[A case of situs inversus totalis associated with the replaced common hepatic artery arising from the superior mesenteric artery].
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
M Urano
Publications and source records attributed to M Urano.
Effect of temperature on blood flow and hypoxic fraction in a murine fibrosarcoma.
The effect of hypo to hyperthermic temperatures on tumor blood flow and hypoxic cell fractions was studied in a murine fibrosarcoma transplanted in the hind leg of anesthetized mice. The blood flow to the tumor was assessed by the determination of the uptake of Thallium-201; the hypoxic cell fraction was estimated from cell survival curves derived from data based on lung colony assay. Over a temperature range of 18 degrees to 46 degrees C, the maximal blood flow occurred at 35 degrees C which was approximately two times greater than that at room temperature (24 degrees C) or at 39 degrees C. The hypoxic cell fraction at 35 degrees C was 11%, and was significantly less than that at 24 degrees C or at 39 degrees C. The hypoxic cell fractions at 24 degrees C and at 39 degrees C were 45% and 32%, respectively. These results suggest that the optimal radiation sensitivity of peripherally located tumors can be obtained by warming the tumors to temperatures where maximal blood flow and minimal hypoxic cell fraction occur.
Animals↗
The effect of hyperglycemia on the tumor response to irradiation given alone or in combination with hyperthermia.
The effect of hyperglycemia (elevated blood glucose level) on the response of a murine tumor to irradiation given alone or in combination with hyperthermia was studied. Tumors were early generation isotransplants of a spontaneous C3H/Sed mouse fibrosarcoma, FSa-II. Single-cell suspensions were transplanted into the foot, and irradiation was given when each tumor reached an average diameter of 7 mm. Following irradiation, the tumor growth time to reach 1000 mm3 was studied and the dose-response curve between the tumor growth time and radiation dose was fitted. Preadministration of glucose increased the size of the hypoxic and chronically hypoxic cell fractions without altering the slope of the dose-response curve where the chronically hypoxic cell fraction is determined as the fraction of cells which were not oxygenated under hyperbaric oxygen conditions. Hyperthermia given prior to irradiation enhanced the tumor response to irradiation, but simultaneously increased the size of the hypoxic and chronically hypoxic cell fractions. Similar results were observed following hyperthermia given after irradiation. When hyperthermia at 43.5 degrees C was given 24 h before irradiation, the size of the hypoxic cell fraction increased with increasing treatment time, while a substantial decrease in the chronically hypoxic cell fraction was observed. Administration of glucose 60 min before hyperthermia further increased the size of the hypoxic cell fraction. Possible mechanisms explaining why glucose administration increases the hypoxic cell fractions are discussed.
Animals↗
Tumor size dependent changes in a murine fibrosarcoma: use of in vivo 31P NMR for non-invasive evaluation of tumor metabolic status.
Tumor tissue contains viable hypoxic regions that are radioresistant and often chemoresistant and may therefore be responsible for some treatment failures. A subject of general interest has been the development of non-invasive means of monitoring tissue oxygen. Pulse Fourier transform 31P NMR spectroscopy can be used to estimate intracellular nucleotide triphosphates (NTP), phosphocreatinine (PCr), inorganic phosphate (Pi) and pH. We have obtained 31P NMR spectra as an indirect estimate of tissue oxygen and metabolic status in a C3H mouse fibrosarcoma FSaII. Sequential spectra were studied during tumor growth in a cohort of animals and peak area ratios for several metabolites were computed digitally by computer. During growth, tumors showed a progressive loss of PCr with increasing Pi, and most tumors greater than 250 mm3 in volume had little or no measurable PCr. The smallest tumors (38 mm3 average volume) had PCr/Pi ratios of 1.03 +/- .24, whereas tumors 250 mm3 or more had an average PCr/Pi ratio of 0.15 +/- .04. Similarly derived NTP/Pi ratios decreased with tumor size, but this change was not significant (p = .17). Radiobiologic hypoxic cell fractions were estimated using the radiation dose required to control tumor in 50% of animals (TCD50) or by the lung colony technique. Tumors less than 100 mm3 had a hypoxic cell fraction of 4% (TCD50) while tumors 250 mm3 had a 40% hypoxic cell fraction (lung colony assay). These hypoxic fraction determinations correlated well with the depletion of PCr and decline in NTP/Pi ratios seen at 250 mm3 tumor volumes. Tumor spectral changes with acute ischemia were studied after ligation of the tumor bearing limb and were similar to changes seen with tumor growth. PCr was lost within 7 minutes, with concurrent increase in Pi and loss of NTP. Complete loss of all high energy phosphates occurred by 40 minutes of occlusion. In vivo tumor 31P NMR spectroscopy can be used to estimate tissue metabolic status and may be useful in non-invasive prediction of hypoxic cell fraction, reoxygenation, and radiation treatment response.
Animals↗
Thermochemotherapy (combined cyclophosphamide and hyperthermia) with or without hyperglycemia as an adjuvant to radiotherapy.
Our previous study demonstrated the presence of a thermochemotherapy-resistant cell fraction in a tumor. The present study investigated whether thermochemotherapy-resistant cells are radioresistant and whether thermochemotherapy changes the size of hypoxic cell fraction in the tumor. Early generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumors, were used. A radiation dose that yields 50% tumor control rate in 150 days after local irradiation, TCD50, was determined. Cyclophosphamide (CY) was the test agent. TCD50 values of the 4 mm tumor following gamma-ray alone given under hypoxic conditions or in air were 80.9 or 65.8 Gy, respectively. Thermochemotherapy reduced TCD50 values congruent to 20 Gy, suggesting that thermochemotherapy resistant cells are not identical to the radioresistant cells. Glucose administered 60 min before thermochemotherapy further reduced TCD50 values. Foot-reaction scored in the tumor-controlled animals was significantly less severe following combined thermochemo- and radiotherapy compared to that following radiotherapy alone. Acute foot reaction studies also supported this observation. These results indicated that thermochemotherapy could be an excellent adjuvant to radiotherapy. Further studies using a 6 mm tumor indicated that thermochemotherapy was less effective on the large tumor than on the small tumor. Indirect analysis showed no significant changes in the size of hypoxic cell fraction following thermochemotherapy.
Animals↗
Differential kinetics of thermal resistance (thermotolerance) between murine normal and tumor tissues.
The kinetics of thermotolerance were studied in mouse normal and tumor tissues. Early generation isotransplants of a spontaneous fibrosarcoma, FSa-II, were used. Tumor cell suspension was transplanted into the C3Hf/Sed mouse foot. Hyperthermia was given by immersing animal feet into a water bath. The TG (tumor growth) time, the time required for half the treated tumors to reach 1000 mm3 from the first treatment day, was the end point. Foot reaction was studied as a normal tissue response. The RD50, the treatment time that induces a loss of one toe or greater reaction in half the treated animals, was analyzed. Thermotolerance developed rapidly and extensively in normal and tumor tissues. A significant difference was observed in the decay of thermotolerance between these tissues. The decay of thermal resistance was incomplete in the murine foot tissue, even at 14 days after the initial heat treatment. Although some experimental difficulties were involved in the tumor study, present results suggest a complete decay of thermotolerance in the FSa-II tumor in 8 days after a 7.5 min treatment of 45.5 degrees C. Thermal resistance again developed in both tissues following the second heat treatment, which was given 7 or 8 days after the first heat treatment. The development, maximum magnitude and decay of the second thermal resistance was comparable to those of the first thermal resistance in each tissue.
Adaptation, Physiological↗
Kinetics of thermotolerance in normal and tumor tissues: a review.
Thermotolerance is a phenomenon in which cells become resistant to elevated temperatures as a result of prior or continuous exposure to hyperthermia. Thermotolerant cells exhibit a decreased slope of the cell survival curve. Recent studies disclosed that thermotolerance developed in rodent tumors and normal tissues as well. Thermotolerance develops during the treatment at a temperature below approximately equal to 43.0 degrees C, or it develops rapidly after the first heat treatment. The decay of thermotolerance is slow and is incomplete over 7 days in many normal tissues, while it appears to be completed in murine tumors. The kinetics of thermotolerance is modified by various factors. In general, the greater the initial heat damage (independently of temperature), the greater is the magnitude of thermotolerance and the longer is the time to reach maximum and the time to decay. Although thermotolerance develops less extensively in cultured cells in low pH medium and the average tumor tissue pH is lower than the normal tissue pH, the magnitude of thermotolerance in tumors thus far examined is at least equal to that in the normal tissues. Data on the interaction between thermotolerance and radiosensitivity are contradictory, although thermotolerance appears to reduce thermal radiosensitization. The kinetics of reduced sensitization is similar to that of thermotolerance. The interaction between chemotherapeutic agents and thermotolerance appears to depend on the drug and the temperature. Experimental data on this topic are still sparse and extensive studies are required.
Animals↗
Effect of 42 degrees C hyperthermia on murine normal and tumor tissues.
The effect of one or two heat treatments at 42.0 degrees C was studied in murine normal and tumor tissues. Early-generation isotransplants of a spontaneous fibrosarcoma, FSa-II tumors, were used. Single-cell suspension was transplanted into the mouse foot. Tumor growth time, the time required for half the treated tumors to reach 1000 cu mm from treatment day was the end point. For normal tissue studies, the foot reaction was scored according to our numerical score system. Hyperthermia was given in a constant temperature water bath. Tumors were treated when they reached an average diameter of 4 (35 cu mm) or 8 mm (270 cu mm). The 4-mm tumor responded poorly to a single heat treatment at 42.0 degrees C, while the 8-mm tumor showed a substantial initial response, followed by the development of thermal resistance. The dose-response curve for the foot reaction was characterized by a large shoulder followed by a linear relationship. Thermal resistance developed in the 8-mm tumor following a continuous treatment of 150 min while in the foot tissue, 800 min were required before the development of thermal resistance. The kinetics of thermal resistance were studied following the first dose of 150 min. Substantial resistance developed in both 4- and 8-mm tumors, as well as in the foot tissue, and reached maximum within 1 day. The decay of thermal resistance in the 8-mm tumor and in the foot was incomplete even at 5 days after the first heat dose, while the analysis was difficult for the 4-mm tumor because of continuous tumor growth. Comparison with treatments at 43.5 degrees C and 45.5 degrees C gave a conclusion that (a) a short single heat treatment of the 8-mm tumor at 42.0 degrees C (below 43.0 degrees C) resulted in a differential response between tumor and foot tissues, but a longer treatment did not; (b) the treatment temperature above 43.0 degrees C was highly recommended; and (c) fractionated heat treatment at 42.0 degrees C was not the choice of treatment for both 4- and 8-mm tumors.
Animals↗
Effect of thermochemotherapy (combined cyclophosphamide and hyperthermia) given at various temperatures with or without glucose administration on a murine fibrosarcoma.
The effect of combined cyclophosphamide (CY) and heat treatments on a murine tumor was studied at various temperatures. FSa-II tumors, the early generation isotransplants of a spontaneous fibrosarcoma in a C3Hf/Sed mouse, were used. A single cell suspension was transplanted into the animal foot. Hyperthermia was given by immersing animal feet into a water bath maintained at a desired temperature +/- 0.1 degrees C. An average diameter of the tumor at the time of treatment was 4 mm. The tumor growth time, the time required for one-half of the treated tumors to reach 1000 mm3, was the end point. Hyperthermia enhanced the effect of CY at test temperatures ranging from 40.5 degrees - 44.5 degrees C. The enhancement was independent of the temperature when CY was administered 30 min before the beginning of hyperthermia. However, the enhancement was most substantial at temperatures of 40.5 degrees -42.5 degrees C when CY was administered immediately before hyperthermia. The most effective timing of the CY administration was immediately before hyperthermia. The glucose administered 60 min before hyperthermia enhanced the effect of combined CY and hyperthermia when CY was given 30 min before heating. This enhancement was lost when CY was given immediately before hyperthermia. The CY dose response curves at elevated temperatures were downward concave, which may indicate the presence of a CY- and heat-resistant cell population in the tumor. Implications of these observations in clinical hyperthermia were discussed.
Animals↗
Relative biological effectiveness of modulated proton beams in various murine tissues.
The relative biological effectiveness (RBE) of proton beams produced by Harvard University 160 MeV synchrocyclotron was studied in various murine tissues. Reference radiation was Cobalt-60 gamma-rays from a teletherapy unit at the Massachusetts General Hospital. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Test tissues are: lens, lung, testes and tail vertebrae. The RBE of the third generation isotransplants of a spontaneous mouse mammary carcinoma was also investigated. The proton and Cobalt-60 irradiations were carried out simultaneously by 2 teams. The dose response curves obtained for testes weight loss and growth stunting of tail vertebrae indicated that the RBE for our protons was independent of radiation dose in the range of 0.4 to 16 Gy. This finding was identical to our previous studies of the murine fibrosarcoma, skin and small intestine. The RBE values for lens and lung tissues were obtained by determining radiation dose to result in a complete cataract in half the irradiated eyes in 210 days and a 50% mortality in 180 days respectively. We have studied proton RBE in 7 normal tissues and 2 tumors including previously reported results. The RBE values for these tissues were found to fall between 1.09 and 1.32. No significant differences in the proton RBE were found between the several normal and tumor tissues studied.
Animals↗
Fractionated hyperthermia given alone or with radiation.
Explore the source record for details and available documents.
Animals↗
Enhancement of thermal response of normal and malignant tissues by Corynebacterium parvum.
Further studies were carried out on the combined effects of Corynebacterium parvum and hyperthermia on animal tissues and cultured Chinese hamster ovary cells. Experimental animals were C3Hf/Sed mice derived from our defined flora mouse colony. Tumors were eighth-generation isotransplants of a spontaneous fibrosarcoma, FSa-II. Hyperthermia was given by immersing the mouse foot or culture flasks in the constant temperature water bath. Present experiments include thermal enhancement of C. parvum at different temperatures, effect of the agent on the kinetics of thermal resistance, and the mechanism of the thermal enhancement. The thermal enhancement by C. parvum was independent of temperature in a range between 42.5 and 46.5 degrees, and it increased with decreasing temperature. The analysis of the Arrhenius plot suggested a comparable activation energy for combined treatments and for heat alone between 42.5 and 46.5 degrees. The thermal resistance developed very rapidly in both normal and tumor tissues. Systemic administration of C. parvum failed to modify the kinetics of thermal resistance. Several experiments were attempted in order to disclose the mechanism. A single injection of C. parvum-induced macrophages failed to enhance thermal response of the mouse foot, while 3 daily injections of the macrophages enhanced the response, indicating that the enhancement by C. parvum is at least partly attributed to the C. parvum-induced macrophages. Whole-body irradiation of 6 Gy and/or administration of anti-mouse T-cell serum and histamine failed to inhibit the C. parvum enhancement of thermal response. No thermal enhancement was observed for Chinese hamster ovary cells treated at 43.0 degrees in vitro with C. parvum or thiomersalate , a preservative supplemented in C. parvum, although cytotoxic effect was shown at a high concentration of thiomersalate .
Animals↗
Studies on fractionated hyperthermia in experimental animals systems III. Uneven daily doses.
The effect of daily hyperthermia on the murine normal and tumor tissues was investigated. Tumors were early generation isotransplants of a fibrosarcoma (FSa-II) and a mammary carcinoma (MCa) in C3Hf/Sed mice. Hyperthermia was given by immersing animal feet into a water bath at 45.5 degrees C. Tumor response was studied by TG time assay (determination of the time required for half of the treated animals' tumors to reach 1000 mm3 from the treatment day). Average peak foot reaction was also investigated to compare the therapeutic effectiveness of various fractionation regimens. In the first experiment the first dose (D1) of 10 min was followed by 10, 20, or 30 min daily doses. The treatment regimen "D1 of 10 min + daily 30 min" resulted in a significant therapeutic gain. The smaller doses were unable to overcome the repopulation of surviving tumor cells and the increasing magnitude of thermal resistance. To overcome tumor cell repopulation and thermal resistance, a regimen of increasing daily doses was attempted without success. These results indicated that doses following a D1 of 10 min must be as large as 30 min to obtain a therapeutic gain. Any fractionation regimens for MCa tumors, which developed the greatest thermal resistance among our animal tumors tested, failed to result in a therapeutic gain.
Animals↗
The change in hypoxic and chronically hypoxic cell fraction in murine tumors treated with hyperthermia.
The effect of hyperthermia on the size of hypoxic and chronically hypoxic cell fractions in murine tumors was studied. The chronically hypoxic cell fraction was defined as a fraction of tumor cells which were not oxygenated under hyperbaric oxygen. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Tumors were FSa-II and MCa which were early generation isotransplants of a spontaneous fibrosarcoma and a mammary carcinoma, respectively. TCD50 (50% tumor control dose) or the radiation dose which yields a local tumor control in half the treated animals and TG (tumor growth) time or the time required for half the treated tumors to reach 1000 mm3 from the first treatment day were experimental end points. Hyperthermia was given by immersing animal feet into a water bath maintained at 43.5 +/- 0.1 degrees C. Animal tumors were irradiated with a 137Cs unit under hypoxic conditions, in air or under O2 30 psi. The hypoxic cell fraction increased immediately after hyperthermia in both MCa and FSa-II tumors. The chronically hypoxic cell fraction was, on the other hand, decreased following hyperthermia. The decrease was more substantial in the MCa than in FSa-II.
Animals↗
Effect of whole-body hyperthermia on cell survival, metastasis frequency, and host immunity in moderately and weakly immunogenic murine tumors.
The effects of whole-body hyperthermia (WBH) on animal tumors and on metastasis frequency were studied. The tumors were a chemically-induced fibrosarcoma, FSa-I, which is moderately immunogenic and a spontaneously arisen fibrosarcoma, FSa-II, which is very weakly immunogenic. The WBH was given at 42.5 degrees in an incubator which had an auxiliary heater for accurate temperature control. Animal core temperature reached 41.5 degrees in 30 min. The lung colony assay revealed that the WBH for 60 min given at 24 hr after i.v. injection of single cells gave no lethal damage to either FSa-I or -II tumor cells. A significant inhibition of tumor growth was found when large tumors were given three daily WBH treatments. The frequency of lung metastasis was enhanced when large weakly immunogenic FSa-II tumors were treated by WBH, although no increase in the frequency was observed for FSa-I tumors of any size. Local hyperthermia did not significantly increase the metastasis rate of both tumors. These results suggest that the WBH might be useful for a treatment of large immunogenic tumors. However, the WBH is not a choice of treatment for possible micro-metastases.
Animals↗
Effect of hyperglycemia on the thermal response of murine normal and tumor tissues.
The effect of an i.p. injection of glucose on the thermal response of murine tissues was studied. Animal tumors were early generation isotransplants of a spontaneous fibrosarcoma, FSa-II. Tumors were transplanted into the foot pad, and hyperthermia was given by immersing the foot into a constant-temperature water bath. The tumor and normal tissue responses were studied by assays of the time required for half the tumors to reach 1000 cu mm from treatment day and of the treatment time required for one-half of the animals to develop a loss of one toe or greater reaction. The glucose administration enhanced tumor response more substantially than normal tissue response. The enhancement was greater for a large tumor than for a small tumor and also greater at 42.0 degrees than at 45.5 degrees. Presumably, the hyperglycemia induced acidosis which eventually enhanced thermal response. Present results suggested that the hyperglycemia is a potential method to specifically enhance tumor response at elevated temperatures.
Animals↗
Effect of hyperglycemia on thermochemotherapy of a spontaneous murine fibrosarcoma.
The effect of hyperglycemia on the cytotoxic effect of a chemotherapeutic agent was studied at elevated temperature. The seventh generation of a spontaneous C3Hf/Sed mouse fibrosarcoma, FSa-II, was transplanted into the footpads of the same strain of mice. Hyperthermia was given by immersing animal feet into a water bath where 41.5 +/- 0.1 degrees (range) was maintained by a constant temperature circulator. Cyclophosphamide (CY), an alkylating agent, was selected as a test agent. Single i.p. doses of glucose and of CY were given 60 and 30 min before the initiation of hyperthermia. Tumor response was assayed by determining the median tumor growth time (time required for one-half of the treated tumors to reach 1000 cu mm), and the dose-response curve was obtained. Hyperthermia enhanced tumor response to CY. The enhancement was greater when a glucose dose of 10 mg/g was administered before CY and heat treatments. The enhancement ratio, calculated as a ratio of the tumor growth time following CY (200 mg/kg) with heat or with glucose and heat to that following CY alone, was 1.31 or 2.86, respectively. Glucose given at ambient temperature did not enhance the effect of CY. A dose-response curve obtained for a glucose dose with fixed CY (200 mg/kg) and heat (90 min at 41.5 degrees) doses demonstrated that a significant enhancement was obtained following a glucose dose as low as 2 mg/g, suggesting that the glucose enhancement could be safely achieved for human cancer treatment.
Animals↗
The effect of step-down heating on murine normal and tumor tissues.
Cultured cells can be sensitized to low-temperature hyperthermia (below 43.0 degrees C) by a prior heat shock at a high temperature (above 43.0 degrees C) if the heat above 43.0 degrees C is immediately followed by the heat below 43.0 degrees C. This effect has been termed step-down heating (SDH). We have studied the effect of SDH on the response of murine tumor and normal tissues treated at 45.5 degrees C. Animal tumors were eighth-generation isotransplants of a spontaneous fibrosarcoma in C3Hf/Sed. mice. Tumor response was studied by TG (tumor growth) time assay, i.e., determination of the time required for half the treated tumors to reach 1000 mm3 from the first day of treatment. Normal tissue response was studied in the mouse foot. End point was the time to induction of a score 4.0 (loss of a toe) or greater reaction in half the treated animals, RD50. The SDH at 41.0 degrees C sensitized the response of tumor and normal tissues to 45.5 degrees C. The enhancement ratios were congruent to 1.7 for both tissues, indicating no differential sensitization between tumor and normal tissues. No sensitization was observed if the SDH was given immediately after a second dose of 45.5 degrees C given 6 hr to 5 days following the first dose of 10 min at 45.5 degrees C. The SDH appeared not to inhibit the development of thermal resistance as evidenced by no appreciable changes in the thermal resistance ratio.
Animals↗