© 2004 by Oxford University Press
© 2004 Oxford University Press
ARTICLE |
Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non–Small-Cell Lung Cancer
Affiliations of authors: Department of Oncologic Sciences, Bellaria-Maggiore Hospital, Bologna, Italy (FC, EM, SB, CL, AC, SD, LL, CC, LC); Division of Radiochemotherapy, Scientific Institute University Hospital San Raffaele-Milano, Italy (GLC, VG, AS, CTP); CINECA—Interuniversity Consortium, Bologna, Italy (ER); Policlinico Monteluce, Division of Medical Oncology, Perugia, Italy (VL, GB, MT)
Correspondence to: Federico Cappuzzo, MD, Bellaria Hospital, Division of Medical Oncology, Via Altura 3, 40139-Bologna, Italy (e-mail: federico.cappuzzo{at}ausl.bo.it)
Background: Gefitinib, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has activity against approximately 10% of unselected non–small-cell lung cancer (NSCLC) patients. Phosphatidylinositol 3'-kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK), the two main EGFR-signaling pathways, mediate EGFR effects on proliferation and survival. Because activation of these pathways is dependent on the phosphorylation status of the components, we evaluated the association between phosphorylation status of Akt (P-Akt) and MAPK (P-MAPK) and gefitinib activity in patients with advanced NSCLC. Methods: Consecutive patients (n = 106) with NSCLC who had progressed or relapsed on standard therapy received gefitinib (250 mg/day) until disease progression, unacceptable toxicity, or patient refusal. P-Akt and P-MAPK positivity was determined with immunohistochemistry using tumor tissues obtained before any anticancer treatment. Association of P-Akt and time to progression was determined by univariable and multivariable analyses. All statistical tests were two-sided. Results: Of the 103 evaluable patients, 51 (49.5%) had tumors that were positive for P-Akt, and 23 (22.3%) had tumors that were positive for P-MAPK. P-Akt–positivity status was statistically significantly associated with being female (P<.001), with never-smoking history (P = .004), and with bronchioloalveolar carcinoma histology (P = .034). Compared with patients whose tumors were negative for P-Akt, patients whose tumors were positive for P-Akt had a better response rate (26.1% versus 3.9%; P = .003), disease control rate (60.9% versus 23.5%; P<.001), and time to progression (5.5 versus 2.8 months; P = .004). Response rate, disease control rate, and time to progression did not differ according to P-MAPK status. The multivariable analysis showed that P-Akt positivity was associated with a reduced risk of disease progression (hazard ratio = 0.58, 95% confidence interval = 0.35 to 0.94). Conclusions: Patients with P-Akt–positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt–negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation.
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Correspondence about this Article
- Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non–Small-Cell Lung Cancer
- Junji Tsurutani and Phillip A. Dennis
J Natl Cancer Inst 2004 96: 1795.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non–Small-Cell Lung Cancer
- Federico Cappuzzo
J Natl Cancer Inst 2004 96: 1795-1796.[Extract] [Full Text] [PDF]
- Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non–Small-Cell Lung Cancer
- Filippo de Braud, Tommaso De Pas, Lorenzo Spaggiari, Giulia Veronesi, Giuseppe Curigliano, Cristina Noberasco, and Giuseppe Pelosi
J Natl Cancer Inst 2005 97: 461-462.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non–Small-Cell Lung Cancer
- Federico Cappuzzo
J Natl Cancer Inst 2005 97: 462-463.[Extract] [Full Text] [PDF]
Editorial about this Article
- Predicting Sensitivity of Non–Small-Cell Lung Cancer to Gefitinib: Is There a Role for P-Akt?
- William Pao, Vincent A. Miller, Ennapadam Venkatraman, and Mark G. Kris
J Natl Cancer Inst 2004 96: 1117-1119.[Extract] [Full Text] [PDF]
Related Memo to the Media
- Press Release: Activated Signaling Pathway May Predict Lung Cancer Patients' Response to Gefitinib
- Sarah L. Zielinski
J Natl Cancer Inst 2004 96: 1115.[Extract] [Full Text]
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|
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|
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|
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|
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|
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|
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|
|
|
|
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|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
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|
 F. Yamasaki, M. J. Johansen, D. Zhang, S. Krishnamurthy, E. Felix, C. Bartholomeusz, R. J. Aguilar, K. Kurisu, G. B. Mills, G. N. Hortobagyi, et al. Acquired Resistance to Erlotinib in A-431 Epidermoid Cancer Cells Requires Down-regulation of MMAC1/PTEN and Up-regulation of Phosphorylated Akt Cancer Res., June 15, 2007; 67(12): 5779 - 5788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
M. Ono and M. Kuwano Molecular Mechanisms of Epidermal Growth Factor Receptor (EGFR) Activation and Response to Gefitinib and Other EGFR-Targeting Drugs Clin. Cancer Res., December 15, 2006; 12(24): 7242 - 7251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
D. J. Raz, B. He, R. Rosell, and D. M. Jablons Current concepts in bronchioloalveolar carcinoma biology. Clin. Cancer Res., June 15, 2006; 12(12): 3698 - 3704. [Full Text] [PDF]
|
|
|
|
|
|
S. Kalyankrishna and J. R. Grandis Epidermal Growth Factor Receptor Biology in Head and Neck Cancer J. Clin. Oncol., June 10, 2006; 24(17): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ramalingam and A. B. Sandler Salvage therapy for advanced non-small cell lung cancer: factors influencing treatment selection. Oncologist, June 1, 2006; 11(6): 655 - 665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Van Schaeybroeck, J. Kyula, D. M. Kelly, A. Karaiskou-McCaul, S. A. Stokesberry, E. Van Cutsem, D. B. Longley, and P. G. Johnston Chemotherapy-induced epidermal growth factor receptor activation determines response to combined gefitinib/chemotherapy treatment in non-small cell lung cancer cells Mol. Cancer Ther., May 1, 2006; 5(5): 1154 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Han, T.-Y. Kim, Y. K. Jeon, P. G. Hwang, S.-A. Im, K.-H. Lee, J. H. Kim, D.-W. Kim, D. S. Heo, N. K. Kim, et al. Optimization of Patient Selection for Gefitinib in Non-Small Cell Lung Cancer by Combined Analysis of Epidermal Growth Factor Receptor Mutation, K-ras Mutation, and Akt Phosphorylation Clin. Cancer Res., April 15, 2006; 12(8): 2538 - 2544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Janmaat, M. I. Gallegos-Ruiz, J. A. Rodriguez, G. A. Meijer, W. L. Vervenne, D. J. Richel, C. Van Groeningen, and G. Giaccone Predictive Factors for Outcome in a Phase II Study of Gefitinib in Second-Line Treatment of Advanced Esophageal Cancer Patients J. Clin. Oncol., April 1, 2006; 24(10): 1612 - 1619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Leone, G. Cavalloni, Y. Pignochino, I. Sarotto, R. Ferraris, W. Piacibello, T. Venesio, L. Capussotti, M. Risio, and M. Aglietta Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma. Clin. Cancer Res., March 15, 2006; 12(6): 1680 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jimeno, P. Kulesza, E. Kincaid, N. Bouaroud, A. Chan, A. Forastiere, J. Brahmer, D. P. Clark, and M. Hidalgo C-fos Assessment as a Marker of Anti-Epidermal Growth Factor Receptor Effect Cancer Res., February 15, 2006; 66(4): 2385 - 2390. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Witta, R. M. Gemmill, F. R. Hirsch, C. D. Coldren, K. Hedman, L. Ravdel, B. Helfrich, R. Dziadziuszko, D. C. Chan, M. Sugita, et al. Restoring E-Cadherin Expression Increases Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cell Lines Cancer Res., January 15, 2006; 66(2): 944 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tsurutani, J. Fukuoka, H. Tsurutani, J. H. Shih, S. M. Hewitt, W. D. Travis, J. Jen, and P. A. Dennis Evaluation of Two Phosphorylation Sites Improves the Prognostic Significance of Akt Activation in Non-Small-Cell Lung Cancer Tumors J. Clin. Oncol., January 10, 2006; 24(2): 306 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ando, T. Ohmori, F. Inoue, T. Kadofuku, T. Hosaka, H. Ishida, T. Shirai, K. Okuda, T. Hirose, N. Horichi, et al. Enhancement of Sensitivity to Tumor Necrosis Factor {alpha} in Non-Small Cell Lung Cancer Cells with Acquired Resistance to Gefitinib Clin. Cancer Res., December 15, 2005; 11(24): 8872 - 8879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dutu, S. Michiels, P. Fouret, F. Penault-Llorca, P. Validire, S. Benhamou, E. Taranchon, L. Morat, D. Grunenwald, T. Le Chevalier, et al. Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers Ann. Onc., December 1, 2005; 16(12): 1906 - 1914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. Lassman, M. R. Rossi, J. R. Razier, L. E. Abrey, F. S. Lieberman, C. N. Grefe, K. Lamborn, W. Pao, A. H. Shih, J. G. Kuhn, et al. Molecular Study of Malignant Gliomas Treated with Epidermal Growth Factor Receptor Inhibitors: Tissue Analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01 Clin. Cancer Res., November 1, 2005; 11(21): 7841 - 7850. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Takano, Y. Ohe, H. Sakamoto, K. Tsuta, Y. Matsuno, U. Tateishi, S. Yamamoto, H. Nokihara, N. Yamamoto, I. Sekine, et al. Epidermal Growth Factor Receptor Gene Mutations and Increased Copy Numbers Predict Gefitinib Sensitivity in Patients With Recurrent Non-Small-Cell Lung Cancer J. Clin. Oncol., October 1, 2005; 23(28): 6829 - 6837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Real, A. Benito, J. Cuevas, M. T. Berciano, A. de Juan, P. Coffer, J. Gomez-Roman, M. Lafarga, J. M. Lopez-Vega, and J. L. Fernandez-Luna Blockade of Epidermal Growth Factor Receptors Chemosensitizes Breast Cancer Cells through Up-Regulation of Bnip3L Cancer Res., September 15, 2005; 65(18): 8151 - 8157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ogino, J. A. Meyerhardt, M. Cantor, M. Brahmandam, J. W. Clark, C. Namgyal, T. Kawasaki, K. Kinsella, A. L. Michelini, P. C. Enzinger, et al. Molecular Alterations in Tumors and Response to Combination Chemotherapy with Gefitinib for Advanced Colorectal Cancer Clin. Cancer Res., September 15, 2005; 11(18): 6650 - 6656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Daw, W. L. Furman, C. F. Stewart, L. C. Iacono, M. Krailo, M. L. Bernstein, J. E. Dancey, R. A. Speights, S. M. Blaney, J. M. Croop, et al. Phase I and Pharmacokinetic Study of Gefitinib in Children With Refractory Solid Tumors: A Children's Oncology Group Study J. Clin. Oncol., September 1, 2005; 23(25): 6172 - 6180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. E. Miller Pathogenesis of Lung Cancer: 100 Year Report Am. J. Respir. Cell Mol. Biol., September 1, 2005; 33(3): 216 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cappuzzo Erlotinib in Gliomas: Should Selection Be Based on EGFR and Akt Analyses? J Natl Cancer Inst, June 15, 2005; 97(12): 868 - 869. [Full Text] [PDF]
|
|
|
|
|
|
D. A. Haas-Kogan, M. D. Prados, T. Tihan, D. A. Eberhard, N. Jelluma, N. D. Arvold, R. Baumber, K. R. Lamborn, A. Kapadia, M. Malec, et al. Epidermal Growth Factor Receptor, Protein Kinase B/Akt, and Glioma Response to Erlotinib J Natl Cancer Inst, June 15, 2005; 97(12): 880 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. L. Mu, L. Y. Li, X. T. Zhang, M. Z. Wang, R. E. Feng, Q. C. Cui, H. S. Zhou, and B. Q. Guo Gefitinib-Sensitive Mutations of the Epidermal Growth Factor Receptor Tyrosine Kinase Domain in Chinese Patients with Non-Small Cell Lung Cancer Clin. Cancer Res., June 15, 2005; 11(12): 4289 - 4294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Altundag, K. Altundag, P. Morandi, and M. Gunduz Association Between Epidermal Growth Factor Receptor Mutation and Improved Survival in Never-Smokers With Primary Adenocarcinoma of the Lung Chest, June 1, 2005; 127(6): 2292 - 2292. [Full Text] [PDF]
|
|
|
|
|
|
G. Giaccone Epidermal Growth Factor Receptor Inhibitors in the Treatment of Non-Small-Cell Lung Cancer J. Clin. Oncol., May 10, 2005; 23(14): 3235 - 3242. [Abstract] [Full Text] [PDF]
|
|
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F. J. Kaye A Curious Link Between Epidermal Growth Factor Receptor Amplification and Survival: Effect of "Allele Dilution" on Gefitinib Sensitivity? J Natl Cancer Inst, May 4, 2005; 97(9): 621 - 623. [Full Text] [PDF]
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F. Cappuzzo, F. R. Hirsch, E. Rossi, S. Bartolini, G. L. Ceresoli, L. Bemis, J. Haney, S. Witta, K. Danenberg, I. Domenichini, et al. Epidermal Growth Factor Receptor Gene and Protein and Gefitinib Sensitivity in Non-Small-Cell Lung Cancer J Natl Cancer Inst, May 4, 2005; 97(9): 643 - 655. [Abstract] [Full Text] [PDF]
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G. J. Kelloff, J. M. Hoffman, B. Johnson, H. I. Scher, B. A. Siegel, E. Y. Cheng, B. D. Cheson, J. O'Shaughnessy, K. Z. Guyton, D. A. Mankoff, et al. Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development Clin. Cancer Res., April 15, 2005; 11(8): 2785 - 2808. [Abstract] [Full Text] [PDF]
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A. Shah, W. A. Swain, D. Richardson, J. Edwards, D. J. Stewart, C. M. Richardson, D. E.B. Swinson, D. Patel, J. L. Jones, and K. J. O'Byrne Phospho-Akt Expression Is Associated with a Favorable Outcome in Non-Small Cell Lung Cancer Clin. Cancer Res., April 15, 2005; 11(8): 2930 - 2936. [Abstract] [Full Text] [PDF]
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S.-W. Han, T.-Y. Kim, P. G. Hwang, S. Jeong, J. Kim, I. S. Choi, D.-Y. Oh, J. H. Kim, D.-W. Kim, D. H. Chung, et al. Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Non-Small-Cell Lung Cancer Patients Treated With Gefitinib J. Clin. Oncol., April 10, 2005; 23(11): 2493 - 2501. [Abstract] [Full Text] [PDF]
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W. Pao and V. A. Miller Epidermal Growth Factor Receptor Mutations, Small-Molecule Kinase Inhibitors, and Non-Small-Cell Lung Cancer: Current Knowledge and Future Directions J. Clin. Oncol., April 10, 2005; 23(11): 2556 - 2568. [Abstract] [Full Text] [PDF]
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G. Giaccone HER1/EGFR-targeted agents: predicting the future for patients with unpredictable outcomes to therapy Ann. Onc., April 1, 2005; 16(4): 538 - 548. [Abstract] [Full Text] [PDF]
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F. Cappuzzo RESPONSE: Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer J Natl Cancer Inst, March 16, 2005; 97(6): 462 - 463. [Full Text] [PDF]
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F. de Braud, T. De Pas, L. Spaggiari, G. Veronesi, G. Curigliano, C. Noberasco, and G. Pelosi Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer J Natl Cancer Inst, March 16, 2005; 97(6): 461 - 462. [Full Text] [PDF]
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 T. Berghmans, A. P. Meert, B. Martin, V. Ninane, and J. P. Sculier Prognostic role of epidermal growth factor receptor in stage III nonsmall cell lung cancer Eur. Respir. J., February 1, 2005; 25(2): 329 - 335. [Abstract] [Full Text] [PDF]
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J. P. Spano, R. Fagard, J.-C. Soria, O. Rixe, D. Khayat, and G. Milano Epidermal growth factor receptor signaling in colorectal cancer: preclinical data and therapeutic perspectives Ann. Onc., February 1, 2005; 16(2): 189 - 194. [Abstract] [Full Text] [PDF]
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J. Tsurutani and P. A. Dennis Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer J Natl Cancer Inst, December 1, 2004; 96(23): 1795 - 1795. [Full Text] [PDF]
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F. Cappuzzo RESPONSE: Re: Akt Phosphorylation and Gefitinib Efficacy in Patients With Advanced Non-Small-Cell Lung Cancer J Natl Cancer Inst, December 1, 2004; 96(23): 1795 - 1796. [Full Text] [PDF]
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D. F. Stern More than a Marker... Phosphorylated Akt in Prostate Carcinoma Clin. Cancer Res., October 1, 2004; 10(19): 6407 - 6410. [Full Text] [PDF]
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W. Pao, V. A. Miller, E. Venkatraman, and M. G. Kris Predicting Sensitivity of Non-Small-Cell Lung Cancer to Gefitinib: Is There a Role for P-Akt? J Natl Cancer Inst, August 4, 2004; 96(15): 1117 - 1119. [Full Text] [PDF]
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