Review of basic concepts of cell kinetics as applied to brain tumors

1975 ◽  
Vol 42 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Takao Hoshino ◽  
Charles B. Wilson
Keyword(s):  
Cell Cycle ◽  
Brain Tumors ◽  
Cycle Time ◽  
Doubling Time ◽  
Cell Kinetics ◽  
Cell Loss ◽  
Growth Fraction ◽  
Cell Cycle Time ◽  
Tumor Doubling Time ◽  
Basic Concepts

✓ The authors review and discuss the basic concepts of cell kinetics as applied to brain tumors. Uncontrolled growth of a neoplasm represents an expanding tumor cell population. Four growth parameters characterize the behavior of a neoplastic population: cell cycle time, growth fraction, tumor doubling time, and cell loss. The concept of provisionally nondividing cells explains the disparity between cell cycle time and tumor doubling time. Human gliomas, like many non-neural solid tumors, contain variable proportions of actively proliferating and nonproliferating tumor cells; this ratio is expressed by the growth fraction. The major kinetic difference between glioblastomas and differentiated astrocytomas resides in their respective growth fractions, in all likelihood an inherent biological characteristic of each tumor. Glioblastoma proliferates at a rapid rate, and only a high rate of cell loss prevents this tumor from doubling its volume in less than 1 week. The selection of drugs and design of drug schedules for treatment of glioblastomas should be made with the knowledge that 60% to 70% of the cells in this tumor are resting (nonproliferating). If experience with other solid tumors is any guide, judicious selection and combined use of drugs according to kinetically sound schedules will produce more effective chemotherapy of brain tumors.

Estimation of growth fraction with bromodeoxyuridine in human central nervous system tumors

1986 ◽  
Vol 65 (5) ◽  
pp. 659-663 ◽  
Author(s):  
Yoshihiko Yoshii ◽  
Yutaka Maki ◽  
Koji Tsuboi ◽  
Yuji Tomono ◽  
Kunio Nakagawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cycle Time ◽  
Doubling Time ◽  
Malignant Gliomas ◽  
Cell Loss ◽  
Growth Fraction ◽  
Cell Cycle Time ◽  
Tumor Doubling Time ◽  
Content Type ◽  
Fine Print

✓ Twenty-five patients with tumors of the central nervous system received bromodeoxyuridine (BUdR), 200 mg/sq m, by intravenous infusion every 8 hours for 3 days before surgery. Excised tumor specimens were fixed in chilled 70% ethanol, embedded in paraffin, and cut into 6-µm sections. Each section was reacted with monoclonal antibodies against BUdR and stained with immunoperoxidase to identify nuclei that had incorporated BUdR. The growth fraction of each tumor was estimated by calculating the ratio of BUdR-positive nuclei to the total number of tumor cells in three to six microscopic fields in viable areas of the tumor. In seven cases, the tumor doubling time was measured from the serial computerized tomography scans and an attempt was made to estimate the cell cycle time. The growth fractions ranged from 9.1% to 46.5% in malignant gliomas, 2.0% to 6.7% in low-grade gliomas, 11.2% to 43.2% in metastatic brain tumors, 0.8% to 1.9% in pituitary adenomas, 3.9% to 4.6% in acoustic neurinomas, and 6.2% to 8.2% in meningiomas and cerebellar hemangioblastomas. The estimated cell cycle time was 5 to 12 days in most malignant gliomas and brain metastases; however, the actual cell cycle time should be substantially shorter because cell loss was not considered in the calculation. Although the growth fraction appeared to correlate with the biological malignancy of each tumor, the tumor doubling time did not reflect growth potential. It is possible that unpredictable cell loss plays an important role in tumor growth at certain sizes. Therefore, the cell cycle times calculated in this study are considerably overestimated and should be interpreted with caution.

Cytokinetic Analysis at Various Ages of an Ascites Tumor after Radiation

1978 ◽  
Vol 64 (5) ◽  
pp. 463-470
Author(s):  
Eva Siracká ◽  
Natasa Pappová
Keyword(s):  
Cell Cycle ◽  
Growth Rate ◽  
Cycle Time ◽  
Doubling Time ◽  
Cell Loss ◽  
Whole Body ◽  
Ascites Tumor ◽  
Cell Cycle Time ◽  
Slowing Down ◽  
Proliferative Phase

A cytokinetic analysis has been made of 5-day and of 10-day old murine 6C3HED ascites lymphosarcoma (Gardner) by using a growth curve, percentage of labeled mitoses curves, and continuous labeling curves. The doubling time increased from 36 h in the proliferative phase of growth to 252 h in the stationary phase. The slowing down of the growth rate was due to prolongation of the cell cycle time, with greatest extension in G1 and increased cell loss. The measurement of the kinetic parameters made immediately after irradiation with a whole-body single dose of 3 Gy (300 rad) showed an increase in duration of the cell cycle in the 5-day-old tumor, while in the 10-day-old tumor the cell cycle time was decreased due to reduce length in the G1 phase.

scholarly journals A method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample

BMC Cancer ◽  
2005 ◽  
Vol 5 (1) ◽  
Author(s):  
Rimantas Eidukevicius ◽  
Dainius Characiejus ◽  
Ramunas Janavicius ◽  
Nijole Kazlauskaite ◽  
Vita Pasukoniene ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cycle Time ◽  
Single Sample ◽  
Growth Fraction ◽  
Cell Cycle Time ◽  
Flow Cytometry Data

Tissue economics of hydra: regulation of cell cycle, animal size and development by controlled feeding rates

1977 ◽  
Vol 28 (1) ◽  
pp. 117-132
Author(s):  
J.J. Otto ◽  
R.D. Campbell
Keyword(s):  
Cell Cycle ◽  
Steady State ◽  
Epithelial Cell ◽  
Cycle Time ◽  
Cell Loss ◽  
Tissue Growth ◽  
Tissue Loss ◽  
Feeding Rates ◽  
Cell Cycle Time ◽  
Steady State Condition

Epithelial cell production and epithelial cell loss in 6 different size classes of Hydra attenuata were examined to understand the relationships between growth and morphogenesis. The sizes of adult hydra, the sizes of their buds, and their budding rates are all nearly proportional to the amount of food the hydra eat. Hydra fed at high rates (4-25 Artemia nauplii per day) all have the same epithelial cell cycle time (about 4 days). Budding accounts for most of their cell loss. Hydra fed 4–12 Artemia per day maintain a steady state condition in which tissue loss balances tissue growth. Animals fed 25 Artemia per day are not in a steady state growth condition and change in size. At the lowest feeding rates (0-1 Artemia per day), the epithelial cell cycle time is lengthened to about 16 days. Cell loss from the tentacles accounts for most of the cell loss, and this loss is not completely balanced by growth. As a consequence these animals cease budding and shrink in size.

scholarly journals Erratum to: a method to estimate cell cycle time and growth fraction using bromodeoxyuridine-flow cytometry data from a single sample

BMC Cancer ◽  
2006 ◽  
Vol 6 (1) ◽  
Author(s):  
Rimantas Eidukevicius ◽  
Dainius Characiejus ◽  
Ramunas Janavicius ◽  
Nijole Kazlauskaite ◽  
Vita Pasukoniene ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Cycle Time ◽  
Single Sample ◽  
Growth Fraction ◽  
Cell Cycle Time ◽  
Flow Cytometry Data

Chemotherapeutic implications of growth fraction and cell cycle time in glioblastomas

1975 ◽  
Vol 43 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Takao Hoshino ◽  
Charles B. Wilson ◽  
Mark L. Rosenblum ◽  
Marvin Barker
Keyword(s):  
Cell Cycle ◽  
Tumor Cell ◽  
Cycle Time ◽  
Malignant Gliomas ◽  
Chemotherapeutic Agents ◽  
Tumor Growth Rate ◽  
Growth Fraction ◽  
Cycle Phase ◽  
Combination Drug ◽  
Cell Cycle Time

✓Four patients received 3H-thymidine 4 to 7 days and vinblastine 4 to 6 hours prior to operation for recurrent malignant gliomas (three glioblastomas and one anaplastic astrocytoma). Tumor biopsies obtained at operation were fixed for routine histological studies and radioautography. The tumors' growth fractions averaged 0.28 with a range of 0.14 to 0.39. The tumor cell cycle time calculated in three patients had a mean duration of 57 hours with a standard deviation of 6 hours. The authors concluded that: 1) single short-term courses of cell-cycle specific chemotherapeutic agents alone will probably fail to achieve either significant reduction in tumor mass or dramatic clinical improvement; 2) cell-cycle phase-specific drugs should be administered to maintain effective blood levels over 2 to 3 days for maximal tumor cell kill. Tumor growth rate appears to correlate with the fraction of proliferating cells rather than the length of the tumor cell cycle. The scientific basis for combination drug and multimodality therapy is discussed.

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