Atemgaswechsel und Glucosestoffwechsel von Tumoren (DS-Carcinosarkom) in vivo

Vaupel, Peter; Günther, H.; Grote, J.; Aumüller, Gerhard

doi:10.1007/bf02045829

Cited by 31 publications

(17 citation statements)

References 15 publications

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“…The reduction of blood flow per unit mass found for many rodent tumours (Vaupel, 1974;Gullino, 1975) leads to a restricted oxygen supply and thus to the development of hypoxic and anoxic areas in malignant tumours . Since the diffusion distance for glucose seems to be larger than that for 02 in tumour tissue (Kallinowski & Vaupel, 1986), hypoxic tumour cells can still cleave glucose to lactic acid for energy production, thus causing tumour acidosis.…”

Section: Resultsmentioning

confidence: 99%

pH distributions in spontaneous and isotransplanted rat tumours

Kallinowski¹,

Vaupel²

1988

Br J Cancer

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Section: Resultsmentioning

confidence: 99%

pH distributions in spontaneous and isotransplanted rat tumours

Kallinowski¹,

Vaupel²

1988

Br J Cancer

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“…10 4 cells ml À1 ). This tumour was originally chemically induced in rats and arose in the auditory canal (Vaupel, 1974). Experimentation had previously been approved by the regional Ethics Committee, and was conducted according to the German Law for Animal Protection of 1987.…”

Section: Animals and Tumoursmentioning

confidence: 99%

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

et al. 2003

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The possibility of enhancing aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) by simultaneous application of localised hyperthermia (HT) was evaluated. Treatments of rat DS-sarcomas included: (i) control, (ii) ALA administration (375 mg kg À1 , i.p.), no illumination, (iii) 'nonthermal' illumination, (iv) ALA-PDT: that is, ALA administration, 'nonthermal' illumination, (v) localised HT, 431C, 60 min (vi) ALA-PDT þ HT: ALA administration with full spectrum irradiation resulting in ALA-PDT and HT. Tumour volume was monitored for 90 days or until a target volume (3.5 ml) was reached. No differences were seen between the first three groups, with all tumours reaching the target volume by 8 -11 days. A total of 13 and 15% of tumours did not reach the target volume by day 90 following HT or ALA-PDT treatment, respectively. ALA-PDT þ HT showed the greatest antitumour effect (P ¼ 0.0001), with 61% of the tumours not reaching the target volume. Viability and in vitro growth were also assessed in cells from tumours excised after treatment. ALA-PDT þ HT reduced the fraction of viable tumour cells by 85%, and in vitro culture showed pronounced growth delay compared to control cells. These results demonstrate an enhanced antitumour effect upon ALA þ HT, which appears to involve direct cell toxicity rather than solely vascular damage.

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“…15 is shown in Figure IA Krogh radius (gm) Figure 6 Plot of the relative values of the Po2 (%) (-A-) and [glucose] (%) (-A-) in glioma tissue (y-axis) and their Krogh radii r (x-axis) for one perfused vessel (x = 0) calculated with use of the following parameters: Oxygen (Kallinowski et al, 1987;Groebe et al, 1988;Dewhirst et al, 1994): mean Po2 = approximately 70 mmHg (mean Po2 vessel), mean consumption rate gliomas (Vaupel et al, 1989b): 0.011 ml g-1 min-', radius of tissue cylinder: 0.01 05 cm, Krogh's diffusion constant: 2.5 x 10-ml cm-' min-' mmHg. Glucose (Vaupel, 1974;Kallinowski et al, 1987) Standard deviations were mostly larger than mean ivds, with the exception of most E98 tumours, which showed a more homogeneously perfused vessel distribution. Therefore, the mean ivd can only be used as a rough indication for differences in the ivd distribution between tumours.…”

Section: Vascular Morphometrical Analysis Of Perfused Vessels and 31pmentioning

confidence: 82%

“…The mean consumption rate of oxygen and glucose was found to be equal in high-grade gliomas, which means an increased aerobic glycolytic activity and/or an increased activity of the pentose phosphate shunt for DNA synthesis (Ikezaki et al, 1992) Rough estimations of the oxygen and glucose Krogh radii is possible, using mean consumption rates, mean concentrations in perfused vessels and constant diffusion coefficients ( Figure 6). The Krogh radii are approximately 100 gm for oxygen and approximately 200 gm for glucose (Vaupel, 1974;Kallinowski et al, 1987;Groebe, 1988;Vaupel et al, 1989b;Dewhirst et al, 1994). In vivo, a large distribution of Krogh radii will be found, depending on: (a) the distance in a perfused capillary from the inlet, because the po2 and the glucose concentration in a capillary decreases between the inlet and outlet; (b) further, the energy metabolism and the related consumption rates of tumour cells may be heterogeneous, i.e.…”

Section: Discussionmentioning

confidence: 99%

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In vivo 31P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice

Sanden

Rijken²,

Heerschap³

et al. 1997

Br J Cancer

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Summary The relationship between the bioenergetic status of human glioma xenografts in nude mice and morphometric parameters of the perfused vascular architecture was studied using 31p magnetic resonance spectroscopy (MRS), fluorescence microscopy and twodimensional digital image analysis. Two tumour lines with a different vascular architecture were used for this study. Intervascular distances and non-perfused area fractions varied greatly between tumours of the same line and tumours of different lines. The inorganic phosphate-nucleoside triphosphate (Pi/NTP) ratio increased rapidly as mean intervascular distances increased from 100 gm to 300 ,um. Two morphometric parameters -the percentage of intervascular distances larger than 200 gm (ivd200) and the non-perfused area fraction at a distance larger than 100 ,um from a nearest perfused vessel (areal0o), -were deduced from these experiments and related to the P/NTP ratio of the whole tumour. It is assumed that an aerobic to anaerobic transition influences the bioenergetic status, i.e. the Pi/NTP ratio increased linearly with the percentage of ivd200 and the area100.Keywords: 31p magnetic resonance spectroscopy; fluorescence microscopy; tumour bioenergetic status; vascular morphology Phosphorus magnetic resonance spectroscopy (31P-MRS) studies of the bioenergetic status of tumours have been compared directly with tumour tissue po2 (Vaupel et al, 1989a) and with several physiological parameters that affect pO2 in tumour tissue, such as the intravascular concentration of oxyhaemoglobin (Rofstad et al, 1988) and tumour blood perfusion (Evelhoch et al, 1986). 31P-MRS has been demonstrated to be sensitive to tumour size (Okunieff et al, 1986;Wendland et al, 1992), with an increase in tumour size being supposed to have a negative influence on perfusion-and diffusion-limited oxygen delivery and nutrient delivery (Vaupel, 1996). The global bioenergetic status of a tumour, expressed as the P/NTP ratio, depends on the balance between the oxygen and nutrient supply, and the consumption rates of the tumour cells, which is related to the type of energy metabolism. This balance between supply and consumption determines the critical diffusion distances for oxygen and nutrients in tumour tissue. The total oxygen supply and nutrient supply depends on the tumour microcirculation and on the diffusion geometry.The purpose of this study was to investigate the existence of a possible relationship between the global bioenergetic status and the diffusion geometry of human glioma xenografts in nude mice. A two-dimensional morphometric analysis of the perfused vascular architecture of complete transverse tumour sections was performed. Morphometric parameters, such as the percentage of large intervascular distances and the fraction of non-perfused areas in a tumour section area, are related to the diffusion-limited

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Atemgaswechsel und Glucosestoffwechsel von Tumoren (DS-Carcinosarkom) in vivo

Cited by 31 publications

References 15 publications

pH distributions in spontaneous and isotransplanted rat tumours

pH distributions in spontaneous and isotransplanted rat tumours

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

In vivo 31P magnetic resonance spectroscopy and morphometric analysis of the perfused vascular architecture of human glioma xenografts in nude mice

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