1,720,968 research outputs found
Data Files, Chronotherapy
No full textTitle: Data Files, Chronotherapy
Research genre: Data
Creator: Axelrod, David E.
Date created: 2020
Extent: 6 Excel files, each 11 KB
Intended Audience: Science
Description: Output of chronotherapy simulated with NetLogo computer program Colon_Crypt_Model_073120.nlogo created in NetLogo version 5.3.1. The model was revised and renamed Colon_Crypt_Model_041321.nlogo in order to run with NetLogo version 6.2.0. The model is described in a separate file. Each data file is the result of cytotoxic chemotherapy during a different 4-hour period during the day. The file names indicate the time period (Phase) that chemotherapy was active. Data in each column include the following, A: run number, with the number of time steps when mutants were initiated and the number of time steps that chemotherapy was initiated; B: whether or not the mutants overflowed the crypt and the mutants were not eliminated from the crypt (cured); C: the time step at which the mutants were eliminated from the crypt (cured); D: time steps between the time that chemotherapy was on and the time that mutants were cured; E: time to cure mutants in hours, assuming one time step equals four hours.; F: time to cure mutants in days; G: time of day, in hours, when chemotherapy was initiated. A forthcoming publication will describe the computer program and simulation results of circadian-timed chemotherapy.
Research Domain: Science
Rights statement: The author owns the copyright to this wor
Colon_Crypt_Model_041321.nlogo
No full textTitle: Colon_Crypt_Model_041321.nlogo
Research genre: Computer program
Creator: Axelrod, David E.
Date Created: 2021
Extent: 1 digital file (393 KB)
Intended Audience: Science
Description: Computer program that simulates and plots the dynamics of stem cells, transient amplifying cells, differentiated cells, and mutant cells in normal human colon crypts and early colon cancer. It has been calibrated with measurements of human biopsy specimens. Includes graphical user interface, detailed information text, and annotated code. Experiments can be run from the GUI without knowledge of coding, or from the Behavior Space Tool using example code or modified code. It has been used to simulate human colon cancer initiation, therapy, and prevention. Different chemotherapy or prevention intermittent dose schedules can be input. Chemotherapy of heterogeneous and drug resistant early colon cancers can be simulated. Circadian cell proliferation can be selected to investigate chronomodulated chemotherapy dose schedules. Simulated output can be saved in spreadsheet format, or as images of plots of cell numbers as function of time.
The model was developed in the application NetLogo version 5.3.1, and revisions made to also run in NetLogo version 6.2.0. The model will not run on the Web version of NetLogo. NetLogo is a multi-agent programmable modeling environment. It is authored by Uri Wilenski and developed at The Center for Connected Learning (CCL) and Computer-Based Modeling. It is multi-platform (Mac, Windows, or Linux) open source application.
NetLogo version 6.2.0, can be downloaded at http://ccl.northwestern.edu/netlogo/download.shtml. To download the computer program click on the red link “NLOGO" to the left.
Earlier versions of the model and its use have been described in the following publications: Theoret Biol Med Model. 2013;10:66-89. Cancer Chemother Pharmcol 2017;79:889-898. Converg Sci Phys Oncol 2017;3:035004. Cancer Inform 2019;18:1-8. JCO Clin Cancer Inform 2020;4:514-520. A forthcoming publication will describe results of circadian-timed chemotherapy.
Research Domain: Science
Subjects: Chronotherapy: Circadian: Colorectal cancer: Chemotherapy: Agent-based model
Rights statement: The author owns the copyright to this work
Intermittent Chemoprevention of Colon Cancer
No full textThis video shows the advantage of intermittent pulse schedules compared to constant schedules, for the chemoprevention of colon cancer in a computer simulation of cell dynamics in human colon crypts.Supplemental data for a manuscript prepared for publication, tentatively entitled: Chemoprevention of Colon Cancer: Advantage of Intermittent Pulse Treatment Schedules Quantified by Computer Simulation of Human Colon Crypt
Evolution of cooperation among tumor cells
No full textThe evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the issue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell???stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as byproduct mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.Author manuscript. Published in final edited form as: Proc Natl Acad Sci U S A. 2006 September 5; 103(36): 13474-13479.The final published version of this article is located at: www.pnas.org/cgi/doi/10.1073/pnas.0606053103NIH U56 CA113004; to David E. AxelrodR.A. was supported by National Science Foundation (NSF) Grant SES-0240852. D.E.A. was supported by NSF Grant IIS-0312953, National Institutes of Health (NIH) Grant U56 CA113004, and New Jersey Commission on Cancer Research Grant 1076-CCR-SO. K.J.P. is an American Cancer Society Clinical Research Professor and is supported by NIH Grants CA69568, CA102872, and CA093900.NIH CA69568; to Kenneth J. PientaNIH CA102872; to Kenneth J. PientaNIH CA093900; to Kenneth J. PientaNSF SES-0240852; to Robert AxelrodNJ Commission on Cancer Research 1076-CCR-SO; to David E. AxelrodAlso available in PubMed Central. PMCID: PMC155738
Data Files, Chronotherapy
No full textOutput of chronotherapy simulated with NetLogo computer program Colon_Crypt_Model_073120. The model is described in a separate file. Each data file is the result of cytotoxic chemotherapy during a different 4 hour period during the day.
The file names (Data Analysis…) indicate the date that they were generated (073120 is Aug. 31, 2020), the time step that circadian cell proliferation was initiated (Circad), the time step the chemotherapy was initiated (Chemo), and the time steps (Phase) that chemotherapy was active.
Data in each column include the following, A: run number, with the number of time steps when mutants were initiated and the number of time steps that chemotherapy was initiated; B: whether or not the mutants overflowed the crypt and the mutants were not eliminated from the crypt (cured); C: the time step at which the mutants were eliminated from the crypt (cured); D: time steps between the time that chemotherapy was on and the time that mutants were cured; E: time to cure mutants in hours, assuming one time step equals four hours.; F: time to cure mutants in days; G: time of day, in hours, when chemotherapy was initiated.
A forthcoming publication will describe the computer program and simulation results of circadian-timed chemotherapy
Colon_Crypt_Model_073120.nlogo
No full textComputer program that simulates and plots the dynamics of stem cells, transient amplifying cells, differentiated cells, and mutant cells in normal human colon crypts and early colon cancer. It has been calibrated with measurements of human biopsy specimens. Includes graphical user interface, detailed information text, and annotated code. Experiments can be run from the GUI without knowledge of coding, or from the Behavior Space Tool using example code or modified code. Has been used to simulate human colon cancer initiation, therapy, and prevention.
Different chemotherapy or prevention intermittent dose schedules can be input. Chemotherapy of heterogeneous and drug resistant early colon cancers can be simulated. Circadian cell proliferation can be selected to investigate chronomodulated chemotherapy dose schedules. Simulated output can be saved in spreadsheet format, or as images of plots of cell numbers as function of time. It runs on the open-source multi-platform NetLogo application version 5.3.1 available at https://ccl.northwestern.edu/netlogo/index.shtml. Described in the following publications: Theoret Biol Med Model. 2013;10:66-89. Cancer Chemother Pharmcol 2017;79:889-898. Converg Sci Phys Oncol 2017;3:035004. Cancer Inform 2019;18:1-8. JCO Clin Cancer Inform 2020;4:514-520.
A forthcoming publication will describe results of circadian-timed chemotherapy.
To download the computer program click on the red link “Download file" to the left
Chemoprevention of colon cancer: Advantage of intermittent pulse treatment schedules quantified by computer simulation of human colon crypts
No full textIntermittent treatment schedules have been proposed to improve the tolerance of drugs for cancer chemoprevention. However, determining a maximum tolerated dose, and the extent of the improvement, has been challenging experimentally and clinically. In order to determine the quantitative advantage of intermittent pulse treatment schedules for the chemoprevention of colon cancer we have used a computer model of human colon crypts calibrated with measurements of human biopsy specimens. In simulations, crypts were treated with an agent that increases the probability that cells, both normal and mutant, would be removed at the top of the crypt. Sulindac, which increases apoptosis at the lumen surface, is such an agent. The effect of intermittent pulse drug treatment schedules were compared with constant drug treatment schedules. Crypts treated with intermittent pulse schedules have three times the maximum tolerated dose than crypts treated with constant schedules, and have a 10 year delay in the appearance of adenomas. Intermittent treatment schedules have previously been proposed for chemoprevention. Here computer simulations have quantified the effect on human colon crypts of intermittent treatment schedules and constant treatment schedules of a chemotherapeutic drug. Intermittent pulses have an advantage, they allow an increased maximum tolerated dose, and result in an increased chemoprevention by delay.Peer reviewe
A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments
No full textA virtual crypt has been developed that simulates the quasi-stationary stochastic cell dynamics of normal human colon crypts. It is unique in that it has been calibrated with measurements of human biopsy specimens, and it can simulate the variation of cell types in addition to the average number of each cell type. The utility of the model was demonstrated with in silico experiments that evaluated cancer therapy protocols. The model is available for others to conduct additional experiments
Evaluation of pathways for progression of heterogeneous breast tumors
No full textTo better understand the progression of heterogeneous breast cancers, four models of progression pathways have been evaluated. The models describe the progression through the grades of ductal carcinoma in situ (DCIS) 1, 2, and 3, and through the grades of invasive ductal carcinoma (IDC) 1, 2, and 3. The first three pathways, termed linear, nonlinear, and branched, describe DCIS as aprogenitor of IDC, and grades of DCIS progressing into grades of IDC. The fourth pathway, termed parallel, describes DCIS and IDC as diverging from a common progenitor and progressing through grades in parallel. The best transition rates for the linear, nonlinear, and branched pathways were sought using a random search in combination with a directed search based on the Nelder–Mead simplex method. Parameter values for the parallel pathway were determined with heuristic graphs. Results of computer simulation were compared with clinically observed frequencies of grades of DCIS and grades of IDC that were reported to occur together in heterogeneous tumors. Each of the four pathways could simulate frequencies that resembled, to varying degrees, the clinical observations. The parallel pathway produced the best correspondence with clinical observations. These results quantify the traditional descriptions in which grades of DCIS are the progenitors of grades of IDC. The results also raise the alternative possibility that, in some tumors with both components, DCIS and IDC may have diverged from a common progenitor
Data adjuvant therapy dose schedules
No full textData file of simulated dose schedules that prevent the recurrence of colon cancer by apoptotic adjuvant therapy. Includes numerical data in columns for Interval, Duration, Treatment, and 50-year dose sum, ranked by 50-year dose sum. Supplementary file for article tentatively titled “Prevention of Colon Cancer Recurrence from Minimal Residual Disease: Computer Optimized Dose Schedule of Intermittent Apoptotic Adjuvant Therapy.”No restriction on public acces
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