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Sample records for cancer hepatocellular carcinoma

  1. 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

  2. Hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Farooqi, J.I.; Farooqi, R.J.

    2001-01-01

    Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC. (author)

  3. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... for the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching...... of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma...

  4. Dynamic CT of hepatocellular carcinoma

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    Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

    1983-03-01

    We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. Detecting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. The dynamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma.

  5. Dynamic CT of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

    1983-01-01

    We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. 1 Decting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. 2 The dinamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. 3 The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma. (author)

  6. 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

  7. Radiosensitivity of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hennequin, C.; Quero, L.; Rivera, S.

    2011-01-01

    The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

  8. Histopathology of hepatocellular carcinoma.

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    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.

  9. 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...

  10. Metastatic breast cancer to the liver with hepatoid features and Hep Par 1 antibody positive mimicking hepatocellular carcinoma.

    Science.gov (United States)

    Affleck, Authur; Lyman, William B; Jacobs, W Carl; Livasy, Chad A; Martinie, John B; Iannitti, David A; Vrochides, Dionisios

    2018-05-09

    The hepatocyte paraffin 1 antibody (Hep Par 1) has a high positive predictive value for differentiating hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma. 1 We report a case of metastatic breast cancer to the liver with hepatoid histology and strong positive staining for Hep Par 1 mimicking hepatocellular carcinoma. To our knowledge, primary breast carcinoma staining Hep Par 1 positive has not been reported in the setting of hepatic metastasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. 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

  12. 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

  13. Clinical analysis of electroacupuncture and multiple acupoint stimulation in relieving cancer pain in patients with advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lili Xu

    2018-01-01

    Conclusion: Cancer pain in patients with advanced hepatocellular carcinoma can be alleviated with electroacupuncture and multiple acupoint stimulation, but the onset pain relief was slow. To improve the analgesic effects of this technique, the combination of various analgesic methods should be necessary in early stage of the treatment.

  14. Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... Treatment Liver Cancer Prevention Liver Cancer Screening Research Liver (Hepatocellular) Cancer Screening (PDQ®)–Patient Version What is ... These are called diagnostic tests . General Information About Liver (Hepatocellular) Cancer Key Points Liver cancer is a ...

  15. Viral hepatitis and hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Juei-Low, Sung [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Department of Internal Medicine; Ding-Shinn, Chen [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Hepatitis Research Center National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Graduate Institute of Clinical Medicine

    1990-01-01

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

  16. Viral hepatitis and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Sung Juei-Low; Chen Ding-Shinn

    1990-01-01

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

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

    International Nuclear Information System (INIS)

    Suetsugu, Atsushi; Nagaki, Masahito; Aoki, Hitomi; Motohashi, Tsutomu; Kunisada, Takahiro; Moriwaki, Hisataka

    2006-01-01

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

  18. CT of hepatocellular carcinoma

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    Nakamura, H; Tanaka, T; Sai, H; Kawamoto, S; Morimoto, K [Osaka Univ. (Japan). Faculty of Medicine

    1982-06-01

    CT was investigated in 125 cases of hepatocelluar carcinoma and 47 cases of metastatic hepatic neoplasm. The entire contour of each tumor was traced and the average CT value in the tumor was estimated. As a result, the CT value for hepatocellular carcinoma tended to be higher on plain CT and also after contrast enhancement. The CT findings seen frequently were as follows: capsule in 76 cases (60.8%) and septum in 67 cases (53.6%); tumor thrombus in portal vein in 39 cases (31.2%) and that in inferior vena cava in 3 cases (2.4%); localized enlargement of hepatic bile duct in 24 cases (19.2%). These findings were rarely seen in the cases of metastatic hepatic neoplasm. As a relatively outstanding feature of hepatic metastases, a double contour, like concentric circles or contour lines, with a relatively large inner circle or contour line, was found in 21 cases (44.7%). By paying attention to the change of CT value on contrast enhancement and the characteristic image of each case, hepatocellular carcinoma could be differentiated from metastatic hepatic neoplasm with high probability.

  19. Ultrasound manifestation of hepatocellular carcinoma

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    Hwang, M S; Yoo, H S; Park, C Y; Choi, H J; Moon, Y M; Lee, S I [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1982-06-15

    With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns.

  20. Ultrasound manifestation of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hwang, M. S.; Yoo, H. S.; Park, C. Y.; Choi, H. J.; Moon, Y. M.; Lee, S. I.

    1982-01-01

    With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns

  1. Polymeric nanoparticles as cancer-specific DNA delivery vectors to human hepatocellular carcinoma.

    Science.gov (United States)

    Zamboni, Camila G; Kozielski, Kristen L; Vaughan, Hannah J; Nakata, Maisa M; Kim, Jayoung; Higgins, Luke J; Pomper, Martin G; Green, Jordan J

    2017-10-10

    Hepatocellular carcinoma (HCC) is the third most deadly cancer in the US, with a meager 5-year survival rate of effective and cancer-specific DNA delivery to human HCC using biodegradable poly(beta-amino ester) (PBAE) nanoparticles (NPs). Varied PBAE NP formulations were evaluated for transfection efficacy and cytotoxicity to a range of human HCC cells as well as healthy human hepatocytes. To address HCC heterogeneity, nine different sources of human HCC cells were utilized. The polymeric NPs composed of 2-((3-aminopropyl)amino) ethanol end-modified poly(1,5-pentanediol diacrylate-co-3-amino-1-propanol) ('536') at a 25 polymer-to-DNA weight-to-weight ratio led to high transfection efficacy to all of the liver cancer lines, but not to hepatocytes. Each individual HCC line had a significantly higher percentage of exogenous gene expression than the healthy liver cells (Peffective DNA transfection in vivo. PBAE-based NPs enabled high and preferential DNA delivery to HCC cells, sparing healthy hepatocytes. These biodegradable and liver cancer-selective NPs are a promising technology to deliver therapeutic genes to liver cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    Science.gov (United States)

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  3. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    Science.gov (United States)

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  4. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

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

    2009-01-01

    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...

  5. Research progress of vascular change after TACE in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kang Zhen; Xiao Enhua

    2013-01-01

    Mortality rate of hepatocellular carcinoma is high. The majority of the patients are diagnosed in advanced stage and lose surgical opportunities. Many studies have reported transcatheter arterial chemoembolization (TACE) is an effective treatment for unresectable hepatocellular carcinoma, and recommended TACE as a standard treatment for hepatocellular carcinoma of Barcelona Clinical Liver Cancer staging (BCLC staging) B. However, TACE can hardly fully embolize tumor blood supply, TACE postoperative hemodynamics and angiogenesis can induce tumor recurrence and metastasis. This paper reviewed characteristics of vascular changes, mechanisms, diagnosis and treatment methods, new progress in the field of hepatocellular carcinoma after TACE. (authors)

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

    International Nuclear Information System (INIS)

    Cao, Lu; Wu, Mengchao; Zhang, Ying; Su, Changqing; Li, Chunguang; Shen, Shuwen; Yan, Yan; Ji, Weidan; Wang, Jinghan; Qian, Haihua; Jiang, Xiaoqing; Li, Zhigang

    2013-01-01

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

  7. Dopamine-induced SULT1A3/4 promotes EMT and cancer stemness in hepatocellular carcinoma.

    Science.gov (United States)

    Zou, Juan; Li, Hong; Huang, Qianling; Liu, Xiaomin; Qi, Xiaoxiao; Wang, Ying; Lu, Linlin; Liu, Zhongqiu

    2017-10-01

    Hepatocellular carcinoma has the second highest incidence rate among malignant cancers in China. Hepatocellular carcinoma development is complex because of the metabolism disequilibrium involving SULT1A3/4, a predominant sulfotransferase that metabolizes sulfonic xenobiotics and endogenous catecholamines. However, the correlation between SULT1A3/4 and hepatocellular carcinoma progression is unclear. By utilizing immunofluorescence and immunohistochemical analysis, we found that in nine hepatocellular carcinoma clinical specimens, SULT1A3/4 was abundantly expressed in tumor tissues compared to that in the adjacent tissues. Moreover, liver cancer cells (HepG2, MHCC97-L, and MHCC97-H) had higher basal expression of SULT1A3/4 than immortalized liver cells (L02 and Chang liver). Ultra-high-pressure liquid chromatography-tandem mass spectrometry assay results further revealed that the concentration of dopamine (a substrate of SULT1A3/4) was negatively correlated with SULT1A3/4 protein expression. As a transcriptional regulator of SULT1A3/4 in turn, dopamine was used to induce SULT1A3/4 in vitro. Interestingly, dopamine significantly induced SULT1A3/4 expression in liver cancer HepG2 cells, while decreased that in L02 cells. More importantly, the expression levels of epithelial-mesenchymal transition biomarkers (N-cadherin and vimentin) and cell stemness biomarkers (nanog, sox2, and oct3/4) considerably increased in HepG2 with dopamine-induced SULT1A3/4, whereas in L02, epithelial-mesenchymal transition and cancer stem cell-associated proteins were contrarily decreased. Furthermore, invasion and migration assays further revealed that dopamine-induced SULT1A3/4 dramatically stimulated the metastatic capacity of HepG2 cells. Our results implied that SULT1A3/4 exhibited bidirectional effect on tumor and normal hepatocytes and may thus provide a novel strategy for hepatocellular carcinoma clinical targeting. In addition, SULT1A3/4 re-expression could serve as a biomarker for

  8. Morphologic Subtypes of Hepatocellular Carcinoma.

    Science.gov (United States)

    Torbenson, Michael S

    2017-06-01

    Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Management consensus guideline for hepatocellular carcinoma: 2016 updated by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan

    Directory of Open Access Journals (Sweden)

    Sheng-Nan Lu

    2018-05-01

    Full Text Available Background: Hepatocellular carcinoma (HCC is one of the leading causes of cancer-related mortality in Taiwan. To help clinical physicians to manage patients with HCC, the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan produced the management consensus guideline for HCC. Methods: The recommendations focus on nine important issues on management of HCC, including surveillance, diagnosis, staging, surgery, local ablation, transarterial chemoembolization/transarterial radioembolization/hepatic arterial infusion chemotherapy, systemic therapy, radiotherapy, and prevention. Results: The consensus statements were discussed, debated and got consensus in each expert team. And then the statements were sent to all of the experts for further discussion and refinement. Finally, all of the experts were invited to vote for the statements, including the level of evidence and recommendation. Conclusion: With the development of the management consensus guideline, HCC patients could benefit from the optimal therapeutic modality. Keywords: Diagnosis, Hepatocellular carcinoma, Staging, Surveillance, Treatment

  10. Targeted Regression of Hepatocellular Carcinoma by Cancer-Specific RNA Replacement through MicroRNA Regulation.

    Science.gov (United States)

    Kim, Juhyun; Won, Ranhui; Ban, Guyee; Ju, Mi Ha; Cho, Kyung Sook; Young Han, Sang; Jeong, Jin-Sook; Lee, Seong-Wook

    2015-07-20

    Hepatocellular carcinoma (HCC) has a high fatality rate and limited therapeutic options with side effects and low efficacy. Here, we proposed a new anti-HCC approach based on cancer-specific post-transcriptional targeting. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically induce therapeutic gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC. The ribozyme activity in vivo was assessed in mouse models orthotopically implanted with HCC. Systemic administration of adenovirus encoding the developed ribozymes caused efficient anti-cancer effect and the least hepatotoxicity with regulation of ribozyme expression by miR-122a in both xenografted and syngeneic orthotopic murine model of multifocal HCC. Of note, the ribozyme induced local and systemic antitumor immunity, thereby completely suppressing secondary tumor challenge in the syngeneic mouse. The cancer specific trans-splicing ribozyme system, which mediates tissue-specific microRNA-regulated RNA replacement, provides a clinically relevant, safe, and efficient strategy for HCC treatment.

  11. Intracranial Metastasis in a Patient with Hepatocellular Carcinoma and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Akinobu Tawada

    2014-03-01

    Full Text Available A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.

  12. 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...

  13. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal

    2018-02-09

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  14. Synthetic Strigolactone Analogues Reveal Anti-Cancer Activities on Hepatocellular Carcinoma Cells

    KAUST Repository

    Hasan, Mohammed Nihal; Choudhry, Hani; Razvi, Syed Shoeb; Moselhy, Said Salama; Kumosani, Taha Abduallah; Zamzami, Mazin A.; Omran, Ziad; Halwani, Majed A.; Al-Babili, Salim; Abualnaja, Khalid Omer; Al-Malki, Abdulrahman Labeed; Alhosin, Mahmoud; Asami, Tadao

    2018-01-01

    Hepatocellular carcinoma (HCC) remains one of the leading causes of death worldwide. The complex etiology is attributed to many factors like heredity, cirrhosis, hepatitis infections or the dysregulation of the different molecular pathways. Nevertheless, the current treatment regimens have either severe side effects or tumors gradually acquire resistance upon prolonged use. Thus, developing a new selective treatment for HCC is the need of the hour. Many anticancer agents derived from plants have been evaluated for their cytotoxicity towards many human cancer cell lines. Strigolactones (SLs)-a newly discovered class of phytohormones, play a crucial role in the development of plant-root and shoot. Recently, many synthetic analogues of SLs have demonstrated pro-apoptotic effects on different cancer cell lines like prostate, breast, colon and lung. In this study, we tested synthetic SLs analogues on HCC cell line-HepG2 and evaluated their capability to induce cell proliferation inhibition and apoptosis. Primary WST-1 assays, followed by annexin-V/7AAD staining, demonstrated the anti-proliferative effects. The SLs analogues TIT3 and TIT7 were found to significantly reduce HepG2 cell viability in a dose- and time-dependent manner and induce apoptosis. Interestingly, though TIT3 and TIT7 strongly affected cancer cell proliferation, both compounds showed moderate anti-proliferative effect on normal cells. Further, migration of cancer cells was suppressed upon treatment with TIT3 and TIT7 in a wound healing assay. In summary, these findings suggest that two SLs analogues TIT3 and TIT7 exert selective inhibitory effects on cancer cells most likely through targeting microtubules. SLs analogues could be used in future as potential anti-cancer candidates in chemotherapy.

  15. Clinical study of liver cancer (Hepatocellular carcinoma) by 166 Ho-CHICO

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. T.; Yoo, H. S.; Lee, J. D.; Lee, D. Y.; Kim, E. K.; Yoo, N. C.; Shin, S. J.; Han, K. H. [Yonsei University, Seoul (Korea); Park, K. B. [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2000-04-01

    As having used Ho-166 Chitosan complex, this study was designed for the development of new therapeutic agent in the treatment of liver cancer (hepatocellular carcinoma). During the period of 3 years from April 1, 1997 to March 31, 2000, this project was successfully performed on the base of clinical experience with percutaneous Ho-166 CHICO injection in the treatment of liver cancer'. In order to evaluate the biodistribution and effect of Ho-166 CHICO was performed in 50 patients, who had the progressed liver cancer with range of 3-10cm in diameter. After the administration of the complex materials, we evaluated the therapeutic effect as well as complication by the follow-up study that included laboratory examination, radioactivity counting and various imaging modalities. 1) In animal experiment, radioactivity of target liver was ranged between 27-33% of total body one, urine excretion between 0.17-0.24 %. White blood cell and platelet counts start diminishing within 7 days and at maximum within 4 weeks after administration of complex materials. In tissue changes of target liver was revealed no significant change in the tumor dose of Ho-166, but periportal fibrosis and massive tissue necrosis in the high ones. 2) In clinical study, total necrosis of tumor is 66%, partial 10% and non-response 24% among 50 patients' liver cancer. The most important complication were leukopenia and thrombocytopenia (82%), the remained was abdominal pain(34%), skin reaction(12%), bile duct obstruction(10%), liver abscess(6%) etc. Conclusively intraarterial injection of Ho-166 CHICO was effective in the treatment of larger and progressed liver cancer. 19 refs., 14 figs., 8 tabs. (Author)

  16. 2014 Korean Liver Cancer Study Group-National Cancer Center Korea Practice Guideline for the Management of Hepatocellular Carcinoma

    Science.gov (United States)

    2015-01-01

    The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC. PMID:25995680

  17. Risk of all-type cancer, hepatocellular carcinoma, non-Hodgkin lymphoma and pancreatic cancer in patients infected with hepatitis B virus

    DEFF Research Database (Denmark)

    Andersen, E S; Omland, L H; Jepsen, Peter

    2015-01-01

    The increased risk of hepatocellular carcinoma (HCC) among patients infected with hepatitis B virus (HBV) is well established; however, long-term risk estimates are needed. Recently, it has been suggested that HBV is associated with non-Hodgkin lymphoma (NHL) and pancreatic cancer (PC). The aim...

  18. Medical treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Granito, Alessandro; Bolondi, Luigi

    2009-12-16

    Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Cirrhosis, most often due to viral hepatitis, is the predominant risk factors for HCC and geographical differences in both risk factors and incidence are largely due to epidemiological variations in hepatitis B and C infection. Hepatic function is a relevant parameter in selecting therapy in HCC. The current clinical classification of HCC split patients into 5 stages, with a specific treatment schedule for any stage. As patients with early stages can receive curative treatments, such as surgical resection, liver transplantation or local ablation, surveillance program in high-risk populations has become mandatory. Sorafenib, a multikinase inhibitor, has recently shown survival benefits in patients at advanced stage of disease. Hopefully, new molecular targeted therapies and their combination with sorafenib or interventional and surgical procedures, should expand the therapeutic armamentarium against HCC.

  19. Promoter hypermethylation mediated downregulation of FBP1 in human hepatocellular carcinoma and colon cancer.

    Directory of Open Access Journals (Sweden)

    Mingquan Chen

    Full Text Available FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10 human hepatocellular carcinoma, 66.7% (6/9 liver cancer cell lines and 100% (6/6 colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2'-deoxycytidine (Aza, indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis.

  20. Diagnostic Value of Early-Phase-Enhanced Computed Tomography for the Differentiation of Pulmonary Metastases from Hepatocellular Carcinoma and Primary Lung Cancer

    International Nuclear Information System (INIS)

    Choi, Joon-Il; Jung, Dae Chul; Kim, Min-Ju; Hong, Eun Kyung; Park, Joong-Won; Kim, Chang-Min; Choi, Hyuck Jae; Jang, Yun-Jin

    2009-01-01

    Background: The lung is the most common site of distant metastases from hepatocellular carcinoma. Correct differentiation between metastatic hepatocellular carcinoma of the lung and primary lung cancer is sometimes difficult without biopsy. Purpose: To evaluate the usefulness of measuring the attenuations of pulmonary nodules on early-phase contrast-enhanced computed tomography (CT) for the differentiation of pulmonary metastases from hepatocellular carcinoma and primary lung cancer. Material and Methods: Thirteen patients with pulmonary metastases from hepatocellular carcinoma (nine men, four women; age 53.9±14.2 years, range 16-70 years) and 25 patients with primary lung cancer (14 men, 11 women; age 62.2±9.4 years, range 43-72 years) were retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after commencing intravenous injection of contrast medium. Attenuation values and the size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and clinical features were analyzed with regard to age, sex, body surface area of the patients, the attenuation values and size of the nodules, and CT machines using univariate analysis (Fisher's exact test for binary data sets and the Mann-Whitney U test for continuous data sets). Multiple linear regression analysis was used to eliminate confounding factors. Results: The mean attenuation value of metastatic pulmonary nodules from hepatocellular carcinoma (75.7±24.9 HU) was higher than that of primary lung cancer nodules (45.8±14.4 HU) (P<0.01). Other variables such as age, sex, body surface area of the patients, CT device, and nodule size were not significant variables on multiple regression analysis. When a cut-off value of 75 HU was applied, the positive predictive value for diagnosing metastatic nodules from hepatocellular carcinoma was 100%. Conclusion: Pending confirmation in a large study, our findings suggest that there is a difference in contrast enhancement between pulmonary

  1. Radioembolization of hepatocellular carcinoma.

    Science.gov (United States)

    Van de Wiele, Christophe

    2010-12-01

    In this review paper, available data on radioembolization of unresectable hepatocellular carcinoma (HCC) using commercially available radiopharmaceuticals, respectively (131)I-Lipiodol, Therasphere (glass-microspheres) and SIRspheres (resin-microspheres) are reviewed. In the palliative setting, (131)I-Lipiodol was shown to yield response rates of 17-92% which in patients with portal vein thrombosis (PVT) translate into a survival benefit as evidenced by a phase III randomized trial. Furthermore, in terms of efficacy, (131)I-Lipiodol is as efficacious as trans-arterial chemoembolization (TACE) but far better tolerated. In the adjuvant setting, improved recurrence-free and overall survival when compared to surgery alone have been reported but these results warrant confirmation by randomized prospective trials. Similar to (131)I-Lipiodol, when administered in a palliative setting, radioembolization using (90)Y microspheres was proven effective for selected cases of non-resectable HCC and well tolerated. Available data suggest that Therasphere treatment outperforms TACE both in terms of response as in terms of event-free survival in unresectable HCC. However, this finding needs confirmation by randomized prospective trials. Therasphere treatment was also shown to limit progression of HCC allowing potential candidates for orthotopic liver transplantation (OLT) more time to wait for donor organs as well as to downstage the HCC disease to such an extent that patients that were initially not, as yet become eligible for OLT with a gain in survival. Finally, Therasphere was shown to be safe and efficacious in HCC patients presenting with PVT, reason for which approval was granted for this indication by the FDA.

  2. Epithelial-to-mesenchymal plasticity of cancer stem cells: therapeutic targets in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Aparna Jayachandran

    2016-08-01

    Full Text Available Abstract Hepatocellular carcinoma (HCC remains one of the most common and lethal malignancies worldwide despite the development of various therapeutic strategies. A better understanding of the mechanisms responsible for HCC initiation and progression is essential for the development of more effective therapies. The cancer stem cell (CSC model has provided new insights into the development and progression of HCC. CSCs are specialized tumor cells that are capable of self-renewal and have long-term repopulation potential. As they are important mediators of tumor proliferation, invasion, metastasis, therapy resistance, and cancer relapse, the selective targeting of this crucial population of cells has the potential to improve HCC patient outcomes and survival. In recent years, the role of epithelial-to-mesenchymal transition (EMT in the advancement of HCC has gained increasing attention. This multi-step reprograming process resulting in a phenotype switch from an epithelial to a mesenchymal cellular state has been closely associated with the acquisition of stem cell-like attributes in tumors. Moreover, CSC mediates tumor metastasis by maintaining plasticity to transition between epithelial or mesenchymal states. Therefore, understanding the molecular mechanisms of the reprograming switches that determine the progression through EMT and generation of CSC is essential for developing clinically relevant drug targets. This review provides an overview of the proposed roles of CSC in HCC and discusses recent results supporting the emerging role of EMT in facilitating hepatic CSC plasticity. In particular, we discuss how these important new insights may facilitate rational development of combining CSC- and EMT-targeted therapies in the future.

  3. 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...

  4. The evolutionary scenario of hepatocellular carcinoma in Italy: an update.

    Science.gov (United States)

    Bucci, Laura; Garuti, Francesca; Lenzi, Barbara; Pecorelli, Anna; Farinati, Fabio; Giannini, Edoardo G; Granito, Alessandro; Ciccarese, Francesca; Rapaccini, Gian Lodovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Sacco, Rodolfo; Cammà, Calogero; Virdone, Roberto; Marra, Fabio; Felder, Martina; Morisco, Filomena; Benvegnù, Luisa; Gasbarrini, Antonio; Svegliati-Baroni, Gianluca; Foschi, Francesco Giuseppe; Missale, Gabriele; Masotto, Alberto; Nardone, Gerardo; Colecchia, Antonio; Bernardi, Mauro; Trevisani, Franco

    2017-02-01

    Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of "metabolic" hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. During the last 15 years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Glutathione treatment of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Ranek, L; Mantoni, M

    1992-01-01

    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...

  6. Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

    Science.gov (United States)

    Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano

    2012-01-01

    During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

  7. Natural History of Untreated Hepatocellular Carcinoma in a US Cohort and the Role of Cancer Surveillance.

    Science.gov (United States)

    Khalaf, Natalia; Ying, Jun; Mittal, Sahil; Temple, Sarah; Kanwal, Fasiha; Davila, Jessica; El-Serag, Hashem B

    2017-02-01

    Determining the natural history and predictors of survival in patients with untreated hepatocellular carcinoma (HCC) in the United States is useful to test existing tumor classifications, identify subgroups of patients likely to benefit from treatment, and estimate lead time related to HCC surveillance. We identified a national cohort of 518 veterans diagnosed with HCC from 2004 through 2011, with follow-up ending in 2014, who received no palliative or curative treatment. We examined the association between postdiagnosis survival and patient factors, tumor characteristics, and prediagnosis surveillance. The mean age at HCC diagnosis was 65.7 years and most patients had hepatitis C (60.6%). Almost all patients (99%) died within the observation period; the median overall survival time was 3.6 months and survival times were 13.4, 9.5, 3.4, and 1.6 months for patients of Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. In addition, model for end-stage liver disease and levels of α-fetoprotein were predictive of survival. Nearly 28% received prediagnosis HCC surveillance, which was associated with detection of disease at an earlier stage (Barcelona Clinic Liver Cancer 0/A/B; 26.4% vs 14.4%; P = .0006) and slightly longer survival than patients with no surveillance overall (5.2 months vs 3.4 months; P = .021); there was no difference in survival times of patients with 0/A stage who did versus did not receive surveillance (10.3 months vs 10.5 months). Patients with HCCs, including those detected through surveillance, survived for short time periods in the absence of treatment, irrespective of their initial stage at diagnosis. Model for end-stage liver disease scores and levels of α-fetoprotein were prognostic factors, independent of Barcelona Clinic Liver Cancer stage. The lead time related to detection by surveillance was modest (<2 months) and therefore unlikely to explain the survival benefit associated with surveillance in previous studies

  8. Metastatic hepatocellular carcinoma on the mandible: a case report

    International Nuclear Information System (INIS)

    Kim, Jin Soo; Kim, Jae Duk

    2005-01-01

    Hepatocellular carcinoma is one of the most common cancer worldwide, primarily affecting those in regions with a high prevalence of viral hepatitis. However, the metastasis of hepatocellular carcinoma to the oral cavity is a rare phenomenon. This report presents a case of metastatic hepatocellular carcinoma in the left mandibular angle and ramus region of a 62-year-old man. Panoramic radiograph revealed an ill-defined radiolucent lesion extending from the retained root of the mandibular left second molar into the ascending ramus. The lesion had irregular and ill-defined margins.

  9. PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.

    Science.gov (United States)

    Xie, Huijun; Tong, Guihui; Zhang, Yupei; Liang, Shu; Tang, Kairui; Yang, Qinhe

    2017-07-27

    During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC -induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

  10. Imaging and embolization of hepatocellular carcinoma supplied by gonadal artery

    International Nuclear Information System (INIS)

    Wu Hongping; Wang Junjie; Lu Yang; You Kaizhi

    2010-01-01

    Objective: To evaluate radiology and embolization for hepatocellular carcinoma supplied by gonadal artery. Methods: The medical records of 3 patients with hepatocellular carcinoma supplied by gonadal artery from August 2002 to September 2008 were reviewed. The demography, gonadal artery location, modus operandi, imaging features of liver cancer and prognosis were retrospectively analyzed. Results: Anatomic variation of gonadal artery occurred with the gonadal artery arising from the upper abdominal aorta in 1 patient and from the middle suprarenal artery in 2 patients. The blood supply of the hepatocellular carcinoma derived from the gonadal artery in all 3 patients. No complications occurred in the 6-month follow-up after embolization. Conclusion: Hepatocellular carcinoma may be supplied by gonadal artery with anomalous origin. This anatomic variant can be readily demonstrated by imaging to guide embolization. (authors)

  11. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

    Science.gov (United States)

    Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

    2018-02-09

    Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

  12. 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.

  13. Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

    International Nuclear Information System (INIS)

    Hanif, R.

    2014-01-01

    To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Methodology: Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Results: Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Conclusion: Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver. (author)

  14. Surgical Treatment of Hepatocellular Carcinoma

    Science.gov (United States)

    Zamora-Valdes, Daniel; Taner, Timucin; Nagorney, David M.

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach. PMID:28975836

  15. New advances in hepatocellular carcinoma

    Science.gov (United States)

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

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

  16. Transhemangioma Ablation of Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Pua, Uei

    2012-01-01

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

  17. Transhemangioma Ablation of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  18. Ultrasonographic finding of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Han Soo; Woo, Seong Ku; Lim, Jae Hoon; Ko, Young Tae; Kim, Ho Kyun; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1983-12-15

    With the development of gray scale ultrasonography, detection and evaluation of hepatic parenchymal disease including space occupying lesion are easily performed and frequently used in the world. Thrity five cases of histopathologically proven and ultrasonographically suggested hepatocellular carcinoma are retrospectively studied. The results were as follows; 1. Ultrasonographic findings of hepatocellular carcinoma show hyperechoic pattern in 22 cases (63%), hypoechoic pattern in 2 cases (6%), and mixed pattern in 11 cases (31%). 2. The margin of tumor is ill-defined in 19 cases (54%) and well defined in16 cases (46%). 3. The size of tumor by sonographic measurement was large than 5 cm in diameter in 33 cases (94%). 4. The number of tumor is solitary in 19 cases and multiple in 16 cases. The sites of involved lobe were right lobe in 22 cases (63%), left lobe in 2 cases (6%), and both lobes in 11 cases (31%). 5. Associated sonographic findings were hepatomegaly with focal contour change in 25 cases (71%), splenomegaly in 16 cases (46%), cirrhosis of liver in 15 cases (43%), ascites in 11 cases (31%) and tumoral thrombosis in portal vein in 8 cases (23%). 6. The sex ratio is 6 : 1 male predominence and the age ranges from 32 to 76 years with highest incidence in 5th and 6th decades.

  19. Expression of Potential Cancer Stem Cell Marker ABCG2 is Associated with Malignant Behaviors of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Guang Zhang

    2013-01-01

    Full Text Available Background. Despite improvement in treatment, the prognosis of hepatocellular carcinoma (HCC remains disastrous. Cancer stem cells (CSCs may be responsible for cancer malignant behaviors. ATP-binding cassette, subfamily G, member 2 (ABCG2 is widely expressed in both normal and cancer stem cells and may play an important role in cancer malignant behaviors. Methods. The expression of ABCG2 in HCC tissues and SMMC-7721 cells was examined, and the relevance of ABCG2 expression with clinical characteristics was analyzed. ABCG2+ and ABCG2− cells were sorted, and the potential of tumorigenicity was determined. Expression level of ABCG2 was manipulated by RNA interference and overexpression. Malignant behaviors including proliferation, drug resistance, migration, and invasion were studied in vitro. Results. Expression of ABCG2 was found in a minor group of cells in HCC tissues and cell lines. ABCG2 expression showed tendencies of association with unfavorable prognosis factors. ABCG2 positive cells showed a superior tumorigenicity. Upregulation of ABCG2 enhanced the capacity of proliferation, doxorubicin resistance, migration, and invasion potential, while downregulation of ABCG2 significantly decreased these malignant behaviors. Conclusion. Our results indicate that ABCG2 is a potential CSC marker for HCC. Its expression level has a close relationship with tumorigenicity, proliferation, drug resistance, and metastasis ability.

  20. 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

  1. Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Meng-Xi; Jin, Lei; Sun, Si-Jia; Liu, Peng; Feng, Xu; Cheng, Zhou-Li; Liu, Wei-Ren; Guan, Kun-Liang; Shi, Ying-Hong; Yuan, Hai-Xin; Xiong, Yue

    2018-03-01

    Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate-limiting step in hepatic gluconeogenesis pathway to maintain blood glucose levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK-C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively. Increased expressions of both PCK genes are found in cancer of several organs, including colon, lung, and skin, and linked to increased anabolic metabolism and cell proliferation. Here, we report that the expressions of both PCK1 and PCK2 genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK expression was associated with poor prognosis in patients with HCC. Forced expression of either PCK1 or PCK2 in liver cancer cell lines results in severe apoptosis under the condition of glucose deprivation and suppressed liver tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy crisis and oxidative stress. Replenishing TCA intermediate α-ketoglutarate or inhibition of reactive oxygen species production blocked the cell death caused by PCK expression. Taken together, our data reveal that PCK1 is detrimental to malignant hepatocytes and suggest activating PCK1 expression as a potential treatment strategy for patients with HCC.

  2. Peroxisome proliferator-activated receptor α (PPARα mRNA expression in human hepatocellular carcinoma tissue and non-cancerous liver tissue

    Directory of Open Access Journals (Sweden)

    Kurokawa Tsuyoshi

    2011-12-01

    Full Text Available Abstract Background Peroxisome proliferator-activated receptor α (PPARα regulates lipid metabolism in the liver. It is unclear, however, how this receptor changes in liver cancer tissue. On the other hand, mouse carcinogenicity studies showed that PPARα is necessary for the development of liver cancer induced by peroxisome proliferators, and the relationship between PPARα and the development of liver cancer have been the focus of considerable attention. There have been no reports, however, demonstrating that PPARα is involved in the development of human liver cancer. Methods The subjects were 10 patients who underwent hepatectomy for hepatocellular carcinoma. We assessed the expression of PPARα mRNA in human hepatocellular carcinoma tissue and non-cancerous tissue, as well as the expression of target genes of PPARα, carnitine palmitoyltransferase 1A and cyclin D1 mRNAs. We also evaluated glyceraldehyde 3-phosphate dehydrogenase, a key enzyme in the glycolytic system. Results The amounts of PPARα, carnitine palmitoyltransferase 1A and glyceraldehyde 3-phosphate dehydrogenase mRNA in cancerous sections were significantly increased compared to those in non-cancerous sections. The level of cyclin D1 mRNA tends to be higher in cancerous than non-cancerous sections. Although there was a significant correlation between the levels of PPARα mRNA and cyclin D1 mRNA in both sections, however the correlation was higher in cancerous sections. Conclusion The present investigation indicated increased expression of PPARα mRNA and mRNAs for PPARα target genes in human hepatocellular carcinoma. These results might be associated with its carcinogenesis and characteristic features of energy production.

  3. 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.

  4. [Radiofrequency ablation of hepatocellular carcinoma].

    Science.gov (United States)

    Widmann, Gerlig; Schullian, Peter; Bale, Reto

    2013-03-01

    Percutaneous radiofrequency ablation (RFA) is well established in the treatment of hepatocellular carcinoma (HCC). Due to its curative potential, it is the method of choice for non resectable BCLC (Barcelona Liver Clinic) 0 and A. RFA challenges surgical resection for small HCC and is the method of choice in bridging for transplantation and recurrence after resection or transplantation. The technical feasibility of RFA depends on the size and location of the HCC and the availability of ablation techniques (one needle techniques, multi-needle techniques). More recently, stereotactic multi-needle techniques with 3D trajectory planning and guided needle placement substantially improve the spectrum of treatable lesions including large volume tumors. Treatment success depends on the realization of ablations with large intentional margins of tumor free tissue (A0 ablation in analogy to R0 resection), which has to be documented by fusion of post- with pre-ablation images, and confirmed during follow-up imaging.

  5. Angiographic findings of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Man Chung; Cho, Byung Jae; Huh, Seung Jae; Bae, Sang Hoon; Kim, Ung Jin; Kim, Chung Yong; Kim, Noe Kyeong [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1985-12-15

    From March 1977 to July 1979, 69 cases of angiograms of hepatocellular carcinoma were observed in Seoul National University Hospital. The findings of selective celiac and/or hepatic arteriography in total 69 cases of confirmed hepatocellular carcinoma, with clinical and laboratory findings, were analyzed. The summarized results are as follows; 1. Among 69 cases od hepatoma, 62 were male and 7 were female with sex ratio of 8.9 : 1. Peak incidence is 5th to 7th decades (72.5%). Epigastric pain, indigestion, and palpable mass in right upper quadrant were common symptoms and sign. Laboratory findings showed elevated serum alkaline phosphatase more than 5 Bodansky unit in 75.4%. Alpha-feto protein was positive in 65.2% of all the patients. 2 All 69 cases were classified into 31 cases of massive type, 22 cases of diffuse type, and 16 cases of nodular type, in accordance with angiographic gross anatomy. The frequency of angiographic findings were hypervascularities and tumor vessels (100%), tumor stainings (98.5%), arteriovenous shunt (71.0%), displacement of intrahepatic arteries (66.7%), vascular lakes and channel (59.4%). Encasement of hepatic artery and portal vein regurgitation was respectively 4 cases. Tumor mass in portal vein were 6 cases and tumor mass in hepatic vein was 1 case. 3. Intraarterial infusion of 5-FU was performed in 15 hepatoma patients, and the results were that angiographic improvement was demonstrated in 3 cases, no improvement in 8 cases, and incomplete infusion in 4 cases. 4. The selective celiac and/or hepatic angiograms are excellent diagnostic tools as well as therapeutic management for intraarterial infusion of anticancerous drugs.

  6. Angiographic findings of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Han, Man Chung; Cho, Byung Jae; Huh, Seung Jae; Bae, Sang Hoon; Kim, Ung Jin; Kim, Chung Yong; Kim, Noe Kyeong

    1985-01-01

    From March 1977 to July 1979, 69 cases of angiograms of hepatocellular carcinoma were observed in Seoul National University Hospital. The findings of selective celiac and/or hepatic arteriography in total 69 cases of confirmed hepatocellular carcinoma, with clinical and laboratory findings, were analyzed. The summarized results are as follows; 1. Among 69 cases od hepatoma, 62 were male and 7 were female with sex ratio of 8.9 : 1. Peak incidence is 5th to 7th decades (72.5%). Epigastric pain, indigestion, and palpable mass in right upper quadrant were common symptoms and sign. Laboratory findings showed elevated serum alkaline phosphatase more than 5 Bodansky unit in 75.4%. Alpha-feto protein was positive in 65.2% of all the patients. 2 All 69 cases were classified into 31 cases of massive type, 22 cases of diffuse type, and 16 cases of nodular type, in accordance with angiographic gross anatomy. The frequency of angiographic findings were hypervascularities and tumor vessels (100%), tumor stainings (98.5%), arteriovenous shunt (71.0%), displacement of intrahepatic arteries (66.7%), vascular lakes and channel (59.4%). Encasement of hepatic artery and portal vein regurgitation was respectively 4 cases. Tumor mass in portal vein were 6 cases and tumor mass in hepatic vein was 1 case. 3. Intraarterial infusion of 5-FU was performed in 15 hepatoma patients, and the results were that angiographic improvement was demonstrated in 3 cases, no improvement in 8 cases, and incomplete infusion in 4 cases. 4. The selective celiac and/or hepatic angiograms are excellent diagnostic tools as well as therapeutic management for intraarterial infusion of anticancerous drugs.

  7. Applications of nanoparticles in cancer detection and diagnostic tool for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Venkatasalam, C.; Nagappan, A.

    2012-01-01

    Cancer nanotechnology is multidisciplinary area of science and technology. In recent days nano particles are used in medical field as diagnostic tools. It is highly precious and accurate measurement tools for detecting many disease. One of the broad application of cancer biology, for detecting molecular imaging, molecular diagnosis of cancer cells. In the present study deals with the nanoparticles are widely used for finding tumor as biomarker imaging for cancer detection and the nanoparticles are have important notice. An ample choice of materials may be used for construct nanoparticles that can cover for increase the capability of delivery or to provide unique structural and electrical properties for imaging. This exclusive properties are worn to several functional nanoparticles have already been demonstrated, including some clinically approved liposome drugs and metallic imaging agents. In early detection of heptocellular carcinoma, the metallic nanoparticles are vital role in the imaging technology. Several functions of nanoparticles that may eventually additional the understanding of producing imaging especially the darkening and enlarging of the images. These nanoparticles may be able to identify malignant cells by means of molecular detection, visualization of their location in the body by providing enhanced contrast in medical imaging technology, Through selective particle targeting and monitoring of identification of multiplied cells in different organs of the body. In the future prospective of medical field, the nanoparticles are having vital role for detecting cancer cells. (author)

  8. Computed tomographic findings of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Jo, In Su; Jong, Woo Yung; Lee, Jong Yul; Choi, Han Yong; Kim, Bong Ki

    1987-01-01

    With Development of Computed Tomography, detection of the Hepatocellular Carcinoma are easily performed and frequently used in the world. During 15 months, from December 1985 to February 1987, 59 patients with hepatocellular carcinoma were evaluated with computed tomography in department of radiology at Wallace Memorial Baptist Hospital. The results were as follow: 1. The most prevalent age group was 5th to 7th decades, male to female ratio was 4.9:1. 2. Classification with incidence of computed tomographic appearance of the hepatocellular carcinoma were solitary type 28 cases (48%), multinodular type 24 cases (40%), and diffuse type 7 cases (12%), Association with liver cirrhosis was noted in 22 cases (38%). 3. Inhomogenous internal consistency of hepatocellular carcinoma due to central necrosis were 35 cases (60%). Portal vein invasion by hepatocellular carcinoma was noted in 15 cases (25%), and particularly most common in diffuse type 4 cases (55%). 4. On precontrast scan, all hepatocellular carcinoma were seen as area of low density except for 3 cases(0.5%) of near isodensity which turned out to be remarkable low density on postcontrast scan. 5. In solitary type, posterior segment of right lobe was most common site of involvement 12 cases (43%). In diffuse type, bilobar involvement was most common, 6 cases (85%)

  9. The Singapore Liver Cancer Recurrence (SLICER Score for relapse prediction in patients with surgically resected hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Soo Fan Ang

    Full Text Available Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC. Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER Score, to predict outcomes of HCC patients who have undergone surgical resection.Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992-2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis.A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities.The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.

  10. Spontaneous development of hepatocellular carcinoma with cancer stem cell properties in PR-SET7-deficient livers

    Science.gov (United States)

    Nikolaou, Kostas C; Moulos, Panagiotis; Chalepakis, George; Hatzis, Pantelis; Oda, Hisanobu; Reinberg, Danny; Talianidis, Iannis

    2015-01-01

    PR-SET7-mediated histone 4 lysine 20 methylation has been implicated in mitotic condensation, DNA damage response and replication licensing. Here, we show that PR-SET7 function in the liver is pivotal for maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 phase arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis, accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic regenerative cycles coupled with oncogenic STAT3 activation led to the spontaneous development of hepatic tumors composed of cells with cancer stem cell characteristics. These include a capacity to self-renew in culture or in xenografts and the ability to differentiate to phenotypically distinct hepatic cells. Hepatocellular carcinoma in PR-SET7-deficient mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes. PMID:25515659

  11. Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Mary Ann Comunale

    2010-08-01

    Full Text Available We previously reported increased levels of protein-linked fucosylation with the development of liver cancer and identified many of the proteins containing the altered glycan structures. One such protein is alpha-1-antitrypsin (A1AT. To advance these studies, we performed N-linked glycan analysis on the five major isoforms of A1AT and completed a comprehensive study of the glycosylation of A1AT found in healthy controls, patients with hepatitis C- (HCV induced liver cirrhosis, and in patients infected with HCV with a diagnosis of hepatocellular carcinoma (HCC.Patients with liver cirrhosis and liver cancer had increased levels of triantennary glycan-containing outer arm (alpha-1,3 fucosylation. Increases in core (alpha-1,6 fucosylation were observed only on A1AT from patients with cancer. We performed a lectin fluorophore-linked immunosorbent assay using Aleuria Aurantia lectin (AAL, specific for core and outer arm fucosylation in over 400 patients with liver disease. AAL-reactive A1AT was able to detect HCC with a sensitivity of 70% and a specificity of 86%, which was greater than that observed with the current marker of HCC, alpha-fetoprotein. Glycosylation analysis of the false positives was performed; results indicated that these patients had increases in outer arm fucosylation but not in core fucosylation, suggesting that core fucosylation is cancer specific.This report details the stepwise change in the glycosylation of A1AT with the progression from liver cirrhosis to cancer and identifies core fucosylation on A1AT as an HCC specific modification.

  12. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

    Science.gov (United States)

    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. 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...

  14. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

    NARCIS (Netherlands)

    Fages, Anne; Duarte-Salles, Talita; Stepien, Magdalena; Ferrari, Pietro; Fedirko, Veronika; Pontoizeau, Clement; Trichopoulou, Antonia; Aleksandrova, Krasimira; Tjonneland, Anne; Olsen, Anja; Clavel-Chapelon, Franoise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kaaks, Rudolf; Kuhn, Tilman; Floegel, Anna; Boeing, Heiner; Lagiou, Pagona; Bamia, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Weiderpass, Elisabete; Agudo, Antonio; Molina-Montes, Esther; Maria Huerta, Jose; Ardanaz, Eva; Dorronsoro, Miren; Sjoberg, Klas; Ohlsson, Bodil; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C.; Schmidt, Julie A.; Cross, Amanda; Gunter, Marc; Riboli, Elio; Scalbert, Augustin; Romieu, Isabelle; Elena-Herrmann, Benedicte; Jenab, Mazda

    2015-01-01

    Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is

  15. Response rates of hepatocellular carcinoma and hepatic colorectal cancer metastases to drug eluting bead regional liver therapy

    Institute of Scientific and Technical Information of China (English)

    Glenn W. Stambo; Deborah Cragan

    2017-01-01

    Aim: The purpose of this study was to evaluate and compare how hepatocellular carcinoma (HCC) and colorectal metastases respond to LC Bead chemoembolization using doxorubicin and irinotecan. Methods: The authors report their experience with doxorubicin and irinotecan eluting beads to treat 13 patients with primary HCC and 25 patients with colorectal metastases over a 1-year period at a single community based oncology practice. Within the colorectal cancer group they compared irinotecan eluting beads to doxorubicin eluting beads. Results:Nine of the 11 (81.8%) doxorubicin treated HCC patients had either complete response or partial response. All of the HCC lesions showed reduction in size and tumor enhancement and 10/11 (91%) HCC patients were alive at 24 months post treatment. Fisher's exact test revealed that among the 22 with colorectal metastases for whom follow-up data were available, those 11 who were treated with doxorubicin were significantly more likely to demonstrate complete or partial response compared to the 11 in the irinotecan treated group (P < 0.001). Conclusion:Overall, HCC and colon metastasis patients clearly demonstrated the effectiveness of drug eluting beads with 91% of the HCC patients alive 24 months after treatment.

  16. CIZ1 is upregulated in hepatocellular carcinoma and promotes the growth and migration of the cancer cells.

    Science.gov (United States)

    Wu, Jinsheng; Lei, Liu; Gu, Dianhua; Liu, Hui; Wang, Shaochuang

    2016-04-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, and the prognosis for the HCC remains very poor. Although dys-regulation of CIZ1 (Cip1 interacting zinc finger protein 1) has been observed in various cancer types, its expression and functions in HCC remain unknown. In this study, the mRNA level of CIZ1 in the HCC tissues were examined using real-time polymerase chain reaction, and the effects of CIZ1 on the growth, migration, and metastasis of HCC cells were examined by crystal violet assay, Boyden chamber assay, and in vivo image system, respectively. In addition, the molecular mechanisms were investigated by luciferase assay. Upregulation of CIZ1 in the clinical HCC samples was observed. Forced expression of CIZ1 promoted the growth and migration of HCC cells, while knocking down the expression of CIZ1 inhibited the growth, migration, and metastasis of HCC cells. Molecular mechanism studies revealed that CIZ1 activated YAP/TAZ signaling in HCC cells. Taken together, our study demonstrated the oncogenic roles of CIZ1 in HCC cells and CIZ1 might be a promising therapeutic target for HCC.

  17. Mammalian-enabled (MENA) protein enhances oncogenic potential and cancer stem cell-like phenotype in hepatocellular carcinoma cells.

    Science.gov (United States)

    Hu, Kunpeng; Huang, Pinzhu; Luo, Hui; Yao, Zhicheng; Wang, Qingliang; Xiong, Zhiyong; Lin, Jizong; Huang, He; Xu, Shilei; Zhang, Peng; Liu, Bo

    2017-08-01

    Mammalian-enabled (MENA) protein is an actin-regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma (HCC) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell (CSC)-like phenotypes in HCC cells. Real-time-PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively. Stable MENA-overexpressing HCC cells were generated from HCC cell lines. Transwell cell migration and colony formation assays were employed to evaluate tumorigenicity. Ectopic expression of MENA significantly enhanced cell migration and colony-forming ability in HCC cells. Overexpression of MENA upregulated several hepatic progenitor/stem cell markers in HCC cells. A high MENA protein level was associated with high mRNA levels of MENA, CD133, cytokeratin 19 (CK19), and epithelial cell adhesion molecule (EpCAM) in human HCC tissues. Overexpression of MENA enhanced epithelial-to-mesenchymal transition (EMT) markers, extracellular signal-regulated kinases (ERK) phosphorylation, and the level of β-catenin in HCC cells. This study demonstrated that overexpression of MENA in HCC cells promoted stem cell markers, EMT markers, and tumorigenicity. These effects may involve, at least partially, the ERK and β-catenin signaling pathways.

  18. Embolotherapy in the management of hepatocellular carcinoma.

    Science.gov (United States)

    Mojtahedi, Alireza; Yang, Xiaoming; Goswami, Gaurav K

    2008-09-01

    Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The incidence of HCC in the United States is rising, primarily due to the number of patients who were infected by hepatitis in the 1960s and 1970s coupled with the rising migrant population from Asia, where hepatitis is widely prevalent. Up to 80% of the patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the option of resection or liver transplantation. The dual blood supply (arterial and portal) to the liver with predominantly arterial supply to the tumor has made embolotherapy a cornerstone in the management of inoperable HCC. The techniques have become refined not only due to the development of microcatheter angiographic capabilities, but also in the ability to deliver a wide variety of therapeutic agents to these tumors. This article reviews the fundamental principles of bland embolization, chemoembolization, and radioembolization in the management of HCC.

  19. Treatment options for hepatocellular carcinoma.

    Science.gov (United States)

    Sandhu, Dalbir S; Tharayil, Vivek S; Lai, Jin-Ping; Roberts, Lewis R

    2008-02-01

    Hepatocellular carcinoma (HCC) is frequently diagnosed at advanced stages and has a high mortality rate. With improved survival of patients with cirrhotic liver disease and increased prevalence of chronic hepatitis C viral infections, a rise in the number of HCC cases is being reported worldwide. Early diagnosis and treatment can significantly improve the prognosis of patients with HCC. Although surgical resection is an important potentially curative therapy for liver tumors, in appropriately selected patients, liver transplantation has been shown to achieve excellent survival rates for a solid tumor. Locally ablative and locoregional therapies in the form of percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization and transcatheter arterial radioembolization (TheraSphere) are viable options in patients with unresectable HCC. Unfortunately, the role of systemic therapy has been very limited in the treatment of these patients. Novel treatment options based on an improved understanding of the molecular pathogenesis of HCC are being explored. These targeted molecular therapies are aimed at growth factors and their receptors, intracellular signal transduction and cell cycle control. A substantial improvement in outcomes of intermediate and advanced stage HCC is expected with the advent of these targeted therapies, used in combination with surgical or locoregional therapies. Recent positive results from a large Phase III study of the receptor tyrosine kinase inhibitor, sorafenib, hold great promise in the treatment of HCC.

  20. Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Zhong; Shen, Gen-Hai; Xie, Jia-Ming; Li, Bin; Gao, Quan-Gen

    2018-01-01

    Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.

    Science.gov (United States)

    Yahagi, Naoya; Shimano, Hitoshi; Hasegawa, Kiyoshi; Ohashi, Kenichi; Matsuzaka, Takashi; Najima, Yuho; Sekiya, Motohiro; Tomita, Sachiko; Okazaki, Hiroaki; Tamura, Yoshiaki; Iizuka, Yoko; Ohashi, Ken; Nagai, Ryozo; Ishibashi, Shun; Kadowaki, Takashi; Makuuchi, Masatoshi; Ohnishi, Shin; Osuga, Jun-ichi; Yamada, Nobuhiro

    2005-06-01

    Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.

  2. Defining Hepatocellular Carcinoma Subtypes and Treatment Responses in Patient-Derived Tumorgrafts

    Science.gov (United States)

    2017-10-01

    Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd leading cause of cancer-related death worldwide. We know that HCC subtypes exist because...italicized descriptions of section contents in your submitted reports. 1. INTRODUCTION: Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd...know the results or have not been harvested to assess tumor engraftment in liver. Overall, we have found that there is a good engraftment rate

  3. CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

    Science.gov (United States)

    Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

    2017-12-15

    CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

  4. Survival of patients with hepatocellular carcinoma in the San Joaquin Valley: a comparison with California Cancer Registry data.

    Science.gov (United States)

    Atla, Pradeep R; Sheikh, Muhammad Y; Mascarenhas, Ranjan; Choudhury, Jayanta; Mills, Paul

    2012-01-01

    Variation in the survival of patients with hepatocellular carcinoma (HCC) is related to racial differences, socioeconomic disparities and treatment options among different populations. A retrospective review of the data from medical records of patients diagnosed with HCC were analyzed at an urban tertiary referral teaching hospital and compared to patients in the California Cancer Registry (CCR) - a participant in the Survival Epidemiology and End Results (SEER)program of the National Cancer Institute (NCI). The main outcome measure was overall survival rates. 160 patients with the diagnosis of HCC (M/F=127/33), mean age 59.7±10 years, 32% white, 49% Hispanic, 12% Asian and 6% African American. Multivariate analysis identified tumor size, model for end-stage liver disease (MELD) score, portal vein invasion and treatment offered as the independent predictors of survival (p <0.05). Survival rates across racial groups were not statistically significant. 5.6% received curative treatments (orthotopic liver transplantation, resection, rediofrequency ablation) (median survival 69 months), 34.4% received nonsurgical treatments (trans-arterial chemoembolization, systemic chemotherapy) (median survival 9 months), while 60% received palliative or no treatment (median survival 3 months) (p <0.001). There was decreased survival in our patient population with HCC beyond 2 years. 60% of our study population received only palliative or no treatment suggesting a possible lack of awareness of chronic liver disease as well as access to appropriate surveillance modalities. Ethnic disparities such as Hispanic predominance in this study in contrast to the CCR/SEER database may have been a contributing factor for poorer outcome.

  5. Infrequent widespread microsatellite instability in hepatocellular carcinomas.

    Science.gov (United States)

    Yamamoto, H; Itoh, F; Fukushima, H; Kaneto, H; Sasaki, S; Ohmura, T; Satoh, T; Karino, Y; Endo, T; Toyota, J; Imai, K

    2000-03-01

    Widespread or high-frequency microsatellite instability (MSI) due to the defective DNA mismatch repair (MMR) occurs in the majority of hereditary non-polyposis colorectal cancer and a subset of sporadic malignant tumors. The incidence of MSI and underlying DNA MMR defects have been well characterized in gastrointestinal carcinogenesis, but not in hepatocarcinogenesis. To address the issue, we analyzed 55 Japanese hepatocellular carcinomas using several indicators of DNA MMR defects, such as microsatellite analysis, loss of heterozygosity (LOH) and mutation analysis of MMR genes, methylation of hMLH1 promoter, and frameshift mutations of mononucleotide repeat sequences within possible target genes. Mutation of beta2-microglobulin gene, which is presumably involved in MSI-positive tumor cell escape from immune surveillance was also examined. Some of these analyses were also carried out in 9 human liver cancer cell lines. None of the 3 quasi-monomorphic mononucleotide markers sensitive for MSI, BAT26, BAT25, and BAT34C4 presented shortened unstable alleles in any of the carcinoma, cirrhosis, chronic hepatitis tissues, or cell lines. LOH at MMR genes was infrequent (4.4 approximately 7.1%), and no mutations were detected. Neither hMLH1 hypermethylation nor frameshift mutation in the target genes was detected. No mutations were found in beta2-microglobulin. Widespread MSI due to the defective DNA MMR appears to play little if any part in Japanese hepatocarcinogenesis.

  6. 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

  7. Current radiologic interventions in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Masoud, I.; Naeem, M.Q.T.; Saeed, F.; Mirza, S.A.M.; Khan, A.; Bhatti, M.A.

    2006-01-01

    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. (author)

  8. 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. PMID:27239288

  9. Hepatocellular carcinoma: a clinico pathological study

    International Nuclear Information System (INIS)

    Abbasi, A.; Butt, N.; Bhutto, A.R.; Gulzar, K.; Munir, S.M.

    2010-01-01

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

  10. MEK-ERK inhibition potentiates WAY-600-induced anti-cancer efficiency in preclinical hepatocellular carcinoma (HCC) models

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kaifeng, E-mail: kaifeng_wangdr@sina.com [Cancer center, the Affiliated Hospital of Hangzhou Normal University, Hangzhou (China); Fan, Yaohua [Oncology Department, No. 1 Hospital of Jiaxing, Zhejiang Province, Jiaxing (China); Chen, Gongying [Oncology Department, The Affiliated Hospital Hangzhou Normal University, Hangzhou (China); Wang, Zhengrong [Taizhou Hospital, Zhejiang Province, Taizhou (China); Kong, Dexin; Zhang, Peng [Oncology Department, Sir Run Run Shaw Hospital, Medical School, Zhejiang University, Hangzhou (China)

    2016-05-27

    The search for novel anti-hepatocellular carcinoma (HCC) agents is important. Mammalian target of rapamycin (mTOR) hyper-activation plays a pivotal role in promoting HCC tumorigenesis and chemoresistance. The current preclinical study evaluated the potential anti-HCC activity by a potent mTOR kinase inhibitor, WAY-600. We showed that WAY-600 inhibited survival and proliferation of HCC cell lines (HepG2 and Huh7) and primary human HCC cells. Caspase-dependent apoptosis was activated by WAY-600 in above HCC cells. Reversely, caspase inhibitors largely attenuated WAY-600's lethality against HCC cells. At the signaling level, WAY-600 blocked mTOR complex 1/2 (mTORC1/2) assemble and activation, yet activated MEK-ERK pathway in HCC cells. MEK-ERK inhibitors, PD-98059 and MEK-162, or MEK1/2 shRNA significantly potentiated WAY-600's cytotoxicity in HCC cells. Further studies showed that WAY-600 intraperitoneal (i.p.) administration in nude mice inhibited p-AKT Ser-473 and displayed significant anti-cancer activity against HepG2 xenografts. Remarkably, co-administration of MEK-162 further potentiated WAY-600's anti-HCC activity in vivo. These preclinical results demonstrate the potent anti-HCC activity by WAY-600, either alone or with MEK-ERK inhibitors. -- Highlights: •WAY-600 inhibits HCC cell survival and proliferation in vitro. •WAY-600 activates caspase-dependent apoptosis in HCC cells. •WAY-600 blocks mTORC1/2 activation, but activates MEK-ERK in HCC cells. •MEK-ERK inhibitors or MEK1/2 shRNA enhances WAY-600's cytotoxicity against HCC cells. •MEK-162 co-administration potentiates WAY-600-induced the anti-HepG2 tumor efficacy.

  11. 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.

  12. Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma

    OpenAIRE

    Zhang, Hai-Jian; Yao, Deng-Fu; Yao, Min; Huang, Hua; Wu, Wei; Yan, Mei-Juan; Yan, Xiao-Di; Chen, Jie

    2012-01-01

    AIM: To investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

  13. Updates in the Management of Hepatocellular Carcinoma

    Science.gov (United States)

    Frenette, Catherine

    2011-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and its increasing incidence worldwide is a cause for concern. Fortunately, advances in diagnostic and therapeutic approaches have contributed to earlier detection and treatment. As cancer epidemiology studies continue to elucidate the natural history of liver diseases, greater understanding of HCC has led to improved risk stratification and earlier enrollment of high-risk patients in cancer screening and surveillance programs. Improved survival rates among HCC patients also reflect significant advances in available treatment options. Advances in surgical techniques are pushing the boundaries of resection for localized disease, and progress in the field of transplantation has led to refinements in listing criteria and improved post-transplantation outcomes. The evolving field of locoregional therapies—including percutaneous ablation and transarterial chemoembolization—continues to provide novel therapeutic options that can be used in place of, or in addition to, surgical approaches. Recent advances in systemic multikinase inhibitor therapies have also demonstrated significant benefits for advanced-stage disease, and these therapies also show promise as adjuvant treatments for earlier-stage disease. This article provides an update on the management of HCC, with a focus on revised guidelines for screening and an in-depth discussion of emerging novel therapies. PMID:21346848

  14. Potentiality of immunotherapy against hepatocellular carcinoma

    Science.gov (United States)

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  15. 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.

  16. Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

    NARCIS (Netherlands)

    Verhoevena, BH; Haagsma, EB; Appeltans, BMG; Slooff, MJH; de Jong, KP

    Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C)

  17. 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.)

  18. Small hepatocellular carcinoma versus small cavernous hemangioma

    International Nuclear Information System (INIS)

    Choi, B.I.; Park, H.W.; Kim, S.H.; Han, M.C.; Kim, C.W.

    1989-01-01

    To determine the optimal pulse sequence for detection and differential diagnosis of small hepatocellular carcinomas and cavernous hemangiomas less than 5 cm in diameter, the authors have analyzed spin-echo (SE) images of 15 small hepatocellular carcinomas and 31 small cavernous hemangiomas obtained at 2.0 T. Pulse sequences used included repetition times (TRs) of 500 and 2,000 msec and echo times (TEs) of 30,60,90,120,150, and 180 msec. Mean tumor-liver contrast-to-noise ratios on the SE 2,000/60 (TR msec/TE msec) sequence were 23.90 ± 16.33 and 62.10 ± 25.94 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences. Mean tumor-liver signal intensity ratios on the SE 2,000/150 sequence were 2.34 ± 1.72 and 6.04 ± 2.72 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences in hemangiomas

  19. 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

  20. 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

  1. Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma.

    Science.gov (United States)

    Nooron, Nattakarn; Ohba, Koji; Takeda, Kazuhisa; Shibahara, Shigeki; Chiabchalard, Anchalee

    2017-08-01

    Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

  2. Genetic alterations in hepatocellular carcinoma: An update

    Science.gov (United States)

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

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

    Lifescience Database Archive (English)

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

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

    Lifescience Database Archive (English)

    Full Text Available His.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Histone Liver Carcinoma, Hepatocellu...lar http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  5. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

    Science.gov (United States)

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

  6. [Expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma].

    Science.gov (United States)

    Gu, C J; Ni, Q C; Ni, K; Zhang, S; Qian, H X

    2018-05-29

    Objective: To investigate the expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma. Methods: A total of 136 cases of primary hepatocellular carcinoma tissues and paired adjacent tissues were collected. Immunohistochemistry and Western blot were used to detect the expression of KIAA1199 in primary hepatocellular carcinoma tissues and paired adjacent tissues. The relationship between KIAA1199 and clinicopathological parameter of primary hepatocellular carcinoma was analyzed. Results: The positive rate of KIAA1199 in primary hepatocellular carcinoma was 82.3% (112/136), which was higher than that in paired para-cancerous tissues (14.7%, 20/136). High expression of KIAA1199 was significantly correlated with age, cirrhosis history, tumor size, tumor number, degree of differentiation, TNM staging and microvenous invasion (MVI) ( P 0.05). The Kaplan-Meier survival curves indicated that high KIAA1199 expression was associated with poor survival ( P hepatocellular carcinoma, which is significantly correlated with the clinicopathological features and prognosis, high expression of KIAA1199 increased the risk of death in patients with primary hepatocellular carcinoma.

  7. Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

    Science.gov (United States)

    Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

    2016-01-01

    Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

  8. Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine

    Directory of Open Access Journals (Sweden)

    Valérie Heron

    2016-05-01

    Full Text Available Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn’s disease. The patient is a 61-year-old with longstanding Crohn’s disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn’s disease who present with elevated liver enzymes, especially those on azathioprine therapy.

  9. 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.

  10. 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.

  11. 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

  12. Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Vicente, R.; Garcia-Gutierrez, J. A.; Fernandez, A.; Santalla, F.

    2001-01-01

    Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopathological 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

  13. Diagnostic Approaches to Metastatic Hepatocellular Carcinoma of the Orbit.

    Science.gov (United States)

    Geske, Michael J; Bloomer, Michele M; Kersten, Robert C; Vagefi, M Reza

    Orbital metastasis of hepatocellular carcinoma is exceedingly rare and caries a grave prognosis. Three cases of metastatic orbital hepatocellular carcinoma in which the primary tumor was initially unknown and the diagnostic challenges encountered are presented. With hepatocellular carcinoma, open biopsy and palliative tumor debulking has an increased bleeding risk due to the highly vascular nature of the tumor and coagulopathy associated with chronic liver disease. As an alternative, fine needle aspiration biopsy should be considered for hepatocellular carcinoma with a readily accessible mass and the availability of an experienced cytopathologist.

  14. Computed tomography diagnosis of hepatocellular carcinoma rupture haemorrhage

    International Nuclear Information System (INIS)

    Zhi Weike; Jiang Bin; Liu Jinquan; Li Sixia; Zhu Zhichang

    2004-01-01

    Objective: To evaluate the diagnostic value of hepatocellular carcinoma rupture hemorrhage using Computed Tomography. Methods: Six cases diagnosed hepatocellular carcinoma rupture hemorrhage were analyzed by morphic and histologic method and investigated the key point of scan in diagnosis. Result: The correct rate of hepatocellular carcinoma rupture hemorrhage by Computed Tomography is above 83 percent, it characteristic representation is strip and would high-density shadow after enhancement. Conclusion: The characteristic representation of hepatocellular carcinoma rupture hemorrhage is attain by Computed Tomography, which provides effective operation evidences for clinical operation. (authors)

  15. Radio-embolization for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Raoul, J.L.; Edeline, J.; Pracht, M.; Boucher, E.; Rolland, Y.; Garin, E.

    2011-01-01

    Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemo-embolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radio-embolization could be an excellent tool for such patients. Currently 131 I-Lipiodol, 188 Re-Lipiodol, 90 Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radio-embolization with systemic chemotherapy or targeted agents (particularly anti-angiogenic drugs) seems very promising. (authors)

  16. Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1.

    Science.gov (United States)

    Yu, W-W; Wang, K; Liao, G-J

    2017-11-01

    This research focuses on the influence of linc-ITGB1 on the metastasis of hepatocellular carcinoma and further explores its underlying mechanism. A total of 70 hepatocellular carcinoma patients were chosen for our study. RT-qPCR was used for detecting the expression level of linc-ITGB1 in their cancer tissues. Moreover, the expression level of linc-ITGB1 was also detected in hepatocellular carcinoma cell lines. Furthermore, whether linc-ITGB1 could affect the migrated and invaded ability of hepatocellular carcinoma cells was determined by wound healing assay and transwell assay. We further explored the potential mechanism by RT-qPCR and Western blot assay. Linc-ITGB1 expression level in hepatocellular carcinoma tissues was remarkably higher than that in adjacent tissues. Moreover, migrated and invaded ability of hepatocellular carcinoma cells was inhibited through knockdown of linc-ITGB1. Further study revealed that silenced linc-ITGB1 inhibited the expression of ZEB1 and then suppressed epithelial to mesenchymal transition (EMT), which was important during the metastasis of hepatocellular carcinoma. Moreover, the inhibition of cell invasion by silenced linc-ITGB1 could be rescued through overexpression of ZEB1 in hepatocellular carcinoma. The results indicate that linc-ITGB1, a novel oncogene in tumorigenesis, could promote the metastasis and EMT via ZEB1, which may offer a possible therapeutic target in hepatocellular carcinoma.

  17. Are metastases from metastases clinical relevant? Computer modelling of cancer spread in a case of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Anja Bethge

    Full Text Available BACKGROUND: Metastasis formation remains an enigmatic process and one of the main questions recently asked is whether metastases are able to generate further metastases. Different models have been proposed to answer this question; however, their clinical significance remains unclear. Therefore a computer model was developed that permits comparison of the different models quantitatively with clinical data and that additionally predicts the outcome of treatment interventions. METHODS: The computer model is based on discrete events simulation approach. On the basis of a case from an untreated patient with hepatocellular carcinoma and its multiple metastases in the liver, it was evaluated whether metastases are able to metastasise and in particular if late disseminated tumour cells are still capable to form metastases. Additionally, the resection of the primary tumour was simulated. The simulation results were compared with clinical data. RESULTS: The simulation results reveal that the number of metastases varies significantly between scenarios where metastases metastasise and scenarios where they do not. In contrast, the total tumour mass is nearly unaffected by the two different modes of metastasis formation. Furthermore, the results provide evidence that metastasis formation is an early event and that late disseminated tumour cells are still capable of forming metastases. Simulations also allow estimating how the resection of the primary tumour delays the patient's death. CONCLUSION: The simulation results indicate that for this particular case of a hepatocellular carcinoma late metastases, i.e., metastases from metastases, are irrelevant in terms of total tumour mass. Hence metastases seeded from metastases are clinically irrelevant in our model system. Only the first metastases seeded from the primary tumour contribute significantly to the tumour burden and thus cause the patient's death.

  18. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dugard, J; Kew, M C; Da Fonseca, M; Levin, J [University of the Witwatersrand, Johannesburg (South Africa)

    1982-08-21

    Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

  19. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Dugard, J.; Kew, M.C.; Da Fonseca, M.; Levin, J.

    1982-01-01

    Having found raised serum calcitonin concentrations is 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1 650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35,5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2 179 pg/ml). If 1 000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma

  20. Grp78 promotes the invasion of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Li Hongdan

    2010-01-01

    Full Text Available Abstract Background Glucose regulated protein 78 (Grp78 is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. Methods The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Results Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased

  1. Grp78 promotes the invasion of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Su, Rongjian; Li, Zhen; Li, Hongdan; Song, Huijuan; Bao, Cuifen; Wei, Jia; Cheng, Liufang

    2010-01-01

    Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued Rho

  2. 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.

  3. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    ... Autoimmune diseases of the liver Hepatitis B or hepatitis C virus infection Inflammation of the liver that is long-term (chronic) Iron overload in the body ( hemochromatosis ) People with hepatitis B or C are at high risk of ...

  4. Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

    Science.gov (United States)

    Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

    2018-06-12

    Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  5. 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....

  6. Selective angiography in fifty patients with primary hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shou-Zhong, Wang; Xing-Rong, Chen; Gong-Xian, Wang

    1983-06-01

    Selective angiography is of great importance in the diagnosis of primary hepatocellular carcinoma. It offers information on the findings, multicentricity, localisation, extension, and type of growth. This paper discusses angiography from the methodical point of view, the findings to be obtained, the types of hepatocellular carcinoma, and the diagnostic efficiency of selective angiography in the evaluation of this type of tumour.

  7. 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 ...

  8. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Geschwind, Jean Francois H; Salem, Riad; Carr, Brian I; Soulen, Michael C; Thurston, Kenneth G; Goin, Kathleen A; Van Buskirk, Mark; Roberts, Carol A; Goin, James E

    2004-11-01

    Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores ( P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively ( P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.

  9. Noninvasive diagnosis of hepatocellular carcinoma: Elaboration on Korean liver cancer study group-National Cancer Center Korea Practice Guidelines compared with other guidelines and remaining issues

    International Nuclear Information System (INIS)

    Yoon, Jeong Hee; Lee, Jeong Min; Park, Joong Won

    2016-01-01

    Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed 'washout' in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule ≥ 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis

  10. Noninvasive diagnosis of hepatocellular carcinoma: Elaboration on Korean liver cancer study group-National Cancer Center Korea Practice Guidelines compared with other guidelines and remaining issues

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jeong Hee; Lee, Jeong Min [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Park, Joong Won [Center for Liver Cancer, National Cancer Center, Goyang (Korea, Republic of)

    2016-02-15

    Hepatocellular carcinoma (HCC) can be diagnosed based on characteristic findings of arterial-phase enhancement and portal/delayed 'washout' in cirrhotic patients. Several countries and major academic societies have proposed varying specific diagnostic criteria for HCC, largely reflecting the variable HCC prevalence in different regions and ethnic groups, as well as different practice patterns. In 2014, a new version of Korean practice guidelines for management of HCC was released by the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC). According to the KLCSG-NCC Korea practice guidelines, if the typical hallmark of HCC (i.e., hypervascularity in the arterial phase with washout in the portal or 3 min-delayed phases) is identified in a nodule ≥ 1 cm in diameter on either dynamic CT, dynamic MRI, or MRI using hepatocyte-specific contrast agent in high-risk groups, a diagnosis of HCC is established. In addition, the KLCSG-NCC Korea practice guidelines provide criteria to diagnose HCC for subcentimeter hepatic nodules according to imaging findings and tumor marker, which has not been addressed in other guidelines such as Association for the Study of Liver Diseases and European Association for the Study of the Liver. In this review, we briefly review the new HCC diagnostic criteria endorsed by the 2014 KLCSG-NCC Korea practice guidelines, in comparison with other recent guidelines; we furthermore address several remaining issues in noninvasive diagnosis of HCC, including prerequisite of sonographic demonstration of nodules, discrepancy between transitional phase and delayed phase, and implementation of ancillary features for HCC diagnosis.

  11. Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Greco, Assunta; De Masi, Roberto; Orlando, Stefania; Metrangolo, Antonio; Zecca, Vittorio; Morciano, Giancarlo; De Donno, Antonella; Bagordo, Francesco; Piccinni, Giancarlo

    At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular carcinoma. This observation underlines the risk of hepatocellular carcinoma cardiac metastasis, manifested in its infiltrative form as hypertrophic cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen as a "red flag" and recommend the introduction of magnetic resonance imaging assessment of transplant candidates.

  12. CT diagnosis of rare histological variant of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Li Huaibo; Feng Zhipeng; Duan Shaoyin; Zhaugn Xiangrong

    2009-01-01

    Objective: To explore and understand the CT findings of 5 rare histological variants of hepatocellular carcinoma. Methods: CT findings of 31 cases of rare histological variants confirmed by surgery and pathology were analyzed retrospectively. Results: 13 cases were clear cell hepatocellular carcinoma. 3 cases of them showed patchy fat density in plain scans. Enhanced CT showed features of 'fast in fast out' which was similar to the common hepatocellular carcinoma. 4 cases belonged to sclerosis hepatocellular carcinoma. They appeared as heterogeneous, slowly enhancement on arterial phase images, and delay enhancement on portal venous phase and delay phase images. 9 cases belonged to mixed hepatocellular carcinoma. 5 cases of them showed inhomogeneous enhancement and 4 without enhancement during arterial phase, 3 cases showed delay enhancement and 4 without during portal venous and delay phase. 3 cases were fibrolamellar hepatocellular carcinoma. All showed obvious and fastly enhancement on arterial phase images, subsided slowly on the portal venous and delay phase images, showing features of 'fast in slow out', no enhancement was seen in the central scar. Shrinkage phenomenon on the surface of liver could be seen on the CT plain scans in sclerosis, mixed and fibrolamellar hepatocellular carcinoma. 2 cases were the type of dense hepatocellular carcinoma. The surrounding part in the 2 cases were slightly enhanced, while the most part of the center were not enhanced similar to necrosis. Conclusion: The CT findings of rate histological variant of hepatocellular carcinoma are characteristic. Analyzing the CT plain and enhancement finding is helpful to the diagnosis of these types of hepatocellular carcinoma. (authors)

  13. An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas.

    Science.gov (United States)

    Cicalese, Luca; Raun, Loren; Shirafkan, Ali; Campos, Laura; Zorzi, Daria; Montalbano, Mauro; Rhoads, Colin; Gazis, Valia; Ensor, Katherine; Rastellini, Cristiana

    2017-11-01

    Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

  14. Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling

    Science.gov (United States)

    2015-01-01

    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. PMID:26560447

  15. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

    Directory of Open Access Journals (Sweden)

    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.

  16. Hepatocellular carcinoma: treatment with transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Acunas, Buelent; Rozanes, Izzet

    1999-01-01

    This article presents a review of the literature regarding the use of transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). There have been two different approaches to the treatment: (a) percutaneous tumor ablation methods which can be divided into injectable and thermal methods; percutaneous ethanol injection (PEI) is the most widely used method, and (b) TACE. PEI is the treatment of choice for single HCCs smaller or equal to 3 cm in size. For patients with large HCCs combined TACE and PEI is probably the most effective nonsurgical treatment. In the presence of multiple HCC nodules, TACE remains the treatment of choice

  17. 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.

  18. Hepatocellular carcinoma directly invading the duodenum

    International Nuclear Information System (INIS)

    Mohamed, Abdelrehman O.; Joshi, Sandhya; Czechowski, Janusz; Branicki, Frank

    2005-01-01

    Recurrent gastrointestinal bleeding from hepatocellular carcinoma (HCC) invading the duodenum is very rare. We present a case of 50-year-old male who was admitted with a history of recurrent upper gastrointestinal tract (UGIT) bleeding, weight loss and anemia. The patient was known to have a chronic hepatitis C. Endoscopic examination showed grade-2 non-bleeding esophageal varices, and a large ulcerated duodenal mass partially obstructing the duodenal bulb outlet and causing recurrent UGIT bleeding. Pathological evaluation of the mass revealed HCC. (author)

  19. Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

    Science.gov (United States)

    Akizue, Naoki; Suzuki, Eiichiro; Yokoyama, Masayuki; Inoue, Masanori; Wakamatsu, Toru; Saito, Tomoko; Kusakabe, Yuko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Maru, Yugo; Matsue, Hiroyuki; Chiba, Tetsuhiro

    2017-11-15

    Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.

  20. Prebiotics: A Novel Approach to Treat Hepatocellular Carcinoma.

    Science.gov (United States)

    Fatima, Naz; Akhtar, Tasleem; Sheikh, Nadeem

    2017-01-01

    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. Current status of liver diseases in Korea: hepatocellular carcinoma.

    Science.gov (United States)

    Song, Il Han; Kim, Kyung Sik

    2009-12-01

    Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. During the last two decades, the incidence rate of primary liver cancer has shown a modest decrease, but its mortality rate has slightly increased. The incidence of HCC, according to age, peaks in the late sixth decade in men and in the early seventh decade in women. Hepatitis B virus (HBV) is the most important risk factor, which represents approximately 70% of all HCC, and hepatitis C virus (HCV) and alcohol are the next in order of major risk factors for the development of HCC in Korea. HBV-associated HCC occurs 10 years earlier than HCV-associated HCC due to a more prolonged exposure to HBV, which is vertically transmitted almost from HBsAg-positive mother in HBV-endemic area. National Cancer Control Institute, which was reorganized in 2005, is now working for several national projects such as National Cancer Registration Program, National R&D Program for Cancer Control and National Cancer Screening Program. International collaboration for the clinico-epidemiologic research would be needed to provide the specific measures for managing HCC in diverse etiologic situations. Finally, the mechanisms of hepatitis virus-associated hepatocellular carcinogenesis might be clarified to provide insights into the advanced therapeutic and preventive approaches for HCC in Korea, where the majority of HCC originate from chronic HBV and HCV infections.

  2. A qualitative signature for early diagnosis of hepatocellular carcinoma based on relative expression orderings.

    Science.gov (United States)

    Ao, Lu; Zhang, Zimei; Guan, Qingzhou; Guo, Yating; Guo, You; Zhang, Jiahui; Lv, Xingwei; Huang, Haiyan; Zhang, Huarong; Wang, Xianlong; Guo, Zheng

    2018-04-23

    Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients. A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early

  3. Bioinformatics functional analysis of let-7a, miR-34a, and miR-199a/b reveals novel insights into immune system pathways and cancer hallmarks for hepatocellular carcinoma.

    Science.gov (United States)

    Soliman, Bangly; Salem, Ahmed; Ghazy, Mohamed; Abu-Shahba, Nourhan; El Hefnawi, Mahmoud

    2018-05-01

    Let-7a, miR-34a, and miR-199 a/b have gained a great attention as master regulators for cellular processes. In particular, these three micro-RNAs act as potential onco-suppressors for hepatocellular carcinoma. Bioinformatics can reveal the functionality of these micro-RNAs through target prediction and functional annotation analysis. In the current study, in silico analysis using innovative servers (miRror Suite, DAVID, miRGator V3.0, GeneTrail) has demonstrated the combinatorial and the individual target genes of these micro-RNAs and further explored their roles in hepatocellular carcinoma progression. There were 87 common target messenger RNAs (p ≤ 0.05) that were predicted to be regulated by the three micro-RNAs using miRror 2.0 target prediction tool. In addition, the functional enrichment analysis of these targets that was performed by DAVID functional annotation and REACTOME tools revealed two major immune-related pathways, eight hepatocellular carcinoma hallmarks-linked pathways, and two pathways that mediate interconnected processes between immune system and hepatocellular carcinoma hallmarks. Moreover, protein-protein interaction network for the predicted common targets was obtained by using STRING database. The individual analysis of target genes and pathways for the three micro-RNAs of interest using miRGator V3.0 and GeneTrail servers revealed some novel predicted target oncogenes such as SOX4, which we validated experimentally, in addition to some regulated pathways of immune system and hepatocarcinogenesis such as insulin signaling pathway and adipocytokine signaling pathway. In general, our results demonstrate that let-7a, miR-34a, and miR-199 a/b have novel interactions in different immune system pathways and major hepatocellular carcinoma hallmarks. Thus, our findings shed more light on the roles of these miRNAs as cancer silencers.

  4. Case of minute hepatocellular carcinoma found by CT scan and diagnosed cytology under the ultrasonic aspiration transducer

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Waichi; Moriai, Norihiko; Komatsu, Kanji [Yuri Kumiai Sogo Hospital, Akita (Japan)

    1983-11-01

    CT scan detected a suspected minute hepatocellular carcinoma in a case of liver cirrhosis followed up for more than 10 years. A definite diagnosis was established by ultrasonic guided aspiration cytology. The cancer was resected using ultrasonic examination during operation.

  5. High-resolution characterization of a hepatocellular carcinoma genome.

    Science.gov (United States)

    Totoki, Yasushi; Tatsuno, Kenji; Yamamoto, Shogo; Arai, Yasuhito; Hosoda, Fumie; Ishikawa, Shumpei; Tsutsumi, Shuichi; Sonoda, Kohtaro; Totsuka, Hirohiko; Shirakihara, Takuya; Sakamoto, Hiromi; Wang, Linghua; Ojima, Hidenori; Shimada, Kazuaki; Kosuge, Tomoo; Okusaka, Takuji; Kato, Kazuto; Kusuda, Jun; Yoshida, Teruhiko; Aburatani, Hiroyuki; Shibata, Tatsuhiro

    2011-05-01

    Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.

  6. Evaluation of transcatheter therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yamada, Toshihiko

    1990-01-01

    The author proposed improvement of the criteria for the effects of transcatheter therapy for hepatocellular carcinoma. 104 patients were treated by transcatheter therapy. Their responses were determined by the usual criteria. Next, they were classified and evaluated in 3 groups, with the area of lipiodol deposition on CT for over 4 weeks regarded as nacrosis. The result was determined, and its relationship to prognosis was studied in light of the repeated therapy. By the usual criteria, only 10% of patients were judged as PR, and there were no differences between therapies. Many of the NC cases had low AFP levels with therapy. At the initial therapy, the ratio of cases with low AFP levels was higher and the survival time was longer in the A group. So the A group was judged as most effective. Clinically, 10 patients were considered most benefitted by therapy. They were considered the A group, but all were judged as NC. Considering the effects of repeated therapy, 10 patients with NC were judged as the A-max group. Prognosis was poor in patients of the B-max and C-max groups. These results indicate that judgement by the usual criteria was inconsistent with clinical condition. It was improved by regarding the area of lipiodol deposition on CT for over 4 weeks as necrosis. Estimations of effects and prognosis were made more accurate by considering repeated therapy. Thus, the proposed improvement of the criteria by CT is more useful to estimate transcatheter therapy of the hepatocellular carcinoma. (author)

  7. Radiological imagings of small hepatocellular carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Hidetoshi; Hayashi, Kuniaki; Futagawa, Sakae; Matsunaga, Naofumi; Maeda, Tohru [Nagasaki Univ. (Japan). School of Medicine

    1984-08-01

    Forty three cases of small hepatocellular carcinoma (measuring less than 3 cm in diameter on imaging modalities) were detected during a period of four years and two months. There were two cases in which hepatoma measured 1 cm in diameter, twenty four cases between 1 and 2 cm, and seventeen cases between 2 and 3 cm. The relative role of each modality and AFP value in the detection of these tumors was evaluated. The detection rate of small hepatocellular carcinoma by liver scintigraphy, ultrasonography (US), computed tomography (CT) and angiography was 8%, 74%, 70% and 95%, respectively. The sensitivity of serum AFP value was 67% (either measuring more than 200ng/ml or showing a tendency of steady rising even if below the level of 200ng/ml). Most hepatomas less than 2 cm in size were hypoechoic on US, and those above 2 cm in size were hyperechoic with peripheral sonolucency (halo). Almost all cases were described as low density area on both plain and enhancement CT. Angiography was the best method for detecting small hepatomas. It may be recommended to perform angiography on every patient with liver cirrhosis at the time of diagnosis of this disease. Periodic examinations by AFP, US and CT should be done if the angiography was negative. Evaluation by US in every three months and by CT in every twelve months may be appropriate.

  8. Skeletal metastases from primary hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

    1988-01-01

    In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

  9. Molecular Mechanisms Underlying Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Christian Trepo

    2009-11-01

    Full Text Available Hepatocarcinogenesis is a complex process that remains still partly understood. That might be explained by the multiplicity of etiologic factors, the genetic/epigenetic heterogeneity of tumors bulks and the ignorance of the liver cell types that give rise to tumorigenic cells that have stem cell-like properties. The DNA stress induced by hepatocyte turnover, inflammation and maybe early oncogenic pathway activation and sometimes viral factors, leads to DNA damage response which activates the key tumor suppressive checkpoints p53/p21Cip1 and p16INK4a/pRb responsible of cell cycle arrest and cellular senescence as reflected by the cirrhosis stage. Still obscure mechanisms, but maybe involving the Wnt signaling and Twist proteins, would allow pre-senescent hepatocytes to bypass senescence, acquire immortality by telomerase reactivation and get the last genetic/epigenetic hits necessary for cancerous transformation. Among some of the oncogenic pathways that might play key driving roles in hepatocarcinogenesis, c-myc and the Wnt/β-catenin signaling seem of particular interest. Finally, antiproliferative and apoptosis deficiencies involving TGF-β, Akt/PTEN, IGF2 pathways for instance are prerequisite for cancerous transformation. Of evidence, not only the transformed liver cell per se but the facilitating microenvironment is of fundamental importance for tumor bulk growth and metastasis.

  10. Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    An, Jun; Liu, Zhiyong; Liang, Qiong; Pan, Yuhang; Li, Haifeng; Wang, Ruizhi; Jin, Yi

    2017-09-01

    The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (Phepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (Phepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (Phepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dosimetry boron neutron capture therapy in liver cancer (hepatocellular carcinoma) by means of MCNP-code with neutron source from thermal column

    International Nuclear Information System (INIS)

    Irhas; Andang Widi Harto; Yohannes Sardjono

    2014-01-01

    Boron Neutron Capture Therapy (BNCT) using physics principle when B 10 (Boron-10) irradiated by low energy neutron (thermal neutron). Boron and thermal neutron reaction produced B 11m (Boron-11m) (t 1/2 =10 -2 s). B 11m decay emitted alpha, Li 7 (Lithium-7) particle and gamma ray. Irradiated time needed to ensure cancer dose enough. Liver cancer was primary malignant who located in liver (Hepatocellular carcinoma). Malignant in liver were different to metastatic from Breast, Colon Cancer, and the other. This condition was Metastatic Liver Cancer. Monte Carlo method used by Monte Carlo N-Particle (MCNP) Software. Probabilistic approach used for probability of interaction occurred and record refers to characteristic of particle and material. In this case, thermal neutron produced by model of Collimated Thermal Column Kartini Research Nuclear Reactor, Yogyakarta. Modelling organ and source used liver organ that contain of cancer tissue and research reactor. Variation of boron concentration was 20, 25, 30, 35, 40, 45, and 47 µg/g cancers. Output of MCNP calculation were neutron scattering dose, gamma ray dose and neutron flux from reactor. Neutron flux used to calculate alpha, proton and gamma ray dose from interaction of tissue material and thermal neutron. Variation of boron concentration result dose rate to every variation were 0,059; 0,072; 0,084; 0,098; 0.108; 0,12; 0,125 Gy/sec. Irradiation time who need to every concentration were 841,5 see (14 min 1 sec); 696,07 sec(11 min 36 sec); 593.11 sec (9 min 53 sec); 461,35 sec (8 min 30 sec); 461,238 sec (7 min 41 sec); 414,23 sec (6 min 54 sec); 398,38 sec (6 min 38 sec). Irradiating time could shortly when boron concentration more high. (author)

  12. [Care pathway of patients with hepatocellular carcinoma in France: State of play in 2017].

    Science.gov (United States)

    Costentin, Charlotte; Ganne-Carrié, Nathalie; Rousseau, Benoit; Gérolami, René; Barbare, Jean-Claude

    2017-09-01

    Hepatocellular carcinoma is a major public health problem with one of the highest overall mortality compared to other cancers. The median overall survival in France in a hospital population with hepatocellular carcinoma is 9.4 months. Several publications reported a positive impact of hepatocellular carcinoma screening on diagnosis at an early-stage, eligibility for curative treatment and overall survival. However, the identification of patients to be included in a hepatocellular carcinoma screening program and the application of screening recommendations are not optimal. Other studies suggest a potentially negative impact of delayed diagnosis or treatment initiation on the patient's prognosis. Finally, marked variations between French regions and departments have been described in terms of access to curative treatment and overall survival. In this review article, we propose a state of play of the hepatocellular carcinoma patient's care pathway in France with the aim of identifying potential breaking points with negative impact on prognosis and of developing proposals for improvement. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

  14. Nanosecond pulsed electric field ablation of hepatocellular carcinoma.

    Science.gov (United States)

    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.

  15. Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features

    OpenAIRE

    Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

    2013-01-01

    Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independen...

  16. 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, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Changing incidence patterns of hepatocellular carcinoma among age groups in Taiwan.

    Science.gov (United States)

    Hung, Giun-Yi; Horng, Jiun-Lin; Yen, Hsiu-Ju; Lee, Chih-Ying; Lin, Li-Yih

    2015-12-01

    This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years after a universal hepatitis B virus immunization program was launched. Data for hepatocellular carcinoma diagnosed in 2003-2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003-2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: -16.6%, 2003-2010) and adolescents and young adults (annual percent change: -7.9%, 2003-2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: -2%, 2003-2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Spontaneous rupture of adrenal metastasis from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chae Hun; Kim, Hyun Jin; Park, Soo Youn; Hwang, Seong Su; Choi, Hyun Joo [St. Vincent Hospital, Suwon (Korea, Republic of)

    2007-03-15

    Rupture of adrenal tumor from various primary origins is a rather rare event. We report here on a ruptured adrenal metastasis from hepatocellular carcinoma, and this ruptured metastasis was observed at the time of the initial diagnosis.

  19. Imaging findings of mimickers of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Tae Kyoung Kim

    2015-12-01

    Full Text Available Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis.

  20. Diagnosis of small hepatocellular carcinoma by incremental dynamic CT

    International Nuclear Information System (INIS)

    Uchida, Masafumi; Kumabe, Tsutomu; Edamitsu, Osamu

    1993-01-01

    Thirty cases of pathologically confirmed small hepatocellular carcinoma were examined by Incremental Dynamic CT (ICT). ICT scanned the whole liver with single-breath-hold technique; therefore, effective early contrast enhancement could be obtained for diagnosis. Among the 30 tumors, 26 were detected. The detection rate was 87%. A high detection rate was obtained in tumors more than 20 mm in diameter. Twenty-two of 26 tumors could be diagnosed correctly. ICT examination was useful for detection of small hepatocellular carcinoma. (author)

  1. Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

    OpenAIRE

    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. La...

  2. 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.......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....

  3. Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease.

    Science.gov (United States)

    Gunjan, Deepak; Shalimar; Nadda, Neeti; Kedia, Saurabh; Nayak, Baibaswata; Paul, Shashi B; Gamanagatti, Shivanand Ramachandra; Acharya, Subrat K

    2017-06-01

    Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma.

  4. Evaluation of CT in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Norio; Miura, Yukio; Ohnishi, Mitsunori; Kamikon-ya, Norihiko; Sakamoto, Yoshisato; Miura, Takashi; Sakamoto, Kiyoshi; Takayasu, Yoshio

    1985-06-01

    In order to evaluate the diagnostic ability of CT in hepatocellular carcinoma, four kinds of CT images were comparatively studied by the accuracy and ROC (receiver operating characteristic) curve analysis. As a result, it was clarified that CT images were evaluated more objectively by ROC curve analysis than by accuracy. The diagnostic ability of existence and differentiation of tumor in the liver were higher in order of plain CT, contrast enhanced CT (CECT), bolus CT and CT arteriography (CTA). Therefore, in an usual CT examination intended to make differential diagnosis in space occupying liver disease, bolus CT seems to be indispensable, and also CTA is essential where diagnosis is difficult even by bolus CT.

  5. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-07

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

  6. Hepatocellular carcinoma detected by iodized oil

    International Nuclear Information System (INIS)

    Yumoto, Y.; Jinno, K.; Tokuyama, K.

    1985-01-01

    This study assesses the diagnostic value of Lipiodol (iodized oil) and computed tomography (CT) in detecting hepatocellular carcinoma (HCC). Twenty-four patients who were suspected of having HCC received injections of a small amount of Lipiodol, along with an antitumor agent, in the hepatic artery following routine celiac angiography. CT scans obtained 7-10 days after Lipiodol administration demonstrated HCC in distinct contrast to the surrounding noncancerous parenchyma. In particular, the CT-Lipiodol procedure disclosed many small HCC lesions that were not shown by celiac angiography, scintigraphy, CT with an without contrast medium enhancement, and ultrasonography. Although this procedure may miss very small or highly fibrotic lesions, it is recommended for patients suspected of having HCC and for patients for whom hepatic resection is being considered

  7. 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.

  8. Computed tomographic findings of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Eun, Chung Kie [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

    1982-09-15

    It is well known that CT is very useful in the evaluation of hepatocellular carcinoma. The computed tomographic findings of 56 patients diagnosed as hepatocellular carcinoma were reviewed and analyzed. The results were as follows: 1. The male to female ratio was 3 : 1 and the age ranged from 31 to 73 years with average age of 54 years. 2. Alpha-fetoprotein was positive in 19 out of 38 cases (50%). HBsAg was positive in 8 out of 33 cases (24%). 3. All lesions were seen as areas of low density except 1 case (0%) of isodensity, and 40 cases (72%) appeared to be solitary while 15 (26%) were multifocal. The low density was homogenous in 13 cases (24%) and inhomogenous in 42 cases (76%), and 18 cases out of 42 cases inhomogenous low density showed peripheal and/or central nodular enhancement. The additional findings were contour changes in 37 cases (66%), metastasis in 35 cases (63%), splenomegaly in 23 cases (42%) and ascities in 22 cases (39%). 4. In postcontrast scans, 41 cases (80%) out of 51 cases showed the change of density after contrast infusion. The presence and extent of tumors were better seen after contrast infusion in 30 cases (59%), better seen before contrast infusion in 11 cases (21%) and no significant difference before and after contrast infusion in 10 cases (20%). 5. The sites of involved lobe were right lobe in 38 cases (68%), left lobe in 5 cases (9%) and both lobes in 13 cases (23%). 6. 35 cases (63%) showed evidence of metastasis to regional lymph nodes, organ or tissues.

  9. The clinical significance and biological function of lncRNA RGMB-AS1 in hepatocellular carcinoma.

    Science.gov (United States)

    Sheng, Nan; Li, Yannan; Qian, Ruikun; Li, Yichun

    2018-02-01

    LncRNA RGMB-AS1 has been suggested to play significant roles in lung cancer progression. However, it remains unknown whether lncRNA RGMB-AS1 is involved in the development and progression of hepatocellular carcinoma. In our results, lncRNA RGMB-AS1 was low-expressed in hepatocellular carcinoma tissues and cell lines, and associated with clinical stage, tumor size and metastasis. Survival analysis indicated that lncRNA RGMB-AS1 high was an independent favorable prognostic factor for hepatocellular carcinoma patients. Gain-of-function studies showed up-regulated lncRNA RGMB-AS1 expression suppressed hepatocellular carcinoma cells proliferation, migration and invasion, and promoted cells apoptosis. There was a positively association between lncRNA RGMB-AS1 and RGMB in hepatocellular carcinoma tissues, and up-regulated lncRNA RGMB-AS1 expression increased RGMB mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, lncRNA RGMB-AS1 serves an anti-oncogenic role in hepatocellular carcinoma. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

    Science.gov (United States)

    Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

    2018-03-24

    Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

  11. 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.

  12. Evaluation of the prognostic value of Okuda, Cancer of the Liver Italian Program, and Japan Integrated Staging systems for hepatocellular carcinoma patients undergoing radiotherapy

    International Nuclear Information System (INIS)

    Seong, Jinsil; Shim, Su Jung; Lee, Ik Jae; Han, Kwang Hyub; Chon, Chae Yoon; Ahn, Sang Hoon

    2007-01-01

    Purpose: The purpose of this study was to compare the validity of staging systems, as well as to identify the staging system with the best prognostic value, in hepatocellular carcinoma (HCC) patients treated with radiotherapy. Methods and Materials: From 1992 to 2003, a total of 305 patients undergoing radiotherapy for HCC were evaluated retrospectively. All patients were classified before radiation therapy by the following systems: tumor-node-metastasis (TNM), Okuda, Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging (JIS) score. Cumulative survival rates were obtained using the Kaplan-Meier method, and were statistically compared using the log-rank test. Results: Median survival time was 11 months. The 1-, 2-, 3-, 4-, and 5-year survival rates were 45.1%, 24.5%, 14.7%, 10.3%, and 6.4%, respectively. Significant differences in survival were observed between all TNM stages, between CLIP scores 2, 3 and 5, 6, as well as between JIS scores 1, 2, and 2, 3. Conclusions: Among the systems studied, the TNM staging approach appeared to be the best predictor of prognosis. Staging systems that reflect liver disease status (Okuda stage, CLIP, and JIS score) showed limitations in stratifying patients undergoing radiotherapy into different prognostic groups

  13. [Comparison liver resection with transarterial chemoembolization for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma patients on long-term survival after SPSS propensity score matching].

    Science.gov (United States)

    Ke, Yang; Zhong, Jianhong; Guo, Zhe; Liang, Yongrong; Li, Lequn; Xiang, Bangde

    2014-03-18

    To compare the long-term survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) undergoing either liver resection or transarterial chemoembolization (TACE) after propensity score matching (PSM). One hundred sixty-seven and 70 BCLC-B HCC patients undergoing liver resection and TACE were retrospectively collected. PSM function of SPSS software was conducted to reduce confounding bias between the groups. And then survival analysis was performed for the matched data. Fifty-three pairs of patients were successfully matched. And then survival analysis showed that the median survival periods and their 95% confidence intervals were 35.0 (26.3-43.7)months in the liver resection group versus 20.0(15.0-25.0) months in the TACE group. The 1, 3, 5 and 7-year survival rates were 91.0%, 49.0%, 30.0% and 17.0% in the liver resection group versus 73.0%, 25.0%, 8.0% and 5.0% respectively in the TACE group (P = 0.001). Cox regression analysis revealed that TACE, total bilirubin ≥ 34.2 µmol/L, alpha fetoprotein ≥ 400 ng/ml and tumor number ≥ 3 were independent risk factors of survival (hazard ratio >1, P < 0.05). The balance of covariates may be achieved through PSM. And for patients with BCLC-B HCC, liver resection provides better long-term overall survival than TACE.

  14. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Sung, Wing-Kin; Zheng, Hancheng; Li, Shuyu

    2012-01-01

    To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) than...

  15. AMACR is not applicable as a diagnostic tool in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Willemoe, Gro Linno; Vainer, Ben

    2010-01-01

    that the demonstration of AMACR expression or its pattern of distribution is useful in the diagnosis of hepatocellular carcinoma (HCC) (Jiang et al., Hum Pathol 2003;34, Guzman et al., Appl Immunohistochem Mol Morphol 2006;14, Li et al., J Exp Clin Cancer Res 2008;27). The aim of the present study was to evaluate...

  16. Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report

    International Nuclear Information System (INIS)

    Casadei Gardini, Andrea; Chiadini, Elisa; Faloppi, Luca; Marisi, Giorgia; Delmonte, Angelo; Scartozzi, Mario; Loretelli, Cristian; Lucchesi, Alessandro; Oboldi, Devil; Dubini, Alessandra; Frassineti, Giovanni Luca; Ulivi, Paola

    2016-01-01

    Sorafenib is a multi-targeted kinase inhibitor with a demonstrated activity in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC), and it is currently used for the treatment of these pathologies. Ongoing clinical trials are studying its activity in other malignancies, such as non-small-cell lung cancer (NSCLC). However, no biological marker is known to define either the sensitivity or resistance to the drug. Here we report a case of a patient with two synchronous tumors, HCC and NSCLC, with metastases in the contralateral lung and bone. The patient was treated with gemcitabine as first line, with a resulting progressive disease after two months, and then with sorafenib at standard dosage in the second line setting. After 6 months of treatment CT scan showed a partial response in the primary lesion of the lung, complete response of the metastasis in the contralateral lung, and stability of HCC. The patient had progression in the lung, liver and bone after 13 months of therapy. A molecular characterization of NSCLC and HCC lesions was performed, revealing a BRAF exon 11 mutation (G469V) only in NSCLC. We hypothesize that the response observed in NSCLC lesions could be due to the presence of BRAF mutation, and that this alteration could be responsible in determining sorafenib sensitivity. Results observed in this case encourage further research on the activity of sorafenib in both HCC and NSCLC, based on the presence of BRAF mutation. This could lead to a selection of HCC patients to be treated with this drug, and could help identify a novel treatment strategy for BRAF-mutated NSCLC patients

  17. BTG2 Is Down-Regulated and Inhibits Cancer Stem Cell-Like Features of Side Population Cells in Hepatocellular Carcinoma.

    Science.gov (United States)

    Huang, Chen-Song; Zhai, Jing-Ming; Zhu, Xiao-Xu; Cai, Jian-Peng; Chen, Wei; Li, Jian-Hui; Yin, Xiao-Yu

    2017-12-01

    Our previous study found that B cell translocation gene 2 (BTG2) was hyper-methylated and down-regulated in side population (SP) cells of hepatocellular carcinoma (HCC) cell line. However, its clinical significances and biological impacts on HCC SP cells remained unclear. To investigate the prognostic value of BTG2 gene in HCC and its influences on cancer stem cells (CSCs)-like traits of HCC cell line SP cells. BTG2 expression in human HCC and adjacent non-cancerous tissues was detected by immunohistochemical staining and quantitative real-time PCR, and also obtained from GEO and TCGA data. Its prognostic values were assessed. Its biological influences on HCC cell line SP cells were evaluated using cell viability, cell cycle, plate clone-forming assay, and chemoresistance in vitro and tumorigenicity in vivo. BTG2 expression was significantly suppressed in human HCC compared to adjacent non-cancerous tissues. BTG2 expression was correlated with TNM stage, tumor size and vascular invasion. Lower expression of BTG2 was associated with poorer overall survival and disease-free survival. In vitro, overexpression of BTG2 substantially suppressed cell proliferation and accumulation of HCC cell line SP cells in G0/G1 phase. Colony formation ability was markedly suppressed by BTG2 overexpression. Moreover, sensitivity of HCC cell line SP cells to 5-fluorouracil was substantially increased by overexpression of BTG2. Furthermore, tumorigenicity of HCC cell line SP cells transfected with BTG2 plasmids was significantly reduced in vivo. BTG2 gene could regulate the CSC-like traits of HCC cell line SP cells, and it represented as a molecular prognostic marker for HCC.

  18. Risks of Liver (Hepatocellular) Cancer Screening

    Science.gov (United States)

    ... cancer. Having hepatitis or cirrhosis can increase the risk of developing liver cancer. Anything that increases the ... clinical trials is available from the NCI website . Risks of Liver (Hepatocellular) Cancer Screening Key Points Screening ...

  19. Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

    Science.gov (United States)

    Sheppard-Law, Suzanne; Zablotska-Manos, Iryna; Kermeen, Melissa; Holdaway, Susan; Lee, Alice; George, Jacob; Zekry, Amany; Maher, Lisa

    2018-07-01

    To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. Multi-site cross-sectional survey. An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus

  20. Scintigraphic demonstration of a metastasizing hepato-cellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, P; Gratz, K F; Schwarzrock, R; Schober, O; Neuhaus, P; Creutzig, H

    1986-01-01

    Adenomas and hepato cellular carcinomas cannot be differentiated by nuclear medicine: both exhibit masked radiodrug trapping at reduced perfusion. Two patients revealed specific accumulation in extrahepatic foci unknown before; hence, the diagnosis of a metastasizing hepatocellular carcinoma had to be verified. One case is demonstrated in full detail. (orig./SHA).

  1. Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C

    DEFF Research Database (Denmark)

    Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte

    2012-01-01

    To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....

  2. Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma.

    Science.gov (United States)

    Galal El-Shemi, A; Mohammed Ashshi, A; Oh, E; Jung, B-K; Basalamah, M; Alsaegh, A; Yun, C-O

    2018-01-01

    Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono- and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.

  3. Hypoxia induces copper stable isotope fractionation in hepatocellular carcinoma, in a HIF-independent manner.

    Science.gov (United States)

    Bondanese, Victor P; Lamboux, Aline; Simon, Melanie; Lafont, Jérôme E; Albalat, Emmanuelle; Pichat, Sylvain; Vanacker, Jean-Marc; Telouk, Philippe; Balter, Vincent; Oger, Philippe; Albarède, Francis

    2016-11-09

    Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer, with increasing incidence worldwide. The unrestrained proliferation of tumour cells leads to tumour hypoxia which in turn promotes cancer aggressiveness. While changes in the concentration of copper (Cu) have long been observed upon cancerization, we have recently reported that the isotopic composition of copper is also altered in several types of cancer. In particular, we showed that in hepatocellular carcinoma, tumour tissue contains heavier copper compared to the surrounding parenchyma. However, the reasons behind such isotopic signature remained elusive. Here we show that hypoxia causes heavy copper enrichment in several human cell lines. We also demonstrate that this effect of hypoxia is pH, HIF-1 and -2 independent. Our data identify a previously unrecognized cellular process associated with hypoxia, and suggests that in vivo tumour hypoxia determines copper isotope fractionation in HCC and other solid cancers.

  4. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

    International Nuclear Information System (INIS)

    Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    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

  5. 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.

  6. 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.

  7. Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

    International Nuclear Information System (INIS)

    Lee, Edward Wolfgang; Alanic, Lourdes; Cho, Sung Ki; Saab, Sammy

    2016-01-01

    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

  8. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

    Science.gov (United States)

    Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    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.

  9. 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.

  10. Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy. Trends and perspectives

    Directory of Open Access Journals (Sweden)

    Guillermo D. Mazzolini

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC

  11. 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.

  12. 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.

  13. Imaging of hepatocellular carcinoma; Bildgebung des hepatozellulaeren Karzinoms

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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.

  15. Tobacco carcinogen (NNK) induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation

    Science.gov (United States)

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carc...

  16. Liver (Hepatocellular) Cancer Prevention

    Science.gov (United States)

    ... factors for some types of cancer, but only smoking can be avoided. Regular exercise and a healthy diet may be protective factors ... may help prevent certain cancers. Risk factors include smoking, being ... enough exercise. Increasing protective factors such as quitting smoking and ...

  17. Nanog regulates self-renewal of cancer stem cells through the insulin-like growth factor pathway in human hepatocellular carcinoma.

    Science.gov (United States)

    Shan, Juanjuan; Shen, Junjie; Liu, Limei; Xia, Feng; Xu, Chuan; Duan, Guangjie; Xu, Yanmin; Ma, Qinghua; Yang, Zhi; Zhang, Qianzhen; Ma, Leina; Liu, Jia; Xu, Senlin; Yan, Xiaochu; Bie, Ping; Cui, Youhong; Bian, Xiu-wu; Qian, Cheng

    2012-09-01

    Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem-cell-related genes are preferentially overexpressed in a fraction of cancer cells of poorly differentiated tumors. However, it is not known whether or how these cancer cells contribute to tumor initiation and progression. Here, our data showed that increased expression of pluripotency transcription factor Nanog in cancer cells correlates with a worse clinical outcome in HCC. Using the Nanog promoter as a reporter system, we could successfully isolate a small subpopulation of Nanog-positive cells. We demonstrate that Nanog-positive cells exhibited enhanced ability of self-renewal, clonogenicity, and initiation of tumors, which are consistent with crucial hallmarks in the definition of cancer stem cells (CSCs). Nanog(Pos) CSCs could differentiate into mature cancer cells in in vitro and in vivo conditions. In addition, we found that Nanog(Pos) CSCs exhibited resistance to therapeutic agents (e.g., sorafenib and cisplatin) and have a high capacity for tumor invasion and metastasis. Knock-down expression of Nanog in Nanog(Pos) CSCs could decrease self-renewal accompanied with decreased expression of stem-cell-related genes and increased expression of mature hepatocyte-related genes. Overexpression of Nanog in Nanog(Neg) cells could restore self-renewal. Furthermore, we found that insulin-like growth factor (IGF)2 and IGF receptor (IGF1R) were up-regulated in Nanog(Pos) CSCs. Knock-down expression of Nanog in Nanog(Pos) CSCs inhibited the expression of IGF1R, and overexpression of Nanog in Nanog(Neg) cells increased the expression of IGF1R. A specific inhibitor of IGF1R signaling could significantly inhibit self-renewal and Nanog expression, indicating that IGF1R signaling participated in Nanog-mediated self-renewal. These data indicate that Nanog could be a novel biomarker for CSCs in HCC, and that Nanog could play a crucial role in maintaining the self-renewal of CSCs through the IGF1R

  18. Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.

    Science.gov (United States)

    An, Jun; Zhang, Zhigang; Liu, Zhiyong; Wang, Ruizhi; Hui, Dayang; Jin, Yi

    2017-12-06

    Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma. In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry. We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion. Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.

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  13. Hepatocellular carcinomas supplied by inferior phrenic arteries.

    Science.gov (United States)

    Tanabe, N; Iwasaki, T; Chida, N; Suzuki, S; Akahane, T; Kobayashi, N; Ishii, M; Toyota, T

    1998-07-01

    To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). A total of 126 consecutive cases of HCC were studied by contract-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 1, 1, and 4. HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography.

  14. 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.

  15. CT findings of exophytic hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    1993-11-15

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

  16. Ectopic hepatocellular carcinoma in a dog.

    Science.gov (United States)

    Burton, I R; Limpus, K; Thompson, K G; Owen, M C; Worth, A J

    2005-12-01

    A 14-year-old neutered male Bearded Collie was presented with a history of recurrent, intermittent urinary incontinence of 7 years duration. A large, firm, non-painful mass was found in the mid-abdominal region on palpation. Ultrasonography of the mass revealed a compartmentalised structure with mixed echogenicity, and which did not appear to be associated with any of the abdominal organs. Ultrasound-guided fine needle aspirates contained several clusters of epithelial cells with cytological features of hepatocytes. At exploratory laparotomy, the mass was found in the gastrosplenic ligament within the greater omentum. PATHOLOGICAL FINDINGS AND DIAGNOSIS: Histopathologically, the mass consisted of sheets of hepatocytes, but without the characteristic hepatic architecture. The cells showed moderate variation in nuclear size and were sometimes binucleate. A diagnosis of hepatocellular carcinoma (HCC) in the mesentery was made. The presence of ectopic hepatic tissue has been reported rarely in man and cats, but not in the dog. Neoplastic transformation of ectopic hepatic tissue is seen in man. This is the first report of the presentation, clinical findings and treatment of a dog with ectopic HCC.

  17. Repeated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hashimoto, Takayuki; Tokuuye, Koichi; Fukumitsu, Nobuyoshi; Igaki, Hiroshi; Hata, Masaharu; Kagei, Kenji; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki

    2006-01-01

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

  18. 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.

  19. Hepatocellular carcinomas supplied by inferior phrenic arteries

    International Nuclear Information System (INIS)

    Tanabe, N.; Iwasaki, T.; Akahane, T.; Kobayashi, N.; Ishii, M.; Toyota, T.; Chida, N.; Suzuki, S.

    1998-01-01

    Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). Material and Methods: A total of 126 consecutive cases of HCC were studied by contrast-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 7, 1, and 4. Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography. (orig.)

  20. Hepatocellular carcinomas supplied by inferior phrenic arteries

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, N.; Iwasaki, T.; Akahane, T.; Kobayashi, N.; Ishii, M.; Toyota, T. [Tohoku Univ. School of Medicine (Japan). Third Dept. of Internal Medicine; Chida, N.; Suzuki, S. [National Sendai Hospital (Japan). Dept. of Gastroenterology

    1998-07-01

    Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). Material and Methods: A total of 126 consecutive cases of HCC were studied by contrast-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 7, 1, and 4. Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography. (orig.)

  1. 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

  2. Combined Primary Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver

    Directory of Open Access Journals (Sweden)

    Chii-Shuenn Yang

    2009-08-01

    Full Text Available We report a unique case of combined primary neuroendocrine carcinoma (NEC and hepatocellular carcinoma (HCC of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.

  3. A Gene Expression Signature Associated With Overall Survival in Patients With Hepatocellular Carcinoma Suggests a New Treatment Strategy

    DEFF Research Database (Denmark)

    Gillet, Jean-Pierre; Andersen, Jesper B; Madigan, James P

    2015-01-01

    Despite improvements in the management of liver cancer, the survival rate for individuals with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure...... are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance-associated genes in two independent cohorts of patients with advanced hepatocellular carcinoma, with the aim of finding ways to improve survival in this poor-prognosis cancer...

  4. Magnetic Resonance Imaging Finding of Metastatic Hepatocellular Carcinoma in Ovary: A Case Report

    International Nuclear Information System (INIS)

    Kwak, Soon Hyuk; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Han, Gi Seok; Cha, Sang Hoon; Park, Kil Sun; Kim, Sung Jin; Choi, Song Yi

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignant tumor of liver. Metastasis of hepatocellular carcinoma occurs in various organs, but metastasis to the ovary is extremely rare. We report MRI finding of metastatic hepatocellular carcinoma of the ovary in a 37-year-old woman who was treated hepatocellular carcinoma transarterial chemoembolization and radiofrequency ablation a year ago. Pelvic MRI revealed a mass in pelvic cavity with heterogeneous signal intensity and centripetal enhancement. Surgical excision and pathologic examination confirmed metastatic hepatocellular carcinoma in the ovary.

  5. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  6. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-03-23

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

  7. 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

  8. Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience

    Science.gov (United States)

    Yeh, Matthew M; Yeung, Raymond S; Apisarnthanarax, Smith; Bhattacharya, Renuka; Cuevas, Carlos; Harris, William P; Hon, Tony Lim Kiat; Padia, Siddharth A; Park, James O; Riggle, Kevin M; Daoud, Sayed S

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics. PMID:26085907

  9. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

    Science.gov (United States)

    Hafeez Bhatti, Abu Bakar; Dar, Faisal Saud; Waheed, Anum; Shafique, Kashif; Sultan, Faisal; Shah, Najmul Hassan

    2016-01-01

    Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level. PMID:26955390

  10. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

    Directory of Open Access Journals (Sweden)

    Abu Bakar Hafeez Bhatti

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3% in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level.

  11. How to detect hepatocellular carcinoma in cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Ward, Janice; Robinson, Philip J. [Department of Clinical Radiology, St. James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom)

    2002-09-01

    Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis. (orig.)

  12. 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

  13. Angiogenic Blockade and Radiotherapy in Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Chi, Kwan-Hwa; Liao, Chao-Sheng; Chang, Chih-Chia; Ko, Hui-Ling; Tsang, Yuk-Wah; Yang, Kuo-Ching; Mehta, Minesh P.

    2010-01-01

    Purpose: We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC. Methods and Materials: Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial α-fetoprotein (AFP) kinetics, and survival. Results: Of 23 evaluable patients, 60% had ≥2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had ≥50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had ≥Grade 2 elevation of liver enzymes, and 15 had ≥Grade 2 thrombocytopenia. Conclusions: These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.

  14. Hemodynamic characteristics of early stage hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kudo, Masatoshi; Tomita, Shusuke; Tochio, Hitoshi

    1992-01-01

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

  15. Diagnosis of small hepatocellular carcinoma by computed tomography. Study in comparison with pathologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Tsunetomi, Shigeyuki; Ohto, Masao; Iino, Yasuo [Chiba Univ. (Japan). School of Medicine

    1984-01-01

    The capability of CT in detecting small hepatocellular carcinoma less than 5 cm in size was studied in 48 patients. Changes in the density of the tumors were analyzed in comparison with the pathologic and angiographic findings. Iso-density was the main cause that made the tumors undetectable in either precontrast or post-contrast scan. By combination of precontrast and postcontrast scans, the majority of the tumors larger than 2 cm were detected. In precontrast scan, the density of the tumors was related to bleeding, necrosis and fatty degeneration in the cancer tissue, and fatty degeneration in the non-cancer tissue. In postcontrast scan, it was related to bleeding, necrosis, fatty degeneration and blood spaces in the cancer tissue. Thus, CT can demonstrate accurately the pathological changes of the tumors as images, and it may be useful not only in the diagnosis of small hepatocellular carcinoma, but also in the assessment of the therapeutic effects.

  16. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    International Nuclear Information System (INIS)

    Hasegawa, Y.; Nakano, S.; Ibuka, K.

    1986-01-01

    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

  17. Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report.

    Science.gov (United States)

    Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

    2015-11-06

    Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism.

  18. Pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism: a case report

    International Nuclear Information System (INIS)

    Tanaka, Tomoko; Hiramatsu, Katsushi; Nosaka, Takuto; Saito, Yasushi; Naito, Tatsushi; Takahashi, Kazuto; Ofuji, Kazuya; Matsuda, Hidetaka; Ohtani, Masahiro; Nemoto, Tomoyuki; Suto, Hiroyuki; Yamamoto, Tatsuya; Kimura, Hirohiko; Nakamoto, Yasunari

    2015-01-01

    Metastasis to the pituitary gland is extremely rare and is often detected incidentally by symptoms associated with endocrine dysfunction. Breast and lung cancer are the most common primary metastasizing to pituitary gland. Metastasis from hepatocellular carcinoma to the pituitary gland is extremely rare, with only 10 cases having been previously reported. We present here the first case of pituitary metastasis of hepatocellular carcinoma presenting with panhypopituitarism diagnosed by magnetic resonance imaging. We report the case of an 80-year-old Japanese woman who presented with the sudden onset of hypotension and bradycardia after having previously been diagnosed with hepatocellular carcinoma. Based on low levels of pituitary hormones, she was diagnosed with panhypopituitarism caused by metastasis of the hepatocellular carcinoma to the pituitary gland. Magnetic resonance imaging with arterial spin-labeling was effective in the differential diagnosis of the intrasellar tumor. The patient died despite hormone replacement therapy because of hypovolemic shock. Metastasis to the pituitary gland causes various non-specific symptoms, so it is difficult to diagnose. The present case emphasizes the importance of diagnostic imaging in identifying these metastases. Clinicians should consider the possibility of pituitary metastasis in patients with malignant tumors who demonstrate hypopituitarism

  19. Correlations of matrix metalloproteinase content and expression with invasion and metastasis of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhang Zhichao; Jia Mingku; Sun Yaxin

    2006-01-01

    Objective: To investigate the correlations of serum matrix metalloproteinase-2, -9 (MMP-2, MMP-9) contents and tissue expressions in hepatocellular carcinoma with tumor invasion and metastasis. Methods: Serum MMP-2, MMP-9 contents were detected in 40 patient with hepatocellular carcinoma and 20 healthy controls by ELISA; the expressions and distributions of MMP-2 and MMP-9 in 40 patients and 10 normal tissues were detected by immunohistochemical method. Results: Serum MMP-2, MMP-9 contents were significantly elevated in cancer samples compared with normal serum (P<0.01), the significant difference was found between contents in the presence and the absence of lymph node metastasis (P<0.05). In hepatocellular carcinoma, the expressions of MMP-2, MMP-9 were increased significantly compared with normal tissue. The expressions of MMP-2, MMP-9 were correlated with histological grade and lymph node metastasis (P<0.05). Conclusion: The serum of MMP-2 and MMP-9 contents and their expressions may provide reliable information for hepatocellular carcinoma prognosis. (authors)

  20. 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.

  1. 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

  2. Regorafenib delays the proliferation of hepatocellular carcinoma by inducing autophagy.

    Science.gov (United States)

    Han, Rui; Li, Shixin

    2018-04-02

    The aim of the present study was to investigate the effects of regorafenib on hepatocellular carcinoma autophagy, thereby supressing the malignancy of HCC. First, HepG2 and Hep3B cell autophagy was investigated using GFP-LC3 transfection after the treatment of regorafenib. Then, the activation of Akt/mTOR signaling was analyzed using western blot. Our data showed that liver cancer cell autophagy was significantly induced by 20 μM regorafenib using GFP-LC3 transfection. Meanwhile, regorafenib-induced cell death could largely be abolished by 3-MA or CQ treatment, suggesting that regorafenib-induced HepG2 cell death was partially dependent on autophagy. Moreover, the activation of Akt/mTOR signaling was inhibited by regorafenib pre-incubation. MTT assay showed the combination use of regorafenib and CDDP led to a stronger growth inhibitory effect on HepG2 and Hep3B cells. In summary, regorafenib may acts an adjunctive therapy for liver cancer patients via modulating autophagy-dependent cell death even when apoptosis resistance is induced in cancer cells.

  3. Research advances in proton beam therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    DAI Shuyang

    2013-10-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the most common malignancies with high prevalence and mortality rate, usually results in poor prognosis and limited survival. A comprehensive analysis on the number and location of tumors, Child-Pugh grade, and Barcelona Clinic Liver Cancer stage will help the development of suitable treatment programs and improve prediction of prognosis. A majority of patients are complicated by cirrhosis, enlarged tumor, multiple lesions, vascular invasion, and even cancer embolus in the portal vein. With the growth of knowledge about the radiation tolerance of normal tissue and the advances in radiotherapy techniques, radiotherapy has become an important tool for step-down therapy and adjuvant therapy for liver cancer. Proton beam therapy (PBT is emerging as a novel radiotherapy for the management of HCC, which, benefiting from the effect of Bragg Peak from PBT, effectively decreases the toxicity of traditional radiotherapies to the liver and does little harm to the uninvolved liver tissue or the surrounding structures while intensifying the destruction in targeted malignant lesions. Furthermore, several previous studies on the treatment of HCC with PBT revealed excellent local control. The distinctive biophysical attributes of PBT in the treatment of HCC, as well as the available literature regarding clinical outcomes and toxicity of using PBT for HCC, are reviewed. Current evidence provides limited indications for PBT, which suggests that further study on the relationship between liver function and PBT is required to gain further insight into its indication and standardization.

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

    Directory of Open Access Journals (Sweden)

    Satoru Murata

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the sixth most common cancer and the third leading cause of cancer-related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation can improve survival in HCC patients diagnosed at an early stage and offer potential long-term curative effects. Patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE, and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced-stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced-stage HCC.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Prognostic significance of XRCC4 expression in hepatocellular carcinoma

    Science.gov (United States)

    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

  7. FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feifei Wang

    Full Text Available F-box only protein 8 (FBX8, a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05. The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.

  8. 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 ...

  9. 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 ...

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

    DEFF Research Database (Denmark)

    Hallager, Sofie; Weis, Nina

    2014-01-01

    Chronic hepatitis C (CHC) affects around 16,000 individuals in Denmark of whom about 50% are diagnosed. In the presence of CHC and cirrhosis the annual risk of hepatocellular carcinoma (HCC) is 1-5%. We report on two patients who presented with disseminated HCC at the time of CHC diagnosis...

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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

  13. MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    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.

  14. Thyroid cancer - medullary carcinoma

    Science.gov (United States)

    Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

  15. Screening for hepatocellular carcinoma by Egyptian physicians

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  16. 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

  17. Hepatocellular carcinoma: illustrated guide to systematic radiologic diagnosis and staging according to guidelines of the American Association for the Study of Liver Diseases.

    LENUS (Irish Health Repository)

    McEvoy, Sinead H

    2013-10-01

    Hepatocellular carcinoma is a malignancy that predominantly occurs in the setting of cirrhosis. Its incidence is rising worldwide. Hepatocellular carcinoma differs from most malignancies because it is commonly diagnosed on the basis of imaging features alone, without histologic confirmation. The guidelines from the American Association for the Study of Liver Diseases (AASLD) are a leading statement for the diagnosis and staging of hepatocellular carcinoma, and they have recently been updated, incorporating several important changes. AASLD advocates the use of the Barcelona Clinic Liver Cancer (BCLC) staging system, which combines validated imaging and clinical predictors of survival to determine stage and which links staging with treatment options. Each stage of the BCLC system is outlined clearly, with emphasis on case examples. Focal liver lesions identified at ultrasonographic surveillance in patients with cirrhosis require further investigation. Lesions larger than 1 cm should be assessed with multiphasic computed tomography or magnetic resonance imaging. Use of proper equipment and protocols is essential. Lesions larger than 1 cm can be diagnosed as hepatocellular carcinoma from a single study if the characteristic dynamic perfusion pattern of arterial hyperenhancement and venous or delayed phase washout is demonstrated. If the imaging characteristics of hepatocellular carcinoma are not met, the alternate modality should be performed. Biopsy should be used if neither modality is diagnostic of hepatocellular carcinoma. Once the diagnosis has been made, the cancer should be assigned a BCLC stage, which will help determine suitable treatment options. Radiologists require a systematic approach to diagnose and stage hepatocellular carcinoma with appropriate accuracy and precision.

  18. Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

    Science.gov (United States)

    Markowitz, Geoffrey J; Yang, Pengyuan; Fu, Jing; Michelotti, Gregory A; Chen, Rui; Sui, Jianhua; Yang, Bin; Qin, Wen-Hao; Zhang, Zheng; Wang, Fu-Sheng; Diehl, Anna Mae; Li, Qi-Jing; Wang, Hongyang; Wang, Xiao-Fan

    2016-04-15

    Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. ©2016 AACR. ©2016 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    Qiao You-Lin

    2011-05-01

    Full Text Available 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 outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country. Methods/Design The global HCC BRIDGE study is a multiregional longitudinal cohort trial including patients newly diagnosed with hepatocellular carcinoma between January 1, 2005, and June 30, 2011, who are receiving treatment for hepatocellular carcinoma via sites in the Asia-Pacific, European, and North American regions. The HCC BRIDGE China national study comprises the portion of the global HCC BRIDGE study conducted within mainland China. Patients will be followed from time of diagnosis of hepatocellular carcinoma (post-January 1, 2005 to time of death or December 31, 2011, whichever comes first. Data will be collected on demographic/clinical characteristics, relevant laboratory values, hepatocellular carcinoma/underlying liver disease treatment, tumor response, adverse events, hospitalizations, and overall survival. The primary study end point is overall survival; secondary end points are disease progression, treatment-limiting adverse events, and treatment failure. Results At the time of writing, 15 sites have selected for participation across all 7 traditional regions of China (North, North-East, East, South, South-West, North-West, and Central. The anticipated study population from the China national study is approximately 9000 patients. Discussion Findings from the

  20. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  1. Guide for diagnosis and treatment of hepatocellular carcinoma

    Science.gov (United States)

    Attwa, Magdy Hamed; El-Etreby, Shahira Aly

    2015-01-01

    Hepatocellular carcinoma (HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosis is determined by several factors; tumour extension, alpha-fetoprotein (AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient’s performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound (US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography (CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC. PMID:26140083

  2. Interventional Oncology in Hepatocellular Carcinoma: Progress Through Innovation.

    Science.gov (United States)

    Mu, Lin; Chapiro, Julius; Stringam, Jeremiah; Geschwind, Jean-François

    The clinical management of hepatocellular carcinoma has evolved greatly in the last decade mostly through recent technical innovations. In particular, the application of cutting-edge image guidance has led to minimally invasive solutions for complex clinical problems and rapid advances in the field of interventional oncology. Many image-guided therapies, such as transarterial chemoembolization and radiofrequency ablation, have meanwhile been fully integrated into interdisciplinary clinical practice, whereas others are currently being investigated. This review summarizes and evaluates the most relevant completed and ongoing clinical trials, provides a synopsis of recent innovations in the field of intraprocedural imaging and tumor response assessment, and offers an outlook on new technologies, such as radiopaque embolic materials. In addition, combination therapies consisting of locoregional therapies and systemic molecular targeted agents (e.g., sorafenib) remain of major interest to the field and are also discussed. Finally, we address the many substantial advances in immune response pathways that have been related to the systemic effects of locoregional therapies. Knowledge of these new developments is crucial as they continue to shape the future of cancer treatment, further establishing interventional oncology along with surgical, medical, and radiation oncology as the fourth pillar of cancer care.

  3. Improving clinical trial design for hepatocellular carcinoma treatments

    Directory of Open Access Journals (Sweden)

    Robert G. Gish

    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.

  4. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ranjit Chauhan

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    Seo, J.M.; Lee, S.J.; Kim, S.H.; Park, C.K.; Ha, S.Y.

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

  8. Open-label phase II clinical trial in 75 patients with advanced hepatocellular carcinoma receiving daily dose of tableted liver cancer vaccine, hepcortespenlisimut-L

    Directory of Open Access Journals (Sweden)

    Tarakanovskaya MG

    2017-04-01

    Full Text Available Marina G Tarakanovskaya,1 Jigjidsuren Chinburen,2 Purev Batchuluun,2 Chogsom Munkhzaya,2 Genden Purevsuren,2 Dorjiin Dandii,3 Tsogkhuu Hulan,3 Dandii Oyungerel,4 Galyna A Kutsyna,5 Alan A Reid,6 Vika Borisova,6 Allen I Bain,7 Vichai Jirathitikal,7 Aldar S Bourinbaiar6–8 1Ekomed LLC, 2National Cancer Center, 3Monserum LLC, 4National Center for Public Health, Ulaanbaatar, Mongolia; 5Department of Infectious Diseases, Luhansk State Medical University, Luhansk, Ukraine; 6Immunitor China Ltd, Beijing, People’s Republic of China; 7Immunitor Inc, Vancouver, BC, Canada; 8Immunitor LLC, Ulaanbaatar, Mongolia Background: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5]—an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA as an orphan drug for treatment of hepatocellular carcinoma (HCC. V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis.Methods: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively. Over a period of 5 years, 75 patients with advanced HCC were enrolled, consisting of 29 (38.7% females and 46 (61.3% males with a median age of 60 years (mean 61.6±8.1 years. Out of these, 23 (30.7% had hepatitis B and 34 (45.3% had hepatitis C infections, including 9 (12% with dual infection, 4 (5.3% negative for both viruses, and 5 (6.7% without established viral diagnosis. Most patients (94.7% had underlying liver cirrhosis of varying severity.Results: After a median of 2 months of treatment, 50 out of 75 patients had experienced a decline in serum levels of the tumor marker, alpha-fetoprotein (AFP (66.7%; P=0.006 by Wilcoxon signed rank test. Baseline median AFP levels were 245.2 IU/mL (mean 4,233; range 7.2–92,407; 95% confidence interval [CI] 1,186–7,280 and post-treatment values were 102.3 IU

  9. 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

  10. Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

    Science.gov (United States)

    Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

    2013-12-01

    Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

  11. Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma.

    Science.gov (United States)

    Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

    2017-09-01

    Rationale of this study was framed to investigate the protective effect and anti-cancer property of nanoparticles based on chitosan isolated from squid, Sepioteuthis lessoniana, on hepatic cells in N-Nitrosodiethylamine-induced hepatocellular carcinoma in rats. The results conferred that the chitosan nanoparticle supplementation had a protective effect on liver cells by reducing the levels of marker enzymes and bilirubin and thus increasing the albumin levels. The level of reduced glutathione, ascorbic acid and α-tocopherol significantly increased in both post- and pre-treatment with chitosan nanoparticles. The levels of antioxidant enzymes were enhanced and lipid peroxidation products were diminished while treating nitrosodiethylamine-induced hepatocellular carcinoma with chitosan nanoparticles. Supplementation of chitosan nanoparticles had potent anti-hyperlipidemic property that was evidenced by monitoring the serum lipid levels and its components. Animals pre-treated with chitosan nanoparticles along with nitrosodiethylamine showed a significant reduction in the total cholesterol and triglycerides levels with increase in the levels of phospholipids and free fatty acids. Chitosan nanoparticles treated rats showed significant increment in high-density lipoprotein cholesterol and reduction in low-density lipoprotein and very low-density lipoprotein cholesterol when compared with levels in nitrosodiethylamine-induced hepatocellular carcinoma. Nitrosodiethylamine-induced carcinoma changes on circulation and hepatic antioxidant defense mechanism were regulated by chitosan nanoparticles, concluding that the chitosan nanoparticles have a potent protective effect on liver cells which might be due to its robust antioxidant and anti-lipidemic property. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. The long non-coding RNA MALAT1 promotes the migration and invasion of hepatocellular carcinoma by sponging miR-204 and releasing SIRT1.

    Science.gov (United States)

    Hou, Zhouhua; Xu, Xuwen; Zhou, Ledu; Fu, Xiaoyu; Tao, Shuhui; Zhou, Jiebin; Tan, Deming; Liu, Shuiping

    2017-07-01

    Increasing evidence supports the significance of long non-coding RNA in cancer development. Several recent studies suggest the oncogenic activity of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in hepatocellular carcinoma. In this study, we explored the molecular mechanisms by which MALAT1 modulates hepatocellular carcinoma biological behaviors. We found that microRNA-204 was significantly downregulated in sh-MALAT1 HepG2 cell and 15 hepatocellular carcinoma tissues by quantitative real-time polymerase chain reaction analysis. Through bioinformatic screening, luciferase reporter assay, RNA-binding protein immunoprecipitation, and RNA pull-down assay, we identified microRNA-204 as a potential interacting partner for MALAT1. Functionally, wound-healing and transwell assays revealed that microRNA-204 significantly inhibited the migration and invasion of hepatocellular carcinoma cells. Notably, sirtuin 1 was recognized as a direct downstream target of microRNA-204 in HepG2 cells. Moreover, si-SIRT1 significantly inhibited cell invasion and migration process. These data elucidated, by sponging and competitive binding to microRNA-204, MALAT1 releases the suppression on sirtuin 1, which in turn promotes hepatocellular carcinoma migration and invasion. This study reveals a novel mechanism by which MALAT1 stimulates hepatocellular carcinoma progression and justifies targeting metastasis-associated lung adenocarcinoma transcript 1 as a potential therapy for hepatocellular carcinoma.

  13. FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1

    OpenAIRE

    Yu, Chun-Peng; Yu, Shui; Shi, Lei; Wang, Song; Li, Zi-Xiang; Wang, Yan-Hua; Sun, Cheng-Jian; Liang, Jun

    2017-01-01

    Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial-mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E-cadherin in hepatocellular carcinoma (HCC) cell lines with various meta...

  14. PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population.

    Science.gov (United States)

    Li, Jiatong; Dou, Dongwei; Li, Ping; Luo, Wenqi; Lv, Wenxin; Zhang, Chengdong; Song, Xiaowei; Yang, Yuan; Zhang, Yuening; Xu, Yanzhen; Xiao, Feifan; Wei, Yan; Qin, Jian; Li, Hongtao; Yang, Xiaoli

    2017-07-01

    PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p  0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

  15. Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

    International Nuclear Information System (INIS)

    Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

    2014-01-01

    Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

  16. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

    Science.gov (United States)

    Jiang, Han-Yu; Chen, Jie; Xia, Chun-Chao; Cao, Li-Kun; Duan, Ting; Song, Bin

    2018-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging (MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines. PMID:29904242

  17. Recent advances in multidisciplinary management of hepatocellular carcinoma

    Science.gov (United States)

    Gomaa, Asmaa I; Waked, Imam

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

  18. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Science.gov (United States)

    Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

    2015-01-01

    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. PMID:28943622

  19. 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.

  20. The multifaceted role of podoplanin expression in hepatocellular carcinoma

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    Andreea Cioca

    2017-02-01

    Full Text Available 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.

  1. The multifaceted role of podoplanin expression in hepatocellular carcinoma.

    Science.gov (United States)

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

    2017-02-13

    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.

  2. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Yezaz Ahmed Ghouri

    2017-01-01

    Full Text Available Since the 1970s, the epidemic of hepatocellular carcinoma (HCC has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

  3. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.

    Science.gov (United States)

    Ghouri, Yezaz Ahmed; Mian, Idrees; Rowe, Julie H

    2017-01-01

    Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

  4. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis.

    Science.gov (United States)

    Tang, An; Hallouch, Oussama; Chernyak, Victoria; Kamaya, Aya; Sirlin, Claude B

    2018-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.

  7. Simultaneous breast cancer and hepatocellular carcinoma in a male patient with alcoholic liver cirrhosis and a normal serum alpha-fetoprotein level

    Directory of Open Access Journals (Sweden)

    Li-Chun Kao

    2017-06-01

    Laparoscopic cholecystectomy and an excision of the left breast mass were performed. The breast mass was pathologically confirmed to be infiltrating ductal carcinoma not otherwise specified and with predominantly cystic degeneration. The patient received chemotherapy with tamoxifen for the breast cancer, and transarterial chemoembolization for the HCC. Concomitant breast cancer and HCC in a male patient were rarely reported in the literature. Herein, we have discussed the possible relationship of these two disease entities.

  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. Diagnostic imaging and interventional radiology of hepatocellular carcinoma: A multicenter study on 290 cases

    International Nuclear Information System (INIS)

    Dalla Palma, Ludovico; Puzzi Mucelli, Roberto; Sponza, Massimo; De Santis, Mario; Gandini, Giovanni; Matricardi, Luigi; Rossi, Cristina

    1997-01-01

    The authors report of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC).The first aim -diagnostic - was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in hepatocellular carcinoma detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning.The second aim - treatment - consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced hepatocellular carcinoma and of intraarterial chemoembolization versus no treatment (NT) in advanced hepatocellular carcinoma. Treatment efficacy was evaluated with the following randomized protocols

  10. Thyroid metastasis in a patient with hepatocellular carcinoma: case report and review of literature

    Directory of Open Access Journals (Sweden)

    Chai Chiah-Yang

    2007-12-01

    Full Text Available Abstract Background Despite the apparent low incidence of cancer metastatic to the thyroid, autopsy and clinical series suggest it is more common than generally. Although lung, renal, and breast cancer are probably the most common primary sites, a number of cancers have been reported to metastasize to the thyroid synchronously with diagnosis of primary tumor or years after apparently curative treatment. Case presentation We report a rare case of a hepatocellular carcinoma metasatic to the thyroid. The patient presented seven months after original diagnosis and treatment with hepatic lobectomy with multiple neck lesions producing a mass effect on the trachea and bilateral lymphadenopathy. Fine-needle aspiration revealed highly anaplastic carcinoma, and immunohistochemistry confirmed hepatocellular carcinoma. The patient received total thyroidectomy as palliative therapy because of the presence of multiple recurrent lesions in the liver. Conclusion Clinicians should consider the possibility of metastatic cancer in each patient who presents with a new thyroid mass, especially those with a history of cancer, however remote. In cases where cytology or histology is not diagnostic, immunohistochemistry may be definitive in making the diagnosis.

  11. Efficacy of intrahepatic absolute alcohol in unrespectable hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Farooqi, J.I.; Hameed, K.; Khan, I.U.; Shah, S.

    2001-01-01

    To determine efficacy of intrahepatic absolute alcohol injection in researchable hepatocellular carcinoma. A randomized, controlled, experimental and interventional clinical trial. Gastroenterology Department, PGMI, Hayatabad Medical Complex, Peshawar during the period from June, 1998 to June, 2000. Thirty patients were treated by percutaneous, intrahepatic absolute alcohol injection sin repeated sessions, 33 patients were not given or treated with alcohol to serve as control. Both the groups were comparable for age, sex and other baseline characteristics. Absolute alcohol therapy significantly improved quality of life of patients, reduced the tumor size and mortality as well as showed significantly better results regarding survival (P< 0.05) than the patients of control group. We conclude that absolute alcohol is a beneficial and safe palliative treatment measure in advanced hepatocellular carcinoma (HCC). (author)

  12. 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.

  13. 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.

  14. TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xin; Wan, Jin-Xiang; Ke, Zun-Ping; Wang, Feng; Chai, Hai-Xia; Liu, Jia-Qiang

    2017-07-01

    Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

  15. Upregulation of MiR-212 Inhibits Migration and Tumorigenicity and Inactivates Wnt/β-Catenin Signaling in Human Hepatocellular Carcinoma.

    Science.gov (United States)

    Jia, Pengbo; Wei, Guangbing; Zhou, Cancan; Gao, Qi; Wu, Yunhua; Sun, Xuejun; Li, Xuqi

    2018-01-01

    MicroRNAs are involved in hepatocellular carcinoma metastasis, a principal cause of hepatocellular carcinoma-related death in patients worldwide. MiR-212 is a microRNA that has been identified in several types of cancers and is postulated to influence cell signaling and subsequent malignant pathogenesis. Despite emerging reports suggesting that miR-212 plays a significant role in the onset, progression, and migration of these types of malignant tumors, its involvement in the development of hepatocellular carcinoma has not been fully elucidated. Quantitative reverse transcription polymerase chain reaction, wound healing, transwell migration and invasion assays, Western blotting, and xenograft tumor growth models were performed to test the expression levels and functions of miR-212 in hepatocellular carcinoma. Luciferase reporter assay, quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to identify and verify the target of miR-212. In this study, we identify significant repression of miR-212 in hepatocellular carcinoma and demonstrate that overexpression of miR-212 inhibits the migration of hepatocellular carcinoma cells in vitro and in vivo. Furthermore, we identify forkhead box M1, whose expression is inversely related to that of miR-212, as a direct target of miR-212. Additionally, reexpression of forkhead box M1 rescues the miR-212-mediated inhibition of cell migration. We observed that inhibition of miR-212 activates forkhead box M1 but inhibits the Wnt/β-catenin pathway by suppressing Wnt, LEF-1, c-Myc, and nuclear β-catenin. Finally, in vivo studies confirmed the inhibitory effect of miR-212 on hepatocellular carcinoma growth. Our present findings indicate that miR-212 is a potential prognostic biomarker of hepatocellular carcinoma and that the miR-212/forkhead box M1 regulatory axis may represent a new therapeutic objective for hepatocellular carcinoma treatment.

  16. Diaphragmatic Hernia After Radiofrequency Ablation for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Yamagami, Takuji; Yoshimatsu, Rika; Matsushima, Shigenori; Tanaka, Osamu; Miura, Hiroshi; Nishimura, Tsunehiko

    2011-01-01

    We describe a 71-year-old woman with a hepatocellular carcinoma who underwent percutaneous radiofrequency ablation (RF) with a single internally cooled electrode under computed tomography (CT) fluoroscopic guidance. Nine months after the procedure, CT images showed herniation of the large intestine into the right pleural cavity. To our knowledge this complication of RF performed with a single internally cooled electrode under CT guidance has not been previously reported.

  17. The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

    OpenAIRE

    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...

  18. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    OpenAIRE

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

    2012-01-01

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

  19. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

    2001-01-01

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

  20. Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Deng L

    2016-01-01

    Full Text Available Liang Deng,1,* Jihong Yang,2,* Hongwu Chen,3 Bo Ma,4 Kangming Pan,1 Caikun Su,1 Fengfeng Xu,1 Jihong Zhang1 1Department of Hepatobiliary Surgery, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 2Department of General Surgery, The Affiliated Hospital of Hebei University, Baoding, 3Department of Emergency, 4Department of Gastroenterology, The Eastern Hospital of the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: TMEM16A plays an important role in cell proliferation in various cancers. However, less was known about the expression and role of TMEM16A in hepatocellular carcinoma. We screened the expression of TMEM16A in patients’ hepatocellular carcinoma tissues, and also analyzed the biological function of hepatocellular carcinoma cells by knockdown of TMEM16A, as well as the expression of MAPK signaling proteins, including p38, p-p38, ERK1/2, p-ERK1/2, JNK, and p-JNK, and cell cycle regulatory protein cyclin D1 in TMEM16A siRNA-transfected SMMC-7721 cells by Western blot. Our results showed that TMEM16A was overexpressed in hepatocellular carcinoma tissues. Inhibition of TMEM16A suppressed the cell proliferation, migration, and invasion, and cell cycle progression but did not influence the cell apoptosis. TMEM16A siRNA-suppressed cancer cell proliferation and tumor growth were accompanied by a reduction of p38 and ERK1/2 activation and cyclin D1 induction, and were not influenced by other tested MAPK signaling proteins. In addition, inhibition of TMEM16A suppressed tumorigenicity in vivo. TMEM16A is overexpressed in hepatocellular carcinoma, and that inhibition of TMEM16A suppressed MAPK and growth of hepatocellular carcinoma. TMEM16A could be a potentially novel therapeutic target for human cancers, including hepatocellular carcinoma.Keywords: TMEM16A, cell cycle, proliferation, apoptosis

  1. Gamma-glutamyltranspeptidase to platelet ratio and albumin to gamma-glutamyltranspeptidase between degrees of the Barcelona clinic liver cancer on hepatocellular carcinoma patients in Haji Adam Malik general hospital Medan during 2015-2016

    Science.gov (United States)

    Siregar, G. A.; Siregar, R. H.

    2018-03-01

    Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in apatient with underlying chronic liver disease and cirrhosis. HCC presented at an advancedstage with right-upper-quadrant pain, weight loss, and signs of decompensated liver disease; it is now increasingly recognized atmuch measurements of the biomarker. Some of them are Gamma-glutamyltranspeptidase to platelet ratio (GPR) and Albumin to Gamma- glutamyltranspeptidase (AGR). This study aimed to know the difference between GPR and AGR between degrees of the Barcelona Clinic Liver cancer (BCLC) on HCC patients. A retrospective study was carried out in 166 outpatient and inpatient HCC in Haji Adam Malik General Hospital from January 2015–December2016.Kruskal-Wallis test showed that there is no significant differentiation of GPR between degrees of BCLC (p=0.23), but there is a considerable differentiation of AGR between degrees of BCLC (p=0.032).

  2. Dietary flavonoid, lignan and antioxidant capacity and risk of hepatocellular carcinoma in the European prospective investigation into cancer and nutrition study

    DEFF Research Database (Denmark)

    Zamora-Ros, Raul; Fedirko, Veronika; Trichopoulou, Antonia

    2013-01-01

    Limited epidemiological evidence suggests a protective role for plant foods rich in flavonoids and antioxidants in hepatocellular cancer (HCC) etiology. Our aim was to prospectively investigate the association between dietary intake of flavonoids, lignans and nonenzymatic antioxidant capacity (NEAC......) and HCC risk. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 477,206 subjects (29.8% male) recruited from ten Western European countries, was analyzed. Flavonoid, lignan and NEAC intakes were calculated using a compilation of existing food composition......, 191 incident HCC cases (66.5% men) were identified. Using Cox regression, multivariable adjusted models showed a borderline nonsignificant association of HCC with total flavonoid intake (highest versus lowest tertile, HR = 0.65, 95% CI: 0.40-1.04; ptrend  = 0.065), but not with lignans. Among...

  3. Trends and practices in diagnosis and treatment of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    2010-01-01

    Hepatocellular carcinoma (HCC), or primary liver cancer, is one of the most common causes of cancer and cancer death globally, and has an increasing incidence. It is currently the fifth most common cancer among men and eighth among women. In some Asian and African countries, its incidence is similar to that of lung cancer. It carries a very poor prognosis; the majority of patients die within a year, making it the third most common cause of cancer death. Currently, the main treatments offering the chance of cure are surgical resection and liver transplantation. However, owing to late presentation and underlying liver cirrhosis, these are suitable only for a small minority of patients. Therefore, new investigative protocols in radiotherapy using the most advanced technologies have been developed with some promise of cure and effective palliation. However, no uniform recommendations exist and the use of radiotherapy is limited by pre-existing liver disease. The IAEA has extensive projects in radiation oncology in low and middle income countries, including areas in Asia and Africa where HCC is a common problem. Since there has been a reported significant increase in the use of radiotherapy in HCC, an expert review was considered timely to assess the role of radiotherapy within the entire framework of HCC management. This publication developed from the need to address this issue. A meeting on the current knowledge of HCC epidemiology and management protocols was convened in October 2008. The given task was to define the current role of radiotherapy in the management of HCC. The greatest number of patients requiring optimal management protocols for HCC lives in Asia and sub-Saharan Africa, where in many countries access to radiotherapy and cancer care in general is limited and resources for research and access to the most advanced technologies are not available. This review is intended for use in training courses and as a source of information on treatment decisions. It

  4. Radiofrequency ablation of hepatocellular carcinoma: Mono or multipolar?

    Science.gov (United States)

    Cartier, Victoire; Boursier, Jérôme; Lebigot, Jérôme; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Aubé, Christophe

    2016-03-01

    Thermo-ablation by radiofrequency is recognized as a curative treatment for early-stage hepatocellular carcinoma. However, local recurrence may occur because of incomplete peripheral tumor destruction. Multipolar radiofrequency has been developed to increase the size of the maximal ablation zone. We aimed to compare the efficacy of monopolar and multipolar radiofrequency for the treatment of hepatocellular carcinoma and determine factors predicting failure. A total of 171 consecutive patients with 214 hepatocellular carcinomas were retrospectively included. One hundred fifty-eight tumors were treated with an expandable monopolar electrode and 56 with a multipolar technique using several linear bipolar electrodes. Imaging studies at 6 weeks after treatment, then every 3 months, assessed local effectiveness. Radiofrequency failure was defined as persistent residual tumor after two sessions (primary radiofrequency failure) or local tumor recurrence during follow-up. This study received institutional review board approval (number 2014/77). Imaging showed complete tumor ablation in 207 of 214 lesions after the first session of radiofrequency. After a second session, only two cases of residual viable tumor were observed. During follow-up, there were 46 local tumor recurrences. Thus, radiofrequency failure occurred in 48/214 (22.4%) cases. By multivariate analysis, technique (P radiofrequency failure. Failure rate was lower with the multipolar technique for tumors radiofrequency, multipolar radiofrequency improves tumor ablation with a subsequent lower rate of local tumor recurrence. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. 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.

  6. Hepatocellular carcinoma: computed tomography assessment after invasive treatment

    International Nuclear Information System (INIS)

    Kozima, Shigeru; Larranaga, Nebil; Wulfson, Gabriela; Eisele, Guillermo; Ridruejo, Ezequiel; Mando, Oscar; Perazzo, Florencia

    2008-01-01

    Objective: To show the computed tomography (CT) usefulness after treatment with transcatheter arterial quimioembolization and radiofrequency ablation of hepatocellular carcinoma. Material and methods: In a period between march 2006 to april 2008 a total of 90 patient presenting 148 nodular lesions with diagnosis of hepatocellular carcinoma were controlled with triphasic CT. All the lesions were treated with minimally invasive procedure. For the treatment, the patients were classified in two groups following Milan criteria. The first group, constituted by 75 patients with 109 nodules, was treated with quimioembolization. The second group, of 15 patients with 25 nodules, was treated with radiofrequency ablation. In our population, a subgroup of 10 patients was treated with both methods. Results: Of 90 patients after CT control on a month, 3 months and for each 3 months during 2 years, on 63 cases (70%) was observed homogeneous accumulation of iodized oil, partial defect without enhancement or absence of enhancement on treated lesions. In these patients a new treatment after initial one was not performed. The remaining 27 patients (30%) underwent new treatment because we founded partial defect or absence of iodized oil with enhancement or peripheral enhancement on arterial phase in treated lesions. In this last group, 16 treated patients (17.7%) had new nodular enhancement on the remaining hepatic parenquimal. Conclusion: The CT unenhanced and the arterial phase on a month and for each 3 months, allow monitoring the effectiveness, residual disease and/or relapse of hepatocellular carcinoma after minimally invasive treatment. (authors) [es

  7. Autophagy‑mediated adaptation of hepatocellular carcinoma cells to hypoxia‑mimicking conditions constitutes an attractive therapeutic target.

    Science.gov (United States)

    Owada, Satoshi; Endo, Hitoshi; Shida, Yukari; Okada, Chisa; Ito, Kanako; Nezu, Takahiro; Tatemichi, Masayuki

    2018-04-01

    Hepatocellular carcinoma has extremely poor prognosis. In cancerous liver tissues, aberrant proliferation of cancer cells leads to the creation of an area where an immature vascular network is formed. Since oxygen is supplied to cancer tissues through the bloodstream, a part of the tumor is exposed to hypoxic conditions. As hypoxia is known to severely reduce the effectiveness of existing anticancer agents, novel valid therapeutic targets must be identified for the treatment of hepatocellular carcinoma. Generally, autophagy has been reported to play an important role in the adaptation of cancer cells to hypoxia. However, the exact role and significance of this process vary depending on the cancer type, requiring detailed analysis in individual primary tumors and cell lines. In the present study, we examined autophagy induced by cobalt chloride, a hypoxia‑mimicking agent, in hepatocellular carcinoma cells with the aim to evaluate the validity of this process as a potential therapeutic target. We observed that treatment with cobalt chloride induced autophagy, including the intracellular quality control mechanism, in an AMPK‑dependent manner. Furthermore, treatment with autophagy inhibitors (bafilomycin and LY294002) resulted in significant, highly‑selective cytotoxicity and apoptosis activation under hypoxia‑mimicking conditions. The knockdown of AMPK also revealed significant cytotoxicity in hypoxia‑mimicking conditions. These results clearly demonstrated that autophagy, especially mitophagy, was induced by the AMPK pathway when hepatocellular carcinoma cells were subjected to hypoxic conditions and played an important role in the adaptation of these cells to such conditions. Thus, autophagy may constitute an attractive therapeutic target for the treatment of hepatocellular carcinoma.

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

    International Nuclear Information System (INIS)

    Nayeb-Hashemi, Hamed; Desai, Anal; Demchev, Valeriy; Bronson, Roderick T.; Hornick, Jason L.; Cohen, David E.; Ukomadu, Chinweike

    2015-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Current management of hepatocellular carcinoma: An Eastern perspective

    Science.gov (United States)

    Yim, Hyung Joon; Suh, Sang Jun; Um, Soon Ho

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress. PMID:25852267

  11. Family history influences the early onset of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    AIM:To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients.METHODS: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.RESULTS: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 < 0.0001).Furthermore,among 1713 HCC patients with HBV infection,the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%),whereas those out of 1577 patients with negative family history was 197 (12.5%),suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P =0.0028).CONCLUSION: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.

  12. Sorafenib prescribed by gastroenterologists and hepatologists for hepatocellular carcinoma

    Science.gov (United States)

    Kaplan, David E.; Mehta, Rajni; D’Addeo, Kathryn; Valderrama, Adriana; Taddei, Tamar H.

    2018-01-01

    Abstract Sorafenib is the only Food and Drug Administration (FDA)-approved first-line therapy shown to have survival benefit for patients with advanced hepatocellular carcinoma (HCC). Patients with advanced HCC are often but not exclusively transferred from non-oncologists to oncologists to initiate systemic therapy. The objective of this study was to assess whether sorafenib prescribing by non-oncologists has any impact on utilization, adverse effects, cost or outcome. This was a retrospective cohort study utilizing data from patients prescribed sorafenib for HCC within Veterans Health Administration hospitals with 100% chart abstraction to confirm HCC diagnosis, identify prescribing provider specialty (oncology versus gastroenterology/hepatology), and obtain data required for cancer staging by the Barcelona Clinic Liver Cancer (BCLC) system. The primary outcome was overall survival from the time of sorafenib prescription. A total of 4903 patients who prescribed sorafenib for HCC were identified, for whom 340 patients (6.9%) were prescribed drug by a non-oncologist (Onc). BCLC Stage, age, Child–Turcotte–Pugh score, and comorbidity indices were similar between patients prescribed sorafenib by oncologists and non-oncologists. Oncologists more often discontinued sorafenib due to progression, whereas non-oncologists were more likely to continue sorafenib until death resulting in greater pill utilization and cost. Overall survival in both unadjusted and multivariable models showed no significant impact of prescriber type on survival (222 vs 217 days, P = .96), confirmed with propensity-matched subcohorts. Similar survival outcomes were observed for patients with HCC prescribed sorafenib by non-oncologists and oncologists, suggesting that non-oncologists with expertise in the management of HCC can safely and effectively administer sorafenib. PMID:29369224

  13. Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

    Science.gov (United States)

    Middleton, Catrin H.; Irving, William; Robertson, John F. R.; Murray, Andrea; Parsy-Kowalska, Celine B.; Macdonald, Isabel K.; McElveen, Jane; Allen, Jared; Healey, Graham F.; Thomson, Brian J.; Ryder, Stephen J.; Holdenrieder, Stefan; Chapman, Caroline J.

    2014-01-01

    Background Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC. Methods Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. Results Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. Conclusions This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung). PMID:25093332

  14. Serum autoantibody measurement for the detection of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Catrin H Middleton

    Full Text Available BACKGROUND: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs in the serum of patients with HCC. METHODS: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. RESULTS: Varying autoantibody specificities (97-100% and sensitivities (0-10% were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. CONCLUSIONS: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography and to similar tests in other cancers (EarlyCDT-Lung.

  15. Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma

    Science.gov (United States)

    Van Hees, Stijn; Michielsen, Peter; Vanwolleghem, Thomas

    2016-01-01

    Chronic hepatitis B virus (HBV) infected patients have an almost 100-fold increased risk to develop hepatocellular carcinoma (HCC). HCC is the fifth most common and third most deadly cancer worldwide. Up to 50% of newly diagnosed HCC cases are attributed to HBV infection. Early detection improves survival and can be achieved through regular screening. Six-monthly abdominal ultrasound, either alone or in combination with alpha-fetoprotein serum levels, has been widely endorsed for this purpose. Both techniques however yield limited diagnostic accuracy, which is not improved when they are combined. Alternative circulating or histological markers to predict or diagnose HCC are therefore urgently needed. Recent advances in systems biology technologies have enabled the identification of several new putative circulating biomarkers. Although results from studies assessing combinations of these biomarkers are promising, evidence for their clinical utility remains low. In addition, most of the studies conducted so far show limitations in design. Attention must be paid for instance to different ethnicities and different etiologies when studying biomarkers for hepatocellular carcinoma. This review provides an overview on the current understandings and recent progress in the field of diagnostic and predictive circulating biomarkers for hepatocellular carcinoma in chronically infected HBV patients and discusses the future prospects. PMID:27729734

  16. Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

    Science.gov (United States)

    Matloub, Azza Abdelmageed; Salama, Alaa Hamed; Aglan, Hadeer Ahmed; AbouSamra, Mona Mahmoud; ElSouda, Sahar Salah Mohamed; Ahmed, Hanaa Hamdy

    2018-04-01

    Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

  17. Emerging role of microRNAs in the treatment of hepatocellular carcinoma

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    Callegari E

    2015-05-01

    Full Text Available Elisa Callegari,1 Marco Domenicali,2 Laura Gramantieri,3 Massimo Negrini,1 Silvia Sabbioni4 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 2Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 3Center for Applied Biomedical Research, S Orsola-Malpighi University Hospital, Bologna, 4Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma. Keywords: hepatocellular carcinoma, microRNA, nanocarriers, therapy 

  18. An efficient model for auxiliary diagnosis of hepatocellular carcinoma based on gene expression programming.

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    Zhang, Li; Chen, Jiasheng; Gao, Chunming; Liu, Chuanmiao; Xu, Kuihua

    2018-03-16

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. The early diagnosis of HCC is greatly helpful to achieve long-term disease-free survival. However, HCC is usually difficult to be diagnosed at an early stage. The aim of this study was to create the prediction model to diagnose HCC based on gene expression programming (GEP). GEP is an evolutionary algorithm and a domain-independent problem-solving technique. Clinical data show that six serum biomarkers, including gamma-glutamyl transferase, C-reaction protein, carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 153, and carbohydrate antigen 199, are related to HCC characteristics. In this study, the prediction of HCC was made based on these six biomarkers (195 HCC patients and 215 non-HCC controls) by setting up optimal joint models with GEP. The GEP model discriminated 353 out of 410 subjects, representing a determination coefficient of 86.28% (283/328) and 85.37% (70/82) for training and test sets, respectively. Compared to the results from the support vector machine, the artificial neural network, and the multilayer perceptron, GEP showed a better outcome. The results suggested that GEP modeling was a promising and excellent tool in diagnosis of hepatocellular carcinoma, and it could be widely used in HCC auxiliary diagnosis. Graphical abstract The process to establish an efficient model for auxiliary diagnosis of hepatocellular carcinoma.

  19. Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival

    Science.gov (United States)

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Mei

    2015-01-01

    Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients. PMID:25624992

  20. TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells.

    Science.gov (United States)

    Li, Yang; Zhu, Danxi; Hou, Lidan; Hu, Bin; Xu, Min; Meng, Xiangjun

    2018-01-01

    Tribbles homolog 3 (TRB3), a type of pseudokinase that contains a consensus serine/threonine kinase catalytic core structure, is upregulated in hepatocellular carcinoma. However, the effect of TRB3 expression in hepatocellular carcinoma and the molecular mechanisms underlying TRB3-mediated effects on tumorigenesis in hepatocellular carcinoma have not been fully elucidated. The present study focused on the effect of TRB3 expression in MHCC97H hepatocellular carcinoma cells and investigated the underlying molecular mechanisms in MHCC97H cells. In the present study, it was revealed that TRB3 was significantly overexpressed in the MHCC97H hepatocellular carcinoma cell compared with L-02 normal hepatic cells. Under endoplasmic reticulum (ER) stress induced by thapsigargin and tunicamycin, the levels of TRB3, CCAAT/enhancer binding protein homologous protein (CHOP), protein kinase B (AKT) and phosphorylated (p)AKT expression were upregulated. Furthermore, when the expression of TRB3 was silenced by short hairpin (sh)RNA, the survival of MHCC97H hepatocellular carcinoma cells was increased. Notably, following transduction with lentiviral containing TRB3-shRNA, cell survival also increased after treatment with chemotherapy drug cisplatin. The present study demonstrated that knockdown of CHOP by shRNA was able to reduce TRB3 expression, and the knockdown of TRB3 markedly increased the level of pAKT. TRB3 was overexpressed in MHCC97H hepatocellular carcinoma cells, particularly under endoplasmic reticulum stress. Knockdown of TRB3 was able to increase cell survival. Therefore, TRB3 expression may induce apoptosis and reverse resistance to chemotherapy in MHCC97H hepatic carcinoma cells. The present study suggests that TRB3 is a key molecule that mediates the crosstalk between ER stress and AKT signal pathways. Furthermore, the present study may provide further insight into the cancer biology of hepatocellular carcinoma and the development of anticancer drugs targeting the ER

  1. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

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    Li Fan

    2010-04-01

    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  2. Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

    Science.gov (United States)

    Sun, Xu; Zhang, Qi; Chen, Wei; Hu, Qida; Lou, Yu; Fu, Qi-Han; Zhang, Jing-Ying; Chen, Yi-Wen; Ye, Long-Yun; Wang, Yi; Xie, Shang-Zhi; Hu, Li-Qiang; Liang, Ting-Bo; Bai, Xue-Li

    2017-07-01

    Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

  3. Hepatocellular Carcinoma in Tyrosinemia Type 1 Without Clear Increase of AFP

    NARCIS (Netherlands)

    van Ginkel, Willem G.; Gouw, Annette S. H.; van der Jagt, Eric J.; de Jong, Koert P.; Verkade, Henkjan J.; van Spronsen, Francjan J.

    Patients with hereditary tyrosinemia type 1 have an elevated risk of developing hepatocellular carcinoma, especially if initiation of treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione is delayed. Hepatocellular carcinoma can usually be suspected when there are increased

  4. A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function

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    Hyun Yang

    2017-06-01

    Full Text Available Background/Aims Metronomic chemotherapy (MET is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC patients with portal vein tumor thrombosis (PVTT. Methods A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. Results The median number of MET cycles was two (1-15. The OS values for the MET group and sorafenib group were 158 days (132-184 and 117 days (92-142, respectively (P=0.029. The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P=0.014 and Child-Pugh class B (HR=1.856, P=0.008. Conclusions MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

  5. Fibrolamellar hepatocellular carcinoma with ovarian metastasis - an unusual presentation.

    Science.gov (United States)

    Ciurea, Silviu Horia; Matei, Emil; Stănescu, CodruŢ Silvian; Lupescu, Ioana Gabriela; Boroş, Mirela; Herlea, Vlad; Luca, Niculina Ioana; DorobanŢu, Bogdan Mihail

    2017-01-01

    Fibrolamellar carcinoma (FLC) has been considered a distinct clinical entity vs. hepatocellular carcinoma, with respect to its epidemiology, etiology, and prognosis. We describe the unusual case of a 23-year-old female patient with FLC and ovarian (Krukenberg) and peritoneal metastases, clinically mimicking an ovarian carcinoma. Multiple recurrences occurred despite initial R0 resection and chemotherapy, requiring surgical treatment. The patient survived five years and died from generalized disease. The particularities of our case are discussed by comparison with the other two similar cases and other date from the literature. To our knowledge, the ovarian involvement encountered in our case is the third case published in literature, being explained by the superficial location of the liver tumor.

  6. Thyroid cancer - papillary carcinoma

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000331.htm Thyroid cancer - papillary carcinoma To use the sharing features on ... the lower neck. Causes About 80% of all thyroid cancers diagnosed in the United States are the papillary ...

  7. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

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    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.

  8. Treatment of hepatocellular carcinoma in Child-Pugh B patients.

    Science.gov (United States)

    Piscaglia, Fabio; Terzi, Eleonora; Cucchetti, Alessandro; Trimarchi, Chiara; Granito, Alessandro; Leoni, Simona; Marinelli, Sara; Pini, Patrizia; Bolondi, Luigi

    2013-10-01

    The frequency with which patients in Child-Pugh B having hepatocellular carcinoma are treated following the international guidelines according to the Barcelona Clinic Liver Cancer stages is unknown. To investigate treatment allocation for Child-Pugh B patients in different tumour stages, with particular interest in the intermediate stage. Patients were retrospectively identified from a consecutively collected series. Treatment was carried out primarily according to the guidelines. Of 86 Child-Pugh B patients, 45 were Barcelona early stage, of which the Child-Pugh scores were 46.7% B7, 33.3% B8, 20.0% B9; 27 patients were intermediate stage (B7 59.3%, B8 37.0% and B9 3.7% respectively), 12 were advanced (41.7% B7, 25.0% B8 and 33.3% B9) and 2 were terminal (both B9). In the intermediate stage, transarterial chemoembolization (or ablation) was performed in 68.8% of the Child-Pugh B7 patients, 50% of the B8 patients and 0% of the B9 patients. Median survival of the intermediate patients was 8.0 months (9.0 in B7 vs. 6.0 in -B8/B9, P=0.048). Survival of the intermediate stage patients undergoing chemoembolisation was 22.0 months in Child-Pugh B7 and 6.0 in B8. Approximately half of the intermediate stage patients can undergo locoregional treatment with good survival when in the Child-Pugh B7. The Child-Pugh numeric score impacts survival, suggesting that this tumour stage be refined. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  9. Circulating CD147 predicts mortality in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Lee, Aimei; Rode, Anthony; Nicoll, Amanda; Maczurek, Annette E; Lim, Lucy; Lim, Seok; Angus, Peter; Kronborg, Ian; Arachchi, Niranjan; Gorelik, Alexandra; Liew, Danny; Warner, Fiona J; McCaughan, Geoffrey W; McLennan, Susan V; Shackel, Nicholas A

    2016-02-01

    The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  10. Local Arterial Therapies in the Management of Unresectable Hepatocellular Carcinoma.

    Science.gov (United States)

    Mouli, Samdeep K; Goff, Laura W

    2017-10-27

    Most patients with hepatocellular carcinoma present with intermediate to advanced disease, where curative therapies are no longer an option. These patients with intermediate to advanced disease represent a heterogeneous population with regard to tumor burden, liver function, and performance status. While the Barcelona Clinic Liver Cancer (BCLC) staging system offers guidelines for the management of these patients, strict adherence to these guidelines may limit treatment options for these patients. Several locoregional therapies exist for these patients, including conventional transarterial chemoembolization (cTACE), transarterial embolization (TAE), drug-eluting embolization (DEE), and radioembolization. Evidence is also emerging for the role of radiation therapy including most notably stereotactic body radiation therapy and proton therapy, although at the current time, clinical trial participation is encouraged. While cTACE is traditionally recommended for BCLC B disease, both cTACE and radioembolization are increasingly used for patients with intermediate disease, as well as in select patients with BCLC A and C disease. TAE and DEE are limited in their use currently, due to lack of clear survival benefits or clinical advantages over cTACE. While several studies have demonstrated similar OS between cTACE and radioembolization, radioembolization provides a longer time to progression and fewer toxicities compared to cTACE. This is particularly relevant in the setting of advanced BCLC B and early BCLC C disease, where patients may have limited reserve. Radioembolization also has additional roles as an alternative to ablation, inducing liver hypertrophy, treating patients with PVT, and downstaging lesions to transplant. Ongoing studies will further define the role of locoregional treatment potentially in combination with and in light of developments in systemic therapy.

  11. A systems biology-based classifier for hepatocellular carcinoma diagnosis.

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    Yanqiong Zhang

    Full Text Available AIM: The diagnosis of hepatocellular carcinoma (HCC in the early stage is crucial to the application of curative treatments which are the only hope for increasing the life expectancy of patients. Recently, several large-scale studies have shed light on this problem through analysis of gene expression profiles to identify markers correlated with HCC progression. However, those marker sets shared few genes in common and were poorly validated using independent data. Therefore, we developed a systems biology based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC diagnosis. METHODS AND RESULTS: In the Oncomine platform, genes differentially expressed in HCC tissues relative to their corresponding normal tissues were filtered by a corrected Q value cut-off and Concept filters. The identified genes that are common to different microarray datasets were chosen as the candidate markers. Then, their networks were analyzed by GeneGO Meta-Core software and the hub genes were chosen. After that, an HCC diagnostic classifier was constructed by Partial Least Squares modeling based on the microarray gene expression data of the hub genes. Validations of diagnostic performance showed that this classifier had high predictive accuracy (85.88∼92.71% and area under ROC curve (approximating 1.0, and that the network topological features integrated into this classifier contribute greatly to improving the predictive performance. Furthermore, it has been demonstrated that this modeling strategy is not only applicable to HCC, but also to other cancers. CONCLUSION: Our analysis suggests that the systems biology-based classifier that combines the differential gene expression and topological features of human protein interaction network may enhance the diagnostic performance of HCC classifier.

  12. STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma.

    Science.gov (United States)

    Tai, Wei-Tien; Chu, Pei-Yi; Shiau, Chung-Wai; Chen, Yao-Li; Li, Yong-Shi; Hung, Man-Hsin; Chen, Li-Ju; Chen, Pei-Lung; Su, Jung-Chen; Lin, Ping-Yi; Yu, Hui-Chuan; Chen, Kuen-Feng

    2014-11-15

    Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of hepatocellular carcinoma (HCC). HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were used to test the therapeutic efficiency of 20 and 40 mg/kg/d treatment with regorafenib ([Formula: see text] mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3. Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (P = 0.009) and poorly differentiated tumors (P = 0.035). Regorafenib induced significant tumor inhibition by relieving the autoinhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC-targeted therapy using regorafenib. ©2014 American Association for Cancer Research.

  13. BLZF1 expression is of prognostic significance in hepatocellular carcinoma

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    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.

  14. Transarterial ablation of hepatocellular carcinoma. Status and developments

    International Nuclear Information System (INIS)

    Radeleff, B.A.; Stampfl, U.; Sommer, C.M.; Bellemann, N.; Kauczor, H.U.; Hoffmann, K.; Ganten, T.; Ehehalt, R.

    2012-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and represents the main cause of death among European patients with liver cirrhosis. Only 30-40% of patients diagnosed with HCC are candidates for curative treatment options (e.g. surgical resection, liver transplantation or ablation). The remaining majority of patients must undergo local regional and palliative therapies. Transvascular ablation of HCC takes advantage of the fact that the hypervascularized HCC receives most of its blood supply from the hepatic artery. In this context transvascular ablation describes different therapy regimens which can be assigned to four groups: cTACE (conventional transarterial chemoembolization), bland embolization (transarterial embolization TAE), DEB-TACE (TACE with drug-eluting beads, DEB) and SIRT (selective internal radiation therapy, radioembolization). Conventional TACE is the most common type of transvascular ablation and represents a combination of intra-arterial chemotherapy and embolization with occlusion of the arterial blood supply. However, there is no standardized regimen with respect to the chemotherapeutic drug, the embolic agent, the usage of lipiodol and the interval between the TACE procedures. Even the exact course of a cTACE procedure (order of chemotherapy or embolization) is not standardized. It remains unclear whether or not intra-arterial chemotherapy is definitely required as bland embolization using very small, tightly calibrated spherical particles (without intra-arterial administration of a chemotherapeutic drug) shows tumor necrosis comparable to cTACE. For DEB-TACE microparticles loaded with a chemotherapeutic drug combine the advantages of cTACE and bland embolization. Thereby, a continuing chemotherapeutic effect within the tumor might cause a further increase in intratumoral cytotoxicity and at the same time a decrease in systemic toxicity. (orig.) [de

  15. Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology.

    Science.gov (United States)

    Santambrogio, Roberto; Cigala, Claudia; Barabino, Matteo; Maggioni, Marco; Scifo, Giovanna; Bruno, Savino; Bertolini, Emanuela; Opocher, Enrico; Bulfamante, Gaetano

    2018-02-01

    Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Function of oval cells in hepatocellular carcinoma in rats.

    Science.gov (United States)

    Fang, Chi-Hua; Gong, Jia-Qing; Zhang, Wei

    2004-09-01

    To study oval cells' pathological characteristics and relationship with the occurrence of hepatocellular carcinoma (HCC); to observe the form and structural characteristics of oval cells; to explore the expression characteristics of C-kit, PCNA mRNA and c-myc gene during the occurrence and development of HCC and the effect of ulinastatin (UTI) on C-kit and PCNA expression. One hundred and twenty-five SD rats fed on 3,3'-diaminobenzidine (DAB) to construct HCC models were divided into control group, cancer-inducing group and UTI intervention group. In each group, rat liver samples were collected at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 respectively to study pathological distribution characteristics of oval cells in the process of carcinogenesis under optical microscope. Oval cells were separated by the methods of improved density gradient centrifugation and their structural characteristics were observed under optical microscope and electronic microscope respectively; the oval cells expressing C-kit and PCNA in the collected samples were observed by the methods of immunohistochemistry and image analysis and the expression of c-myc mRNA was also detected by reverse transcription polymerase chain reaction (RT-PCR). Oval cells proliferated firstly in the portal area then gradually migrated into hepatic parenchyma in the inducing group and intervention group. The oval cells distributed inside and outside the carcinoma nodes. The oval cells presented the characteristics of undifferentiated cells: a high ratio of nucleolus and cellular plasm and obvious nucleoli, rare organelle in plasm. Only a few mitochondria and endoplasmic reticulum and some villus-like apophysis on surface of cells could be seen. Cells stained with C-kit and PCNA antibody were mainly oval cells distributed in the portal area. The expression of c-myc mRNA increased with the progression of HCC. However, in the intervention group, UTI could retard its increase. Oval cells work throughout

  17. CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

    Science.gov (United States)

    Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

    2018-02-23

    Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

  18. Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

    1984-02-01

    Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

  19. Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma.

    Science.gov (United States)

    Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

    2017-03-21

    Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-08-01

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

  1. Computed tomography of hepatocellular carcinoma. Comparison with scintigraphy and ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Kuniyuki; Nakata, Hajime; Honda, Hiroshi [University of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    1983-09-01

    The detectability of hepatocellular carcinoma by computed tomography (CT) was evaluated on 76 cases. The detectability by plain CT was 93% with only slight improvement following a drip infusion of contrast medium. A comparison of scintigraphy, ultrasonography, and CT was also done on 63 cases. From the standpoint of the overall detectability of the tumor, CT was as good as ultrasonography or scintigraphy. Several cases were positive only on either CT or ultrasonography but no case was positive on scintigraphy alone. We believe that the combination of CT and ultrasonography is the most reliable as the screening method.

  2. 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.

  3. 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.

  4. Recent advances in targeted drug therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    FAN Yongqiang

    2018-02-01

    Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

  5. Bone metastases as initial presentation of hepatocellular carcinoma.

    Science.gov (United States)

    Monteserin, Luzdivina; Mesa, Alicia; Fernandez-Garcia, Maria Soledad; Gadanon-Garcia, Arantza; Rodriguez, Manuel; Varela, María

    2017-10-18

    Extra-hepatic spread is present in 5% to 15% of patients with hepatocellular carcinoma (HCC) at the time of diagnosis. The most frequent sites are lung and regional lymph nodes. Here, we report 3 cases of unsuspected HCC with symptoms due to bone lesions as initial presentation. Morphological characteristics and immunohistochemistry from the examined bone were the key data for diagnosis. None of the patients had an already known chronic liver disease. Differential diagnoses with HCC upon ectopic liver disease or hepatoid adenocarcinoma were shown. Therapy with the orally active multikinase inhibitor sorafenib plus symptomatic treatment was indicated.

  6. 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.

  7. Extrahepatic spread of hepatocellular carcinoma: a pictorial review

    International Nuclear Information System (INIS)

    Hong, Seong Sook; Kim, Tae Kyoung; Sung, Kyu-Bo; Kim, Pyo Nyun; Ha, Hyun Kwon; Kim, Ah Young; Lee, Moon-Gyu

    2003-01-01

    Although extrahepatic spread of hepatocellular carcinoma (HCC) is uncommon, it can be found anywhere in the body. Most extrahepatic metastases of HCC occur in patients with advanced-stage intrahepatic tumor, but incidental extrahepatic lesions have also occasionally been found in patients with early-stage intrahepatic HCC. The detection of extrahepatic metastatic disease is crucial when planning therapy for patients with HCC and should be used to avoid unnecessary surgical intervention. In this study we illustrate the radiologic findings of extrahepatic metastases of HCC involving various sites. The presumed mechanism of extrahepatic extension of HCC is also discussed. (orig.)

  8. Delayed hepatobiliary imaging in the diagnosis of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Chen, S.; Ma, Z.; Tang, Z.

    2000-01-01

    In recent years, the use of ultrasonography (US), X-CT and MRI has reduced the employment of isotopic explorations in the detection of hepatocellular carcinoma (HCC). But sometime the results of US, X-CT or MRI were different and diagnosis was very difficult. This present investigation was aimed to assess the usefulness of delayed hepatobiliary imaging in the diagnosis of HCC in these patients. Forty-eight patients consisting of 33 males and 15 females were entered into the research protocol. The mean age was 46 yr old (range 12-71 yr old). All of the patients were performed by surgery and verified histologically after nuclear examination. The subject was in a supine position under a gamma camera (Elscint, Apex Ap-6) and 555 MBq of Tc-99m-PMT were injected intravenously. The initial scinphotos obtained within 1 min after injection were used to image the blood pool phase. Subsequently, hepatic scans were obtained at 5 min, 1,2 and 5 hr. Anterior, right lateral and posterior hepatic images were recorded. According to the radioactive uptake by the lesion in delayed phase, the negative (no or minor uptake), positive (equal or greater uptake) or very strong positive (almost equal to the activity, of gallbladder) were judged. The positive were considered as diagnostic of HCC. And the very strong positive, were considered as diagnostic of benign hepatoma, such as adenoma or FNH. Thirty-seven of the forty-eight patients were HCC based on histology. Delayed imaging revealed increased or equilibrated uptake of radioactivity by the tumors in 22 of 37 patients with hepatocellular carcinoma. The sensitivity was 59.5%. One patient final diagnosis based on histology was focal nodular regenerative hyperplasia, and only the diagnosis with delayed hepatobiliary imaging before surgery was correct. Compared with US, X-CT and MRI, delayed hepatobiliary imaging had the highest specificity for diagnosis of hepatocellular carcinoma. In recent group, the specificity of Tc-99m-PMT delayed

  9. Prevention and management of recurrence and metastasis of hepatocellular carcinoma after liver transplantation

    Directory of Open Access Journals (Sweden)

    JI Ru

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC is still a prevalent gastrointestinal cancer. Liver transplantation (LT is one of the main means in the comprehensive treatment of HCC because it radically removes the tumor. However, tumor recurrence and metastasis after LT remain the main obstacles to long-term survival. In recent years, substantial progress has been made in the diagnosis and treatment of HCC thanks to the technological improvement and experience accumulation worldwide. The HCC indications for LT, prediction of HCC recurrence and metastasis, perioperative management in LT, and comprehensive treatment of recurrent HCC after LT are reviewed.

  10. Quality of Life in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

    Directory of Open Access Journals (Sweden)

    Saleem Ahmed

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Majority of patients with HCC are diagnosed in the advanced stages of disease and hence they are only suitable for palliative therapy. TACE (transarterial chemoembolization is the most commonly used treatment for unresectable HCC. It is however unclear if TACE improves the quality of life (QoL in patients with HCC. The aim of this review is to evaluate the impact of TACE on QoL of HCC patients.

  11. Long-term effect of stereotactic body radiation therapy for primary hepatocellular carcinoma ineligible for local ablation therapy or surgical resection. Stereotactic radiotherapy for liver cancer

    International Nuclear Information System (INIS)

    Kwon, Jung Hyun; Bae, Si Hyun; Kim, Ji Yoon; Choi, Byung Ock; Jang, Hong Seok; Jang, Jeong Won; Choi, Jong Young; Yoon, Seung Kew; Chung, Kyu Won

    2010-01-01

    We evaluated the long-term effect of stereotactic body radiation therapy (SBRT) for primary small hepatocellular carcinoma (HCC) ineligible for local therapy or surgery. Forty-two HCC patients with tumors ≤ 100 cc and ineligible for local ablation therapy or surgical resection were treated with SBRT: 30-39 Gy with a prescription isodose range of 70-85% (median 80%) was delivered daily in three fractions. Median tumor volume was 15.4 cc (3.0-81.8) and median follow-up duration 28.7 months (8.4-49.1). Complete response (CR) for the in-field lesion was initially achieved in 59.6% and partial response (PR) in 26.2% of patients. Hepatic out-of-field progression occurred in 18 patients (42.9%) and distant metastasis developed in 12 (28.6%) patients. Overall in-field CR and overall CR were achieved in 59.6% and 33.3%, respectively. Overall 1-year and 3-year survival rates were 92.9% and 58.6%, respectively. In-field progression-free survival at 1 and 3 years was 72.0% and 67.5%, respectively. Patients with smaller tumor had better in-field progression-free survival and overall survival rates (<32 cc vs. ≥32 cc, P < 0.05). No major toxicity was encountered but one patient died with extrahepatic metastasis and radiation-induced hepatic failure. SBRT is a promising noninvasive-treatment for small HCC that is ineligible for local treatment or surgical resection

  12. Hepatocellular carcinoma in Asia: Prevention strategy and planning.

    Science.gov (United States)

    Ashtari, Sara; Pourhoseingholi, Mohamad Amin; Sharifian, Afsaneh; Zali, Mohamad Reza

    2015-06-28

    To review all of epidemiological and etiological aspects of hepatocellular carcinoma (HCC) and examined the prevention of this disease in Asia. We conducted a systematic review according to the PRISMA guidelines. We were chosen articles that published previously, from PubMed (MEDLINE), the Cochrane database and Scopus. The key words used in this research were as follows: HCC in Asia and the way of prevention of this disease, with no language limitations. We selected those papers published before 2014 that we considered to be most important and appropriate. All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed. More than 70% of all new cases of liver cancer were diagnosed in Asia, a region that 75% of all those chronically infected with hepatitis B virus (HBV) in the world. Chronic HBV infection is the main cause of HCC in Asia, where the virus is endemic and vertical transmission is common. Japan, Saudi Arabia, Egypt and Pakistan are exception because of high prevalence of HCV infection in these regions. The prevalence of this cancer is high in Eastern and South-Eastern Asia, But Middle Eastern countries are characterized as moderate prevalence rate of HCC region and Central Asia and some part of Middle Eastern countries are known as low prevalence rate of HCC. In addition of HBV and HCV the other factors such as aflatoxin, alcohol, obesity, diabetes and non-alcoholic fatty liver disease (NAFLD) might be responsible for a low prevalence of HCC in Asian countries. Currently available HCC therapies, chemotherapy, surgical are inefficient, mainly due to usually late diagnosis and high recurrence rates after surgical resection, and usually end with treatment failure. Liver transplantation also remains as a difficult strategy in patients with HCC. Thus prevention of HCC by treating and prevention HBV and HCV infection, the major causative agents of HCC, and the other risk factors such as aflatoxin, alcohol, obesity

  13. Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K

    1986-01-01

    A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

  14. Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

    Directory of Open Access Journals (Sweden)

    Farazuddin M

    2014-03-01

    Full Text Available Mohammad Farazuddin,1 Bhavyata Dua,2 Qamar Zia,1 Aijaz Ahmad Khan,3 Beenu Joshi,2 Mohammad Owais1 1Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 2Immunology Division, National JALMA Institute for Leprosy and Other Mycobacterial Diseases (NJIL, Agra, 3Department of Anatomy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, India Abstract: Curcumin (diferuloylmethane is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. Keywords: diferuloylmethane, carcinogenesis, microparticle, nanocells, cancer, Curcuma longa

  15. Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Koduru P

    2015-10-01

    Full Text Available Pramoda Koduru,1 Rei Suzuki,2 Sundeep Lakhtakia,3 Mohan Ramchandani,3 Dadang Makmun,4 Manoop S Bhutani,1 1Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Gastroenterology and Rheumatology, Fukushima University School of Medicine, Fukushima, Japan; 3Asian Institute of Gastroenterology, Hyderabad, India; 4University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia Abstract: Hepatocellular carcinoma (HCC is an aggressive tumor and a leading cause of cancer-related deaths globally. The mortality rate remains high despite many advances in treatment. HCC is frequently diagnosed late in its course due to lack of classical symptoms at earlier stages. Endoscopic ultrasound (EUS has emerged as an important diagnostic tool for the diagnostic evaluation, staging, and treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration has been a valuable addition to EUS by being able to obtain tissue under direct visualization. Here, we review the potential role of EUS in the diagnosis and management of HCC. EUS seems to be a safe and reliable alternative method for obtaining tissue for diagnosis of liver cancer, especially for lesions that are inaccessible by traditional methods. EUS could play an important role in the diagnosis and management of HCC. Keywords: endoscopic ultrasound, fine needle aspiration, hepatocellular carcinoma, hepatoma

  16. Effects of marital status on survival of hepatocellular carcinoma by race/ethnicity and gender.

    Science.gov (United States)

    Wu, Wenrui; Fang, Daiqiong; Shi, Ding; Bian, Xiaoyuan; Li, Lanjuan

    2018-01-01

    It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship. We identified eligible patients from Surveillance, Epidemiology and End Results (SEER) database during 2004-2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan-Meier curves. We also estimated crude hazard ratios (CHRs) and adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models. A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married) was highest for Hispanic (AHR =1.25, 95% CI, 1.13-1.39; P married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality.

  17. Deep convolutional neural network for the classification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Midya, Abhishek; Chakraborty, Jayasree; Pak, Linda M.; Zheng, Jian; Jarnagin, William R.; Do, Richard K. G.; Simpson, Amber L.

    2018-02-01

    Liver cancer is the second leading cause of cancer-related death worldwide.1 Hepatocellular carcinoma (HCC) is the most common primary liver cancer accounting for approximately 80% of cases. Intrahepatic cholangiocarcinoma (ICC) is a rare liver cancer, arising in patients with the same risk factors as HCC, but treatment options and prognosis differ. The diagnosis of HCC is based primarily on imaging but distinguishing between HCC and ICC is challenging due to common radiographic features.2-4 The aim of the present study is to classify HCC and ICC in portal venous phase CT. 107 patients with resected ICC and 116 patients with resected HCC were included in our analysis. We developed a deep neural network by modifying a pre-trained Inception network by retraining the final layers. The proposed method achieved the best accuracy and area under the receiver operating characteristics curve of 69.70% and 0.72, respectively on the test data.

  18. Sonographic evolution of hepatocellular carcinoma associated with cirrhosis

    International Nuclear Information System (INIS)

    Mazzola, G.; Virdone, R.; Orlando, A.; Turri, A.; Caltagirone, M.; Fusco, G.; Parisi, P.; Cottone, M.

    1989-01-01

    To study the sonographic (US) evolution of hepatocellular carcinoma, 53 tumors in 45 untreated patients were observed regulary with real-time US for a period of 6 to 56 months. At the beginning, 25 tumors were hypoechoic, 18 isoechoic, 4 hyperechoic, and 6 had mixed hypo/hyper echopatterns. At the follow-up, 7 initially hypoechoic tumors had changed to hyperechoic or to mixed echopatterns; 8 hypoechoic tumors had becom isoechoic; 9 of the 25 initially hypoechoic neoplastic lesions had maintained the same echodensity. Ten of the 15 initially isoechoic tumors had changed to mixed echopatterns and 5 had remained unchanged. Three initially isoechoic lesions and a hypoechoic one had turned into diffuse patterns; 2 initially hyperechoic neoplastic lesions had remained unchanged; 1 had switched into hypoechoic, and 1 changed to mixed echopattern; 4 out of 6 tumors with echopattern had remained unchanged, 1 had become hyperechoic and 1 hypoechoic. The current study has proven variou tumors ≤3 cm in diameter to be isoechoic and most tumors >3 in diameter to have mixed hypo/hyper echopatterns. The echogenicity of small hepatocellular carcinomas increases with the tumor growth and remains unchanged when they do not increase in size

  19. Intraarterial digital subtraction angiography applied to diagnosis of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishizawa, Sadahiko; Sano, Akira; Imanaka, Kazufumi; Sasai, Keisuke; Nagae, Toshiyuki; Mizutani, Masaru; Hatabu, Hiroto; Sadatou, Norihiro; Kuroda, Yasumasa

    1985-12-01

    This paper deals with diagnostic values of intraarterial digital subtraction angiography (IADSA) for evaluating hepatocellular carcinoma. The present series consists of 44 patients with hepatocellular carcinoma, who underwent IADSA combined with conventional hepatic angiography 67 times in total. The evaluated vessels by IADSA included 70 hepatic arteries and 36 portal veins. Comparative studies on the image quality of IADSA with conventional angiography were made in referring to the tumor stain for arteriograms and resolution of intrahepatic portal branches for portograms. Diagnostic superiority including equality of DSA image to conventional was noted in arteriograms: 72.7 % in the right lobe and 86 % in the left. Most deteriorated DSA images were caused by misregistration artifacts. IADSA portography revealed basically diagnostic values to demonstrate lobar, segmental or more peripheral branches in about 95 % of cases studied. DSA, characterized by high contrast resolution and real-time subtraction, offered important and effective informations for interventional angiography as well as resectability of the tumors, requiring less contrast medium.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Hepatocellular carcinoma: a retrospective analysis of 118 cases

    International Nuclear Information System (INIS)

    Aman-ur-Rehman; Murad, S.

    2002-01-01

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

  2. Safety validation of decision trees for hepatocellular carcinoma.

    Science.gov (United States)

    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.

  3. Understanding the tumor suppressor PTEN in chronic alcoholism and hepatocellular carcinoma.

    Science.gov (United States)

    Shearn, Colin T; Petersen, Dennis R

    2015-01-01

    The tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a phosphatidylinositol (PtdIns) phosphatase that regulates Akt activation via PtdIns 3 kinase. Changes in PTEN expression and/or activity have been identified in a variety of chronic hepatocellular disorders including obesity, NAFLD, NASH, and alcoholism. In cancer biology, PTEN is frequently mutated or deleted in a wide variety of tumors. Mutations, decreased promoter activity, and decreased expression in PTEN are frequently identified in patients with hepatocellular carcinoma. While the majority of research on PTEN concerns obesity and NASH, PTEN clearly has a role in hepatic insulin sensitivity and in the development of steatosis during chronic alcoholism. Yet, in chronic alcoholics and HCC, very little is known concerning PTEN mutation/deletion or low PTEN expression. This review is focused on an overview of the current knowledge on molecular mechanisms of dysregulation of PTEN expression/activity in the liver and their relationship to development of ethanol-induced hepatocellular damage and cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-04-01

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

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

    Science.gov (United States)

    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.

  6. Persistence of hepatocellular carcinoma risk in hepatitis C patients with a response to IFN and cirrhosis regression.

    Science.gov (United States)

    D'Ambrosio, Roberta; Aghemo, Alessio; Rumi, Maria Grazia; Degasperi, Elisabetta; Sangiovanni, Angelo; Maggioni, Marco; Fraquelli, Mirella; Perbellini, Riccardo; Rosenberg, William; Bedossa, Pierre; Colombo, Massimo; Lampertico, Pietro

    2018-01-27

    In patients with HCV-related cirrhosis, a sustained virological response may lead to cirrhosis regression. Whether histological changes translate into prevention of long-term complications, particularly hepatocellular carcinoma is still unknown. This was investigated in a cohort of histological cirrhotics who had been prospectively followed-up for 10 years after the achievement of a sustained virological response to IFN. In all, 38 sustained virological response cirrhotics who underwent a liver biopsy 5 years post-SVR were prospectively followed to assess the impact of cirrhosis regression on clinical endpoints. During a follow-up of 86 (30-96) months from liver biopsy, no patients developed clinical decompensation, whilst 5 (13%) developed hepatocellular carcinoma after 79 (7-88) months. The 8-year cumulative probability of hepatocellular carcinoma was 17%, without differences between patients with or without cirrhosis regression (19% [95% CI 6%-50%] vs 14% [95% CI 4%-44%], P = .88). Patients who developed or did not an hepatocellular carcinoma had similar rates of residual cirrhosis (P = 1.0), collagen content (P = .48), METAVIR activity (P = .34), portal inflammation (P = .06) and steatosis (P = .17). At baseline, patients who developed an hepatocellular carcinoma had higher γGT (HR 1.03, 95% CI 1.00-1.06; P = .014) and glucose (HR 1.02, 95% CI 1.00-1.02; P = .012) values; moreover, they had increased Forns Score (HR 12.8, 95% CI 1.14-143.9; P = .039), Lok Index (HR 6.24, 95% CI 1.03-37.6; P = .046) and PLF (HR 19.3, 95% CI 1.72-217.6; P = .016) values. One regressor died of lung cancer. The 8-year cumulative survival probability was 97%, independently on cirrhosis regression (96% vs 100%, P = 1.0) or hepatocellular carcinoma (100% vs 97%, P = 1.0). Post-SVR cirrhosis regression does not prevent hepatocellular carcinoma occurrence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  8. Genomic portrait of resectable hepatocellular carcinomas: implications of RB1 and FGF19 aberrations for patient stratification.

    Science.gov (United States)

    Ahn, Sung-Min; Jang, Se Jin; Shim, Ju Hyun; Kim, Deokhoon; Hong, Seung-Mo; Sung, Chang Ohk; Baek, Daehyun; Haq, Farhan; Ansari, Adnan Ahmad; Lee, Sun Young; Chun, Sung-Min; Choi, Seongmin; Choi, Hyun-Jeung; Kim, Jongkyu; Kim, Sukjun; Hwang, Shin; Lee, Young-Joo; Lee, Jong-Eun; Jung, Wang-Rim; Jang, Hye Yoon; Yang, Eunho; Sung, Wing-Kin; Lee, Nikki P; Mao, Mao; Lee, Charles; Zucman-Rossi, Jessica; Yu, Eunsil; Lee, Han Chu; Kong, Gu

    2014-12-01

    Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P = 0.038 and P = 0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P = 0.017). RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients. © 2014 by the American Association for the Study of Liver Diseases.

  9. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma.

    Science.gov (United States)

    Liu, Rui; Zhang, Haiyang; Zhang, Yan; Li, Shuang; Wang, Xinyi; Wang, Xia; Wang, Cheng; Liu, Bin; Zen, Ke; Zhang, Chen-Yu; Zhang, Chunni; Ba, Yi

    2017-04-01

    Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor

  10. Strengthening the case that elevated levels of programmed death ligand 1 predict poor prognosis in hepatocellular carcinoma patients

    Directory of Open Access Journals (Sweden)

    Zhong J

    2016-12-01

    Full Text Available Jian-Hong Zhong,1,* Cheng-Piao Luo,2,* Chun-Yan Zhang,2 Le-Qun Li1 1Hepatobiliary Surgery Department, 2Experimental Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Abstract: Immunotherapy targeting programmed death receptor 1 and programmed death ligand 1 (PD-L1 has shown impressive antitumor efficacy in several solid cancers, including advanced hepatocellular carcinoma (HCC. Since response rates of various cancers to such immunotherapy appear to correlate with PD-L1 expression levels, several studies have examined whether PD-L1 expression correlates with HCC pathology and patient prognosis. In this paper, we analyzed the strength and limitations of a recent meta-analysis of associations of PD-L1 with HCC characteristics and patient prognosis. Keywords: hepatocellular carcinoma, programmed death ligand 1, hepatic resection, prognoses

  11. INFLUENCE OF HEPATOCELLULAR CARCINOMA ETIOLOGY IN THE SURVIVAL AFTER RESECTION.

    Science.gov (United States)

    Lopes, Felipe de Lucena Moreira; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Fonseca, Gilton Marques; Araujo, Raphael Leonardo Cunha de; Jeismann, Vagner Birk; Herman, Paulo

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and its incidence is increasing around the world in the last decades, making it the third cause of death by cancer in the world. Hepatic resection is one of the most effective treatments for HCC with five-year survival rates from 50-70%, especially for patients with a single nodule and preserved liver function. Some studies have shown a worse prognosis for HCC patients whose etiology is viral. That brings us to the question about the existence of a difference between the various causes of HCC and its prognosis. To compare the prognosis (overall and disease-free survival at five years) of patients undergoing hepatectomy for the treatment of HCC with respect to various causes of liver disease. Was performed a review of medical records of patients undergoing hepatectomy between 2000 and 2014 for the treatment of HCC. They were divided into groups according to the cause of liver disease, followed by overall and disease-free survival analysis for comparison. There was no statistically significant difference in the outcomes of the groups of patients divided according to the etiology of HCC. Overall and disease-free survival at five years of the patients in this sample were 49.9% and 40.7%, respectively. From the data of this sample, was verified that there was no prognostic differences among the groups of HCC patients of the various etiologies. O carcinoma hepatocelular (CHC) é o mais frequente tipo de câncer primário do fígado e a sua incidência vem aumentando nas últimas décadas, tornando-o hoje a terceira causa de morte por câncer no mundo. A ressecção hepática é um dos tratamentos mais eficazes para ele com taxas de sobrevida em cinco anos de 50-70%, especialmente para pacientes com nódulo único e função hepática preservada. Alguns estudos mostraram pior prognóstico para os pacientes com CHC cuja causa é a infecção por vírus B ou C. Isso leva à questão sobre a

  12. Clinical significance of CMTM4 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    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

  13. Chemotherapeutic potential of curcumin-bearing microcells against hepatocellular carcinoma in model animals

    Science.gov (United States)

    Farazuddin, Mohammad; Dua, Bhavyata; Zia, Qamar; Khan, Aijaz Ahmad; Joshi, Beenu; Owais, Mohammad

    2014-01-01

    Curcumin (diferuloylmethane) is found in large quantities in the roots of Curcuma longa. It possesses strong antioxidant and anti-inflammatory properties, and inhibits chemically-induced carcinogenesis in the skin, forestomach, colon, and liver. Unfortunately, the poor bioavailability and hydrophobicity of curcumin pose a major hurdle to its use as a potent anticancer agent. To circumvent some of these problems, we developed a novel, dual-core microcell formulation of curcumin. The encapsulation of curcumin in microcells increases its solubility and bioavailability, and facilitates slow release kinetics over extended periods. Besides being safe, these formulations do not bear any toxicity constraints, as revealed by in vitro and in vivo studies. Histopathological analysis revealed that curcumin-bearing microcells helped in regression of hepatocellular carcinoma and the maintenance of cellular architecture in liver tissue. Free curcumin had a very mild effect on cancer suppression. Empty (sham) microcells and microparticles failed to inhibit cancer cells. The novel curcumin formulation was found to suppress hepatocellular carcinoma efficiently in Swiss albino mice. PMID:24627632

  14. Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

    Science.gov (United States)

    Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

  15. Radiofrequency ablation vs. surgery for perivascular hepatocellular carcinoma: Propensity score analyses of long-term outcomes.

    Science.gov (United States)

    Lee, Sunyoung; Kang, Tae Wook; Cha, Dong Ik; Song, Kyoung Doo; Lee, Min Woo; Rhim, Hyunchul; Lim, Hyo Keun; Sinn, Dong Hyun; Kim, Jong Man; Kim, Kyunga

    2018-07-01

    The therapeutic outcomes of surgical resection (SR) or radiofrequency ablation (RFA) for perivascular hepatocellular carcinoma (HCC) have not been compared. The aim of this study was to compare SR with RFA as first-line treatment in patients with perivascular HCC and to evaluate the long-term outcomes of both therapies. This retrospective study was approved by the institutional review board. The requirement for informed consent was waived. Between January 2006 and December 2010, a total of 283 consecutive patients with small perivascular HCCs (≤3 cm, Barcelona Clinic Liver Cancer stage 0 or A) underwent SR (n = 182) or RFA (n = 101) as a first-line treatment. The progression-free survival (PFS) and overall survival (OS) rates were compared by propensity score matching. Subgroup analysis of these outcomes was conducted according to the type of hepatic vessels. The median follow-up was 7.8 years. Matching yielded 62 pairs of patients. In the two matched groups, the PFS rates at 5 and 10 years were 58.0% and 17.8%, respectively, in the SR group, and 25.4% and 14.1%, respectively, in the RFA group (p radiofrequency ablation are both treatment options for perivascular hepatocellular carcinoma. We compared outcomes in patients treated with either method. Surgical resection provided better long-term tumor control and overall survival than radiofrequency ablation for patients with a small perivascular hepatocellular carcinoma (≤3 cm) as a first-line treatment, particularly for periportal tumors. The location of the tumor and the type of peritumoral hepatic vessels need to be considered when choosing between surgical resection and radiofrequency ablation for small HCCs. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  16. Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure.

    Science.gov (United States)

    Granito, Alessandro; Marinelli, Sara; Terzi, Eleonora; Piscaglia, Fabio; Renzulli, Matteo; Venerandi, Laura; Benevento, Francesca; Bolondi, Luigi

    2015-06-01

    No standard second-line treatments are available for hepatocellular carcinoma patients who fail sorafenib therapy. We assessed the safety and efficacy of metronomic capecitabine after first-line sorafenib failure. Retrospective analysis of consecutive hepatocellular carcinoma patients receiving metronomic capecitabine between January 2012 and November 2014. The primary end-point was safety, secondary end-point was efficacy, including time-to-progression and overall survival. Twenty-six patients (80% Child-Pugh A, 80% Barcelona Clinic Liver Cancer stage C) received metronomic capecitabine (500 mg/bid). Median treatment duration was 3.2 months (range 0.6-31). Fourteen (53%) patients experienced at least one adverse event. The most frequent drug-related adverse events were bilirubin elevation (23%), fatigue (15%), anaemia (11%), lymphoedema (11%), and hand-foot syndrome (7.6%). Treatment was interrupted in 19 (73%) for disease progression, in 4 (15%) for liver deterioration, and in 1 (3.8%) for adverse event. Disease control was achieved in 6 (23%) patients. Median time-to-progression was 4 months (95% confidence interval 3.2-4.7). Median overall survival was 8 months (95% confidence interval 3.7-12.3). Metronomic capecitabine was well tolerated in hepatocellular carcinoma patients who had been treated with sorafenib. Preliminary data show potential anti-tumour activity with long-lasting disease control in a subgroup of patients that warrants further evaluation in a phase III study. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  17. Janus Kinase 2 (JAK2) Dissociates Hepatosteatosis from Hepatocellular Carcinoma in Mice.

    Science.gov (United States)

    Shi, Sally Yu; Luk, Cynthia T; Schroer, Stephanie A; Kim, Min Jeong; Dodington, David W; Sivasubramaniyam, Tharini; Lin, Lauren; Cai, Erica P; Lu, Shun-Yan; Wagner, Kay-Uwe; Bazinet, Richard P; Woo, Minna

    2017-03-03

    Hepatocellular carcinoma is an end-stage complication of non-alcoholic fatty liver disease (NAFLD). Inflammation plays a critical role in the progression of non-alcoholic fatty liver disease and the development of hepatocellular carcinoma. However, whether steatosis per se promotes liver cancer, and the molecular mechanisms that control the progression in this disease spectrum remain largely elusive. The Janus kinase signal transducers and activators of transcription (JAK-STAT) pathway mediates signal transduction by numerous cytokines that regulate inflammation and may contribute to hepatocarcinogenesis. Mice with hepatocyte-specific deletion of JAK2 (L-JAK2 KO) develop extensive fatty liver spontaneously. We show here that this simple steatosis was insufficient to drive carcinogenesis. In fact, L-JAK2 KO mice were markedly protected from chemically induced tumor formation. Using the methionine choline-deficient dietary model to induce steatohepatitis, we found that steatohepatitis development was completely arrested in L-JAK2 KO mice despite the presence of steatosis, suggesting that JAK2 is the critical factor required for inflammatory progression in the liver. In line with this, L-JAK2 KO mice exhibited attenuated inflammation after chemical carcinogen challenge. This was associated with increased hepatocyte apoptosis without elevated compensatory proliferation, thus thwarting expansion of transformed hepatocytes. Taken together, our findings identify an indispensable role of JAK2 in hepatocarcinogenesis through regulating critical inflammatory pathways. Targeting the JAK-STAT pathway may provide a novel therapeutic option for the treatment of hepatocellular carcinoma. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Lipid-coated iron oxide nanoparticles for dual-modal imaging of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Liang J

    2017-03-01

    Full Text Available Jinying Liang,1–3 Xinxin Zhang,2 Yunqiu Miao,2 Juan Li,1 Yong Gan2 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 3School of Pharmacy, Xinxiang Medical University, Xinxiang, People’s Republic of China Abstract: The development of noninvasive imaging techniques for the accurate diagnosis of progressive hepatocellular carcinoma (HCC is of great clinical significance and has always been desired. Herein, a hepatocellular carcinoma cell-targeting fluorescent magnetic nanoparticle (NP was obtained by conjugating near-infrared fluorescence to the surface of Fe3O4 (NIRF-Fe3O4 NPs, followed by coating the lipids consisting of tumoral hepatocytes-targeting polymer (Gal-P123. This magnetic NP (GPC@NIRF-Fe3O4 with superparamagnetic behavior showed high stability and safety in physiological conditions. In addition, GPC@NIRF-Fe3O4 achieved more specific uptake of human liver cancer cells than free Fe3O4 NPs. Importantly, with superparamagnetic iron oxide and strong NIR absorbance, GPC@NIRF-Fe3O4 NPs demonstrate prominent tumor-contrasted imaging performance both on fluorescent and T2-weighted magnetic resonance (MR imaging modalities in a living body. The relative MR signal enhancement of GPC@NIRF-Fe3O4 NPs achieved 5.4-fold improvement compared with NIR-Fe3O4 NPs. Therefore, GPC@NIRF-Fe3O4 NPs may be potentially used as a candidate for dual-modal imaging of tumors with information covalidated and directly compared by combining fluorescence and MR imaging. Keywords: dual-imaging, magnetic resonance imaging, hepatocellular carcinoma, tumor-targeting

  19. Association of social class in HBsAg and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Pervez, T.; Anwar, M. S.

    2001-01-01

    Objective: To find out the social class difference in relation to frequency of HBsAg and hepatocellular carcinoma in our population. Design: An analytical study. Place and Duration of Study: This study was conducted in Oncology Department, Services Hospital, Lahore from December 1997 to December 2000. Subjects and Methods: The HBsAg positive voluntary and apparently healthy blood donors were grouped into three, based on monthly income. Lower socioeconomic group and had monthly income less than 3,000 Pakistani rupees, middle socioeconomic group had monthly income between 3,000-10,000 rupees and upper socioeconomic group had income of more than 10,000 Pakistani rupees. On the same pattern patients suffering from hepatocellular carcinoma coming for treatment were also grouped. During this period, 1000 blood donors were screened for HBsAg and 95 biopsy proven liver cancer by causes were treated. Medical and demographic data of all subjects were recorded. HBsAg test was performed immuno-chromatographic technique using Daina Screen HBsAg kit manufactured by Dainabot Co. Ltd, Tokyo, Japan. Results: Patients from lower and middle social class had higher percentage (80% and 75%) of hepatocellular carcinoma as compared to higher social class (66.6%). In the healthy asymptomatic blood donors lower social class had higher (13.76%) HBsAg positively as compared to middle social class (11.25%) and higher social class (8.06%). Conclusion: Preventive measures should be taken in identifying and reducing factors predisposing high frequency of these conditions. (author)

  20. Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

    Science.gov (United States)

    Yang, Rui; Tang, Qiusha; Miao, Fengqin; An, Yanli; Li, Mengfei; Han, Yong; Wang, Xihui; Wang, Juan; Liu, Peidang; Chen, Rong

    2015-01-01

    Purpose To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia. Conclusion The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo. PMID:26677324

  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. Full Length Article Role of glypican-3 immunocytochemistry in differentiating hepatocellular carcinoma from metastatic carcinoma of the liver utilizing fine needle aspiration cytology

    International Nuclear Information System (INIS)

    Zaakook, M.; Abu Sinna, E.; Ayoub, M.; El-Sheikh, S.

    2013-01-01

    Purpose: Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods: Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results: 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion: Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver

  3. Ultrasound and computed tomographic demonstration of portal vein thrombosis in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pauls, C H

    1981-07-15

    Two cases of multinodular hepatocellular carcinoma (HCC) in which ultrasound and computed tomography (CT) revealed portal vein thrombosis are presented. The diagnostic value of determining the presence of portal vein thrombosis in patients with suspected HCC is discussed.

  4. Hepatocellular carcinoma localized in the bile duct lumen: two case report

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyeung Kug; Chang, Jay Chun [Yeungnam Univ. School of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    Intrabile duct tumor growth of hepatocellular carcinoma is an uncommon manifestation, but intraluminal bile duct hepatocellular carcinoma without primary hepatic parenchymal lesions is extremely rare. To our knowledge, only a few case reports have been published. We encountered two cases of primary hepatocellular carcinoma arising in the bile duct;serum alpha-fetoprotein levels were within the normal limits. Both showed the following characteristic radiologic features: (1) Cholangiography revealed filling defects within the dilated bile duct; (2) two-phase abdominal CT showed enhancement during the arterial-dominant phase and washout during the tissue equilibrium phase, as in typical HCC; and (3) hepateic arteriography revealed hypervascular tumor staining. Surgery was performed and the resected specimen showed no detectable primary hepatic parenchymal mass;on the basis of the pathologic finding, intraluminal bile duct hepatocellular carcinoma was confirmed. We cautiously assume that this peculiar type of HCC may arise primarily from bile duct mucosa.=20.

  5. The application of Fasudil in treating vascular spasm occurred in interventional treatment for hepatocellular carcinomas

    International Nuclear Information System (INIS)

    Fan Xiaoqiang; Shen Jie; Zhang Xuena; Liu Qiuru; Ma Aiying

    2011-01-01

    Objective: To explore an effective way to treat the vascular spasm occurred during TACE for hepatocellular carcinomas. Methods: During interventional chemoembolization for hepatocellular carcinomas, Fasudil of 2.5 mg was injected via the catheter if vessel spasm occurred, which was followed by DSA to determine the dilatation of the arteries. Adverse effect was observed and recorded. Results: After the injection of Fasudil the vascular spasm was completely relieved in all the 30 cases. The interventional procedure for hepatocellular carcinomas was successfully accomplished in all patients. No obvious side effect occurred. Conclusion: The injection of Fasudil via the catheter is an effective and safe method to eliminate vessel spasm occurred during TACE for hepatocellular carcinomas. (authors)

  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. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan; Duan, Fangfang; Zhang, Mingming; Song, Shushu; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

    2015-01-01

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC

  8. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai (China); Zhang, Mingming; Song, Shushu [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Institute of Biomedical Science, Fudan University, Shanghai (China)

    2015-08-07

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC.

  9. Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

    Science.gov (United States)

    Huang, Shujing; Jiang, Feifei; Wang, Ying; Yu, Yanhua; Ren, Siqian; Wang, Xiaowei; Yin, Peng; Lou, Jinli

    2017-06-01

    Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better

  10. Expression of the Long Intergenic Non-Protein Coding RNA 665 (LINC00665) Gene and the Cell Cycle in Hepatocellular Carcinoma Using The Cancer Genome Atlas, the Gene Expression Omnibus, and Quantitative Real-Time Polymerase Chain Reaction.

    Science.gov (United States)

    Wen, Dong-Yue; Lin, Peng; Pang, Yu-Yan; Chen, Gang; He, Yun; Dang, Yi-Wu; Yang, Hong

    2018-05-05

    BACKGROUND Long non-coding RNAs (lncRNAs) have a role in physiological and pathological processes, including cancer. The aim of this study was to investigate the expression of the long intergenic non-protein coding RNA 665 (LINC00665) gene and the cell cycle in hepatocellular carcinoma (HCC) using database analysis including The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and quantitative real-time polymerase chain reaction (qPCR). MATERIAL AND METHODS Expression levels of LINC00665 were compared between human tissue samples of HCC and adjacent normal liver, clinicopathological correlations were made using TCGA and the GEO, and qPCR was performed to validate the findings. Other public databases were searched for other genes associated with LINC00665 expression, including The Atlas of Noncoding RNAs in Cancer (TANRIC), the Multi Experiment Matrix (MEM), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) networks. RESULTS Overexpression of LINC00665 in patients with HCC was significantly associated with gender, tumor grade, stage, and tumor cell type. Overexpression of LINC00665 in patients with HCC was significantly associated with overall survival (OS) (HR=1.47795%; CI: 1.046-2.086). Bioinformatics analysis identified 469 related genes and further analysis supported a hypothesis that LINC00665 regulates pathways in the cell cycle to facilitate the development and progression of HCC through ten identified core genes: CDK1, BUB1B, BUB1, PLK1, CCNB2, CCNB1, CDC20, ESPL1, MAD2L1, and CCNA2. CONCLUSIONS Overexpression of the lncRNA, LINC00665 may be involved in the regulation of cell cycle pathways in HCC through ten identified hub genes.

  11. Induction of apoptosis by Armillaria mellea constituent armillarikin in human hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chen YJ

    2016-08-01

    Full Text Available Yu-Jen Chen,1–4 Chien-Chih Chen,5 Huey-Lan Huang6 1Department of Medical Research, 2Department of Radiation Oncology, Mackay Memorial Hospital, 3Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 4Institute of Pharmacology, Taipei Medical University, Taipei, 5Department of Biotechnology, HungKuang University, Taichung, 6Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan Abstract: Armillaria mellea is a honey mushroom often used in the traditional Chinese medicine “Tianma”. Currently, this medicinal mushroom is also used as a dietary supplement in numerous Western and Eastern countries. Armillarikin was isolated from A. mellea, and we previously discovered that it induced cytotoxicity in human leukemia cells. In this study, we further investigated the cytotoxicity of armillarikin against liver and intrahepatic bile duct cancer cells. Armillarikin was cytotoxic against human hepatocellular carcinoma Huh7, HA22T, and HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium and alamarBlue® assays. Armillarikin treatment also induced the collapse of the mitochondrial transmembrane potential of these cells. Furthermore, armillarikin-induced apoptotic cell death was demonstrated by sub-G1 chromosomal DNA formation by using flow cytometry. In addition, the apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-fmk. Immunoblotting also revealed the armillarikin-induced activation of procaspase-3, -8, and -9 and upregulation of the apoptosis- and cell cycle arrest-related phospho-histones 2 and 3, respectively. Moreover, reactive oxygen species scavengers also inhibited the armillarikin-induced apoptosis in human hepatocellular carcinoma, suggesting that reactive oxygen species formation played an important role in the armillarikin-induced apoptosis of human hepatocellular carcinoma. In

  12. Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

    2018-06-01

    Little evidence is available on the relationship between oral corticosteroids use and hepatocellular carcinoma. The objective of this study was to investigate whether oral corticosteroids use correlates with the risk of hepatocellular carcinoma in high risk populations in Taiwan. Using representative claims database established from the Taiwan National Health Insurance Program with a population coverage rate of 99.6%, we identified 102,182 subjects aged 20-84 years with newly diagnosed hepatocellular carcinoma in 2000-2011 as the cases and 102,182 randomly selected subjects aged 20-84 years without hepatocellular carcinoma as the matched controls. In subjects with any one of comorbidities including alcohol-related disease, chronic liver disease, and diabetes mellitus, the adjusted OR of hepatocellular carcinoma was 29.9 (95% CI 28.7, 31.1) for subjects with never use of oral corticosteroids, and the adjusted OR would increase to 33.7 (95% CI 32.3, 35.3) for those with ever use of oral corticosteroids. The adjusted OR of hepatocellular carcinoma was 1.03 for subjects with increasing cumulative duration of oral corticosteroids use for every one year (95% CI 1.01, 1.06), with a duration-dependent effect. The largest OR occurred in subjects with ever use of oral corticosteroids and concurrently comorbid with alcohol-related disease, chronic liver disease, and diabetes mellitus (adjusted OR 122.7, 95% CI 108.5, 138.8). There is a synergistic effect between oral corticosteroids use and the traditional risk factors on the risk of hepatocellular carcinoma. People with risk factors for hepatocellular carcinoma should receive regular ultrasound surveillance, particularly when they currently use oral corticosteroids. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  13. Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma.

    OpenAIRE

    Kew, M C; Miller, R H; Chen, H S; Tennant, B C; Purcell, R H

    1993-01-01

    Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariab...

  14. 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

    INTRODUCTION: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Knowledge on biomarkers may contribute to better surveillance based on the patients' risk of recurrence. Reviewing the literature, we aimed to identify serological...... 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...

  15. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier.

    Science.gov (United States)

    Ates, Ihsan; Kaplan, Mustafa; Demirci, Selim; Altiparmak, Emin

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Hepatitis B virus infection is one of the most important etilogical factors of HCC. In this case report, a patient with HCC previously infected and having ongoing immunity against hepatitis B virus will be discussed. Ates I, Kaplan M, Demirci S, Altiparmak E. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier. Euroasian J Hepato-Gastroenterol 2016;6(1):82-83.

  16. Clinical significance of computed tomographic arteriography for minute hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, H; Matsui, O; Suzuki, M; Ida, M; Kitagawa, K [Kanazawa Univ. (Japan). School of Medicine

    1982-03-01

    Computed tomographic arteriography (CTA) can clearly demonstrate minute hepatocellular carcinoma (H.C.C.) more than 2 cm in diameter as an enhanced mass lesion. In this case the precise localization of H.C.C. becomes so obvious that CTA plays an important role to evaluate its resectability. However, H.C.C. of the size from 2 cm to 1 cm indiameter, which is visualized with celiac and infusion hepatic angiography, becomes more difficult in detection, and particularly H.C.C. of less than 1 cm in diameter can hardly be recognized, nor be diagnosed as a malignant nodule by CTA, therefore it appears that in these sizes of H.C.C. the detectability of CTA is not superior to the hepatic angiography.

  17. Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Dmitry Konstantinov

    2016-09-01

    Full Text Available The purpose of the study was to examine the clinical and epidemiological data in patients with chronic hepatitis C (CHC and hepatocellular carcinoma (HCC before they sought specialized medical care. The study included 92 patients with CHC. All patients were divided into 2 groups: Group 1 consisted of CHC patients with HCC (n=45, and Group 2 (n=47 consisted of CHC patients without HCC. With the development of HCC in CHC patients, clinical manifestations were absent only in 2.2% of patients. Determining factors in HCC development are male sex, mature age, the maintained HCV replication, moderate and severe fibrosis, disease duration of more than 10 years, and the lack of effect of antiviral treatment.

  18. Hepatocellular carcinoma with cavernous transformation of the protal vein

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Heung Suk; Lee, Seung Ro; Hahm, Chang Kok [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1985-10-15

    Twenty cases of hepatocellular carcinoma were examined by selective celiac and superior mesenteric arteriography. Obstruction of the main portal vein due to tumor thrombus was revealed in 7 cases and 3 of these cases had cavernous transformation of the portal vein (CTPV). The authors intended in this study to evaluate CTPV group and non-CTPV group clinically and radiologically. The results obtained are as follows: 1. The duration of illness was shorter in CTPV group than non- CTPV group. 2. There was no significant difference in tumor size between two groups ,and main portion of tumor was located in the right lobe in both groups. 3. Arterio portal shunt was present in 2 of 4 cases in non-CTPV group, but was no present at all in CRPV groups. 5. There wa no significant difference in blood chemistry between two groups. 6. CTPV may play an important role maintain the hepatic blood flow.

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

    Directory of Open Access Journals (Sweden)

    Chen-Yi Liao

    2015-01-01

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

  20. 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.

  1. Radioembolization for hepatocellular carcinoma using TheraSphere®.

    Science.gov (United States)

    Ali, Safiyya Mohamed

    2011-01-01

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

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

    Science.gov (United States)

    Al-Kalbani, Abdullah; Kamel, Yasser

    2008-04-01

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

  3. 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.

  4. Hyperintense hepatocellular carcinoma on gadolinium-enhanced hepatic MRI

    International Nuclear Information System (INIS)

    Yoshikawa, Jun; Matsui, Osamu; Kadoya, Masumi; Gabata, Toshifumi; Arai, Kazunori; Takashima, Tsutomu

    1992-01-01

    We reported a phenomenon in which some hepatocellular carcinomas (HHCs) visualized as hypointense on plain T1 weighted MR images became hyperintense on gadolinium-DTPA (Gd-DTPA) (0.06∼0.23 mmol/kg) enhanced delayed images. Gd-DTPA enhanced images (using a super conducting magnet operating at 1.5T) of 44 HCCs were studied in comparison with contrast enhanced CT using 30∼80g of iodine. Six of 44 HCCs (14%) which were visualized as hypointense on plain T1 weighted image became hyperintense on delayed Gd-DTPA enhanced images. Although these were visualized as low intensity areas on both plain and enhanced CT, the contrast between HCC and the surrounding liver was small on post contrast CT. These findings were thought to be due to a stronger enhancement effect of Gd-DTPA than that of iodine. (author)

  5. Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Qin JM

    2012-01-01

    Full Text Available Jian-Min Qin1, Pei-Hao Yin1, Qi Li1, Zhong-Qiu Sa1, Xia Sheng1, Lin Yang1, Tao Huang1, Min Zhang1, Ke-Pan Gao2, Qing-Hua Chen2, Jing-Wei Ma3, He-Bai Shen31Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 2National Pharmaceutical Engineering Research Center; Shanghai Institute of Pharmaceutical Industry, 3Department of Physical Chemistry, Shanghai Normal University, Shanghai, People's Republic of ChinaBackground: Hepatocellular carcinoma is difficult to diagnose early, and most patients are already in the late stages of the disease when they are admitted to hospital. The total 5-year survival rate is less than 5%. Recent studies have showed that brucine has a good anti-tumor effect, but high toxicity, poor water solubility, short half-life, narrow therapeutic window, and a toxic dose that is close to the therapeutic dose, which all limit its clinical application. This study evaluated the effects of brucine immuno-nanoparticles (BIN on hepatocellular carcinoma.Materials and methods: Anionic polymerization, chemical modification technology, and phacoemulsification technology were used to prepare a carboxylated polyethylene glycol-polylactic acid copolymer carrier material. Chemical coupling technology was utilized to develop anti-human AFP McAb-polyethylene glycol-polylactic acid copolymer BIN. The size, shape, zeta potential, drug loading, encapsulation efficiency, and release of these immune-nanoparticles were studied in vitro. The targeting, and growth, invasion, and metastasis inhibitory effects of this treatment on liver cancer SMMC-7721 cells were tested.Results: BIN were of uniform size with an average particle size of 249 ± 77 nm and zeta potential of -18.7 ± 4.19 mV. The encapsulation efficiency was 76.0% ± 2.3% and the drug load was 5.6% ± 0.2%. Complete uptake and even distribution around the liver cancer cell membrane were observed.Conclusion: BIN had even size distribution, was

  6. Transarterial chemoembolization through collateral vessels in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hye; Han, Joon Koo; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1993-11-15

    We performed 70 procedures of transarterial chemoembolization (TAE) through extrahepatic collateral vessels (n=27) or parasitic feeders (n=18) in 45 hepatocellular carcinoma patients. The collaterals developed after interruption of the hepatic artery due to repeated TAE (n=17), surgical ligation (n=7)and primary celiac occlusion (n=3). Radiologic findings suggest the existence of parasitic or collateral supply for hepatocellular carcinoma were 1) a focal defect of Lipiodol retention on CT or plain film after TAE via the hepatic artery, 2) dilated and tortuous vessels around the mass on angiography, 3) persistent elevation of the level of serum alpha-fetoprotein or continuous clinical symptoms in spite of sufficient devascularization of the tumor via the hepatic artery, and 4) radiological findings of direct invasion into adjacent organ. The sites of the catheter placement were the inferior phrenic artery(n=19), omental branches(n=16), periportal collaterals (n=6), pancreaticodenal arcade (n=3), gastroduodenal artery(n=3), internal mammary artery (n=2), intercosal artery (n=2), lateral thoracic artery (n=1), bronchial artery (n=1), and colic branches (n=1). Masses feeded by the inferior phrenic and chest wall collaterals were usually located at the dome area of the liver, and the omental and gastroduodenal collaterals developed in the masses located at the inferior tip of the liver. After TAE via collateral vessels, 37 patients underwent follow-up study. In 18 cases(48%), the tumor favorably responded to TAE. Specific complications of collateral TAE were epigastric soreness (n=10), severe shoulder pain (n=4), and embolization of the spinal artery during embolization through the intercostal artery (n=1). In conclusion, various extrahepatic collateals are important alternative or addition routes for effective chemoembolization in patients with advanced hepatoma, and early recognition of the parasitic supply and the effort to perform TAE via collaterals is very

  7. Transarterial chemoembolization through collateral vessels in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Ji Hye; Han, Joon Koo; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung

    1993-01-01

    We performed 70 procedures of transarterial chemoembolization (TAE) through extrahepatic collateral vessels (n=27) or parasitic feeders (n=18) in 45 hepatocellular carcinoma patients. The collaterals developed after interruption of the hepatic artery due to repeated TAE (n=17), surgical ligation (n=7)and primary celiac occlusion (n=3). Radiologic findings suggest the existence of parasitic or collateral supply for hepatocellular carcinoma were 1) a focal defect of Lipiodol retention on CT or plain film after TAE via the hepatic artery, 2) dilated and tortuous vessels around the mass on angiography, 3) persistent elevation of the level of serum alpha-fetoprotein or continuous clinical symptoms in spite of sufficient devascularization of the tumor via the hepatic artery, and 4) radiological findings of direct invasion into adjacent organ. The sites of the catheter placement were the inferior phrenic artery(n=19), omental branches(n=16), periportal collaterals (n=6), pancreaticodenal arcade (n=3), gastroduodenal artery(n=3), internal mammary artery (n=2), intercosal artery (n=2), lateral thoracic artery (n=1), bronchial artery (n=1), and colic branches (n=1). Masses feeded by the inferior phrenic and chest wall collaterals were usually located at the dome area of the liver, and the omental and gastroduodenal collaterals developed in the masses located at the inferior tip of the liver. After TAE via collateral vessels, 37 patients underwent follow-up study. In 18 cases(48%), the tumor favorably responded to TAE. Specific complications of collateral TAE were epigastric soreness (n=10), severe shoulder pain (n=4), and embolization of the spinal artery during embolization through the intercostal artery (n=1). In conclusion, various extrahepatic collateals are important alternative or addition routes for effective chemoembolization in patients with advanced hepatoma, and early recognition of the parasitic supply and the effort to perform TAE via collaterals is very

  8. Hepatocellular carcinoma with bile duct involvement : computed Tomographic (CT) findings

    International Nuclear Information System (INIS)

    Lee, Joon Woo; Han, Joon Koo; Kim, Tae Kyoung; And others

    2000-01-01

    To describe the radiologic features of computed tomography (CT) in hepatocellular carcinoma (HCC) with bile duct involvement. We retrospectively analyzed the two phase spiral CT findings of 31 patients in whom HCC with bile duct invasion (n=3D28) or compression (n=3D3), was diagnosed. Eight of these underwent follow up CT after transarterial chemoembolization. We analyzed the size, type, location, enhancement pattern, and lipiodol retention of parenchymal and intraductal masses, as well as their lymphadenopathy. In all patients with bile duct invasion, single or multiple masses were demonstrated in the bile ducts. Intraductal masses showed the same enhancement characteristics as the parenchymal mass (kappa 0.550, p less than 0.001), and were contiguous to this mass. In 14 of 28 patients, intraductal masses filled the peripheral intrahepatic bile ducts and extended to the common bile ducts. In the other 14, the parenchymal mass extended to the area of the porta hepatis and then directly invaded the large ducts. In nine of the 28 patients, there was a hypoattenuated cleft between the intraductal mass and ductal wall. In six, a parenchymal mass was not apparent (n=3D2), or was smaller than 2cm (n=3D4). In five of eight patients (62.5%), follow-up CT after transarterial chemoembolization showed compact or partial lipiodol retention within the intraductal mass. In patients with bile duct compression, perihilar lymph nodes were noted along with the dilated intrahepatic duct but no intra ductal mass was demonstrated in the duct. Hepatocellular carcinomas cause bile duct dilatation either by direct invasion or by extrinsic compression of the bile duct with surrounding enlarged nodes. For the diagnosis of this condition, CT is helpful. (author)

  9. Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis.

    Science.gov (United States)

    Granito, Alessandro; Bolondi, Luigi

    2017-02-01

    Underlying liver cirrhosis is present in most patients with hepatocellular carcinoma, and liver transplantation is the only treatment strategy to cure both diseases. All other hepatocellular carcinoma treatment strategies have to take into account residual liver function that concurs with the patient's prognosis and might limit their feasibility. In patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B (CPT-B), owing to borderline liver function, any intervention might be offset by liver function deterioration. In this setting, the decision for hepatocellular carcinoma treatment requires a comprehensive assessment of liver function, not restricted to the CPT classification, in addition to a careful evaluation of the prognostic effect of hepatocellular carcinoma compared with cirrhosis. In this Review, we provide an overview of the literature regarding the benefits and harms of non-transplant therapies in patients with hepatocellular carcinoma and CPT-B cirrhosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Natural history of untreatable hepatocellular carcinoma: A retrospective cohort study.

    Science.gov (United States)

    Cabibbo, Giuseppe; Maida, Marcello; Genco, Chiara; Parisi, Pietro; Peralta, Marco; Antonucci, Michela; Brancatelli, Giuseppe; Cammà, Calogero; Craxì, Antonio; Di Marco, Vito

    2012-09-27

    To investigate the clinical course of untreatable hepatocellular carcinoma (HCC) identified at any stage and to identify factors associated with mortality. From January 1999 to December 2010, 320 out of 825 consecutive patients with a diagnosis of HCC and not appropriate for curative or palliative treatments were followed and managed with supportive therapy. Cirrhosis was diagnosed by histological or clinical features and liver function was evaluated according to Child-Pugh score. The diagnosis of HCC was performed by Ultra-Sound guided biopsy or by multiphasic contrast-enhanced computed tomography or gadolinium-enhanced magnetic resonance imaging. Data were collected for each patient including all clinical, laboratory and imaging variables necessary for the outcome prediction staging systems considered. HCC staging was performed according Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program scores. Follow-up time was defined as the number of months from the diagnosis of HCC to death. Prognostic baseline variables were analyzed by multivariate Cox analysis to identify the independent predictors of survival. Seventy-five per cent of patients had hepatitis C. Ascites was present in 169 patients (53%), while hepatic encephalopathy was present in 49 patients (15%). The Child-Pugh score was class A in 105 patients (33%), class B in 142 patients (44%), and class C in 73 patients (23%). One hundred patients (31%) had macroscopic vascular invasion and/or extra-hepatic spread of the tumor. A single lesion > 10 cm was observed in 34 patients (11%), while multinodular HCC was present in 189 patients (59%). Thirty nine patients (12%) were BCLC early (A) stage, 55 (17%) were BCLC intermediate (B) stage, 124 (39%) were BCLC advanced (C) stage, and 102 (32%) were end-stage BCLC (D). At the time of this analysis (July 2011), 28 (9%) patients were still alive. Six (2%) patients who were lost during follow-up were censored at the last visit. The overall

  11. [Metastasis of Hepatocellular Carcinoma to the Membrane of Chronic Subdural Hematomas:A Case Report].

    Science.gov (United States)

    Oshita, Jumpei; Ohba, Shinji; Itou, Yoko; Yonezawa, Koki; Hosogai, Masahiro

    2017-10-01

    An 81-year-old man presented with gait disturbance. Two months previously, he suffered from hepatocellular carcinoma and transarterial chemoembolization was performed. A head computed tomography(CT)scan revealed bilateral chronic subdural hematomas. The patient's gait disturbance was improved after achievement of bilateral burr hole drainage. A head CT two months after treatment revealed no recurrence of the hematomas. However, head CT images obtained four months after treatment revealed an abnormal mass in the right parietal region attached to the internal surface of the skull. The mass was located in the same region from where the chronic subdural hematomas were previously removed via burr hole drainage, and was suspected to have originated from the dura mater. We performed craniotomy and total removal of the mass. The dura mater was intact, and macroscopically, the mass originated from the organized membrane of the chronic subdural hematoma. A pathological examination revealed metastasis of hepatocellular carcinoma to the membrane of the chronic subdural hematomas. Head magnetic resonance imaging(MRI)performed 39 days after craniotomy presented a new lesion in the left parietal region attached to the internal surface of the skull. The patient subsequently died 46 days post-operation. When examining chronic subdural hematomas in cancer patients, histological examination of the dura mater, hematoma, and membrane of the hematoma are important. The possibility of metastasis to the capsule of the hematoma should be considered.

  12. Synergistic Antitumor Effect of Doxorubicin and Tacrolimus (FK506 on Hepatocellular Carcinoma Cell Lines

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    Francesca Capone

    2014-01-01

    Full Text Available Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506 has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i a strong cell apoptosis induction, (ii contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.

  13. Chemiluminescence enzyme immunoassay based on magnetic nanoparticles for detection of hepatocellular carcinoma marker glypican-3

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    Qian-Yun Zhang

    2011-08-01

    Full Text Available Glypican-3 (GPC3 is reported as a great promising tumor marker for hepatocellular carcinoma (HCC diagnosis. Highly sensitive and accurate analysis of serum GPC3 (sGPC3, in combination with or instead of traditional HCC marker alpha-fetoprotein (AFP, is essential for early diagnosis of HCC. Biomaterial-functionalized magnetic particles have been utilized as solid supports with good biological compatibility for sensitive immunoassay. Here, the magnetic nanoparticles (MnPs and magnetic microparticles (MmPs with carboxyl groups were further modified with streptavidin, and applied for the development of chemiluminescence enzyme immunoassay (CLEIA. After comparing between MnPs- and MmPs-based CLEIA, MnPs-based CLEIA was proved to be a better method with less assay time, greater sensitivity, better linearity and longer chemiluminescence platform. MnPs-based CLEIA was applied for detection of sGPC3 in normal liver, hepatocirrhosis, secondary liver cancer and HCC serum samples. The results indicated that sGPC3 was effective in diagnosis of HCC with high performance. Keywords: Magnetic nanoparticle, Magnetic microparticle, Chemiluminescence enzyme immunoassay, Glypican-3, Hepatocellular carcinoma

  14. A middle-aged man with a troubled liver: Combination therapy in advanced (BCLC Stage C hepatocellular carcinoma

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    Zamri Zuhdi

    2018-03-01

    Full Text Available Advanced hepatocellular carcinoma carries a bad prognosis with a survival of only few months. Barcelona Clinic Liver Cancer (BCLC Guidelines recommended sorafenib monotherapy as the treatment modality for advanced BCLC Stage C disease, citing a two-month increase in survival rates. Here, we highlight a case with advanced HCC (BCLC Stage C treated with combination therapy of liver resection and Sorafenib therapy. The patient’s current survival rate was beyond 10 months. We also discuss the current evidence on liver resection with Sorafenib therapy in hepatocellular carcinoma. The description of the case may benefit in future diagnosis and treatment. [Arch Clin Exp Surg 2018; 7(1.000: 29-32

  15. Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

    Science.gov (United States)

    Rosmorduc, Olivier

    2013-05-01

    Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  16. Knockdown of Pokemon protein expression inhibits hepatocellular carcinoma cell proliferation by suppression of AKT activity.

    Science.gov (United States)

    Zhu, Xiaosan; Dai, Yichen; Chen, Zhangxin; Xie, Junpei; Zeng, Wei; Lin, Yuanyuan

    2013-01-01

    Overexpression of Pokemon, which is an erythroid myeloid ontogenic factor protein, occurs in different cancers, including hepatocellular carcinoma (HCC). Pokemon is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of Pokemon knockdown on the regulation of HCC growth. POK shRNA suppressed the expression of Pokemon protein in HepG2 cells compared to the negative control vector-transfected HCC cells. Pokemon knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. AKT activation and the expression of various cell cycle-related genes were inhibited following Pokemon knockdown. These data demonstrate that Pokemon may play a role in HCC progression, suggesting that inhibition of Pokemon expression using Pokemon shRNA should be further evaluated as a novel target for the control of HCC.

  17. Management of small hepatocellular carcinoma in cirrhosis: Focus on portal hypertension

    Science.gov (United States)

    Hernandez-Gea, Virginia; Turon, Fanny; Berzigotti, Annalisa; Villanueva, Augusto

    2013-01-01

    The incidence of hepatocellular carcinoma (HCC) is rising worldwide being currently the fifth most common cancer and third cause of cancer-related mortality. Early detection of HCC through surveillance programs have enabled the identification of small nodules with higher frequency, and nowadays account for 10%-15% of patients diagnosed in the West and almost 30% in Japan. Patients with small HCC can be candidates for potential curative treatments: liver transplantation, surgical resection and percutaneous ablation, depending on the presence of portal hypertension and co-morbidities. This review will analyze recent advancements in the clinical management of these individuals, focusing on issues related to the role of portal hypertension, the debate between resection and ablative therapies and the future impact of molecular technologies. PMID:23482437

  18. 2014 KLCSG-NCC Korea Practice Guideline for the Management of Hepatocellular Carcinoma

    Science.gov (United States)

    2015-01-01

    The guideline for the management of hepatocellular carcinoma (HCC) was first developed in 2003 and revised in 2009 by the Korean Liver Cancer Study Group and the National Cancer Center, Korea. Since then, many studies on HCC have been carried out in Korea and other countries. In particular, a substantial body of knowledge has been accumulated on diagnosis, staging, and treatment specific to Asian characteristics, especially Koreans, prompting the proposal of new strategies. Accordingly, the new guideline presented herein was developed on the basis of recent evidence and expert opinions. The primary targets of this guideline are patients with suspicious or newly diagnosed HCC. This guideline provides recommendations for the initial treatment of patients with newly diagnosed HCC. PMID:25918260

  19. Research advances in traditional Chinese medicine combined with interventional therapy for hepatocellular carcinoma

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    LIU Yang

    2015-01-01

    Full Text Available Interventional therapy has become the first choice of non-surgical treatment for hepatocellular carcinoma (HCC due to its advantages such as little trauma and marked local effect. However, the clinical efficiency is less than expected. One of the possibilities is the resistance of cancer cells to anti-cancer drugs. Increasing attention has been paid to the combination of traditional Chinese medicine (TCM and interventional therapy in HCC treatment. This paper reviews the progress in TCM combined with interventional therapy for HCC at animal experiment and clinical study levels in recent ten years. It is pointed out that the combination therapy with TCM and intervention for HCC has a unique advantage.

  20. Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma.

    Science.gov (United States)

    Chen, Shao-Ru; Qiu, Hong-Cong; Hu, Yang; Wang, Ying; Wang, Yi-Tao

    2016-06-01

    Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/β-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. The role of micro-RNAs in hepatocellular carcinoma: from molecular biology to treatment.

    Science.gov (United States)

    D'Anzeo, Marco; Faloppi, Luca; Scartozzi, Mario; Giampieri, Riccardo; Bianconi, Maristella; Del Prete, Michela; Silvestris, Nicola; Cascinu, Stefano

    2014-05-19

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary conserved small non-coding RNA that negatively regulate gene expression and protein translation. Recent evidences have shown that they are involved in many biological processes, from development and cell-cycle regulation to apoptosis. miRNAs can behave as tumor suppressor or promoter of oncogenesis depending on the cellular function of their targets. Moreover, they are frequently dysregulated in HCC. In this review we summarize the latest findings of miRNAs regulation in HCC and their role as potentially diagnostic and prognostic biomarkers for HCC. We highlight development of miRNAs as potential therapeutic targets for HCC.

  2. Dihydromyricetin promotes hepatocellular carcinoma regression via a p53 activation-dependent mechanism

    Science.gov (United States)

    Zhang, Qingyu; Liu, Jie; Liu, Bin; Xia, Juan; Chen, Nianping; Chen, Xiaofeng; Cao, Yi; Zhang, Chen; Lu, Caijie; Li, Mingyi; Zhu, Runzhi

    2014-04-01

    The development of antitumor chemotherapy drugs remains a key goal for oncologists, and natural products provide a vast resource for anti-cancer drug discovery. In the current study, we found that the flavonoid dihydromyricetin (DHM) exhibited antitumor activity against liver cancer cells, including primary cells obtained from hepatocellular carcinoma (HCC) patients. In contrast, DHM was not cytotoxic to immortalized normal liver cells. Furthermore, DHM treatment resulted in the growth inhibition and remission of xenotransplanted tumors in nude mice. Our results further demonstrated that this antitumor activity was caused by the activation of the p53-dependent apoptosis pathway via p53 phosphorylation at serine (15Ser). Moreover, our results showed that DHM plays a dual role in the induction of cell death when administered in combination with cisplatin, a common clinical drug that kills primary hepatoma cells but not normal liver cells.

  3. 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.

  4. CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma

    DEFF Research Database (Denmark)

    Engelholm, Lars H; Riaz, Anjum; Serra, Denise

    2017-01-01

    BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1...

  5. Spinal cord compression secondary to bone metastases from hepatocellular carcinoma

    Science.gov (United States)

    Doval, Dinesh Chandra; Bhatia, Komal; Vaid, Ashok Kumar; Pavithran, Keechelat; Sharma, Jai Bhagwan; Hazarika, Digant; Jena, Amarnath

    2006-01-01

    Bone metastases are rare in primary hepatocellular carcinoma (HCC). Spinal cord compression (SCC) due to bone metastases occur commonly in patients with lung and breast carcinomas, and metastatic HCC is an unusual cause of SCC. Spinal cord compression is an oncologic emergency and treatment delays can lead to irreversible consequences. Thus, the awareness that SCC could be a potential complication of bone metastases due to HCC is of significance in initiation of early treatment that can improve the quality of life and survival of the patients, if diagnosed earlier. This paper describes four cases of primary HCC with varied manifestations of SCC due to bone metastases. The first patient presented primarily with the symptoms of bone pains corresponding to the bone metastases sites rather than symptoms of associated hepatic pathology and eventually developed SCC. The second patient, diagnosed as having HCC, developed extradural SCC leading to paraplegia during the course of illness, for which he underwent emergency laminectomy with posterior fixation. The third patient developed SCC soon after the primary diagnosis and had to undergo emergency laminectomy. Post laminectomy he had good neurological recovery. The Fourth patient presented primarily with radicular pains rather than frank paraplegia as the first manifestation of SCC. PMID:16937544

  6. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    DEFF Research Database (Denmark)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte

    2013-01-01

    Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular...... and growth of hepatocellular carcinoma. Rodent and in vitro studies support the hypothesis, but clinical verification is needed. Different study designs may be considered. The feasibility of a randomized controlled trial is limited due to the necessary large number of patients and long follow......-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient....

  7. Negative correlation of LIV-1 and E-cadherin expression in hepatocellular carcinoma cells.

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    Rongxi Shen

    Full Text Available LIV-1, a zinc transporter, is a mediator downstream of STAT3 both in zebrafish and mammalian cells, and is involved in epithelial-mesenchymal transition (EMT. Despite LIV-1 participates in cancer growth and metastasis, little is known about the association of LIV-1 with human liver cancer development. Therefore, the expression of LIV-1 mRNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR in 4 cultured cell lines (3 carcinoma and 1 normal liver cell lines, and the localization of LIV-1 protein was investigated by immunohistochemistry. Expression of LIV-1 protein was analyzed by Western blot both in 4 cultured cell lines and 120 liver tissues (100 carcinoma and 20 histologically normal tissues, and the relationship between its expression and clinicopathological finding was investigated in 100 hepatocellular carcinoma(HCC tissues. Then stable siRNA expressing Hep-G2 cells were generated to assess the function of LIV-1 in liver cancer cells. We found that LIV-1 mRNA was more highly expressed in liver cancer cell lines compared to normal liver cell line. Western blot showed the expression of LIV-1 was higher in 61% liver carcinoma tissues than that in normal liver tissues. Down-regulated LIV-1 cells showed significant inhibition of proliferation in vitro and reduction of tumor growth in vivo. Furthermore, E-cadherin expression increased in LIV-1 siRNA expressing Hep-G2. These findings indicated that LIV-1 may induce the EMT in HCC cells.

  8. Effects of marital status on survival of hepatocellular carcinoma by race/ethnicity and gender

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    Wu W

    2018-01-01

    Full Text Available Wenrui Wu,1,2 Daiqiong Fang,1,2 Ding Shi,1,2 Xiaoyuan Bian,1,2 Lanjuan Li1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China Purpose: It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship.Patients and methods: We identified eligible patients from Surveillance, Epidemiology and End Results (SEER database during 2004–2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan–Meier curves. We also estimated crude hazard ratios (CHRs and adjusted hazard ratios (AHRs with 95% confidence intervals (CIs for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models.Results: A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married was highest for Hispanic (AHR =1.25, 95% CI, 1.13–1.39; P<0.001 and lowest for Asian or Pacific Islander (AHR =1.13; 95% CI, 1.00–1.28; P=0.042. Stratified by gender, the AHR was higher in males (AHR =1.27; 95% CI, 1.20–1.33; P<0.001.Conclusion: We demonstrated that married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality. Keywords: primary hepatocellular

  9. Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients.

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    Jinpu Yu

    Full Text Available AIM: To investigate the role of neurotensin (NTS in hepatocellular carcinoma (HCC sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. METHODS: The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, β-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC staining method. The clinical outcome and overall survival (OS were compared. RESULTS: A subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS(+ HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036, which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68(+ macrophages and more cancer cells displaying EMT features were found in NTS(+IL-8(+ samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS(+IL-8(+ HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022. Accordingly, the OS of NTS(+IL-8(+ HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR of 3.457. CONCLUSION: Dysfunctional activation of the NTS/IL-8 pathway was detected in

  10. Traditional herbal medicine prevents postoperative recurrence of small hepatocellular carcinoma: A randomized controlled study.

    Science.gov (United States)

    Zhai, Xiao-Feng; Liu, Xiao-Lin; Shen, Feng; Fan, Jia; Ling, Chang-Quan

    2018-05-15

    To explore the clinical efficacy of traditional herbal medicine (THM) in the prevention of disease recurrence of small hepatocellular carcinoma after surgery, a prospective randomized controlled study was conducted between October 2006 and May 2010. The results indicated that THM prevented the recurrence of SHCC with an efficacy that was superior to that of transarterial chemoembolization (TACE) during a median follow-up of 26.61 months. The patients were followed up every 6 months, and the clinical data before October 20, 2015 were analyzed. The primary outcome measure was recurrence-free survival (RFS), and the secondary outcome measure was overall survival (OS). The 364 patients included 180 in the THM group and 184 in the TACE group. At the time of the data cutoff of October 20, 2015, a total of 205 patients demonstrated disease recurrence, including 85 patients in the THM group and 120 patients in the TACE group. The median RFS of the THM and TACE groups demonstrated a statistically significant difference (P<.001). Until October 20, 2105, there were 91 deaths, including 34 in the THM group and 57 in the TACE group. The median OS demonstrated a significant difference between the 2 groups (P = .008). Multivariate analysis indicated that THM was an independent factor influencing RFS and OS. The efficacy of THM was found to be superior to that of TACE in preventing disease recurrence in patients with small hepatocellular carcinoma and prolonging OS. Cancer 2018;124:2161-8. © 2018 American Cancer Society. © 2018 American Cancer Society.

  11. Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma

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    Chávez-López MG

    2016-09-01

    Full Text Available María de Guadalupe Chávez-López,1 Violeta Zúñiga-García,1 Julio Isael Pérez-Carreón,2 Arturo Avalos-Fuentes,3 Yesenia Escobar,4 Javier Camacho1 1Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 2Instituto Nacional de Medicina Genómica, 3Department of Physiology, Biophysics and Neuroscience, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 4Centro de Investigación Clínica Acelerada Sc, Mexico City, Mexico Abstract: Hepatocellular carcinoma (HCC is a major cause of cancer death worldwide. HCC is usually asymptomatic at potential curative stages, and it has very poor prognosis if detected later. Thus, the identification of early biomarkers and novel therapies is essential to improve HCC patient survival. Ion channels have been proposed as potential tumor markers and therapeutic targets for several cancers including HCC. Especially, the ether à-go-go-1 (Eag1 voltage-gated potassium channel has been suggested as an early marker for HCC. Eag1 is overexpressed during HCC development from the cirrhotic and the preneoplastic lesions preceding HCC in a rat model. The channel is also overexpressed in human HCC. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including Eag1. Actually, in vivo studies have shown that astemizole may have clinical utility for HCC prevention and treatment. Here, we will review first some general aspects of HCC including the current biomarkers and therapies, and then we will focus on Eag1 channels as promising tools in the early diagnosis of HCC. Keywords: ion channels, Eag1, hepatocellular carcinoma, astemizole, diethylnitrosamine

  12. Phase II trial of SOM230 (pasireotide LAR in patients with unresectable hepatocellular carcinoma

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    Feun LG

    2018-01-01

    Full Text Available Lynn G Feun,¹ Medhi Wangpaichitr,² Ying-Ying Li,¹ Deukwoo Kwon,³ Stephen P Richman,¹ Peter J Hosein,¹ Niramol Savaraj¹,² ¹Department of Medicine, Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, ²Department of Surgery, Miami VA Healthcare System, Research Service, ³Biostatistics and Bioinformatics Core, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA Background: A phase II trial of pasireotide was performed to assess its efficacy and safety in advanced or metastatic hepatocellular carcinoma (HCC.Patients and methods: Patients with advanced HCC and Child–Pugh score ≤7 received pasireotide LAR 60 mg intramuscularly every 28 days. Primary endpoint was disease control rate. Secondary endpoints were time to tumor progression, response rate, treatment-related adverse events, and overall survival. Serum insulin growth factor-1 was measured before and after pasireotide.Results: Twenty patients were treated and evaluable. Eighteen patients (90% had prior therapy; 16 patients (80% had multiple therapies. Median age was 65, 75% had Barcelona Clinic Liver Cancer stage C, and 55% had metastatic disease. The main toxicity was hyperglycemia. Rare adverse effects included reversible grade 4 elevation in alanina transaminase/aspartate transaminase in one patient. The best response was stable disease in 9 patients (45%. Median time to tumor progression for the 20 patients was 3 months, and median survival was 9 months.Conclusion: Pasireotide had limited clinical benefit as second-line or third-line treatment in patients with advanced or metastatic HCC. Low baseline insulin growth factor-1 level may be indicative when SOM230 treatment may be ineffective, and decreasing levels after treatment may be indicative of disease control. Keywords: pasireotide, hepatocellular carcinoma, insulin growth factor-1 

  13. Liposomes equipped with cell penetrating peptide BR2 enhances chemotherapeutic effects of cantharidin against hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xue; Lin, Congcong; Lu, Aiping; Lin, Ge; Chen, Huoji; Liu, Qiang; Yang, Zhijun; Zhang, Hongqi

    2017-11-01

    A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.

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

    Science.gov (United States)

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

    2012-09-01

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

  15. Ultrasonographic detection of hepatocellular carcinoma: correlation of preoperative ultrasonography and resected liver pathology

    International Nuclear Information System (INIS)

    Lim, J.H.; Kim, S.H.; Lee, W.J.; Choi, D.; Kim, S.H.; Lim, H.K.

    2006-01-01

    AIM: The aim of this study was to determine the sensitivity of ultrasonography for detecting hepatocellular carcinoma in patients who underwent surgical liver resection. MATERIALS AND METHODS: The preoperative ultrasonography reports of 103 patients who underwent hepatic resection surgery were retrospectively reviewed. The patients had chronic liver disease with good liver function and a relatively normal liver echotexture. The presence of a mass or masses in the resected part of the liver segments on preoperative ultrasonography was regarded as possible hepatocellular carcinoma, and these results were compared with the surgically resected hepatic lobes or segments. Accuracy for detection was assessed on a lesion-by-lesion basis, on a segment-by-segment basis, and on a patient basis. RESULTS: One hundred and fifty-seven hepatocellular carcinomas were found in 244 hepatic segments of 103 patients. One hundred and one of 157 hepatocellular carcinomas were detected using ultrasonography in 97 patients resulting in a sensitivity of 64%. In six patients, a solitary hepatocellular carcinoma was missed in each patient, a patient sensitivity being 94%. Using ultrasonography, 87 of 100 (87%) hepatocellular carcinomas larger than 2 cm in diameter, and 14 of 57 (25%) hepatocellular carcinomas 2 cm or smaller in diameter were revealed. On the basis of segment-by-segment analysis, the sensitivity was 78% (99 of 127 segments), specificity was 97% (114 of 117 segments), accuracy was 87% (213 of 244 segments), positive predictive value was 97% (99 of 102 segments), and negative predictive value was 80% (114 of 142 segments). CONCLUSION: In patients with chronic liver disease and good hepatic function, ultrasonography has a sensitivity of 94% in the identification of affected patients, but for individual lesions, the sensitivity is only 64%

  16. Glycogen metabolism in radiation induced hepatocellular carcinoma in Swiss albino mice

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    Gupta, N.K.; Kumar, Ashok

    1988-01-01

    Glycogen content and the activities of phosphorylase, glycogen sythetase (GS), glucose 6-phosphatase (G6Pase), phosphohexose isomerase (PHI), glucose 6-phosphodehydrogenase were biochemically determined in the heparocellular carcinoma induced in swiss albino mice following radiocalcium internal irradiation. The content glycogen and the activities of phosphorylase, glycogen synthetase, G6Pase, PHI, GPT and GOT are considerably reduced in the hepatocellular carcinoma compared to that in control liver. However, the activity of G6PDH shows an increased activity. Results indicate that the decreas ed glycogen content in the hepatocellular carcinoma is due to the reduced glycogen synthetase activity and utilization of glucose by HMP pathway. (author). 2 tabs., 24 refs

  17. Prospective Evaluation of Transcatheter Arterial Chemoembolization (TACE) with Multiple Anti-Cancer Drugs (Epirubicin, Cisplatin, Mitomycin C, 5-Fluorouracil) Compared with TACE with Epirubicin for Treatment of Hepatocellular Carcinoma

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    Sahara, Shinya; Kawai, Nobuyuki; Sato, Morio, E-mail: morisato@mail.wakayama-med.ac.jp; Tanaka, Takami; Ikoma, Akira; Nakata, Kouhei; Sanda, Hiroki; Minamiguchi, Hiroki; Nakai, Motoki; Shirai, Shintaro; Sonomura, Tetsuo [Wakayama Medical University, Department of Radiology (Japan)

    2012-12-15

    Purpose: To compare the efficacy of transcatheter arterial chemoembolization (TACE) using multiple anticancer drugs (epirubicin, cisplatin, mitomycin C, and 5-furuorouracil: Multi group) with TACE using epirubicin (EP group) for hepatocellular carcinoma (HCC). Materials and Methods: The study design was a single-center, prospective, randomized controlled trial. Patients with unrespectable HCC confined to the liver, unsuitable for radiofrequency ablation, were assigned to the Multi group or the EP group. We assessed radiographic response as the primary endpoint; secondary endpoints were progression-free survival (PFS), safety, and hepatic branch artery abnormality (Grade I, no damage or mild vessel wall irregularity; Grade II, overt stenosis; Grade III, occlusion; Grades II and III indicated significant hepatic artery damage). A total of 51 patients were enrolled: 24 in the Multi group vs. 27 in the EP group. Results: No significant difference in HCC patient background was found between the groups. Radiographic response, PFS, and 1- and 2-year overall survival of the Multi vs. EP group were 54% vs. 48%, 6.1 months vs. 8.7 months, and 95% and 65% vs. 85% and 76%, respectively, with no significant difference. Significantly greater Grade 3 transaminase elevation was found in the Multi group (p = 0.023). Hepatic artery abnormality was observed in 34% of the Multi group and in 17.1% of the EP group (p = 0.019). Conclusion: TACE with multiple anti-cancer drugs was tolerable but appeared not to contribute to an increase in radiographic response or PFS, and caused significantly more hepatic arterial abnormalities compared with TACE with epirubicin alone.

  18. Mechanistic background and clinical applications of indocyanine green fluorescence imaging of hepatocellular carcinoma.

    Science.gov (United States)

    Ishizawa, Takeaki; Masuda, Koichi; Urano, Yasuteru; Kawaguchi, Yoshikuni; Satou, Shouichi; Kaneko, Junichi; Hasegawa, Kiyoshi; Shibahara, Junji; Fukayama, Masashi; Tsuji, Shingo; Midorikawa, Yutaka; Aburatani, Hiroyuki; Kokudo, Norihiro

    2014-02-01

    Although clinical applications of intraoperative fluorescence imaging of liver cancer using indocyanine green (ICG) have begun, the mechanistic background of ICG accumulation in the cancerous tissues remains unclear. In 170 patients with hepatocellular carcinoma cells (HCC), the liver surfaces and resected specimens were intraoperatively examined by using a near-infrared fluorescence imaging system after preoperative administration of ICG (0.5 mg/kg i.v.). Microscopic examinations, gene expression profile analysis, and immunohistochemical staining were performed for HCCs, which showed ICG fluorescence in the cancerous tissues (cancerous-type fluorescence), and HCCs showed fluorescence only in the surrounding non-cancerous liver parenchyma (rim-type fluorescence). ICG fluorescence imaging enabled identification of 273 of 276 (99%) HCCs in the resected specimens. HCCs showed that cancerous-type fluorescence was associated with higher cancer cell differentiation as compared with rim-type HCCs (P Fluorescence microscopy identified the presence of ICG in the canalicular side of the cancer cell cytoplasm, and pseudoglands of the HCCs showed a cancerous-type fluorescence pattern. The ratio of the gene and protein expression levels in the cancerous to non-cancerous tissues for Na(+)/taurocholate cotransporting polypeptide (NTCP) and organic anion-transporting polypeptide 8 (OATP8), which are associated with portal uptake of ICG by hepatocytes that tended to be higher in the HCCs that showed cancerous-type fluorescence than in those that showed rim-type fluorescence. Preserved portal uptake of ICG in differentiated HCC cells by NTCP and OATP8 with concomitant biliary excretion disorders causes accumulation of ICG in the cancerous tissues after preoperative intravenous administration. This enables highly sensitive identification of HCC by intraoperative ICG fluorescence imaging.

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

    Science.gov (United States)

    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

    2015-01-01

    AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: 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 × W2) × 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. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm3; 30 mg/kg per day, 612 ± 46 mm3; 50 mg/kg per day, 563 ± 38 mm3; and 70 mg/kg per day, 221 ± 26 mm3. 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

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

    Science.gov (United States)

    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

  1. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Granito A

    2015-04-01

    Full Text Available Alessandro Granito,1 Elena Guidetti,1 Laura Gramantieri2,3 1Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna, Bologna, Italy; 2Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Centro di Ricerca Biomedica Applicata (CRBA, Azienda Ospedaliero-Universitaria Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, Italy Abstract: c-MET is the membrane receptor for hepatocyte growth factor (HGF, also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC. In particular, c-MET amplification is a rare event, accounting for 4%–5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC. Keywords: hepatocellular carcinoma, c-MET, clinical trials

  2. Cyclooxygenase-2 inhibitor is a robust enhancer of anticancer agents against hepatocellular carcinoma multicellular spheroids

    Directory of Open Access Journals (Sweden)

    Cui J

    2014-02-01

    Full Text Available Jie Cui,1,2 Ya-Huan Guo,3 Hong-Yi Zhang,4 Li-Li Jiang,1 Jie-Qun Ma,1 Wen-Juan Wang,1 Min-Cong Wang,1 Cheng-Cheng Yang,1 Ke-Jun Nan,1 Li-Ping Song5 1Department of Oncology, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, 2Department of Oncology, Yan'an University Affiliated Hospital, Yan'an, 3Department of Oncology, Shaanxi Province Cancer Hospital, Xi'an, 4Department of Urology, Yan'an University Affiliated Hospital, Yan'an, 5Department of Radiotherapy, First Affiliated Hospital, College of Medicine of Xi'an Jiaotong University, Xi'an, People's Republic of China Purpose: Celecoxib, an inhibitor of cyclooxygenase-2 (COX2, was investigated for enhancement of chemotherapeutic efficacy in cancer clinical trials. This study aimed to determine whether celecoxib combined with 5-fluorouracil or sorafenib or gefitinib is beneficial in HepG2 multicellular spheroids (MCSs, as well as elucidate the underlying mechanisms. Methods: The human hepatocellular carcinoma cell line HepG2 MCSs were used as in vitro models to investigate the effects of celecoxib combined with 5-fluorouracil or sorafenib or gefitinib treatment on cell growth, apoptosis, and signaling pathway. Results: MCSs showed resistance to drugs compared with monolayer cells. Celecoxib combined with 5-fluorouracil or sorafenib exhibited a synergistic action. Exposure to celecoxib (21.8 µmol/L plus 5-fluorouracil (8.1 × 10-3 g/L or sorafenib (4.4 µmol/L increased apoptosis but exerted no effect on COX2, phosphorylated epidermal growth-factor receptor (p-EGFR and phosphorylated (p-AKT expression. Gefitinib (5 µmol/L, which exhibits no growth-inhibition activity as a single agent, increased the inhibitory effect of celecoxib. Gefitinib (5 µmol/L plus celecoxib (21.8 µmol/L increased apoptosis. COX2, p-EGFR, and p-AKT were inhibited. Conclusion: Celecoxib combined with 5-fluorouracil or sorafenib or gefitinib may be superior to single-agent therapy in HepG2

  3. The antitumor effect of arsenic trioxide on hepatocellular carcinoma is enhanced by andrographolide.

    Science.gov (United States)

    Duan, Xuhua; Li, Tengfei; Han, Xinwei; Ren, Jianzhuang; Chen, Pengfei; Li, Hao; Gong, Shaojun

    2017-10-31

    High concentrations of arsenic trioxide (As 2 O 3 ) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As 2 O 3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo . Furthermore, results from our microarray assays and experiments with mouse xenografts showed that EphB4 was downregulated by the combination of As 2 O 3 plus andrographolide. These findings suggest that the combination of andrographolide and As 2 O 3 could yield therapeutic benefits in the treatment of HCC.

  4. Pekinenin E Inhibits the Growth of Hepatocellular Carcinoma by Promoting Endoplasmic Reticulum Stress Mediated Cell Death

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    Lu Fan

    2017-06-01

    Full Text Available Hepatocellular carcinoma (HCC is a malignant primary liver cancer with poor prognosis. In the present study, we report that pekinenin E (PE, a casbane diterpenoid derived from the roots of Euphorbia pekinensis, has a strong antitumor activity against human HCC cells both in vitro and in vivo. PE suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE-mediated endoplasmic reticulum (ER stress caused increasing expressions of C/EBP homologous protein (CHOP, leading to apoptosis in HCC cells both in vitro and in vivo. Inhibition of ER stress with CHOP small interfering RNA or 4-phenyl-butyric acid partially reversed PE-induced cell death. Furthermore, PE induced S cell cycle arrest, which could also be partially reversed by CHOP knockdown. In all, these findings suggest that PE causes ER stress-associated cell death and cell cycle arrest, and it may serve as a potent agent for curing human HCC.

  5. By inhibiting PFKFB3, aspirin overcomes sorafenib resistance in hepatocellular carcinoma.

    Science.gov (United States)

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

    2017-12-15

    Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC. © 2017 UICC.

  6. Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Cuiyun

    2016-02-01

    Full Text Available Non-coding RNAs (ncRNA are RNA molecules without protein coding functions owing to the lack of an open reading frame (ORF. Based on the length, ncRNAs can be divided into long and short ncRNAs; short ncRNAs include miRNAs and piRNAs. Hepatocellular carcinoma (HCC is among the most frequent forms of cancer worldwide and its incidence is increasing rapidly. Studies have found that ncRNAs are likely to play a crucial role in a variety of biological processes including the pathogenesis and progression of HCC. In this review, we summarized the regulation mechanism and biological functions of ncRNAs in HCC with respect to its application in HCC diagnosis, therapy and prognosis.

  7. Endogenous network states predict gain or loss of functions for genetic mutations in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Gaowei; Su, Hang; Yu, Helin; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

    2016-02-01

    Cancers have been typically characterized by genetic mutations. Patterns of such mutations have traditionally been analysed by posteriori statistical association approaches. One may ponder the possibility of a priori determination of any mutation regularity. Here by exploring biological processes implied in a mechanistic theory recently developed (the endogenous molecular-cellular network theory), we found that the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. With hepatocellular carcinoma (HCC) as an example, we found that the normal hepatocyte and cancerous hepatocyte can be represented by robust stable states of one single endogenous network. These stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable predictions on accumulated and preferred mutation spectra in normal tissue. The validation of predicted cancer state mutation patterns demonstrates the usefulness and potential of a causal dynamical framework to understand and predict genetic mutations in cancer. © 2016 The Author(s).

  8. Substrate stiffness promotes latent TGF-β1 activation in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Pang, Mingshu; Teng, Yao; Huang, Jianyong; Yuan, Yuan; Lin, Feng; Xiong, Chunyang

    2017-01-01

    Hepatocellular carcinoma (HCC) was usually coupled with increased stiffness of the extracellular matrix (ECM) and elevated level of transforming growth factor-β1 (TGF-β1). However, the mechanism by which substrate rigidity modulated TGF-β1 signaling transduction remained unknown. This paper investigated the molecular mechanism of how matrix stiffness regulating TGF-β1 signaling in HCC cells. By means of stiffness tunable collagen I-coated polyacrylamide (PA) gels, we found that the expressions of β1 integrin, p-FAK Y397 and p-Smad2 upregulated on stiffer gels as well as the content of TGF-β1 in culture media of HCC cells, which were inhibited by RGD blocking peptides, Y-27632 (ROCK inhibitor) or Blebbistatin (myosin II inhibitor). Cellular traction force was also significantly higher when plated on stiffer substrates but dramatically decreased after treatment with Y-27632 or Blebbistatin. Furthermore, the upregulation of p-Smad2 in the HCC cells on stiffer PA gels induced by exogenetic latent TGF-β1 was downregulated in the presence of RGD peptides. The nuclear translocation of Smad2 induced by latent TGF-β1 was inhibited by Y-27632 or Blebbistatin. Our results suggested that the extracellular matrix stiffness regulated latent TGF-β1 activation by cytoskeletal tension in HCC cells, showing that matrix stiffness was a key regulator involving the TGF-β1 activity in HCC cells. The current study presented a mechanism of how hepatocirrhosis developed into liver cancer. - Highlights: • TGF-β1 signaling pathway regulated by ECM stiffness was studied in hepatocellular carcinoma. • Matrix stiffness promoted latent TGF-β1 activation via β1 integrin-FAK-Rho GTPase pathway. • A mechanism of how hepatocirrhosis developed into liver cancer was presented.

  9. Role of microRNAs in hepatocellular carcinoma: a clinical perspective

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    Callegari E

    2013-09-01

    Full Text Available Elisa Callegari,1 Bahaeldin K Elamin,1,2 Silvia Sabbioni,3,5 Laura Gramantieri,4 Massimo Negrini1,5 1Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy; 2Department of Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Sudan; 3Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Ferrara, 4Centro di Ricerca Biomedica Applicata e Dipartimento di Medicina Interna, Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, 5Tecnopolo "Laboratorio per le Tecnologie delle Terapie Avanzate", Università di Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma (HCC is one of the most deadly tumors, and current treatments for the disease are often ineffective. The discovery of the involvement of microRNAs (miRNAs in hepatocarcinogenesis represents an important area of investigation for the development of their clinical applications. These molecules may act as oncogenes or tumor suppressors by directly or indirectly controlling the expression of key proteins involved in cancer-associated pathways. On the clinical side, because of their tumor-specific expression and stability in tissues and in the circulation, miRNAs have been proposed as novel diagnostic tools for classification and prognostic stratification of HCC. In recent years, the therapeutic potential of miRNAs has been demonstrated in various preclinical studies. Anti-miRNA oligonucleotides and miRNA mimics have been found to have antitumor activity. Moreover, by exploiting tumor-specific expression of miRNA, efforts have been aimed at improving targeting of tumor cells by replicative oncolytic viruses while sparing normal cells. These areas are expected to be explored further in the upcoming years to assess the clinical value of miRNA-based approaches in HCC and cancer in general. Keywords: hepatocellular carcinoma, microRNA, micromarkers, oncolytic viruses

  10. Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

    International Nuclear Information System (INIS)

    Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

    2008-01-01

    To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

  11. 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.

  12. 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.

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

    Science.gov (United States)

    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

  14. Value of radiofrequency ablation in the treatment of hepatocellular carcinoma

    Science.gov (United States)

    Feng, Kai; Ma, Kuan-Sheng

    2014-01-01

    Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretransplantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue. PMID:24876721

  15. 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.

  16. Factors associated with tumor size of hepatocellular carcinoma

    Science.gov (United States)

    Siregar, G. A.; Buulolo, B. A.

    2018-03-01

    Determining the association of age and laboratory parameters with tumor size of hepatocellular carcinoma (HCC). The study was at Adam Malik Hospital Medan from June- December 2016. 100 HCC patients were enrolled; those with excluding liver metastatic. Baseline characteristics of gender, age, obtaining etiology of HCC. Liver function tests, viral marker, and INR were done. Based on tumor size from abdomen CT, patients were three groups: tumor size below 3 cm, 3-5 cm, and above 5 cm size. Patients were also divided based on Child-Pugh class. Correlation of age and laboratory results with tumor size of HCC patients were analyzed. Age have negative correlation with tumor size in HCC patients (r=-0.297, p=0.032) while AFP have positive correlation with tumor size (r0.446, p=<0.001). Total bilirubin, AST, and ALT have negative correlation but non-significant (r=-0.045, -0.078, - 0.126 respectively). Albumin and INR have positive correlation but non-significant (r=0.021, 0.112 respectively). Our study suggests that older age correlates with smaller tumor size, while AFP level has a significant correlation with tumor size in HCC patients. AFP level may be a useful marker for determining the prognosis of HCC patients.

  17. Computed tomography of hepatocellular carcinoma: Usefulness of dynamic CT

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    Takemoto, Kazumasa; Inoue, Yuichi; Matsuoka, Toshiyuki; Nakatsuka, Haruki; Oda, Junro [Osaka City Univ. (Japan). Faculty of Medicine

    1983-04-01

    Dynamic computed tomography (CT) scans in 65 hepatocellular carcinomas were analyzed and compared to plain and drip infusion contrast CT scans of those. Scans were obtained before, 10, 30, and 50 seconds after an intravenous bolus injection of 50ml 65% Angiografin. By this method, 49 hepatomas had moderate to marked enhancement at the arterial phase while the enhancement of normal liver parenchyma was only slight at the arterial phase and peaked at the portal phase. Compared to a drip infusion contrast CT, a dynamic CT had advantages to detect an isodense hepatoma in 4 and daughter tumors in 16 both of which were not appreciated by a plain and a drip infusion contrast CT. The tumor extension was also better delineated by a dynamic CT because a part of hepatoma had an isodense area. An arterio-portal shunt was visualized in one. Tumor thrombus in the portal vein was clearly demonstrated in 6 at the portal phase of a dynamic CT. Since a dynamic CT is convenient to perform without any special program or soft wear and gives us very useful information, we believe that it should be routinely employed as a part of a liver CT examination.

  18. Radiofrequency ablation of hepatocellular carcinoma: pros and cons.

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    Rhim, Hyunchul; Lim, Hyo K

    2010-09-01

    Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents.

  19. 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.

  20. Transcatheter arterial embolization for bone metastases from hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Uemura, Akihiro; Fujimoto, Hajime; Osaka, Iwao; Yasuda, Shigeo; Goto, Nobuaki; Shinozaki, Masami; Ito, Hisao

    2001-01-01

    The objective of this study was to determine which of the following three methods is the most effective for the treatment of bone metastases from hepatocellular carcinoma (HCC): transcatheter arterial embolization (TAE); combination of TAE and external radiotherapy; or external radiotherapy alone. Thirty-nine metastatic bone lesions from HCC in 33 patients were retrospectively reviewed. Each lesion underwent either TAE alone (group A, n=11), TAE followed by radiotherapy (group B, n=17), or radiotherapy alone (group C, n=11). They were evaluated on the following subjects: pain relief; improvement of daily activities; and complications. Each treatment was effective for pain relief (89-94%) and improvement of daily activities (73-82%). The mean time interval from the beginning of each treatment to the onset of initial pain relief was 4.7 days in group A, 4.8 days in group B, and 15 days in group C. Recurrence of the pain after the initial pain relief was noted in 75% in group A, 20% in group B, and 88% in group C. Pyrexia and local pain commonly occurred after TAE. In conclusion, TAE is effective in relieving pain immediately and in improving the patients' daily activities. The combination of TAE and radiotherapy is recommended for permanent pain relief. (orig.)

  1. Regorafenib for the treatment of unresectable hepatocellular carcinoma.

    Science.gov (United States)

    Rimassa, Lorenza; Pressiani, Tiziana; Personeni, Nicola; Santoro, Armando

    2017-07-01

    Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC) and well preserved liver function. However, until recent approval of regorafenib by the Food and Drug Administration (FDA), no effective therapeutic options were available for patients resistant to sorafenib. Areas covered: The present article reviews the preclinical and clinical data of regorafenib, putting them into the context of current and future landscape of treatment options for patients with HCC. Recently, the randomized, placebo-controlled, Phase III RESORCE trial, demonstrated a statistically and clinically significant increase in overall survival from 7.8 months with placebo to 10.6 months with regorafenib in patients progressing on sorafenib. Furthermore, the study showed a significant improvement in all the other efficacy endpoints. Main adverse events were hypertension, hand-foot skin reaction, fatigue and diarrhea, with no negative impact on quality of life. Expert commentary: Regorafenib is a recently approved treatment option for HCC patients who have been previously treated with sorafenib. The RESORCE trial demonstrates the beneficial effect of a sequential approach involving two multikinase inhibitors, namely sorafenib and regorafenib, whose antitumor activity extends beyond their antiangiogenic functions.

  2. Reversibility of regorafenib effects in hepatocellular carcinoma cells

    Science.gov (United States)

    D’Alessandro, Rosalba; Refolo, Maria G.; Lippolis, Catia; Messa, Caterina; Cavallini, Aldo; Rossi, Roberta; Resta, Leonardo; Di Carlo, Antonio

    2013-01-01

    Purpose Multikinase growth inhibitors inhibit their target kinases with varying potency. Patients often require lower doses or therapy breaks due to drug toxicities. To evaluate the effects of drug withdrawal on hepatocellular carcinoma cells after incubation with growth-inhibitory concentrations of regorafenib, cell growth, migration and invasion, and signaling were examined. Methods Cell proliferation, motility, and invasion were analyzed by MTT, wound healing, and invasion assays, respectively, and MAPK pathway protein markers were analyzed by Western blot. Results After regorafenib removal, cell growth, migration, and invasion recovered. Repeated drug exposure resulted in changes in cell growth patterns. Recovery could be blocked by sub-growth-inhibitory concentrations of either doxorubicin or vitamin K1. Recovery of growth was associated with increased phospho-JNK, phospho-p38, and phospho-STAT3 levels. The recovery of growth, migration, and signaling were blocked by a JNK inhibitor. Conclusions Removal of regorafenib from growth-inhibited cells resulted in a JNK-dependent recovery of growth and migration. PMID:23959464

  3. 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.

  4. Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

    Science.gov (United States)

    Nam, Hee Chul; Jang, Bohyun; Song, Myeong Jun

    2016-01-01

    Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads®) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads® can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads® substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities. PMID:27833376

  5. Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

    2018-03-01

    This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62-92 GyE 10 . Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

  6. Transcatheter arterial chemoembolization of hepatocellular carcinoma with portal vein invasion

    International Nuclear Information System (INIS)

    Lee, Young Rahn; Lee, Ki Yeol; Cho, Seong Beom; Cha, In Ho; Chung, Kyoo Byung

    1993-01-01

    Transcatheter arterial chemoembolization(TACE) is an imperative method for the management of inoperable hepatocellular carcinoma(HCC). It is well known that primary HCC frequently invades the portal venous system and forms a tumor thrombus obstructing the portal blood flow which makes unfavorable prognosis of patient. We retrospectively reviewed 58 patients who reviewed TACE(minimum 3 times) of HCC invading into portal venous system. Group 1(n=29) which showed peripheral portal vein invasion had better clinical and laboratory response. Group 2(n=17) which showed first order portal branch invasion had similar response to Group 3(n=12), which had main portal invasion. Group 1 showed no difference in survival time between TAC and TACE, but, in Group 2 and 3, embolization with chemotherapy made longer survival than chemotherapy only. Clinical level of AFP was meaningful in Group 1 and 2 as decreasing value. Our results provides that careful selection of TAE and case by case Coil/Gelfoam embolization can improve the mean survival and clinical response when HCC evidently invades portal venous system

  7. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  8. Surgical outcomes of hepatocellular carcinoma invading hepatocaval confluence.

    Science.gov (United States)

    Li, Wei; Wu, Hong; Han, Jun

    2016-12-01

    Combined liver and inferior vena cava (IVC) resection followed by IVC and/or hepatic vein reconstruction (HVR) is a curative operation for selected patients with hepatocellular carcinoma (HCC) invading the hepatocaval confluence. The present study aimed to elucidate the prognostic factors for patients with HCC invading the hepatocaval confluence. Forty-two consecutive patients underwent hepatectomy, combined with IVC replacement and/or HVR for HCC between January 2009 and December 2014 were included in this study. The cases were divided into three groups based on the surgical approaches of HVR: group 1 (n=13), tumor invaded the hepatocaval confluence but with one or two hepatic veins intact in the residual liver, thus only the replacement of IVC, not HVR; group 2 (n=23), the hepatic vein of the residual liver was also partially invaded, and the hepatic vein defect was repaired with patches locally; group 3 (n=6), three hepatic veins at the hepatocaval confluence were infiltrated, and the hepatic vein remnant was re-implanted onto the side of the tube graft. The patient characteristics, intra- and postoperative results, and long-term overall survival were compared among the three groups. The survival-related factors were analyzed by univariate and multivariate analysis. The group 1 had higher preoperative alpha-fetoprotein level (PHVR (PHVR (group 1). HVR was one of the unfavorable prognostic factors of overall survival.

  9. Liver transplantation for hepatocellular carcinoma: the Hong Kong experience.

    Science.gov (United States)

    Ng, Kelvin K; Lo, Chung Mau; Chan, See Ching; Chok, Kenneth S; Cheung, Tan-To; Fan, Sheung Tat

    2010-09-01

    Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors' experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. "Fast-track" LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.

  10. Adrenalectomy for metastases from hepatocellular carcinoma - a single center experience.

    Science.gov (United States)

    Popescu, Irinel; Alexandrescu, Sorin; Ciurea, Silviu; Brasoveanu, Vlad; Hrehoret, Doina; Gangone, Eliza; Boros, Mirela; Herlea, Vlad; Croitoru, Adina

    2007-05-01

    Adrenal metastases (AM) from hepatocellular carcinoma (HCC) are rarely seen in clinical practice. The treatment is not standardized, the indications and efficacy of different therapeutic approaches being still controversial. Between January 1995 and December 2005, 174 patients underwent liver resection for HCC in our center. AM were detected in four patients (2.3%): three of them had HCC and synchronous AM, and the remaining one developed AM 10 months after liver resection. All the patients with AM were treated by adrenalectomy (simultaneously with liver resection in synchronous metastases), followed by systemic chemotherapy. Non-resectable multifocal liver recurrences occurred in two patients, one of them having also a contralateral adrenal metastasis; these two patients are presently alive 26 and 43 months after adrenalectomy, respectively. Another patient died by liver recurrence 27 months postoperatively. The fourth patient is disease-free at 17 months after the initial operation. Adrenalectomy for AM from HCC should be performed whenever the primary tumor is well therapeutically controlled and the patient has a good performance status. Adrenalectomy offers the chance of more than 2 years survival in many patients. However, once AM are detected, the prognosis remains poor.

  11. Changes in arginase isoenzymes pattern in human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Chrzanowska, Alicja; Krawczyk, Marek; Baranczyk-Kuzma, Anna

    2008-01-01

    Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, and those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.

  12. 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%.

  13. Treatment of hepatocellular carcinoma: A single-center experience

    International Nuclear Information System (INIS)

    Florio, Francesco; Nardella, Michele; Balzano, Silverio; Caturelli, Eugenio; Siena, Domenico; Cammisa, Mario

    1997-01-01

    Purpose. The comparative efficacy of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) was investigated. Methods. Two hundred and sixty consecutive patients were retrospectively analyzed: 156 had received between one and six chemoembolization sessions at 3-month intervals, 33 had had PEI, and the remaining 71 patients refused any treatment. The follow-up ranged from 3 to 36 months. Survival rates were statistically analyzed by life-table analysis. Results. Patients' survival was affected by the number of nodules and by the Child's and Okuda's classes; no relationship was found between survival rates and the histologic grade or vascular supply of the tumor. In the case of a single lesion of Okuda's class I, TACE was more effective than PEI. In multifocal HCC, TACE was better than no treatment in Okuda's class I and Child's class A. Conclusion. We suggest TACE as the treatment of choice in Child A or Okuda I patients with multifocal HCCs; it seems of little help in Child B-C or Okuda II-III patients

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

    International Nuclear Information System (INIS)

    Kawashima, Mitsuhiko; Tokuuye, Koichi; Sumi, Minako; Kagami, Yashikazu; Murayama, Shigeyuki; Nakayama, Hidetsugu; Imai, Atsushi; Ando, Kou; Ikeda, Hiroshi

    1997-01-01

    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)

  15. 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.

  16. Diagnostic value of α-fetoprotein in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hernández Perera, Julio César

    2009-01-01

    In the world the hepatocellular carcinoma (HCC) is the fifth to sixth most common malignancy. An increase in its incidence is looming in Cuba as a result of the population aging and the increase of morbi-mortality due to liver cirrhosis (CH). α-fetoprotein (AFP) by SUMA®, was used in this work as a tumor marker technique in 189 Cirrhotic patients evaluated at the CIMEQ, between January 1999 and September 2005. The main factors associated with an elevation of AFP were HCC, viral cirrhosis, and the age of 50 years or more. Presented CHC 22 (11.64%) patients, who had an average age of 55 years