Abstract

The optical redox ratio (fluorescence intensity of NADH divided by that of FAD), was acquired for a panel of breast cancer cell lines to investigate how overexpression of human epidermal growth factor receptor 2 (HER2) affects tumor cell metabolism, and how tumor metabolism may be altered in response to clinically used HER2-targeted therapies. Confocal fluorescence microscopy was used to acquire NADH and FAD auto-fluorescent images. The optical redox ratio was highest in cells overexpressing HER2 and lowest in triple negative breast cancer (TNBC) cells, which lack HER2, progesterone receptor, and estrogen receptor (ER). The redox ratio in ER-positive/HER2-negative cells was higher than what was seen in TNBC cells, but lower than that in HER2 overexpressing cells. Importantly, inhibition of HER2 using trastuzumab significantly reduced the redox ratio in HER2 overexpressing cells. Furthermore, the combinatorial inhibition of HER2 and ER decreased the redox ratio in ER+/HER2+ breast cancer cells to a greater extent than inhibition of either receptor alone. Interestingly, trastuzumab had little impact upon the redox ratio in a cell line selected for acquired resistance to trastuzumab. Taken together, these data indicate that the optical redox ratio measures changes in tumor metabolism that reflect the oncogenic effects of HER2 activity within the cell, as well as the response of the cell to therapeutic inhibition of HER2. Therefore, optical redox imaging holds the promise of measuring response and resistance to receptor-targeted breast cancer therapies in real time, which could potentially impact clinical decisions and improve patient outcome.

© 2011 OSA

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2011 (7)

M. A. Jacobs, R. Ouwerkerk, A. C. Wolff, E. Gabrielson, H. Warzecha, S. Jeter, D. A. Bluemke, R. Wahl, and V. Stearns, “Monitoring of neoadjuvant chemotherapy using multiparametric, ²³Na sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer,” Breast Cancer Res. Treat.128(1), 119–126 (2011).
[CrossRef] [PubMed]

L. K. Dunnwald, R. K. Doot, J. M. Specht, J. R. Gralow, G. K. Ellis, R. B. Livingston, H. M. Linden, V. K. Gadi, B. F. Kurland, E. K. Schubert, M. Muzi, and D. A. Mankoff, “PET tumor metabolism in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy: value of static versus kinetic measures of fluorodeoxyglucose uptake,” Clin. Cancer Res.17(8), 2400–2409 (2011).
[CrossRef] [PubMed]

S. P. Li, A. Makris, M. J. Beresford, N. J. Taylor, M. L. W. Ah-See, J. J. Stirling, J. A. d’Arcy, D. J. Collins, R. Kozarski, and A. R. Padhani, “Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy,” Radiology260(1), 68–78 (2011).
[CrossRef] [PubMed]

L. Wang, Q. Zhang, J. Zhang, S. Sun, H. Guo, Z. Jia, B. Wang, Z. Shao, Z. Wang, and X. Hu, “PI3K pathway activation results in low efficacy of both trastuzumab and lapatinib,” BMC Cancer11(1), 248–257 (2011).
[CrossRef] [PubMed]

B. N. Rexer, A.-J. L. Ham, C. Rinehart, S. Hill, N. de Matos Granja-Ingram, A. M. González-Angulo, G. B. Mills, B. Dave, J. C. Chang, D. C. Liebler, and C. L. Arteaga, “Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition,” Oncogene30(40), 4163–4174 (2011).
[CrossRef] [PubMed]

Y. Zhao, H. Liu, Z. Liu, Y. Ding, S. P. Ledoux, G. L. Wilson, R. Voellmy, Y. Lin, W. Lin, R. Nahta, B. Liu, O. Fodstad, J. Chen, Y. Wu, J. E. Price, and M. Tan, “Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism,” Cancer Res.71(13), 4585–4597 (2011).
[CrossRef] [PubMed]

R. W. Cheyne, L. Trembleau, A. McLaughlin, and T. A. Smith, “Changes in 2-fluoro-2-deoxy-D-glucose incorporation, hexokinase activity and lactate production by breast cancer cells responding to treatment with the anti-HER-2 antibody trastuzumab,” Nucl. Med. Biol.38(3), 339–346 (2011).
[CrossRef] [PubMed]

2010 (3)

J. M. Specht, B. F. Kurland, S. K. Montgomery, L. K. Dunnwald, R. K. Doot, J. R. Gralow, G. K. Ellis, H. M. Linden, R. B. Livingston, K. H. Allison, E. K. Schubert, and D. A. Mankoff, “Tumor metabolism and blood flow as assessed by positron emission tomography varies by tumor subtype in locally advanced breast cancer,” Clin. Cancer Res.16(10), 2803–2810 (2010).
[CrossRef] [PubMed]

J. H. Ostrander, C. M. McMahon, S. Lem, S. R. Millon, J. Q. Brown, V. L. Seewaldt, and N. Ramanujam, “Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status,” Cancer Res.70(11), 4759–4766 (2010).
[CrossRef] [PubMed]

F. J. Esteva, D. H. Yu, M. C. Hung, and G. N. Hortobagyi, “Molecular predictors of response to trastuzumab and lapatinib in breast cancer,” Nat Rev Clin Oncol7(2), 98–107 (2010).
[CrossRef] [PubMed]

2009 (2)

T. W. Miller, J. T. Forbes, C. Shah, S. K. Wyatt, H. C. Manning, M. G. Olivares, V. Sanchez, T. C. Dugger, N. de Matos Granja, A. Narasanna, R. S. Cook, J. P. Kennedy, C. W. Lindsley, and C. L. Arteaga, “Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells,” Clin. Cancer Res.15(23), 7266–7276 (2009).
[CrossRef] [PubMed]

K. McLarty, A. Fasih, D. A. Scollard, S. J. Done, D. C. Vines, D. E. Green, D. L. Costantini, and R. M. Reilly, “18F-FDG small-animal PET/CT differentiates trastuzumab-responsive from unresponsive human breast cancer xenografts in athymic mice,” J. Nucl. Med.50(11), 1848–1856 (2009).
[CrossRef] [PubMed]

2008 (2)

S. Basu, W. Chen, J. Tchou, A. Mavi, T. Cermik, B. Czerniecki, M. Schnall, and A. Alavi, “Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization,” Cancer112(5), 995–1000 (2008).
[CrossRef] [PubMed]

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer122(2), 363–371 (2008).
[CrossRef] [PubMed]

2007 (4)

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

C. A. Ritter, M. Perez-Torres, C. Rinehart, M. Guix, T. Dugger, J. A. Engelman, and C. L. Arteaga, “Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network,” Clin. Cancer Res.13(16), 4909–4919 (2007).
[CrossRef] [PubMed]

K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, and R. Bernards, “A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer,” Cancer Cell12(4), 395–402 (2007).
[CrossRef] [PubMed]

K. Kawada, K. Murakami, T. Sato, Y. Kojima, H. Ebi, H. Mukai, M. Tahara, K. Shimokata, and H. Minami, “Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors,” Jpn. J. Clin. Oncol.37(1), 44–48 (2007).
[CrossRef] [PubMed]

2006 (2)

W. Xia, S. Bacus, P. Hegde, I. Husain, J. Strum, L. Liu, G. Paulazzo, L. Lyass, P. Trusk, J. Hill, J. Harris, and N. L. Spector, “A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer,” Proc. Natl. Acad. Sci. U.S.A.103(20), 7795–7800 (2006).
[CrossRef] [PubMed]

J. A. Engelman, J. Luo, and L. C. Cantley, “The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism,” Nat. Rev. Genet.7(8), 606–619 (2006).
[CrossRef] [PubMed]

2005 (4)

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

H. A. Burris, H. I. Hurwitz, E. C. Dees, A. Dowlati, K. L. Blackwell, B. O’Neil, P. K. Marcom, M. J. Ellis, B. Overmoyer, S. F. Jones, J. L. Harris, D. A. Smith, K. M. Koch, A. Stead, S. Mangum, and N. L. Spector, “Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas,” J. Clin. Oncol.23(23), 5305–5313 (2005).
[CrossRef] [PubMed]

M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
[CrossRef] [PubMed]

D. Zhang, L. K. Tai, L. L. Wong, L. L. Chiu, S. K. Sethi, and E. S. Koay, “Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer,” Mol. Cell. Proteomics4(11), 1686–1696 (2005).
[CrossRef] [PubMed]

2004 (1)

C. Cooper, G. Y. Liu, Y. L. Niu, S. Santos, L. C. Murphy, and P. H. Watson, “Intermittent hypoxia induces proteasome-dependent down-regulation of estrogen receptor alpha in human breast carcinoma,” Clin. Cancer Res.10(24), 8720–8727 (2004).
[CrossRef] [PubMed]

2002 (1)

C. L. Vogel, M. A. Cobleigh, D. Tripathy, J. C. Gutheil, L. N. Harris, L. Fehrenbacher, D. J. Slamon, M. Murphy, W. F. Novotny, M. Burchmore, S. Shak, S. J. Stewart, and M. Press, “Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer,” J. Clin. Oncol.20(3), 719–726 (2002).
[CrossRef] [PubMed]

2001 (3)

C. M. Cheng, M. Cohen, J. Wang, and C. A. Bondy, “Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex,” FASEB J.15(6), 907–915 (2001).
[CrossRef] [PubMed]

E. Suárez, D. Bach, J. Cadefau, M. Palacin, A. Zorzano, and A. Gumá, “A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells,” J. Biol. Chem.276(21), 18257–18264 (2001).
[CrossRef] [PubMed]

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol.73(6), 636–641 (2001).
[CrossRef] [PubMed]

2000 (1)

J. Chang, T. J. Powles, D. C. Allred, S. E. Ashley, A. Makris, R. K. Gregory, C. K. Osborne, and M. Dowsett, “Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients,” Clin. Cancer Res.6(2), 616–621 (2000).
[PubMed]

1998 (1)

J. S. Ross and J. A. Fletcher, “The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy,” Stem Cells16(6), 413–428 (1998).
[CrossRef] [PubMed]

1996 (1)

C. J. Gulledge and M. W. Dewhirst, “Tumor oxygenation: a matter of supply and demand,” Anticancer Res.16(2), 741–749 (1996).
[PubMed]

1992 (1)

E. Furman, E. Rushkin, R. Margalit, P. Bendel, and H. Degani, “Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging,” J. Steroid Biochem. Mol. Biol.43(1-3), 189–195 (1992).
[CrossRef] [PubMed]

1989 (1)

J. Eng, R. M. Lynch, and R. S. Balaban, “Nicotinamide adenine dinucleotide fluorescence spectroscopy and imaging of isolated cardiac myocytes,” Biophys. J.55(4), 621–630 (1989).
[CrossRef] [PubMed]

1979 (1)

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

1972 (1)

J. B. Griffiths, “Role of serum, insulin and amino acid concentration in contact inhibition of growth of human cells in culture,” Exp. Cell Res.75(1), 47–56 (1972).
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1956 (1)

O. Warburg, “On the origin of cancer cells,” Science123(3191), 309–314 (1956).
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Ah-See, M. L. W.

S. P. Li, A. Makris, M. J. Beresford, N. J. Taylor, M. L. W. Ah-See, J. J. Stirling, J. A. d’Arcy, D. J. Collins, R. Kozarski, and A. R. Padhani, “Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy,” Radiology260(1), 68–78 (2011).
[CrossRef] [PubMed]

Alavi, A.

S. Basu, W. Chen, J. Tchou, A. Mavi, T. Cermik, B. Czerniecki, M. Schnall, and A. Alavi, “Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization,” Cancer112(5), 995–1000 (2008).
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Allison, K. H.

J. M. Specht, B. F. Kurland, S. K. Montgomery, L. K. Dunnwald, R. K. Doot, J. R. Gralow, G. K. Ellis, H. M. Linden, R. B. Livingston, K. H. Allison, E. K. Schubert, and D. A. Mankoff, “Tumor metabolism and blood flow as assessed by positron emission tomography varies by tumor subtype in locally advanced breast cancer,” Clin. Cancer Res.16(10), 2803–2810 (2010).
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Allred, D. C.

J. Chang, T. J. Powles, D. C. Allred, S. E. Ashley, A. Makris, R. K. Gregory, C. K. Osborne, and M. Dowsett, “Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients,” Clin. Cancer Res.6(2), 616–621 (2000).
[PubMed]

Andersson, M.

M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
[CrossRef] [PubMed]

Arteaga, C. L.

B. N. Rexer, A.-J. L. Ham, C. Rinehart, S. Hill, N. de Matos Granja-Ingram, A. M. González-Angulo, G. B. Mills, B. Dave, J. C. Chang, D. C. Liebler, and C. L. Arteaga, “Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition,” Oncogene30(40), 4163–4174 (2011).
[CrossRef] [PubMed]

T. W. Miller, J. T. Forbes, C. Shah, S. K. Wyatt, H. C. Manning, M. G. Olivares, V. Sanchez, T. C. Dugger, N. de Matos Granja, A. Narasanna, R. S. Cook, J. P. Kennedy, C. W. Lindsley, and C. L. Arteaga, “Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells,” Clin. Cancer Res.15(23), 7266–7276 (2009).
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C. A. Ritter, M. Perez-Torres, C. Rinehart, M. Guix, T. Dugger, J. A. Engelman, and C. L. Arteaga, “Human breast cancer cells selected for resistance to trastuzumab in vivo overexpress epidermal growth factor receptor and ErbB ligands and remain dependent on the ErbB receptor network,” Clin. Cancer Res.13(16), 4909–4919 (2007).
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Ashley, S. E.

J. Chang, T. J. Powles, D. C. Allred, S. E. Ashley, A. Makris, R. K. Gregory, C. K. Osborne, and M. Dowsett, “Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients,” Clin. Cancer Res.6(2), 616–621 (2000).
[PubMed]

Bach, D.

E. Suárez, D. Bach, J. Cadefau, M. Palacin, A. Zorzano, and A. Gumá, “A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells,” J. Biol. Chem.276(21), 18257–18264 (2001).
[CrossRef] [PubMed]

Backman, V.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer122(2), 363–371 (2008).
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Bacus, S.

W. Xia, S. Bacus, P. Hegde, I. Husain, J. Strum, L. Liu, G. Paulazzo, L. Lyass, P. Trusk, J. Hill, J. Harris, and N. L. Spector, “A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer,” Proc. Natl. Acad. Sci. U.S.A.103(20), 7795–7800 (2006).
[CrossRef] [PubMed]

Balaban, R. S.

J. Eng, R. M. Lynch, and R. S. Balaban, “Nicotinamide adenine dinucleotide fluorescence spectroscopy and imaging of isolated cardiac myocytes,” Biophys. J.55(4), 621–630 (1989).
[CrossRef] [PubMed]

Baldwin, A.

C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer122(2), 363–371 (2008).
[CrossRef] [PubMed]

Barrios, C. H.

M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
[CrossRef] [PubMed]

Baselga, J.

M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
[CrossRef] [PubMed]

Basu, S.

S. Basu, W. Chen, J. Tchou, A. Mavi, T. Cermik, B. Czerniecki, M. Schnall, and A. Alavi, “Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization,” Cancer112(5), 995–1000 (2008).
[CrossRef] [PubMed]

Beelen, K.

K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, and R. Bernards, “A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer,” Cancer Cell12(4), 395–402 (2007).
[CrossRef] [PubMed]

Beijersbergen, R. L.

K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, and R. Bernards, “A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer,” Cancer Cell12(4), 395–402 (2007).
[CrossRef] [PubMed]

Bell, R.

M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
[CrossRef] [PubMed]

Bendel, P.

E. Furman, E. Rushkin, R. Margalit, P. Bendel, and H. Degani, “Tamoxifen induced changes in MCF7 human breast cancer: in vitro and in vivo studies using nuclear magnetic resonance spectroscopy and imaging,” J. Steroid Biochem. Mol. Biol.43(1-3), 189–195 (1992).
[CrossRef] [PubMed]

Beresford, M. J.

S. P. Li, A. Makris, M. J. Beresford, N. J. Taylor, M. L. W. Ah-See, J. J. Stirling, J. A. d’Arcy, D. J. Collins, R. Kozarski, and A. R. Padhani, “Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy,” Radiology260(1), 68–78 (2011).
[CrossRef] [PubMed]

Bernards, R.

K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, and R. Bernards, “A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer,” Cancer Cell12(4), 395–402 (2007).
[CrossRef] [PubMed]

Berns, K.

K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, and R. Bernards, “A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer,” Cancer Cell12(4), 395–402 (2007).
[CrossRef] [PubMed]

Blackwell, K. L.

H. A. Burris, H. I. Hurwitz, E. C. Dees, A. Dowlati, K. L. Blackwell, B. O’Neil, P. K. Marcom, M. J. Ellis, B. Overmoyer, S. F. Jones, J. L. Harris, D. A. Smith, K. M. Koch, A. Stead, S. Mangum, and N. L. Spector, “Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas,” J. Clin. Oncol.23(23), 5305–5313 (2005).
[CrossRef] [PubMed]

Bluemke, D. A.

M. A. Jacobs, R. Ouwerkerk, A. C. Wolff, E. Gabrielson, H. Warzecha, S. Jeter, D. A. Bluemke, R. Wahl, and V. Stearns, “Monitoring of neoadjuvant chemotherapy using multiparametric, ²³Na sodium MR, and multimodality (PET/CT/MRI) imaging in locally advanced breast cancer,” Breast Cancer Res. Treat.128(1), 119–126 (2011).
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Boiko, I.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol.73(6), 636–641 (2001).
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Bondy, C. A.

C. M. Cheng, M. Cohen, J. Wang, and C. A. Bondy, “Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex,” FASEB J.15(6), 907–915 (2001).
[CrossRef] [PubMed]

Brands, W. R.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
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Brewer, M. A.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Brookner, C.

R. Drezek, C. Brookner, I. Pavlova, I. Boiko, A. Malpica, R. Lotan, M. Follen, and R. Richards-Kortum, “Autofluorescence microscopy of fresh cervical-tissue sections reveals alterations in tissue biochemistry with dysplasia,” Photochem. Photobiol.73(6), 636–641 (2001).
[CrossRef] [PubMed]

Brown, J. Q.

J. H. Ostrander, C. M. McMahon, S. Lem, S. R. Millon, J. Q. Brown, V. L. Seewaldt, and N. Ramanujam, “Optical redox ratio differentiates breast cancer cell lines based on estrogen receptor status,” Cancer Res.70(11), 4759–4766 (2010).
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Burchmore, M.

C. L. Vogel, M. A. Cobleigh, D. Tripathy, J. C. Gutheil, L. N. Harris, L. Fehrenbacher, D. J. Slamon, M. Murphy, W. F. Novotny, M. Burchmore, S. Shak, S. J. Stewart, and M. Press, “Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer,” J. Clin. Oncol.20(3), 719–726 (2002).
[CrossRef] [PubMed]

Burris, H. A.

H. A. Burris, H. I. Hurwitz, E. C. Dees, A. Dowlati, K. L. Blackwell, B. O’Neil, P. K. Marcom, M. J. Ellis, B. Overmoyer, S. F. Jones, J. L. Harris, D. A. Smith, K. M. Koch, A. Stead, S. Mangum, and N. L. Spector, “Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas,” J. Clin. Oncol.23(23), 5305–5313 (2005).
[CrossRef] [PubMed]

Cadefau, J.

E. Suárez, D. Bach, J. Cadefau, M. Palacin, A. Zorzano, and A. Gumá, “A novel role of neuregulin in skeletal muscle. Neuregulin stimulates glucose uptake, glucose transporter translocation, and transporter expression in muscle cells,” J. Biol. Chem.276(21), 18257–18264 (2001).
[CrossRef] [PubMed]

Cameron, D.

M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
[CrossRef] [PubMed]

Cantley, L. C.

J. A. Engelman, J. Luo, and L. C. Cantley, “The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism,” Nat. Rev. Genet.7(8), 606–619 (2006).
[CrossRef] [PubMed]

Cermik, T.

S. Basu, W. Chen, J. Tchou, A. Mavi, T. Cermik, B. Czerniecki, M. Schnall, and A. Alavi, “Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization,” Cancer112(5), 995–1000 (2008).
[CrossRef] [PubMed]

Chance, B.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

Chang, J.

J. Chang, T. J. Powles, D. C. Allred, S. E. Ashley, A. Makris, R. K. Gregory, C. K. Osborne, and M. Dowsett, “Prediction of clinical outcome from primary tamoxifen by expression of biologic markers in breast cancer patients,” Clin. Cancer Res.6(2), 616–621 (2000).
[PubMed]

Chang, J. C.

B. N. Rexer, A.-J. L. Ham, C. Rinehart, S. Hill, N. de Matos Granja-Ingram, A. M. González-Angulo, G. B. Mills, B. Dave, J. C. Chang, D. C. Liebler, and C. L. Arteaga, “Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition,” Oncogene30(40), 4163–4174 (2011).
[CrossRef] [PubMed]

Chen, J.

Y. Zhao, H. Liu, Z. Liu, Y. Ding, S. P. Ledoux, G. L. Wilson, R. Voellmy, Y. Lin, W. Lin, R. Nahta, B. Liu, O. Fodstad, J. Chen, Y. Wu, J. E. Price, and M. Tan, “Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism,” Cancer Res.71(13), 4585–4597 (2011).
[CrossRef] [PubMed]

Chen, W.

S. Basu, W. Chen, J. Tchou, A. Mavi, T. Cermik, B. Czerniecki, M. Schnall, and A. Alavi, “Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization,” Cancer112(5), 995–1000 (2008).
[CrossRef] [PubMed]

Cheng, C. M.

C. M. Cheng, M. Cohen, J. Wang, and C. A. Bondy, “Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex,” FASEB J.15(6), 907–915 (2001).
[CrossRef] [PubMed]

Cheyne, R. W.

R. W. Cheyne, L. Trembleau, A. McLaughlin, and T. A. Smith, “Changes in 2-fluoro-2-deoxy-D-glucose incorporation, hexokinase activity and lactate production by breast cancer cells responding to treatment with the anti-HER-2 antibody trastuzumab,” Nucl. Med. Biol.38(3), 339–346 (2011).
[CrossRef] [PubMed]

Chiu, L. L.

D. Zhang, L. K. Tai, L. L. Wong, L. L. Chiu, S. K. Sethi, and E. S. Koay, “Proteomic study reveals that proteins involved in metabolic and detoxification pathways are highly expressed in HER-2/neu-positive breast cancer,” Mol. Cell. Proteomics4(11), 1686–1696 (2005).
[CrossRef] [PubMed]

Cobleigh, M. A.

C. L. Vogel, M. A. Cobleigh, D. Tripathy, J. C. Gutheil, L. N. Harris, L. Fehrenbacher, D. J. Slamon, M. Murphy, W. F. Novotny, M. Burchmore, S. Shak, S. J. Stewart, and M. Press, “Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer,” J. Clin. Oncol.20(3), 719–726 (2002).
[CrossRef] [PubMed]

Cohen, M.

C. M. Cheng, M. Cohen, J. Wang, and C. A. Bondy, “Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex,” FASEB J.15(6), 907–915 (2001).
[CrossRef] [PubMed]

Collins, D. J.

S. P. Li, A. Makris, M. J. Beresford, N. J. Taylor, M. L. W. Ah-See, J. J. Stirling, J. A. d’Arcy, D. J. Collins, R. Kozarski, and A. R. Padhani, “Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy,” Radiology260(1), 68–78 (2011).
[CrossRef] [PubMed]

Cook, R. S.

T. W. Miller, J. T. Forbes, C. Shah, S. K. Wyatt, H. C. Manning, M. G. Olivares, V. Sanchez, T. C. Dugger, N. de Matos Granja, A. Narasanna, R. S. Cook, J. P. Kennedy, C. W. Lindsley, and C. L. Arteaga, “Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells,” Clin. Cancer Res.15(23), 7266–7276 (2009).
[CrossRef] [PubMed]

Cooper, C.

C. Cooper, G. Y. Liu, Y. L. Niu, S. Santos, L. C. Murphy, and P. H. Watson, “Intermittent hypoxia induces proteasome-dependent down-regulation of estrogen receptor alpha in human breast carcinoma,” Clin. Cancer Res.10(24), 8720–8727 (2004).
[CrossRef] [PubMed]

Costantini, D. L.

K. McLarty, A. Fasih, D. A. Scollard, S. J. Done, D. C. Vines, D. E. Green, D. L. Costantini, and R. M. Reilly, “18F-FDG small-animal PET/CT differentiates trastuzumab-responsive from unresponsive human breast cancer xenografts in athymic mice,” J. Nucl. Med.50(11), 1848–1856 (2009).
[CrossRef] [PubMed]

Czerniecki, B.

S. Basu, W. Chen, J. Tchou, A. Mavi, T. Cermik, B. Czerniecki, M. Schnall, and A. Alavi, “Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization,” Cancer112(5), 995–1000 (2008).
[CrossRef] [PubMed]

d’Arcy, J. A.

S. P. Li, A. Makris, M. J. Beresford, N. J. Taylor, M. L. W. Ah-See, J. J. Stirling, J. A. d’Arcy, D. J. Collins, R. Kozarski, and A. R. Padhani, “Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy,” Radiology260(1), 68–78 (2011).
[CrossRef] [PubMed]

Dave, B.

B. N. Rexer, A.-J. L. Ham, C. Rinehart, S. Hill, N. de Matos Granja-Ingram, A. M. González-Angulo, G. B. Mills, B. Dave, J. C. Chang, D. C. Liebler, and C. L. Arteaga, “Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition,” Oncogene30(40), 4163–4174 (2011).
[CrossRef] [PubMed]

de Matos Granja, N.

T. W. Miller, J. T. Forbes, C. Shah, S. K. Wyatt, H. C. Manning, M. G. Olivares, V. Sanchez, T. C. Dugger, N. de Matos Granja, A. Narasanna, R. S. Cook, J. P. Kennedy, C. W. Lindsley, and C. L. Arteaga, “Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells,” Clin. Cancer Res.15(23), 7266–7276 (2009).
[CrossRef] [PubMed]

de Matos Granja-Ingram, N.

B. N. Rexer, A.-J. L. Ham, C. Rinehart, S. Hill, N. de Matos Granja-Ingram, A. M. González-Angulo, G. B. Mills, B. Dave, J. C. Chang, D. C. Liebler, and C. L. Arteaga, “Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition,” Oncogene30(40), 4163–4174 (2011).
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Dees, E. C.

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M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
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M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
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S. P. Li, A. Makris, M. J. Beresford, N. J. Taylor, M. L. W. Ah-See, J. J. Stirling, J. A. d’Arcy, D. J. Collins, R. Kozarski, and A. R. Padhani, “Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy,” Radiology260(1), 68–78 (2011).
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M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
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B. N. Rexer, A.-J. L. Ham, C. Rinehart, S. Hill, N. de Matos Granja-Ingram, A. M. González-Angulo, G. B. Mills, B. Dave, J. C. Chang, D. C. Liebler, and C. L. Arteaga, “Phosphoproteomic mass spectrometry profiling links Src family kinases to escape from HER2 tyrosine kinase inhibition,” Oncogene30(40), 4163–4174 (2011).
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Y. Zhao, H. Liu, Z. Liu, Y. Ding, S. P. Ledoux, G. L. Wilson, R. Voellmy, Y. Lin, W. Lin, R. Nahta, B. Liu, O. Fodstad, J. Chen, Y. Wu, J. E. Price, and M. Tan, “Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism,” Cancer Res.71(13), 4585–4597 (2011).
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Y. Zhao, H. Liu, Z. Liu, Y. Ding, S. P. Ledoux, G. L. Wilson, R. Voellmy, Y. Lin, W. Lin, R. Nahta, B. Liu, O. Fodstad, J. Chen, Y. Wu, J. E. Price, and M. Tan, “Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism,” Cancer Res.71(13), 4585–4597 (2011).
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[CrossRef] [PubMed]

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[CrossRef] [PubMed]

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T. W. Miller, J. T. Forbes, C. Shah, S. K. Wyatt, H. C. Manning, M. G. Olivares, V. Sanchez, T. C. Dugger, N. de Matos Granja, A. Narasanna, R. S. Cook, J. P. Kennedy, C. W. Lindsley, and C. L. Arteaga, “Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells,” Clin. Cancer Res.15(23), 7266–7276 (2009).
[CrossRef] [PubMed]

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K. Berns, H. M. Horlings, B. T. Hennessy, M. Madiredjo, E. M. Hijmans, K. Beelen, S. C. Linn, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Hauptmann, R. L. Beijersbergen, G. B. Mills, M. J. van de Vijver, and R. Bernards, “A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer,” Cancer Cell12(4), 395–402 (2007).
[CrossRef] [PubMed]

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Y. Zhao, H. Liu, Z. Liu, Y. Ding, S. P. Ledoux, G. L. Wilson, R. Voellmy, Y. Lin, W. Lin, R. Nahta, B. Liu, O. Fodstad, J. Chen, Y. Wu, J. E. Price, and M. Tan, “Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism,” Cancer Res.71(13), 4585–4597 (2011).
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Liu, L.

W. Xia, S. Bacus, P. Hegde, I. Husain, J. Strum, L. Liu, G. Paulazzo, L. Lyass, P. Trusk, J. Hill, J. Harris, and N. L. Spector, “A model of acquired autoresistance to a potent ErbB2 tyrosine kinase inhibitor and a therapeutic strategy to prevent its onset in breast cancer,” Proc. Natl. Acad. Sci. U.S.A.103(20), 7795–7800 (2006).
[CrossRef] [PubMed]

Liu, Z.

Y. Zhao, H. Liu, Z. Liu, Y. Ding, S. P. Ledoux, G. L. Wilson, R. Voellmy, Y. Lin, W. Lin, R. Nahta, B. Liu, O. Fodstad, J. Chen, Y. Wu, J. E. Price, and M. Tan, “Overcoming trastuzumab resistance in breast cancer by targeting dysregulated glucose metabolism,” Cancer Res.71(13), 4585–4597 (2011).
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Livingston, R. B.

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K. Kawada, K. Murakami, T. Sato, Y. Kojima, H. Ebi, H. Mukai, M. Tahara, K. Shimokata, and H. Minami, “Prospective study of positron emission tomography for evaluation of the activity of lapatinib, a dual inhibitor of the ErbB1 and ErbB2 tyrosine kinases, in patients with advanced tumors,” Jpn. J. Clin. Oncol.37(1), 44–48 (2007).
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M. J. Piccart-Gebhart, M. Procter, B. Leyland-Jones, A. Goldhirsch, M. Untch, I. Smith, L. Gianni, J. Baselga, R. Bell, C. Jackisch, D. Cameron, M. Dowsett, C. H. Barrios, G. Steger, C. S. Huang, M. Andersson, M. Inbar, M. Lichinitser, I. Láng, U. Nitz, H. Iwata, C. Thomssen, C. Lohrisch, T. M. Suter, J. Rüschoff, T. Suto, V. Greatorex, C. Ward, C. Straehle, E. McFadden, M. S. Dolci, R. D. Gelber, and Herceptin Adjuvant (HERA) Trial Study Team, “Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer,” N. Engl. J. Med.353(16), 1659–1672 (2005).
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C. Mujat, C. Greiner, A. Baldwin, J. M. Levitt, F. Tian, L. A. Stucenski, M. Hunter, Y. L. Kim, V. Backman, M. Feld, K. Münger, and I. Georgakoudi, “Endogenous optical biomarkers of normal and human papillomavirus immortalized epithelial cells,” Int. J. Cancer122(2), 363–371 (2008).
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Figures (6)

Fig. 1
Fig. 1

Western blot analysis demonstrates overexpression of HER2 in the SKBR3 and BT474 cells and expression of ER in the MCF7 and BT474 cells.

Fig. 2
Fig. 2

Addition of CN to MCF10A cells (n = 6) results in an increase in redox ratio and NADH fluorescence and a decrease in FAD fluorescence. Bar height represents mean and error bars represent SE.

Fig. 3
Fig. 3

Representative NADH, FAD, and redox ratio images for MCF10A, MDA-231, MCF7, BT474 and SKBr3 cells. Optical redox ratio increases with ER and HER2 expression.

Fig. 4
Fig. 4

Quantitative representation (mean +/− SE) of the redox ratio values for the MCF10A (n = 30), MDA-MB-231 (n = 15), MCF7 (n = 15), BT474 (n = 15), and SKBr3 cells (n = 15). Redox ratio is elevated in cells overexpressing HER2.

Fig. 5
Fig. 5

Redox ratio divided by proliferation rate mean +/− SE for MCF10A (n = 30), MCF7 (n = 15) and BT474 (n = 15) cells.

Fig. 6
Fig. 6

(A) The redox ratio (mean +/−SE) of responsive BT474 cells is different from the trastuzumab (HR6) and lapatinib (BT-LR) resistant cells (n = 15), and there was no change in the redox ratio of trastuzumab-resistant HR6 cells with trastuzumab-treatment. (B) The redox ratio of responsive BT474 cells decreased with tamoxifen (2 µM), trastuzumab (25 µg/ml), and tamoxifen + trastuzumab treatment (n = 15).

Tables (1)

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Table 1 Breast cancer cell lines with corresponding ER and HER2 expression

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