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Abstract:"Cells maintain intracellular pH (pHi) within a narrow range (7.1–7.2) by controlling membrane proton pumps and transporters whose activity is set by intra-cytoplasmic pH sensors." p.1 left column:"The physical microenvironment of solid tumors is heterogeneous. A combination of poor vascular perfusion, regional hypoxia, and increased flux of carbons through fermentative glycolysis leads to extracellular acidosis in solid tumors with extracellular pH (pHe) values as low as 6.5 (Hashim et al., 2011)." p.2 caption to figure 1:"Reversed extracellular and intracellular pH in cancer cells compared to normal cells: Cancer cells have a reversed pH gradient compared with normal differentiated cells that is cancer cells have a higher pHi and a lower pHe than normal cells in acute acidosis conditions. The pHe becomes even lower (~6.7) in chronic acidosis. This disruption facilitates the adaptive behaviors of cancer cells such as cytoskeleton remodeling and directed migration, apoptosis evasion, extracellular matrix (ECM) remodeling, invasion, and metastasis." p.7 left column bottom paragraph:"Historically, the effect of extracellular acidosis had been thought to be transduced via acidification of the pHi. However, cells in general, and cancer cells in particular, have redundant and highly active proton exporting mechanisms to maintain the pHi within tight bounds (7.2–7.4) even in the presence of severe extracellular acidosis." [wiki]:"Acidosis is an increased acidity in the blood and other body tissue (i.e. an increased hydrogen ion concentration)." "Ductal carcinoma in situ (DCIS), also known as intraductal carcinoma, is a pre-cancerous or non-invasive cancerous lesion of the breast." |