Couplage d'un modèle vasculaire bi-niveau et d'un modèle d'acquisition d'images : application à la simulation d'IRM dynamique du Carcinome Hépatocellulaire

La modélisation physiologique permet de mieux comprendre les images médicales et de mettre en évidence, dans l'image, des marqueurs de la pathologie. Dans cet article, nous proposons de coupler un modèle de la vascularisation hépatique à un modèle d'acquisition d'Images de - Résonance Magnétique (IRM), et d'appliquer ces modèles à la simulation d'IRM dynamique du Carcinome Hépatocellulaire (CHC). Le modèle vasculaire intègre les propriétés anatomiques et fonctionnelles clos vaisseaux, modifiées au cours du développement tumoral (densité vasculaire, débits, perméabilité, etc). Il permet de simuler la propagation de différents produits de contraste, ou tenant compte de leurs principales propriétés physiques et magnétiques, aux niveaux macro- et micro-vasculaire. Les images simulées à clos temps d'acquisition différents (phase artérielle, phase portale) présentent clos contrastes proches de ceux observés sur clos images réelles

Assessing Doppler-Derived Pressure Gradients and Liver Echogenicity to Predict Liver Disease

Liver disease causes an estimated 36,000 deaths in the United States each year. Currently, to detect liver disease, an invasive biopsy is required. Other, less invasive diagnostic alternatives are needed. The purpose of this study was to assess the efficacy of a modified form of sonographic screening, including portal, hepatic, and splenic venous pressure, hepatic venous waveform analysis, portal vein diameter, and echogenicity of liver parenchyma in predicting liver disease. The study was based on conversion of a velocity measurement to a pressure gradient, allowing a fluid comparison between known catheterization venous pressures and sonographic Doppler-derived pressure gradients. This study was a secondary data analysis of a data set from 546 patients who received abdominal sonograms at a medical facility in the western United States between March 2010 and December 2010. The dependent variable was liver disease and the independent variables were ECHOGRADE, hepatic venous waveform (HVW), splenic vein pressure gradient (SVPG), modified portal vein pressure gradient (MPVPG), and hepatic vein pressure gradient (HVPG). Logistic regression was used to analyze the data. ECHOGRADE, HVW, and MPVPG in males were found to be statistically significant in detecting liver disease, supporting the theoretical framework and thus documenting a novel use of Doppler for the detection of liver disease. The social change significance of these results is to provide clinicians with an alternative, noninvasive method of diagnosing early liver disease before it progresses into chronic liver disease. With earlier detection, severe adverse health outcomes leading to irreversible liver cirrhosis may be avoided

Liver Biopsy

Liver biopsy is recommended as the gold standard method to determine diagnosis, fibrosis staging, prognosis and therapeutic indications in patients with chronic liver disease. However, liver biopsy is an invasive procedure with a risk of complications which can be serious. This book provides the management of the complications in liver biopsy. Additionally, this book provides also the references for the new technology of liver biopsy including the non-invasive elastography, imaging methods and blood panels which could be the alternatives to liver biopsy. The non-invasive methods, especially the elastography, which is the new procedure in hot topics, which were frequently reported in these years. In this book, the professionals of elastography show the mechanism, availability and how to use this technology in a clinical field of elastography. The comprehension of elastography could be a great help for better dealing and for understanding of liver biopsy

Management of Gastric Cancer

Gastric cancer is the fifth most common cancer and the second most common cause of cancer death worldwide. More than 50% of the patients have advanced disease at diagnosis and in this case the disease has a poor outcome. The staging of gastric cancers is based on endoscopic ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography, in addition to the laparoscopic staging. Many improvements in the surgical techniques have been seen in the last decade. Laparoscopic surgery is an emerging approach which offers important advantages: less blood loss, reduced postoperative pain, accelerated recovery, early return to normal bowel function and reduced hospital stay. D1 lymphadenectomy, with a goal of examining 15 or greater lymph nodes is a standard. D2 dissection is considered as a standard in several institutions especially in eastern Asia. Perioperative chemotherapy and adjuvant concurrent radiochemotherapy are recognized as standards treatments. Palliative chemotherapy is the mainstay treatment of advanced stages of the disease (metastatic and non-operable tumors). Despite these treatment advances, the prognosis of gastric cancer remains poor with a 5-year survival ranging from 10 to 15% in all stages combined

Apoptosis and Medicine

This book looks at the latest research studies on apoptosis in medicine. It is divided into three sections for convenient and easy reading. The first section which comprises two chapters is an introduction of the subject of apoptosis to the uninitiated. The second section which comprises a single solitary chapter looks at apoptosis in normal physiology during bone resorption under mechanical stress. The third and the final section reviews apoptosis in a number of pathological conditions with an emphasis on cancer

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system

Mechanisms of cell cycle arrest and apoptosis induction by sulforaphane and compinatorial effects of sulforaphane and 3,3'-Diindolylmethane on cancer cell growth inhibition

The chemopreventive isothiocyanate sulforaphane, which is derived from broccoli, was shown to induce a mitotic cell cycle arrest in the human colon cancer cell line 40-16. This arrest was followed by mitochondria-dependent apoptosis. Sulforaphane potently inhibited NF-B activation upstream of its nuclear translocation and decreased the expression of a series of anti-apoptotic, NF-B-dependent genes, which supposedly facilitated apoptosis induction. Transient exposure of 40-16 cells to sulforaphane for up to 6 h resulted in reversible G2/M cell cycle arrest and cytostatic growth inhibition, whereas a minimum continuous exposure time of 12 h was necessary for sulforaphane to irreversibly arrest cells in G2/M and subsequently induce apoptosis. Low concentrations of sulforaphane caused a transient decrease in cytoplasmic glutathione levels followed by glutathione induction after 24 h. However, depletion of glutathione did not seem to play a role for sulforaphane-induced apoptosis. Combination effects of sulforaphane and 3,3’-diindolylmethane were investigated in terms of cell growth inhibition in the 40-16 cell line. Sulforaphane and 3,3’-diindolylmethane inhibited cell proliferation antagonistically at low concentrations, but synergistically at cytotoxic concentrations

Integration Of Extracellular And Intracellular Signals Via The Calcium Sensing Receptor (CASR)

The Ca2+-sensing receptor (CaSR) regulates the calcium homeostasis in the human body via sensing fluctuations in the extracellular Ca2+ concentration. Naturally occurring mutations in the CaSR could result in Ca2+ regulation disorders. In the present study, we use several complementary approaches including imaging [Ca2+]i response in living cells at the cellular level and using molecular dynamic (MD) simulations at the atomic level to provide important insights into the behavior of the receptor in both normal and disease statuses. We demonstrated that the molecular connectivity between [Ca2+]o–binding sites is responsible for the functional positive homotropic cooperativity in the CaSR’s response to [Ca2+]o. Naturallyoccurring disease mutations near Site 1 disrupted the cooperativity. We further identified an L-Phe-binding pocket adjacent to Ca2+-binding Site 1, which is essential for functional positive heterotropic cooperativity by having a global impact on all five of the predicted Ca2+-binding sites in the ECD with regards to [Ca2+]o-evoked [Ca2+]i signaling. Furthermore, the CaSR’s ECDs have been expressed using both bacteria and mammalian systems and were characterized using the fluorescence titration spectroscopy, circular dichroism technique as well as the NMR spectroscopy. Our studies show calcium and Phe directly bind to the ECD domain directly and interactively. Moreover, we also demonstrated that intracellular trafficking of the CaSR is a complex process, which involves modulation by calmodulin and can possibly be affected by different CaSR isoforms when expressing in various cell lines. The studies on the isolated proteins will pave the way for future protein crystallization and related structural research

Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common form of liver cancer, has become a major global health problem and is responsible for a steadily increasing number of cancer-related deaths. Although the risk factors for HCC development are well known and great advances have been made through HBV vaccinations, direct-acting antivirals for HCV treatment, and aflatoxin eradication programs, the overall incidence and mortality rates of HCC are still rising. To tackle the burden of HCC, it is essential to understand the principle molecular and cellular processes as well as fundamental clinical challenges. This book provides an overview on several important disease aspects. Chapter 1 reviews recent studies assessing the potential cellular origins of HCC. Chapter 2 describes the newly discovered regulatory roles of the tumor microenvironment on tumor growth and progression. Chapters 3 and 4 outline the most commonly used in vitro systems and animal models of chronic liver disease and HCC in detail. Chapter 5 provides an overview of metabolic reprogramming and dysregulation of lipid metabolism as a newly recognized hallmark of HCC. Chapter 6 details the currently accepted standards and challenges for the surgical management of HCC, while Chapter 7 provides an overview of the recent developments in the field of tyrosine kinase inhibitors. Chapter 8 discusses multidrug resistance to chemotherapy and potential approaches to overcome this clinical obstacle. The book, written by experts from several countries, addresses each topic in sophisticated detail. It will be a valuable resource for clinicians and investigators who are interested in HCC