References of "Castronovo, Vincenzo"
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See detailStudy of the role of histone deacetylases in myofibroblastic differenciation
Glénisson, Wendy; Waltregny, David ULg; Castronovo, Vincenzo ULg

Scientific conference (2007)

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See detailAnti-proliferative properties of prenylated flavonoids from hops (Humulus lupulus L.) in human prostate cancer cell lines
Delmulle, L.; Bellahcene, Akeila ULg; Dhooge, W. et al

in Phytomedicine : International Journal of Phytotherapy and Phytopharmacology (2006), 13(9-10), 732-734

Chalcones xanthohumol (X) and desmethylxanthohumol (DMX), present in hops (Humulus lupulus L.), and the corresponding flavanones isoxanthohumol (IX, from X), 8-prenylnaringenin (8-PN, from DMX), and 6 ... [more ▼]

Chalcones xanthohumol (X) and desmethylxanthohumol (DMX), present in hops (Humulus lupulus L.), and the corresponding flavanones isoxanthohumol (IX, from X), 8-prenylnaringenin (8-PN, from DMX), and 6-prenylnaringenin (6-PN, from DMX), have been examined in vitro for their anti-proliferative activity on human prostate cancer cells PC-3 and DU145. X proved to be the most active compound in inhibiting the growth of the cell lines with IC50 values of 12.3 +/- 1.1 mu M for DU145 and 13.2 +/- 1.1 mu M for PC-3. 6-PN was the second most active growth inhibitor, particularly in PC-3 cells (IC50 of 18.4 +/- 1.2 mu M). 8-PN, a highly potent phytoestrogen, exhibited pronounced anti-proliferative effects on PC-3 and DU145 (IC50 of 33.5 +/- 1.0 and 43.1 +/- 1.2 mu M, respectively), and IX gave comparable activities (IC50 of 45.2 +/- 1.1 mu M for PC-3 and 47.4 +/- 1.1 mu M for DU145). DMX was the least active compound. It was evidenced for the first time that this family of prenylated flavonoids from hops effectively inhibits proliferation of prostate cancer cells in vitro. (c) 2006 Elsevier GmbH. All rights reserved. [less ▲]

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See detailA chemical proteomics approach for the identification of accessible antigens expressed in human kidney cancer
Castronovo, Vincenzo ULg; Waltregny, David ULg; Kischel, Philippe ULg et al

in Molecular & Cellular Proteomics (2006), 5(11), 2083-2091

A promising avenue toward the development of more selective anticancer drugs consists in the targeted delivery of bioactive molecules to the tumor environment by means of binding molecules specific to ... [more ▼]

A promising avenue toward the development of more selective anticancer drugs consists in the targeted delivery of bioactive molecules to the tumor environment by means of binding molecules specific to tumor-associated markers. We have used a chemical proteomics approach based on the ex vivo perfusion and biotinylation of accessible structures within surgically resected human kidneys with tumor to gain information about accessible and abundant antigens that are overexpressed in human cancer. This procedure led to the selective labeling with biotin of vascular structures. Biotinylated proteins were purified on streptavidin resin and identified using mass spectrometric methodologies, revealing 637 proteins, 184 of which were only found in tumor specimens and 223 of which were only found in portions of normal kidneys. Immunohistochemical and PCR analysis confirmed that several of the putative cancer antigens identified in this study are indeed preferentially expressed in tumors. In conclusion, we have developed a methodology that allows the identification of accessible biomarkers in human tissues. The tumor-associated antigens identified in this study may be suitable targets for antibody-based anticancer therapies. The experimental approach described here should be applicable to other surgical specimens and to other pathologies as well as to the study of basic physiological and immunological processes. [less ▲]

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See detailActivation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage
Dassesse, Thibaut; de Leval, Xavier; de Leval, Laurence ULg et al

in European Urology (2006), 50(5), 1021-311031

OBJECTIVE: We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa). METHODS: Expression of cyclooxygenase-2 (COX-2), TXA(2) synthase (TXS), and ... [more ▼]

OBJECTIVE: We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa). METHODS: Expression of cyclooxygenase-2 (COX-2), TXA(2) synthase (TXS), and TXA(2) receptors (TPRs), the main actors of the TXA(2) pathway, was analyzed on serial tissue sections from 46 human PCa specimens. RESULTS: The expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells. Increased immunoreactivity for these antigens was also observed in high-grade prostate intraepithelial neoplasia (HGPIN) glands. COX-2, TXS, and TPR proteins usually displayed a coordinated overexpression pattern in PCa lesions, as assessed in serial tissue sections. Increased levels of these proteins in the tumors were all significantly associated with higher Gleason scores and pathologic stages. CONCLUSIONS: Proteins specifically involved in the TXA(2) pathway are up-regulated in human PCa and their level of expression is associated with tumor extraprostatic extension and loss of differentiation. Our study is the first to examine simultaneously all key proteins involved in this pathway including TXA(2) receptors and results suggest that the TXA(2) pathway may be a potential target for PCa prevention/therapy. [less ▲]

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See detailEvaluation of original dual thromboxane A2 modulators as antiangiogenic agents
de Leval, Xavier; Dassesse, Thibaut; Dogné, Jean-Michel ULg et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2006), 318(3), 1057-1067

Angiogenesis is a promising target for the therapy of several diseases including cancer. This study was undertaken to characterize the antiangiogenic properties of a series of original dual thromboxane A ... [more ▼]

Angiogenesis is a promising target for the therapy of several diseases including cancer. This study was undertaken to characterize the antiangiogenic properties of a series of original dual thromboxane A(2) (TXA(2)) inhibitors derived from torasemide, a marketed loop diuretic with TXA(2) antagonistic properties, by evaluating their effects on human endothelial cell migration, adhesion, and viability in vitro, as well as in the ex vivo rat aortic ring assay. All drugs tested exhibited a marked affinity toward human platelet TXA(2) receptor, significantly prevented platelet aggregation induced by U-46,619, a stable TXA(2) receptor agonist, and inhibited platelet TXA(2) synthase without affecting cyclooxygenase (COX)-1 or COX-2 enzymatic activities. These dual TXA(2) inhibitors dose dependently inhibited endothelial cell migration in chemotaxis assays using vascular endothelial growth factor ( VEGF) as a chemoattractant but failed to affect cell adhesion and viability. The highest rates of cell migration inhibition were obtained with original compounds BM-567 and BM-573 (50.3 and 59.4% inhibition, respectively) when used at the final concentration of 10 mu M. In addition, pretreatment of endothelial cells with these two drugs significantly prevented U-46,619-induced intracellular Ca2+ pool mobilization, thus suggesting a mechanistic link between inhibition of the TXA(2) pathway and reduced endothelial cell migration. Treatment of rat aortic explants with U-46,619 (9,11- dideoxy- 9,11- methanoepoxyprostaglandin F 2) significantly enhanced vessel sprouting whereas aortic rings treated with some of the compounds, including BM-567 (N-n-pentyl-N'-[2-(cyclohexylamino)-5-nitrobenzenesulfonyl] urea) and BM-573 (N-tert-butyl-N'-[5-nitro-2p- toluylaminobenzenesulfonyl]urea), showed a significant decrease in vessel sprouting, which was not reversed by the addition of VEGF. These data suggest that our original dual TXA(2) inhibitors bear antiangiogenic properties, mainly by inhibiting endothelial cell migration. [less ▲]

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See detailNovel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders
Wedel, Thilo; Van Eys, Guillaume; Waltregny, David ULg et al

in Neurogastroenterology and Motility (2006), 18(7), 526-538

Histopathological studies of gastrointestinal motility disorders have mainly focused on enteric nerves and interstitial cells of Cajal, but rarely considered the enteric musculature. Here we used both ... [more ▼]

Histopathological studies of gastrointestinal motility disorders have mainly focused on enteric nerves and interstitial cells of Cajal, but rarely considered the enteric musculature. Here we used both classical and novel smooth muscle markers and transmission electron microscopy (TEM) to investigate muscular alterations in severe colorectal motility disorders. Full-thickness specimens from Hirschsprung's disease, idiopathic megacolon, slow-transit constipation and controls were stained with haematoxylin/eosin (HE) and Masson's trichrome (MT), incubated with antibodies against smooth muscle alpha-actin (alpha-SMA), smooth muscle myosin heavy chain (SMMHC), smoothelin (SM) and histone deacetylase 8 (HDAC8) and processed for TEM. Control specimens exhibited homogeneous immunoreactivity for all antibodies. Diseased specimens showed normal smooth muscle morphology by HE and MT. While anti-alpha-SMA staining was generally normal, immunoreactivity for SMMHC, HDAC8 and/or SM was either absent or focally lacking in Hirschsprung's disease (80%), idiopathic megacolon (75%) and slow-transit constipation (70%). Ultrastructurally, clusters of myocytes with noticeably decreased myofilaments were observed in all diseases. SMMHC and the novel smooth muscle markers SM and HDAC8 often display striking abnormalities linked to the smooth muscle contractile apparatus unnoticed by both routine stainings and alpha-SMA, suggesting specific defects of smooth muscle cells involved in the pathogenesis of gastrointestinal motility disorders. [less ▲]

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See detailUse of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus
de Leval, Laurence ULg; Waltregny, David ULg; Boniver, Jacques ULg et al

in American Journal of Surgical Pathology (2006), 30(3), 319-327

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common ... [more ▼]

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic. Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD 10. All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs. In conclusion: 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors. [less ▲]

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See detailThe biology of HDAC8
Waltregny, David ULg; Castronovo, Vincenzo ULg

Book published by The Humana Press Inc. (2006)

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See detailExpression of dentin sialophosphoprotein in human prostate cancer and its correlation with tumor aggressiveness
Chaplet, Michael; Waltregny, David ULg; Detry, Cédric ULg et al

in International Journal of Cancer = Journal International du Cancer (2006), 118(4), 850-856

Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer. The expression of these proteins is associated ... [more ▼]

Recent studies have demonstrated that two SIBLING family members, bone sialoprotein (BSP) and osteopontin (OPN), are overexpressed in human prostate cancer. The expression of these proteins is associated with the acquisition of a metastatic phenotype by cancer cells and a poor prognosis for the patient. Dentin sialophosphoprotein (DSPP) shares several structural and genetic features with OPN and BSP. The presence of DSPP has been recently established in salivary glands, indicating that its expression is not restricted to mineralized tissues. However, its potential expression in human tumors has not been addressed yet. In this study, we sought to evaluate the expression of DSPP in human prostate cancer. Immunohistochemistry was performed on 69 prostate cancer specimens using LFMb-21 anti-DSPP monoclonal antibody. All of the prostate cancer lesions examined expressed detectable levels of DSPP, as compared with no or low level of expression in adjacent normal glands (p < 0.0001). High grade prostatic intraepithelial neoplasia (HGPIN) glands generally displayed DSPP expression levels that were similar to those found in neighboring cancer glands. DSPP expression was significantly associated with the pathological stage (p = 0.0087) and the Gleason score (p = 0.0176) of the tumors. Western Blot was performed on 5 representative prostate tumor extracts and 3 prostatic tumor cell lines (PC3, LNCaP and DU145). All tumor extracts and cell lines analyzed have been found to express DSPP. In addition, in situ hybridization was used to assess the presence of DSPP mRNA. DSPP was detected at the RNA level in both HGPIN and tumoral glands. This study shows for the first time that DSPP is ectopically expressed in human prostate cancer. The expression of this SIBLING protein strongly correlates with conventional histopathological prognostic indicators of prostate cancer progression. (c) 2005 Wiley-Liss, Inc. [less ▲]

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See detailHistone deacetylase HDAC7 as a key regulator of the angiogenic process
Mottet, Denis; Bellahcene, Akeila ULg; Waltregny, David ULg et al

Poster (2006, January 20)

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See detailHistone deacetylase HDAC8 associates with smooth muscle alpha–actin and is essential for smooth muscle cell contractility
Glénisson, Wendy; Waltregny, David ULg; Tran, Syv Li et al

Conference (2006)

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See detailStudy of the role of histone deacetylases in myofibroblastic differenciation
Glénisson, Wendy; Waltregny, David ULg; Castronovo, Vincenzo ULg

Scientific conference (2006)

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See detailEvaluation of original dual thromboxane A2 modulators as anti-angiogenic agents
Dassesse, Thibaut; de Leval, Xavier; Dogné, Jean-Michel et al

Scientific conference (2006)

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See detailIdentification of accessible proteins expressed in human breast cancer
Castronovo, Vincenzo ULg; Kischel, Philippe; Guillonneau, François et al

Scientific conference (2006)

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See detailHistone deacetylase 7 is involved in the control of angiogenesis by regulating platelet-derived growth factor-β
Mottet, Denis; Bellahcene, Akeila ULg; Deroanne, Christophe et al

Conference (2006)

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See detailRole of tumor-associated lipogenesis in the formation and composition of membrane microdomains
Timmermans, L.; Kischel, Philippe; Beckers, Albert ULg et al

Conference (2006)

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See detailRole of histone deacetylases in myofibroblastic differenciation
Glénisson, Wendy; Waltregny, David ULg; Castronovo, Vincenzo ULg

Conference (2006)

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