This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ngan, R. K. C. Articles by Lau, W.-H. Search for Related Content PubMed PubMed Citation Articles by Ngan, R. K. C. Articles by Lau, W.-H.

Circulating Epstein-Barr Virus DNA in Serum of Patients with Lymphoepithelioma-like Carcinoma of the Lung

A Potential Surrogate Marker for Monitoring Disease

Departments of Clinical Oncology [R. K. C. N., T. T. C. Y., W-W. C., W. C. S. C., V. W. S. M., S-K. A., C-K. L., W-H. L.] and Pathology [J. K. C. C.], Queen Elizabeth Hospital, and Gene Pro Laboratory Limited [K-K. W.], Hong Kong Special Administrative Region, China

Purpose: The purpose of this work was to study the sera of patients with lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA.

Experimental Design: Prospectively collected serum samples from five female patients with advanced, inoperable LELC of the lung were measured for free circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA (EBER)-1 was assayed in serial serum samples of three of the five patients, either from the start or during the initial phase of chemotherapy/radiotherapy until their terminal event or last follow-up. There was only a single-point sample for analysis in the fourth and fifth patients. Six other patients with LELC of the lung were also retrospectively identified, and their sera were tested for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the first visit only (n = 2), or the last follow-up visit only (n = 2).

Results: Prospectively collected serum samples from five patients and retrospectively collected serum samples from two patients who had clinical disease at initial serum measurement showed detectable levels of EBER-1. Retrospectively collected serum samples from four patients with no clinical disease had negative sera. There is consistent correlation between the clinical response to treatment and subsequent clinical course of LELC and serum EBER-1 levels in the three prospective patients with longitudinal serum monitoring.

Conclusions: This study shows for the first time that free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases.

This article has been cited by other articles:

				D. S. Welsbie, J. Xu, Y. Chen, L. Borsu, H. I. Scher, N. Rosen, and C. L. Sawyers Histone Deacetylases Are Required for Androgen Receptor Function in Hormone-Sensitive and Castrate-Resistant Prostate Cancer Cancer Res., February 1, 2009; 69(3): 958 - 966. [Abstract] [Full Text] [PDF]

				C. M.-E. Sauvageot, J. L. Weatherbee, S. Kesari, S. E. Winters, J. Barnes, J. Dellagatta, N. R. Ramakrishna, C. D. Stiles, A. L.-J. Kung, M. W. Kieran, et al. Efficacy of the HSP90 inhibitor 17-AAG in human glioma cell lines and tumorigenic glioma stem cells Neuro-oncol, January 1, 2009; 11(2): 109 - 121. [Abstract] [Full Text] [PDF]

				U. Banerji Heat Shock Protein 90 as a Drug Target: Some Like It Hot Clin. Cancer Res., January 1, 2009; 15(1): 9 - 14. [Abstract] [Full Text] [PDF]

				R. Snoek, H. Cheng, K. Margiotti, L. A. Wafa, C. A. Wong, E. C. Wong, L. Fazli, C. C. Nelson, M. E. Gleave, and P. S. Rennie In vivo Knockdown of the Androgen Receptor Results in Growth Inhibition and Regression of Well-Established, Castration-Resistant Prostate Tumors Clin. Cancer Res., January 1, 2009; 15(1): 39 - 47. [Abstract] [Full Text] [PDF]

				E. I. Heath, D. W. Hillman, U. Vaishampayan, S. Sheng, F. Sarkar, F. Harper, M. Gaskins, H. C. Pitot, W. Tan, S. P. Ivy, et al. A Phase II Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Hormone-Refractory Metastatic Prostate Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7940 - 7946. [Abstract] [Full Text] [PDF]

				A. N. Tse, D. S. Klimstra, M. Gonen, M. Shah, T. Sheikh, R. Sikorski, R. Carvajal, J. Mui, C. Tipian, E. O'Reilly, et al. A Phase 1 Dose-Escalation Study of Irinotecan in Combination with 17-Allylamino-17-Demethoxygeldanamycin in Patients with Solid Tumors Clin. Cancer Res., October 15, 2008; 14(20): 6704 - 6711. [Abstract] [Full Text] [PDF]

				S. Basak, D. Pookot, E. J. Noonan, and R. Dahiya Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function Mol. Cancer Ther., October 1, 2008; 7(10): 3195 - 3202. [Abstract] [Full Text] [PDF]

				D. Song, R. Chaerkady, A. C. Tan, E. Garcia-Garcia, A. Nalli, A. Suarez-Gauthier, F. Lopez-Rios, X. F. Zhang, A. Solomon, J. Tong, et al. Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer Mol. Cancer Ther., October 1, 2008; 7(10): 3275 - 3284. [Abstract] [Full Text] [PDF]

				S. S. Ramalingam, M. J. Egorin, R. K. Ramanathan, S. C. Remick, R. P. Sikorski, T. F. Lagattuta, G. S. Chatta, D. M. Friedland, R. G. Stoller, D. M. Potter, et al. A Phase I Study of 17-Allylamino-17-Demethoxygeldanamycin Combined with Paclitaxel in Patients with Advanced Solid Malignancies Clin. Cancer Res., June 1, 2008; 14(11): 3456 - 3461. [Abstract] [Full Text] [PDF]

				S. A. Eccles, A. Massey, F. I. Raynaud, S. Y. Sharp, G. Box, M. Valenti, L. Patterson, A. de Haven Brandon, S. Gowan, F. Boxall, et al. NVP-AUY922: A Novel Heat Shock Protein 90 Inhibitor Active against Xenograft Tumor Growth, Angiogenesis, and Metastasis Cancer Res., April 15, 2008; 68(8): 2850 - 2860. [Abstract] [Full Text] [PDF]

				A. Sawai, S. Chandarlapaty, H. Greulich, M. Gonen, Q. Ye, C. L. Arteaga, W. Sellers, N. Rosen, and D. B. Solit Inhibition of Hsp90 Down-regulates Mutant Epidermal Growth Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to Paclitaxel Cancer Res., January 15, 2008; 68(2): 589 - 596. [Abstract] [Full Text] [PDF]

				S. Chandarlapaty, A. Sawai, Q. Ye, A. Scott, M. Silinski, K. Huang, P. Fadden, J. Partdrige, S. Hall, P. Steed, et al. SNX2112, a Synthetic Heat Shock Protein 90 Inhibitor, Has Potent Antitumor Activity against HER Kinase Dependent Cancers Clin. Cancer Res., January 1, 2008; 14(1): 240 - 248. [Abstract] [Full Text] [PDF]

				S. Modi, A. T. Stopeck, M. S. Gordon, D. Mendelson, D. B. Solit, R. Bagatell, W. Ma, J. Wheler, N. Rosen, L. Norton, et al. Combination of Trastuzumab and Tanespimycin (17-AAG, KOS-953) Is Safe and Active in Trastuzumab-Refractory HER-2 Overexpressing Breast Cancer: A Phase I Dose-Escalation Study J. Clin. Oncol., December 1, 2007; 25(34): 5410 - 5417. [Abstract] [Full Text] [PDF]

				C. Moser, S. A. Lang, S. Kainz, A. Gaumann, S. Fichtner-Feigl, G. E. Koehl, H. J. Schlitt, E. K. Geissler, and O. Stoeltzing Blocking heat shock protein-90 inhibits the invasive properties and hepatic growth of human colon cancer cells and improves the efficacy of oxaliplatin in p53-deficient colon cancer tumors in vivo Mol. Cancer Ther., November 1, 2007; 6(11): 2868 - 2878. [Abstract] [Full Text] [PDF]

				J. Bae, C. Mitsiades, Y.-T. Tai, R. Bertheau, M. Shammas, R. B. Batchu, C. Li, L. Catley, R. Prabhala, K. C. Anderson, et al. Phenotypic and Functional Effects of Heat Shock Protein 90 Inhibition on Dendritic Cell J. Immunol., June 15, 2007; 178(12): 7730 - 7737. [Abstract] [Full Text] [PDF]

				A. Maloney, P. A. Clarke, S. Naaby-Hansen, R. Stein, J.-O. Koopman, A. Akpan, A. Yang, M. Zvelebil, R. Cramer, L. Stimson, et al. Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin Cancer Res., April 1, 2007; 67(7): 3239 - 3253. [Abstract] [Full Text] [PDF]

				W. Xu and L. Neckers Targeting the Molecular Chaperone Heat Shock Protein 90 Provides a Multifaceted Effect on Diverse Cell Signaling Pathways of Cancer Cells Clin. Cancer Res., March 15, 2007; 13(6): 1625 - 1629. [Full Text] [PDF]

				D. B. Solit, S. P. Ivy, C. Kopil, R. Sikorski, M. J. Morris, S. F. Slovin, W. K. Kelly, A. DeLaCruz, T. Curley, G. Heller, et al. Phase I Trial of 17-Allylamino-17-Demethoxygeldanamycin in Patients with Advanced Cancer Clin. Cancer Res., March 15, 2007; 13(6): 1775 - 1782. [Abstract] [Full Text] [PDF]

				B. J. Weigel, S. M. Blaney, J. M. Reid, S. L. Safgren, R. Bagatell, J. Kersey, J. P. Neglia, S. P. Ivy, A. M. Ingle, L. Whitesell, et al. A Phase I Study of 17-Allylaminogeldanamycin in Relapsed/Refractory Pediatric Patients with Solid Tumors: A Children's Oncology Group Study Clin. Cancer Res., March 15, 2007; 13(6): 1789 - 1793. [Abstract] [Full Text] [PDF]

				J. Szwaya, C. Bruseo, E. Nakuci, D. McSweeney, X. Xiang, D. Senator, D. France, and C.-R. Chen A Novel Platform for Accelerated Pharmacodynamic Profiling for Lead Optimization of Anticancer Drug Candidates J Biomol Screen, March 1, 2007; 12(2): 159 - 166. [Abstract] [PDF]

				D. L. Marrocco, W. D. Tilley, T. Bianco-Miotto, A. Evdokiou, H. I. Scher, R. A. Rifkind, P. A. Marks, V. M. Richon, and L. M. Butler Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation Mol. Cancer Ther., January 1, 2007; 6(1): 51 - 60. [Abstract] [Full Text] [PDF]

				L. Pootrakul, R. H. Datar, S.-R. Shi, J. Cai, D. Hawes, S. G. Groshen, A. S. Lee, and R. J. Cote Expression of Stress Response Protein Grp78 Is Associated with the Development of Castration-Resistant Prostate Cancer. Clin. Cancer Res., October 15, 2006; 12(20): 5987 - 5993. [Abstract] [Full Text] [PDF]

				R. K. Allan, D. Mok, B. K. Ward, and T. Ratajczak Modulation of Chaperone Function and Cochaperone Interaction by Novobiocin in the C-terminal Domain of Hsp90: EVIDENCE THAT COUMARIN ANTIBIOTICS DISRUPT Hsp90 DIMERIZATION J. Biol. Chem., March 17, 2006; 281(11): 7161 - 7171. [Abstract] [Full Text] [PDF]

				S. A. Compton, L. W. Elmore, K. Haydu, C. K. Jackson-Cook, and S. E. Holt Induction of Nitric Oxide Synthase-Dependent Telomere Shortening after Functional Inhibition of Hsp90 in Human Tumor Cells Mol. Cell. Biol., February 15, 2006; 26(4): 1452 - 1462. [Abstract] [Full Text] [PDF]

				X. Zhang, A. F. Clark, and T. Yorio Heat Shock Protein 90 Is an Essential Molecular Chaperone for Nuclear Transport of Glucocorticoid Receptor {beta} Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 700 - 708. [Abstract] [Full Text] [PDF]

				F. Paduano, R. Villa, M. Pennati, M. Folini, M. Binda, M. G. Daidone, and N. Zaffaroni Silencing of survivin gene by small interfering RNAs produces supra-additive growth suppression in combination with 17-allylamino-17-demethoxygeldanamycin in human prostate cancer cells Mol. Cancer Ther., January 1, 2006; 5(1): 179 - 186. [Abstract] [Full Text] [PDF]

				G. K. Schwartz and M. A. Shah Targeting the Cell Cycle: A New Approach to Cancer Therapy J. Clin. Oncol., December 20, 2005; 23(36): 9408 - 9421. [Abstract] [Full Text] [PDF]

				C. W. Gregory, X. Fei, L. A. Ponguta, B. He, H. M. Bill, F. S. French, and E. M. Wilson Epidermal Growth Factor Increases Coactivation of the Androgen Receptor in Recurrent Prostate Cancer J. Biol. Chem., February 20, 2004; 279(8): 7119 - 7130. [Abstract] [Full Text] [PDF]

				C. Calabrese, A. Frank, K. Maclean, and R. Gilbertson Medulloblastoma Sensitivity to 17-Allylamino-17-demethoxygeldanamycin Requires MEK/ERK J. Biol. Chem., July 4, 2003; 278(27): 24951 - 24959. [Abstract] [Full Text] [PDF]

				G. Chiosis, H. Huezo, N. Rosen, E. Mimnaugh, L. Whitesell, and L. Neckers 17AAG: Low Target Binding Affinity and Potent Cell Activity--Finding an Explanation Mol. Cancer Ther., February 1, 2003; 2(2): 123 - 129. [Abstract] [Full Text] [PDF]

				P. Workman Auditing the Pharmacological Accounts for Hsp90 Molecular Chaperone Inhibitors: Unfolding the Relationship between Pharmacokinetics and Pharmacodynamics Mol. Cancer Ther., February 1, 2003; 2(2): 131 - 138. [Full Text] [PDF]

				L. Neckers Heat Shock Protein 90 Inhibition by 17-Allylamino-17- demethoxygeldanamycin: A Novel Therapeutic Approach for Treating Hormone-refractory Prostate Cancer : Commentary re: D. B. Solit et al., 17-Allylamino-17-demethoxygeldanamycin Induces the Degradation of Androgen Receptor and Her-2/neu and Inhibits the Growth of Prostate Cancer Xenografts. Clin. Cancer Res., 8: 986-993, 2002. Clin. Cancer Res., May 1, 2002; 8(5): 962 - 966. [Full Text] [PDF]