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J Overgaard

Publications and source records attributed to J Overgaard.

At least 199 records · Page 11Linked to original sources
PubMed1992

Early and late changes in the normal mouse bladder reservoir function due to irradiation and cis-DDP.

Early and late changes in the reservoir function of the mouse bladder were investigated after radiation alone or a combination of radiation and cisplatinum (cis-DDP). Bladder function was investigated by repeated cystometries. Treatments consisted of either single fraction radiation (5-10-15-25-30 Gy) or 20 Gy in combination with cis-DDP (6 mg kg-1; i.p.) administered at various time intervals from 14 days before until 14 days after radiation. At two selected time intervals (15 min and 4 h before) radiation was given at different dose levels (5-10-15-20 Gy). Within 30 days after irradiation a dose-dependent early response was noticed both in the radiation alone group and the group where cis-DDP was administered 15 min before radiation. The dose-response curve showed a slight but non-significant shift to the left in the combined treatment group (dose effect factor (DEF) = 1.18). Investigation of the early change in bladder reservoir function in the animals treated with 20 Gy alone or a combination of 20 Gy plus cis-DDP at various intervals in relation to irradiation demonstrated a significant increase in response when cis-DDP was administered 24 h and 15 min before and 4 h, 72 h and 336 h after 20 Gy (P less than 0.05). The reversible nature of the early damage was demonstrated. Late response was irreversible and significantly increased in most groups were cis-DDP was administered from 168 h before until 72 h after compared to radiation alone. Comparing groups treated with radiation alone with groups where cis-DDP was administered 15 min and 4 h before radiation revealed DEF values up to 1.45 (P less than 0.05), reflecting the significantly larger response in combined treatment groups. Survival was significantly decreased in all combined treatment groups compared to groups treated with radiation only and likewise survival was decreased in the group treated by cis-DDP alone compared to control (no treatment at all).

Animals↗
PubMed1992

Malignant parotid tumors in 110 consecutive patients: treatment results and prognosis.

The UICC 1987 classification system was used to retrospectively analyze the treatment results and prognostic factors in 110 consecutive patients. All of the patients had malignant parotid tumors which had been diagnosed and treated during the period from 1970 to 1986. Treatment consisted of surgery, radiotherapy, or a combination. Malignant mixed tumors were seen in 28% of the patients, mucoepidermoid tumors in 18%, adenoid cystic tumors in 15%, acinic tumors in 13%, undifferentiated tumors in 11%, adenocarcinomas in 10%, and other types in 5%. Ten-year corrected survival rate was 52%, and significant differences of survival were found between: 1. patients with disease stages I through IV (I: 85%; II: 69%; III: 43%; IV: 14%); 2. those with local tumor extension (34%) and without local tumor extension (79%); 3. patients with facial nerve palsy (0%) and without facial nerve palsy (57%); and 4. those with low- or intermediate-grade malignant tumors (69% combined) and those with high-grade malignant tumors (30%). After primary treatment, 45% of the patients were cured, and, additionally, 22% were salvaged after local or neck node recurrences. It is concluded that there is a good correlation between TNM classification of UICC 1987 (stage and local extension of tumor) and prognosis, and that facial nerve palsy and grade of malignancy are important prognostic factors.

Adolescent↗
PubMed1992

Cisplatin and hyperthermia treatment of a C3H mammary carcinoma in vivo. Importance of sequence, interval, drug dose, and temperature.

The effect of combining cisplatin and hyperthermia was investigated in a C3H mammary carcinoma in vivo, using a regrowth delay assay. Cisplatin (6 mg/kg) was given i.p. at intervals ranging from 24 h before to 24 h after a 43.5 degrees C/60 min treatment. A supra-additive effect was obtained by giving cisplatin 15 min before heat, whereas an additive effect was obtained at all other intervals. The importance of cisplatin dose and heating temperature were investigated by giving variable cisplatin doses (2-8 mg/kg) 4 h or 15 min before a 60 min heating at temperatures in the range 40.5-43.5 degrees C. Linear relationships between length of regrowth delay and cisplatin dose were obtained both for cisplatin alone and for the combined treatment. The effect of the combined treatment could therefore be quantitated by a ratio (ER) between the slopes of dose-response curves. The ER values for cisplatin give 4 h before a 60 min heating at 42.5 or 43.5 degrees C were not significantly different from 1 (p greater than 0.5). In contrast, significant ER values were obtained above 40.5 degrees C (p less than 0.05) for cisplatin given 15 min before heat. The data demonstrates the possibility of achieving chemosensitization at clinically relevant temperatures.

Animals↗
PubMed1991

Interaction of hyperthermia and cis-diamminedichloroplatinum(II) alone or combined with radiation in a C3H mammary carcinoma in vivo.

The interaction between hyperthermia and cis-diamminedichloroplatinum(II) (c-DDP) given in various schedules as an adjuvant to radiation treatment was investigated in a C3H mouse mammary carcinoma in vivo. Both hyperthermia (43.5 degrees C for 60 min) and c-DDP (6 mg/kg i.p.) caused a delay in tumor growth when given individually. When c-DDP was given 4 h prior to hyperthermia, the increase in tumor growth time corresponded to an additive effect, but when the interval was reduced to 15 min, the tumor growth delay was significantly greater than additive. The modifying effect of these schedules on radiation was studied using local tumor control (50% tumor control dose) as the endpoint. c-DDP alone did not result in any enhancement of tumor control, irrespective of whether it was given 15 min or 4 h after irradiation. In contrast, heat treatment at 43.5 degrees C for 60 min given 4 h after irradiation resulted in a significant reduction in the 50% tumor control dose, with an enhancement ratio of 1.8. From a clamped local tumor control assay, it was found that c-DDP selectively killed aerobic cells, whereas hyperthermia was primarily directed toward the hypoxic clonogenic cells in the tumors. Combining the two modalities (simultaneously) resulted in a significant additional increase in the killing of well-oxygenated clonogenic cells, but the destruction of hypoxic cells was not different from that obtained after heat alone.

Animals↗
PubMed1991

The use of blood flow modifiers to improve the treatment response of solid tumors.

There is now considerable interest in the possible use of agents which can change blood flow in solid tumors and thereby alter the response of tumors to different treatments. In the current presentation we briefly review the types of agents which have the potential to modify tumor blood flow, using nicotinamide. hydralazine, and pyrazinamide as examples and illustrate how they can be used to improve the response of murine tumors to radiation, hyperthermia and cyclophosphamide.

Animals↗
PubMed1991

The potential of using hyperthermia to eliminate radioresistant hypoxic cells.

It is known that cells in a nutritionally deprived and acidic environment are sensitive to heat. In general these same cells are chronically hypoxic and therefore heat possesses the potential to eliminate (some) of this radioresistant population. A direct radiosensitization is observed when heat is given simultaneously with radiation. This effect occurs to the same extent in both aerobic and hypoxic cells, thus the oxygen enhancement ratio is unchanged. By giving heat several hours after radiation the direct radiosensitization is avoided and the specific heat killing of the acidic, chronically hypoxic, tumor cells may be utilized to improve the therapeutic gain. The current investigation clearly demonstrates this concept in a C3H mammary carcinoma using a local tumor control assay. This effect could be further enhanced by adding hypoxic radiosensitizers (nimorazole, misonidazole) or a blood flow modifier (nicotinamide) which can eliminate acutely hypoxic cells.

Animals↗
PubMed1991

Nimorazole as a hypoxic radiosensitizer in the treatment of supraglottic larynx and pharynx carcinoma. First report from the Danish Head and Neck Cancer Study (DAHANCA) protocol 5-85.

Between January 1986 and September 1990, 442 patients with pharynx and supraglottic larynx carcinoma were randomized to receive the hypoxic cell radiosensitizer nimorazole (NIM) or placebo in association with a course of conventional primary radiotherapy. A preliminary analysis including the first 288 patients showed that the stratification parameters were significant (3-year actuarial local-regional tumor control, p less than 0.05) for sex (females 52% vs males 34%), tumor size (T1-T2 47% vs T3-T4 32%) and pre-irradiation hemoglobin (Hb) concentration (high 41% vs low 34%). Overall, the NIM group showed a significantly better local-regional control rate than the placebo group (46% vs 32%). There was an apparent additive effect of Hb concentration and NIM. Thus, in the male group, placebo patients with low Hb had a 23% control rate compared to 46% in NIM treated patients with Hb above 9 mmol/l (p less than 0.05). The similar effect in females could not be evaluated due to the small number of women with this disease. NIM was well tolerated and drug-related side effects were minor and tolerable, with transient nausea and vomiting as the most frequent complication. A final conclusion of the study must await an evaluation including all patients and a longer observation time.

Carcinoma↗
PubMed1991

Radiosensitizing and cytotoxic properties of mitomycin C in a C3H mouse mammary carcinoma in vivo.

The radiosensitizing and cytotoxic properties of Mitomycin C (MMC) was investigated in vivo using regrowth delay and tumor control assays. MMC significantly enhanced the radiation-induced growth delay when administered 15 min before irradiation; the slope of the dose response curve significantly increased and corresponded to a Dose Modifying Factor (DMF) of 1.9 (1.5-2.3; p less than 0.001). When MMC was given 4 hr after irradiation, the additional regrowth delay resulted in a parallel shift of the dose response curve, and MMC was not significantly dose modifying (DMF 1.3 (0.9-1.3); p less than 0.05). From isobologram analysis it was found that the preirradiation MMC schedule resulted in supra-additive responses, whereas MMC given after irradiation had an additive effect. The enhancement of radiation-induced tumor control was similarly found to peak when MMC was given 6 hr to 15 min prior to irradiation. At these intervals, the observed TCD50 for the combined treatments relative to radiation alone corresponded to Enhancement Ratios of 1.27 and 1.29, respectively (p less than 0.001). Longer intervals between the modalities reduced the enhancement, but the combined treatments were still significantly better than radiation alone (ER 1.12, 1.16 and 1.17; p less than 0.001). The significant enhancement of tumor control correlated with a substantial drug-induced cytotoxic effect toward hypoxic tumor cells, as determined by clamped TCD50 experiments. A single dose of MMC (3 mg/kg) was found to kill up to 97% of all hypoxic tumor cells.

Animals↗
PubMed1991

Clinical radiobiology of squamous cell carcinoma of the oropharynx.

Local tumor control is analyzed in a series of 181 patients treated with definitive megavoltage radiotherapy (RT) for histologically proven squamous cell carcinoma of the oropharynx. Considerable variation in treatment time stemmed from the general use of a split-course technique in 49 patients treated from 1978 to 1985. Incomplete follow-up, in those patients alive and well at the termination of the study or who have died from metastases or intercurrent disease before developing a local recurrence, was allowed for by using a multi-variate mixture model. The tumor control probability (TCP) after radiotherapy showed a significant dependence on the following tumor and treatment characteristics: (a) tumor size: the number of tumor target cells increases approximately as the fourth root of estimated tumor volume; (b) sex: the estimated TCP in males is lower than in females with the same characteristics; (c) histopathological differentiation: well-differentiated tumors have a lower TCP than poorly and intermediately differentiated; (d) hemoglobin concentration: patients in the upper normal range have a significantly higher TCP than others; (e) total dose: there is a significant dose-response relationship; and (f) overall treatment time: TCP decreased with increasing overall time, the dose equivalent of proliferation with 2 Gy per fraction was 0.68 Gy/day with 95% confidence limits [0.05, 1.3] Gy/day. The TCP did not depend significantly on subsite within the oropharynx or nodal disease at presentation. The data were consistent with an alpha/beta ratio of the linear-quadratic model of 10 Gy.

Carcinoma, Squamous Cell↗
PubMed1991

Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma.

The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.

Adult↗
PubMed1991

Effect of step-down heating on the interaction between heat and radiation in a C3H mammary carcinoma in vivo.

The effect of step-down heating (SDH) on the interaction between heat and radiation was investigated in a C3H mammary carcinoma in vivo. SDH consisted of an initial sensitizing treatment (ST) performed at 44.5 degrees C or 43.5 degrees C followed by a lower temperature test treatment (TT) in the range 41.0-43.0 degrees C. Step-up heating (SUH), i.e. TT followed by ST, and single heating were used as controls. The end-point was the radiation dose needed to control 50% of the tumours (TCD50). The results were evaluated by calculating the thermal enhancement ratio (TER) defined as TER = TCD50 (radiation alone)/TCD50 (radiation and heat). For a simultaneous application of TT and radiation a significant enhancement of direct heat radiosensitization was observed with increasing ST time or ST temperature using SDH. In contrast, only a minor increase was seen with SUH. A comparison between TCD50 values for the corresponding SUH and SDH schedules revealed that the SDH effect was largest at 41.0-42.0 degrees C and decreased with increasing TT temperature. The radiosensitizing effect of SDH also decreased if an interval was allowed between ST and TT or between TT and radiation. However, as a result of an increased cytotoxicity towards hypoxic tumour cells, the TCD50 value for SDH remained significantly smaller than for SUH, even with a sequential combination of radiation and heat.

Animals↗
PubMed1991

Resources and productivity in radiation oncology in Denmark, Finland, Iceland, Norway and Sweden during 1987.

Data concerning megavoltage equipment and use of megavoltage external beams in cancer management during 1987 in Denmark, Finland, Iceland, Norway, and Sweden were collected from all 37 centres serving a population of 23 million in these countries. Population per Linear Accelerator Equivalent (LAE) unit ranged from 0.30 million/LAE unit (Denmark) to 0.19 million/LAE unit (Sweden). The number of field treatments were 227,548 (Denmark), 259,917 (Finland), 10,426 (Iceland), 147,960 (Norway) and 490,126 (Sweden). The number of field treatments per million population per year ranged from 35,229 (Norway) to 58,438 (Sweden). The number of field treatments per LAE unit/year ranged from 13,192 (Denmark) to 9,546 (Norway). The fraction of cancer patients receiving megavoltage radiotherapy in 1987 out of all newly diagnosed cancer patients during 1987 was 24% in Denmark, 37% in Iceland, 25% in Norway, and 34% in Finland and Sweden. We conclude that Denmark and Norway probably did not provide adequate levels of radiotherapy for their cancer patients during 1987.

Denmark↗
PubMed1991

Hydralazine-induced changes in tissue perfusion and radiation response in a C3H mammary carcinoma and mouse normal tissues.

Hydralazine has been reported to reduce blood perfusion in tumours, thereby increasing hypoxia and subsequently enhancing tumour sensitivity to certain drugs and hyperthermia. We have investigated the ability of hydralazine to induce such changes in a C3H mouse mammary carcinoma and various normal tissues. In tumours, hydralazine (5 mg/kg; i.v.) modified the radiation response, measured by a local tumour control assay, producing an effect equivalent to that seen in tumours made fully hypoxic by clamping. This effect was time-dependent and correlated with the decrease in tissue perfusion estimated by the 86-RbCl extraction procedure. Similar effects were seen in normal skin, although the changes were less dramatic and of a shorter duration. Hydralazine also reduced 86-RbCl uptake in liver, kidney, gut and spleen, but not in bladder, muscle and lung, suggesting that it may have the potential to increase the sensitivity of some normal tissues to hypoxic cell cytotoxins.

Animals↗
PubMed1990

Combination of nicotinamide and hyperthermia to eliminate radioresistant chronically and acutely hypoxic tumor cells.

The interaction among nicotinamide, radiation, and heat was studied in vivo using a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Response following local tumor treatment was assessed by tumor control and regrowth delay. Nicotinamide (1000 mg/kg i.p.) produced maximal radiosensitization when injected 30 min to 2 h before irradiation [enhancement ratios (ERs), 1.2-1.5]. Radiation damage was also increased by heating tumors (43.5 degrees C for 60 min) 4 h after irradiation (ERs = 1.6-2.6). This combined radiation and heat treatment was enhanced by nicotinamide but the effect depended on the assay procedure, such that although a significant increase was observed with the tumor control assay, only a slight increase was seen using regrowth delay as the end point. The development of moist desquamation in normal feet was used to estimate skin damage after irradiation. Nicotinamide and heat both resulted in a small yet significant increase in skin damage (ERs less than 1.2 and 1.1, respectively). A combined treatment resulted in a greater ER of 1.7, but when compared to the tumor response it still gave a therapeutic gain. A histological fluorescent staining technique was used to assess functional tumor vasculature at two periods in time separated by 20 min. Under normal conditions 7.7% of the vessels in this tumor were functional at one time but not the other. This value was reduced to 2.8% after nicotinamide administration. Since these fluctuations in blood flow can result in acute hypoxia we conclude that while heat eliminates chronically hypoxic tumor cells, nicotinamide probably removes the presence of acute hypoxia.

Animals↗
PubMed1990

The potentiation of radiation damage by nicotinamide in the SCCVII tumour in vivo.

We have continued our assessment of the ability of nicotinamide to sensitize tumours to radiation. Using the SCCVII carcinoma and estimating tumour response by either a regrowth delay or an in vivo/in vitro survival assay, it was found that a large single dose of nicotinamide (1000 mg/kg) increased radiation-induced tumour damage. This effect was observed regardless of whether the tumour was grown intramuscularly, subcutaneously or intradermally, or whether the nicotinamide was administered intraperitoneally, intravenously or orally. The enhancement was maximal when the drug was given between 30 min and 2 h prior to irradiation and resulted in enhancement ratios ranging from 1.1 to 1.7. Although the radiation response of tumours was dependent on tumour size, the radiation enhancement produced by nicotinamide was not. Utilizing the technique of labelling tumour cells with the fluorescent stain Hoechst 33342, we were able to identify the presence of both chronic and acutely hypoxic cells in this tumour model and obtained results suggesting that apart from reducing chronic hypoxia, nicotinamide may also have the ability to decrease the level of radioresistant acute hypoxia.

Animals↗
PubMed1990

Effect of radiation on glucose absorption in the mouse jejunum in vivo.

In an attempt to develop a clinical assay for intestinal damage, the relationship between radiation dose and glucose absorption in the jejunum has been investigated. Lightly anesthetised C3D2F1 mice had their upper abdomen irradiated. The intestine was exteriorized and a 10-cm segment of the jejunum was isolated and included in a closed circuit perfusion loop. An isotonic solution containing 2 mg/ml D-glucose was perfused in 2 h and the rate of glucose absorption calculated. The absorption decreased as a function of dose and time after irradiation with the most prominent reduction after 4-5 days, returning to normal within a week after irradiation. A dose-response relationship was found after single doses between 5 and 17.5 Gy. Split-dose recovery of approximately 7.5 Gy was found within 2-4 h. This absorption insufficiency was only found to be present acutely, and no late abnormalities were seen for times greater than 12 months after irradiation. The results correlated with other functional endpoints such as absorptive surface. This assay seems suitable to demonstrate (acute) functional intestinal radiation damage and has obvious clinical applicability.

Animals↗
PubMed1990

Blood transfusion and prognosis in Dukes' B and C colorectal cancer.

To evaluate the prognostic influence of blood transfusion in cancer patients, transfusion data were reviewed on 468 radically operated patients (260 Dukes' B and 208 Dukes' C) with carcinoma of the rectum and the rectosigmoid. Data on whole blood and packed red blood cell transfusions were recorded together with a number of clinical, pathological and histochemical characteristics. The endpoint used was death with cancer. All patients were followed for 2-7 years or until time of death. Univariate statistical methods revealed a highly significant trend towards worsened prognosis with increasing volume of transfusion blood. However, this effect was insignificant when multivariate statistical methods were employed: patients receiving whole blood or packed red blood cell transfusions did no worse than expected from their clinico-pathological characteristics. It is concluded that in this series the observed association between transfusion status and prognosis is adequately explained by a multivariate prognostic model including well-established prognostic factors.

Aged↗