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)

Several different strategies to improve the in vitro cytocidal effect of 5-fluorouracil/leucovorin (5FU/LV), including modulation of dosage and schedule and combination with other cytotoxic agents or biochemical modulators, were examined in the COLO 320DM and Ht-29 cell lines by means of the Bactec system. Modest enhancement of 5FU activity by coadministration of LV was observed in both human colon cancer cell lines. Neither increased concentrations of LV nor prolonged drug exposure or preincubation with LV were found to enhance significantly the growth inhibitory activity of combined 5FU/LV. The only parameter that was found to affect the killing potential of the combination was the concentration of 5-FU, suggesting that lower doses of the antimetabolite would be more effective (COLO 320DM: P less than 0.003; Ht-29 P less than 0.02). The addition of either cisplatin, hyaluronidase or dipyridamole to 5-FU/LV yielded synergistic growth inhibition in 3/6, 2/6 and 2/6 human colon cancer cell lines, respectively. Strictly additive effects were noted for the combination with BCNU as well as concurrent exposure of the cells to 42 degrees C hyperthermia. Whether or not certain combined 5FU/LV drug regimens will result in an improved therapeutic index, however, remains to be determined in properly designed clinical trials.
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PMID:A study of various strategies to enhance the cytotoxic activity of 5-fluorouracil/leucovorin in human colorectal cancer cell lines. 262 28

260 patients with malignant disease received intravenous, intramuscular or intravesical hyaluronidase (H.) (Permease by Sanabo), 7,000 to 25,500 IU (10 to 30, 750 IU vials) or 200,000 IU (1 vial of H.) in addition to systemic or intravesical chemotherapy. Treatment was well tolerated except for 20 transient allergic episodes, 2 of which consisted in local symptoms at the injection site. Results are presented for 103 patients not responding to previous chemotherapy, 53 patients with primary and secondary brain tumours, and 51 patients with superficial bladder cancer. Adjuvant hyaluronidase was found to restore responsiveness in a large percentage of non-responders. The remaining systemically treated patients received H. together with their initial chemotherapy or with a modified cytostatic regimen. Intravesical H. in combination with mitomycin C was well tolerated and did not enhance mitomycin C plasma levels. In a randomized trial 5 of 23 patients with superficial bladder cancer receiving adjuvant intravesical mitomycin C alone developed tumour regrowth versus 1 of 21 patients receiving additional H. Adjuvant H. decreased 5-FU plasma saturation rates during arterial perfusion in colorectal cancer with metastatic spread to the liver, probably reflecting enhanced 5-FU extraction. Colorectal cancer stem cell assays with 5-FU showed a significant reduction of colony counts in the presence of H. Action mechanismus of hyaluronidase in malignant diseases are discussed, experimental data suggesting an effect of H. on immunologic events in malignant disease are presented.
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PMID:[Hyaluronidase in the therapy of malignant diseases]. 331 Apr 18

This study examines the performance of novel hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-polyethylene glycol-gelatin polymer nanocomposites, which were prepared using an ionic gelation technique, as targeted and controlled drug delivery vehicles. These hyaluronidase-loaded nanoparticles have recently been proposed as targeted and controlled drug delivery vehicle systems to tissues due to their ability to loosen the intercellular connective matrix of hyaluronic acid. The encapsulation efficiency and loading capacities of the nanoparticles demonstrated that these nanocomposites displayed sufficient binding ability, which depends on the pH and initial concentration of the drug. The cytotoxic effects of the chitosan-hyaluronidase-5-fluorouracil (CS-HYL-5-FU), chitosan-hyaluronidase-5-fluorouracil polyethylene glycol (CS-HYL-5-FU-PEG), and chitosan-hyaluronidase-5-fluorouracil polyethylene glycol-gelatin (CS-HYL-5-FU-PEG-G) nanoparticles were assessed using MTT assays, and the nanovectors were found to be less cytotoxic than the chemotherapeutic 5-FU after incubation for 3-12h. The particle sizes of the CS-HYL-5-FU, CS-HYL-5-FU-PEG and CS-HYL-5-FU-PEG-G polymer composites were between 300 and 580 nm, as determined by a Zetasizer. Scanning electron microscopy (SEM) analysis indicated that the nanocomposites exhibit a clear, smooth surface and fine morphology. Linkages of the polymers, enzyme, and drug were confirmed by FTIR spectroscopy. Atomic fluorescence microscopy (AFM) analysis confirmed the size of the polymer composite nanoparticles. Therefore, this work established that the drug can be successfully encapsulated in chitosan-polyethylene glycol-gelatin-accompanied hyaluronidase nanoparticles with a homogeneous distribution. These nanoparticles can be potential carriers for targeted and controlled drug delivery to cancer cells.
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PMID:Hyaluronidase enzyme core-5-fluorouracil-loaded chitosan-PEG-gelatin polymer nanocomposites as targeted and controlled drug delivery vehicles. 2379 28