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Sample records for human liver carcinoma

  1. 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.

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

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    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. Effects of sodium phenylbutyrate on differentiation and induction of the P21WAF1/CIP1 anti-oncogene in human liver carcinoma cell lines.

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    Meng, Mei; Jiang, Jun Mei; Liu, Hui; In, Cheng Yong; Zhu, Ju Ren

    2005-01-01

    To explore the effects of sodium phenylbutyrate on the proliferation, differentiation, cell cycle arrest and induction of the P(21WAF1/CIP1) anti-oncogene in human liver carcinoma cell lines Bel-7402 and HepG2. Bel-7402 and HepG2 human liver carcinoma cells were treated with sodium phenylbutyrate at different concentrations. Light microscopy was used to observe morphological changes in the carcinoma cells. Effects on the cell cycle were detected by using flow cytometry. P(21WAF1/CIP1) expression was determined by both reverse transcription-polymerase chain reaction and western blotting. Statistical analysis was performed by using one-way anova and Student's t-test. Sodium phenylbutyrate treatment caused time- and dose-dependent growth inhibition of Bel-7402 and HepG2 cells. This treatment also caused a decline in the proportion of S-phase cells and an increase in the proportion of G(0)/G(1) cells. Sodium phenylbutyrate increased the expression of P(21WAF1/CIP1). Sodium phenylbutyrate inhibits the proliferation of human liver carcinoma cells Bel-7402 and HepG2, induces partial differentiation, and increases the expression of P(21WAF1/CIP1).

  4. The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver.

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    Meijer, Joost; Zeelenberg, Ingrid S; Sipos, Bence; Roos, Ed

    2006-10-01

    The chemokine receptor CXCR5 is expressed by B cells and certain T cells and controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is present in lymph nodes and spleen and also in the liver. Surprisingly, we detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was particularly prominent in pancreatic carcinoma cell lines and was also detected by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost when cells were explanted in vitro. CXCL13 strongly promoted proliferation of CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic injection, these CXCR5 transfectants initially grew faster than controls, but the growth rate of control tumors accelerated later to become similar to the transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5 function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL "intrakine," had no effect on initial growth of liver foci but later caused a prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and intrakine-transfected cells grew at similar rates as controls. We conclude that expression of CXCR5 on tumor cells promotes the growth of tumor cells in the liver and, at least for CT26 cells, seems to be required for outgrowth to large liver tumors. Given the limited expression on normal cells, CXCR5 may constitute an attractive target for therapy, particularly for pancreatic carcinoma.

  5. Liver cirrhosis and primary carcinoma of the liver among atomic bomb survivors. Study of autopsy cases

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    Hamada, T [Hiroshima Atomic Bomb Hospital (Japan)

    1980-11-01

    Liver cirrhosis and primary carcinoma of the liver were investigated in 1699 autopsies of atomic bomb survivors carried out in Hiroshima from 1956 to 1980. Liver cirrhosis, hepatocellular carcinoma and intrahepatic biliary carcinoma were observed in 116, 111, and 17 cases respectively, the ratios of man to woman and were 2.3, 3.9, and 1.8 with a mean age of 56, 60, and 67 years respectively. There was no evidence that exposure to a-bomb increased the risk of these diseases significantly. About 90% of the hepatocellular carcinomas was combined with liver cirrhosis. Weight of liver and spleen, amount of ascites, hemorrhage from the digestive canals, esophageal varix, combination with other diseases, and histologic correlation with the activities of HBs antigen and ..cap alpha..-fetoprotein were discussed with the relation to the exposure.

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

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    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.

  7. 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.

  8. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

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    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  9. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

    International Nuclear Information System (INIS)

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-01-01

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma. The online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users

  10. Liver transplantation for unresectable hepatocellular carcinoma in patients without liver cirrhosis

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    Mergental, Hynek; Porte, Robert J.

    P>Hepatocellular carcinoma (HCC) arising in noncirrhotic and nonfibrotic liver (NC-HCC) is a rare type of malignancy frequently found in healthy young individuals. Partial liver resection is the treatment of choice with expected 5-year survival rates between 40% and 70%. As a result of absence of

  11. Liver transplantation in patients with hepatocellular carcinoma

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    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

  12. Percutaneous laser ablation of hepatocellular carcinoma in patients with liver cirrhosis awaiting liver transplantation

    International Nuclear Information System (INIS)

    Pompili, Maurizio; Pacella, Claudio Maurizio; Francica, Giampiero; Angelico, Mario; Tisone, Giuseppe; Craboledda, Paolo; Nicolardi, Erica; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

    2010-01-01

    Objective: The aim of this study was to determine the effectiveness and safety of percutaneous laser ablation for the treatment of cirrhotic patients with hepatocellular carcinoma awaiting liver transplantation. Materials and methods: The data of 9 male cirrhotic patients (mean age 50 years, range 45-60 years) with 12 biopsy proven nodules of hepatocellular carcinoma (mean diameter 2.0 cm, range 1.0-3.0 cm) treated by laser ablation before liver transplantation between June 2000 and January 2006 were retrospectively reviewed. Laser ablation was carried out by inserting 300 nm optical fibers through 21-Gauge needles (from two to four) positioned under ultrasound guidance into the target lesions. A continuous wave Neodymium:Yttrium Aluminium Garnet laser was used. Transarterial chemoembolization prior to liver transplantation was performed in two incompletely ablated tumors. Results: No procedure-related major complications were recorded. During the waiting time to liver transplantation local tumor progression after ablation occurred in 3 nodules (25%). At histological examination of the explanted livers complete necrosis was found in 8 nodules (66.7%, all treated exclusively with laser ablation), partial necrosis >50% in 3 nodules (25%), and partial necrosis <50% in 1 nodule. Conclusion: In patients with cirrhotic livers awaiting liver transplantation, percutaneous laser ablation is safe and effective for the management of small hepatocellular carcinoma.

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

    Czech Academy of Sciences Publication Activity Database

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

    2014-01-01

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

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

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    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.

  15. 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 ...

  16. 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%

  17. Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

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    Kim, Young; Stahl, Christopher C; Makramalla, Abouelmagd; Olowokure, Olugbenga O; Ristagno, Ross L; Dhar, Vikrom K; Schoech, Michael R; Chadalavada, Seetharam; Latif, Tahir; Kharofa, Jordan; Bari, Khurram; Shah, Shimul A

    2017-12-01

    Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for

  18. Management of Liver Metastasis from Colo-Rectal Carcinoma with ...

    African Journals Online (AJOL)

    Background: Worldwide, colo-rectal carcinoma is the second most common cancer with liver metastases as its major cause of mortality.This malignant condition is now seen more frequently in our environment typically at a late stage with distant metastasis especially to the liver. This study aims at highlighting the current use ...

  19. DNA methylation-dependent regulation of TrkA, TrkB, and TrkC genes in human hepatocellular carcinoma

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    Jin, Wook [Laboratory of Molecular Disease and Cell Regulation, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon (Korea, Republic of); Lee, Jong-Joo [Department of Environmental Medical Biology, Institute of Tropical Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kim, Min Soo [Laboratory of Molecular Disease and Cell Regulation, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon (Korea, Republic of); Son, Byung Ho [Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 108 Pyung-dong, Jongro-gu, Seoul 110-746 (Korea, Republic of); Cho, Yong Kyun, E-mail: choyk2004@hanmail.net [Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, 108 Pyung-dong, Jongro-gu, Seoul 110-746 (Korea, Republic of); Kim, Hyoung-Pyo, E-mail: kimhp@yuhs.ac [Department of Environmental Medical Biology, Institute of Tropical Medicine, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

    2011-03-04

    Research highlights: {yields} Expression of TrkA, TrkB, and TrkC is significantly elevated in human hepatocellular carcinoma. {yields} Downregulation of Trks is correlated with their promoter hypermethylation. {yields} Inhibiting DNA methylation restored expression of Trks in normal liver cell lines. {yields} Trks promote the proliferation of hepatocellular carcinoma. {yields} Trks induce expression of the metastatic regulator, Twist. -- Abstract: The tropomyosin-related kinase (Trk) family of neurotrophin receptors, TrkA, TrkB and TrkC, has been implicated in the growth and survival of human cancers. Here we report that Trks are frequently overexpressed in hepatocellular carcinoma (HCC) from patients and human liver cancer cell lines. To unravel the underlying molecular mechanism(s) for this phenomenon, DNA methylation patterns of CpG islands in TrkA, TrkB, and TrkC genes were examined in normal and cancer cell lines derived from liver. A good correlation was observed between promoter hypermethylation and lower expression of TrkA, TrkB, and TrkC genes, which was supported by the data that inhibiting DNA methylation with 5-azacytidine restored expression of those genes in normal liver cell lines. Furthermore, Trks promoted the proliferation of HepG2 and induced expression of the metastatic regulator, Twist. These results suggest that Trks may contribute to growth and metastasis of liver cancer.

  20. DNA methylation-dependent regulation of TrkA, TrkB, and TrkC genes in human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Jin, Wook; Lee, Jong-Joo; Kim, Min Soo; Son, Byung Ho; Cho, Yong Kyun; Kim, Hyoung-Pyo

    2011-01-01

    Research highlights: → Expression of TrkA, TrkB, and TrkC is significantly elevated in human hepatocellular carcinoma. → Downregulation of Trks is correlated with their promoter hypermethylation. → Inhibiting DNA methylation restored expression of Trks in normal liver cell lines. → Trks promote the proliferation of hepatocellular carcinoma. → Trks induce expression of the metastatic regulator, Twist. -- Abstract: The tropomyosin-related kinase (Trk) family of neurotrophin receptors, TrkA, TrkB and TrkC, has been implicated in the growth and survival of human cancers. Here we report that Trks are frequently overexpressed in hepatocellular carcinoma (HCC) from patients and human liver cancer cell lines. To unravel the underlying molecular mechanism(s) for this phenomenon, DNA methylation patterns of CpG islands in TrkA, TrkB, and TrkC genes were examined in normal and cancer cell lines derived from liver. A good correlation was observed between promoter hypermethylation and lower expression of TrkA, TrkB, and TrkC genes, which was supported by the data that inhibiting DNA methylation with 5-azacytidine restored expression of those genes in normal liver cell lines. Furthermore, Trks promoted the proliferation of HepG2 and induced expression of the metastatic regulator, Twist. These results suggest that Trks may contribute to growth and metastasis of liver cancer.

  1. Risk factors for postoperative liver failure after hepatectomy for hepatocellular carcinoma.

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    Maeda, Yoshitaka; Nishida, Minekatsu; Takao, Takashi; Mori, Naohide; Tamesa, Takao; Tangoku, Akira; Oka, Masaaki

    2004-01-01

    Selection of patients for hepatectomy for hepatocellular carcinoma conventionally has been based upon Child-Pugh grading. However, postoperative liver failure after hepatectomy is a major cause of hospital mortality. A new predictor of postoperative liver failure is required. The objective of this study was to identify risk factors for postoperative liver failure after hepatectomy. Perioperative risk factors for liver failure after hepatectomy were analyzed in 112 patients with hepatocellular carcinoma Eight of these patients died of liver failure. Stepwise multivariate logistic regression was performed to investigate significant independent factors among 17 variables, including the serum alkaline phosphatase ratio (ALPR) on the first day after hepatectomy. ALPR was calculated as the postoperative ALP level divided by the ALP level before surgery. Significant risk factors of postoperative liver failure were ALPR on postoperative day 1 (ALPR1), sex, operative blood loss, and operative procedure. As an indicator of liver failure, the diagnostic accuracy of the ALPR1 was 93.7% when the ALPR was less than 0.4 on the first postoperative day. The ALPR and the serum total bilirubin concentration after hepatectomy were uncorrelated. ALPR1 is a useful predictor of liver failure after hepatectomy.

  2. Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas

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    Anna Kakehashi

    2017-02-01

    Full Text Available To uncover mechanisms of nonalcoholic steatohepatitis (NASH associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1, and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.

  3. Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

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    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...

  4. Trends in Incidences and Risk Factors for Hepatocellular Carcinoma and Other Liver Events in HIV and Hepatitis C Virus-coinfected Individuals From 2001 to 2014

    DEFF Research Database (Denmark)

    Gjærde, Lars Iversen; Shepherd, Leah; Jablonowska, Elzbieta

    2016-01-01

    BACKGROUND: While liver-related deaths in human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We describe the epidemiology of HCC and other liver events in a multicohort...

  5. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

    1988-01-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  6. ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling

    DEFF Research Database (Denmark)

    Le Pabic, Hélène; Bonnier, Dominique; Wewer, Ulla M

    2003-01-01

    "A disintegrin and metalloproteinases" (ADAMs) form a family of cell-surface glycoproteins with potential protease and cell-adhesion activities. We have investigated ADAM expression in human liver cancers and their regulation by several cytokines involved in liver injury. Using degenerative RT...... carcinomas (up to 3- and 6-fold, respectively) and liver metastases from colonic carcinomas (up to 40- and 60-fold, respectively). The up-regulation of both ADAM9 and ADAM12 was correlated with an increase in matrix metalloproteinase 2 expression and activity. In conclusion, in liver cancers ADAM9 and ADAM12......-PCR, cDNA encoding sequences for ADAM9 and ADAM12 were identified in human activated hepatic stellate cells (HSCs). Northern blot analyses showed that HSCs, but not hepatocytes, expressed transcripts for ADAM9 messenger RNA (mRNA) and both the long and short forms of ADAM12. This expression...

  7. Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor

    International Nuclear Information System (INIS)

    Chen, Zhi-ao; Bao, Mei-yan; Xu, Yong-fen; Zha, Ruo-peng; Shi, Hai-bing; Chen, Tao-yang; He, Xiang-huo

    2012-01-01

    To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC. The expression levels of GABA receptor subunit genes in various HCC cell lines and patients‘ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABA A receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system

  8. [A Distal Bile Duct Carcinoma Patient Who Underwent Surgical Resection for Liver Metastasis].

    Science.gov (United States)

    Komiyama, Sosuke; Izumiya, Yasuhito; Kimura, Yu; Nakashima, Shingo; Kin, Syuichi; Kawakami, Sadao

    2018-03-01

    A 70-year-old man with distal bile duct carcinoma underwent a subtotal stomach-preserving pancreaticoduodenectomy without adjuvant chemotherapy. One and a half years after the surgery, elevated levels of serum SPan-1(38.1 U/mL)were observed and CT scans demonstrated a solitary metastasis, 25mm in size, in segment 8 of the liver. The patient received 2 courses of gemcitabine-cisplatin combination chemotherapy. No new lesions were detected after chemotherapy and the patient underwent a partial liver resection of segment 8. The pathological examination revealed a metachronous distant metastasis originating from the bile duct carcinoma. Subsequently, the patient received S-1 adjuvant chemotherapy for 6 months. Following completion of all therapies, the patient survived without tumor recurrence for 3 years and 10 months after the initial operation. Thus, surgical interventions might be effective in improving prognosis among selected patients with postoperative liver metastasis of bile duct carcinoma.

  9. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    Energy Technology Data Exchange (ETDEWEB)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Hop Paul Brousse, INSERM, Hepatobiliary Ctr, U785, F-94800 Villejuif (France); Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J. [Univ Paris Sud, Fac Med, F-94800 Villejuif (France); Boisgard, R.; Tavitian, B. [INSERM, U803, F-91400 Orsay (France); Boisgard, R.; Tavitian, B. [CEA, Serv Hosp Frederic Joliot, Lab Imagerie Mol Expt, F-91400 Orsay (France); Roux, J.; Cales, P. [Univ Angers, UPRES EA 3859, Lab Hemodynam Interact Fibrose et Invas Tumorale H, Angers (France); Clerc, J. [Hop Cochin, AP HP, Dept Nucl Med, F-75014 Paris (France)

    2008-07-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III {alpha}, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of {sup 131}I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. {sup 131}I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  10. Internal radiotherapy of liver cancer with rat hepato-carcinoma-intestine-pancreas gene as a liver tumor-specific promoter

    International Nuclear Information System (INIS)

    Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Herve, J.; Cunha, A. Sa; Liu, B.; Valogne, Y.; Longuet, M.; Bregerie, O.; Guettier, C.; Samuel, D.; Brechot, C.; Faivre, J.; Boisgard, R.; Tavitian, B.; Boisgard, R.; Tavitian, B.; Roux, J.; Cales, P.; Clerc, J.

    2008-01-01

    The hepato-carcinoma-intestine-pancreas (HIP) gene, also called pancreatitis-associated protein-1 (PAP1) or Reg III α, is activated in most human hepatocellular carcinomas (HCCs) but not in normal liver, which suggests that HIP regulatory sequence could be used as efficient liver tumor-specific promoters to express a therapeutic polynucleotide in liver cancer. The sodium iodide sym-porter (NIS), which has recognized therapeutic and reporter gene properties, is appropriate to evaluate the transcriptional strength and specificity of the HIP promoter in HCC. For this purpose, we constructed a recombinant rat HIP-NIS adeno-viral vector (AdrHIP-NIS), and evaluated its performance as a mediator of selective radio-iodide uptake in tumor hepatocytes. Western blot, immunofluorescence, and iodide uptake assays were performed in AdrHIP-NIS-infected primary hepatocytes and transformed hepatic and non-hepatic cells. Nuclear imaging, tissue counting and immuno-histo-chemistry were performed in normal and HCC-bearing Wistar rats infected with AdrHIP-NIS intra-tumorally or via the hepatic artery. In AdrHIP-NIS-infected transformed hepatic cells, functional NIS was strongly expressed, as in cells infected with a cytomegalovirus-NIS vector. No NIS expression was found in AdrHIP-NIS-infected normal hepatocytes or transformed non-hepatic cells. In rats bearing multi-nodular HCC, AdrHIP-NIS triggered functional NIS expression that was preferential in tumor hepatocytes. Administration of 18 mCi of 131 I resulted in the destruction of AdrHIP-NIS-injected nodules. This study has identified the rHIP regulatory sequence as a potent liver tumor-specific promoter for the transfer of therapeutic genes, and AdrHIP-NIS-mediated. 131 I therapy as a valuable option for the treatment of multi-nodular HCC. (authors)

  11. Relation of Serum Alkaline Phosphatase to liver scintigram in patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, H; Harada, T; Nawata, J; Hayakawa, M; Nishioka, M; Takemoto, T; Yokoyama, T; Takahashi, M

    1982-12-01

    Serum Alkaline Phosphatase (ALP) was studied in relation to liver scintigrams of 54 patients with hepatocellular carcinoma. The ALP activity was higher with larger tumors and in multiple tumors. Within the single tumor group, the activity was higher when the tumor was located in the hilum than in the periphery. The incidence of ALP-1 isoenzyme (bile ALP) roughly paralleled the total ALP activity. These results suggest that the variation of serum ALP seen in each individual patients with hepatocellular carcinoma reflects the volume of cholestatic liver tissue, which is changed by the number, size and localization of the tumor nodules in the liver.

  12. Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Melum, Espen; Friman, Styrbjörn; Bjøro, Kristian

    2007-01-01

    BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries...

  13. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

    Directory of Open Access Journals (Sweden)

    Myklebost Ola

    2007-01-01

    Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

  14. 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.

  15. Prediction of posthepatectomy liver failure using transient elastography in patients with hepatitis B related hepatocellular carcinoma.

    Science.gov (United States)

    Lei, Jie-Wen; Ji, Xiao-Yu; Hong, Jun-Feng; Li, Wan-Bin; Chen, Yan; Pan, Yan; Guo, Jia

    2017-12-29

    It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13-1.29; P hepatocellular carcinoma.

  16. Studies on cellular distribution of elements in human hepatocellular carcinoma samples by molecular activation analysis

    International Nuclear Information System (INIS)

    Deng Guilong; Chen Chunying; Zhang Peiqun; Zhao Jiujiang; Chai Zhifang

    2005-01-01

    The distribution patterns of 17 elements in the subcellular fractions of nuclei, mitochondria, lysosome, microsome and cytosol of human hepatocellular carcinoma (HCC) and normal liver samples were investigated by using molecular activation analysis (MAA) and differential centrifugation. Their significant difference was checked by the Studient's t-test. These elements exhibit inhomogeneous distributions in each subcellular fraction. Some elements have no significant difference between hepatocellular carcinoma and normal liver samples. However, the concentrations of Br, Ca, Cd and Cs are significantly higher in each component of hepatocarcinoma than in normal liver. The content of Fe in microsome of HCC is significantly lower, almost half of normal liver samples, but higher in other subcellular fractions than in those of normal tissues. The rare earth elements of La and Ce have the patterns similar to Fe. The concentrations of Sb and Zn in nuclei of HCC are obviously lower (P<0.05, P<0.05). The contents of K and Na are higher in cytosol of HCC (P<0.05). The distributions of Ba and Rb show no significant difference between two groups. The relationships of Fe, Cd and K with HCC were also discussed. The levels of some elements in subcellular fractions of tumor were quite different from those of normal liver, which suggested that trace elements might play important roles in the occurrence and development of hepatocellular carcinoma. (authors)

  17. Studies on cellular distribution of elements in human hepatocellular carcinoma samples by molecular activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Guilong, Deng [Chinese Academy of Sciences, Beijing (China). Inst. of High Energy Physics, Key Laboratory of Nuclear Analytical Techniques; Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang Univ., Hangzhou (China); Chunying, Chen; Peiqun, Zhang; Jiujiang, Zhao; Zhifang, Chai [Chinese Academy of Sciences, Beijing (China). Inst. of High Energy Physics, Key Laboratory of Nuclear Analytical Techniques; Yingbin, Liu; Jianwei, Wang; Bin, Xu; Shuyou, Peng [Department of General Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang Univ., Hangzhou (China)

    2005-07-15

    The distribution patterns of 17 elements in the subcellular fractions of nuclei, mitochondria, lysosome, microsome and cytosol of human hepatocellular carcinoma (HCC) and normal liver samples were investigated by using molecular activation analysis (MAA) and differential centrifugation. Their significant difference was checked by the Studient's t-test. These elements exhibit inhomogeneous distributions in each subcellular fraction. Some elements have no significant difference between hepatocellular carcinoma and normal liver samples. However, the concentrations of Br, Ca, Cd and Cs are significantly higher in each component of hepatocarcinoma than in normal liver. The content of Fe in microsome of HCC is significantly lower, almost half of normal liver samples, but higher in other subcellular fractions than in those of normal tissues. The rare earth elements of La and Ce have the patterns similar to Fe. The concentrations of Sb and Zn in nuclei of HCC are obviously lower (P<0.05, P<0.05). The contents of K and Na are higher in cytosol of HCC (P<0.05). The distributions of Ba and Rb show no significant difference between two groups. The relationships of Fe, Cd and K with HCC were also discussed. The levels of some elements in subcellular fractions of tumor were quite different from those of normal liver, which suggested that trace elements might play important roles in the occurrence and development of hepatocellular carcinoma. (authors)

  18. 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

  19. CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

    Science.gov (United States)

    Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

    2017-08-01

    CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

  20. Aldolase A isoenzyme levels in serum and tissues of patients with liver diseases

    International Nuclear Information System (INIS)

    Asaka, M.; Nagase, K.; Miyazaki, T.; Alpert, E.

    1983-01-01

    A radioimmunoassay specific for human aldolase A was used to measure human aldolase A levels in human tissue and serum of patients with various liver diseases. The method was a double-antibody technique using radio-iodinated purified aldolase A, chicken antibody to aldolase A, and rabbit antibody to chicken immunoglobulin G. Normal liver tissue contains only a small amount of aldolase A. In contrast, aldolase A predominates in liver cell carcinoma tissue. Aldolase A levels in the sera of normal subjects were 171 +/- 39 ng/ml (mean +/- 2 SD). In almost all of the nonmalignant liver diseases, the aldolase A levels remained less than 210 ng/ml. The serum aldolase A levels increased remarkable only in fulminant hepatitis. in contrast, 32 of 34 patients with liver cell carcinoma and all of 29 patients with metastatic liver carcinoma showed clearly increased serum aldolase A levels. More patients with primary liver cell carcinoma had increased serum aldolase A levels than elevations of serum alpha-fetoprotein. These results suggest that the determination of aldolase A by radioimmunoassay may be useful to differentiate malignant form nonmalignant liver diseases

  1. Liver metastases of breast carcinoma detected on /sup 99m/Tc-methylene diphosphonate bone scan

    International Nuclear Information System (INIS)

    Baumert, J.E.; Lantieri, R.L.; Horning, S.; McDougall, I.R.

    1980-01-01

    The accumulation of bone-seeking radiopharmaceuticals has been reported in liver metastases from colon carcinoma and oat cell carcinoma of the lung. Two patients with breast carcinoma in whom hepatic metastases were visualized on /sup 99m/Tc-methylene diphosphonate bone images are described. This has not been previously reported

  2. Expression of hsa_circ_PVT1 in human hepatocellular carcinoma and its clinical significance

    Directory of Open Access Journals (Sweden)

    Yuan-xin ZHU

    2018-03-01

    Full Text Available Objective To determine the expression and clinical significance of circ-PVT1 in human hepatocellular carcinoma (HCC and its effect on HCC cell proliferation. Methods The expressions of circ-PVT1 in hepatocellular carcinoma and the matched tumor-adjacent tissues were detected by RT-qPCR and the relationship between pathological indexes and the expression level was analyzed in 46 patients. The expressions of circ-PVT1 in human normal liver cell line (L02 and hepatocellular carcinoma cell lines (HepG2, SMMC-7721, MHCC-97H, MHCC-97L, HCC-LM3 were detected by RT-qPCR and were compared thereafter. With knocking down the expression of circ-PVT1, si-circPVT1 was transfected into HepG2 and SMMC-7721 cells by using lipofectamine technique in vitro, with the si-NC being taken as negative control. After interfering the expression of circ-PVT1, the effect on the proliferation of hepatocellular carcinoma cells was detected by CCK-8 and EDU experiments and flow cytometry was conducted to observe the effect of circ-PVT1 on cell cycle. Results The expression level of circ-PVT1 was significantly higher in HCC tissues than in adjacent tissues (P<0.01, and its high expression level was significantly correlated with tumor size, TNM stage and differentiation degree. Similarly, in human hepatocellular carcinoma cell lines (HepG2, SMMC-7721, MHCC-97H, MHCC-97L, HCC-LM3, the expression level of circ-PVT1 was also higher than that in human normal liver cell line L02 (P<0.05. Compared with the negative control group, silencing of circ-PVT1 resulted in remarkable reduction in cell proliferation of HepG2 and SMMC-7721. Conclusion circ-PVT1 may act as a potential biomarker for HCC diagnosis and may become a novel proliferation factor. DOI: 10.11855/j.issn.0577-7402.2018.03.06

  3. Cryotherapy of employing Argon/Helium assisted with TACE in treating unresectable primary liver carcinoma

    International Nuclear Information System (INIS)

    Zhang Zhiliang; Yang Xuedong; Cao Yongwei; Lin Xiangyang; Zhang Yongping; Liu Yayuan

    2004-01-01

    Objective: To investigate the effect of cryotherapy of employing Argon/Helium assisted with TACE for the unresectable primary liver carcinoma. Methods: 124 cases with primary liver carcinoma were randomly divided into two groups: 60 cases were treated by TACE and cryotherapy; the other 64 cases were simply done by TACE as control. In general, TACE was undertaken once a month and altogether three times for a course. Cryotherapy was undergone 1-3 times for a course. Results: The total effective rates (CR + PR) were 45.3% for the control group and 68.3% for the combined therapy group, with an obvious difference between the two groups, 0.5, 1, 1.5 years survival rate were 81.3%, 62.5%, 43.8% respectively in the control group; 93.3%, 83.3%, 63.3% respectively for the combined group. There was an obvious difference between the two groups of 1, 1.5 years of survival rates. Conclusions: Cryotherapy of employing Argon/Helium assisted with TACE for the unresectable primary liver carcinoma is feasible with raising the effective rate and prolonging survival time. (authors)

  4. Clinical significance of Tc-99m colloid liver angiography for the diagnosis of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Odano, I; Sakai, K; Sueyama, H [Niigata Univ. (Japan). School of Medicine

    1982-03-01

    Tc-99m phytate liver angiography was accomplished in 191 cases with focal liver disease at the same time of performing conventional liver scintigraphy from July 1978 to Feb. 1981. This simple method was considered to be useful to appreciate tumor vascularity in the liver, which was shown as dynamic radioactivity in the defect of the liver scintigram. Hypervascular pattern was defined as a high-radioactivity on the arterial phase of RI angiography, which corresponded to the filling defect on the static liver scintigram. This pattern was influenced by three factors, i.e. pathological vascularization of the tumor, size of the filling defect and position of the defect in the liver. In 29 cases (74%) of 39 hepatocellular carcinoma, hypervascular pattern was observed. When mean diameter of defect was more than 5.5 cm on liver scintigram, it was supposed that hypervascular pattern should be observed in probability of 84%. The smallest mean diameter of defect in which this pattern was seen was 3.0 cm. When a filling defect was situated at the posterior region of the right lobe of the liver, it was sometimes difficult to appreciate the vascular pattern. Tc-99m phytate liver angiography was considered to be a useful method for screening hepatocellular carcinoma.

  5. Long-term survival after liver transplant for recurrent hepatocellular carcinoma with bile duct tumor thrombus: case report.

    Science.gov (United States)

    Liu, Chao; Wang, Jie

    2012-12-01

    Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 μg/L, total bilirubin level was 327 μmol/L, direct bilirubin level was 261 μmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.

  6. AGE WISE HISTOMORPHOLOGICAL CHANGES IN HUMAN LIVER

    Directory of Open Access Journals (Sweden)

    Tribeni

    2015-11-01

    Full Text Available CONTEXT: Hepato cellular carcinoma (HCC results in between 2.5 lakhs to 1million deaths globally per annum. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. AIMS: Keeping this concept in view, a study was conducted in the Guwahati Zone of Northeast India, to compare the histomorphological features of the human liver in different age groups. SETTING AND DESIGN: Apparently healthy livers were obtained from 21 subjects on whom medicolegal post-mortems had been performed. Their ages varied from newborn to 90 years. Subjects were divided into 3 groups. 7 specimens were taken from each group. (1 Pediatric (2 Adult (3 Old age. METHODS AND MATERIALS: In all the above age groups, immediately after removal of the livers, they were washed in normal saline, dried with blotting paper and weighed in an electronic weighing machine. Sections of liver were fixed, processed, cut and stained with Harris Haematoxylin and Eosin stain. RESULTS: The liver loses weight from 50 years onwards. There appears to be racial and environmental differences in the change in liver weight in old age. Autopsy studies show a diminution of nearly 46% in liver weight between the 3rd and 10th decades of life. The liver decreases in size with age. The hepatocytes are radially disposed in the liver lobule. They are piled up, forming a layer one cell thick (except in young children in a fashion similar to the bricks of a wall. These plates are directed from the periphery of the lobule to its centre and anastomose freely forming a complex labyrinthine and sponge-like structure. CONCLUSIONS: From the findings in the present study it can be concluded that: 1. Nowadays, the measurement of liver volume has gained practical use in relation to liver transplantation. 2. We have compared the histomorphology of adult liver with a child. The findings in both the groups are very similar. This feature is important, since in

  7. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... is not synthesised locally in breast tissue but derived by leakage from vessels, followed by extracellular accumulation in patterns distinctly different in carcinomas and normal tissue. The observation of a high vitronectin content in the carcinomas and its localisation in the tissue contributes to the clarification...

  8. IS RESECTION OF HEPATOCELLULAR CARCINOMA IN THE ERA OF LIVER TRANSPLANTATION WORTHWILE? A single center experience

    Directory of Open Access Journals (Sweden)

    Paulo HERMAN

    Full Text Available ABSTRACT Background - Liver resection for hepatocellular carcinoma is a potentially curative therapeutic procedure that can be performed readily after its indication, without the need of a long waiting time and lower costs when compared to liver transplantation, being a good alternative in patients with preserved/good liver function. Objective - Evaluate long-term results of liver resection from a high volume single center for selected patients with hepatocellular carcinoma in a context of a long waiting list for liver transplant. Methods - One hundred and one patients with hepatocellular carcinoma, with a mean age of 63.1 years, and preserved liver function were submitted to liver resection. Clinical and pathological data were evaluated as prognostic factors. Mean follow-up was 39.3 months. Results - All patients had a single nodule and 57 (58.2% patients were within the Milan criteria. The size of the nodule ranged from 1 to 24 cm in diameter. In 74 patients, liver resection was performed with the open approach and in 27 (26.7% was done laparoscopically. Postoperative morbidity was 55.3% being 75.5% of the complications classified as Dindo-Clavien I and II and operative mortality was 6.9%. Five-year overall and disease free survival rates were 49.9% and 40.7%, respectively.After a log-rank univariate analysis, the levels of preoperative alpha-fetoprotein (P=0.043, CA19-9 (P=0.028, capsule invasion (P=0.03, positive margin (R1-R2 (P=0.004 and Dindo-Claviens' morbidity classification IV (P=0.001 were the only parameters that had a significant negative impact on overall survival. On the odds-ratio evaluation, the only significant factors for survival were high levels of alpha-fetoprotein (P=0.037, and absence of free margins (P=0.008. Conclusion - Resection, for selected cases, is a potentially curative treatment with acceptable morbidity and mortality and, in a context of a long waiting list for transplant, plays an important role for the

  9. Results after surgical treatment of liver metastases in patients with high-grade gastroenteropancreatic neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Galleberg, R B; Knigge, U; Tiensuu Janson, E

    2017-01-01

    Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce......., particularly for the group with a Ki-67 in the relatively lower G3 range. Our findings indicate a possible role for surgical treatment of liver metastases in the management of this patient population.......Background: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC) are generally characterized by synchronous metastases, high aggressiveness and a dismal prognosis. Current international guidelines do not recommend surgical treatment of liver metastases, however the existing data are scarce....... The aim of this study was to evaluate the results of curatively intended resection/radiofrequency ablation (RFA) of liver metastases in patients with metastatic GEP-NEC. Methods: 32 patients with a diagnosis of high-grade gastroenteropancreatic neuroendocrine neoplasm (Ki-67 > 20%) and with intended...

  10. 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.

  11. Detection of an occult hepatocellular carcinoma using ultrasound with liver-specific microbubbles

    International Nuclear Information System (INIS)

    Harvey, Christopher J.; Lim, Adrian K.P.; Blomley, Martin J.K.; Cosgrove, David O.; Taylor-Robinson, Simon D.; Gedroyc, Wladyslaw M.W.

    2002-01-01

    The radiological surveillance of cirrhosis to detect the development of hepatocellular carcinoma (HCC) is problematic because no highly sensitive and specific imaging investigation is available. Ultrasound is typically the first modality used but is less accurate than other imaging modalities. We report the first case of a patient with cirrhosis in whom US imaging with liver-specific microbubbles detected an HCC prior to its detection by MR. The use of liver-specific microbubble US contrast agents is an exciting development in the detection of HCC in chronic liver disease and may help to rectify some of the shortcomings of US. (orig.)

  12. Liver stiffness measurement by transient elastography predicts late posthepatectomy outcomes in patients undergoing resection for hepatocellular carcinoma.

    Science.gov (United States)

    Rajakannu, Muthukumarassamy; Cherqui, Daniel; Ciacio, Oriana; Golse, Nicolas; Pittau, Gabriella; Allard, Marc Antoine; Antonini, Teresa Maria; Coilly, Audrey; Sa Cunha, Antonio; Castaing, Denis; Samuel, Didier; Guettier, Catherine; Adam, René; Vibert, Eric

    2017-10-01

    Postoperative hepatic decompensation is a serious complication of liver resection in patients undergoing hepatectomy for hepatocellular carcinoma. Liver fibrosis and clinical significant portal hypertension are well-known risk factors for hepatic decompensation. Liver stiffness measurement is a noninvasive method of evaluating hepatic venous pressure gradient and functional hepatic reserve by estimating hepatic fibrosis. Effectiveness of liver stiffness measurement in predicting persistent postoperative hepatic decompensation has not been investigated. Consecutive patients with resectable hepatocellular carcinoma were recruited prospectively and liver stiffness measurement of nontumoral liver was measured using FibroScan. Hepatic venous pressure gradient was measured intraoperatively by direct puncture of portal vein and inferior vena cava. Hepatic venous pressure gradient ≥10 mm Hg was defined as clinically significant portal hypertension. Primary outcome was persistent hepatic decompensation defined as the presence of at least one of the following: unresolved ascites, jaundice, and/or encephalopathy >3 months after hepatectomy. One hundred and six hepatectomies, including 22 right hepatectomy (20.8%), 3 central hepatectomy (2.8%), 12 left hepatectomy (11.3%), 11 bisegmentectomy (10.4%), 30 unisegmentectomy (28.3%), and 28 partial hepatectomy (26.4%) were performed in patients for hepatocellular carcinoma (84 men and 22 women with median age of 67.5 years; median model for end-stage liver disease score of 8). Ninety-day mortality was 4.7%. Nine patients (8.5%) developed postoperative hepatic decompensation. Multivariate logistic regression bootstrapped at 1,000 identified liver stiffness measurement (P = .001) as the only preoperative predictor of postoperative hepatic decompensation. Area under receiver operating characteristic curve for liver stiffness measurement and hepatic venous pressure gradient was 0.81 (95% confidence interval, 0.506-0.907) and 0

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

    International Nuclear Information System (INIS)

    El-fouly, N.F.

    2007-01-01

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

  14. Tissue-based quantitative proteome analysis of human hepatocellular carcinoma using tandem mass tags.

    Science.gov (United States)

    Megger, Dominik Andre; Rosowski, Kristin; Ahrens, Maike; Bracht, Thilo; Eisenacher, Martin; Schlaak, Jörg F; Weber, Frank; Hoffmann, Andreas-Claudius; Meyer, Helmut E; Baba, Hideo A; Sitek, Barbara

    2017-03-01

    Human hepatocellular carcinoma (HCC) is a severe malignant disease, and accurate and reliable diagnostic markers are still needed. This study was aimed for the discovery of novel marker candidates by quantitative proteomics. Proteomic differences between HCC and nontumorous liver tissue were studied by mass spectrometry. Among several significantly upregulated proteins, translocator protein 18 (TSPO) and Ras-related protein Rab-1A (RAB1A) were selected for verification by immunohistochemistry in an independent cohort. For RAB1A, a high accuracy for the discrimination of HCC and nontumorous liver tissue was observed. RAB1A was verified to be a potent biomarker candidate for HCC.

  15. The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis

    International Nuclear Information System (INIS)

    Arrieta, Oscar; Cacho, Bernardo; Morales-Espinosa, Daniela; Ruelas-Villavicencio, Ana; Flores-Estrada, Diana; Hernández-Pedro, Norma

    2007-01-01

    Hepatocellular carcinoma is the most common cause of primary liver neoplasms and is one of the main causes of death in patients with liver cirrhosis. High Alpha fetoprotein serum levels have been found in 60–70% of patients with Hepatocellular carcinoma; nevertheless, there are other causes that increase this protein. Alpha fetoprotein levels ≥200 and 400 ng/mL in patients with an identifiable liver mass by imaging techniques are diagnostic of hepatocellular carcinoma with high specificity. We analysed the sensitivity and specificity of the progressive increase of the levels of alpha fetoprotein for the detection of hepatocellular carcinoma in patients with liver cirrhosis. Seventy-four patients with cirrhosis without hepatocellular carcinoma and 193 with hepatic lesions diagnosed by biopsy and shown by image scans were included. Sensitivity and specificity of transversal determination of alpha fetoprotein ≥ 200 and 400 ng/mL and monthly progressive elevation of alpha fetoprotein were analysed. Areas under the ROC curves were compared. Positive and negative predictive values adjusted to a 5 and 10% prevalence were calculated. For an elevation of alpha fetoprotein ≥ 200 and 400 ng/mL the specificity is of 100% in both cases, with a sensitivity of 36.3 and 20.2%, respectively. For an alpha fetoprotein elevation rate ≥7 ng/mL/month, sensitivity was of 71.4% and specificity of 100%. The area under the ROC curve of the progressive elevation was significantly greater than that of the transversal determination of alpha fetoprotein. The positive and negative predictive values modified to a 10% prevalence are of: 98.8% and 96.92%, respectively; while for a prevalence of 5% they were of 97.4% and 98.52%, respectively. The progressive elevation of alpha fetoprotein ≥7 ng/mL/month in patients with liver cirrhosis is useful for the diagnosis of hepatocellular carcinoma in patients that do not reach αFP levels ≥200 ng/mL. Prospective studies are required to

  16. Predictors of Liver Toxicity Following Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Velec, Michael [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Haddad, Carol R. [Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, New South Wales (Australia); Craig, Tim [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Wang, Lisa [Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Lindsay, Patricia; Brierley, James; Brade, Anthony; Ringash, Jolie; Wong, Rebecca; Kim, John [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Dawson, Laura A., E-mail: Laura.Dawson@rmp.uhn.on.ca [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada)

    2017-04-01

    Purpose: To identify risk factors associated with a decline in liver function after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma. Methods and Materials: Data were analyzed from patients with hepatocellular carcinoma treated on clinical trials of 6-fraction SBRT. Liver toxicity was defined as an increase in Child-Pugh (CP) score ≥2 three months after SBRT. Clinical factors, SBRT details, and liver dose-volume histogram (DVH) parameters were tested for association with toxicity using logistic regression. CP class B patients were analyzed separately. Results: Among CP class A patients, 101 were evaluable, with a baseline score of A5 (72%) or A6 (28%). Fifty-three percent had portal vein thrombus. The median liver volume was 1286 cc (range, 766-3967 cc), and the median prescribed dose was 36 Gy (range, 27-54 Gy). Toxicity was seen in 26 patients (26%). Thrombus, baseline CP of A6, and lower platelet count were associated with toxicity on univariate analysis, as were several liver DVH-based parameters. Absolute and spared liver volumes were not significant. On multivariate analysis for CP class A patients, significant associations were found for baseline CP score of A6 (odds ratio [OR], 4.85), lower platelet count (OR, 0.90; median, 108 × 10{sup 9}/L vs 150 × 10{sup 9}/L), higher mean liver dose (OR, 1.33; median, 16.9 Gy vs 14.7 Gy), and higher dose to 800 cc of liver (OR, 1.11; median, 14.3 Gy vs 6.0 Gy). With 13 CP-B7 patients included or when dose to 800 cc of liver was replaced with other DVH parameters (eg, dose to 700 or 900 cc of liver) in the multivariate analysis, effective volume and portal vein thrombus were associated with an increased risk. Conclusions: Baseline CP scores and higher liver doses (eg, mean dose, effective volume, doses to 700-900 cc) were strongly associated with liver function decline 3 months after SBRT. A lower baseline platelet count and portal vein thrombus were also associated with an

  17. Hepatocellular carcinoma in the native liver of a 38-year-old female patient with biliary atresia

    Directory of Open Access Journals (Sweden)

    Yutaka Kanamori

    2015-11-01

    Full Text Available We report a rare case of hepatocellular carcinoma in native liver in a case of biliary atresia. The patient was a 38-year-old female with three children who had an aggressive tumor, resulting in her subsequent death. We also review 14 reports, published previously in the English language medical literature, concerning hepatocellular carcinoma originating from native liver in biliary atresia cases and discuss the possible etiology, and propose more careful follow up for the patients with biliary atresia who suffer from repetitive cholangitis and/or experience the child delivery.

  18. Effects of radiosensibilization by metronidazole on liver tissue in patients with gastric carcinomas

    International Nuclear Information System (INIS)

    D'yakova, A.M.; Stefani, N.V.; Zagrebin, V.M.; Senokosov, N.I.; Berdov, B.A.

    1985-01-01

    Metronidazole, used as radiosensitizer in preoperative radiotherapy of gastric carcinoma caused an increased glycogen accumulation in the left lobe of the liver with a radiation dose of 80-100 % of the isodose. The glycogen level was higher not only in comparison with the same liver area in patients without radiosensitizer but also with the right lobe of the own liver within in the area of stray radiation. The effect observed after radiation was considered as result of the sensitizing influence on liver tissue. The sensitizing effect of metronidazole depended on its concentration in the patient's serum. In the right lobe of the liver the glycogen level showed no alteration under metronidazole. Metronidazole reduced the activity of lactate dehydrogenase and cholinesterase in liver tissue independently of its concentration in the serum and of the radiation dose on particular parts of the liver. (author)

  19. Elevated renin levels in patients with liver cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Lotfy, Mahmoud; El-Kenawy, Ayman El-Meghawry; Abdel-Aziz, Mohamed M; El-Kady, Ibrahim; Talaat, Ayman

    2010-01-01

    Liver fibrosis is the common consequence of chronic liver injury of any etiology, disrupting the normal architecture,and causing hepatocellular dysfunction and portal hypertension. Since the renin-angiotensin system (RAS) may be involved in chronic liver diseases, in the present study we assayed renin levels using ELISA in groups of Egyptian patients with liver cirrhosis (N=32) and hepatocellular carcinoma (HCC) (N=67), for comparison with twenty five healthy controls. The results showed significant differences between the control and liver cirrhosis patients (P<0.001) and also the controls and HCC patients (P<0.001), without significant variation between the patient groups. Furthermore, in HCC patients, it was found that the renin levels negatively correlated with serum albumin and prothrombin time (P=0.003 for each) and positively with α-fetoprotein (P=0.04). Thus, it is concluded that renin levels are elevated in patients with liver cirrhosis and HCC and suitable medical intervention should be placed for management of such alteration. Moreover, further studies are warranted to explore its prognostic significance.

  20. Curative salvage liver transplantation in patients with cirrhosis and hepatocellular carcinoma : An intention-to-treat analysis

    NARCIS (Netherlands)

    de Haas, Robbert J.; Lim, Chetana; Bhangui, Prashant; Salloum, Chady; Compagnon, Philippe; Feray, Cyrille; Calderaro, Julien; Luciani, Alain; Azoulay, Daniel

    The salvage liver transplantation (SLT) strategy was conceived for initially resectable and transplantable (R&T) hepatocellular carcinoma (HCC) patients, to try to obviate upfront liver transplantation, with the safety net of SLT in case of postresection recurrence. The SLT strategy is successful or

  1. Demonstration of Hepatitis C Virus RNA with In Situ Hybridization Employing a Locked Nucleic Acid Probe in Humanized Liver of Infected Chimeric Mice and in Needle-Biopsied Human Liver

    Directory of Open Access Journals (Sweden)

    Kazuya Shiogama

    2013-01-01

    Full Text Available Background. In situ hybridization (ISH with high sensitivity has been requested to demonstrate hepatitis C virus (HCV RNA in formalin-fixed, paraffin-embedded (FFPE sections of the liver. Methods. ISH employing a locked-nucleic-acid- (LNA-modified oligonucleotide probe and biotin-free catalyzed signal amplification system (CSAII was applied to HCV-RNA detection in the liver tissue. Nested reverse-transcription polymerase chain reaction (RT-PCR was performed for HCV genotyping using total RNA extracted from FFPE sections. The target tissues included FFPE tissue sections of humanized livers in HCV-infected chimeric mice (HCV genotypes 1a, 1b, and 2a and noninfected and of needle-biopsied livers from HCV-infected patients. Results. HCV-RNA was demonstrated with the ISH technique in HCV-infected liver tissues from both chimeric mice and 9 (82% of 11 patients with HCV infection. The HCV signals were sensitive to RNase. Nested RT-PCR confirmed the genotype in 8 (73% of 11 livers (type 1b: 6 lesions and type 2a: 2 lesions. HCV-RNA was not identified in chronic hepatitis B lesions, fatty liver, autoimmune hepatitis, and hepatocellular carcinoma. Conclusion. ISH using the LNA-modified oligonucleotide probe and CSAII was applicable to detecting HCV-RNA in routinely prepared FFPE liver specimens.

  2. MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver.

    Directory of Open Access Journals (Sweden)

    Erkko Ylösmäki

    Full Text Available MicroRNAs (miRNAs are important and ubiquitous regulators of gene expression that can suppress their target genes by translational inhibition as well as mRNA destruction. Cell type-specific miRNA expression patterns have been successfully exploited for targeting the expression of experimental and therapeutic gene constructs, for example to reduce pathogenic effects of cancer virotherapy in normal tissues. In order to avoid liver damage associated with systemic or intrahepatic delivery of oncolytic adenoviruses we have introduced the concept of suppressing adenovirus replication in hepatic cells by inserting target elements for the liver-specific miR122 into the viral genome. Here we show using ex vivo cultured tissue specimens that six perfectly complementary miR122 target sites in the 3' untranslated region of the viral E1A gene are sufficient in the absence of any other genetic modifications to prevent productive replication of serotype 5 adenovirus (Ad5 in normal human liver. This modification did not compromise the replicative capacity of the modified virus in cancer tissue derived from a colon carcinoma liver metastasis or its oncolytic potency in a human lung cancer xenograft mouse model. Unlike wild-type Ad5, the modified virus did not result in increased serum levels of liver enzymes in infected mice. These results provide a strong preclinical proof of concept for the use of miR122 target sites for reducing the risk of liver damage caused by oncolytic adenoviruses, and suggest that ectopic miR122 target elements should be considered as an additional safety measure included in any therapeutic virus or viral vector posing potential hazard to the liver.

  3. Carcinogen-Induced Hepatic Tumors in KLF6+/- Mice Recapitulate Aggressive Human Hepatocellular Carcinoma Associated with p53 Pathway Deregulation

    NARCIS (Netherlands)

    Tarocchi, Mirko; Hannivoort, Rebekka; Hoshida, Yujin; Lee, Ursula E.; Vetter, Diana; Narla, Goutham; Villanueva, Augusto; Oren, Moshe; Llovet, Josep M.; Friedman, Scott L.

    Inactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental

  4. Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report

    NARCIS (Netherlands)

    Clavien, Pierre-Alain; Lesurtel, Mickael; Bossuyt, Patrick M. M.; Gores, Gregory J.; Langer, Bernard; Perrier, Arnaud; Abecassis, M.; Balabaud, C.; Bhoori, S.; Breitenstein, S.; Broelsch, C.; Burra, P.; Cherqui, D.; Colombo, M.; d'Albuquerque, C.; D'Alessandro, A.; de Santibanes, E.; Dufour, J. F.; Durand, F.; Dutkowski, P.; El-Serag, H.; Fan, S. T.; Fisher, R.; Forner, A.; Fung, J.; Geier, A.; Germani, G.; Gouw, A. S. H.; Gurusamy, K.; Heaton, N.; Heim, M.; Hemming, A.; Hubscher, S.; Ichida, T.; Kahn, D.; Kew, M.; Kita, Y.; Kiuchi, T.; Kudo, M.; Lee, S. G.; Lencioni, R.; Livraghi, T.; Lodge, P.; McCaughan, G.; Madoff, D.; Marrero, J.; Mergental, H.; Merle, P.; Miksad, R.; Mornex, F.; Paradis, V.; Pestalozzi, B.; Poon, R.; Porte, R.; Prasad, K. R.; Roskams, T.; Rossi, M.; Schlitt, H.; Shaked, A.; Sherman, M.; Siegler, M.; Suh, K.; Todo, S.; Toso, C.; Trevisani, F.; Valdecasas, J. C. G.; Vauthey, J. N.; Vilgrain, V.; Villamil, F.; Wald, C.; Weber, A.; Wiesner, R.; Wright, L.; Zheng, S.; Zucman-Rossi, J.; Bertschi, V.; Clavien, P. A.; Meyer, M.; Müllhaupt, B.; Munson, A.; Lesurtel, M.; Raptis, D.; Vonlanthen, R.

    2012-01-01

    Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2-4, 2010, in Zurich, Switzerland, with the aim of reviewing current

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

    Directory of Open Access Journals (Sweden)

    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

  6. 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.

  7. 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.

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Ozand Pinar T

    2010-06-01

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

  10. Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

    Science.gov (United States)

    Rayes, Roni F; Milette, Simon; Fernandez, Maria Celia; Ham, Boram; Wang, Ni; Bourdeau, France; Perrino, Stephanie; Yakar, Shoshana; Brodt, Pnina

    2018-03-20

    The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls. However, unlike controls, these neutrophils did not acquire the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF expression and arginase production, all characteristic of the (pro-inflammatory) phenotype. This coincided with an increase in apoptotic tumor cells and reduced metastasis. Neutrophils isolated from these mice also had reduced IGF-IR expression levels. These changes were not observed in iLID mice with a short-term (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I levels, indicating that a sustained IGF-I deficiency was necessary to alter the neutrophil phenotype. Similar results were obtained with the highly metastatic Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap that blocks IGF-IR signaling by reducing ligand bioavailability. Our results implicate the IGF axis in neutrophil polarization and the induction of a pro-metastatic microenvironment in the liver.

  11. Cytotoxic effects of some animal and vegetable extracts and some chemicals on liver and colon carcinoma and myosarcoma

    International Nuclear Information System (INIS)

    Bayazit, Vahdettin

    2004-01-01

    To study, the cytotoxic effects of some biological and chemical agents on G, S, G, M and G phases of liver and colon carcinomas and myosarcoma cells obtained with chemical carcinogens dimethylbenzanthracene (Dmba) and cadmium chloride. Eight rabbit livers, colon carcinoma and myosarcoma cell lines were obtained by injection of Dmba in the Biology Laboratory, of the University of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003. All lines were grown at 37degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml) and streptomycin (50 ug/ml) (complete medium). Cells were grown on standard tissue culture plastic flasks to 80% confluence and passed by trypsinization. Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0 phases (p<0.01). The mistletoe (Viscum album) extract had more effect in only the G0 phase (p<0.05). Genistein, genistin, glycitein, glycitin, daitzein and daitzin have significantly decreased in the cancer cells tests, particularly, genistein and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01). Cesium chloride, a mixture of cesium chloride with magnesium chloride had the most effect on tumor cells (p<0.01). AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi, AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer cells (p<0.05, p<0.01). This data suggest that some biological extracts and chemicals tested may be useful chemotherapeutic agents to inhibit the growth of cancer cells. This study sheds some light for new anti cancerogenic experiments preventing various cancers on humans. (author)

  12. in Human Liver Diseases

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    Minoru Fujimoto

    2010-01-01

    Full Text Available Toll-like receptor (TLR signaling pathways are strictly coordinated by several mechanisms to regulate adequate innate immune responses. Recent lines of evidence indicate that the suppressor of cytokine signaling (SOCS family proteins, originally identified as negative-feedback regulators in cytokine signaling, are involved in the regulation of TLR-mediated immune responses. SOCS1, a member of SOCS family, is strongly induced upon TLR stimulation. Cells lacking SOCS1 are hyperresponsive to TLR stimulation. Thus, SOCS1 is an important regulator for both cytokine and TLR-induced responses. As an immune organ, the liver contains various types of immune cells such as T cells, NK cells, NKT cells, and Kupffer cells and is continuously challenged with gut-derived bacterial and dietary antigens. SOCS1 may be implicated in pathophysiology of the liver. The studies using SOCS1-deficient mice revealed that endogenous SOCS1 is critical for the prevention of liver diseases such as hepatitis, cirrhosis, and cancers. Recent studies on humans suggest that SOCS1 is involved in the development of various liver disorders in humans. Thus, SOCS1 and other SOCS proteins are potential targets for the therapy of human liver diseases.

  13. Risk factors of radiation-induced liver disease after three-dimensional conformal radiotherapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Liang Shixiong; Zhu Xiaodong; Lu Haijie; Pan Chaoyang; Huang Qifang; Li Fuxiang; Wang Anyu; Liang Guoliang; Fu Xiaolong

    2005-01-01

    Objective: To identify the risk factors of radiation-induced liver disease (RILD) after three-dimensional radiotherapy (3DCRT) for primary liver carcinoma (PLC) and the dosimetric threshold of RILD. Methods: Between April 1999 and August 2003, 128 PLC patients who were treated with 3DCRT received a mean dose of 53.6 ± 6.6 Gy with a 4-8 Gy/f, 3f/w, qod regimen. The relation between RILD and the possible clinical factors, such as gender, age, UICC/ AJCC T stage, GTV, HBV status, PTV, TACE, Child-Pugh grade of liver cirrhosis, BED calculated by LQ model and fraction size were analyzed. Among 84 patients who had full dose- volume histogram (DVH) data, the relation between RILD and dosimetric parameters were analyzed. Results: Nineteen patients (14.8%) developed RILD. It was found that T stage, GTV, PTV, Child-Pugh grade of liver cirrhosis and the acute hepatic toxicity proposed by common toxicity criteria version 2.0 (CTC2.0) were correlated with RILD (P=0.024, 0.002, 0.001, 0.000, 0.000, respectively). Multivariate analysis showed that only the Child-Pugh grade of liver cirrhosis was independent factor (P=0.000). The mean liver dose was significantly higher in patients with RILD (P=0.027). In patients with Child-Pugh grade A, V5 (percentage of normal liver volume with radiation dose > 5 Gy), V 10 and V 20 ≤81%, 69% and 42%, mean liver dose ≤28 Gy, RILD was not observed, whereas in patients with Child-Pugh grade B, the possibility of developing RILD was 53.3%(8/15). Conclusions: Comprehensive consideration of T stage, GTV, PTV and Child-Pugh grade of liver cirrhosis, especially the Child-Pugh grade of liver cirrhosis, when planning 3DCRT for PLC, may lower the incidence of RILD. (authors)

  14. Nonalcoholic fatty liver disease and hepatocellular carcinoma

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    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. VX2 Carcinoma in rabbit liver: Different radiologic features according to innoculation methods

    International Nuclear Information System (INIS)

    Lee, Joon Woo; Chung, Jin Wook; Choi, Guk Myeong; Kim, Chong Jai; Kim, Se Hyung; Choi, Joon Il; Lee, Kyoung Ho; Kim, Seung Hyup; Park, Jae Hyung

    2000-01-01

    To investigate radiologic features about hepatic VX2 carcinoma induced by two methods, direct intraparenchymal innoculation vs transpotal approach, focus on enhancement pattern and comparison of each imaging modalities and innoculation methods. VX2 carcinomas were induced in 11 rabbit livers by direct inoculation (n=7) or infusion into mesenteric vein (n=4). After two weeks, spiral CT, digital subtraction angiography (DSA), intravenous contrast-enhanced power Doppler sonography, intraarterial CO 2 sonography were done. The enhancement patterns were assessed independently and correlated with histopathologic features. With direct intraprenchymal innoculation, localized hepatic VX2 tumors were developed. Considering all imaging modalities, six of 7 tumors appeared peripheral hypervascularity, one hypovascularity. On pathologic and radiologic correlations, the enhancing portions of 4 tumors corresponded to viable tumor and pseudo-capsule portion, the other enhancing portions of 2 tumors corresponded to sinusoidal vascular spaces. With the transportal approaches, diffuse hepatic tumors were developed. Spiral CT and DSA revealed these tumors as marked peripheral hypervascular tumors with multiple A-P shunts. On pathologic findings, multiple thin walled sinusoidal spaces were seen at periphery of nodule. Spiral CT was superior to the other modalities in evaluation of enhancement characteristics. VX2 carcinomas in rabbit livers showed different radiologic and histopathologic features according to the innoculation methods.

  16. Assessment of triple-phase CT findings for the differentiation of fat-deficient hepatic angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver

    International Nuclear Information System (INIS)

    Jeon, Tae Yeon; Kim, Seong Hyun; Lim, Hyo K.; Lee, Won Jae

    2010-01-01

    Background: To evaluate the triple-phase CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver. Methods: We retrospectively reviewed contrast-enhanced triple-phase CT images of 10 patients with fat-deficient hepatic angiomyolipoma and 28 patients with 29 hepatocellular carcinomas in non-cirrhotic liver proved on histologic examination. The CT findings for the two types of tumors were compared using Fisher's exact test. Results: Early draining vein depicted on arterial or portal phases was seen in eight (80%) angiomyolipomas and two hepatocellular carcinomas (7%) (p < 0.001), in which the early draining vein was connected with tumoral vessels. The tumoral vessels in the angiomyolipoma were more prominent and ectatic, were distributed both centrally and peripherally, and were seen in smaller tumors than in the hepatocellular carcinoma. Tumor capsule enhancement was absent in all angiomyolipomas as compared with two (7%) hepatocellular carcinomas with no tumor capsule (p < 0.001). The other CT findings were not significantly different for the two different types of tumors. Conclusions: The presence of early draining vein connecting with prominent tumoral vessels and absent tumor capsule were useful CT findings for the differentiation of fat-deficient angiomyolipoma from hepatocellular carcinoma in non-cirrhotic liver.

  17. Orthotopic liver transplantation as a rescue operation for recurrent hepatocellular carcinoma after partial hepatectomy

    OpenAIRE

    Shao, Zhuo; Lopez, Rocio; Shen, Bo; Yang, Guang-Shun

    2008-01-01

    AIM: To compare post-orthotopic liver transplantation (OLT) survival between patients with recurrent hepatocellular carcinoma (HCC) after partial hepatectomy and those who received de novo OLT for HCC and to assess the risk factors associated with post-OLT mortality.

  18. Molecular signatures associated with HCV-induced hepatocellular carcinoma and liver metastasis.

    Directory of Open Access Journals (Sweden)

    Valeria De Giorgi

    Full Text Available Hepatocellular carcinomas (HCCs are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis.A diagnostic molecular signature complementing conventional pathologic assessment was identified.

  19. MicroRNAs as Biomarkers for Liver Disease and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    C. Nelson Hayes

    2016-02-01

    Full Text Available Serum levels of liver enzymes, such as alanine transaminase, aspartate transaminase, and α-fetoprotein, provide insight into liver function and are used during treatment of liver disease, but such information is limited. In the case of hepatocellular carcinoma (HCC, which is often not detected until an advanced stage, more sensitive biomarkers may help to achieve earlier detection. Serum also contains microRNAs, a class of small non-coding RNAs that play an important role in regulating gene expression. miR-122 is specific to the liver and correlates strongly with liver enzyme levels and necroinflammatory activity, and other microRNAs are correlated with the degree of fibrosis. miR-122 has also been found to be required for hepatitis C virus (HCV infection, whereas other microRNAs have been shown to play antiviral roles. miR-125a-5p and miR-1231 have been shown to directly target hepatitis B virus (HBV transcripts, and others are up- or down-regulated in infected individuals. MicroRNA profiles also differ in the case of HBV and HCV infection as well as between HBeAg-positive and negative patients, and in patients with occult versus active HBV infection. In such patients, monitoring of changes in microRNA profiles might provide earlier warning of neoplastic changes preceding HCC.

  20. [Gender-specific influencing factors on incidence, risk factors and outcome of carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas].

    Science.gov (United States)

    Grundmann, R T; Meyer, F

    2014-04-01

    This overview comments on gender-specific differences in incidence, risk factors and prognosis in patients with carcinoma of the liver, gallbladder, extrahepatic bile duct and pancreas. For the literature review, the MEDLINE database (PubMed) was searched under the key words "liver cancer", "gallbladder cancer", "extrahepatic bile duct carcinoma", "pancreatic cancer" AND "gender". There were significant gender differences in the epidemiology of the analysed carcinomas. The incidence of hepatocellular carcinoma (HCC) is much higher in men than in women, one of 86 men, but only 1 out of 200 women develop a malignant primary liver tumour in Germany in the course of their life. The lifetime risk for carcinomas of the gallbladder and extrahepatic bile ducts in Germany amounts to about 0.6 % for women and 0.5 % for men, specifically gallbladder carcinomas are observed more frequently in women than in men. For pancreatic cancer, no clear gender preference exists in Germany, although the mortality risk for men is higher than that for women (age-adjusted standardised death rate in men 12.8/100, 000 persons, in women 9.5). Remarkable is furthermore the shift of the tumour incidence in the last decades. Liver cancer has increased among men in Germany by about 50 % in the last 30 years, the incidence of gallbladder carcinoma has inversely dropped. The prognosis of these cancers across all tumour stages is uniformly bad in an unselected patient population. This is probably the main reason why only little - if any - gender differences in survival are described. In addition to avoiding the known risk factors such as hepatitis B and C virus infection, alcohol abuse, and smoking, the avoidance of overweight and obesity plays an increasingly important role in the prevention of these cancers. Georg Thieme Verlag KG Stuttgart · New York.

  1. 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.

  2. Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

    Science.gov (United States)

    Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

    2013-08-01

    Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

  3. 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.

  4. 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.

  5. Dietary Omega-3 polyunsaturated fatty acids promote colon carcinoma metastasis in rat liver

    NARCIS (Netherlands)

    Griffini, P.; Fehres, O.; Klieverik, L.; Vogels, I. M.; Tigchelaar, W.; Smorenburg, S. M.; van Noorden, C. J.

    1998-01-01

    The effects of Ohm-3 polyunsaturated fatty acids (PUFAs) and Ohm-6 PUFAs on the development of experimentally induced colon carcinoma metastasis in rat liver were investigated quantitatively in vivo. Rats mere kept on either a lon-fat diet or on a fish oil (Ohm-3 PUFAs) or safflower oil (Ohm-6

  6. A case of Esophageal small cell carcinoma with multiple liver metastases responding to chemotherapy with Irinotecan plus Cisplatin

    International Nuclear Information System (INIS)

    Endo, K.; Kohnoe, S.; Toh, Y.; Haraguchi, M.; Okamura, T.; Nishiyama, K.; Baba, H.; Maehara, Y.

    2005-01-01

    We report a case of small cell esophageal carcinoma (SCEC) with multiple liver metastases treated with some success by chemotherapy with irinotecan (CPT-11) plus cisplatin (CDDP). Radiologic and endoscopic examination of a 75-year-old man with multiple liver tumors disclosed a 4.0-cm type 2 tumor in the middle third of the esophagus. An endoscopically obtained biopsy specimen was diagnosed as undifferentiated small cell carcinoma. Multiple liver metastases were confirmed but lymph node metastases and distant metastases other than those in the liver were not detected. After six courses of chemotherapy with CPT-11 plus CDDP, the primary lesion showed complete response and liver metastases showed partial response. However, because all lesions almost immediately relapsed or progressed, arterial infusion chemotherapy for liver metastases and radiation for the primary lesion were given as second-line treatment. The primary lesion showed complete response with radiation. Arterial infusion chemotherapy prevented the progression of liver metastases once, but the patient died of liver failure at last. No distant lesions including metastatic lymph nodes were confirmed over the course of his illness, and the patient survived for a year after first diagnosis. Although the prognosis of SCEC is quite unfavorable due to highly aggressive behavior, a better prognosis is possible with effective chemotherapy and second-line treatment is important in improving prognosis

  7. Effect of New Water-Soluble Dendritic Phthalocyanines on Human Colorectal and Liver Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ebru YABAŞ

    2017-08-01

    Full Text Available Human hepatocellular carcinoma (HepG2 cells and colorectal adenocarcinoma (DLD-1 cells were treated with the synthesized water soluble phthalocyanine derivatives to understand the effect of the compounds both on colorectal and liver cancer cells. The compounds inhibited cell proliferation and displayed cytotoxic effect on these cancer cell lines however; the effect of the compounds on healthy control fibroblast cell line was comparatively lower. The compounds can be employed for cancer treatment as anticancer agents.

  8. Possible role of the scintigraphic estimation of the relative liver perfusion in the choice of treatment of liver carcinomas

    International Nuclear Information System (INIS)

    Artiko, V.; Obradovic, V.; Davidovic, B.; Petrovic, N.; Vlajkoviae, M.; Kostic, K.

    2005-01-01

    Full text: In the pre-evaluation and diagnosis of the patients with liver tumors, significant nuclear medicine methods used are: radiocolloid, blood pool, hepatobiliary scintigraphy, angioscintigraphy with radiolabeled microspheres as well as 'first pass' radionuclide angiography, which can precede all of the above mentioned methods, during single injection application. The aim of the study is evaluation of the possible role of the scintigraphic estimation of the relative liver perfusion in the choice of treatment of liver carcinomas. The study was performed in 120 patients: 24 controls (C), 35 with benign liver tumors (BT), 35 with hepatocellular carcinomas (HCC), 19 with metastases of colorectal carcinomas (MCC) as well as 7 with metastases of other tumors (MOT-bronchus, lung carcinoma and lymphoma). 7/35 HCC had cavernous portal vein developed after tumor thrombosis, 2 had complete thrombosis and 5 had incomplete thrombosis (thrombosis of the either of portal venous branches (3) and incomplete portal venous thrombosis -2). 2/19 patients with MCC had cavernous portal vein developed after tumor thrombosis, 3 had complete portal venous occlusion and 4 incomplete thrombosis (thrombosis of the either of branches). The study was performed with ROTA scintillation camera and Micro Delta computer, during 60 sec (1f/sec) from i.v.application of 740 MBq 99mTc-pertecnetate. TA curves were generated using liver ROI, spleen ROI and left kidney ROI, and curves were generated. Hepatic perfusion index was calculated using slope analysis (Portal slope Ps and arterial slope As) method according to following formula HPI=Ps/(Ps+As). Complementary methods used were Doppler ultrasonography, CT, MRI, tumor marker assays (CEA, Ca19-9, AFP) laboratory analyses, pathohistological finding and clinical diagnosis. In C, HPI was 0.68±0.06 which did not differ from the value in BT (0.64 ±0.08) (p>0.05). However, in HCC ( X=0.26±0.20), and LM (X=0.40±0.28), HPI values were significantly

  9. In vitro metabolism of [14C]-toluene by human and rat liver microsomes and liver slices

    International Nuclear Information System (INIS)

    Chapman, D.E.; Moore, T.J.; Michener, S.R.; Powis, G.

    1990-01-01

    Toluene metabolites produced by liver microsomes from six human donors included benzylalcohol (Balc), benzaldehyde (Bald) and benzoic acid (Bacid). Microsomes from only one human donor metabolized toluene to p-cresol and o-cresol. Human liver microsomes also metabolized Balc to Bald. Balc metabolism required NADPH, was inhibited by carbon monoxide, and was decreased at a buffer pH of 10. Balc metabolism was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P450 is responsible for the in vitro metabolism of Balc by human liver microsomes. Toluene metabolites formed by human liver slices and released into the incubation media included hippuric acid, and Bacid. Cresols or cresol-conjugates were not detected in liver slice incubation media from any human donor. Toluene metabolism by human liver was compared to metabolism by comparable liver preparations from male Fischer F344 rats. Rates of toluene metabolism by human liver microsomes and liver slices were 9-fold and 1.3-fold greater than for rat liver, respectively. Covalent binding of toluene to human liver microsomes and liver slices was 21-fold and 4-fold greater than for comparable rat liver preparations. Covalent binding of toluene to human microsomes required NADPH, was significantly decreased by coincubation with 4 mM cysteine or 4 mM glutathione, and radioactivity associated with microsomes was decreased by subsequent digestion of microsomes with protease. These results suggest that toluene metabolism and covalent binding of toluene are underestimated if the male Fischer 344 rat is used as a model for human toluene metabolism

  10. Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I. [Ural State Technical University - UPI, Division of Applied Biophysics, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University - UPI, Faculty of Experimental Physics (Russian Federation); Prokopenko, P. G. [Russian State Medical University, Faculty of Biochemistry (Russian Federation); Malakheeva, L. I. [Simbio Holding, Science Consultation Department (Russian Federation)

    2004-12-15

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  11. Comparative Study of Human Liver Ferritin and Chicken Liver by Moessbauer Spectroscopy. Preliminary Results

    International Nuclear Information System (INIS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-01-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Moessbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Moessbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  12. 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.

  13. 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

  14. HUMAN LIVER SLICES EXPRESS THE SAME LIDOCAINE BIOTRANSFORMATION RATE AS ISOLATED HUMAN HEPATOCYTES

    NARCIS (Netherlands)

    OLINGA, P; MEIJER, DKF; SLOOFF, MJH; GROOTHUIS, GMM; Merema, M.T.

    1993-01-01

    In order to investigate whether liver slices are a valuable tool for the assessment of drug metabolism in human liver, we compared the phase I metabolism of lidocaine in human liver slices and hepatocytes prepared from three human livers. Lidocaine is mainly metabolised to monoethylglycinexylidide

  15. Combination hyperthermia and intraarterial 5-FU for metastatic colon carcinoma to liver

    International Nuclear Information System (INIS)

    Moseley, H.S.; Palmquist, M.

    1984-01-01

    Metastatic colorectal carcinoma to the liver remains a formidable challenge. Responses to chemotherapy are brief and the number of effective drugs is very limited. A phase II trial of hepatic hyperthermia and intraarterial chemotherapy was undertaken to attempt to improve response rates and duration. Patients were given a 10 day course of IA 5-FU at 15 mg/kg. During the infusion hyperthermia was given five times using the BSD Annular Phased Array (APA). Thermistors were placed percutaneously into normal liver and tumor using ultrasound or CT scan guidance. Six patients have been treated. Significant problems in positioning ill patients in the APA were encountered, and there was difficulty also in preventing heating throughout the abdominal cavity. Four patients, all with poor performance status, failed to benefit. One patient had improvement in liver function studies for two months and failed to respond on a repeat course. One patient had a complete response which is continuing over 18 months with a liver scan reverting to normal and CEA returning to normal. These preliminary results are promising and warrant further trials

  16. 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)

  17. Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+ Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report

    Directory of Open Access Journals (Sweden)

    S. Guerriero

    2011-01-01

    Full Text Available Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year-old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end-stage liver disease with hepatocellular carcinoma and recurrent HCC, who presented with proptosis and diplopia of the left eye. CT scans of the head revealed a large, irregular mass in the left orbit causing superior and lateral destruction of the orbital bone. Biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of HCC metastasis to the orbit have been described in literature, and this is the first case in a previously transplanted HIV+, HBV+ patient.

  18. 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.

  19. Particle radiotherapy, a novel external radiation therapy, versus liver resection for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus: A matched-pair analysis.

    Science.gov (United States)

    Komatsu, Shohei; Kido, Masahiro; Asari, Sadaki; Toyama, Hirochika; Ajiki, Tetsuo; Demizu, Yusuke; Terashima, Kazuki; Okimoto, Tomoaki; Sasaki, Ryohei; Fukumoto, Takumi

    2017-12-01

    Hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus carries a dismal prognosis, and the feasibility of local treatment has remained controversial. The present study aimed to compare the outcomes of particle radiotherapy and liver resection in patients with hepatocellular carcinoma with inferior vena cava tumor thrombus. Thirty-one and 19 patients, respectively, underwent particle radiotherapy and liver resection for hepatocellular carcinoma with inferior vena cava tumor thrombus. A matched-pair analysis was undertaken to compare the short- and long-term outcomes according to tumor stage determined using the tumor-node-metastasis classification. Both stages IIIB and IV (IVA and IVB) patients were well-matched for 12 factors, including treatment policy and patient and tumor characteristics. The median survival time of matched patients with stage IIIB tumors in the particle radiotherapy group was greater than that in the liver resection group (748 vs 272 days, P = .029), whereas no significant difference was observed in the median survival times of patients with stage IV tumors (239 vs 311 days, respectively). There were significantly fewer treatment-related complications of grade 3 or greater in the particle radiotherapy group (0%) than in the liver resection group (26%). Particle radiotherapy is potentially preferable in hepatocellular carcinoma patients with stage IIIB inferior vena cava tumor thrombus and at least equal in efficiency to liver resection in those with stage IV disease, while causing significantly fewer complications. Considering the relatively high survival and low invasiveness of particle radiotherapy when compared to liver resection, this approach may represent a novel treatment modality for hepatocellular carcinoma with inferior vena cava tumor thrombus. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    Science.gov (United States)

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  1. Resultados do transplante hepático em portadores de hepatocarcinoma Results of orthotopic liver transplantation for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Mônica Beatriz PAROLIN

    2001-10-01

    hepatocarcinoma em fase inicial. Com seleção adequada, o transplante hepático oferece excelentes índices de sobrevida livre de recurrência tumoral.Background - Hepatocellular carcinoma is one of the most common malignancies worldwide. Liver transplantation has emerged as a good option for early-stage hepatocellular carcinoma yielding survival rates as good as for recipients without this type of tumor. Objective - To assess the outcome of cirrhotic patients with hepatocellular carcinoma undergoing liver transplantation at the Liver Transplantation Service of the "Hospital de Clínicas", Federal University of Paraná, Curitiba, PR, Brazil. Methods - Retrospective study of cirrhotic patients with hepatocellular carcinoma undergoing orthotopic liver transplantation at the mentioned Institution between September 1991 and September 2000. The diagnosis of hepatocellular carcinoma was established during the pretransplant workup in five patients and the tumor was an incidental finding in the native liver in three. The indication for liver transplantation was restricted to solitary tumor equal to or less than 5 cm or up to 3 nodules, with each nodule measuring less than 3 cm, and no evidence of vascular invasion or extrahepatic spread. Patient survival and evidence of tumoral recurrence posttransplant were evaluated. Results - The most common cause for pretransplantation liver disease was hepatitis C virus (50%. On examination of the explanted liver, the majority of patients (6/8, 75% had a single lesion; one patient had two nodules and one had a multifocal hepatocellular carcinoma found incidentally in the native liver. Tumor size ranged from 0,2 to 5,0 cm. All cases had neither vascular invasion nor linfonodal envolvement. All patients remained alive and free of tumor recurrence at the time of the study with a mean follow-up of 18,5 months (range, 5-29 months. Conclusion - Liver transplantation is a good therapeutic option for early stage hepatocellular carcinoma arising in

  2. Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

    Science.gov (United States)

    Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

    1989-01-01

    A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Roberta Resaz

    2014-09-01

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

  5. Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

    Science.gov (United States)

    Hamada, Yoshihiro; Nakayama, Yoshifuku

    Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  6. Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Kathy Han

    2007-01-01

    Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

  7. Diagnosis of Hepatocellular Carcinoma Complicating Liver Cirrhosis: Utility of Repeat Ultrasound-Guided Biopsy after Unsuccessful First Sampling

    International Nuclear Information System (INIS)

    Caturelli, Eugenio; Biasini, Elisabetta; Bartolucci, Francesca; Facciorusso, Domenico; Decembrino, Francesco; Attino, Vito; Bisceglia, Michele

    2002-01-01

    Purpose: To evaluate the utility of a second ultrasound-guided fine-needle biopsy of liver nodules thought to be hepatocellular carcinoma when the original biopsy has failed to provide a reliable diagnosis. Methods: Thirty-seven cirrhotic patients underwent ultrasound-guided fine-needle biopsy of liver nodules that were subsequently diagnosed as hepatocellular carcinoma. Each biopsy involved a single puncture with a 20 G cutting needle, which yielded pathologic material used both for cytologic and histologic studies. In 23 cases (mean diameter of nodules 48 mm) the biopsy furnished exclusively necrotic material (non-diagnostic subgroup); in the other 14 cases (mean diameter 26 mm) the biopsy yielded no neoplastic elements (false-negative subgroup). All 37 nodules were subjected to repeat biopsies performed in the same manner. Results: The repeat biopsies provided a diagnosis of hepatocellular carcinoma in six of the 23 patients from the non-diagnostic subgroup and in seven of the 14 in the false-negative subgroup. Overall, repeat biopsy produced a diagnostic gain of 35.1%. Conclusion: The chance of success with repeat biopsy of hepatocellular carcinoma is limited and may depend to some extent on the characteristics of the lesions (i.e., areas of necrosis in large nodules, well-differentiated cellular populations in small ones)

  8. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  9. [Conversion Therapy Using Etoposide and Cisplatin Chemotherapy for Liver Metastases from Advanced Gastric Mixed Adenoneuroendocrine Carcinoma - A Case Report].

    Science.gov (United States)

    Inaba, Yoko; Fujita, Maiko; Ninomiya, Riki; Hashimoto, Daijo

    2017-11-01

    Gastric mixed adenoneuroendocrine carcinoma(MANEC)with multiple liver metastases is a rare condition with most data being derived from case reports. We present a case with liver metastases from gastric MANEC that respond remarkably to chemotherapy. Sixty-one-year-old male with severe anemia referred to surgical consultation due to advanced gastric cancer with multiple liver metastases. To relieve uncontrollable tumor bleeding, simple distal gastrectomy for symptom palliation was performed. Based on the tentative diagnosis with gastric poorly differentiated adenocarcinoma, a course of TS-1 and oxaliplatin therapy was administrated. Thereafter final diagnosis with neuroendocrine carcinoma with tubular adenocarcinoma was made, and the chemotherapy was switched to etoposide and cisplatin. Follow up abdominal CT scan after the third course of the therapy showed remarkable tumor shrinkages(PR). In anticipation of the chemotherapy effects in the adjuvant setting, we performed liver metastasectomy for curative intent. Two of 6 resected liver specimens showed no viable cancer cells at all (pCR). However, immediately after the surgery, multiple liver metastases developed, and the recurrent masses had kept growing up rapidly. The third line carboplatin and etoposide chemotherapy was given once but was withdrawn because of bone marrow suppression. At the present, the patient is alive with recurrent diseases for 18 months after initial diagnosis.

  10. Primary liver carcinoma and liver cirrhosis in atomic bomb survivors, Hiroshima and Nagasaki, 1961-75, with special reference to HBs antigen

    International Nuclear Information System (INIS)

    Asano, Masahide; Kato, Hiroo; Yoshimoto, Keiko; Seyama, Shinichi; Itakura, Hideyo.

    1982-03-01

    During 1961-75, 128 cases of primary liver carcinoma (PLC) in the RERF Life Span Study extended sample and 301 cases of liver cirrhosis in the RERF Pathology Study sample were observed. All cases were assessed for hepatitis B surface antigen (HB sub(s) Ag) using orcein and aldehyde fuchsin staining. The incidence of PLC was 2.0 times higher in Nagasaki than in Hiroshima which was statistically significant, but the prevalence of liver cirrhosis showed hardly any difference between the two cities. Meaningful findings that may possibly explain the higher incidence of PLC in Nagasaki were that the presence of HB sub(s) Ag in the liver of patients without overt liver disease was 2.3 times higher in Nagasaki than in Hiroshima, and the prevalence of liver cirrhosis associated with PLC, especially that of posthepatitic cirrhosis with PLC, was almost 2.0 times higher in Nagasaki than in Hiroshima. In both cities a suggestive relationship of radiation dose with the prevalence of liver cirrhosis was noted but not with PLC. We believe that the higher incidence of PLC in Nagasaki is attributable to HB virus infection, though other factors, such as immunological competence affected by radiation, cannot be excluded. (author)

  11. Functional role of CCL5/RANTES for HCC progression during chronic liver disease

    NARCIS (Netherlands)

    Mohs, Antje; Kuttkat, Nadine; Reissing, Johanna; Zimmermann, Henning Wolfgang; Sonntag, Roland; Proudfoot, Amanda; Youssef, Sameh A.; de Bruin, Alain; Cubero, Francisco Javier; Trautwein, Christian

    Background & Aims: During liver inflammation, triggering fibrogenesis and carcinogenesis immune cells play a pivotal role. In the present study we investigated the role of CCL5 in human and in murine models of chronic liver inflammation leading to hepatocellular carcinoma (HCC) development. Methods:

  12. Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice

    OpenAIRE

    Xu, Xiaoling; Kobayashi, Shogo; Qiao, Wenhui; Li, Cuiling; Xiao, Cuiying; Radaeva, Svetlana; Stiles, Bangyan; Wang, Rui-Hong; Ohara, Nobuya; Yoshino, Tadashi; LeRoith, Derek; Torbenson, Michael S.; Gores, Gregory J.; Wu, Hong; Gao, Bin

    2006-01-01

    Cholangiocellular carcinoma (CC), the second most common primary liver cancer, is associated with a poor prognosis. It has been shown that CCs harbor alterations of a number of tumor-suppressor genes and oncogenes, yet key regulators for tumorigenesis remain unknown. Here we have generated a mouse model that develops CC with high penetrance using liver-specific targeted disruption of tumor suppressors SMAD4 and PTEN. In the absence of SMAD4 and PTEN, hyperplastic foci emerge exclusively from ...

  13. Isolation of primary human hepatocytes from normal and diseased liver tissue: a one hundred liver experience.

    Directory of Open Access Journals (Sweden)

    Ricky H Bhogal

    2011-03-01

    Full Text Available Successful and consistent isolation of primary human hepatocytes remains a challenge for both cell-based therapeutics/transplantation and laboratory research. Several centres around the world have extensive experience in the isolation of human hepatocytes from non-diseased livers obtained from donor liver surplus to surgical requirement or at hepatic resection for tumours. These livers are an important but limited source of cells for therapy or research. The capacity to isolate cells from diseased liver tissue removed at transplantation would substantially increase availability of cells for research. However no studies comparing the outcome of human hepatocytes isolation from diseased and non-diseased livers presently exist. Here we report our experience isolating human hepatocytes from organ donors, non-diseased resected liver and cirrhotic tissue. We report the cell yields and functional qualities of cells isolated from the different types of liver and demonstrate that a single rigorous protocol allows the routine harvest of good quality primary hepatocytes from the most commonly accessible human liver tissue samples.

  14. Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery

    Energy Technology Data Exchange (ETDEWEB)

    Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kumita, Shin-ichiro [Nippon Medical School, Department of Radiology, Center for Advanced Medical Technology, Tokyo (Japan); Kawamoto, Chiaki [Nippon Medical School, Department of Internal Medicine, Tokyo (Japan); Uchida, Eiji [Nippon Medical School, Department of Surgery, Tokyo (Japan)

    2017-06-15

    To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. (orig.)

  15. American Liver Foundation

    Science.gov (United States)

    ... Cirrhosis Clinical Trials Galactosemia Gilbert Syndrome Hemochromatosis Hepatic Encephalopathy Hepatitis A Hepatitis B Hepatitis C Hepatocellular Carcinoma Lysosomal Acid Lipase Deficiency(LALD) Intrahepatic Cholestasis of Pregnancy (ICP) Liver Biopsy Liver Cancer Liver Cysts Liver Function Tests ...

  16. 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.

  17. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  18. Development of models to predict early post-transplant recurrence of hepatocellular carcinoma that also integrate the quality and characteristics of the liver graft: A national registry study in China.

    Science.gov (United States)

    Ling, Qi; Liu, Jimin; Zhuo, Jianyong; Zhuang, Runzhou; Huang, Haitao; He, Xiangxiang; Xu, Xiao; Zheng, Shusen

    2018-04-27

    Donor characteristics and graft quality were recently reported to play an important role in the recurrence of hepatocellular carcinoma after liver transplantation. Our aim was to establish a prognostic model by using both donor and recipient variables. Data of 1,010 adult patients (training/validation: 2/1) undergoing primary liver transplantation for hepatocellular carcinoma were extracted from the China Liver Transplant Registry database and analyzed retrospectively. A multivariate competing risk regression model was developed and used to generate a nomogram predicting the likelihood of post-transplant hepatocellular carcinoma recurrence. Of 673 patients in the training cohort, 70 (10.4%) had hepatocellular carcinoma recurrence with a median recurrence time of 6 months (interquartile range: 4-25 months). Cold ischemia time was the only independent donor prognostic factor for predicting hepatocellular carcinoma recurrence (hazard ratio = 2.234, P = .007). The optimal cutoff value was 12 hours when patients were grouped according to cold ischemia time at 2-hour intervals. Integrating cold ischemia time into the Milan criteria (liver transplantation candidate selection criteria) improved the accuracy for predicting hepatocellular carcinoma recurrence in both training and validation sets (P hepatocellular carcinoma recurrence after liver transplantation. Additionally, donor anti-hepatitis B core antibody positivity, prolonged cold ischemia time, and anhepatic time were linked to the intrahepatic recurrence, whereas older donor age, prolonged donor warm ischemia time, cold ischemia time, and ABO incompatibility were relevant to the extrahepatic recurrence. The graft quality integrated models exhibited considerable predictive accuracy in early hepatocellular carcinoma recurrence risk assessment. The identification of donor risks can further help understand the mechanism of different patterns of recurrence. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Human papillomavirus DNA in aerodigestive squamous carcinomas ...

    African Journals Online (AJOL)

    A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...

  20. Radiological evaluation of a liver simulator in comparison to a human real liver

    International Nuclear Information System (INIS)

    Toledo, Janine M.; Campos, Tarcisio P.R. de

    2009-01-01

    The present study evaluates the radiological features of a human real healthy liver reproducing its characteristics on a developed liver simulator. The radiological evaluation will be performed through radiological methods such as CT and X-ray images, density and weight measurements, as well as representation of the coloration and texture. According to literature, the liver is the highest weight organ and gland of the body, weighing approximately 1,5 kg. On the liver, the nutrients are absorbed from the digestive tract and are prosecuted and stored for future use by other organs. Also the liver is responsible for the neutralization and elimination of various toxic substances. Thus, it is an interface between the digestive system and the blood. Besides, this organ is the principal source of plasmatic proteins like the albumin, transport of graxos oily acids. Due to its proprieties, the liver holds a large amount of radionuclides on any uptake from external source. The liver simulator was designed to have the same density, weight and corresponding shape. The radiographic image was produced by conventional X-rays machine, in which the radiographic applied parameters were the same applied to abdomen. The result of the radiographic and CT images demonstrates radiological equivalence between the simulator and human real liver. Hounsfield number of the synthetic liver tissue was found on the range of human livers. Therefore, due to its similar shape, chemical composition, radiological response, the liver simulator can be used to investigate ionizing radiation procedures during radiation therapy intervention. (author)

  1. Lyman NTCP model analysis of radiation-induced liver disease in hypofractionated conformal radiotherapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu Zhiyong; Zhu Yi; Zhao Jiaodong; Fu Xiaolong; Jiang Guoliang; Liang Shixiong; Zhu Xiaodong

    2006-01-01

    Objective: To identify the factors associated with radiation-induced liver disease (RILD) and to describe the probability of RILD using the Lyman normal tissue complication(NTCP) model for primary liver carcinoma(PLC) treated with hypofractionated conformal therapy (CRT). Methods: A total of 109 PLC patients treated with hypofractionated CRT were prospectively followed according to the Child-Pugh classification for liver cirrhosis, 93 patients in class A and 16 in class B. The mean dose of radiation to the isocenter was (53.5±5.5) Gy, fractions of (4.8±0.5) Gy, with interfraction interval of 48 hours and irradiation 3 times per week. Maximal likelihood analysis yielded the best estimates of parameters of the Lyman NTCP model for all patients; Child-Pugh A and Child-Pugh B patients, respectively. Results: Of all the patients, 17 developed RILD (17/109), 8 in Child-Pugh A (8/93) and 9 in Child-Pugh B (9/16). By multivariate analysis, only the Child-Pugh Grade of liver cirrhosis was the independent factor (P=0.000) associated with the developing of BILD. The best estimates of the NTCP parameters for all 109 patients were n=1.1, m=0.35 and TD 50 (1)=38.5 Gy. The n, m, TD 50 (1) estimated from patients with Child-Pugh A was 1.1, 0.28, 40.5 Gy, respectively, compared with 0.7, 0.43, 23 Gy respectively, for patients with Child-Pugh B. Conclusions: Primary liver cancer patients who possess Child-Pugh B cirrhosis would present a significantly greater susceptibility to RILD after hypofractionated CRT than patients with Child-Pugh A cirrhosis. The predominant risk factor for developing RILD is the severity of hepatic cirrhosis in the liver of PLC patients. (authors)

  2. Radiofrequency ablation of hepatocellular carcinoma located in the liver dome under intermittent CT fluoroscopy guidance

    Energy Technology Data Exchange (ETDEWEB)

    Park, Darlene; Cho, Yun Ku; Cho, Hyun Je; KIm, Mi Young [Dept. of Radiology, VHS Medical Center, Seoul (Korea, Republic of)

    2014-02-15

    To evaluate the clinical effectiveness of an intermittent computed tomography (CT) fluoroscopy-guided radiofrequency (RF) ablation of hepatocellular carcinoma located in the liver dome. Between 2005 and 2010 23 patients with hepatocellular carcinoma (HCC) nodules located in the liver dome underwent an intermittent CT fluoroscopy-guided RF ablation. The primary endpoint was the local tumor progression. Procedure-related complications occurred in 3 of 23 patients. To evaluate the prognostic factors for the local tumor progression, univariate and multivariate analyses were performed using the Cox proportional hazards model. The chi-squared test was performed to evaluate the association of access route and procedure-related complication. The study was approved by the Institutional Review Board of our hospital. The Tumor sizes ranged between 1.0 and 2.9 cm. An initial complete ablation was achieved in all patients. The median follow-up period was 31 months and the major complication rate was 4.3%. The cumulative rate of local tumor progression at 3 years was 20%. The univariate analysis revealed that only serum total bilirubin level (p = 0.048) and prior chemoembolization were statistically significant (p = 0.044), but there was no independently significant prognostic factor on multivariate analysis. Procedure-related complications occurred in 3 of 23 patients. For HCC located in the liver dome an intermittent CT fluoroscopy-guided RF ablation could be performed safely and effectively.

  3. Small hepatocellular carcinomas in chronic liver disease: Detection with SPECT

    Energy Technology Data Exchange (ETDEWEB)

    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%.

  4. Liver damage and senescence increases in patients developing hepatocellular carcinoma.

    Science.gov (United States)

    Rey, Silvia; Quintavalle, Cristina; Burmeister, Katharina; Calabrese, Diego; Schlageter, Manuel; Quagliata, Luca; Cathomas, Gieri; Diebold, Joachim; Molinolo, Alfredo; Heim, Markus H; Terracciano, Luigi M; Matter, Matthias S

    2017-08-01

    Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes a continuous damage leading to liver cirrhosis and eventually HCC. However, only a minority of cirrhotic patients develop HCC. To assess a possible differential impact of liver inflammation in patients developing HCC versus patients remaining tumor-free, we designed a longitudinal study and analysed liver tissue of the same patients (n = 33) at two points in time: once when no HCC was present and once several years later when an HCC was present. As a control group, we followed cirrhotic patients (n = 37) remaining tumor-free over a similar time frame. We analysed cell damage and senescence of hepatocytes by measuring γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, nuclear size, and telomere length. γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, in the first liver biopsy was similar in patients developing HCC later on and cirrhotic patients remaining tumor free. In contrast, γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, was significantly higher in the second non-tumoral liver biopsy of HCC patients than in the control patients. Consequently, the individual increase in γ-H2AX positivity, p16 INK4 and p21 WAF/Cip1 expression, from the first biopsy to the second biopsy was significantly higher in patients developing HCC than in patients remaining tumor free. In addition, changes in nuclear size and telomere length revealed a more pronounced cell aging in patients developing HCC than in patients remaining tumor free. Hepatocytes from patients developing HCC go through more pronounced cell damage and senescence in contrast to cirrhotic patients remaining tumor free. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  5. Prevention of carcinoma of cervix with human papillomavirus vaccine.

    Science.gov (United States)

    Gavarasana, S; Kalasapudi, R S; Rao, T D; Thirumala, S

    2000-01-01

    Carcinoma of cervix is the most common cancer found among the women of India. Though cervical cytology screening was effective in preventing carcinoma of cervix in developed nations, it is considered unsuitable in developing countries. Recent research has established an etiological link between human papillomavirus infection and carcinoma of cervix. In this review, an attempt is made to answer the question, 'whether carcinoma of cervix can be prevented with human papillomavirus vaccine?' Literature search using Pubmed and Medline was carried out and relevant articles were reviewed. There is ample experimental evidence to show that DNA of human papillomavirus integrates with cervical cell genome. Viral genes E6 and E7 of HPV type 16 and 18 inactivate p53 function and Rb gene, thus immortalize the cervical epithelial cells. Recombinant vaccines blocked the function of E6 and E7 genes preventing development of papillomas in animals. Vaccination with HPV-VLPs encoding for genes of E6 and E7 neutralizes HPV integrated genome of malignant cells of uterine cervix. Based on experimental evidence, it is possible to prevent carcinoma of cervix with human papillomavirus vaccine, Further research is necessary to identify a effective and safe HPV vaccine, routes of administration and characteristics of potential beneficiaries.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Comparison of the multi-drug resistant human hepatocellular carcinoma cell line Bel-7402/ADM model established by three methods

    Directory of Open Access Journals (Sweden)

    Zhong Xingguo

    2010-08-01

    Full Text Available Abstract Background To compare the biological characteristics of three types of human hepatocellular carcinoma multi-drug resistant cell sub-lines Bel-7402/ADM models established by three methods. Methods Established human hepatocellular carcinoma adriamycin (ADM multi-drug resistant cell sub-lines models Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS by three methods of in vitro concentration gradient increased induction, nude mice liver-implanted induction and subcutaneous-implanted induction respectively. Phase contrast microscopy was used to observe the cells and the MTT (methyl thiazolyl tetrazolium method was used to detect drug resistance of the three different sub-lines of cells. Results The three groups of drug resistant cells, Bel-7402/ADMV, Bel-7402/ADML and Bel-7402/ADMS generated cross-resistance to ADM and CDDP (cis-Diaminedichloroplatinum, but showed a significant difference in resistance to Bel-7402 IC50 value (P V, 46 h (Bel-7402/ADML, and 45 h (Bel-7402/ADMS. The excretion rates of ADM were significantly increased compared with the parent cell (34.14% line and were 81.06% (Bel-7402/ADMV, 66.56% (Bel-7402/ADML and 61.56% (Bel-7402/ADMS. Expression of P-gp and MRP in the three groups of resistant cells was significantly enhanced (P P > 0.05. Conclusions Stable resistance was involved in the resistant cell line model established by the above three methods. Liver implantation was a good simulation of human hepatocellular and proved to be an ideal model with characteristics similar to human hepatocellular biology and the pharmacokinetics of anticancer drugs.

  8. Multifocal manifestation does not affect vascular invasion of hepatocellular carcinoma: implications for patient selection in liver transplantation

    NARCIS (Netherlands)

    Löhe, Florian; Angele, Martin K.; Rentsch, Markus; Graeb, Christian; Gerbes, Alexander; Löhrs, Udo; Beuers, Ulrich; Jauch, Karl-Walter

    2008-01-01

    BACKGROUND AND AIMS: Liver transplantation (OLT) for hepatocellular carcinoma (HCC) improves patient survival when tumor size and number are limited according to the Milan criteria. However, the impact of tumor size vs. the number of lesions for tumor recurrence after OLT is unclear. Microvascular

  9. Rising Rates of Hepatocellular Carcinoma Leading to Liver Transplantation in Baby Boomer Generation with Chronic Hepatitis C, Alcohol Liver Disease, and Nonalcoholic Steatohepatitis-Related Liver Disease.

    Science.gov (United States)

    Cholankeril, George; Yoo, Eric R; Perumpail, Ryan B; Liu, Andy; Sandhu, Jeevin S; Nair, Satheesh; Hu, Menghan; Ahmed, Aijaz

    2017-09-26

    We aim to study the impact of the baby boomer (BB) generation, a birth-specific cohort (born 1945-1965) on hepatocellular carcinoma (HCC)-related liver transplantation (LT) in patients with chronic hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic steatohepatitis (NASH). We performed a retrospective analysis using the United Network for Organ Sharing (UNOS)/Organ Procurement Transplant Network (OPTN) database from 2003 to 2014 to compare HCC-related liver transplant surgery trends between two cohorts-the BB and non-BB-with a secondary diagnosis of HCV, ALD, or NASH. From 2003-2014, there were a total of 8313 liver transplant recipients for the indication of HCC secondary to HCV, ALD, or NASH. Of the total, 6658 (80.1%) HCC-related liver transplant recipients were BB. The number of liver transplant surgeries for the indication of HCC increased significantly in NASH (+1327%), HCV (+382%), and ALD (+286%) during the study period. The proportion of BB who underwent LT for HCC was the highest in HCV (84.7%), followed by NASH (70.3%) and ALD (64.7%). The recommendations for birth-cohort specific HCV screening stemmed from a greater understanding of the high prevalence of chronic HCV and HCV-related HCC within BB. The rising number of HCC-related LT among BB with ALD and NASH suggests the need for increased awareness and improved preventative screening/surveillance measures within NASH and ALD cohorts as well.

  10. Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons

    DEFF Research Database (Denmark)

    Nielsen, Lene Ryom; Lundgren, Jens Dilling; De Wit, Stéphane

    2016-01-01

    OBJECTIVES: Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. DESIGN: Prospective...

  11. Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons

    NARCIS (Netherlands)

    Ryom, Lene; Lundgren, Jens Dilling; de Wit, Stéphane; Kovari, Helen; Reiss, Peter; Law, Matthew; El-Sadr, Wafa; Monforte, Antonella D.'Arminio; Mocroft, Amanda; Smith, Colette; Fontas, Eric; Dabis, Francois; Phillips, Andrew; Sabin, Caroline

    2016-01-01

    Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown. Prospective cohort study. Data

  12. 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 ...

  13. Treatment of unresectable hepatocellular carcinoma with intrahepatic yttrium 90 microspheres: factors associated with liver toxicities.

    Science.gov (United States)

    Goin, James E; Salem, Riad; Carr, Brian I; Dancey, Janet E; Soulen, Michael C; Geschwind, Jean Francois H; Goin, Kathleen; Van Buskirk, Mark; Thurston, Kenneth

    2005-02-01

    Intraarterial injection of yttrium 90 microspheres (TheraSpheres) is used in the treatment of hepatocellular carcinoma (HCC). This article presents an analysis of the incidence of liver toxicities (liver-related events) and pretreatment factors associated with liver toxicities after TheraSphere treatment. Eighty-eight TheraSphere-treated patients with low 90-day mortality risk were selected for analysis, with liver toxicities coded with use of standard oncology criteria. Descriptive and inferential statistical methods were applied to estimate the incidence of liver toxicities and to evaluate the influence of liver radiation dose and various pretreatment factors on the risk of their occurrence. Sixty-eight liver toxicities occurred in 37 of the 88 patients (42%). Thirty-two patients (36%) experienced 50 liver toxicities after the first treatment and nine of 23 patients (39%) who received a second treatment experienced 18 liver toxicities. Pretreatment total bilirubin and liver radiation dose were found to be associated with the risk of at least one liver toxicity and with the time to first occurrence of a liver toxicity after first treatment. Pretreatment total bilirubin also was associated with liver toxicities after the second treatment. Most of the toxicities resolved; however, those that did not resolve were attributed to tumor progression or advancing cirrhosis. The risk of liver toxicities in patients with unresectable HCC treated with TheraSpheres increases with increasing pretreatment total bilirubin level and liver radiation dose to a maximum of 150 Gy for a single administration. The toxicities attributed to treatment resolved over time, and none of the patients studied had confirmed radiation-induced liver disease. Consequently, doses as high as 150 Gy on a single administration and as high as 268 Gy on repeated administrations were well tolerated.

  14. Alpha?fetoprotein elevation in NUT midline carcinoma: a case report

    OpenAIRE

    D?Ambrosio, Lorenzo; Palesandro, Erica; Moretti, Marina; Pelosi, Giuseppe; Fabbri, Alessandra; Carnevale Schianca, Fabrizio; Aglietta, Massimo; Grignani, Giovanni

    2017-01-01

    Background Nuclear protein in testis (NUT) midline carcinoma is a rarely diagnosed and potentially under-recognized type of squamous carcinoma that is considered one of the most aggressive human solid tumors. Alpha-fetoprotein elevation has been associated with chronic liver diseases and a limited number of cancers. In particular, in presence of a mediastinal mass in a young man, alpha-fetoprotein elevation is considered nearly pathognomonic of a non-seminoma germ-cell tumor. Case presentatio...

  15. Accuracy of hepatocellular carcinoma detection on multidetector CT in a transplant liver population with explant liver correlation

    International Nuclear Information System (INIS)

    Addley, H.C.; Griffin, N.; Shaw, A.S.; Mannelli, L.; Parker, R.A.; Aitken, S.; Wood, H.; Davies, S.; Alexander, G.J.; Lomas, D.J.

    2011-01-01

    Aim: To evaluate the diagnostic accuracy of multidetector computed tomography (MDCT) for hepatocellular carcinoma (HCC) in cirrhotic patients undergoing liver transplantation. Secondary aims were to examine the effect of radiologist experience and lesion size on diagnostic accuracy. Materials and methods: Thirty-nine patients (72% male with a mean age of 56.5 years) underwent liver transplantation following preoperative triple-phase MDCT examination of the liver. MDCT examinations were retrospectively independently reviewed by three radiologists for the presence and location of suspected HCCs, with the diagnostic confidence recorded using a five-point confidence scale. MDCT examinations were compared with explant specimens for histopathological correlation. Results: Histopathological results demonstrated 46 HCCs in 29 of the 39 patients. Analysis demonstrated a sensitivity of 65-75% and specificity of 47-88% for detection of HCC lesions. The sensitivity dropped to 48-57% for lesions of size ≤20 mm. As the diagnostic confidence increased, there was a further decrease in the sensitivity (4-26%). The radiologist with the greatest number of years experience was found to have a significantly higher accuracy of detection of HCC lesions compared with the least experienced radiologist. Conclusion: Larger lesion size of HCC and greater number of years experience of the radiologist resulted in significantly higher accuracy of HCC lesion detection. The overall sensitivity and specificity results for MDCT detection of HCC are comparable to previous helical CT imaging.

  16. Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption of Smad4 and Pten in mice.

    Science.gov (United States)

    Xu, Xiaoling; Kobayashi, Shogo; Qiao, Wenhui; Li, Cuiling; Xiao, Cuiying; Radaeva, Svetlana; Stiles, Bangyan; Wang, Rui-Hong; Ohara, Nobuya; Yoshino, Tadashi; LeRoith, Derek; Torbenson, Michael S; Gores, Gregory J; Wu, Hong; Gao, Bin; Deng, Chu-Xia

    2006-07-01

    Cholangiocellular carcinoma (CC), the second most common primary liver cancer, is associated with a poor prognosis. It has been shown that CCs harbor alterations of a number of tumor-suppressor genes and oncogenes, yet key regulators for tumorigenesis remain unknown. Here we have generated a mouse model that develops CC with high penetrance using liver-specific targeted disruption of tumor suppressors SMAD4 and PTEN. In the absence of SMAD4 and PTEN, hyperplastic foci emerge exclusively from bile ducts of mutant mice at 2 months of age and continue to grow, leading to tumor formation in all animals at 4-7 months of age. We show that CC formation follows a multistep progression of histopathological changes that are associated with significant alterations, including increased levels of phosphorylated AKT, FOXO1, GSK-3beta, mTOR, and ERK and increased nuclear levels of cyclin D1. We further demonstrate that SMAD4 and PTEN regulate each other through a novel feedback mechanism to maintain an expression balance and synergistically repress CC formation. Finally, our analysis of human CC detected PTEN inactivation in a majority of p-AKT-positive CCs, while about half also lost SMAD4 expression. These findings elucidate the relationship between SMAD4 and PTEN and extend our understanding of CC formation.

  17. 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

  18. 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

  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. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  1. Extracellular Matrix Molecular Remodeling in Human Liver Fibrosis Evolution.

    Directory of Open Access Journals (Sweden)

    Andrea Baiocchini

    Full Text Available Chronic liver damage leads to pathological accumulation of ECM proteins (liver fibrosis. Comprehensive characterization of the human ECM molecular composition is essential for gaining insights into the mechanisms of liver disease. To date, studies of ECM remodeling in human liver diseases have been hampered by the unavailability of purified ECM. Here, we developed a decellularization method to purify ECM scaffolds from human liver tissues. Histological and electron microscopy analyses demonstrated that the ECM scaffolds, devoid of plasma and cellular components, preserved the three-dimensional ECM structure and zonal distribution of ECM components. This method has been then applied on 57 liver biopsies of HCV-infected patients at different stages of liver fibrosis according to METAVIR classification. Label-free nLC-MS/MS proteomics and computation biology were performed to analyze the ECM molecular composition in liver fibrosis progression, thus unveiling protein expression signatures specific for the HCV-related liver fibrotic stages. In particular, the ECM molecular composition of liver fibrosis was found to involve dynamic changes in matrix stiffness, flexibility and density related to the dysregulation of predominant collagen, elastic fibers and minor components with both structural and signaling properties. This study contributes to the understanding of the molecular bases underlying ECM remodeling in liver fibrosis and suggests new molecular targets for fibrolytic strategies.

  2. 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

  3. Multi-slice CT three dimensional volume measurement of tumors and livers in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yu Yuanlong; Li Liangcai; Tang Binghang; Hu Zemin

    2004-01-01

    Objective: To examine the accuracy of multi-slice CT (MSCT) three dimensional (3D) volume measurement of tumors and livers in hepatocellular carcinoma cases by using immersion method as the standard. Methods: (1) The volume of 25 porkling livers was measured using immersion method in experiment group in vitro. Then the models were built according to Matsumoto's method and CT scanning and special software were used to measure the volume of the livers. (2) The volume of the tumors in 25 cases of hepatocellular carcinoma was measured using diameter measurement method and special volume measurement software (tissue measurements). Two tumors of them were measured respectively using MSCT 3D measurement, diameter measurement before the operation and immersion method after the operation. The data of the two groups were examined using pairing t test. Results: (1) The volume range of 25 porkling livers was 68.50-1150.10 ml using immersion method and 69.78-1069.97 ml using MSCT 3D measurement. There was no significant difference of the data in these two groups using t-test (t=1.427, P>0.05). (2) The volume range of 25 hepatocellular tumors was 395.16-2747.7 ml using diameter measurement and 203.10-1463.19 ml using MSCT 3D measurement before the operation. There was significant difference of the data in these two groups using t-test (t=7.689, P<0.001). In 2 ablated tumors, 1 case's volume was (21.75±0.60) ml using MSCT 3D measurement and 33.73 ml using diameter measurement before the operation and 21.50 ml using immersion measurement after the operation. The other case's volume was (696.13±5.30) ml using MSCT 3D measurement and 1323.51 ml using diameter measurement before the operation and 685.50 ml using immersion measurement after the operation. Conclusion: MSCT 3D volume measurement can accurately measure the volume of tumor and liver and has important clinical application value. There is no significant difference between MSCT 3D volume measurement and immersion method

  4. Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

    Science.gov (United States)

    Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

    2018-01-01

    Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

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

    Science.gov (United States)

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

    2016-09-01

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

  6. Perfusion computed tomography for detection of hepatocellular carcinoma in patients with liver cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Michael A.; Kartalis, Nikolaos; Grigoriadis, Aristeidis; Loizou, Louiza; Leidner, Bertil; Aspelin, Peter; Brismar, Torkel B. [Karolinska Institute, Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Stockholm (Sweden); Karolinska University Hospital, Department of Radiology, Stockholm (Sweden); Staal, Per [Karolinska University Hospital, Department of Hepatology, Stockholm (Sweden)

    2015-11-15

    To evaluate the diagnostic performance of dynamic perfusion CT (P-CT) for detection of hepatocellular carcinoma (HCC) in the cirrhotic liver. Twenty-six cirrhotic patients (19 men, aged 69 ± 10 years) with suspicion of HCC prospectively underwent P-CT of the liver using the 4D spiral-mode (100/80 kV; 150/175mAs/rot) of a dual-source system. Two readers assessed: (1) arterial liver-perfusion (ALP), portal-venous liver-perfusion (PLP) and hepatic perfusion-index (HPI) maps alone; and (2) side-by-side with maximum-intensity-projections of arterial time-points (art-MIP) for detection of HCC using histopathology and imaging follow-up as standard of reference. Another reader quantitatively assessed perfusion maps of detected lesions. A total of 48 HCCs in 21/26 (81 %) patients with a mean size of 20 ± 10 mm were detected by histopathology (9/48, 19 %) or imaging follow-up (39/48, 81 %). Detection rates (Reader1/Reader2) of HPI maps and side-by-side analysis of HPI combined with arterial MIP were 92/88 % and 98/96 %, respectively. Positive-predictive values were 63/63 % and 68/71 %, respectively. A cut-off value of ≥85 % HPI and ≥99 % HPI yielded a sensitivity and specificity of 100 %, respectively, for detection of HCC. P-CT shows a high sensitivity for detection of HCC in the cirrhotic liver. Quantitative assessment has the potential to reduce false-positive findings improving the specificity of HCC diagnosis. (orig.)

  7. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    International Nuclear Information System (INIS)

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  8. 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

  9. Ultrasound manifestation of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. A mouse radiation-induced liver disease model for stereotactic body radiation therapy validated in patients with hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wu, Zhi-Feng; Zhang, Jian-Ying; Shen, Xiao-Yun; Gao, Ya-Bo; Hu, Yong; Zeng, Zhao-Chong; Zhou, Le-Yuan

    2016-01-01

    Purpose: Lower radiation tolerance of the whole liver hinders dose escalations of stereotactic body radiation therapy (SBRT) in hepatocellular carcinoma (HCC) treatment. This study was conducted to define the exact doses that result in radiation-induced liver disease (RILD) as well as to determine dose constraints for the critical organs at risk (OARs) in mice; these parameters are still undefined in HCC SBRT. Methods: This study consisted of two phases. In the primary phase, mice treated with helical tomotherapy-based SBRT were stratified according to escalating radiation doses to the livers. The pathological differences, signs [such as mouse performance status (MPS)], and serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/albumin levels were observed. Radiation-induced disease severities of the OARs were scored using systematic evaluation standards. In the validation phase in humans, 13 patients with HCC who had undergone radiotherapy before hepatectomy were enrolled to validate RILD pathological changes in a mouse study. Results: The evaluation criteria of the mouse liver radiotherapy-related signs were as follows: MPS ≥ 2.0 ± 0.52, AST/ALT ≥ 589.2 ± 118.5/137.4 ± 15.3 U/L, serum albumin ≤ 16.8 ± 2.29 g/L. The preliminary dose constraints of the OARs were also obtained, such as those for the liver (average dose ≤ 26.36 ± 1.71 Gy) and gastrointestinal tract (maximum dose ≤ 22.63 Gy). Mouse RILD models were able to be developed when the livers were irradiated with average doses of ≥31.76 ± 1.94 Gy (single fraction). RILD pathological changes in mice have also been validated in HCC patients. Conclusions: Mouse RILD models could be developed with SBRT based on the dose constraints for the OARs and evaluation criteria of mouse liver radiotherapy-related signs, and the authors’ results favor the study of further approaches to treat HCC with SBRT.

  11. Salvage liver transplantation for patients with recurrent hepatocellular carcinoma after curative resection.

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    LinWei Wu

    Full Text Available OBJECTIVE: To summarize the experience with salvage liver transplantation (SLT for patients with recurrent hepatocellular carcinoma (HCC after primary hepatic resection in a single center. METHODS: A total of 376 adult patients with HCC underwent orthotopic liver transplantation (OLT at Organ Transplantation Center, the First Affiliated Hospital of Sun Yat-sen University, between 2004 and 2008. Among these patients, 36 underwent SLT after primary liver curative resection due to intrahepatic recurrence. During the same period, one hundred and forty-seven patients with HCC within Milan criteria underwent primary OLT (PLTW group, the intra-operative and post-operative parameters were compared between these two groups. Furthermore, we compared tumor recurrence and patient survival of patients with SLT to 156 patients with HCC beyond Milan criteria (PLTB group. Cox Hazard regression was made to identify the risk factors for tumor recurrence. RESULTS: The median interval between initial liver resection and SLT was 35 months (1-63 months. The intraoperative blood loss (P0.05. When compared to those patients with HCC beyond Milan criteria undergoing primary OLT, patients undergoing SLT achieved a better survival and a lower tumor recurrence. Cox Proportional Hazards model showed that vascular invasion, including macrovascular and microvascular invasion, as well as AFP level >400 IU/L were risk factors for tumor recurrence after LT. CONCLUSIONS: In comparison with primary OLT, although SLT is associated with increased operation difficulties, it provides a good option for patients with HCC recurrence after curative resection.

  12. Bone mineral density predicts posttransplant survival among hepatocellular carcinoma liver transplant recipients.

    Science.gov (United States)

    Sharma, Pratima; Parikh, Neehar D; Yu, Jessica; Barman, Pranab; Derstine, Brian A; Sonnenday, Christopher J; Wang, Stewart C; Su, Grace L

    2016-08-01

    Hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). Recent data suggest that body composition features strongly affect post-LT mortality. We examined the impact of body composition on post-LT mortality in patients with HCC. Data on adult LT recipients who received Model for End-Stage Liver Disease exception for HCC between February 29, 2002, and December 31, 2013, and who had a computed tomography (CT) scan any time 6 months prior to LT were reviewed (n = 118). All available CT scan Digital Imaging and Communication in Medicine files were analyzed using a semiautomated high throughput methodology with algorithms programmed in MATLAB. Analytic morphomics measurements including dorsal muscle group (DMG) area, visceral and subcutaneous fat, and bone mineral density (BMD) were taken at the bottom of the eleventh thoracic vertebral level. Thirty-two (27%) patients died during the median follow-up of 4.4 years. The number of HCC lesions (hazard ratio [HR], 2.81; P DMG area did not affect post-LT survival. In conclusion, in addition to number of HCC lesions and pre-LT locoregional therapy, low BMD, a surrogate for bone loss rather than DMG area, was independently associated with post-LT mortality in HCC patients. Bone loss may be an early marker of deconditioning that precedes sarcopenia and may affect transplant outcomes. Liver Transplantation 22 1092-1098 2016 AASLD. © 2016 American Association for the Study of Liver Diseases.

  13. Pure Laparoscopic Versus Open Liver Resection for Primary Liver Carcinoma in Elderly Patients: A Single-Center, Case-Matched Study.

    Science.gov (United States)

    Wang, Xi-Tao; Wang, Hong-Guang; Duan, Wei-Dong; Wu, Cong-Ying; Chen, Ming-Yi; Li, Hao; Huang, Xin; Zhang, Fu-Bo; Dong, Jia-Hong

    2015-10-01

    Pure laparoscopic liver resection (PLLR) has been reported to be as safe and effective as open liver resection (OLR) for liver lesions, and it is associated with less intraoperative blood loss, shorter hospital stay, and lower complication rate. However, studies comparing PLLR with OLR in elderly patients were limited. The aim of this study was to analyze the short-term outcome of PLLR versus OLR for primary liver carcinoma (PLC) in elderly patients.Between January 2008 and October 2014, 30 consecutive elderly patients (≥70 years) who underwent PLLR for PLC were included into analysis. Sixty patients who received OLR for PLC during the same study period were also included as a case-matched control group. Patients were well matched in terms of age, sex, comorbid illness, Child Pugh class, American Society of Anesthesiologists grade, tumor size, tumor location, and extent of hepatectomy.No significant differences were observed with regard to patient preoperative baseline status, median tumor size (Group PLLR 4.0 cm vs Group OLR 5.0 cm, P = 0.125), tumor location, extent of hepatectomy, and operation time (Group PLLR 133 minutes vs Group OLR 170 minutes, P = 0.073). Compared with OLR, the PLLR group displayed a significantly less frequent Pringle maneuver application (10.0% vs 70.0%, P PLC is as safe and feasible as OLR, but with less blood loss, shorter hospital stay, and lower hospitalization cost for selected elderly patients.

  14. A high level of liver-specific expression of oncogenic KrasV12 drives robust liver tumorigenesis in transgenic zebrafish

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    Anh Tuan Nguyen

    2011-11-01

    Human liver cancer is one of the deadliest cancers worldwide, with hepatocellular carcinoma (HCC being the most common type. Aberrant Ras signaling has been implicated in the development and progression of human HCC, but a complete understanding of the molecular mechanisms of this protein in hepatocarcinogenesis remains elusive. In this study, a stable in vivo liver cancer model using transgenic zebrafish was generated to elucidate Ras-driven tumorigenesis in HCC. Using the liver-specific fabp10 (fatty acid binding protein 10 promoter, we overexpressed oncogenic krasV12 specifically in the transgenic zebrafish liver. Only a high level of krasV12 expression initiated liver tumorigenesis, which progressed from hyperplasia to benign and malignant tumors with activation of the Ras-Raf-MEK-ERK and Wnt–β-catenin pathways. Histological diagnosis of zebrafish tumors identified HCC as the main lesion. The tumors were invasive and transplantable, indicating malignancy of these HCC cells. Oncogenic krasV12 was also found to trigger p53-dependent senescence as a tumor suppressive barrier in the pre-neoplastic stage. Microarray analysis of zebrafish liver hyperplasia and HCC uncovered the deregulation of several stage-specific and common biological processes and signaling pathways responsible for krasV12-driven liver tumorigenesis that recapitulated the molecular hallmarks of human liver cancer. Cross-species comparisons of cancer transcriptomes further defined a HCC-specific gene signature as well as a liver cancer progression gene signature that are evolutionarily conserved between human and zebrafish. Collectively, our study presents a comprehensive portrait of molecular mechanisms during progressive Ras-induced HCC. These observations indicate the validity of our transgenic zebrafish to model human liver cancer, and this model might act as a useful platform for drug screening and identifying new therapeutic targets.

  15. Human immunodeficiency virus infection and the liver.

    Science.gov (United States)

    Crane, Megan; Iser, David; Lewin, Sharon R

    2012-03-27

    Liver disease in human immunodeficiency virus (HIV)-infected individuals encompasses the spectrum from abnormal liver function tests, liver decompensation, with and without evidence of cirrhosis on biopsy, to non-alcoholic liver disease and its more severe form, non-alcoholic steatohepatitis and hepatocellular cancer. HIV can infect multiple cells in the liver, leading to enhanced intrahepatic apoptosis, activation and fibrosis. HIV can also alter gastro-intestinal tract permeability, leading to increased levels of circulating lipopolysaccharide that may have an impact on liver function. This review focuses on recent changes in the epidemiology, pathogenesis and clinical presentation of liver disease in HIV-infected patients, in the absence of co-infection with hepatitis B virus or hepatitis C virus, with a specific focus on issues relevant to low and middle income countries.

  16. 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

  17. CARCINOMA OF THE LARYNX AND HUMAN PAPILLOMA VIRUS INFECTION

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    Georgi N. Nikolov

    2016-03-01

    Full Text Available Background: Laryngeal carcinoma is one of the most common form of head and neck cancer. During the last two decades, it has been recognized that this cancer is causally related to human papillomavirus (HPV. Objective: We presented a study on prevalence of human papilloma viruses (HPV in patients with laryngeal carcinoma. Methods: This study consists of 43 patients with laryngeal carcinoma who were diagnosed and treated with surgical techniques in Department of Otorhinolaryngology, University Hospital, Pleven, Bulgaria. Immunohistochemistry of p16INK4a and Ki-67 were used to prove the relationship between high-risk-HPV (HR-HPV and carcinogenesis. Results: Papilloma virus infection with high-risk oncogenic types of HPV was determined in more than 39.5% of surgically treated patients with histologically proven laryngeal cancer. HPV-induced carcinogenesis was assumed in 17 (13.9% of all patients whose spouses were operated from cervical cancer. The patients with HPV-positive laryngeal carcinoma were younger than the others in the group (8 years on average. Risk factors for development of HPV-associated laryngeal carcinoma were related to higher number of sexual partners and the practice of oral sex. Frequently, in patients with HPV-associated laryngeal carcinoma we find data for so-called “family’s carcinogenesis”. The possibility of appearance (either preceding or following the treatment of a second carcinoma and/or tumour recurrence is higher in HPV-positive laryngeal carcinomas. Conclusion: It is recommended to extend the diagnostic methods for laryngeal and hypo pharyngeal cancer with a routine search for high-risk oncogenic HPV strains.

  18. Prevalence of hepatocellular carcinoma in patients of liver cirrhosis: an experience in North West Frontier province (NWFP)

    International Nuclear Information System (INIS)

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

    2000-01-01

    A study was conducted to find out the prevalence of hepatocellular carcinoma (HCC) in 410 patients of liver cirrhosis. Hepatocellular carcinoma was found in 45 (10.98%) patients with predominance of males. (P < 0.05). Most of HCC patients (77.78% P <0.05) were seropositive for hepatitis C virus (HCV), whereas only 2 patients (4.44%) for hepatitis B virus (HBC) infections. Eight (17.78%) patients were seronegative for both HBC and HCV infections. Out of these 8 patients, one (2.22%) was associated with haemochromatosis. We concluded that HCC is a common complication of cirrhosis (occurrence rate = 10.98%), especially HCV associated cirrhosis. (author)

  19. LAT1 acts as a crucial transporter of amino acids in human thymic carcinoma cells

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    Keitaro Hayashi

    2016-11-01

    Full Text Available L-type amino acid transporter 1 (LAT1, SLC7A5 incorporates essential amino acids into cells. Recent studies have shown that LAT1 is a predominant transporter in various human cancers. However, the function of LAT1 in thymic carcinoma remains unknown. Here we demonstrate that LAT1 is a critical transporter for human thymic carcinoma cells. LAT1 was strongly expressed in human thymic carcinoma tissues. LAT1-specific inhibitor significantly suppressed leucine uptake and growth of Ty82 human thymic carcinoma cell lines, suggesting that thymic carcinoma takes advantage of LAT1 as a quality transporter and that LAT1-specific inhibitor might be clinically beneficial in therapy for thymic carcinoma.

  20. Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular CarcinomaSummary

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    Zeribe Chike Nwosu

    2017-09-01

    Full Text Available Background & Aims: Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC. Methods: We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers (ECM2 and MMP9 (Pearson correlation P < .05 were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. Results: We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350 are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism. In contrast, among consistently up-regulated metabolic genes (n = 284 are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434 correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. Conclusions: We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts. Keywords: Liver Cancer, HCC, Tumor Metabolism

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

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    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.

  2. Enhanced laser thermal ablation for the in vitro treatment of liver cancer by specific delivery of multiwalled carbon nanotubes functionalized with human serum albumin.

    Science.gov (United States)

    Iancu, Cornel; Mocan, Lucian; Bele, Constantin; Orza, Anamaria Ioana; Tabaran, Flaviu A; Catoi, Cornel; Stiufiuc, Rares; Stir, Ariana; Matea, Cristian; Iancu, Dana; Agoston-Coldea, Lucia; Zaharie, Florin; Mocan, Teodora

    2011-01-17

    The main goal of this investigation was to develop and test a new method of treatment for human hepatocellular carcinoma (HCC). We present a method of carbon nanotube-enhanced laser thermal ablation of HepG2 cells (human hepatocellular liver carcinoma cell line) based on a simple multiwalled carbon nanotube (MWCNT) carrier system, such as human serum albumin (HSA), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. Both HepG2 cells and hepatocytes were treated with HSA-MWCNTs at various concentrations and at various incubation times and further irradiated using a 2 W, 808 nm laser beam. Transmission electron, phase contrast, and confocal microscopy combined with immunochemical staining were used to demonstrate the selective internalization of HSA-MWCNTs via Gp60 receptors and the caveolin-mediated endocytosis inside HepG2 cells. The postirradiation apoptotic rate of HepG2 cells treated with HSA-MWCNTs ranged from 88.24% (for 50 mg/L) at 60 sec to 92.34% (for 50 mg/L) at 30 min. Significantly lower necrotic rates were obtained when human hepatocytes were treated with HSA-MWCNTs in a similar manner. Our results clearly show that HSA-MWCNTs selectively attach on the albondin (aka Gp60) receptor located on the HepG2 membrane, followed by an uptake through a caveolin-dependent endocytosis process. These unique results may represent a major step in liver cancer treatment using nanolocalized thermal ablation by laser heating.

  3. [Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

    Science.gov (United States)

    Hagymási, Krisztina; Tulassay, Zsolt

    2008-03-23

    Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

  4. Dataset of protein species from human liver

    Directory of Open Access Journals (Sweden)

    Stanislav Naryzhny

    2017-06-01

    Full Text Available This article contains data related to the research article entitled “Zipf׳s law in proteomics” (Naryzhny et al., 2017 [1]. The protein composition in the human liver or hepatocarcinoma (HepG2 cells extracts was estimated using a filter-aided sample preparation (FASP protocol. The protein species/proteoform composition in the human liver was determined by two-dimensional electrophoresis (2-DE followed by Electrospray Ionization Liquid Chromatography-Tandem Mass Spectrometry (ESI LC-MS/MS. In the case of two-dimensional electrophoresis (2-DE, the gel was stained with Coomassie Brilliant Blue R350, and image analysis was performed with ImageMaster 2D Platinum software (GE Healthcare. The 96 sections in the 2D gel were selected and cut for subsequent ESI LC-MS/MS and protein identification. If the same protein was detected in different sections, it was considered to exist as different protein species/proteoforms. A list of human liver proteoforms detected in this way is presented.

  5. Long-term culture of human liver tissue with advanced hepatic functions.

    Science.gov (United States)

    Ng, Soon Seng; Xiong, Anming; Nguyen, Khanh; Masek, Marilyn; No, Da Yoon; Elazar, Menashe; Shteyer, Eyal; Winters, Mark A; Voedisch, Amy; Shaw, Kate; Rashid, Sheikh Tamir; Frank, Curtis W; Cho, Nam Joon; Glenn, Jeffrey S

    2017-06-02

    A major challenge for studying authentic liver cell function and cell replacement therapies is that primary human hepatocytes rapidly lose their advanced function in conventional, 2-dimensional culture platforms. Here, we describe the fabrication of 3-dimensional hexagonally arrayed lobular human liver tissues inspired by the liver's natural architecture. The engineered liver tissues exhibit key features of advanced differentiation, such as human-specific cytochrome P450-mediated drug metabolism and the ability to support efficient infection with patient-derived inoculums of hepatitis C virus. The tissues permit the assessment of antiviral agents and maintain their advanced functions for over 5 months in culture. This extended functionality enabled the prediction of a fatal human-specific hepatotoxicity caused by fialuridine (FIAU), which had escaped detection by preclinical models and short-term clinical studies. The results obtained with the engineered human liver tissue in this study provide proof-of-concept determination of human-specific drug metabolism, demonstrate the ability to support infection with human hepatitis virus derived from an infected patient and subsequent antiviral drug testing against said infection, and facilitate detection of human-specific drug hepatotoxicity associated with late-onset liver failure. Looking forward, the scalability and biocompatibility of the scaffold are also ideal for future cell replacement therapeutic strategies.

  6. 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...

  7. Acute Exacerbation of Hepatitis in Liver Cirrhosis with Very High Levels of alpha-Fetoprotein But No Occurrence of Hepatocellular Carcinoma

    Science.gov (United States)

    Park, Sang Jong; Park, Kwang Bo; Paik, So Ya; Ryu, Jin Kyung; Choi, Chang Kyu; Hwang, Tae Joon

    2005-01-01

    Aminotransferase levels do not always increase during acute hepatitis or during an acute flare-up of chronic hepatitis. Persistently increased levels of serum alpha-Fetoprotein in an adult with liver disease suggest not only the presence or progression of hepatocellular carcinoma or its recurrence after hepatic resection or after other therapeutic approaches such as chemotherapy or chemoembolization, but also it suggests that there is an acute exacerbation of hepatitis or liver cirrhosis. We report here on two unusual cases of HBV- & HCV-related liver cirrhosis with acute exacerbation of hepatitis in which there was an insignificant elevation of the aminotransferase levels, but there were markedly increased alpha-Fetoprotein levels observed. The levels of alpha-Fetoprotein decreased gradually in both cases since the beginning of antiviral therapy, which implies that the increased levels were due to aggravation of the accompanying hepatitis. These cases also emphasize that using only the measurement of alpha-Fetoprotein is not sufficient for the diagnosis of hepatocellular carcinoma, and that this diagnosis also requires a more specific measurement such as AFP L3 along with the standard imaging studies. PMID:15906959

  8. Living-donor vs deceased-donor liver transplantation for patients with hepatocellular carcinoma.

    Science.gov (United States)

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kokudo, Norihiro

    2014-09-27

    With the increasing prevalence of living-donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC), some authors have reported a potential increase in the HCC recurrence rates among LDLT recipients compared to deceased-donor liver transplantation (DDLT) recipients. The aim of this review is to encompass current opinions and clinical reports regarding differences in the outcome, especially the recurrence of HCC, between LDLT and DDLT. While some studies report impaired recurrence - free survival and increased recurrence rates among LDLT recipients, others, including large database studies, report comparable recurrence - free survival and recurrence rates between LDLT and DDLT. Studies supporting the increased recurrence in LDLT have linked graft regeneration to tumor progression, but we found no association between graft regeneration/initial graft volume and tumor recurrence among our 125 consecutive LDLTs for HCC cases. In the absence of a prospective study regarding the use of LDLT vs DDLT for HCC patients, there is no evidence to support the higher HCC recurrence after LDLT than DDLT, and LDLT remains a reasonable treatment option for HCC patients with cirrhosis.

  9. 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.

  10. A study of human liver ferritin and chicken liver and spleen using Moessbauer spectroscopy with high velocity resolution

    Energy Technology Data Exchange (ETDEWEB)

    Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation)

    2008-01-15

    Lyophilized samples of human liver ferritin and chicken liver and spleen were measured at room temperature using Moessbauer spectroscopy with high velocity resolution. An increase in the velocity resolution of Moessbauer spectroscopy permitted us to increase accuracy and decrease experimental error in determining the hyperfine parameters of human liver ferritin and chicken liver and spleen. Moessbauer spectroscopy with high velocity resolution may be very useful for revealing small differences in hyperfine parameters during biomedical research.

  11. Leptin as a critical regulator of hepatocellular carcinoma development through modulation of human telomerase reverse transcriptase

    Directory of Open Access Journals (Sweden)

    Stefanou Nikolaos

    2010-08-01

    Full Text Available Abstract Background Numerous epidemiological studies have documented that obesity is associated with hepatocellular carcinoma (HCC. The aim of this study was to investigate the biological actions regulated by leptin, the obesity biomarker molecule, and its receptors in HCC and the correlation between leptin and human telomerase reverse transcriptase (hTERT, a known mediator of cellular immortalization. Methods We investigated the relationship between leptin, leptin receptors and hTERT mRNA expression in HCC and healthy liver tissue samples. In HepG2 cells, chromatin immunoprecipitation assay was used to study signal transducer and activator of transcription-3 (STAT3 and myc/mad/max transcription factors downstream of leptin which could be responsible for hTERT regulation. Flow cytometry was used for evaluation of cell cycle modifications and MMP1, 9 and 13 expression after treatment of HepG2 cells with leptin. Blocking of leptin's expression was achieved using siRNA against leptin and transfection with liposomes. Results We showed, for the first time, that leptin's expression is highly correlated with hTERT expression levels in HCC liver tissues. We also demonstrated in HepG2 cells that leptin-induced up-regulation of hTERT and TA was mediated through binding of STAT3 and Myc/Max/Mad network proteins on hTERT promoter. We also found that leptin could affect hepatocellular carcinoma progression and invasion through its interaction with cytokines and matrix mettaloproteinases (MMPs in the tumorigenic microenvironment. Furthermore, we showed that histone modification contributes to leptin's gene regulation in HCC. Conclusions We propose that leptin is a key regulator of the malignant properties of hepatocellular carcinoma cells through modulation of hTERT, a critical player of oncogenesis.

  12. Hypervascular hyperplastic nodules appearing in chronic alcoholic liver disease: benign intrahepatic nodules mimicking hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Won Kyu; Chang, Jay Chun; Kim, Jae Woon

    2006-01-01

    Hypervascular hyperplastic nodules in those patients with chronic alcoholic liver disease and who are hepatitis B and C negative have recently been reported on. The purpose of this study was to correlate the radiologic and pathologic findings with the clinical significance of these hypervascular hyperplastic nodules in chronic alcoholic liver disease. The study included eight hypervascular nodules of seven patients with chronic alcoholic liver disease, and these patients abused alcohol for more than 20 years. Eight hypervascular nodules were seen on the arterial phase of dynamic CT scans, but the possibility of HCC was excluded pathologically (n=4) or clinically. The radiologic and pathologic findings, and the changes of these nodules on follow up CT scans were retrospectively analyzed. All nodules showed good enhancement on the arterial phase. The tissue equilibrium phase of the dynamic CT scans showed isodensity in seven patients and low density in one patient. Ultrasound scans revealed hypoechoic findings for three nodules, isoechoic findings for two nodules, hyperechoic findings for one nodules, and two nodules were not detected. Angiograms (n=6) showed late incremental tumor staining, and all the nodules were well seen on the sinusoidal phase. CT during hepatic angiography (n=4) showed well stained tumor. CT during arterial portography (n=4) showed no defect in three nodules and nodular defect in on nodule. The MR images (n=3) showed low signal intensity in two nodules and iso-signal intensity in one nodule on T2WI. Five of six cases for which follow up CT scans were performed showed decrease in size and one was disappeared. Radiologically, it is often difficult to differentiate the hypervascular hyperplastic nodules seen in the chronic alcoholic liver disease from hepatocellular carcinoma, and histological confirmation is needed for excluded hepatocellular carcinoma. However, late tumor staining during the sinusoidal phase without any blood supply by feeding

  13. Hypervascular hyperplastic nodules appearing in chronic alcoholic liver disease: benign intrahepatic nodules mimicking hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Won Kyu; Chang, Jay Chun; Kim, Jae Woon [College of Medicine, Yeungnam University, Daegu (Korea, Republic of)] (and others)

    2006-02-15

    Hypervascular hyperplastic nodules in those patients with chronic alcoholic liver disease and who are hepatitis B and C negative have recently been reported on. The purpose of this study was to correlate the radiologic and pathologic findings with the clinical significance of these hypervascular hyperplastic nodules in chronic alcoholic liver disease. The study included eight hypervascular nodules of seven patients with chronic alcoholic liver disease, and these patients abused alcohol for more than 20 years. Eight hypervascular nodules were seen on the arterial phase of dynamic CT scans, but the possibility of HCC was excluded pathologically (n=4) or clinically. The radiologic and pathologic findings, and the changes of these nodules on follow up CT scans were retrospectively analyzed. All nodules showed good enhancement on the arterial phase. The tissue equilibrium phase of the dynamic CT scans showed isodensity in seven patients and low density in one patient. Ultrasound scans revealed hypoechoic findings for three nodules, isoechoic findings for two nodules, hyperechoic findings for one nodules, and two nodules were not detected. Angiograms (n=6) showed late incremental tumor staining, and all the nodules were well seen on the sinusoidal phase. CT during hepatic angiography (n=4) showed well stained tumor. CT during arterial portography (n=4) showed no defect in three nodules and nodular defect in on nodule. The MR images (n=3) showed low signal intensity in two nodules and iso-signal intensity in one nodule on T2WI. Five of six cases for which follow up CT scans were performed showed decrease in size and one was disappeared. Radiologically, it is often difficult to differentiate the hypervascular hyperplastic nodules seen in the chronic alcoholic liver disease from hepatocellular carcinoma, and histological confirmation is needed for excluded hepatocellular carcinoma. However, late tumor staining during the sinusoidal phase without any blood supply by feeding

  14. 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.

  15. Hepatic cholesterol ester hydrolase in human liver disease.

    Science.gov (United States)

    Simon, J B; Poon, R W

    1978-09-01

    Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

  16. Proteomic analysis of human oral verrucous carcinoma

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... This study is about proteomic analysis of oral verrucous carcinoma (OVC). The total proteins ..... receptor protein (recoverin) through autoimmunity ..... chromosome 8q21.1 and overexpressed in human prostate cancer. Cancer ...

  17. Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver

    DEFF Research Database (Denmark)

    Vestentoft, Peter S; Jelnes, Peter; Hopkinson, Branden M

    2011-01-01

    BACKGROUND: During liver development, intrahepatic bile ducts are thought to arise by a unique asymmetric mode of cholangiocyte tubulogenesis characterized by a series of remodeling stages. Moreover, in liver diseases, cells lining the Canals of Hering can proliferate and generate new hepatic...... in normal liver and in the extensive ductular reactions originating from intrahepatic bile ducts and branching into the parenchyma of the acetaminophen intoxicated liver. In the developing human liver, three-dimensional reconstructions using multiple marker proteins confirmed that the human intrahepatic...

  18. 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

  19. Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh.

    Science.gov (United States)

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-03-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18.

  20. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    Science.gov (United States)

    Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell carcinoma were included in the study. Extracted DNA from the cancerous tissues was checked for PCR reaction to detect the subtypes of human papilloma virus. Data of the present study suggest that oral squamous cell carcinoma are almost absent in Bangladeshi patients with human papilloma virus, particularly HPV 16 and 18. PMID:23617206

  1. Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria: Multidisciplinary Approach to Improve Outcome

    Science.gov (United States)

    Kornberg, A.

    2014-01-01

    The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with “early-stage” HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients. PMID:27335840

  2. Transcriptomic profiling of trichloroethylene exposure in male mouse liver

    Directory of Open Access Journals (Sweden)

    Yan Jiang

    2015-03-01

    Full Text Available Chronic Trichloroethylene (TCE exposure could induce hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE for 5 days. As a beginning step, we profiled gene expression alterations induced by the TCE in mouse livers. Here we describe in detail the experimental methods, quality controls, and other information associated with our data deposited into Gene Expression Omnibus (GEO under GSE58819. Our data provide useful information for gene expression responses to TCE in mouse liver.

  3. [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.

  4. Curative Intent Treatment of Hepatocellular Carcinoma - 844 Cases Treated in a General Surgery and Liver Transplantation Center.

    Science.gov (United States)

    Grigorie, Răzvan; Alexandrescu, Sorin; Smira, Gabriela; Ionescu, Mihnea; Hrehoreţ, Doina; Braşoveanu, Vladislav; Dima, Simona; Ciurea, Silviu; Boeţi, Patricia; Dudus, Ionut; Picu, Nausica; Zamfir, Radu; David, Leonard; Botea, Florin; Gheorghe, Liana; Tomescu, Dana; Lupescu, Ioana; Boroş, Mirela; Grasu, Mugur; Dumitru, Radu; Toma, Mihai; Croitoru, Adina; Herlea, Vlad; Pechianu, Cătălin; Năstase, Anca; Popescu, Irinel

    2017-01-01

    Background: The objective of this study is to assess the outcome of the patients treated for hepatocellular carcinoma (HCC) in a General Surgery and Liver Transplantation Center. Methods: This retrospective study includes 844 patients diagnosed with HCC and surgically treated with curative intent methods. Curative intent treatment is mainly based on surgery, consisting of liver resection (LR), liver transplantation (LT). Tumor ablation could become the choice of treatment in HCC cases not manageable for surgery (LT or LR). 518 patients underwent LR, 162 patients benefited from LT and in 164 patients radiofrequency ablation (RFA) was performed. 615 patients (73%) presented liver cirrhosis. Results: Mordidity rates of patient treated for HCC was 30% and mortality was 4,3% for the entire study population. Five year overall survival rate was 39 % with statistically significant differences between transplanted, resected, or ablated patients (p 0.05) with better results in case of LT followed by LR and RFA. Conclusions: In HCC patients without liver cirrhosis, liver resection is the treatment of choice. For early HCC occurred on cirrhosis, LT offers the best outcome in terms of overall and disease free survival. RFA colud be a curative method for HCC patients not amenable for LT of LR. Celsius.

  5. RITA inhibits growth of human hepatocellular carcinoma through induction of apoptosis.

    Science.gov (United States)

    Wang, Haihe; Chen, Guofu; Wang, Hongzhi; Liu, Chunbo

    2013-01-01

    RBP-J-interacting and tubulin-associated (RITA) is a novel RBP-J-interacting protein that downregulates Notch-mediated transcription. The current study focuses on the antitumor effect of RITA in human hepatocellular carcinoma (HCC) and aims to explore its molecular mechanism. Thirty paired HCC and adjacent non-tumoral liver samples were analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RITA overexpression was induced by transfection of a pcDNA3.1-Flag-RITA plasmid into HepG2 cells. RITA knockdown was achieved by siRNA transfection. mRNA and protein expression of target genes were quantified by qRT-PCR and Western blotting, respectively. Cell proliferation and apoptosis were measured using MTT assay and flow cytometry. Our results demonstrate that adjacent nontumoral liver samples exhibited increased RITA expression compared to HCC tissues (p RITA levels were associated with tumor differentiation status. Overexpression of RITA suppressed cell proliferation and promoted early apoptosis, while its silencing promoted cell growth dramatically (p RITA overexpression upregulated p53 and reduced cyclin E levels, whereas silencing of RITA had the opposite effect on p53 and cyclin E expression. Our in vitro results represent the first evidence that RITA might suppress tumor growth and induce apoptosis in HCCs, and may be a potent antitumoral agent for HCC treatment that deserves further exploration.

  6. IL-15 Overcomes Hepatocellular Carcinoma-Induced NK Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Nicholas J. W. Easom

    2018-05-01

    Full Text Available NK cells have potent antitumor capacity. They are enriched in the human liver, with a large subset specialized for tissue-residence. The potential for liver-resident versus liver-infiltrating NK cells to populate, and exert antitumor functions in, human liver tumors has not been studied. We examined liver-resident and liver-infiltrating NK cells directly ex vivo from human hepatocellular carcinomas (HCCs and liver colorectal (CRC metastases, compared with matched uninvolved liver tissue. We found that NK cells were highly prevalent in both HCC and liver CRC metastases, although at lower frequencies than unaffected liver. Up to 79% of intratumoral NK cells had the CXCR6+CD69+ liver-resident phenotype. Direct ex vivo staining showed that liver-resident NK cells had increased NKG2D expression compared to their non-resident counterparts, but both subsets had NKG2D downregulation within liver tumors compared to uninvolved liver. Proliferation of intratumoral NK cells (identified by Ki67 was selectively impaired in those with the most marked NKG2D downregulation. Human liver tumor NK cells were functionally impaired, with reduced capacity for cytotoxicity and production of cytokines, even when compared to the hypo-functional tissue-resident NK cells in unaffected liver. Coculture of human liver NK cells with the human hepatoma cell line PLC/PRF/5, or with autologous HCC, recapitulated the defects observed in NK cells extracted from tumors, with downmodulation of NKG2D, cytokine production, and target cell cytotoxicity. Transwells and conditioned media confirmed a requirement for cell contact with PLC/PRF/5 to impose NK cell inhibition. IL-15 was able to recover antitumor functionality in NK cells inhibited by in vitro exposure to HCC cell lines or extracted directly from HCC. In summary, our data suggest that the impaired antitumor function of local NK cells reflects a combination of the tolerogenic features inherent to liver-resident NK cells

  7. Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

    Science.gov (United States)

    Jin, Haojie; Zhang, Yurong; You, Haiyan; Tao, Xuemei; Wang, Cun; Jin, Guangzhi; Wang, Ning; Ruan, Haoyu; Gu, Dishui; Huo, Xisong; Cong, Wenming; Qin, Wenxin

    2015-06-23

    Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both pKMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC.

  8. Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

    Science.gov (United States)

    Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

    2017-09-01

    The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  9. 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.

  10. 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...

  11. Effect of the Human Amniotic Membrane on Liver Regeneration in Rats

    Directory of Open Access Journals (Sweden)

    Mesut Sipahi

    2015-01-01

    Full Text Available Introduction. Operations are performed for broader liver surgery indications for a better understanding of hepatic anatomy/physiology and developments in operation technology. Surgery can cure some patients with liver metastasis of some tumors. Nevertheless, postoperative liver failure is the most feared complication causing mortality in patients who have undergone excision of a large liver mass. The human amniotic membrane has regenerative effects. Thus, we investigated the effects of the human amniotic membrane on regeneration of the resected liver. Methods. Twenty female Wistar albino rats were divided into control and experimental groups and underwent a 70% hepatectomy. The human amniotic membrane was placed over the residual liver in the experimental group. Relative liver weight, histopathological features, and biochemical parameters were assessed on postoperative day 3. Results. Total protein and albumin levels were significantly lower in the experimental group than in the control group. No difference in relative liver weight was observed between the groups. Hepatocyte mitotic count was significantly higher in the experimental group than in the control group. Hepatic steatosis was detected in the experimental group. Conclusion. Applying the amniotic membrane to residual liver adversely affected liver regeneration. However, mesenchymal stem cell research has the potential to accelerate liver regeneration investigations.

  12. Cystic degeneration of liver malignancies. Study by US and CT

    Energy Technology Data Exchange (ETDEWEB)

    Kumada, Takashi; Nakano, Satoshi; Kitamura, Kimio; Watahiki, Hajime; Takeda, Isao

    1983-03-01

    CT and US were carried out on 81 patients with hepatocellular carcinoma, 20 patients with cholangiocellular carcinoma and 94 patients with metastatic liver cancer. 1) Cystic degeneration was observed in one with hepatocellular carcinoma (1.2%), one with cholangiocellular carcinoma (5.0%) and 12 with metastatic liver cancer (12.8%) by US, but this change was observed in only 5 by CT (1,0,4, respectively). Metastatic liver cancer showed the highest incidence among these tumors. 2) The characteristics of cystic degeneration of the liver tumors were thickened wall and irregularity of the inner surface of the wall. 3) Judging from macroscopic and histopathological findings, liquefactive necrosis in the tumors was shown as ''echoluent'' area. We concluded that cystic degeneration was one of the important findings in metastatic liver cancer and that careful observation by US and CT avoided the confusion with other hepatic cystic diseases.

  13. 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.

  14. Molecular Structure of Human-Liver Glycogen.

    Directory of Open Access Journals (Sweden)

    Bin Deng

    Full Text Available Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite α particles made up of linked β particles. Previous studies have shown that the binding which links β particles into α particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of β into α particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.

  15. Identification of the Consistently Altered Metabolic Targets in Human Hepatocellular Carcinoma.

    Science.gov (United States)

    Nwosu, Zeribe Chike; Megger, Dominik Andre; Hammad, Seddik; Sitek, Barbara; Roessler, Stephanie; Ebert, Matthias Philip; Meyer, Christoph; Dooley, Steven

    2017-09-01

    Cancer cells rely on metabolic alterations to enhance proliferation and survival. Metabolic gene alterations that repeatedly occur in liver cancer are largely unknown. We aimed to identify metabolic genes that are consistently deregulated, and are of potential clinical significance in human hepatocellular carcinoma (HCC). We studied the expression of 2,761 metabolic genes in 8 microarray datasets comprising 521 human HCC tissues. Genes exclusively up-regulated or down-regulated in 6 or more datasets were defined as consistently deregulated. The consistent genes that correlated with tumor progression markers ( ECM2 and MMP9) (Pearson correlation P < .05) were used for Kaplan-Meier overall survival analysis in a patient cohort. We further compared proteomic expression of metabolic genes in 19 tumors vs adjacent normal liver tissues. We identified 634 consistent metabolic genes, ∼60% of which are not yet described in HCC. The down-regulated genes (n = 350) are mostly involved in physiologic hepatocyte metabolic functions (eg, xenobiotic, fatty acid, and amino acid metabolism). In contrast, among consistently up-regulated metabolic genes (n = 284) are those involved in glycolysis, pentose phosphate pathway, nucleotide biosynthesis, tricarboxylic acid cycle, oxidative phosphorylation, proton transport, membrane lipid, and glycan metabolism. Several metabolic genes (n = 434) correlated with progression markers, and of these, 201 predicted overall survival outcome in the patient cohort analyzed. Over 90% of the metabolic targets significantly altered at the protein level were similarly up- or down-regulated as in genomic profile. We provide the first exposition of the consistently altered metabolic genes in HCC and show that these genes are potentially relevant targets for onward studies in preclinical and clinical contexts.

  16. Liver metastasis from neuroendocrine carcinoma after the use of the new direct-action antivirals against hepatitis C virus in a patient with past history of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    María Caldas

    Full Text Available The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process. However, due to the controversy concerning this subject and the absence of long-term follow-up studies in clinical practice, caution is needed before definitive conclusions are settled. We present the case report of a patient diagnosed of chronic liver disease secondary to hepatitis C virus infection and a past history of hepatocellular carcinoma in complete remission after radiofrequency ablation. He was treated with the new direct-action antivirals reaching sustained viral response. Six months later, the patient was diagnosed with liver metastasis from a small-cell neuroendocrine tumor of unknown primary site.

  17. Recurrence of hepatocellular carcinoma after liver transplantation presenting as anastomotic biliary stricture Presentación del carcinoma hepatocelular recurrente tras el trasplante de hígado en forma de estenosis biliar anastomótica

    Directory of Open Access Journals (Sweden)

    S. Y. Chen

    2008-07-01

    Full Text Available A 52-year-old man visited our hospital complaining of anorexia and fatigue two months after receiving orthotopic liver transplantation for hepatocellular carcinoma. A laboratory investigation demonstrated a clinical picture of obstructive jaundice. T-tube cholangiography showed biliary stricture over the anastomotic site. Percutaneous transluminal balloon dilatation and stenting was attempted but failed. Magnetic resonance cholangiography showed possible tumor recurrence over the site of the anastomotic biliary stricture. A biopsy sample was obtained via ultrasound-guided aspiration and histopathological study revealed inflammatory and fibrotic changes. With high suspicion of recurrence of the hepatocellular carcinoma, surgical exploration was performed and an intraoperative frozen section proved the recurrence. We thus diagnosed this case as a recurrence of hepatocellular carcinoma after liver transplantation. To our knowledge, there have been no previous reports of early tumor recurrence after liver transplantation being the cause of an anastomotic biliary stricture.Un varón de 52 años visitó nuestro hospital quejándose de anorexia y fatiga a los dos meses de haber recibido un trasplante hepático ortotópico a causa de un carcinoma hepatocelular. La analítica mostró un cuadro clínico de ictericia obstructiva. La colangiografía con tubo en T mostró una estenosis biliar sobre la anastomosis. Se intentó una dilatación transluminal percutánea con globo y colocación de endoprótesis, que fracasó. La colangiografía por resonancia magnética mostró una posible recurrencia tumoral sobre el lugar de la estenosis biliar anastomótica. Se extrajo una muestra de biopsia mediante aspiración bajo guía ecográfica y el estudio histopatológico mostró alteraciones inflamatorias y fibróticas. Al sospecharse la recurrencia del carcinoma hepatocelular, se realizó una exploración quirúrgica; un corte intraoperatorio congelado demostr

  18. What effects performance status of patients with hepatocellular carcinoma: stage of tumor versus underlying liver status

    International Nuclear Information System (INIS)

    Sarwar, S.; Tarique, S.

    2015-01-01

    Objective: To identify variables associated with poor performance status of hepatocellular carcinoma (HCC) patients and to compare impact of stage of liver disease and that of hepatoma on functional status of patient. Patients and Methods: We included 254 confirmed cases of liver cancer in a crosssectional analytical study carried out at Doctors Hospital Lahore. Patient's clinical, biochemical and radiological variables were correlated with Karnofsky's performance status (KPS) using pearson correlation. Model for End stage Liver Disease (MELD) and Cancer of Liver Italian Program (CLIP) were evaluated for predicting performance status using Receiver Operating Characteristic (ROC) curve. Results: Mean age of patients was 56.69 (±10.34) and male to female ratio was 2.47: 1 (181/73). On KPS evaluation 84 (33.1%) patients scored between 80-100, 147 (57.9%) had score of 50-70 while in 23 (9.1%) KPS score was between 0-40. Variables associated with poor performance status were bilirubin> 3mg/dl (p value 0.00), albumin< 2.5 g/dl (p value 0.00), creatinine > 1.2mg/dl (p 0.00), prothrombin time> 16seconds (p value 0.00), size of tumor >7cm (p value 0.02), tumor involving > 50% of liver mass (p value 0.00) and vascular invasion (p value 0.00). Both stage of liver disease as determined by MELD and stage of liver cancer as per CLIP scores had strong correlation (p value 0.00) with poor performance status of patient. Area under ROC curve was 0.764 for MELD score and 0.785 for CLIP score. Conclusion: Performance status of liver cancer patients is affected by both stage of liver disease and that of liver tumor. Patients with MELD score above 16 and CLIP score above 4 have poor performance status. (author)

  19. Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

    Science.gov (United States)

    Kitamura, Shigeyuki; Sugihara, Kazumi

    2014-01-01

    1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

  20. Study on stability of labeled yttrium-90 with lipiodol by chemical extraction for liver cancer

    International Nuclear Information System (INIS)

    Mu, P.Y.; Jiang, X.L.; Chen, J.; Zhu, Y.J.

    2005-01-01

    Liver cancer, particularly hepatocellular carcinoma, is one of the most common malignant diseases in many developed and developing countries. It is also one of the most common diseases endangering the people's lives and health heavily. Surgery is very effective in early-stage patients. Unfortunately, there is less than 10% of the patients with hepatocellular carcinoma fitting for surgical therapy. Instead of surgical therapy, other methods are considered for patients in whom surgery may not work well. Systemic administration of chemotherapeutic agents is not often considered in liver cancer patients, due to discouraging result and adverse side effects. Also, hepatocellular carcinoma is not keen on usual radioactive therapy. However, method of inner interventional radioactive nuclide is a potential way to cure liver tumors. Hepatocellular carcinoma would be cured with inner interventional radioactive nuclide, which is a hot topic in experimental research on hepatocellular carcinoma at home and abroad. The purpose of the study is to label Yttrium-90 with lipiodol by means of the chemical extraction method and research the stability of labeled Yttrium-90 ( 90 Y-P204-Lipiodol) in serum of a newly-born cattle and human's blood. We chose to label steady yttrium with lipiodol, because radioactive yttrium has great nuclear character for liver cancer, yttrium-90 can eradiate pure β radial, and it's half time is 64 hours. Average energy of it is 0.93 Mev, the highest energy is 2.27 Mev. Yttrium-90 can be labeled with lipiodol by means of the chemical extraction method, which is mature in chemical techniques, combined with method of radioactive nuclide labeled in. nuclear medicine. At first, yttrium-90 is extracted in certain condition(pH, temperature, whisk time, whisk frequency, etc ) after adding yttrium-90 solution. We use some distilled water to balance the labeled organic phase twice, and test the stability of labeled yttrium-90 in serum of a newly-born cattle and

  1. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  2. Findings in multidetector computed tomography in the diagnosis of hepatocellular carcinoma in patients with cirrhosis and correlation with pathology of liver explants

    International Nuclear Information System (INIS)

    Haberman, D.; Castignola, M.; Mela, M.; Paladini, H.; Santilli, J.P.; Gruz, F.; Gondolesi, G.

    2013-01-01

    Objectives: To describe the imagenological behavior of hepatocellular carcinoma in cirrhotic patients using a dynamic multidetector computed tomography (MDCT) technique, and correlate these findings with histological tumor grades. Materials and methods: A retrospective, descriptive observational study was conducted to evaluate 51 nodules in 32 liver transplant patients diagnosed with liver cirrhosis. The pathology of liver explants was used as a reference. Nodules with hepatocellular carcinoma histopathology were retrospectively analyzed by computed tomography scans performed pre-transplant. Using a dynamic multidetector computed tomography technique, we evaluated the most common imagenological behavior reported in the literature: arterial enhancement, washout, capsule, and intratumoral arterial vessels. Results: Forty-six of 51 (90%) tumors showed arterial enhancement. Of the 46 tumors with arterial enhancement, 39 (85%) had washout in portal-late phase. Five of 51 (10%) were hypovascular. Twenty-two of 51 (43%) had capsule and 12 of 51 (24%) showed intratumoral arterial vessels. The more frequent image combination was the combination of arterial enhancement and washout (39 of 51 tumors or 76%). The most frequent histological grade was II (35 of 51 tumors or 69%). Statistically significant relationships were found between histological grade tumors and imagenological behavior: arterial enhancement and hypovascular. Conclusion: In our population, arterial enhancement with washout in portal-late phases was observed in most of the tumors. Our results are consistent with previously reported studies, demonstrating the high reliability of this imaging pattern for the diagnosis of hepatocellular carcinoma. (authors) [es

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

    Science.gov (United States)

    Engelholm, Lars H; Riaz, Anjum; Serra, Denise; Dagnæs-Hansen, Frederik; Johansen, Jens V; Santoni-Rugiu, Eric; Hansen, Steen H; Niola, Francesco; Frödin, Morten

    2017-12-01

    Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects children and 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) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis. We used the CRISPR/Cas9 technique to delete in mice the syntenic region on chromosome 8 to create a Dnajb1-Prkaca fusion and monitored the mice for liver tumor development. We delivered CRISPR/Cas9 vectors designed to juxtapose exon 1 of Dnajb1 with exon 2 of Prkaca to create the Dnajb1-Prkaca gene fusion associated with FL-HCC, or control Cas9 vector, via hydrodynamic tail vein injection to livers of 8-week-old female FVB/N mice. These mice did not have any other engineered genetic alterations and were not exposed to liver toxins or carcinogens. Liver tissues were collected 14 months after delivery; genomic DNA was analyzed by PCR to detect the Dnajb1-Prkaca fusion, and tissues were characterized by histology, immunohistochemistry, RNA sequencing, and whole-exome sequencing. Livers from 12 of the 15 mice given the vectors to induce the Dnajb1-Prkaca gene fusion, but none of the 11 mice given the control vector, developed neoplasms. The tumors contained the Dnajb1-Prkaca gene fusion and had histologic and cytologic features of human FL-HCCs: large polygonal cells with granular, eosinophilic, and mitochondria-rich cytoplasm, prominent nucleoli, and markers of hepatocytes and cholangiocytes. In comparing expression levels of genes between the mouse tumor and non-tumor liver cells, we identified changes similar to those detected in human FL-HCC, which included genes that affect cell cycle and mitosis regulation. Genomic analysis of mouse neoplasms induced by

  4. 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.

  5. Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study

    Energy Technology Data Exchange (ETDEWEB)

    Motosugi, Utaroh; Ichikawa, Tomoaki; Koshiishi, Tsuyota; Sano, Katsuhiro; Morisaka, Hiroyuki; Ichikawa, Shintaro; Araki, Tsutomu [University of Yamanashi, Department of Radiology, Yamanashi-ken (Japan); Enomoto, Nobuyuki [University of Yamanashi, 1st Department of Internal Medicine, Yamanashi (Japan); Matsuda, Masanori; Fujii, Hideki [University of Yamanashi, 1st Department of Surgery, Yamanashi (Japan)

    2013-01-15

    To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease. By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II. Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95 % confidence interval) of 1.38 (1.05-1.84). Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease. (orig.)

  6. Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells.

    Science.gov (United States)

    Cocciadiferro, Letizia; Miceli, Vitale; Granata, Orazia M; Carruba, Giuseppe

    2017-09-01

    The product of neurofibromatosis type 2 (NF2) gene, also known as Merlin/neurofibromin 2, homeostatically regulates liver stem cells by controlling abundance and signaling of epidermal growth factor receptor (EGFR), with a mechanism independent of the Hippo pathway. We have reported that locally elevated estrogen formation, driven by abnormally high expression and function of aromatase, may be implicated in development and progression of human hepatocellular carcinoma (HCC) through activation of a rapid signaling pathway mediated by amphiregulin (AREG) and EGFR. We have recently presented a model by which the aromatase-estrogen-amphiregulin-EGFR axis is activated in response to tissue injury and/or inflammatory disease, with its alteration eventually leading to development of major human tumors (liver, breast, prostate) and other chronic diseases (diabetes, obesity, Alzheimer's and heart disease). In this study, we investigated NF2 expression in liver cancer cells and tissues in relation to aromatase expression/function, estrogen receptor (ER) status and amphiregulin. Our data indicate that NF2 expression is associated with aromatase and AREG expression, being elevated in HCC tissues and HepG2 cells, intermediate in cirrhotic tissues and Huh7 cells, and lower in nontumoral liver and HA22T cells. In addition, NF2 expression is inversely related to wild type hERα66 and proportional to the expression of the membrane-associated hERα36 splice variant, as measured by exon-specific RT-PCR analysis, both in vivo and in vitro. Furthermore, incubation with estradiol induced a significant decrease of NF2 expression in both HA22T and Huh7 cells (over 54% and 22%, respectively), while no change could be observed in HepG2 cells, this effect being inversely related to aromatase expression and activity in HCC cell lines. Based on the above combined evidence, we hypothesize that NF2 behaves as a protein sensing tissue damage and aromatase-driven local estrogen formation

  7. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    Science.gov (United States)

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  8. 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)

  9. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  10. A pilot systematic genomic comparison of recurrence risks of hepatitis B virus-associated hepatocellular carcinoma with low- and high-degree liver fibrosis.

    Science.gov (United States)

    Yoo, Seungyeul; Wang, Wenhui; Wang, Qin; Fiel, M Isabel; Lee, Eunjee; Hiotis, Spiros P; Zhu, Jun

    2017-12-07

    Chronic hepatitis B virus (HBV) infection leads to liver fibrosis, which is a major risk factor in hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. The HBV genome can be inserted into the human genome, and chronic inflammation may trigger somatic mutations. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regards to the different degree of liver fibrosis is not clearly understood. We sequenced mRNAs of 21 pairs of tumor and distant non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analyses of our RNAseq data and public available HBV-HCC sequencing data. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations showed that our method outperformed existing methods. Applying it to our data, 374 and 106 HBV host genes were identified in non-neoplastic liver and tumor tissues, respectively. When applying it to other RNA sequencing datasets, consistently more HBV integrations were identified in non-neoplastic liver than in tumor tissues. HBV host genes identified in non-neoplastic liver samples significantly overlapped with known tumor suppressor genes. More significant enrichment of tumor suppressor genes was observed among HBV host genes identified from patients with tumor recurrence, indicating the potential risk of tumor recurrence driven by HBV integration in non-neoplastic liver tissues. We also compared SNPs of each sample with SNPs in a cancer census database and inferred samples' pathogenic SNP loads. Pathogenic SNP loads in non-neoplastic liver tissues were consistently higher than those in normal liver tissues. Additionally, HBV host genes identified in non-neoplastic liver tissues significantly overlapped with pathogenic somatic mutations, suggesting that HBV integration and somatic mutations targeting the same set of genes are important to tumorigenesis. HBV

  11. The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Behnke, Martha, E-mail: mbehnke@mcvh-vcu.edu [Transplant Program Administration, Virginia Commonwealth University Health System, 1200 E. Broad St., Richmond, VA 23298 (United States); Reimers, Mark [Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, 800 E Leigh St., Richmond, VA 23298 (United States); Fisher, Robert [Department of Surgery, Virginia Commonwealth University, 1200 E. Broad St., Richmond, VA 23298 (United States)

    2012-09-18

    Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55%) genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST) in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC.

  12. Lipid Biomarkers Identified for Liver Cancer | Center for Cancer Research

    Science.gov (United States)

    Hepatocellular carcinoma (HCC) is an aggressive cancer of the liver with poor prognosis and growing incidence in developed countries. Pathology and genetic profiles of HCC are heterogeneous, suggesting that it can begin growing in different cell types. Although human tumors such as HCC have been profiled in-depth by genomics-based studies, not much is known about their overall

  13. Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Alexander, HR.; Libutti, S. K.; Barlett, D. L.; Pingpank, J. F.; Kranda, Karel; Helsabeck, C.; Beresnev, T.

    2002-01-01

    Roč. 95, č. 4 (2002), s. 730-736 ISSN 0008-543X R&D Projects: GA AV ČR KSK4055109 Keywords : colorectal carcinoma * liver metastases * regional chemotherapy Subject RIV: FD - Oncology ; Hematology Impact factor: 1.000, year: 2002

  14. The outcome of surgical resection versus assignment to the liver transplant waiting list for hepatocellular carcinoma.

    Science.gov (United States)

    Pierie, Jean-Pierre E N; Muzikansky, Alona; Tanabe, Kenneth K; Ott, Mark J

    2005-07-01

    Optimal management of patients with hepatocellular carcinoma (HCC) is controversial. This study was conducted to evaluate the outcome of tumor resection versus assignment to a liver transplant waiting list (WL) in patients with HCC. Prospectively collected patient data from 1970 to 1997 on 313 patients with HCC were retrospectively analyzed by multivariate analysis to determine the effect of liver disease, method of treatment, and tumor-related factors on survival. A total of 199 patients underwent nonsurgical palliative care (PC), 81 underwent partial liver resection (LR), and 33 were assigned to a liver transplant WL, of which 22 received a donor liver. A total of 91%, 53%, and 91% of the patients had cirrhotic livers in the PC, LR, and WL groups, respectively (P < .001). In the LR group, the absence of a tumor capsule (P < .0001) and a poorly differentiated tumor (P = .027) were both adverse prognostic factors. In the WL group, hepatitis B (P = .02) and American Joint Committee on Cancer tumor stage III (P = .019) were adverse prognostic factors. The 3-year survival rates were 4%, 33%, and 38% for the PC, LR, and WL patients, respectively (P < .0001). The 3-year survival rate in the LR patients was 51% in patients without cirrhosis and 15% in patients with cirrhosis (P < .0001). Patients with locally unresectable tumors, distant disease, or both will continue to receive PC. Patients assigned to liver transplant WLs run the risk of not receiving a donor liver, in which case their survival is predicted to be poor. Survival after resection in a group of patients with advanced tumors is worse than that after transplantation; however, shortages of donor livers presently preclude transplantation in this population of patients.

  15. Evaluation of computed tomography for the diagnosis of malignant lesions in the liver

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, S; Hamano, H; Kitamura, K [Ogaki Municipal Hospital, Gifu (Japan)

    1980-01-01

    Thirty seven cases with malignant lesions in the liver underwent computed tomography and diagnostic evaluation was studied comparing with liver scanning, echogram and blood biochemistry. 1) In the cases with hepatocellular carcinoma, irregular shaped, low density area was detected in 94%. CT was superior to liver scanning and echogram in detection of space occupying lesion in the liver. 2) Remarkable dilatation of the intra-hepatic bile duct was observed in the cases with intra-hepatic biliary carcinoma and the visualization of the tumor was rather difficult. 3) Round shaped, low density area with various size were detected in the cases with metastatic liver carcinoma in 94%. The CT number of the tumors were significantly lower than that of hepatocellular carcinoma. Almost all cases accompanied remarkable hepatomegaly.

  16. A Roadmap for Human Liver Differentiation from Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Lay Teng Ang

    2018-02-01

    Full Text Available How are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs. Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses. However, these signaling combinations were temporally re-interpreted: cellular competence to respond to retinoid, WNT, TGF-β, and other signals sharply changed within 24 hr. Consequently, temporally dynamic manipulation of extracellular signals was imperative to suppress the production of unwanted cell fates across six consecutive developmental junctures. This efficiently generated 94.1% ± 7.35% TBX3+HNF4A+ human liver bud progenitors and 81.5% ± 3.2% FAH+ hepatocyte-like cells by days 6 and 18 of hPSC differentiation, respectively; the latter improved short-term survival in the Fah−/−Rag2−/−Il2rg−/− mouse model of liver failure.

  17. PVA matches human liver in needle-tissue interaction.

    Science.gov (United States)

    de Jong, Tonke L; Pluymen, Loes H; van Gerwen, Dennis J; Kleinrensink, Gert-Jan; Dankelman, Jenny; van den Dobbelsteen, John J

    2017-05-01

    Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were used for reference. Six PVA samples were created by varying the mass percentage of PVA to water (4m% and 7m%) and the number of freeze-thaw cycles (1, 2 and 3 cycles, 16hours of freezing at -19°C, 8hours of thawing). The inner needle of an 18 Gauge trocar needle with triangular tip was inserted 13 times into each of the samples, using an insertion velocity of 5 mm/s. In addition, 39 insertions were performed in two ex-vivo human livers. Axial forces on the needle were captured during insertion and retraction and characterized by friction along the needle shaft, peak forces, and number of peak forces per unit length. The concentration of PVA and the number of freeze-thaw cycles both influenced the mechanical interaction between needle and specimen. Insertions into 4m% PVA phantoms with 2 freeze-thaw cycles were comparable to human liver in terms of estimated friction along the needle shaft and the number of peak forces. Therefore, these phantoms are considered to be suitable liver mimicking materials for image-guided needle interventions. The mechanical properties of PVA hydrogels can be influenced in a controlled manner by varying the concentration of PVA and the number of freeze-thaw cycles, to mimic liver tissue characteristics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Cong Wang

    Full Text Available Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, gamma-glutamyl transferase (GGT, total protein (TP and albumin (ALB indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.

  19. Temporal morphologic changes in human colorectal carcinomas following xenografting.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  20. Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice.

    Science.gov (United States)

    Shimizu, Makiko; Suemizu, Hiroshi; Mitsui, Marina; Shibata, Norio; Guengerich, F Peter; Yamazaki, Hiroshi

    2017-10-01

    1. Pomalidomide has been shown to be potentially teratogenic in thalidomide-sensitive animal species such as rabbits. Screening for thalidomide analogs devoid of teratogenicity/toxicity - attributable to metabolites formed by cytochrome P450 enzymes - but having immunomodulatory properties is a strategic pathway towards development of new anticancer drugs. 2. In this study, plasma concentrations of pomalidomide, its primary 5-hydroxylated metabolite, and its glucuronide conjugate(s) were investigated in control and humanized-liver mice. Following oral administration of pomalidomide (100 mg/kg), plasma concentrations of 7-hydroxypomalidomide and 5-hydroxypomalidomide glucuronide were slightly higher in humanized-liver mice than in control mice. 3. Simulations of human plasma concentrations of pomalidomide were achieved with simplified physiologically-based pharmacokinetic models in both groups of mice in accordance with reported pomalidomide concentrations after low dose administration in humans. 4. The results indicate that pharmacokinetic profiles of pomalidomide were roughly similar between control mice and humanized-liver mice and that control and humanized-liver mice mediated pomalidomide 5-hydroxylation in vivo. Introducing one aromatic amino group into thalidomide resulted in less species differences in in vivo pharmacokinetics in control and humanized-liver mice.

  1. Liver transplantation:Yesterday,today and tomorrow

    Institute of Scientific and Technical Information of China (English)

    Osman Abbasoglu

    2008-01-01

    With the advances in technical skills,management of postoperative complications and improvements in immunosuppressive drugs,liver transplantation is the standard treatment for many patients with chronic liver disease.Today,shortage of donor organs seems to be the major limiting factor for the application of liver transplantation.This review focuses on five issues that are challenging to clinical practice of liver transplantation and relevant to gastroenterologists.These include living donor liver transplantation,recurrent viral hepatitis,non-heart-beating donors,hepatocellular carcinoma,and ABO incompatible livertransplantation.Living donor and non-heart beating donor transplantations were initiated as a solution to increase the donor organ pool and it is expected that there will be an increase in the number of these donors.Recurrent hepatitis C and hepatocellular carcinoma following liver transplantation are among major problems and ongoing research in these diseases may lead to better outcomes in these recipients.

  2. Cell sources for in vitro human liver cell culture models

    Science.gov (United States)

    Freyer, Nora; Damm, Georg; Seehofer, Daniel; Knöspel, Fanny

    2016-01-01

    In vitro liver cell culture models are gaining increasing importance in pharmacological and toxicological research. The source of cells used is critical for the relevance and the predictive value of such models. Primary human hepatocytes (PHH) are currently considered to be the gold standard for hepatic in vitro culture models, since they directly reflect the specific metabolism and functionality of the human liver; however, the scarcity and difficult logistics of PHH have driven researchers to explore alternative cell sources, including liver cell lines and pluripotent stem cells. Liver cell lines generated from hepatomas or by genetic manipulation are widely used due to their good availability, but they are generally altered in certain metabolic functions. For the past few years, adult and pluripotent stem cells have been attracting increasing attention, due their ability to proliferate and to differentiate into hepatocyte-like cells in vitro. However, controlling the differentiation of these cells is still a challenge. This review gives an overview of the major human cell sources under investigation for in vitro liver cell culture models, including primary human liver cells, liver cell lines, and stem cells. The promises and challenges of different cell types are discussed with a focus on the complex 2D and 3D culture approaches under investigation for improving liver cell functionality in vitro. Finally, the specific application options of individual cell sources in pharmacological research or disease modeling are described. PMID:27385595

  3. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

    Science.gov (United States)

    Koo, Seung-Hoi

    2013-09-01

    Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

  4. Molecular Aging of Human Liver: An Epigenetic/Transcriptomic Signature.

    Science.gov (United States)

    Bacalini, Maria Giulia; Franceschi, Claudio; Gentilini, Davide; Ravaioli, Francesco; Zhou, Xiaoyuan; Remondini, Daniel; Pirazzini, Chiara; Giuliani, Cristina; Marasco, Elena; Gensous, Noémie; Di Blasio, Anna Maria; Ellis, Ewa; Gramignoli, Roberto; Castellani, Gastone; Capri, Miriam; Strom, Stephen; Nardini, Christine; Cescon, Matteo; Grazi, Gian Luca; Garagnani, Paolo

    2018-03-15

    The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes. Notably, these age-associated changes tended to level off after the age of 60, as confirmed by Horvath's clock. Using stringent selection criteria we further identified a DNA methylation signature of aging liver including 75 genomic regions. We demonstrated that this signature is specific for liver compared to other tissues and that it is able to detect biological age-acceleration effects associated with obesity. Finally we combined DNA methylation measurements with available expression data. Although the intersection between the two omic characterizations was low, both approaches suggested a previously unappreciated role of epithelial-mesenchymal transition and Wnt signaling pathways in the aging of human liver.

  5. Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry

    NARCIS (Netherlands)

    de Wiele, Christophe Van; Phonteyne, Philippe; Pauwels, Patrick; Goethals, Ingeborg; Van den Broecke, Rudi; Cocquyt, Veronique; Dierckx, Rudi Andre

    This study reports on the uptake of (99m)Tc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRIP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5

  6. Cross-species hybridization of woodchuck hepatitis virus-induced hepatocellular carcinoma using human oligonucleotide microarrays

    Institute of Scientific and Technical Information of China (English)

    Paul W Anderson; Bud C Tennant; Zhenghong Lee

    2006-01-01

    AIM: To demonstrate the feasibility of using woodchuck samples on human microarrays, to provide insight into pathways involving positron emission tomography (PET) imaging tracers and to identify genes that could be potential molecular imaging targets for woodchuck hepatocellular carcinoma.METHODS: Labeled cRNA from woodchuck tissue samples were hybridized to Affymetrix U133 plus 2.0 GeneChips(R). Ten genes were selected for validation using quantitative RT-PCR and literature review was made.RESULTS: Testis enhanced gene transcript (BAX Inhibitor 1), alpha-fetoprotein, isocitrate dehydrogenase 3 (NAD+) beta, acetyl-CoA synthetase 2, carnitine palmitoyltransferase 2, and N-myc2 were up-regulated and spermidine/spermine N1-acetyltransferase was down-regulated in the woodchuck HCC. We also found previously published results supporting 8 of the 10 most up-regulated genes and all 10 of the 10 most downregulated genes.CONCLUSION: Many of our microarray results were validated using RT-PCR or literature search. Hence, we believe that woodchuck HCC and non-cancerous liver samples can be used on human microarrays to yield meaningful results.

  7. The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes

    International Nuclear Information System (INIS)

    Parkinson, Andrew; Mudra, Daniel R.; Johnson, Cory; Dwyer, Anne; Carroll, Kathleen M.

    2004-01-01

    We have measured cytochrome P450 (CYP) activity in nearly 150 samples of human liver microsomes and 64 samples of cryopreserved human hepatocytes, and we have performed induction studies in over 90 preparations of cultured human hepatocytes. We have analyzed these data to examine whether the expression of CYP enzyme activity in liver microsomes and isolated hepatocytes or the inducibility of CYP enzymes in cultured hepatocytes is influenced by the gender, age, or ethnicity of the donor (the latter being limited to Caucasians, African Americans, and Hispanics due to a paucity of livers from Asian donors). In human liver microsomes, there were no statistically significant differences (P > 0.05) in CYP activity as a function of age, gender, or ethnicity with one exception. 7-Ethoxyresorufin O-dealkylase (CYP1A2) activity was greater in males than females, which is consistent with clinical observation. Liver microsomal testosterone 6β-hydroxylase (CYP3A4) activity was slightly greater in females than males, but the difference was not significant. However, in cryopreserved human hepatocytes, the gender difference in CYP3A4 activity (females = twice males) did reach statistical significance, which supports the clinical observation that females metabolize certain CYP3A4 substrates faster than do males. Compared with those from Caucasians and African Americans, liver microsomes from Hispanics had about twice the average activity of CYP2A6, CYP2B6, and CYP2C8 and half the activity of CYP1A2, although this apparent ethnic difference may be a consequence of the relatively low number of Hispanic donors. Primary cultures of hepatocytes were treated with β-naphthoflavone, an inducer of CYP1A2, phenobarbital or rifampin, both of which induce CYP2B6, CYP2C9, CYP2C19, and CYP3A4, albeit it to different extents. Induction of these CYP enzymes in freshly cultured hepatocytes did not appear to be influenced by the gender or age of the donor. Furthermore, CYP3A4 induction in

  8. Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer

    Science.gov (United States)

    2013-06-03

    Adult Primary Cholangiocellular Carcinoma; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Extrahepatic Bile Duct; Cholangiocarcinoma of the Gallbladder; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  9. Gadobenate dimeglumine-enhanced MR of VX2 carcinoma in rabbit liver: usefulness of the delayed phase imaging and optimal pulse sequence

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Seung Il; Lee, Jeong Min; Kim, Young Kon; Kim, Chong Soo [College of Medicine, Chonbuk National Univ., Chonju (Korea, Republic of)

    2002-07-01

    To assess the diagnostic value of delayed imaging using gadobenate dimeglumine (MultiHance) and to determine the optimal pulse sequence for the detection of VX2 carcinoma lesions in the rabbit. Twelve VX2 carcinomas implanted in the livers of eleven New Zealand rabbits were studied. All patients underwent an MR protocal consisting of precontrast T2-and T1-weighted sequences, followed by repetition of the T1-weighted sequence at 0 to 30 (arterial phase). 31-60 (portal phase), and 40 minutes (delayed phase) after the intravenous administration of 0.1 mmol/kg of gadobenate dimeglumine. The signal-to-noise ratio (SNR) of the liver and VX2 tumor, and the lesion-to-liver contrast-to-noise ratio (CNR) of precontrast and postcontrast MR images were quantitatively analyzed, and two experienced radiologists evaluated image quality in terms of lesion conspicuity, artifact, mass delineation, and vascular anatomy. Liver SNR was significantly higher at delayed imaging than at precontrast, arterial, and portal imaging (p<0.05), while lesion SNR was significantly higher at delayed imaging than at precontrast imaging (p<0.05). Lesion CNR was higher at delayed imaging than at precontrast and portal phase imaging (p<0.05), but there was no difference between arterial and delayed imaging. The latter provided better mass delineation than precontrast, arterial and portal phase imaging (p<0.05). While in terms of lesion conspicuity and vascular anatomy, the delayed phase was better than the arterial phase (p<0.05) but similar to the precontrast and portal phase. During the delayed phase, the gradient-echo sequence showed better results than the spin-echo in terms of liver SNR, and lesion SNR and CNR (p<0.05). Because it provides better lesion conspicuity and mass delineation by improving liver SNR and lesion-to-liver CNR, the addition of the delayed phase to a dynamic MRI sequence after gadobenate dimeglumine adminstration facilitates lesion detection. For delayed-phase imaging, the

  10. Gadobenate dimeglumine-enhanced MR of VX2 carcinoma in rabbit liver: usefulness of the delayed phase imaging and optimal pulse sequence

    International Nuclear Information System (INIS)

    Cho, Seung Il; Lee, Jeong Min; Kim, Young Kon; Kim, Chong Soo

    2002-01-01

    To assess the diagnostic value of delayed imaging using gadobenate dimeglumine (MultiHance) and to determine the optimal pulse sequence for the detection of VX2 carcinoma lesions in the rabbit. Twelve VX2 carcinomas implanted in the livers of eleven New Zealand rabbits were studied. All patients underwent an MR protocal consisting of precontrast T2-and T1-weighted sequences, followed by repetition of the T1-weighted sequence at 0 to 30 (arterial phase). 31-60 (portal phase), and 40 minutes (delayed phase) after the intravenous administration of 0.1 mmol/kg of gadobenate dimeglumine. The signal-to-noise ratio (SNR) of the liver and VX2 tumor, and the lesion-to-liver contrast-to-noise ratio (CNR) of precontrast and postcontrast MR images were quantitatively analyzed, and two experienced radiologists evaluated image quality in terms of lesion conspicuity, artifact, mass delineation, and vascular anatomy. Liver SNR was significantly higher at delayed imaging than at precontrast, arterial, and portal imaging (p<0.05), while lesion SNR was significantly higher at delayed imaging than at precontrast imaging (p<0.05). Lesion CNR was higher at delayed imaging than at precontrast and portal phase imaging (p<0.05), but there was no difference between arterial and delayed imaging. The latter provided better mass delineation than precontrast, arterial and portal phase imaging (p<0.05). While in terms of lesion conspicuity and vascular anatomy, the delayed phase was better than the arterial phase (p<0.05) but similar to the precontrast and portal phase. During the delayed phase, the gradient-echo sequence showed better results than the spin-echo in terms of liver SNR, and lesion SNR and CNR (p<0.05). Because it provides better lesion conspicuity and mass delineation by improving liver SNR and lesion-to-liver CNR, the addition of the delayed phase to a dynamic MRI sequence after gadobenate dimeglumine adminstration facilitates lesion detection. For delayed-phase imaging, the

  11. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired

  12. Time of hepatocellular carcinoma recurrence after liver resection and alpha-fetoprotein are important prognostic factors for salvage liver transplantation.

    Science.gov (United States)

    Lee, Sanghoon; Hyuck David Kwon, Choon; Man Kim, Jong; Joh, Jae-Won; Woon Paik, Seung; Kim, Bong-Wan; Wang, Hee-Jung; Lee, Kwang-Woong; Suh, Kyung-Suk; Lee, Suk-Koo

    2014-09-01

    Salvage liver transplantation (LT) is considered a feasible option for the treatment of recurrent hepatocellular carcinoma (HCC). We performed this multicenter study to assess the risk factors associated with the recurrence of HCC and patient survival after salvage LT. Between January 2000 and December 2011, 101 patients who had previously undergone liver resection (LR) for HCC underwent LT at 3 transplant centers in Korea. Sixty-nine patients' data were retrospectively reviewed for the analysis. The recurrence of HCC was diagnosed at a median of 10.6 months after the initial LR, and patients underwent salvage LT. Recurrences were within the Milan criteria in 48 cases and were outside the Milan criteria in 21 cases. After salvage LT, 31 patients had HCC recurrence during a median follow-up period of 24.5 months. There were 24 deaths, and 20 were due to HCC recurrence. The 5-year overall survival rate was approximately 54.6%, and the 5-year recurrence-free survival rate was 49.3%. HCC recurrence within the 8 months after LR [hazard ratio (HR) = 3.124, P = 0.009], an alpha-fetoprotein level higher than 200 ng/mL (HR = 2.609, P = 0.02), and HCC outside the Milan criteria at salvage LT (HR = 2.219, P = 0.03) were independent risk factors for poor recurrence-free survival after salvage LT. In conclusion, the timing and extent of HCC recurrence after primary LR both play significant roles in the outcome of salvage LT. © 2014 American Association for the Study of Liver Diseases.

  13. Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo.

    Science.gov (United States)

    Jung, Hong-Ryul; Kang, Hyun Mi; Ryu, Jea-Woon; Kim, Dae-Soo; Noh, Kyung Hee; Kim, Eun-Su; Lee, Ho-Joon; Chung, Kyung-Sook; Cho, Hyun-Soo; Kim, Nam-Soon; Im, Dong-Soo; Lim, Jung Hwa; Jung, Cho-Rok

    2017-09-05

    We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs). HUVECs promoted proliferation and gene expression of HCC-related genes and cancer stem cell markers in the Huh7 spheroidsby activating cytokine signalling, mimicking gene expression in liver cancer. HUVECs induced angiogenesis and vessel maturation in Huh7 spheroids in vivo by activating epithelial-mesenchymal transition and angiogenic pathways. The large Huh7 cell spheroids containing HUVECs survived at higher concentrations of anti-cancer drugs (doxorubicin and sorafenib) than did monolayer cells. Our large cell spheroid provides a useful in vitro HCC model to enable intuitive observation for anti-cancer drug testing.

  14. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    International Nuclear Information System (INIS)

    Martinez, V. D.; Becker-Santos, D. D.; Vucic, E. A.; Lam, S.; Lam, W. L.

    2011-01-01

    Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epi genomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

  15. Assessment of emerging biomarkers of liver injury in human subjects.

    Science.gov (United States)

    Schomaker, Shelli; Warner, Roscoe; Bock, Jeff; Johnson, Kent; Potter, David; Van Winkle, Joyce; Aubrecht, Jiri

    2013-04-01

    Hepatotoxicity remains a major challenge in drug development. Although alanine aminotransferase (ALT) remains the gold standard biomarker of liver injury, alternative biomarker strategies to better predict the potential for severe drug-induced liver injury (DILI) are essential. In this study, we evaluated the utility of glutamate dehydrogenase (GLDH), purine nucleoside phosphorylase (PNP), malate dehydrogenase (MDH), and paraxonase 1 (PON1) as indicators of liver injury in cohorts of human subjects, including healthy subjects across age and gender, subjects with a variety of liver impairments, and several cases of acetaminophen poisoning. In the healthy subjects, levels of GLDH and MDH were not affected by age or gender. Reference ranges for GLDH and MDH in healthy subjects were 1-10 and 79-176U/L, respectively. In contrast, the levels of PON1 and PNP were not consistent across cohorts of healthy subjects. Furthermore, GLDH and MDH had a strong correlation with elevated ALT levels and possessed a high predictive power for liver injury, as determined by ROC analysis. In contrast, PON1 and PNP did not detect liver injury in our study. Finally, evaluation of patients with acetaminophen-induced liver injury provided evidence that both GLDH and MDH might have utility as biomarkers of DILI in humans. This study is the first to evaluate GLDH, MDH, PON1, and PNP in a large number of human subjects and, and it provides an impetus for prospective clinical studies to fully evaluate the diagnostic value of GLDH and MDH for detection of liver injury.

  16. Cranberry juice suppressed the diclofenac metabolism by human liver microsomes, but not in healthy human subjects

    Science.gov (United States)

    Ushijima, Kentarou; Tsuruoka, Shu-ichi; Tsuda, Hidetoshi; Hasegawa, Gohki; Obi, Yuri; Kaneda, Tae; Takahashi, Masaki; Maekawa, Tomohiro; Sasaki, Tomohiro; Koshimizu, Taka-aki; Fujimura, Akio

    2009-01-01

    AIM To investigate a potential interaction between cranberry juice and diclofenac, a substrate of CYP2C9. METHODS The inhibitory effect of cranberry juice on diclofenac metabolism was determined using human liver microsome assay. Subsequently, we performed a clinical trial in healthy human subjects to determine whether the repeated consumption of cranberry juice changed the diclofenac pharmacokinetics. RESULTS Cranberry juice significantly suppressed diclofenac metabolism by human liver microsomes. On the other hand, repeated consumption of cranberry juice did not influence the diclofenac pharmacokinetics in human subjects. CONCLUSIONS Cranberry juice inhibited diclofenac metabolism by human liver microsomes, but not in human subjects. Based on the present and previous findings, we think that although cranberry juice inhibits CYP2C9 activity in vitro, it does not change the pharmacokinetics of medications metabolized by CYP2C9 in clinical situations. PMID:19694738

  17. Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis

    NARCIS (Netherlands)

    Westra, Inge M.; Mutsaers, Henricus A. M.; Luangmonkong, Theerut; Hadi, Mackenzie; Oosterhuis, Dorenda; de Jong, Koert P.; Groothuis, Geny M. M.; Olinga, Peter

    Liver fibrosis is the progressive accumulation of connective tissue ultimately resulting in loss of organ function. Currently, no effective antifibrotics are available due to a lack of reliable human models. Here we investigated the fibrotic process in human precision-cut liver slices (PCLS) and

  18. Interaction of rocuronium with human liver cytochromes P450

    OpenAIRE

    Anzenbacherova, Eva; Spicakova, Alena; Jourova, Lenka; Ulrichova, Jitka; Adamus, Milan; Bachleda, Petr; Anzenbacher, Pavel

    2015-01-01

    Rocuronium is a neuromuscular blocking agent acting as a competitive antagonist of acetylcholine. Results of an inhibition of eight individual liver microsomal cytochromes P450 (CYP) are presented. As the patients are routinely premedicated with diazepam, possible interaction of diazepam with rocuronium has been also studied. Results indicated that rocuronium interacts with human liver microsomal CYPs by binding to the substrate site. Next, concentration dependent inhibition of liver micro...

  19. Cytotoxicity and Expression of c-fos, HSP70, and GADD45/153 Proteins in Human Liver Carcinoma (HepG2 Cells Exposed to Dinitrotoluenes

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-08-01

    Full Text Available Dinitrotoluenes (DNTs are byproducts of the explosive trinitrotoluene (TNT, and exist as a mixture of 2 to 6 isomers, with 2,4-DNT and 2,6-DNT being the most significant. The main route of human exposure at ammunition facilities is inhalation. The primary targets of DNTs toxicity are the hematopoietic system, cardiovascular system, nervous system and reproductive system. In factory workers, exposure to DNTs has been linked to many adverse health effects, including: cyanosis, vertigo, headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite, nausea, and vomiting. Other symptoms including pain or parasthesia in extremities, abdominal discomfort, tremors, paralysis, chest pain, and unconsciousness have been documented. An association between DNTs exposure and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats, as well as renal tumors in mice, has been established. This research was therefore designed targeting the liver to assess the cellular and molecular responses of human liver carcinoma cells following exposure to 2,4-DNT and 2,6-DNT. Cytotoxicity was evaluated using the MTT assay. Upon 48 hrs of exposure, LC50 values of 245 + 14.72μg/mL, and 300 + 5.92μg/mL were recorded for 2,6-DNT and 2,4-DNT respectively, indicating that both DNTs are moderately toxic, and 2,6-DNT is slightly more toxic to HepG2 cells than 2,4-DNT. A dose response relationship was recorded with respect to the cytotoxicity of both DNTs. Western blot analysis resulted in a significant expression (p<0.05 of the 70-kDa heat shock protein in 2,6-DNT-treated cells compared to the control cells and at the 200 μg/mL dose for 2,4-DNT. A statistically significant expression in c-fos was also observed at the 200 and 250 μg/mL treatment level for 2,4- and 2,6-DNT, respectively. However, no statistically significant expression of this protooncogene-related protein was observed at the doses of 0, 100, or 300

  20. 3-Tesla MRI Response to TACE in HCC (Liver Cancer)

    Science.gov (United States)

    2016-08-22

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Resectable Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Stage A Adult Primary Liver Cancer (BCLC); Stage B Adult Primary Liver Cancer (BCLC)

  1. Aggressive treatment of metastatic squamous cell carcinoma of the rectum to the liver: a case report and a brief review of the literature

    Directory of Open Access Journals (Sweden)

    Carvounis Eleni E

    2006-08-01

    Full Text Available Abstract Background Rectal squamous cell carcinoma (SCC is a rare tumor. The incidence of this malignancy has been reported to be 0.25 to 1 per 1000 colorectal carcinomas. From a review of the English literature 55 cases of SCC of the rectum have been published. In this study we report a rectal metastatic SCC to the liver, discussing the efficacy of aggressive adjuvant and neo-adjuvant therapies on survival and prognosis. Case presentation A 39-year-old female patient with a pure SCC of the rectum diagnosed endoscopically is presented. The patient underwent initially neoadjuvant chemo-radiotherapy and then abdominoperineal resection with concomitant bilateral oophorectomy and hysterectomy, followed by adjuvant chemo-radiotherapy. Five months after the initial operation liver metastasis was demonstrated and a liver resection was carried out, followed by adjuvant chemotherapy. Eighteen months after the initial operation the patient is alive. Conclusion Although prognosis of rectal SCC is worse than that of adenocarcinoma, an aggressive therapeutic approach with surgery as the primary treatment, followed by combined neo- and adjuvant chemo-radiotherapy, may be necessary in order to improve survival and prognosis.

  2. Chemoembolization Decreases Drop-Off Risk of Hepatocellular Carcinoma Patients on the Liver Transplant List

    International Nuclear Information System (INIS)

    Frangakis, Constantine; Geschwind, Jean-Francois; Kim, Daniel; Chen, Yong; Koteish, Ayman; Hong, Kelvin; Liapi, Eleni; Georgiades, Christos S.

    2011-01-01

    Introduction: The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk. Patients and Methods: Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher’s, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan–Meier estimators (log-rank test) were used to determine survival rates. Results: Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078). Conclusions: Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

  3. Inflammatory markers as selection criteria of hepatocellular carcinoma in living-donor liver transplantation.

    Science.gov (United States)

    Na, Gun Hyung; Kim, Dong Goo; Han, Jae Hyun; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

    2014-06-07

    To investigate that inflammatory markers can predict accurately the prognosis of hepatocelluar carcinoma (HCC) patients in living-donor liver transplantation (LDLT). From October 2000 to November 2011, 224 patients who underwent living donor liver transplantation for HCC at our institution were enrolled in this study. We analyzed disease-free survival (DFS) and overall survival (OS) after LT in patients with HCC and designed a new score model using pretransplant neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP). The DFS and OS in patients with an NLR level ≥ 6.0 or CRP level ≥ 1.0 were significantly worse than those of patients with an NLR level < 6.0 or CRP level < 1.0 (P = 0.049, P = 0.003 for NLR and P = 0.010, P < 0.001 for CRP, respectively). Using a new score model using the pretransplant NLR and CRP, we can differentiate HCC patients beyond the Milan criteria with a good prognosis from those with a poor prognosis. Combined with the Milan criteria, new score model using NLR and CRP represent new selection criteria for LDLT candidates with HCC, especially beyond the Milan criteria.

  4. Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Ilowski, Maren [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Kleespies, Axel [Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Toni, Enrico N. de [Department of Medicine II, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Donabauer, Barbara [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Jauch, Karl-Walter [Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Hengstler, Jan G. [Leibniz Research Centre for Working Environment and Human Factors, Technical University, Dortmund (Germany); Thasler, Wolfgang E., E-mail: wolfgang.thasler@med.uni-muenchen.de [Liver Regeneration Group, Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany); Department of Surgery, Grosshadern Hospital, Ludwig Maximilians University, Munich (Germany)

    2011-01-07

    Research highlights: {yields} ALR decreases cytochrome c release from mitochondria. {yields} ALR protects hepatocytes against apoptosis induction by ethanol, TRAIL, anti-Apo, TGF-{beta} and actinomycin D. {yields} ALR exerts a liver-specific anti-apoptotic effect. {yields} A possible medical usage of ALR regarding protection of liver cells during apoptosis inducing therapies. -- Abstract: Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-{beta}, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-{beta} and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

  5. Augmenter of liver regeneration (ALR) protects human hepatocytes against apoptosis

    International Nuclear Information System (INIS)

    Ilowski, Maren; Kleespies, Axel; Toni, Enrico N. de; Donabauer, Barbara; Jauch, Karl-Walter; Hengstler, Jan G.; Thasler, Wolfgang E.

    2011-01-01

    Research highlights: → ALR decreases cytochrome c release from mitochondria. → ALR protects hepatocytes against apoptosis induction by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. → ALR exerts a liver-specific anti-apoptotic effect. → A possible medical usage of ALR regarding protection of liver cells during apoptosis inducing therapies. -- Abstract: Augmenter of liver regeneration (ALR) is known to support liver regeneration and to stimulate proliferation of hepatocytes. However, it is not known if ALR exerts anti-apoptotic effects in human hepatocytes and whether this protective effect is cell type specific. This is relevant, because compounds that protect the liver against apoptosis without undesired effects, such as protection of metastatic tumour cells, would be appreciated in several clinical settings. Primary human hepatocytes (phH) and organotypic cancer cell lines were exposed to different concentrations of apoptosis inducers (ethanol, TRAIL, anti-Apo, TGF-β, actinomycin D) and cultured with or without recombinant human ALR (rhALR). Apoptosis was evaluated by the release of cytochrome c from mitochondria and by FACS with propidium iodide (PI) staining. ALR significantly decreased apoptosis induced by ethanol, TRAIL, anti-Apo, TGF-β and actinomycin D. Further, the anti-apoptotic effect of ALR was observed in primary human hepatocytes and in HepG2 cells but not in bronchial (BC1), colonic (SW480), gastric (GC1) and pancreatic (L3.6PL) cell lines. Therefore, the hepatotrophic growth factor ALR acts in a liver specific manner with regards to both its mitogenic and its anti-apoptotic effect. Unlike the growth factors HGF and EGF, rhALR acts in a liver specific manner. Therefore, ALR is a promising candidate for further evaluation as a possible hepatoprotective factor in clinical settings.

  6. Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

    International Nuclear Information System (INIS)

    Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

    2006-01-01

    Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

  7. Cytosolic and nuclear caspase-8 have opposite impact on survival after liver resection for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Koschny, Ronald; Schemmer, Peter; Schirmacher, Peter; Ganten, Tom M; Brost, Sylvia; Hinz, Ulf; Sykora, Jaromir; Batke, Emanuela M; Singer, Stephan; Breuhahn, Kai; Stremmel, Wolfgang; Walczak, Henning

    2013-01-01

    An imbalance between proliferation and apoptosis is one of the main features of carcinogenesis. TRAIL (TNF-related apoptosis-inducing ligand) induces apoptosis upon binding to the TRAIL death receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2, whereas binding to TRAIL-R3 and TRAIL-R4 might promote cell survival and proliferation. The anti-tumor activity of TRAIL-R1 and TRAIL-R2 agonists is currently investigated in clinical trials. To gain further insight into the regulation of apoptosis in hepatocellular carcinoma (HCC), we investigated the TRAIL pathway and the regulators of apoptosis caspase-8, Bcl-xL and Mcl-1 in patients with HCC regarding patient survival. We analyzed 157 hepatocellular carcinoma patients who underwent partial liver resection or orthotopic liver transplantation and healthy control liver tissue using immunohistochemistry on tissue microarrays for the expression of TRAIL-R1 to TRAIL-R4, caspase-8, Bcl-xL and Mcl-1. Immunohistochemical data were evaluated for potential associations with clinico-pathological parameters and survival. Whereas TRAIL-R1 was downregulated in HCC in comparison to normal liver tissue, TRAIL-R2 and –R4 were upregulated in HCC, especially in G2 and G3 tumors. TRAIL-R1 downregulation and upregulation of TRAIL-R2 and TRAIL-R4 correlated with tumor dedifferentiation (G2/G3). TRAIL-R3, Bcl-xL and Mcl-1 showed no differential expression in tumor tissue compared to normal tissue. The expression levels of TRAIL receptors did not correlate with patient survival after partial hepatectomy. Interestingly, in tumor tissue, but not in normal hepatocytes, caspase-8 showed a strong nuclear staining. Low cytosolic and high nuclear staining intensity of caspase-8 significantly correlated with impaired survival after partial hepatectomy, which, for cytosolic caspase-8, was independent from tumor grade. Assessment of TRAIL-receptor expression patterns may have therapeutic implications for the use of TRAIL receptor agonists in HCC therapy

  8. Usefulness of technetium-99m tetrofosmin liver imaging to detect hepatocellular carcinoma and related to expression of P-glycoprotein or multidrug resistance associated protein-a preliminary report

    International Nuclear Information System (INIS)

    Ding, H.J.; Huang, W.T.; Tsai, C.S.; Chang, C.S.; Kao, A.

    2003-01-01

    Technetium-99m Tetrofsomin (Tc-TF) has been shown to be useful in identifying several types of tumors, such as breast, lung, and thyroid cancers. There was no report in the literature for Tc-TF uptake in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the usefulness of Tc-TF liver imaging to detect HCC and investigate the relationship between Tc-TF liver imaging findings and P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP) expression. Before any therapy, 22 patients with HCC were enrolled in this study. Tc-TF liver images were performed l0 minutes after intravenous injection of 20mCi Tc-TF. All patients had liver biopsy or surgery within l week after Tc-TF liver imaging. Immunohistochemical study of the biopsy or resected HCC specimens was performed using anti-human Pgp and MRP antibodies. Twenty of the 22 (90.9%) patients showed negative Tc-TF liver imaging results without significant Tc-TF uptake in HCC, whereas only the remaining 2 (9.1%) patients showed positive Tc-TF liver imaging results with significant Tc-TF uptake in HCC. Positive Pgp expression was observed in 13 of 20 patients with negative Tc-TF liver imaging results, whereas positive MRP expression was observed in 6 of the remaining 7 patients with negative both Tc-TF liver imaging results and Pgp expression. However, negative Pgp expression but positive MRP expression was observed in all of the remaining 2 patients with positive Tc-TF liver imaging results. The correlation between Tc-TF liver imaging findings and Pgp expression was significant and better than between Tc-TF liver imaging findings and MRP expression. Pgp or MRP expression in HCC may induce no significant Tc-TF uptake in HCC resulting in negative Tc-TF liver imaging findings. Therefore, Tc-TF liver imaging is potential to be a non-invasive method to predict Pgp or MRP expression in HCC. However, further studies with a larger series of patients and longer follow-up time are necessary to confirm

  9. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

    Science.gov (United States)

    Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

    2015-12-01

    Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

  10. Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls

    Science.gov (United States)

    Yin, Wei-Li; Wang, Feng-Mei; Han, Tao

    2016-01-01

    Background Conflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D) of human HFE (hereditary hemochromatosis) gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD), liver cirrhosis and hepatocellular carcinoma (HCC). Methods An updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis. Results In total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, PassociationHFE C282Y and H63D (all Passociation>0.05). In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, PassociationHFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion. PMID:27657935

  11. The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

    International Nuclear Information System (INIS)

    Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan; Tiollais, Pierre; Li, Tsaiping; Zhao, Mujun

    2011-01-01

    Highlights: → LIS1 mRNA and protein levels are decreased in 70% HCC tissues. → Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. → LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. → Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. → Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the development and

  12. The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

    Energy Technology Data Exchange (ETDEWEB)

    Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Tiollais, Pierre [Unite' d' Organisation Nucleaire et Oncogenese, INSERM U.579, Institut Pasteur, Paris (France); Li, Tsaiping [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Zhao, Mujun, E-mail: mjzhao@sibs.ac.cn [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

    2011-06-03

    Highlights: {yields} LIS1 mRNA and protein levels are decreased in 70% HCC tissues. {yields} Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. {yields} LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. {yields} Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. {yields} Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the

  13. From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Hong Yang

    2017-03-01

    Full Text Available Background Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. Methods Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values. Results A list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, ‘pathways in cancer,’ was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982–0.998], P < 0.001, sensitivity: 96.0%, specificity: 96.5%. BIRC5 (P = 0.021 and CCNE1 (P = 0.027 were associated with poor prognosis, while CDKN2A (P = 0.066 and E2F1 (P = 0.088 demonstrated no statistically significant differences. Discussion The study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, ‘pathways in cancer.’ The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be

  14. Metabolic fate of 18F-FDG in mice bearing either SCCVII squamous cell carcinoma or C3H mammary carcinoma

    DEFF Research Database (Denmark)

    Kaarstad, Katrin; Bender, Dirk; Bentzen, Lise

    2002-01-01

    in mice. METHODS: 18F-FDG was given intravenously to mice with either SCCVII squamous cell carcinoma or C3H mammary carcinoma grown on the back. 18F-Labeled metabolites were determined by radio-high-performance liquid chromatography in tumor tissue biopsies, in a time course of 180 min (12 mice of each...... tumor type), and in liver tissue biopsies 80 min after tracer injection (2 mice of each type). RESULTS: After the tracer injection, not only 18F-FDG and 18F-FDG-6-P but also 18F-FD-PG1 and 2-18F-fluoro-2-deoxy-1,6-biphosphate were detected in both tumors, relatively more in SCCVII carcinoma than in C3H...... carcinoma. Both tumors accumulated radioactivity throughout the 180-min measurement period, 4-fold more in SCCVII carcinoma than in C3H carcinoma. At 80 min, the radioactivity was approximately 6 and 1.2 times higher in the respective tumors than in liver tissue. CONCLUSION: Our results agree...

  15. The radiographic appearance of primary liver neoplasia in dogs

    Energy Technology Data Exchange (ETDEWEB)

    Evans, S. M.

    1987-11-15

    The signalment, anamnesis, and histopathologic, gross pathologic, and radiographic findings in 22 dogs with nonvascular, nonhematopoletic primary liver tumors were reviewed. The tumor types represented were hepatoma (8), bile duct cystadenoma (1), hepatocellular carcinoma (5), and cholangiocellular carcinoma (8). The dogs averaged 11.1 years of age. Females were predisposed to cholangiocellular carcinoma. The most common presenting clinical signs were general malaise, anorexia, PU/PD, vomiting, and seizures. Tumors ranged in size from diffuse 0.5-1 cm nodules to an 18-cm solitary mass and were located in any of the liver lobes. Four of the five diffuse tumors were cholangiocellular carcinomas. The most common radiographic appearance for any type of liver tumor was a right cranial abdominal mass causing caudal and left gastric displacement. In 54.5% of the dogs, radiographic evidence of intraperitoneal disease was identified. Nodular interstitial pulmonary masses were seen in 3 of the 22 dogs.

  16. The radiographic appearance of primary liver neoplasia in dogs

    International Nuclear Information System (INIS)

    Evans, S.M.

    1987-01-01

    The signalment, anamnesis, and histopathologic, gross pathologic, and radiographic findings in 22 dogs with nonvascular, nonhematopoletic primary liver tumors were reviewed. The tumor types represented were hepatoma (8), bile duct cystadenoma (1), hepatocellular carcinoma (5), and cholangiocellular carcinoma (8). The dogs averaged 11.1 years of age. Females were predisposed to cholangiocellular carcinoma. The most common presenting clinical signs were general malaise, anorexia, PU/PD, vomiting, and seizures. Tumors ranged in size from diffuse 0.5-1 cm nodules to an 18-cm solitary mass and were located in any of the liver lobes. Four of the five diffuse tumors were cholangiocellular carcinomas. The most common radiographic appearance for any type of liver tumor was a right cranial abdominal mass causing caudal and left gastric displacement. In 54.5% of the dogs, radiographic evidence of intraperitoneal disease was identified. Nodular interstitial pulmonary masses were seen in 3 of the 22 dogs

  17. LP-THAE induced tumor cell apoptosis of rabbit VX2 liver carcinoma

    International Nuclear Information System (INIS)

    Chen Shengli; Quan Yi; Huang Zicheng; Chen Guodong; Zhu Dongliang

    2007-01-01

    Objective: To research tumor cell apoptosis induced by Lp-THAE of rabbit VX2 liver implanted tumor. Methods: 27 New Zealand white rabbits implanted with VX2 tumor at left middle lobe of the liver divided into three groups: Group A(n= 9) Lp-THAE: treated through transhepatic artery catheterization; Group B(n=9) THAI and Group C(n=9) as control. The rabbits were executed at second to fifth day after treatment. HE dye microscopy was taken for counting the typical apoptosis cells and calculating apoptosis index (ApI). FITC-AnnexinV/PI assay was used for measuring apoptosis by flow cytometry. Results: The ApI of tumor central area and marginal area were (17.769±2.417)%, (4.129±1.172)%, P<0.01. The percentages of tumor cell apoptosis and tumor cell necrosis were (16.483±1.404)%, (9.478±0.964)%, P<0.01 and (43.559±5.053)%, (33.460±1.840)%, P=0.093. The total percentages of tumor cell apoptosis and necrosis were (60.042±13.979)%, (42.938±8.979)%, P< 0.01, at tumor center and marginal area in THAE group respectively. The ApI, percentages of tumor cell apoptosis and necrosis in THAE group were significantly higher than those of THAI group (P<0.01). The percentages of tumor cell apoptosis at tumor center area in THAE group were significantly higher than those of tumor marginal area(P<0.01). Conclusion: Induced tumor cell apoptosis and necrosis are two mechanisms of action for Lp-THAE treatment of liver carcinoma. (authors)

  18. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  19. Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

    Science.gov (United States)

    Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

    1985-08-01

    Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

  20. Molecular cloning and nucleotide sequence of cDNA for human liver arginase

    International Nuclear Information System (INIS)

    Haraguchi, Y.; Takiguchi, M.; Amaya, Y.; Kawamoto, S.; Matsuda, I.; Mori, M.

    1987-01-01

    Arginase (EC3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, the authors isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in λ gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated λ hARG6 and λ hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted M/sub r/, 34,732), a 5'-untranslated sequence of 56 base pairs, a 3'-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying λ hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat, and yeast enzymes

  1. Constitutional and functional genetics of human alcohol-related hepatocellular carcinoma.

    Science.gov (United States)

    Nahon, Pierre; Nault, Jean-Charles

    2017-11-01

    Exploration of the constitutional genetics of hepatocellular carcinoma (HCC) has identified numerous variants associated with a higher risk of liver cancer in alcoholic cirrhotic patients. Although Genome-Wide Association studies have not been carried out in the field of alcohol-related HCC, common single nucleotide polymorphisms conferring a small increase in the risk of liver cancer risk have been identified and shown to modulate ethanol metabolism, inflammation, oxidative stress, iron or lipid metabolism. Specific patterns of gene mutations including CTNNB1, TERT, ARID1A and SMARCA2 exist in alcohol-related HCC. Moreover, a specific mutational process observed at the nucleotide level by next generation sequencing has revealed cooperation between alcohol and tobacco in the development of HCC. Combining this genetic information with epidemiological and clinical data that might define specific HCC risk classes and refine surveillance strategies needs to be assessed in large prospective cohorts of patients with alcoholic cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Voll, Renate

    2008-07-01

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

  3. Liver and Bile Duct Cancer—Patient Version

    Science.gov (United States)

    Liver cancer includes hepatocellular carcinoma and bile duct cancer (cholangiocarcinoma). Risk factors for HCC include chronic infection with hepatitis B or C and cirrhosis of the liver. Start here to find information on liver and bile duct cancer treatment, causes and prevention, screening, research, and statistics.

  4. Differential metabonomic profiles of primary hepatocellular carcinoma tumors from alcoholic liver disease, HBV-infected, and HCV-infected cirrhotic patients

    OpenAIRE

    Cao, Ding; Cai, Can; Ye, Mingxin; Gong, Junhua; Wang, Menghao; Li, Jinzheng; Gong, Jianping

    2017-01-01

    Our objective was to comparatively profile the metabolite composition of primary hepatocellular carcinoma (HCC) tumors from alcoholic liver disease (ALD), hepatitis B virus (HBV)-infected, and hepatitis C virus (HCV)-infected cirrhotic patients. Primary HCC tumors were collected from ALD, HBV-infected, and HCV-infected cirrhotic patients (n=20 each). High-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and metabonomic data analysis were performed to compare HCC ...

  5. Real-time image guidance in laparoscopic liver surgery

    DEFF Research Database (Denmark)

    Kenngott, Hannes G.; Wagner, Martin; Gondan, Matthias

    2014-01-01

    Background: Laparoscopic liver surgery is particularly challenging owing to restricted access, risk of bleeding and lack of haptic feedback. Navigation systems have the potential to improve information on the exact position of intrahepatic tumors, and thus facilitate oncological resection....... This study aims to evaluate the feasibility of a commercially available augmented reality (AR) guidance system employing intraoperative robotic C-arm cone-beam computed tomography (CBCT) for laparoscopic liver surgery. Methods: A human liver-like phantom with sixteen target fiducials was used to evaluate...... the Syngo iPilot® AR system. Subsequently, the system was used for the laparoscopic resection of a hepatocellular carcinoma in segment 7 of a 50-year-old male patient. Results: In the phantom experiment the AR system showed a mean target registration error of 0.96 mm ± 0.52 mm with a maximum error of 2...

  6. Preoperative Right Portal Vein Embolization in Patients with metastatic liver disease. Metastatic liver volumes after RPVE

    International Nuclear Information System (INIS)

    Barbaro, B.; Stasi, C.D.I.; Marano, P.; Nuzzo, G.; Vellone, M.; Giuliante, F.

    2003-01-01

    Purpose:To quantify liver metastases and future remnant liver (FRL) volumes in patients who underwent right portal vein embolization (RPVE) and to evaluate the effects of this procedure on metastase growth. Material and Methods:Nine patients with liver metastases from primary colon (n = 5), rectal lesions (n = 1) and carcinoid tumors (n = 3) underwent spiral CT to evaluate the ratio of the non-tumorous parenchymal volume of the resected liver to that of the whole liver volume (R2). Hand tracing was used to isolate the entire liver, the resected liver and metastase volumes. All patients with R2 > 60% underwent RPVE. Results:FRL exhibited a 101-336 cm3 (average 241 cm3) increase in volume 1 month after RPVE. One patient refused surgery for 2 months and before surgery the increase in volume of the FRL was similar to that of other patients (180.64 cm3). Percent metastases volume from colorectal carcinoma in embolized liver parenchyma increased from 62.4% to 138.4% at 1 month and to 562% at 2 months after RPVE. Metastase volume from carcinoid tumors was unchanged. Conclusion:One month after RPVE, hypertrophy of the FRL is evident. In the embolized liver, there was a progressive increase in metastase volume from colorectal carcinoma while metastase volume from carcinoid tumor was unchanged in embolized and non-embolized liver

  7. Dynamic CT of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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.

  8. Automatic liver contouring for radiotherapy treatment planning

    International Nuclear Information System (INIS)

    Li, Dengwang; Kapp, Daniel S; Xing, Lei; Liu, Li

    2015-01-01

    To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems.The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV-L1), which has the characteristic of multi-scale decomposition and an edge-preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours.The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group

  9. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

    International Nuclear Information System (INIS)

    Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

    2009-01-01

    The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

  10. Expression pattern of thymosin beta 4 in the adult human liver

    Directory of Open Access Journals (Sweden)

    S. Nemolato

    2011-09-01

    Full Text Available Thymosin beta-4 (Tβ4 is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1. At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.

  11. Recellularization of rat liver: An in vitro model for assessing human drug metabolism and liver biology.

    Directory of Open Access Journals (Sweden)

    Matthew J Robertson

    Full Text Available Liver-like organoids that recapitulate the complex functions of the whole liver by combining cells, scaffolds, and mechanical or chemical cues are becoming important models for studying liver biology and drug metabolism. The advantages of growing cells in three-dimensional constructs include enhanced cell-cell and cell-extracellular matrix interactions and preserved cellular phenotype including, prevention of de-differentiation. In the current study, biomimetic liver constructs were made via perfusion decellularization of rat liver, with the goal of maintaining the native composition and structure of the extracellular matrix. We optimized our decellularization process to produce liver scaffolds in which immunogenic residual DNA was removed but glycosaminoglycans were maintained. When the constructs were recellularized with rat or human liver cells, the cells remained viable, capable of proliferation, and functional for 28 days. Specifically, the cells continued to express cytochrome P450 genes and maintained their ability to metabolize a model drug, midazolam. Microarray analysis showed an upregulation of genes involved in liver regeneration and fibrosis. In conclusion, these liver constructs have the potential to be used as test beds for studying liver biology and drug metabolism.

  12. Application of chimeric mice with humanized liver for study of human-specific drug metabolism.

    Science.gov (United States)

    Bateman, Thomas J; Reddy, Vijay G B; Kakuni, Masakazu; Morikawa, Yoshio; Kumar, Sanjeev

    2014-06-01

    Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively assessed and/or mitigated if human metabolic profile of the drug candidate could reliably be determined in early development. However, currently available in vitro human models (e.g., liver microsomes, hepatocytes) are often inadequate in this regard. Furthermore, the conduct of definitive radiolabeled human ADME studies is an expensive and time-consuming endeavor that is more suited for later in development when the risk of failure has been reduced. We evaluated a recently developed chimeric mouse model with humanized liver on uPA/SCID background for its ability to predict human disposition of four model drugs (lamotrigine, diclofenac, MRK-A, and propafenone) that are known to exhibit human-specific metabolism. The results from these studies demonstrate that chimeric mice were able to reproduce the human-specific metabolite profile for lamotrigine, diclofenac, and MRK-A. In the case of propafenone, however, the human-specific metabolism was not detected as a predominant pathway, and the metabolite profiles in native and humanized mice were similar; this was attributed to the presence of residual highly active propafenone-metabolizing mouse enzymes in chimeric mice. Overall, the data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation.

  13. Insulin Resistance and Hyperinsulinemia in Patients with Chronic Liver Disease and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Valter Donadon

    2009-01-01

    Full Text Available Objectives To investigate the role of insulin resistance (IR and insulin plasma levels (IRI in patients with chronic liver disease (CLD and hepatocellular carcinoma (HCC. Methods We recruited the following patients: 125 with HCC, 128 with liver cirrhosis (LC and 133 with chronic hepatitis C (CHC. IR was assessed by the HOMA-IR method. To define IR and hyperinsulinemia we selected as a cut-off level, the value of the 80th percentile for HOMA-IR (2.72 and IRI (11.18 in 113 healthy subjects. Results The mean levels of HOMA-IR and IRI increase progressively among CHC (2.7 ± 2.9 and 11.5 ± 10.5, respectively, LC (5.4 ± 4.5 and 17.6 ± 11.2 and HCC (6.4 ± 9.8 and 18.2 ± 18.8. In the upper quintiles for HOMA-IR and IRI, the frequency of patients in the LC and HCC groups was twice as much in CHC cases. HCC with DM2 have the greatest percentage above the 80th percentile of HOMA-IR, their quintiles distribution is inverted and HOMA-IR mean values are significantly higher in comparison with HCC without DM2 cases. Discussion Our study shows that the association between IR and CLD begins in the early stages of liver fibrosis. DM2 increases HOMA-IR and IRI mean levels in HCC patients and these metabolic factors could play a major role in the link between diabetes mellitus and hepatocarcinoma.

  14. N-Acetyl-L-Cysteine Affords Protection against Lead-Induced Cytotoxicity and Oxidative Stress in Human Liver Carcinoma (HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2007-06-01

    Full Text Available Although lead exposure has declined in recent years as a result of change to lead-free gasoline, several epidemiological have pointed out that it represents a medical and public health emergency, especially in young children consuming high amounts of lead-contaminated flake paints. A previous study in our laboratory indicated that lead exposure induces cytotoxicity in human liver carcinoma cells. In the present study, we evaluated the role of oxidative stress in lead-induced toxicity, and the protective effect of the anti-oxidant n-acetyl-l-cysteine (NAC. We hypothesized that oxidative stress plays a role in lead-induced cytotoxicity, and that NAC affords protection against this adverse effect. To test this hypothesis, we performed the MTT [3-(4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide] assay and the trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that NAC significantly increased the viability of HepG2 cells in a dosedependent manner upon 48 hours of exposure. Similar trend was obtained with the trypan blue exclusion test. Data generated from the thiobarbituric acid test showed a significant (p ≤ 0.05 increase of MDA levels in lead nitrate-treated HepG2 cells compared to control cells. Interestingly, the addition of NAC to lead nitrate-treated HepG2 cells significantly decreased cellular content of reactive oxygen species (ROS, as evidenced by the decrease in lipid peroxidation byproducts. Overall, findings from this study suggest that NAC inhibits lead nitrate-induced cytotoxicity and oxidative stress in HepG2 cells. Hence, NAC may be used as a salvage therapy for lead-induced toxicity in exposed persons.

  15. Metastatic Squamous Cell Carcinoma of the Stomach.

    Science.gov (United States)

    Hamzaoui, Lamine; Bouassida, Mahdi; Kilani, Houda; Medhioub, Mouna; Chelbi, Emna

    2015-11-01

    Primary squamous cell carcinoma of the stomach is very rare. Its pathogenesis is unclear and the treatment strategy is controversial. We report an agressive primary squamous cell carcinoma of the stomach with liver and lung metastases in a 55-year-old man. The patient presented with a 1-month history of abdominal pain, vomiting and weight loss. Abdominal ultrasound revealed multiple liver metastases. Endoscopic examination showed two tumour masses on the fundus of the stomach. Biopsy of the lesions revealed squamous cell carcinoma of the stomach. Chest x-ray showed multiple large pulmonary nodules highly suggestive of pulmonary metastases. The patient died ten days after he was admitted because of progression of the tumour and before any therapeutic decision.

  16. Phosphorus-31 spectroscopic imaging of the human liver

    International Nuclear Information System (INIS)

    Biran, M.; Raffard, G.; Canioni, P.; Kien, P.

    1993-01-01

    During the last decade, progresses in the field of nuclear magnetic resonance spectroscopy (M.R.S.), have allowed the metabolic studies of complex biological systems. Since the coming out of whole body magnets, clinical applications are possible; they utilize magnetic field gradients coupled with selective pulse sequences. Study of the phosphorylated metabolism of human liver can be performed with sequences as ISIS, FROGS or 1D-CSI. But they present some disadvantages (for instance contamination by phosphocreatine from muscle). In the present work, we have studied the human liver in vivo by 31 P spectroscopic imaging. Several spectra could be acquired with only one acquisition. This study has needed the building of radiofrequency coils (surface coils), specially designed for liver observation (15 cm diameter 31 P coil and 19 cm diameter proton coil, both transmitter and receiver coils). Preliminary studies have been done on a phantom followed by in vivo measurements on healthy subject livers. We have obtained localized 31 P N.M.R. spectra corresponding to different voxels within the hepatic tissue. The conditions of acquisition of spectra and the problems related to the saturation of phosphorylated metabolite signals (in particular phosphodiesters) are discussed. (author). 5 figs., 15 refs

  17. 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

  18. Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Takanori Takebe

    2017-12-01

    Full Text Available Summary: Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC. By conducting massive “reverse” screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>108. Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations. : With the goal of clinical translation of liver bud transplant therapy, Takebe et al. established a massive organoid production platform from endoderm, endothelial, and mesenchymal progenitor populations specified entirely from human iPSCs, reproducibly demonstrating functionality both in vitro and in vivo. Keywords: iPSC, liver bud, organoid, transplantation, self-organization, endothelial, mesenchymal, liver failure, clinical grade

  19. Operative outcome of liver resections for hepatocellular carcinoma: Retrospective case control study of a twelve-years pioneer experience in the Sudan

    Directory of Open Access Journals (Sweden)

    Osama Mohamed Elsanousi

    Full Text Available Introduction: Modern liver surgery in the Sudan started at our institution, The National Ribat University Hospital, in 2002. This study aimed to assess the perioperative events of hepatocellular carcinoma (HCC resection in our institution during the period January 2002 to December 2013 compared to hepatectomies for benign liver pathologies. Methods: The medical records of 114 patients subjected to hepatectomy were divided into the HCC group (cases, and benign group (controls. The characteristics and perioperative events of both groups were assessed and compared. Results: The mean age of the HCC patients was 58.6 ± 7.7 years. The majority of liver resections in the HCC group were minor (72.7%. The mean intraoperative blood loss was 918.8 ml in the HCC group and 720 ml in benign resections group and the difference between them was not significant, p = 0.129. The mean operative duration of HCC resection was 4 hours. The major postoperative complications were encountered in 16 patients (36.4% in the HCC group. HCC group thirty-day postoperative mortality was 9.1%, (n = 4 patients while no patient of the benign group (n = 60 died within that duration, p = .030. Logistic regression multivariate analysis revealed massive bleeding as an independent predictor for major postoperative morbidity, Odds ratio [OR] = 5.899, 95%, Confidence Interval [95% CI], 1.129–30.830, p = .035. Discussion: Our results revealed outcome parameters comparable with the international reports. Conclusion: Further improvements in hepatic surgery in general, and HCC in particular is inevitable. Keywords: Outcomes, Hepatocellular carcinoma, Liver

  20. Combined CT-guided radiofrequency ablation with systemic chemotherapy improves the survival for nasopharyngeal carcinoma with oligometastasis in liver: Propensity score matching analysis.

    Science.gov (United States)

    Li, Wang; Bai, Yutong; Wu, Ming; Shen, Lujun; Shi, Feng; Sun, Xuqi; Lin, Caijin; Chang, Boyang; Pan, Changchuan; Li, Zhiwen; Wu, Peihong

    2017-08-08

    The aim of this study was to retrospectively compare the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (Chemo-RFA) to chemotherapy alone (Chemo-only) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Between 2003 and 2011, 328 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center were enrolled. One-to-one matched pairs between Chemo-RFA group with the Chemo-only group were generated using propensity score matching. The associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Of the patients enrolled, 37 patients (11.8 %) received combined treatment, 291 (82.2) received chemotherapy alone. The patients in Chemo-RFA group were more frequently classified as lower number (≤3) of liver metastatic lesions (Poligometastasis in liver, and should be considered if the ablation is technically feasible.

  1. Epidermal growth factor and its receptors in human pancreatic carcinoma

    International Nuclear Information System (INIS)

    Chen, Y.F.; Pan, G.Z.; Hou, X.; Liu, T.H.; Chen, J.; Yanaihara, C.; Yanaihara, N.

    1990-01-01

    The role of epidermal growth factor (EGF) in oncogenesis and progression of malignant tumors is a subject of vast interest. In this study, radioimmunoassay and radioreceptor assay of EGF were established. EGF contents in malignant and benign pancreatic tumors, in normal pancreas tissue, and in culture media of a human pancreatic carcinoma cell line were determined. EGF receptor binding studies were performed. It was shown that EGF contents in pancreatic carcinomas were significantly higher than those in normal pancreas or benign pancreatic tumors. EGF was also detected in the culture medium of a pancreatic carcinoma cell line. The binding of 125I-EGF to the pancreatic carcinoma cells was time and temperature dependent, reversible, competitive, and specific. Scatchard analysis showed that the dissociation constant of EGF receptor was 2.1 X 10(-9) M, number of binding sites was 1.3 X 10(5) cell. These results indicate that there is an over-expression of EGF/EGF receptors in pancreatic carcinomas, and that an autocrine regulatory mechanism may exist in the growth-promoting effect of EGF on tumor cells

  2. Hyperdensity liver tumor on plain CT

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Shozo; Hanaguri, Katsuro [Kochi Municipal Central Hospital (Japan); Shimizu, Masahumi; Sako, Masao; Harada, Yasushi

    1984-12-01

    Most liver tumors on plain CT have been recognized as low density or iso-density masses. Sometimes calcified high density masses were shown on plain CT in case of cysts or metastatic liver tumors. However, hyperdensity mass of the liver on CT, of which the density was a little higher than surrounding tissues, was very rare. Recently 7 patients with hyperdensity liver masses on plain CT were experienced: 6 hepatocellular carcinomas and 1 hepatic cavernous hemangioma. A single hyperdensity mass was shown in 4 patients, a hyperdensity mass of multiple hepatic tumors was shown in 2 patients, and some hyperdensity masses of multiple hepatic tumors were shown in 1 patient. Lesions are classified in 3 types according to the appearance of hyperdensity masses: diffuse hyperdensity all over the mass, ring like hyperdensity, creascent like hyperdensity. Intravenous contrast enhancement was performed in 2 patients: one with a primary hepatocellular carcinoma, and another with a hepatic cavernous hemangioma. In the former case the tumor margin had changed unclear, in the latter case the tumor was markedly enhanced. Our results revealed that hyperdensity liver tumors were divided into 2 types: One type, shown in a cavernous hemangioma with fatty liver, demonstrated relative hyperdensity due to lower density of the surrounding tissue. Another type, shown in 6 hepatocellular carcinomas, showed hyperdensity since the density of the tumor was hyperdensity relative to the surrounding tissue of the liver. It was suggested that the tumor with the latter type had been strongly probable of malignant one, and been recommended to receive further examination. Cause of hyperdensity was thought to be due to hemorrhage, though microcalcification could not be denyed. In Japan, no hyperdensity liver tumor had been reported partly due to a wide window width with which CT photographs were taken.

  3. miR-183 inhibits TGF-β1-induced apoptosis by downregulation of PDCD4 expression in human hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Li, Jipeng; Fu, Hanjiang; Xu, Chengwang; Tie, Yi; Xing, Ruiyun; Zhu, Jie; Qin, Yide; Sun, Zhixian; Zheng, Xiaofei

    2010-01-01

    In recent years, some miRNAs have been reported to be connected closely with the development of human hepatocellular carcinoma. In our previous studies, a set of miRNAs were revealed to be dysregulated in HCC tissues. However, the functions of these miRNAs in HCC remain largely undefined. The expression profiles of miR-183 were compared between HCC tissues and adjacent normal liver tissues using qRT-PCR method. This method was used to screen the potential target genes of miR-183. A luciferase reporter assay was conducted to confirm target association. Finally, the functional effect of miR-183 in hepatoma cells was examined. Among the 25 HCC samples analyzed, microRNA-183 was significantly up-regulated (twofold to 367-fold) in 17 samples compared with the matching nontumoral liver tissues. Programmed cell death 4 (PDCD4) was identified as the target gene of miR-183. Moreover, PDCD4 is a proapoptotic molecule involved in TGF-β1-induced apoptosis in human HCC cells, we found that miR-183 transfectants were resistant to apoptosis induced by TGF-β1. We conclude that miR-183 can inhibit apoptosis in human HCC cells by repressing the PDCD4 expression, and miR-183 may play an important role in HCC development

  4. In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma

    Directory of Open Access Journals (Sweden)

    Satolli Maria A

    2006-11-01

    Full Text Available Abstract Background Besides being the effectors of native anti-tumor cytotoxicity, NK cells participate in T-lymphocyte responses by promoting the maturation of dendritic cells (DC. Adherent NK (A-NK cells constitute a subset of IL-2-stimulated NK cells which show increased expression of integrins and the ability to adhere to solid surface and to migrate, infiltrate, and destroy cancer. A critical issue in therapy of metastatic disease is the optimization of NK cell migration to tumor tissues and their persistence therein. This study compares localization to liver metastases of autologous A-NK cells administered via the systemic (intravenous, i.v. versus locoregional (intraarterial, i.a. routes. Patients and methods A-NK cells expanded ex-vivo with IL-2 and labeled with 111In-oxine were injected i.a. in the liver of three colon carcinoma patients. After 30 days, each patient had a new preparation of 111In-A-NK cells injected i.v. Migration of these cells to various organs was evaluated by SPET and their differential localization to normal and neoplastic liver was demonstrated after i.v. injection of 99mTc-phytate. Results A-NK cells expressed a donor-dependent CD56+CD16+CD3- (NK or CD56+CD16+CD3+ (NKT phenotype. When injected i.v., these cells localized to the lung before being visible in the spleen and liver. By contrast, localization of i.a. injected A-NK cells was virtually confined to the spleen and liver. Binding of A-NK cells to liver neoplastic tissues was observed only after i.a. injections. Conclusion This unique study design demonstrates that A-NK cells adoptively transferred to the liver via the intraarterial route have preferential access and substantial accumulation to the tumor site.

  5. Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype

    DEFF Research Database (Denmark)

    Matter, Matthias S; Marquardt, Jens U; Andersen, Jesper B

    2016-01-01

    The majority of hepatocellular carcinoma (HCC) develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or non-alcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated...... with transcriptome profiles from human HCCs further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRAS(G12V) tumors and primarily enhanced...... by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and β-catenin (CAT) followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4 ). Also...

  6. Association between the HFE C282Y, H63D Polymorphisms and the Risks of Non-Alcoholic Fatty Liver Disease, Liver Cirrhosis and Hepatocellular Carcinoma: An Updated Systematic Review and Meta-Analysis of 5,758 Cases and 14,741 Controls.

    Directory of Open Access Journals (Sweden)

    Qing Ye

    Full Text Available Conflicting results have been obtained for the association between two common polymorphisms (C282Y, H63D of human HFE (hereditary hemochromatosis gene and the risks of the liver diseases, including non-alcoholic fatty liver disease (NAFLD, liver cirrhosis and hepatocellular carcinoma (HCC.An updated systematic review and meta-analysis was conducted to evaluate the potential role of HFE polymorphisms in the susceptibility to NAFLD, liver cirrhosis and HCC. After retrieving articles from online databases, eligible studies were enrolled according to the selection criteria. Stata/SE 12.0 software was utilized to perform the statistical analysis.In total, 43 articles with 5,758 cases and 14,741 controls were selected. Compared with the control group, a significantly increased risk of NAFLD was observed for the C282Y polymorphism in the Caucasian population under all genetic models and for the H63D polymorphism under the allele, heterozygote and dominant models (all OR>1, Passociation0.05. In addition, we found that HFE C282Y was statistically associated with increased HCC susceptibility in the overall population, while H63D increased the odds of developing non-cirrhotic HCC in the African population (all OR>1, Passociation<0.05. Moreover, a positive association between compound heterozygosity for C282Y/H63D and the risk of NAFLD and HCC, but not liver cirrhosis, was observed.Our meta-analysis provides evidence that the HFE C282Y and H63D polymorphisms confer increased genetic susceptibility to NAFLD and HCC but not liver cirrhosis. Additional well-powered studies are required to confirm our conclusion.

  7. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  8. Behavior of HepG2 liver cancer cells using microfluidic-microscopy: a preliminary study

    Science.gov (United States)

    Karamahmutoglu, Hande; ćetin, Metin; Yaǧcı, Tamer; Elitaş, Meltem

    2018-02-01

    Hepatocellular carcinoma is one of the most common types of liver cancer causing death all over the world. Although early-stage liver cancer can sometimes be treated with partial hepatectomy, liver transplantation, ablation, and embolization, sorafenib treatment is the only approved systemic therapy for advanced HCC. The aim of this research is to develop tools and methods to understand the individuality of hepatocellular carcinoma. Microfluidic cell-culture platform has been developed to observe behavior of single-cells; fluorescence microscopy has been implemented to investigate phenotypic changes of cells. Our preliminary data proved high-level heterogeneity of hepatocellular carcinoma while verifying limited growth of liver cancer cell lines on the silicon wafer.

  9. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

    Science.gov (United States)

    2010-01-01

    Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

  10. Rare primary malignant tumors of the liver

    International Nuclear Information System (INIS)

    Dahan, H.; Zoppardo, P.; Chagnon, S.; Vilgrain, V.; Blery, M.

    1991-01-01

    Angiosarcoma, epithelioid hemangio-endothelioma (EHE) and fibrolamellar carcinoma (FLC) are far less frequent malignant primary tumors of the liver than liver-cell carcinoma, and usually do not occur in a chronic liver disease. Their diagnosis is histological but a few radiological criteria are suggestive: in younger subjects, a solitary, hypervascularized mass containing calcifications and/or a central fibrous scar suggests an FLC; nodular lesions merging into patches, scattered about the periphery, containing calcified clusters and showing a low and late contrast enhancement after injections suggest an EHE; lastly, in case of occupational exposure, an heterogeneous, hypervascularized mass with a centripetal blush but containing central areas that are opacified early should suggest angiosarcoma. (4 figs) [fr

  11. Completion of hepatitis C virus replication cycle in heterokaryons excludes dominant restrictions in human non-liver and mouse liver cell lines.

    Directory of Open Access Journals (Sweden)

    Anne Frentzen

    2011-04-01

    Full Text Available Hepatitis C virus (HCV is hepatotropic and only infects humans and chimpanzees. Consequently, an immunocompetent small animal model is lacking. The restricted tropism of HCV likely reflects specific host factor requirements. We investigated if dominant restriction factors expressed in non-liver or non-human cell lines inhibit HCV propagation thus rendering these cells non-permissive. To this end we explored if HCV completes its replication cycle in heterokaryons between human liver cell lines and non-permissive cell lines from human non-liver or mouse liver origin. Despite functional viral pattern recognition pathways and responsiveness to interferon, virus production was observed in all fused cells and was only ablated when cells were treated with exogenous interferon. These results exclude that constitutive or virus-induced expression of dominant restriction factors prevents propagation of HCV in these cell types, which has important implications for HCV tissue and species tropism. In turn, these data strongly advocate transgenic approaches of crucial human HCV cofactors to establish an immunocompetent small animal model.

  12. Hepatic tuberculosis mimicking metastasis in a case of carcinoma sigmoid colon

    Directory of Open Access Journals (Sweden)

    Musharraf Husain

    2015-01-01

    Full Text Available Tuberculosis (TB presenting as isolated liver mass without clinical evidence of TB is difficult to diagnose preoperatively and is usually mimicked by primary or metastatic carcinoma of the liver. Hepatic TB associated with carcinoma colon is a rare association which has very rarely been reported in the literature. This case illustrates the diagnostic difficulties of hepatic TB and the need to consider it in the differential diagnosis of hepatic nodular lesions in carcinoma colon patients. Here, we report a case of 48-year-old female who presented in the casualty with features of acute intestinal obstruction. Preoperatively a mass was seen at the hepatic flexure along with three lesions in the liver presumed to be metastatic in origin. However, histopathology of the mass revealed adenocarcinoma colon and the liver lesion proved to be hepatic TB. We wish to highlight that on encountering a hepatic lesion in a carcinoma colon patient the possibility of hepatic TB should also be kept in mind apart from the obvious possibility of metastasis especially in an endemic country like India.

  13. 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)

  14. Dipeptidyl peptidase-4 greatly contributes to the hydrolysis of vildagliptin in human liver.

    Science.gov (United States)

    Asakura, Mitsutoshi; Fujii, Hideaki; Atsuda, Koichiro; Itoh, Tomoo; Fujiwara, Ryoichi

    2015-04-01

    The major metabolic pathway of vildagliptin in mice, rats, dogs, and humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7 (LAY151), whereas the major metabolic enzyme of vildagliptin has not been identified. In the present study, we determined the contribution rate of dipeptidyl peptidase-4 (DPP-4) to the hydrolysis of vildagliptin in the liver. We performed hydrolysis assay of the cyano group of vildagliptin using mouse, rat, and human liver samples. Additionally, DPP-4 activities in each liver sample were assessed by DPP-4 activity assay using the synthetic substrate H-glycyl-prolyl-7-amino-4-methylcoumarin (Gly-Pro-AMC). M20.7 formation rates in liver microsomes were higher than those in liver cytosol. M20.7 formation rate was significantly positively correlated with the DPP-4 activity using Gly-Pro-AMC in liver samples (r = 0.917, P vildagliptin hydrolysis in the liver. Additionally, we established stable single expression systems of human DPP-4 and its R623Q mutant, which is the nonsynonymous single-nucleotide polymorphism of human DPP-4, in human embryonic kidney 293 (HEK293) cells to investigate the effect of R623Q mutant on vildagliptin-hydrolyzing activity. M20.7 formation rate in HEK293 cells expressing human DPP-4 was significantly higher than that in control HEK293 cells. Interestingly, R623Q mutation resulted in a decrease of the vildagliptin-hydrolyzing activity. Our findings might be useful for the prediction of interindividual variability in vildagliptin pharmacokinetics. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Outcome of liver transplantation for hepatocellular carcinoma -- a single center experience.

    Science.gov (United States)

    Iacob, R; Iacob, S; Gheorghe, L; Gheorghe, C; Hrehoreţ, D; Brașoveanu, V; Croitoru, A; Herlea, V; Popescu, I

    2013-01-01

    Liver transplantation (LT) is a promising treatment for patients with liver cirrhosis associated with hepatocellular carcinoma (HCC). The aim of our study was to evaluate our experience regarding the clinical and pathological staging of HCC in patients who underwent LT, as well as recurrence free and overall survival. From January 2006 to December 2011, 38 patients with diagnosis of HCC, underwent LT in our Center. Demographic, clinical, imaging and pathologic information were recorded. A Cox proportional hazards survival analysis was performed in order to identify significant predictors of tumor recurrence and patient's death after LT. Eighteen patients (47.4%) in our study group were within Milan criteria. The mean follow-up was 22 months and the recurrence rate of HCC after LT was 13.2%. The 1, 3- year recurrence free survival rates were 85%, 74.3% respectively. The 1 and 3-year overall survival rates were 83.5% and 63.6% respectively. No significant predictor for HCC recurrence was identified in our study group by survival analysis, taking into account 13 different variables. As independent predictors of patient'ss death after LT for HCC however, the presence of diabetes mellitus (p=0.001), presence of more than 3 HCC nodules (p=0.03) and tumor recurrence after LT (p=0.03) were identified by multivariate Cox proportional hazards survival analysis. In our cohort HCC recurrence rate after LT was 13.2%. Diabetes mellitus, presence of more than 3 HCC nodules and HCC recurrence were significant predictors of poor overall survival after LT. Celsius.

  16. MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ronald, J A; Katzenberg, R; Nielsen, Carsten Haagen

    2013-01-01

    In hepatocellular carcinoma (HCC), tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs (miRNAs) are powerful negative regulators of gene expression and many are downregulated in human HCC. We identified seven miRNAs that are also downregulated in tumors...

  17. Liver resection over the last decade

    DEFF Research Database (Denmark)

    Wettergren, A.; Larsen, P.N.; Rasmussen, A.

    2008-01-01

    after resection of hepatic metastases from colorectal cancer and hepatocellular carcinoma was estimated. RESULTS: 141 patients (71M/70F), median age 58 years (1-78), underwent a liver resection in the ten-year period. The number of resections increased from two in 1995 to 32 in 2004. Median hospital...... stay was 9 days (3-38). The most frequent complication was biliary leakage (7.8%), haemorrhage (2.8%) and hepatic insufficiency (2.8%). 30-days mortality was 1.4%. The actuarial 5-survival after hepatic resection for colorectal liver metastases and hepatocellular carcinoma was 39% and 42%, respectively...

  18. Liver resection over the last decade

    DEFF Research Database (Denmark)

    Wettergren, A.; Larsen, P.N.; Rasmussen, A.

    2008-01-01

    of hepatic metastases from colorectal cancer and hepatocellular carcinoma in our institution. MATERIALS AND METHODS: The patients who underwent their primary liver resection from 1.1.1995-31.12.2004 in our institution were included. The surgical outcome was reviewed retrospectively and the five-year survival...... after resection of hepatic metastases from colorectal cancer and hepatocellular carcinoma was estimated. RESULTS: 141 patients (71M/70F), median age 58 years (1-78), underwent a liver resection in the ten-year period. The number of resections increased from two in 1995 to 32 in 2004. Median hospital...

  19. Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice.

    Science.gov (United States)

    Yamazaki-Nishioka, Miho; Shimizu, Makiko; Suemizu, Hiroshi; Nishiwaki, Megumi; Mitsui, Marina; Yamazaki, Hiroshi

    2018-02-01

    1. Benzydamine is used clinically as a nonsteroidal anti-inflammatory drug in oral rinses and is employed in preclinical research as a flavin-containing monooxygenase (FMO) probe substrate. In this study, plasma concentrations of benzydamine and its primary N-oxide and N-demethylated metabolites were investigated in control TK-NOG mice, in humanized-liver mice, and in mice whose liver cells had been ablated with ganciclovir. 2. Following oral administration of benzydamine (10 mg/kg) in humanized-liver TK-NOG mice, plasma concentrations of benzydamine N-oxide were slightly higher than those of demethyl benzydamine. In contrast, in control and ganciclovir-treated TK-NOG mice, concentrations of demethyl benzydamine were slightly higher than those of benzydamine N-oxide. 3. Simulations of human plasma concentrations of benzydamine and its N-oxide were achieved using simplified physiologically based pharmacokinetic models based on data from control TK-NOG mice and from reported benzydamine concentrations after low-dose administration in humans. Estimated clearance rates based on data from humanized-liver and ganciclovir-treated TK-NOG mice were two orders magnitude high. 4. The pharmacokinetic profiles of benzydamine were different for control and humanized-liver TK-NOG mice. Humanized-liver mice are generally accepted human models; however, drug oxidation in mouse kidney might need to be considered when probe substrates undergo FMO-dependent drug oxidation in mouse liver and kidney.

  20. Association of Human Papilloma Virus Infection and Oral Squamous Cell Carcinoma in Bangladesh

    OpenAIRE

    Akhter, Mahmuda; Ali, Liaquat; Hassan, Zahid; Khan, Imran

    2013-01-01

    Oral squamous cell carcinoma is the sixth most common malignancy worldwide. In Bangladesh, it comprises 20% of the whole body malignancies. Several studies found that 15% to 25% of oropharyngeal cancer cases are associated with human papilloma virus (HPV). This study is done to find the association of human papilloma virus subtypes, particularly HPV type 16 and HPV type 18, with the oral squamous cell carcinoma in Bangladeshi patients. In total, 34 diagnosed patients of oral squamous cell car...

  1. The potential of cell sheet technique on the development of hepatocellular carcinoma in rat models.

    Directory of Open Access Journals (Sweden)

    Alaa T Alshareeda

    Full Text Available Hepatocellular carcinoma (HCC is considered the 3rd leading cause of death by cancer worldwide with the majority of patients were diagnosed in the late stages. Currently, there is no effective therapy. The selection of an animal model that mimics human cancer is essential for the identification of prognostic/predictive markers, candidate genes underlying cancer induction and the examination of factors that may influence the response of cancers to therapeutic agents and regimens. In this study, we developed a HCC nude rat models using cell sheet and examined the effect of human stromal cells (SCs on the development of the HCC model and on different liver parameters such as albumin and urea.Transplanted cell sheet for HCC rat models was fabricated using thermo-responsive culture dishes. The effect of human umbilical cord mesenchymal stromal cells (UC-MSCs and human bone marrow mesenchymal stromal cells (BM-MSCs on the developed tumour was tested. Furthermore, development of tumour and detection of the liver parameter was studied. Additionally, angiogenesis assay was performed using Matrigel.HepG2 cells requires five days to form a complete cell sheet while HepG2 co-cultured with UC-MSCs or BM-MSCs took only three days. The tumour developed within 4 weeks after transplantation of the HCC sheet on the liver of nude rats. Both UC-MSCs and BM-MSCs improved the secretion of liver parameters by increasing the secretion of albumin and urea. Comparatively, the UC-MSCs were more effective than BM-MSCs, but unlike BM-MSCs, UC-MSCs prevented liver tumour formation and the tube formation of HCC.Since this is a novel study to induce liver tumour in rats using hepatocellular carcinoma sheet and stromal cells, the data obtained suggest that cell sheet is a fast and easy technique to develop HCC models as well as UC-MSCs have therapeutic potential for liver diseases. Additionally, the data procured indicates that stromal cells enhanced the fabrication of HepG2

  2. HCV-related liver cancer in people with haemophilia

    NARCIS (Netherlands)

    Meijer, K.; Haagsma, E. B.

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

  3. Phosphatase of Regenerating Liver-3 Promotes Motility and Metastasis of Mouse Melanoma Cells

    Science.gov (United States)

    Wu, Xiaopeng; Zeng, Hu; Zhang, Xianming; Zhao, Ying; Sha, Haibo; Ge, Xiaomei; Zhang, Minyue; Gao, Xiang; Xu, Qiang

    2004-01-01

    Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was up-regulated in human liver carcinoma compared with normal liver. PRL-3 was also highly expressed in metastatic melanoma B16-BL6 cells but not in its lowly metastatic parental cell line, B16 cells. B16 cells transfected with PRL-3 cDNA displayed morphological transformation from epithelial-like shape to fibroblast-like shape. PRL-3-overexpressed cells showed much higher migratory ability, which could be reversed by specific anti-sense oligodeoxynucleotide and the phosphatase inhibitors sodium orthovanadate or potassium bisperoxo oxovanadate V. Meanwhile, the expression of the catalytically inactive PRL-3 mutations (D72A or C104S) significantly reduced the cell migratory capability. In addition, PRL-3 transfectants demonstrated altered extracellular matrix adhesive property and up-regulated integrin-mediated cell spreading efficiency. Furthermore, we confirmed that PRL-3 could facilitate lung and liver metastasis of B16 cells in an experimental metastasis model in mice, consistent with accelerated proliferation and growth rate both in vitro and in vivo. Together, these observations provide convincing evidence that PRL-3 truly plays a causal role in tumor metastasis. PMID:15161639

  4. Human germline hedgehog pathway mutations predispose to fatty liver.

    Science.gov (United States)

    Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

    2017-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

  5. Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

    Science.gov (United States)

    Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

    2009-07-01

    Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

  6. Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver.

    Science.gov (United States)

    Deyashiki, Y; Tamada, Y; Miyabe, Y; Nakanishi, M; Matsuura, K; Hara, A

    1995-08-01

    Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase activity, and multiple cDNAs for the enzymes have been cloned from human liver cDNA libraries. To understand the relationship of the multiple enzyme froms to the genes, a cDNA, which has been reported to code for an isoenzyme of human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in Escherichia coli. The recombinant enzyme showed structural and functional properties almost identical to those of the isoenzyme purified from human liver. In addition, the recombinant isoenzyme efficiently reduced 5 alpha-dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously purified, which suggests that these human liver enzymes are identical. Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol oxidation by the recombinant isoenzyme were consistent with a sequential ordered mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme much more potently than it did the other human liver dihydrodiol dehydrogenases, and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+ complex.

  7. Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

    Directory of Open Access Journals (Sweden)

    Alessandro Federico

    2017-01-01

    Full Text Available Silymarin is the extract of Silybum marianum, or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

  8. Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood liver cancer has two major histologic subgroups: hepatoblastoma and hepatocellular carcinoma. Less common histologies are undifferentiated embryonal sarcoma of the liver, infantile choriocarcinoma, and vascular liver tumors. Get detailed information about newly diagnosed and recurrent childhood liver cancers including tumor biology, presentation, prognosis, staging, and treatment in this summary for clinicians.

  9. Mechanism of cisplatin resistance in human urothelial carcinoma cells.

    Science.gov (United States)

    Yu, Hui-Min; Wang, Tsing-Cheng

    2012-05-01

    An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Living donor liver transplantation for hepatocellular carcinoma achieves better outcomes.

    Science.gov (United States)

    Lin, Chih-Che; Chen, Chao-Long

    2016-10-01

    Liver transplantation (LT) for hepatocellular carcinoma (HCC) at Kaohsiung Chang Gung Memorial Hospital mainly relies on live donor LT (LDLT). Owing to taking the risk of LD, we are obligated to adopt strict selection criteria for HCC patients and optimize the pre-transplant conditions to ensure a high disease-free survival similar to those without HCC, even better than deceased donor LT (DDLT). Better outcomes are attributed to excellent surgical results and optimal patient selection. The hospital mortality of primary and salvage LDLT are lower than 2% in our center. Although Taiwan Health Insurance Policy extended the Milan to University of California, San Francisco (UCSF) criteria in 2006, selection criteria will not be consolidated to take into account only by the morphologic size/number of tumors but also by their biology. The criteria are divided into modifiable image morphology, alpha fetoprotein (AFP), and positron emission tomography (PET) scan with standard uptake value (SUV) and unmodifiable unfavorable pathology such as HCC combined with cholangiocarcinoma (CC), sarcomatoid type, and poor differentiation. Downstaging therapy is necessary for HCC patients beyond criteria to fit all modifiable standards. The upper limit of downstaging treatment seems to be extended by more effective drug eluting transarterial chemoembolization in cases without absolute contraindications. In contrast, the pitfall of unmodifiable tumor pathology should be excluded by the findings of pretransplant core biopsy/resection if possible. More recently, achieving complete tumor necrosis in explanted liver could almost predict no recurrence after transplant. Necrotizing therapy is advised if possible before transplant even the tumor status within criteria to minimize the possibility of tumor recurrence. LDLT with low surgical mortality in experienced centers provides the opportunities of optimizing the pre-transplant tumor conditions and timing of transplant to achieve better

  11. Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Palard, Xavier; Edeline, Julien; Rolland, Yan; Le Sourd, Samuel; Pracht, Marc; Laffont, Sophie; Lenoir, Laurence; Boudjema, Karim; Ugen, Thomas; Brun, Vanessa; Mesbah, Habiba; Haumont, Laure-Anne; Loyer, Pascal; Garin, Etienne

    2018-01-01

    This study aimed at identifying prior therapy dosimetric parameters using 99m Tc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with 90 Y-loaded glass microspheres. The dosimetry data of 73 HCC patients were collected prior to the treatment with 90 Y-loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated. Mean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the 90 Y-microspheres injection (r = -0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm 3 in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm 3 (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%. This study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm these promising results

  12. Dosimetric parameters predicting contralateral liver hypertrophy after unilobar radioembolization of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Palard, Xavier [Cancer Institute Eugene Marquis, Department of Nuclear Medicine, Rennes (France); University of Rennes 1, Rennes (France); Edeline, Julien [University of Rennes 1, Rennes (France); INSERM, INRA, Univ Rennes 1, Univ Bretagne Loire, Nutrition Metabolisms and Cancer (NuMeCan), Rennes (France); Cancer Institute Eugene Marquis, Department of Medical Oncology, Rennes (France); Rolland, Yan [Cancer Institute Eugene Marquis, Department of Medical Imaging, Rennes (France); Le Sourd, Samuel; Pracht, Marc [Cancer Institute Eugene Marquis, Department of Medical Oncology, Rennes (France); Laffont, Sophie; Lenoir, Laurence [Cancer Institute Eugene Marquis, Department of Nuclear Medicine, Rennes (France); Boudjema, Karim [CHU Pontchaillou, Department of Hepatobiliary Surgery, Rennes (France); Ugen, Thomas [CHU Pontchaillou, Department of Hepatology, Rennes (France); Brun, Vanessa [CHU Pontchaillou, Department of Medical Imaging, Rennes (France); Mesbah, Habiba; Haumont, Laure-Anne [Cancer Institute Eugene Marquis, Department of Medical Information, Rennes (France); Loyer, Pascal [INSERM, INRA, Univ Rennes 1, Univ Bretagne Loire, Nutrition Metabolisms and Cancer (NuMeCan), Rennes (France); Garin, Etienne [Cancer Institute Eugene Marquis, Department of Nuclear Medicine, Rennes (France); University of Rennes 1, Rennes (France); INSERM, INRA, Univ Rennes 1, Univ Bretagne Loire, Nutrition Metabolisms and Cancer (NuMeCan), Rennes (France)

    2018-03-15

    This study aimed at identifying prior therapy dosimetric parameters using {sup 99m}Tc-labeled macro-aggregates of albumin (MAA) that are associated with contralateral hepatic hypertrophy occurring after unilobar radioembolization of hepatocellular carcinoma (HCC) performed with {sup 90}Y-loaded glass microspheres. The dosimetry data of 73 HCC patients were collected prior to the treatment with {sup 90}Y-loaded microspheres for unilateral disease. The injected liver dose (ILD), the tumor dose (TD) and healthy injected liver dose (HILD) were calculated based on MAA quantification. Following treatment, the maximal hypertrophy (MHT) of an untreated lobe was calculated. Mean MHT was 35.4 ± 40.4%. When using continuous variables, the MHT was not correlated with any tested variable, i.e., injected activity, ILD, HILD or TD except with a percentage of future remnant liver (FRL) following the {sup 90}Y-microspheres injection (r = -0.56). MHT ≥ 10% was significantly more frequent for patients with HILD ≥ 88 Gy, (52% of the cases), i.e., in 92.2% versus 65.7% for HILD < 88 Gy (p = 0.032). MHT ≥ 10% was also significantly more frequent for patients with a TD ≥ 205 Gy and a tumor volume (VT) ≥ 100 cm{sup 3} in patients with initial FRL < 50%. MHT ≥10% was seen in 83.9% for patients with either an HILD ≥ 88 Gy or a TD ≥ 205 Gy for tumors larger than 100cm{sup 3} (85% of the cases), versus only 54.5% (p = 0.0265) for patients with none of those parameters. MHT ≥10% was also associated with FRL and the Child-Pugh score. Using multivariate analysis, the Child-Pugh score (p < 0.0001), FRL (p = 0.0023) and HILD (p = 0.0029) were still significantly associated with MHT ≥10%. This study demonstrates for the first time that HILD is significantly associated with liver hypertrophy. There is also an impact of high tumor doses in large lesions in one subgroup of patients. Larger prospective studies evaluating the MAA dosimetric parameters have to be conducted to confirm

  13. Liver cancer: expression features of hepatitis B antigens

    Directory of Open Access Journals (Sweden)

    V. A. Tumanskiy

    2013-12-01

    Full Text Available Introduction. Hepatocellular carcinoma (HCC is currently the fifth most common malignancy in men and the eighth in women worldwide. According to the latest European Union countries’ statistics the incidence of HC cancer is about 8,29 per 100000 accidents, cholangiocellular (CC cancer – 0,9-1,3 per 100 thousand of population per year[10,14]. Hepatitis B virus (HBV is the major etiologic factor for the development of HCC [18]. People chronically infected with HBV are 20 times more likely to develop liver cancer than uninfected people [1,22,28]. Many studies have shown the association between Hepatitis B virus (HBV and hepatitis C virus (HCV infections and the development of cholangiocarcinoma (CCA [4,6,9,11,12]. At the same time, the expression features of HBsAg, HBcAg in HCC and CCA have not been studied clearly yet. Aim of investigation: to study the expression features of hepatitis B antigens in tumor tissue from patients with hepatocellular carcinoma and cholangiocarcinoma. Materials and methods. The complex pathomorphological research was performed using liver biopsies of 87 patients aged from 33 up to 83 years, where 50 (57,47% of them had HCC carcinoma and 37 (42,53% had cholangiocellular cancer. 15 patients among examined 87 ones were ill with chronic viral hepatitis (11 were ill with HCV, 3 – HBV B, 1 – HBV + HCV before, 72 cancer patients, corresponding to the clinical data, never had this one in their past medical history. The localization of hepatitis B surface antigen (HBsAg and core antigen (HBcAg was investigated by an indirect immunoperoxidase method in formalin-fixed, paraffin-embedded liver specimens obtained from 50 (57,47% patients with hepatocellular carcinoma and 37 (42,53% patients with cholangiocarcinoma. using antibodies Rb a-Hu Primary Hepatitis B Virus Core Antigen (HBcAg and Mo a-Hu Primary Hepatitis B Virus Surface Antigen (HBsAg, Сlone 3E7, and visualization system DAKO EnVision+ with diaminobenzidine. Liver

  14. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    Science.gov (United States)

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  15. Chronic Liver Disease and the Detection of Hepatocellular Carcinoma by [18F]fluorocholine PET/CT

    Directory of Open Access Journals (Sweden)

    Sandi A. Kwee

    2015-05-01

    Full Text Available Positron emission tomography (PET using the radiopharmaceutical tracer fluorine-18 fluorocholine (FCh can elucidate tumors based on differences in choline phospholipid metabolism between tumor and surrounding tissue. The feasibility of detecting hepatocellular carcinoma (HCC using FCh PET has been shown despite constitutively high parenchymal choline metabolism in the liver. Since HCC frequently develops in the setting of chronic liver disease, we comparatively evaluated FCh PET/CT between cirrhotic and non-cirrhotic patients with HCC to investigate the effects of hepatic dysfunction on tumor detection and the tumor-to-background ratio (TBR of FCh uptake. FCh PET/CT was performed prospectively in 22 consecutive patients with HCC (7 newly diagnosed, 15 previously treated. Of these 22 patients, 14 were cirrhotic and 8 non-cirrhotic. Standardized uptake value (SUV measurements were obtained by region of interest analysis of the PET images. Tumor FCh uptake and the TBR were compared between cirrhotic and non-cirrhotic patients. Liver lesions were confirmed to be HCC by biopsy in 10 patients and by Barcelona criteria in 4 patients. There was correspondingly increased liver tumor FCh uptake in 13/14 of those patients, and iso-intense tumor FCh uptake (TBR 0.94 in one non-cirrhotic patient with newly diagnosed HCC. FCh PET/CT also showed metastatic disease without local tumor recurrence in 2 previously treated patients, and was negative in 6 treated patients without tumor recurrence by radiographic and clinical follow-up. Tumor maximum SUV ranged from 6.4 to 15.3 (mean 12.1 and liver TBR ranged from 0.94 to 2.1 (mean 1.6, with no significant differences between cirrhotic and non-cirrhotic patients (SUVmax 11.9 vs. 12.2, p = 0.83; TBR 1.71 vs. 1.51, p = 0.29. Liver parenchyma mean SUV was significantly lower in cirrhotic patients (6.4 vs. 8.7, p < 0.05. This pilot study supports the general feasibility of HCC detection by FCh PET/CT. However, a broad

  16. Adult Primary Liver Cancer Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Adult primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma. Treatments include surveillance, surgery, liver transplant, ablation therapy, embolization therapy, targeted therapy, and radiation therapy. Get comprehensive information about liver cancer and treatment in this clinician summary.

  17. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...

  18. Carcinogenesis induction with diethylnitrosamine in mice: A tumor model for the evaluation of unresectable primary or metastatic liver carcinoma treatment with radioisotopes

    International Nuclear Information System (INIS)

    Riccardi, F.; Anselmi, C.E.; Hunsche, A.; Fernandes, D.D.; Berdichevski, E.H.; Cembrani, L.; Anselmi, O.E.

    2004-01-01

    Full text: Several agents such as chemical substances, radiation and virus are capable of experimentally inducing cancer in the liver. The pathogenic mechanisms involved in this disease are still obscure, but despite the etiological agents varying widely, the alterations induced by them demonstrate notable similarities. Considering the possibility of treatment of inoperable human hepatocarcinomas with Lipiodol-131I, Lipiodol-188Rhenium or 90YMicrospheres as a novel alternative, we developed a rat tumour model to test the effects of these radiopharmaceutical therapies. It was intended to verify the potential of hepatic carcinogenesis induced by diethylnitrosamine (DEN) after partial hepatectomy (HP 70%) in Wistar rats, to analyze the histological modifications produced in the liver of the rats subjected to tumor induction and to verify the immuno-histochemical alterations through the antibody Ki67 and of the protein GSTpi after this process. The experiment was performed on 50 Wistar rats in the laboratory of the Department of Pathology - FFFCMPA. Diethylnitrosamine was administered 24 hrs. after surgery in continuous doses of 0.5 mg/kg of body weight through the drinkable water ingested by the rats. The dose was changed on a weekly basis during the period of 90 days. These rats were divided in four groups. Group-1: 5 rats subjected to pilot experiment for improvement of the anaesthetic and operative techniques. Group-2: 15 rats subjected to HP. Group-3: 15 rats that received DEN. Group-4: 15 rats subjected to HP plus DEN. After sacrificing animals (121 days after the surgical procedure) the livers were removed for histological and immuno-histochemical verification. During macroscopic evaluation, numerous frankly carcinomatous lesions of different dimensions were noticed, and in microscopic examination 100% of the lesions were hepatocarcinomas in group-4, with 73% expression of GSTpi and 67% occurrence of Ki67. In group-2 no tumour was noticed though there was 7

  19. Development of Murine Cyp3a Knockout Chimeric Mice with Humanized Liver.

    Science.gov (United States)

    Kato, Kota; Ohbuchi, Masato; Hamamura, Satoko; Ohshita, Hiroki; Kazuki, Yasuhiro; Oshimura, Mitsuo; Sato, Koya; Nakada, Naoyuki; Kawamura, Akio; Usui, Takashi; Kamimura, Hidetaka; Tateno, Chise

    2015-08-01

    We developed murine CYP3A knockout ko chimeric mice with humanized liver expressing human P450S similar to those in humans and whose livers and small intestines do not express murine CYP3A this: approach may overcome effects of residual mouse metabolic enzymes like Cyp3a in conventional chimeric mice with humanized liver, such as PXB-mice [urokinase plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice repopulated with over 70% human hepatocytes] to improve the prediction of drug metabolism and pharmacokinetics in humans. After human hepatocytes were transplanted into Cyp3a KO/uPA/SCID host mice, human albumin levels logarithmically increased until approximately 60 days after transplantation, findings similar to those in PXB-mice. Quantitative real-time-polymerase chain reaction analyses showed that hepatic human P450s, UGTs, SULTs, and transporters mRNA expression levels in Cyp3a KO chimeric mice were also similar to those in PXB-mice and confirmed the absence of Cyp3a11 mRNA expression in mouse liver and intestine. Findings for midazolam and triazolam metabolic activities in liver microsomes were comparable between Cyp3a KO chimeric mice and PXB-mice. In contrast, these activities in the intestine of Cyp3a KO chimeric mice were attenuated compared with PXB-mice. Owing to the knockout of murine Cyp3a, hepatic Cyp2b10 and 2c55 mRNA levels in Cyp3a KO/uPA/SCID mice (without hepatocyte transplants) were 8.4- and 61-fold upregulated compared with PXB-mice, respectively. However, human hepatocyte transplantation successfully restored Cyp2b10 level nearly fully and Cyp2c55 level partly (still 13-fold upregulated) compared with those in PXB-mice. Intestinal Cyp2b10 and 2c55 were also repressed by human hepatocyte transplantation in Cyp3a KO chimeric mice. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Chronic liver disease in the Hispanic population of the United States.

    Science.gov (United States)

    Carrion, Andres F; Ghanta, Ravi; Carrasquillo, Olveen; Martin, Paul

    2011-10-01

    Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. CT portography in the presence of liver steatosis. Potential for a false-negative result

    International Nuclear Information System (INIS)

    Steiner, W.; Scheidler, J.; Kohz, P.; Staebler, A.; Reiser, M.

    1994-01-01

    CT portography is the most sensitive technique currently available for the preoperative diagnosis of liver metastases. We report on a patient with liver steatosis in whom ultrasound examination revealed two liver metastases in the follow up after resection of a papillary carcinoma. The liver metastases could be clearly identified both on plain CT and on enhanced CT with dynamic bolus contrast medium injection. Because of the small difference in attenuation values between liver parenchyma and metastases the two liver metastases had not been recognized on CT portography. When severe and diffuse liver steatosis is present CT portography may fail to detect metastases or small hepatocellular carcinoma. (orig.)

  2. Human papillomas virus infection in the case of larynx carcinoma

    International Nuclear Information System (INIS)

    Makowska, W.; Rogozinski, T.; Zawadowski, J.; Waloryszak, B.

    1993-01-01

    The case of 59 year old man treated (with surgery and radiotherapy) for larynx carcinoma was presented. The potentially oncogenic human papillomavirus type 16/18 was detected in the tissue surrounding the tumor. (author)

  3. 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

  4. Evaluation of immunological escape mechanisms in a mouse model of colorectal liver metastases

    International Nuclear Information System (INIS)

    Grimm, Martin; Thalheimer, Andreas; Gasser, Martin; Bueter, Marco; Strehl, Johanna; Wang, Johann; Nichiporuk, Ekaterina; Meyer, Detlef; Germer, Christoph T; Waaga-Gasser, Ana M

    2010-01-01

    The local and systemic activation and regulation of the immune system by malignant cells during carcinogenesis is highly complex with involvement of the innate and acquired immune system. Despite the fact that malignant cells do have antigenic properties their immunogenic effects are minor suggesting tumor induced mechanisms to circumvent cancer immunosurveillance. The aim of this study is the analysis of tumor immune escape mechanisms in a colorectal liver metastases mouse model at different points in time during tumor growth. CT26.WT murine colon carcinoma cells were injected intraportally in Balb/c mice after median laparotomy using a standardized injection technique. Metastatic tumor growth in the liver was examined by standard histological procedures at defined points in time during metastatic growth. Liver tissue with metastases was additionally analyzed for cytokines, T cell markers and Fas/Fas-L expression using immunohistochemistry, immunofluorescence and RT-PCR. Comparisons were performed by analysis of variance or paired and unpaired t test when appropriate. Intraportal injection of colon carcinoma cells resulted in a gradual and time dependent metastatic growth. T cells of regulatory phenotype (CD4+CD25+Foxp3+) which might play a role in protumoral immune response were found to infiltrate peritumoral tissue increasingly during carcinogenesis. Expression of cytokines IL-10, TGF-β and TNF-α were increased during tumor growth whereas IFN-γ showed a decrease of the expression from day 10 on following an initial increase. Moreover, liver metastases of murine colon carcinoma show an up-regulation of FAS-L on tumor cell surface with a decreased expression of FAS from day 10 on. CD8+ T cells express FAS and show an increased rate of apoptosis at perimetastatic location. This study describes cellular and macromolecular changes contributing to immunological escape mechanisms during metastatic growth in a colorectal liver metastases mouse model simulating the

  5. Radiation-induced liver disease after stereotactic body radiotherapy for small hepatocellular carcinoma: clinical and dose-volumetric parameters

    International Nuclear Information System (INIS)

    Jung, Jinhong; Choi, Eun Kyung; Kim, Jong Hoon; Yoon, Sang Min; Kim, So Yeon; Cho, Byungchul; Park, Jin-hong; Kim, Su Ssan; Song, Si Yeol; Lee, Sang-wook; Ahn, Seung Do

    2013-01-01

    To investigate the clinical and dose–volumetric parameters that predict the risk of radiation-induced liver disease (RILD) for patients with small, unresectable hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). Between March 2007 and December 2009, 92 patients with HCC treated with SBRT were reviewed for RILD within 3 months of completing treatment. RILD was evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. A dose of 10–20 Gy (median, 15 Gy) per fraction was given over 3–4 consecutive days for a total dose of 30–60 Gy (median, 45 Gy). The following clinical and dose–volumetric parameters were examined: age, gender, Child-Pugh class, presence of hepatitis B virus, gross tumor volume, normal liver volume, radiation dose, fraction size, mean dose to the normal liver, and normal liver volumes receiving from < 5 Gy to < 60 Gy (in increments of 5 Gy). Seventeen (18.5%) of the 92 patients developed grade 2 or worse RILD after SBRT (49 patients in grade 1, 11 in grade 2, and 6 in ≥ grade 3). On univariate analysis, Child-Pugh class was identified as a significant clinical parameter, while normal liver volume and normal liver volumes receiving from < 15 Gy to < 60 Gy were the significant dose–volumetric parameters. Upon multivariate analysis, only Child-Pugh class was a significant parameter for predicting grade 2 or worse RILD. The Child-Pugh B cirrhosis was found to have a significantly greater susceptibility to the development of grade 2 or worse RILD after SBRT in patients with small, unresectable HCC. Additional efforts aimed at testing other models to predict the risk of RILD in a large series of HCC patients treated with SBRT are needed

  6. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  7. 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 ...

  8. 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 ...

  9. Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

    Science.gov (United States)

    Nakagawa, Shin-ichiro; Hirata, Yuichi; Kameyama, Takeshi; Tokunaga, Yuko; Nishito, Yasumasa; Hirabayashi, Kazuko; Yano, Junichi; Ochiya, Takahiro; Tateno, Chise; Tanaka, Yasuhito; Mizokami, Masashi; Tsukiyama-Kohara, Kyoko; Inoue, Kazuaki; Yoshiba, Makoto; Takaoka, Akinori; Kohara, Michinori

    2013-01-01

    The interferon (IFN) system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV) and hepatitis B virus (HBV). This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC). Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs) in the livers and sera of these humanized chimeric mice. Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level) of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic) tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS) and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1), suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

  10. Changes of the liver volume and the Child-Pugh score after high dose hypofractionated radiotherapy in patients with small hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Young Il; Park, Hee Chul; Lim, Do Hoon; Park, Hyo Jung; Park, Su Yeon; Kim, Jin Sung; Han, Young Yih; Kang, Sang Won; Paik, Seung Woon

    2012-01-01

    To investigate the safety of high dose hypofractionated radiotherapy (RT) in patients with small hepatocellular carcinoma (HCC) in terms of liver volumetric changes and clinical liver function. We retrospectively reviewed 16 patients with small HCC who were treated with high dose hypofractionated RT between 2006 and 2009. The serial changes of the liver volumetric parameter were analyzed from pre-RT and follow-up (FU) computed tomography (CT) scans. We estimated linear time trends of whole liver volume using a linear mixed model. The serial changes of the Child-Pugh (CP) scores were also analyzed in relation to the volumetric changes. Mean pre-RT volume of entire liver was 1,192.2 mL (range, 502.6 to 1,310.2 mL) and mean clinical target volume was 14.7 mL (range, 1.56 to 70.07 mL). Fourteen (87.5%) patients had 4 FU CT sets and 2 (12.5%) patients had 3 FU CT sets. Mean interval between FU CT acquisition was 2.5 months. After considering age, gender and the irradiated liver volume as a fixed effects, the mixed model analysis confirmed that the change in liver volume is not significant throughout the time course of FU periods. Majority of patients had a CP score change less than 2 except in 1 patient who had CP score change more than 3. The high dose hypofractionated RT for small HCC is relatively safe and feasible in terms of liver volumetric changes and clinical liver function.

  11. Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis

    Directory of Open Access Journals (Sweden)

    Huimin Li

    2017-01-01

    Full Text Available A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted from Arachniodes exilis (TFAE in vivo. Several biochemical assays including hematoxylin-eosin (HE staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted from Arachniodes exilis (TFAE. The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.

  12. Usefulness of Pure Laparoscopic Hepatectomy for Hepatocellular Carcinoma in a Severely Cirrhotic Patient

    Directory of Open Access Journals (Sweden)

    Isamu Hosokawa

    2013-07-01

    Full Text Available The number of patients undergoing laparoscopic hepatectomy has rapidly increased in recent years, and indications for this procedure are gradually expanding. Pure laparoscopic hepatectomy is reportedly useful in cases with severe liver cirrhosis. A 55-year-old woman under observation for liver cirrhosis was found to have hepatocellular carcinoma in liver segment III and was referred to our hospital for surgery. The tumor was located in the edge of liver segment III, where percutaneous ablation therapy was unsuitable. Since her hepatic functional reserve was poor, pure laparoscopic partial hepatectomy was performed. The postoperative course was favorable, with no ascites retention, edema or weight gain. The greatest advantage of pure laparoscopic hepatectomy for hepatocellular carcinoma with concomitant liver cirrhosis is that postoperative ascites retention is minimal, meaning that there is little risk of water-electrolyte imbalance associated with ascites retention or hypoproteinemia. This is believed to be because the abdominal incision is small and mobilization of the liver is minimized, reducing the destruction of the routes of collateral lymph flow and blood flow generated in patients with liver cirrhosis. Pure laparoscopic hepatectomy may be a treatment choice for patients with hepatocellular carcinoma and concomitant severe liver cirrhosis.

  13. File list: DNS.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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

    Lifescience Database Archive (English)

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  18. Liver and Bile Duct Cancer—Health Professional Version

    Science.gov (United States)

    Liver cancer includes two major types: hepatocellular carcinoma (HCC) and intrahepatic bile duct cancer, also known as cholangiocarcinoma. Find evidence-based information on liver and bile duct cancer treatment, causes and prevention, screening, research, genomics and statistics.

  19. 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)

  20. A rapid and simple method for cryopreservation of human liver slices

    NARCIS (Netherlands)

    de Kanter, R; Olinga, Peter; Hof, I.H; de Jager, M.H; Verwillegen, W.A; Slooff, M.JH; Meijer, D.K F; Groothuis, Geny; Koster, H

    1. Precision-cut liver slices represent a suitable and convenient in vitro preparation for studying metabolism and toxicity mechanisms of drugs and toxic chemicals. Particularly in the case of human liver slices, cryopreservation would enable more efficient utilization of this scarce and irregularly

  1. Coffee and Liver Disease.

    Science.gov (United States)

    Wadhawan, Manav; Anand, Anil C

    2016-03-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

  2. Overexpression of peroxiredoxin I and thioredoxin1 in human breast carcinoma

    Directory of Open Access Journals (Sweden)

    Kim Il-Han

    2009-06-01

    Full Text Available Abstract Background Peroxiredoxins (Prxs are a novel group of peroxidases containing high antioxidant efficiency. The mammalian Prx family has six distinct members (Prx I-VI in various subcellular locations, including peroxisomes and mitochondria, places where oxidative stress is most evident. The function of Prx I in particular has been implicated in regulating cell proliferation, differentiation, and apoptosis. Since thioredoxin1 (Trx1 as an electron donor is functionally associated with Prx I, we investigated levels of expression of both Prx I and Trx1. Methods We investigated levels of expression of both Prx I and Trx1 in breast cancer by real-time polymerase chain reaction (RT-PCR and Western blot. Results Levels of messenger RNA (mRNA for both Prx I and Trx1 in normal human breast tissue were very low compared to other major human tissues, whereas their levels in breast cancer exceeded that in other solid cancers (colon, kidney, liver, lung, ovary, prostate, and thyroid. Among members of the Prx family (Prx I-VI and Trx family (Trx1, Trx2, Prx I and Trx1 were preferentially induced in breast cancer. Moreover, the expression of each was associated with progress of breast cancer and correlated with each other. Western blot analysis of different and paired breast tissues revealed consistent and preferential expression of Prx I and Trx1 protein in breast cancer tissue. Conclusion Prx I and Trx1 are overexpressed in human breast carcinoma and the expression levels are associated with tumor grade. The striking induction of Prx I and Trx1 in breast cancer may enable their use as breast cancer markers.

  3. Heterogeneity of uroplakin localization in human normal urothelium, papilloma and papillary carcinoma

    International Nuclear Information System (INIS)

    Zupancic, Dasa; Romih, Rok

    2013-01-01

    Uroplakins are differentiation-related membrane proteins of urothelium. We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma. Because of high recurrence rate of these tumours, treated by transurethral resection, we investigated urothelial tumour, resection border and uninvolved urothelium. Urinary bladder samples were obtained from tumour free control subjects and patients with papilloma and papillary carcinoma. Immunohistochemical and immunoelectron labelling of uroplakins were performed. In normal human urothelium with continuous uroplakin-positive superficial cell layer uroplakins were localized to flattened mature fusiform vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin expression was found in papilloma and papillary carcinoma. Three aberrant differentiation stages of urothelial cells, not found in normal urothelium, were recognized in tumours. Diverse uroplakin expression and aberrant differentiation were occasionally found in resection border and in uninvolved urothelium. We demonstrated here that uroplakin expression and localization in urothelial tumours is altered when compared to normal urothelium. In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation. It is possible that aberrant differentiation stages of urothelial cells in resection border and in uninvolved urothelium contribute to high recurrence rate

  4. Gadoxetic acid-enhanced magnetic resonance imaging characteristics of hepatocellular carcinoma occurring in liver transplants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mimi [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Hanyang University of Hospital, Department of Radiology, Seoul (Korea, Republic of); Kang, Tae Wook; Jeong, Woo Kyoung; Kim, Young Kon; Kim, Seong Hyun [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Jong Man [Sungkyunkwan University School of Medicine, Department of Surgery, Samsung Medical Center, Seoul (Korea, Republic of); Sinn, Dong Hyun [Sungkyunkwan University School of Medicine, Division of hepatology, Department of Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Min-Ji; Jung, Sin-ho [Samsung Medical Center, Biostatics and Clinical Epidemiology Center, Seoul (Korea, Republic of)

    2017-08-15

    Characteristics of hepatocellular carcinoma (HCC) on magnetic resonance (MR) images were compared in patients who did or did not undergo liver transplantation (LT), and we evaluated the relationship of these findings with overall survival (OS) and time-to-tumour recurrence (TTR) after transplantation. The enhancement pattern of gadoxetic acid-enhanced MR images of 25 patients with recurrent HCCs (LT group) and 25 surgically confirmed HCC patients in the non-transplanted (control) group were compared. Typical enhancement was defined as 1) arterial enhancement and delayed wash-out and 2) absence of typical features of cholangiocarcinoma consisting of arterial rim enhancement and target appearance on hepatobiliary phase images. OS and TTR were analyzed in the LT group according to these patterns using the log-rank test. HCCs in the LT group significantly more often had an atypical enhancement pattern (16/25, 64.0%) than those in the control group (5/25, 20.0%; p = 0.004). However, OS and TTR did not differ significantly according to these enhancement patterns of recurrent HCC (p > 0.05). Although enhancement patterns of recurrent HCC in transplanted liver did not affect OS and TTR, these HCCs that arise after LT frequently revealed atypical enhancement on gadoxetic acid-enhanced MR imaging. (orig.)

  5. Gadoxetic acid-enhanced magnetic resonance imaging characteristics of hepatocellular carcinoma occurring in liver transplants

    International Nuclear Information System (INIS)

    Kim, Mimi; Kang, Tae Wook; Jeong, Woo Kyoung; Kim, Young Kon; Kim, Seong Hyun; Kim, Jong Man; Sinn, Dong Hyun; Kim, Min-Ji; Jung, Sin-ho

    2017-01-01

    Characteristics of hepatocellular carcinoma (HCC) on magnetic resonance (MR) images were compared in patients who did or did not undergo liver transplantation (LT), and we evaluated the relationship of these findings with overall survival (OS) and time-to-tumour recurrence (TTR) after transplantation. The enhancement pattern of gadoxetic acid-enhanced MR images of 25 patients with recurrent HCCs (LT group) and 25 surgically confirmed HCC patients in the non-transplanted (control) group were compared. Typical enhancement was defined as 1) arterial enhancement and delayed wash-out and 2) absence of typical features of cholangiocarcinoma consisting of arterial rim enhancement and target appearance on hepatobiliary phase images. OS and TTR were analyzed in the LT group according to these patterns using the log-rank test. HCCs in the LT group significantly more often had an atypical enhancement pattern (16/25, 64.0%) than those in the control group (5/25, 20.0%; p = 0.004). However, OS and TTR did not differ significantly according to these enhancement patterns of recurrent HCC (p > 0.05). Although enhancement patterns of recurrent HCC in transplanted liver did not affect OS and TTR, these HCCs that arise after LT frequently revealed atypical enhancement on gadoxetic acid-enhanced MR imaging. (orig.)

  6. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

    Science.gov (United States)

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

  7. 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.

  8. Chip-based human liver-intestine and liver-skin co-cultures--A first step toward systemic repeated dose substance testing in vitro.

    Science.gov (United States)

    Maschmeyer, Ilka; Hasenberg, Tobias; Jaenicke, Annika; Lindner, Marcus; Lorenz, Alexandra Katharina; Zech, Julie; Garbe, Leif-Alexander; Sonntag, Frank; Hayden, Patrick; Ayehunie, Seyoum; Lauster, Roland; Marx, Uwe; Materne, Eva-Maria

    2015-09-01

    Systemic repeated dose safety assessment and systemic efficacy evaluation of substances are currently carried out on laboratory animals and in humans due to the lack of predictive alternatives. Relevant international regulations, such as OECD and ICH guidelines, demand long-term testing and oral, dermal, inhalation, and systemic exposure routes for such evaluations. So-called "human-on-a-chip" concepts are aiming to replace respective animals and humans in substance evaluation with miniaturized functional human organisms. The major technical hurdle toward success in this field is the life-like combination of human barrier organ models, such as intestine, lung or skin, with parenchymal organ equivalents, such as liver, at the smallest biologically acceptable scale. Here, we report on a reproducible homeostatic long-term co-culture of human liver equivalents with either a reconstructed human intestinal barrier model or a human skin biopsy applying a microphysiological system. We used a multi-organ chip (MOC) platform, which provides pulsatile fluid flow within physiological ranges at low media-to-tissue ratios. The MOC supports submerse cultivation of an intact intestinal barrier model and an air-liquid interface for the skin model during their co-culture with the liver equivalents respectively at (1)/100.000 the scale of their human counterparts in vivo. To increase the degree of organismal emulation, microfluidic channels of the liver-skin co-culture could be successfully covered with human endothelial cells, thus mimicking human vasculature, for the first time. Finally, exposure routes emulating oral and systemic administration in humans have been qualified by applying a repeated dose administration of a model substance - troglitazone - to the chip-based co-cultures. Copyright © 2015. Published by Elsevier B.V.

  9. [Primary study on fluro [ 19F] berberine derivative for human hepatocellular carcinoma targetting in vitro].

    Science.gov (United States)

    Zhang, Tong; Wu, Xiaoai; Cai, Huawei; Liang, Meng; Fan, Chengzhong

    2017-04-01

    [ 18 F]HX-01, a Fluorine-18 labeled berberine derivative, is a potential positron emission tomography (PET) tumor imaging agent, while [ 19 F]HX-01 is a nonradioactive reference substance with different energy state and has the same physical and chemical properties. In order to collect data for further study of [ 18 F]HX-01 PET imaging of hepatocellular carcinoma in vivo , this study compared the uptake of [ 19 F]HX-01 by human hepatocellular carcinoma and normal hepatocytes in vitro . The target compound, [ 19 F]HX-01, was synthesized in one step using berberrubine and 3-fluoropropyl 4-methylbenzenesulfonate. Cellular uptake and localization of [ 19 F]HX-01 were performed by a fluorescence microscope in human hepatocellular carcinoma HepG2, SMMC-7721 and human normal hepatocyte HL-7702. Cellular proliferation inhibition and cell cytotoxicity assay of the [ 19 F]HX-01 were conducted using cell counting kit-8 (CCK-8) on HepG2, SMMC-7721 and HL-7702 cells. Fluorescent microscopy showed that the combining ability of [ 19 F]HX-01 to the carcinoma SMMC-7721 and HepG2 was higher than that to the normal HL-7702. Cellular proliferation inhibition assay demonstrated that [ 19 F]HX-01 leaded to a dose-dependent inhibition on SMMC-7721, HepG2, and HL-7702 proliferation. Cell cytotoxicity assay presented that the cytotoxicity of [ 19 F]HX-01 to SMMC-7721 and HepG2 was obviously higher than that to HL-7702. This in vitro study showed that [ 19 F]HX-01 had a higher selectivity on human hepatocellular carcinoma cells (SMMC-7721, HepG2) but has less toxicity to normal hepatocytes (HL-7702). This could set up the idea that the radioactive reference substance [ 18 F]HX-01 may be worthy of further development as a potential molecular probe targeting human hepatocellular carcinoma using PET.

  10. Optimal imaging surveillance schedules after liver-directed therapy for hepatocellular carcinoma.

    Science.gov (United States)

    Boas, F Edward; Do, Bao; Louie, John D; Kothary, Nishita; Hwang, Gloria L; Kuo, William T; Hovsepian, David M; Kantrowitz, Mark; Sze, Daniel Y

    2015-01-01

    To optimize surveillance schedules for the detection of recurrent hepatocellular carcinoma (HCC) after liver-directed therapy. New methods have emerged that allow quantitative analysis and optimization of surveillance schedules for diseases with substantial rates of recurrence such as HCC. These methods were applied to 1,766 consecutive chemoembolization, radioembolization, and radiofrequency ablation procedures performed on 910 patients between 2006 and 2011. Computed tomography or magnetic resonance imaging performed just before repeat therapy was set as the time of "recurrence," which included residual and locally recurrent tumor as well as new liver tumors. Time-to-recurrence distribution was estimated by Kaplan-Meier method. Average diagnostic delay (time between recurrence and detection) was calculated for each proposed surveillance schedule using the time-to-recurrence distribution. An optimized surveillance schedule could then be derived to minimize the average diagnostic delay. Recurrence is 6.5 times more likely in the first year after treatment than in the second. Therefore, screening should be much more frequent in the first year. For eight time points in the first 2 years of follow-up, the optimal schedule is 2, 4, 6, 8, 11, 14, 18, and 24 months. This schedule reduces diagnostic delay compared with published schedules and is cost-effective. The calculated optimal surveillance schedules include shorter-interval follow-up when there is a higher probability of recurrence and longer-interval follow-up when there is a lower probability. Cost can be optimized for a specified acceptable diagnostic delay or diagnostic delay can be optimized within a specified acceptable cost. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

  11. The role of hypoxia, p53, and apoptosis in human cervical carcinoma pathogenesis

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell H.; Osmanian, Cynthia; Calkins, Dennise P.; Graeber, Thomas G.; Greenspan, David L.; Kennedy, Andrew S.; Rinker, Lillian H.; Varia, Mahesh A.; DiPaolo, Joseph A.; Peehl, Donna M.; Raleigh, James A.; Giaccia, Amato J.

    1997-01-01

    Objective: Low oxygen tension in the tumor microenvironment may have an important role during tumor growth, and is of particular prognostic significance in human cervical carcinoma. Because some human papillomavirus (HPV) infections are associated with cervical neoplasia, the relationship between hypoxia and apoptosis in primary cervical epithelial cells containing HPV16 E6 and E7, intact HPV 16 genome, and HPV positive cervical carcinoma cell lines, was examined. In addition, the relationship between hypoxia and apoptosis in spontaneous human cervical carcinomas was determined in situ. Materials and Methods: Primary normal human cervical epithelial cells were infected with retroviral vectors containing HPV16 E6 and E7 or transfected with a plasmid containing the whole HPV 16 genome. Clones were selected in neomycin containing medium. Exponentially growing cells were incubated under aerobic conditions (20% O 2 ), anaerobic conditions (0.02% O 2 ), or irradiated with 6 Gy. Analysis of apoptotic cells was performed by staining with Hoechst dye and propidium iodide and viewing with a fluorescent microscope. To determine the level of expression of the apoptotic modulators p53 and Bax, immunoblots were performed on whole cell extracts from treated cells. A clinical tumor hypoxia study was conducted at the University of North Carolina utilizing pimonidazole, a 2-nitroimidazole compound which binds irreversibly to cellular macromolecules under low oxygen conditions. Nine patients were enrolled with biopsy proven squamous cell carcinoma of the cervix and no prior treatment. Biopsies of the gross tumor were obtained after pimonidazole infusion. Contiguous histological sections were analyzed for hypoxia using a immunohistochemical technique and for apoptosis using TUNEL. Results: In vitro, hypoxia uncoupled p53 from E6 mediated degradation, and stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes. In contrast

  12. Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

    Science.gov (United States)

    2014-01-01

    Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

  13. Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines.

    Science.gov (United States)

    Manzini, Giulia; Henne-Bruns, Doris; Porzsolt, Franz; Kremer, Michael

    2017-01-01

    Liver resection (LR) and transplantation are the most reliable treatments for hepatocellular carcinoma (HCC). Aim was to compare different guidelines regarding indication for resection and transplantation because of HCC with and without underlying cirrhosis. We compared the following guidelines published after 1 January 2010: American (American Association for the Study of Liver Diseases (AASLD)), Spanish (Sociedad Espanola de Oncologia Medica (SEOM)), European (European Association for the study of liver-European Organization for Research and Treatment of Cancer (EASL-EORTC) and European Society for Medical Oncology-European Society of Digestive Oncology (ESMO-ESDO)), Asian (Asian Pacific Association for the Study of Liver (APASL)), Japanese (Japan Society of Hepatology (JSH)), Italian (Associazione Italiana Oncologia Medica (AIOM)) and German (S3) guidelines. All guidelines recommend resection as therapy of choice in healthy liver. Guidelines based on the Barcelona Clinic Liver Cancer staging system recommend resection for single HCCguidelines recommend LR for patients with Child-Pugh A/B with HCC without tumour size restriction; APASL guidelines in general exclude patients with Child-Pugh A from transplantation. In patients with Child-Pugh B, transplantation is the second-line therapy, if resection is not possible for patients within Milan criteria. German and Italian guidelines recommend transplantation for all patients within Milan criteria. Whereas resection is the standard therapy of HCC in healthy liver, a standard regarding the indication for LR and transplantation for HCC in cirrhotic liver does not exist, although nearly all guidelines claim to be evidence based. Surprisingly, despite European guidelines, Germany and Italy use their own national guidelines which partially differ from the European. Possible solutions of the problems are discussed.

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

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  18. Human Papilloma Virus and Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2013-04-01

    Full Text Available Human papilloma virus (HPV has been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in substantial number of esophageal SCCs in our region is unlikely.

  19. Human papilloma virus and esophageal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Hayedeh Haeri

    2014-03-01

    Full Text Available Human papillomavirus (HPV has also been suggested as an etiology of esophageal squamous cell carcinoma (SCC. The aim of this study was to investigate the prevalence of HPV infection in esophageal SCCs in our region with strict contamination control to prevent false positive results. Thirty cases of esophageal squamous cell carcinomas were chosen by simple random selection in a period of two years. PCR for target sequence of HPV L1 gene was performed on nucleic acid extracted from samples by means of GP5+/GP6+ primers. All tissue samples in both case and control groups were negative for HPV-DNA. Although the number of cases in this study was limited, the contribution of HPV in the substantial number of esophageal SCCs in our region is unlikely.

  20. 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

  1. Recurrence of hepatocellular carcinoma after liver transplantation presenting as anastomotic biliary stricture Presentación del carcinoma hepatocelular recurrente tras el trasplante de hígado en forma de estenosis biliar anastomótica

    OpenAIRE

    S. Y. Chen; C. H. Lin; J. C. Yu; C. Y. Yu; C. B. Hsieh

    2008-01-01

    A 52-year-old man visited our hospital complaining of anorexia and fatigue two months after receiving orthotopic liver transplantation for hepatocellular carcinoma. A laboratory investigation demonstrated a clinical picture of obstructive jaundice. T-tube cholangiography showed biliary stricture over the anastomotic site. Percutaneous transluminal balloon dilatation and stenting was attempted but failed. Magnetic resonance cholangiography showed possible tumor recurrence over the site of the ...

  2. Genomic instability in human actinic keratosis and squamous cell carcinoma

    Science.gov (United States)

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  3. Mercury-Induced Externalization of Phosphatidylserine and Caspase 3 Activation in Human Liver Carcinoma (HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2006-03-01

    Full Text Available Apoptosis arises from the active initiation and propagation of a series of highly orchestrated specific biochemical events leading to the demise of the cell. It is a normal physiological process, which occurs during embryonic development as well as in the maintenance of tissue homeostasis. Diverse groups of molecules are involved in the apoptosis pathway and it functions as a mechanism to eliminate unwanted or irreparably damaged cells. However, inappropriate induction of apoptosis by environmental agents has broad ranging pathologic implications and has been associated with several diseases including cancer. The toxicity of several heavy metals such as mercury has been attributed to their high affinity to sulfhydryl groups of proteins and enzymes, and their ability to disrupt cell cycle progression and/or apoptosis in various tissues. The aim of this study was to assess the potential for mercury to induce early and late-stage apoptosis in human liver carcinoma (HepG2 cells. The Annexin-V and Caspase 3 assays were performed by flow cytometric analysis to determine the extent of phosphatidylserine externalization and Caspase 3 activation in mercury-treated HepG2 cells. Cells were exposed to mercury for 10 and 48 hours respectively at doses of 0, 1, 2, and 3 μg/mL based on previous cytotoxicity results in our laboratory indicating an LD50 of 3.5 ± 0.6 μg/mL for mercury in HepG2 cells. The study data indicated a dose response relationship between mercury exposure and the degree of early and late-stage apoptosis in HepG2 cells. The percentages of cells undergoing early apoptosis were 0.03 ± 0.03%, 5.19 ± 0.04%, 6.36 ± 0.04%, and 8.84 ± 0.02% for 0, 1, 2, and 3 μg/mL of mercury respectively, indicating a gradual increase in apoptotic cells with increasing doses of mercury. The percentages of Caspase 3 positive cells undergoing late apoptosis were 3.58 ± 0.03%, 17.06 ± 0

  4. Early dynamic 18F-FDG PET to detect hyperperfusion in hepatocellular carcinoma liver lesions.

    Science.gov (United States)

    Schierz, Jan-Henning; Opfermann, Thomas; Steenbeck, Jörg; Lopatta, Eric; Settmacher, Utz; Stallmach, Andreas; Marlowe, Robert J; Freesmeyer, Martin

    2013-06-01

    In addition to angiographic data on vascularity and vascular access, demonstration of hepatocellular carcinoma (HCC) liver nodule hypervascularization is a prerequisite for certain intrahepatic antitumor therapies. Early dynamic (ED) (18)F-FDG PET/CT could serve this purpose when the current standard method, contrast-enhanced (CE) CT, or other CE morphologic imaging modalities are unsuitable. A recent study showed ED (18)F-FDG PET/CT efficacy in this setting but applied a larger-than-standard (18)F-FDG activity and an elaborate protocol likely to hinder routine use. We developed a simplified protocol using standard activities and easily generated visual and descriptive or quantitative endpoints. This pilot study assessed the ability of these endpoints to detect HCC hyperperfusion and, thereby, evaluated the suitability in of the protocol everyday practice. Twenty-seven patients with 34 HCCs (diameter ≥ 1.5 cm) with hypervascularization on 3-phase CE CT underwent liver ED (18)F-FDG PET for 240 s, starting with (18)F-FDG (250-MBq bolus injection). Four frames at 15-s intervals, followed by 3 frames at 60-s intervals were reconstructed. Endpoints included focal tracer accumulation in the first 4 frames (60 s), subsequent focal washout, and visual and quantitative differences between tumor and liver regions of interest in maximum and mean ED standardized uptake value (ED SUVmax and ED SUVmean, respectively) 240-s time-activity curves. All 34 lesions were identified by early focal (18)F-FDG accumulation and faster time-to-peak ED SUVmax or ED SUVmean than in nontumor tissue. Tumor peak ED SUVmax and ED SUVmean exceeded liver levels in 85% and 53%, respectively, of lesions. Nadir tumor signal showed no consistent pattern relative to nontumor signal. HCC had a significantly shorter time to peak and significantly faster rate to peak for both ED SUVmax and ED SUVmean curves and a significantly higher peak ED SUVmax but not peak ED SUVmean than the liver. This pilot study

  5. Liver Fibrosis: Current Principles of Diagnosis

    Directory of Open Access Journals (Sweden)

    A.K. Duda

    2014-09-01

    Full Text Available Liver fibrosis — a natural consequence of almost all liver diseases of any origin. We are faced with a number of standard stereotype processes that take place in the liver tissue. Mostly it is the processes of chronic inflammation, which oppose the processes of liver tissue regeneration. The basis of imbalance between the processes of fibrosis and regeneration is an accumulation of extracellular matrix. Liver fibrosis in its development leads to liver cirrhosis, hepatocellular carcinoma, and the increase in morbidity rate is observed worldwide. Furthermore, the process is genetically determined, but modifiable factors play an important role in the progression of this disease. Current data indicate the possibility of reversible liver fibrosis.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Lifescience Database Archive (English)

    Full Text Available ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 All antigens Liver Carcinoma, Hepato...cellular SRX467209,SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

  8. [Liver transplantation].

    Science.gov (United States)

    Pompili, Maurizio; Mirante, Vincenzo Giorgio; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

    2004-01-01

    Liver transplantation represents the first choice treatment for patients with fulminant acute hepatitis and for patients with chronic liver disease and advanced functional failure. Patients in the waiting list for liver transplantation are classified according to the severity of their clinical conditions (evaluated using staging systems mostly based on hematochemical parameters related to liver function). This classification, together with the blood group and the body size compatibility, remains the main criterion for organ allocation. The main indications for liver transplantation are cirrhosis (mainly HCV-, HBV- and alcohol-related) and hepatocellular carcinoma emerging in cirrhosis in adult patients, biliary atresia and some inborn errors of metabolism in pediatric patients. In adults the overall 5-year survival ranges between 60 and 70%, in both American and European series. Even better results have been reported for pediatric patients: in fact, the 5-year survival rate for children ranges between 70 and 80% in the main published series. In this study we evaluated the main medical problems correlated with liver transplantation such as immunosuppressive treatment, acute and chronic rejection, infectious complications, the recurrence of the liver disease leading to transplantation, and cardiovascular and metabolic complications.

  9. 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

  10. Synchronous resection of colorectal liver metastasis- a case report ...

    African Journals Online (AJOL)

    We present a case report of a young patient of. Carcinoma sigmoid colon with multiple liver metastases who was managed with synchronous resection of colorectal liver metastasis. The patient had an ulceroproliferative growth in the sigmoid colon 18 cm from the anal verge with multiple bilobar liver metastases. The CEA

  11. Research advances in association between Golgi protein 73 and liver diseases

    Directory of Open Access Journals (Sweden)

    WEI Fengxian

    2017-08-01

    Full Text Available Golgi protein 73 (GP73 has a very low expression level in normal people, while it has a significantly higher expression level in patients with liver diseases and hepatocellular carcinoma (HCC, and therefore, it may become a new marker for HCC. This article introduces the distribution of GP73 in human body and definitions of different subtypes of GP73 and elaborates on its association with benign/malignant liver diseases and surgical operation based on the subtypes of GP73, as well as the application of GP73 in the differentiation of benign/malignant liver diseases. Since GP73 is closely associated with the development, progression, and prognosis of liver diseases, this article summarizes the latest advances in basic research, introduces the structural basis of fucosylated GP73 and proliferation, migration, and invasion of hepatoma cells and known signaling pathways, and lists the factors which affect the expression of GP73.

  12. 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.

  13. Various factors affecting /sup 67/Ga scintigraphy of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Motoki, T; Morinari, H; Oono, K [Tokyo Univ. (Japan). Faculty of Medicine

    1980-10-01

    Various factors affecting /sup 67/Ga accumulation in liver cancer were studied in 38 patients with liver cancer (19 with hepatocellular carcinoma and 19 with metastatic liver cancer) who had received /sup 67/Ga-scintigraphy and liver scintigraphy. Besides histological types, the size, necrosis, vascularity and treatments of liver cancer, concentrations of transferrin (/sup 67/Ga binding protein) and iron in blood probably affected /sup 67/Ga accumulation in liver cancer.

  14. Targeted induction of interferon-λ in humanized chimeric mouse liver abrogates hepatotropic virus infection.

    Directory of Open Access Journals (Sweden)

    Shin-ichiro Nakagawa

    Full Text Available BACKGROUND & AIMS: The interferon (IFN system plays a critical role in innate antiviral response. We presume that targeted induction of IFN in human liver shows robust antiviral effects on hepatitis C virus (HCV and hepatitis B virus (HBV. METHODS: This study used chimeric mice harboring humanized livers and infected with HCV or HBV. This mouse model permitted simultaneous analysis of immune responses by human and mouse hepatocytes in the same liver and exploration of the mechanism of antiviral effect against these viruses. Targeted expression of IFN was induced by treating the animals with a complex comprising a hepatotropic cationic liposome and a synthetic double-stranded RNA analog, pIC (LIC-pIC. Viral replication, IFN gene expression, IFN protein production, and IFN antiviral activity were analyzed (for type I, II and III IFNs in the livers and sera of these humanized chimeric mice. RESULTS: Following treatment with LIC-pIC, the humanized livers of chimeric mice exhibited increased expression (at the mRNA and protein level of human IFN-λs, resulting in strong antiviral effect on HBV and HCV. Similar increases were not seen for human IFN-α or IFN-β in these animals. Strong induction of IFN-λs by LIC-pIC occurred only in human hepatocytes, and not in mouse hepatocytes nor in human cell lines derived from other (non-hepatic tissues. LIC-pIC-induced IFN-λ production was mediated by the immune sensor adaptor molecules mitochondrial antiviral signaling protein (MAVS and Toll/IL-1R domain-containing adaptor molecule-1 (TICAM-1, suggesting dual recognition of LIC-pIC by both sensor adaptor pathways. CONCLUSIONS: These findings demonstrate that the expression and function of various IFNs differ depending on the animal species and tissues under investigation. Chimeric mice harboring humanized livers demonstrate that IFN-λs play an important role in the defense against human hepatic virus infection.

  15. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  16. 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...

  17. Expression of toll-like receptors in hepatic cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Sun, L; Dai, J J; Hu, W F; Wang, J

    2016-07-14

    Toll-like receptors (TLRs) can specifically identify pathogen-associated molecular patterns (PAMPs) by recognizing structural patterns in diverse microbial molecules, and can provide an effective defense against multiple microbial infectious. A variety of TLRs can be expressed on the surface of liver parenchymal as well as nonparenchymal cells. Kupffer cells are a type of hepatic nonparenchymal macrophage, and are positively associated with the severity of liver fibrosis. They play an important role in the synthesis and deposition of the extracellular matrix by upregulating the expression of tissue inhibitor of metalloproteinases and downregulating the activity of matrix metalloproteinases. Cirrhosis, a chronic diffuse lesion usually accompanying extensive liver fibrosis and nodular regeneration, is caused by liver parenchymal cells repeating injury-repair following reconstruction of organizational structure in the hepatic lobules. Hepatocellular carcinoma is caused by repeated and persistent chronic severe liver injury, and partial hepatocytes can eventually transform into hepatoma cells. Multiple TLRs such as TLR2, TLR3, TLR4, and TLR9, as well as other receptors, can be expressed in cirrhosis and hepatocellular carcinoma. About 53 and 85% of hepatocellular carcinoma patients frequently express TLR3 and TLR9, respectively. The chronic and repeated liver injury caused by alcohol, and HBV, HCV, or other pathogens can be recognized by TLRs through the PAMP pathway, which directly increases the risk for hepatic cirrhosis and hepatocellular carcinoma. In this review, we briefly present evidence that the novel cellular molecular mechanisms of TLRs may provide more information about new therapeutics targets of the anti-inflammatory immune response.

  18. HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

    Science.gov (United States)

    Berndt, Nikolaus; Bulik, Sascha; Wallach, Iwona; Wünsch, Tilo; König, Matthias; Stockmann, Martin; Meierhofer, David; Holzhütter, Hermann-Georg

    2018-06-19

    The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

  19. Characteristic gene expression profiles in the progression from liver cirrhosis to carcinoma induced by diethylnitrosamine in a rat model

    Directory of Open Access Journals (Sweden)

    Zhu Jin

    2009-07-01

    Full Text Available Abstract Background Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma. Methods A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues. Results The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated. Conclusion In this study, we provide the global gene expression profiles during the development and

  20. The value of "liver windows" settings in the detection of small renal cell carcinomas on unenhanced computed tomography.

    Science.gov (United States)

    Sahi, Kamal; Jackson, Stuart; Wiebe, Edward; Armstrong, Gavin; Winters, Sean; Moore, Ronald; Low, Gavin

    2014-02-01

    To assess if "liver window" settings improve the conspicuity of small renal cell carcinomas (RCC). Patients were analysed from our institution's pathology-confirmed RCC database that included the following: (1) stage T1a RCCs, (2) an unenhanced computed tomography (CT) abdomen performed ≤ 6 months before histologic diagnosis, and (3) age ≥ 17 years. Patients with multiple tumours, prior nephrectomy, von Hippel-Lindau disease, and polycystic kidney disease were excluded. The unenhanced CT was analysed, and the tumour locations were confirmed by using corresponding contrast-enhanced CT or magnetic resonance imaging studies. Representative single-slice axial, coronal, and sagittal unenhanced CT images were acquired in "soft tissue windows" (width, 400 Hounsfield unit (HU); level, 40 HU) and liver windows (width, 150 HU; level, 88 HU). In addition, single-slice axial, coronal, and sagittal unenhanced CT images of nontumourous renal tissue (obtained from the same cases) were acquired in soft tissue windows and liver windows. These data sets were randomized, unpaired, and were presented independently to 3 blinded radiologists for analysis. The presence or absence of suspicious findings for tumour was scored on a 5-point confidence scale. Eighty-three of 415 patients met the study criteria. Receiver operating characteristics (ROC) analysis, t test analysis, and kappa analysis were used. ROC analysis showed statistically superior diagnostic performance for liver windows compared with soft tissue windows (area under the curve of 0.923 vs 0.879; P = .0002). Kappa statistics showed "good" vs "moderate" agreement between readers for liver windows compared with soft tissue windows. Use of liver windows settings improves the detection of small RCCs on the unenhanced CT. Copyright © 2014 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  1. Asymptomatic renal cell carcinoma incidentally detected by abdominal CT

    International Nuclear Information System (INIS)

    Yoneda, Fumio; Miyake, Noriaki; Tsujimura, Haruhiro; Nakajima, Mikio; Akiyama, Hajime

    1987-01-01

    Four cases of renal cell carcinoma that were incidentally detected by abdominal CT are reported. Abdominal CT was performed during gastro-intestinal examination in two patients and for suspected liver disease in the other two. No patient had symptoms of renal cell carcinoma, or hematuria. In all cases, the histopathological diagnosis was renal cell carcinoma of a low stage. (author)

  2. Human Liver Cells Expressing Albumin and Mesenchymal Characteristics Give Rise to Insulin-Producing Cells

    Directory of Open Access Journals (Sweden)

    Irit Meivar-Levy

    2011-01-01

    Full Text Available Activation of the pancreatic lineage in the liver has been suggested as a potential autologous cell replacement therapy for diabetic patients. Transcription factors-induced liver-to-pancreas reprogramming has been demonstrated in numerous species both in vivo and in vitro. However, human-derived liver cells capable of acquiring the alternate pancreatic repertoire have never been characterized. It is yet unknown whether hepatic-like stem cells or rather adult liver cells give rise to insulin-producing cells. Using an in vitro experimental system, we demonstrate that proliferating adherent human liver cells acquire mesenchymal-like characteristics and a considerable level of cellular plasticity. However, using a lineage-tracing approach, we demonstrate that insulin-producing cells are primarily generated in cells enriched for adult hepatic markers that coexpress both albumin and mesenchymal markers. Taken together, our data suggest that adult human hepatic tissue retains a substantial level of developmental plasticity, which could be exploited in regenerative medicine approaches.

  3. Adult Liver Cancer Symptoms, Tests, Prognosis, and Stages (PDQ®)—Patient Version

    Science.gov (United States)

    Hepatocellular carcinoma is the most common type of adult primary liver cancer. The Barcelona Clinical Liver Cancer (BCLC) Staging System is used to stage liver cancer. Learn more about risk factors, signs and symptoms, tests to diagnose, prognosis, and stages of adult primary liver cancer.

  4. Human Precision-Cut Liver Slices as an ex Vivo Model to Study Idiosyncratic Drug-Induced Liver Injury

    NARCIS (Netherlands)

    Hadi, Mackenzie; Westra, Inge M.; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, M.T.; Groothuis, Geny M. M.

    Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Because of the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict

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

    Lifescience Database Archive (English)

    Full Text Available NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  6. File list: NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  7. The Interleukin-20 Cytokine Family in Liver Disease

    Directory of Open Access Journals (Sweden)

    Esther Caparrós

    2018-05-01

    Full Text Available The three main causes of inflammation and chronic injury in the liver are viral hepatitis, alcohol consumption, and non-alcoholic steatohepatitis, all of which can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma, which in turn may prompt the need for liver transplant. The interleukin (IL-20 is a subfamily part of the IL-10 family of cytokines that helps the liver respond to damage and disease, they participate in the control of tissue homeostasis, and in the immunological responses developed in this organ. The best-studied member of the family in inflammatory balance of the liver is the IL-22 cytokine, which on the one hand may have a protective role in fibrosis progression but on the other may induce liver tissue susceptibility in hepatocellular carcinoma development. Other members of the family might also carry out this dual function, as some of them share IL receptor subunits and signal through common intracellular pathways. Investigators are starting to consider the potential for targeting IL-20 subfamily members in liver disease. The recently explored role of miRNA in the transcriptional regulation of IL-22 and IL-24 opens the door to promising new approaches for controlling the local immune response and limiting organ injury. The IL-20RA cytokine receptor has also been classified as being under miRNA control in non-alcoholic steatohepatitis. Moreover, researchers have proposed combining anti-inflammatory drugs with IL-22 as a hepatoprotective IL for alcoholic liver disease (ALD treatment, and clinical trials of ILs for managing severe alcoholic-derived liver degeneration are ongoing. In this review, we focus on exploring the role of the IL-20 subfamily of cytokines in viral hepatitis, ALD, non-alcoholic steatohepatitis, and hepatocellular carcinoma, as well as delineating the main strategies explored so far in terms of therapeutic possibilities of the IL-20 subfamily of cytokines in liver disease.

  8. Gastric metastasis of triple negative invasive lobular carcinoma

    OpenAIRE

    Caglayan Geredeli; Osman Dogru; Ethem Omeroglu; Farise Yilmaz; Faruk Cicekci

    2015-01-01

    Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis o...

  9. Laparoscopic liver resection for hepatocellular carcinoma in cirrhotic patients. Feasibility of nonanatomic resection in difficult tumor locations

    Directory of Open Access Journals (Sweden)

    Marco Casaccia

    2011-01-01

    Full Text Available Background: Surgical resection for hepatocellular carcinoma (HCC in cirrhotic patients remains controversial because of high morbidity and recurrence rates. Laparoscopic resection of liver tumors has recently been developed and could reduce morbidity. The aim of this study was to evaluate retrospectively our results for laparoscopic liver resection (LLR for HCC including lesions in the posterosuperior segments of the liver in terms of feasibility, outcome, recurrence and survival. Materials and Methods: Between June 2005 and February 2009, we performed 20 LLR for HCC. Median age of the patients was 66 years. The underlying cirrhosis was staged as Child A in 17 cases and Child B in 3. Results: LLR included anatomic resection in six cases and nonanatomic resection in 14. Eleven procedures were associated in nine (45% patients. Median tumor size and surgical margins were 3.1 cm and 15 mm, respectively. A conversion to laparotomy occurred in one (5% patient for hemorrhage. Mortality and morbidity rates were 0% and 15% (3/20. Median hospital stay was 8 days (range: 5-16 days. Over a mean follow-up period of 26 months (range: 19-62 months, 10 (50% patients presented recurrence, mainly at distance from the surgical site. Treatment of recurrence was possible in all the patients, including orthotopic liver transplantation in three cases. Conclusions: LLR for HCC in selected patients is a safe procedure with good short-term results. It can also be proposed in tumor locations with a difficult surgical access maintaining a low morbidity rate and good oncological adequacy. This approach could have an impact on the therapeutic strategy of HCC complicating cirrhosis as a treatment with curative intent or as a bridge to liver transplantation.

  10. Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2012-01-01

    Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

  11. PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

    Science.gov (United States)

    Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

    2014-01-01

    Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

  12. Impact of etiology of chronic liver disease on hepatocellular carcinoma biomarkers.

    Science.gov (United States)

    Ricco, Gabriele; Cavallone, Daniela; Cosma, Chiara; Caviglia, Gian Paolo; Oliveri, Filippo; Biasiolo, Alessandra; Abate, Maria Lorena; Plebani, Mario; Smedile, Antonina; Bonino, Ferruccio; Pontisso, Patrizia; Brunetto, Maurizia Rossana

    2018-02-14

    The role of serum biomarkers in the surveillance of hepatocellular carcinoma (HCC) is controversial. We assessed the diagnostic performances of alpha-fetoprotein (AFP) and protein-induced by vitamin-K-absence/antagonist-II (PIVKA-II) in 388 cirrhotic patients with chronic liver disease (CLD). Biomarkers were quantified by automated chemiluminescent-enzyme-immunoassays (Fujirebio, Tokyo, Japan) at HCC diagnosis in 258 patients (204 males; median age 66.9 years) and in 130 cirrhotics without HCC (104 males; median-age 60.6 years). CLD etiology in HCC/non-HCC was CHB in 48/35, CHC in 126/56 and Non-Viral in 84/39. Overall AUROC values for AFP and PIVKA-II were 0.698 (95%CI = 0.642-0.753, PCLD. AFP/PIVKA-II diagnostic accuracy was 40.5-59.8%/62.7-73.5% and combining both markers 78.2% for CHB, 77% for Non-Viral-CLD and 75% for CHC. AFP correlated with ALT in HCC patients with CHC (ρ= 0.463/PCLD (ρ= 0.359/P= 0.047), but not in CHB (treated with antivirals). PIVKA-II correlated with tumour size independently of CLD-etiology (PCLD; their combination provides a better diagnostic accuracy.

  13. An in vivo cytogenetic analysis of human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Abhimanyu Mohanta

    2015-01-01

    Full Text Available Background: Oral cancer ranks in the top three of all cancers in India, which accounts for over 30% of all cancers reported in the country. The micronucleus test (MNT is one of the most widely applied short term tests used in genetic toxicology to evaluate the mutagenicity and carcinogenicity. Aims: The present study aims at an in vivo cytogenetic analysis of human oral squamous cell carcinoma and to assess the applicability of MNT in diagnosing early detection of oral carcinoma. Materials and Methods: Exfoliated scrape smears were collected from the clinically diagnosed 136 patients suffering from oral precancerous and cancerous lesions. The wet fixed smears were stained by adopting Papanicolaou's staining protocol and counter-stained with Giemsa's solution. Results: The frequency of micronucleated cells has been observed to be in increasing order with the increase of the age-groups and from control to precancerous to cancerous cases significantly in both sexes. Conclusion: Micronucleus formation in the oral mucosa could be a biomarker of genetic damage and also a potential onco-indicator in the long run of oral carcinogenesis. Therefore, MNT can be applied for the early detection of oral carcinoma in the human being.

  14. Human precision-cut liver slices as an ex vivo model to study idiosyncratic drug-induced liver injury

    NARCIS (Netherlands)

    Hadi, Mackenzie; Westra, Inge; Starokozhko, Viktoriia; Dragovic, Sanja; Merema, Maja; Groothuis, Genoveva

    2013-01-01

    Idiosyncratic drug-induced liver injury (IDILI) is a major problem during drug development and has caused drug withdrawal and black-box warnings. Due to the low concordance of the hepatotoxicity of drugs in animals and humans, robust screening methods using human tissue are needed to predict and to

  15. Comparison of anamnestic history, alcohol intake and smoking, nutritional status, and liver dysfunction between thorotrast patients who developed primary liver cancer and those who did not

    International Nuclear Information System (INIS)

    Kiyosawa, K.; Imai, H.; Sodeyama, T.; Franca, S.T.; Yousuf, M.; Furuta, S.; Fujisawa, K.; Kido, C.

    1989-01-01

    In order to clarify the differences in past history, nutritional condition and, consumption of alcohol and tobacco, and liver dysfunction between the thorotrast patients who developed primary liver cancer and those who did not, 103 persons who had no primary liver cancer in January 1980 were studied. All subjects were military men who had undergone angiography with thorotrast between 1943 and 1946. Twenty persons developed hepatocellular carcinoma and 16 developed intrahepatic bile duct carcinoma by April 1987, whereas 67 are still alive without any cancer. There was no difference in age or period after thorotrast infusion between those two groups of patients in January 1980. A difference in history of hepatitis and/or jaundice and presence of hepatic dysfunction was found between the subjects who developed primary liver cancers and those who did not. These findings suggest that an anamnestic history of hepatitis and liver dysfunction are risks for development of thorotrast-induced liver cancer. On the basis of the above findings, early detection of liver dysfunction offers a possibility of early diagnosis of primary liver cancer

  16. Intravenous miR-144 inhibits tumor growth in diethylnitrosamine-induced hepatocellular carcinoma in mice.

    Science.gov (United States)

    He, Quan; Wang, Fangfei; Honda, Takashi; Lindquist, Diana M; Dillman, Jonathan R; Timchenko, Nikolai A; Redington, Andrew N

    2017-10-01

    Previous in vitro studies have demonstrated that miR-144 inhibits hepatocellular carcinoma cell proliferation, invasion, and migration. We have shown that miR-144, injected intravenously, is taken up by the liver and induces endogenous hepatic synthesis of miR-144. We hypothesized that administered miR-144 has tumor-suppressive effects on liver tumor development in vivo. The effects of miR-144 on tumorigenesis and tumor growth were tested in a diethylnitrosamine-induced hepatocellular carcinoma mouse model. MiR-144 injection had no effect on body weight but significantly reduced diethylnitrosamine-induced liver enlargement compared with scrambled microRNA. MiR-144 had no effect on diethylnitrosamine-induced liver tumor number but reduced the tumor size above 50%, as evaluated by magnetic resonance imaging (scrambled microRNA 23.07 ± 5.67 vs miR-144 10.38 ± 2.62, p hepatocellular carcinoma tumorigenesis. Exogenously delivered miR-144 may be a therapeutic strategy to suppress tumor growth in hepatocellular carcinoma.

  17. 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.

  18. Lucidumol C, a new cytotoxic lanostanoid triterpene from Ganoderma lingzhi against human cancer cells.

    Science.gov (United States)

    Amen, Yhiya M; Zhu, Qinchang; Tran, Hai-Bang; Afifi, Mohamed S; Halim, Ahmed F; Ashour, Ahmed; Mira, Amira; Shimizu, Kuniyoshi

    2016-07-01

    A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

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

    Lifescience Database Archive (English)

    Full Text Available InP.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  20. File list: InP.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

  1. Adding Liver Stiffness Measurement to the Routine Evaluation of Hepatocellular Carcinoma Resectability Can Optimize Clinical Outcome.

    Science.gov (United States)

    Cucchetti, Alessandro; Cescon, Matteo; Colecchia, Antonio; Neri, Flavia; Cappelli, Alberta; Ravaioli, Matteo; Mazzotti, Federico; Ercolani, Giorgio; Festi, Davide; Pinna, Antonio Daniele

    2017-10-01

    Purpose  Liver stiffness (LS) has been shown to be of use in chronic liver disease patients but its utility in surgical judgment still needs to be proven. A decision-making approach was applied to evaluate whether LS measurement before surgery of hepatocellular carcinoma (HCC) can be useful in avoiding post-hepatectomy liver failure (PHLF). Materials and Methods  Decision curve analysis (DCA) was applied to 202 HCC patients (2008 - 14) with LS measurement prior to hepatectomy to verify whether the occurrence of PHLF grades B/C should be reduced through a decision-making approach with LS.  Results  Within 90 days of surgery, 4 patients died (2 %) and grades B/C PHLF occurred in 29.7 % of cases. Ascites and/or pleural effusion, treatable with medical therapy, were the most frequent complications. DCA showed that using the "expected utility theory" LS measurement can reduce up to 39 % of cases of PHLF without the exclusion of any patient from surgery that duly undergoes an uncomplicated postoperative course. LS measurement does not add any information to normal clinical judgment for patients with a low (expected utility theory" fulfilment. However, the degree of PHLF can be minor and "risk seeking" individuals can accept such a risk on the basis of surgical benefits. © Georg Thieme Verlag KG Stuttgart · New York.

  2. ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Na, Seong K; Yim, Sun Y; Suh, Sang J; Jung, Young K; Kim, Ji H; Seo, Yeon S; Yim, Hyung J; Yeon, Jong E; Byun, Kwan S; Um, Soon H

    2018-04-01

    The prognostic performance of the albumin-bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated. Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child-Pugh (C-P) grade for different stages or treatments. The median follow up duration was 16.2 months (range: 1.0-124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4 months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C-P grade. In curative treatments, ALBI grade also showed better discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs 0.667 [ALBI grade]). ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C-P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC. © 2018 Wiley Periodicals, Inc.

  3. Cutaneous features seen in primary liver cell (Hepatocellular ...

    African Journals Online (AJOL)

    Primary liver cell carcinoma (PLCC), predominantly hepatocellular carcinoma is a killer. In the southwestern region of Nigeria it occupies the second position, behind prostate cancer in males. Females account for about a third of diagnosed cases. Children are not spared. Over 80 % of PLCC cases present to the hospital at ...

  4. Mice with humanized liver endothelium

    NARCIS (Netherlands)

    el Filali, E.

    2014-01-01

    The only curative treatment option for a large proportion of patients suffering from a liver disorder is liver transplantation. The use of ex vivo genetically modified autologous liver cells instead of whole liver transplantation could overcome the problem of donor scarcity. Even though clinical

  5. Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

    Science.gov (United States)

    Naritomi, Yoichi; Sanoh, Seigo; Ohta, Shigeru

    2018-02-01

    Predicting human drug metabolism and pharmacokinetics (PK) is key to drug discovery. In particular, it is important to predict human PK, metabolite profiles and drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using human biological samples, such as hepatic microsomes and hepatocytes, and in vivo studies using experimental animals. However, prediction studies using these methods are often inconclusive due to discrepancies between in vitro and in vivo results, and interspecies differences in drug metabolism. Further, the prediction methods have changed from qualitative to quantitative to solve these issues. Chimeric mice with humanized liver have been developed, in which mouse liver cells are mostly replaced with human hepatocytes. Since human drug metabolizing enzymes are expressed in the liver of these mice, they are regarded as suitable models for mimicking the drug metabolism and PK observed in humans; therefore, these mice are useful for predicting human drug metabolism and PK. In this review, we discuss the current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  6. Liver stem/progenitor cells in the canals of Hering: cellular origin of hepatocellular carcinoma with bile duct tumor thrombi?

    Science.gov (United States)

    Peng, Ningfu; Li, Lequn; Cai, Xiang; Tan, Shaozao; Wu, Ting

    2010-12-01

    It is generally believed that the invasion of hepatocellular carcinoma (HCC) into the biliary tree ultimately leads to the formation of bile duct tumor thrombi (BDTT). However, recent studies revealed that primary tumor might be small, even undetectable, and there was no histopathologic evidence of direct tumor invasion into bile duct wall in some patients. During the last decade, efforts on stem cell biology may shed light on the pathogenesis of BDTT. Presently, accumulating evidence supports the following notions: (1) the canals of Hering (CoH) are the most likely origin of liver stem/progenitor cells (LSPCs) in adult livers; (2) similar signalling pathways may regulate self-renewal in LSPCs and liver cancer cells, and a substantial proportion of liver tumors may often originate from the transformation of LSPCs; and (3) liver cancer contains rare cells with stem cell-like properties, which could derive from malignant transformation of LSPCs. Herein, we propose that HCC with BDTT, especially with small or undetectable primary lesion and/or no histopathologic evidence for bile duct invasion, might arise from LSPCs residing in the CoH and, possibly, some primary lesions are formed firstly within the intrahepatic biliary tree. When "tumor thrombi" extends mainly along bile duct, there might be "BDTT" alone; when it invades into surrounding parenchyma, there might often be small "primary tumor" with "BDTT". If this holds true, the putative type may be a particular subset of HCC, and most importantly it would facilitate our understanding of stem-cell origin of HCC.

  7. Fatty liver disease--a practical guide for GPs.

    Science.gov (United States)

    Iser, David; Ryan, Marno

    2013-07-01

    Non-alcoholic fatty liver disease (NAFLD), encompassing both simple steatosis and non-alcoholic steato-hepatitis (NASH), is the most common cause of liver disease in Australia. Non-alcoholic fatty liver disease needs to be considered in the context of the metabolic syndrome, as cardiovascular disease will account for much of the mortality associated with NAFLD. To provide an approach to the identification of NAFLD in general practice, the distinction between simple steatosis and NASH, and the management of these two conditions. Non-alcoholic steato-hepatitis is more common in the presence of diabetes, obesity, older age and increased inflammation, and is more likely to progress to cirrhosis. Cirrhosis may be complicated by hepatocellular carcinoma or liver failure. Hepatocellular carcinoma has also been described in NASH without cirrhosis. Assessment and treatment of features of the metabolic syndrome may reduce associated cardiovascular mortality. Numerous agents have been evaluated, but weight loss remains the only effective treatment for NAFLD.

  8. Proteomic profiling in incubation medium of mouse, rat and human precision-cut liver slices for biomarker detection regarding acute drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P L; Hadi, Mackenzie; Laarakkers, Coby M M; Masereeuw, R.|info:eu-repo/dai/nl/155644033; Groothuis, Geny M M; Russel, Frans G M

    Drug-induced liver injury is one of the leading causes of drug withdrawal from the market. In this study, we investigated the applicability of protein profiling of the incubation medium of human, mouse and rat precision-cut liver slices (PCLS) exposed to liver injury-inducing drugs for biomarker

  9. Coffee and liver health.

    Science.gov (United States)

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

  10. Expression of Leukemia/Lymphoma-Related Factor (LRF/POKEMON) in Human Breast Carcinoma and Other Cancers

    Science.gov (United States)

    Aggarwal, Anshu; Hunter, William J.; Aggarwal, Himanshu; Silva, Edibaldo D.; Davey, Mary S.; Murphy, Richard F.; Agrawal, Devendra K.

    2010-01-01

    The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. PMID:20471975

  11. Development of Cerebral Metastasis after Medical and Surgical Treatment of Anal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Andrew Austin Gassman

    2012-01-01

    Full Text Available Squamous cell carcinoma of the anus is a relatively uncommon GI malignancy. When it does occur, it metastasizes in only a small minority of patients. Spread of anal squamous cell carcinoma to the brain is exceedingly rare, and has been previously reported only three times in the medical literature. We report the case of a 67 year old male who was diagnosed on presentation with a poorly differentiated anal squamous cell carcinoma that already had a solitary metastasis to the liver. While the tumors were initially responsive to chemoradiotherapy, the patient’s primary and liver lesions recurred. The patient then underwent synchronous abdominoperineal resection for the primary lesion and a liver lobectomy for the metastasis. Soon thereafter, the patient developed focal neurologic symptoms and was found to have an intracranial lesion that on biopsy demonstrated metastatic squamous cell carcinoma. This case highlights the fact that patients with a previous history of anal squamous cell carcinoma can occasionally develop cerebral metastasis. Furthermore, cerebral metastases from anal squamous cell carcinoma portend a dismal prognosis even in the face of aggressive medical and surgical therapy.

  12. Angiomyolipoma of the liver

    International Nuclear Information System (INIS)

    Murakami, T.; Nakamura, H.; Hori, S.; Nakanishi, K.; Mitani, T.; Kozuka, T.; Kimura, Y.; Monden, M.; Wakasa, K.; Sakurai, M.

    1993-01-01

    Angiomyolipoma, a rare benign liver tumor, was observed in a 50-year-old woman examined with US, CT, MR imaging and angiography. Dynamic studies using CT and MR imaging were valuable in differentiating the disease from hepatocellular carcinoma with fat deposits. (orig.)

  13. Review fantastic medical implications of 3D-printing in liver surgeries, liver regeneration, liver transplantation and drug hepatotoxicity testing: A review.

    Science.gov (United States)

    Wang, Jing-Zhang; Xiong, Nan-Yan; Zhao, Li-Zhen; Hu, Jin-Tian; Kong, De-Cheng; Yuan, Jiang-Yong

    2018-06-07

    The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc. Copyright © 2018. Published by Elsevier Ltd.

  14. 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.

  15. PNPLA3 expression and its impact on the liver: current perspectives

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    Bruschi FV

    2017-11-01

    Full Text Available Francesca Virginia Bruschi, Matteo Tardelli, Thierry Claudel, Michael Trauner Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology & Hepatology, Department of Internal Medicine III, Medical University of Vienna, Austria Abstract: A single-nucleotide polymorphism occurring in the sequence of the human patatin-like phospholipase domain-containing 3 gene (PNPLA3, known as I148M variant, is one of the best characterized and deeply investigated variants in several clinical scenarios, because of its tight correlation with increased risk for developing hepatic steatosis and more aggressive part of the disease spectrum, such as nonalcoholic steatohepatitis, advanced fibrosis and cirrhosis. Further, the I148M variant is positively associated with alcoholic liver diseases, chronic hepatitis C–related cirrhosis and hepatocellular carcinoma. The native gene encodes for a protein that has not yet a fully defined role in liver lipid metabolism and, according to recent observations, seems to be divergently regulated among distinct liver cells type, such as hepatic stellate cells. Therefore, the aim of this review is to collect the latest data regarding PNPLA3 expression in human liver and to analyze the impact of its genetic variant in human hepatic pathologies. Moreover, a description of the current biochemical and metabolic data pertaining to PNPLA3 function in both animal models and in vitro studies is summarized to allow a better understanding of the relevant pathophysiological role of this enzyme in the progression of hepatic diseases. Keywords: adiponutrin, liver disease, genetic polymorphism, gene expression, metabolism

  16. Curative salvage liver transplantation in patients with cirrhosis and hepatocellular carcinoma: An intention-to-treat analysis.

    Science.gov (United States)

    de Haas, Robbert J; Lim, Chetana; Bhangui, Prashant; Salloum, Chady; Compagnon, Philippe; Feray, Cyrille; Calderaro, Julien; Luciani, Alain; Azoulay, Daniel

    2018-01-01

    The salvage liver transplantation (SLT) strategy was conceived for initially resectable and transplantable (R&T) hepatocellular carcinoma (HCC) patients, to try to obviate upfront liver transplantation, with the "safety net" of SLT in case of postresection recurrence. The SLT strategy is successful or curative when patients are recurrence free following primary resection alone, or after SLT for recurrence. The aim of the current study was to determine the SLT strategy's potential for cure in R&T HCC patients, and to identify predictors for its success. From 1994 to 2012, all R&T HCC patients with cirrhosis were enrolled in the SLT strategy. An intention-to-treat (ITT) analysis was used to determine this strategy's outcomes and predictors of success according to the above definition. In total, 110 patients were enrolled in the SLT strategy. Sixty-three patients (57%) had tumor recurrence after initial resection, and in 30 patients SLT could be performed (recurrence transplantability rate = 48%). From the time of initial resection, ITT 5-year overall and disease-free survival rates were 69% and 60%, respectively. The SLT strategy was successful in 60 patients (56%), either by resection alone (36%), or by SLT for recurrence (19%). Preresection predictors of successful SLT strategy at multivariate analysis included Model for End-Stage Liver Disease (MELD) score >10, and absence of neoadjuvant transarterial chemoembolization (TACE). Additional postresection predictive factors were absence of postresection morbidity, and T-stage 1-2 at the resection specimen. The SLT strategy is curative in only 56% of cases. Higher MELD score at inception of the strategy and no pre-resection TACE are predictors of successful SLT strategy. (Hepatology 2018;67:204-215). © 2017 by the American Association for the Study of Liver Diseases.

  17. Protocol for Isolation of Primary Human Hepatocytes and Corresponding Major Populations of Non-parenchymal Liver Cells

    Science.gov (United States)

    Pfeiffer, Elisa; Zeilinger, Katrin; Seehofer, Daniel; Damm, Georg

    2016-01-01

    Beside parenchymal hepatocytes, the liver consists of non-parenchymal cells (NPC) namely Kupffer cells (KC), liver endothelial cells (LEC) and hepatic Stellate cells (HSC). Two-dimensional (2D) culture of primary human hepatocyte (PHH) is still considered as the "gold standard" for in vitro testing of drug metabolism and hepatotoxicity. It is well-known that the 2D monoculture of PHH suffers from dedifferentiation and loss of function. Recently it was shown that hepatic NPC play a central role in liver (patho-) physiology and the maintenance of PHH functions. Current research focuses on the reconstruction of in vivo tissue architecture by 3D- and co-culture models to overcome the limitations of 2D monocultures. Previously we published a method to isolate human liver cells and investigated the suitability of these cells for their use in cell cultures in Experimental Biology and Medicine1. Based on the broad interest in this technique the aim of this article was to provide a more detailed protocol for the liver cell isolation process including a video, which will allow an easy reproduction of this technique. Human liver cells were isolated from human liver tissue samples of surgical interventions by a two-step EGTA/collagenase P perfusion technique. PHH were separated from the NPC by an initial centrifugation at 50 x g. Density gradient centrifugation steps were used for removal of dead cells. Individual liver cell populations were isolated from the enriched NPC fraction using specific cell properties and cell sorting procedures. Beside the PHH isolation we were able to separate KC, LEC and HSC for further cultivation. Taken together, the presented protocol allows the isolation of PHH and NPC in high quality and quantity from one donor tissue sample. The access to purified liver cell populations could allow the creation of in vivo like human liver models. PMID:27077489

  18. Mini-review. Liver transplantation for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    V. Visag-Castillo

    2018-04-01

    Full Text Available Liver transplantation is the gold standard treatment for end stage liver disease, including patients with cirrhosis and hepatocarcinoma falling within Milan criteria. HCC is the sixth most common cancer around the world, and leading cause of death among cirrhotic patients. Diagnosis is based upon radiological characteristics and rarely biopsy results; the Barcelona Clinic Liver Cancer staging system is the most used guideline for treatment. With several treatment options available transplantation and resection continue to be the major curative therapeutic option for this patients. However treatment must be individualized to each patient to improve recurrences and outcomes. The aim of this paper is to review the present role of liver transplantation in the management of hepatocarcinoma. Resumen: El trasplante hepático es el estándar de oro en el tratamiento de enfermedad hepática avanzada, incluyendo pacientes cirróticos que han desarrollado hepatocarcinoma pero que se encuentran dentro de los criterios de Milán. El hepatocarcinoma es el sexto tumor más común alrededor del mundo y es la principal causa de muerte en pacientes cirróticos. El diagnóstico se basa principalmente en las características radiológicas del tumor y raras veces en resultados de patología. El sistema de estatificación desarrollado por el Clinic de Barcelona es la guía más usada para el tratamiento. Existen diferentes opciones terapéuticas para el hepatocarcinoma; sin embargo, el trasplante y la resección quirúrgica siguen siendo la opción curativa con mejores resultados. El tratamiento debe de ser individualizado para cada paciente con el fin de mejorar los resultados y minimizar recurrencias. El objetivo de este artículo es revisar el rol actual del trasplante hepático en el manejo del hepatocarcinoma. Keywords: Chronic hepatitis C, End stage liver disease, Recurrence, Non-alcoholic fatty liver disease, Cirrhosis, Palabras clave: Hepatitis C cr

  19. The Prevalence of Human Papilloma Virus in Esophageal Squamous Cell Carcinoma

    Science.gov (United States)

    Noori, Sadat; Monabati, Ahmad; Ghaderi, Abbasali

    2012-01-01

    Background: Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus (HPV) is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma (ESCC) cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences. Methods: DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control (HPV-18 and HPV positive biopsies of uterine exocervix) and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 (CTLA4). Result: Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed. Conclusion: There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated. PMID:23115442

  20. The Prevalence of Human Papilloma Virus in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Sadat Noori

    2012-06-01

    Full Text Available Background: Carcinomas of esophagus, mostly squamous cell carcinomas, occur throughout the world. There are a number of suspected genetic or environmental etiologies. Human papilloma virus (HPV is said to be a major etiology in areas with high incidence of esophageal carcinoma, while it is hardly detectable in low incidence regions. This study was designed to evaluate the prevalence of HPV in esophageal squamous cell carcinoma (ESCC cases diagnosed in Pathology Department, Medical School, Shiraz University of Medical Sciences.Methods: DNA material for PCR amplification of HPV genome was extracted from formalin-fixed paraffin-embedded tissue blocks of 92 cases of ESCC, diagnosed during 20 years from 1982 to 2002. Polymerase chain reaction was performed for amplification and detection of common HPV and type specific HPV-16 and HPV-18 genomic sequences in the presence of positive control (HPV-18 and HPV positive biopsies of uterine exocervix and additional internal controls i.e. beta-globin and cytotoxic T lymphocyte antigen 4 (CTLA4.Result: Good amplification of positive control and internal controls was observed. However, no amplification of HPV genome was observed.Conclusion: There is no association between HPV infection and the development of esophageal squamous cell carcinoma in the cases evaluated.

  1. Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

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    Dan Xu

    2014-04-01

    Full Text Available Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU] developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers.Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers.FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology

  2. Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing.

    Science.gov (United States)

    Xu, Dan; Nishimura, Toshi; Nishimura, Sachiko; Zhang, Haili; Zheng, Ming; Guo, Ying-Ying; Masek, Marylin; Michie, Sara A; Glenn, Jeffrey; Peltz, Gary

    2014-04-01

    Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers. Control and chimeric TK-NOG mice with humanized livers were treated orally with FIAU 400, 100, 25, or 2.5 mg/kg/d. The response to drug treatment was evaluated by measuring plasma lactate and liver enzymes, by assessing liver histology, and by electron microscopy. After treatment with FIAU 400 mg/kg/d for 4 d, chimeric mice developed clinical and serologic evidence of liver failure and lactic acidosis. Analysis of liver tissue revealed steatosis in regions with human, but not mouse, hepatocytes. Electron micrographs revealed lipid and mitochondrial abnormalities in the human hepatocytes in FIAU-treated chimeric mice. Dose-dependent liver toxicity was detected in chimeric mice treated with FIAU 100, 25, or 2.5 mg/kg/d for 14 d. Liver toxicity did not develop in control mice that were treated with the same FIAU doses for 14 d. In contrast, treatment with another nucleotide analogue (sofosbuvir 440 or 44 mg/kg/d po) for 14 d, which did not cause liver toxicity in human trial participants, did not cause liver toxicity in mice with humanized livers. FIAU-induced liver toxicity could be readily detected using chimeric TK-NOG mice with humanized livers, even when the mice were treated with a FIAU dose that was only 10-fold above the dose used in human participants. The clinical features, laboratory abnormalities, liver histology, and ultra-structural changes observed in FIAU-treated chimeric mice mirrored those of FIAU-treated human participants. The use of chimeric mice in preclinical toxicology studies could improve

  3. High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

    International Nuclear Information System (INIS)

    Herrera-Goepfert, Roberto; Vela-Chávez, Teresa; Carrillo-García, Adela; Lizano-Soberón, Marcela; Amador-Molina, Alfredo; Oñate-Ocaña, Luis F; Hallmann, Rita Sotelo-Regil

    2013-01-01

    Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. Mastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate. High-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR). High-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones

  4. Unusual manifestations of secondary urothelial carcinoma

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    Chaohui Lisa Zhao

    2016-03-01

    Full Text Available High-grade papillary urothelial carcinoma regularly invades the bladder wall, adjacent prostate, seminal vesicles, ureters, vagina, rectum, retroperitoneum, and regional lymph nodes. In advanced stages, it may disseminate to the liver, lungs, and bone marrow. On rare occasions, unusual metastatic foci like skin have been reported. The incidence of urothelial carcinoma has increased with associated rise in variants of urothelial carcinoma and unusual metastatic foci. It is imperative that urologists and pathologists are aware of the unusual variants and unusual metastatic locations to expedite the diagnostic process. Hereby we report an unusual case of secondary involvement of spinal nerve by conventional urothelial carcinoma. Also a second case of rhabdoid variant of urothelial carcinoma showing synchronous involvement of bladder and subcutaneous tissue of upper extremity is presented.

  5. A protein-based set of reference markers for liver tissues and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Sun, Stella; Yi, Xin; Poon, Ronnie TP; Yeung, Chun; Day, Philip JR; Luk, John M

    2009-01-01

    During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify 'housekeeping' markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression. A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers. The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples. Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference

  6. A report from the European Association for the Study of the Liver's 50th International Liver Congress (April 22-26 - Vienna, Austria).

    Science.gov (United States)

    Rabasseda, X

    2015-04-01

    While Vienna's Prater park offers a varied selection of options, from theme parks to lush gardens and prairies to enjoy the sun, the nearby Messe Wien convention center was the focus of attention in April 2015 for all the scientists, researchers and clinicians interested in viral hepatitis, nonalcoholic steatohepatitis, hepatocellular carcinoma and a variety of other liver diseases. Treatments and potential new therapeutic strategies for these hepatopathies were discussed during the 50th International Liver Congress organized by the European Association for the Study of the Liver. Echoing epidemiological facts and a high social interest for hepatitis C virus infection, new findings with investigational and potential new therapies for the disease centered much of the attention at the conference. Nevertheless, new research was also reported related to potential improvements in how other liver diseases, particularly hepatitis B virus infection, hepatocellular carcinoma and a range of inflammatory and immune-mediated liver diseases, including rare hereditary diseases that should never be forgotten. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  7. Lineage fate of ductular reactions in liver injury and carcinogenesis.

    Science.gov (United States)

    Jörs, Simone; Jeliazkova, Petia; Ringelhan, Marc; Thalhammer, Julian; Dürl, Stephanie; Ferrer, Jorge; Sander, Maike; Heikenwalder, Mathias; Schmid, Roland M; Siveke, Jens T; Geisler, Fabian

    2015-06-01

    Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.

  8. Human Papilloma Virus in Oral Squamous Cell Carcinoma - The Enigma Unravelled.

    Science.gov (United States)

    Khot, Komal P; Deshmane, Swati; Choudhari, Sheetal

    2016-03-01

    Squamous cell carcinoma of the head and neck (HNSCC) has long been regarded as a disease entity having a remarkable incidence worldwide and a fairly onerous prognosis; thus encouraging further research on factors that might modify disease outcome. Squamous cell carcinomas encompass at least 90% of all oral malignancies. Several factors like tobacco and tobacco-related products, alcohol, genetic predisposition and hormonal factors are suspected as possible causative factors. Human papilloma virus (HPV), the causal agent of cervical cancer also appears to be involved in the aetiology of oral and oropharyngeal cancer. HPVpositive squamous cell carcinoma (SCC) seems to differ from HPV-negative SCC. Many questions about the natural history of oral HPV infection remain under investigation. The aim of this review is to highlight the current understanding of HPV-associated oral cancer with an emphasis on its prognosis, detection and management.

  9. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    International Nuclear Information System (INIS)

    Klopfleisch, Robert; Lenze, Dido; Hummel, Michael; Gruber, Achim D

    2010-01-01

    Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a

  10. [Human papilloma viruses: other risk factor of head and neck carcinoma].

    Science.gov (United States)

    Woto-Gaye, G; M'Farrej, M K; Doh, K; Thiam, I; Touré, S; Diop, R; Dial, C

    2016-08-01

    Head and neck carcinoma (HNC) occupy the sixth place as the most frequent type of cancer worldwide. Next to alcohol and tobacco intoxication, other risk factors (RF) are suspected, including the human papilloma viruses (HPVs). The aim of this study was to highlight the prevalence of HPVs and histo-epidemiological characteristics of HNC HPV+ in Senegal. This is a prospective, multicenter preliminary study of 18 months (January 1, 2012-June 30, 2014). The cases of HNC histologically confirmed in Senegal were then sent to the bio-pathology department of the Curie Institute in Paris to search HPVs. In the 90 included cases, the PCR technique was successful in 54 cases (60%). HPVs were found in seven cases, that is, a prevalence of 13%. HPVs were associated with 5 cases of hypopharyngeal carcinoma and 2 cases of carcinoma of the oral cavity. Patients with HNC HPV+ had a median age of 42 years against 49 years for HPV-patients. Three patients (42.8%) with HPV+ carcinomas were smokers. Of the 47 HPV-patients, 40 patients (87.1%) had alcohol intoxication and/or smoking. The concept of oral sex was refuted by all our patients. Squamous cell carcinoma was the only histological type found. HPV+ cell carcinoma showed no specific histological appearance. HPVs are another certain RF of HNC in Senegal. The major therapeutic and prognostic impact of HPVinduced cancers requires the systematic search of the viruses by the PCR technique.

  11. The histopathological pattern of liver biopsies at the University of ...

    African Journals Online (AJOL)

    %; malignant neoplasms, 22.5%, and liver cirrhosis in 6.3% of cases. Other less common lesions were alcoholic liver disease and steatosis. This peak age incidence of chronic hepatitis precedes that of hepatocellular carcinoma by about two ...

  12. Experimental models of liver fibrosis.

    Science.gov (United States)

    Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

    2016-05-01

    Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

  13. Primary neuroendocrine carcinoma of breast with liver and bone metastasis detected with fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography

    International Nuclear Information System (INIS)

    Kamaleshwaran, Koramadai Karuppusamy; Mohanan, Vyshak; Shibu, Deepu; Radhakrishnan, Edathuruthy Kalarikal; Shinto, Ajit Sugunan

    2014-01-01

    Cases of primary neuroendocrine carcinoma (NEC) of the breast have been reported, though rare. We report the case of a 45-year-old woman presented with jaundice and evaluated to have liver metastasis from neuroendocrine origin. She underwent whole body positron emission tomography/computed tomography, which showed left breast lesion and bone metastasis. Fine-needle aspiration (FNA) of breast revealed a NEC. A diagnosis of a primary NEC of the breast was rendered with hepatic and bone metastasis. She was treated with peptide receptor radionuclide therapy and is on follow-up

  14. Fat in the liver: diagnosis and characterization

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-10-15

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

  15. Comparison of MRI of liver cancer (preoperative and resected liver specimen) and pathological feature

    International Nuclear Information System (INIS)

    Tanaka, Toshihiko

    1990-01-01

    Twenty-one nodules of hepatocellular carcinoma (HCC) and eighteen nodules of liver metastasis, which were confirmed pathologically, were investigated by MRI before operation and MRI of resected liver specimen. Pre-operative MRI pointed out all HCCs and seventeen metastases. STIR method was most useful for detection of HCCs. T2WI and STIR method were most useful for detection of liver metastases. Pre-operative MRI also revealed 93% of capsule formation, 29% of septal formation, 75% of fatty metamorphosis of HCC and 75% of necrosis of liver metastasis, and post-operative MRI of resected specimens revealed 100% of capsule formation, 71% of septal formation, 75% of fatty metamorphosis of HCC and 88% of necrosis of liver metastasis. T1WI showed a high intensity halo surrounding metastasis. This characteristic peripheral halo was seen in 22% of metastases. These findings corresponded to pathological feature of liver cancer. MRI was thought to be useful diagnostic modality of liver cancer. (author)

  16. 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

  17. The Impact of Liver Graft Injury on Cancer Recurrence Posttransplantation.

    Science.gov (United States)

    Li, Chang-Xian; Man, Kwan; Lo, Chung-Mau

    2017-11-01

    Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma. However, cancer recurrence, posttransplantation, remains to be the critical issue that affects the long-term outcome of hepatocellular carcinoma recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute-phase liver graft injury is a result of hepatic ischemia reperfusion injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation. The liver grafts from living donors, donors after cardiac death, and steatotic donors have been considered as promising sources of organs for liver transplantation and are associated with high incidence of liver graft injury. The acute-phase liver graft injury will trigger a series of inflammatory cascades, which may not only activate the cell signaling pathways regulating the tumor cell invasion and migration but also mobilize the circulating progenitor and immune cells to facilitate tumor recurrence and metastasis. The injured liver graft may also provide the favorable microenvironment for tumor cell growth, migration, and invasion through the disturbance of microcirculatory barrier function, induction of hypoxia and angiogenesis. This review aims to summarize the latest findings about the role and mechanisms of liver graft injury resulted from hepatic ischemia reperfusion injury on tumor recurrence posttransplantation, both in clinical and animal cohorts.

  18. Cholangitis and multiple liver abscesses after percutaneous ethanol injection (PEI for recurrent hepatocellular carcinoma (HCC Colangitis y abscesos hepáticos múltiples tras la inyección percutánea de etanol (IPE en el tratamiento del carcinoma hepatocelular recurrente

    Directory of Open Access Journals (Sweden)

    Fernando Macias-García

    2013-02-01

    Full Text Available Percutaneous ablation procedures are minimally invasive treatments for unresectable early stage hepatocellular carcinoma (HCC. These techniques are usually safe, but rare and even fatal complications have been described. We present a fatal result after percutaneous ethanol injection (PEI for the treatment of a recurrent HCC in a non-cirrhotic liver, with subsequent development of diffuse cholangitis and multiple liver abscesses. Although percutaneous drainage and intensive antibiotic treatment were employed, the patient finally died. We discuss about the etiology and the physiopathology of this rare complication in which the therapeutic options are limited and usually unsuccessful.

  19. Performance of Alpha Fetoprotein in Combination with Alpha-1-acid Glycoprotein for Diagnosis of Hepatocellular Carcinoma Among Liver Cirrhosis Patients

    Directory of Open Access Journals (Sweden)

    Rino A Gani

    2016-05-01

    Full Text Available Aim: to evaluate the use of alpha-1-acid glycoprotein (AAG for diagnosing hepatocellular carcinoma (HCC, and to combine with alpha fetoprotein (AFP as part of routine examination in liver cirrhosis patients. Methods: this is a diagnostic study using cross-sectional design. A hundred and six patients were included in this study. Baseline data such as age, gender, AFP, AAG, peripheral blood count, AST and ALT were consecutively collected from liver cirrhosis patients with or without HCC. Serum AAG were measured quantitatively using immunoturboditimetric assay and AFP with enzyme immune assay (EIA. Statistical analysis were done using SPSS 13.0. Data comparisons between group were done using Mann-Whitney test. Diagnostic performance for each marker alone was compared to the surrogate use of both markers (combined parallel approach in HCC cases. Results: receiver operating characteristic (ROC analysis showed that area under the curve for AFP AAG combination was 88.1% and higher than AFP only (86.2% or AAG only (76.5% with sensitivity of 83%, 73% and 44%, respectively, at specificity of >80%. Conclusion: our study showed that combination of AFP and AAG is superior than either marker alone in diagnosing HCC in liver cirrhosis patients. Combination of AFP and AAG may be used to prompt early diagnosis screening of HCC. Key words: alpha fetoprotein, alpha-1-acid glycoprotein, biomarker, liver cancer

  20. 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.

  1. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    Science.gov (United States)

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  2. Failure of Chemotherapy in Hepatocellular Carcinoma Due to Impaired and Dysregulated Primary Liver Drug Metabolizing Enzymes and Drug Transport Proteins: What to Do?

    Science.gov (United States)

    Ul Islam, Salman; Ahmed, Muhammad Bilal; Shehzad, Adeeb; Ul-Islam, Mazhar; Lee, Young Sup

    2018-05-28

    Most of the drugs are metabolized in the liver by the action of drug metabolizing enzymes. In hepatocellular carcinoma (HCC), primary drug metabolizing enzymes are severely dysregulated, leading to failure of chemotherapy. Sorafenib is the only standard systemic drug available, but it still presents certain limitations, and much effort is required to understand who is responsive and who is refractory to the drug. Preventive and therapeutic approaches other than systemic chemotherapy include vaccination, chemoprevention, liver transplantation, surgical resection, and locoregional therapies. This review details the dysregulation of primary drug metabolizing enzymes and drug transport proteins of the liver in HCC and their influence on chemotherapeutic drugs. Furthermore, it emphasizes the adoption of safe alternative therapeutic strategies to chemotherapy. The future of HCC treatment should emphasize the understanding of resistance mechanisms and the finding of novel, safe, and efficacious therapeutic strategies, which will surely benefit patients affected by advanced HCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans.

    Science.gov (United States)

    Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

    2009-01-31

    To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis.

  5. High mobility group box associated with cell proliferation appears to play an important role in hepatocellular carcinogenesis in rats and humans

    International Nuclear Information System (INIS)

    Suzuki, Shugo; Takeshita, Kentaro; Asamoto, Makoto; Takahashi, Satoru; Kandori, Hitoshi; Tsujimura, Kazunari; Saito, Fumiyo; Masuko, Kazuo; Shirai, Tomoyuki

    2009-01-01

    To identify genes important in hepatocellular carcinogenesis, especially processes involved in malignant transformation, we focused on differences in gene expression between adenomas and carcinomas by DNA microarray. Eighty-one genes for which expression was specific in carcinomas were analyzed using Ingenuity Pathway Analysis software and Gene Ontology, and found to be associated with TP53 and regulators of cell proliferation. In the genes associated with TP53, we selected high mobility group box (HMGB) for detailed analysis. Immunohistochemistry revealed expression of HMGBs in carcinomas to be significantly higher than in other lesions among both human and rat liver, and a positive correlation between HMGBs and TP53 was detected in rat carcinomas. Knock-down of HMGB 2 expression in a rat hepatocellular carcinoma cell line by RNAi resulted in inhibition of cell growth, although no effects on invasion were evident in vitro. These results suggest that acquisition of malignant potential in the liver requires specific signaling pathways related to high cell proliferation associated with TP53. In particular, HMGBs appear to have an important role for progression and cell proliferation associated with loss of TP53 function in rat and in human hepatocarcinogenesis

  6. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  7. A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax.

    Science.gov (United States)

    March, Sandra; Ng, Shengyong; Velmurugan, Soundarapandian; Galstian, Ani; Shan, Jing; Logan, David J; Carpenter, Anne E; Thomas, David; Sim, B Kim Lee; Mota, Maria M; Hoffman, Stephen L; Bhatia, Sangeeta N

    2013-07-17

    The Plasmodium liver stage is an attractive target for the development of antimalarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable, and reproducible in vitro liver-stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum, including the release of infected merozoites and infection of overlaid erythrocytes, as well as the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput antimalarial drug screening and vaccine development. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Liver Progenitor Cell Line HepaRG Differentiated in a Bioartificial Liver Effectively Supplies Liver Support to Rats with Acute Liver Failure

    NARCIS (Netherlands)

    Nibourg, Geert A. A.; Chamuleau, Robert A. F. M.; van der Hoeven, Tessa V.; Maas, Martinus A. W.; Ruiter, An F. C.; Lamers, Wouter H.; Oude Elferink, Ronald P. J.; van Gulik, Thomas M.; Hoekstra, Ruurdtje

    2012-01-01

    A major roadblock to the application of bioartificial livers is the need for a human liver cell line that displays a high and broad level of hepatic functionality. The human bipotent liver progenitor cell line HepaRG is a promising candidate in this respect, for its potential to differentiate into

  9. Evaluation of Focal Liver Reaction after Proton Beam Therapy for Hepatocellular Carcinoma Examined Using Gd-EOB-DTPA Enhanced Hepatic Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Shigeyuki Takamatsu

    Full Text Available Proton beam therapy (PBT achieves good local control for hepatocellular carcinoma (HCC, and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR; the threshold doses (TDs for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC.Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area.FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy, TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]. There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months.This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT.

  10. Prediction of radiation-induced liver disease by Lyman normal-tissue complication probability model in three-dimensional conformal radiation therapy for primary liver carcinoma

    International Nuclear Information System (INIS)

    Xu ZhiYong; Liang Shixiong; Zhu Ji; Zhu Xiaodong; Zhao Jiandong; Lu Haijie; Yang Yunli; Chen Long; Wang Anyu; Fu Xiaolong; Jiang Guoliang

    2006-01-01

    Purpose: To describe the probability of RILD by application of the Lyman-Kutcher-Burman normal-tissue complication (NTCP) model for primary liver carcinoma (PLC) treated with hypofractionated three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: A total of 109 PLC patients treated by 3D-CRT were followed for RILD. Of these patients, 93 were in liver cirrhosis of Child-Pugh Grade A, and 16 were in Child-Pugh Grade B. The Michigan NTCP model was used to predict the probability of RILD, and then the modified Lyman NTCP model was generated for Child-Pugh A and Child-Pugh B patients by maximum-likelihood analysis. Results: Of all patients, 17 developed RILD in which 8 were of Child-Pugh Grade A, and 9 were of Child-Pugh Grade B. The prediction of RILD by the Michigan model was underestimated for PLC patients. The modified n, m, TD 5 (1) were 1.1, 0.28, and 40.5 Gy and 0.7, 0.43, and 23 Gy for patients with Child-Pugh A and B, respectively, which yielded better estimations of RILD probability. The hepatic tolerable doses (TD 5 ) would be MDTNL of 21 Gy and 6 Gy, respectively, for Child-Pugh A and B patients. Conclusions: The Michigan model was probably not fit to predict RILD in PLC patients. A modified Lyman NTCP model for RILD was recommended

  11. Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient uPA mice.

    Directory of Open Access Journals (Sweden)

    Marina E Fomin

    Full Text Available Liver sinusoidal endothelial cells (LSECs form a semi-permeable barrier between parenchymal hepatocytes and the blood. LSECs participate in liver metabolism, clearance of pathological agents, immunological responses, architectural maintenance of the liver and synthesis of growth factors and cytokines. LSECs also play an important role in coagulation through the synthesis of Factor VIII (FVIII. Herein, we phenotypically define human LSECs isolated from fetal liver using flow cytometry and immunofluorescence microscopy. Isolated LSECs were cultured and shown to express endothelial markers and markers specific for the LSEC lineage. LSECs were also shown to engraft the liver when human fetal liver cells were transplanted into immunodeficient mice with liver specific expression of the urokinase-type plasminogen activator (uPA transgene (uPA-NOG mice. Engrafted cells expressed human Factor VIII at levels approaching those found in human plasma. We also demonstrate engraftment of adult LSECs, as well as hepatocytes, transplanted into uPA-NOG mice. We propose that overexpression of uPA provides beneficial conditions for LSEC engraftment due to elevated expression of the angiogenic cytokine, vascular endothelial growth factor. This work provides a detailed characterization of human midgestation LSECs, thereby providing the means for their purification and culture based on their expression of CD14 and CD32 as well as a lack of CD45 expression. The uPA-NOG mouse is shown to be a permissive host for human LSECs and adult hepatocytes, but not fetal hepatoblasts. Thus, these mice provide a useful model system to study these cell types in vivo. Demonstration of human FVIII production by transplanted LSECs encourages further pursuit of LSEC transplantation as a cellular therapy for the treatment of hemophilia A.

  12. Transformation of Nonfunctioning Pancreatic Neuroendocrine Carcinoma Cells into Insulin Producing Cells after Treatment with Sunitinib

    Directory of Open Access Journals (Sweden)

    Jung Hun Ohn

    2013-06-01

    Full Text Available We report a rare case of severe hypoglycemia after sunitinib treatment for pancreatic neuroendocrine carcinoma. We describe the initial clinical presentation, laboratory results, pathologic findings, and managment in a patient with a nonfunctioning pancreatic neuroendocrine carcinoma with liver metastases who developed life threatening hypoglycemia after 2 months of sunitinib therapy. A 46-year-old woman presented to the emergency department with loss of consciousness from hypoglycemia. Serum C-peptide and insulin levels at fasting state revealed that the hypoglycemia resulted from endogenous hyperinsulinemia. She had been diagnosed with nonfunctioning pancreatic neuroendocrine carcinoma based on a biopsy of metastatic cervical lymph node and was being treated with sunitinib, a small molecule tyrosine kinase inhibitor. Immunohistochemical stain of the metastatic liver mass demonstrated that the initially nonfunctioning neuroendocrine carcinoma cells had changed into insulin-producing cells after sunitinib therapy. Transarterial chemoembolization of the liver masses and systemic chemotherapy with streptozotocin/adriamycin relieved the hypoglycemia. A nonfunctioning pancreatic neuroendocrine carcinoma was transformed into an insulin-producing tumor after treatment with sunitinib, causing endogenous hyperinsulinemia and severe hypoglycemia.

  13. Detection of the E7 transform gene of human papilloma virus type 16 in human oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, J; Li, J; Huang, H; Fu, Y

    1998-12-01

    To determine, with the use of polymerase chain reaction, the prevalence of human papillomavirus (HPV) 16 in 30 patients with primary oral squamous cell carcinoma (OSCC) and 30 healthy control patients. DNA was extracted from freshly frozen tumor tissues of 30 patients with primary oral squamous cell carcinoma and from the oral mucosa of 30 controls. A pair of specific primers of the E7 early gene of HPV 16 were designed. PCR products were run by 1.5% agarose gel and the results of electrophoresis were photographed. HPV 16 was detected in 36.7% (11/30) of oral squamous cell carcinoma patients and 11.1% (4/30) of controls. HPV 16 has a significant association with oral squamous cell carcinoma. However, the role HPV 16 plays in the tumorigenesis of oral cancer and its clinical significance remain to be investigated.

  14. Differentiation of focal liver lesions by contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Heintz, P.; Ehrenheim, C.

    1989-01-01

    47 patients with liver tumours (haemangioma, focal nodular hyperplasia, hepatocellular carcinoma) underwent MRI of the liver before and after i.v. injection of 0.2 ml./kg. gadolinium-DTPA in addition to other imaging methods. The demarcation of focal nodular hyperplasia is not influenced by use of the contrast agent as it almost behaves like surrounding normal liver tissue, thus only indirectly facilitating its identification. With regard to liver haemangiomas that show the most intensive uptake of gadolinium-DTPA, the contrast enhanced image does not reach to contrast and sensitivity of a native T 2 -weighted SE image, especially in cases of small haemangiomas. The contrast agent is helpful, however, in the recognition of large cavernous haemangiomas that are partially fibrotic or thrombotic. Emphasis is given to the contrast agent in hepatomas: gadolinium-DTPA presents a pattern of uptake and distribution frequently found in hepatocellular carcinoma providing additional information on the delineation of internal tumour details. (orig.) [de

  15. Arterio-portal shunts in the cirrhotic liver: perfusion computed tomography for distinction of arterialized pseudolesions from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Michael A. [University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich (Switzerland); Karolinska Institutet, Division of Medical Imaging and Technology. Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden); Marquez, Herman P.; Gordic, Sonja; Alkadhi, Hatem [University Hospital Zurich, Department of Diagnostic and Interventional Radiology, Zurich (Switzerland); Leidner, Bertil; Aspelin, Peter; Brismar, Torkel B. [Karolinska Institutet, Division of Medical Imaging and Technology. Department of Clinical Science, Intervention and Technology (CLINTEC), Stockholm (Sweden); Klotz, Ernst [Computed Tomography and Radiation Oncology, Siemens Healthcare, Forchheim (Germany)

    2017-03-15

    To determine perfusion computed tomography (P-CT) findings for distinction of arterial pseudolesions (APL) from hepatocellular carcinoma (HCC) in the cirrhotic liver. 32 APL and 21 HCC in 20 cirrhotic patients (15 men; 65 ± 10 years), who underwent P-CT for evaluation of HCC pre- (N = 9) or post- (N = 11) transarterial chemoembolization, were retrospectively included using CT follow-up as the standard of reference. All 53 lesions were qualitatively (visual) and quantitatively (perfusion parameters) analysed according to their shape (wedge, irregular, nodular), location (not-/adjunct to a fistula), arterial liver perfusion (ALP), portal venous liver perfusion (PLP), hepatic perfusion index (HPI). Accuracy for diagnosis of HCC was determined using receiver operating characteristics. 18/32 (56 %) APL were wedge shaped, 10/32 (31 %) irregular and 4/32 (12 %) nodular, while 11/21 (52 %) HCC were nodular or 10/21 (48 %) irregular, but never wedge shaped. Significant difference between APL and HCC was seen for lesion shape in pretreated lesions (P < 0.001), and for PLP and HPI in both pre- and post-treated lesions (all, P < 0.001). Diagnostic accuracy for HCC was best for combined assessment of lesion configuration and PLP showing an area under the curve of 0.901. Combined assessment of lesion configuration and portal venous perfusion derived from P-CT allows best to discriminate APL from HCC with high diagnostic accuracy. (orig.)

  16. 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.

  17. 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 children and 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) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1–PRKACA gene fusion has not been shown to induce liver tumorigenesis. We used the CRISPR/Cas9 technique to delete in mice the syntenic region...... on chromosome 8 to create a Dnajb1–Prkaca fusion and monitored the mice for liver tumor development. Methods We delivered CRISPR/Cas9 vectors designed to juxtapose exon 1 of Dnajb1 with exon 2 of Prkaca to create the Dnajb1–Prkaca gene fusion associated with FL-HCC, or control Cas9 vector, via hydrodynamic tail...

  18. Utility of liver scintigraphy and angiography in preoperative detection of liver metastasis from gastrointestinal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Konomi, K; Aso, M; Nakayama, F [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1980-12-01

    One hundred and seventy cases of cancer of digestive tract were separated into three groups, advanced gastric cancer, biliary and/or pancreatic cancer and colorectal cancer. The presence of liver metastasis in each group was studied preoperatively by either liver scintigraphy or celiac and superior mesenteric angiography. In advanced gastric cancer and colorectal cancer, false negative ranged between 6.7 - 12.7 per cent by both scintigraphy and angiography. In biliary tract and/or pancreatic cancer, the ratio of false negative was significantly higher i.e. 18.8 - 22.6 per cent, which suggests the difficulty in diagnosing liver metastasis correctly in this group. The most frequent occurrences of false positive either in scintigraphy or angiography were those of masses of less than 2 cm in diameter. The difference in correct diagnosis rates for liver metastasis between scintigraphy and angiography in all three groups was only 2.9 per cent. Hence, liver scintigraphy seems to be preferable for the purpose of detecting liver metastasis prior to surgery, since further angiographical examination entails irradiation, possible complications and economic factors.

  19. Utility of liver scintigraphy and angiography in preoperative detection of liver metastasis from gastrointestinal carcinoma

    International Nuclear Information System (INIS)

    Konomi, Kohki; Aso, Masakazu; Nakayama, Fumio

    1980-01-01

    One hundred and seventy cases of cancer of digestive tract were separated into three groups, advanced gastric cancer, biliary and/or pancreatic cancer and colorectal cancer. The presence of liver metastasis in each group was studied properatively by either liver scintigraphy or celiac and superior mesenteric angiography. In advanced gastric cancer and colorectal cancer, false negative ranged between 6.7 - 12.7 per cent by both scintigraphy and angiography. In biliary tract and/or pancreatic cancer, the ratio of false negative was significantly higher i.e. 18.8 - 22.6 per cent, which suggests the difficulty in diagnosing liver metastasis correctly in this group. The moist frequent occurrences of false positive either in scintigraphy or angiography were those of masses of less than 2 cm in diameter. The difference in correct diagnosis ratio for liver metastasis between scintigraphy and angiography in all three groups was only 2.9 per cent. Hence, liver scintigraphy seems to be preferable for the purpose of detecting liver metastasis prior to surgery,