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

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

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.

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.

scholarly journals Cell cycle dynamics of NG2 cells in the postnatal and ageing brain

2009 ◽  
Vol 5 (3-4) ◽  
pp. 57-67 ◽  
Author(s):  
Konstantina Psachoulia ◽  
Francoise Jamen ◽  
Kaylene M. Young ◽  
William D. Richardson
Keyword(s):  
Cell Cycle ◽  
Corpus Callosum ◽  
Biological Significance ◽  
Growth Fraction ◽  
Cell Cycle Time ◽  
Active Population ◽  
Dorsal Telencephalon ◽  
Ng2 Cells ◽  
Cell Cycle Dynamics ◽  
Ageing Brain

Oligodendrocyte precursors (OLPs or ‘NG2 cells’) are abundant in the adult mouse brain, where they continue to proliferate and generate new myelinating oligodendrocytes. By cumulative BrdU labelling, we estimated the cell cycle timeTCand the proportion of NG2 cells that is actively cycling (the growth fraction) at ~ postnatal day 6 (P6), P60, P240 and P540. In the corpus callosum,TCincreased from <2 days at P6 to ~9 days at P60 to ~70 days at P240 and P540. In the cortex,TCincreased from ~2 days to >150 days over the same period. The growth fraction remained relatively invariant at ~50% in both cortex and corpus callosum – that is, similar numbers of mitotically active and inactive NG2 cells co-exist at all ages. Our data imply that a stable population of quiescent NG2 cells appears before the end of the first postnatal week and persists throughout life. The mitotically active population acts as a source of new oligodendrocytes during adulthood, while the biological significance of the quiescent population remains to be determined. We found that the mitotic status of adult NG2 cells is unrelated to their developmental site of origin in the ventral or dorsal telencephalon. We also report that new oligodendrocytes continue to be formed at a slow rate from NG2 cells even after P240 (8 months of age).

Nuclear DNA content and minimum generation time in herbaceous plants

1972 ◽  
Vol 181 (1063) ◽  
pp. 109-135 ◽  
Keyword(s):  
Cell Cycle ◽  
Dna Content ◽  
Cycle Time ◽  
Generation Time ◽  
Nuclear Dna ◽  
Nuclear Dna Content ◽  
Annual Species ◽  
Cell Cycle Time ◽  
Developmental Processes ◽  
The Mean

Many components of cell and nuclear size and mass are correlated with nuclear DNA content in plants, as also are the durations and rates of such developmental processes as mitosis and meiosis. It is suggested that the multiple effects of the mass of nuclear DNA which affect all cells and apply throughout the life of the plant can together determine the minimum generation time for each species. The durations of mitosis and of meiosis are both positively correlated with nuclear DNA content and, therefore, species with a short minimum generation time might be expected to have a shorter mean cell cycle time and mean meiotic duration, and a lower mean nuclear DNA content, than species with a long mean minimum generation time. In tests of this hypothesis, using data collated from the literature, it is shown that the mean cell cycle time and the mean meiotic duration in annual species is significantly shorter than in perennial species. Furthermore, the mean nuclear DNA content of annual species is significantly lower than for perennial species both in dicotyledons and monocotyledons. Ephemeral species have a significantly lower mean nuclear DNA content than annual species. Among perennial monocotyledons the mean nuclear DNA content of species which can complete a life cycle within one year (facultative perennials) is significantly lower than the mean nuclear DNA content of those which cannot (obligate perennials). However, the mean nuclear DNA content of facultative perennials does not differ significantly from the mean for annual species. It is suggested that the effects of nuclear DNA content on the duration of developmental processes are most obvious during its determinant stages, and that the largest effects of nuclear DNA mass are expressed at times when development is slowest, for instance, during meiosis or at low temperature. It has been suggested that DNA influences development in two ways, directly through its informational content, and indirectly by the physical-mechanical effects of its mass. The term 'nucleotype' is used to describe those conditions of the nucleus which effect the phenotype independently of the informational content of the DNA. It is suggested that cell cycle time, meiotic duration, and minimum generation time are determined by the nucleotype. In addition, it may be that satellite DNA is significant in its nucleotypic effects on developmental processes.

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