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Biomedical subjects

J F Fowler

Publications and source records attributed to J F Fowler.

At least 217 records · Page 12Linked to original sources
PubMed1980

Misonidazole in fractionated radiotherapy: are many small fractions best?

Computer simulations have been made of four radiotherapy fractionation regimes either in current use or proposed for clinical trials of misonidazole. A variety of cell-survival parameters and reoxygenation patterns have been used. The models allow the relative importance of repair capacity, reoxygenation rate, and dose per fraction to be assessed for these four schedules in the presence or absence of misonidazole. Unlike hyperbaric oxygen, the dose of misonidazole and the fractionation scheme to be used are critically interdependent, because the total drug dose is limited to 12 g/m2 by its neurotoxicity, regardless of the extent to which it is fractionated. The largest sensitizing effect is always demonstrated with six fractions, each given with 2 g/m2 of misonidazole. In the absence of reoxygenation a sensitizer enhancement ratio of 1.7 is predicted, but this falls to 1.1--1.2 if extensive reoxy-generation occurs. Less sensitization is observed with 30 fractions, each with 0.4 g/m2 of drug. However, for clinical use, the important question is which treatment kills the maximum number of tumour cells. Many of the simulations predict a marked disadvantage of reducing the fraction number for X rays alone. The circumstances in which this disadvantage is offset by the large SER values with a six-fraction schedule are few. The model calculations suggest that many small fractions, each with a low drug dose, are safest unless the clinician has some prior knowledge that a change in fraction number is not disadvantageous.

Animals↗
PubMed1979

The effect of recovery from potentially lethal damage on the determination of reoxygenation in a murine tumour.

The pattern of reoxygenation in the murine anaplastic MT tumour was investigated using the established method of determining the hypoxic fraction, at intervals after a priming X-ray dose, from test doses given either to unclamped or clamped-off tumours. Little reoxygenation was apparent whilst the tumour was increasing in size for 12--72 hours after a single dose of 20.3 Gy, but extensive reoxygenation was evident whilst the tumour was shrinking at nine days after a dose of 50 Gy. However, the degree of reoxygenation may have been underestimated, especially after the smaller priming dose. This is because only the chronically hypoxic cells in this tumour have the ability to recover from potentially lethal damage (PLD) and so are more radioresistant than cells rendered acutely hypoxic by clamping. Because of this, even when tumours are clamped off during irradiation, the resulting survival curve is biphasic and the apparent effect of the clamp becomes a function of the X-ray dose used. The larger the dose, the smaller the observed effect of the clamp, so the greater the apparent hypoxic fraction and hence the smaller the apparent degree of reoxygenation.

Animals↗
PubMed1978

Sixth interim progress report of the British Institute of Radiology fractionation study of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx.

The results are reported of the multicentre BIR fractionation trial of 3F/week versus 5F/week in radiotherapy of the laryngo-pharynx. 687 patient records have been analysed with respect to survival rates, recurrence-free rates and laryngectomy-free rates. For the group as a whole these analyses show no difference between the two fractionation regimes. Analysis of the sub-group which had early disease confined to the vocal cords does, however, show a better recurrence-free and laryngectomy-free rate for those patients treated with 5F/week, though the survival rate for the two groups remains similar. Acute and late normal tissue reactions are reported for up to six years after treatment. It appears that treatment with 3F/week can be given safely to patients with advanced disease. The differences between the two treatment groups who had early disease of the vocal cords are discussed, but until more data become available in the future the problems raised cannot be resolved.

Dose-Response Relationship, Radiation↗
PubMed1977

Radiosensitizing and cytocidal effects on hypoxic cells of RO-07-0582, and repair of x-ray injury, in an experimental mouse tumour.

The delay in regrowth to 10 mm diameter of a transplanted carcinoma in mice was used to estimate the effect of the hypoxic-cell radiosensitizer Ro-07-0582. When 1 mg/g body wt. was given before a single dose of X-rays, a dose-enhancement ratio of 2-0 was found. When the drug was given immediately after irradiation, a large cytotoxic effect was observed, equivalent to an enhancement ratio of 1-3. These results were confirmed by determining the X-ray doses required for the local control of 50% of the tumours at 80 days after irradiation. The capacity of the tumour for repair of sublethal X-ray injury within 24 h was similar to that for several normal tissues.

Animals↗
PubMed1976

Hypoxic cell sensitisers in radiotherapy.

Solid tumours contain poorly oxygenated cells, and these are disproportionately resistant to therapeutic radiation. Several methods of overcoming this problem have been used clinically, including the administration of hyperbaric oxygen during irradiation, radiotherapy with heavy nuclear particles such as neutrons from cyclotrons, optimum size and spacing of multiple doses of conventional radiation, and, most recently, chemical radiosensitisers. These radiosensitisers mimic the sensitising effect of oxygen and are active only against hypoxic cells. They do not, therefore, increase radiation response in well-oxygenated normal tissues. They are not rapidly metabollised and so can penetrate further than oxygen from the vascular capillaries and effectively reach the hypoxic cells in the tumour. Some of these drugs are of considerable clinical promise. The results of in vitro and in vivo studies with radiosensitisers are summarised and preliminary clinical work is described.

Animals↗
PubMed1976

The effect of low-dose pre-operative X-irradiation of implanted mouse mammary carcinomas on local recurrence and metastasis.

Pre-operative X-irradiation of s.c. implanted first-generation mammary tumours in C3H mice, using either 500 rad or two fractions of 350 rad, produced no improvement in the success of surgery in causing local control or in reduction of distant metastases. The metastasis rate was just significantly higher after the two-fraction treatment of the implanted tumour than after surgical removal alone. The results are in agreement with previously published results on carcinomas and a sarcoma but contrast with those for murine lymphomas.

Animals↗
PubMed1976

Changes in mouse blood pressure, tumor blood flow, and core and tumor temperatures following nembutal or urethane anesthesia.

Female CBA and WHT mice with tumors transplanted into the right leg were immobilized in insulated capsules. Tumor blood flow, blood pressure, and core and tumor temperatures were monitored prior to and during anesthesia with either Nembutal or urethane. Nembutal caused a 5 degree C drop in both core and tumor temperatures in 20 minutes. Urethane induced a small fall in temperatures. Urethane initially caused a small drop in blood pressure followed by recovery; Nembutal caused a steady fall in blood pressure to 50% of resting value.

Anesthesia, Intravenous↗
PubMed1976

Radiosensitization of C3H mouse mammary tumours using fractionated doses of x rays with the drug Ro-07-0582.

Three fractionated X-ray schedules were used, with and without the electron-affinic radiosensitizer of hypoxic cells, Ro-07-0582, to determine the local control of first-generation transplants of spontaneous mammary tumours in C3H mice. Three or five fractions were given in either four or nine days overall time. The results were compared with acute skin reactions in other mice caused by the same treatment schedules. For a given skin reaction, the local control of tumours varied widely, from good to bad, when different X-ray only schedules were used. All three schedules using Ro-07-0582 however yielded good results. It appears that the use of the hypoxic-cell radiosensitizer took the unreliability out of these short fractionated treatments.

Animals↗