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

Hyaluronic acid–paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts,10.1007/s00280-010-1462-2,Cancer

Hyaluronic acid–paclitaxel: effects of intraperitoneal administration against CD44(+) human ovarian cancer xenografts   (Citations: 1)
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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.
Journal: Cancer Chemotherapy and Pharmacology - CANCER CHEMOTHER PHARMACOL , vol. 68, no. 1, pp. 107-116, 2011
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