Hyaluronidase enhances the activity of Adriamycin in breast cancer models in vitro and in vivo

Abstract

Summary.The effect ofhyaluronidase and a combination of hyaluronidase with Adriamycin was investigated on several breast cancer models in vitro and in vivo. In vitro enzyme treatment (using concentrations up to 80 000 IU/ 1) of routine (MXT-, MXT -+, and MXT +) and human (MCF-7, ZR-75-1 and T-47-D) breast cancer cell lines did not inhibit tumour cell proliferation (measured by a kinetic crystal violet assay) in either case. Although highdose hyaluronidase (1.2 x 106 IU/kg) was ineffective, when administered peritumourally to the MXT M3.2 mammary carcinoma of the B6D2F 1 mouse, it is remarkable that five "megadoses" were excellently tolerated. However, the antineoplastic activity of Adriamycin against the oestrogen-receptor-positive variant of the MXT tumour was significantly enhanced by combination with concentrations of hyaluronidase that were inactive per se, both in vitro and in vivo. Interestingly, the enhancement of the in vivo antitumour activity was not compromised by toxic side-effects.

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

“…The enzyme hyaluronidase degrading hyaluronan is reported, in phase I and II trials, to prevent regrowth of various tumour types and to improve clinical outcome when given adjuvant to chemotherapy (Baumgartner, 1987;Maier and Baumgartner, 1989;Smith et al, 1997), and delays the growth of human breast cancer xenografts compared with doxorubicin given alone, when given as a pretreatment to doxorubicin (Beckenlehner et al, 1992). However, it has been reported that such pretreatment may induce drug resistance (Chang, 2001).…”

Hyaluronidase in the treatment of papular dermal mucinosis: First case reported in North America

“…Our patient was specifically treated with a purified preparation of hyaluronidase derived from recombinant human deoxyribonucleic acid (DNA) called Hylenex ® . The method of action of intralesional hyaluronidase in these cases deserves further investigation, though it has been used as a successful adjuvant therapy in the treatment of various epithelial and mesenchymal cell-driven processes including dermatofibrosarcoma protuberans prior to excision, bladder cancer, breast cancer and Kaposi's sarcoma [23][24][25][26] . Our success in this case further suggests a role for hyaluronidase in the treatment of papular mucinosis.…”

Some properties of testicular hyaluronidases

“…Some bacteria such as Streptococcus pyogenes and Clostridium perfringens produce hyaluronidase (Ohya T., 1970). Hyaluronidase resists spreading of venoms and virulence of bacteria and may play a role in cancer metastasis and angiogenesis (Beckenlehner K., 1992). Therefore it is used in medicine (Schomberg D., 1991).…”