----- Original Message -----
From: "Paleo Phil" <[log in to unmask]>
> Cordain says that urine pH can drop to 5 on an acidifying diet, and
> calcium is leached to keep it at 5 when the pH drops further.
>
>
A high acid diet is not only implicated in osteoporosis, it contributes to
cancer growth. Cancer loves an acid environment. So... when we eat paleo
(no grains or dairy) we can balance the acidic meat in our diet w/ veg &
fruit. The average American diet is quite acidic compared to ours.
Kath (small breast cancer tumor 7+ yrs. ago)
Robert J. Gillies
Professor of Biochemistry, Physiology and Radiology
Ph.D. 1979, University of California, Davis
Web Site: Laboratory Homepage
Tumor Metabolism
Research Interests
The research in my group centers on investigating cancer cell and
tumor physiology and metabolism using non-invasive imaging and spectroscopic
methods. The results we have obtained are important to the basic mechanisms
of carcinogenesis, as well as to cancer diagnosis and treatment. Cancer is
often characterized as a genetic disease, since it invariably results from
genomic alterations or mutations. However, only 20% of cancers are clearly
heritable, meaning that the majority of cancers have environmental triggers.
We have shown that the environmental (interstitial) pH of tumors is quite
acidic. This was determined using Nuclear Magnetic Resonance Spectroscopy
(MRS) of human tumors grown in SCID mice. Using magnetic resonance imaging
(MRI) we are determining the relationship between angiogenesis, the
metabolism and low pH in tumors. This acidic pH affects therapeutic efficacy
and may impact on carcinogenesis itself. A major research project in my lab
is focused on improving measurement of acid pH by MRS and defining the
impact of acid pH on chemotherapy. Acidic pH makes tumors physiologically
resistant to weakly basic chemotherapeutic drugs, such as doxorubicin
(adriamycin). Raising the tumor pH reverses this resistance. We have also
shown that this acid pH induces tumor cells to become more invasive, which
is a hallmark of malignancy. Transfection of metastatic cells with nm23,
which inhibits metastasis, has a significant impact on cellular lipid
metabolism and cellular pH homeostasis. Changes in lipid metabolism is an
important diagnostic marker for cancer progression.
Cell pH is regulated by three distinct families of transporters: Na/H
exchange, bicarbonate transport and proton ATPases. A significant number of
human tumor cells express Vacuolar-type H(+)-ATPases (V-ATPase) in their
plasma membranes. We have cloned one of the subunits of this pump from human
cDNA libraries and are using expression clones to raise antibodies against
extracellular epitopes of this pump. Research using antibodies which
recognize these extracellular epitopes suggests that these ATPases are
constantly and rapidly turned over between intracellular organelles and the
cell surface. This activity could have a significant effect on resistance of
tumor cells to weakly basic chemotherapeutic drugs, such as adriamycin
doxorubicin) or mitoxantrone.
Recent Publications
Gillies RJ, Bhujwalla ZM, Evelhoch J, Garwood M, Neeman M, Robinson
SP, Sotak, CH and Van Der Sanden B (2000) Applications of Magnetic Resonance
in Model Systems: Tumor Biology and Physiology. Neoplasia 2:139-151
Evelhoch JL, Gillies RJ, Karczmar GS, Koutcher JA, Maxwell RJ,
Nalcioglu O, Raghunand N, Ronen SM, Ross BD and Swartz HM. (2000)
Applications of Magnetic Resonance in Model Systems: Cancer Therapeutics.
Neoplasia 2, 152-165.
Pilatus U, Ackerstaff E, Artemov D, Mori N, Gillies RJ and Bhujwalla
ZM (2000) Imaging Prostate Cancer Invasion with Multi-Nuclear Magnetic
Resonance Methods: The Metabolic Boyden Chamber: Neoplasia 2:273-279
Raghunand N and Gillies RJ (2000) pH and drug resistance in tumors.
Drug Resistance Updates 3:39-47
Gillies RJ, Bhujwalla ZM, Stubbs M, Griffiths JM (2001) The Tumor
Microenvironment: Causes and Consequences of hypoxia and acidity. Novartis
Foundation Symposium 240. RJ Gillies (chair)
Raghunand N, Mahoney B, Van Sluis R, Baggett B, Gillies RJ. (2001)
Acute metabolic alkalosis enhances response of C3H mouse mammary tumors to
the weak-base mitoxantrone. Neoplasia 3:227-235.
Raghunand N and Gillies RJ (2001) pH and Chemotherapy. Novartis Fdn.
Symposium 240: 199-211
Gillies RJ (2001) The Tumour Microenvironment: Causes and Consequences
of Hypoxia and Acidity. Novartis Foundation Symposium 240. John Wiley &
Sons, Ltd., England.
Gillies RJ (2001) Causes and consequences of hypoxia and acidity in
tumors. Trends Mol. Med. 7:47-49
Gillies RJ and Lynch RM (2001) Frontiers in the measurement of pH in
vivo. Novartis Fdn. Symp. 240:7-18
Gillies RJ and Raghunand N (2001) Nuclear Magnetic Resonance (NMR)
Spectroscopy in the Study of Whole-Animal Metabolism. Encyclopedia of Life
Sciences 1-6.
Bhujwalla ZM, Artemov D, Aboagye E, Ackerstaff E, Gillies RJ,
Natarajan K and Solaiyappan M (2001) The Physiological Environment in Cancer
Vascularization, Invasion and Metastasis. Novartis Fdn. Symp. 240:23-37
Bhujwalla ZM, Artemov D, Ballesteros P, Cerdan S, Gillies RJ and
Solaiyappan M. (2002) Combined vascular and extracellular pH imaging of
solid tumors. NMR in Biomedicine 15:114-119.
Gillies RJ, Raghunand N, Karczmar G and Bhujwalla ZM (2002) MR Imaging
of the tumor microenvironment. J Magn. Reson. Imaging 16:430-450.
Gillies RJ (2002) In vivo Molecular Imaging. J. Cell. Biochem. (suppl)
39: 231-238.
Jennings D, Hatton N, Trouard T, Galons J-P, Guo J, Baggett B, and
Gillies RJ (2002) Changes in water mobility measured by diffusion MRI
predicts the magnitude of response of prostate cancer xenografts to Taxotere
chemotherapy. Neoplasia 4:255-260.
Raghunand N, Howison CM, Zhang S, Sherry AD, Gillies RJ (2003) Renal
and Systemic pH Imaging by Contrast-Enhanced MRI. Magn. Reson. Med. 49:
249-257.
Morse DL and Gillies RJ (2003) Choline containing compounds as
diagnostic, prognostic and therapeutic response indicators for breast
cancer. MRS and MRI in Oncology. N.R. Jagannathan, ed. Jaypee Brothers
Medical Publishers, New Delhi (in press)
Schornack PA and Gillies RJ (2003) Contributions of metabolism and H+
diffusion to the acidic pH of tumors. Neoplasia 5: 135-145.
Gillies RJ and Hruby VH (2003) Expression-Driven Reverse Engineering
of Targeted Imaging and Therapeutic Agents. Expert Opinion on Therapeutic
Targets 7: 137-139.
Contact Information
Mailing:
Dr. Robert J. Gillies, Professor
Department of Biochemistry & Molecular Biophysics
University of Arizona
Arizona Cancer Center
1515 N. Campbell #0985
Tucson AZ 85724
Telephone: 520-626-5050, -5052
Fax: 520-621-5051
[log in to unmask]
|
