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A compelling opinion piece, in which the authors convincingly argue that the molecular phenotypes of metastatic cancers arose early during carcinogenesis. Although somatic evolution is implied in this work, the environmental nature of the selection pressures are not discussed.
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In this timely review, Semenza describes the relation between HIF1α and the regulation of glycolysis.
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A comprehensive review of extant literature. The authors convincingly document the very high sensitivity and specificity of FdG PET in diagnosing and staging diverse types of metastatic cancers.
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This well-conducted study quantitatively analysed the molecular phenotypes of tumours that had either high or low rates of FdG trapping.
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One of many papers in this issue of the Journal of Bioenergetics and Biomembranes that dealt with the molecular controls of glucose metabolism. In this review, primary data were presented to support the importance and molecular controls of the glucose transporter and its regulation by MYC.
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One of many papers that demonstrates the important role of the glucose transporter in regulating glycolytic flux.
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Provides a cogent argument for the role of hexokinase in regulating glycolytic flux and its regulation by oncogenes and subcellular localization.
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This careful study is one of many that document the diagnostic importance of GLUT1 and glycolysis in carcinomas.
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Determined proton production rates in breast cancer lines with low and high metastatic capability, and related these to glycolytic rate. These rates were used in a reaction–diffusion model to predict steady-state tumour pH values.
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Used spectroscopic imaging to measure the spatial variations in tumour pH, and these were related to vascular perfusion measures in the same tumours.
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Documents that necrosis in tumours occurs at distances from blood vessels and that this was consistent with the oxygen diffusion distances.
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Despite its title, this very well conducted study documents the correlation between pH and oxygenation as they decrease with distances from feeding capillaries.
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Documents the somatic evolutionary pressure mediated by hypoxia.
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Mathematical methods and empirical evidence were used to demonstrate the acid-induced tumour-invasion model for the first time.
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The formal mathematical development of evolutionary game theory in carcinogenesis.
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Introduced the molecular genetic changes that occur during gastrointestinal carcinogenesis and discussed the concept of clonal outgrowth in this context. There was no discussion of environmental selection pressures.
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This work shows, with histopathology, the expression of CA IX and CA XII in carcinoma in situ lesions. These two carbonic anhydrases are sensitive to hypoxia and these data are consistent with significant hypoxia in in situ lesions.
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References 38–46 document the periodic nature of tumour oxygenation.
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References 47–49 deal with pH-induced apoptosis. Grinstein's review concludes that cytoplasmic acidification is unlikely to be part of the apoptosis paradigm, but that externally lowered pH might promote apoptotic cell death.
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References 50–53 describe mechanisms of pH regulation that are documented to be upregulated in cancers.
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Demonstrates that vacuolar H+-ATPase activity is anti-apoptotic.
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References 58–63 describe the role of HIF1α in regulating aerobic and anaerobic glycolysis.
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Describes the observation of increased lactate in non-enhancing grade III gliomas, indicating that metabolic upregulation might precede angiogenesis.
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A comprehensive review describing MRI of clinical and experimental tumours.
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A watershed paper describing the microenvironmental behaviour of lung metastases using a novel microscopy method. This paper challenges the paradigm that extravasation is a necessary component of the metastasis programme.
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Provides clear evidence that pretreatment with acute hypoxia can increase the efficiency of metastasis.
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