulated and nine genes were downregulated. Downregulated TFDP-1, CDKN2D, and SPK2 and upregulated CDC2 and CCNB1 might affect cell cycle of tumor cells. Furthermore, we checked the transcription pattern using 2D gel method to find different expression of proteins in human hepatocellular carcinoma cells after exposure to calycosin. Fourteen proteins were identified by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS. Twelve proteins expression were increased such as transgelin 2, pyridoxine 5′-phosphate, stress-induced-phosphoprotein 1, peroxiredoxin 1, endoplasmic reticulum protein 29, and phosphoglycerate mutase 1. Only thioredoxin peroxidase and high-mobility group box1 proteins’ expression decreased. Both genes and proteins changes might be relate to the mechanism of antitumor effect under treatment of calycosin. In conclusion, calycosin has a potential effect to inhibit the BEL-7402 cell growth by inhibiting some oncogene expression and increasing anticancer genes expression, what is more, by blocking cell cycle.

  4. The Effect of Alendronate on Proteome of Hepatocellular Carcinoma Cell Lines

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    Amber Ilyas

    2014-01-01

    Full Text Available Cancer is a life threatening disorder effecting 11 million people worldwide annually. Among various types of cancers, Hepatocellular carcinoma (HCC has a higher rate of mortality and is the fifth leading cause of cancer related deaths around the world. Many chemotherapeutic drugs have been used for the treatment of HCC with many side effects. These drugs are inhibitors of different cell regulatory pathways. Mevalonate (MVA pathway is an important cellular cascade vital for cell growth. A variety of inhibitors of MVA pathway have been reported for their anticancerous activity. Bisphosphonates (BPs are members of a family involved in the treatment of skeletal complications. In recent years, their anticancer potential has been highlighted. Current study focuses on exploring the effects of alendronate (ALN, a nitrogen containing BP, on hepatocellular carcinoma cell line using genomic and proteomics approach. Our results identified ten differentially expressed proteins, of which five were up regulated and five were down regulated in ALN treated cells. Furthermore, we also performed gene expression analysis in treated and control cell lines. The study may help in understanding the molecular mechanism involved in antitumor activity of ALN, identification of possible novel drug targets, and designing new therapeutic strategies for HCC.

  5. Gene and functional up-regulation of the BCRP/ABCG2 transporter in hepatocellular carcinoma.

    Science.gov (United States)

    Sukowati, Caecilia Hc; Rosso, Natalia; Pascut, Devis; Anfuso, Beatrice; Torre, Giuliano; Francalanci, Paola; Crocè, Lory S; Tiribelli, Claudio

    2012-11-15

    The Breast Cancer Resistance Protein (BCRP/ABCG2) is one member of ABC transporters proteins super family responsible of drug resistance. Since data on ABCG2 expression in liver malignances are scanty, here we report the expression of ABCG2 in adult human hepatocellular carcinoma (HCC) in both in vivo and in vitro models with different degree of malignancy. In cell lines derived from human hepatocellular carcinoma, ABCG2 gene expression was assessed by reverse transcription quantitative real time PCR and function by Hoechst 33342 efflux assay; protein content was assessed by SDS-PAGE Western blot. ABCG2 expression was found to be highest in the most undifferentiated cell lines, and this was related with a higher functional activity. ABCG2 expression was sensitive to antineoplastic drugs since exposure to 5 μM doxorubicin for 24 hours resulted in significant up-regulations of ABCG2 in all cell lines, particularly in those lines with low basal ABCG2 expression (pexpression was also investigated in 51 adult liver tissues with HCC and related cirrhosis; normal liver tissue was used as control. ABCG2 gene expression was higher in HCC than both cirrhotic paired tissue and normal tissue. This up-regulation was greater (pexpression and differentiation stage both in human and HCC derived cell lines. The rapid up-regulation of ABCG2 to exposure to doxorubicin emphasizes the importance of this transporter in accounting for drug resistance in liver tumors.

  6. Gene expression profile analysis in human hepatocellular carcinoma by cDNA microarray.

    Science.gov (United States)

    Chung, Eun Jung; Sung, Young Kwan; Farooq, Mohammad; Kim, Younghee; Im, Sanguk; Tak, Won Young; Hwang, Yoon Jin; Kim, Yang Il; Han, Hyung Soo; Kim, Jung-Chul; Kim, Moon Kyu

    2002-12-31

    We performed gene expression profiling of normal and hepatocellular carcinoma (HCC) liver tissues using a high-density microarray that contained 3,063 human cDNA. The results of a microarray hybridization experiment from eight different HCC tissues were analyzed and classified by the Cluster program. Among these differentially-expressed genes, the galectin-3, serine/threonine kinase SGK, translation factor eIF-4A, -4B, -3, fibroblast growth factor receptor, and ribosomal protein L35A were up-regulated; the mRNAs of Nip3, decorin, and the insulin-like growth factor binding protein-3 were down-regulated in HCC. The differential expression of these genes was further confirmed by an RT-PCR analysis. In addition, our data suggest that the gene expression profile of HCC varies according to the histological types.

  7. Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma; Carcinomatosis peritoneal como forma de presentacion infrecuente del hepatocarcinoma fibrolamelar

    Energy Technology Data Exchange (ETDEWEB)

    Vicente, R.; Garcia-Gutierrez, J. A.; Fernandez, A.; Santalla, F. [Hospital Comarcal de la Axarquia. Malaga (Spain)

    2001-07-01

    Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopahtological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs.

  8. Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma

    OpenAIRE

    Qiao You-Lin; Orsini Lucinda S; Therneau Terry; Chen Minshan

    2011-01-01

    Abstract Background More than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the country's second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated ...

  9. Quantitative proteome analysis reveals the correlation between endocytosis-associated proteins and hepatocellular carcinoma dedifferentiation.

    Science.gov (United States)

    Naboulsi, Wael; Bracht, Thilo; Megger, Dominik A; Reis, Henning; Ahrens, Maike; Turewicz, Michael; Eisenacher, Martin; Tautges, Stephanie; Canbay, Ali E; Meyer, Helmut E; Weber, Frank; Baba, Hideo A; Sitek, Barbara

    2016-11-01

    The majority of poorly differentiated hepatocellular carcinomas (HCCs) develop from well-differentiated tumors. Endocytosis is a cellular function which is likely to take part in this development due to its important role in regulating the abundances of vital signaling receptors. Here, we aimed to investigate the abundance of endocytosis-associated proteins in HCCs with various differentiation grades. Therefore, we analyzed 36 tissue specimens from HCC patients via LC-MS/MS-based label-free quantitative proteomics including 19 HCC tissue samples with different degrees of histological grades and corresponding non-tumorous tissue controls. As a result, 277 proteins were differentially regulated between well-differentiated tumors and controls. In moderately and poorly differentiated tumors, 278 and 1181 proteins, respectively, were significantly differentially regulated compared to non-tumorous tissue. We explored the regulated proteins based on their functions and identified thirty endocytosis-associated proteins, mostly overexpressed in poorly differentiated tumors. These included proteins that have been shown to be up-regulated in HCC like clathrin heavy chain-1 (CLTC) as well as unknown proteins, such as secretory carrier-associated membrane protein 3 (SCAMP3). The abundances of SCAMP3 and CLTC were immunohistochemically examined in tissue sections of 84 HCC patients. We demonstrate the novel association of several endocytosis-associated proteins, in particular, SCAMP3 with HCC progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Prediagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: A nested case‐control study

    National Research Council Canada - National Science Library

    Fedirko, Veronika; Duarte‐Salles, Talita; Bamia, Christina; Trichopoulou, Antonia; Aleksandrova, Krasimira; Trichopoulos, Dimitrios; Trepo, Elisabeth; Tjønneland, Anne; Olsen, Anja; Overvad, Kim; Boutron‐Ruault, Marie‐Christine; Clavel‐Chapelon, Françoise; Kvaskoff, Marina; Kühn, Tilman; Lukanova, Annie; Boeing, Heiner; Buijsse, Brian; Klinaki, Eleni; Tsimakidi, Chrysanthi; Naccarati, Alessio; Tagliabue, Giovanna; Panico, Salvatore; Tumino, Rosario; Palli, Domenico; Bueno‐de‐Mesquita, H. Bas; Siersema, Peter D; Peters, Petra H; Lund, Eiliv; Brustad, Magritt; Olsen, Karina Standahl; Weiderpass, Elisabete; Zamora‐Ros, Raul; Sánchez, María‐José; Ardanaz, Eva; Amiano, Pilar; Navarro, Carmen; Quirós, J. Ramón; Werner, Mårten; Sund, Malin; Lindkvist, Björn; Malm, Johan; Travis, Ruth C; Khaw, Kay‐Tee; Stepien, Magdalena; Scalbert, Augustin; Romieu, Isabelle; Lagiou, Pagona; Riboli, Elio; Jenab, Mazda

    2014-01-01

    The association between vitamin D status and hepatocellular carcinoma (HCC) has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology...

  11. Evaluation of Photoelectron Therapy Effect on Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    bahram Mofid

    2007-10-01

    Full Text Available Mofid B1, Navabpoor M2, Alizadeh Azimi M3 1. Assistant professor, Department of Radiotherapy, Faculty of Para-Medicine, Shahid Beheshti University of medical sciences 2. Instructor, Department of Technology of radiology, Faculty of Para-Medicine, Shahid Beheshti University of medical sciences Abstract Background: Photoelectron therapy method has been usad successfully, on the body phantom, cancer cells culture and animals. In this method, drugs containing x-Ray opaque factors–with high atomic numbers–are injected into the patient’s vein. After appropriate drug accumulation, about at least ten percent of the total injected amounts, 200kev. up to 300kev. of localized x-Ray beams is radiated to the site of the tumor. The Ethic Committee of Shahid Beheshti University of Medical Education and Health Services authorized the implementation of this new cancer treatment method, initially only on the group of patients who suffered from hepato-cellular carcinoma. Hepato cellular carcinoma is one of the most current malignancies of liver. In some cases, in addition to surgery, several approaches exist to come near the aim of predominating hepato-cellular carcinoma such as chemotherapy, current Radiation Therapy, Radio-Frequency application (RF, Trans-Artepical Chemo Embolization, (TACE, and Percutaneous Ethanol Injection (PEI. The effectiveness of the above-mentioned methods is about 10%-47%, applied alone or along side each other. Materials and methods: This study was a clinical-trial one. In this study, first, lipiodol (an x-ray opaque material with a high atomic number was transferred into the main vessel terminating to the tumor by angio-catheterization. Then,200kev. up to 250kev. of localized x-ray was radiated to the site of the tumor in one session. The drug volume was proportionally selected to the volume of the tumor, and the irradiation intensity was between 400 to 600cent.Gy. the beam energy absorption capacity of this drug is as times as

  12. Hypofractionated stereotactic radiotherapy after transarterial chemoembolisation failure in an unresectable hepatocellular carcinoma: a case presentation.

    Science.gov (United States)

    Fiorica, Francesco; Greco, Carlo; Boccia, Sergio; Sartori, Sergio; Stefanelli, Antonio; Cartei, Francesco; Ursino, Stefano

    2013-01-01

    Introduction. Transarterial chemoembolization is the first-line treatment in unresectable hepatocellular carcinoma. There is no standard treatment after transarterial chemoembolization failure. We report the case of a patient with advanced hepatocellular carcinoma who showed a complete response and a long cancer control with hypofractionated stereotactic radiotherapy after transarterial chemoembolization failure. Case Presentation. A 70-year-old Caucasian woman was treated with transarterial chemoembolization for advanced hepatocellular, but no cancer control was obtained. A hypofractionated stereotactic radiotherapy was planned delivering 40 Gy in 5 fractions. A dramatic reduction in alpha-fetoprotein was observed. Contrast-enhanced ultrasonography at 1 and 2 months showed large necrotic areas. Computerised tomography scan showed a 90% objective tumour response, then a complete remission at 3 and 6 months after treatment, respectively. Status of patient remained unchanged for 2 years. Conclusions. Hypofractionated stereotactic radiotherapy can improve survival and prognosis of unresectable hepatocellular carcinoma patient.

  13. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

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    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-09-28

    To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which

  14. Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

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    Farina M. Hanif

    2014-10-01

    Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

  15. 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

  16. Identification of MicroRNAs and target genes involvement in hepatocellular carcinoma with microarray data.

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    Wang, Dadong; Tan, Jingwang; Xu, Yong; Tan, Xianglong; Han, Mingming; Tu, Yuliang; Zhu, Ziman; Zen, Jianping; Dou, Chunqing; Cai, Shouwang

    2015-01-01

    The aim of the study is to identify the differentially expressed microRNAs (miRNAs) between hepatocellular carcinoma (HCC) samples and controls and provide new diagnostic potential miRNAs for HCC. The miRNAs expression profile data GSE20077 included 7 HCC samples, 1 HeLa sample and 3 controls. Differentially expressed miRNAs (DE-miRNAs) were identified by t-test and wilcox test. The miRNA with significantly differential expression was chosen for further analysis. Target genes for this miRNA were selected using TargetScan and miRbase database. STRING software was applied to construct the target genes interaction network and topology analysis was carried out to identify the hub gene in the network. And we identified the mechanism for affecting miRNA function. A total of 54 differentially expressed miRNAs were identified, in which there were 13 miRNAs published to be related to HCC. The differentially expressed hsa-miR-106b was chosen for further analysis and PTPRT (Receptor-type tyrosine-protein phosphatase T) was its potential target gene. The target genes interaction network was constructed among 33 genes, in which PTPRT was the hub gene. We got the conclusion that the differentially expressed hsa-miR-106b may play an important role in the development of HCC by regulating the expression of its potential target gene PT-PRT.

  17. Metastatic Hepatocellular Carcinoma in the Urinary Bladder with Radiation-induced Hemorrhagic Cystitis

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    Shiu-Dong Chung

    2007-10-01

    Full Text Available Metastatic hepatocellular carcinoma (HCC to the urinary bladder is very rare. We present the case of a 58-year-old female patient who was diagnosed to have both HCC and cervical cancer. She developed hemorrhagic cystitis 2 years after radiation therapy for cervical cancer. During endoscopic electrocauterization for hemorrhagic cystitis, three small reddish tumors measuring less than 1 cm in diameter and with a raspberry-like appearance were found. Transurethral bladder tumor resection was performed. Pathology confirmed metastatic HCC to the bladder. Due to the similar appearance, these tumors are liable to be misinterpreted as engorged vessels secondary to irradiation if biopsies are not taken. Differential diagnosis by pathology is mandatory for such patients.

  18. 188rhenium-TDD-lipiodol in treatment of inoperable primary hepatocellular carcinoma--a case report.

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    Sundram, F X; Yu, S W; Jeong, J M; Somanesan, S; Premaraj, J; Saw, M M; Tan, B S

    2001-09-01

    The aim of this study was to investigate the potential of using 188Re Lipiodol for selective internal radiation therapy of inoperable hepatocellular carcinoma (HCC). A 33-year-old female with poorly-differentiated multicentric HCC, elevated alpha-fetoprotein (AFP) and increased serum alkaline phosphatase. Over a 2-month interval, the patient was treated twice with 4GBq of 188Re-TDD-Lipiodol. There was good localisation of 188Re Lipiodol in the tumours, but also in thyroid (first treatment) and gastrointestinal tract (both treatments). So far (5 months post-treatment), the patient remains well with stable disease. 188Re Lipiodol can be an effective radiopharmaceutical for the treatment of HCC; however, more work must be done to minimise the uptake in bowel.

  19. Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

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    Miny Peter

    2011-08-01

    Full Text Available Abstract Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney. This unique case of hepatocellular carcinoma arising from liver cell adenoma in a patient with an uncharacterised condition featuring a large ectopic liver invites discussion of the role of local factors in carcinogenesis in the parent liver but not the ectopic liver. It also underlines the imperative ongoing need for clinical autopsies.

  20. Does herbal medicine reduce the risk of hepatocellular carcinoma?

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    Rino, Yasushi; Yukawa, Norio; Yamamoto, Naoto

    2015-10-07

    Many herbal medicines are effective anti-inflammatory agents and may therefore suppress the development of hepatocellular carcinoma (HCC). Recently, treatment with a single-tablet regimen containing ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with hepatitis C virus genotype 1 infection who did not respond to prior interferon-based treatment. Patients with chronic hepatitis C are expected to receive this treatment worldwide. However, many patients have hepatitis-like fatty liver and nonalcoholic steatohepatitis. A strategy to prevent the development of HCC in this subgroup of patients is urgently required. Whether herbal medicines can suppress the development of HCC remains to be established. However, herbal medicines are effective anti-inflammatory agents and may inhibit the development of HCC. Clinical trials exploring the effectiveness of herbal medicines in the prevention and treatment of HCC are therefore warranted. The current lack of knowledge and of educational programs is a barrier to increasing the use of potentially effective herbal medicines and performing prospective clinical trials.

  1. Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver Lipidomics

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    Zhao Li

    2017-11-01

    Full Text Available Background: The aim of this study was to characterize the disorder of lipid metabolism in hepatocellular carcinoma (HCC. HCC is a worldwide disease. The research into the disorder of lipid metabolism in HCC is very limited. Study of lipid metabolism in liver cancer tissue may have the potential to provide new insight into HCC mechanisms. Methods: A lipidomics study of HCC based on Ultra high performance liquid chromatography-electronic spray ionization-QTOF mass spectrometer (UPLC-ESI-QTOF MS and Matrix assisted laser desorption ionization-fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS was performed. Results: Triacylglycerols (TAGs with the number of double bond (DB > 2 (except 56:5 and 56:4 TAG were significantly down-regulated; conversely, others (except 52:2 TAG were greatly up-regulated in HCC tissues. Moreover, the more serious the disease was, the higher the saturated TAG concentration and the lower the polyunsaturated TAG concentration were in HCC tissues. The phosphatidylcholine (PC, phosphatidylethanolamine (PE and phosphatidylinositol (PI were altered in a certain way. Sphingomyelin (SM was up-regulated and ceramide (Cer were down-regulated in HCC tissues. Conclusions: To our knowledge, this is the first such report showing a unique trend of TAG, PC, PE and PI. The use of polyunsaturated fatty acids, like eicosapentanoic and docosahexanoic acid, as supplementation, proposed for the treatment of Non-alcoholic steatohepatitis (NASH, may also be effective for the treatment of HCC.

  2. 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%.

  3. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

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    Riad, Sandra; Bougherara, Habiba

    2015-01-01

    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). PMID:25685789

  4. Advances in Hypoxia-Mediated Mechanisms in Hepatocellular Carcinoma.

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    Xiong, Xin Xin; Qiu, Xin Yao; Hu, Dian Xing; Chen, Xiao Qian

    2017-09-01

    Hepatocellular carcinoma (HCC) is the fifth most common and the third most deadly malignant tumor worldwide. Hypoxia and related oxidative stress are heavily involved in the process of HCC development and its therapies. However, direct and accurate measurement of oxygen concentration and evaluation of hypoxic effects in HCC prove difficult. Moreover, the hypoxia-mediated mechanisms in HCC remain elusive. Here, we summarize recent major evidence of hypoxia in HCC lesions shown by measuring partial pressure of oxygen (pO2), the clinical importance of hypoxic markers in HCC, and recent advances in hypoxia-related mechanisms and therapies in HCC. For the mechanisms, we focus mainly on the roles of oxygen-sensing proteins (i.e., hypoxia-inducible factor and neuroglobin) and hypoxia-induced signaling proteins (e.g., matrix metalloproteinases, high mobility group box 1, Beclin 1, glucose metabolism enzymes, and vascular endothelial growth factor). With respect to therapies, we discuss mainly YQ23, sorafenib, 2-methoxyestradiol, and celastrol. This review focuses primarily on the results of clinical and animal studies. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  5. Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

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    Nguyen, Khanh; Jack, Kerri; Sun, Weijing

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC. PMID:28933381

  6. Hepatocellular Carcinoma: Past and Future of Molecular Target Therapy

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    Khanh Nguyen

    2015-12-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common causes of cancer related mortality worldwide. The incidence of HCC has been increasing annually. Viral infection, alcohol usage, and other causes of cirrhosis have been identified as major risk factors for HCC development. The underlying pathogenesis has not been as well defined. There have been multiple hypotheses to the specific mechanisms of hepatocarcinogenesis and they share the common theme of chronic inflammation, increase oxidative stress, and genomic alteration. Therapeutic options of HCC have been primarily local and/or regional including transplantation, resection, and radial frequency ablation, chemoembolization or radio-embolization. For unresectable or metastatic disease, the options are limited. Conventional chemotherapeutic options have been noted to have limited benefit. Sorafenib has been the one and only systemic therapy which has demonstrated modest overall survival benefit. This has led to more extensive research with focus on targeted therapy. Numerous pre-clinical and early phase clinical studies have been noted but failed to show efficacy in later phase clinical trials. In an effort to identify new potential therapeutic options, new understanding of underlying pathways to hepatocarcinogenesis should be one of the main focuses. This leads to development of more molecularly targeted agents to specific pathways, and immunotherapy. This article provides a review of major studies of molecular targeted agents which attempts to target these specific pathways in HCC.

  7. ANGIOGENESIS INHIBITORS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

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    Massimiliano Berretta

    2016-11-01

    Full Text Available Background: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC patients. The achievement of Sorafenib in prolonging overall survival of patients with HCC makes therapeutic inhibition of angiogenesis a fundamental element of the treatment of HCC. Considering the heterogeneous aspects of HCC and to enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, the combination of antiangiogenic drugs with antiblastic chemotherapy (AC, radiotherapy or other targeted drugs have been evaluated. The issue is further complicated by the combination of antiangiogenesis with other AC or biologic drugs. To date, there is no planned approach to determine which patients are more responsive to a given type of antiangiogenic treatment. Conclusion: Large investments in the clinical research are essential to improve treatment response and minimize toxicities for patients with HCC. Future investigations will need to focus on utilizing patterns of genetic information to classify HCC into groups that display similar prognosis and treatment sensitivity, and combining targeted therapies with AC producing enhanced anti-tumor effect. In this review the current panel of available antiangiogenic therapies for the treatment of HCC have been analyzed. In addition current clinical trials are also reported herein.

  8. Local Anesthetics Inhibit the Growth of Human Hepatocellular Carcinoma Cells.

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    Le Gac, Grégoire; Angenard, Gaëlle; Clément, Bruno; Laviolle, Bruno; Coulouarn, Cédric; Beloeil, Hélène

    2017-11-01

    Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapeutic options. Retrospective studies have shown that the administration of local anesthetics (LAs) during cancer surgery could reduce cancer recurrence. Besides, experimental studies reported that LAs could inhibit the growth of cancer cells. Thus, the purpose of this study was to investigate the effects of LAs on human HCC cells. The effects of 2 LAs (lidocaine and ropivacaine) (10 to 10 M) were studied after an incubation of 48 hours on 2 HCC cell lines, namely HuH7 and HepaRG. Cell viability, cell cycle analysis, and apoptosis and senescence tests were performed together with unsupervised genome-wide expression profiling and quantitative real-time polymerase chain reaction for relevant genes. We showed that LAs decreased viability and proliferation of HuH7 cells (from 92% [P lidocaine) and HepaRG progenitor cells (from 58% at 5 × 10 M [P lidocaine and 59% [P Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/β-catenin pathway. Both LAs increased apoptosis in Huh7 and HepaRG progenitor cells (P < .01). The data demonstrate that LAs induced profound modifications in gene expression profiles of tumor cells, including modulations in the expression of cell cycle-related genes that result in a cytostatic effect and induction of apoptosis.

  9. Microsatellite instability and p53 mutations in hepatocellular carcinoma.

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    Karachristos, A; Liloglou, T; Field, J K; Deligiorgi, E; Kouskouni, E; Spandidos, D A

    1999-01-01

    We have studied 27 hepatocellular carcinomas (HCCs) to identify possible relationships between microsatellite instability (MSI), p53 mutations, and HBV infection in hepatocarcinogenesis. MSI was assessed using 19 polymorphic markers and the poly(A) tract BAT-26. All coding regions of p53 were examined for mutations. Tumors were also examined for presence of hepatitis B virus (HBV) DNA sequences; 66.6% of the samples exhibit MSI in at least one microsatellite locus and 44% in two or three loci. None of the tumors examined showed alterations in BAT-26. Moreover, 73.3% of samples with indication of HBV infection showed instability in at least one marker. No association between MSI and pathological profile was found. Five (18.5%) samples harbored mutations in p53, three missense, and two insertions, all in exons 5 and 8 not previously reported. No mutations were detected in codon 249, which has been linked with dietary intake of aflatoxins. Our results support the hypothesis that HCC is a "low" MSI tumor. Only 1/5 samples with MSI in more than two markers harbored a mutation in p53. Although the number of samples is too small to support a statistical significance, this finding may indicate an inverse relationship between p53 mutations and MSI in HCC.

  10. A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma.

    Science.gov (United States)

    Luo, Zai-Li; Cheng, Shu-Qun; Shi, Jie; Zhang, Hui-Lu; Zhang, Cun-Zhen; Chen, Hai-Yang; Qiu, Bi-Jun; Tang, Liang; Hu, Cong-Li; Wang, Hong-Yang; Li, Zhong

    2015-10-07

    Merlin, which is encoded by the tumour suppressor gene Nf2, plays a crucial role in tumorigenesis and metastasis. However, little is known about the functional importance of Merlin splicing forms. In this study, we show that Merlin is present at low levels in human hepatocellular carcinoma (HCC), particularly in metastatic tumours, where it is associated with a poor prognosis. Surprisingly, a splicing variant of Merlin that lacks exons 2, 3 and 4 ((Δ2-4)Merlin) is amplified in HCC and portal vein tumour thrombus (PVTT) specimens and in the CSQT2 cell line derived from PVTT. Our studies show that (Δ2-4)Merlin interferes with the capacity of wild-type Merlin to bind β-catenin and ERM, and it is expressed in the cytoplasm rather than at the cell surface. Furthermore, (Δ2-4)Merlin overexpression increases the expression levels of β-catenin and stemness-related genes, induces the epithelium-mesenchymal-transition phenotype promoting cell migration in vitro and the formation of lung metastasis in vivo. Our results indicate that the (Δ2-4)Merlin variant disrupts the normal function of Merlin and promotes tumour metastasis.

  11. Radiofrequency Ablation of Hepatocellular Carcinoma: A Literature Review

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    Yasunori Minami

    2011-01-01

    Full Text Available Radiofrequency ablation (RFA of liver cancers can be performed safely using percutaneous, laparoscopic, or open surgical techniques, and much of the impetus for the use of RFA has come from cohort series that have provided an evidence base for this technique. Here, we give an overview of the current status of radiofrequency ablation (RFA for hepatocellular carcinoma (HCC, including its physical properties, to assess the characteristics that make this technique applicable in clinical practice. We review the technical development of probe design and summarize current indications and outcomes of reported clinical use. An accurate evaluation of treatment response is very important to secure successful RFA therapy since a sufficient safety margin (at least 0.5 cm can prevent local tumor recurrences. We also provide a profile of side effects and information on the integration of this technique into the general management of patients with HCC. To minimize complications of RFA, physicians should be familiar with each feature of complication. Appropriate management of complications is essential for successful RFA treatment. Moreover, adjuvant therapy, such as molecular targeted therapies following curative therapy, is expected to further improve survival after RFA.

  12. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

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    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    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 resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC.

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

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    Wachsmann, Jason; Peng, Fangyu

    2016-01-07

    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 other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.

  14. Targeting hepatocellular carcinoma: what did we discover so far?

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    Ana Filipa Brito

    2016-10-01

    Full Text Available Hepatocellular carcinoma (HCC is increasingly considered an issue of global importance. Its rates of incidence and mortality have been markedly increasing over the last decades. Among risk factors, some should be highlighted, namely the infections by hepatitis B and C virus, as well as clinical cases of cirrhosis. HCC is characterized as asymptomatic disease in the initial stages which most often leads to a late diagnosis. At molecular and genetic level HCC represents a highly complex tumor entity, including a wide variety of mutations, thus accounting for different mechanisms of resistance towards therapeutic approaches. In particular, mutations of the TP53 gene, as well as a deregulation between the expression of pro- and anti-apoptotic proteins of the BCL-2 family are observed. Regarding treatment modalities, surgical procedures offer the best chance of cure, however, due to a late diagnosis, most of concerned patients cannot be subjected to them. Chemotherapy and radiotherapy are also ineffective, and currently, the treatment with sorafenib is the most commonly used systemic therapy although it can only increase the patient survival for some months. In this sense, a quick and accurate investigation is of utmost importance in order to develop ways of early diagnosis as well as new therapies for HCC.

  15. Oncogene dependent requirement of fatty acid synthase in hepatocellular carcinoma.

    Science.gov (United States)

    Che, Li; Pilo, Maria G; Cigliano, Antonio; Latte, Gavinella; Simile, Maria M; Ribback, Silvia; Dombrowski, Frank; Evert, Matthias; Chen, Xin; Calvisi, Diego F

    2017-03-19

    Hepatocellular carcinoma (HCC), the most frequent primary tumor of the liver, is an aggressive cancer type with limited treatment options. Cumulating evidence underlines a crucial role of aberrant lipid biosynthesis (a process known as de novo lipogenesis) along carcinogenesis. Previous studies showed that suppression of fatty acid synthase (FASN), the major enzyme responsible for de novo lipogenesis, is highly detrimental for the in vitro growth of HCC cell lines. To assess whether de novo lipogenesis is required for liver carcinogenesis, we have generated various mouse models of liver cancer by stably overexpressing candidate oncogenes in the mouse liver via hydrodynamic gene delivery. We found that overexpression of FASN in the mouse liver is unable to malignantly transform hepatocytes. However, genetic deletion of FASN totally suppresses hepatocarcinogenesis driven by AKT and AKT/c-Met protooncogenes in mice. On the other hand, liver tumor development is completely unaffected by FASN depletion in mice co-expressing β-catenin and c-Met. Our data indicate that tumors might be either addicted to or independent from de novo lipogenesis for their growth depending on the oncogenes involved. Additional investigation is required to unravel the molecular mechanisms whereby some oncogenes render cancer cells resistant to inhibition of de novo lipogenesis.

  16. Hepatitis B and C Viruses and Hepatocellular Carcinoma

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    Birke Bartosch

    2010-07-01

    Full Text Available Chronic liver disease is responsible for over 1.4 million deaths annually  [1] and is characterized by permanent inflammatory processes that predispose to liver cancer and in particular hepatocellular carcinoma (HCC. In healthy liver, inflammatory processes stimulate growth and repair and restore normal liver architecture. However, if liver inflammation becomes chronic, the balance of damage versus regeneration in the liver is disrupted and can lead to the formation of excessive scar tissue, termed fibrosis. In the long-term, an exacerbation of fibrosis will lead to cirrhosis, which is characterized by abnormal liver architecture and function and is associated with a significant reduction in overall health and wellbeing. At cirrhotic stages, liver damage is often irreversible or difficult to treat. Cirrhosis leads frequently to death from liver failure or to HCC (Figure 1. Indeed, HCC is the first cause of death in cirrhotic patients [2], and is a tumor with poor prognosis, ranking third in terms of death by cancer. Furthermore, it is the fifth most prevalent cancer worldwide, with 800,000 new cases per year in the world [2,3]. [...

  17. Diagnosis and treatment of hepatocellular carcinoma: An update

    Science.gov (United States)

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

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium “washout” in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion’s stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib. PMID:25848464

  18. Prognostic significance of XRCC4 expression in hepatocellular carcinoma

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    Huang, Xiao-Ying; Yao, Jin-Guang; Wang, Chao; Wei, Zhong-Hong; Ma, Yun; Wu, Xue-Min; Luo, Chun-Ying; Xia, Qiang; Long, Xi-Dai

    2017-01-01

    Background Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. Materials and Methods We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50). Results XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin. Conclusions These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma. PMID:29152133

  19. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

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    Claire Faltermeier

    2015-09-01

    Full Text Available Hepatocellular carcinoma (HCC, the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.

  20. Transcatheter Arterial Chemoembolization Based on Hepatic Hemodynamics for Hepatocellular Carcinoma

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    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. Circulating AIM Prevents Hepatocellular Carcinoma through Complement Activation

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    Natsumi Maehara

    2014-10-01

    Full Text Available Hepatocellular carcinoma (HCC is a widespread fatal disease and the third most common cause of cancer deaths. Here, we show the potent anti-HCC effect of the circulating protein AIM. As in adipocytes, AIM is incorporated into normal hepatocytes, where it interferes with lipid storage. In contrast, AIM accumulates on the HCC cell surface and activates the complement cascade via inactivating multiple regulators of complement activation. This response provokes necrotic cell death specifically in AIM-bound HCC cells. Accordingly, AIM−/− mice were highly susceptible to steatosis-associated HCC development, whereas no AIM+/+ mouse developed the disease despite comparable liver inflammation and fibrosis in response to a long-term high-fat diet. Administration of AIM prevented tumor development in AIM−/− mice, and HCC induction by diethylnitrosamine was more prominent in AIM−/− than wild-type mice. These findings could be the basis for novel AIM-based therapeutic strategies for HCC.

  2. Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.

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    Yu-Chi Su

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.

  3. Radiotherapy for hepatocellular carcinoma. Regarding solitary tumor on radiologic examinations

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    Kawashima, Mitsuhiko; Tokuuye, Koichi; Sumi, Minako; Kagami, Yashikazu; Murayama, Shigeyuki; Nakayama, Hidetsugu; Imai, Atsushi; Ando, Kou; Ikeda, Hiroshi [National Cancer Center, Tokyo (Japan)

    1997-09-01

    To evaluate the effect of radiotherapy (RT) on hepatocellular carcinoma (HCC) that appears as a solitary nodule on radiologic studies. We irradiated 17 patients with solitary HCC lesions (25-150 mm in diameter) with approximately 60 Gy (range 50-70 Gy). Patients underwent dynamic CT and/or ultrasound imaging at 3-month intervals after treatment. Patients were classified based on lesion size, degree of cirrhosis (Child A. 6; Child B, 6; Child C, 5), and whether they had received other therapy such as transarterial chemoembolization (TACE). The responses were classified as complete, partial, no change, or progression. The median survival was 12.8 months for all 17 patients, with 1-, 2-, and 3-year cumulative survival rates of 59%, 35% and 24%, respectively. Patients classified as Child A showed significantly longer survival than those classified as either Child B (p<0.04) or C (p<0.01). Four of the five Child C patients died of liver failure within 6 months after RT despite the absence of tumor recurrence. The initial tumor diameter, concurrent treatment with TACE, and radiation dose showed no significant effect on survival. Survival in patients with solitary HCC lesions appears to be affected mainly by the degree of liver dysfunction, and not the initial tumor diameter, radiation dose, or concurrent use of TACE. (author)

  4. MicroRNA-429 Modulates Hepatocellular Carcinoma Prognosis and Tumorigenesis

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    Xiao-Ying Huang

    2013-01-01

    Full Text Available MicroRNA-429 (miR-429 may modify the development and progression of cancers; however, the role of this microRNA in the hepatocellular carcinoma (HCC has not been well elaborated. Here, we tested miR-429 expression in 138 pathology-diagnosed HCC cases and SMMC-7721 cells. We found that miR-429 was upregulated in HCC tumor tissues and that the high expression of miR-429 was significantly correlated with larger tumor size (odd ratio (OR, 2.70; 95% confidence interval (CI, 1.28–5.56 and higher aflatoxin B1-DNA adducts (OR = 3.13, 95% CI = 1.47–6.67. Furthermore, this microRNA overexpression modified the recurrence-free survival and overall survival of HCC patients. Functionally, miR-429 overexpression progressed tumor cells proliferation and inhibited cell apoptosis. These results indicate for the first time that miR-429 may modify HCC prognosis and tumorigenesis and may be a potential tumor therapeutic target.

  5. Silymarin nanoemulsion against human hepatocellular carcinoma: development and optimization.

    Science.gov (United States)

    Ahmad, Usama; Akhtar, Juber; Singh, Satya Prakash; Ahmad, Farhan Jalees; Siddiqui, Sahabjada

    2018-03-01

    Nanoemulsion of silymarin was developed and optimized. Nanoemulsion was made by aqueous titration method. Sefsol 218 (5.8% v/v), Kolliphor RH40 and polyethylene glycol 400 (Smix; 2:1; 28.99% v/v) were used as oil phase, surfactant and co-surfactant while distilled water (65.22% v/v) acted as an aqueous phase. Nanoemulsion was characterized on the basis of particle size, viscosity, electrical conductivity and refractive index. Further, in vitro release, in vivo pharmacokinetic study, stability study and cancer cell line studies were also performed. The optimized formulation (NE9) with mean particle size of 21.24 nm showed a minimum viscosity of 9.59 cps, maximum drug release (97.75%) in 24 h. The NE9 formulation also showed higher AUC (p  .05). The cancer cell line studies also confirmed that silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation (p nanoemulsion may be an efficient carrier for oral delivery of silymarin against human hepatocellular carcinoma without damaging normal cells.

  6. The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

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    Cioca, Andreea; Ceausu, Amalia R.; Marin, Irina; Raica, Marius; Cimpean, Anca Maria

    2017-01-01

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation. PMID:28348421

  7. Surveillance for Hepatocellular Carcinoma in Patients with NASH

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    Philippe Kolly

    2016-06-01

    Full Text Available European and American guidelines recommend surveillance for hepatocellular carcinoma (HCC by performing ultrasonography on a six-month basis on an at risk population, defined by presence of cirrhosis. HCC, due to non-alcoholic steatohepatitis (NASH, is rising. Patients with NASH have a high risk of developing HCC and, therefore, have to be enrolled in a screening program. One of the challenges with NASH-induced HCC is that half of the cases arise in non-cirrhotic patients. There is a need to identify those patients in order to screen them for HCC. The obesity of these patients is another challenge, it makes ultrasound screening more difficult. Other radiological methods, such as computer tomography (CT scans or magnetic resonance imaging (MRI, are available, but the surveillance program would no longer be cost-effective. There is a need to prospectively acquire information on cohorts of patients with NASH in order to improve the tools we have to diagnose early tumors in these patients.

  8. Treatment allocation in hepatocellular carcinoma: Assessment of the BCLC algorithm.

    Science.gov (United States)

    Richani, Mandy; Kolly, Philippe; Knoepfli, Marina; Herrmann, Evelyn; Zweifel, Martin; von Tengg-Kobligk, Hendrik; Candinas, Daniel; Dufour, Jean-François

    2016-01-01

    The Barcelona Clinic Liver Cancer (BCLC) staging system is the algorithm most widely used to manage patients with hepatocellular carcinoma (HCC). We aimed to investigate the extent to which the BCLC recommendations effectively guide clinical practice and assess the reasons for any deviation from the recommendations. The first-line treatments assigned to patients included in the prospective Bern HCC cohort were analyzed. Among 223 patients included in the cohort, 116 were not treated according to the BCLC algorithm. Eighty percent of the patients in BCLC stage 0 (very early HCC) and 60% of the patients in BCLC stage A (early HCC) received recommended curative treatment. Only 29% of the BCLC stage B patients (intermediate HCC) and 33% of the BCLC stage C patients (advanced HCC) were treated according to the algorithm. Eighty-nine percent of the BCLC stage D patients (terminal HCC) were treated with best supportive care, as recommended. In 98 patients (44%) the performance status was disregarded in the stage assignment. The management of HCC in clinical practice frequently deviates from the BCLC recommendations. Most of the curative therapy options, which have well-defined selection criteria, were allocated according to the recommendations, while the majority of the palliative therapy options were assigned to patients with tumor stages not aligned with the recommendations. The only parameter which is subjective in the algorithm, the performance status, is also the least respected.

  9. Surveillance for Hepatocellular Carcinoma in Patients with NASH.

    Science.gov (United States)

    Kolly, Philippe; Dufour, Jean-François

    2016-06-07

    European and American guidelines recommend surveillance for hepatocellular carcinoma (HCC) by performing ultrasonography on a six-month basis on an at risk population, defined by presence of cirrhosis. HCC, due to non-alcoholic steatohepatitis (NASH), is rising. Patients with NASH have a high risk of developing HCC and, therefore, have to be enrolled in a screening program. One of the challenges with NASH-induced HCC is that half of the cases arise in non-cirrhotic patients. There is a need to identify those patients in order to screen them for HCC. The obesity of these patients is another challenge, it makes ultrasound screening more difficult. Other radiological methods, such as computer tomography (CT) scans or magnetic resonance imaging (MRI), are available, but the surveillance program would no longer be cost-effective. There is a need to prospectively acquire information on cohorts of patients with NASH in order to improve the tools we have to diagnose early tumors in these patients.

  10. Integrated Multiple "-omics" Data Reveal Subtypes of Hepatocellular Carcinoma.

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    Gang Liu

    Full Text Available Hepatocellular carcinoma is one of the most heterogeneous cancers, as reflected by its multiple grades and difficulty to subtype. In this study, we integrated copy number variation, DNA methylation, mRNA, and miRNA data with the developed "cluster of cluster" method and classified 256 HCC samples from TCGA (The Cancer Genome Atlas into five major subgroups (S1-S5. We observed that this classification was associated with specific mutations and protein expression, and we detected that each subgroup had distinct molecular signatures. The subclasses were associated not only with survival but also with clinical observations. S1 was characterized by bulk amplification on 8q24, TP53 mutation, low lipid metabolism, highly expressed onco-proteins, attenuated tumor suppressor proteins and a worse survival rate. S2 and S3 were characterized by telomere hypomethylation and a low expression of TERT and DNMT1/3B. Compared to S2, S3 was associated with less copy number variation and some good prognosis biomarkers, including CRP and CYP2E1. In contrast, the mutation rate of CTNNB1 was higher in S3. S4 was associated with bulk amplification and various molecular characteristics at different biological levels. In summary, we classified the HCC samples into five subgroups using multiple "-omics" data. Each subgroup had a distinct survival rate and molecular signature, which may provide information about the pathogenesis of subtypes in HCC.

  11. Long Noncoding RNAs as a Key Player in Hepatocellular Carcinoma

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    Mehra, Mrigaya; Chauhan, Ranjit

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major malignancy in the liver and has emerged as one of the main cancers in the world with a high mortality rate. However, the molecular mechanisms of HCC are still poorly understood. Long noncoding RNAs (lncRNAs) have recently come to the forefront as functional non–protein-coding RNAs that are involved in a variety of cellular processes ranging from maintaining the structural integrity of chromosomes to gene expression regulation in a spatiotemporal manner. Many recent studies have reported the involvement of lncRNAs in HCC which has led to a better understanding of the underlying molecular mechanisms operating in HCC. Long noncoding RNAs have been shown to regulate development and progression of HCC, and thus, lncRNAs have both diagnostic and therapeutic potentials. In this review, we present an overview of the lncRNAs involved in different stages of HCC and their potential in clinical applications which have been studied so far. PMID:29147078

  12. Preoperative assessment of microvascular invasion in hepatocellular carcinoma

    Science.gov (United States)

    Chakraborty, Jayasree; Zheng, Jian; Gönen, Mithat; Jarnagin, William R.; DeMatteo, Ronald P.; Do, Richard K. G.; Simpson, Amber L.

    2017-03-01

    Hepatocellular carcinoma (HCC) is the most common liver cancer and the third leading cause of cancer-related death worldwide.1 Resection or liver transplantation may be curative in patients with early-stage HCC but early recurrence is common.2, 3 Microvascular invasion (MVI) is one of the most important predictors of early recurrence.3 The identification of MVI prior to surgery would optimally select patients for potentially curative resection or liver transplant. However, MVI can only be diagnosed by microscopic assessment of the resected tumor. The aim of the present study is to apply CT-based texture analysis to identify pre-operative imaging predictors of MVI in patients with HCC. Texture features are derived from CT and analyzed individually as well as in combination, to evaluate their ability to predict MVI. A two-stage classification is employed: HCC tumors are automatically categorized into uniform or heterogenous groups followed by classification into the presence or absence of MVI. We achieve an area under the receiver operating characteristic curve (AUC) of 0.76 and accuracy of 76.7% for uniform lesions and AUC of 0.79 and accuracy of 74.06% for heterogeneous tumors. These results suggest that MVI can be accurately and objectively predicted from preoperative CT scans.

  13. Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death.

    Science.gov (United States)

    Li, Sainan; Li, Jingjing; Dai, Weiqi; Zhang, Qinghui; Feng, Jiao; Wu, Liwei; Liu, Tong; Yu, Qiang; Xu, Shizan; Wang, Wenwen; Lu, Xiya; Chen, Kan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Fan, Xiaoming; Mo, Wenhui; Xu, Ling; Guo, Chuanyong

    2017-11-07

    Genistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear. Cell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation. Lentivirus-expressed glucose transporter 1 (GLUT1) or/and hexokinase 2 (HK2) and siRNA of HIF-1α were used to test the direct target of genistein. Subcutaneous xenograft mouse models were used to measure in vivo efficacy of genistein and its combination with sorafenib. Genistein inhibited aerobic glycolysis and induced mitochondrial apoptosis in HCC cells. Neither inhibitors nor overexpression of HK2 or GLUTs enhance or alleviate this effect. Although stabiliser of HIF-1α reversed the effect of genistein, genistein no longer has effects on HIF-1α siRNA knockdown HCC cells. In addition, genistein enhanced the antitumour effect of sorafenib in sorafenib-resistant HCC cells and HCC-bearing mice. Genistein sensitised aerobic glycolytic HCC cells to apoptosis by directly downregulating HIF-1α, therefore inactivating GLUT1 and HK2 to suppress aerobic glycolysis. The inhibitory effect of genistein on tumour cell growth and glycolysis may help identify effective treatments for HCC patients at advanced stages.

  14. Recurrent AAV2-related insertional mutagenesis in human hepatocellular carcinomas.

    Science.gov (United States)

    Nault, Jean-Charles; Datta, Shalini; Imbeaud, Sandrine; Franconi, Andrea; Mallet, Maxime; Couchy, Gabrielle; Letouzé, Eric; Pilati, Camilla; Verret, Benjamin; Blanc, Jean-Frédéric; Balabaud, Charles; Calderaro, Julien; Laurent, Alexis; Letexier, Mélanie; Bioulac-Sage, Paulette; Calvo, Fabien; Zucman-Rossi, Jessica

    2015-10-01

    Hepatocellular carcinomas (HCCs) are liver tumors related to various etiologies, including alcohol intake and infection with hepatitis B (HBV) or C (HCV) virus. Additional risk factors remain to be identified, particularly in patients who develop HCC without cirrhosis. We found clonal integration of adeno-associated virus type 2 (AAV2) in 11 of 193 HCCs. These AAV2 integrations occurred in known cancer driver genes, namely CCNA2 (cyclin A2; four cases), TERT (telomerase reverse transcriptase; one case), CCNE1 (cyclin E1; three cases), TNFSF10 (tumor necrosis factor superfamily member 10; two cases) and KMT2B (lysine-specific methyltransferase 2B; one case), leading to overexpression of the target genes. Tumors with viral integration mainly developed in non-cirrhotic liver (9 of 11 cases) and without known risk factors (6 of 11 cases), suggesting a pathogenic role for AAV2 in these patients. In conclusion, AAV2 is a DNA virus associated with oncogenic insertional mutagenesis in human HCC.

  15. Hepatitis B Virus Infection, Genetic Susceptibility and Hepatocellular Carcinoma

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    Juan Wen

    2015-12-01

    Full Text Available Liver cancer is a sever cancer burden in the world, especially in developing countries. Its late diagnosis and high mortality rate urges early prediction. Hepatocellular carcinoma (HCC is the major histopathological type of liver cancer. Chronic infection with hepatitis B virus (HBV is a well-established risk factor for HCC. On one side, HBV sequence variation may influence the outcome of HBV infection and the development of HCC. At least ten HBV genotypes (A to J are identified. Several HBV genotypes and mutations in pre-S and pre-core/core promoter regions are closely associated with HCC pathogenesis, and have been regarded as biomarkers to predict the occurrence of HCC. On the other side, only a small fraction of chronic hepatitis B patients developed HCC, and some HCC cases were diagnosed with no known predisposing risk factors, suggesting host genetic variations may also play important roles in the carcinogenesis. In this review, we summarized current findings of HBV genotypes and mutations, host genetic variations and their interactions involved in HCC carcinogenesis. Understanding the key viral and host genetic variations is essential for generating effective predictive biomarkers for HCC development.

  16. Family history influences the early onset of hepatocellular carcinoma.

    Science.gov (United States)

    Park, Chung-Hwa; Jeong, Seung-Hee; Yim, Hyeon-Woo; Kim, Jin Dong; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    2012-06-07

    To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients. We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008, whose family history of primary liver cancer was clearly described in the medical records. Of the 2242 patients, 165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not. The male to female ratio was 3.6:1, and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%, chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%. The median ages at diagnosis in the positive- and negative-history groups were 52 years (range: 29-79 years) and 57 years (range: 18-89 years), respectively (P population (P = 0.0028). More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.

  17. Yttrium 90 microspheres for the treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Memon, Khairuddin; Lewandowski, Robert J; Riaz, Ahsun; Salem, Riad

    2013-01-01

    Yttrium-90 microspheres are radioactive particles which are increasingly being employed for treating patients with unresectable hepatocellular carcinoma (HCC). The procedure is called radioembolization. It involves the injection of micron-sized embolic particles loaded with a radioisotope by use of transarterial techniques. Because of the sensitivity of liver parenchyma and relative insensitivity of tumor, external radiation has played a limited role in treating HCC. (90)Y administered via arterial route directs the highly concentrated radiation to the tumor while healthy liver parenchyma is relatively spared due to its preferential blood supply from portal venous blood. This technique has proven useful for the majority of patients with HCC as most of them present in advanced stage, beyond potentially curative options (resection/liver transplantation). (90)Y microspheres can be used in downstaging large tumors to bring within transplantable criteria, in patients with portal venous thrombosis due to tumor invasion and as palliative therapy. There are two available devices for (90)Y administration; TheraSphere® (glass based) and SIR-Spheres® (resin based). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, GI ulcers, and vascular injury; however, these can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article explores the technical and clinical aspects of (90)Y radioembolization with keeping emphasis on patient selection, uses, and complications.

  18. Improving clinical trial design for hepatocellular carcinoma treatments

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    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.

  19. Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

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    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.

  20. Genome-wide identification of RNA editing in hepatocellular carcinoma.

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    Kang, Lin; Liu, Xiaoqiao; Gong, Zhoulin; Zheng, Hancheng; Wang, Jun; Li, Yingrui; Yang, Huanming; Hardwick, James; Dai, Hongyue; Poon, Ronnie T P; Lee, Nikki P; Mao, Mao; Peng, Zhiyu; Chen, Ronghua

    2015-02-01

    We did whole-transcriptome sequencing and whole-genome sequencing on nine pairs of Hepatocellular carcinoma (HCC) tumors and matched adjacent tissues to identify RNA editing events. We identified mean 26,982 editing sites with mean 89.5% canonical A→G edits in each sample using an improved bioinformatics pipeline. The editing rate was significantly higher in tumors than adjacent normal tissues. Comparing the difference between tumor and normal tissues of each patient, we found 7 non-synonymous tissue specific editing events including 4 tumor-specific edits and 3 normal-specific edits in the coding region, as well as 292 edits varying in editing degree. The significant expression changes of 150 genes associated with RNA editing were found in tumors, with 3 of the 4 most significant genes being cancer related. Our results show that editing might be related to higher gene expression. These findings indicate that RNA editing modification may play an important role in the development of HCC. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

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    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.

  2. Lactate Dehydrogenase in Hepatocellular Carcinoma: Something Old, Something New

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    Luca Faloppi

    2016-01-01

    Full Text Available 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.

  3. Effects of AFP gene silencing on apoptosis and proliferation of a hepatocellular carcinoma cell line.

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    Zhang, Ling; He, Tao; Cui, Hong; Wang, Yunjian; Huang, Changshan; Han, Feng

    2012-08-01

    Alpha fetoprotein (AFP) is an oncoembryonal protein that is highly expressed in the majority of hepatocellular carcinomas. Previous studies have shown that AFP may be involved in multiple cell growth regulating, differentiating, and immunosuppressive activities. We investigated the effects of AFP gene silencing by siRNA on apoptosis and proliferation of hepatocellular carcinoma cell line EGHC-9901, which highly expresses AFP and may serve as an ideal model for investigation of AFP functions. siRNA expressing plasmid targeting the AFP gene was first established and subsequently transfected into hepatocellular carcinoma cell line EGHC-9901; cells were then divided into three groups: siRNA-afp, transfected with AFP-siRNA; siRNA-beta-actin, transfected with siRNA-beta-actin as the positive group; and vector control, transfected with empty vector as the blank control group. After G418 positive clone selection for a couple of weeks, Western blot and RT (reverse transcription)-PCR assay demonstrated that AFP expression was almost completely inhibited by siRNA-afp, which indicates that siRNA expressing plasmid targeting the AFP gene has been successfully established. Furthermore, MTT (methyl thiazolyl tetrazelium) assay showed that cells transfected with siRNA-afp proliferated at a significantly lower speed than the other two groups and flat plate clone formation assay also witnessed less clones with diameters of more than 75 μm in siRNA-afp immunofluorescence indicating that the apoptosis rate of cells transfected with siRNA-afp was significantly higher than the other two groups. Furthermore, flow cytometry manifested approximately 20% more cells of siRNA-afp within G1 phase than those of the negative group, indicating that inhibition of AFP expression may cause G1 phase arrest. Finally, Western blot and RT-PCR assay demonstrated that siRNA-afp induced a higher expression of caspase-3 than the other two groups whereas there was no difference in expression of caspase-8

  4. Radiation recall dermatitis triggered by sorafenib after radiation therapy for hepatocellular carcinoma

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    Kim, Gwi Eon; Song, Hee-Sung; Ahn, Ki Jung; Kim, Young Suk

    2017-01-01

    Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention. PMID:29037022

  5. Radiation recall dermatitis triggered by sorafenib after radiation therapy for hepatocellular carcinoma

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    Kim, Gwi Eon; Song, Hee Sung; Kim, Young Suk [Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of); Ahn, Ki Jung [Dept. of Radiation Oncology, Inje University Busan Paik Hospital, Inje University of Medicine, Busan (Korea, Republic of)

    2017-09-15

    Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention.

  6. CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation.

    Science.gov (United States)

    Hao, Xue-Jia; Li, Jin-Ping; Jiang, Hui-Jie; Li, Da-Qing; Ling, Zai-Sheng; Xue, Li-Ming; Feng, Guang-Long

    2013-12-01

    Assessment of tumor response after argon-helium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma. This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion. The control group comprised 40 volunteers without liver disease. The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation. Computed tomography perfusion parameters were measured: hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. After treatment, in the tumor foci, permeability of capillary vessel surface was higher, and hepatic blood flow, hepatic blood volume, hepatic arterial fraction, and hepatic arterial perfusion values were lower (P0.05). Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.

  7. An overview of loco-regional treatments in patients and mouse models for hepatocellular carcinoma.

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Palaia, Raffaele; Leongito, Maddalena; Albino, Vittorio; Piccirillo, Mauro; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Hepatocellular carcinoma is a highly aggressive malignancy and is the third leading cause of cancer-related deaths worldwide. Although surgery is currently considered the most effective curative treatment for this type of cancer, it is note that most of patients have a poor prognosis due to chemioresistence and tumor recurrence. Loco-regional therapies, including radiofrequency ablation, surgical resection and transcatheter arterial chemoembolization play a major role in the clinical management of hepatocellular carcinoma. In order to improve the treatment outcome of patients diagnosed with this disease, several in vivo studies by using different techniques on cancer mouse models have been performed. This review will focus on the latest papers on the efficacy of loco-regional therapy and combined treatments in patients and mouse models of hepatocellular carcinoma.

  8. Promising Urinary Protein Biomarkers for the Early Detection of Hepatocellular Carcinoma among High-Risk Hepatitis C Virus Egyptian Patients

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    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%.

  9. An atypical age-specific pattern of hepatocellular carcinoma in Peru: a threat for Andean populations.

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    Stéphane Bertani

    Full Text Available BACKGROUND: In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country. METHODS: A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin. RESULTS: Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics. CONCLUSIONS: The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

  10. Higher Bilirubin Levels of Healthy Living Liver Donors Are Associated With Lower Posttransplant Hepatocellular Carcinoma Recurrence.

    Science.gov (United States)

    Han, Sangbin; Yang, Ju Dong; Sinn, Dong Hyun; Ko, Justin Sangwook; Kim, Jong Man; Shin, Jun Chul; Son, Hee Jeong; Gwak, Mi Sook; Joh, Jae-Won; Kim, Gaab Soo

    2016-09-01

    Serum bilirubin level, which may reflect the host defense against increased oxidative stress, is inversely associated with the risk of cancer development. In liver transplantation, the intrinsic bilirubin metabolism of donor liver is subsequently translated into recipient. Thus, we hypothesized that liver transplantation conducted with living donors with higher serum bilirubin reduces hepatocellular carcinoma (HCC) recurrence. Two hundred fifty recipients who underwent liver transplantation for treating HCC within the Milan criteria were included in the study. The association between donor preoperative total bilirubin concentration and the risk of HCC recurrence was analyzed using the Fine and Gray regression model with posttransplant death as a competing risk event with adjustment for tumor biology including α-fetoprotein, histological differentiation, and microvascular invasion. All donors were confirmed to have no underlying hepatobiliary diseases or hematological disorders. Donor preoperative total bilirubin concentration was 0.7 mg/dL in median and ranged from 0.2 to 2.7 mg/dL. Thirty-five (14.0%) recipients developed HCC recurrence. Multivariable analysis demonstrated that donor preoperative total bilirubin concentration was inversely associated with the recurrence risk (hazard ratio, 0.22; 95% confidence interval, 0.07-0.72; P = 0.013). The highest (≥1.0 mg/dL) versus lowest (≤0.6 mg/dL) tertile of donor preoperative total bilirubin showed a significant reduction of the recurrence risk (hazard ratio, 0.28; 95% confidence interval, 0.11-0.70; P = 0.006). Hepatocellular carcinoma recurrence risk decreases in relation to the increase in total serum bilirubin level of healthy living donors without underlying hepatobiliary or hematological disorders. Further validation of bilirubin as a potent anticancer substance against HCC is warranted.

  11. Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

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    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  12. A clinical perspective of the link between metabolic syndrome and hepatocellular carcinoma

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    Cauchy F

    2015-02-01

    Full Text Available François Cauchy, Jacques BelghitiHPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, FranceAbstract: Metabolic syndrome (MS, which is defined as a constellation of clinico-biological features closely related to insulin-resistance has reached epidemic levels in Western Europe and Northern America. Non-alcoholic fatty liver disease (NAFLD represents the hepatic manifestation of MS. As its incidence parallels that of MS, NAFLD is currently becoming one of the most frequent chronic liver diseases in Western countries. On one hand, MS favors the development of hepatocellular carcinoma (HCC either through NAFLD liver parenchymal alterations (steatosis; steatohepatitis; fibrosis, or in the absence of significant underlying liver parenchyma changes. In this setting, HCC are often diagnosed incidentally, tend to be larger than in patients developing HCC on cirrhosis and therefore frequently require major liver resections. On the other hand, MS patients are at increased risk of both liver-related postoperative complications and increased cardiorespiratory events leading to non-negligible mortality rates following liver surgery. These deleterious effects seem to be related to the existence of impaired liver function even in the absence of severe fibrosis but also higher cardiorespiratory sensitivity in a setting of MS/NAFLD. Hence, specific medical and surgical improvements in the perioperative management of these patients are required. These include complete preoperative cardiorespiratory work-up and the wide use of preoperative liver volume modulation. Finally, the long-term prognosis after curative surgery for MS-related HCC does not seem to be worse than for other HCC occurring on classical chronic liver diseases. This is probably related to less aggressive tumor behavior with lower micro vascular invasion and decreased rates of poorly differentiated lesions. In this setting, several medical therapies

  13. Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma

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    Tong Aiping

    2010-04-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. There is an urgent need to develop novel biomarkers for early diagnosis, as well as to identify new drug targets for therapeutic interventions. Patients and methods 54 paired HCC samples and 21 normal liver tissues were obtained from West China Hospital of Sichuan University. Informed consent was obtained from all the patients or their relatives prior to analysis, and the project was approved by the Institutional Ethics Committee of Sichuan University. Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC-based proteomics was employed to profile the differentially expressed proteins between a HepG2 human hepatoma cell line and an immortal hepatic cell line L02. Validation of PGAM1 expression was performed by semi-quantitative RT-PCR, immunoblot and immunohistochemistry using clinical samples. shRNA expressing plasmids specifically targeting PGAM1 were designed and constructed by GenePharma Corporation (Shanghai, China, and were utilized to silence expression of PGAM1 in vitro and in vivo. Cell proliferation was measured by a combination of colony formation assay and Ki67 staining. Apoptosis was examined by flow cytometry and TUNEL assay. Results A total of 63 dysregulated proteins were identified, including 51 up-regulated proteins, and 12 down-regulated proteins (over 2-fold, p p in vitro and in vivo. Conclusion Our studies suggested that PGAM1 plays an important role in hepatocarcinogenesis, and should be a potential diagnostic biomarker, as well as an attractive therapeutic target for hepatocellular carcinoma.

  14. Major liver resection for hepatocellular carcinoma in the morbidly obese: A proposed strategy to improve outcome

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    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.

  15. Hericium erinaceus enhances doxorubicin-induced apoptosis in human hepatocellular carcinoma cells.

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    Lee, Jong Seok; Hong, Eock Kee

    2010-11-28

    It has been demonstrated that the Hericium erinaceus (HE) mushroom, which primarily consists of polysaccharides, possesses anti-tumor activities. However, the mechanisms by which HE inhibits human hepatocellular carcinoma growth remain unknown. Our study demonstrates that HE acts as an enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this sensitization can be achieved by reducing c-FLIP expression via JNK activation and enhancing intracellular Dox accumulation via the inhibition of NF-κB activity. These findings suggest that HE in combination with Dox serves as an effective tool for treating drug-resistant human hepatocellular carcinoma. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Advanced Hepatocellular Carcinoma with Subtotal Occlusion of the Inferior Vena Cava and a Right Atrial Mass

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    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.

  17. Excessive Hepatic Arterial-portal Venous Shunting May Predict Failure of Microparticle Localization in Hepatocellular Carcinomas.

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    Tan, Andrew Eik Hock; Kao, Yung Hsiang; Xie, Wanying

    2013-01-01

    Locoregional treatment of hepatocellular carcinomas using yttrium-90 (Y-90) microspheres is an emerging modality, and involves the administration of such radioactive particles directly into the hepatic arterial vasculature. We present the case of a 58-year-old gentleman undergoing evaluation for Y-90 microsphere therapy for hepatocellular carcinoma, in which our findings suggest that significant hepatic arterial portal venous shunting detected during the angiogram maybe a predictor of poor localization of microspheres in the turmor, and that centers that utilize body surface area (BSA) approaches for dosimetry should take note of such findings.

  18. Hepatocellular Carcinoma Masquerading as a Large Renal Mass with Hepatic Invasion

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    Joseph R. N. Zabell

    2010-01-01

    Full Text Available Large masses are evaluated with imaging to assess primary origin and tumor spread. We present the unusual case of a 53-year-old male with a 17-cm right upper quadrant mass suspected to be renal or adrenal in origin based on radiographic findings. After surgical excision, the mass was subsequently discovered to be primary hepatocellular carcinoma with direct extension to the kidney and adrenal gland. A diagnosis of chronic hepatitis B was made postoperatively. Primary hepatocellular carcinoma with direct renal extension is an exceedingly rare occurrence based on our experience and review of the published literature.

  19. Prevenção do carcinoma hepatocelular Prevention of hepatocellular carcinoma

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    Francine Papaiordanou

    2009-06-01

    Full Text Available INTRODUÇÃO: O carcinoma hepatocelular (CHC é uma das principais doenças malignas da atualidade. Devido à alta incidência e prognóstico habitualmente sombrio torna-se relevante a necessidade de ações preventivas, levando em consideração a característica peculiar de sua etiologia: estrita relação de sua gênese a fatores ambientais. Os principais fatores de risco geograficamente melhor distribuídos são a associação de CHC com infecções por hepatite B crônica, hepatite C e cirrose hepática (associação em mais de 80% dos casos, independente de seu fator causal. Ele é o quinto tumor maligno mais frequente em todo o mundo (5º em homens e 8º em mulheres; representa 85% dos tumores hepáticos primários e é responsável por quase dois terços das mortes por câncer. MÉTODO: Revisão da literatura nacional e internacional dos últimos 12 anos (1997-2009, de 25 artigos pesquisados nas bases eletrônicas de dados MedLine, Scielo e LILACS. CONCLUSÃO: Apesar dos avanços científicos e da implementação de medidas para detecção precoce do CHC em pacientes pertencentes a grupos de risco, não houve melhora na taxa de sobrevida durante as três últimas décadas. O motivo que pode explicar esse fato é que a maioria dos pacientes começa a apresentar sintomas somente quando a doença já está em estágio avançado, e nesse caso as opções terapêuticas são limitadas.BACKGROUND: Hepatocellular carcinoma is one of the major malignant diseases in the world today. Due to the high incidence and difficult prognosis, preventive measures became an important need taking into consideration that its etiology is strictly connected with environmental factors. The main risk factors are the association of hepatocellular carcinoma with chronic hepatitis B and C virus infections and cirrhosis, whatever its cause. Hepatocellular carcinoma is the fifth most common global cancer, representing 85% of the hepatic primary tumors and it is

  20. Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma

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    Wang, Mingchao; Tian, Fang; Ying, Wantao; Qian, Xiaohong

    2017-01-01

    Hepatocellular carcinoma (HCC) is a serious threat to human health. The carbohydrate recognition domain of Galectin-3 (Gal3C) has been reported to be an anti-tumour molecule. In this study, we aim to explore effects of Gal3C in HCC and its possible molecular mechanism with quantitative proteomics approach. We found that rGal3C stimulation could inhibit cell viability, migration and invasion of HepG2. After rGal3C stimulating, 190 proteins were differentially expressed. Eighty up-regulated pro...

  1. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

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    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

  2. Sorafenib in liver function impaired advanced hepatocellular carcinoma.

    Science.gov (United States)

    Ji, You-xin; Zhang, Zhong-fa; Lan, Ke-tao; Nie, Ke-ke; Geng, Chuan-xin; Liu, Shi-chao; Zhang, Ling; Zhuang, Xing-jun; Zou, Xiao; Sun, Lei; Zhang, Zong-chun

    2014-03-01

    To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). 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. 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<0.001). The main adverse effect of sorafenib was rash and acne of the skin (in 51.7% patients). The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2% in the sorafenib group. One patient reached partial response in the sorafenib group. 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.

  3. Gamma knife surgery for brain metastasis from hepatocellular carcinoma.

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    Qingsheng Xu

    Full Text Available 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 patients (57.1% presented with a single brain lesion. Intracranial hemorrhages occurred in 13 (59.1% of the 22 lesions. The mean KPS score was 81±14 (range 50-100. Eleven (78.6% patients were classified as RTOG RPA Class 2. The mean tumor volume was 8.16±8.15 cm(3 (range 0.59-27.0 cm(3. The mean marginal dose prescribed was 18.7±3.2 Gy (range 10.0-22.0 Gy. The mean number of shots administered was 10±9 (range 1-27. The median overall survival time after GKS was 5.0±0.93 months (95% CI 3.2-6.8. No complications related to the radiosurgical treatment were identified. Multivariate analysis showed that the total volume of brain metastases, the RTOG RPA class and serum AFP level were significantly correlated with patients' survival time. CONCLUSIONS: Although survival was extremely poor in patients with brain metastasis (BM from HCC, GKS was shown to lead to prolongation of the survival time. Accordingly, GKS can be considered as a valuable treatment option for proper patients with HCC BM.

  4. Radiation Therapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

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    Park, Seung Gyu; Kim, Jin Hee; Byun, Sang Jun; Kim, Ok Bae; Hwang, Jae Seok; Oh, Young Kee; Choi, Tae Jin [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2011-03-15

    To evaluate the effectiveness of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to analyze the prognostic factors. From December 2004 to April 2009, 70 patients who had HCC with PVTT were treated with RT at Keimyung University Dongsan Medical Center. Nineteen patients whose total dose was below 30 Gy and one patient who underwent liver transplantation were excluded. The remaining 50 patients (45 males, 5 females; median age 55 years) were analyzed. According to the LCSGJ TNM stage, there were 27 patients (54.0%) with stage III and 23 (46.0%) with stage IV. Total dose of 30-54 Gy was administered (median 45). Thirty patients (60.0%) were treated with concurrent chemoradiation therapy (CCRT). The median follow-up duration was from 13.5 months (range, 3 to 70 months). The median survival time from the start of RT was 9 months. One-year and 2-year overall survival rates were 24.9% and 11.2%, respectively. At the follow-up time, three patients (6.0%) displayed no evidence of disease. Seven patients (14.0%) were alive with disease, and 40 (80.0%) patients had expired due to disease progression. CCRT was associated with worse survival than RT alone (p=0.034). Response to RT (p=0.037), CLIP stage (p=0.017), and TNM stage (p=0.041) were statistically significant prognostic factors. There was no radiation-induced liver disease. RT is an effective and safe modality for HCC with PVTT. Further studies such as prospective randomized trials are needed to confirm the role of RT for HCC with PVTT.

  5. Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

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    Zhijia Cao

    2017-10-01

    Full Text Available Background/Aims: Hepatocellular carcinoma (HCC is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. Luteolin, a flavonoid from traditional Chinese medicine, shows anti-cancer activity in many cancer cells, including HCC. However, the mechanism underlying the action of luteolin in HCC, especially its role in regulating cell autophagy, remains unclear. In the present study, we investigated the role of luteolin in regulating cell autophagy and the role of autophagy in luteolin-induced apoptosis. Methods: The 3-(4,5-dimethythiazol-2-yl-2,5-diphenyl tetrazolium bromide assay (MTT was used to investigate cell viability. Flow cytometry analysis was used to detect the cell cycle and cell apoptosis. Hoechst 33342 staining was used to detect cell apoptosis. Transmission electron microscopy was used to investigate autophagy. qRT-PCR and western blotting were used to detect apoptosis- and autophagy-related mRNAs and proteins. Results: Luteolin reduced the viability of SMMC-7721 cells in a time and dose-dependent manner, and induced significant G0/G1-phase arrest. In addition, the results of flow cytometry analysis and Hoechst 33342 staining showed that luteolin treatment increased the number of apoptotic cells obviously, and the results of qRT-PCR and western blotting showed that luteolin treatment increased caspase 8 and decreased bcl-2 at the mRNA and protein levels. Furthermore, luteolin increased the number of intracellular autophagosomes, promoted LC3B-I conversion to LC3B-II, and increased Beclin 1 expression. Finally, co-treatment with the autophagy inhibitor chloroquine weakened the effects of luteolin on cell apoptosis. Conclusion: Luteolin induced apoptosis in human liver cancer SMMC-7721 cells, partially via autophagy. Thus, luteolin could be used as a regulator of autophagy in HCC treatment.

  6. Intraparenchymal Hemorrhage due to Brain Metastasis of Hepatocellular Carcinoma

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    Rafael Sartori Balbinot

    2017-09-01

    Full Text Available Although extrahepatic metastases from hepatocellular carcinoma (HCC are present in only 5–15% of cases, they are certainly factors associated with poor prognosis. The main sites include lung, lymph nodes, bones, and adrenal glands, in descending order. Metastasis in the central nervous system is extremely rare, and the incidences vary from 0.6 to 1.7%. We report a case of a 54-year-old man previously diagnosed with alcohol-induced cirrhosis of the liver and HCC. The patient was admitted presenting progressive left hemiparesis and headache which started 2 days earlier, with no history of cranioencephalic trauma. After admission, cranial computed tomography revealed an intraparenchymal hemorrhage area with surrounding edema in the right frontal lobe. An angioresonance requested showed a large extra-axial mass lesion located in the right frontal region with well-defined contours and predominantly hypointense signal on T2 sequence. At first, the radiological findings suggested meningioma as the first diagnostic hypothesis. However, the patient underwent surgery. The tumor was completely removed, and the morphological and immunohistochemical findings were consistent with metastatic hepatocarcinoma associated with meningioma. In postoperative care, the patient did not recover from the left hemiparesis and manifested Broca’s aphasia. He had a survival time of 24 weeks, presenting acute liver failure as his cause of death. There is a lack of evidence supporting a specific management of patients with brain metastasis from HCC. Furthermore, there are no studies that evaluate different modalities of therapeutics in brain metastasis of HCC due to the rarity of this condition. Therefore, management must be individualized depending on probable prognostic factors in these patients.

  7. Increased HCMV seroprevalence in patients with hepatocellular carcinoma

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    Lepiller Quentin

    2011-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is the most common primary liver cancer, usually arising after years of chronic liver inflammation that could result from viral infections such as hepatitis B virus (HBV and hepatitic C virus (HCV infections. Human cytomegalovirus (HCMV infects primary human hepatocytes and remains an important cause of morbidity in immunocompromised persons where it may manifest as symptomatic end-organ disease including hepatitis. The goal of the present study was to determine a potential correlation between HCMV infection and the appearance of HCC. Methods First, we analyzed the seroprevalence of HCMV in a cohort of 11,318 patients hospitalized between 2003 and 2009 in different departments of a French University Hospital. Second, we studied HCMV seroprevalence in a cohort of 190 subjects who were stratified on the basis of age, gender, HCC, cirrhosis (Cir, and the exposition to hepatotropic viruses (HCV, HBV. We further determined whether HCMV DNA was present specifically in tumour area in liver biopsies from HCC-positive patients by using nested PCR. Results We found that the HCMV seroprevalence was high in the Hepatology department. The HCMV seroprevalence was significantly higher in patients infected with HCV and/or HBV than in patients who were not infected by those later viruses (76.2% versus 56.5%, p Conclusions Our results indicate that HCMV seroprevalence in patients with HCC is significantly higher than in patients without HCC, is positively correlated with serum IL-6 levels in cirrhotic patients, and is positively associated with the presence of other hepatotropic viruses such as HCV and HBV.

  8. Failure rates in the hepatocellular carcinoma surveillance process.

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    Singal, Amit G; Yopp, Adam C; Gupta, Samir; Skinner, Celette Sugg; Halm, Ethan A; Okolo, Eucharia; Nehra, Mahendra; Lee, William M; Marrero, Jorge A; Tiro, Jasmin A

    2012-09-01

    Hepatocellular carcinoma (HCC) surveillance is underutilized among patients with cirrhosis. Understanding which steps in the surveillance process are not being conducted is essential for designing effective interventions to improve surveillance rates. The aim of our study was to characterize reasons for failure in the HCC surveillance process among a cohort of cirrhotic patients with HCC. We conducted a retrospective cohort study of cirrhotic patients diagnosed with HCC at a large urban safety-net hospital between 2005 and 2011. Patients were characterized by receipt of HCC surveillance over a two-year period before HCC diagnosis. Among patients without HCC surveillance, we classified reasons for failure into four categories: failure to recognize liver disease, failure to recognize cirrhosis, failure to order surveillance, and failure to complete surveillance despite orders. Univariate and multivariate analyses were conducted to identify predictors of failures. We identified 178 patients with HCC, of whom 20% had undergone surveillance. There were multiple points of failure-20% had unrecognized liver disease, 19% had unrecognized cirrhosis, 38% lacked surveillance orders, and 3% failed to complete surveillance despite orders. Surveillance was more likely among patients seen by hepatologists [OR, 6.11; 95% confidence interval (CI), 2.5-14.8] and less likely in those with alcohol abuse (OR, 0.14; 95% CI, 0.03-0.65). Although a retrospective analysis in a safety-net hospital, our data suggest that only one in five patients received surveillance before HCC diagnosis. There are multiple points of failure in the surveillance process, with the most common being failure to order surveillance in patients with known cirrhosis. Future interventions must target multiple failure points in the surveillance process to be highly effective.

  9. Proton beam therapy for hepatocellular carcinoma patients with severe cirrhosis

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    Hata, M.; Tokuuye, K.; Fukumitsu, N.; Hashimoto, T.; Akine, Y. [Proton Medical Research Center, Univ. of Tsukuba, Ibaraki (Japan); Dept. of Radiation Oncology, Univ. of Tsukuba, Ibaraki (Japan); Sugahara, S.; Ohnishi, K.; Nemoto, K.; Ohara, K. [Dept. of Radiation Oncology, Univ. of Tsukuba, Ibaraki (Japan); Matsuzaki, Y. [Dept. of Gastroenterology and Hepatology, Univ. of Tsukuba, Ibaraki (Japan)

    2006-12-15

    Background and purpose: hepatocellular carcinoma (HCC) patients with severe cirrhosis are usually treated with supportive care because of their poor prognosis. However, the survival of severe cirrhotic patients has recently improved due to advanced treatments. The aim of this study was to define the role of proton beam therapy for HCC patients with severe cirrhosis. Patients and methods: 19 HCC patients with Child-Pugh class C cirrhosis received proton beam therapy. The hepatic tumors were solitary in 14 patients and multiple in five, and the tumor size was 25-80 mm (median 40 mm) in maximum diameter. No patient had regional lymph node or distant metastasis. Total doses of 50-84 Gy (median 72 Gy) in ten to 24 fractions (median 16) were delivered to the tumors. Results: of the 19 patients, six, eight and four died of cancer, liver failure and intercurrent diseases, respectively, during the follow-up period of 3-63 months (median 17 months) after treatment. A remaining patient was alive with no evidence of disease 33 months after treatment. All but one of irradiated tumors were controlled during the follow-up period. Ten patients had new intrahepatic tumors outside the irradiated volume. The overall and progression-free survival rates were 53% and 47% at 1 year, respectively, and 42% each at 2 years. Performance status and Child-Pugh score were significant prognostic factors for survival. Therapy-related toxicity of grade 3 or more was not observed. Conclusion: proton beam therapy for HCC patients with severe cirrhosis was tolerable. It may improve survival for patients with relatively good general condition and liver function. (orig.)

  10. Functional and topological properties in hepatocellular carcinoma transcriptome.

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    Ignat Drozdov

    Full Text Available Hepatocellular carcinoma (HCC is a leading cause of global cancer mortality. However, little is known about the precise molecular mechanisms involved in tumor formation and pathogenesis. The primary goal of this study was to elucidate genome-wide molecular networks involved in development of HCC with multiple etiologies by exploring high quality microarray data. We undertook a comparative network analysis across 264 human microarray profiles monitoring transcript changes in healthy liver, liver cirrhosis, and HCC with viral and alcoholic etiologies. Gene co-expression profiling was used to derive a consensus gene relevance network of HCC progression that consisted of 798 genes and 2,012 links. The HCC interactome was further confirmed to be phenotype-specific and non-random. Additionally, we confirmed that co-expressed genes are more likely to share biological function, but not sub-cellular localization. Analysis of individual HCC genes revealed that they are topologically central in a human protein-protein interaction network. We used quantitative RT-PCR in a cohort of normal liver tissue (n = 8, hepatitis C virus (HCV-induced chronic liver disease (n = 9, and HCC (n = 7 to validate co-expressions of several well-connected genes, namely ASPM, CDKN3, NEK2, RACGAP1, and TOP2A. We show that HCC is a heterogeneous disorder, underpinned by complex cross talk between immune response, cell cycle, and mRNA translation pathways. Our work provides a systems-wide resource for deeper understanding of molecular mechanisms in HCC progression and may be used further to define novel targets for efficient treatment or diagnosis of this disease.

  11. Local ablative treatments for hepatocellular carcinoma: An updated review

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    Facciorusso, Antonio; Serviddio, Gaetano; Muscatiello, Nicola

    2016-01-01

    Ablative treatments currently represent the first-line option for the treatment of early stage unresectable hepatocellular carcinoma (HCC). Furthermore, they are effective as bridging/downstaging therapies before orthotopic liver transplantation. Contraindications based on size, number, and location of nodules are quite variable in literature and strictly dependent on local expertise. Among ablative therapies, radiofrequency ablation (RFA) has gained a pivotal role due to its efficacy, with a reported 5-year survival rate of 40%-70%, and safety. Although survival outcomes are similar to percutaneous ethanol injection, the lower local recurrence rate stands for a wider application of RFA in hepato-oncology. Moreover, RFA seems to be even more cost-effective than liver resection for very early HCC (single nodule ≤ 2 cm) and in the presence of two or three nodules ≤ 3 cm. There is increasing evidence that combining RFA to transarterial chemoembolization may increase the therapeutic benefit in larger HCCs without increasing the major complication rate, but more robust prospective data is still needed to validate these pivotal findings. Among other thermal treatments, microwave ablation (MWA) uses high frequency electromagnetic energy to induce tissue death via coagulation necrosis. In comparison to RFA, MWA has several theoretical advantages such as a broader zone of active heating, higher temperatures within the targeted area in a shorter treatment time and the lack of heat-sink effect. The safety concerns raised on the risks of this procedure, due to the broader and less predictable necrosis areas, have been recently overcome. However, whether MWA ability to generate a larger ablation zone will translate into a survival gain remains unknown. Other treatments, such as high-intensity focused ultrasound ablation, laser ablation, and cryoablation, are less investigated but showed promising results in early HCC patients and could be a valuable therapeutic option in

  12. Hepatocellular carcinoma in a green iguana – a case study

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    Zdeněk Knotek

    2011-01-01

    Full Text Available A 3.10 kg, six-year old male green iguana (Iguana iguana suffered several weeks of decreased activity, loss of body weight, anorexia and change of skin colour. Physical examination revealed a cachectic depressed lizard, with marked pale mucous membranes. The complete blood count revealed a leukocytosis (46.5 × 109/l, elevated heterophils (23.25 × 109/l and azurophils (23.25 × 109/l, decreased haemoglobin concentration (29.00 g/l, low haematocrit (0.16 l/l and erythropenia (0.35 × 1012/l. Abnormalities of the plasma chemistry panel included increased activity of aspartate aminotransferase (6.05 μkat/l and creatinephosphokinase (217.91 μkat/l, increased concentrations of uric acid (321.58 μmol/l, phosphorus (4.04 mmol/l and bile acids (120.21 μmol/l, as well as a decreased concentration of glucose (3.72 mmol/l, cholesterol (0.637 mmol/l and triglycerides (0.09 mmol/l. A lateral radiograph revealed soft-tissue opacity present in the region of the liver. Magnetic resonance imaging showed a markedly enlarged left liver lobe distended caudally and displacing the other abdominal organs. The signal intensity of the liver parenchyma was slightly hyperintense, the ventro-medial part of the left lobe showed a hypointense signal. Endoscopic examination of the coelomic cavity revealed a greatly enlarged pale liver and the presence of a straw-coloured modified transudate. Based on histopathological examination of the liver hepatocellular carcinoma was diagnosed. Despite supportive treatment the patient died on the sixth day of hospitalisation.

  13. Family history of liver cancer and hepatocellular carcinoma.

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    Turati, Federica; Edefonti, Valeria; Talamini, Renato; Ferraroni, Monica; Malvezzi, Matteo; Bravi, Francesca; Franceschi, Silvia; Montella, Maurizio; Polesel, Jerry; Zucchetto, Antonella; La Vecchia, Carlo; Negri, Eva; Decarli, Adriano

    2012-05-01

    Familial clustering of hepatocellular carcinoma (HCC) has been frequently reported in eastern Asiatic countries, where hepatitis B infection is common. Little is known about the relationship between family history of liver cancer and HCC in Western populations. We carried out a case-control study in Italy, involving 229 HCC cases and 431 hospital controls. Data on family history were summarized through a binary indicator (yes/no) and a family history score (FHscore), considering selected family characteristics. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were obtained from unconditional multiple logistic regression models, including terms for age, sex, study center, education, tobacco smoking, alcohol drinking, hepatitis B surface antigen, and/or anti-hepatitis C virus positivity. We also performed a meta-analysis on family history of liver cancer and liver cancer updated to April 2011 using random-effects models. After adjustment for chronic infection with hepatitis B/C viruses, family history of liver cancer was associated with HCC risk, when using both the binary indicator (OR, 2.38; 95% CI, 1.01-5.58) and the FHscore, with increasing ORs for successive score categories. Compared to subjects without family history and no chronic infection with hepatitis B/C viruses, the OR for those exposed to both risk factors was 72.48 (95% CI, 21.92-239.73). In the meta-analysis, based on nine case-control and four cohort studies, for a total of approximately 3,600 liver cancer cases, the pooled relative risk for family history of liver cancer was 2.50 (95% CI, 2.06-3.03). A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk. Copyright © 2011 American Association for the Study of Liver Diseases.

  14. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

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    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  15. Radiologic-pathologic correlation of hepatocellular carcinoma treated with chemoembolization.

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    Riaz, Ahsun; Lewandowski, Robert J; Kulik, Laura; Ryu, Robert K; Mulcahy, Mary F; Baker, Talia; Gates, Vanessa; Nayar, Ritu; Wang, Ed; Miller, Frank H; Sato, Kent T; Omary, Reed A; Abecassis, Michael; Salem, Riad

    2010-12-01

    To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre- and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa (κ) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have ≥85% specificity for predicting complete pathologic necrosis. The κ coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.

  16. Intermediate hepatocellular carcinoma: How to choose the best treatment modality?

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    Di Costanzo, Giovan Giuseppe; Tortora, Raffaella

    2015-05-28

    Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma (HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large (> 5 cm) solitary HCC should be firstly considered for liver resection (LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization (TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization (TARE)-plus percutaneous ablation] is "a priori" preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases (patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be "patient-tailored" and made by a multidisciplinary team.

  17. Comparative diagnostic efficacy of serum squamous cell carcinoma antigen in hepatocellular carcinoma.

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    Soyemi, Olufemi Michael; Otegbayo, Jesse Abiodun; Ola, Samuel Olawale; Akere, Adegboyega; Soyemi, Temitope

    2012-08-03

    Hepatocellular carcinoma (HCC) is a common liver malignancy in Nigeria. Hepatitis B and C viruses, alcohol and Aflatoxin B are among the various aetiologies. More work needs to be done in the search for markers that will aid early detection of this condition as it is uniformly fatal once advanced. Alphafetoprotein (AFP) remains the most widely used tumour marker of HCC detection in spite of its known shortcomings. The objective of this study was to determine the efficacy of serum squamous cell carcinoma antigen (SCCA) , in comparison to alphafetoprotein in the detection of HCC. Sixty patients with HCC and thirty apparently healthy controls attending the Medical Outpatient Department(MOPD) of the University College Hospital Ibadan(UCH) Nigeria were selected for the study. Questionnaire was used to collect clinical data while AFP, SCCA levels, serum HBsAg and anti-HCV were determined using ELISA method- (Diagnostic Automation Inc. Canada). Abdominal ultrasound scan was also done. Thirty one (51.7%) out of 60 selected cases were positive for HBsAg while six (20%) out of 30 controls were positive for HBsAg(p = 0.004). Out of the 60 cases selected for this study, only 2 (3.3.%) cases were positive for hepatitis C virus, while only 1(3.3%) out of 30 control was positive for hepatitis C virus(p = 0.74).The mean AFP value for cases with HCC was 393.21 ng/ml ±386.97 compared to the control group which was 5.60 ± 13.03 ng/ml (p value 0.001). The mean SCCA level was 0.64 ± 0.56 ng/ml and 0.71 ± 0.65 ng/ml for cases and controls respectively (p = 0.631). Alphafetoprotein remains a good tumour marker for the diagnosis of HCC. Serum squamous cell carcinoma antigen(SCCA) has no discriminatory power and may not be useful as a tumour marker for Nigerians with hepatocellular carcinoma.

  18. Comparative diagnostic efficacy of serum squamous cell carcinoma antigen in hepatocellular carcinoma

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    Soyemi Olufemi

    2012-08-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is a common liver malignancy in Nigeria. Hepatitis B and C viruses, alcohol and Aflatoxin B are among the various aetiologies. More work needs to be done in the search for markers that will aid early detection of this condition as it is uniformly fatal once advanced. Alphafetoprotein (AFP remains the most widely used tumour marker of HCC detection in spite of its known shortcomings. The objective of this study was to determine the efficacy of serum squamous cell carcinoma antigen (SCCA , in comparison to alphafetoprotein in the detection of HCC. Method Sixty patients with HCC and thirty apparently healthy controls attending the Medical Outpatient Department(MOPD of the University College Hospital Ibadan(UCH Nigeria were selected for the study. Questionnaire was used to collect clinical data while AFP, SCCA levels, serum HBsAg and anti-HCV were determined using ELISA method- (Diagnostic Automation Inc. Canada. Abdominal ultrasound scan was also done. Result Thirty one (51.7% out of 60 selected cases were positive for HBsAg while six (20% out of 30 controls were positive for HBsAg(p = 0.004. Out of the 60 cases selected for this study, only 2 (3.3.% cases were positive for hepatitis C virus, while only 1(3.3% out of 30 control was positive for hepatitis C virus(p = 0.74. The mean AFP value for cases with HCC was 393.21 ng/ml ±386.97 compared to the control group which was 5.60 ± 13.03 ng/ml (p value 0.001. The mean SCCA level was 0.64 ± 0.56 ng/ml and 0.71 ± 0.65 ng/ml for cases and controls respectively (p = 0.631. Conclusion Alphafetoprotein remains a good tumour marker for the diagnosis of HCC. Serum squamous cell carcinoma antigen(SCCA has no discriminatory power and may not be useful as a tumour marker for Nigerians with hepatocellular carcinoma.

  19. Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling.

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    Arpit D Shah

    Full Text Available Hepatocellular carcinoma (HCC is the most common form of liver cancer (~80%, and it is one of the few cancer types with rising incidence in the United States. This highly invasive cancer is very difficult to detect until its later stages, resulting in limited treatment options and low survival rates. There is a dearth of knowledge regarding the mechanisms associated with the effects of biomechanical forces such as interstitial fluid flow (IFF on hepatocellular carcinoma invasion. We hypothesized that interstitial fluid flow enhanced hepatocellular carcinoma cell invasion through chemokine-mediated autologous chemotaxis. Utilizing a 3D in vitro invasion assay, we demonstrated that interstitial fluid flow promoted invasion of hepatocellular carcinoma derived cell lines. Furthermore, we showed that autologous chemotaxis influences this interstitial fluid flow-induced invasion of hepatocellular carcinoma derived cell lines via the C-X-C chemokine receptor type 4 (CXCR4/C-X-C motif chemokine 12 (CXCL12 signaling axis. We also demonstrated that mitogen-activated protein kinase (MEK/extracellular signal-regulated kinase (ERK signaling affects interstitial fluid flow-induced invasion; however, this pathway was separate from CXCR4/CXCL12 signaling. This study demonstrates, for the first time, the potential role of interstitial fluid flow in hepatocellular carcinoma invasion. Uncovering the mechanisms that control hepatocellular carcinoma invasion will aid in enhancing current liver cancer therapies and provide better treatment options for patients.

  20. Canonical Wnt signaling is antagonized by noncanonical Wnt5a in hepatocellular carcinoma cells

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    Yilmaz Mustafa

    2009-10-01

    Full Text Available Abstract Background β-catenin mutations that constitutively activate the canonical Wnt signaling have been observed in a subset of hepatocellular carcinomas (HCCs. These mutations are associated with chromosomal stability, low histological grade, low tumor invasion and better patient survival. We hypothesized that canonical Wnt signaling is selectively activated in well-differentiated, but repressed in poorly differentiated HCCs. To this aim, we characterized differentiation status of HCC cell lines and compared their expression status of Wnt pathway genes, and explored their activity of canonical Wnt signaling. Results We classified human HCC cell lines into "well-differentiated" and "poorly differentiated" subtypes, based on the expression of hepatocyte lineage, epithelial and mesenchymal markers. Poorly differentiated cell lines lost epithelial and hepatocyte lineage markers, and overexpressed mesenchymal markers. Also, they were highly motile and invasive. We compared the expression of 45 Wnt pathway genes between two subtypes. TCF1 and TCF4 factors, and LRP5 and LRP6 co-receptors were ubiquitously expressed. Likewise, six Frizzled receptors, and canonical Wnt3 ligand were expressed in both subtypes. In contrast, canonical ligand Wnt8b and noncanonical ligands Wnt4, Wnt5a, Wnt5b and Wnt7b were expressed selectively in well- and poorly differentiated cell lines, respectively. Canonical Wnt signaling activity, as tested by a TCF reporter assay was detected in 80% of well-differentiated, contrary to 14% of poorly differentiated cell lines. TCF activity generated by ectopic mutant β-catenin was weak in poorly differentiated SNU449 cell line, suggesting a repressive mechanism. We tested Wnt5a as a candidate antagonist. It strongly inhibited canonical Wnt signaling that is activated by mutant β-catenin in HCC cell lines. Conclusion Differential expression of Wnt ligands in HCC cells is associated with selective activation of canonical Wnt

  1. 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

  2. Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B

    DEFF Research Database (Denmark)

    Thiele, Maja; Gluud, Lise Lotte; Dahl, Emilie K

    2013-01-01

    The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV....

  3. Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Xin-Yu; Yang, Shu-Meng; Zhang, Hao-Peng; Yang, Yue; Sun, Shi-Bo; Chang, Jian-Ping; Tao, Xuan-Chen; Yang, Tuo-Yun; Liu, Chun; Yang, Yan-Mei

    2015-11-01

    Arsenic trioxide has been proven to trigger apoptosis in human hepatocellular carcinoma cells. Endoplasmic reticulum stress has been known to be involved in apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein. However, it is unknown whether endoplasmic reticulum stress mediates arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Our data showed that arsenic trioxide significantly induced apoptosis in human hepatocellular carcinoma cells. Furthermore, arsenic trioxide triggered endoplasmic reticulum stress, as indicated by endoplasmic reticulum dilation, upregulation of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein. We further found that 4-phenylbutyric acid, an inhibitor of endoplasmic reticulum stress, alleviated arsenic trioxide-induced expression of CCAAT/enhancer-binding protein homologous protein. More important, knockdown of CCAAT/enhancer-binding protein homologous protein by siRNA or inhibition of endoplasmic reticulum stress by 4-phenylbutyric acid alleviated apoptosis induced by arsenic trioxide. Consequently, our results suggested that arsenic trioxide could induce endoplasmic reticulum stress-mediated apoptosis in hepatocellular carcinoma cells, and that CCAAT/enhancer-binding protein homologous protein might play an important role in this process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Hepatocellular carcinoma bone metastasis in an 11-year-old boy

    Energy Technology Data Exchange (ETDEWEB)

    Lucarini, Silvia [Schulich School of Medicine and Dentistry, University of Western Ontario, Department of Diagnostic Radiology and Nuclear Medicine, London, ON (Canada); Fortier, Marielle [Children' s Hospital of Western Ontario, Department of Radiology, London, ON (Canada); Leaker, Michael [Children' s Hospital of Western Ontario, Department of Oncology, London, ON (Canada); Chhem, Rethy [Schulich School of Medicine and Dentistry, University of Western Ontario, Department of Diagnostic Radiology and Nuclear Medicine, London, ON (Canada); London Health Sciences Centre, University Hospital of Windermere, Department of Radiology, London, ON (Canada)

    2008-01-15

    Hepatocellular carcinoma (HCC) is the second most common primary hepatic malignant tumor in children older than 4 years. We describe a rare case of an 11-year-old boy with HCC who presented with HCC of the right liver lobe followed by multiple osseous metastases, confirmed by imaging and biopsy. (orig.)

  5. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  6. Relevance of non-ceruloplasmin copper to oxidative stress in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Geetha, Arumugam; Saranya, Panneerselvam; Annie Jeyachristy, Sam; Surendran, Rajagopal; Sundaram, Arunachalam

    2009-09-01

    Altered copper homeostasis and oxidative stress have been observed in patients with hepatocellular carcinoma. Non-ceruloplasmin copper, the free form, is a potent pro-oxidant than the protein bound copper. The aim of the present study was to evaluate which form of copper can be correlated with the oxidative stress in the circulation and in the malignant liver tissues of hepatocellular carcinoma patients. Hepatocellular carcinoma patients (grades II and III, n = 18) were enrolled in this study. Serum levels of total, free and bound copper, ceruloplasmin, iron, iron-binding capacity, lipid peroxidation products, and enzymatic and non-enzymatic antioxidants were quantified in serum and in malignant liver tissues and compared with those of normal samples (n = 20). A significant positive correlation between the serum non-ceruloplasmin copper and lipid peroxidation products and negative correlation with antioxidants were observed in hepatocellular carcinoma patients. In liver tissue, glutathione peroxidase, superoxide dismutase, and catalase activity were significantly decreased with concomitant elevation in oxidative stress markers. Our experiment revealed that the elevation in non-ceruloplasmin copper has high relevance with the oxidative stress than the bound copper.

  7. Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob Hornstrup Frølunde; Rosenberg, Jacob

    2016-01-01

    and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation. METHODS: A literature search was performed in the databases PubMed and Scopus to identify observational studies evaluating serological or molecular biomarkers for recurrence of HCC after LT using adjusted analysis...

  8. Minimally invasive image-guided therapy for inoperable hepatocellular carcinoma: What is the evidence today?

    NARCIS (Netherlands)

    Seinstra, Beatrijs A.; van Delden, Otto M.; van Erpecum, Karel J.; van Hillegersberg, Richard; Mali, Willem P. Th M.; van den Bosch, Maurice A. A. J.

    2010-01-01

    Hepatocellular carcinoma (HCC) is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10-15% of HCC patients are suitable candidates for hepatic resection and liver transplantation due to the advanced stage of the disease at time of diagnosis and

  9. Surveillance for hepatocellular carcinoma in chronic liver disease: Evidence and controversies

    NARCIS (Netherlands)

    S. van Meer (Suzanne); R.A. de Man (Robert); P.D. Siersema (Peter); K.J. van Erpecum (Karel)

    2013-01-01

    textabstractPrimary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis,

  10. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report

    NARCIS (Netherlands)

    Clavien, Pierre-Alain; Lesurtel, Mickael; Bossuyt, Patrick M. M.; Gores, Gregory J.; Langer, Bernard; Perrier, Arnaud; Abecassis, M.; Balabaud, C.; Bhoori, S.; Breitenstein, S.; Broelsch, C.; Burra, P.; Cherqui, D.; Colombo, M.; d'Albuquerque, C.; D'Alessandro, A.; de Santibanes, E.; Dufour, J. F.; Durand, F.; Dutkowski, P.; El-Serag, H.; Fan, S. T.; Fisher, R.; Forner, A.; Fung, J.; Geier, A.; Germani, G.; Gouw, A. S. H.; Gurusamy, K.; Heaton, N.; Heim, M.; Hemming, A.; Hubscher, S.; Ichida, T.; Kahn, D.; Kew, M.; Kita, Y.; Kiuchi, T.; Kudo, M.; Lee, S. G.; Lencioni, R.; Livraghi, T.; Lodge, P.; McCaughan, G.; Madoff, D.; Marrero, J.; Mergental, H.; Merle, P.; Miksad, R.; Mornex, F.; Paradis, V.; Pestalozzi, B.; Poon, R.; Porte, R.; Prasad, K. R.; Roskams, T.; Rossi, M.; Schlitt, H.; Shaked, A.; Sherman, M.; Siegler, M.; Suh, K.; Todo, S.; Toso, C.; Trevisani, F.; Valdecasas, J. C. G.; Vauthey, J. N.; Vilgrain, V.; Villamil, F.; Wald, C.; Weber, A.; Wiesner, R.; Wright, L.; Zheng, S.; Zucman-Rossi, J.; Bertschi, V.; Clavien, P. A.; Meyer, M.; Müllhaupt, B.; Munson, A.; Lesurtel, M.; Raptis, D.; Vonlanthen, R.

    2012-01-01

    Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2-4, 2010, in Zurich, Switzerland, with the aim of reviewing current

  11. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study.

    Science.gov (United States)

    Fedirko, Veronika; Tran, Hao Quang; Gewirtz, Andrew T; Stepien, Magdalena; Trichopoulou, Antonia; Aleksandrova, Krasimira; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Carbonnel, Franck; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Boeing, Heiner; Bamia, Christina; Lagiou, Pagona; Grioni, Sara; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Naccarati, Alessio; Peeters, Petra H; Bueno-de-Mesquita, H B; Weiderpass, Elisabete; Castaño, José María Huerta; Barricarte, Aurelio; Sánchez, María-José; Dorronsoro, Miren; Quirós, J Ramón; Agudo, Antonio; Sjöberg, Klas; Ohlsson, Bodil; Hemmingsson, Oskar; Werner, Mårten; Bradbury, Kathryn E; Khaw, Kay-Tee; Wareham, Nick; Tsilidis, Konstantinos K; Aune, Dagfinn; Scalbert, Augustin; Romieu, Isabelle; Riboli, Elio; Jenab, Mazda

    2017-04-04

    Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

  12. Silencing the Girdin gene enhances radio-sensitivity of hepatocellular carcinoma via suppression of glycolytic metabolism.

    Science.gov (United States)

    Yu, Li; Sun, Yifan; Li, Jingjing; Wang, Yan; Zhu, Yuxing; Shi, Yong; Fan, Xiaojun; Zhou, Jianda; Bao, Ying; Xiao, Jie; Cao, Ke; Cao, Peiguo

    2017-08-15

    Radiotherapy has been used increasingly to treat primary hepatocellular carcinoma. Clinically, the main cause of radiotherapy failure is cellular radioresistance, conferred via glycolytic metabolism. Our previous study demonstrated that Girdin is upregulated in primary hepatocellular carcinoma and promotes the invasion and metastasis of tumor cells. However, whether Girdin underlies the radio-sensitivity of hepatocellular carcinoma remains unclear. A short hairpin RNA (shRNA) was used to silence CCDC88A (encoding Girdin), and real-time PCR was performed to determine CCDC88A mRNA expression. Then, cell proliferation, colony formation, flow cytometric, scratch, and transwell assays were to examine the influence of Girdin silencing on cellular radiosensitivity. Glycolysis assays were conducted to exam cell glycolysis process. Western blotting was performed to explore the signaling pathway downstream of Girdin. Finally, animal experiments were performed to demonstrate the effect of CCDC88A silencing on the radiosensitivity of hepatoma in vivo. shRNA-induced Girdin silencing suppressed glycolysis and enhanced the radio-sensitivity of hepatic cell lines, HepG2 and Huh-7. Furthermore, silencing of Girdin inhibited the PI3K/AKT/HIF-1α signaling pathway, which is a central regulator of glycolysis. Girdin can regulate glycolysis in hepatocellular carcinoma cells through the PI3K/AKT/HIF-1α signaling pathway, which decreases the sensitivity of tumor cells to radiotherapy.

  13. Factors associated with ethnical disparity in overall survival for patients with hepatocellular carcinoma

    NARCIS (Netherlands)

    J. Li (Juan); B.E. Hansen (Bettina); M.P. Peppelenbosch (Maikel); R.A. de Man (Robert); Q. Pan (Qiuwei); D. Sprengers (Dave)

    2017-01-01

    textabstractHepatocellular carcinoma (HCC) is an important cause of cancer-related death worldwide. Ethnical disparity in overall survival has been demonstrated for HCC patients in the United States (U.S.). We aimed to evaluate the contributors to this survival disparity. The SEER database was used

  14. Recently introduced biomarkers for screening of hepatocellular carcinoma: A systematic review and meta-analysis

    NARCIS (Netherlands)

    C.D.M. Witjes (Carlijn); S.M. van Aalten (Susanna); E.W. Steyerberg (Ewout); G.J.J.M. Borsboom (Gerard); R.A. de Man (Robert); C. Verhoef (Kees); J.N.M. IJzermans (Jan)

    2013-01-01

    textabstractPurpose: Early detection of hepatocellular carcinoma (HCC) is essential for improved prognosis and long-term survival. To date, screening for HCC depends on serological testing (alpha-fetoprotein, AFP) and imaging (ultrasonography), both of which are not highly sensitive. A meta-analysis

  15. Differences in health-related quality of life between European and Asian patients with hepatocellular carcinoma.

    Science.gov (United States)

    Chie, Wei-Chu; Blazeby, Jane M; Hsiao, Chin-Fu; Chiu, Herng-Chia; Poon, Ronnie T; Mikoshiba, Naoko; Al-Kadhim, Gillian; Heaton, Nigel; Calara, Jozer; Collins, Peter; Caddick, Katharine; Costantini, Anna; Vilgrain, Valerie

    2017-10-01

    The aim of this study is to explore the possible effects of clinical and cultural characteristics of hepatocellular carcinoma on patients' health-related quality of life (HRQoL). Patients with hepatocellular carcinoma from Asian and European countries completed the EORTC QLQ-C30 and the EORTC QLQ-HCC18. Comparisons were made using Student's t-test and Wilcoxon rank-sum test with method of false discovery to correct multiple comparisons. Multiway analysis of variance and model selection were used to assess the effects of clinical characteristics and geographic areas. Two hundred and twenty-seven patients with hepatocellular carcinoma completed questionnaires. After adjusting for demographic and clinical characteristics, Asian patients still had significantly better HRQoL scores in emotional functioning, insomnia, (QLQ-C30) and in sexual interest (QLQ-HCC18). We also found an interaction in physical functioning (QLQ-C30) and fatigue (QLQ-HCC18) between geographic region and marital status, married European had worse HRQoL scores than Asian singles. Both clinical characteristics and geographic areas affected the HRQoL in with hepatocellular carcinoma. Cultural differences and clinical differences in the pattern of disease due to active surveillance of Asian countries may explain the results. © 2016 John Wiley & Sons Australia, Ltd.

  16. Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Kathy Han

    2007-01-01

    Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

  17. [The methylation of ZHX2 gene promoter enhances AFP gene expression in hepatocellular carcinoma].

    Science.gov (United States)

    Lv, Zili; DU, Yangjun; Wen, Jianming

    2013-07-01

    To investigate the relationship between Zinc-fingers and homeoboxes 2 (ZHX2) promoter methylation and alpha-fetoprotein (AFP) gene expression, and analyze the mechanism of AFP gene expression. HepG2 cell line was cultured with 0.5, 1.0 or 5.0 μmol/L of 5-aza-deoxycytidine (5-Aza-Dc). RT-PCR and Western blotting were used to detect the expressions of ZHX2 and AFP in HepG2 cell line. Methylation-specific PCR was used to detect ZHX2 promoter methylation in 38 hepatocellular carcinoma tissues. The HepG2 cell line showed a low level of ZHX2 mRNA, negative expression of ZHX2 protein, but high expression of AFP at both mRNA and protein levels. After the HepG2 cells were treated with 1.0 or 5.0 μmol/L 5-Aza-Dc for 6 d, the expression of ZHX2 mRNA and protein increased and the expression of AFP mRNA and protein decreased. Among 38 hepatocellular carcinoma tissues, ZHX2 promoter methylation was found in 16 hepatocellular carcinoma tissues with AFP>25 ng/mL in serum. No methylation of ZHX2 promoter was found in 8 hepatocellular carcinoma tissues with AFPexpression.

  18. [Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liver].

    Science.gov (United States)

    Horváth, Evelin; Balla, Bernadett; Kósa, János; Lakatos, Péter András; Lazáry, Áron; Németh, Dániel; Jozilan, Hasan; Somorácz, Áron; Korompay, Anna; Gyöngyösi, Benedek; Borka, Katalin; Kiss, András; Kupcsulik, Péter; Schaff, Zsuzsa; Szalay, Ferenc

    2016-11-01

    1,25-Dihydroxy vitamin D 3 mediates antitumor effects in hepatocellular carcinoma. We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D 3 -inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (pexpressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D 3 , providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016, 157(48), 1910-1918.

  19. High-intensity focused ultrasound ablation for treatment of hepatocellular carcinoma and hypersplenism: preliminary study.

    Science.gov (United States)

    Zhu, Jing; Zhu, Hui; Mei, Zhechuan; Jin, Chengbing; Ran, Lifeng; Zhou, Kun; Yang, Wei; Zhang, Lian; She, Chaokun

    2013-10-01

    The purpose of this work was to preliminarily investigate the efficacy and safety of high-intensity focused ultrasound treatment of hepatocellular carcinoma and hypersplenism. Nine patients with hepatocellular carcinoma complicated by hypersplenism (5 male and 4 female; median age, 56 years; range, 51-66 years) were treated with ultrasound-guided high-intensity focused ultrasound. Complications were recorded. Laboratory examination and magnetic resonance imaging were used to evaluate the efficacy. After high-intensity focused ultrasound treatment, mean spleen ablation ± SD of 28.76% ± 6.1% was discovered; meanwhile, the white blood cell count, platelet count, and liver function of the patients were substantially improved during the follow-up period. In addition, symptoms such as epistaxis and gingival bleeding were ameliorated or even eliminated, and the quality of life was improved. Follow-up imaging showed a nonperfused volume in the spleen and an absence of a tumor blood supply at the treated lesions in the liver. For the first time to our knowledge, high-intensity focused ultrasound ablation was used to treat hepatocellular carcinoma complicated by hypersplenism. High-intensity focused ultrasound may be an effective and safe alternative for treatment of hepatocellular carcinoma complicated by hypersplenism, but further studies are necessary to clarify the mechanisms.

  20. Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma

    Science.gov (United States)

    Williet, Nicolas; Dubreuil, Olivier; Boussaha, Tarek; Trouilloud, Isabelle; Landi, Bruno; Housset, Martin; Botti, Muriel; Rougier, Philippe; Belghiti, Jacques; Taieb, Julien

    2011-01-01

    This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin, with a partial response and normalization of α fetoprotein, which allowed curative surgery. The potential synergy between these three drugs needs to be confirmed, and is currently being investigated in a randomized phase II trial. PMID:21633538

  1. Phase I study investigating everolimus combined with sorafenib in patients with advanced hepatocellular carcinoma.

    NARCIS (Netherlands)

    Finn, R.S.; Poon, R.T.; Yau, T.; Klumpen, H.J.; Chen, L.T.; Kang, Y.K.; Kim, T.Y.; Gomez-Martin, C.; Rodriguez-Lope, C.; Kunz, T.; Paquet, T.; Brandt, U.; Sellami, D.; Bruix, J.

    2013-01-01

    BACKGROUND & AIMS: Sorafenib is the only therapy shown to improve overall survival in advanced hepatocellular carcinoma (HCC). Combination therapy targeting multiple signaling pathways may improve outcomes. This phase I study was designed to determine the maximum tolerated dose (MTD) of everolimus

  2. Implante subcutáneo de un carcinoma hepatocelular tras la punción aspiración con aguja fina Subcutaneous seeding of hepatocellular carcinoma after fine-needle percutaneous biopsy

    Directory of Open Access Journals (Sweden)

    D. Martínez Ramos

    2007-06-01

    Full Text Available Los implantes subcutáneos son una complicación rara tras la punción aspiración con aguja fina de los carcinomas hepatocelulares. Los autores describen un caso de implante subcutáneo neoplásico en una mujer de 70 años con cirrosis hepática por virus C complicada con un carcinoma hepatocelular. Se efectuó una punción aspiración con aguja fina en el segmento II hepático. El implante tumoral se desarrolló en el trayecto de la punción aspiración. La tumoración subcutánea fue extirpada quirúrgicamente y el estudio anatomopatológico confirmó que se trataba de un carcinoma hepatocelular bien diferenciado.Subcutaneous tumor seeding after fine-needle percutaneous biopsy for hepatocellular carcinoma is a rarely seen complication. The authors describe a case of subcutaneous neoplastic seeding in a 70-year-old woman with chronic hepatitis C virus complicated by hepatocellular carcinoma. Ultrasonically guided fine-needle aspiration biopsy was performed in segment II of the liver. The neoplastic seeding developed along the needle track used to carry out the fine-needle biopsy. The subcutaneous tumor was excised, and histological examination revealed a well-differentiated hepatocellular carcinoma.

  3. SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation

    Directory of Open Access Journals (Sweden)

    Oztas Emin

    2011-06-01

    Full Text Available Abstract Background Smad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers. In this study, we investigated mutations and promoter hypermethylation of the SIP1 gene in human hepatocellular carcinomas. Methods SIP1 expression was analyzed in HCC cell lines and primary tumors in comparison to normal and non-tumor liver tissues by using semi-quantitative RT-PCR, quantitative real-time RT-PCR and immunohistochemistry. Mutation and deletion screening of the SIP1 gene were performed by direct sequencing in HCC-derived cells. Restoration of SIP1 expression was sought by treating HCC cell lines with the DNA methyl transferase inhibitor, 5-AzaC, and the histone deacetylase inhibitor, TSA. SIP1 promoter methylation was analyzed by the combined bisulfite restriction analysis assay in in silico-predicted putative promoter and CpG island regions. Results We found that the expression of SIP1 was completely lost or reduced in five of 14 (36% HCC cell lines and 17 of 23 (74% primary HCC tumors. Immunohistochemical analysis confirmed that SIP1 mRNA downregulation was associated with decreased expression of the SIP1 protein in HCC tissues (82.8%. No somatic mutation was observed in SIP1 exons in any of the 14 HCC cell lines. Combined treatment with DNA methyl transferase and histone deacetylase inhibitors synergistically restored SIP1 expression in SIP1-negative cell lines. Analysis of three putative gene regulatory regions revealed tumor-specific methylation in more than half of the HCC cases. Conclusions Epigenetic mechanisms contribute significantly to the downregulation of SIP1 expression in HCC. This finding adds a new level of

  4. Multidisciplinary management of hepatocellular carcinoma: a model for therapy

    Directory of Open Access Journals (Sweden)

    Cohen GS

    2013-05-01

    Full Text Available Gary S Cohen1, Martin Black2 1Liver Tumor Program, Temple University Hospital, 2Liver Transplantation, Temple University School of Medicine, Philadelphia, PA, USA Abstract: A multidisciplinary model is a useful approach in the management of hepatocellular carcinoma (HCC to coordinate, individualize, and optimize care. The HCC Multidisciplinary Team (MDT at Temple University Hospital was established in 2008 and comprises hepatologists, interventional radiologists, transplant surgeons, oncologists, residents, midlevel providers, and support staff. Patients may be enrolled by referral from (1 oncologists at Temple, (2 the hepatitis screening clinic recently established at Temple and staffed by hepatology residents, or (3 community practices. MDT conferences are held weekly, during which cases are discussed (based on medical history, interpretation of images, and laboratory analyses and treatment plans are formulated. The Temple treatment algorithm follows current standards of care, guided by tumor volume and morphology, but the novel multidisciplinary interaction challenges members to tailor therapy to achieve the best possible outcomes. Patients with a solitary lesion ≤2 cm may receive no treatment until eligible for transplantation or locoregional therapy or resection, with imaging every 3 to 6 months to monitor tumor progression. In patients with tumors > 2 cm and ≤5 cm, microwave ablation therapy is used if lesions are discrete and accessible. Conventional transarterial chemoembolization (TACE or drug-eluting bead TACE (DEB-TACE or yttrium-90 microspheres are utilized in multifocal disease. Patients with lesions > 5 cm are candidates for TACE for downstaging the tumor. Sorafenib is typically reserved for unresectable lesions between 2 cm and 5 cm. Frequently, we administer sorafenib continuously and in combination with DEB-TACE. In our experience, sorafenib does not produce effects on the tumor vasculature or blood flow that would impair

  5. Case report evidence of relationships between hepatocellular carcinoma and ochratoxicosis.

    Directory of Open Access Journals (Sweden)

    Ahmed S Ibrahim

    Full Text Available PURPOSE: The incidence of Hepatocellular carcinoma (HCC is on the rise, but what is causing that trend has remained a mystery. Mycotoxins are almost entirely ignored health problems, and sometimes actually naively belittled in advanced medical care. Ochratoxin A (OTA is one of the most abundant food contaminating mycotoxins worldwide that is carcinogenic, but no studies have evaluated its levels in HCC patients. Therefore, this study was designed to monitor the presence of OTA in the serum of HCC patients and to quantify the strength of the association between OTA and HCC. METHODS: We conducted a case control-based study on 61 participants. Thirty-nine were HCC cases identified between 2010 and 2012 and individually matched by age, sex, residence and date of recruitment to 22 healthy controls. Serum OTA and alpha-fetoprotein levels were measured by using high-performance liquid chromatography (HPLC and enzyme-linked immunosorbent assay, respectively. RESULTS: HPLC analysis of 61 serum samples indicated that the highest incidence of elevated OTA was found in the HCC group and was 5-fold higher than in the control group. The concentration of OTA in the HCC group ranged between 0.129 and 10.93 ng/mL with a mean value±SD of 1.1±0.3 ng/mL, while in the normal group it ranged between 0.005 and 0.50 ng/mL with a mean value±SD of 0.201±0.02 ng/mL. The odds ratio for HCC patients presenting OTA levels above the cut-off of 0.207 (calculated by the receiver operating characteristic curve was 9.78 (95% confidence interval = 2.9095-32.9816, P = 0.0002 with respect to normal controls, suggesting that HCC is 9.8 times as frequent in the exposed group to OTA. CONCLUSION: Our results reveal a strong association between the presence of OTA and HCC, which may offer a coherent explanation for much of the descriptive epidemiology of HCC and suggest new avenues for analytical research.

  6. Statin-Based Palliative Therapy for Hepatocellular Carcinoma.

    Science.gov (United States)

    Shao, Joni Yu-Hsuan; Lee, Fei-Peng; Chang, Chia-Lun; Wu, Szu-Yuan

    2015-10-01

    Most hepatocellular carcinoma (HCC) patients worldwide do not receive curative treatments. Alternative treatments for most HCC patients include palliative treatments, such as transarterial chemoembolization (TACE), chemotherapy, and radiotherapy. Although statins may be a chemopreventive treatment option for reducing hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related HCC risks, their therapeutic effects are unknown. This study evaluated the effects of statin on HCC patients receiving palliative treatment.Data from the National Health Insurance claims database and cancer registry databases of The Collaboration Center of Health Information Application, Taiwan, were analyzed. We included HCC patients who were treated between January 1, 2001, and December 31, 2010, and followed them from the index date to December 31, 2012. The inclusion criteria were presence of HBV carrier-related HCC, age >20 years, and having received TACE, radiotherapy, or chemotherapy as palliative treatment. The exclusion criteria were cancer diagnosis before HCC was confirmed, surgery, liver transplantation, radiofrequency ablation, or percutaneous ethanol injection as curative treatment, missing sex-related information, HCC diagnosis before HBV, and age palliative treatment with and without statin use, respectively. HCC patients who received palliative treatment with statin use had lower HCC-specific deaths in all stages than those who received palliative treatment without statin use (P = 0.0001, 0.0002, 0.0012, and 0.0002, and relative risk (RR) = 0.763, 0.775, 0.839, and 0.718, for stages I-IV, respectively). In all-cause and HCC-specific deaths, decreasing trends (P for trend palliative treatment only, and palliative treatment plus statin use. The aHRs of all-cause and HCC-specific deaths increased with the progress in cancer stage and reduced with the use of advanced therapeutic modalities (P for trend Palliative treatments are critical for HCC patients. Multiple therapeutic

  7. A synchronous hepatocellular carcinoma and renal cell carcinoma treated with radio-frequency ablation

    Directory of Open Access Journals (Sweden)

    Yoon Serk Lee

    2014-09-01

    Full Text Available Radio-frequency ablation (RFA is a curative treatment for hepatocellular carcinoma (HCC. Percutaneous RFA has been shown to be beneficial for patients with small renal cell carcinoma (RCC lacking indications for resection. We experienced the case of a 53-year-old male who had conditions that suggested HCC, RCC, and alcoholic liver cirrhosis. Abdominal contrast-enhanced computed tomography (CT and magnetic resonance image showed liver cirrhosis with 2.8 cm ill-defined mass in segment 2 of the liver and 1.9 cm hypervascular mass in the left kidney. These findings were compatible with the double primary cancers of HCC and RCC. Transarterial chemoembolization (TACE was performed to treat the HCC. After the TACE, a focal lipiodol uptake defect was noticed on a follow up CT images and loco-regional treatment was recommended. Therefore, we performed RFAs to treat HCC and RCC. There was no evidence of recurrence in the follow up image after 1 month.

  8. Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Alarifi S

    2013-02-01

    Full Text Available Saud Alarifi,1 Daoud Ali,1 Saad Alkahtani,1 Maqsood A Siddiqui,2 Bahy A Ali2,31Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 2DNA Research Chair, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 3Genetic Engineering & Biotechnology Research Institute City for Scientific Research and Technology Applications, Alexandria, EgyptBackground: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells.Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl-2, 5-diphenyl tetrazolium bromide and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01 reduction in glutathione (15.67% and 26.52%, with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01, superoxide dismutase (76.42% and 81.09%; P < 0.01, catalase (73.33% and 76.47%; P < 0.01, and reactive oxygen species generation (44.04% and 56.14%; P < 0.01 after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01 induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide.Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.Keywords: arsenic trioxide, DNA damage, hepatocellular carcinoma

  9. Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

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    Tarek, Marwa; Louka, Manal Louis; Khairy, Eman; Ali-Labib, Randa; Zakaria Zaky, Doaa; Montasser, Iman F

    2017-05-01

    There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

  10. MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma.

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    Yin-Hung Chu

    Full Text Available BACKGROUND: Micro RNAs (miRNAs are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: A total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a (rs2910164, miRNA149 (rs2292832, miRNA196 (rs11614913, and miRNA499 (rs3746444 genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88-4.30. In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52-8.70; AOR = 3.38, 95% CI = 1.68-6.80. CONCLUSIONS: These results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility.

  11. The Silencing of Pokemon Attenuates the Proliferation of Hepatocellular Carcinoma Cells In Vitro and In Vivo by Inhibiting the PI3K/Akt Pathway

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    Chan-Chan Lin; Jing-Ping Zhou; Yun-Peng Liu; Jing-Jing Liu; Xiao-Ning Yang; Amarsanaa Jazag; Zhi-Ping Zhang; Bayasi Guleng; Jian-Lin Ren

    2012-01-01

    Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell prolifer...

  12. The association of Schistosoma mansoni infection with hepatocellular carcinoma

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    Fausto Edmundo Lima Pereira

    1984-06-01

    Full Text Available The association of Schistosoma mansoni infection with hepatocellular carcinoma (HCC was studied in Espirito Santo State, Brazil. Schistosoma infection was diagnosed by stool examinations or by histological finding at autopsy. HCC was diagnosed by biopsy, laparoscopy and biopsy or at autopsy. Among 45 cases of HCC six had Schistosoma mansoni infection (13.04%. The occurrence of Schistosoma infection among HCC HBs Ag positive or negative was similar (13.3 3% and 13.63% respectively. The chi squared comparison showed no significant differences between the frequency of schistosomiasis in patients with HCC and the frequency of Schistosoma infection among people living in the Espirito Santo State (5.9% among children of elementary school from all the counties of the State and 6.7% in people that attended medical care in Vitoria, the capital of the State. Therefore, the authors believe that the association of schistosomiasis mansoni with HCC may be casual, specially in areas where the Schistosoma mansoni infection is frequent.Foi estudada a associação de infecção pelo Schistosoma mansoni em pacientes portadores de carcinoma hepatocelular (CHC diagnosticados no Espírito Santo. O diagnóstico de esquistossomosefoi feito pelo exame parasitológico das fezes ou pelos achados histológicos à necrópsia. O diagnóstico de CHC foi feito por laparoscopia e biópsia, somente biópsia ou por necrópsia. Entre 45 casos de CHC, seis apresentavam infecção pelo S. mansoni (13,04%. A ocorrência de infecção esquistossomótica nos CHC HBsAg positivos ou negativos foi semelhante (13,33 e 13,63% respectivamente. A comparação pelo método do qui quadrado não mostrou diferença significativa entre a freqüência de infeccção esquistossomótica nos pacientes com CHC e a freqüência de esquistossomose na população que vive no E. Santo (5,97% entre crianças do curso primário de todas as regiões do Estado e 6,75% entre a população que procura recursos m

  13. Motile hepatocellular carcinoma cells preferentially secret sugar metabolism regulatory proteins via exosomes.

    Science.gov (United States)

    Zhang, Jing; Lu, Shaohua; Zhou, Ye; Meng, Kun; Chen, Zhipeng; Cui, Yizhi; Shi, Yunfeng; Wang, Tong; He, Qing-Yu

    2017-07-01

    Exosomes are deliverers of critically functional proteins, capable of transforming target cells in numerous cancers, including hepatocellular carcinoma (HCC). We hypothesize that the motility of HCC cells can be featured by comparative proteome of exosomes. Hence, we performed the super-SILAC-based MS analysis on the exosomes secreted by three human HCC cell lines, including the non-motile Hep3B cell, and the motile 97H and LM3 cells. More than 1400 exosomal proteins were confidently quantified in each MS analysis with highly biological reproducibility. We justified that 469 and 443 exosomal proteins represented differentially expressed proteins (DEPs) in the 97H/Hep3B and LM3/Hep3B comparisons, respectively. These DEPs focused on sugar metabolism-centric canonical pathways per ingenuity pathway analysis, which was consistent with the gene ontology analysis on biological process enrichment. These pathways included glycolysis I, gluconeogenesis I and pentose phosphate pathways; and the DEPs enriched in these pathways could form a tightly connected network. By analyzing the relative abundance of proteins and translating mRNAs, we found significantly positive correlation between exosomes and cells. The involved exosomal proteins were again focusing on sugar metabolism. In conclusion, motile HCC cells tend to preferentially export more sugar metabolism-associated proteins via exosomes that differentiate them from non-motile HCC cells. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. MNT inhibits the migration of human hepatocellular carcinoma SMMC7721 cells

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    Wu, Jian [Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 ZhongShan 2nd Road, Guangzhou, Guangdong 510080 (China); Zhou, Qi, E-mail: Zhouqi197195@126.com [Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 ZhongShan 2nd Road, Guangzhou, Guangdong 510080 (China); Wang, Yafeng; Zhou, Xiangbing [Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 ZhongShan 2nd Road, Guangzhou, Guangdong 510080 (China); Li, Jiaping, E-mail: Jpli3s@126.com [Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, 58 ZhongShan 2nd Road, Guangzhou, Guangdong 510080 (China)

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer MNT is a member of the Myc/Max/Mad network that plays a role in cell proliferation. Black-Right-Pointing-Pointer Our study further emphasized the role of MNT in migration inhibition of SMMC7721 cells. Black-Right-Pointing-Pointer MNT might be a promising target for HCC chemotherapy. -- Abstract: Max binding protein (MNT) is a member of the Myc/Max/Mad network that plays a role in cell proliferation, differentiation and apoptosis. We previously observed that MNT was differentially expressed in hepatocellular carcinoma (HCC) and interacted with Nck1 by 2-DE. Nck family adaptor proteins function to couple tyrosine phosphorylation signals, regulate actin cytoskeletal reorganization and lead to cell motility. In order to investigate the regulatory role of MNT in HCC migration, we used transient transfection with a MNT expressing vector to overexpress MNT protein in SMMC7721 cells, and MNT siRNA to knockdown MNT expression. Rho Family Small GTPase activation assay, Western blots and transwell assay were used to determine the migration potential of cells. We found that knockdown of MNT expression might promote SMMC7721 cell migration, while the overexpressed MNT could significantly inhibit cell migration. It further emphasized the role of MNT in inhibition of cell migration that might be a promising target for HCC chemotherapy.

  15. Gene Expression Profile Related to the Progression of Preneoplastic Nodules toward Hepatocellular Carcinoma in Rats

    Directory of Open Access Journals (Sweden)

    Julio Isael Pérez-Carréon

    2006-05-01

    Full Text Available In this study, we investigated the time course gene expression profile of preneoplastic nodules and hepatocellular carcinomas (HCC to define the genes implicated in cancer progression in a resistant hepatocyte model. Tissues that included early nodules (1 month, ENT-1, persistent nodules (5 months, ENT-5, dissected HCC (12 months, and normal livers (NIL from adult rats were analyzed by cDNA arrays including 1185 rat genes. Differential genes were derived in each type of sample (n = 3 by statistical analysis. The relationship between samples was described in a Venn diagram for 290 genes. From these, 72 genes were shared between tissues with nodules and HCC. In addition, 35 genes with statistical significance only in HCC and with extreme ratios were identified. Differential expression of 11 genes was confirmed by comparative reverse transcription-polymerase chain reaction, whereas that of 2 genes was confirmed by immunohistochemistry. Members involved in cytochrome P450 and second-phase metabolism were downregulated, whereas genes involved in glutathione metabolism were upregulated, implicating a possible role of glutathione and oxidative regulation. We provide a gene expression profile related to the progression of nodules into HCC, which contributes to the understanding of liver cancer development and offers the prospect for chemoprevention strategies or early treatment of HCC.

  16. The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Robert Fisher

    2012-09-01

    Full Text Available Hepatocellular carcinoma (HCC remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55% genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC.

  17. 3D analysis of apparent diffusion coefficient histograms in hepatocellular carcinoma: correlation with histological grade.

    Science.gov (United States)

    Moriya, Tomohisa; Saito, Kazuhiro; Tajima, Yu; Harada, Taiyo L; Araki, Yoichi; Sugimoto, Katsutoshi; Tokuuye, Koichi

    2017-01-05

    To evaluate the usefulness of differentiation of histological grade in hepatocellular carcinoma (HCC) using three-dimensional (3D) analysis of apparent diffusion coefficient (ADC) histograms retrospectively. The subjects consisted of 53 patients with 56 HCCs. The subjects included 12 well-differentiated, 35 moderately differentiated, and nine poorly differentiated HCCs. Diffusion-weighted imaging (b-values of 100 and 800 s/mm(2)) were obtained within 3 months before surgery. Regions of interest (ROIs) covered the entire tumor. The data acquired from each slice were summated to derive voxel-by-voxel ADCs for the entire tumor. The following parameters were derived from the ADC histogram: mean, standard deviation, minimum, maximum, mode, percentiles (5th, 10th, 25th, 50th, 75th, and 90th), skew, and kurtosis. These parameters were analyzed according to histological grade. After eliminating steatosis lesions, these parameters were re-analyzed. A weak correlation was observed in minimum ADC and 5th percentile for each histological grade (r = -0.340 and r = -0.268, respectively). The minimum ADCs of well, moderately, and poorly differentiated HCC were 585 ± 388, 411 ± 278, and 235 ± 102 × 10(-6) mm(2)/s, respectively. Minimum ADC showed significant differences among tumor histological grades (P = 0.009). The minimum ADC of poorly differentiated HCC and that of combined well and moderately differentiated HCC were 236 ± 102 and 437 ± 299 × 10(-6) mm(2)/s. The minimum ADC of poorly differentiated HCC was significantly lower than that of combined well and moderately differentiated HCC (P = 0.001). The sensitivity and specificity, when a minimum ADC of 400 × 10(-6) mm(2)/s or lower was considered to be poorly differentiated HCC, were 100 and 54%, respectively. After exclusion of the effect of steatosis, the sensitivity and specificity did not change, although the statistical differences became strong (P < 0

  18. [The effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma patients].

    Science.gov (United States)

    Huang, Cheng; Fan, Jia; Zhou, Jian; Liu, Yin-kun; Cui, Jie-feng

    2006-04-01

    To investigate the effects of different clinicopathologic variables on serum protein fingerprint in hepatocellular carcinoma (HCC) patients. Serum samples were collected from 112 HCC patients, Special serum protein or peptide spectra was determined by surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) measurement after treating the sample onto weak cation exchange (WCX2) protein chip for each case. The serum protein profiles were compared by BioMarker Wizard Software among the patients stratified according to gender, AFP, presence of portal vein tumor thrombus (PVTT), tumor size, tumor number, presence of cirrhosis, respectively. According to serum protein fingerprints of 112 HCC patients, a total of 100 protein peaks were identified at the m/z value ranging from 1100 to 30,000. (1) Sixteen significant differential proteins were found between the groups of HCC with single tumor and those with multiple tumors (P 3 cm and those with tumor size 5 cm and those with tumor size 10 cm and those with tumor size differential proteins were found between the groups of macroscopic portal vein tumor thrombus (Ma-PVTT) and those without PVTT (N-PVTT); Only 2 significant differential protein were found between the groups of microscopic portal vein tumor thrombus (Mi-PVTT) and N-PVTT (P < 0.01); eight significant differential proteins were found between the groups of Ma-PVTT and Mi-PVTT (P < 0.01). (4) No significant differential protein was found when patients stratified according to gender, presence of cirrhosis and AFP. PVTT, tumor number and tumor size had significant effects on serum protein fingerprint, while no significant effect on serum protein from gender, presence of cirrhosis and AFP. The most profound impact on the serum protein was attained when cutoff was chosen to be presence of Ma-PVTT compared to less effect from Mi-PVTT and 5cm for tumor size.

  19. Specific expression of osteopontin and S100A6 in hepatocellular carcinoma.

    Science.gov (United States)

    Hua, Zhan; Chen, Jingzhou; Sun, Baishun; Zhao, Gonghua; Zhang, Yuanchun; Fong, Yuman; Jia, Zhengeng; Yao, Li

    2011-06-01

    Our aim was to identify differential expression of genes in hepatocellular carcinoma (HCC) with the ultimate goal of discovering novel diagnostic and therapeutic targets. We examined differences in gene expression between HCC and noncancerous liver tissue using a cDNA array with probes for 15,843 genes/clones. Two genes, osteopontin (OPN) and S100A6, were found to be >10-fold differentially expressed, and were selected for further immunohistochemical staining in 51 HCC and 10 nonmalignant liver specimens. The relation between OPN and S100A6 alterations and various clinicopathologic parameters was also evaluated. We found a total of 219 genes that were differentially expressed >3-fold. Of these, 109 were upregulated and 110 downregulated. Within this group, 123 genes, including 59 upregulated and 64 downregulated, had been identified previously. These known genes were mainly involved in cell migration, cytoskeleton dynamics, the signaling pathway and cell cycle, and metabolism. OPN expression and S100A6 expression were seen in 26 of 51 (51.0 %) and 16 of 51 (31.4 %) HCC samples, respectively. More importantly, proteins coded by these genes were not found in any noncancerous liver specimen by immunohistochemical analysis. Expression of these genes correlated with poor differentiation (OPN: P = .013; S100A6: P = .008). OPN, a secreted phosphoprotein that has been increasingly implicated in the progression and metastasis of cancer, and S100A6, a member of the S100 protein family that can perform cell proliferation, differentiation, migration, and cytoskeletal dynamics, may be promising diagnostic markers and therapeutic targets for HCC. In addition, the results encourage future studies involving the roles of these proteins in the development and progression of this cancer. Copyright © 2011 Mosby, Inc. All rights reserved.

  20. Manganese-enhanced MRI predicts the histological grade of hepatocellular carcinoma in potential surgical candidates

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    Sutcliffe, R.P. [Institute of Liver Studies, King' s College Hospital, London (United Kingdom); Lewis, D.; Kane, P.A. [Department of Radiology, King' s College Hospital, London (United Kingdom); Portmann, B.C.; O' Grady, J.G. [Institute of Liver Studies, King' s College Hospital, London (United Kingdom); Karani, J.B. [Department of Radiology, King' s College Hospital, London (United Kingdom); Rela, M. [Institute of Liver Studies, King' s College Hospital, London (United Kingdom); Heaton, N.D., E-mail: Nigel.Heaton@kch.nhs.u [Institute of Liver Studies, King' s College Hospital, London (United Kingdom)

    2011-03-15

    Aim: To evaluate the role of manganese-enhanced magnetic resonance (Mn-MRI) in predicting tumour differentiation prior to liver transplant or resection for hepatocellular carcinoma (HCC). Materials and methods: The inclusion criteria were patients with HCC who underwent Mn-MRI prior to transplantation or resection from 2001-2008. T1-weighted MRI images were acquired at 0 and 24 h after manganese dipyridoxal diphosphate (MnDPDP) intravenous contrast medium and reviewed prospectively. Manganese retention at 24 h was correlated with tumour differentiation and disease-free survival. Results: Eighty-six patients underwent Mn-MRI (transplantation 60, resection 26); 114/125 lesions (91%) that were arterialised as evidenced at computed tomography (CT) and had manganese uptake on MRI were HCC. There were 11 false positives (9%) that were regenerative nodules. Ten of fourteen non-manganese-retaining HCC (71%) were poorly differentiated, compared with only 13/114 manganese-retaining HCC (11%) (p < 0.0001). Sensitivity, specificity, positive and negative predictive values of non-retention of MnDPDP in predicting poorly differentiated tumours were 0.43, 0.96, 0.71 and 0.88. Median disease-free survival of patients with non-manganese-retaining HCC was less than for patients with manganese-retaining HCC (14 {+-} 5 months versus 39 {+-} 3 months, log rank p = 0.025). Conclusion: Non-manganese-retaining HCCs are likely to be poorly differentiated and have a poor prognosis. Manganese-enhanced MRI appears to have a role in preoperative assessment of HCC and warrants further evaluation.

  1. From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Hong Yang

    2017-03-01

    Full Text Available Background Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. Methods Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values. Results A list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, ‘pathways in cancer,’ was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982–0.998], P < 0.001, sensitivity: 96.0%, specificity: 96.5%. BIRC5 (P = 0.021 and CCNE1 (P = 0.027 were associated with poor prognosis, while CDKN2A (P = 0.066 and E2F1 (P = 0.088 demonstrated no statistically significant differences. Discussion The study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, ‘pathways in cancer.’ The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be

  2. Induction of hepatocellular carcinoma in mice and the role of melatonin

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    Ashour A. Abdel-Mawla

    2013-08-01

    Full Text Available 2-Nitropropane (2-NP is suggested to be a human carcinogen, a genotoxicant and hepatocarcinogen in rodents. The present study was designed to evaluate the role of melatonin (Mel as an anticancerous agent in hepatocellular carcinoma (HCC induced by 2-NP. Forty eight male Swiss albino mice were divided into 5 groups. Group I, II and III served as controls. Group IV was injected IP with 2-NP every other day for 14 weeks. Group V was injected IP with melatonin 30 min prior to 2-NP injection. Mice were sacrificed after 4, 8 and 14 weeks. Histopathological results showed poorly differentiated HCC; pleomorphic atypical hepatocytes after 8 weeks of receiving 2-NP. Proliferating streaks and cords of malignant hepatocytes were prominent after 14 weeks of 2-NP injection. (Mel + 2-NP treatment revealed histological features more or less similar to normal control with dilated sinusoids, evidence of apoptosis, eosinophilic cytoplasm, few large necrotic cells, microsteatosis and well defined Kupffer cells. Histochemically, group IV showed continuous decrease in catalase activity and very weak activity was reached after 14 weeks. In group V, marked and moderate catalase activity was observed after 4 and 8 weeks, respectively as well as marked diffused reaction after 14 weeks. Immunohistochemically, PCNA and VEGF expressions were significantly increased in group IV and this increment was time dependant. Decreased numbers of PCNA and VEGF expressions in group V were seen as compared with their counterparts. It was concluded that 2-NP was a hepatocellular carcinogen in mice and melatonin exerted its anticancerous role through its antiproliferative and antiangiogenic effects.

  3. A discussion of serum albumin level in advanced-stage hepatocellular carcinoma: a medical oncologist's perspective.

    Science.gov (United States)

    Tanriverdi, Ozgur

    2014-11-01

    Hepatocellular carcinoma is the most common primary malignant tumor of the liver, and it is particularly prevalent in East and Southeast Asia. With surgical and/or local interventional treatment methods, survival rates for early-stage hepatocellular cancers have increased. However, it is not yet clear which staging systems are more applicable in hepatocellular carcinoma. Serum albumin level is already being used as a criterion in most staging systems. Albumin is an important serum protein in human bodily functions, but only 5 % of the daily amount needed is synthesized by the liver. The serum albumin level is affected by multifactorial situations, including capillary permeability, drugs, liver insufficiency, inflammation and/or infections, dehydration or overhydration, protein loosing disorders, and decreased nutrition intake in anorexia-malnutrition syndrome and cancer cachexia. Because of this complex situation, serum albumin level may affect many staging systems for hepatocellular carcinoma by leading to false-negative results. In this paper, the statuses of current staging systems are reviewed, and possible negative events regarding the serum albumin levels found in these staging systems are discussed.

  4. Anticancer and cytotoxic properties of the latex of Calotropis procera in a transgenic mouse model of hepatocellular carcinoma

    OpenAIRE

    Choedon, Tenzin; Mathan, Ganeshan; Arya, Soneera; Kumar, Vijay L.; Kumar, Vijay

    2006-01-01

    AIM: To evaluate the anticancer property of the dried latex (DL) of Calotropis procera, a tropical medicinal plant, in the X15-myc transgenic mouse model of hepatocellular carcinoma and to elucidate its mechanism of action in cell culture.

  5. Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

    NARCIS (Netherlands)

    Geissler, Edward K.; Schnitzbauer, Andreas A.; Zuelke, Carl; Lamby, Philipp E.; Proneth, Andrea; Duvoux, Christophe; Burra, Patrizia; Jauch, Karl-Walter; Rentsch, Markus; Ganten, Tom M.; Schmidt, Jan; Settmacher, Utz; Heise, Michael; Rossi, Giorgio; Cillo, Umberto; Kneteman, Norman; Adam, Rene; van Hoek, Bart; Bachellier, Philippe; Wolf, Philippe; Rostaing, Lionel; Bechstein, Wolf O.; Rizell, Magnus; Powell, James; Hidalgo, Ernest; Gugenheim, Jean; Wolters, Heiner; Brockmann, Jens; Roy, Andre; Mutzbauer, Ingrid; Schlitt, Angela; Beckebaum, Susanne; Graeb, Christian; Nadalin, Silvio; Valente, Umberto; Sanchez Turrion, Victor; Jamieson, Neville; Scholz, Tim; Colledan, Michele; Faendrich, Fred; Becker, Thomas; Soderdahl, Gunnar; Chazouilleres, Olivier; Makisalo, Heikki; Pageaux, Georges-Philippe; Steininger, Rudolf; Soliman, Thomas; de Jong, Koert P.; Pirenne, Jacques; Margreiter, Raimund; Pratschke, Johann; Pinna, Antonio D.; Hauss, Johann; Schreiber, Stefan; Strasser, Simone; Klempnauer, Juergen; Troisi, Roberto I.; Bhoori, Sherrie; Lerut, Jan; Bilbao, Itxarone; Klein, Christian G.; Koenigsrainer, Alfred; Mirza, Darius F.; Otto, Gerd; Mazzaferro, Vincenzo; Neuhaus, Peter; Schlitt, Hans J.

    Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target

  6. Adverse genomic alterations and stemness features are induced by field cancerization in the microenvironment of hepatocellular carcinomas

    DEFF Research Database (Denmark)

    Castven, Darko; Fischer, Michael; Becker, Diana

    2017-01-01

    Hepatocellular Carcinoma (HCC) commonly develops in chronically damaged liver tissues. The resulting regenerative and inflammatory processes create an adverse milieu that promotes tumor-initiation and progression. A better understanding of the hepatic tumor-microenvironment interaction might infe...

  7. The Effectiveness of Ultrasound Surveillance for Hepatocellular Carcinoma in a Canadian Centre and Determinants of Its Success

    Directory of Open Access Journals (Sweden)

    Korosh Khalili

    2015-01-01

    Full Text Available BACKGROUND: The effectiveness of surveillance for hepatocellular carcinoma (HCC using ultrasound (US in North America has been questioned due to the predominance of patients of Caucasian ethnicity and larger body habitus.

  8. Solid papillary breast carcinoma with mucinous differentiation

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    Kostov Miloš

    2003-01-01

    Full Text Available A case is reported of a solid variant of infiltrating papillary carcinoma of the breast with mucinous differentiation in a 74-year-old woman. Macroscopically, the tumor was solid and lobular, 4.5 cm in diameter. Light microscopy showed solid papillary invasive carcinoma mixed with infiltrating ductal carcinoma, not otherwise specified. Abundant intracellular and extracellular acid mucin produced by the solid papillary tumor cells was proven histochemically by: PAS, PAS-D, mucicarmine and alcian blue. Immunohistochemically, the papillary carcinoma cells were strongly reactive to estrogen receptors, and weakly to moderately reactive to smooth muscle actin. We suggest that papillary carcinoma of the breast could have potentially high degree of aggressiveness, and that differential diagnosis of these rare tumors might be a histopathological problem.

  9. Anti Cancerous Efficacy of Ayurvedic Milk Extract of Semecarpus Anacardium Nuts on Hepatocellular Carcinoma in Wistar Rats

    OpenAIRE

    Joseph, Joice P; Raval, Sunant K.; Sadariya, Kamlesh A.; Jhala, Mayur; Kumar, Pranay

    2013-01-01

    The objective of the study was to determine the anticancerous efficacy of Ayurvedic preparation made of Semecarpus anacardium (SA) nuts. Five groups of rats were used for the study. Group I served as water control. Hepatocellular carcinoma (HCC) was induced in groups II, III and IV animals using N-nitrosodiethylamine as inducing agent followed by phenobarbitone as promoter for 13 weeks. Group-II animals were kept untreated as hepatocellular carcinoma control. Group-III animals were treated wi...

  10. Validation and ranking of seven staging systems of hepatocellular carcinoma.

    Science.gov (United States)

    Chen, Zhan-Hong; Hong, Ying-Fen; Lin, Jinxiang; Li, Xing; Wu, Dong-Hao; Wen, Jing-Yun; Chen, Jie; Ruan, Dan-Yun; Lin, Qu; Dong, Min; Wei, Li; Wang, Tian-Tian; Lin, Ze-Xiao; Ma, Xiao-Kun; Wu, Xiang-Yuan; Xu, Ruihua

    2017-07-01

    The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0

  11. Radiofrequency thermal ablation of hepatocellular carcinoma: using contrast-enhanced harmonic power doppler sonography to assess treatment outcome.

    Science.gov (United States)

    Cioni, D; Lencioni, R; Rossi, S; Garbagnati, F; Donati, F; Crocetti, L; Bartolozzi, C

    2001-10-01

    We evaluated the accuracy of contrast-enhanced harmonic power Doppler sonography in assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma. Fifty patients with 65 hepatocellular carcinoma nodules (1-5 cm in diameter; mean diameter, 2.5 cm) were studied using unenhanced and contrast-enhanced harmonic power Doppler sonography before and after IV administration of a microbubble contrast agent. The examinations were repeated after treatment of the tumors with radiofrequency ablation. Findings of the Doppler studies were compared with those of dual-phase helical CT, which were used as points of reference for assessing treatment outcome. Before radiofrequency treatment, intratumoral blood flow was revealed by unenhanced power Doppler sonography in 48 (74%) of 65 hepatocellular carcinoma nodules. After injection of the contrast agent, intratumoral enhancement was observed in 61 (94%) of 65 hepatocellular carcinomas (p enhancement on power Doppler sonograms. In nine of the 10 lesions that showed a residual viable tumor on helical CT scans, persistent intratumoral enhancement-matching the enhancing areas on helical CT images-was revealed by power Doppler sonography. These nine hepatocellular carcinomas were subjected to repeated radiofrequency thermal ablation with the guidance of contrast-enhanced power Doppler sonography. Complete necrosis was seen after the second treatment session in six of the nine lesions. Contrast-enhanced harmonic power Doppler sonography is an accurate technique for assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma and may be useful in guiding additional treatment in patients with incomplete response to initial efforts.

  12. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Edward Wolfgang; Alanis, Lourdes [Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Cho, Sung-Ki [Division of Interventional Radiology, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Saab, Sammy [Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA 90024 (United States)

    2016-11-01

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

  13. Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Edward Wolfgang; Alanic, Lourdes [Div. of Interventional Radiology, Dept. of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles (United States); Cho, Sung Ki [Div. of Interventional Radiology, Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Saab, Sammy [Div. of Hepatology, Dept. of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles (United States)

    2016-07-15

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

  14. Chromatin assembly factor 1, subunit A (P150 facilitates cell proliferation in human hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Xu M

    2016-07-01

    Full Text Available Meng Xu, Yuli Jia, Zhikui Liu, Linglong Ding, Run Tian, Hua Gu, Yufeng Wang, Hongyong Zhang, Kangsheng Tu, Qingguang Liu Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China Abstract: Several studies have revealed that the abnormal expression of chromatin assembly factor 1, subunit A (P150 (CHAF1A was involved in the development of some types of malignant tumors. However, CHAF1A expression and its role in hepatocellular carcinoma (HCC remain poorly characterized. In this study, we first investigated CHAF1A expression in six cell lines and 116 pairs of HCC and matched normal tumor-adjacent tissues to evaluate the clinicopathological characteristics of CHAF1A in HCC. Then, we detected the proliferation and apoptosis in HCC cells. In addition, a subcutaneous tumor model in nude mice was performed to evaluate tumor growth in vivo. We found that the expression of CHAF1A was significantly higher in HCC tissues than that in adjacent nontumor tissues (P<0.01. Clinical analysis indicated that CHAF1A expression was significantly correlated with the tumor–node–metastasis stage, tumor number, and tumor differentiation in HCC tissues (P<0.05, respectively. We also found that CHAF1A may potentially function as a poor prognostic indicator for 5-year overall and disease-free survival in patients with HCC (P<0.05, respectively. The elevated expression of CHAF1A was also observed in HCC cell lines compared with that in normal LO2 hepatic cell line (P<0.01. HCC cancer cells exhibited inhibition of cell growth, reduction in colony-formation ability, increased cell apoptosis rate, and impaired tumorigenicity in nude mice after CHAF1A knockdown. Collectively, we propose that CHAF1A by potentially mediating cancer cell proliferation plays an imp