References of "Waltregny, David"
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See detailOverexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation
Waltregny, David ULg; Alami, Younes; Clausse, Nathalie et al

in Prostate (2002), 50(3), 162-169

BACKGROUND. Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in development and differentiation. Recent data also suggest a ... [more ▼]

BACKGROUND. Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in development and differentiation. Recent data also suggest a possible involvement of HOX genes in malignant transformation and/or progression. We have previously shown that HOXC8 expression was selectively turned on in human cervix cancer cells compared with normal keratinocytes, suggesting that HOXC8 may be involved in the process leading to the transformation of cervix keratinocytes [Alami et al.: Biochem Biophys Res Commun 257:738-745,1999]. METHODS. RT-PCR and in situ hybridization experiments were performed to investigate the expression and cell type localization of HOXC8 transcripts in human prostate cancer cell lines and tissues. In situ hybridization was performed with the use of an HOXC8 anti-sense digoxigenin-labeled probe to investigate HOXC8 mRNA expression in 27 prostate cancer tissue specimens. RESULTS. Out of the three human prostate cancer cell lines tested, DU-145 and PC3 but not LNCaP cells expressed detectable amount of HOXC8 transcripts. Results from in situ hybridization experiments demonstrated that HOXC8 gene was expressed mainly in malignant epithelial cells. Furthermore, the staining intensity in epithelial cells was significantly increased in high Gleason score carcinomas (scores 7-9, n = 12; labeling intensity 2 + to 3 +) compared with the one observed in low and intermediate Gleason score tumors (scores 3-6, n = 15; labeling intensity 0 and 1 +) (ANOVA test, P < 0.0001). CONCLUSIONS. Our data showing that HOXC8 overexpression is associated with the loss of tumor differentiation in human prostate cancer suggests that HOXC8 may play a role in the acquisition of the invasive and metastatic phenotype of this malignancy. (C) 2002 Wiley-Liss, Inc. [less ▲]

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See detailGene transcript quantitation by real-time RT-PCR in cells selected by immunohistochemistry-laser capture microdissection.
Lindeman, Neal; Waltregny, David ULg; Signoretti, Sabina et al

in Diagnostic Molecular Pathology : The American Journal of Surgical Pathology, Part B (2002), 11(4), 187-92

Studying tissue-based gene expression in different cell populations often requires immunohistochemistry-guided microdissection. However, mRNA degradation occurs during long staining procedures. We ... [more ▼]

Studying tissue-based gene expression in different cell populations often requires immunohistochemistry-guided microdissection. However, mRNA degradation occurs during long staining procedures. We combined a novel rapid immunoperoxidase technique with laser capture microdissection (LCM) and real-time quantitative RT-PCR to compare p27 mRNA expression in prostatic basal/secretory cells. Eight frozen prostate sections were immunostained with antibody 34betaE12 (high-molecular-weight keratin). Secretory and basal cells were separately collected by LCM. p27 transcripts from each cell group were quantitated by real-time RT-PCR, with GAPDH as standard. Immunostaining took 22 minutes, with RNA extraction from approximately 40 dissected cells from each compartment initiated within 40 minutes. Qualitative RT-PCR gave a product of the expected size from each sample. Quantitative RT-PCR gave basal/secretory p27/GAPDH ratios of 0.99-16.24 (mean 5.53 +/- 0.643). Immunostaining for keratin 34betaE12 can be done on frozen sections in approximately 20 minutes, and mRNA from pure cell populations can be quantitated by RT-PCR. We used this technique to show that p27 transcript levels are greater in basal than in secretory prostate cells, suggesting, when combined with prior studies, that regulation of p27 occurs at the protein level in normal cells. This technique may have wide applicability to studies of gene expression in distinct cell populations in heterogeneous tissues. [less ▲]

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See detailThe role of bone sialoprotein and other members of the SIBLING family in bone metastases formation
Castronovo, Vincenzo ULg; Waltregny, David ULg; Fisher, Larry et al

in 3rd International Conference on Osteopontin and SIBLING (Small Integrin-Binding Ligand, N-linked Glycoprotein) Proteins (2002)

Bone metastasis is a major health and social-economic problem in well-developed countries because they are frequent and generate major morbidity in cancer patients. Although virtually all cancer cells can ... [more ▼]

Bone metastasis is a major health and social-economic problem in well-developed countries because they are frequent and generate major morbidity in cancer patients. Although virtually all cancer cells can metastasize to bone, the majority of bone metastases are due to a few types of cancers that exhibit a high osteotropism. These include carcinoma of the breast, lung, prostate, thyroid, kidney, and multiple myeloma. The exact molecular mechanisms by which certain cancer cells preferentially implant to specific sites are not yet fully understood. [less ▲]

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See detailLes risques d’incontinence après prostatectomie radicale dépendent-ils du bilan lésionnel ?
de Leval, Jean ULg; Waltregny, David ULg

in Opsomer, Reinier (Ed.) La prostatectomie radicale : Facteurs prédictifs d’incontinence et d’impuissance, Rapport du XXVème Congrès de la Société Internationale Francophone d’Urodynamique (2002)

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See detailPyelonephrite xanthogranulomateuse pseudotumorale: diagnostic par la biopsie percutanee et succes du traitement conservateur
Reul, Olivier ULg; Waltregny, David ULg; Boverie, Jacques ULg et al

in Progrès en Urologie (2001), 11(6), 1274-6

Focal xanthogranulomatous pyelonephritis is an unusual form of chronic renal infection that is difficult to diagnose prior to surgery. We report on a 19-year-old woman who presented with a renal mass that ... [more ▼]

Focal xanthogranulomatous pyelonephritis is an unusual form of chronic renal infection that is difficult to diagnose prior to surgery. We report on a 19-year-old woman who presented with a renal mass that mimicked malignancy. The diagnosis of focal xanthogranulomatous pyelonephritis was first suspected by radiological findings and further confirmed by histopathologic examination of percutaneous biopsy specimens of the lesion. Successful treatment of the patient was achieved with antibiotic therapy alone. Maximal efforts, including percutaneous renal biopsy, should be made to establish the diagnosis of focal xanthogranulomatous pyelonephritis before a therapeutic decision is reached. We recommend the use of antibiotics as a first-line treatment for patients with focal xanthogranulomatous pyelonephritis. [less ▲]

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See detailIncreased Expression of Galectin-1 in Carcinoma-Associated Stroma Predicts Poor Outcome in Prostate Carcinoma Patients
van den Brule, Frederic; Waltregny, David ULg; Castronovo, Vincenzo ULg

in Journal of Pathology (The) (2001), 193(1), 80-7

Galectin-1, a member of the beta-galactoside-binding galectin family, is a pleiotropic dimeric protein participating in a variety of normal and pathological processes, including cancer progression ... [more ▼]

Galectin-1, a member of the beta-galactoside-binding galectin family, is a pleiotropic dimeric protein participating in a variety of normal and pathological processes, including cancer progression. Modulation of the interactions with the basement membrane glycoprotein laminin and induction of apoptosis in activated T lymphocytes are well-known functions of this galectin. In this study, the expression of galectin-1 was examined in 148 human primary prostate carcinoma samples. Immunohistochemical staining of paraffin sections of prostate tissues revealed that galectin-1 was not detected in normal, PIN (prostatic intraepithelial neoplasia) or carcinoma cells, but accumulated in the stroma and associated fibroblasts. Galectin-1 expression was significantly increased in the tumour-associated stroma compared with the non-neoplastic gland-associated stroma in 21.3% of the cases (Mantel-Haenszel test, p=0.001; Wilcoxon signed rank test, p<0.0001). Increased galectin-1 expression in the cancer-associated stroma compared to the normal gland-associated stroma (p=0.03) was identified by multivariate analysis as a strong independent predictor of prostate-specific antigen (PSA) recurrence, just after the pathological stage (p<0.0001). The association between accumulation of galectin-1 in the stroma of the malignant tissue and aggressiveness of the tumour adds weight to the body of evidence that identifies a role for galectin-1 in the acquisition of the invasive phenotype. In addition to modulating cancer cell interactions with laminin, galectin-1 accumulated around the cancer cells may act as an immunological shield by inducing activated T-cell apoptosis. This exciting hypothesis warrants further investigation. [less ▲]

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See detailSodium butyrate and trichostatin A induce growth arrest and apoptosis in breast cancer cells while normal breast epithelial cells are unaffected
Locigno, Roberto; Waltregny, David ULg; Verheyen, Véronique et al

Conference (2001, January)

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See detailDetection of the 67-kD laminin receptor in prostate cancer biopsies as a predictor of recurrence after radical prostatectomy.
Waltregny, David ULg; De Leval, Laurence ULg; Coppens, Luc ULg et al

in European Urology (2001), 40(5), 495-503

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a ... [more ▼]

OBJECTIVES: Reliable prognostic indicators are needed for a better pretherapeutic assessment of the agressiveness of organ-confined prostate cancer (PC) lesions. The 67-kD laminin receptor (67LR) is a cell-surface-associated protein involved in the acquisition of the invasive and metastatic phenotype of a variety of human cancer cell types. We have previously shown that 67LR detection in PC tissues from radical prostatectomy (RP) specimens is an independent predictor of biochemical (PSA) relapse in patients with clinically localized PC. In this study, we assessed 67LR detection in diagnostic PC biopsies as a predictor of biochemical relapse after RP. METHODS: Diagnostic biopsy and subsequent RP tissue specimens from 151 patients with clinically localized PC were immunohistochemically analyzed for 67LR expression. The level of 67LR expression was evaluated by both intensity and extent of the staining. Clinicopathological preoperative and postoperative parameters, including 67LR expression, were correlated with each other and tested as predictors of biochemical relapse. RESULTS: 67LR was detected in 67.5 and 68.2% of biopsies and RPs, respectively. 67LR detection in RP specimens was an independent predictor of relapse. The level of 67LR expression in the biopsy was significantly associated with the biopsy Gleason score (p<0.05) but failed to predict the pathological stage (p>0.1). Biochemical progression-free estimates for patients whose biopsy did or did not express the protein differed with only borderline statistical significance (p = 0.05). Multivariate analysis identified biopsy Gleason score as the only independent preoperative predictor of recurrence. Significant discrepancies in levels of 67LR expression were found between matched biopsy and RP specimens (p<0.05), with exact agreement rates <40%. CONCLUSIONS: 67LR detection in PC biopsies was not a significant preoperative predictor of outcome after RP. Heterogeneity of 67LR expression and biopsy sampling errors most likely represented the main reasons for discordant results between biopsy and RP specimens. [less ▲]

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See detailAndrogen-driven prostate epithelial cell proliferation and differentiation in vivo involve the regulation of p27.
Waltregny, David ULg; Leav, Irwin; Signoretti, Sabina et al

in Molecular Endocrinology (2001), 15(5), 765-82

Androgens control both growth and differentiation of the normal prostate gland. However, the mechanisms by which androgens act upon the cell cycle machinery to regulate these two fundamental processes are ... [more ▼]

Androgens control both growth and differentiation of the normal prostate gland. However, the mechanisms by which androgens act upon the cell cycle machinery to regulate these two fundamental processes are largely unknown. The cyclin-dependent kinase (cdk) inhibitor p27 is a negative cell cycle regulator involved in differentiation-associated growth arrest. Here, we investigate the role and regulation of p27 in the testosterone proprionate (TP)-stimulated regeneration of the ventral prostate (VP) of castrated rats. Continuous TP administration to castrated rats triggered epithelial cell proliferation, which peaked at 72 h, and then declined despite further treatment. Castration-induced atrophy of the VP was associated with a significant increase in p27 expression as compared with the VP of intact animals. Twelve hours after the initiation of androgen treatment, total p27 levels as well as its fraction bound to cdk2, its main target, significantly dropped in the VP of castrated rats. Thereafter, concomitantly to the induction of epithelial cell proliferation, the glandular morphology of VP was progressively restored at 48-96 h of TP treatment. During this period of the regenerative process, whereas both proliferating basal and secretory epithelial cells did not express p27, the protein was selectively up-regulated in the nonproliferating secretory epithelial compartment. This up-regulation of p27 expression was coincident with an increase in its association with, and presumably inhibition of, cdk2. At each time point of TP treatment, p27 abundance in the VP was inversely correlated with the level of its proteasome-dependent degradation activity measured in vitro in VP lysates, whereas only slight changes in the amount of p27 transcripts were detected. In addition, the antiandrogen flutamide blocked maximal TP-induced p27 degradation completely. Finally, the expression of skp2, the ubiquitin ligase that targets p27 for degradation, was seen to increase with androgen administration, preceding maximal proliferation and concomitantly to augmented p27 degradation activity. Taken together, our data indicate that androgens mediate both proliferation and differentiation signals in normal prostate epithelial cells in vivo, through regulation of p27. [less ▲]

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See detailSodium butyrate and trichostatin-a induce apoptosis in human breast cancer cells but not in normal human mammary epithelial cells
Locigno, Roberto; Henno, Audrey ULg; Waltregny, David ULg et al

in Proceedings of the American Association for Cancer Research (2001), 42

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See detailRapid immunostaining of frozen sections: a tool for laser capture microdissection and quantitative RT-PCR
Lindeman, Neal; Waltregny, David ULg; Signoretti, Sabina et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2001), 81

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See detailThe p27 ubiquitin ligase skp2 is overexpressed in breast cancer
Signoretti, Sabina; Monti, Francesca; Isaac, Beth et al

in Laboratory Investigation : Journal of Technical Methods & Pathology (2001), 81

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See detailBone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression in localized human prostatic adenocarcinoma as predictors of clinical outcome: a clinicopathological and immunohistochemical study of 43 cases.
De Pinieux, Gonzague; Flam, Thierry; Zerbib, Marc et al

in Journal of Urology (The) (2001), 166(5), 1924-30

PURPOSE: Skeletal metastases are the hallmark of advanced prostate cancer and recurrence after local surgery is common. Currently to our knowledge no biological markers predict the risk of disease ... [more ▼]

PURPOSE: Skeletal metastases are the hallmark of advanced prostate cancer and recurrence after local surgery is common. Currently to our knowledge no biological markers predict the risk of disease progression in individuals with localized prostate cancer. In a search for predictive markers we evaluated the expression of bone sialoprotein and bone morphogenetic protein 6, 2 bone related proteins, and the angiogenic factor thymidine phosphorylase. MATERIALS AND METHODS: The study population included 43 men who presented with localized prostate cancer treated with radical prostatectomy. Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression was assessed by immunohistochemical testing. Results were analyzed in relation to pathological disease stage, Gleason score and clinical outcome. Clinical followup was 4.3 to 11.4 years after surgery (median 7.9). RESULTS: Disease did not progress in 17 of the 43 cases, while recurrence and/or metastasis developed in the other 26 at a median of 6.5 and 6.9 years, respectively. Bone sialoprotein and bone morphogenetic protein 6 expression detected in 28 (65%) and 29 (67%) of the 43 samples, respectively, was significantly associated (p = 0.0001). Thymidine phosphorylase detected in 26 samples (60%) was not related to bone sialoprotein and/or bone morphogenetic protein 6 positivity. Bone sialoprotein and/or bone morphogenetic protein 6 expression correlated with bone metastasis, while thymidine phosphorylase expression was related to local recurrence (p = 0.002 and/or 0.007, and 0.00007, respectively). On multivariate analysis only the correlation of thymidine phosphorylase expression with recurrence remained statistically significant (p = 0.002). Co-expression of the 3 markers was observed in the samples of 10 of the 11 patients (90%) with bone metastases and only in 5 of the 17 (29%) who were disease-free. CONCLUSIONS: This study indicates that the expression of bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase determined at a clinically early stage of disease by a simple immunohistochemical technique would enable subgroups of patients to be identified that are at different risks of bone metastasis or recurrence. Detection of such markers would provide additional prognostic information that would be useful for patients with intermediate or low Gleason score or stage disease. These patients would benefit from a more adapted clinical follow-up. [less ▲]

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