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Biomedical subjects

F Bataille

Publications and source records attributed to F Bataille.

18 recordsLinked to original sources
PubMed2006

Functional implication of BMP4 expression on angiogenesis in malignant melanoma.

Analyses of malignant melanomas revealed a strong expression of bone morphogenic proteins (BMPs) and their autocrine effect in promoting cell invasion and migration. Here, we report a paracrine effect of BMPs on the vascular network. Both BMP2 and BMP4 induced tube formation as well as the migratory efficiency of microvascular endothelial cells. Melanoma cells with reduced BMP activity attracted less endothelial cells in invasion assays than control cells. Furthermore, reduction of BMPs in melanoma cells had a strong effect on vasculogenic mimicry. Tube formation on matrigel was analysed for melanoma cells as well as in co-cultures of endothelial and melanoma cells. Melanoma cells with reduced BMP activity were not capable of forming cord-like structures by themselves and additionally inhibited tube formation of the endothelial cells. Genes involved in angiogenesis turned out to be strongly downregulated in these cell clones. Tumors derived from cells with impaired BMP activity showed reduced tumor growth or large necrotic areas owing to lack of angiogenesis in in vivo analyses.

Animals↗
PubMed2006

Soluble galectin-3 is a strong, colonic epithelial-cell-derived, lamina propria fibroblast-stimulating factor.

BACKGROUND: Colonic lamina propria fibroblasts (CLPFs) play an important role in the pathogenesis of fibrosis and strictures in Crohn's disease. AIM: To identify colonic epithelial cell (CEC)-derived factors that activate CLPFs. METHODS: Primary human CECs and CLPFs were isolated from control mucosa and interleukin 8 (IL8) of CLPF cultures was quantified by ELISA. Activation of nuclear factor kappaB (NF-kappaB) was shown, and translocation of NF-kappaB was inhibited by a dominant-negative IkappaB-expressing adenovirus. The major CLPF-activating and IL8 inducing protein was purified using fast-performance liquid chromatography (HiPrep 16/60 Sephacryl S-200 High Resolution Column) and sodium dodecyl sulphate gel electrophoresis. RESULTS: A considerable increase in IL8 secretion by CLPFs cultured in CEC-conditioned media compared with that in unconditioned media (155.00 (10.00) pg/microg v 1.434 (0.695) pg/microg) was found. The effect of CEC-conditioned media on CLPF IL8 secretion was NF-kappaB dependent. A protein or DNA array confirmed the involvement of NF-kappaB and activator protein-1. Purification of a candidate band isolated with the use of sodium dodecyl sulphate-polyacrylamide gel electrophoresis and subsequent sequencing showed soluble galectin-3 to be a strong CLPF-activating factor. Depletion of galectin-3 from conditioned media by immunoprecipitation abolished the CLPF stimulatory effect. CONCLUSIONS: Using a classical biochemical approach, soluble galectin-3 was identified as a strong activator of CLPFs produced by CEC. Galectin-3 induced NF-kappaB activation and IL8 secretion in these cells and may be a target for future therapeutic approaches to reduce or avoid stricture formation.

Adult↗
PubMed2006

Expression of Dickkopf genes is strongly reduced in malignant melanoma.

The Dickkopf (DKK) genes were originally identified as factors inducing head formation in Xenopus. The genes code for inhibitors that are involved in Wnt signaling. We speculate that loss of DKK expression plays a role in development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of DKK, especially DKK-3 transcription. We found that DKK-1, -2 and -3 were downregulated or lost in all cell lines and in most of the tumor samples analysed. Reduced DKK-3 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction RT-PCR analysis. Functional assays with stable DKK-3 transfected cell lines revealed that DKK-3 expression increased cell-cell adhesion and decreased cell migration. Further, downregulation of fibronectin, snail-1 and re-expression of E-cadherin was found in the DKK-3 expressing cell clones supporting a role of DKK-3 in tumor progression. Our studies thus indicate that loss of DKK-3 expression may contribute to melanoma progression.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Prognostic relevance of P-cadherin expression in melanocytic skin tumours analysed by high-throughput tissue microarrays.

AIM: To investigate whether protein expression or cellular localisation of P-cadherin is associated with clinicopathological characteristics in benign and malignant melanocytic skin tumours. EXPERIMENTAL DESIGN: P-cadherin expression and the Ki-67 labelling index were analysed immunohistochemically by using tissue microarrays (TMAs). Membranous and cytoplasmic expression was scored semiquantitatively (0 to 2+). RESULTS: P-cadherin protein expression of any intensity (1+ to 2+) was detected in the membrane in 41.5% (132/318) and in the cytoplasm in 64.2% (204/318) of patients. In general, P-cadherin expression was significantly reduced in malignant melanomas (p<0.001) and melanoma metastases (p<0.001), compared with benign nevi. Additionally, loss of membranous P-cadherin was associated with Clark level (p = 0.011) and tumour thickness (p<0.001). Interestingly, a significantly lower P-cadherin expression was shown by dermal nevi than by compound and junctional nevi (p = 0.005; p = 0.025). In primary melanomas, a Ki-67 labelling index <5% was not associated with P-cadherin protein expression, suggesting that loss of P-cadherin expression was not associated with proliferation. None of the other clinical and histological factors analysed was significantly related to P-cadherin expression. Low cytoplasmic P-cadherin expression was associated with tumour recurrence (p = 0.03) in all the patients who were analysed. After testing various multivariate Cox regression models, loss of cytoplasmic P-cadherin expression remained a highly significant adverse risk factor for tumour recurrence in patients with tumours <2 mm. CONCLUSIONS: Loss of cytoplasmic P-cadherin expression is common in advanced melanomas and can be a prognostic marker of progression in patients with melanoma, most useful in patients with primary tumours <2 mm in thickness.

Aged↗
PubMed2006

Expression of Hugl-1 is strongly reduced in malignant melanoma.

The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelial-mesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction (RT-PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.

Blotting, Western↗
PubMed2006

Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo.

The cathepsins D (CTSD), B (CTSB) and L (CTSL) are important for the intracellular degradation of proteins. Increased cathepsin expression is associated with inflammatory diseases. We have shown previously an induction of CTSD expression in intestinal macrophages (IMAC) in inflamed mucosa of patients with inflammatory bowel disease (IBD). Here we investigated the regulation of CTSB and CTSL in IMAC during IBD and effects of CTSD and CTSB/CTSL inhibition in vivo. Human IMAC were isolated from normal and inflamed mucosa. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for CTSB and CTSL mRNA. Immunostaining was used to confirm PCR results. Cathepsin inhibition was investigated in the dextran-sulphate-sodium (DSS) colitis model in mice with application of pepstatin A (CTSD inhibitor), CA-074 (CTSB inhibitor) and Z-Phe-Tyr-aldehyde (CTSL inhibitor). CTSL mRNA was significantly up-regulated in IMAC isolated from IBD mucosa. Up-regulated protein expression was found mainly in areas of mucosal damage by immunostaining. Inhibition of CTSD in mouse DSS colitis was followed by an amelioration of the disease. Inhibitor-treated mice showed a significant lower histological score (HS) and less colon reduction in comparison to controls. Similarly, simultaneous inhibition of CTSB/CTSL was followed by a significant amelioration of colitis. Expression of tissue-degrading cathepsins is increased in IMAC in IBD. Inhibition of CTSD as well as CTSB/CTSL is followed by an amelioration of experimental colitis. The prevention of mucosal damage by cathepsin inhibition could represent a new approach for the therapy of IBD.

Animals↗
PubMed2005

Analysis of intestinal haem-oxygenase-1 (HO-1) in clinical and experimental colitis.

Haem-oxygenase-1 (HO-1) has been shown to exert anti-inflammatory, anti-apoptotic and anti-proliferative effects. We investigated HO-1 expression in patients with inflammatory bowel disease (IBD) and could demonstrate a scattered expression of HO-1 in the intestinal epithelium of severely inflamed colonic mucosa of patients with IBD compared to control specimens such as diverticulitis, suggesting dysregulated expression in IBD. To further analyse potential mechanisms of HO-1 induction in the intestine we employed an in vitro epithelial cell apoptosis model and an experimental colitis model. In vitro induction of HO-1 by the HO-1 inducer cobalt protoporphyrin (CoPP) resulted in a dose-dependent down-regulation of caspase-3 activation in HT-29 cells, indicating an anti-apoptotic function of HO-1 in the intestine. In vivo, preventive HO-1 induction by CoPP in acute dextran sodium sulphate (DSS)-induced colitis led to a significant down-regulation of colonic inflammation (P < 0.01) with a concomitant reduction in interferon (IFN)-gamma - but unaffected interleukin (IL)-10-secretion by isolated mesenteric lymph nodes (P < 0.01). Additionally, TUNEL staining of colonic sections demonstrated fewer apoptotic epithelial cells in the colon of CoPP treated animals. No beneficial effects were observed if HO-1 was induced by CoPP after the onset of acute colitis or in chronic DSS-induced colitis. In conclusion, the data suggest a protective role of HO-1 if it is induced before the onset of inflammation. However, as shown by the lack of effects in established acute or in chronic colitis, the induction of HO-1 may not be a promising approach for the treatment of IBD.

Acute Disease↗
PubMed2005

Expression of augmenter of liver regeneration (ALR) in human liver cirrhosis and carcinoma.

AIMS: To determine the expression of a protein termed augmenter of liver regeneration (ALR), recently found to have a specific and beneficial effect on the process of liver regeneration in normal and diseased human liver. METHODS AND RESULTS: ALR expression in normal and cirrhotic human livers with various underlying diseases as well as in tissue samples of hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) was analysed by immunohistochemistry and quantitative reverse transciptase-polymerase chain reaction (RT-PCR). Expression analysis of ALR in total liver protein extracts by Western blotting showed mainly dimeric ALR protein. Immunohistochemically, cytosolic and perinuclear immunosignals were found in hepatocytes and cholangiocytes in normal, cirrhotic or cancerous liver tissue and only weak signals in some endothelial cells in normal livers. Quantitative mRNA analysis revealed significantly increased ALR expression in cirrhosis compared with normal liver tissue. In HCC and CCC ALR mRNA expression was also significantly enhanced compared with normal liver tissue, but expression levels did not differ from the matching non-neoplastic tissue in the same patient. CONCLUSIONS: The findings suggest an important role for ALR in hepatocellular regeneration in liver cirrhosis as well as in hepatocarcinogenesis and therefore its potential value in the clinical diagnosis of hepatic cirrhosis and cancer.

Aged↗
PubMed2005

Glycoprotein (gp) 96 expression: induced during differentiation of intestinal macrophages but impaired in Crohn's disease.

BACKGROUND: The glycoprotein (gp) 96 links the adaptive with the innate immune system. It is a chaperone with a binding domain for peptides generated by proteasomal degradation. During cellular stress, peptide loaded gp96 can be released and presented to T cells by antigen presenting cells (APCs). METHODS: mRNAs from in vitro differentiated macrophages (iv mac) and normal intestinal macrophages (IMACs) were compared by subtractive hybridisation and Affymetrix GeneChip analysis. Differentiation induced expression of gp96 was investigated in the multicellular spheroid (MCS) model. In vivo gp96 protein expression was detected by double labelling immunohistochemistry of human colon and in the CD4+ CD62L+ T cell transfer mouse model. RESULTS: Five of 76 clones obtained by subtractive hybridisation revealed >99% sequence homology to gp96. Affymetrix GeneChip analysis confirmed induction of gp96 in IMACs. Gp96 mRNA was detected in IMACs from normal and intestinal bowel disease mucosa. Induction of gp96 protein was observed after seven days in the MCS model of IMAC differentiation. Immunohistochemistry confirmed the presence of gp96 protein in IMACs in normal mucosa as well as in mucosa from patients with ulcerative colitis and diverticulitis. In mucosa from Crohn's disease (CD) patients, gp96 protein was not detectable. In the CD4+ CD62L+ T cell transfer mouse model, gp96 was verifiable in non-activated IMACs. CONCLUSION: Gp96 is induced during differentiation of normal IMACs but is not detected in IMACs in CD mucosa. As gp96 has been described as having a role in tolerance induction, this may be relevant for loss of tolerance against luminal bacteria found in CD patients.

Animals↗
PubMed2004

[Angiosarcoma as a rare differential diagnosis in spontaneous rupture of the spleen].

A splenectomy was performed in a 37-year-old woman because of spontaneous rupture of the spleen. Primary angiosarcoma of the spleen was diagnosed postoperatively based on histology. Primary angiosarcoma of the spleen is a very rare neoplasm with disastrous prognosis. Immunohistochemical and ultrastructural examinations are necessary to verify the diagnosis because the histopathological picture of the tumor is variable. Due to the small number of reported cases, there are no guidelines for adjuvant or palliative therapy, and up to today all adjuvant means of radiotherapy and chemotherapy have not improved the prognosis of the patients.

Adult↗
PubMed2004

Morphological characterisation of Crohn's disease fistulae.

BACKGROUND: Fistulae are a common complication in up to 35% of all patients with Crohn's disease. Their therapy is difficult and frequently unsatisfactory. To date, no histological comparison of Crohn's disease fistulae with non-inflammatory bowel disease fistulae has been performed. In addition, Crohn's disease fistulae have not been well characterised morphologically. METHODS: Eighty four fistulae from Crohn's disease patients were compared with 13 fistulae from controls. Haematoxylin-eosin staining, electron microscopy, and immunohistochemistry for panCytokeratin (epithelial cells), CD20 (B cells), CD45R0 (T cells), and CD68 (macrophages) were performed according to standard techniques. In addition, histopathological findings were compared with clinical and laboratory data. RESULTS: In 31.0% of controls and 27.4% of Crohn's disease specimens, fistulae had a lining of flattened intestinal epithelium without goblet cells or, in the case of cutaneous/perianal disease, narrow squamous epithelium. Non-epithelialised fistulae were covered by a thin layer of (myo)fibroblasts, focally forming a new basement membrane, as demonstrated by electron microscopy. All fistulae were surrounded by granulation tissue. Crohn's disease fistulae presented with central infiltration by CD45R0+ T cells, followed by a small band of CD68+ macrophages and dense accumulation of CD20+ B cells. In contrast, in controls, there was dense infiltration by CD68+ macrophages with only few CD20+ B cells and CD45R0+ T lymphocytes. CONCLUSIONS: Fistulae in Crohn's disease differ markedly from non-Crohn's disease fistulae with regard to their cellular composition. The presence of an epithelial lining in a subgroup of fistulae may be important for the therapeutic approach and healing process.

Adolescent↗
PubMed2003

A multimodal treatment approach including high-dose chemotherapy in very advanced gastric cancer: evidence for control of metastatic disease.

The present multimodal treatment approach was designed to achieve prolonged tumor control in advanced gastric cancer. A total of 26 patients with stage IV gastric cancer (metastatic disease n=25), ECOG performance status 0-3 and laparoscopically evaluated peritoneal status received a modified EAP schedule to prove chemosensitivity and to mobilize autologous peripheral blood stem cells (aPBSC). Patients without progressive disease proceeded to tandem high-dose chemotherapy (HD-CT) and aPBSCT. Patients with >50% reduction of the target lesion received a second cycle of HD-CT. Responders were selected for local R0 resections (D2 resection) according clinical criteria. Of 26 patients, 20(77%) achieved partial remission after dose-intensive chemotherapy: local R0 resection was achieved in 12 out of 14 patients selected for surgery (46% of all patients). Eight of these R0-resected patients initially had peritoneal carcinomatosis. With a median follow-up of 3.2 years, four patients are still alive. The median overall survival was 8.4 months (CI 2.5-14.4 months), for histologic regression grade 3 (seven out of 25 patients, 28%) 29 months (CI 12-46 months). The combined treatment approach is tolerable and feasible in advanced disease and opens a therapeutic window for a significant proportion of patients, even in cases with histologically proven peritoneal carcinomatosis.

Adult↗
PubMed2003

Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancer.

AIMS: To evaluate the usefulness of molecular markers in predicting histopathological and clinical response to preoperative high dose chemotherapy (HDCT) and survival of patients with advanced gastric cancer. METHODS: In a phase II trial, 25 patients with metastatic gastric cancer received preoperative tandem HDCT consisting of etoposide, cisplatin, and mitomycin, followed by autologous bone marrow transplantation to achieve surgical resectability. Samples before and after treatment, from normal and tumour tissue, were characterised histopathologically, and both p53 and BAX expression was analysed by immunohistochemistry. Pretreatment formalin fixed, paraffin wax embedded samples from normal and tumour tissue were microdissected, and the extracted DNA was preamplified using improved primer extension preamplification polymerase chain reaction. Detection of microsatellite instability (MSI) or loss of heterozygosity (LOH) was performed using markers for p53, BAX, BAT25, BAT26, D2S123, D17S250, and APC. Exons 5-9 of the p53 gene were sequenced directly on ABI 373. RESULTS: Four parameters were significantly associated with response to chemotherapy and prolonged overall survival: positive p53 immunostaining, positive p53 mutation status before chemotherapy, strong histological regression induced by preoperative HDCT, and surgical treatment. Patients's sex or age, tumour location or stage, lymph node status, Lauren classification, MSI, or LOH did not influence duration of survival significantly in this high risk population. CONCLUSION: Positive p53 immunostaining and p53 mutation status in pretreatment tumour biopsies might be useful molecular predictors of response and prognosis in patients with advanced gastric cancer treated by preoperative HDCT.

Adult↗
PubMed2001

MedB-1, a human tumor cell line derived from a primary mediastinal large B-cell lymphoma.

Primary mediastinal B-cell lymphoma is a locally highly aggressive but poorly disseminating tumor composed of medium sized or large cells most probably of thymic medullary origin. It has a mature B-cell phenotype, typically lacks immunoglobulin expression and has variable defects in expression of HLA-molecules. We present here a cell line, MedB-1, derived from such a tumor. As is frequently found in mediastinal B-cell lymphomas in situ, MedB-1 is CD10(-), CD19(+), CD21(-), CD22(+), CD23(+), CD25(-), CD37(+), CD38(-), CD39(+), CD40(+), CD54(+), CD95(+). Like the parental tumor, MedB-1 lacks HLA-A,B,C alpha-chains and beta(2)microglobulin and expresses HLA-D molecules at decreased levels. Both parental tumor and MedB-1 cells are clonally related as shown by immunoglobulin heavy chain gene rearrangement analysis. Unlike the parental tumor tissue, the MedB-1 cell line cytoplasmically expresses IgG/kappa in a very small subset of cells under standard culture conditions. MedB-1 does not contain any Epstein-Barr virus DNA. In a tissue adhesion assay MedB-1 cells showed an extensive binding to the medullary region of normal thymus. Altogether, MedB-1 is a suitable tool for functional and molecular analysis of this distinct lymphoma entity.

B-Lymphocytes↗
PubMed2001

Comparison between two models of cooling surfaces using blowing.

To protect surfaces against high temperatures, the blowing through a porous material is studied. The geometry is that of a circular cylinder in cross-flow and the effectiveness of the blowing for the thermal protection is numerically investigated. Two models are developed for the blowing simulation and comparisons are made with experimental data obtained in a heated wind-tunnel. It is shown that the blowing strongly affects the dynamical and thermal profiles over the surface, thickening the boundary layers and decreasing the external transfer coefficients. It results in a lower viscous drag and thermal stress. The wall temperature dramatically decreases with blowing and the heat flux is also affected.

Journal Article↗
PubMed1999

Nature of the energy transfer process in compressible turbulence.

Using a two-point closure theory, the eddy-damped-quasinormal-Markovian approximation, we have investigated the energy transfer process and triadic interactions of compressible turbulence. In order to analyze the compressible mode directly, the Helmholtz decomposition is used. The following issues were addressed: (1) What is the mechanism of energy exchange between the solenoidal and compressible modes, and (2) is there an energy cascade in the compressible energy transfer process? It is concluded that the compressible energy is transferred locally from the solenoidal part to the compressible part. It is also found that there is an energy cascade of the compressible mode for high turbulent Mach number. Since we assume that the compressibility is weak, the magnitude of the compressible (radiative or cascade) transfer is much smaller than that of the solenoidal cascade. These results are further confirmed by studying the triadic energy transfer function, the most fundamental building block of the energy transfer.

Journal Article↗