Hyaluronidase enhances the therapeutic effect of vinblastine in intralesional treatment of Kaposi's sarcoma☆, ☆☆, ★

Smith, Kathleen J.; Skelton, Henry G.; Turiansky, George W.; Wagner, Kenneth F.

doi:10.1016/s0190-9622(97)70288-3

Cited by 53 publications

(26 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The comparison of collagenase and hyaluronidase thus shows that the degradation of the structural protein network is more efficient than the degradation of the hyaluronan gel, with respect to macromolecule uptake. Although hyaluronidase is reported to improve the therapeutic outcome of chemotherapy (30,31), caution must be taken when using collagenase clinically as the enzyme may favor metastases (16,32).…”

Section: Discussionmentioning

confidence: 99%

Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts

Eikenes¹,

et al. 2004

View full text Add to dashboard Cite

Cancer therapy based on tumor-selective macromolecules may fail due to the elevated interstitial fluid pressure (IFP) that reduces the transvascular and interstitial convection in solid tumors. Modulation of the tumor extracellular matrix (ECM) may reduce IFP and enhance transvascular filtration and interstitial transport of macromolecules. We therefore measured the effect of the ECM-degrading enzyme collagenase on IFP and microvascular pressure (MVP) in human osteosarcoma xenografts using the wick-in-needle and micropipette methods, respectively. The tumor uptake and distribution of a systemically administered osteosarcoma-associated monoclonal antibody (TP-3) after i.v. injection of collagenase were analyzed using confocal laser scanning microscopy. Collagenase (0.1%) reduced both IFP (45%) and MVP (60%), but the kinetics of the recoveries differed, because MVP had recovered by the time IFP reached its minimum level. Thus, collagenase increased the transcapillary pressure gradient, inducing a 2-fold increase in the tumor uptake and improving the distribution of the monoclonal antibody, which was localized further into the tumor. To study the mechanism of the reduction in MVP, mean arterial blood pressure was measured and found not to be affected by the collagenase treatment. The reduction in MVP was rather due to reduced vascular resistance because microvascular-associated collagen was totally or partially disintegrated. Although collagenase may favor metastasis and thus not be clinically relevant, this study shows proof of principle that degradation of the ECM leads to a favorable change in the transvascular pressure gradient, thereby increasing antibody penetration and binding to tumor cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts

Eikenes¹,

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The discomfort due to intramuscular injection of drugs can be greatly alleviated by the activity of hyaluronidase. 79 The hyaluronidase isolated from Heloderma h. horridum increased the haemorrhagic area in mice that were injected with the purified hemorrhagic toxin from Trimeresurus flavoviridis venom. 72 Naja naja venom hyaluronidases (NNH1 and NNH2) showed in vitro absolute specificity for hyaluronic acid, selectively degrading HA in human skin and muscle and in chick embryo limb tissue sections.…”

Section: Hyaluronidasesmentioning

confidence: 99%

Snake venom hyaluronidase: a therapeutic target

Kemparaju

Girish

2005

Cell Biochem. Funct.

152

View full text Add to dashboard Cite

The diffusion of toxins from the site of a bite into the circulation is essential for successful envenomation. Degradation of hyaluronic acid in the extracellular matrix (ECM) by venom hyaluronidase is a key factor in this diffusion. Hyaluronidase not only increases the potency of other toxins but also damages the local tissue. In spite of its important role, little attention has been paid to this enzyme. Hyaluronidase exists in various isoforms and generates a wide range of hyaluronic acid degradation products. This suggests that beyond its role as a spreading factor venom hyaluronidase deserves to be explored as a possible therapeutic target for inhibiting the systemic distribution of venom and also for minimizing local tissue destruction at the site of the bite.

show abstract

“…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).…”

mentioning

confidence: 99%

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

et al. 2005

View full text Add to dashboard Cite

Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome.

show abstract

Hyaluronidase enhances the therapeutic effect of vinblastine in intralesional treatment of Kaposi's sarcoma☆, ☆☆, ★

Cited by 53 publications

References 20 publications

Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts

Collagenase Increases the Transcapillary Pressure Gradient and Improves the Uptake and Distribution of Monoclonal Antibodies in Human Osteosarcoma Xenografts

Snake venom hyaluronidase: a therapeutic target

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

Contact Info

Product

Resources

About