scholarly journals Optimization of Dose Schedules for Chemotherapy of Early Colon Cancer Determined by High-Performance Computer Simulations

2019 ◽  
Vol 18 ◽  
pp. 117693511882280 ◽  
Author(s):  
Chase Cockrell ◽  
David E Axelrod
Keyword(s):  
Colon Cancer ◽  
High Performance ◽  
Human Colon ◽  
Cell Dynamics ◽  
Treatment Conditions ◽  
Early Colon Cancer ◽  
High Performance Computer ◽  
The Stability ◽  
Mutant Cells ◽  
Accumulated Dose

Cancer chemotherapy dose schedules are conventionally applied intermittently, with dose duration of the order of hours, intervals between doses of days or weeks, and cycles repeated for weeks. The large number of possible combinations of values of duration, interval, and lethality has been an impediment to empirically determine the optimal set of treatment conditions. The purpose of this project was to determine the set of parameters for duration, interval, and lethality that would be most effective for treating early colon cancer. An agent-based computer model that simulated cell proliferation kinetics in normal human colon crypts was calibrated with measurements of human biopsy specimens. Mutant cells were simulated as proliferating and forming an adenoma, or dying if treated with cytotoxic chemotherapy. Using a high-performance computer, a total of 28 800 different parameter sets of duration, interval, and lethality were simulated. The effect of each parameter set on the stability of colon crypts, the time to cure a crypt of mutant cells, and the accumulated dose was determined. Of the 28 800 parameter sets, 434 parameter sets were effective in curing the crypts of mutant cells before they could form an adenoma and allowed the crypt normal cell dynamics to recover to pretreatment levels. A group of 14 similar parameter sets produced a minimal time to cure mutant cells. A different group of nine similar parameter sets produced the least accumulated dose. These parameter sets may be considered as candidate dose schedules to guide clinical trials for early colon cancer.

scholarly journals Optimization of Dose Schedules for Chemotherapy of Early Colon Cancer Determined by High Performance Computer Simulations

2018 ◽  
Author(s):  
Chase Cockrell ◽  
David E. Axelrod
Keyword(s):  
Colon Cancer ◽  
High Performance ◽  
Human Colon ◽  
Cell Dynamics ◽  
Treatment Conditions ◽  
Early Colon Cancer ◽  
High Performance Computer ◽  
The Stability ◽  
Mutant Cells ◽  
Accumulated Dose

AbstractCancer chemotherapy dose schedules are conventionally applied intermittently, with dose duration of the order of hours, intervals between doses of days or weeks, and cycles repeated for weeks. The large number of possible combinations of values of duration, interval, and lethality has been an impediment to empirically determine the optimal set of treatment conditions. The purpose of this project was to determine the set of parameters for duration, interval, and lethality that would be most effective for treating early colon cancer. An agent-based computer model that simulated cell proliferation kinetics in normal human colon crypts was calibrated with measurements of human biopsy specimens. Mutant cells were simulated as proliferating and forming an adenoma, or dying if treated with cytotoxic chemotherapy. Using a high performance computer, a total of 28,800 different parameter sets of duration, interval, and lethality were simulated. The effect of each parameter set on the stability of colon crypts, the time to cure a crypt of mutant cells, and the accumulated dose was determined. Of the 28,800 parameter sets, 434 parameter sets were effective in curing the crypts of mutant cells before they could form an adenoma and allowed the crypt normal cell dynamics to recover to pretreatment levels. A group of 14 similar parameter sets produced a minimal time to cure mutant cells. A different group of 9 similar parameter sets produced the least accumulated dose. These parameter sets may be considered as candidate dose schedules to guide clinical trials for early colon cancer.

Improved 3-D reconstruction using stereo computer graphics and multiple tilt EM images

1995 ◽  
Vol 53 ◽  
pp. 630-631
Author(s):  
Lee D. Peachey ◽  
Lou Fodor ◽  
John C. Haselgrove ◽  
Stanley M. Dunn ◽  
Junqing Huang
Keyword(s):  
Computer Graphics ◽  
High Performance ◽  
Transverse Section ◽  
Three Dimensional ◽  
Stereo Pair ◽  
3D Reconstructions ◽  
Video Cameras ◽  
Biological Objects ◽  
Microscope Images ◽  
High Performance Computer

Stereo pairs of electron microscope images provide valuable visual impressions of the three-dimensional nature of specimens, including biological objects. Beyond this one seeks quantitatively accurate models and measurements of the three dimensional positions and sizes of structures in the specimen. In our laboratory, we have sought to combine high resolution video cameras with high performance computer graphics systems to improve both the ease of building 3D reconstructions and the accuracy of 3D measurements, by using multiple tilt images of the same specimen tilted over a wider range of angles than can be viewed stereoscopically. Ultimately we also wish to automate the reconstruction and measurement process, and have initiated work in that direction.Figure 1 is a stereo pair of 400 kV images from a 1 micrometer thick transverse section of frog skeletal muscle stained with the Golgi stain. This stain selectively increases the density of the transverse tubular network in these muscle cells, and it is this network that we reconstruct in this example.

Leptin is a growth factor for human colon cancer cells

2001 ◽  
Vol 120 (5) ◽  
pp. A493-A493
Author(s):  
J HARDWICK ◽  
G VANDENBRINK ◽  
S VANDEVENTER ◽  
M PEPPELENBOSCH
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Human Colon Cancer Cells

Dietary Vitamin and Stability of Oral Anticoagulation: Proposal of a Diet with Constant Vitamin K1 Content

1997 ◽  
Vol 77 (03) ◽  
pp. 504-509 ◽  
Author(s):  
Sarah L Booth ◽  
Jacqueline M Charnley ◽  
James A Sadowski ◽  
Edward Saltzman ◽  
Edwin G Bovill ◽  
...  
Keyword(s):  
Dietary Intake ◽  
Vitamin K ◽  
High Performance ◽  
Case Reports ◽  
Food Composition ◽  
Dietary Guidelines ◽  
Dietary Vitamin ◽  
Vitamin K1 ◽  
The Stability ◽  
The Impact

SummaryCase reports cited in Medline or Biological Abstracts (1966-1996) were reviewed to evaluate the impact of vitamin K1 dietary intake on the stability of anticoagulant control in patients using coumarin derivatives. Reported nutrient-drug interactions cannot always be explained by the vitamin K1 content of the food items. However, metabolic data indicate that a consistent dietary intake of vitamin K is important to attain a daily equilibrium in vitamin K status. We report a diet that provides a stable intake of vitamin K1, equivalent to the current U.S. Recommended Dietary Allowance, using food composition data derived from high-performance liquid chromatography. Inconsistencies in the published literature indicate that prospective clinical studies should be undertaken to clarify the putative dietary vitamin K1-coumarin interaction. The dietary guidelines reported here may be used in such studies.

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