pH-dependent antitumor activity of proton pump inhibitors against human melanoma is mediated by inhibition of tumor acidity.
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...Therefore, inhibition of the H pump can be a new strategy for cancer treatment [117-119]....
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"pH-dependent antitumor activity of ..." refers background in this paper
...Acidity of human solid tumors is involved in tumor progression and malignancy, mostly by inducing a selection of cells adapted through an altered metabolism to survive in hostile conditions.(2) Recent in vivo studies on animal models and also in patients with oral cancer have shown an acidic extracellular pH (pHe) and neutral-to-alkaline intracellular pH (pHi) in tumor lesions....
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...The adaptive response to metabolic stress occurring in cancer cells includes indeed the upregulation of proton extrusion,(2,43,44) which represents a detoxification mechanism significantly contributing to tumor microenvironment acidification.(2) We showed in previous reports that inhibition of proton pumps by PPI impairs Figure 4....
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...Tumor cell metabolism is being nowadays object of renewed consideration for better understanding of cancer biology and therapeutic strategies.(2,43) The adaptive response to metabolic stress occurring in cancer cells includes indeed the upregulation of proton extrusion,(2,43,44) which represents a detoxification mechanism significantly contributing to tumor microenvironment acidification....
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...This may have important consequences not only on the capacity of malignant cells to proliferate and survive in acidic conditions but also on distribution and penetration of chemotherapeutics in tumor microenvironment and tumor cells.(3,5,48) Consistent with the derangement of tumor pH gradients, ESOM clearly inhibited tumor growth and dramatically prolonged survival of melanoma-bearing animals....
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