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Published in: Journal of Translational Medicine 1/2011

Open Access 01-12-2011 | Research

Cancer/Testis antigens as potential predictors of biochemical recurrence of prostate cancer following radical prostatectomy

Authors: Takumi Shiraishi, Naoki Terada, Yu Zeng, Takahito Suyama, Jun Luo, Bruce Trock, Prakash Kulkarni, Robert H Getzenberg

Published in: Journal of Translational Medicine | Issue 1/2011

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Abstract

Background

The Cancer/Testis Antigens (CTAs) are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs could serve as unique biomarkers for cancer diagnosis/prognosis. The aim of this study was to identify promising CTAs that are associated with prostate cancer (PCa) recurrence following radical prostatectomy (RP).

Methods

The expression of 5 CTAs was measured by quantitative multiplex real-time PCR using prostate tissue samples obtained from 72 patients with apparently clinically localized PCa with a median of two years follow-up (range, 1 to 14 years).

Results

The expression of CTAs namely, CEP55, NUF2, PBK and TTK were significantly higher while PAGE4 was significantly lower in patients with recurrent disease. All CTAs with the exception of TTK were significantly correlated with the prostatectomy Gleason score, but none were correlated with age, stage, or preoperative PSA levels. In univariate proportional hazards models, CEP55 (HR = 3.59, 95% CI: 1.50-8.60), p = 0.004; NUF2 (HR = 2.28, 95% CI: 1.11-4.67), p = 0.024; and PAGE4 (HR = 0.44, 95% CI: 0.21-0.93), p = 0.031 were significantly associated with the risk of PCa recurrence. However, the results were no longer significant after adjustment for prostatectomy Gleason score.

Conclusions

To our knowledge, this is the first study to identify CTAs as biomarkers that can differentiate patients with recurrent and non-recurrent disease following RP and underscores its potential impact on PCa prognosis and treatment.
Appendix
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Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59: 225-249. 10.3322/caac.20006.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59: 225-249. 10.3322/caac.20006.CrossRefPubMed
2.
go back to reference Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, Feuer E, de Koning H: Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009, 101: 374-383. 10.1093/jnci/djp001.PubMedCentralCrossRefPubMed Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, Feuer E, de Koning H: Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009, 101: 374-383. 10.1093/jnci/djp001.PubMedCentralCrossRefPubMed
3.
go back to reference Scanlan MJ, Simpson AJ, Old LJ: The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004, 4: 1-PubMed Scanlan MJ, Simpson AJ, Old LJ: The cancer/testis genes: review, standardization, and commentary. Cancer Immun. 2004, 4: 1-PubMed
4.
go back to reference Hofmann O, Caballero OL, Stevenson BJ, Chen YT, Cohen T, Chua R, Maher CA, Panji S, Schaefer U, Kruger A: Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci USA. 2008, 105: 20422-20427. 10.1073/pnas.0810777105.PubMedCentralCrossRefPubMed Hofmann O, Caballero OL, Stevenson BJ, Chen YT, Cohen T, Chua R, Maher CA, Panji S, Schaefer U, Kruger A: Genome-wide analysis of cancer/testis gene expression. Proc Natl Acad Sci USA. 2008, 105: 20422-20427. 10.1073/pnas.0810777105.PubMedCentralCrossRefPubMed
5.
go back to reference Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ: Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005, 5: 615-625. 10.1038/nrc1669.CrossRefPubMed Simpson AJ, Caballero OL, Jungbluth A, Chen YT, Old LJ: Cancer/testis antigens, gametogenesis and cancer. Nat Rev Cancer. 2005, 5: 615-625. 10.1038/nrc1669.CrossRefPubMed
6.
go back to reference Andrade VC, Vettore AL, Felix RS, Almeida MS, Carvalho F, Oliveira JS, Chauffaille ML, Andriolo A, Caballero OL, Zago MA, Colleoni GW: Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun. 2008, 8: 2-PubMedCentralPubMed Andrade VC, Vettore AL, Felix RS, Almeida MS, Carvalho F, Oliveira JS, Chauffaille ML, Andriolo A, Caballero OL, Zago MA, Colleoni GW: Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun. 2008, 8: 2-PubMedCentralPubMed
7.
go back to reference Grigoriadis A, Caballero OL, Hoek KS, da Silva L, Chen YT, Shin SJ, Jungbluth AA, Miller LD, Clouston D, Cebon J: CT-X antigen expression in human breast cancer. Proc Natl Acad Sci USA. 2009, 106: 13493-13498. 10.1073/pnas.0906840106.PubMedCentralCrossRefPubMed Grigoriadis A, Caballero OL, Hoek KS, da Silva L, Chen YT, Shin SJ, Jungbluth AA, Miller LD, Clouston D, Cebon J: CT-X antigen expression in human breast cancer. Proc Natl Acad Sci USA. 2009, 106: 13493-13498. 10.1073/pnas.0906840106.PubMedCentralCrossRefPubMed
8.
go back to reference Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJ, Chen YT, Old LJ, Altorki NK: Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res. 2005, 11: 8055-8062. 10.1158/1078-0432.CCR-05-1203.CrossRefPubMed Gure AO, Chua R, Williamson B, Gonen M, Ferrera CA, Gnjatic S, Ritter G, Simpson AJ, Chen YT, Old LJ, Altorki NK: Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small cell lung cancer. Clin Cancer Res. 2005, 11: 8055-8062. 10.1158/1078-0432.CCR-05-1203.CrossRefPubMed
9.
go back to reference Napoletano C, Bellati F, Tarquini E, Tomao F, Taurino F, Spagnoli G, Rughetti A, Muzii L, Nuti M, Benedetti Panici P: MAGE-A and NY-ESO-1 expression in cervical cancer: prognostic factors and effects of chemotherapy. Am J Obstet Gynecol. 2008, 198 (1): 99. e1-7.CrossRefPubMed Napoletano C, Bellati F, Tarquini E, Tomao F, Taurino F, Spagnoli G, Rughetti A, Muzii L, Nuti M, Benedetti Panici P: MAGE-A and NY-ESO-1 expression in cervical cancer: prognostic factors and effects of chemotherapy. Am J Obstet Gynecol. 2008, 198 (1): 99. e1-7.CrossRefPubMed
10.
go back to reference Svobodova S, Browning J, Macgregor D, Pollara G, Scolyer RA, Murali R, Thompson JF, Deb S, Azad A, Davis ID, Cebon JS: Cancer-testis antigen expression in primary cutaneous melanoma has independent prognostic value comparable to that of Breslow thickness, ulceration and mitotic rate. Eur J Cancer. 2011 Feb, 47 (3): 460-9.CrossRefPubMed Svobodova S, Browning J, Macgregor D, Pollara G, Scolyer RA, Murali R, Thompson JF, Deb S, Azad A, Davis ID, Cebon JS: Cancer-testis antigen expression in primary cutaneous melanoma has independent prognostic value comparable to that of Breslow thickness, ulceration and mitotic rate. Eur J Cancer. 2011 Feb, 47 (3): 460-9.CrossRefPubMed
11.
go back to reference Velazquez EF, Jungbluth AA, Yancovitz M, Gnjatic S, Adams S, O'Neill D, Zavilevich K, Albukh T, Christos P, Mazumdar M: Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)--correlation with prognostic factors. Cancer Immun. 2007, 7: 11-PubMedCentralPubMed Velazquez EF, Jungbluth AA, Yancovitz M, Gnjatic S, Adams S, O'Neill D, Zavilevich K, Albukh T, Christos P, Mazumdar M: Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM)--correlation with prognostic factors. Cancer Immun. 2007, 7: 11-PubMedCentralPubMed
12.
go back to reference Suyama T, Shiraishi T, Zeng Y, Yu W, Parekh N, Vessella RL, Luo J, Getzenberg RH, Kulkarni P: Expression of cancer/testis antigens in prostate cancer is associated with disease progression. Prostate. 2010, 70: 1778-1787.PubMedCentralPubMed Suyama T, Shiraishi T, Zeng Y, Yu W, Parekh N, Vessella RL, Luo J, Getzenberg RH, Kulkarni P: Expression of cancer/testis antigens in prostate cancer is associated with disease progression. Prostate. 2010, 70: 1778-1787.PubMedCentralPubMed
13.
go back to reference Luo J, Duggan DJ, Chen Y, Sauvageot J, Ewing CM, Bittner ML, Trent JM, Isaacs WB: Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Cancer Res. 2001, 61: 4683-4688.PubMed Luo J, Duggan DJ, Chen Y, Sauvageot J, Ewing CM, Bittner ML, Trent JM, Isaacs WB: Human prostate cancer and benign prostatic hyperplasia: molecular dissection by gene expression profiling. Cancer Res. 2001, 61: 4683-4688.PubMed
14.
go back to reference Bova GS, Fox WM, Epstein JI: Methods of radical prostatectomy specimen processing: a novel technique for harvesting fresh prostate cancer tissue and review of processing techniques. Mod Pathol. 1993, 6: 201-207.PubMed Bova GS, Fox WM, Epstein JI: Methods of radical prostatectomy specimen processing: a novel technique for harvesting fresh prostate cancer tissue and review of processing techniques. Mod Pathol. 1993, 6: 201-207.PubMed
15.
go back to reference Suzuki H, Freije D, Nusskern DR, Okami K, Cairns P, Sidransky D, Isaacs WB, Bova GS: Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res. 1998, 58: 204-209.PubMed Suzuki H, Freije D, Nusskern DR, Okami K, Cairns P, Sidransky D, Isaacs WB, Bova GS: Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues. Cancer Res. 1998, 58: 204-209.PubMed
16.
go back to reference Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, Han M, Partin AW, Vessella RL, Isaacs WB: Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 2009, 69: 16-22.PubMedCentralCrossRefPubMed Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, Han M, Partin AW, Vessella RL, Isaacs WB: Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res. 2009, 69: 16-22.PubMedCentralCrossRefPubMed
17.
go back to reference Liu W, Laitinen S, Khan S, Vihinen M, Kowalski J, Yu G, Chen L, Ewing CM, Eisenberger MA, Carducci MA: Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med. 2009, 15: 559-565. 10.1038/nm.1944.PubMedCentralCrossRefPubMed Liu W, Laitinen S, Khan S, Vihinen M, Kowalski J, Yu G, Chen L, Ewing CM, Eisenberger MA, Carducci MA: Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med. 2009, 15: 559-565. 10.1038/nm.1944.PubMedCentralCrossRefPubMed
18.
go back to reference Khan MA, Partin AW, Mangold LA, Epstein JI, Walsh PC: Probability of biochemical recurrence by analysis of pathologic stage, Gleason score, and margin status for localized prostate cancer. Urology. 2003, 62: 866-871. 10.1016/S0090-4295(03)00674-5.CrossRefPubMed Khan MA, Partin AW, Mangold LA, Epstein JI, Walsh PC: Probability of biochemical recurrence by analysis of pathologic stage, Gleason score, and margin status for localized prostate cancer. Urology. 2003, 62: 866-871. 10.1016/S0090-4295(03)00674-5.CrossRefPubMed
19.
go back to reference Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC: Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol. 2003, 169: 517-523. 10.1016/S0022-5347(05)63946-8.CrossRefPubMed Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC: Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol. 2003, 169: 517-523. 10.1016/S0022-5347(05)63946-8.CrossRefPubMed
20.
go back to reference Fabbro M, Zhou BB, Takahashi M, Sarcevic B, Lal P, Graham ME, Gabrielli BG, Robinson PJ, Nigg EA, Ono Y, Khanna KK: Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Dev Cell. 2005, 9: 477-488. 10.1016/j.devcel.2005.09.003.CrossRefPubMed Fabbro M, Zhou BB, Takahashi M, Sarcevic B, Lal P, Graham ME, Gabrielli BG, Robinson PJ, Nigg EA, Ono Y, Khanna KK: Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Dev Cell. 2005, 9: 477-488. 10.1016/j.devcel.2005.09.003.CrossRefPubMed
21.
go back to reference Zhao WM, Seki A, Fang G: Cep55, a microtubule-bundling protein, associates with centralspindlin to control the midbody integrity and cell abscission during cytokinesis. Mol Biol Cell. 2006, 17: 3881-3896. 10.1091/mbc.E06-01-0015.PubMedCentralCrossRefPubMed Zhao WM, Seki A, Fang G: Cep55, a microtubule-bundling protein, associates with centralspindlin to control the midbody integrity and cell abscission during cytokinesis. Mol Biol Cell. 2006, 17: 3881-3896. 10.1091/mbc.E06-01-0015.PubMedCentralCrossRefPubMed
22.
go back to reference Nabetani A, Koujin T, Tsutsumi C, Haraguchi T, Hiraoka Y: A conserved protein, Nuf2, is implicated in connecting the centromere to the spindle during chromosome segregation: a link between the kinetochore function and the spindle checkpoint. Chromosoma. 2001, 110: 322-334. 10.1007/s004120100153.CrossRefPubMed Nabetani A, Koujin T, Tsutsumi C, Haraguchi T, Hiraoka Y: A conserved protein, Nuf2, is implicated in connecting the centromere to the spindle during chromosome segregation: a link between the kinetochore function and the spindle checkpoint. Chromosoma. 2001, 110: 322-334. 10.1007/s004120100153.CrossRefPubMed
23.
go back to reference Wigge PA, Kilmartin JV: The Ndc80p complex from Saccharomyces cerevisiae contains conserved centromere components and has a function in chromosome segregation. J Cell Biol. 2001, 152: 349-360. 10.1083/jcb.152.2.349.PubMedCentralCrossRefPubMed Wigge PA, Kilmartin JV: The Ndc80p complex from Saccharomyces cerevisiae contains conserved centromere components and has a function in chromosome segregation. J Cell Biol. 2001, 152: 349-360. 10.1083/jcb.152.2.349.PubMedCentralCrossRefPubMed
24.
go back to reference Brinkmann U, Vasmatzis G, Lee B, Yerushalmi N, Essand M, Pastan I: PAGE-1, an × chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus. Proc Natl Acad Sci USA. 1998, 95: 10757-10762. 10.1073/pnas.95.18.10757.PubMedCentralCrossRefPubMed Brinkmann U, Vasmatzis G, Lee B, Yerushalmi N, Essand M, Pastan I: PAGE-1, an × chromosome-linked GAGE-like gene that is expressed in normal and neoplastic prostate, testis, and uterus. Proc Natl Acad Sci USA. 1998, 95: 10757-10762. 10.1073/pnas.95.18.10757.PubMedCentralCrossRefPubMed
25.
go back to reference Prakash K, Pirozzi G, Elashoff M, Munger W, Waga I, Dhir R, Kakehi Y, Getzenberg RH: Symptomatic and asymptomatic benign prostatic hyperplasia: molecular differentiation by using microarrays. Proc Natl Acad Sci USA. 2002, 99: 7598-7603. 10.1073/pnas.112191399.PubMedCentralCrossRefPubMed Prakash K, Pirozzi G, Elashoff M, Munger W, Waga I, Dhir R, Kakehi Y, Getzenberg RH: Symptomatic and asymptomatic benign prostatic hyperplasia: molecular differentiation by using microarrays. Proc Natl Acad Sci USA. 2002, 99: 7598-7603. 10.1073/pnas.112191399.PubMedCentralCrossRefPubMed
26.
go back to reference Iavarone C, Wolfgang C, Kumar V, Duray P, Willingham M, Pastan I, Bera TK: PAGE4 is a cytoplasmic protein that is expressed in normal prostate and in prostate cancers. Mol Cancer Ther. 2002, 1: 329-335.CrossRefPubMed Iavarone C, Wolfgang C, Kumar V, Duray P, Willingham M, Pastan I, Bera TK: PAGE4 is a cytoplasmic protein that is expressed in normal prostate and in prostate cancers. Mol Cancer Ther. 2002, 1: 329-335.CrossRefPubMed
28.
go back to reference Harao M, Hirata S, Irie A, Senju S, Nakatsura T, Komori H, Ikuta Y, Yokomine K, Imai K, Inoue M: HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL. Int J Cancer. 2008, 123: 2616-2625. 10.1002/ijc.23823.CrossRefPubMed Harao M, Hirata S, Irie A, Senju S, Nakatsura T, Komori H, Ikuta Y, Yokomine K, Imai K, Inoue M: HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL. Int J Cancer. 2008, 123: 2616-2625. 10.1002/ijc.23823.CrossRefPubMed
29.
go back to reference Inoda S, Hirohashi Y, Torigoe T, Nakatsugawa M, Kiriyama K, Nakazawa E, Harada K, Takasu H, Tamura Y, Kamiguchi K: Cep55/c10orf3, a tumor antigen derived from a centrosome residing protein in breast carcinoma. J Immunother. 2009, 32: 474-485. 10.1097/CJI.0b013e3181a1d109.CrossRefPubMed Inoda S, Hirohashi Y, Torigoe T, Nakatsugawa M, Kiriyama K, Nakazawa E, Harada K, Takasu H, Tamura Y, Kamiguchi K: Cep55/c10orf3, a tumor antigen derived from a centrosome residing protein in breast carcinoma. J Immunother. 2009, 32: 474-485. 10.1097/CJI.0b013e3181a1d109.CrossRefPubMed
30.
go back to reference Inoda S, Morita R, Hirohashi Y, Torigoe T, Asanuma H, Nakazawa E, Nakatsugawa M, Tamura Y, Kamiguchi K, Tsuruma T: The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma. Exp Mol Pathol. 2011 Feb, 90 (1): 55-60.CrossRefPubMed Inoda S, Morita R, Hirohashi Y, Torigoe T, Asanuma H, Nakazawa E, Nakatsugawa M, Tamura Y, Kamiguchi K, Tsuruma T: The feasibility of Cep55/c10orf3 derived peptide vaccine therapy for colorectal carcinoma. Exp Mol Pathol. 2011 Feb, 90 (1): 55-60.CrossRefPubMed
31.
go back to reference Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT: Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol. 2002, 167: 528-534. 10.1016/S0022-5347(01)69079-7.CrossRefPubMed Hull GW, Rabbani F, Abbas F, Wheeler TM, Kattan MW, Scardino PT: Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urol. 2002, 167: 528-534. 10.1016/S0022-5347(01)69079-7.CrossRefPubMed
32.
go back to reference Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ: Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 2004, 172: 910-914. 10.1097/01.ju.0000134888.22332.bb.CrossRefPubMed Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ: Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 2004, 172: 910-914. 10.1097/01.ju.0000134888.22332.bb.CrossRefPubMed
33.
go back to reference Shyamsundar R, Kim YH, Higgins JP, Montgomery K, Jorden M, Sethuraman A, van de Rijn M, Botstein D, Brown PO, Pollack JR: A DNA microarray survey of gene expression in normal human tissues. Genome Biol. 2005, 6: R22-10.1186/gb-2005-6-3-r22.PubMedCentralCrossRefPubMed Shyamsundar R, Kim YH, Higgins JP, Montgomery K, Jorden M, Sethuraman A, van de Rijn M, Botstein D, Brown PO, Pollack JR: A DNA microarray survey of gene expression in normal human tissues. Genome Biol. 2005, 6: R22-10.1186/gb-2005-6-3-r22.PubMedCentralCrossRefPubMed
34.
go back to reference Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM: ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004, 6: 1-6.PubMedCentralCrossRefPubMed Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM: ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia. 2004, 6: 1-6.PubMedCentralCrossRefPubMed
Metadata
Title
Cancer/Testis antigens as potential predictors of biochemical recurrence of prostate cancer following radical prostatectomy
Authors
Takumi Shiraishi
Naoki Terada
Yu Zeng
Takahito Suyama
Jun Luo
Bruce Trock
Prakash Kulkarni
Robert H Getzenberg
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2011
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/1479-5876-9-153

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