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J Kummermehr

Publications and source records attributed to J Kummermehr.

At least 19 recordsLinked to original sources
PubMed1995

Radiation-induced impairment of osseous healing: quantitative studies using a standard drilling defect in rat femur.

The femora of adult Wistar rats were locally irradiated with single doses of X rays and 1 day later were wounded by a standardized drilling defect that extended through the diaphyseal cortex into the marrow cavity. Healing of the lesion was followed over 30 weeks to assess the time course of osseous closure. In unirradiated bones healing was complete by week 7. Irradiation with doses up to 15 Gy imparted a dose-dependent delay in the formation of primary callus and its subsequent replacement by more mature bone, while after higher doses healing remained permanently compromised or even suppressed. Using histomorphometry, osseous closure was also measured quantitatively for healing periods of 7, 10, 16 and 30 weeks and the data were expressed as the percentage of responders with < or = 40% fractional closure. The resulting dose-response curves were steep, displaying a large threshold dose and ED50 values between 16.8 to 17.5 Gy (7 to 16 weeks) and 19.4 Gy (30 weeks), respectively.

Animals↗
PubMed1992

Increased radiation tolerance of mouse tongue epithelium after local conditioning.

The effect of local stimulation on mitotic activity and radiation tolerance was studied in mouse tongue mucosa. Silver nitrate solution (0.5-20%) was used for local conditioning. The most effective protocol comprised three daily treatments (days 0-2), yielding a delayed increase in 24 h mitotic counts by about 30% on days 5-7. The stimulating effect was independent of silver nitrate concentration. Sham treatment with saline or anaesthesia alone clearly depressed mitotic activity on days 2-4 without any subsequent overshoot. Radiation treatment was initiated on day 5 after three daily treatments with 3% silver nitrate solution. A top-up technique was employed, consisting of fractionated irradiation (300 kV X-rays) of the whole snout, followed by graded local test doses (25 kV X-rays) to induce denudation in a confined area of the inferior tongue surface. Silver nitrate conditioning did not alter the radiosensitivity of the epithelium to single local doses, but shortened the latency to denudation from 11 to 8 days. In contrast, a clear increase in tolerance to fractionated irradiation, delivering 5 x 2.5, 5 x 3.5, 5 x 4.5 Gy or 3 x 5.2 Gy in 7 days, was observed, equivalent to about four, two, one and two extra dose fractions. This approach may be a suitable way to increase radiation tolerance of oral mucosa in clinical radiotherapy.

Animals↗
PubMed1991

Proliferation kinetics of mouse tongue epithelium under normal conditions and following single dose irradiation.

Epithelial proliferation in the ventral surface of mouse tongue follows a pronounced circadian rhythm with a peak in mitotic activity at 10.00 a.m., preceded by a wave of DNA synthesis 8 h earlier. Nearly all cells (85%) pass through G2 and mitosis immediately after the S-phase; they subsequently divide again, usually after 2 or 3 days, indicating cohorts of cells with different G1-duration. The fraction of all nucleated cells comprised in one daily proliferation wave is about 20%, indicating a turnover time of the nucleated cell compartment of about 5 days. Cytotoxic injury by a single radiation dose of 20 Gy causes a steep decrease in cell counts, leading to complete denudation after 9-13 days. The difference between the latent period before ulceration and the tissue turnover time is explained by a marked proliferative activity of the doomed cells. The mitotic index increases steeply after day 1 to three times the control level, but most mitotic figures display gross abnormalities such as multipolar spindles or chromosome clumping. As a consequence cells with abnormal or multiple nuclei appear in the basal layers 3 days post irradiation and subsequently migrate to the upper layers. After denudation the epithelium rapidly becomes restored, with a phase of transient hyperplasia on days 13-14. Normal architecture is regained by day 15. Over the whole healing period the mitotic index remains at a high level, with most of the mitoses appearing histologically normal.

Animals↗
PubMed1991

Rapid repopulation in radiotherapy: a debate on mechanism. Accelerated repopulation in tumours and normal tissues.

Accelerated repopulation is a well established response pattern of normal epithelial to fractionated irradiation. It is delayed until the tissue recognises functional injury. It is well regulated to maintain a steady state and continues until integrity of the tissue is restored. We assume that some of these features of the parental normal tissue are preserved and still operate in squamous cell carcinoma, although probably in a less well controlled and organised manner.

Carcinoma, Squamous Cell↗
PubMed1991

Tumour cell repopulation during fractionated radiotherapy: correlation between flow cytometric and radiobiological data in three murine tumours.

This study tested whether the potential doubling time of tumour cells measured before or during treatment could predict the repopulation rate of surviving clonogens during fractionated radiotherapy. Tumours used for the study were a fibrosarcoma (SSK 2), an adenocarcinoma (AT 7) and a squamous cell carcinoma (AT 478), all grown subcutaneously in the C3H mouse. Potential doubling times (Tpot) were measured using the thymidine nanalogue iododexyuridine (IUdR) and flow cytometry. Results were compared with previous radiobiological studies on these tumours in which repopulation rates during radiotherapy were estimated using the tumour growth delay and tumour cure assays. Fractionated treatments consisted of daily doses of 4 or 8 Gy to clamped (hypoxic) tumours, 6 days per week for 1-3 weeks. Tpot values increased markedly during therapy for two of the tumours (SSK 2 and AT 478), by a factor of more than 10 for AT 478 in the third treatment week. Tpot remained approximately constant for the third tumour (AT 7). In no case was there evidence from the labelling studies of a shortening of Tpot which would suggest accelerated repopulation. From the radiobiological data, effective clonogen doubling times during radiotherapy were calculated from the doses required to produce a given effect in short and long treatment schedules. In the second week of treatment, effective clonogen doubling times in two tumours were approximately equal to the pretreatment Tpot, and shorter than the pretreatment Tpot in the third tumour. At some time during treatment, the surviving clonogens in these tumours therefore proliferated at the same rate or faster than before treatment. The difference between the labelling and radiobiological measurements was ascribed to the fact that, shortly after the start of a fractionated treatment, the IUdR labelling technique measures primarily doomed cells. These results show that kinetic measurements using DNA labelling techniques made during fractionated radiotherapy in most cases do not reflect the proliferation status of the surviving cells which are responsible for treatment outcome. Pretreatment Tpot measurements give a much better indication of the proliferation rate of surviving cells but in some cases may underestimate repopulation during radiotherapy.

Adenocarcinoma↗
PubMed1991

A nonparametric method for the derivation of alpha/beta ratios from the effect of fractionated irradiations.

Multifractionation isoeffect data are commonly analysed under the assumption that cell survival determines the observed tissue or tumour response, and that it follows a linear-quadratic dose dependence. The analysis is employed to derive the alpha/beta ratios of the linear-quadratic dose dependence, and different methods have been developed for this purpose. A common method uses the so-called Fe plot. A more complex but also more rigorous method has been introduced by Lam et al. (1979). Their method, which is based on numerical optimization procedures, is generalized and somewhat simplified in the present study. Tumour-regrowth data are used to explain the nonparametric procedure which provides alpha/beta ratios without the need to postulate analytical expressions for the relationship between cell survival and regrowth delay.

Animals↗
PubMed1990

Kinetics of recovery from sublethal radiation damage in four murine tumors.

The kinetics of repair of sublethal radiation damage (SLD) was studied in four transplantable C3H mouse tumors, i.e. mammary carcinoma AT17, fibrosarcoma SSK2, and squamous cell carcinomas AT51 and AT478. Tumors were irradiated with 4 fractions of 300 kV X-rays given under local hypoxia at intervals ranging from 0 to 6 h. Radiation response was measured by growth delay, which was directly analyzed using a general curve description based on the extended linear-quadratic model (exponential repair kinetics). In contrast to existing methods all growth delay values were utilized to estimate the alpha/beta ratios and the half-times as well as their confidence limits in a non-linear least squares analysis. The half-times were 42, 44, 54 and 31 min, respectively. It is concluded that repair of SLD is virtually complete after 5 h in these tumors. This is also due to the relatively small proportion of repairable damage in these tumors reflected in their alpha/beta values, which were 38, 30, 54 and 42 Gy, respectively.

Animals↗
PubMed1990

Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses.

Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered.

Animals↗
PubMed1989

[Optimal fractionation from the radiobiological viewpoint].

Not only in experiment on animal but also from analysis of clinical data important knowledges could be obtained in the last years, that deal with the course of biological processes in tumor and normal tissue during fractionated irradiation. In centre there are differences in the capacity for recovery from sublethal radiation injury and in repopulation. Chronically reacting normal tissues show a clearly higher repair capacity than tumors, that can be used for hyperfractionation with reduced single doses. With it higher attention must be given to repairing time yet, that the selective benefit is not endangered by incomplete recovery. On the other side clinical analyses have confirmed that the stem cell repopulation--going on in several tumor types, so e.g. in squamous cell carcinomas, during the time of conventional treatment--can make a considerable contribution to radioresistance. The actual level of knowledge justifies further clinical experiments with unconventional fractionation, especially with accelerated hyperfractionation.

Humans↗
PubMed1989

Biological effectiveness of neutrons and pi-mesons in gut, bone, and transplantable tumours.

At the Munich RENT-facility a screening project was performed to define the biological characteristics of a fission neutron beam envisaged for radiotherapy. The quantitative endpoints used were jejunal crypt survival, late rectal stenosis in rats, osseous healing in traumatized rat femur and regrowth delay of murine transplantable tumours. The results obtained in normal tissues (with the possible exception of bone) demonstrate a high RBE, in accordance with the well documented dependence of RBE on neutron energy. The RBE-values measured in tumours after single dose treatment endorsed the high effectiveness, although--as has been the case with other beams--they gave no conclusive evidence of a therapeutic advantage. Nevertheless, the specific beam characteristics, i.e. a high RBE at the surface and a fast decline of the biologically effective depth dose suggest possible advantages of the RENT beam when applied in the treatment of selected superficial tumours.

Animals↗
PubMed1989

First experiences with fission neutrons in the radiation therapy of cancer patients.

16 patients have been treated until October 1987 at the mixed reactor beam of the RENT-facility in Munich-Garching. All of them received a single dose of 200 to 250 cGy after complete conventional radiotherapy and in same cases also surgery because of the lack of complete tumor resection or local tumor control after radiation control. The ages ranged from 40 to 84 years. The follow-up amounted between two and 28 months, 8.5 months on the average. The tumors selected appeared to be particularly suitable because of their growth in poorly perfused tissues, after the previous surgery and/or radiotherapy. All cases are briefly reported. The general experience from the very limited study is promising. The local effects to the tumor tissue so far are impressive. No severe side effects which could be related to the RENT-session were observed until now.

Adult↗
PubMed1988

[Intracellular recovery--basis of hyperfractionation].

The radiobiological basis of a hyperfractionated radiation therapy versus conventional fractionation with respect to therapeutic gain, i.e., improved normal tissue sparing for the same level of tumour cell inactivation, will be presented. Data on the recovery potential of various tissues as well as the kinetics of repair will be given. The problem of incomplete repair with short irradiation intervals will be discussed.

Animals↗
PubMed1988

[Repopulation in normal tissues].

Apart from dose fractionation, treatment time is a factor that determines the tolerable radiation dose in many normal tissues. Empirical isoeffect formulae have failed to account for this dependency because they are based on oversimplified and non-biological premises. Compensatory repopulation is initiated by tissue damage, presumably cell depletion, and therefore is related to tissue turnover time. Tissues with slow cell renewal thus show little or no benefit from treatment prolongation. In acutely reacting tissues enhanced repopulation is mounted within days or weeks, also depending on the aggressiveness of treatment. Oral mucositis is taken as an example to discuss factors that modify the regenerative response and some aspects how it can be exploited in clinical radiotherapy.

Animals↗
PubMed1986

Response of human tumour xenografts to fractionated X-irradiation.

The response of two human tumour xenografts to single dose and fractionated X-rays has been tested using regrowth delay as the assay. The tumours were line transplanted cells from a moderately well-differentiated squamous carcinoma of the tonsillar fossa (XJ) and an undifferentiated carcinoma of the floor of the mouth (XR). Comparison of the dose response curves for single doses in air, clamped, or after misonidazole administration, led to estimates of the hypoxic fraction (approximately 15%) and the sensitizer enhancement ratio (less than or equal to 1.6). When 5 daily fractions were used, the effect of misonidazole (miso) was lost and reoxygenation appeared to be effective in both tumours. Comparison of single doses and 5 fractions in clamped tumours, and in those sensitized by miso, allowed the sparing effect of fractionation to be estimated. When analysed by the linear quadratic model the alpha/beta ratios were found to be in the range of 6.4-9.2 Gy and 6.8-16.0 Gy for the two tumours. These values are in good agreement with murine tumours (assayed in vivo or in vitro), with human tumour cells assayed in vitro, and with analyses of fractionated clinical data for skin cancer.

Animals↗