Search

MOV file - 1MB, Time lapse video microscopy of HEK293 cells transfected with empty

MOV file - 2.3MB, Time lapse video microscopy of CCLP1 cells transfected with siRNA

MOV file - 3MB, Time lapse video microscopy of Hek293 cells stably expressing NISwt and transfected with siRNA scrumble

MOV file - 1MB, Time lapse video microscopy of HEK293 cells expressing the NISdeltaTNL

A number of solute carrier (SLC) proteins are subject to changes in expression and activity during carcinogenesis. Whether these changes play a role in carcinogenesis is unclear, except for some nutrients and ion carriers whose deregulation ensures the necessary reprogramming of energy metabolism in cancer cells. In this study, we investigated the functional role in tumor progression of the sodium/iodide symporter (NIS; aka SLC5A5), which is upregulated and mislocalized in many human carcinomas. Notably, we found that NIS enhanced cell migration and invasion without ion transport being involved. These functions were mediated by NIS binding to leukemia-associated RhoA guanine exchange factor, a Rho guanine exchange factor that activates the small GTPase RhoA. Sequestering NIS in intracellular organelles or impairing its targeting to the cell surface (as observed in many cancers) led to a further increase in cell motility and invasiveness. In sum, our results established NIS as a carrier protein that interacts with a major cell signaling hub to facilitate tumor cell locomotion and invasion. Cancer Res; 72(21); 5505–15. ©2012 AACR.

MOV file - 1.3, Time lapse video microscopy of CCLP1 cells transfected with siRNA NIS

MOV file - 490K, Time lapse video microscopy of HEK293 cells expressing the NISdeltaCter

PDF file - 234K

MOV file - 1.9MB, Time lapse video microscopy of Hek293 cells stably expressing NISwt and transfected with siRNA LARG

MOV file - 2MB, Time lapse video microscopy of HEK293 cells expressing full-length NIS

BackgroundViruses are dependent on cellular energy metabolism for their replication, the drug Nitazoxanide (Alinia) was shown to interfere with both. An effect of Alinia on cellular energy metabolism is the uncoupling of mitochondrial oxidative phosphorylation (OXPHOS). Our hypothesis was that uncoupling grounds the antiviral properties of Alinia.MethodsAlinia or an unrelated uncoupler were applied to a viral releasing cell line to obtain the same increasing levels of uncoupling hence identical interference with OXPHOS.FindingsDecrease in infectious viral particles release reflected the intensity of interference irrespective of the nature of the drug and was significant with modest deviation (≤25%) from normal.InterpretationsA mild interference on cellular energy metabolism impacts significantly on viral replication cycle. This would explain Alinia’s antiviral properties in vitro moreover antiviral action of Alinia is supported by clinical trials.PerspectivesAltogether this indicates that moderate interference with mitochondrial bioenergetics should be considered as a ground for a therapeutic effect. In addition, Alinia would constitute example for a safe therapeutical use of an uncoupler, which deserves consideration for a wider range of applications.

Background: Hepatocellular carcinoma (HCC) is an inflammation-associated cancer. However, the lipid pro-inflammatory mediators have only been seldom investigated in HCC pathogenesis. Activation of NF-κB and expression of c-Myc are negatively regulated by cylindromatosis (CYLD) in hepatocarcinogenesis. But it remains largely unknown whether lipid pro-inflammatory mediators are involved in CYLD suppression. Here, we aimed to evaluate the significance of hepatic lipid pro-inflammatory metabolites of arachidonate affected CYLD expression via 5-lipoxygenase (5-LO)-pathway.Methods: Resection liver tissues from HCC patients or donors were evaluated for the correlation of 5-LO/cysteinyl leukotrienes (CysLTs)-signaling to expression of CYLD. The impact of functional components in 5-LO/CysLTs cascade on survival of HCC patients was subsequently assessed. Both livers from canines, a routine animal for drug safety evaluation, and genetic-modified human HCC cells treated with hepatocarcinogen aristolochic acid I (AAI) were further used to reveal the possible relevance between 5-LO pathway activation and CYLD depression. Results: 5-LO-activating protein (FLAP), an essential partner of 5-LO, significantly overexpressed and was parallel to CYLD depression, CD34 neovascular localization, and high Ki-67 expression in the resection tissues from HCC patients. Importantly, high hepatic FLAP transcription markedly shortened the median survival time of HCC patients after surgical resection. In the livers of AAI-treated canines, FLAP overexpression was parallel to enhanced CysLTs contents, simultaneous attenuated CYLD expression. Moreover, knock-in FLAP significantly diminished the expression of CYLD in AAI-treated human HCC cells.Conclusions: Hepatic FLAP/CysLTs axis is a crucial suppressor of CYLD in HCC pathogenesis, which highlights a novel mechanism in hepatocarcinogenesis and development. FLAP therefore can be explored for the early HCC detection and a target of anti-HCC therapy.

Background: SARS-CoV-2 belongs to a subgroup of coronaviruses rampant in bats for centuries. It has caused the COVID-19 pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 has been facilitated by the increasing intensity of air travel, urban congestion and human contact during the last half century. Until therapies and vaccines are available, tests for virus and exposure, confinement measures and physical distancing have helped curb the pandemic. Vision: The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. A myriad of self-organizing initiatives by scientists and citizens is developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21st century. Mission: For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have now formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies. Funding: This work was supported during its preparation phases by the State Key Laboratory of Medical Genomics, Overseas Expertise Introduction Project for Discipline Innovation (111 Project, B17029) to SJC, LH, CA; European Union grants CASyM (FP7-n°305033) to CA, RB, JR, DR, DS, JT, OW; eTRIKS (IMI-1-n°115446) to CA, RB, YG; PREPARE (FP7n°602525) to CA, PO, SV; and initial funds in support of the deep phenotyping clinical study from philanthropic donors, Gilead, Merck and Novartis to JG, JH, LH; the Ricerca Corrente Program by the Italian Ministry of Health to AC, CPr, GS, AU, VV; the National Megaprojects of China for Infectious Diseases (2017ZX10103009-001, 2018ZX10305409-001-005), Double Firstclass projects from the Ministry of Education to the National Research Center for Translational Medicine Shanghai to SJC; Shanghai Municipal Science and Technology Major Project (2017SHZDZX01) to LJ. Conflict of Interest: Rudi Balling reports being a founder/shareholder of ITTM S.A. and Megeno S.A., outside the submitted work, he is co-inventor and holder of two issued patents; James Heath reports personal fees and other from PACT Pharma, outside the submitted work; Hiroaki Kitano reports grants from Minister of Health, Welfare, and Labor of Japanese Government, grants from Okinawa Prefecture Government, outside the submitted work; Doron Lancet reports personal fees from Weizmann Institute of Science and LifeMap Science Inc., outside the submitted work; Catherine Larue reports personal fees from Genfit, outside the submitted work; Peter Openshaw reports personal fees for consultancy work with Janssen, JJ Susanna Palkonen reports grants from Aimmune, Astra Zeneca, Boehringer Ingelheim, Chiesi, DBV Technologies, GSK, Leo Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, outside the submitted work, is employed by the EFA who receives unrestricted grants from corporate entities as above, represents EFA in the following advisory groups of these entities: Astra Zeneca COPD Advisory Committee, GSK Health Advisory Board and Novartis European Patient Advisory Group, receives no personal gain, honoraria, when applicable expenses are payed to her organization, is in a voluntary function the Chair of the Patient Access Partnership PACT who receives unrestricted grants from EFPIA, MedTech Europe, EUCOPE and Medicines for Europe for core operations, and project grants from individual companies, outside the submitted work; Christophe Pison reports personal fees and non-financial support from AstraZeneca, Boehringer Ingelheim, GSK, Novartis, outside the submitted work; Mihael Polymeropulos reports other from Vanda Pharmaceuticals, outside the submitted work; Ulrike Protzer reports grants from VIR Biotechnology, grants and non-financial support from Roche, grants from Alios-JJ Peter Sterk reports other from Breathomix BV, outside the submitted work; Giulio Superti-Furga reports being a shareholder of Proxygen GmbH, Haplogen GmbH and Allcyte GmbH, outside the submitted work; Vincenzo Valentini reports personal fees from Merck Serono, Betaglue, outside the submitted work; Sylvie van der Werf reports other from Sanofi Pasteur, outside the submitted work; she is the holder of four issued patents. The other authors have declared no conflict of interest.

Introduction: REG3A (Regenerating islet-derived protein 3A) is a carbohydrate-binding protein belonging to the family of C-type lectins. REG3A has antioxidant and anti-inflammatory properties modulating glucose and lipid homeostasis. We report a study of the effects of the administration of the human recombinant REG3A protein ALF-5755 on glucose and lipid homeostasis in insulin-resistant mice. Materials and Methods: 4-week-old C57Bl/6N male mice were fed HFD for 12 weeks. The control group received a standard chow diet. 12-week-old Ob/Ob mice were used. Mice were given ALF-5755 (43µg/day, ALF group) or a formulation buffer (buffer group) by subcutaneous infusion for 28 days. We measured: body weight, blood glucose, fasting insulin, glucose tolerance and insulin sensitivity, glucose turnover and uptake during hyperinsulinemic/euglycemic clamps and AMPK activity. Results: In both models, ALF-5755 administration significantly decreased basal blood glucose with no change in basal insulin levels. The changes in blood glucose levels in response to an oral glucose load in the ALF and buffer groups were similar in HFD-fed mice but were lowered by ALF-5755 in Ob/Ob mice. Insulin secretion at 15 and 30 min was significantly reduced in the ALF group compared to Buffer group in both models. During clamp, glycolytic muscles exhibited an increase in glucose uptake in HFD-fed mice, and an increase in AMPK activity in both models treated with ALF-5755. Insulin sensitivity was increased in ALF group. The plasma TG was significantly decreased in the ALF compared to Buffer group. No difference in body weight was observed whatever the administered molecules. Conclusion: Administration of ALF-5775 improves blood glucose and insulin sensitivity in insulin-resistant mice. This effect is mediated by an increase of skeletal muscle glucose uptake through AMPK activation. REG3A is a potential therapeutic drug for the management of insulin resistance syndrome. Disclosure M. Darnaud: None. C. Cruciani-Guglielmacci: Consultant; Self; The Healthy Aging Company. P. Gonzalez: None. P. Amouyal: None. G. Amouyal: None. L. Jamot: None. N. Moniaux: None. F. Andreelli: Consultant; Self; Lilly Diabetes, THAC. Speaker’s Bureau; Self; Lilly Diabetes. Other Relationship; Self; Lilly Diabetes. C.B. Bréchot: Consultant; Self; Romark. Employee; Self; The Healthy Aging Company. C. Magnan: None. J. Faivre: None.

As microbiome science expands, academic centres scramble to fill many needs, from service provider to industry liaison. A newly created network aims to share strategies and accelerate knowledge transfer, and invites others to join the efforts.

Chronic hepatitis B virus (HBV) infection is a global public health challenge on the same scale as tuberculosis, HIV, and malaria. The International Coalition to Eliminate HBV (ICE-HBV) is a coalition of experts dedicated to accelerating the discovery of a cure for chronic hepatitis B. Following extensive consultation with more than 50 scientists from across the globe, as well as key stakeholders including people affected by HBV, we have identified gaps in our current knowledge and new strategies and tools that are required to achieve HBV cure. We believe that research must focus on the discovery of interventional strategies that will permanently reduce the number of productively infected cells or permanently silence the covalently closed circular DNA in those cells, and that will stimulate HBV-specific host immune responses which mimic spontaneous resolution of HBV infection. There is also a pressing need for the establishment of repositories of standardised HBV reagents and protocols that can be accessed by all HBV researchers throughout the world. The HBV cure research agenda outlined in this position paper will contribute markedly to the goal of eliminating HBV infection worldwide.

More than 250 million people worldwide are chronically infected with the hepatitis B virus (HBV). In this Comment, members of the International Coalition to Eliminate HBV appraise the current policy environment and the need for appropriate cure research and preparedness to complement the WHO global elimination strategy, the HBV vaccine and the well-tolerated but poorly accessed therapy.

International audience; BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic (TG) expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice. METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter. In these mice, hREG3A travels via the bile to the intestinal lumen. Some mice were given dextran sodium sulfate (DSS) to induce colitis. Feces were collected from mice and the composition of the microbiota was analyzed by 16S ribosomal RNA sequencing. The fecal microbiome was also analyzed from mice that express only 1 copy of human REG3A transgene but were fed feces from control mice (not expressing hREG3A) as newborns. Mice expressing hREG3A were monitored for DSS-induced colitis after co-housing or feeding feces from control mice. Colitis was induced in another set of control and hREG3A-TG mice by administration of trinitrobenzene sulfonic acid; some mice were given intrarectal injections of the hREG3A protein. Colon tissues were collected from mice and analyzed by histology and immunohistochemistry to detect mucin 2, as well as by 16S ribosomal RNA fluorescence in situ hybridization, transcriptional analyses, and quantitative polymerase chain reaction. We measured levels of reactive oxygen species (ROS) in bacterial cultures and fecal microbiota using 20,70-dichloro-fluorescein diacetate and flow cytometry. RESULTS: The fecal microbiota of mice that express hREG3A had a significant shift in composition, compared with control mice, with enrichment of Clostridiales (Ruminococcaceae, Lachnospiraceae) and depletion of Bacteroidetes (Prevotellaceae); the TG mice developed less-severe colitis following administration of DSS than control mice, associated with preserved gut barrier integrity and reduced bacterial translocation, epithelial inflammation, and oxidative damage. A similar shift in the composition of the fecal microbiota occurred after a few months in TG mice heterozygous for REG3A that harbored a wild-type maternal microbiota at birth; these mice developed less-severe forms of colitis following DSS administration. Cohoused and germ-free mice fed feces from REG3A-TG mice and given DSS developed less-severe forms of colitis and had reduced lipopolysaccharide activation of the toll-like receptor 4 and increased survival times compared with mice not fed feces from REG3A-TG mice. REG3A TG mice developed only mild colonic inflammation after exposure to 2,4,6-trinitrobenzene sulfonic acid, compared with control mice. Control mice given intrarectal hREG3A and exposed to 2,4,6-trinitrobenzene sulfonic acid showed less colon damage and inflammation than mice not given intrarectal hREG3A. Fecal samples from REG3A-TG mice had lower levels of ROS than feces from control mice during DSS administration. Addition of hREG3A to bacterial cultures reduced levels of ROS and increased survival of oxygen-sensitive commensal bacteria (Faecalibacterium prausnitzii and Roseburia intestinalis). CONCLUSIONS: Mice with hepatocytes that express hREG3A, which travels to the intestinal lumen, are less sensitive to colitis than control mice. We found hREG3A to alter the colonic microbiota by decreasing levels of ROS. Fecal microbiota from REG3A-TG mice protect non-TG mice from induction of colitis. These findings indicate a role for reduction of oxidative stress in preserving the gut microbiota and its ability to prevent inflammation.

ispartof: Progress in preventive medicine pages:1-2 status: published

Biological resources (cells, tissues, bodily fluids or biomolecules) are considered essential raw material for the advancement of health-related biotechnology, for research and development in life sciences, and for ultimately improving human health. Stored in local biobanks, access to the human biological samples and related medical data for transnational research is often limited, in particular for the international life science industry. The recently established pan-European Biobanking and BioMolecular resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC) aims to improve accessibility and interoperability between academic and industrial parties to benefit personalized medicine, disease prevention to promote development of new diagnostics, devices and medicines. BBMRI-ERIC is developing the concept of Expert Centre as public–private partnerships in the precompetitive, not-for-profit field to provide a new structure to perform research projects that would face difficulties under currently established models of academic–industry collaboration. By definition, Expert Centres are key intermediaries between public and private sectors performing the analysis of biological samples under internationally standardized conditions. This paper presents the rationale behind the Expert Centres and illustrates the novel concept with model examples.

The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 52 GVN Centers of Excellence and 9 Affiliate laboratories in 32 countries. The 11th International GVN meeting was held from June 9–11, 2019 in Barcelona, Spain and was jointly organized with the Spanish Society of Virology. A common theme throughout the meeting was globalization and climate change. This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including severe virus epidemics, anticipation and preparedness for changing disease dynamics, host-pathogen interactions, zoonotic virus infections, ethical preparedness for epidemics and pandemics, one health and antivirals., Instituto de Biotecnologia y Biologia Molecular

Over 257 million people live with chronic hepatitis B virus (HBV) infection and there is no known cure. The effective preventative vaccine has no impact on existing infection. Despite the existence of drugs which efficiently suppress viral replication, treatment is usually life-long and finite therapies that cure HBV infection are urgently required. However, even if such therapies were available today, it is unlikely they would reach all of those who need it most, due to chronic hepatitis B (CHB) being largely undiagnosed across the globe and to the dire need for health systems promoting access to therapy. Considerable challenges to developing and implementing an effective HBV cure remain. Nonetheless, important advances towards a cure are being made, both in the development of a multitude of new therapeutic agents currently undergoing clinical trials, and through the establishment of a new global initiative dedicated to an HBV cure, ICE-HBV, that is working together with existing organisations to fast-track an HBV cure available to all.

The accumulation of lipid droplets (LD) is frequently observed in hepatitis C virus (HCV) infection and represents an important risk factor for the development of liver steatosis and cirrhosis. The mechanisms of LD biogenesis and growth remain open questions. Here, transcriptome analysis reveals a significant upregulation of septin 9 in HCV-induced cirrhosis compared with the normal liver. HCV infection increases septin 9 expression and induces its assembly into filaments. Septin 9 regulates LD growth and perinuclear accumulation in a manner dependent on dynamic microtubules. The effects of septin 9 on LDs are also dependent on binding to PtdIns5P, which, in turn, controls the formation of septin 9 filaments and its interaction with microtubules. This previously undescribed cooperation between PtdIns5P and septin 9 regulates oleate-induced accumulation of LDs. Overall, our data offer a novel route for LD growth through the involvement of a septin 9/PtdIns5P signalling pathway., The accumulation of lipid droplets is often observed in hepatitis C virus infection, but the mechanism of their formation is not known. Here the authors show that septin 9 expression is increased in infected livers, and a septin 9/phosphatidylinositol 5-phosphate signalling pathway regulates the growth of lipid droplets.

Summary Diagnostics are crucial in mitigating the effect of disease outbreaks. Because diagnostic development and validation are time consuming, they should be carried out in anticipation of epidemics rather than in response to them. The diagnostic response to the 2014–15 Ebola epidemic, although ultimately effective, was slow and expensive. If a focused mechanism had existed with the technical and financial resources to drive its development ahead of the outbreak, point-of-care Ebola tests supporting a less costly and more mobile response could have been available early on in the diagnosis process. A new partnering model could drive rapid development of tests and surveillance strategies for novel pathogens that emerge in future outbreaks. We look at lessons learned from the Ebola outbreak and propose specific solutions to improve the speed of new assay development and ensure their effective deployment.

Background & Aims Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. As complementary biomarkers, protein induced by vitamin K absence (PIVKA-II), osteopontin (OPN), and Dickkopf-1 (DKK-1) have been proposed. This study aimed to perform a head-to-head comparison of the diagnostic performance of AFP, PIVKA-II, OPN and DKK-1 as single or in combination to seek the best biomarker or panel, and to investigate the clinical factors affecting their performance. Methods Using 401 stored plasma samples obtained from 208 HCC patients and 193 liver cirrhosis control patients, plasma AFP, PIVKA-II, OPN and DKK-1 levels were measured by ELISA, and receiver operating characteristic curve analyses were performed for each biomarker and for every combination of two to four markers. Results Of the four biomarkers, AFP showed the highest area under the curve (0.786). The sensitivity and specificity for each single biomarker was 62% and 90.2% (AFP>20 ng/mL), 51.0% and 91.2% (PIVKA-II>10 ng/mL), 46.2% and 80.3% (OPN>100 ng/mL), and 50.0% and 80.8% (DKK-1>500 pg/mL), respectively. Among the combinations of two biomarkers, AFP>20 ng/mL or DKK-1>500 pg/mL showed the best diagnostic performance (sensitivity 78.4%, specificity 72.5%). Triple or quadruple combination did not improve the diagnostic performance further. The patient’s age, etiology and tumor invasiveness of HCC affected the performance of each marker. Conclusions AFP was the most useful single biomarker for HCC diagnosis, and the combined measurement of AFP and DKK-1 could maximize the diagnostic yield. Clinical decision should be based on the consideration of various factors affecting the diagnostic performance of each biomarker. Efforts to seek novel HCC biomarkers should be continued.

Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation. Among the eukaryotic initiation factors that govern the translational machinery, 4E-BP1 represents a master regulator of protein synthesis that is associated with the development and progression of cancers due to its ability to increase protein expression of oncogenic pathways. Enhanced levels of 4E-BP1 in non-modified and phosphorylated forms were validated in human hepatoma cells and in mouse primary hepatocytes expressing HCV core, in the livers of HCV core transgenic mice as well as in HCV-infected human primary hepatocytes. The contribution of HCV core in carcinogenesis and the status of 4E-BP1 expression and phosphorylation were studied in HCV core/Myc double transgenic mice. HCV core increased the levels of 4E-BP1 expression and phosphorylation and significantly accelerated the onset of Myc-induced tumorigenesis in these double transgenic mice. These results reveal a novel function of HCV core in liver carcinogenesis potentiation. They position 4E-BP1 as a tumor-specific target of HCV core and support the involvement of the 4E-BP1/eIF4E axis in hepatocarcinogenesis.

© the American Society for Biochemistry and Molecular Biology"; International audience; Obtaining accurate protein profiles from homogeneous cell populations in heterogeneous tissues can enhance the capability to discover protein biomarkers. In this context, methodologies to access specific cellular populations and analyze their proteome with exquisite sensitivity have to be selected. We report here the results of an investigation using a combination of laser microdissection and accurate mass and time tag proteomics. The study was aimed at the precise determination of proteome alterations in intrahepatic cholangiocarcinoma ICC, a markedly heterogeneous tumor. This cancer, which is difficult to diagnose and carries a very poor prognosis, has shown an unexplained increase in incidence over the last few years. Among a pool of 574 identified proteins, we were able to report on altered abundance patterns affecting 39 proteins conforming to a variety of potential tumorigenic pathways. The reliability of the proteomics results was confirmed by Western blot and immunohistochemistry on matched samples. Most of the proteins displaying perturbed abundances had not yet been described in the setting of ICC. These include proteins involved in cell mobility and actin cytoskeleton remodeling, which may participate in the epithelial to mesenchymal transition, a process invoked in migration and invasion of cancer cells. The biological relevance of these findings was explored using a tissue microarray. An increased abundance of vimentin was thus detected in 70% of ICC and none of the controls. These results suggest that vimentin could play a role in the aggressiveness of ICC and provide a basis for the serious outcome of this cancer.

Chronic hepatitis B (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Most HCCs complicate the evolution of an active or inactive cirrhosis. However, some tumors occur on livers with minimal histological changes; the prevalence of such cases varies from one geographical region to the other, being much higher in the Southern half of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least 90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a reflection of different environmental and genetic factors. This review will summarise the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. It will show in particular how viruses can be viewed as tools to discover and dissect new cellular pathways involved in cancer development and emphasize the potential synergistic effects between HBV and hepatitis C virus (HCV), as well as between viral infections and other environmental factors, such as alcohol.