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Sylvie Dubois

Publications and source records attributed to Sylvie Dubois.

12 recordsLinked to original sources
PubMed2006

Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas.

Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, plays a role in cell growth, differentiation, and migration. The objectives of this study were to assess the diagnostic value of GPC3 immunostaining in hepatocellular carcinomas (HCCs) and to analyze its expression profile in preneoplastic lesions. Tissue microarrays were built by sampling 54 HCCs and adjacent liver tissues (21 developing from cirrhosis and 33 from normal liver) and 94 cirrhotic macronodules. Fourteen typical liver cell adenomas and 5 with malignant foci were also included. Sections were assessed for GPC3 expression by immunohistochemistry. GPC3 staining was observed in 19 (90%) of 21 HCC cases with cirrhosis and in 18 (64%) of 28 HCC cases with normal liver (P < .01). When staining was positive, it was both membranous and cytoplasmic. Positive staining was observed in 1 case of nonneoplastic adjacent liver. In cases of adenomas, only malignant foci were positive. Among the 94 macronodules, GPC3 immunostaining was noted in 48% (14/29) of high-grade dysplastic or early HCC and in 3% (2/65, P < .001) of benign or low-grade dysplastic macronodules. This study shows that GPC3 is an efficient diagnostic marker of HCC, potentially useful in the differential diagnosis of liver cell adenomas and well-differentiated HCC. Our results also suggest that GPC3 may be considered as an early marker of liver carcinogenesis because it is able to identify some cirrhotic macronodules with malignant potential.

Adult↗
PubMed2006

The Joint Venture Model of Knowledge Utilization: a guide for change in nursing.

Knowledge utilization (KU) is an essential component of today's nursing practice and healthcare system. Despite advances in knowledge generation, the gap in knowledge transfer from research to practice continues. KU models have moved beyond factors affecting the individual nurse to a broader perspective that includes the practice environment and the socio-political context. This paper proposes one such theoretical model the Joint Venture Model of Knowledge Utilization (JVMKU). Key components of the JVMKU that emerged from an extensive multidisciplinary review of the literature include leadership, emotional intelligence, person, message, empowered workplace and the socio-political environment. The model has a broad and practical application and is not specific to one type of KU or one population. This paper provides a description of the JVMKU, its development and suggested uses at both local and organizational levels. Nurses in both leadership and point-of-care positions will recognize the concepts identified and will be able to apply this model for KU in their own workplace for assessment of areas requiring strengthening and support.

Attitude of Health Personnel↗
PubMed2005

Alcohol increases tumor necrosis factor alpha and decreases nuclear factor-kappab to activate hepatic apoptosis in genetically obese mice.

Both obesity and alcohol can cause oxidative stress, cytokine induction, and steatohepatitis. To determine the consequences of their combination, we compared the hepatic effects of moderate ethanol binges in lean and obese ob/ob mice. Mice received water or ethanol (2.5 g/kg) by gastric intubation daily for 4 days, and were killed 2 hours after the last administration. Some obese mice also received pentoxifylline, an inhibitor of tumor necrosis factor-alpha (TNF-alpha) production, before each ethanol administration. In lean mice, these moderate ethanol doses did not increase plasma TNF-alpha and hepatic caspase-3 activity, but triggered some apoptotic hepatocytes. Naive ob/ob mice had a few necrotic and apoptotic hepatocytes, but exhibited little oxidative stress, possibly because of adaptive increases in manganese superoxide dismutase, heat shock protein 70 (Hsp70), mitochondrial cytochrome c, and mitochondrial DNA. Alcohol administration to ob/ob mice did not increase oxidative stress despite increased CYP2E1, but increased plasma TNF-alpha, further increased Hsp70, and profoundly decreased p65 nuclear factor kappaB (NF-kappaB) protein and DNA-binding activity in nuclear extracts. Caspase-3 was activated, and more apoptotic hepatocytes were found in intoxicated obese mice than naive obese mice. In intoxicated obese mice, pentoxifylline fully prevented the increase in plasma TNF-alpha the decrease in nuclear NF-kappaB activity, and the increase in hepatic caspase-3, and it also decreased hepatic triglycerides. In conclusion, obese mice develop adaptations that may limit oxidative stress. Moderate ethanol intoxication does not increase oxidative stress in obese mice, but increases TNF-alpha and also decreases nuclear NF-kappaB activity, thus unleashing the apoptotic effects of TNF-alpha.

Animals↗
PubMed2004

Human chorionic gonadotrophin beta expression in malignant Barrett's oesophagus.

BACKGROUND: Human chorionic gonadotrophin beta (hCGbeta) is expressed in several non-trophoblastic tumours, and this is usually associated with aggressive behaviour. Little is known about hCGbeta expression in Barrett's adenocarcinoma. MATERIALS AND METHODS: We determined the hCGbeta profile in a large series of surgically resected Barrett's adenocarcinoma (a) at mRNA level using real-time quantitative reverse-transcription polymerase chain reaction analysis and (b) at protein level using immunohistochemistry with a polyclonal antibody and with a monoclonal antibody specific for free hCGbeta. We then sought links between the hCGbeta protein expression pattern and clinical and pathological parameters, including patient outcome as well as vascular endothelial growth factor (VEGF) expression. RESULTS: hCGbeta protein expression was observed in 43 of 76 (57%) Barrett's adenocarcinomas. We showed a strong correlation between hCGbeta protein abundance and CGB mRNA level. We observed a statistical link between hCGbeta protein expression and infiltrative tumour type ( P=0.023), perineural neoplastic invasion ( P=0.007) and VEGF protein expression ( P=0.016). hCGbeta expression tended to be associated with a poor outcome (16% versus 36% survival 8 years after resection). CONCLUSION: Expression of hCGbeta correlates with specific infiltrative characteristics and is associated with higher VEGF expression. Both molecules may play a co-ordinated role in the development of Barrett's adenocarcinomas.

Adenocarcinoma↗
PubMed2004

Role of replicative senescence in the progression of fibrosis in hepatitis C virus (HCV) recurrence after liver transplantation.

BACKGROUND: Although hepatitis C virus (HCV) recurrence is almost universal after orthotopic liver transplantation (OLT), the impact of viral infection on liver graft is highly variable and difficult to predict. Because of the possible relationship between replicative senescence (RS) and the accelerated development of liver fibrosis, we aimed to assess the potential role of RS in the severity of HCV-related chronic hepatitis recurrence after OLT. METHODS: One hundred three liver biopsies from 56 patients receiving transplants for HCV-related cirrhosis were studied, including 30 revascularization biopsies and 52 and 21 biopsies performed during and beyond the first year of OLT, respectively. The presence of senescent cells in liver grafts was assessed by the senescence-associated beta-galactosidase (SA-beta-Gal) staining method. Chronic hepatitis was defined by fibrosis stage and necrotico-inflammatory activity grade using the METAVIR score. RESULTS: A total of 34 of the 103 (33%) frozen liver biopsies displayed SA-beta-Gal-positive cells, including 6 (20%) of the revascularization biopsies, 14 (34%) of the biopsies performed within the first year, and 10 (46%) of the biopsies performed beyond 1 year of follow-up. The presence of senescent cells in revascularization biopsies was significantly associated with the degree of ischemic necrosis at time of OLT (P = 0.01) and hepatitis C recurrence in the first year after OLT (P = 0.05). Furthermore, the presence of RS in the biopsy performed within the first year was associated with further development of fibrosis (P = 0.05). CONCLUSIONS: These data show that RS has a significant impact upon the course of liver transplantation, especially in the long-term progression of fibrosis observed in HCV-infected patients.

Adult↗
PubMed2003

Differential expression of perforin and granzyme B in the liver of patients with chronic hepatitis C.

T lymphocytes have been reported to be the predominant inflammatory cells in the liver of patients with chronic hepatitis C. On activation, CD8+ T lymphocytes can exert their cytolytic activity by releasing their granule components, notably perforin and granzyme B. The aim of the present study was to assess whether the granule cytolytic pathway was used by liver-infiltrating CD8+ T lymphocytes. Immunostaining for perforin and granzyme B was performed in 25 patients with chronic hepatitis C, according to the disease activity and their virologic status. Cells stained for perforin and for granzyme B represented 0.15% and 0.10% of the total liver-infiltrating CD8+ T lymphocytes, respectively. Perforin was expressed mainly by activated CD8+ T lymphocytes located in liver lobules. In contrast, granzyme B was expressed mainly by activated CD8+ T lymphocytes located in interface hepatitis and portal tracts. The results were similar in the different groups of patients, whatever the disease activity. In conclusion, this is the first study showing a differential expression of granule components of CD8+ T lymphocytes in the same tissue in vivo. Perforin and granzyme B may be differently expressed by liver-infiltrating CD8+ T lymphocytes, according to their localization in the different specific compartments of the liver, in patients with chronic hepatitis C.

Adult↗
PubMed2003

Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3.

Metalloproteinases (MMPs) and their natural inhibitors (TIMPs) contribute to the regulation of tumor microenvironment. Their expressions are deregulated in almost all human cancers. We report a novel approach to gene therapy of hepatocellular carcinoma (HCC), using repeated injections of DNA plasmids encoding the tissue inhibitors of metalloproteinases (TIMPs) TIMP-2 or TIMP-3, and a novel competent formulation of gene transfer based on nontoxic cationic cholesterol derivatives. The new gene delivery system was efficient in demonstrating the antitumor efficiency of TIMP-2 or TIMP-3 in inhibiting tumor growth of human HuH7 HCC cells xenografted into nude mice. We show, for the first time, an in vivo effect of TIMP-3 in delaying HCC tumor growth. No treatment-related toxicity was noted. An inhibition of angiogenesis and tumor necrosis accompanied the inhibitory effects of TIMP-2 or TIMP-3 on tumor expansion and invasion. We also report a bystander effect produced by transfected HuH7 tumor cells mixed with untransfected cells in 1:1 ratio in culture that resulted in killing 98% of cells within 96 h. In addition, the soluble forms of TIMP-2 and TIMP-3 expressed by transfected cells exerted a cytotoxic effect on untransfected HuH7 cell cultures. Taken together, these results demonstrate the potential efficacy of repeated treatment of secreted TIMP-2 and TIMP-3 for the design of nonviral gene therapy for hepatocarcinoma.

Animals↗
PubMed2002

Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions.

Intraductal papillary-mucinous tumours (IPMTs) of the pancreas are heterogeneous proliferations characterized by a malignant potential. The molecular mechanisms underlying the tumourigenesis process are not well understood. Recently, it has been shown that IPMTs secreting the mucin antigen MUC2 have a better prognosis, but the complete pattern of MUC gene expression has not yet been established. The aims of this study were to evaluate the mucin gene expression in 57 IPMTs and eight related lesions surgically resected and to relate MUC gene expression to the histological diagnosis. In situ hybridization (ISH) was performed in 28 cases with probes specific for the MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes. An immunohistochemical analysis was carried in all 65 cases and in 90 conventional ductal adenocarcinomas of the pancreas using MUC1, MUC2, and MUC5AC antibodies. IPMTs of adenoma (dysplasia) type exhibited high expression of MUC2 (93%), MUC5AC (97%), and, to a lesser extent, of MUC4 (71%), all of which were also observed in colloid carcinomas associated with IPMTs. In contrast, IPMTs with simple hyperplasia, intraductal oncocytic papillary neoplasms, and pyloric glandular adenomas exhibited little or no expression of MUC2. The mucin expression profile supports the existence of two types of invasive tumour associated with IPMTs: a colloid and an ordinary form. The latter shows a pattern similar to the conventional ductal adenocarcinomas with a loss of MUC2 and a gain of MUC1 and has a greater tendency to metastasize. In conclusion, the altered expression of mucin, characteristic of IPMT of adenoma type and of colloid carcinomas, may contribute to the better clinical outcome of these neoplasms, compared to conventional pancreatic ductal adenocarcinomas.

Adenocarcinoma, Mucinous↗
PubMed2002

Inhibition of rat hepatocellular carcinoma tumor growth after multiple infusions of recombinant Ad.AFPtk followed by ganciclovir treatment.

BACKGROUND/AIMS: The antitumor efficiency of thymidine kinase (tk) in Herpes Simplex virus-tk-based gene therapy of rat hepatocellular carcinoma (HCC) was examined by specific transcriptional targeting of tk to tumor cells by the alpha-fetoprotein (AFP) gene promoter and by multiple infusions of recombinant adenovirus Ad.AFPtk. METHODS: We developed a surgical procedure that allows efficient, non-invasive delivery (during 2 months) of recombinant Ad via the intra-hepatic artery (IHA) route. RESULTS: Treatment of tumor-bearing rats with either three or five doses of 5x10(9)pfu Ad.AFPtk, administered every 3 days, and followed by intra-peritoneal treatment with ganciclovir (GCV), resulted in tumor growth inhibition and apoptosis, when compared to untreated tumor-bearing rats or animals treated with Ad.AFPlacZ or buffered saline. No treatment-related toxicity was noted. Antitumor efficacy, based on tumor size and number of tumors, was demonstrated in more than 50% of Ad.AFPtk+GCV-treated rats, as compared to control rats (P<0.0005). CONCLUSIONS: Our results demonstrate the safety and potential of multiple Ad.AFPtk administrations by the IHA route to inhibit HCC tumor growth, and support further clinical investigation of Ad.AFPtk gene therapy for treatment of multifocal tumor lesions in most primary liver cancers.

Adenoviridae↗