Search

Copyright of Environnement, Risques & Santé is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Les adénocarcinomes de l'intestin grêle (AIG) sont des tumeurs rares mais leur incidence est en augmentation. La localisation primitive la plus fréquente est le duodénum. Même si les AIG sont le plus souvent sporadiques, certaines maladies sont des facteurs de risque comme la maladie de Crohn, et il existe des prédispositions génétiques à ce cancer comme le syndrome de Lynch et la polypose adénomateuse familiale. Le phénotypage moléculaire révèle des différences entre les AIG et les adénocarcinomes colorectaux. Le diagnostic précoce des AIG reste difficile malgré des progrès de l'endoscopie et des examens radiologiques. Après résection chirurgicale R0, un envahissement ganglionnaire est le principal facteur pronostique. Un essai randomisé international (essai BALLAD) est en cours pour évaluer l'intérêt d'une chimiothérapie adjuvante. Pour les maladies métastatiques, des études rétrospectives ont suggéré que les schémas de chimiothérapie à base de sels de platines étaient les plus efficaces mais aucun progrès notable n'a été réalisé depuis des décennies. Un effet spectaculaire de l'immunothérapie est rapporté en cas de tumeur avec un défaut de réparation de l'ADN. D'autres thérapies ciblées pourraient être efficaces en cas d'altérations moléculaires spécifiques. Small bowel adenocarcinomas (SBA) are rare tumors, but their incidence is increasing. The commonest primary location is the duodenum. Even though SBA are more often sporadic, some diseases are risk factors, such as Crohn's disease and some genetic predispositions to cancer as Lynch syndrome or familial adenomatous polyposis. Molecular phenotyping revealed some differences between SBA and colorectal cancer. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiological and endoscopic progresses. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD study) is ongoing to evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospective studies suggest that platinum-based chemotherapy is the most effective treatment, but no significant improvement has been achieved since decades. A dramatic effect has been reported with immunotherapy in tumor with deficient mismatch repair system. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA. Other targeted therapies may be efficient in case of specific molecular alterations. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection is one of the most common factors associated with hepatocellular carcinoma (HCC). However, the pathogenesis of HBV-mediated hepatocarcinogenesis is not clearly defined. Persistence of HBV infection is associated with HCC pathogenesis, and various HBV proteins appear to be involved in promoting this persistence. Currently available data suggest that the core protein, a structural component of the viral nucleocapsid, and the HBe protein, a non-structural HBV protein that can act as both a tolerogen and an immunogen, play a potential role in the development of HCC. Research shows that both proteins are capable of disrupting various pathways involved in liver carcinogenesis, including the sustenance of proliferative signaling, resistance to cell death, tumor-promoting inflammation and avoid immune destruction. This review summarizes the various signaling pathways by which HBc and HBe proteins (and their precursors) can promote hepatocarcinogenesis.

Currently, more than 10% of human cancers are associated with viral infection. Studies on oncoviruses led to the development of clinical intervention strategies and elucidated fundamental cellular events altered upon cell transformation. Cancer cells exhibit several hallmarks including genomic instability, defined as a high frequency of mutations including gain or loss of chromosomes. The centrosome is an organelle that governs mitotic chromosome segregation and that functions as a signaling platform downstream of the DNA damage response. Here, we review the current literature to highlight how oncoviruses induce genomic instability via the deregulation of the centrosome. Viral interference with the centrosome duplication cycle, leading to centrosome amplification, is illustrated, with a special emphasis on mechanisms shared by several viral families. In addition, we discuss how oncoviruses could alter the signaling functions of the centrosome, and we comment on the bibliographic gaps that could be addressed by future research. [ABSTRACT FROM AUTHOR]

Résumé: Le cancer colorectal (CCR) développé sur colite chronique (rectocolite hémorragique ou maladie de Crohn) représente un sous-groupe très distinct du CCR sporadique. Sur le plan épidémiologique, l'âge de survenue moyen est d'environ vingt ans plus précoce. L'impact des traitements de fond des colites chroniques sur le risque de dégénérescence tumorale est peu connu en raison de la complexité de son évaluation. Or, la prise en charge préventive de ce cancer est essentielle mais demeure difficile comme le démontre un taux d'échec de détection des lésions pré-cancéreuses plus important dans cette forme de CCR que dans le CCR sporadique. L'histoire naturelle de la maladie est différente, la classique séquence adénome-cancer du CCR sporadique devient la séquence colite-dysplasie-cancer. Cette différence macroscopique se caractérise par des profils de tumeurs distincts en histologie, par des différences immunologiques et par une séquence mutationnelle inversée entre les deux types de CCR. Alors qu'une dysbiose est observée dans le CCR sur colite chronique et dans le CCR sporadique, des différences importantes existent dans la composition de la flore intestinale reflétant des mécanismes de cancérogenèse distincts. La compréhension de l'ensemble de ces différences constitue un enjeu majeur pour les évolutions thérapeutiques à venir tant sur les versants thérapeutiques purs que préventifs. The chronic colitis-associated colorectal cancer (CAC) represents subtype of colorectal cancer (CRC) considerably different from the sporadic CRC. Epidemiologically, the average age of diagnosis is about 20 years earlier. The impact of the treatments of the chronic colitis on the risk of tumor degeneration is poorly known because of the complexity of its evaluation. However, the preventive management of this cancer is essential but difficult. For example, the failure rate of detection of pre-cancerous lesions is significantly higher in this form of CRC compared to sporadic CRC. The history of the disease is also different, the classic sporadic CR Cadenoma-cancer sequence becomes the colitis-dysplasia-cancer sequence. This macroscopic difference is also highlighted histologically by distinct tumor profiles, immunologically by the major implication of the chronic inflammation and the cytokinic microenvironnement and genetically by a profile of mutations almost opposite from sporadic CRC. While dysbiosis is found in CAC and in sporadic CRC, the type of dysbiosis is not similar, indicating distinct mechanisms of tumorigenesis. The understanding of all these differences will be a major challenge in future therapeutic developments on both therapeutic and preventive aspects. [ABSTRACT FROM AUTHOR]

Introduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease caused by the mutation of the MEFV gene, which, for several authors, presents a particular risk for the development of malignant peritoneal mesothelioma (MPM). The aim of this paper is to focus on the relation between FMF and MPM, as well as the different mechanisms involved in this carcinogenesis. Method: A systematic review of the medical literature in the world targeting malignant mesothelioma cases reported during FMF. Results: The incidence of MPM in FMF, significantly higher than that in the general population in the concerned countries, as well as its epidemiological and clinical characteristics, suggest the 'promoting' nature of the neoplastic graft presented by this disease. This carcinogenesis seems to be multifactorial incriminating underlying chronic inflammation, a direct carcinogenic effect of the MEFV gene and its resulting mutant pyrin, oxidative stress, immune dysfunction mainly of innate immunity, and certain used immunosuppressive and biological treatments. Recurrent peritoneal irritation (classic peritonitis of FMF peritoneal access) is the primary starting point for MMP. [ABSTRACT FROM AUTHOR]

Copyright of Bulletin de la Société de Pathologie Exotique is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé La radiothérapie constitue avec la chirurgie les deux piliers majeurs du traitement locorégional du cancer. Le risque de second cancer devient mieux évalué et représente un souci majeur en termes de radioprotection. Parmi les lésions malignes découvertes chez des patients traités, l’apparition d’un sarcome est un évènement rare mais de pronostic sombre puisque le taux de survie des patients est estimé entre 10 à 35 % à 5 ans. Le protocole SARI, conçu et écrit en 2011, a permis l’inclusion de 120 patients atteints d’un sarcome développé en territoire irradié appariés à 240 témoins, irradiés dans les mêmes conditions, mais sans avoir vu se développer la maladie. L’objectif principal de l’essai était de déterminer les facteurs de risque clinique et biologique prédictifs, de survenu d’un sarcome en territoire irradié. Les objectifs secondaires étaient de décrire les caractéristiques de la radiothérapie chez l’ensemble des patients ayant vu se développer un sarcome sur territoire irradié. Les résultats préliminaires seront présentés lors du congrès 2016 de la Société française de radiothérapie oncologie. Radiotherapy and surgery are the two main pillars of the locoregional treatment of cancer. The risk of second malignancy is better evaluated and constitutes a major issue regarding radioprotection of the patients. Among malignant disease observed in the surviving irradiated patients, the occurrence of sarcoma is a rare event but associated with a poor outcome since the 5 year overall survival is estimated at 10 to 35 %. The SARI protocol, written in 2011, included 120 patients and 240 controlled patients, irradiated in the same conditions but without sarcoma observed during the follow up. The main objective was to identify the clinical and biological factors associated with the occurrence of such a complication. The secondary objective was to identify the dosimetric characteristics of the treatment of the primary. Preliminary results will be presented during the 2016 meeting of the French radiation oncology society. [ABSTRACT FROM AUTHOR]

Copyright of Colon & Rectum is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The aim of this article is to describe the natural history and peculiarities of carcinogenesis of upper tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed on the Medline database (Pub- Med) using different combinations of the following key words: upper tract urothelial carcinoma, clonality, carcinogenesis, mutation, chromosomal instability, Lynch syndrome, and genetic polymorphism. Local development of UTUC is characterized by a highly prevalent multifocality that might be explained by the overlap of 'field change' and 'intra-luminal seeding and implantation' theories. UTUC and bladder tumors share common carcinogenesis mechanisms, such as mutations of FGFR3 and TP53, defining two distinct pathways of pathogenesis. The estimated UTUC incidence is 1.2 cases/100,000 inhabitants per year in Europe. The incidence of renal pelvis tumor has been stable for 30 years, while the frequency of ureteral locations has increased over time. Locally advanced stage and high grade are more frequent factors at the time of diagnosis. The median age for diagnosis is 70 years. Male-to-female ratio is nearly 2. Main carcinogenic factors are tobacco consumption and occupational exposure. There are specific risk factors for UTUC, such as Aristolochic acid (Balkan nephropathy and Chinese herbes nephropathy). Furthermore, specific genetic risk factors for UTUC includes Lynch syndrome, and different polymorphisms might explain an individual's susceptibility for developing these tumors. [ABSTRACT FROM AUTHOR]

Copyright of Journal Africain D'Hépato-Gastroentérologie is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Les infections sont une cause importante de cancer dans le monde, représentant environ 16 % des cas. Dix agents infectieux ont été classés carcinogènes avérés du groupe I. Quatre de ces agents (Helicobacter pylori, virus des hépatites B et C et certains papillomavirus humains) sont responsables de 95 % des cas de cancers attribuables aux infections. Les mécanismes oncogénétiques sont multiples, soit directs via notamment certaines protéines des microorganismes, soit indirects le plus souvent par le biais d’une inflammation chronique. Ceci a permis d’envisager une prévention de certains cancers avec par exemple une stratégie vaccinale prophylactique. Des avancées ont également été réalisées dans le domaine curatif. Des progrès restent toutefois à accomplir pour découvrir de nouvelles étiologies infectieuses et affiner la compréhension des mécanismes de carcinogenèse, garant d’un meilleur ciblage des thérapeutiques anticancéreuses. [ABSTRACT FROM AUTHOR]

Copyright of Colon & Rectum is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The recent emergence of tumor organoid cultures, or tumoroids, has enriched the repertoire of preclinical models in oncology. These microtumors are obtained in vitro by including cells from patient tumor samples in an extracellular matrix and cultured in specific media. Very close to the tumor of origin, tumoroids can be amplified fairly rapidly from a small quantity of tissue, established with high success rate for most tumor types, easily genetically engineered, and stored in biobanks. Tumoroids thus offer numerous possibilities in terms of basic research, such as the study of carcinogenesis or mechanisms of chemoresistance, but also the identification of new targets and preclinical validation of new anti-cancer compounds or personalized medicine. Technological developments and enrichment of tumoroids with other cell types are currently ongoing to optimally exploit the full potential of these models., (© 2022 médecine/sciences – Inserm.)

Résumé: L’infection à Helicobacter pylori est reconnue comme la principale cause de cancer attribuable à une infection dans le monde. Elle est responsable de l’essentiel des adénocarcinomes gastriques de type intestinal comme diffus, qui sont la conséquence à long terme de l’infection chronique de la muqueuse gastrique. Des études cas témoins ont montré l’association, reconnue déjà en 1994, confortée par des études d’intervention par éradication de H. pylori qui ont montré la possibilité de prévenir au moins partiellement le cancer gastrique. Des études expérimentales ont permis d’observer le rôle des cellules souches mésenchymateuses originaires de la moelle osseuse à l’origine du processus néoplasique dans environ un quart des cas et éventuellement celui d’une transition épithélio-mésenchymateuse dans les autres cas. L’évolution vers le cancer gastrique peut être liée à des facteurs génétiques (polymorphisme des gènes de certaines cytokines), des facteurs environnementaux (consommation de sel, régime carné…) mais les facteurs bactériens sont prédominants. Certaines souches de H. pylori possèdent un îlot de pathogénicité appelé cag et produisent une oncoprotéine appelé CagA qui modifie les voies de signalisation cellulaire et est un élément essentiel dans la transformation cellulaire. [Copyright &y& Elsevier]

Psychoanalysis studies the human being defined as a theorizing and self-theorizing being. Its metapsychology tries to understand the enacted penetration of the unconscious in these theorizing processes either in their defensive or their structuring dimensions. This paper describes how the genesis of psychoanalytic theories has been modelized from four of its elective objects: the individual in his ontogenesis, the patient in his pathogenesis, the group and the analytic cure in their development. [ABSTRACT FROM AUTHOR]

Copyright of Obésité is the property of Lavoisier and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Gynecological tumors comprise a heterogeneous group of lesions, with each organ of female genital tract displaying distinct tumor pathology and oncogenesis. We report herein the newly described molecular abnormalities in carcinomas and sex cord-stromal tumors of the ovary as well as in epithelial and mesenchymal uterine neoplasms. The biomarkers such as immunohistochemical antibodies and molecular testing help the pathologists in their every day practice. Our better understanding of the molecular bases of gynecological tumors represents the first step in the development of targeted therapies in the near future. [ABSTRACT FROM AUTHOR]

In cancer stem cell (CSC) hypothesis, tumors are organized in a hierarchical model with CSC at the top of the hierarchy. CSCs display both stem cell properties (self-renewal and differentiation) and specific tumoral properties (tumorigenicity, metastatic capacity, resistance to conventional therapies). Recent works on breast cancer allow CSCs isolation and help deciphering CSC biology and targeting with specific therapies. In clinical trials, CSC biology has to be taken into account and the criteria to judge therapeutic efficiency have to change. [ABSTRACT FROM AUTHOR]

Abstract: Context: Scientific advances in molecular biology and understanding of oncogenesis have lead to anticancer molecular targeted therapies. They encompass monoclonal antibodies binding to active membrane epitopes and small molecules interfering with enzymatic reactions essential to cancer cell survival (oncogene addiction). These pathways may be optimal targets. Clinical benefits achieved using these targeted agents have been outstanding both in localized and metastatic disease. Method: We conducted a survey of literature analyzing activity and safety of targeted agents approved by FDA and/or FDA for the treatment of patients with breast cancer: anti-HER2 and antiangiogenic agents. Results: Activity and main toxicities of these targeted agents are described according to signaling pathway targeted as well as stage of breast cancer. Conclusions: Availability of these targeted therapies has indeed transformed the outcome of subgroups of breast cancer to the expense of acceptable and manageable side effects, as compared to classical cytotoxics to which they are nevertheless combined. [Copyright &y& Elsevier]

Abstract: The oncologist is confronted daily by questions related to the fact that any patient presents a specific evolution for his cancer: he is challenged by very different, unexpected and often unpredictable outcomes, in some of his patients. The mathematical approach used today to describe this evolution has recourse to statistics and probability laws: such an approach does not ultimately apply to one particular patient, but to a given more or less heterogeneous population. This approach therefore poorly characterizes the dynamics of this disease and does not allow to state whether a patient is cured, to predict if he will relapse and when this could occur, and in what form, nor to predict the response to treatment and, in particular, to radiation therapy. Chaos theory, not well known by oncologists, could allow a better understanding of these issues. Developed to investigate complex systems producing behaviours that cannot be predicted due to a great sensitivity to initial conditions, chaos theory is rich of suitable concepts for a new approach of cancer dynamics. This article is three-fold: to provide a brief introduction to chaos theory, to clarify the main connecting points between chaos and carcinogenesis and to point out few promising research perspectives, especially in radiotherapy. [Copyright &y& Elsevier]

In the evolution of a cancer, tumorigenesis is the stage at which the initial molecular and cellular process develops a tissue dimension and, in particular, takes on a clinical aspect. This stage is made possible by the establishment and development of interactions between transformed epithelial cells and their stromal tissue matrix. The cells which are recruited from the stroma and activated are fibroblast precursors, macrophages, haematopoietic stem cells and inflammatory cells. Through these cells the stroma becomes an active partner in tumour development. As a result of these interactions neoangiogenesis is a key factor for tumour progression, invasion and metastasis. The tumoral cell proliferation is limited by normoxy, fast growing induce hypoxic cell status, and the hypoxic tumoral cell secrete chimioattractant and activating molecules, such as adrenomedullin. Fibroblast precursors, macrophages, inflammatory cells and hypoxic cancerous cells cooperate in the activation of a cascadé of proteases and growth factors, which interact with endothelial cells and pericytes. This destabilises capillary vessels and initiates angiogenesis. The new vessels are constantly refashioned and partially compensate for the tumoral hypoxia caused by rapid tumour growth. However, they constitute an important route for the metastatic spread of tumour. All of these interactions are only a distortion of the physiological processes seen during tissue repair. This latter is limited in its time frame and definitively terminated by healing, whereas the interactions between malignant cells and the micro-environment do not have a mechanism to block them. [ABSTRACT FROM AUTHOR]

The improvement in the knowledge of the pathways involved in cancerogenesis has led to the development of original targeted therapies that are being evaluated in recent clinical trials applied to hepatobiliary cancers. Primary hepatobiliary cancers, like other cancers, are considered somatic genetic diseases whose a mapping of the genetic defects will be available at the whole genome scale. Using genetic anomalies as markers is still an emerging approach but is promising to decipher the heterogeneity of the hepatobiliary cancers to classify them at themolecular scale, refine the prognosis and offer a personalized treatment. [ABSTRACT FROM AUTHOR]

Abstract: Pancreatic carcinoma is the fifth leading cause of cancer-related mortality. The 5-year overall survival is less than 5 %. This very poor prognosis can be explained both by late diagnosis and by treatment resistance, including resistance to radiation therapy. A better understanding of the pancreatic tumorigenesis and knowledge of the most frequent mutations in pancreatic adenocarcinoma (KRAS, p16, TP53, Smad4) open new perspectives for the development of more effective treatments. This review presents the major genetic and molecular alterations in pancreatic cancer that could be targeted to improve radiosensitization. [Copyright &y& Elsevier]

Abstract: ZNF689, a C2H2-type of zinc finger transcription factor, was suggested to play a key role in hepatocarcinogenesis. However, none of the target genes or potential roles of ZNF689 in hepatocellular carcinoma (HCC) have been elucidated. Here, we investigated the role of ZNF689 in HCC cell lines focusing on cell viability and apoptosis. We found that the knockdown of ZNF689 by its specific siRNA decreased cell viability of Huh7. Cell cycle analysis revealed that the ZNF689 knockdown increased the proportion of the sub-G1 population, accompanied by an increase of annexin V- and TUNEL-positive cells. Western blot analysis revealed that ZNF689 knockdown induced the expression of pro-apoptotic factors of Bcl-2 family, Bax, Bak and jBid. There was a correlation between the expression of ZNF689 and an anticancer drug 5-fluorouracil (5-FU) resistance of HCC cells. In vivo, ZNF689 siRNA reduced tumor viability in HepG2-bearing mice with statistical significance. Furthermore, immunohistochemical analysis demonstrated that nuclei of a significant portion of human HCC surgical specimens were positive for ZNF689. Taken together, our results indicate that ZNF689 blocks pro-apoptotic signaling by suppressing the Bak/Bax/Bid pathway, resulting in the progression of liver cancer and resistance to 5-FU. ZNF689 may be a promising chemotherapeutic target against liver cancer. [Copyright &y& Elsevier]

Abstract: Cryofibrinogenemia (CF) is an unrecognized disorder and is rarely symptomatic. CF represents 10 % of the whole cryoproteins. Mean age at diagnosis is between 50 and 60years. The skin is the most frequently involved organ, in 80 % of patients at diagnosis. Skin lesions include purpura, livedo and Raynaud''s phenomenon. In severe cases, skin ulcerations or necrosis and gangrene may occur. Arterial thrombosis is frequently reported (20 to 40 % of cases). Defect in the fibrinolysis process may lead to the cryofibrinogen accumulation and clotting in small and medium arteries and provide a rationale for the use of fibrinolytic agents at least in the most severe cases. In this article, we review the clinical presentation, pathogenesis and treatment of CF. [Copyright &y& Elsevier]

Abstract: Ovarian carcinogenesis and the early stages of malignant transformation are limited because of the lack of a candidate precursor. There have been several proposed hypotheses: first, ovary and the ovarian surface epithelium and more recently observations have increasingly focused attention of the Fallopian tube. Moreover, molecular genetic analysis has designed two main pathways of tumorogenesis. In this review, we discuss the different and perhaps complementary hypotheses about ovarian carcinogenesis. [Copyright &y& Elsevier]

Abstract: Merkel cell carcinoma (MCC) is a neuroendocrine carcinoma of the skin of poor outcome. A new type of virus, isolated in 2008, was found to be strongly associated with CCM. This virus, belonging to the family of polyomavirus, was called MCPyV for Merkel Carcinoma Polyomavirus. Recent data favour a causative role of MCPyV in oncogenesis. MCC represents thus a new model for the understanding of the mechanisms of oncogenesis. The distinct molecular viral signature in every case of MCC represents an original tool for the follow-up of the disease. New therapeutic perspectives are to be drawn using this model. [Copyright &y& Elsevier]

Abstract: The aim of diagnosis imaging is to detect hepatocellular carcinoma at an early stage, when a curative treatment is available. Biopsy is no longer required prior to treatment, and diagnosis of hepatocellular carcinoma is heavily dependent of imaging characteristics. Therefore, the purpose of this article is to describe the typical features of small (<20mm) and larger hepatocellular carcinomas with noninvasive diagnostic criteria, including ultrasound, computed tomography and MRI. Advances in these imaging modalities have greatly improved the detection of small hepatic nodules on liver cirrhosis, including the different steps of carcinogenesis, from regenerative to dysplastic nodules, and we emphasize the difficulties of radiological differentiation of precancerous lesions and small hepatocellular carcinomas. [Copyright &y& Elsevier]

Abstract: Hepatocellular carcinoma (HCC) is the main type of primary liver cancers and the third most common cause of cancer mortality worldwide. In France, rising number between 5000 and 6000 cases are diagnosed each year. The major risk factor for hepatocellular carcinoma is chronic hepatitis: viral hepatitis B, viral hepatitis C, consumption of alcohol, hemochromatosis. Hepatocellular carcinoma is closely associated to liver cirrhosis, which is a true precancerous state. Because hepatocarcinogenesis is a long and heterogeneous process, there is still much to understand. Many genetic and epigenetic alterations are described leading to changes in cellular signalling cascades involved in regulation of growth, differentiation, apoptosis, motility. Hepatitis viruses play a direct oncogenic role through the interaction between viral and cellular proteins, which control cell homeostasis, or by the integration of hepatitis B virus genome into the host genome. Furthermore, hepatitis viruses play an indirect oncogenic role by causing chronic inflammation and hepatocyte regeneration related to viral hepatopathy. In expectation of a better understanding of hepatocarcinogenesis and new treatments, prevention from risk factors and ultrasonographic screening of patients with cirrhosis should increase prognosis. [Copyright &y& Elsevier]

Abstract: New perspectives for radiosensitization in hepatocellular carcinoma (HCC) have emerged with the increasing knowledge of mechanisms involved in liver oncogenesis. As a matter of fact, some of these mechanisms have also a role in the response to ionizing radiation. We review some of the major molecular pathways involved in the oncogenesis of hepatocellular carcinoma. These include cellular proliferation patways, repair systems, apoptosis, and angiogenesis. However, there are few preclinical data on concurrent targeted therapies and ionizing radiation in hepatocellular carcinoma models. Preliminary studies are ongoing. Their results might help to better define the potential benefit of such radiosensitizing strategies in the management of hepatocellular carcinoma. [Copyright &y& Elsevier]