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Early Diagnosis of Hepatocellular Carcinoma by MicroRNAs: Shining a Light from the Genome's "Dark Matter"

DIGESTIVE DISEASES AND SCIENCES 2012年第11期57卷 2737-2739页

作者： Corvalan, Alejandro H. Pontificia Univ Catolica Chile Sch Med Dept Hematol & Oncol Santiago 8330074 Chile

Hepatocellular carcinoma (HCC) is the leading cause of death among patients with chronic hepatitis and cirrhosis [1]. Chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the most frequent etiological factors for cirrhosis and accounts for approximately 50 and 25 % of all HCC cases, respectively [2]. Other important risk factors for HCC include alcohol consumption and HIV infection. Both are susceptible to exerting a more rapid progression from cirrhosis to HCC due to a synergistic effect in individuals with HBV and/or HCV infections [3]. Accordingly, 80-90 % of patients with HCC have an established background of chronic hepatitis and cirrhosis [4]; consequently, both conditions should be considered components of the HCC-associated multistep process.

关键词： Early Diagnosis Genome MicroRNAs Risk Factors Liver Cirrhosis Dark matter Hepatitis B virus Cause of Death Alcohol Consumption Alcohol Drinking Patterns Hepatocellular Cancer HIV Infections Synergism human-centered computing Chronic Hepatitis

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Igf1 expression in mouse model of liver carcinogenesis

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DOKLADY BIOCHEMISTRY AND BIOPHYSICS 2012年第1期442卷 1-3页

作者： Zinevich, L. S. Mikaelyan, A. S. Russian Acad Sci Koltsov Inst Dev Biol Moscow 119334 Russia

This work is a part of a comparative study of mechanisms of early embryogenesis and development of hepatocellular carcinoma (HCC). Numerous data indicate the similarity of carcinogenesis and early ontogeny in terms of both cell function and molecular-genetic mechanisms [1]. Hepatocellular carcinoma is a common type of malignant liver tumor with a rapidly progressing course and poor prognosis. Despite the large number of known risk factors for HCC, the molecular mechanisms of this disease remain obscure.

关键词： Cancer of Liver poor prognosis Hepatocellular Cancer Hepatocarcinogenesis Risk Factors mouse model human-centered computing Cell Physiological Phenomena Carcinogenesis

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Risk assessment for hepatocellular carcinoma in chronic hepatitis B: scores and surveillance

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INTERNATIONAL JOURNAL OF CLINICAL PRACTICE 2012年第1期66卷 7-10页

作者： Gonzalez, S. A. Keeffe, E. B. Baylor All Saints Med Ctr Div Gen & Transplant Hepatol Baylor Reg Transplant Inst Ft Worth TX USA Baylor Univ Med Ctr Dallas TX USA Stanford Univ Med Ctr Div Gastroenterol & Hepatol Stanford CA 94305 USA

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death (1). Chronic infection with hepatitis B virus (HBV) is a major risk factor for HCC, accounting for more than one half of cases worldwide (2). Early detection of HCC in populations with chronic HBV infection through surveillance methods is critically important in providing definitive treatment for HCC and has a major impact on patient outcomes (3), including a survival benefit as demonstrated in one prospective randomised controlled trial (4). Efforts to identify populations and individuals with HBV infection who are at high risk may contribute to the development of surveillance strategies with the greatest impact on patient outcomes;however, the implementation of an individualised approach to surveillance can be challenging. This Perspective aims to explore risk factors associated with HCC in patients with chronic HBV infection, recent data on developing scoring systems to assess risk, and how these may impact surveillance strategies.

关键词： clinical outcome Chronic Hepatitis B Patient Outcome Assessment Hepatocellular Cancer Risk Assessment Hepatitis B virus Early Diagnosis human-centered computing Risk Factors Risk Management

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Conflicting Roles of Molecules in Hepatocarcinogenesis: Paradigm or Paradox

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CANCER CELL 2012年第2期21卷 150-154页

作者： Feng, Gen-Sheng Univ Calif San Diego Sch Med Dept Pathol La Jolla CA 92093 USA Univ Calif San Diego Mol Biol Sect Div Biol Sci La Jolla CA 92093 USA

In delineating the molecular pathogenesis of hepatocellular carcinoma (HCC), recent experiments in mouse tumor models have revealed unexpected tumor-suppressing effects in genes previously identified as pro-oncogenic. This contradiction underscores the complexity of hepatocarcinogenesis and predicts uncertainty in targeting these molecules for HCC therapy. Deciphering the underlying mechanisms for these paradoxical functions will elucidate the complex molecular and cellular communications driving HCC development, and will also suggest more thoughtful therapeutic strategies for this deadly disease.

关键词： Cellular communications Decryption Hepatocarcinogenesis tumor model Underscore human-centered computing

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Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: Comparable survival and recurrence

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LIVER TRANSPLANTATION 2012年第3期18卷 315-322页

作者： Sandhu, Lakhbir Sandroussi, Charbel Guba, Markus Selzner, Markus Ghanekar, Anand Cattral, Mark S. McGilvray, Ian D. Levy, Gary Greig, Paul D. Renner, Eberhard L. Grant, David R. Univ Toronto Multiorgan Transplant Program Toronto Gen Hosp Univ Hlth Network Toronto ON M5G 2N2 Canada

Several studies have reported higher rates of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT). It is unclear whether this difference is due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared the overall survival (OS) rates and the rates of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. The OS rates were calculated with the Kaplan-Meier method, whereas competing risks methods were used to determine the HCC recurrence rates. The LDLT and DDLT groups were similar with respect to most clinical parameters, but they had different median waiting times (3.1 versus 5.3 months, P = 0.003) and median follow-up times (30 versus 38.1 months, P = 0.02). The type of transplant did not affect any of the measured cancer outcomes. The OS rates at 1, 3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1-, 3-, and 5-year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%, respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for the DDLT group (P = 0.54). A regression analysis identified microvascular invasion (but not the graft type) as a predictor of HCC recurrence. In conclusion, in well-matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similarly low recurrence rates and high survival rates for the treatment of HCC. Liver Transpl 18:315322, 2012. (c) 2012 AASLD.

关键词： osmium Survival Rate Repetition rate human-centered computing Relapse

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Developments in Liver Transplantation for Hepatocellular Carcinoma

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SEMINARS IN ONCOLOGY 2012年第4期39卷 510-521页

作者： Melloul, Emmanuel Lesurtel, Mickael Carr, Brian I. Clavien, Pierre-Alain Univ Zurich Hosp Dept Surg Swiss Hepatopancreatobiliary HPB CH-8091 Zurich Switzerland Univ Zurich Hosp Transplantat Ctr CH-8091 Zurich Switzerland IRCCS S De Bellis Med Res Inst Dept Nutr & Exptl Biol Bari Italy

Hepatocellular carcinoma (HCC) is a serious health problem worldwide because of its association with hepatitis B and C viruses. In this setting, liver transplantation (LT) has become one of the best treatments since it removes both the tumor and the underlying liver disease. Due to the improvement of imaging techniques and surveillance programs, HCC are being detected earlier at a stage at which effective treatment is feasible. The prerequisite for long term success of LT for HCC depends on tumor load and strict selection criteria with regard to the size and number of tumor nodules. The need to obtain the optimal benefit from the limited number of organs available has prompted the maintenance of selection criteria in order to list only those patients with early HCC who have a better long-term outcome after LT. The indications for LT and organ allocation system led to many controversies around the use of LT in HCC patients. This review aims at giving the latest updated developments in LT for HCC focusing on selection criteria, diagnostic tools, prognostic factors, treatment on the waiting list, role of living donor liver transplantation and adjuvant therapy, and the impact of immunosuppression on HCC recurrence after LT.

关键词： Tumor Burden human-centered computing Level Trigger Number of tumor nodules Hepatitis B Liver Transplantation

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HCC and NASH: How strong is the clinical demonstration?

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CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY 2012年第3期36卷 202-208页

作者： Rosmorduc, O. Fartoux, L. Univ Paris 06 INSERM Serv Hepatol Hop St AntoineUMP S938 Paris France

Obesity and the metabolic syndrome (MS) 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 rare cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to nonalcoholic fatty liver disease (NAFLD). Moreover, MS 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 MS to improve the screening guidelines and develop prophylactic treatments in this setting. (C) 2011 Elsevier Masson SAS. All rights reserved.

关键词： Cancer of Liver Risk Factors Liver Cirrhosis Liver Diseases human-centered computing Non-alcoholic Fatty Liver Disease Viral Hepatitis

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How Can We Treat a Patient With Liver Cirrhosis (Hepatitis C Virus), Hepatocellular Carcinoma, and Synchronous Colon Cancer?

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TRANSPLANTATION PROCEEDINGS 2012年第9期44卷 2745-2747页

作者： Antoniou, E. Mantas, D. Paraskeva, P. Dimitroulis, D. Smyrnis, A. Nikitakis, N. Labadariou, A. Tsavaris, N. Vernicos, P. Kostakis, A. Univ Athens Dept Propaedut Surg 2 Sch Med Laikon Hosp GR-11527 Athens Greece Univ Athens Dept Anaesthet GR-11527 Athens Greece Univ Athens Laikon Hosp Dept Pathophysiol Sch Med GR-11527 Athens Greece Laikon Gen Hosp Intens Care Unit Athens Greece

Introduction. The coexistence of liver cirrhosis with hepatocellular carcinoma (HCC) and colon cancer (Ca), which is a rare clinical condition, was treated in a liver transplant recipient. Patients and Methods. A 46-year-old man, diagnosed incidentally during an ultrasound (US) examination with a 3.5-cm HCC in segment VII related to chronic hepatitis C virus (HCV), was referred for liver resection. He underwent a laparoscopic protocol evaluation for liver cirrhosis. Liver appearance and biopsy of the left lobe showed Child B/C liver cirrhosis. Because he fulfilled the Milan criteria, we suggested an orthotopic liver transplantation (OLT). During protocol colonoscopy, we discovered an ulcerative sigmoid colon Ca. Three weeks after completing the pre-OLT assessment he underwent an OLT and was discharged home on day 9 on an immunosuppressive regimen of Everolimus, Myfortic, and Prezolone. Two months after transplantation, the patient underwent a sigmoidectomy and for nearly 1 month thereafter received chemotherapy for colon Ca (6 cycles of FOLFOX:Folinic Acid+Fluorouracil+ Oxaliplatin). One and a half years after OLT, patient was in good condition but presented with an increased alpha fetoprotein (a-FP) without other findings. A couple of months later we discovered a colon Ca recurrence and 3 small liver metastases. Patient underwent a bowel resection with Hartmarm's procedure. Almost immediately after the last operation, he was found to suffer multiple myeloma. He underwent chemotherapy for both malignancies with good responses, but a few months later died of severe sepsis. Discussion. The relevant literature regarding treatment of liver cirrhosis complicated with HCC and synchronous colon Ca reveals poor and controversial outcomes. Our patient underwent chemotherapy immediately after colon resection in the presence of with a good functioning liver. Although his condition was satisfactory after OLT, the optimal treatment of such complicated patients is as yet uncertai

关键词： enterectomy Patients Colectomy sigmoid colectomy Cancer of Colon human-centered computing Optical Line Terminal helium

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Sorafenib for the Treatment of Recurrent Hepatocellular Carcinoma After Liver Transplantation?

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TRANSPLANTATION PROCEEDINGS 2012年第7期44卷 1989-1991页

作者： Vitale, A. Boccagni, P. Kertusha, X. Zanus, G. D'Amico, F. Lodo, E. Pastorelli, D. Morales, R. Ramirez Lombardi, G. Senzolo, M. Burra, P. Cillo, U. Azienda Univ Padova Unita Chirurg Epatobiliare & Trapianto Epat Dipartimento Chirurg Gen & Trapianti I-35128 Padua Italy Azienda Univ Padova Ist Oncol Veneto IOV IRCCS I-35128 Padua Italy Azienda Univ Padova Div Gastroenterol I-35128 Padua Italy

Background. There are scarce data on the use of sorafenib for the treatment of recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). Patients and Methods. Ten patients were treated with sorafenib after OLT following the Italian Drug Agency guidelines: they had well-compensated liver function (Child-Pugh class A in the case of cirrhosis), intermediate-or advanced-stage HCC, good general condition (performance status 0), and not suitable for loco-regional therapies. Patients with HCC recurrence after OLT were treated with sorafenib (400 mg twice daily). Adverse events (AEs) were assessed using National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI-CTCAE) v3.0 with tumor responses evaluated acording to modified Response Evaluation Criteria in Select Tumors) criteria. Results. Median duration of treatment was 10 months (range, 2-18). Seven patients (70%) received an additionally targeted therapy with mTOR inhibitors as part of their immunosuppressive regimen. Most common grade 3 AEs included diarrhea (50%), hand-foot skin reaction (30%), and fatigue (20%). Sorafenib had to be discontinued in 3 patients (30%) due to AEs and 4 additional patients (40%) required a dose adjustment. No deterioration of liver graft function occurred. Three patients (30%) stopped treatment due to radiological progression of HCC, whereas 3 are still using the drug. Median time to progression was 8 months (range, 2-16). Median survival from start of therapy was 18 months (range, 4-36). Conclusion. Our preliminary results suggest that sorafenib is a safe effective therapy for recurrent HCC after OLT.

关键词： mTOR Inhibitor sorafenib Common Terminology Criteria for Adverse Events Recurrent Hepatocellular Carcinoma human-centered computing treatment duration Optical Line Terminal Liver Transplantation

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CYLD and HCC: When Being Too Sensitive to Your Dirty Neighbors Results in Self-Destruction

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CANCER CELL 2012年第6期21卷 711-712页

作者： Font-Burgada, Joan Seki, Ekihiro Karin, Michael Univ Calif San Diego Sch Med Dept Pharmacol Lab Gene Regulat & Signal Transduct La Jolla CA 92093 USA Univ Calif San Diego Sch Med Dept Pathol La Jolla CA 92093 USA Univ Calif San Diego Sch Med Dept Med La Jolla CA 92093 USA

Hepatocellular carcinoma is the outcome of ongoing cycles of cell death and regeneration in chronic liver disease. In this issue of Cancer Cell, Nikolaou et al. show that the deubiquitinating enzyme CYLD is critical f... 详细信息

关键词： Hepatocellular Cancer Hepatocytes chronic liver disease Regeneration Cell Death cancer cell human-centered computing CYLD gene

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