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Gonzague De Pinieux

Publications and source records attributed to Gonzague De Pinieux.

9 recordsLinked to original sources
PubMed2006

Characterization and functional consequences of underexpression of clusterin in rheumatoid arthritis.

We previously compared by microarray analysis gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) tissues. Among the set of genes identified as a molecular signature of RA, clusterin (clu) was one of the most differentially expressed. In the present study we sought to assess the expression and the role of CLU (mRNA and protein) in the affected joints and in cultured fibroblast-like synoviocytes (FLS) and to determine its functional role. Quantitative RT-PCR, Northern blot, in situ hybridization, immunohistochemistry, and Western blot were used to specify and quantify the expression of CLU in ex vivo synovial tissue. In synovial tissue, the protein was predominantly expressed by synoviocytes and it was detected in synovial fluids. Both full-length and spliced isoform CLU mRNA levels of expression were lower in RA tissues compared with OA and healthy synovium. In synovium and in cultured FLS, the overexpression of CLU concerned all protein isoforms in OA whereas in RA, the intracellular forms of the protein were barely detectable. Transgenic overexpression of CLU in RA FLS promoted apoptosis within 24 h. We observed that CLU knockdown with small interfering RNA promoted IL-6 and IL-8 production. CLU interacted with phosphorylated IkappaBalpha. Differential expression of CLU by OA and RA FLS appeared to be an intrinsic property of the cells. Expression of intracellular isoforms of CLU is differentially regulated between OA and RA. We propose that in RA joints, high levels of extracellular CLU and low expression of intracellular CLU may enhance NF-kappaB activation and survival of the synoviocytes.

Arthritis, Rheumatoid↗
PubMed2006

Case reports: enlargement of a calcaneal osteochondroma after skeletal maturity.

Growth or radiologic modification of an osteochondroma after the epiphyseal plate closes suggests the diagnosis of malignant transformation to a chondrosarcoma. However, extensive growth of an osteochondroma in a skeletally mature patient whose tumor proved benign has been reported. We report a similar case in an adult who had a solitary osteochondroma of the calcaneus. The lesion showed marked growth and was removed. Histologic examination showed no evidence of malignancy, and there was no recurrence during the 4-year followup.

Adult↗
PubMed2005

Surgical treatment of pigmented villonodular synovitis of the hip.

BACKGROUND: Pigmented villonodular synovitis of the hip is a rare disease. Synovectomy is generally accepted as the only surgical treatment for the disorder, but there have been few studies with a sufficient sample size and duration of follow-up to allow the evaluation of long-term outcomes. The aim of this study was to determine the long-term outcome of the treatment in sixteen patients. METHODS: Sixteen patients (nine men and seven women), with a mean age of 35.5 years at the time of surgery, were treated between 1970 and 1996. Complete synovectomy was performed in all patients; in addition, three had a cup arthroplasty, four had a total hip arthroplasty, and one had a monopolar arthroplasty. Clinical and radiographic outcomes were evaluated retrospectively at a mean of 16.7 years postoperatively. Only one patient was followed for less than eight years. RESULTS: Nine patients needed repeat surgery, but only one had recurrent synovitis, as detected with pathological examination fourteen years after treatment with synovectomy and cup arthroplasty. Secondary osteoarthritis developed in all eight patients who had been treated with synovectomy alone, and four of them required a total hip arthroplasty within the follow-up period. CONCLUSIONS: These results support earlier data indicating that osteoarthritis consistently develops in patients with pigmented villonodular synovitis of the hip. Complete synovectomy seems to be effective in preventing recurrence of the synovitis, but it does not appear to prevent the development of secondary osteoarthritis.

Adult↗
PubMed2005

Chondroblastoma of the lumbar spine. Report of two cases and review of the literature.

Chondroblastoma is a benign cartilaginous neoplasm that generally affects the appendicular skeleton. Twenty-six cases of spinal chondroblastoma have been reported in the past 50 years, only six of which were located in the lumbar region. The authors report two cases involving this exceptional location. In both patients, low-back pain, in the absence of radicular pain, was the presenting symptom. In both cases, plain radiography and computerized tomography scanning revealed an osteolytic lesion surrounded by marginal sclerosis. Magnetic resonance imaging allowed the authors to study the tumor's local extension. Examination of a percutaneous fluoroscopy-guided biopsy sample revealed the following typical histological features of chondroblastoma: chondroid tissue, focally alternating with cellular areas, and no nuclear atypia or pleomorphism. To reduce the risk of local recurrence, vertebrectomy and anterior-posterior fusion were performed in both cases. In one case, a structural lumbar scoliosis was corrected during the posterior procedure. There was no postoperative complication. No recurrence was observed during the 3- to 6-year follow-up period. The surgery-related results were deemed successful. Although exceptional, the diagnosis of chondroblastoma is possible in lesions involving the lumbar spine. Other spinal locations are described in the literature, and frequency of recurrence is stressed. A vertebrectomy is advised to reduce the risk of local recurrence.

Adult↗
PubMed2004

Non-Leydig sex-cord tumors of the testis. The place of immunohistochemistry in diagnosis and prognosis. A study of twenty cases.

In 20 sex-cord tumors of the testes, we investigated immunohistochemistry as a possible method for histopathological diagnosis and evaluation of prognosis. We examined the following molecules: inhibin, CD99, cytokeratin, vimentin, MIB-1, estrogen receptors and progesterone receptors. These tumors of the testes comprised 18 Sertoli cell tumors (ScT) and two undifferentiated sex-cord tumors (USCT). Four tumors have been considered as malignant, because of metastatic spread. Inhibin was expressed by the tumor cells in 80% of sex cord tumors, without any correlation to the degree of differentiation and only in 25% of the malignant cases. Inhibin is a specific marker for sex-cord tumors of the testis and is particularly useful for the diagnosis of USCT. CD99, vimentin, keratin, progesterone and estrogen receptors were expressed in, respectively, 60%, 75%, 35%, 65% and 20% of cases; 95% expressed one of the three following markers: inhibin, CD99 or vimentin. Proliferation index MIB-1 was equal to or higher than 30% in the four malignant cases versus less than 20% in other cases. Lack of inhibin expression and a proliferation index (MIB-1) greater than 30% should be considered as a criterion in favor of malignancy.

Adolescent↗
PubMed2003

IL-18 is produced by prostate cancer cells and secreted in response to interferons.

Murine models have shown that IL-18 has antiangiogenic and antitumor effects, but little is known about IL-18 production in human tumors. We investigated IL-18 expression in clinically localized prostate cancers by immunohistochemistry and showed that 75% of the prostate cancers studied (27/36 cases) presented with tumor cells producing IL-18. Prostate tumor cell lines PC-3, DU 145 and LNCaP synthesized the immature form of IL-18 (p24). IFN-gamma produced in prostate cancers induced caspase-1 mRNA and IL-18 secretion of tumor cell lines, which was inhibited by the cell-permeable Tyr-Val-Ala-Asp-aldehyde caspase-1 inhibitor (YVAD-CHO). Interestingly, IFN-alpha also induced IL-18 secretion of the poorly differentiated cell line PC-3. PC-3 and DU 145, but not the well-differentiated cell line LNCaP, expressed IL-18R alpha (IL-1Rrp) protein and transcripts for IL-18R beta (AcPL). Exogenous IL-18 increased mitochondrial activity of both cell lines evaluated by the tetrazolium (MTT) assay but did not influence their proliferation. This indicated that prostate tumor cells could secrete IL-18 in response to IFN-gamma in the tumor microenvironment and that IL-18 could act as a autocrine/paracrine factor for the tumor. In the cohort of patients studied, IL-18 expression in prostate cancers (with up to 10% of tumor cells stained) was associated with a favorable outcome and equally predictive as pathologic stage on multivariate analysis (log rank test, p = 0.02). Tumor IL-18 production is a novel physiopathologic feature of prostate cancer and appears to be a favorable event in the course of the disease. Modulation of IL-18 production by interferons could have a beneficial clinical effect, which deserves further investigation.

Antineoplastic Agents↗
PubMed2002

Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo.

The mitochondrial peripheral benzodiazepine receptor (mPBR) is involved in a functional structure designated as the permeability transition pore, which controls apoptosis. Binding of Fas/APO-1/CD95 triggers a prototypic apoptosis-inducing pathway. Using four different human tumor cell lines (T-cell Jurkat, neuroblastoma SHEP, osteosarcoma 143N2, and glioblastoma SNB79 cell lines), all of which express CD95 and mPBR, we investigated the potential role of mPBR ligands in CD95-induced apoptosis. We show that, in vitro, the three mPBR ligands tested (RO5-4864, PK11195, and diazepam) enhanced apoptosis induced by anti-CD95 antibody in Jurkat cells, as demonstrated by mitochondrial transmembrane potential drop and DNA fragmentation. In contrast, RO5-4864, but not PK11195 or diazepam, enhanced anti-CD95 apoptosis in all other cell lines. These effects were obtained in Bcl-2-overexpressing SHEP cell lines, but not in Bcl-X(L) SHEP cell lines. Enhancement of anti-CD95 antibody-induced apoptosis by RO5-4864 was characterized by an increased mitochondrial release of cytochrome c and Smac/DIABLO proteins and an enhanced activation of caspases 9 and 3, suggesting a mitochondrion-dependent mechanism. Preincubation of cells with the different mPBR ligands or anti-CD95 did not affect the levels of expression of either mPBR or CD95. In vivo, we found that the RO5-4864 mPBR ligand significantly increased the growth inhibition induced by two chemotherapeutic agents, etoposide and ifosfamide, using two human small cell lung cancers xenografted into nude mice. Peripheral benzodiazepine receptor ligands may therefore act as chemosensitizing agents for the treatment of human neoplasms.

Antibodies, Monoclonal↗