References of "Waltregny, David"
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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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See detailAlteration of the Cytoplasmic/Nuclear Expression Pattern of Galectin-3 Correlates with Prostate Carcinoma Progression
van den Brule, Frédéric; Waltregny, David ULg; Liu, Fu Tong et al

in International Journal of Cancer = Journal International du Cancer (2000), 89(4), 361-7

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in a variety of biological events including interactions with galactose-containing glycoconjugates, cell proliferation ... [more ▼]

Galectin-3, a member of the beta-galactoside-binding lectin family, is involved in a variety of biological events including interactions with galactose-containing glycoconjugates, cell proliferation, differentiation and apoptosis. Galectin-3 appears to intervene during tumor progression and altered expression patterns have been reported in a variety of malignancies. In our study, we have examined the expression of galectin-3 in a population of 145 prostate carcinoma samples using immunohistochemistry. We found that most of the non-tumoral prostatic glands exhibited moderate immunostaining for galectin-3 localized in both nucleus and cytoplasm. In prostatic cancer cells, galectin-3 was usually not expressed or decreased compared with the normal glands. Interestingly, when galectin-3 was detected in the cancer cells, it was consistently excluded from the nucleus and only present in the cytoplasmic compartment. The latter observation was also made for prostatic intraepithelial neoplasia (PIN) cells. Furthermore, we found that the levels of galectin-3 expression in the cancer cells were significantly associated with prostate-specific antigen (PSA) relapse in univariate analysis (p = 0.044). Cytoplasmic expression of galectin-3 in the carcinoma cells was an independent predictor of disease progression in multivariate analysis, after the pathological stage and the Gleason score. Our data demonstrate that galectin-3 is generally down-regulated in human prostate carcinoma cells, and consistently excluded from the nucleus. Interestingly, specific cytoplasmic expression of galectin-3 in a subset of lesions is associated with disease progression. These results suggest that galectin-3 might play anti-tumor activities when present in the nucleus, whereas it could favor tumor progression when expressed in the cytoplasm. Further studies should determine the exact role and mechanisms by which galectin-3 differentially affects cell behavior in the different locations where it is expressed. [less ▲]

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See detailIncreased Expression of Bone Sialoprotein in Bone Metastases Compared with Visceral Metastases in Human Breast and Prostate Cancers
Waltregny, David ULg; Bellahcene, Akeila ULg; de Leval, Xavier et al

in Journal of Bone and Mineral Research (2000), 15(5), 834-43

The recent demonstration that bone sialoprotein (BSP) is expressed in osteotropic cancers suggests that this bone matrix protein might be implicated in the preferential seed and growth of metastatic cells ... [more ▼]

The recent demonstration that bone sialoprotein (BSP) is expressed in osteotropic cancers suggests that this bone matrix protein might be implicated in the preferential seed and growth of metastatic cells in bone. High expression of BSP in breast and prostate primary carcinomas is associated with progression and bone metastases development. The exact mechanisms by which BSP may favor bone metastases formation are not clearly established yet. Although BSP expression has been detected in breast, prostate, lung, thyroid, and neuroblastoma primary tumors, no information regarding its expression in metastases is available to date. In this study, we have examined BSP expression in 15 bone and 39 visceral metastatic lesions harvested from 8 breast cancer patients and 7 prostate cancer patients who died of disseminated disease. We were able to retrieve the primary lesions from 5 of the 8 breast cancer patients as well as from all 7 prostate cancer patients. All the primary breast tumor patients and 5 of the 7 primary prostate cancer patients expressed a detectable level of BSP. Bone metastases from all 8 breast cancer patients and from 5 out of 7 prostate cancer patients exhibited detectable levels of the protein. Metastatic cells in close contact with bone trabeculae usually were highly positive for BSP. BSP also was detected in secondary lesions developed at visceral sites including liver, thyroid, lung, and adrenal glands. However, BSP expression was significantly lower in visceral metastases than in skeletal ones (Mann-Whitney test, p < 0.05). Our data represent the first demonstration of an increased expression of BSP in bone metastases compared with nonskeletal metastases in human breast and prostate cancers and add weight to the body of evidence attributing a significant role to this protein in the genesis of bone metastases. [less ▲]

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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

Conference (2000)

INTRODUCTION & OBJECTIVES: The identification of reliable prognostic indicators for prostate cancer (PC) is a major challenge of today cancer research. The 67-KD laminin receptor (67LR) is a cell surface ... [more ▼]

INTRODUCTION & OBJECTIVES: The identification of reliable prognostic indicators for prostate cancer (PC) is a major challenge of today cancer research. The 67-KD laminin receptor (67LR) is a cell surface associated molecule whose increased expression is associated with the aggressiveness of a variety of human cancers. We recently showed that 67LR detection in PC tissues from radical prostatectomy (RP) specimens was an independent predictor of biochemical relapse in patients with clinically localized PC (JNCI, 89:1224-1227, 1997). In this study, we assessed 67LR detection in diagnostic biopsies as a predictor of biochemical relapse after RP. MATERIAL & METHODS: A total of 151 patients with clinically confined PC underwent RP. PC tissue sections from both biopsy and RP specimens were immunohistochemically analyzed for 67LR expression. The importance of 67LR expression was evaluated according to the intensity and extent of the staining. Preoperative and postoperative clinicopathological 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, with exact agreement rates <40% (p<0.05). 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 raisons for discordant prognostic results depending on whether 67LR expression was evaluated either in biopsies or in RPs. [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, Frédéric; Waltregny, David ULg; Castronovo, Vincenzo ULg

in Proceedings of the American Association for Cancer Research (2000), 41

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See detailp63 is a prostate basal cell marker and is required for prostate development.
Signoretti, Sabina; Waltregny, David ULg; Dilks, James et al

in American Journal of Pathology (2000), 157(6), 1769-75

The p53 homologue p63 encodes for different isotypes able to either transactivate p53 reporter genes (TAp63) or act as p53-dominant-negatives (DeltaNp63). p63 is expressed in the basal cells of many ... [more ▼]

The p53 homologue p63 encodes for different isotypes able to either transactivate p53 reporter genes (TAp63) or act as p53-dominant-negatives (DeltaNp63). p63 is expressed in the basal cells of many epithelial organs and its germline inactivation in the mouse results in agenesis of organs such as skin appendages and the breast. Here, we show that prostate basal cells, but not secretory or neuroendocrine cells, express p63. In addition, prostate basal cells in culture predominantly express the DeltaNp63alpha isotype. In contrast, p63 protein is not detected in human prostate adenocarcinomas. Finally, and most importantly, p63(-/-) mice do not develop the prostate. These results indicate that p63 is required for prostate development and support the hypothesis that basal cells represent and/or include prostate stem cells. Furthermore, our results show that p63 immunohistochemistry may be a valuable tool in the differential diagnosis of benign versus malignant prostatic lesions. [less ▲]

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See detailChirurgie, radiotherapie ou hormonotherapie dans le traitement du cancer de la prostate
Bonnet, Pierre ULg; Coppens, Luc ULg; Andrianne, Robert ULg et al

in Revue Médicale de Liège (1999), 54(11), 875-85

Prostatic cancer (PC) became the first diagnosed cancer in western men and is the second leading cause of cancer death in men. Wide utilisation of serum PSA and free PSA measurements, identifies patients ... [more ▼]

Prostatic cancer (PC) became the first diagnosed cancer in western men and is the second leading cause of cancer death in men. Wide utilisation of serum PSA and free PSA measurements, identifies patients requiring transrectalultrasonography (TRUS) and TRUS guided biopsies. Most prostatic cancers diagnosed today are locally limited and may be treated by radical surgery or radiotherapy. In case of disseminated disease, hormonal manipulations remain the treatment of choice. In that field, many new drugs have been designed to allow medical castration with less complications, especially regarding sexual potency. [less ▲]

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See detailThe role of bone sialoprotein in bone metastasis
Bellahcene, Akeila ULg; Waltregny, David ULg; Castronovo, Vincenzo ULg

in Skouteris, G. G.; Nicolson, G. L. (Eds.) Intermolecular Cross-Talk in Tumor Metastasis (1999, May)

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See detailFemoral Anastomotic Aneurysms: Pathogenic Factors, Clinical Presentations and Treatment. A Study of 142 Cases
Demarche, Martine; Waltregny, David ULg; Van Damme, Hendrik ULg et al

in Cardiovascular Surgery (1999), 7(3), 315-22

In this study, the files of 112 patients with a total of 142 femoral anastomotic aneurysms were reviewed. Eighty-five patients (76%) were initially operated upon for obstructive aorto-iliac disease, while ... [more ▼]

In this study, the files of 112 patients with a total of 142 femoral anastomotic aneurysms were reviewed. Eighty-five patients (76%) were initially operated upon for obstructive aorto-iliac disease, while the remaining 27 (24%) had abdominal aortic aneurysms repaired. The majority of the patients (104/112) were male and their mean age was 64.5 years (range 45-88). Ninety-three per cent of the subjects were smokers prior to the first operation and 43% continued to smoke at the time of their femoral anastomotic aneurysms operation. The mean delay between the initial surgery and the repair of the femoral anastomotic aneurysms was 74.5 months (range 1-228). The diagnosis was made because of a painless pulsatile mass (91/142), acute leg ischaemia (27/142), a painful pulsatile mass (12/142), haemorrhage (10/142), pseudo-post-phlebitic oedema (1/142) and microemboli of the toes (1/142). The operative mortality was 2.7% (3/112) of which two-thirds were patients with infected grafts. Two subgroups were distinguished: 10 patients with an infected femoral anastomotic aneurysm and 12 patients with recurrent femoral anastomotic aneurysms, 11 with a single recurrence and one with a double recurrence. In the infected group, the time to development of anastomotic aneurysm was shorter than for the group with non-infected femoral anastomotic aneurysms (41 versus 74.5 months) and the operative mortality was 20% (2/10). One patient developed a recurrent femoral anastomotic aneurysm and another was lost to follow-up. Two subsequent deaths occurred, which were unrelated to the femoral anastomotic aneurysms. In the group of recurrent femoral anastomotic aneurysms one patient was lost to follow-up and two patients died, but not as a result of recurrent femoral anastomotic aneurysms. A total of 122 cases underwent interposition of a new prosthetic segment between the proximal prosthesis and the distal artery (89 at the common femoral, 21 at the femoral profundis, eight at the superficial femoral and four at an existing femoro-popliteal graft). [less ▲]

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