Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyaluronidase has gained increasing interest as an adjuvant in local and systemic cancer therapy, despite the incomplete knowledge of its physiological function. To this end, direct intratumoral injection of bovine testicular hyaluronidase (500, 1600 or 7500 U in 50 microl phosphate-buffered saline (PBS)) was performed in orthotopic (o.t.) osteosarcoma xenografts grown in the hind leg of nude mice. Control tumours received 50 microl PBS alone or supplemented with 10% bovine serum albumin (BSA). Central tumour interstitial fluid pressure (IFP) and mean arterial blood pressure (MABP) were measured using the wick-in-needle technique and after cannulation of the carotid artery, respectively. IFP was 32 +/- 8 mmHg (n = 44, mean +/- SD) in untreated tumours and there was a significant correlation between tumour IFP and volume (P < 0.01). The hyaluronidase injection reduced IFP to 63-84% after 1 h compared with controls (P < 0.05) and in a non-linear concentration-dependent manner. MABP was not affected significantly. In conclusion, an intratumoral hyaluronidase injection might reduce IFP temporally in solid osteosarcoma xenografts.
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PMID:Hyaluronidase reduces the interstitial fluid pressure in solid tumours in a non-linear concentration-dependent manner. 983 21

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.
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PMID:Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx) in human osteosarcoma xenografts. 1594 37