PubMed Health⌕ Search

Biomedical subjects

M Urano

Publications and source records attributed to M Urano.

At least 91 records · Page 5Linked to original sources

Studies on fractionated hyperthermia in experimental animal systems II. Response of murine tumors to two or more doses.

The effect of multiple hyperthermia and the kinetics of thermal resistance were studied in experimental murine tumors. A spontaneous C3Hf mouse mammary carcinoma, MCa had a chemically-induced fibrosarcoma, FAa-1, were used. Assay methods included determination of the TCD50, i.e., the treatment time to yield a tumor control in half the treated animals and TG (tumor growth) time analysis, i.e., the time required for a tumor to reach a given size after first treatment. After equal dose fractions the TCD50 of MCa increased with increasing overall treatment time. This increase was most predominant when treatments were given with a time interval of one day. Isoeffect curves for the MCa were comparable to those for normal tissue damage (foot reaction), which was reported in the first part of this series of communications. The kinetics of thermal resistance in the MCa was compared with that in FSa-I since the fractionated hyperthermia for the FSa-I was reported to have resulted in an appreciable therapeutic gain. The magnitude of thermal resistance was far greater in the MCa than in the FSa-I, although the kinetics of thermal resistance was similar in both tumors; i.e., (a) the resistance reached a maximum in 24 hours after treatment and then decayed slowly, and (b) the development of thermal resistance increased with increasing initial dose. The thermal resistance in these tumors appeared to be greater than that in animal feet.

Animals↗

Evaluation of the clinical applicability of proton beams in definitive fractionated radiation therapy.

We report on the treatment of 317 patients treated either wholly or in part with proton beams at the Harvard Cyclotron Laboratory. These include: 130 patients treated for definitive radiation therapy of choroidal melanoma; 17 patients treated for tumors of the base of skull, cervical spine and cranium, which abut structures of the central nervous system (CNS); 23 patients treated for sarcomas of soft tissue and bone; 65 patients treated for carcinoma of the prostate; 14 patients treated for carcinoma of the rectum and anus; and 23 patients treated for squamous carcinoma of the oral cavity and oro-pharynx. Data on causes of failure and morbidity of treatment are presented. Overall the results are judged to be extremely encouraging. In particular, the treatment of the choroidal melanomas and sarcomas abutting CNS structures have clear clinical value, and the treatment of prostatic tumors and tumors of the head and neck are thought to be promising.

Bone Neoplasms↗

Thermal resistance in a spontaneous murine tumour.

Resistance to subsequent hyperthermia as a result of prior heating was investigated using a spontaneous murine tumour implanted into the feet of C3H/Sed mice. Tumours were treated by immersing the tumour-bearing foot into a constant-temperature hot water bath set at 45.5 degrees C and were given single and split doses of heat. Response was assessed using a tumour-growth time assay. Three aspects of thermally-induced resistance were particularly considered: the time course of development and decay; the importance of the magnitude of the priming dose and the influence of the size of the tumour at the time of treatment. Substantial resistance was induced in this tumour by short priming doses at 45.5 degrees C, rising rapidly 1-2 days after the first treatment and then starting to decay. There was no significant difference in the kinetics of thermal resistance induced in tumours treated at 4mm and those treated at 8 mm in size, although the large tumours were more sensitive to single doses of heat. Increasing the magnitude of the priming dose of heat resulted in an increase in the magnitude of resistance to the second dose. The results of this study are compared with results of similar studies in this and other laboratories using murine normal tissues and cells in culture. Possible clinical implications are considered.

Animals↗

Comparison of the effects of neutron and/or photon irradiation on spontaneous squamous-cell carcinoma in mice.

The effect of 30MeV D+ leads to Be NIRS cyclotron neutrons on a spontaneous NR-S1 squamous-cell carcinoma was studied. The TD50 (number of tumor cells required for transplantation in half the sites) and tumor growth delay time (TGD) were determined. The RBE of 200-kVp x rays at the 10% survival level was 1.9 for aerobic cells and 2.0 for hypoxic cells; the OER at the same level was congruent to 1.7. Tumor cells irradiated with neutrons were unable to repair potentially lethal damage, in contrast to x-irradiated tumor cells. The RBE of 50-MeV D+ leads to Be neutrons was inversely related to deuteron energy for hypoxic cells. The relationship between TGD and peak skin indicated no benefit from mixed beams or 5 neutron doses.

Animals↗

Clinical experience with proton beam radiation therapy.

Our experience with modulated energy proton beams in the definitive treatment of cancer patients indicates that, for the patients accepted, treatment volumes have been smaller and total doses higher than would have obtained for photon techniques alone used in our institution. The reactions of normal tissue have, with very few exceptions, been readily acceptable. The higher radiation doses employed should yield higher tumor control frequencies. Clearly, we cannot assess the efficacy of this modality because of the small number of patients followed for short periods. However, the results are judged by use to warrant intensive evaluation of this modality.

Child↗

The radiosensitivity of a murine fibrosarcoma as measured by three cell survival assays.

The radiation sensitivity of a weakly immunogenic spontaneous fibrosarcoma of the C3Hf/Sed mouse (designated FSa-II) was assessed by three in vivo cell survival methods: end-point dilution (TD50) assay, lung colony (LC) assay, and agar diffusion chamber (ADC) assay. The hypoxic fraction of this tumour was also determined by the ADC method. Although there was a good agreement of the cell survival data between the ADC and LC methods, the TD50 method yielded a considerably less steep cell survival curve. Beneficial aspects and limitations of each assay are discussed. In addition, the use of the ADC method for the growth of xenogeneic cell lines and a preliminary experiment with human tumour cells in non-immunosuppressed hosts suggest that this method may be a valuable adjunct for studying the growth and therapeutic responses of human tumour cells.

Agar↗

Insignificant tumor bed effect after pretransplantation hyperthermia.

Effect of pretransplantation hyperthermia of tumor bed on tumor growth was studied. Experimental tumors were isotransplants of a fibrosarcoma which arose spontaneously in C3Hf/Sed mice. The pretransplantation hyperthermia was given at 43.5 degrees fro 120 min by immersing the mouse foot into a constant temperature water bath. This treatment resulted in a similar foot reaction to a single gamma-ray dose of 3500 rads, namely, complete epilation or partial moist desquamation. The pretransplantation hyperthermia failed to retard tumor growth, while the concurrent experiment on pretransplantation irradiation demonstrated marked retardation of tumor growth. No retardation was observed when tumor cells were transplanted into the contralateral untreated feet or into the untreated skin.

Animals↗

Secondary malignant neoplasms following radiotherapy of a mouse mammary carcinoma.

Long-term observations were made for the development of secondary neoplasms following radiotherapy of animal tumors. Experimental tumors were 3rd generation isotransplants of a mammary carcinoma which arose spontaneously in a C3Hf/He mouse. A single dose of TCD20-TCD98 was followed by weekly observations. Most recurrences were observed in the first 150 days, while only a few were seen in the subsequent 150 days. Secondary neoplasms developed frequently following this period, i.e., 41 out of 67 animals surviving more than 300 days developed secondary neoplasms. They were osteogenic and soft tissue sarcomas, and half the new tumors were found within 490 days after radiotherapy. The results obtained were compared with literature reports of secondary neoplasms following postoperative radiotherapy for carcinoma of the breast and treatment of retinoblastomas. Most of these secondary human neoplasms were nonepithelial sarcomas as in the present study. Secondary carcinomas have been reported following radiotherapy of carcinoma in other locations, i.e., the cervix or head and neck; however, only a limited number of studies have been reported.

Animals↗

Enhancement of the thermal response of animal tumors by Corynebacterium parvum.

The effect of Corynecbacterium parvum treatment on the thermal response of animal tumors was studied. Tumors were methylcholanthrene-induced (FSa-II) and spontaneous (FSa-I) fibrosarcomas in C3Hf/Sed mice. C. parvum was given i.v. and was followed by local hyperthermia at 43.5 degrees 3 days later. Cell survival determined by lung colony assays showed that preadministration of C. parvum insignificantly enhanced the thermal response of both tumors. Studies of delay of tumor growth for FSa-II demonstrated that the enhancement ratio decreased with increasing time of treatment and reached a minimum of approximately equal to 1.7. The enhancement ratio for the time at hyperthermia which achieved tumor control in one-half of the treated tumors was 1.7. Together with our previous results on normal tissue responses, the therapeutic gain factor for obtaining 50% tumor control was found to be 1.1 (1.7/1.55) for the weekly immunogenic FSa-II tumor, while it was 2.3 for moderately immunogenic FSa-I as reported previously.

Animals↗