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Biomedical subjects

Jean-Yves Scoazec

Publications and source records attributed to Jean-Yves Scoazec.

At least 19 recordsLinked to original sources
PubMed2007

Intestinal MUC2 and gastric M1/MUC5AC in preneoplastic lesions induced by 1,2-dimethylhydrazine in rat: a sequential analysis.

Our study was performed to sequentially analyze the expression of the intestinal mucin MUC2 and of the gastric mucin MUC5AC as indicators during progression of preneoplastic biomarkers in rat colon. F344 rats were sacrificed 2, 4, 8, 12, 24 and 36 weeks after injection of 1,2-dimethylhydrazine (DMH, 200 mg/kg, i.p.). The expression of MUC2 and of MUC5AC was studied by immunohistochemistry in preneoplastic lesions classified in two categories: histologically altered foci (HAF) and beta-catenin accumulated crypts (BCAC). HAF appeared 4 weeks after DMH injection. Their crypt multiplicity stagnated with time (3-4 crypts/foci) but gastric MUC5AC mucin was always observed in some goblet cells of the lesions of this category. In contrast, MUC2-immunostaining was not modified compared to the adjacent crypts. Double-immunofluorescence revealed that goblet cells which produced MUC5AC continued to express MUC2. In BCAC, crypt multiplicity and mucin expression strongly evolved with time. These lesions were observed only 8 weeks after DMH-injection. At this stage, 20% of BCAC showed a decreased MUC2 expression and 33% were MUC5AC immunopositive. At the 36-week point, 43% of BCAC had a reduced MUC2 staining and 90% were positive for MUC5AC. This immunopositivity was often observed in all the cells of these lesions. Seldom, some BCAC were depleted at the same time in MUC2 and in MUC5AC. Similar alterations in mucin expression were observed in human colonic pre-neoplastic lesions. These findings suggest that a decrease in MUC2 expression and staining of MUC5AC in non-goblet-like cells predicts histological progression of preneoplastic lesions.

1,2-Dimethylhydrazine↗
PubMed2006

Matrilysin 1 influences colon carcinoma cell migration by cleavage of the laminin-5 beta3 chain.

Matrilysin 1 [matrix metalloproteinase 7 (MMP7)] is one of the most important metalloproteinases expressed in human tissues. This enzyme is generally not expressed by normal differentiated epithelial colon cells, but has been shown to be up-regulated in human colon adenomas and adenocarcinomas. Little is known about the role of MMP7 in cell invasion and its involvement in proteolytic processes. By searching the ligands of MMP7 in the colonic carcinoma cells HT29, we identified laminin-5/laminin-332 (LN5) as a specific target for MMP7 enzymatic activity. LN5, composed of alpha3, beta3, and gamma2 chains, is an important component of epithelial basement membranes where it induces firm adhesion and hemidesmosome formation. In this study, we show that LN5 and MMP7 are coexpressed in HT29 cells as well as in HT29 xenograft tumors and human colorectal adenocarcinomas. We provide evidence that human LN5 is a ligand for MMP7 and that a specific cleavage occurs in its beta3 chain, giving rise to a carboxyl-terminal beta3 chain fragment of 90 kDa. We have identified the MMP7 cleavage site at position Ala(515)-Ile(516) in the beta3 chain. Videomicroscopic analysis of HT29 cells plated on LN5 substrates reveals that the MMP7-processed LN5 significantly enhances cell motility. Moreover, the delayed migration of HT29 cells obtained after specific inhibition of MMP7 reinforces the hypothesis supporting its involvement in cell migration. Altogether, our results show that MMP7 is likely to play a crucial role in the regulation of carcinoma cell migration by targeting specific proteolytic processing of the LN5 beta3 chain.

Adenocarcinoma↗
PubMed2006

Liver regeneration and hemodynamics in pigs with mesocaval shunt.

BACKGROUND: A surgical technique using a mesocaval shunt and downstream ligation of the superior mesenteric vein has been recently proposed to overcome the size limitations that restrict the use of partial liver grafts. We designed an experimental study in pigs to evaluate the capacities of liver regeneration and hemodynamic changes after completion of this procedure. MATERIAL AND METHODS: Liver regeneration after left hepatectomy was compared between two groups of five pigs, with or without mesocaval shunt, sacrificed 11 to 14 days after surgery. A third group of five animals was used for hemodynamic studies. RESULTS: Liver regeneration in study animals was 45.3% of controls. This was obtained despite a reduction of the venous inflow to 15.6% of the control, resulting in a net decrease of the total blood inflow to 56% of the control, despite a compensatory increase in the arterial inflow. There was no significant difference in mitotic index, hepatocellular size, and glycogen content between study and control animals. CONCLUSION: Our experimental study confirms that the regenerative capacities of the pig liver are largely preserved despite the dramatic reduction of the venous blood inflow, reduced to its gastroduodenosplenopancreatic component. This lends further support to the hypothesis that the gastroduodenosplenopancreatic blood is enriched in hepatotrophic factors, likely to originate from the pancreas and duodenum.

Anastomosis, Surgical↗
PubMed2006

Evaluation of IGL-1 preservation solution using an orthotopic liver transplantation model.

AIM: To compare, in a pig liver transplantation model, the protective effect of UW with that of IGL-1, a high-sodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply. METHODS: All livers were harvested and grafted orthotopically according to standard techniques. The livers were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7) at 4 degree centigrade. In a sham group (n = 4), the livers underwent a 60-min warm ischemia at 37 degree centigrade. The hepatocellular injury was assessed in organ preservation solution washed out from the graft at the end of ischemic storage (before revascularization), and in serum 2 h after reperfusion and daily for up to 6 d. RESULTS: Livers preserved in IGL-1 solution released markedly less AST than that preserved in the UW solution before and after revascularization (P < 0.05). Besides, the activity of creatine kinase-BB, a marker of sinusoidal lining cells injury, was higher in the UW group than in the IGL-1 group (P < 0.05). Histological results showed less necrotic regions in livers preserved in IGL-1 solution; however, no difference was observed for inflammation. CONCLUSION: IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against preservation-reperfusion injuries.

Animals↗
PubMed2006

Feasibility of preoperative combined radiation therapy and chemotherapy with 5-fluorouracil and cisplatin in potentially resectable pancreatic adenocarcinoma: The French SFRO-FFCD 97-04 Phase II trial.

PURPOSE: More than 80% of patients who undergo a potentially curative resection for pancreatic cancer develop local or distant recurrence. Neoadjuvant chemoradiotherapy might offer potential benefits regarding local and systemic control and survival. This multi-institutional Phase II trial explored the feasibility of preoperative chemoradiation in this situation. METHODS AND MATERIALS: Treatment consisted of concurrent radiotherapy (50 Gy within 5 weeks), and chemotherapy with 5-fluorouracil (300 mg/m(2)/day, 5 days/week, 5 consecutive weeks) and cisplatin (20 mg/m(2)/day, Days 1-5 and 29-33), followed by surgical resection of the pancreatic tumor in patients without progression. RESULTS: A total of 41 patients were enrolled. Of these, 38 (93%) received > or =47 Gy; 30 patients (73%) received > or =75% of the prescribed doses of chemotherapy. Surgical resection was performed in 26 patients (63%). Because of local or metastatic progression, 5 patients (12%) did not undergo surgery and 10 underwent surgery without resection of the pancreatic tumor. Operative mortality was 2.8%. Among 40 evaluable patients, 27 were successfully treated (67.5%; 95% CI, 50.9-81.4%). CONCLUSIONS: Pancreatic cancer is chemo-radiosensitive. The proposed pre-operative scheme is feasible, does not prevent successful surgery, and must be tested on a Phase III setting. Yet, the large proportion of tumor progression during and after chemoradiation justifies the use of more efficient drugs such as Gemcitabine, and optimized radiotherapy including new techniques such as intensity-modulated radiation therapy.

Adenocarcinoma↗
PubMed2006

HIP/PAP, a member of the reg family, is expressed in glucagon-producing enteropancreatic endocrine cells and tumors.

Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) protein, a member of the reg family, is constitutively expressed by some specialized epithelial cell subsets in the digestive tract and the pancreas. We performed a detailed analysis of the expression of HIP/PAP protein in normal digestive endocrine cells according to their localization, lineage, and differentiation stage, and in digestive endocrine tumors according to their site of origin and hormonal profile. In both adult and fetal normal tissues, HIP/PAP expression was detected only in endocrine cells of the small intestine, ascending colon, and pancreas. Two different expression patterns were identified: (a) a strong cytoplasmic labeling observed in the endocrine cells of the digestive mucosa and the outer rim of Langerhans islets specialized in the synthesis of glucagon and glucagon-like peptides; (b) a weak cytoplasmic immunoreactivity observed in the other pancreatic endocrine cell populations. HIP/PAP expression was detected in 36 of the 184 cases of digestive endocrine tumors examined; 32 of these cases (89%) were pancreatic. The 2 patterns observed in the normal state were retained: (a) a strong labeling was observed in 5% to 100% of tumor cells in 26 tumors, all expressing glucagon or glucagon-like peptides; (b) a weak labeling was present in 10 tumors, presenting various hormonal profiles. In conclusion, a strong expression of HIP/PAP is characteristic of glucagon-producing normal and neoplastic enteropancreatic endocrine cells. Our results lend further support to the concept that members of the reg family play regulatory roles in various endocrine cell populations and that their expression in endocrine cells is lineage-specific.

Adolescent↗
PubMed2006

Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.

Hepatocellular adenomas are benign tumors that can be difficult to diagnose. To refine their classification, we performed a comprehensive analysis of their genetic, pathological, and clinical features. A multicentric series of 96 liver tumors with a firm or possible diagnosis of hepatocellular adenoma was reviewed by liver pathologists. In all cases, the genes coding for hepatocyte nuclear factor 1alpha (HNF1alpha) and beta-catenin were sequenced. No tumors were mutated in both HNF1alpha and beta-catenin enabling tumors to be classified into 3 groups, according to genotype. Tumors with HNF1alpha mutations formed the most important group of adenomas (44 cases). They were phenotypically characterized by marked steatosis (P < 10(-4)), lack of cytological abnormalities (P < 10(-6)), and no inflammatory infiltrates (P < 10(-4)). In contrast, the group of tumors defined by beta-catenin activation included 13 lesions with frequent cytological abnormalities and pseudo-glandular formation (P < 10(-5)). The third group of tumors without mutation was divided into two subgroups based on the presence of inflammatory infiltrates. The subgroup of tumors consisting of 17 inflammatory lesions, resembled telangiectatic focal nodular hyperplasias, with frequent cytological abnormalities (P = 10(-3)), ductular reaction (P < 10(-2)), and dystrophic vessels (P = .02). In this classification, hepatocellular carcinoma associated with adenoma or borderline lesions between carcinoma and adenoma is found in 46% of the beta-catenin-mutated tumors whereas they are never observed in inflammatory lesions and are rarely found in HNF1alpha mutated tumors (P = .004). In conclusion, the molecular and pathological classification of hepatocellular adenomas permits the identification of strong genotype-phenotype correlations and suggests that adenomas with beta-catenin activation have a higher risk of malignant transformation.

Adenoma, Liver Cell↗
PubMed2006

[Multiple gastro-intestinal stromal tumors (GIST) in a patient with type I neurofibromatosis revealed by chronic bleeding: pre-operative radiological diagnosis].

Recent studies have pointed out a high incidence of GIST, usually multiple and of small intestinal location, in patients with type I neurofibromatosis. We here report an additional case, revealed by chronic gastro-intestinal bleeding and diagnosed at pre-operative imaging studies. A 56-year-old patient, with known type I neurofibromatosis, was referred to our department for the exploration of chronic gastro-intestinal bleeding during anti-aggregant therapy. Endoscopical examination was negative. Enteroscanner showed the presence of four tumor lesions, 3 in the jejunum and 1 in the ileum. Segmental surgical resections were performed. At histological examination, 2 of among the 3 jejunal lesions were diagnosed as typical GIST, of low risk of malignancy, CD117+, CD34+, whereas the last jejunal and ileal lesions were identified as fibroid tumors. Mutations of c-kit gene and of the gene coding for PDGF-Ralpha were not detected. Post-operative recovery was uneventful; no recurrent bleeding was observed. Our case report underlines the potential role of enteroscanner in the management of patients with type I neurofibromatosis with possible digestive complications. It also emphasizes the importance of an accurate diagnosis of the digestive tumors associated with type I neurofibromatosis: GISTs are frequent in this setting and must not be misdiagnosed as neurofibromas.

Chronic Disease↗
PubMed2006

MUC5AC, a gel-forming mucin accumulating in gallstone disease, is overproduced via an epidermal growth factor receptor pathway in the human gallbladder.

Despite evidence that mucin overproduction is critical in the pathogenesis of gallstones, the mechanisms triggering mucin production in gallstone disease are unknown. Here, we tested the potential implication of an inflammation-dependent epidermal growth factor receptor (EGF-R) pathway in the regulation of gallbladder mucin synthesis. In gallbladder tissue sections from subjects with cholesterol gallstones, mucus accumulation was associated with neutrophil infiltration and with increased expressions of EGF-R and of tumor necrosis factor-alpha (TNF-alpha). In primary cultures of human gallbladder epithelial cells, TNF-alpha induced EGF-R overexpression. In the presence of TNF-alpha, EGF-R ligands (either EGF or transforming growth factor-alpha) caused significant increases in MUC5AC mRNA and protein production, whereas expression of the other gallbladder mucins MUC1, MUC3, and MUC5B was unchanged. In addition, on gallbladder tissue sections from subjects with gallstones, increased MUC5AC immunoreactivity was detected in the epithelium and within mucus gel in the lumen. Studies in primary cultures demonstrated that MUC5AC up-regulation induced by the combination of TNF-alpha with EGF-R ligands was completely blunted by inhibitors of EGF-R tyrosine kinase and mitogen-activated protein/extracellular signal-related kinase kinase. In conclusion, an inflammation-dependent EGF-R cascade causes overproduction of the gel-forming mucin MUC5AC, which accumulates in cholesterol gallstone disease. The ability to interrupt this cascade is of potential interest in the prevention of cholesterol gallstones.

Cells, Cultured↗
PubMed2005

beta-Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a mu-opioid pathway.

We have recently shown that beta-casomorphin-7, a milk opioid peptide, strongly stimulates mucin secretion in the rat jejunum through a nervous pathway and opioid receptor activation. In this study, the hypothesis that beta-casomorphin-7 may also act directly on intestinal goblet cells was investigated in vitro in rat and human intestinal mucin-producing cells (DHE and HT29-MTX) using quantitative and semiquantitative RT-PCR and ELISA. The presence of mu-opioid receptors was demonstrated in rat goblet cells in the upper half of the colonic crypt and in the two cell lines by immunohistochemistry and RT-PCR. In rat DHE cells, beta-casomorphin-7 increased the expression of rat mucin (rMuc)2 and rMuc3 but not rMuc1, rMuc4, and rMuc5AC. This effect was time and dose dependent, with the maximum of increase in transcripts being noticed for a concentration of 10(-4) M after 2 h of stimulation for rMuc2 (225% of controls) and 4 h of stimulation for rMuc3 (208% of controls). Mucin secretion was maximally increased after 8 h of stimulation. Interestingly, these effects were prevented by pretreatment of the cells with the mu-opioid antagonist cyprodime. In human HT29-MTX cells, beta-casomorphin-7 (10(-4) M) also increased MUC5AC mRNA levels (219% after 24 h of stimulation) and the secretion of this mucin (169% of controls). In conclusion, beta-casomorphin-7 may contribute significantly to mucin production via a direct effect on intestinal goblet cells and the activation of mu-opioid receptors. Because intestinal mucins have a crucial mucosal protective function, dairy products containing beta-casomorphin-7 may improve intestinal protection and could have dietary and health applications.

Animals↗
PubMed2005

High-resolution MR imaging appearance of colonic tissue in rabbits using an endoluminal coil.

PURPOSE: This study assessed the value of high-resolution magnetic resonance imaging (MRI) of the distal colon by means of a dedicated endoluminal magnetic resonance receiver coil on a 1.5-T clinical scanner. MATERIALS AND METHODS: To this end, single-loop, receive-only radio-frequency coils, housed in 18 F sheaths, were built. A 1.5-T clinical imager was used. A 18 French diameter internal MRI receiver coil was inserted into the distal colon in 15 New Zealand rabbits to obtain high-resolution magnetic resonance images by using T1-weighted Flash sequences with and without Fat Saturation (FS), T2-weighted True-Fisp, turbo spin-echo, and T1-weighted Flash FS after contrast media injection. Images were compared to histological sections. RESULTS: An adequate image quality was obtained in all specimens without significant artefacts. Based on histological reports, a five-layer structure of the wall was considered normal. On different MR sequences, only two layers were identified on the images of all rabbits specimens. The nearest layer to the mucosal surface was usually seen as a hyper intense layer and likely corresponds to the mucosa. The highest difference of signal value between internal and external layers was performed on 2D Fat saturation T1 weighted gradient echo. Comparison of mean signal value between the internal and external layers was statistically different in for each sequence used in our protocol (P < 0.05). CONCLUSION: Dedicated endoluminal RF coil provides good spatial resolution at the region of interest. On this prospective study of in vivo rabbit, evaluation of colon walls allowed to provide detailed information.

Animals↗
PubMed2005

Preoperative evaluation of intraductal papillary mucinous tumors performed by pancreatic magnetic resonance imaging and correlated with surgical and histopathologic findings.

PURPOSE: To evaluate the effectiveness of magnetic resonance imaging (MRI) in predicting the location, type of ductal involvement, and malignant transformation of intraductal papillary mucinous (IPM) pancreatic tumors made in a preoperative routine exam. MATERIALS AND METHODS: A total of 24 patients with histologic confirmation of IPM tumor (IPMT) were included in this study. The MR images obtained in operation patients were retrospectively assessed. Two radiologists who were unaware of the initial interpretations of the images independently analyzed the MRI studies and characterized the type of lesions, location, and signs of malignant transformation. Interobserver agreement was determined with weighted kappa statistics. After consensus of both radiologists, the observer performances for the MRI interpretations were compared with surgical and histologic results using weighted kappa statistics and Fisher test. RESULTS: At macroscopic examination, lesions were of combined type in 17 cases and of branch duct type in seven cases. At histologic analysis, three cases were classified as benign, three as borderline tumors, and 18 as carcinomas (eight in situ, 10 invasive). The lesions were located mainly in the head or uncinate process (N = 16) or were diffuse or multifocal (N = 2). Excellent agreement was found between the interpreters (0.90) in the evaluation of ductal involvement, good in the evaluation of lesion location (0.80) and in the diagnosis of malignant transformation (0.74). The correlation between MRI and histopathologic results was excellent in the evaluation of ductal involvement (0.90, sensitivity = 100%, specificity = 94%) and moderate in the evaluation of lesion location (0.57, sensitivity = 87%, specificity = 56%) and in the diagnosis of malignant transformation (0.60, sensitivity = 83%, specificity = 83%). CONCLUSION: MRI is an effective method of characterizing IPMT in preoperative practice. The predictive sign of IPM pancreatic tumor malignancy at MRI included only the presence of solid mass or mural nodules.

Adenocarcinoma, Mucinous↗
PubMed2005

Adaptative bile duct proliferative response in experimental bile duct ischemia.

BACKGROUND/AIMS: A rat model of bile duct ischemia was established and used to examine the potential of bile duct proliferation to provide an adaptative response in cholestatic disorders. METHODS: Rats underwent partial or complete arterial deprivation of the liver. Serum biochemical tests, histological analyses and bile secretion measurements were performed at different time points up to 6 weeks after surgery. RESULTS: Rats developed biochemical signs of cholestasis exclusively after complete arterial deprivation. Within 4h, cholangiocytes in these rats showed morphological signs of cell damage. After 48h, they displayed VEGF expression and became proliferative. The proportion of Ki67-labeled cholangiocytes ( approximately 30%) was similar in interlobular bile ducts and periportal ductules. A ductular reaction made of well-formed bile ducts confined to portal tracts developed within 1 week. Bile flow which was initially decreased, was restored at 3 weeks, while the biochemical signs of cholestasis completely resolved at 6 weeks. At this time, the number of bile duct sections was maximal. Fibrosis intensity was also maximal, although moderate (<F2 METAVIR staging) as assessed by Sirius-red staining morphometry. CONCLUSIONS: In the present model of bile duct ischemia, ductular reaction derives from bile ducts of all anatomical compartments, and provides a poorly fibrogenic functional response to biliary dysfunction.

Animals↗