Oxygen diffusivity in tumor tissue (DS-Carcinosarcoma) under temperature conditions within the range of 20?40�C

Grote, J.; Süsskind, R.; Vaupel, Peter

doi:10.1007/bf00582204

Cited by 135 publications

(56 citation statements)

References 30 publications

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“…The 02 diffusion conductivity (K3) in the spheroids, which was derived from the Po2 gradient in the viable zones of the spheroids (MuellerKlieser, 1984), was essentially the same under all growth conditions investigated being 1.85-1.89 x 10-5 cm32 -cCm-1 min-1 atm-'. This value is in good agreement with the values found in solid tumours (Grote et al, 1977). The values obtained for K3 and Q and the data from histological investigation on the thickness of the viable rims allow the theoretical calculation of P02 profiles that are in accordance with the Po2 distributions measured (see Figure 1).…”

Section: Resultssupporting

confidence: 88%

Influence of glucose and oxygen supply conditions on the oxygenation of multicellular spheroids

Mueller‐Klieser¹,

Freyer²,

Sutherland³

1986

Br J Cancer

165

133

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Summary The interrelationship among external 02 and glucose supply, oxygenation status, oxygen consumption rates and cellular viability in tumour microregions was studied using the multicellular spheroid model. For chronic exposure to various supply conditions multicellular EMT6/Ro spheroids were cultured in stirred media equilibrated either with 20% (v/v) or 5% (v/v) oxygen and containing four different glucose concentrations ranging from 0.8mm to 16.5mM. Spheroids were investigated using histology and 02-sensitive microelectrodes for measuring oxygen tension (PO ) values. A chronic decrease of the glucose concentration in the medium is associated with a substantial reduction in the thickness of the viable rim of cells and with a persistent increase in the cellular respiration rate. In general, both viable rim size and respiration are decreased through restriction of 02 supply during spheroid growth at a given external glucose concentration. The 02 consumption in spheroids appears to decrease with increasing spheroid size under most of the growth conditions investigated. These findings provide evidence for a large capacity of the spheroid cells to chronically adapt their metabolic rates to different supply situations. The experimental data and theoretical considerations indicate that necrosis may develop in the centre of these spheroids due to the lack of 02 and/or glucose under some of the growth conditions, but central necrosis can also occur despite sufficient 02 and glucose supply. Consequently, cellular metabolism and viability in tumour microregions may not be determined by the diffusion limitation of O2 or specific substrates alone, such as glucose, but may be influenced by a complex interaction of factors in the micromilieu the majority of which are still unknown.

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Section: Resultssupporting

confidence: 88%

Influence of glucose and oxygen supply conditions on the oxygenation of multicellular spheroids

Mueller‐Klieser¹,

Freyer²,

Sutherland³

1986

Br J Cancer

165

133

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“…In both tumor types, large areas exceeding the diffusion distance of oxygen (the critical diffusion distance for oxygen approximates 120 Am; ref. 26) occurred that were neither necrotic nor hypoxic, as defined by undetectable levels of EF5 staining (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

Spatial Heterogeneity and Oxygen Dependence of Glucose Consumption in R3230Ac and Fibrosarcomas of the Fischer 344 Rat

et al. 2005

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To examine the oxygen-dependence of glucose consumption in solid tumors, we monitored gradients of glucose, lactate, and hypoxia in R3230Ac and FSA tumors growing in Fischer 344 rats. Bioluminescence imaging, detection of Hoechst 33342, and immunostaining of the hypoxia marker EF5 [2-8-N-(2,2,3,3,3-pentafluoropropyl)acetamide] were done in serial tumor slices. Glucose and lactate levels were also determined in liver and blood. Cells were further tested for glucose consumption and lactate production in vitro. In both tumor types, EF5 staining indicated similar maximum levels of hypoxia; the most intense staining occurred in perinecrotic regions. Glucose concentrations were highest in liver, declined from blood to tumor edge, further into vital tumor regions, and were lowest close to necrosis. Glucose was significantly lower in FSA than in R3230Ac tumors. Glucose concentrations in R3230Ac tumors were consistently higher in nonhypoxic than in hypoxic areas, with maximum values equal to systemic blood levels. Glucose in FSA tumors was close to zero, regardless of the presence or absence of hypoxia. Lactate did not differ significantly between the tumor types. FSA cells in culture showed a trend towards higher aerobic glucose consumption versus R3230Ac. Both cell lines increased their lactate production to similar levels under hypoxia. We conclude that both R3230Ac and FSA tumors retain the Pasteur effect, i.e., hypoxia triggers increased glycolysis. However, our results imply that increased aerobic glucose utilization leads to low glucose levels in FSA and a situation where supply limits uptake. This explains the repeatedly observed correlation between tumor blood flow and 18 Fdeoxyglucose uptake. (Cancer Res 2005; 65(12): 5163-71)

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“…where pO 2 (r) ϭ pO 2 at r, pO 2 (s) ϭ pO 2 at the surface, D ϭ oxygen diffusion coefficient for tumor tissue, A ϭ oxygen solubility coefficient for tumor tissue [20], R ϭ radius of the spheroid, r ϭ distance to the center.…”

Section: Methodsmentioning

confidence: 99%

The influence of nickel and cobalt on putative members of the oxygen‐sensing pathway of erythropoietin‐producing HepG2 cells

Porwol

Ehleben

Zierold

et al. 1998

European Journal of Biochemistry

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Cobalt and nickel stimulate, as does hypoxia, the production of erythropoietin (EPO) in HepG2 cells. Under hypoxic conditions, a decrease in the level of intracellular reactive oxygen species (ROS) is thought to stimulate EPO expression. Cobalt and nickel may interact with the putative oxygen sensor by changing the redox state of the central iron atom of heme proteins, similar to the effects of hypoxia. It was investigated, therefore, whether cobalt and nickel interact with hemeproteins or ROS scavenging systems in the control of intracellular ROS level. Cobalt chloride (100 µM, 24 h) oxidized non respiratory as well respiratory hemeproteins and increased the oxygen consumption. In contrast, nickel chloride (300 µM, 24 h) primarily reduced respiratory hemeproteins and decreased the oxygen consumption. In HepG2 cells treated with CoCl 2 , iron and cobalt were localized in cytosolic granules close to the cell nucleus and in mitochondria at concentrations up to 12 mM or 41 mM, respectively. Intracellular nickel was not measurable. Three-dimensional reconstruction of confocal laser microscopy images revealed hot spots of hydroxyl radical generation by a Fenton reaction at the sites of cytosolic iron accumulation. The ᠨOH levels decreased in cobalt-treated (to 81%) as well as in nickel-treated (to 67%) HepG2 cells, accompanied by an increase of EPO expression to 167% and 150%, respectively. Our results underline the importance of ᠨOH formed by a Fenton reaction for triggerimg EPO production. Identification of the primary hemeprotein being the oxygen sensor was not possible due to the antagonistic effects of cobalt and nickel on the redox state of detectable hemeproteins.

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Oxygen diffusivity in tumor tissue (DS-Carcinosarcoma) under temperature conditions within the range of 20?40�C

Cited by 135 publications

References 30 publications

Influence of glucose and oxygen supply conditions on the oxygenation of multicellular spheroids

Influence of glucose and oxygen supply conditions on the oxygenation of multicellular spheroids

Spatial Heterogeneity and Oxygen Dependence of Glucose Consumption in R3230Ac and Fibrosarcomas of the Fischer 344 Rat

The influence of nickel and cobalt on putative members of the oxygen‐sensing pathway of erythropoietin‐producing HepG2 cells

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