Potential role of the glycolytic oscillator in acute hypoxia in tumors

Fru, Leonard Che; Adamson, E; Campos, D; Fain, Sean B.; Jacques, Steven L.; Kogel, Albert J. van der; Nickel, K.P.; Song, C.; Kimple, Randall J.; Kissick, M

doi:10.1088/0031-9155/60/24/9215

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…Tumor glycolysis can oscillate under certain conditions, which has been demonstrated in cells that develop a hypoglycemic phenotype [7][8][9]. This phenomenon is verified through temporary oscillations in the concentration of glycolytic intermediates.…”

Section: Introductionmentioning

confidence: 87%

“…The variation of the control parameter C showed that the sustained periodic behavior occurs in a range of glucose input rate limited by two critical values (0,02 and 0,15 mM min -1 approximately). According to Fru et al [8] this oscillatory domain could be within the physiological range. Values of C less than the lower limit or greater than the upper limit lead the system to a stable steady state.…”

Section: Characterization Of the Autonomous Systemmentioning

confidence: 92%

“…Parameter C was set at 0,0325 mM min -1 a value where the system exhibits sustained periodic oscillations. It was considered that this value represents a physiological flux of glucose, based on the conjecture of Fru et al [8], who stated that glycolytic oscillations could occur in vivo tumors. Then a periodic perturbation was applied to the autonomous model (2.1).…”

Section: Periodic Perturbation Of the Autonomous Model: Nonautonomous Modelmentioning

confidence: 99%

“…This phenomenon is verified through temporary oscillations in the concentration of glycolytic intermediates. Experimental evidence suggests that these oscillations may give certain advantages to cancer, including resistance to therapies [8]. In fact, it is known that periodic behavior gives biological systems certain properties such as greater adaptability, synchronization possibilities and greater resistance to fluctuations and environmental perturbations [10].…”

Section: Introductionmentioning

confidence: 99%

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Phase transitions in tumor growth VII: The effect of periodic glucose pulses and privations in a cancer model

Jp¹,

Silva²,

Rr³

et al. 2019

Integr Cancer Sci Therap

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Tumor glycolysis is a self-organized nonlinear mechanism that can exhibit oscillations under certain conditions. Experimental evidence suggests that glycolytic oscillations may give certain advantages to cancer, including resistance to therapies. A previously developed oscillating glycolysis model was modified with the objective of theoretically evaluating the effect of pulses and periodic glucose deprivations in a frequency range that included values close to the autonomous frequency. The dynamics of the model before the perturbation were characterized. Then the model was perturbed with periodic pulses and deprivations of glucose. The dynamics obtained were characterized and compared with the model before the perturbation. The methods for the characterization of the dynamics were: stability analysis of the steady state, stroboscopic analysis and Lempel-Ziv index; while the cellular energy charge of the simulations was evaluated by the normalized ATP/ADP ratio. The results obtained indicate that periodic glucose pulses can lead to an increase in the energy charge. Surprisingly, sustained increases in glucose influx causes a decrease in the complexity of glycolytic oscillations, but cause increase in the cellular energy charge. On the other hand, periodically depriving the tumor microenvironment of glucose at high perturbation frequencies, regardless of the amplitude of perturbation, prevent the increase in the complexity of glycolytic oscillations and cause a decrease in the cellular energy charge of tumor cells. This strategy can increase the efficacy of antitumor therapies.

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Section: Introductionmentioning

confidence: 87%

Section: Characterization Of the Autonomous Systemmentioning

confidence: 92%

Section: Periodic Perturbation Of the Autonomous Model: Nonautonomous Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Phase transitions in tumor growth VII: The effect of periodic glucose pulses and privations in a cancer model

Jp¹,

Silva²,

Rr³

et al. 2019

Integr Cancer Sci Therap

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“…Also, Baudelet, et al [13] showed periods of approximately 20 minutes using the BOLD-MRI technique. We have previously demonstrated the presence of cyclic hypoxia with a regular periodicity in a bladder cancer xenograft [14,15].…”

Section: Introductionmentioning

confidence: 96%

Interstitial diffuse optical probe with spectral fitting to measure dynamic tumor hypoxia

Fru¹,

Jacques²,

Nickel³

et al. 2020

Biomed. Phys. Eng. Express

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Understanding the dynamic nature of tumor hypoxia is vital for cancer therapy. The presence of oxygen within a tumor during radiation therapy increases the likelihood of local control. We used a novel interstitial diffuse optical probe to make real-time measurements of blood volume fraction and hemoglobin oxygen saturation within a tumor at a high temporal resolution. This device was initially characterized and benchmarked using a customized vessel designed to control hemoglobin oxygen saturation and blood volume in a solution of blood with different concentrations of an oxygen scavenger, tetrakis (hydroxymethyl) phosphonium chloride. The optical device was found to consistently monitor the changes in oxygen saturation and these changes correlated to the concentration of the oxygen scavenger added. In near-simultaneous measurements of blood volume and oxygen saturation in tumor-bearing mice, the changes in blood volume fraction and oxygen saturation measured with the interstitial diffuse optical probe were benchmarked against photoacoustic imaging system to track and compare temporal dynamics of oxygen saturation and blood volume in a patient-derived xenograft model of hypopharyngeal carcinoma. Positive correlations between our device and photoacoustic imaging in measuring blood volume and oxygen saturation were observed.

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