References of "Castronovo, Vincenzo"
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See detailPrognostic Value of Bone Sialoprotein Expression in Clinically Localized Human Prostate Cancer
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Journal of the National Cancer Institute (1998), 90(13), 1000-8

BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the ... [more ▼]

BACKGROUND: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate whether BSP might also be expressed in human prostate cancer, which often metastasizes to bone, and be predictive for progression risk. METHODS: Tissue sections from 180 patients who had undergone a radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided. RESULTS: Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses. After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%-47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% CI = 2.3%-20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P<.05) among patients with moderately differentiated tumors or with pathologically confined tumors. CONCLUSIONS: To our knowledge, this study is the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas. [less ▲]

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See detailCancer du col de l'utérus: analyse du coût-bénéfice et de l'efficacité du dépistage opportuniste versus le dépistage organisé
Castronovo, Vincenzo ULg; Foidart, Jean-Michel ULg; Boniver, Jacques ULg

in Revue Médicale de Liège (1998), 53(5), 305-7

Cervical cancer is the fourth cancer in women. It is the first malignancy for which mass population screening has been demonstrated to significantly reduce the mortality due to this disease. In Belgium ... [more ▼]

Cervical cancer is the fourth cancer in women. It is the first malignancy for which mass population screening has been demonstrated to significantly reduce the mortality due to this disease. In Belgium, the mortality associated to cervical cancer decreased from 6 to 4 per 100,000 women-years from 1955-1959 to 1985-1989. European recommendations regarding cervical cancer screening are to perform a cervical smear each three years in women aged 25 to 65 years. In Belgium, while the Flemish region has decided to organize the cervical cancer screening according to the European recommendations, the screening in the French part of the country is essentially opportunistic. In this short review, the cost/benefit of the organized screening versus the opportunistic screening is discussed. [less ▲]

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See detailEvidence That Breast Cancer Associated Microcalcifications Are Mineralized Malignant Cells
Castronovo, Vincenzo ULg; Bellahcene, Akeila ULg

in International Journal of Oncology (1998), 12(2), 305-8

Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only ... [more ▼]

Microcalcifications are often associated with both benign and malignant human breast lesions. Around 40% of mammary carcinoma present such ectopic mineralization and frequently, they are the only mammographic feature that indicate the presence of a tumoral lesion. Microcalcifications associated with breast cancer are usually composed of hydroxyapatite, the bone specific mineral. The mechanisms responsible for the formation of such crystals within breast malignant tissue have not been elucidated. A possible clue could be provided by the recent demonstration that breast cancer cells express several bone matrix proteins including osteonectin, osteopontin and bone sialoprotein (BSP). This latter phospho-protein is involved in the initiation of hydroxyapatite crystallisation and its expression in breast cancer has been associated to the presence of hydroxyapatite microcalcifications. We examined 10 human breast cancer lesions which were characterized by the presence of microcalcifications and high expression of BSP. Histological examination of the lesions suggested, in most of the cases, that the microcalcifications were breast cancer cells which became mineralized. Hydroxyapatite stained in blue by hematoxylin appears concentrated around single of associated cancer cells. Staining of these tissue sections with 4',6 diamidino-2-phenylindole which specifically labels DNA led us to demonstrate that the mineralizated structures contain cells. These data are the first direct demonstration that breast microcalcifications are fossils of cancer cells. The mechanisms for such a phenomenon remain to be demonstrated. We speculate that the high expression of BSP could create an appropriate microenvironment for the crystallisation of calcium and phosphate into hydroxyapatite. [less ▲]

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See detailExpression of bone sialoprotein in human prostate is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

Conference (1998, January 23)

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See detailExpression of bone sialoprotein in human prostate cancer is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Acta Clinica Belgica (1998, January), 53(3), 221-240

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See detailThe 67-kDa laminin receptor originated from a ribosomal protein that acquired a dual function during evolution.
Ardini, E.; Pesole, G.; Tagliabue, E. et al

in Molecular Biology and Evolution (1998), 15(8), 1017-25

The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that mediates high-affinity interactions between cells and laminin. Overexpression of this protein in tumor cells has been related ... [more ▼]

The 67-kDa laminin receptor (67LR) is a nonintegrin cell surface receptor that mediates high-affinity interactions between cells and laminin. Overexpression of this protein in tumor cells has been related to tumor invasion and metastasis. Thus far, only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated. The finding that the cDNA for the 37LRP is virtually identical to a cDNA encoding the ribosomal protein p40 has suggested that 37LRP is actually a component of the translational machinery, with no laminin-binding activity. On the other hand, a peptide of 20 amino acids deduced from the sequence of 37LR/p40 was shown to exhibit high laminin-binding activity. The evolutionary relationship between 23 sequences of 37LRP/p40 proteins was analyzed. This phylogenetic analysis indicated that all of the protein sequences derive from orthologous genes and that the 37LRP is indeed a ribosomal protein that acquired the novel function of laminin receptor during evolution. The evolutionary analysis of the sequence identified as the laminin-binding site in the human protein suggested that the acquisition of the laminin-binding capability is linked to the palindromic sequence LMWWML, which appeared during evolution concomitantly with laminin. [less ▲]

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See detailTumor angiogenesis : basis for new prognostic factors and new anticancer therapies.
Belotti, D.; Castronovo, Vincenzo ULg

in Clinical and Biological Basis of Lung Cancer Prevention. (1998)

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See detailBone sialoprotein is expressed in both human neuroblastoma tissues and cell lines
Bellahcene, Akeila ULg; Albert, Valérie; Nyabi, Omar et al

in Proceedings of the American Association for Cancer Research (1998), 39

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See detailExpression of bone sialoprotein in human prostate cancer is associated with progression
Waltregny, David ULg; Bellahcene, Akeila ULg; Van Riet, Ivan et al

in Proceedings of the American Association for Cancer Research (1998), 39

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See detailFormation of the 67-kDa laminin receptor by acylation of the precursor.
Buto, S.; Tagliabue, E.; Ardini, E. et al

in Journal of Cellular Biochemistry (1998), 69(3), 244-51

Even though the involvement of the 67-kDa laminin receptor (67LR) in tumor invasiveness has been clearly demonstrated, its molecular structure remains an open problem, since only a full-length gene ... [more ▼]

Even though the involvement of the 67-kDa laminin receptor (67LR) in tumor invasiveness has been clearly demonstrated, its molecular structure remains an open problem, since only a full-length gene encoding a 37-kDa precursor protein (37LRP) has been isolated so far. A pool of recently obtained monoclonal antibodies directed against the recombinant 37LRP molecule was used to investigate the processing that leads to the formation of the 67-kDa molecule. In soluble extracts of A431 human carcinoma cells, these reagents recognize the precursor molecule as well as the mature 67LR and a 120-kDa molecule. The recovery of these proteins was found to be strikingly dependent upon the cell solubilization conditions: the 67LR is soluble in NP-40-lysis buffer whereas the 37LRP is NP-40-insoluble. Inhibition of 67LR formation by cerulenin indicates that acylation is involved in the processing of the receptor. It is likely a palmitoylation process, as indicated by sensitivity of NP-40-soluble extracts to hydroxylamine treatment. Immunoblotting assays performed with a polyclonal serum directed against galectin3 showed that both the 67- and the 120-kDa proteins carry galectin3 epitopes whereas the 37LRP does not. These data suggest that the 67LR is a heterodimer stabilized by strong intramolecular hydrophobic interactions, carried by fatty acids bound to the 37LRP and to a galectin3 cross-reacting molecule. [less ▲]

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See detailExpression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells.
Sarafian, V.; Jadot, Michel ULg; Foidart, Jean-Michel ULg et al

in International Journal of Cancer = Journal International du Cancer (1998), 75(1), 105-11

Lysosomal-membrane-associated glycoproteins (Lamps) 1 and 2 are rarely found on the plasma membranes of normal cells. There is evidence suggesting an increase in their cell-surface expression in tumor ... [more ▼]

Lysosomal-membrane-associated glycoproteins (Lamps) 1 and 2 are rarely found on the plasma membranes of normal cells. There is evidence suggesting an increase in their cell-surface expression in tumor cells, with some data indicating that the adhesion of some cancer cells to the extracellular matrix is partly mediated by interactions between Lamps and E-selectin and between Lamps and galectins (endogenous-galactoside-binding lectins). The present study examined the expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in different human tumor cell lines. Indirect immunofluorescence staining revealed accumulation of Lamp molecules at the edges of A2058 human metastasizing melanoma cells suggesting that these glycoproteins could participate in cell adhesion. Flow cytometry showed the presence of cell-surface Lamps in A2058, HT1080 (human fibrosarcoma) and CaCo-2 (human colon-adenocarcinoma) cells. Treatment with 2 mM sodium butyrate for 24 and 48 hr resulted in a significant increase in Lamps surface expression. A strong binding of A2058 to recombinant galectin-3 was detected by FACS. The application of 2 and 5 mM butyrate for the same incubation period enhanced galectin-3 binding to Lamps-expressing cells. Our results support the idea that Lamps may be considered a new family of adhesive glycoproteins participating in the complex process of tumor invasion and metastasis. [less ▲]

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See detailExpression of Bone Sialoprotein in Human Lung Cancer
Bellahcene, Akeila ULg; Maloujahmoum, Naïma ULg; Fisher, L. W. et al

in Calcified Tissue International (1997), 61(3), 183-8

Lung cancer belongs to the group of malignant lesions that specifically select bone as secondary implantation site. The molecular bases for this property, defined as osteotropism, is still largely unknown ... [more ▼]

Lung cancer belongs to the group of malignant lesions that specifically select bone as secondary implantation site. The molecular bases for this property, defined as osteotropism, is still largely unknown. The recent demonstration that human breast cancer cells express and attach to bone sialoprotein (BSP), a sulfated phosphoprotein rich in bone and other mineralized tissues, could provide a clue to elucidating bone metastases formation. BSP contains the integrin binding peptide Arg-Gly-Asp (RGD), as well as non-RGD cell attachment domain. Using an immunoperoxidase technique and a specific polyclonal antibody directed against a BSP synthetic peptide, we examined the expression of BSP in 48 lung lesions including 25 squamous carcinoma, 21 adenocarcinoma, and 2 bronchioloalveolar cancers, as well as 38 human ovarian carcinoma that constitute a group of generally nonosteotropic cancers. BSP was not specifically detected in normal lung tissue with the exception of cartilage associated with bronchi. Most of the adenocarcinoma (74%) and all squamous carcinoma of the lung examined exhibited detectable levels of BSP. Staining was mainly cytoplasmic and membrane associated. The two bronchioloalveolar lung cancers examined did not show detectable amounts of BSP. When microcalcifications were observed in pulmonary malignant lesions, they were usually associated with cancer cells expressing BSP. Only 21% of the ovarian cancers examined contained malignant cells with 2+ or 3+ positivity for BSP. We further demonstrated that in 8 of 10 additional lung cancers, BSP was detected at the mRNA level. Our observation is the first demonstration that BSP is expressed in non-small cell lung carcinoma. Lung cancer cells are now the second type of osteotropic malignant cells described to express BSP. Added to the observation that BSP expression is not frequent in ovarian carcinoma, a low osteotropic cancer, our study supports our hypothesis that BSP could play a role in determining the affinity of cancer cells to bone. [less ▲]

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See detailDifferential expression of galectin-1 and galectin-3 during first trimester human embryogenesis.
van den Brûle, Frédéric; Fernandez, Pedro L.; Buicu, Crina et al

in Developmental Dynamics : An Official Publication of the American Association of Anatomists (1997), 209(4), 399-405

Development of complex organisms requires specific temporospatial differentiation and expression of the correct phenotype through activation of a variety of genes. Galectins are mammalian lectins able to ... [more ▼]

Development of complex organisms requires specific temporospatial differentiation and expression of the correct phenotype through activation of a variety of genes. Galectins are mammalian lectins able to interact with various extracellular matrix glycoconjugates and have been implicated in several biological events including cell attachment, differentiation, apoptosis, embryogenesis, and cancer invasion and metastasis. In this study, we have examined the expression of galectin-1 and galectin-3 during human first trimester embryogenesis using immunohistochemistry and Western blotting. Variable amounts of galectin-1 and galectin-3 were detected in all tissue protein extracts. Galectin-1 expression was demonstrated in the connective tissue and derived tissues such as smooth and striated muscle cells, and in some epithelia, such as in the basal layers of the skin after 14 weeks and in the epithelial cells of the gonads. Galectin-3 was detected mainly in epithelia, such as the skin, epithelial lining of the digestive and respiratory tract, and urothelium and excretory tubes of the kidney, but also in the myocardial cells, in the peripheral and preossifying hypertrophic chondrocytes, and in the notochord and in the liver. Our study constitutes the first demonstration of galectin-1 and galectin-3 during human embryogenesis. The differential expression of these two lectins suggests that they could participate in the complex processes of tissue differentiation. [less ▲]

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See detailThe 37 LRP/P40 polypeptide: a multifunctional pleiotropic molecule involved in tumorigenesis and metastasis - A review
Clausse, Nathalie; Jackers, Pascale ULg; Castronovo, Vincenzo ULg

in Belgian Journal of Zoology (1997), 127(issue 1), 3-11

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See detailExpression of the 67 Kd Laminin Receptor in Human Cervical Preneoplastic and Neoplastic Squamous Epithelial Lesions: An Immunohistochemical Study
al-Saleh, W.; Delvenne, Philippe ULg; van den Brule, F. A. et al

in Journal of Pathology (The) (1997), 181(3), 287-93

Interactions of cancer cells with laminin play a critical role during the progression of solid malignant tumours. Increased expression of the 67 kD laminin receptor (67LR), one of the several laminin ... [more ▼]

Interactions of cancer cells with laminin play a critical role during the progression of solid malignant tumours. Increased expression of the 67 kD laminin receptor (67LR), one of the several laminin binding proteins, is associated with the invasive and metastatic capacity of various types of cancer, including breast, colon, ovary, lung, and endometrial carcinoma. In this study, 67LR expression was analysed in a series of cervical biopsy specimens including 16 normal cervical tissues, 36 low-grade squamous intraepithelial lesions (SILs), 24 high-grade SILs, and 11 invasive carcinomas. Detection of the 67LR was performed using immunoperoxidase staining and the monoclonal antibody MLuC5 which specifically recognizes the 67LR. Immunostaining of the 67LR was correlated with human papillomavirus (HPV) type detected by in situ hybridization and with proliferative activity of the lesion determined by immunohistochemistry with the MIB-1 monoclonal antibody, specific for the Ki67 antigen. Increased expression of the 67LR was correlated with the histological severity of the lesions, with the strongest immunoreactivity being found in invasive carcinomas. Significant differences in 67LR expression were found between normal cervical epithelium and high-grade SILs (P < 0.05, non-parametric Mann-Whitney test) or invasive carcinomas (P < 0.001), as well as between low- or high-grade SILs and invasive carcinoma (P < 0.01 and P < 0.05, respectively). Ki67 antigen expression also increased with the severity of the lesions. There was a positive correlation for each type of lesion between expression of the 67LR and of the Ki67 antigen. No specific relationship was found between 67LR or Ki67 antigen immunostaining and HPV type detected in SILs, segregated into low-grade and high-grade lesions. These data add weight to the evidence that increased expression of the 67LR is a consistent, but not sufficient feature of the invasive and metastatic phenotype and suggest that high expression of the 67LR might be associated with both more proliferative and more aggressive cervical (pre)neoplastic lesions. [less ▲]

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See detailIndependent value of the 67-kilodalton laminin receptor in human prostate cancer
Waltregny, David ULg; de Leval, Laurence ULg; Ménard, Sylvie et al

Conference (1997, January 17)

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See detailExpression of Bone Matrix Proteins in Human Breast Cancer: Potential Roles in Microcalcification Formation and in the Genesis of Bone Metastases
Bellahcene, Akeila ULg; Castronovo, Vincenzo ULg

in Bulletin du Cancer (1997), 84(1), 17-24

The skeleton is the privileged target of metastatic human breast cancer cells. Bone metastases are indeed found in virtually all advanced breast cancer patients and generate major morbidity. The high ... [more ▼]

The skeleton is the privileged target of metastatic human breast cancer cells. Bone metastases are indeed found in virtually all advanced breast cancer patients and generate major morbidity. The high osteotropism of breast cancer cells suggests that they exhibit a selective affinity for mineralized tissues. The observation that mammary malignant cells are able to induce hydroxyapatite crystals deposition within the primary tumour suggests that they can generate a microenvironment that favors the crystallization of calcium and phosphate ions into the bone specific hydroxyapatite. Osteonectin (OSN), osteopontin (OPN) and bone sialoprotein (BSP), 3 bone matrix proteins involved in bone matrix mineralization, are expressed in human breast cancers. BSP, an RGD (Arg-Gly-Asp) containing phosphoprotein, initiates hydroxyapatite deposition and mediates attachment of osteoclast to the same crystals prior to their resorption. Detection of BSP at both the protein and the mRNA levels in human breast cancer and in human breast cancer cell lines (MCF-7, T47-D and MDA-MB 231) indicates that mammary malignant cells synthesize directly BSP rather than uptaking it from the serum. Interestingly, the level of BSP expression correlates with the development of bone metastases and with poor survival. These data suggest that the ectopic expression of bone matrix proteins could be involved in conferring osteotropic properties to circulating metastatic breast cancer cells. These observations open new alleys of investigation for the identification of the molecular mechanisms responsible for the genesis of bone metastases. [less ▲]

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See detailGalectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue.
Fernandez, P. L.; Merino, M. J.; Gomez, M. et al

in Journal of Pathology (The) (1997), 181(1), 80-6

Galectin-3 is a 31 kD beta-galactoside-binding lectin which is expressed by several types of non-neoplastic and neoplastic cells and which may be involved in cell-extracellular matrix interactions. An ... [more ▼]

Galectin-3 is a 31 kD beta-galactoside-binding lectin which is expressed by several types of non-neoplastic and neoplastic cells and which may be involved in cell-extracellular matrix interactions. An immunohistochemical study has been made of the expression of galectin-3, as well as its ligand, laminin, in a spectrum of benign and malignant thyroid neoplasms and in some non-neoplastic conditions. Immunohistochemistry with anti-human recombinant galectin-3 antibody showed consistent, intense positivity in the neoplastic cells of 18 cases of papillary carcinoma and less intense staining in the five anaplastic carcinomas studied. In addition, two out of three poorly differentiated carcinomas, three out of six medullary carcinomas, and four out of eight follicular carcinomas had less intense or focal positivity. One case of Hurthle cell carcinoma showed scattered strongly positive cells. Eight follicular adenomas, three hyperplastic nodules, five nodular goitres, and normal thyroid tissue were negative. Galectin-3 mRNA expression was also evaluated in three of the papillary carcinomas, two follicular adenomas, and one hyperplastic nodule with matched normal tissue. Northern blot analysis demonstrated mRNA overexpression in the three cases of papillary carcinomas, whereas normal and benign tissues were negative. Laminin distribution in neoplastic and non-neoplastic tissue varied with architectural patterns but did not correlate with galectin-3 immunohistochemical expression. We conclude that expression of galectin-3 is limited to inflammatory foci in normal and benign thyroid tissue and is a phenotypic feature of malignant thyroid neoplasms, especially papillary carcinomas. [less ▲]

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See detailCo-regulation and physical association of the 67-kDa monomeric laminin receptor and the alpha6beta4 integrin.
Ardini, E.; Tagliabue, E.; Magnifico, A. et al

in Journal of Biological Chemistry (1997), 272(4), 2342-5

The interactions between tumor cells and laminin or other components of the extracellular matrix have been shown to play an important role in tumor invasion and metastasis. However, the role of the ... [more ▼]

The interactions between tumor cells and laminin or other components of the extracellular matrix have been shown to play an important role in tumor invasion and metastasis. However, the role of the monomeric 67-kDa laminin receptor (67LR) remains unclear. We analyzed the regulation of 67LR expression under different culture conditions with respect to the expression of other well characterized laminin receptors. In A431 cells treated with laminin for different time periods, the regulation of 67LR expression correlated with expression of the alpha6 integrin subunit but not with the expression of other laminin receptors. Moreover, cytokine treatment resulted in down-modulated expression of the alpha6 integrin subunit and the 67LR. Co-regulation of the expression of the two receptors was further suggested by the observation that specific down-modulation of the alpha6-chain by antisense oligonucleotides was accompanied by a proportional decrease in the cell surface expression of 67LR. Biochemical analyses indicated co-immunoprecipitation of 67LR and the alpha6 subunit with an anti-alpha6 but not an anti-beta1 monoclonal antibody. Co-regulation of 67LR and alpha6 subunit expression, together with the physical association between the two receptors, supports the hypothesis that 67LR is an auxiliary molecule involved in regulating or stabilizing the interaction of laminin with the alpha6beta4 integrin. [less ▲]

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