Comparative Ames-test study with dyes.
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Biomedical subjects
Publications and source records attributed to D Gericke.
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Mutagenicity tests using microorganisms are the Salmonella-typhimurium test (Ames), the test with a polymerase A deficient Escherichia coli, the Saccharomyces cerevisiae D3 system and the Neurospora crassa test. Differences in results of Ames-test may be due to differences preserving the tester strains, the choice of solvent and the dosage of the test compounds, last not least is the production of S-9. The polymerase A deficient Escherichia coli system seems easier to handle than the Saccharomyces cerevisiae- or Neurospora crassa-test. The metabolic activation with different forms of S-9 is needed in the Salmonella- and the Escherichia coli-system. Nevertheless it is not possible to decide if a substance is carcinogenic for human beings or animals with microbial mutagenicity tests only.
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On the basis of controversial results from clinical use of hyperthermal irrigation of the bladder lumen published by various authors a procedure was developed for transurethral local high frequency hyperthermia using phantom experiments and experimental bladder tumors. Encouraging results from experiments on animals led to clinical use of this technique with pretreated recurring bladder tumors (n = 64) at various stages. Poorly differentiated tumors at higher stages responded especially well. Typical pathohistological findings induced by hyperthermia were in these cases extensive tumor-necroses, and as late finding stromahyalinoses. Permanent changes of tumorfree urothelium have not been observed. During the observation period up to the present (maximum 48 month) the 3-year-survival rate has been 92.5% (T1G2-3), 59.4% (T2G3) and 22.0% (T3G3).
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It takes 24 months to induce preinvasive carcinomas in the urinary bladder of dogs as reported in the literature. The transplantation of chemically induced carcinomas has never been successful. Therefore, it was looked for methods which enable a shortening of the latency period and to transplant such tumors. 12 of 22 female beagle whelps were injected transurethrally with fast polymerizing plastics and then they have been treated subcutaneously with ortho-aminodiphenyl, formylaminonitrofurylthiazole or with the two carcinogens together. The dogs have been controlled by endoscopy, cytology and histology every 4 weeks. The first invasive urothelial carcinomas were observed 13 months after starting the treatment. Totally 7 carcinomas of the bladder and 3 in the pelvis of the kidney were found. It was possible to cultivate tumor material in tissue culture, gained by biopsy transurethrally. The transplantation of tissue culture material into nude mice was successful in 19 of 23 animals. In 2 of 10 beagles tumors started to grow transiently after transplantation of tissue culture cells. In the bacterial mutagenicity test (Ames) and in animals ortho-aminodiphenyl was neither mutagenic nor carcinogenic. However, it was cocarcinogenic if used together with formylaminonitrofurylthiazole.
We attempted to reduce the carcinoma induction latency period and to produce a transplantable urinary bladder cancer in dogs. After transurethral pellet application, 12 of 22 female beagles were given subcutaneous injections of orthoaminodiphenyl, FANFT, or both. Monthly cytologic and histologic checks yielded the earliest evidence yet obtained for invasive urothelial urinary bladder carcinoma (15 months); seven urothelial carcinomas of the urinary bladder and three of the renal pelvis were established. Tissue cultures of the urothelial carcinomas in vitro were successful. Transplantation of tumor cells to 23 nude mice resulted in tumor growth in 19. Transplantation to 10 beagles yielded 2 tumors very quickly, but the tumors were rejected within 4 weeks.
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Experiments are performed to ascertain the mutagenic properties of four new cytostatic methyl-hydrazones in the Ames test using different strains of Salmonella typhimurium. As could be demonstrated all four hydrazones are mutagenic per se without a metabolic activation through rat liver microsomes (S-9 fraction). Whereas the beta-chloroethyl hydrazones B1 and B2 cause a base-pair substitution with the strains TA100 and TA1535 the methyl-hydrazones EB4 and CyB4 both cause base-pair substitution with TA100 and frameshift mutation with TA98. At both strains the mutagenic activity of Cy84 ist powerful. Furthermore, no relation could be detected between the mutagenic properties of the methyl-hydrazones and their alkylating behaviour on 4-(4-nitrobenzyl)-pyridine.
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The cellular uptake of 67Ga-labelled transferrin was studied in the carcinoma of the human respiratory tract and in the Morris hepatoma 5123 C of the rat. In both types of tumors a positive tumor imaging by 67Ga-transferrin scintigraphy was evident. The intracellular distribution pattern of the radioactivity showed that the incorporated 67Ga-transferrin is accumulated within the lysosomes of the tumors. The uptake of 67Ga-transferrin by the tumor cells resulted in a faster disappearance of the tracer from the blood. The accelerated disappearance of 67Ga-transferrin from the blood showed a direct correlation to the mass of tumor cells. The loss of circulating 67Ga-transferrin from the blood showed a close parallelism to the grade of the anemia observed in the tumor bearing rats. We conclude from these findings that the uptake of transferrin into the tumor cells is one of the factors which are responsible for the anemia observed in malignant diseases.
Cl. onc. apathogenic for human beings and small animals is not able to cure tumor-bearing hosts. Combined treatments with local X-irradiation and local HFH have decreased the death rate of Harding-Passey-Melanoma-bearing mice. A cure rate of ca. 20% has resulted for the first time in such experiments. The survival time has increased significantly, however relapses occured on the sites of transplantation which finally killed the animals. Therefore it was tried to repeat the threefold-combined treatment. The animals with a relapse tolerated such a second and third series well. After the second series of treatment some animals became free of relapse and some after the third series. That means, if repeating treatment with local HFH, local X-irradiation, and i.v. spore-application of Cl. onc., it is possible to cure the Harding-Passey-Melanoma of the mouse at a high percentage.
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The latency period for induction of urinary bladder carcinoma is at least 2 years in animals that can be followed endoscopically. We studied the possibility of producing a model of malignant urniary bladder tumor in rabbits in less time by transplanting tumor cells. Each of 80 male mixed bred rabbits received 1 ml of tumor cell suspension of Brown-Pearce carcinoma. Transplantation was done subcutaneously, intratesticularly, transurethrally, or aftet cystotomy via injection into the bladder submucosa. Within 2 to 3 weeks malignant tumor growth in the bladder could be shown. Superficial scarification of the mucosa, performed at the same time as transplantation, led to exulceration of the tumor into the bladder lumen. Tumor incidence reached a 80 to 95 per cent level. Metastases in these animals were analogous to human urothelial bladder carcinoma. This malignant tumor model seems especially suitable to study new methods of transurethral therapy for cancer of the urinary bladder.
The article describes the clinical course of a non-hormone-producing granulosacell carcinoma in a 21 year old woman, and reviews the recent clinical literature.
Our knowledge of antigens which are associated with different types of malignant tumours is steadily increasing. These antigens exist in considerable numbers, but, so far with few exceptions, only their presence can be demonstrated by certain methods; to isolate and identify them has not yet been possible. These antigens are, therefore, suitable not so much for the primary diagnosis, but rather, like the carcinoembryonic antigen, the tissue-polypeptide antigen or the alpha-feto-protein, for assessing the success of treatment. Active immunization has recently received a fresh impulse by the use of the enzyme neuraminidase, derived from Vibrio cholerae, in the treatment of tumour cells. There is no passive specific immunotherapy in human cancer. As to specific active immunotherapy BCG, Corynebacterium parvum and preparations of these and other micro-organisms together with polynucleotides, levamisol, statolon, tilorone have been employed. Although the results are not uniform they are promising. Attempts at cellular transfer of immunity are not very encouraging. It should be emphasized that the findings apply to human cancer. Experimental studies have produced very interesting results.