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Biomedical subjects

M D DeFuria

Publications and source records attributed to M D DeFuria.

8 recordsLinked to original sources
PubMed1993

Taxol commercial supply strategy.

Evidence of Taxol's safety and efficacy for treatment of refractory ovarian cancer convinced the National Cancer Institute (NCI) to seek a pharmaceutical partner and approval. After an open competition, NCI entered a Cooperative Research and Development Agreement with Bristol-Myers Squibb Company (BMS) to obtain approval of a New Drug Application (NDA) so that Taxol could be marketed as well as to provide supplies for clinical trials and compassionate use. To assure a successful commercialization of Taxol, BMS developed a strategic plan for expanding drug supplies. The strategy included immediately increasing the amount of Taxol derived from yew bark and establishing a broad research program to evaluate alternative sourcing options and their commercial feasibility. The options included precursor isolation and semisynthesis, yew plantations for biomass production, plant cell culture, and total synthesis. A number of both academic and industrial investigators, already interested in various Taxol supply issues, were enlisted for collaborations with the company. Progress on this research during the first 18 months has enabled BMS to do the following: 1) double the yield of Taxol from bark extraction; 2) exceed NCI's request for drug supplies in 1991, permitting establishment of an ovarian cancer treatment referral center (TRC) with a national network of comprehensive cancer centers; 3) increase NCI supplies from 5000 to 50,000 vials/month in 1992, permitting establishment of TRC protocol for breast cancer; 4) identify several potentially viable alternative sources; 5) schedule production of large amounts of Taxol by precursor conversion during 1993; and 6) ensure that sufficient quantities of the product will be available for treatment and continued clinical research.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1982

Intravesical therapy of low stage bladder carcinoma with mitomycin C: comparison of results in untreated and previously treated patients.

There were 28 patients with superficial bladder carcinoma (Ta, Tl or TIS) entered into protocols for intravesical therapy with mitomycin C. Of the 28 patients 16 had failed previously on thio-tepa (group A), 7 had responded successfully to thio-tepa (group B) and 5 had never received thio-tepa (group C). There were 5 complete responses and 9 failures to mitomycin C therapy in group A. There were 5 and 4 complete responses to mitomycin C therapy in groups B and C, respectively. The treatment plan consisted of the instillation of 40 mg. mitomycin C in 40 cc water weekly for 8 weeks. Because of severe local irritative symptoms 3 of the 28 patients did not complete the course of therapy. In another patient a diffuse body rash developed after the third instillation. Mitomycin C seems effective in ablating low stage bladder carcinoma, although it is less effective in patients who have failed prior thio-tepa therapy.

Adult↗
PubMed1981

The effect of mitomycin C on superficial bladder cancer.

A course of intravesical mitomycin C, consisting of 8 weekly doses of 30 or 40 mg., was evaluated in 16 patients with superficial bladder cancer (stages O and A). Cystoscopically documented tumor was destroyed completely in 11 patients (69 per cent), while 3 patients exhibited partial tumor regression. Two patients had only multifocal, grade 3 carcinoma in situ and both had a complete response with negative biopsies and cytology at the 12-week evaluation. Toxicity was minimal. Further data, including longer followup, are needed to define the potentially promising role of this agent in the over-all management of superficial bladder cancer.

Aged↗
PubMed1980

Morphological effects of mitomycin C administered intravesically to normal mice and mice with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induce bladder neoplasms.

The intravesical administration of mitomycin C to normal and N-[4-(5-nitro-2-furyl)-2-thiozolyl]formamide-induced bladder tumor-carrying mice at initial concentrations of 2 and 5 mg/ml for 2 hr resulted in marked morphological effects including cytoplasmic and nuclear abnormalities and disruption of surface architecture. Tumors cells and normal urothelial cells were sensitive to the effects of mitomycin C. These effects were limited to epithelial cells.

Animals↗
PubMed1976

Amikacin, an aminoglycoside with marked activity against antibiotic-resistant clinical isolates.

A total of 319 clinical isolates known to be resistant to one or more aminoglycoside antibiotics were tested for their susceptibility to 10 aminoglycosides. The percentages of isolates found by an agar dilution method to be susceptible were: amikacin, 83.7%; tobramycin, 41.4%; butirosin A, 33.2%; dideoxykanamycin B, 32.6%; gentamicin C, 27.3%; lividomycin A, 17.6%; neomycin B, 10.7%; paromomycin, 10.3%; kanamycin A, 10.0%; and ribostamycin, 7.2%. The effectiveness of the antibiotics was related to their degree of resistance to bacterial enzymes; e.g., of the nine enzymes known to inactivate antibiotics containing 2-deoxystreptamine, amikacin was affected by one enzyme, tobramycin by five, and gentamicin and kanamycin by six. Examination of cell-free extracts from the 52 strains resistant to amikacin revealed that only four contained the amikacin-inactivating enzyme aminoglycoside-6'-acetyltransferase, a finding indicating that this mechanism of resistance is rare. Other experiments suggest that most amikacin-resistant strains, which are almost invariably resistant to all aminoglycosides, lack the ability to accumulate effectively either amikacin or presumably the other antibiotics intracellularly.

Acinetobacter↗
PubMed1974

Activity of BB-K8 (amikacin) against clinical isolates resistant to one or more aminoglycoside antibiotics.

One hundred fifty-two bacterial strains that possess resistance to kanamycin A, gentamicin, or tobramycin, or to more than one of these antibiotics, were collected from various sources in Canada, Europe, Japan, and the United States. This collection was composed of Staphylococcus aureus and Pseudomonas aeruginosa and members of the Enterobacteriaceae family. Their susceptibility to BB-K8 (amikacin), a new broad-spectrum semisynthetic derivative of kanamycin A, and to the other agents, was determined on Mueller-Hinton Medium by the twofold agar dilution method. Test results revealed that 60.5% of the isolates were resistant to 8 mug of tobramycin per ml, 67.1% to 8 mug of gentamicin per ml, 86.2% to 20 mug of kanamycin A per ml, and only 8.6% to 20 mug of amikacin per ml. Of interest is the fact that the amikacin-resistant strains were generally resistant to all of the other aminoglycosides. The broad spectrum of amikacin was not totally unexpected, because the compound has been shown to be a poor substrate for most enzymes that inactivate other aminoglycosides through O-phosphorylation, O-adenylylation, or N-acetylation. A number of susceptibility profiles were obtained when the organisms were tested against a series of nine aminoglycosides. The majority of these profiles resembled those found for organisms that possess known mechanisms of enzymatic inactivation.

Aminobutyrates↗
PubMedDate not supplied

Phase I-II study of mitomycin C topical therapy for low-grade, low stage transitional cell carcinoma of the bladder: an interim report.

Intravesical mitomycin C therapy was administered to 63 patients with noninvasive bladder carcinoma in a phase I-II study. Doses ranged from 20 to 60 mg once a week for 8 weeks. The overall response rate was 67% including a complete remission rate of 45%. The median duration of complete remission for the two lowest dose groups was > 14 months, with a range of 1-36+ months. Followup is not yet adequate to determine the median duration of complete remission for the higher dose groups. No bone marrow suppression or other systemic toxic effects were noted. Adverse effects were localized and occurred infrequently. No mitomycin C was detected in serial serum samples after intravesical instillation.

Absorption↗