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J Overgaard

Publications and source records attributed to J Overgaard.

At least 199 records · Page 11Linked to original sources
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↗
PubMed1990

Primary radiotherapy of T1 squamous cell carcinoma of the larynx: analysis of 478 patients treated from 1963 to 1985.

Radiotherapy was administered to 478 consecutively treated patients with laryngeal T1 squamous cell carcinoma between 1963-1985. One hundred and seventeen had a supraglottic, 358 a glottic, and 3 a subglottic tumor. Supraglottis: 71% males; 49% T1a; 14 patients with nodes. Glottis: 90% males; 82% T1a; 1 patient with node. The 10-year value for local control in the supraglottic group was 55% and in the glottic group 81%. No difference was observed between T1a and T1b. Regional nodes and distant metastases were seldom seen in the glottic, but frequently observed in the supraglottic group. The treatment results appeared to be most favorable in women. The 10-year corrected survival for supraglottic and glottic tumors demonstrated a highly significant difference, 67% compared to 94%. There was a significantly increasing incidence of events with lower tumor differentiation. Split-course and conventional radiotherapy gave equal treatment results, but late complications were significantly more common with the former. A major problem was new primary cancers, which within 20 years occurred in 34% of patients surviving a supraglottic tumor and in 23% of the glottic patients. The predominant new site was the lung (23% and 13%, respectively). Thus, in the glottic group more patients died from the new cancer than from the glottic carcinoma.

Adult↗
PubMed1990

Cytotoxic effect of misonidazole and cyclophosphamide on aerobic and hypoxic cells in a C3H mammary carcinoma in vivo.

The chemosensitising effect of the nitroaromatic radiosensitiser misonidazole (MISO) on the alkylating agent cyclophosphamide (CTX) has been investigated in a C3H mammary carcinoma in CDF1 mice. The selective cytotoxicity against aerobic and hypoxic cells was measured indirectly, using a local tumour control (TCD50) assay. The hypoxic fraction was calculated from the dose difference between the TCD50S for tumours irradiated either in air or under clamped conditions. The relative survival of tumour cells after drug therapy was expressed as a surviving fraction (SF). CTX (100 mg kg-1) was found to be considerably more toxic towards hypoxic than aerobic cells (SF 4% versus 52%). MISO (1000 mg kg-1) was almost exclusively toxic to hypoxic cells (SF 22%). When MISO and CTX were administered simultaneously a decrease in the surviving fraction was observed. The effect on aerated cells was found to be 10-fold more than expected from addition of toxicities, suggesting a chemosensitising effect on these cells by MISO when used in combination with CTX. No synergistic effect was found on radiobiologically hypoxic cells. The exact role of hypoxia for the development of chemosensitisation seems to be complex and requires additional research in the future.

Animals↗
PubMed1990

Does variation in the in vitro cellular radiosensitivity explain the shallow clinical dose-control curve for malignant melanoma?

In radiotherapy, clinical dose-control curves are generally more shallow than what should be expected from in vitro dose-survival curves for human cells of the same histology. One possible explanation is that a considerable inter-tumor heterogeneity in radiosensitivity flattens out the presumably steep individual dose-control curves. This paper compares dose-control curves for malignant melanomas derived from clinical data with curves derived from in vitro cell-survival experiments. Although inter-tumour variability in the in vitro dose and fractionation sensitivity may explain parts of the discrepancy between the steepness of clinical and in vitro dose-control curves, the present calculation indicates that a considerable additional variability, undetected by current in vitro assays, must be assumed to exist in order to resolve the discrepancy.

Cell Survival↗
PubMed1990

Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH.

The relation between angiographically determined cerebral vasospasm following a subarachnoid hemorrhage and regional cerebral blood flow (CBF) was studied in 63 investigations of 45 patients. The CBF was measured using the intra-arterial 133-Xe clearance technique within one hour of angiography. A positive correlation between regional CBF and diameter of major supplying vessel was observed. However, in the 13 cases with focal vasospasm the reduction in CBF was global and not restricted to the area of the spastic vessel. The cerebral oxygen extraction was reduced but independent of the degree of vasospasm, speaking against vasospasm as the cause for the reduction in CBF. The observed association between reduction in CBF and vasospasms could be caused by a common factor responsible for development of both. Thus, it is proposed that the amount of blood escaping at time of aneurysm rupture determines 1) the amount of reduction in cerebral oxygen uptake and thereby the reduction in CBF and 2) the degree of vasospasm. If so a correlation, yet not causal, between reduction in CBF and degree of vasospasm, will be observed.

Cerebral Angiography↗
PubMed1990

Squamous cell carcinoma of the oropharynx: an analysis of 213 consecutive patients scheduled for primary radiotherapy.

Radiotherapy was administered to 213 consecutively treated patients with oropharyngeal squamous cell carcinoma. The classification (Union Internationale Contre le Cancer, 1982) showed primary tumors (T1, 13%; T2, 51%; T3, 34%; T4, 2%) and regional lymph nodes (N0, 38%; N1, 38%; N2, 4%; N3, 20%). The 10-year actuarial value for local control was 48%; for regional control, it was 66%. Distant failure occurred in 20 patients. The 10-year actuarially corrected survival rate was 40% (stage I, 57%; stage II, 51%; stage III, 43%; stage VI, 21%). Locoregional tumor control was significantly influenced by irradiation parameters (total dose and treatment time), tumor volume, sex, and hemoglobin value. It is concluded that local control of the tumor while still in the T position is the parameter most crucial to success. This end point is currently being aimed at evaluating primary surgery and testing a radiation technique with larger total doses and shrinking fields and a new radiosensitizer, while at the same time investigating the influence of hemoglobin concentration.

Adult↗
PubMed1990

The in vivo response of a C3H mammary carcinoma to treatment with misonidazole, cyclophosphamide and radiation.

The potential chemosensitizing effect of the nitroaromatic radiosensitizer misonidazole (MISO) on the alkylating agent cyclophosphamide (CTX), and the interactions of these agents with radiation, have been investigated in a C3H mammary carcinoma in CDF1 mice. MISO at 1,000 mg/kg caused a small increase in tumour growth time (TGT; time to reach 3 times treatment volume) from 3.6 days to 4.5 days. CTX (100 mg/kg) increased the TGT to 15.7 days. The combined treatment of MISO and CTX given with intervals of either 15 min or 4 h increased the TGT to 23.3 and 23.8 days respectively. The radiation enhancement ratio (ER) was found to be 2.13 and 1.10 for MISO administered before or after x-rays respectively. The corresponding ERs for CTX were 1.16 and 1.22. The two drugs given in combination resulted in significant radiation ERs of 2.68 (both drugs given within 30 min before x-rays), 3.00 (MISO 30 min before and CTX 3 1/2 h after x-rays) and 1.40 (both drugs given after x-rays). In contrast to what has previously been reported, and in contrast to the tumour regrowth delay data, the results of the tumour control experiments were found to reflect no more than an additive action of the two drugs when used together with radiation in vivo.

Animals↗
PubMed1990

[Radiation enteritis: mucosal regeneration and stromal reaction of the small intestine after irradiation].

D-glucose absorption in vivo in mice decreased as a function of dose and time after irradiation returning to normal within a week after irradiation. The lamina propria is seen full of polymorphonuclear leukocytes, other infiltrative cells, capillary and lymphatic network, which seem closely related to chronic enteritis. Since acute and chronic diarrhea after irradiation can be reduced by cholestyramine or acetylsalicylate, malabsorption of bile salts or prostaglandin E of the luminal content has been regarded as a cause of radiation-induced diarrhea. LD 50 of irradiated mice was increased by SOD. From the clinical data, thin physique, previous operation, and total dose of more than 50 Gy could be predisposing factors of radiation-related enteritis.

Adult↗
PubMed1990

The influence of radiation dose on the magnitude and kinetics of reoxygenation in a C3H mammary carcinoma.

The variation in hypoxic fraction as a function of time after various priming doses of radiation has been investigated in a C3H mouse mammary carcinoma in situ. The hypoxic fraction was calculated from data for local tumor control. Untreated tumors were found to contain 4.8% radiobiologically hypoxic cells. Within minutes after a priming dose of 20 Gy given in air, the hypoxic fraction increased to a value not significantly different from 100%. After 4 h, reoxygenation was complete (hypoxic fraction 1.3%), and the hypoxic fraction stabilized at a level significantly below the untreated value. Following a priming dose of 40 Gy the reoxygenation pattern was different: The hypoxic fraction stayed above the pretreatment value for 4 h, and pronounced reoxygenation occurred after 12 h (hypoxic fraction 0.4%). At longer time intervals the hypoxic fraction again increased to--and slightly above--the oxygenation level of untreated tumors. The present findings show that reoxygenation in solid tumors is a function of radiation dose, and the data suggest that mechanisms other than a decrease in tumor cell O2 consumption are involved in tumor reoxygenation.

Animals↗
PubMed1989

[Prognosis in synchronous liver metastasis from colorectal cancer. A multicenter study of patients with cancer of the rectum and cancer of the rectosigmoid colon].

A prospective investigation of 188 patients with cancer of the rectum and rectosigmoid colon with synchronous liver metastases is described. The mean survival time for 183 patients who did not receive any treatment for the liver metastases was six months and only one survived for longer than 37 months. After extirpation of the primary tumour, the most significant prognostic factors were etrahepatic metastases, enlarged liver on account of metastases and more than three liver metastases. Serum basic phosphatases had the greatest significance among a series of laboratory tests. In the sub-groups with the best possible prognoses, the mean survival time was 12 months. 25% five-year survival has been described in the literature following resection of the liver in patients with a maximum of three metastases, no other metastases and age under 70 years. Provided this holds true, liver surgery will be a therapeutic possibility in at least 100 patients per annum in Denmark with synchronous liver metastases and 25 of these will be cured. This figure requires an improved programme for the diagnosis of synchronous liver metastases than at present and the same high frequency of extirpation of the primary colorectal cancer on a national basis which was achieved in the present material.

Aged↗
PubMed1989

Clinical radiobiology of malignant melanoma.

Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127, 53%) were treated with electron beams, and more deeply seated tumors (112, 47%) with 60Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the alpha/beta ratio in the multifraction linear-quadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07, 2.5] Gy. Treatment time had no demonstrable influence on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits [0.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose-response data could be removed by accounting for size. Thus, the weak or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a "hidden parameter" (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of-fit showed that the variation between predicted and observed results could be explained by the binomial variation on quantal response data.

Cobalt Radioisotopes↗