The kinetics of cell proliferation in Wilms' tumours: investigations with an autoradiographic in vitro method.
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Biomedical subjects
Publications and source records attributed to U Willnow.
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The sensitivity of 37 solid tumours of children was tested in vitro towards cytostatic agents by means of an autoradiographic short-term method. Sensitivity was measured as the magnitude of inhibition of 3 H-thymidine incorporation. The test was performed with the cytotoxic agents Cyclophosphamide, Trenimon, Bleomycin, Adriamycin, Daunomycin, Actinomycin D, and Cytosin-Arabinosid in 9 Wilms' tumours, 9 neuroblastomas, 7 non-Hodgkin-lymphomas, 5 osteogenic sarcomas, 3 soft tissue sarcomas, and 4 special tumours. None of the tumours is resistant to all cytotoxic substances. The tumours show a marked individual sensitivity pattern, and, with few exceptions, they are sensitive against 2 or more cytostatics. This behaviour is explained mainly by the usually high proliferative activity of dysontogenetic tumours, malignant lymphomas and various sarcomas. The possibilities and limits of the short-term methods for sensitivity-testing are discussed critically and in detail. For the evaluation of the results of in vitro testing and of in vivo effectiveness the close coreelations are not always taken into consideration between the type of cytostatic agent and effect on tumour metabolism, cytostatic agent and proliferation kinetics of the tumour as well as the effect of the cytostatics and the nucleic acid precursor used for the test. Despite the methodological limitations preclinical testing should be preferred in comparison with unselected chemotherapy.
The proliferation kinetics of 11histologically undifferentiated neuroblastomas were studied with an autoradiographic in vitro method (labelling with 3H-thymidine and double labelling with 3H- and 14C-thymidine). The cytokinetic parameters revealed a marked individual pattern: LI between 3.0 and 27.8%, Ts 7.2 to 17.8 hr, Tc 13.1 to 266.3 hr, Tm 0.6 to 5.1 hr, T(G1 + G2) 4.3 to 247.6 hr. The potential tumour doubling time (without cell loss) ranges from 20.4 to 415.4 hr. The growth fraction is between 0.48 and 0.58. Cytokinetic investigations of human tumours are extraordinarily important. They cannot only characterize the growth behaviour of malignant tumours, but also provide the basis for an individual therapy. The close correlation between proliferation kinetics and tumour therapy are discussed. These relations may also be summarized in a "cytokinetic therapy index", which allows the general prediction of chemosensitivity. This index is in the field of good or sufficient sensitivity in 9 neuroblastomas; in 2 cases the response to cytostatic agents is questionable from the view-point of cytokinetics.
Supranormal temperatures inhibit selectively the growth of malignant cells more than that of normal cells. The autoradiographic determination of the 3H-thymidine-labelling-index (LI) in vitro is a suitable method for the examination of thermosensitivity of individual human tumours. 44 solid tumours of children (Wilms' tumours, neuroblastomas, osteogenic sarcomas, non-Hodgkin-Lymphomas and other tumours) were studied by the temperatures 37.5 and 42.5 degrees C/120 min, with this method. 90% of the histologically undifferentiated tumours showed a highly significant inhibition of the 3H-thymidine incorporation between 28.6 and 79.9% with an average of 51.1%. In 4 histologically mature tumours (carcinoma of the adrenal cortex, malignant hepatoblastoma, fibrosarcoma, hamartoblastoma) no significant decrease of the LI was present. The inhibition of incorporation with hyperthermia cannot be correlated with the primary magnitude of the LI with normothermia. In 1 neuroblastoma a 75% rise of the LI was found possibly due to exogenic caused thermotolerance. The individuality of the reaction towards heat may contribute to the biological characterization of tumours.
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A rare cause of the congenital hydronephrosis is the proximal atresia of the ureter. With the help of 6 own cases morphology, clinic and therapy of this clinical picture are discussed. The differentiation from Wilms's tumour renders differential-diagnostic difficulties. It seems that a clinical description of this picture of a disease is hitherto not yet existing.
Congenital obstructions of the uretero-pelvic junction of the urinary tract have severe sequelae: urine retention, hydronephrosis, and infections, leading to renal insufficiency without adequate therapy. As the operative results are not always optimal, we studied the morphology of 56 operative specimens and analyzed the structural changes. We found the following conditions causing stenosis of the proximal ureter: 47 localized hypoplasia of the proximal segments of the ureter, systematic hypoplasia in 4 cases, and hypertrophy of the total upper urinary tract in 5 cases. The intrapelvic increase of pressure and the necessary additional work cause characteristic changes of the renal pelvis in the form of hypertrophy of the muscularis and the tunica propria, fibrous destruction of the wall, and secondary formation of valves, which eventually enhance the stenotic effect of the proximal ureter. In the kidneys caliectasis, reduction and hypoplasia of the renal medulla with minor reduction of the renal cortex may be observed. Finally, infections complicate the clinical course. The choice of the surgical procedure should be determined by type and progression of the structural changes and not by personal opinions.
The morphologic analysis of 24 operation specimens of small bowel atresia and stenosis reveals: 1. The classification in the 4 common types of atresia is without importance for the operative management in the newborn. 2. Widely important are systemic structural changes of the atretic, preatretic, and the oral small bowel, the associated intraabdominal malformations, and the mucoviscidosis. The morphological damages at the small bowel in atresia are shown in detail. In some cases the results of the histological examination elucidate vascular alterations caused by small bowel obstruction, The severe destructing pre-atretic small bowel should be resected.
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