Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin necrosis following subcutaneous Adriamycin extravasation is a significant clinical problem. In this study Adriamycin dilution and various drugs were tested for their ability to ameliorate this toxic effect. When Adriamycin was diluted to a concentration of less than or equal to 0.25 mg/ml, no skin ulceration was observed. Drugs such as hydrocortisone, dexamethasone, lidocaine, bupivacaine, phentolamine, and hyaluronidase were ineffective in modifying Adriamycin skin necrosis. Care in iv drug administration and dilution of Adriamycin are the best means of preventing the sequelae of subcutaneous Adriamycin extravasation.
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PMID:Amelioration of adriamycin skin necrosis: an experimental study. 46 41

The effect of hyaluronidase 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 murine (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 high-dose hyaluronidase (1.2 x 10(6) IU/kg) was ineffective, when administered peritumourally to the MXT M3.2 mammary carcinoma of the B6D2F1 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.
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PMID:Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo. 151 81

Full-thickness skin ulceration after extravasation of the commonly used vesicant chemotherapeutic agent doxorubicin hydrochloride (Adriamycin) is a significant source of morbidity in cancer patients. Controversy exists regarding the appropriate management of this extravasation injury. Current therapy includes local hypothermia, local clysis with hyaluronidase, and surgical excision of the involved tissue. Experimental data supporting local clysis with hyaluronidase are limited despite its current use clinically. The purpose of this study was to determine the efficacy of local infiltration with heparin sodium, hyaluronidase, and saline in the prevention of extravasation ulcers in a rat model. One hundred fifty male Sprague-Dawley rats (Upjohn, Milan, Italy) weighing 240 to 260 g, anesthetized with sodium pentobarbital, were used in this study. One hundred thirty rats received a 0.3-ml subcutaneous flank injection of doxorubicin (1.5 mg/ml) followed 15 minutes later by local infiltration with saline (n = 10), 25 to 100 units of heparin (n = 30), or 2.5 to 10.0 units of hyaluronidase (n = 90). Control animals received either subcutaneous doxorubicin (n = 10) or subcutaneous saline alone (n = 10). Volumes of the infiltration solution were less than 1 ml in all groups. All animals were sacrificed at 4 weeks; presence and size of ulcers at the injection site were quantified. Statistical analysis was performed using the two-sided Fisher's exact test and Student's t test. Control rats injected with saline alone did not develop ulceration in any case. All rats injected with doxorubicin alone developed ulcers with an average size of 33 mm2. Heparin infiltration decreased ulcer rate by 20 to 40 percent and decreased ulcer size by up to 67 percent. Local infiltration with hyaluronidase decreased ulcer rate by 50 to 60 percent (p < 0.05, two-sided Fisher's exact test) and decreased ulcer size by up to 50 percent ( p < 0.05, Student's t test). In this rat extravasation injury model, local infiltration with saline, heparin, or hyaluronidase decreased ulcer size after doxorubicin extravasation. This effect may be secondary to dilution of the extravasant. Additionally, local infiltration with hyaluronidase decreased ulcer rate by at least 50 percent. The mechanism of this phenomenon presumably relates to the ability of hyaluronidase to temporarily decrease the viscosity of the hyaluronic acid component of ground substance, thus allowing greater diffusion of doxorubicin into the surrounding tissue and therefore decreasing its local concentration.
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PMID:Prevention of adriamycin-induced full-thickness skin loss using hyaluronidase infiltration. 946 69

Proposed mechanisms of action for ascorbic acid (ascorbate, vitamin C) in the prevention and treatment of cancer include enhancement of the immune system, stimulation of collagen formation necessary for "walling off" tumors, inhibition of hyaluronidase which keeps the ground substance around the tumor intact and prevents metastasis, prevention of oncogenic viruses, correction of an ascorbate deficiency often seen in cancer patients, expedition of wound healing after cancer surgery, enhancement of the effect of certain chemotherapy drugs, reduction of the toxicity of other chemotherapeutic agents such as Adriamycin, prevention of free radical damage, and neutralization of carcinogenic substances. Scottish as well as Japanese studies have pointed to the potential benefit of high dose vitamin C for the treatment of "terminal" cancer. Mayo Clinic studies, however, have contradicted the Scottish and Japanese findings, resulting in accusations of methodological flaws from both sides. Numerous epidemiological studies have pointed to the importance of dietary and supplemental ascorbate in the prevention of various types of cancer including bladder, breast, cervical, colorectal, esophageal, lung, pancreatic, prostate, salivary gland, stomach, leukemia, and non-Hodgkin's lymphoma.
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PMID:Ascorbic acid in the prevention and treatment of cancer. 963 Jul 35