Biomedical subjects
T Graewe
Publications and source records attributed to T Graewe.
Cell cycle dependence of N-methyl-N-nitrosourea-induced tumour development in the proliferating, partially resected rat urinary bladder.
In the present experiments the dependence of tumour induction upon the different phases of the cell cycle in the proliferating urinary bladder was examined. For stimulation of urothelial proliferation, a one-third resection of the bladder was performed in female Wistar rats. To synchronize the proliferating urothelial cells, hydroxyurea (HU) was given in 23 fractionated, consecutive intraperitoneal doses (0.1 mg/g body weight each) at hourly intervals shortly prior to and during maximal proliferation (between 33 and 55 h following partial cystectomy). The direct-acting urothelial carcinogen N-methyl-N-nitrosourea (MNU) was administered as a single, intravesicular pulse dose (5 mg/kg body weight) during the different cell cycle phases and to control animals with a non-resected, quiescent bladder (G0-phase). The incidence of urothelial bladder tumours was 32.6% in the controls. By comparison, the tumour incidences were 18.9, 9.3, 21.7, 26.3, 25.0 and 30.0%, respectively, when MNU was instilled during the late G1-, early and late S-, G2 + M-, and the early and late postmitotic phase. The results obtained from a total of 283 rats thus clearly document a cell-cycle-specific inhibition of MNU-induced tumour development in the proliferating urinary bladder, particularly when the carcinogen was administered during the early S-phase (P less than 0.016). There were no differences in the histology and extension of the urothelial bladder tumours found in the different experimental groups. MNU has also been shown to produce urothelial tumours in the renal pelvis (overall tumour incidence: 3.2%) and ureters (1.4%) as well as mesenchymal tumours in the bladder (4.9%) and kidneys (1.4%). Conclusions are tentatively drawn about the mechanisms underlying the observed cell-cycle-specific inhibition of urothelial carcinogenesis.
Synchronization of stimulated urothelial proliferation. Experimental models for cell cycle specific testing of bladder carcinogens.
In the present experiments an attempt was made to synchronize urothelial proliferation in the urinary bladder of rats stimulated by either a partial cystectomy (one-third resection) or a single i.p. administration (100 mg/kg) of CP. To temporarily inhibit DNA synthesis HU was given intraperitoneally in multiple fractionated doses (0.1 mg/g each) at hourly intervals during the period of most pronounced proliferative activity between 33 and 55 h after partial cystectomy and between 26 and 44 h after injection of CP. Following partial cystectomy the 3H-TdR index rapidly increased after termination of the HU administration reaching peak values of 54% and 56% at 6 and 8 h, respectively. Thereafter, there was a sharp decline of the percentage of DNA synthesizing cells within 2 h to 24% at 10 h. Then 16 h after removal of the HU block the 3H-TdR index amounted to 15%. At 20 h the labeling increased again to 22%, indicating that the initially blocked cells were capable of going through another cell cycle. After 1 week the 3H-TdR index was 2.5% and after 15 days 0.2%. Synchronously with the decrease of DNA synthesis the mitotic index rapidly increased reaching a maximum value of 4.3% at 10 h. The total fraction of 3H-TdR-labeled cells (growth fraction) was 57%. Following administration of CP 3H-TdR incorporation increased steeply after the last injection of HU and at 6 h a maximum value of 50% was obtained. Subsequently, the 3H-TdR index gradually decreased to 11% after 12 h. At 8, 15, and 30 days labeling indices of 1.9%, 0.5%, and 0.3% were determined. The mitotic index was highest with 0.21-0.22% between 12 and 16 h after removal of the HU block. The growth fraction amounted to 53%. The results reported here show a satisfactory degree of synchrony of stimulated urothelial proliferation obtained by multiple fractionated doses of HU. In particular the cystectomy model will be useful for testing possible cell cycle specificity of urothelial carcinogenesis.
Histology and biology of metastatic chondroblastoma. Report of a case with a review of the literature.
This case report of a metastasizing chondroblastoma with a review of the literature was undertaken to gain a better understanding of the biologic behavior of this exceedingly rare tumor and thus to facilitate its clinical management. The lung was by far the most frequent metastatic site. Thus, all 7 patients with a proven metastatic chondroblastoma recorded up to now including the present case had developed multiple pulmonary metastases. The interval between the initial diagnosis of the primary and manifestation of lung metastases proved to be long, with a mean of 8.4 years. The average survival time was at least 12.3 years. The mean interval between diagnosis of metastatic disease and death amounted to at least 6.3 years. The histomorphologic features of metastatic chondroblastoma, its local recurrences and of the metastatic lesions differed in no way from conventional chondroblastomas. Because of the lack of cellular criteria of malignancy it is impossible to predict the potential biologic behavior of chondroblastomas, in particular with respect to their ability to metastasize. However, the presence of tumor emboli in the primary lesion is highly suggestive of a subsequent development of metastatic disease. The delayed induction of hematogenous metastases is best explained by a limited growth potential of the tumor cells. In case of a large primary tumor--especially in flat bones--with soft tissue invasion or in the presence of tumor emboli an aggressive surgical approach is suggested. When lung metastases have developed their surgical removal is recommended to hopefully prolong live expectancy or even to obtain a curative effect.
[Case report on the immunocytochemical differential diagnosis of serous effusions and cyst fluids].
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Effect of phenacetin and caffeine on N-butyl-N-(4-hydroxybutyl)-nitrosamine-initiated urothelial carcinogenesis in rats.
The present experimental study was undertaken to clarify whether phenacetin and caffeine exert a cocarcinogenic and/or promoting effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-initiated urothelial carcinogenesis. BBN was initially administered to female Wistar rats by gavage in 3 consecutive fractionated doses of 100 mg/kg body weight each at 24-hour intervals. Phenacetin was continuously fed at a daily dose of 500 mg/kg body weight, and caffeine was given in the drinking water at a dose of 110 mg/kg body weight/day throughout the experiment. After an experimental period of 21 months the incidence of BBN-induced tumors in the urinary bladder (number of rats with a bladder tumor) had not increased following additional administration of phenacetin alone (47%) or in combination with caffeine (48%) compared with the control group, the animals of which received exclusively BBN (44%). However, there was a significant enhancement of a multifocal tumor development (number of rats with more than 1 tumor in the bladder), when additionally phenacetin was fed alone (44% of the tumor-bearing animals) or in combination with caffeine (47%) compared with the control rats treated with BBN alone which showed only solitary tumors. Similarly, the incidence of a multicentric tumor development had increased, although not significantly, following administration of phenacetin alone or simultaneously with caffeine for 15 months. Caffeine revealed no complete initiating carcinogenic potential for the resting as well as the regenerating bladder urothelium stimulated to proliferate by either a partial cystectomy or cyclophosphamide. Furthermore, no cocarcinogenic and/or promoting activity of caffeine on BBN-initiated bladder tumor development was observed.(ABSTRACT TRUNCATED AT 250 WORDS)