Human primordial germ cells and mouse neonatal and adult germline stem cells are pluripotent and show similar properties to embryonic stem cells. Here we report the successful establishment of human adult germline stem cells derived from spermatogonial cells of adult human testis. Cellular and molecular characterization of these cells revealed many similarities to human embryonic stem cells, and the germline stem cells produced teratomas after transplantation into immunodeficient mice. The human adult germline stem cells differentiated into various types of somatic cells of all three germ layers when grown under conditions used to induce the differentiation of human embryonic stem cells. We conclude that the generation of human adult germline stem cells from testicular biopsies may provide simple and non-controversial access to individual cell-based therapy without the ethical and immunological problems associated with human embryonic stem cells.

Treatment units for radiosurgery, like Leksell Gamma Knife and adapted, or dedicated, linear accelerators use small circular beams of ionizing radiation down to 4 mm in diameter at the isocenter. By cross-firing, these beams generate a high dose region at the isocenter together with steep dose gradients of up to 30% per mm. These units are used to treat small complex shaped lesions, often located close to critical structures within the brain, by superimposing several single high dose regions. In order to commission such treatment units for stereotactic irradiations, to carry out quality assurance and to simulate treatment conditions, as well as to collect input data for treatment planning, a precise dosimetric system is necessary. Commercially available radiation dosimeters only partially meet the requirements for narrow photon beams and small field sizes as used in stereotactic treatment modalities. The aim of this study was the experimental determination of the output factors for the field defining collimators used in Gamma Knife radiosurgery, in particular for the smallest, the 4 mm collimator helmet. For output factor measurements a pin point air ionization chamber, a liquid ionization chamber, a diode detector, a diamond detector, TLD microcubes and microrods, alanine pellets, and radiochromic films were used. In total, more than 1000 measurements were performed with these different detection systems, at the sites in Munich and Zurich. Our results show a resultant output factor for the 4 mm collimator helmet of 0.8741 +/- 0.0202, which is in good agreement with recently published results and demonstrates the feasibility of such measurements. The measured output factors for the 8 mm and 14 mm collimator helmets are 0.9578 +/- 0.0057 and 0.9870 +/- 0.0086, respectively.

PurposeCancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer.Materials and methodsIn this work a dose-response relationship for breast cancer is derived based on(i) the analysis of breast cancer induction after Hodgkin's disease,(ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and(iii) the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy,(iv) the breast cancer induction of the A-bomb survivor data.ResultsThe fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data.ConclusionsThe dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

Treatment units for radiosurgery, brachytherapy, implementation of seeds, and IMRT generate small high dose regions together with steep dose gradients of up to 30%-50% per mm. Such devices are used to treat small complex-shaped lesions, often located close to critical structures, by superimposing several single high dose regions. In order to test and verify these treatment techniques, to perform quality assurance tasks and to simulate treatment conditions as well as to collect input data for treatment planning, a GAFCHROMIC film based dosimetry system for measuring two-dimensional (2-D) and three-dimensional (3-D) dose distributions was developed. The nearly tissue-equivalent radiochromic GAFCHROMIC film was used to measure dose distributions. A drum scanner was investigated and modified. The spectral emission of the light source and the filters together with the efficiency of the CCD filters for the red color were matched and balanced with the absorption spectra of the film. Models based on refined studies have been developed to characterize theoretically the physics of film exposure and to calibrate the film. Mathematical descriptions are given to calculate optical densities from spectral data. The effect of darkening has been investigated and is described with a mathematical model. The influence of the scan temperature has been observed and described. In order to cope with the problem of individual film inhomogeneities, a double irradiation technique is introduced and implemented that yields dose accuracies as good as 2%-3%. Special software routines have been implemented for evaluating and handling the film data.

Outpatient repeated radiosurgery is an effective and only minimally invasive treatment for multiple brain metastases from renal cell cancer and is recommended as being the method of choice to control intracranial disease, especially in selected patients with limited extracranial disease. Physicians dealing with such patients should be aware of the characteristic aspects of LRT.