Modelling of tumour repopulation after chemotherapy

Marcu, Loredana G.; Bezak, Eva

doi:10.1007/s13246-010-0026-4

Cited by 15 publications

(11 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accelerated tumor repopulation after radiation therapy is not a new concept [63–67] and has been noted following chemotherapy as well [68–70]. Early studies carried out by H. Rodney Withers in both mice and later in human clinical trials detailed the occurrence of accelerated tumor repopulation after treatments with ionizing radiation [63, 71] and pioneered the work on modifying radiation treatment regimens to circumvent this effect [72, 73].…”

Section: Tumor Repopulation a Key Issue In Radiation Biology And Thementioning

confidence: 99%

Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy

Zimmerman

Huang

et al. 2013

Seminars in Radiation Oncology

View full text Add to dashboard Cite

Summary Death of all the cancer cells in a tumor is the ultimate goal of cancer therapy. Therefore much of the current effort in cancer research is focused on activating cellular machinery that facilitates cell death such as factors involved in causing apoptosis. However, recently a number of studies point to some counter-intuitive roles for apoptotic caspases in radiation therapy as well as in tissue regeneration. It appears that a major function of apoptotic caspases is to facilitate tissue regeneration and tumor cell repopulation during cancer therapy. Because tumor cell repopulation has been shown to be important for local tumor relapse, understanding the molecular mechanisms behind tumor repopulation will be important to enhance cancer radiotherapy. In this review, we discuss our current knowledge of these potentially paradigm-changing phenomena and mechanisms in various organisms and their implications on the development of novel cancer therapeutics and strategies.

show abstract

Section: Tumor Repopulation a Key Issue In Radiation Biology And Thementioning

confidence: 99%

Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy

Zimmerman

Huang

et al. 2013

Seminars in Radiation Oncology

View full text Add to dashboard Cite

show abstract

“…A model in which fractionated doses allow recruitment of quiescent cells into the mitotic cycle after each dose has been described [66]. …”

Section: Introductionmentioning

confidence: 99%

A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments

Bravo

Axelrod

2013

Theor Biol Med Model

100

View full text Add to dashboard Cite

BackgroundNormal colon crypts consist of stem cells, proliferating cells, and differentiated cells. Abnormal rates of proliferation and differentiation can initiate colon cancer. We have measured the variation in the number of each of these cell types in multiple crypts in normal human biopsy specimens. This has provided the opportunity to produce a calibrated computational model that simulates cell dynamics in normal human crypts, and by changing model parameter values, to simulate the initiation and treatment of colon cancer.ResultsAn agent-based model of stochastic cell dynamics in human colon crypts was developed in the multi-platform open-source application NetLogo. It was assumed that each cell’s probability of proliferation and probability of death is determined by its position in two gradients along the crypt axis, a divide gradient and in a die gradient. A cell’s type is not intrinsic, but rather is determined by its position in the divide gradient. Cell types are dynamic, plastic, and inter-convertible. Parameter values were determined for the shape of each of the gradients, and for a cell’s response to the gradients. This was done by parameter sweeps that indicated the values that reproduced the measured number and variation of each cell type, and produced quasi-stationary stochastic dynamics. The behavior of the model was verified by its ability to reproduce the experimentally observed monocolonal conversion by neutral drift, the formation of adenomas resulting from mutations either at the top or bottom of the crypt, and by the robust ability of crypts to recover from perturbation by cytotoxic agents. One use of the virtual crypt model was demonstrated by evaluating different cancer chemotherapy and radiation scheduling protocols.ConclusionsA 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.

show abstract

“…As shown by Davis and Tannock [109] the impact of repopulation between cycles of chemotherapy on treatment response may be comparable to that of intrinsic or acquired chemoresistance. These findings have been confirmed by a stochastic model of tumour growth and response to chemotherapy [110]. Cellular recruitment was modelled by releasing various percentages of quiescent cells into the mitotic cycle after each drug-caused cell kill.…”

Section: In Silico Cancer Treatment Modelsmentioning

confidence: 78%

In SilicoModelling of Treatment-Induced Tumour Cell Kill: Developments and Advances

Marcu

Harriss-Phillips

2012

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Mathematical and stochastic computer (in silico) models of tumour growth and treatment response of the past and current eras are presented, outlining the aims of the models, model methodology, the key parameters used to describe the tumour system, and treatment modality applied, as well as reported outcomes from simulations. Fractionated radiotherapy, chemotherapy, and combined therapies are reviewed, providing a comprehensive overview of the modelling literature for current modellers and radiobiologists to ignite the interest of other computational scientists and health professionals of the ever evolving and clinically relevant field of tumour modelling.

show abstract

Modelling of tumour repopulation after chemotherapy

Cited by 15 publications

References 15 publications

Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy

Cell Death–Stimulated Cell Proliferation: A Tissue Regeneration Mechanism Usurped by Tumors During Radiotherapy

A calibrated agent-based computer model of stochastic cell dynamics in normal human colon crypts useful for in silico experiments

In SilicoModelling of Treatment-Induced Tumour Cell Kill: Developments and Advances

Contact Info

Product

Resources

About