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Biomedical subjects

J Boniver

Publications and source records attributed to J Boniver.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dendritic cells induce the death of human papillomavirus-transformed keratinocytes.

Although human papillomavirus (HPV) antigens are expressed in a majority of (pre)neoplastic lesions (squamous intraepithelial lesions; SILs) of the uterine cervix, progression to invasive cancer may occur, which suggests that the presentation of viral antigens to the immune system is deficient in some SILs. To determine whether professional antigen-presenting cells die in SILs, we assayed for the apoptosis of immature dendritic cells (DC) in organotypic cultures of HPV-transformed keratinocytes, which reproduce many features of in vivo observed SILs. Unexpectedly, the infiltration of organotypic cultures by DC specifically induced the apoptosis of HPV+ tumor cells, whereas DC were not affected. In the same conditions and in coculture experiments, apoptosis was not observed in normal keratinocytes. The induction of apoptosis required membrane contacts between DC and HPV-transformed keratinocytes. Although the HPV+cell lines were sensitive to the effects of TRAIL, soluble TRAILR2-Fc did not block the DC-induced apoptosis. Furthermore, although FasL and Fas were detected on DC and HPV+ cell lines, respectively, functional analysis revealed that this pathway is not responsible for the apoptosis induced by the DC. All together these results suggest that DC may be at the interface between innate and adaptive immunity by inducing the apoptosis of (pre)neoplastic cells.

Antibodies↗
PubMed2001

Genetic imbalances in preleukemic thymuses.

To understand the molecular mechanisms involved in preleukemia, the suppression subtractive hybridization method was used in a murine radiation-induced thymic lymphoma model. Seventeen mRNAs overexpressed in preleukemic thymuses were identified: mouse laminin binding protein (p40/37LBP), E25 protein, Rattus norvegicus clone BB.1.4.1, profilin, poly(A) binding protein (PABP), mouse high mobility group protein 1, topoisomerase I, clusterin, proteasome RC1 subunit, rat prostatein C3 and C1 subunits; two ESTs and four unknown genes. The overexpression of PABP, clusterin, profilin, and the p40/37LBP mRNAs was confirmed in preleukemic thymuses and can be related to some cellular events observed during the preleukemic period, i.e., alterations of cell cycle and apoptosis properties. The p40/37LBP and 67-kDa laminin receptor proteins were upregulated during the preleukemic period. The data suggest that additional studies on p40/37LBP and 67-kDa laminin receptor regulation are required to evaluate their potential role in the lymphoma prevention by TNF-alpha and IFN-gamma.

Animals↗
PubMed2001

The organotypic culture of HPV-transformed keratinocytes: an effective in vitro model for the development of new immunotherapeutic approaches for mucosal (pre)neoplastic lesions.

The purpose of this study is to develop a reliable in vitro human model to test new immunotherapeutic approaches for squamous cell carcinoma that develop on mucosal surfaces. The organotypic (raft) culture permits cells to proliferate and differentiate at an air-liquid interface on a dermal equivalent support. Normal keratinocytes stratify and fully differentiate in a manner similar to the normal squamous epithelial tissues, while human papillomavirus-immortalized and established squamous carcinoma cell lines exhibit dysplastic morphologies similar to (pre)neoplastic lesions seen in vivo. We have demonstrated the ability of these organotypic cultures to be manipulated by altering the epithelial stratification with cytokines (interferon-gamma and tumor necrosis factor-alpha) and by integrating activated lymphocytes or dendritic cells into the in vitro formed epithelial sheet. This model may provide a useful tool to investigate the factors contributing to the presence and function of immunocompetent cells within a neoplastic epithelium that develops on a mucosal surface.

Cancer Vaccines↗
PubMed2001

[Clinical case of the month. Von Hippel-Lindau disease].

VHL disease is a rare genetical disease with a poor long-term prognosis. Clinical features include retineous angiomas, CNS hemangioblastomas, pheochromocytomas and renal cysts. Renal cysts are bilateral and frequently lead to malignant transformation. Surgical treatment of renal cysts is preferably delayed until a minimum of 3 cm diameter has been reached. Treatment has to be as conservative as possible, knowing that uni- or bilateral nephrectomy often has to be carried out later.

Adrenal Gland Neoplasms↗
PubMed2001

[Alpha-1-antitrypsin deficiency. An indication for pediatric liver transplantation].

Alpha-1-antitrypsin deficiency is the most common inborn error of metabolism leading to liver transplantation, and the second cause of liver transplantation in children after biliary atresia. The authors report the case of a 6-year-old girl, who was suffering from end-stage liver disease secondary to alpha-1-antitrypsin deficiency. She was successfully treated by whole liver transplantation, the hepatic graft coming from a 3-year-old donor. Three months later she went back to school. The authors discuss the pathogenesis and the natural history of this frequent cause of liver transplantation in children.

Child↗
PubMed2000

Assessment of tumor angiogenesis in invasive breast carcinomas: absence of correlation with prognosis and pathological factors.

Different retrospective studies have shown that microvessel counting (MVC) is an independent prognostic marker for clinical outcome in breast cancer. The aim of this study was to evaluate the prognostic value of MVC alone or in association with classical clinicopathological parameters, as well as the reproducibility of the technique. We analyzed a retrospective series of 216 cases of breast carcinoma. Tissue sections were stained for Factor-VIII-related antigen. Microvessel quantification was performed at x400 magnification in the three most vascular areas of the tumors (hot spots). Mean and highest values were studied. Furthermore, a semi-quantitative evaluation of MVC was performed by use of an image-analysis system. The effect of multiple factors on survival was tested under a Cox multivariate proportional hazards model. In ten cases, a study of the reproducibility was done by evaluating MVC in different sections of the same block and in different blocks of a same tumor. There was no association between MVC (determined at a microscopic level or by image analysis) and overall survival or relapse-free survival. No association was found with tumor size, tumor grade, and lymph-node status. The study of reproducibility showed a very high intra-tumoral variation of MVC. The intra-individual coefficient of variation (CV) varied between 20 and 80%. This study did not show any significant correlation between angiogenesis, as assessed by MVC, and relapse-free survival or overall survival in infiltrating breast carcinomas. The low reproducibility of the MVC for the same tumors suggests that this technique must still be optimized before routine application.

Aged↗
PubMed2000

Increased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease.

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10.

Adult↗
PubMed2000

[Pancreatic adenocarcinoma: role of pathologic anatomy].

Duct cell adenocarcinoma is by far the most frequent neoplasm of the pancreas, accounting for about 80% of malignant tumors. In this report, we describe the main diagnostic pitfalls of this cancer in routine or frozen sections, as well as the help of immunohistology to make the differential diagnosis. We also discuss the potential interest of tumor markers for evaluating the prognosis of these tumors and provide information about the creation of a Web site (URL: http://www.ebm.lib.ulg.ac.be/index.htm) created to help clinicians exploit the laboratory results.

Adenocarcinoma↗
PubMed2000

[How I investigate...fetal pathology. Technique and value of the fetal and placental examination and the perinatal autopsy].

Fetal pathology is a recent field in pathological anatomy, knowing at the present time an important technical and theoretical development. However, it is still insufficiently used to resolve cases of fetal death in utero, or peripartum or perinatal. In this paper, we describe the basics and the techniques used during the fetal examination. We underline the values of these techniques for the understanding of failures of pregnancy and for orientation of the genetical advice for future pregnancies.

Amniocentesis↗
PubMed2000

[Clinical case of the month. Disseminated fusariosis in a immunocompromised patient].

Fusarium spp are ubiquitous soil saprophytes and occasional plant pathogens. Fusariosis in humans is usually limited to superficial mycoses. We report the case of a disseminated fungal infection due to Fusarium spp in an immunosuppressed patient suffering from acute lymphoblastic leukemia. This report and review of the recent literature suggest that Fusarium spp are emerging fungal pathogens in immunosuppressed patients.

Adult↗
PubMed2000

[Anatomic clinical case. Septic state in a patient with chronic obstructive lung disease].

Invasive aspergillosis is a mycelial infection, associated in 15 to 30% of cases with a malignant hemopathy or with other types of cancers. It also constitutes a complication induced by high dosage corticotherapy or long term antibiotherapy. On the occasion of an autopsy of invasive aspergillosis, we review the anatomo-clinical entities associated with aspergillus, the etiopathogenic factors and the diagnostic difficulties.

Aged↗
PubMed1999

Generation of T lymphocytes from the epithelium and stroma of squamous pre-neoplastic lesions of the uterine cervix.

In this study, we have developed a simple and efficient technique for the isolation of viable lymphocytes from the epithelium and stroma of small pre-neoplastic squamous intraepithelial lesions (SIL) of the uterine cervix. Following the separation of the epithelium from the stroma using dispase II, both biopsy fragments were used to generate T lymphocytes. The stroma-derived lymphocytes were obtained by collecting and culturing the cells migrating out of the biopsy in the presence of IL2 (50 U/ml). An average of 0.7 x 10(6) and 1.4 x 10(6) lymphocytes could be obtained after 20 and 30 days of culture, respectively. For the expansion of lymphocytes derived from the pre-neoplastic epithelium (SIL) it was necessary to use a combination of irradiated peripheral blood mononuclear cells (PBMC) as a feeder layer with PHA (0.1%), in addition to IL2 (50 U/ml). Interestingly, these lymphocytes could be obtained using either allogeneic or syngeneic PBMCs. With this protocol, we were able to generate up to 100 x 10(6) lymphocytes from the epithelium, the majority of which were T lymphocytes.

Carcinoma in Situ↗
PubMed1999

Colonization of in vitro-formed cervical human papillomavirus- associated (pre)neoplastic lesions with dendritic cells: role of granulocyte/macrophage colony-stimulating factor.

The purpose of this study was to investigate the ability of CD1a+ Langerhans/dendritic cells (LCs/DCs) to infiltrate human papillomavirus (HPV)-associated (pre)neoplastic lesions of the uterine cervix. Migration of LCs/DCs in the presence of keratinocytes derived from normal cervix and HPV-transformed cell lines was evaluated in Boyden chambers and in organotypic cultures and correlated with granulocyte/macrophage colony-stimulating factor (GM-CSF) production by the cells, as determined by ELISA. Conditioned media of HPV-transformed keratinocytes contained lower amounts of GM-CSF and induced a decreased motile response of LCs/DCs in the Boyden chamber assay compared with those of normal cervical keratinocytes. The migration of LCs/DCs in the presence of conditioned media from normal keratinocytes could be blocked by an anti-GM-CSF antibody, and the migration of LCs/DCs in the presence of conditioned media from HPV-transformed keratinocytes could be increased by supplementing the media with recombinant GM-CSF. GM-CSF was also a potent factor in enhancing the colonization of LCs/DCs into organotypic cultures of HPV-transformed keratinocytes, as the infiltration of LCs/DCs in the in vitro-formed (pre)neoplastic epithelium was minimal under basal conditions and dramatically increased after the addition of GM-CSF to the cultures. These results suggest that GM-CSF could play an important role in the recruitment of LCs/DCs into the HPV-transformed (pre)neoplastic cervical epithelium and be useful as a new immunotherapeutic approach for cervical (pre)cancers.

Antibodies↗
PubMed1999

Nuclear localization of a new c-cbl related protein, CARP 90, during in vivo thymic apoptosis in mice.

This study investigates the involvement of the c-cbl protooncogene in thymocyte apoptosis occurring in vivo after hydrocortisone treatment. In the thymus of untreated mice, a few medullary and cortical thymocytes expressed p120cbl, mainly in the cytoplasm. In the cortex, their number and distribution resemble that of apoptotic cells evidenced by TUNEL staining. The expression of Cbl is rapidly increased when apoptosis is triggered by hydrocortisone. This Cbl-specific immunostaining was detected in the nucleus and is due to a Cbl-related 90 kDa protein (CARP 90). These results show that a c-cbl product could localize in the nucleus and suggest that it could be involved as a regulator of thymic apoptosis.

Animals↗