Cellular pH gradient in tumor versus normal tissue : Potential exploitation for the treatment of cancer

Although limited data exist, electrode-measured pH values of human tumors and adjacent normal tissues, which are concurrently obtained by the same investigator in the same patient, consistently show that the electrode pH (believed to primarily represent tissue extracellular pH) is substantially and...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1996-03, Vol.56 (6), p.1194-1198
Main Authors: GERWECK, L. E, SEETHARAMAN, K
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacokinetics
Biological and medical sciences
Brain - metabolism
Brain Chemistry
Brain Neoplasms - chemistry
Brain Neoplasms - drug therapy
Brain Neoplasms - metabolism
Cell Membrane - metabolism
General aspects
Glioblastoma - chemistry
Glioblastoma - drug therapy
Glioblastoma - metabolism
Humans
Hydrogen-Ion Concentration
Medical sciences
Microelectrodes
Neoplasms - chemistry
Neoplasms - drug therapy
Neoplasms - metabolism
Pharmacology. Drug treatments
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Summary:Although limited data exist, electrode-measured pH values of human tumors and adjacent normal tissues, which are concurrently obtained by the same investigator in the same patient, consistently show that the electrode pH (believed to primarily represent tissue extracellular pH) is substantially and consistently lower in the tumor than in normal tissue. In contrast, the 31P-magnetic resonance spectroscopy estimated that intracellular pH is essentially identical or slightly more basic in tumor compared to normal tissue. As a consequence, the cellular pH gradient is substantially reduced or reversed in tumor compared to normal tissue: in normal tissue the extracellular pH is relatively basic, and in tumor tissue the magnitude of the pH gradient is reduced or reversed. The difference provides an exploitable avenue for the treatment of cancer. The extent to which drugs exhibiting weakly acid or basic properties are ionized is strongly dependent on the pH of their milieu. Weakly acidic drugs which are relatively lipid soluble in their nonionized state may diffuse freely across the cell membrane and, upon entering a relatively basic intracellular compartment, become trapped and accumulate within a cell, leading to substantial differences in the intracellular/extracellular drug distribution between tumor and normal tissue for drugs exhibiting appropriate pKas.
ISSN:0008-5472
1538-7445