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Biomedical subjects

C Streffer

Publications and source records attributed to C Streffer.

At least 163 records · Page 9Linked to original sources
PubMed1988

[Heterotransplantation of a human glioma and brain metastases in the athymic nude mouse--a preclinical model for radiation oncology. 1. Basic principles and methodology].

In spite of the great efforts undertaken in the different disciplines, the prognosis of patients with highly malignant gliomas, i.e. astrocytomas of degrees III and IV remains unfavorable. Up to now, new findings about an improvement of radiooncologic therapy methods are obtained retrospectively from the results of complex and time-consuming clinical studies. The heterotransplantation of human tumor tissue in immune-deficient nu/nu mice gives the opportunity to check preclinically the efficiency of different fractionation schemes and cytostatic drugs already. The author's experiences and therapy results are presented in order to demonstrate the possibilities as well as the limits of this in-vivo model performed with a view to clinical conditions.

Animals↗
PubMed1988

[Radiobiological bases of time and dose distribution in radiotherapy].

After the very rapid perception in the beginning of this century, that a fractionated radiotherapy is favourable on the ground of intracellular recovery, it has lasted for a long time until conceptions have been indicated for the timing of dose distribution. The used formalisms have been based on clinical empiricism. More recent concepts have shown that dose effect relations can be described by a linear-quadratic function of dose not only for cell killing but also for tumour control and radiation effects in tissues. This concept has been discussed. Some examples of fractionated irradiation have been described for which the linear-quadratic dose model gives good results and these can be described by the alpha-/beta-ratio. However, it has been demonstrated that besides intracellular recovery the repopulation of cells has a considerable significance which is considered only to a small degree by the linear-quadratic model. These factors which are very different in individual cases have to be considered in the future.

Animals↗
PubMed1987

Effects on intermediary metabolism in mouse tissues by Ro-03-8799.

Glucose and lipid metabolism in the brain, liver and in a transplanted tumour were found to be variously altered within 2 to 3 h of administering single doses of the radiosensitizer Ro-03-8799 to normal and tumour-bearing mice. Hepatic lactate and glycerol-3-phosphate (G3P) levels were decreased but those of the ketone body beta-hydroxybutyrate (beta-HOBu) were raised. However, in the tumour, these levels were all enhanced. The lactate levels in brain remained relatively constant but both beta-HOBu and G3P levels were altered in a manner similar to that in the liver. The levels of glucose were approximately doubled in blood, brain and tumour, but whereas tumour G6P levels increased, those in the brain were lowered to below the limits of detection. Hepatic glucose levels were significantly decreased after 1 h but G6P levels were not affected. These changes could neither be related to inhibitory effects on hepatic glucokinase or brain hexokinase activity nor to limiting amounts of ATP in both tissues. However, the activity of glucose-6-phosphatase (G6P'ase) was distinctly raised in the liver and the hepatic glycogen stores were also rapidly lowered. Overall, the results suggest that Ro-03-8799 exerts a stimulatory effect on glucose production in the liver. In both liver and brain the levels of free fatty acids and phospholipids were increased whereas those of esterified fatty acids were lowered. Most importantly, the changes in metabolite levels affect the cellular redox couples; those of the cytosol (lactate/pyruvate; G3P/dihydroxyacetone phosphate (DAP] are directed towards the oxidised state in the liver but to a more reduced state in the tumour. The mitochondrial couple (beta-HOBu/acetoacetate (AcAc)) in both tissues is shifted towards the reduced state. These metabolic changes may result in an increase in the degree of hypoxia in the tumour and may well play an important role in the development of neuropathies.

Adenocarcinoma↗
PubMed1987

Dose-effect relationships and general mechanisms of combined exposures.

Organisms are exposed to a multitude of physical, chemical and biological agents. Many data are available on the risks associated with these agents when applied individually. However, an assessment of the overall risk has to take into consideration the possibility of unexpected risks after combined exposures. There is no way of testing all conceivable combinations of agents. Thus, we have to look for general mechanisms that permit extrapolations to situations not yet tested. The study of mechanisms requires the knowledge of the shape of the dose-response relations for all agents participating in the combined exposure. Possibilities for the analysis of effects after combined exposures are described. It emerges that very specific processes in the chain of events must be affected in order to influence radiation risk by another agent. Two such specific processes of importance are recovery phenomena and cell proliferation.

Cell Survival↗
PubMed1987

Risk to preimplantation mouse embryos of combinations of heavy metals and radiation.

The influence of arsenic, cadmium, lead or mercury on radiation risk to preimplantation mouse embryos in vitro was studied under various conditions. Morphological development, cell proliferation, and formation of micronuclei were used for assessment of risk after combined exposure to these metals and X-rays. No conditions were found under which arsenic altered radiation risk; the effects were merely additive. Cadmium acted similarly, though a few results indicated that morphological development might be impaired more strongly after combined exposure than expected from the addition of the single effects. Lead enhanced radiation risk with regard to micronucleus formation, but had an additive effect only in the case of morphological development and cell proliferation. Of all four metals, mercury had the greatest potential for enhancement of radiation risk, when morphological development and cell proliferation were studied. The observed combination effects exceeded even those effects which were calculated by taking into account the shape of the dose-effect curves (isobologram analysis, envelope of additivity). Mercury neither induced micronuclei nor enhanced their formation in combination experiments.

Animals↗
PubMed1987

Does tributyl phosphate influence the radiation risk of a highly proliferating system--the early mouse embryo in vitro?

Two-cell mouse embryos were exposed in vitro to tributyl phosphate, x rays, or a combination of both. In-vitro development of the embryos was followed microscopically (cleavage to four- and eight-cell embryos, formation of morulae and blastocysts, and hatching of blastocysts). Effects on proliferation were estimated by counting the number of cells per embryo early (48 h p.c. = 48 hours post conceptionem) and late (144 h p.c.) in the preimplantation period. Cytogenetic damage was studied using micronucleus formation as the end point. Tributyl phosphate did not reveal toxic effects up to a concentration of about 5 microM after an exposure time of 18 h. At a concentration of about 15 microM, 50% of late preimplantation embryos showed effects on morphological development and on cell proliferation, and at about 40 microM, 90% of the embryos were affected. Tributyl phosphate did not induce micronuclei. Small effects by x irradiation were observed between 0.25 Gy and 0.5 Gy, depending on the end point measured in the late preimplantation stage. Fifty percent of the embryos were affected by a dose slightly higher than 1 Gy, and 90% after about 4 Gy. No enhancement in risk was found after combined treatment of the embryos with tributyl phosphate and x rays.

Animals↗
PubMed1987

Radiotoxicities of [3H]thymidine and of [3H]arginine compared in mouse embryos in vitro.

Tritium that is bound to organic molecules is of special risk for living systems, in particular when such molecules are components of the cell nucleus. Therefore, [3H]thymidine and [3H]arginine were studied for radiotoxicity in early mammalian embryo development. Starting with the two-cell stage, mouse embryos were incubated in vitro with [3H]thymidine or [3H]arginine at either 370 Bq/ml (10 nCi/ml) or 925 Bq/ml (25 nCi/ml). Development in vitro was followed up to the formation of the inner cell mass at 192 h postconception (p.c.). There was no difference in radiotoxicity of the two substances with respect to cell proliferation; however, formation of blastocysts, hatching of blastocysts, trophoblast outgrowth, and formation of inner cell mass were impaired more strongly by [3H]arginine than by [3H]thymidine when the external exposure concentrations were the same. Similarly, micronuclei were seen in blastocysts at 96 h p.c. at higher frequency after incubation with [3H]arginine. However, uptake of [3H]arginine by the embryos was considerably faster than that of [3H]thymidine, and this most probably accounts for the apparent difference in radiotoxicity.

Animals↗
PubMed1986

Toxicity of sodium arsenite in mouse embryos in vitro and its influence on radiation risk.

Mouse embryos at the preimplantation stage were used in vitro for assessing the risk exerted by arsenic on early stages of embryonal development. We studied the effects of sodium arsenite on morphological development, proliferation, and micronucleus formation. A concentration of 100 microM sodium arsenite immediately killed the embryos, and 1 microM almost completely inhibited formation of blastocysts. Micronuclei were induced starting from 0.7 microM arsenite. Concentrations below 0.1 microM (0.1 microM corresponds to 7.5 ppm arsenic) did not show significant effects with respect to any of the end-points examined. Arsenic did not influence radiation risk under various experimental conditions; all the effects after combining moderately toxic doses of sodium arsenite and X-rays corresponded to the effect obtained by the addition of the single effects.

Animals↗
PubMed1986

Enhancement of radiation effects by mercury in early postimplantation mouse embryos in vitro.

Two-cell mouse embryos were X-irradiated (1 Gy) and immediately thereafter exposed to mercuric chloride (3 microM) up to the blastocyst stage. When combined treatment started shortly (about 1 to 2 h) before mitosis to the four-cell stage, blastocyst formation, hatching of blastocysts, trophoblast outgrowth and ICM formation were impaired stronger than expected from the addition of the single effects. The enhancement of risk was maximal for hatching of blastocysts and no further increase was observed for trophoblast outgrowth and ICM formation. When exposure of embryos to X-rays and mercury began about 5 to 6 h before mitosis to the four-cell stage, only additive effects were obtained for the endpoints mentioned above.

Animals↗
PubMed1986

Decreased hypoxic toxicity and binding of misonidazole by low glucose concentration.

The modulation of the hypoxic toxicity and binding of Misonidazole (MISO) by glucose and lactate was studied by exposing exponential EMT6/Ro cells to 5 mM MISO under hypoxic conditions. The concentrations of glucose used were 0.015 mM and 5 mM, and the concentrations of lactate were 0, 3 and 10 mM. There was no significant hypoxic toxicity due to MISO in the absence of glucose. However, with 5 mM glucose, after a latent period of 0.5 hours, there was a rapid decrease in cell survival to less than 0.1% at 2.5 hours incubation in 5 mM MISO. The binding of MISO was also increased by glucose. The amount of MISO bound to cells in 0.015 mM glucose leveled off at 2 nmoles MISO/7 X 10(5) cells at 1 hour, whereas the binding in 5 mM glucose continued to increase to more than 5 nmoles MISO/7 X 10(5) cells after 3 hours incubation. There was no detectable effect of lactate on the binding of MISO to the cells either in 0.015 mM or 5 mM glucose. The high affinity of this binding was indicated by the lack of exchange of radioactive MISO with non-radioactive MISO even after 2 hours of incubation. These data showed that glucose concentrations could modify the toxicity and binding of MISO to hypoxic cells.

Animals↗
PubMed1986

Predictive assays for the therapy of rectum carcinoma.

Cytofluorometric DNA measurements showed that about 55% of rectum carcinoma (129 patients) had tumours with an abnormal DNA content (DNA aneuploidy). For patients with such a tumour the prognosis was worse than for patients with DNA diploid tumours. From the DNA histograms the number of S-phase cells was calculated. In tumours with the stage pT3, which disseminated to lymph nodes or metastasized, a higher number of S-phase cells was found than in tumours with the staging pT3N0M0. In all untreated tumours cells with micronuclei were found. This demonstrated cell loss. In most tumours this effect was considerable. The ratio:number of S-phase cells/number of cells with micronuclei may allow a rough estimate for cell turnover. In patients with a bad prognosis and in those patients who had a local recurrence after resection of the tumour this ratio was high. In 34 patients the parameters were measured before and after preoperative radiotherapy. In some tumours a rapid increase of S-phase cells occurred after irradiation, this effect might express repopulation. In these patients a local recurrence was frequently found. From the data obtained so far a prediction for local recurrences might be possible from the determination of nuclear protein bound SH-groups. The determination of micronuclei indicated that it can be used as a measure for radiation response in tumours. All parameters show a high variability between individual tumours. A further study is useful whether the measured parameters are suitable as predictors.

Adenocarcinoma↗