Limits...
The Role of Oxygen in Avascular Tumor Growth.

Grimes DR, Kannan P, McIntyre A, Kavanagh A, Siddiky A, Wigfield S, Harris A, Partridge M - PLoS ONE (2016)

Bottom Line: These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation.The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement.Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Old Road Campus, Oxford, OX3 7DQ, United Kingdom.

ABSTRACT
The oxygen status of a tumor has significant clinical implications for treatment prognosis, with well-oxygenated subvolumes responding markedly better to radiotherapy than poorly supplied regions. Oxygen is essential for tumor growth, yet estimation of local oxygen distribution can be difficult to ascertain in situ, due to chaotic patterns of vasculature. It is possible to avoid this confounding influence by using avascular tumor models, such as tumor spheroids, a much better approximation of realistic tumor dynamics than monolayers, where oxygen supply can be described by diffusion alone. Similar to in situ tumours, spheroids exhibit an approximately sigmoidal growth curve, often approximated and fitted by logistic and Gompertzian sigmoid functions. These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation. This work examines the oxygen dynamics of spheroids and demonstrates that this growth can be derived mechanistically with cellular doubling time and oxygen consumption rate (OCR) being key parameters. The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement. Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model.

No MeSH data available.


Related in: MedlinePlus

Best fit degeneracy for U-87 growth curve.While most values of rl / td yield negative co-efficients of determination, there is a relatively narrow-band (shown in color) that produces a good fit to observed data (R2 > 0.95). In this case, values of rl between 160–215 μm (8.56–15.46 ×10−7 m3 kg−1 s−1) can yield good fits, with these values yielding doubling times between 0.6–2.1 days. The range value is due to inherent degeneracy between diffusion limit and doubling time.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835055&req=5

pone.0153692.g006: Best fit degeneracy for U-87 growth curve.While most values of rl / td yield negative co-efficients of determination, there is a relatively narrow-band (shown in color) that produces a good fit to observed data (R2 > 0.95). In this case, values of rl between 160–215 μm (8.56–15.46 ×10−7 m3 kg−1 s−1) can yield good fits, with these values yielding doubling times between 0.6–2.1 days. The range value is due to inherent degeneracy between diffusion limit and doubling time.

Mentions: For the MDA-MB-231, U-87, SCC-25 and V-79 cell lines, theoretical fitting methods were employed to find best OCR and doubling time parameters for a given growth curve. The resultant fits in good agreement (0.96 ≤ R2 ≤ 0.99) for all cases. There is some unavoidable uncertainty on these fits due to the fact that doubling time td and diffusion limit rl (and by extension OCR) are degenerate parameters, as illustrated in Fig 6. In principle if the OCR can be estimated, then this degeneracy can be circumvented.


The Role of Oxygen in Avascular Tumor Growth.

Grimes DR, Kannan P, McIntyre A, Kavanagh A, Siddiky A, Wigfield S, Harris A, Partridge M - PLoS ONE (2016)

Best fit degeneracy for U-87 growth curve.While most values of rl / td yield negative co-efficients of determination, there is a relatively narrow-band (shown in color) that produces a good fit to observed data (R2 > 0.95). In this case, values of rl between 160–215 μm (8.56–15.46 ×10−7 m3 kg−1 s−1) can yield good fits, with these values yielding doubling times between 0.6–2.1 days. The range value is due to inherent degeneracy between diffusion limit and doubling time.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835055&req=5

pone.0153692.g006: Best fit degeneracy for U-87 growth curve.While most values of rl / td yield negative co-efficients of determination, there is a relatively narrow-band (shown in color) that produces a good fit to observed data (R2 > 0.95). In this case, values of rl between 160–215 μm (8.56–15.46 ×10−7 m3 kg−1 s−1) can yield good fits, with these values yielding doubling times between 0.6–2.1 days. The range value is due to inherent degeneracy between diffusion limit and doubling time.
Mentions: For the MDA-MB-231, U-87, SCC-25 and V-79 cell lines, theoretical fitting methods were employed to find best OCR and doubling time parameters for a given growth curve. The resultant fits in good agreement (0.96 ≤ R2 ≤ 0.99) for all cases. There is some unavoidable uncertainty on these fits due to the fact that doubling time td and diffusion limit rl (and by extension OCR) are degenerate parameters, as illustrated in Fig 6. In principle if the OCR can be estimated, then this degeneracy can be circumvented.

Bottom Line: These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation.The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement.Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Old Road Campus, Oxford, OX3 7DQ, United Kingdom.

ABSTRACT
The oxygen status of a tumor has significant clinical implications for treatment prognosis, with well-oxygenated subvolumes responding markedly better to radiotherapy than poorly supplied regions. Oxygen is essential for tumor growth, yet estimation of local oxygen distribution can be difficult to ascertain in situ, due to chaotic patterns of vasculature. It is possible to avoid this confounding influence by using avascular tumor models, such as tumor spheroids, a much better approximation of realistic tumor dynamics than monolayers, where oxygen supply can be described by diffusion alone. Similar to in situ tumours, spheroids exhibit an approximately sigmoidal growth curve, often approximated and fitted by logistic and Gompertzian sigmoid functions. These describe the basic rate of growth well, but do not offer an explicitly mechanistic explanation. This work examines the oxygen dynamics of spheroids and demonstrates that this growth can be derived mechanistically with cellular doubling time and oxygen consumption rate (OCR) being key parameters. The model is fitted to growth curves for a range of cell lines and derived values of OCR are validated using clinical measurement. Finally, we illustrate how changes in OCR due to gemcitabine treatment can be directly inferred using this model.

No MeSH data available.


Related in: MedlinePlus