Endoglin: An accessory component of the TGF‐β‐binding receptor‐complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies

Fonsatti, Ester; Vecchio, Luigi Del; Altomonte, Maresa; Sigalotti, Luca; Nicotra, Maria Rita; Coral, Sandra; Natali, Pier Giorgio; Maio, Michele

doi:10.1002/jcp.1095

Cited by 158 publications

(171 citation statements)

References 43 publications

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“…CD105 or endoglin is a more recently recognised endothelial antigen that is strongly expressed on proliferating EC, but little or not on resting EC. Therefore, CD105 represents a powerful marker of neovascularisation (Fonsatti et al, 2000(Fonsatti et al, , 2001). Blood vessel counts using CD105 are a better prognostic factor than CD34 in patients with breast cancer (Kumar et al, 1999).…”

Section: Anti-vegf Mab Reduces Tumour Vdmentioning

confidence: 99%

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Wildiers¹,

Guetens²,

Boeck³

et al. 2003

Br J Cancer

304

150

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Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P ¼ 0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.

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Section: Anti-vegf Mab Reduces Tumour Vdmentioning

confidence: 99%

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Wildiers¹,

Guetens²,

Boeck³

et al. 2003

Br J Cancer

304

150

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“…35,36 In CIMF, TGF-b is strongly expressed by megakaryocytes, 37,38 a large proportion of which express CD105.…”

Section: Endoglin In Myelofibrosismentioning

confidence: 99%

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

et al. 2004

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Microvascular density (MVD) is substantially increased in bone marrow biopsies of patients with chronic idiopathic myelofibrosis (CIMF). CD105, a useful molecule for assessing MVD in various malignancies, is preferentially expressed by recently formed microvessels. Increased serum-soluble CD105 in patients with chronic myeloproliferative disorders, including CIMF, was documented. CD105 MVD has not so far been investigated in CIMF: to this end, the results in 55 patients with CIMF and 21 controls were compared with the conventional CD34 immunostaining as well as traditional histological and clinical disease features. The MVD mean values estimated by both CD105 and CD34 were significantly higher in CIMF patients than in controls (Po0.00001). In addition, the proportion of CD105-positive megakaryocytes was significantly higher in CIMF than in controls (Po0.0001). A degree of reticulin fibrosis 42 correlated with increased CD105 MVD (P ¼ 0.05). A multivariate analysis confirmed that CD105-positive MVD was an independent adverse prognosticator. This study demonstrates that while MVD, as assessed by both CD34 and CD105 immunostaining, is significantly increased in CIMF, only CD105-determined MVD correlates with the degree of fibrosis and is prognostically relevant. These findings provide a rationale for the investigational use of anti-CD105-targeted drugs in CIMF.

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“…The genes in Group 1 included a number of protein phosphatases that may act to down-regulate signal transduction pathways that promote cell growth, 56 TGF-␤1, a potent inhibitor of cellular proliferation, 57 and endoglin, a member of the TGF-␤ superfamily of receptors. 58 The genes in Group 1 of Table 4 also include two members of the AP-1 (activating protein-1) family of transcription factors that con- sists of homodimers and heterodimers of Jun (v-Jun, c-Jun, JunB, JunD), Fos (v-Fos, c-Fos, FosB, Fra1, Fra2), Jun dimerization partners (JDP1 and JDP2), or activating transcription factor (ATF2, ATF3, B-ATF) proteins. 59 In contrast to c-Jun, a well-known promoter of cell proliferation, JunB and JunD are both potent negative regulators of proliferation.…”

Section: Expression Profiling Of T(14;18)-positive Cell Lines 131mentioning

confidence: 99%

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

Robetorye

Bohling

Morgan

et al. 2002

The Journal of Molecular Diagnostics

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The t(14;18) is the most common genetic alteration in follicular lymphoma, and is detectable in a subset of diffuse large B-cell lymphomas (DLBCL), resulting in over-expression of the anti-apoptotic protein BCL-2. Although the t(14;18)-induced over-expression of BCL-2 is an important step in lymphomagenesis,The t(14;18) is a frequent chromosomal alteration in nonHodgkin's lymphomas (NHL), occurring in up to 90% of follicular lymphomas 1 and 20 to 30% of diffuse large B-cell lymphomas (DLBCL). 2,3 This translocation is acquired early in B-cell development and results in juxtaposition of the bcl-2 gene on chromosome 18 with the immunoglobulin heavy-chain locus on chromosome 14, resulting deregulated expression of a structurally intact BCL-2 protein. 4 -8 BCL-2 is located in the inner mitochondrial membrane and functions as an anti-apoptotic protein that inhibits programmed cell death, 9 resulting in accumulation of B-lymphocytes by virtue of increased cell survival. 9 -11 Although the t(14;18)-induced over-expression of bcl-2 is an important step in lymphomagenesis, this alteration alone is not sufficient to produce malignant lymphoma. This has been demonstrated in in vitro gene transfer experiments using cell lines and transgenic mice studies in which forced over-expression of bcl-2 was insufficient to cause lymphoma. 12,13 Indeed, low numbers of t(14; 18)-carrying cells can be detected in benign lymphoid tissues such as follicular hyperplasias and the hyperplastic tonsils of young children. 14 These studies indicate that cumulative genetic and cellular alterations superimposed on the t(14;18) are necessary for the development of lymphoma and underscore the need for further analysis of t(14;18)-containing DLBCLs to identify additional genes involved in lymphomagenesis and progression.cDNA microarray technology allows large scale parallel analyses of gene expression and permits simultaneous comparison of the relative gene expression levels of several thousand genes in different cell types. 15,16 This approach has now been used successfully by a number

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Endoglin: An accessory component of the TGF‐β‐binding receptor‐complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies

Cited by 158 publications

References 43 publications

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

Microarray Analysis of B-Cell Lymphoma Cell Lines with the t(14;18)

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