PURPOSE: Hyaluronan (HA)-receptors (mainly CD44 and RHAMM) are overexpressed in a wide variety of cancers including ovarian tumors, and HA-bioconjugates have been developed to enhance selective entry of cytotoxic drugs into HA receptor-expressing cancerous cells. Here, we evaluated the potential application of a new HA-paclitaxel bioconjugate, ONCOFID-P, for intraperitoneal (IP) treatment of ovarian cancer. METHODS: In vitro cytotoxic effect of ONCOFID-P was first assessed on CD44(+) OVCAR-3 and SKOV-3 human ovarian cancer cell lines. Studies were performed in female Balb/c athymic mice IP implanted with OVCAR-3 or SKOV-3 and treated with IP ONCOFID-P, and IP and intravenous (IV) free paclitaxel, at their maximum tolerated dose (MTD 168, 80 and 80 mg/kg, total dose, respectively). The potential detrimental effect of the IP ONCOFID-P and IP free paclitaxel on hematopoiesis was also assessed on peripheral blood, bone marrow and spleen. RESULTS: Results show that ONCOFID-P cytotoxicity against both OVCAR-3 and SKOV-3 cell lines was somewhat less effective than free paclitaxel. Conversely, in in vivo experiments, IP treatment with ONCOFID-P was overall more effective than IV and IP free paclitaxel in inhibiting intra-abdominal tumor dissemination, abrogating ascites, prolonging survival and curing mice. ONCOFID-P and IP free paclitaxel were equivalent in terms of myelotoxicity, although the former was administered at a two-fold higher dose. CONCLUSIONS: Present data strongly support the development of ONCOFID-P for locoregional treatment of ovarian cancer.

De Stefano, I., Battaglia, A., Zannoni, G. F., Prisco, M. G., Fattorossi, A., Travaglia, D., Baroni, S., Renier, D., Scambia, G., Ferlini, C., Gallo, D., Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts., <<CANCER CHEMOTHERAPY AND PHARMACOLOGY>>, 2011; (68): 107-116 [http://hdl.handle.net/10807/198368]

Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts.

De Stefano, Ilaria;Battaglia, Alessandra;Zannoni, Gian Franco;Fattorossi, Andrea;Travaglia, Daniele;Scambia, Giovanni;Ferlini, Cristiano;Gallo, Daniela
2010

Abstract

PURPOSE: Hyaluronan (HA)-receptors (mainly CD44 and RHAMM) are overexpressed in a wide variety of cancers including ovarian tumors, and HA-bioconjugates have been developed to enhance selective entry of cytotoxic drugs into HA receptor-expressing cancerous cells. Here, we evaluated the potential application of a new HA-paclitaxel bioconjugate, ONCOFID-P, for intraperitoneal (IP) treatment of ovarian cancer. METHODS: In vitro cytotoxic effect of ONCOFID-P was first assessed on CD44(+) OVCAR-3 and SKOV-3 human ovarian cancer cell lines. Studies were performed in female Balb/c athymic mice IP implanted with OVCAR-3 or SKOV-3 and treated with IP ONCOFID-P, and IP and intravenous (IV) free paclitaxel, at their maximum tolerated dose (MTD 168, 80 and 80 mg/kg, total dose, respectively). The potential detrimental effect of the IP ONCOFID-P and IP free paclitaxel on hematopoiesis was also assessed on peripheral blood, bone marrow and spleen. RESULTS: Results show that ONCOFID-P cytotoxicity against both OVCAR-3 and SKOV-3 cell lines was somewhat less effective than free paclitaxel. Conversely, in in vivo experiments, IP treatment with ONCOFID-P was overall more effective than IV and IP free paclitaxel in inhibiting intra-abdominal tumor dissemination, abrogating ascites, prolonging survival and curing mice. ONCOFID-P and IP free paclitaxel were equivalent in terms of myelotoxicity, although the former was administered at a two-fold higher dose. CONCLUSIONS: Present data strongly support the development of ONCOFID-P for locoregional treatment of ovarian cancer.
eng
De Stefano, I., Battaglia, A., Zannoni, G. F., Prisco, M. G., Fattorossi, A., Travaglia, D., Baroni, S., Renier, D., Scambia, G., Ferlini, C., Gallo, D., Hyaluronic acid-paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts., <>, 2011; (68): 107-116 [http://hdl.handle.net/10807/198368]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/198368
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