Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status of subcutaneous RIF-1 tumors

Nadal‐Desbarats, Lydie; Poptani, Harish; Oprysko, Patricia R.; Jenkins, W. Timothy; Busch, Theresa M.; Nelson, David S.; Glickson, Jerry D.; Koch, Cameron J.; Evans, Sydney M.

doi:10.3892/ijo.21.1.103

Cited by 4 publications

(3 citation statements)

References 29 publications

(34 reference statements)

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“…The region of positive τ i , K trans correlation in the rat gliosarcoma rim coincides with the region of the implanted rat glioma that stains positive with EF5 , a marker for hypoxia . This correlation is also positive for the RIF‐1 tumor , which is known to be highly hypoxic . New results in a rat model of head and neck cancer show extensive overlap of an elevated τ i region with that of EF5 staining .…”

Section: Discussionmentioning

confidence: 84%

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Intratumor mapping of intracellular water lifetime: metabolic images of breast cancer?

et al. 2014

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Shutter-speed pharmacokinetic analysis of [Dynamic-Contrast-Enhanced] DCE-MRI data allows evaluation of equilibrium inter-compartmental water interchange kinetics. The process measured here – transcytolemmal water exchange – is characterized by the mean intracellular water molecule lifetime (τi). The τi biomarker is a true intensive property not accessible by any formulation of the tracer pharmacokinetic paradigm, which inherently assumes it effectively zero when applied to DCE-MRI. We present population-averaged in vivo human breast whole tumor τi changes induced by therapy, along with those of other pharmacokinetic parameters. In responding patients, the DCE parameters change significantly after only one neoadjuvant chemotherapy cycle: while Ktrans [measuring mostly contract agent (CA) extravasation] and kep [CA intravasation rate constant] decrease, τi increases. However, high-resolution, (1 mm)2, parametric maps exhibit significant intra-tumar heterogenity, which is lost by averaging. A typical 400 ms τi value means a trans-membrane water cycling flux of 1013 H2O molecules/s/cell for a 12 µm diameter cell. Analyses of intra-tumor variations (and therapy-induced changes) of τi in combination with concomitant changes of Ve [extracellular volume fraction] inducate the former are dominated by alterations of the equilibrium cell membrane water permeability coefficient, Pw, not of cell size. These can be interpreted in light of literature results showing τi changes are dominated by a Pw(active) component that reciprocally reflects the membrane driving P-type ATPase ion pump turnover. For mammalian cells, this is the Na+,K+-ATPase pump. These results promise the potential to discriminate metabolic and microenvironmental states of regions within tumors in vivo, and their changes with therapy.

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Section: Discussionmentioning

confidence: 84%

“…Though the delivery of glucose is sufficient, it is not metabolized efficiently w.r.t. ATP synthesis .…”

Section: Discussionmentioning

confidence: 99%

Intratumor mapping of intracellular water lifetime: metabolic images of breast cancer?

et al. 2014

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“…MIBG is a known inhibitor of mitochondrial respiration (Smets et al, 1988;Biaglow et al, 1998;Loesberg et al, 1990) and a hyperglycaemia-induced shift to glycolysis has been shown to alter cellular oxygen consumption (Nadal-Desbarats et al, 2002). Therefore, we examined whether the glucose þ MIBG treatment could result in an increase in tumour pO 2 as reported by others (Burd et al, 2001(Burd et al, , 2003.…”

Section: Effects Of Tumour Acidification On Pomentioning

confidence: 87%

Effects of tumour acidification with glucose+MIBG on the spontaneous metastatic potential of two murine cell lines

Kalliomäki

Hill

2004

Br J Cancer

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In addition to hypoxia, acidic extracellular pH (pH e ) is recognised as one of the microenvironmental characteristics of solid tumours. A number of studies have examined ways to increase tumour acidity in order to improve tumour-specific targeting of certain drugs and the effectiveness of hyperthermia. However, previous data have shown that exposure of murine tumour cells to acid conditions in culture can enhance their metastatic potential when injected subsequently into mice, raising the concern that deliberate tumour acidification might increase the probability of metastasis. In this study, we examined the effects of in vivo tumour acidification and hypoxia on the spontaneous metastatic potential of the murine KHT-C fibrosarcoma and B16F1 melanoma cell lines. A tumourspecific increase in extracellular acidity, demonstrated by measurements with pH electrodes, was achieved by daily intraperitoneal injections of meta-iodo-benzylguanidine (MIBG) and/or glucose. This method of tumour acidification during tumour growth did not significantly enhance the spontaneous metastatic potential of the two murine cell lines.

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Tumor Oxygenation and Acidification are Increased in Melanoma Xenografts after Exposure to Hyperglycemia andmeta-Iodo-benzylguanidine

et al. 2003

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Tumor oxygen tension and extracellular pH (pH(e)) are physiological parameters that can be manipulated to improve current cancer therapies. Many human tumors consist of cells that are chronically exposed to low pH(e). Exposure of tumor cells in culture to glucose decreases oxygen consumption (oxygen sparing or Crabtree effect), and while this effect is absent in low pH-adapted tumor cells, it can be restored by combining the respiratory inhibitor meta-iodo-benzylguanidine (MIBG) with glucose (Burd et al., Cancer Res. 61, 5630-5635, 2001). The effects of hyperglycemia and MIBG on tumor oxygen tension and on pH(e) were investigated in human melanoma xenografts in SCID mice. An oral gavage of 1 M glucose (2 g/kg) increased the average blood glucose concentration from <140 mg/dl to approximately 400 mg/dl. Although tumor pH(e) decreased from pH 6.7 to pH 6.5 (P < 0.01) after about 60 min, no change in tumor oxygen tension was observed. However, when oral glucose and MIBG (15 mg/kg) were administered together, oxygen tension increased from 2.8 mmHg to approximately 17 mmHg, and tumor pH(e) decreased from pH 6.7 to pH 6.3 (P < 0.01) after about 115 min. In conclusion, administration of glucose together with MIBG increases tumor oxygen tension and also increases the magnitude and duration of acidification. Hyperglycemia plus MIBG has the potential to improve response to radiation therapy as well as to hyperthermia and some chemotherapies.

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Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status of subcutaneous RIF-1 tumors

Cited by 4 publications

References 29 publications

Intratumor mapping of intracellular water lifetime: metabolic images of breast cancer?

Intratumor mapping of intracellular water lifetime: metabolic images of breast cancer?

Effects of tumour acidification with glucose+MIBG on the spontaneous metastatic potential of two murine cell lines

Tumor Oxygenation and Acidification are Increased in Melanoma Xenografts after Exposure to Hyperglycemia andmeta-Iodo-benzylguanidine

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