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Biomedical subjects

T Corbett

Publications and source records attributed to T Corbett.

24 records · Page 2Linked to original sources

Phase I trial of spiromustine (NSC 172112) and evaluation of toxicity and schedule in a murine model.

Phase I evaluation of spiromustine was performed using an every-3-week schedule and a weekly X 3 schedule. Neurotoxicity was the dose-limiting toxicity presenting as alterations in cortical integrative functions (orientation, language, coordination), leading to a decrease in the level of consciousness. Traditional criteria for grading neurotoxicity poorly characterized these toxicities. The maximum tolerated dose was 6 mg/m2 every 3 weeks and 3 mg/m2 weekly X 3. Concurrent murine studies confirmed spiromustine as a schedule independent drug with toxicity correlating with peak plasma levels. Physostigmine had little effect on decreasing neurotoxicity in the murine model. The solvating agent used was not responsible for the neurotoxicity. Injection of spiromustine on a split-dose schedule decreased the acute neurological toxicity in mice and allowed a larger total dosage to be delivered (compared to single bolus dosage). Based on these results a split-dose schedule is suggested for future clinical trials.

Animals↗

Solid tumor preparation for flow cytometry using a standard murine model.

The application of flow cytometry (FCM) to solid human tumors has been hindered by the difficulty in producing high yield, viable, unaltered single cell suspensions. Carcinomas containing a high desmosomal content, such as well-differentiated squamous cell (SCC) cancers of the head and neck (H&N) region, are particularly difficult to prepare. The desire to employ FCM to study cellular DNA parameters of these tumors led to the use of a 3-methylcholanthrene induced murine SCC for the comparative testing of preparative techniques. Dissociation techniques, including mechanical, enucleation, chemical, single and combination enzymes methods, were comparatively tested. Of these, the combination enzyme treatment employing trypsin and collagenase produced the highest cell yields in the shortest time with the highest dye exclusion viability and the least expense. Several fixation systems including glutaraldehyde, paraformaldehyde, acetic acid, and ethanol were comparatively tested using percent of cell loss and quality of the DNA histograms produced as end points. Ethanol-water systems with added fetal calf serum provided minimal cell loss and high quality histograms which were stable for extended periods of time. A murine tumor, closely mimicking the histology of the human tumor of interest, may be used as a model for the determination of optimum techniques of solid tumor preparation for flow cytometric analysis.

Animals↗

Flavone acetic acid (LM 975, NSC 347512). A novel antitumor agent.

Flavone acetic acid (FAA) is a synthetic flavonoid compound which has recently begun clinical trials as an antitumor agent based on its striking activity in solid tumor model systems. The pharmacologic behavior of FAA in animals appears to be predictive of both its cytotoxic efficacy and its toxicity to normal tissues (principally the central nervous system and gastrointestinal tract). The design and conduct of phase I studies in man are based upon these principles, with the goal of maximizing their safety and efficacy.

Animals↗

Correlations between anthracycline resistance, drug accumulation and membrane glycoprotein patterns in solid tumors of mice.

Both impaired drug accumulation and appearance of a new membrane glycoprotein species (mol. wt. approx. 180,000) are often associated with high levels of drug-induced resistance to a group of natural products which includes adriamycin (ADR) and daunorubicin (DNR). In this study, we examined solid murine mammary, pancreatic and colon tumors varying in degrees of inherent or (in vivo) induced adriamycin resistance. Neither impaired drug accumulation nor alterations in membrane glycoprotein patterns were correlated with drug resistance in these tumors. These results suggest that permeability and glycoprotein alterations may only be associated with very high degrees of drug resistance.

Animals↗

Surgical periodontal treatment in the radiotherapy-treated head and neck cancer patient.

A series of clinical cases is presented in which surgical periodontal therapy was conducted within the high-dose volume of prior radiation therapy. Close oral supervision is required in patients following head and neck radiation therapy. Non-surgical periodontal management is crucial in the care of these patients following radiation therapy. Careful selection of patients for possible surgical therapy and care in performing the procedure may allow successful periodontal management, as is demonstrated in the cases reviewed.

Adult↗