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The kinetics of human glioblastomas maintained in an organ culture system (1983)

Hess, J. R. ; Michaud, J. ; Sobel, R. A. ; [et al.]

Springer

Acta neuropathologica 61 (1983), S. 1-9

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ISSN: 1432-0533

Keywords: Glioblastomas ; Organ culture method ; Autoradiography ; Kinetics ; Growth fraction

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Summary Five human glioblastomas maintained in an organ culture system were studied by autoradiography to determine, after 8 days in vitro, the growth fraction (GF) of the explants, their total cell cycle time (T C) and cell cycle phase durations (T S,T G1,T G2 andT M), and their potential doubling time (T pot) after pulse-labeling with [3H] TdR for 1 h. These parameters were derived from computer analysis of fraction of labeled mitoses (FLM) curves. The results fell into two groups. In two tumors, the cultures had a GF of 0.25 and 0.23. From the FLM curves were derived aT C of 89 and 83 h, aT S of 16.5 and 9.5 h, and aT G1 of 60 and 61 h.T M was estimated at 0.9 and 0.6 h, andT G2 12h. TheT pot was 12 days. These values approximate those reported for glioblastomas and other human malignancies in vivo. The explants of three other glioblastomas gave different FLM curves: the derivedT S were increased to 36 and 55 h, estimatedT M ranged from 2.4 to 4.5 h, andT G2 ranged from 11 to 20 h.T C andT G1 could not be estimated. In two tumors the GF was reduced to 0.12 and 0.11, with aT pot of respectively 52 and 39 days. These values are comparable to those reported for astrocytomas of intermediate malignancy. In the third tumor, the GF was only 0.014. The reduction in GF and the lengthening of cell cycle components in this group of explants are similar to the kinetic changes reported in some in vivo tumors and three-dimensional in vitro systems that have reached a plateau stage of growth. They are probably related to the greater opportunities for cell-to-cell contacts and the resulting increased differentiation favored by the organ culture technique.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/BF00688379

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Selective high metabolic lability of uridine triphosphate in response to glucosamine feeding of untransformed and polyoma virus-transformed hamster fibroblasts (1980)

Rapaport, Eliezer ; Christopher, C. William ; Ullrey, Donna ; [et al.]

New York, NY [u.a.] : Wiley-Blackwell

Journal of Cellular Physiology 104 (1980), S. 253-259

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ISSN: 0021-9541

Keywords: Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Medicine

Notes: Derepression of hexose transport in a line of Syrian hamster fibroblasts (Nil) and polyoma-transformed (PyNil) hamster fibroblasts is obtained when cells are either starved for glucose or fed with fructose as the only hexose source. D-glucosamine feeding of these cells does not alter the repressed state with regard to hexose transport. High, derepressed rates of galactose transport were changed to low, repressed rates, within 18 hours of refeeding glucose-starved cells with D-glucosamine as the only hexose source. Nil and PyNil cells, when cultured in the presence of D-glucosamine, undergo rapid reductions in total cellular uridine 5′-triphosphate (UTP) pool sizes. By contrast, the total cellular pools of adenosine 5′-triphosphate, guanosine 5′-triphosphate, and cytosine 5′-triphosphate (ATP, GTP, and CTP) were only moderately affected by the treatment of the cells with glucosamine. The metabolic drain of the UTP pools in PyNil cells was much more pronounced than in the untransformed cells. The larger and more rapid metabolic lability of UTP pools in the transformed cells may be the primary reason for the selective toxicity of glucosamine on tumor cells. A comparison of the effects of glucosamine on hexose-starved Nil and PyNil cells demonstrated that only the untransformed cells were able to utilize glucosamine to increase the hexose starvation-depleted pools of all nucleoside triphosphates. Accumulation of UDP-glucosamine and UDP-N-acetylglucosamine followed the reduction in the UTP pools. Inhibition of protein synthesis by cycloheximide during glucosamine feeding led to higher levels of UDP-glucosamine and UDP-N-acetylglucosamine accumulation. It is suggested that the drain of UTP pools during glucosamine treatment proceeds through the formation of the UDP-aminosugars which turn over due to the action of intracellular UDP-aminosugar pyrophosphatase activities.

Additional Material: 2 Ill.