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Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 271 records · Page 15Linked to original sources
PubMed1982

Postoperative radiotherapy in rectosigmoid cancer Dukes' B and C: interim report from a randomized multicentre study.

The design, and complications seen during the first 2 years, of a randomized trial of postoperative radiotherapy for rectosigmoid cancer Dukes' B and C are presented and discussed. It is concluded that the present complication rate-below 10% in 221 patients-permits continuation of the intake, which is planned to include 550 patients, to demonstrate a possible increase in crude 5-year survival by 15% (60-75% in Dukes' B and 25-40% in Dukes' C), on the basis of a 0·01 significance level and a probability that the experiment will be successful of 0·90.

Clinical Trials as Topic↗
PubMed1982

Importance of preheating temperature and time for the induction of thermotolerance in a solid tumour in vivo.

The importance of the priming heat treatment temperature and heating time for the degree and kinetics of thermotolerance was investigated in a C3H mammary carcinoma inoculated into the feet of CDF1 mice. A single heat treatment in the range 41.5-44.5 degrees C resulted in a linear relationship between heating time and tumour growth time (i.e. the time for tumours to reach a volume five times that of the first treatment day). An Arrhenius plot showed an inflection point at 42.5 degrees C with activation energies of 635 and 1508 kJ/mol, respectively, above and below 42.5 degrees C. The degree and kinetics of thermotolerance were independent of the preheating temperature, if the heating time was adjusted to give the same level of heat damage. A pretreatment at these temperatures with a tumour growth time of approximately 10 days, equivalent to 30 min at 43.5 degrees C, resulted in maximal thermotolerance at a 16-h interval with a thermotolerance ratio (TTRmax) of approximately 5.2. Preheating of the tumours at 43.5 degrees C for 3.5, 7.5, 15, 30, or 45 min, showed that if the preheating time was increased, both the TTRmax and the time interval necessary to develop TTRmax increased, both being linear functions of the duration of the preheating time. Maximal thermotolerance was obtained at intervals of 2, 4, 8, 16, and 28 h with TTRmax of 1.6, 2.2, 3.7, 5.2, and 7.7, respectively.

Animals↗
PubMed1982

A comparative investigation of nimorazole and misonidazole as hypoxic radiosensitizers in a C3H mammary carcinoma in vivo.

The hypoxic cell radiosensitizing properties of nimorazole have been investigated in a C3H mammary carcinoma transplanted to the feet of C3D2F1. The results have been compared with those obtained with misonidazole (MISO) in the same animal tumour system. For single-dose irradiation in air, nimorazole gives an enhancement ratio (ER) of approximately 1.4, independent of the dose of drug administered over the range 0.1-1.0 mg/g. MISO yields a similar ER at the 0.1 mg/g level but, unlike nimorazole, shows a steep dose-response curve with an ER of 2.2 when given in a concentration of 1.0 mg/g. No such dose-response relationship is seen with nimorazole despite the fact that tumour and plasma concentrations of the 2 drugs have an identical dose relationship. With irradiation given in 5 daily fractions, nimorazole and MISO at a dose of 0.3 mg/g per fraction both show an ER of approximately 1.3. The high drug doses used in single-fraction radiation experiments in animals bear little relation to those applicable to clinical practice since these would result in unacceptable toxicity. The results of the present studies are therefore of interest as nimorazole is potentially less toxic than MISO in humans but demonstrates similar radiosensitizing properties at clinically relevant dose levels.

Animals↗
PubMed1982

Development of thermotolerance during fractionated hyperthermia in a solid tumor in vivo.

The effect of 43.5 degrees water bath heating on a C3H mammary carcinoma inoculated into the foot of BALB/c x DBA F1 (hereafter called CD2F1 mice was investigated. A single heat treatment resulted in a linear dose-response relationship between heating time and tumor growth time (i.e., the time for tumors to reach 5 times the initial volume of the first treatment day). Recovery from hyperthermic damage, demonstrated by two-dose fractionation experiments (30 min + 60 min at 43.5 degrees), increased with increasing fractionation interval and reached its maximum at a 16-hr interval. Preheating for 30 min at 43.5 degrees induced thermal resistance to a second heat treatment at 43.5 degrees (thermotolerance) which was evidenced by a decrease in the slope of the dose-response curves. This thermotolerance gradually increased with increasing interval and reached a maximum at a 16-hr interval with a thermotolerance ratio of 5.2. Subsequently, the thermotolerance gradually decayed and completely disappeared at a 120-hr interval. No detectable repair of hyperthermic damage was found in this tumor. In principle, there data confirm the observations on thermotolerance reported previously for cell cultures in vitro and for several normal tissues in vivo.

Animals↗
PubMed1982

Influence of time and temperature on the kinetics of thermotolerance in L1A2 cells in vitro.

The overall importance of the primary heat treatment temperature and heating time for the degree and kinetics of thermotolerance was investigated in L1A2 cells in vitro. The degree and time course of thermotolerance developed following primary heating were independent of the priming temperature (in the range 41-44 degrees), if the heating time was adjusted to give identical survival levels. A pretreatment at these temperatures with a survival level of approximately 8%, equivalent to 90 min at 42 degrees, resulted in maximal thermotolerance at a 10-hr interval with a thermotolerance ratio (TTRmax) of approximately 4.3. This was also found irrespective of the temperature (in the range 41-45 degrees) of the second heat treatment. Preheating of cells at 42 degrees for 45, 90, 110, or 135 min corresponding to survival levels of approximately 40, 8, 3.2, and 1.8%, respectively, induced a subsequent delay of 0.8 to 5.8 hr in the onset of thermotolerance. In addition, with more severe primary heat treatments, the delay period, the TTRmax, and the time interval at 37 degrees necessary to develop TTRmax increased. Maximal thermotolerance was obtained at an interval of 6, 10, 13, and 16 hr, respectively, with TTRmax's of 2.9, 4.2, 5.3, and 5.9, respectively. In contrast, the rate of both development and decay of thermotolerance was independent of the primary heating time. These data indicate that the degree and kinetics of thermotolerance in L1A2 cells depend on the survival level following the primary heating irrespective of the treatment temperature and heating time used to obtain this survival level.

Acclimatization↗
PubMed1982

Influence of sequence and interval on the biological response to combined hyperthermia and radiation.

Experimental studies on the influence of sequence and interval between hyperthermia and radiation are reviewed. In general, experimental data in vitro and in tumor and normal tissues agree and indicate that maximal thermal enhancement occurs after simultaneous application of heat and radiation. However, such treatment is likely to enhance both tumor and normal tissue to the same degree and therefore does not increase the therapeutic effect. In normal tissue, sequential treatment with heat before radiation causes a higher and longer thermal enhancement than with the opposite sequence in which the thermal enhancement generally disappears with intervals greater than 4 hours. However, in most solid tumors, a moderate thermal enhancement exists with long intervals between the modalities independent of sequence and is probably a consequence of a direct hyperthermic destruction of the acidic and chronically hypoxic cells. Based on this biological conclusion, the clinical application of hyperthermia and radiation is discussed in the light of the technical problems related to the application of a homogeneous and selective local tumor heating.

Animals↗
PubMed1981

Fractionated radiation and hyperthermia: experimental and clinical studies.

The effect of fractionated radiation and hyperthermia was experimentally studied in a C3H mammary carcinoma and its surrounding skin. Simultaneous radiation and heat (42.5 C-60 minutes) with one or five fractions gave thermal enhancement ratios (TER) of approximately 2.5 in both tumor and surrounding skin, and no improved therapeutic effect was obtained. Five fractions of sequential treatment with heating four hours after radiation reduced the tumor TER to about 1.4, but when 72 hours were allowed between the fractions, no thermal enhancement of the skin was observed. Thus, an improved therapeutic ratio was observed. Clinically the combined treatment was studied in 12 patients with 49 metastases from malignant melanoma treated with different schedules of radiation and hyperthermia (approximately 43 C for 30 minutes). Simultaneous treatment with three fractions in eight days gave TER values in the skin between 1.2-1.4, but a similar effect was found in the tumor. Three fractions of sequential treatment in eight days did not produce any thermal enhancement of the skin response, but still presented an apparent gain of the tumor response, and so seemed to increase the therapeutic effect. Bases on these findings, the strategy for further clinical use of combined hyperthermia and radiation is discussed.

Animals↗
PubMed1981

Effect of hyperthermia on the hypoxic fraction in an experimental mammary carcinoma in vivo.

The influence of hyperthermia on the fraction of clonogenic hypoxic cells in a CaH mammary carcinoma was investigated using the TCD50 values for radiation treatment under normal or clamped conditions. A one-hour heat treatment at 41.5 and 42.5 degree C given four hours after radiation reduced the hypoxic fraction to 2.3 X 10(-1), 7.4 X 10(-3) and 6.5 X 10(-3) respectively, when compared with the content of hypoxic cells in non-heated tumours. The results indicate that moderate hyperthermia is able to destroy selectively a large proportion of the fraction of radioresistant hypoxic cells in a solid tumour. This effect is probably due to the increased heat sensitivity of cells in a chronically hypoxic and nutritionally deprived acidic environment.

Animals↗
PubMed1980

Effect of misonidazole and hyperthermia on the radiosensitivity of a C3H mouse mammary carcinoma and its surrounding normal tissue.

Both misonidazole (MISO) and hyperthermia are known to enhance the radiation response of hypoxic cells, and to be selectively cytotoxic against cells in a hypoxic and acidic environment. The ability of these conditions to modify the effect of irradiation and their individual relationship was studied in a C3H mammary carcinoma and its surrounding skin. Simultaneous treatment with MISO, hyperthermia and radiation increased the radiation effect, with enhancement ratios (ER) of up to about 15 (1 mg/g MISO and 43.5 degrees C for 60 min.). However, such treatment also caused a smaller hyperthermic radiosensitization of the normal tissue, so that the therapeutic ratio was only increased by a factor of about 3 compared to radiation alone. Simultaneous MISO and radiation followed by hyperthermia 4 h later gave a moderate enhancement, with ER up to 3 in the tumour, but with no enhancement of the normal tissue, so that there is a similar 3-fold increase in therapeutic gain. The mechanism by which MISO and hyperthermia enhanced the radiation response may be explained as an independent action of the hypoxic radiosensitization of MISO and the selective hyperthermic cytotoxicity against acidic and chronic hypoxic cells; simultaneous hyperthermia added a further heat-induced general radiosensitization. Surprisingly, no MISO cytotoxicity could be detected in this tumour system, with or without simultaneous hyperthermia. The results indicate that in the proper treatment schedule, MISO may be a valuable addition to a combined hyperthermia and radiation treatment.

Animals↗