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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
1999-6-24
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pubmed:abstractText |
The extracellular (interstitial) pH (pHe) of solid tumours is significantly more acidic compared to normal tissues. In-vitro, low pH reduces the uptake of weakly basic chemotherapeutic drugs and, hence, reduces their cytotoxicity. This phenomenon has been postulated to contribute to a 'physiological' resistance to weakly basic drugs in vivo. Doxorubicin is a weak base chemotherapeutic agent that is commonly used in combination chemotherapy to clinically treat breast cancers. This report demonstrates that MCF-7 human breast cancer cells in vitro are more susceptible to doxorubicin toxicity at pH 7.4, compared to pH 6.8. Furthermore 31P-magnetic resonance spectroscopy (MRS) has shown that the pHe of MCF-7 human breast cancer xenografts can be effectively and significantly raised with sodium bicarbonate in drinking water. The bicarbonate-induced extracellular alkalinization leads to significant improvements in the therapeutic effectiveness of doxorubicin against MCF-7 xenografts in vivo. Although physiological resistance to weakly basic chemotherapeutics is well-documented in vitro and in theory, these data represent the first in vivo demonstration of this important phenomenon.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-10796075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-13298683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-1333263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-1676902,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-1996613,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-2545340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-27851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-3205159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-3812988,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-6097949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-7083221,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-7909602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-8611717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9049456,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9106927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9216640,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9220288,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9296948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9422471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9584137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10362108-9890558
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0007-0920
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
80
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1005-11
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10362108-Animals,
pubmed-meshheading:10362108-Breast Neoplasms,
pubmed-meshheading:10362108-Cell Division,
pubmed-meshheading:10362108-Doxorubicin,
pubmed-meshheading:10362108-Female,
pubmed-meshheading:10362108-Humans,
pubmed-meshheading:10362108-Hydrogen-Ion Concentration,
pubmed-meshheading:10362108-Magnetic Resonance Spectroscopy,
pubmed-meshheading:10362108-Mice,
pubmed-meshheading:10362108-Mice, SCID,
pubmed-meshheading:10362108-Neoplasm Transplantation,
pubmed-meshheading:10362108-Sodium Bicarbonate,
pubmed-meshheading:10362108-Survival Rate,
pubmed-meshheading:10362108-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Enhancement of chemotherapy by manipulation of tumour pH.
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pubmed:affiliation |
Arizona Cancer Center, Tucson 85724-5024, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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