Pharmacokinetics and tissue distribution of bovine testicular hyaluronidase and vinblastine in mice: an attempt to optimize the mode of adjuvant hyaluronidase administration in cancer chemotherapy

Muckenschnabel, I.; Bernhardt, Günther; Spruß, Thilo; Buschauer, Armin

doi:10.1016/s0304-3835(98)00203-1

Cited by 31 publications

(19 citation statements)

References 32 publications

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“…Brekken et al (34) also reported that periodic lowering of tumor IFP might increase the in vivo delivery of monoclonal antibodies to solid tumors. Muckenschnabel and colleagues (15) independently showed that peritumoral hyaluronidase administration increased the intratumoral concentration of s.c. coadministered vinblastine. These and other studies (35) have collectively suggested a potential therapeutic role for hyaluronidase in reducing HA-mediated tumor IFP, which may in turn increase delivery of antitumor drugs in tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated HA (stromal and/or pericellular staining) in tumor biopsies has been correlated with local invasion, the presence of distal metastasis, higher tumor grade, and poorer overall survival (13). Previous work has suggested a role for HA in drug resistance and hyaluronidase in cancer therapy (14,15). The abundance of HA in the ECM is regulated by the local-regional balance between HA synthase activity and degradation by membrane-associated and lysosomal hyaluronidases.…”

Section: Introductionmentioning

confidence: 99%

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Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

Thompson

Shepard²,

O’Connor³

et al. 2010

Molecular Cancer Therapeutics

257

278

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Hyaluronan (HA) is a glycosaminoglycan polymer that often accumulates in malignancy. Megadalton complexes of HA with proteoglycans create a hydrated connective tissue matrix, which may play an important role in tumor stroma formation. Through its colloid osmotic effects, HA complexes contribute to tumor interstitial fluid pressure, limiting the effect of therapeutic molecules on malignant cells. The therapeutic potential of enzymatic remodeling of the tumor microenvironment through HA depletion was initially investigated using a recombinant human HA-degrading enzyme, rHuPH20, which removed HA-dependent tumor cell extracellular matrices in vitro. However, rHuPH20 showed a short serum half-life (t 1/2 < 3 minutes), making depletion of tumor HA in vivo impractical. A pegylated variant of rHuPH20, PEGPH20, was therefore evaluated. Pegylation improved serum half-life (t 1/2 = 10.3 hours), making it feasible to probe the effects of sustained HA depletion on tumor physiology. In high-HA prostate PC3 tumors, i.v. administration of PEGPH20 depleted tumor HA, decreased tumor interstitial fluid pressure by 84%, decreased water content by 7%, decompressed tumor vessels, and increased tumor vascular area >3-fold. Following repeat PEGPH20 administration, tumor growth was significantly inhibited (tumor growth inhibition, 70%). Furthermore, PEGPH20 enhanced both docetaxel and liposomal doxorubicin activity in PC3 tumors (P < 0.05) but did not significantly improve the activity of docetaxel in low-HA prostate DU145 tumors. The ability of PEGPH20 to enhance chemotherapy efficacy is likely due to increased drug perfusion combined with other tumor structural changes. These results support enzymatic remodeling of the tumor stroma with PEGPH20 to treat tumors characterized by the accumulation of HA. Mol Cancer Ther; 9(11); 3052-64. ©2010 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

Thompson

Shepard²,

O’Connor³

et al. 2010

Molecular Cancer Therapeutics

257

278

View full text Add to dashboard Cite

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“…The colorimetric determination of the hyaluronidase activity was based on the method of Reissig et al [29] and performed as described previously [12]. For determination of the pH profiles the incubation mixtures consisted of McIlvaine's buffer (citrate/phosphate 44 mM/88 mM), containing 44 mM NaCl, 0.56 mg/ml HA and 44 μg/ml BSA.…”

Section: Methodsmentioning

confidence: 99%

“…However, a problem in the determination of the hydrolytic activity of these enzymes arises from the fact that BTH, and presumably all mammaliantype hyaluronidases, additionally have transglycosylase activity [9,10]. Data on the pH-dependent activity of BTH reported in the literature are inconsistent in part or even contradictory: optimum activity of BTH was found at acidic pH (pH 3.5-4.0) [11][12][13] as well as at weakly acidic pH (pH 5.0-6.0) [14][15][16] and at neutral pH [17,18]. However, the pH optimum of human Hyal-1, located in lysosomes of the liver, in plasma and in urine, was reported consistently to be at acidic pH (pH 3.5-3.8) [19][20][21] by several authors.…”

Section: Introductionmentioning

confidence: 99%

Isoenzyme-specific differences in the degradation of hyaluronic acid by mammalian-type hyaluronidases

et al. 2007

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Bovine testicular hyaluronidase (BTH) has been used as a spreading factor for many years and was primarily characterized by its enzymatic activity. As recombinant human hyaluronidases are now available the bovine preparations can be replaced by the human enzymes. However, data on the pH-dependent activity of hyaluronidases reported in literature are inconsistent in part or even contradictory. Detection of the pH-dependent activity of PH-20 type hyaluronidases, i.e. recombinant human PH-20 (rhPH-20) and BTH, showed a shift of the pH optimum from acidic pH values in a colorimetric activity assay to higher pH values in a turbidimetric activity assay. Contrarily, recombinant human Hyal-1 (rhHyal-1) and bee venom hyaluronidase (BVH) exhibited nearly identical pH profiles in both commonly used types of activity assays. Analysis of the hyaluronic acid (HA) degradation products by capillary zone electrophoresis showed that hyaluronan was catabolized by rhHyal-1 continuously into HA oligosaccharides. BTH and, to a less extent, rhPH-20 exhibited a different mode of action: at acidic pH (pH 4.5) HA was degraded as described for rhHyal-1, while at elevated pH (pH 5.5) small oligosaccharides were produced in addition to HA fragments of medium molecular weight, thus explaining the pH-dependent discrepancies in the activity assays. Our results suggest a sub-classification of mammalian-type hyaluronidases into a PH-20/BTH and a Hyal-1/BVH subtype. As the biological effects of HA fragments are reported to depend on the size of the molecules it can be speculated that different pH values at the site of hyaluronan degradation may result in different biological responses.

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“…Sperm hyaluronidase plays an important role in successful fertilization in most mammals, including human (Manzel and Farr, 1988;Frost et al, 1996;Borrelli et al, 1986;Primakoff et al, 1985;Lin et al, 1994;Klocker et al, 1995). Hyaluronidase has been investigated as an additive to chemotherapeutic drugs for augmentation of anticancer activity (Muckenschnabel et al, 1997(Muckenschnabel et al, , 1998Spruss et al, 1995;Baumgartner, 1998). There is evidence that hyaluronidase may have intrinsic anticancer effects and can suppress tumor development.…”

Section: Medical Application Of Hyaluronidasementioning

confidence: 99%

The magic glue hyaluronan and its eraser hyaluronidase: A biological overview

2007

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Pharmacokinetics and tissue distribution of bovine testicular hyaluronidase and vinblastine in mice: an attempt to optimize the mode of adjuvant hyaluronidase administration in cancer chemotherapy

Cited by 31 publications

References 32 publications

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

Enzymatic Depletion of Tumor Hyaluronan Induces Antitumor Responses in Preclinical Animal Models

Isoenzyme-specific differences in the degradation of hyaluronic acid by mammalian-type hyaluronidases

The magic glue hyaluronan and its eraser hyaluronidase: A biological overview

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