Synthesis and structure—anticoagulant property relationships of functionalized dextrans: CMDBS

Chaubet, Frédéric; Champion, J.; Maïga, Oumou; Mauray, Sandrine; Jozefonvicz, J.

doi:10.1016/0144-8617(95)00084-4

Cited by 49 publications

(52 citation statements)

References 18 publications

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“…Dextran derivative preparation W'ater-soluble dextran derivatixve (CMDB7) >-as prepared from dextran T40 as prexiously described (Chaubet et al 1995 (Lebeau et al 1991). The HH9 cell line used in this studx is a clone of HBL 100 cells transformed wxith the FGF-4 oncogene (Souttou et al 1996) …”

Section: Methodsmentioning

confidence: 99%

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Bagheri‐Yarmand

Kourbali²,

Mabilat³

et al. 1998

Br J Cancer

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Summary Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL1 00), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with the hst/FGF4 gene, has been shown to be highly proliferative in vitro and to induce angiogenic tumours in nude mice. We show here that CMDB7 inhibits the mitogenic activities of the conditioned media from HBL 100 and HH9 cells in a dose-dependent manner. When HH9 cells were injected s.c. into nude mice, CMDB7 treatment (300 mg kg-' week-') suppressed the tumour take and the tumour growth by about 5Oi/o and 80% respectivety. Immunohistochemical analysis showed a highly significant decrease, by more than threefold, in the endothelial density of viable tumour regions, together with a significant increase in the necrosis area. This antiangiogenic activity of CMDB7 was further demonstrated by direct inhibition of calf pulmonary artery (CPAE) and human umbilical vein (HUVEC) endothelial cell proliferation and migration in vitro. In addition, we showed that CMDB7 inhibits specifically the mitogenic effects of the growth factors that bind to hepann such as FGF-2, FGF-4, platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGF-p1), but not those of epidermal growth factor (EGF) and insulin-like growth factor (IGF-1). These results demonstrate that CMDB7 inhibits FGF-2/FGF-4-dependent tumour growth and angiogenesis, most likety by disrupting the autocrine and paracrine effects of growth factors released from the tumour cells.

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Section: Methodsmentioning

confidence: 99%

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Bagheri‐Yarmand

Kourbali²,

Mabilat³

et al. 1998

Br J Cancer

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“…A water-soluble dextran derivative (CMDB7) was prepared as previously described (Chaubet et al, 1995). Its chemical composition, determined by acidimetric titration and elementary analysis of nitrogen, is 0% dextran, 70% carboxymethyl and 30% benzylamide.…”

Section: Dextran Derivative Preparationmentioning

confidence: 99%

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

et al. 2003

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Vascular endothelial growth factor (VEGF) expression is elevated in a wide variety of solid tumours. Inhibition of VEGF activities is able to reduce angiogenesis and tumour growth. We have recently shown in vitro that carboxymethyl dextran benzylamide (CMDB7) prevents the binding of VEGF 165 to its cell surface receptors and thus inhibits VEGF activities on endothelial cells. In the present study, we explored the effects of CMDB7 on highly aggressive human epidermoid carcinoma A431 cells known to overexpress epidermal growth factor receptors (EGFRs) and produce a high amount of VEGF and a minor quantity of bFGF. In vitro, CMDB7 blocked the mitogenic activity of A431-conditioned medium on endothelial cells. Concerning A431 cells, CMDB7 inhibited their proliferation and the VEGF 165 binding to them. In vivo, administration of CMDB7 (10 mg kg À1 ) three times per week for 2 weeks inhibited the growth of A431 xenografts in nude mice by 73% as compared to the control group. Immunostaining of endothelial cells with mouse-specific GSL-1 lectin in tumour sections revealed that CMDB7 also inhibited the density of intratumour endothelial cells by 66%. These findings demonstrate that CMDB7 has an efficient antiangiogenic and antitumour action in vivo even when tumour cells produce a high level of VEGF and EGFRs.

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“…CMDB was synthesized by Sterilyo Laboratories (Levallois-Perret, France) with some modi®cations of the procedure described previously (Mauzac & Jozefonvicz, 1984;Chaubet et al, 1995). Brie¯y, CMDB was prepared in one step by simultaneous carboxymethylation and benzylamidation of dextran T40.…”

Section: Compound Preparationmentioning

confidence: 99%

Aponecrotic, antiangiogenic and antiproliferative effects of a novel dextran derivative on breast cancer growth in vitro and in vivo

Benedetto

Starzec

Colombo

et al. 2002

British J Pharmacology

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1 1 Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory eect of carboxymethyl benzylamide dextran (CMDB) on the breast cancer growth, we performed the esteri®cation of CMDB with NaPa to obtain a new drug carrying the characteristics of these two components. A new molecule, phenylacetate carboxymethyl benzylamide dextran, was named NaPaC. 2 We investigated in vitro and in vivo the eects of NaPaC on MCF-7ras cell growth as well as its apoptotic and antiangiogenic eects in comparison to NaPa and CMDB. In addition, we assessed in vitro the antiproliferative eects of these drugs on other breast cancer cells, including MDA-MB-231, MDA-MB-435 and MCF-7. 3 In vitro, NaPaC inhibited MCF-7ras cell proliferation by 40% at concentration lower than that of CMDB and NaPa (12 mM vs 73 mM and 10 mM). IC 50 s were 6 and 28 mM for NaPaC and CMDB, respectively. The similar results were obtained for three other breast cancer cell lines. NaPaC reduced the DNA replication and induced cell recruitment in G 0 /G 1 phase more eciently than its components. Moreover, it induced a cell death at concentration 1000-fold lower than NaPa. In vivo, CMDB (150 mg kg 71) and NaPa (40 mg kg 71) inhibited the MCF-7ras tumour growth by 37 and 57%, respectively, whereas NaPaC (15 mg kg 71 ) decreased tumour growth by 66% without toxicity. 5 NaPa or CMDB reduced the microvessel number in tumour by 50% after 7 weeks of treatment. NaPaC had the same eect after only 2 weeks. After 7 weeks, it generated a large necrosis area without detectable microvessels. In vitro, NaPaC inhibited human endothelial cell proliferation more eciently than CMDB or NaPa. NaPaC interacts with vascular endothelial growth factor as observed by anity electrophoresis. 6 NaPaC acts like NaPa and CMDB but in more potent manner than components used separately. Its antiproliferative, aponecrotic and anti-angiogenic actions make it a good candidate for a new anti-cancer drug.

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Synthesis and structure—anticoagulant property relationships of functionalized dextrans: CMDBS

Cited by 49 publications

References 18 publications

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

Aponecrotic, antiangiogenic and antiproliferative effects of a novel dextran derivative on breast cancer growth in vitro and in vivo

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