Relationship between oxygen and glucose consumption by transplanted tumors in vivo

Gullino, P M; Grantham, Flora H.; Courtney, Anita H.; Losonczy, Ilona

doi:10.1097/00007890-196801000-00019

Cited by 55 publications

(70 citation statements)

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“…However, differences in the spatial and temporal courses of the response exist and must be considered carefully (Figure 6c). In contrast, the present study (Table II), as well as the data of Jahde and Rajewsky (1982), do not confirm the initial report on selective tumour acidification induced by sodium bicarbonate ingestion (Gullino et al, 1965). Thus, selective bicarbonate-induced decrease in interstitial tumour pH appears to be more species-and/or tumour-specific than hyperglycaemia-induced tumour acidification.…”

Section: Resultscontrasting

confidence: 99%

“…pH gradients could be further steepened by poor removal of metabolic waste products, owing to inadequate vascularisation and/or insufficient local blood flow (Jain, 1988). Enhanced glycolysis (Casciari et al, 1992b), higher pCO2 and dissolved carbon dioxide levels (Gullino et al, 1965), and lower bicarbonate concentration (Gullino et al, 1965) in the interstitium would then all contribute to decreasing pH values away from the blood vessel. Interestingly, not all pH profiles were symmetric about the midpoint of the intervessel distance.…”

Section: Resultsmentioning

confidence: 99%

“…Tumour pH has traditionally been measured with techniques which either (1) are invasive [H+-sensitive electrodes (Ashby, 1966)]; (2) do not provide sufficient spatial resolution [e.g. nuclear magnetic resonance (Daly and Cohen, 1989), positron emission tomography (Hawkins and Phelps, 1988), implantable microchambers (Gullino et al, 1965)]; (3) are not adequate for repeated measurements at a given location (electrodes, microchambers); or (4) do not provide a quantitative analysis of tumour pH with respect to the local haemodynamics.…”

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confidence: 99%

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Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose on spatial and temporal gradients

Dellian

Helmlinger²,

Yuan³

et al. 1996

Br J Cancer

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Summary Tumour pH plays a significant role in cancer treatment. However, because of the limitations of the current measurement techniques, spatially and temporally resolved pH data, obtained non-invasively in solid tumours, are not available. Fluorescence ratio imaging microscopy (FRIM) has been used previously for noninvasive, dynamic evaluation of pH in neoplastic tissue in vivo (Martin GR, Jain RK 1994, Cancer Res., 54, 5670 -5674

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Section: Resultscontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose on spatial and temporal gradients

Dellian

Helmlinger²,

Yuan³

et al. 1996

Br J Cancer

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“…As the tumour mass increases, passive diffusion is no longer adequate to supply metabolic demands (Vaupel et al, 1989). Tumours therefore induce their own microcirculation (angiogenesis) but despite this, areas with low levels of oxygen and essential nutrients persist (Gullino et al, 1967;Wendling et al, 1984). Glucose levels in normal tissues are approximately 5 mM, whereas values for tumours are usually between 0 to 2 mM (Gullino et al, 1967).…”

mentioning

confidence: 99%

“…Tumours therefore induce their own microcirculation (angiogenesis) but despite this, areas with low levels of oxygen and essential nutrients persist (Gullino et al, 1967;Wendling et al, 1984). Glucose levels in normal tissues are approximately 5 mM, whereas values for tumours are usually between 0 to 2 mM (Gullino et al, 1967). Low tumour glucose levels are exacerbated because tumour cells preferentially metabolise glucose by either aerobic or anaerobic glycolysis, rather than by oxidative phosphorylation (Warberg, 1956).…”

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confidence: 99%

Aminolaevulinic acid-induced photodynamic therapy: cellular responses to glucose starvation

et al. 2002

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Photodynamic therapy is a cancer treatment based on the interaction of light, oxygen and a photosensitiser. Protoporphyrin. IX is an endogenous photosensitiser derived from the pro-drug aminolaevulinic acid. Tumours contain areas of hypoxia and hypoglycaemia. Tumour cells adapt to these conditions by stress protein induction which may induce resistance to cancer therapies. The effect of chronic hypoglycaemia on sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro was studied in MCF-7, human breast cancer cells. Following chronic exposure to 0, 1 or 25 mM, glucose, cells were treated with aminolaevulinic acid and the generation of intracellular protoporphyrin. IX measured by spectrofluorimetry. Aminolaevulinic acid-induced photodynamic therapy sensitivity was compared between cells following chronic exposure to 0, 1 or 25 mM glucose. Percentage cell survival was determined by clonogenic assay. Cells cultured in low glucose generated higher levels of protoporphyrin IX compared to standard glucose medium (0 mM glucose: 0.88610 75 ng cell 71 , 1 mM: 0.86610 75 ng cell 71 , 25 mM: 0.605610 75 ng cell 71 , P50.05). However, photodynamic therapy sensitivity was reduced in glucose deprived cells (0 mM glucose: 61% survival, 1 mM: 80.5% and 25 mM: 39.6%, P50.05). Chronic exposure to low glucose induces photodynamic therapy resistance despite increased intracellular concentrations of protoporphyrin IX and may reflect cellular adaptation to chronic glucose deprivation.

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Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cell masses

Panteli

Forbes

2016

Biotech & Bioengineering

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Tumor heterogeneity makes cancer difficult to treat. Many small molecule cancer drugs target rapidly dividing cells on the periphery of tumors but have difficulty in penetrating deep into tumors and are ineffective at treating entire tumors. Targeting both rapidly dividing and slower growing regions of tumors is essential to effectively treat cancer. A cancer drug carrier that penetrates deep into tumors and identifies metabolically activity could supply treatment to those areas based on the local microenvironment. We hypothesized that glucose sensing bacteria could identify sugar gradients in solid tumors. To test this hypothesis, a genetic circuit was designed to trigger expression of a green fluorescent protein (GFP) reporter through the chemotaxis-osmoporin fusion protein, Trz1, a receptor for sensing glucose and ribose sugars. E. coli equipped with the Trz1-GFP expression system, were administered to an in vitro model of a continuously perfused tumor tissue that mimics systemic delivery and clearance of bacteria through a blood vessel adjacent to a solid tumor. The level of GFP expressed, per bacterium, was time independent and indicated the glucose concentration as a function of penetration depth within the microfluidic tumors. The measured glucose concentration, correlated (P-value = 2.6×10−5) with tumor cell viability as a function of depth. Mathematical analysis predicted drug delivery by glucose-sensing bacteria would eliminate a higher percentage of the viable tumor cell population than a systemically administered drug. Glucose-sensing bacteria could deliver cancer therapies with increased drug penetration and nutrient-dependent dosing to continuously treat viable regions of cancer tissue that have a higher prevalence for metastatic dissemination.

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Relationship between oxygen and glucose consumption by transplanted tumors in vivo

Cited by 55 publications

References 0 publications

Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose on spatial and temporal gradients

Fluorescence ratio imaging of interstitial pH in solid tumours: effect of glucose on spatial and temporal gradients

Aminolaevulinic acid-induced photodynamic therapy: cellular responses to glucose starvation

Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cell masses

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