Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2018 Oct 16;115(42):10548-10550.
doi: 10.1073/pnas.1814212115. Epub 2018 Oct 9.

A potential solution for eliminating hypoxia as a cause for radioresistance

Mark W Dewhirst  1
Affiliations
Comment

A potential solution for eliminating hypoxia as a cause for radioresistance

Mark W Dewhirst. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The author declares no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Sensitivity study examining three methods to reduce tumor hypoxia. This sensitivity study used oxygen transport modeling with Green’s functions to compare three methods for eliminating hypoxia in tumors. The Green’s function method allows for input of actual experimental data: (i) vascular geometry; (ii) flow direction, flow velocity, and vascular pO2 of the vascular segments within the network; and (iii) oxygen consumption rate. The Green’s function computes the pO2 at each location within the field, assuming O2 diffusion from the microvessels. This simulation used confocal imaging to obtain vascular geometry from a tumor growing in skin fold window chamber (Left). Baseline oxygen consumption rate of 1.5 cm3 O2·100 g−1·min−1 was measured previously. Center depicts the network from the bottom, where the feeding vessels are located (vascular pO2 = 50 mmHg). The baseline condition for the central plane of the 500-μm × 500-μm × 200-μm tissue cube is 125 μm from the feeding vessels. Note that the pO2 of this plane is not influenced by the feeding vessels because distance between the plane and these vessels is near the diffusion distance of oxygen. The pO2 distribution depicts radial gradients of oxygen concentration from the vasculature, with significant variation, from near zero, to a maximum close to that of the feeding vessels (40 mmHg). The sensitivity study addressed the question of what relative change in vascular pO2 (Prel), flow rate (Qrel), or oxygen consumption rate (Mrel) would be required to reduce the hypoxic fraction to zero. Right shows the predictions. At baseline, the hypoxic fraction (percent volume <1 mmHg) is ∼12%. Increasing vascular pO2 required a 10× increase in O2 content of breathing gas, above air breathing conditions to eliminate hypoxia. This translates to hyperbaric treatment at 2 atm O2. A threefold increase in flow velocity is of intermediate efficiency in eliminating hypoxia. However, the most efficient means to eliminate hypoxia is by reducing oxygen consumption rate by 30%. Mrel, Prel, and Qrel all compared to the baseline condition, as depicted in Center. Left and Right reprinted with permission from ref. , Springer Nature: Advances in Experimental Medicine and Biology, copyright (1998). Center has not been published previously.
See this image and copyright information in PMC

Comment on

References

    1. Benej M, et al. Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism. Proc Natl Acad Sci USA. 2018;115:10756–10761. - PMC - PubMed
    1. Wouters BG, Brown JM. Cells at intermediate oxygen levels can be more important than the “hypoxic fraction” in determining tumor response to fractionated radiotherapy. Radiat Res. 1997;147:541–550. - PubMed
    1. Thomlinson RH, Gray LH. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955;9:539–549. - PMC - PubMed
    1. Vaupel P, Mayer A. Hypoxia in cancer: Significance and impact on clinical outcome. Cancer Metastasis Rev. 2007;26:225–239. - PubMed
    1. Nordsmark M, et al. Prognostic value of tumor oxygenation in 397 head and neck tumors after primary radiation therapy. An international multi-center study. Radiother Oncol. 2005;77:18–24. - PubMed

LinkOut - more resources