The Experts below are selected from a list of 165 Experts worldwide ranked by ideXlab platform

Michel Crepin - One of the best experts on this subject based on the ideXlab platform.

  • cytostatic and pro apoptotic effects of a novel phenylacetate Dextran Derivative napac on breast cancer cells in interactions with endothelial cells
    Anti-Cancer Drugs, 2004
    Co-Authors: S Malherbe, Michel Crepin, Chantal Legrand
    Abstract:

    We have tested a novel hybrid molecule made of carboxymethylbenzylamide Dextran (CMDB) and sodium phenylacetate (NaPa) groups, called the CMDB-NaPa ester (NaPaC), on the proliferation of breast cancer and endothelial cells as well as paracrine effects between these two cell types. Our results showed that NaPaC inhibited the proliferation of MDA-MB-231 cells and MCF-7 cells in a dose-dependent manner. NaPaC was 20-fold more active on highly invasive MDA-MB-231 cells than the NaPa parental molecule. On MCF-7 cells, which present a less aggressive phenotype, NaPaC was only 3-fold more active than the NaPa parental molecule. Furthermore, NaPaC had only a slight effect on the proliferation of primary cultured endothelial cells (HUVEC). A cytostatic effect of NaPaC on tumor cells was observed with cells accumulating in G 0 /G 1 phase after 96 h of treatment In addition, NaPaC induced a strong apoptotic effect on the two breast cancer cell lines. Conditioned media (CM) from tumor cells inhibited HUVEC proliferation, and this effect was enhanced in the presence of NaPaC (6 mM) and NaPa (10 mM). In addition to this cytostatic effect, CM from tumor cells induced a HUVEC early apoptosis which was increased, mainly, in the presence of NaPa (15 mM). Thus, this study shows that NaPaC is a more powerful anti-proliferative molecule than its parental NaPa molecule, with cytostatic and pro-apoptotic effects on MDA-MB-231 and MCF-7 tumor cells. Also, both molecules increased a pro-apoptotic effect of tumor cells on HUVEC.

  • inhibition of epidermoid carcinoma a431 cell growth and angiogenesis in nude mice by early and late treatment with a novel Dextran Derivative
    British Journal of Cancer, 2003
    Co-Authors: M Di Benedetto, Michel Crepin, Anna Starzec, Roger Vassy, Gerardyves Perret, Michel Kraemer
    Abstract:

    We investigated the effect of a new Dextran Derivative, phenylacetate carboxymethyl benzylamide Dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC50=5 μ M). Also, NaPaC decreased the binding of radiolabelled VEGF165 to endothelial cells (IC50=0.2 μ M). In vivo, we explored the effects of NaPaC (15 mg kg−1) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

  • aponecrotic antiangiogenic and antiproliferative effects of a novel Dextran Derivative on breast cancer growth in vitro and in vivo
    British Journal of Pharmacology, 2002
    Co-Authors: Melanie Di Benedetto, Anna Starzec, Michel Kraemer, Dominique Briane, Bruno M Colombo, Gerard Y Perret, Michel Crepin
    Abstract:

    1 Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory effect of carboxymethyl benzylamide Dextran (CMDB) on the breast cancer growth, we performed the esterification 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. We investigated in vitro and in vivo the effects of NaPaC on MCF-7ras cell growth as well as its apoptotic and antiangiogenic effects in comparison to NaPa and CMDB. In addition, we assessed in vitro the antiproliferative effects of these drugs on other breast cancer cells, including MDA-MB-231, MDA-MB-435 and MCF-7. In vitro, NaPaC inhibited MCF-7ras cell proliferation by 40% at concentration lower than that of CMDB and NaPa (12 μMvs 73 μM and 10 mM). IC50s were 6 and 28 μM 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 G0/G1 phase more efficiently than its components. Moreover, it induced a cell death at concentration 1000-fold lower than NaPa. In vivo, CMDB (150 mg kg−1) and NaPa (40 mg kg−1) inhibited the MCF-7ras tumour growth by 37 and 57%, respectively, whereas NaPaC (15 mg kg−1) decreased tumour growth by 66% without toxicity. NaPa or CMDB reduced the microvessel number in tumour by 50% after 7 weeks of treatment. NaPaC had the same effect 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 efficiently than CMDB or NaPa. NaPaC interacts with vascular endothelial growth factor as observed by affinity electrophoresis. 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. British Journal of Pharmacology (2002) 135, 1859–1871; doi:10.1038/sj.bjp.0704645

  • sodium phenylacetate enhances the inhibitory effect of Dextran Derivative on breast cancer cell growth in vitro and in nude mice
    British Journal of Cancer, 2001
    Co-Authors: M Di Benedetto, Michel Crepin, J Jozefonvicz, Anna Starzec, Roger Vassy, Gerardyves Perret, Yamina Kourbali, Michel Kraemer
    Abstract:

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran Derivative (CMDBLS4) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDBLS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDBLS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDBLS4 and NaPa concentrations. In nude mice, CMDBLS4 (150 mg kg−1) or NaPa (40 mg kg−1) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDBLS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDBLS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDBLS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDBLS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of Dextran Derivatives with NaPa to inhibit the breast tumour growth. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

  • a novel phenylacetate Dextran Derivative napac inhibits breast cancer cell proliferation and modifies their interactions with endothelial cells
    Breast Cancer Research, 2001
    Co-Authors: S Malherbe, Michel Crepin, M Di Benedetto, M Berard, Nicole Peyri, Chantal Legrand
    Abstract:

    Breast cancer treatments are limited by secondary effects and chemoresistances or hormone resistances. Sodium phenylacetate (NaPa), a nontoxic metabolite, has been shown to induce in vivo and in vitro antiproliferative effects on various cell types in our laboratory. We have previously shown that NaPa treatment induced breast tumor cell apoptosis without acquired drug resistance. On the other hand, we have demonstrated that a Dextran Derivative (CMDB) was not only antitumoral but also antiangiogenic in a MCF-7ras tumor model in animals. Recently, we have synthesized a novel hybrid molecule, CMDB-NaPa ester, called NaPaC, and tested its effect on the proliferation of MDA-MB-231 and MCF-7 breast tumor cells. NaPaC inhibits, dose dependently, the proliferation of MDA-MB-231 cell (IC50 0.5 mmol/l) and of MCF-7 cell (IC50 1.5 mmol/l). Primary cultured endothelial cells (HUVEC) are weakly affected by NaPaC treatment. Cytostatic effect of NaPaC was evidenced from the accumulation of tumor cells in G0/G1 phase after 96 h of treatment. As compared with the NaPa parent molecule, this new molecule was 10-fold more efficient on these two tumor cell lines. Moreover, NaPaC induces a strong apoptotic effect, as measured with Annexin V-positive cells, on these tumor cells. In order to understand the interactions between tumor cells and endothelial cells, the conditioned media were prepared and added to HUVEC cells. Our results showed a clear killing effect on HUVEC cells. However, this killing effect can be rescued by adding NaPaC. Taken together, our results showed that NaPaC is a powerful anti-tumoral molecule, with cytostatic and proapoptotic effects on MDA-MB-231 and MCF-7 tumor cells. Further studies should be conducted to better understand the mechanism of these mutual interactions between tumor cells and endothelial cells, especially the killing effect on HUVEC cells.

M Di Benedetto - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of epidermoid carcinoma a431 cell growth and angiogenesis in nude mice by early and late treatment with a novel Dextran Derivative
    British Journal of Cancer, 2003
    Co-Authors: M Di Benedetto, Michel Crepin, Anna Starzec, Roger Vassy, Gerardyves Perret, Michel Kraemer
    Abstract:

    We investigated the effect of a new Dextran Derivative, phenylacetate carboxymethyl benzylamide Dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC50=5 μ M). Also, NaPaC decreased the binding of radiolabelled VEGF165 to endothelial cells (IC50=0.2 μ M). In vivo, we explored the effects of NaPaC (15 mg kg−1) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

  • sodium phenylacetate enhances the inhibitory effect of Dextran Derivative on breast cancer cell growth in vitro and in nude mice
    British Journal of Cancer, 2001
    Co-Authors: M Di Benedetto, Michel Crepin, J Jozefonvicz, Anna Starzec, Roger Vassy, Gerardyves Perret, Yamina Kourbali, Michel Kraemer
    Abstract:

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran Derivative (CMDBLS4) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDBLS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDBLS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDBLS4 and NaPa concentrations. In nude mice, CMDBLS4 (150 mg kg−1) or NaPa (40 mg kg−1) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDBLS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDBLS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDBLS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDBLS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of Dextran Derivatives with NaPa to inhibit the breast tumour growth. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

  • a novel phenylacetate Dextran Derivative napac inhibits breast cancer cell proliferation and modifies their interactions with endothelial cells
    Breast Cancer Research, 2001
    Co-Authors: S Malherbe, Michel Crepin, M Di Benedetto, M Berard, Nicole Peyri, Chantal Legrand
    Abstract:

    Breast cancer treatments are limited by secondary effects and chemoresistances or hormone resistances. Sodium phenylacetate (NaPa), a nontoxic metabolite, has been shown to induce in vivo and in vitro antiproliferative effects on various cell types in our laboratory. We have previously shown that NaPa treatment induced breast tumor cell apoptosis without acquired drug resistance. On the other hand, we have demonstrated that a Dextran Derivative (CMDB) was not only antitumoral but also antiangiogenic in a MCF-7ras tumor model in animals. Recently, we have synthesized a novel hybrid molecule, CMDB-NaPa ester, called NaPaC, and tested its effect on the proliferation of MDA-MB-231 and MCF-7 breast tumor cells. NaPaC inhibits, dose dependently, the proliferation of MDA-MB-231 cell (IC50 0.5 mmol/l) and of MCF-7 cell (IC50 1.5 mmol/l). Primary cultured endothelial cells (HUVEC) are weakly affected by NaPaC treatment. Cytostatic effect of NaPaC was evidenced from the accumulation of tumor cells in G0/G1 phase after 96 h of treatment. As compared with the NaPa parent molecule, this new molecule was 10-fold more efficient on these two tumor cell lines. Moreover, NaPaC induces a strong apoptotic effect, as measured with Annexin V-positive cells, on these tumor cells. In order to understand the interactions between tumor cells and endothelial cells, the conditioned media were prepared and added to HUVEC cells. Our results showed a clear killing effect on HUVEC cells. However, this killing effect can be rescued by adding NaPaC. Taken together, our results showed that NaPaC is a powerful anti-tumoral molecule, with cytostatic and proapoptotic effects on MDA-MB-231 and MCF-7 tumor cells. Further studies should be conducted to better understand the mechanism of these mutual interactions between tumor cells and endothelial cells, especially the killing effect on HUVEC cells.

  • a novel sodium phenylacetate Dextran Derivative ester inhibits the growth and angiogenesis of mcf 7ras breast cancer xenografts
    Breast Cancer Research, 2001
    Co-Authors: M Di Benedetto, J Jozefonvicz, Michel Kraemer, Dominique Briane, Olivier Oudar, Sainte O Catherine, Michel Crepin
    Abstract:

    We previously showed that sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran (CMDB) are both able to block the tumor growth of the breast cancer cell line MCF-7ras in athymic mice. In this study, we studied the effect of a new molecule: a CMDB esterified by phenylacetic acid (NaPaC). In vitro, NaPaC can inhibit threefold to fourfold more MCF-7ras proliferation than NaPa alone. Furthermore, we showed that the antiproliferative activity of NaPaC was dependent on phenylacetate substitution. In vivo studies showed that a very low dose of NaPaC (15 mg/kg) inhibited the MCF-7ras tumor growth of 60% without animal toxicity. The inhibition of tumor growth was concomitant with a reduction in angiogenesis and an increase in necrosis. Moreover, we demonstrated that NaPaC inhibited the paracrine mitogenic effect of MCF-7ras conditioned medium (CM) on fibroblasts and endothelial cells proliferation.

Michel Kraemer - One of the best experts on this subject based on the ideXlab platform.

  • inhibition of epidermoid carcinoma a431 cell growth and angiogenesis in nude mice by early and late treatment with a novel Dextran Derivative
    British Journal of Cancer, 2003
    Co-Authors: M Di Benedetto, Michel Crepin, Anna Starzec, Roger Vassy, Gerardyves Perret, Michel Kraemer
    Abstract:

    We investigated the effect of a new Dextran Derivative, phenylacetate carboxymethyl benzylamide Dextran (NaPaC), on epidermoid carcinoma A431 cells secreting a large quantity of angiogenic factor, vascular endothelial growth factor (VEGF). In vitro, NaPaC inhibited the proliferation of A431 cells (IC50=5 μ M). Also, NaPaC decreased the binding of radiolabelled VEGF165 to endothelial cells (IC50=0.2 μ M). In vivo, we explored the effects of NaPaC (15 mg kg−1) on A431 xenograft growth starting the drug administration at the time of tumour cell inoculation (early treatment) and 1 week later, when tumours were well established (late treatment). Early treatment was more efficient on tumour inhibition (70% vs control) than late treatment (50% vs control). Early and late NaPaC-treatment increased the aponecrosis in tumour by 70 and 30%, respectively. Whatever treatment, NaPaC inhibited the intratumour endothelial cell density in the same manner. In contrast, vessel area was decreased only when NaPaC was injected early (35%). These results show that NaPaC has a potent inhibitory effect, dependent on treatment outset, on epidermoid carcinoma growth associated with an intratumour microvascular network diminution and an aponecrosis increase. As this drug is nontoxic at efficient dose, it offers interesting perspectives for the therapy of malignant lesions.

  • aponecrotic antiangiogenic and antiproliferative effects of a novel Dextran Derivative on breast cancer growth in vitro and in vivo
    British Journal of Pharmacology, 2002
    Co-Authors: Melanie Di Benedetto, Anna Starzec, Michel Kraemer, Dominique Briane, Bruno M Colombo, Gerard Y Perret, Michel Crepin
    Abstract:

    1 Since the sodium phenylacetate (NaPa) was reported to enhance the inhibitory effect of carboxymethyl benzylamide Dextran (CMDB) on the breast cancer growth, we performed the esterification 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. We investigated in vitro and in vivo the effects of NaPaC on MCF-7ras cell growth as well as its apoptotic and antiangiogenic effects in comparison to NaPa and CMDB. In addition, we assessed in vitro the antiproliferative effects of these drugs on other breast cancer cells, including MDA-MB-231, MDA-MB-435 and MCF-7. In vitro, NaPaC inhibited MCF-7ras cell proliferation by 40% at concentration lower than that of CMDB and NaPa (12 μMvs 73 μM and 10 mM). IC50s were 6 and 28 μM 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 G0/G1 phase more efficiently than its components. Moreover, it induced a cell death at concentration 1000-fold lower than NaPa. In vivo, CMDB (150 mg kg−1) and NaPa (40 mg kg−1) inhibited the MCF-7ras tumour growth by 37 and 57%, respectively, whereas NaPaC (15 mg kg−1) decreased tumour growth by 66% without toxicity. NaPa or CMDB reduced the microvessel number in tumour by 50% after 7 weeks of treatment. NaPaC had the same effect 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 efficiently than CMDB or NaPa. NaPaC interacts with vascular endothelial growth factor as observed by affinity electrophoresis. 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. British Journal of Pharmacology (2002) 135, 1859–1871; doi:10.1038/sj.bjp.0704645

  • sodium phenylacetate enhances the inhibitory effect of Dextran Derivative on breast cancer cell growth in vitro and in nude mice
    British Journal of Cancer, 2001
    Co-Authors: M Di Benedetto, Michel Crepin, J Jozefonvicz, Anna Starzec, Roger Vassy, Gerardyves Perret, Yamina Kourbali, Michel Kraemer
    Abstract:

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran Derivative (CMDBLS4) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDBLS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDBLS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDBLS4 and NaPa concentrations. In nude mice, CMDBLS4 (150 mg kg−1) or NaPa (40 mg kg−1) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDBLS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDBLS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDBLS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDBLS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of Dextran Derivatives with NaPa to inhibit the breast tumour growth. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

  • a novel sodium phenylacetate Dextran Derivative ester inhibits the growth and angiogenesis of mcf 7ras breast cancer xenografts
    Breast Cancer Research, 2001
    Co-Authors: M Di Benedetto, J Jozefonvicz, Michel Kraemer, Dominique Briane, Olivier Oudar, Sainte O Catherine, Michel Crepin
    Abstract:

    We previously showed that sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran (CMDB) are both able to block the tumor growth of the breast cancer cell line MCF-7ras in athymic mice. In this study, we studied the effect of a new molecule: a CMDB esterified by phenylacetic acid (NaPaC). In vitro, NaPaC can inhibit threefold to fourfold more MCF-7ras proliferation than NaPa alone. Furthermore, we showed that the antiproliferative activity of NaPaC was dependent on phenylacetate substitution. In vivo studies showed that a very low dose of NaPaC (15 mg/kg) inhibited the MCF-7ras tumor growth of 60% without animal toxicity. The inhibition of tumor growth was concomitant with a reduction in angiogenesis and an increase in necrosis. Moreover, we demonstrated that NaPaC inhibited the paracrine mitogenic effect of MCF-7ras conditioned medium (CM) on fibroblasts and endothelial cells proliferation.

J Jozefonvicz - One of the best experts on this subject based on the ideXlab platform.

  • effect of a Dextran Derivative associated with tgf β1 or fgf 2 on dermal fibroblast behaviour in dermal equivalents
    Journal of Biomaterials Science-polymer Edition, 2004
    Co-Authors: Laetitia Frank, Corinne Lebretondecoster, G Godeau, Bernard Coulomb, J Jozefonvicz
    Abstract:

    Dextran Derivatives that mimic the action of heparin have been shown to protect heparinbinding growth factors, such as Transforming Growth Factor-β1 (TGF-β1) and Fibroblast Growth Factor-2 (FGF-2). The aim of this study was to investigate the effect of LS21 DMCBSu, a Dextran Derivative which contains methylcarboxylate, benzylamide and sulfate groups, both by itself and when combined with TGF-β1 and FGF-2, on the behaviour of fibroblasts. Two systems were assessed: a monolayer culture and three-dimensional collagenous matrices (dermal equivalent). Polymeric biomaterial LS21 DMCBSu and LS21 DMCBSu associated with either TGF-β1 or FGF-2, were added to the monolayer culture on day 3. After 7 days of culture the number of cells was determined. Two treatments were carried out on the dermal equivalents: 9 days of treatment from day 0 to day 9 of culture and 9 days of treatment from day 21 to day 30 of culture for the premature and the mature dermal equivalents respectively. In the monolayer culture, the bioactiv...

  • sodium phenylacetate enhances the inhibitory effect of Dextran Derivative on breast cancer cell growth in vitro and in nude mice
    British Journal of Cancer, 2001
    Co-Authors: M Di Benedetto, Michel Crepin, J Jozefonvicz, Anna Starzec, Roger Vassy, Gerardyves Perret, Yamina Kourbali, Michel Kraemer
    Abstract:

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran Derivative (CMDBLS4) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDBLS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDBLS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDBLS4 and NaPa concentrations. In nude mice, CMDBLS4 (150 mg kg−1) or NaPa (40 mg kg−1) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDBLS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDBLS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDBLS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDBLS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of Dextran Derivatives with NaPa to inhibit the breast tumour growth. © 2001 Cancer Research Campaignhttp://www.bjcancer.com

  • a novel sodium phenylacetate Dextran Derivative ester inhibits the growth and angiogenesis of mcf 7ras breast cancer xenografts
    Breast Cancer Research, 2001
    Co-Authors: M Di Benedetto, J Jozefonvicz, Michel Kraemer, Dominique Briane, Olivier Oudar, Sainte O Catherine, Michel Crepin
    Abstract:

    We previously showed that sodium phenylacetate (NaPa) and carboxymethyl benzylamide Dextran (CMDB) are both able to block the tumor growth of the breast cancer cell line MCF-7ras in athymic mice. In this study, we studied the effect of a new molecule: a CMDB esterified by phenylacetic acid (NaPaC). In vitro, NaPaC can inhibit threefold to fourfold more MCF-7ras proliferation than NaPa alone. Furthermore, we showed that the antiproliferative activity of NaPaC was dependent on phenylacetate substitution. In vivo studies showed that a very low dose of NaPaC (15 mg/kg) inhibited the MCF-7ras tumor growth of 60% without animal toxicity. The inhibition of tumor growth was concomitant with a reduction in angiogenesis and an increase in necrosis. Moreover, we demonstrated that NaPaC inhibited the paracrine mitogenic effect of MCF-7ras conditioned medium (CM) on fibroblasts and endothelial cells proliferation.

  • effects of the binding of a Dextran Derivative on fibroblast growth factor 2 secondary structure and receptor binding studies
    Biochemical Pharmacology, 1999
    Co-Authors: Patrick Bittoun, Rozita Bagheriyarmand, Michel Crepin, J Jozefonvicz, Frederic Chaubet, Serge Fermandjian
    Abstract:

    Abstract CMDB (carboxymethylDextran-benzylamide) are Dextrans statistically substituted with carboxymethyl and benzylamide groups which can mimick some of the biological properties of heparin. It has previously been shown that CMDB inhibit autocrine growth of breast tumor cells (Bagheri-Yarmand et al ., Biochem Biophys Res Commun 239 : 424–428, 1997) and selectively displace fibroblast growth factor 2 (FGF-2) from its receptor. Here, we used circular dichroism and fluorescence anisotropy measurements to show that the conformation of FGF-2 was significantly altered upon its binding to CMDB and to short CMDB fragments prepared within this study. CMDB and fragments formed a stable 1:1 complex with FGF-2, with affinities being estimated as 20 ± 10 nM from fluorescence anisotropy analysis. No such a complex was formed with insulin-like growth factor (IGF-1) or epidermal growth factor (EGF). CMDB competed with the FGF-2 receptor for binding to FGF-2 but did not disturb the binding of IGF-1 and EGF to their receptors. Thus, our results highlight the selectivity of CMDB and their fragments towards FGF-2. Heparin, however, competes with CMDB and their fragments for binding to FGF-2. The carboxymethyl and benzylamide groups of these molecules likely interact directly with a heparin-binding region of FGF-2. The resulting change in conformation disturbs the binding of FGF-2 to its receptor and consecutively its mitogenic activity.

  • 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
    British Journal of Cancer, 1998
    Co-Authors: Rozita Bagheriyarmand, J Jozefonvicz, Yamina Kourbali, C Mabilat, J F Morere, A Martin, He Lu, C Soria, Michel Crepin
    Abstract:

    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 (HBL100), 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(-1) week(-1)) suppressed the tumour take and the tumour growth by about 50% and 80% respectively. 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 heparin such as FGF-2, FGF-4, platelet-derived growth factor (PDGF-BB) and transforming growth factor (TGF-beta1), 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 likely by disrupting the autocrine and paracrine effects of growth factors released from the tumour cells.

Yeli Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Thermal and mechanical properties of biodegradable hydrophilic-hydrophobic hydrogels based on Dextran and poly (lactic acid)
    Journal of Materials Science: Materials in Medicine, 2002
    Co-Authors: Yeli Zhang
    Abstract:

    The thermal and mechanical properties of a new family of biodegradable hydrogels made of photocrosslinked Dextran Derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) were studied. The changes of thermal and mechanical properties of the dex-AI/PDLLAM hydrogels as functions of dex-AI to PDLLAM composition ratio and immersion time in phosphate buffer solution at 37 °C were also investigated. Thermal property data showed that the chemical modification, crosslinking, swelling and hydrolytic degradation affected the glass transition and melting temperatures. Based on thermal data, no phase separation was observed in the bicomponent dex-AI/PDLLAM hydrogels. Mechanical property data showed that, by changing the composition ratio, dex-AI/PDLLAM hydrogels having a wide range of dry and swollen compression moduli could be obtained. The moduli of the dex-AI/DPLLAM hydrogels in dry state decreased with an increase in the PDLLAM composition due to the reduction in glass transition temperature of the hydrogels. The loss of mechanical strength in buffer solutions was attributed to the swelling-induced formation of 3D porous network structure in the early stage of immersion and the hydrolytic degradation of the PDLLAM in the late stage via the chain scission of ester linkages located in the PDLLAM backbone. Because swelling and degradation were composition dependent, the magnitude of the loss of mechanical strength was also composition-dependent.

  • Thermal and mechanical properties of biodegradable hydrophilic-hydrophobic hydrogels based on Dextran and poly (lactic acid).
    Journal of materials science. Materials in medicine, 2002
    Co-Authors: Yeli Zhang, Chih-chang Chu
    Abstract:

    The thermal and mechanical properties of a new family of biodegradable hydrogels made of photocrosslinked Dextran Derivative of allyl isocyanate (dex-AI) and poly (D,L) lactide diacrylate macromer (PDLLAM) were studied. The changes of thermal and mechanical properties of the dex-AI/PDLLAM hydrogels as functions of dex-AI to PDLLAM composition ratio and immersion time in phosphate buffer solution at 37 degrees C were also investigated. Thermal property data showed that the chemical modification, crosslinking, swelling and hydrolytic degradation affected the glass transition and melting temperatures. Based on thermal data, no phase separation was observed in the bicomponent dex-AI/PDLLAM hydrogels. Mechanical property data showed that, by changing the composition ratio, dex-AI/PDLLAM hydrogels having a wide range of dry and swollen compression moduli could be obtained. The moduli of the dex-AI/DPLLAM hydrogels in dry state decreased with an increase in the PDLLAM composition due to the reduction in glass transition temperature of the hydrogels. The loss of mechanical strength in buffer solutions was attributed to the swelling-induced formation of 3D porous network structure in the early stage of immersion and the hydrolytic degradation of the PDLLAM in the late stage via the chain scission of ester linkages located in the PDLLAM backbone. Because swelling and degradation were composition dependent, the magnitude of the loss of mechanical strength was also composition-dependent.