Theoretical Simulation of Oxygen Transport to Tumors by Three-Dimensional Networks of Microvessels

Secomb, Timothy W.; Hsu, Richard; Braun, Rosemary; Ross, Julia M.; Gross, Joseph F.; Dewhirst, Mark W.

doi:10.1007/978-1-4615-4863-8_74

Cited by 84 publications

(71 citation statements)

References 7 publications

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“…Oxygen consumption rate, vascular density and vascular architecture are among the main physiologic determinants of oxygen transport in tumors [10,21]. In this paper, we demonstrate that all three features are affected by Her2/neu overexpression.…”

Section: Discussionmentioning

confidence: 52%

“…Oxygen consumption rates for proliferating cells are approximately 3-5-fold higher than that of quiescent cells [12,22]. This 20% difference in proliferation could easily induce a large difference in hypoxia based on previous modeling by Secomb et al [10].…”

Section: Discussionmentioning

confidence: 83%

“…The poorer oxygenation is a result of either inefficiencies in oxygen transport created by lower vascular density, more irregular vascular geometry or tumor cell proliferation [10]. The results of the MDVS are helpful in this regard.…”

Section: Discussionmentioning

confidence: 99%

“…The factors that contribute most to limiting oxygen transport are low vascular density coupled with irregular geometry and oxygen consumption that is out of balance with supply [9,10]. Oxygen consumption rates in proliferating cells are 3-5 times greater than cells in G o [11,12], and variations in oxygen consumption rate of this order of magnitude would be expected to completely dominate oxygen transport, producing hypoxic tissue [9].…”

Section: Introductionmentioning

confidence: 99%

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Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Hardee

Eapen²,

Rabbani

et al. 2008

Cancer Chemother Pharmacol

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Purpose Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25-30% of breast tumors. Tumors that are Her2 + may have an altered state of oxygenation, relative to Her2 -tumors, due to differences in tumor growth rate and angiogenesis. Methods Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2 + and Her2 -MCF7 xenograft tumors.Results Treatment with trastuzumab in Her2 + tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her2 + tumors. The Her2 + xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture). Conclusions These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Hardee

Eapen²,

Rabbani

et al. 2008

Cancer Chemother Pharmacol

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“…The gene chip analysis showed in Table 2 confirmed that the BT-20-HNO cell line was more glycolytic than the 'parent' cell line (see "Gene chip analysis"). Prior work reported presumptive evidence of a conferred selective growth advantage for these tumor cells [26,29].…”

Section: Cell Viability Glycolysis Level Production and Acid Resistmentioning

confidence: 99%

Part III. Molecular changes induced by high nitric oxide adaptation in human breast cancer cell line BT-20 (BT-20-HNO): a switch from aerobic to anaerobic metabolism

et al. 2012

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Nutrient deprivation and reactive oxygen species (ROS) play an important role in breast cancer mitochondrial adaptation. Adaptations to these conditions allow cells to survive in the stressful microenvironment of the tumor bed. This study is directed at defining the consequences of High Nitric Oxide (HNO) exposure to mitochondria in human breast cancer cells. The breast cancer cell line BT-20 (parent) was adapted to HNO as previously reported, resulting in the BT-20-HNO cell line. Both cell lines were analyzed by a variety of methods including MTT, LDH leakage assay, DNA sequencing, and Western blot analysis. The LDH assay and the gene chip data showed that BT-20-HNO was more prone to use the glycolytic pathway than the parent cell line. The BT-20-HNO cells were also more resistant to the apoptotic inducing agent salinomycin, which suggests that p53 may be mutated in these cells. Polymerase chain reaction (PCR) followed by DNA sequencing of the p53 gene showed that it was, in fact, mutated at the DNA-binding site (L194F). Western blot analysis showed that p53 was significantly upregulated in these cells. These results suggest that free radicals, such as nitric oxide (NO), pressure human breast tumor cells to acquire an aggressive phenotype and resistance to apoptosis. These data collectively provide a mechanism by which the dysregulation of ROS in the mitochondria of breast cancer cells can result in DNA damage.Keywords Breast cancer . Nitric oxide . p53 . Reactive oxygen species (ROS) . Glycolysis and apoptosis . Aerobic and anaerobic metabolisms

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MR imaging of tumor microcirculation: Promise for the new millenium

Taylor

Tofts

Port

et al. 1999

J. Magn. Reson. Imaging

207

114

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Theoretical Simulation of Oxygen Transport to Tumors by Three-Dimensional Networks of Microvessels

Cited by 84 publications

References 7 publications

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors

Part III. Molecular changes induced by high nitric oxide adaptation in human breast cancer cell line BT-20 (BT-20-HNO): a switch from aerobic to anaerobic metabolism

MR imaging of tumor microcirculation: Promise for the new millenium

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