A one-step optimization method based on a least squares fit of the linear quadratic model to quantitative tissue response data after fractionated irradiation is proposed. Suitable end-points that can be analysed by this method are growth delay, host survival and quantitative biochemical or clinical laboratory data. The functional dependence between the transformed dose xn (dn) = n (alpha dn + beta dn2) and the measured response is approximated by a polynomial. The method allows for the estimation of the alpha/beta ratio and its confidence limits from all observed responses of the different fractionation schedules. Censored data can be included in the analysis. A method to test the appropriateness of the fit is presented. A computer simulation illustrates the method and its accuracy as examplified by the growth delay end point. A comparison with a fit of the linear quadratic model to interpolated isoeffect doses shows the advantages of the direct method.

Humans↗

PubMed1989

Establishment and characterization of human tumours in nu/nu-mice.

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Animals↗

PubMed1988

Preliminary experimental results with the nitrosourea derivative ACNU in the treatment of malignant gliomas.

Comparative studies were carried out to evaluate the cytotoxic effectiveness of the nitrosureas ACNU (Nimustine) and BCNU (Carmustine) at equitoxic dose levels in xenografts from two astrocytomas grades III/IV (Li, Re) and one oligodendroglioma grade III (Oe) on nude mice. Growth delay was measured as the endpoint. All tumours were characterized initially and at regular intervals in later passages as to their histomorphologic pattern, expression of glial fibrillary acid protein and DNA-content by means of flow cytometry. These characteristics were shown to be unchanged in our xenografts over more than 27 passages. Growth delays of 18.7 days (ACNU) and 2.4 days (BCNU) for the Li-xenograft (p less than 0.01) were observed at an LD10 for both drugs. For the Re- and Oe-xenografts, growth delays of 18.0 vs. 14.0 days (p less than 0.001) and greater than 27.0 vs. 14.2 days (p less than 0.02) were observed at an equitoxic dose of 33 mg/kg ACNU or BCNU i.p., respectively. These preclinical data suggest a therapeutic advantage with ACNU for these high grade gliomas and should encourage further experimental and clinical investigations.

Animals↗

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

[Computed tomography guided positioning of catheters for temperature measurement in hyperthermia of malignant tumors].

Prior to a combined treatment with ionizing radiation and hyperthermia, 38 patients with superficial, semi-deep, and deep tumors received catheters for temperature measuring probes which were introduced under CT control. After having established a localization diagnosis and determined the angle for the puncture as well as the length of the puncture canal, a puncture needle containing a closed teflon catheter was introduced subsequent to local anaesthesia and puncture incision of the skin. None of the patients needed a general analgetic and sedative treatment. 10% of the patients presented a dislocation making necessary a reimplantation. Local infections at the catheter insertion point were observed in three cases, a phlegmonous inflammation was seen only in one patient who had undergone an immunosuppression by means of cytostatic drugs. In one patient a temporary bleeding led to a slight haemoglobin reduction which, however, did not require further therapeutic measures. The insertion of catheters for intratumoral temperature measurement was well tolerated by the patients. It could be performed in out-patients with good general condition and no further risk factors.

Adolescent↗

PubMed1986

Serial xenotransplantation of a human embryonal carcinoma in experimental urology.

The rare incidence of testicular germ cell tumours makes it necessary for clinicians to look for a valid experimental model to investigate basic tumour properties and different therapeutic modalities preclinically in order to improve clinical cure rates. A human embryonal carcinoma with hCG-production was successfully established in nude mice for more than 40 passages. We were able to show striking maintenance of histological and ultrastructural features, tumour markers (Beta-hCG) and DNA indices of the original tumour during subsequent xenograft passages as well as stability of tumour growth. Dedifferentiation of the tumour with changing growth fractions or loss of hCG production was not evident.

Animals↗

PubMed1985

Insulin effect on translational diffusion of lipids and proteins in the plasma membrane of isolated rat hepatocytes.

The effects of insulin (10(-10)-10(-8) mol/l) on lateral diffusion of three fluorescent lipid probes, 1-acyl-2-(N-4-nitrobenzo-2-oxa-1,3-diazole)aminocaproyl phosphatidylcholine (NBD-PC), 5-(N-hexadecanoyl)aminofluorescein (F-C16), 5-(N-dodecanoyl)aminofluorescein (F-C12), and of fluorescein isothiocyanate-labeled proteins in the plasma membrane of intact rat hepatocytes were studied by the technique of fluorescence recovery after photobleaching. The absolute lateral diffusion coefficients of the lipid analogues NBD-PC, F-C16 and F-C12 at 21 degrees C were 2.5 X 10(-9) cm2/s, 5.4 X 10(-9) cm2/s and 19 X 10(-9) cm2/s, respectively. The diffusion coefficient mean of proteins labeled with fluorescein isothiocyanate was 6.4 X 10(-10) cm2/s. Insulin at 10(-9) and 10(-8) mol/l reduced the lateral diffusion coefficient for F-C12- and F-C16-labeled cells by 20% and for NBD-PC-labeled cells by 30% (P less than 0.025). The insulin effect was specific as tested by cell incubation with proinsulin and desoctapeptide insulin (10(-8) mol/l) and was detectable after 7 min of insulin preincubation. In contrast to lateral diffusion of lipid probes, lateral mobility of unselected membrane proteins was not altered by insulin. The observed modulation of lipid dynamics in the plasma membrane of intact hepatocytes, by which a variety of membrane functions can be influenced, may be an important step in the mechanism of insulin action.

Animals↗

PubMedDate not supplied

Biliodigestive anastomosis after intraoperative irradiation in swine.

A large animal model was established to investigate the feasibility and suitable dosage of intraoperative radiation therapy (IORT) to the hepatic hilum before biliary-enteric anastomosis is performed. Twenty-two Pietrain Hampshire pigs underwent gallbladder and proximal bile duct resection followed by IORT using 20-40 Gy and performing biliary-enteric anastomosis. In the follow-up period of 56 days, pigs developed dose-dependent complications like stenosis of the biliary-enteric anastomosis. Results demonstrate that IORT of the liver hilum up to 20 Gy is safe with acceptable early complications in the presented animal model. The porcine biliary-enteric anastomosis can tolerate intraoperative irradiation up to a dosage of 40 Gy without disruption.

Anastomosis, Roux-en-Y↗