Cancer Immunology and Immunotherapy Center

Recent Publications

Frequencies of an Immunogenic HER-2/neu Epitope of CD8+ T Lymphocytes Predict Favorable Clinical Outcomes in Prostate Cancer.

Goulielmaki M, Stokidis S, Anagnostou T, Voutsas IF, Gritzapis AD, Baxevanis CN, Fortis SP.

Int J Mol Sci 2023, 24 (6).

The thin red line between the immune system and cancer evolution.

Baxevanis CN, Goulielmaki M, Adamaki M, Fortis SP.

Transl Oncol 2023, 27, 101555.

Immune Checkpoint Inhibitors in Cancer Therapy-How Can We Improve Clinical Benefits?

Baxevanis CN.

Cancers (Basel) 2023, 15 (3).

DNA Damage Response Mechanisms in Head and Neck Cancer: Significant Implications for Therapy and Survival.

Papalouka C, Adamaki M, Batsaki P, Zoumpourlis P, Tsintarakis A, Goulielmaki M, Fortis SP, Baxevanis CN, Zoumpourlis V.

Int J Mol Sci 2023, 24 (3).

Biomarkers in the Era of Precision Oncology.

Baxevanis N.

Cancers (Basel) 2023, 15 (6).

Promising Biomarkers in Head and Neck Cancer: The Most Clinically Important miRNAs.

Thomaidou AC, Batsaki P, Adamaki M, Goulielmaki M, Baxevanis CN, Zoumpourlis V, Fortis SP.

Int J Mol Sci 2022, 23 (15).

The impact of radiation therapy on the TCR Vbeta chain repertoire in patients with prostate cancer.

Goulielmaki M, Davanos N, Kogionou P, Batsaki P, Stokidis S, Adamaki M, Mosa E, Vasilakou E, Zambatis C, Gritzapis AD, Zoumpourlis V, Baxevanis CN, Fortis SP.

Int J Oncol 2022, 60 (6).

Association between Intratumoral CD8+ T Cells with FoxP3+ and CD163+ Cells: A Potential Immune Intrinsic Negative Feedback Mechanism for Acquired Immune Resistance.

Fortis SP, Sofopoulos M, Goulielmaki M, Arnogiannaki N, Ardavanis A, Perez SA, Gritzapis AD, Baxevanis CN.

Cancers (Basel) 2022, 14 (24).

Radiotherapy-Related Gene Signature in Prostate Cancer.

Fortis SP, Goulielmaki M, Aubert N, Batsaki P, Ouzounis S, Cavouras D, Marodon G, Stokidis S, Gritzapis AD, Baxevanis CN.

Cancers (Basel) 2022, 14 (20).

T-Cell Repertoire in Tumor Radiation: The Emerging Frontier as a Radiotherapy Biomarker.

Baxevanis CN, Gritzapis AD, Voutsas IF, Batsaki P, Goulielmaki M, Adamaki M, Zoumpourlis V, Fortis SP.

Cancers (Basel) 2022, 14 (11).

Combination Immunotherapy in Prostate Cancer.

Baxevanis CN, Goulielmaki M, Gritzapis AD, Fortis SP.

Cancers (Basel) 2022, 14 (24).

4th Summer School in Immuno-Oncology, July 1st-3rd, 2021, Athens, Greece.

Kostopoulos IV, Orologas-Stavrou N, Angelis N, Pateras Is, Kotsakis A, Georgoulias V, Baxevanis CN, Pawelec G, Tsitsilonis OE.

Front Biosci (Landmark Ed) 2021, 26 (11), 1373-1382.

The balance between breast cancer and the immune system: Challenges for prognosis and clinical benefit from immunotherapies.

Baxevanis CN, Fortis SP, Perez SA.

Semin Cancer Biol 2021, 72, 76-89.

HLA Class I Allele Expression and Clinical Outcome in De Novo Metastatic Prostate Cancer.

Stokidis S, Fortis SP, Kogionou P, Anagnostou T, Perez SA, Baxevanis CN.

Cancers (Basel) 2020, 12 (6).

Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence.

Brown TA, Mittendorf EA, Hale DF, Myers JW, Peace KM, Jackson DO, Greene JM, Vreeland TJ, Clifton Gt, Ardavanis A, Litton JK, Shumway Nm, Symanowski J, Murray JL, Ponniah S, Anastasopoulou EA, Pistamaltzian NF, Baxevanis CN, Perez SA, Papamichail M, Peoples GE.

Breast Cancer Res Treat 2020, 181 (2), 391-401.

Exploring Essential Issues for Improving Therapeutic Cancer Vaccine Trial Design.

Baxevanis CN, Fortis SP, Ardavanis A, Perez SA.

Cancers (Basel) 2020, 12 (10).

Tumor-infiltrating and circulating granulocytic myeloid-derived suppressor cells correlate with disease activity and adverse clinical outcomes in mycosis fungoides.

Argyropoulos KV, Pulitzer M, Perez S, Korkolopoulou P, Angelopoulou M, Baxevanis C, Palomba Ml, Siakantaris M.

Clin Transl Oncol 2020, 22 (7), 1059-1066

The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer.

Sofopoulos M, Fortis SP, Vaxevanis CK, Sotiriadou NN, Arnogiannaki N, Ardavanis A, Vlachodimitropoulos D, Perez SA, Baxevanis CN.

Cancer Immunol Immunother 2019, 68 (11), 1733-1745.

Serum miRNA-based distinct clusters define three groups of breast cancer patients with different clinicopathological and immune characteristics.

Fortis SP, Vaxevanis CK, Mahaira LG, Sofopoulos M, Sotiriadou NN, Dinou A, Arnogiannaki N, Stavropoulos-Giokas C, Thanos D, Baxevanis CN, Perez SA.

Cancer Immunol Immunother 2019, 68 (1), 57-70.

4th Symposium on Advances in Cancer Immunology and Immunotherapy, November 29-December 1, 2018, Athens, Greece.

Fortis SP, Kotsakis A, Le Tourneau C, Tsitsilonis OE, Georgoulias V, Baxevanis CN.

Cancer Immunol Immunother 2019, 68 (8), 1391-1400.

The role of immune infiltrates as prognostic biomarkers in patients with breast cancer. Cancer Immunol

Baxevanis CN, Sofopoulos M, Fortis SP, Perez SA.

Immunother 2019, 68 (10), 1671-1680.

Prostate cancer: any room left for immunotherapies?

Baxevanis CN, Fortis SP, Perez SA.

Immunotherapy 2019, 11 (2), 69-74.

T-cell recognition of non-mutated tumor antigens in healthy individuals: connecting endogenous immunity and tumor dormancy.

Baxevanis CN.

Cancer Immunol Immunother 2019, 68 (5), 705-707.

2nd Symposium on Advances in Cancer Immunology and Immunotherapy, December 15-17, 2016, Athens, Greece.

Samara P, Kotsakis A, Tsitsilonis O, Georgoulias V, Pawelec G, Baxevanis CN.

Cancer Immunol Immunother 2018, 67 (1), 153-159.

Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients.

Janssen N, Fortis SP, Speigl L, Haritos C, Sotiriadou NN, Sofopoulos M, Arnogiannaki N, Stavropoulos-Giokas C, Dinou A, Perez S, Pawelec G, Baxevanis CN, Shipp C.

Breast Cancer Res Treat 2017, 161 (1), 51-62.

Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer.

Fortis SP; Sofopoulos M, Sotiriadou, NN, Haritos C, Vaxevanis CK, Anastasopoulou EA, Janssen N, Arnogiannaki N, Ardavanis A, Pawelec G, Perez SA, Baxevanis CN.

J Immunother Cancer 2017, 5, 39.

Immune profiling of melanoma tumors reflecting aggressiveness in a preclinical model.

Fortis SP, Mahaira LG, Anastasopoulou EA, Voutsas IF, Perez SA, Baxevanis CN

Cancer Immunol Immunother 2017, 66 (12), 1631-1642.

Potential Prognostic Molecular Signatures in a Preclinical Model of Melanoma.

Fortis SP, Anastasopoulou EA, Voutsas IF, Baxevanis CN, Perez SA, Mahaira LG.

Anticancer Res. 2017 Jan;37(1):143-148.

Peripheral T cell responses to tumour antigens are associated with molecular, immunogenetic and cellular features of breast cancer patients.

Janssen N, Fortis SP, Speigl L, Haritos C, Sotiriadou NN, Sofopoulos M, Arnogiannaki N, Stavropoulos-Giokas C, Dinou A, Perez S, Pawelec G, Baxevanis CN, Shipp C.

Breast Cancer Res Treat. 2017 Jan;161(1):51-62.

Unraveling the role of preexisting immunity in prostate cancer patients vaccinated with a HER-2/neu hybrid peptide.

Voutsas IF, Anastasopoulou EA, Tzonis P, Papamichail M, Perez SA, Baxevanis CN.

J Immunother Cancer. 2016 Nov 15;4:75.

Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence.
Mittendorf EA, Ardavanis A, Litton JK, Shumway NM, Hale DF, Murray JL, Perez SA, Ponniah S, Baxevanis CN, Papamichail M, Peoples GE.
Oncotarget. 2016 Oct 4;7(40):66192-66201.

Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence.
Mittendorf EA, Ardavanis A, Symanowski J, Murray JL, Shumway NM, Litton JK, Hale DF, Perez SA, Anastasopoulou EA, Pistamaltzian NF, Ponniah S, Baxevanis CN, von Hofe E, Papamichail M, Peoples GE.

Ann Oncol. 2016 Jul;27(7):1241-8.

Cancer vaccines: limited success but the research should remain viable.
Baxevanis CN, Perez SA.
Expert Rev Vaccines. 2016 Jun;15(6):677-80.

Cancer Dormancy: A Regulatory Role for Endogenous Immunity in Establishing and Maintaining the Tumor Dormant State.
Baxevanis CN, Perez SA.
Vaccines (Basel). 2015 Jul 30;3(3):597-619.
A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA-DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit.
 
Anastasopoulou EA, Voutsas IF, Keramitsoglou T, Gouttefangeas C, Kalbacher H, Thanos A, Papamichail M, Perez SA, Baxevanis CN., Papamichail M, Perez SA.
Cancer Immunol Immunother. 2015 Sep;64(9):1123-36.

Prostate cancer vaccines: the long road to clinical application.

Baxevanis CN, Papamichail M, Perez SA.
Cancer Immunol Immunother. 2015 Feb 19.

Immune biomarkers: how well do they serve prognosis in human cancers?
Baxevanis CN, Anastasopoulou EA, Voutsas IF, Papamichail M, Perez SA.
Expert Rev Mol Diagn. 2014 Oct 27:1-11. 
AE37 peptide vaccination in prostate cancer: identification of biomarkers in the context of prognosis and prediction.
Perez SA, Anastasopoulou EA, Papamichail M, Baxevanis CN.
Cancer Immunol Immunother. 2014 Nov;63(11):1141-50. 
New use for old drugs? Prospective targets of chloroquines in cancer therapy.
Vlahopoulos S, Critselis E, Voutsas IF, Perez SA, Moschovi M, Baxevanis CN, Chrousos GP.
Curr Drug Targets. 2014;15(9):843-51.
IGF2BP1 expression in human mesenchymal stem cells significantly affects their proliferation and is under the epigenetic control of TET1/2 demethylases.
Mahaira LG, Katsara O, Pappou E, Iliopoulou EG, Fortis S, Antsaklis A, Fotinopoulos P, Baxevanis CN, Papamichail M, Perez SA.
Stem Cells Dev. 2014 Oct 15;23(20):2501-12.

Invariant chain-Peptide fusion vaccine using her-2/neu.
Perez SA, Peoples GE, Papamichail M, Baxevanis CN.
Methods Mol Biol. 2014;1139:321-36.

Immunologic biomarkers in prostate cancer: The AE37 paradigm.

Baxevanis CN, Papamichail M, Perez SA.
Hum Vaccin Immunother. 2014 Feb 19;10(5).
Therapeutic cancer vaccines: a long and winding road to success.

Baxevanis CN, Papamichail M, Perez SA.
Expert Rev Vaccines. 2014 Jan;13(1):131-44.
AE37 peptide vaccination in prostate cancer: a 4-year immunological assessment updates on a phase I trial.
  
Perez SA, Anastasopoulou EA, Tzonis P, Gouttefangeas C, Kalbacher H, Papamichail M, Baxevanis CN.
Cancer Immunol Immunother. 2013 Aug 10.

Toll-like receptor agonists: current status and future perspective on their utility as adjuvants in improving anticancer vaccination strategies.
Baxevanis CN, Voutsas IF, Tsitsilonis OE.
Immunotherapy. 2013 May;5(5):497-511. doi: 10.2217/imt.13.24.
Gamma-irradiation induces her2/neu overexpression in breast cancer cell lines and sensitivity to treatment with trastuzumab
.
Voutsas IF, Mahaira LG, Fotopoulou K, Kapranos N, Reclos JG, Gritzapis AD, Papamichail M, Perez SA, Baxevanis CN.
Int J Radiat Biol. 2013 Feb 1.

Immune classification of colorectal cancer patients: impressive but how complete?
Baxevanis CN, Papamichail M, Perez SA.
Expert Opin Biol Ther. 2013 Jan 6.
Toxicity profiles of HER2/neu peptide anticancer vaccines: the picture from Phase/I and II clinical trials.
Baxevanis CN, Papamichail M, Perez SA.
Expert Rev Vaccines. 2012 Jun;11(6):637-40. doi: 10.1586/erv.12.33. 

New insights into the role of NK cells in cancer immunotherapy.
Maria Salagianni, Constantin N. Baxevanis, Michael Papamichail, and Sonia A. Perez
Oncoimmunology. 2012 March 1; 1(2): 205–207.

Outlining novel scenarios for improved therapeutic cancer vaccines: the PANVAC paradigm.
Baxevanis CN.
Expert Rev Vaccines. 2012 Mar;11(3):275-7.

Ontak reduces the immunosuppressive tumor environment and enhances successful therapeutic vaccination in HER-2/neu-tolerant mice.
Gritzapis AD, Voutsas IF, Baxevanis CN.
Cancer Immunol Immunother. 2012 Mar;61(3):397-407.

AE37: a novel T-cell-eliciting vaccine for breast cancer.
Sears AK, Perez SA, Clifton GT, Benavides LC, Gates JD, Clive KS, Holmes JP, Shumway NM, Van Echo DC, Carmichael MG, Ponniah S, Baxevanis CN, Mittendorf EA, Papamichail M, Peoples GE.
Expert Opin Biol Ther. 2011 Nov;11(11):1543-50.

Developing effective cancer vaccines. 
Baxevanis CN, Perez SA, Papamichail M.
Eur J Cancer. 2011 Sep;47 Suppl 3:S364-5.

Effect of the simultaneous administration of glucocorticoids and IL-15 on human NK cell phenotype, proliferation and function.
Moustaki A, Argyropoulos KV, Baxevanis CN, Papamichail M, Perez SA.
Cancer Immunol Immunother. 2011 Jun 26.

NK cell adoptive transfer combined with Ontak-mediated regulatory T cell elimination induces effective adaptive antitumor immune responses.
Salagianni M, Lekka E, Moustaki A, Iliopoulou EG, Baxevanis CN, Papamichail M, Perez SA.
J Immunol. 2011 Mar 15;186(6):3327-35.

Effects of Donor Age, Gender, and In Vitro Cellular Aging on the Phenotypic, Functional, and Molecular Characteristics of Mouse Bone Marrow-Derived Mesenchymal Stem Cells.
Katsara O, Mahaira LG, Iliopoulou EG, Moustaki A, Antsaklis A, Loutradis D, Stefanidis K, Baxevanis CN, Papamichail M, Perez SA.
Stem Cells Dev. 2011 Feb 15.

Combined treatment with Bevacizumab and standard chemotherapy restores abnormal immune parameters in advanced colorectal cancer patients.
Tsavaris N, Voutsas IF, Kosmas C, Gritzapis AD, Baxevanis CN.
Invest New Drugs. 2010 Sep 7.

A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer.
Iliopoulou EG, Kountourakis P, Karamouzis MV, Doufexis D, Ardavanis A, Baxevanis CN, Rigatos G, Papamichail M, Perez SA.
Cancer Immunol Immunother. 2010 Dec;59(12):1781-9.

HER-2/neu as a target for cancer vaccines.
Baxevanis CN, Voutsas IF, Gritzapis AD, Perez SA, Papamichail M.
Immunotherapy. 2010 Mar;2(2):213-26. Review.

Results from a phase I clinical study of the novel Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine in patients with prostate cancer.
Perez SA, Kallinteris NL, Bisias S, Tzonis PK, Georgakopoulou K, Varla-Leftherioti M, Papamichail M, Thanos A, von Hofe E, Baxevanis CN.
Clin Cancer Res. 2010 Jul 1;16(13):3495-506.

Peptide vaccination breaks tolerance to HER-2/neu by generating vaccine-specific FasL(+) CD4(+) T cells: first evidence for intratumor apoptotic regulatory T cells.
Gritzapis AD, Voutsas IF, Lekka E, Papamichail M, Baxevanis CN.
Cancer Res. 2010 Apr 1;70(7):2686-96.

A new era in anticancer peptide vaccines.
Perez SA, von Hofe E, Kallinteris NL, Gritzapis AD, Peoples GE, Papamichail M, Baxevanis CN.
Cancer. 2010 May 1;116(9):2071-80. Review.

Identification and characterization of a HER-2/neu epitope as a potential target for cancer immunotherapy.
Lekka E, Gritzapis AD, Perez SA, Tsavaris N, Missitzis I, Mamalaki A, Papamichail M, Baxevanis CN.
Cancer Immunol Immunother. 2010 May;59(5):715-27.

The mannosylated extracellular domain of Her2/neu produced in P. pastoris induces protective antitumor immunity.
Dimitriadis A, Gontinou C, Baxevanis CN, Mamalaki A.
BMC Cancer. 2009 Oct 30;9:386.

HER-2/neu (657-665) represents an immunogenic epitope of HER-2/neu oncoprotein with potent antitumor properties.
Gritzapis AD, Fridman A, Perez SA, La Monica N, Papamichail M, Aurisicchio L, Baxevanis CN.
Vaccine. 2009 Dec 10;28(1):162-70.

Cancer immunotherapy.
Baxevanis CN, Perez SA, Papamichail M.
Crit Rev Clin Lab Sci. 2009;46(4):167-89. Review.

Mannose addition by yeast Pichia Pastoris on recombinant HER-2 protein inhibits recognition by the monoclonal antibody herceptin.
Vlahopoulos S, Gritzapis AD, Perez SA, Cacoullos N, Papamichail M, Baxevanis CN.
Vaccine. 2009 Jul 23;27(34):4704-8.

Combinatorial treatments including vaccines, chemotherapy and monoclonal antibodies for cancer therapy.
Baxevanis CN, Perez SA, Papamichail M.
Cancer Immunol Immunother. 2009 Mar;58(3):317-24. Review.

Identification of a novel immunogenic HLA-A*0201-binding epitope of HER-2/neu with potent antitumor properties.
Gritzapis AD, Voutsas IF, Lekka E, Tsavaris N, Missitzis I, Sotiropoulou P, Perez S, Papamichail M, Baxevanis CN.
J Immunol. 2008 Jul 1;181(1):146-54.

The proteome profile of two cell lines and their xenografts isolated from a patient with clear cell sarcoma (soft tissue melanoma).
Dimas K, Tsimplouli C, Anagnostopoulos AK, Mahaira L, Iliopoulou E, Perez S, Vougas K, Tsangaris GT.
Cancer Genomics Proteomics. 2008 May-Aug;5(3-4):175-237.

Translating immunity into cancer therapy: new findings from the first conference of the European Society for Cancer Immunology and Immunotherapy, an ESMO-EIS held in Athens, 15-17 November 2007.
Pawelec G, Perez S.
Cancer Immunol Immunother. 2008 Oct;57(10):1505-9.

Cancer immunotherapy: perspectives and prospects.
Perez SA, Papamichail M.
Adv Exp Med Biol. 2008;622:235-53. Review.

Clinical grade expansion of human bone marrow mesenchymal stem cells.
Sotiropoulou PA, Perez SA, Papamichail M.
Methods Mol Biol. 2007;407:245-63.

Immune properties of mesenchymal stem cells.
Sotiropoulou PA, Papamichail M.
Methods Mol Biol. 2007;407:225-43. Review.

Induction of potent CD4+ T cell-mediated antitumor responses by a helper HER-2/neu peptide linked to the Ii-Key moiety of the invariant chain.
Voutsas IF, Gritzapis AD, Mahaira LG, Salagianni M, von Hofe E, Kallinteris NL, Baxevanis CN.
Int J Cancer. 2007 Nov 1;121(9):2031-41.

A novel quantitative flow cytometric method for measuring glucocorticoid receptor (GR) in cell lines: correlation with the biochemical determination of GR.
Voutsas IF, Gritzapis AD, Alexis MN, Katsanou ES, Perez S, Baxevanis CN, Papamichail M.
J Immunol Methods. 2007 Jul 31;324(1-2):110-9.

Increased frequency of CD4+ cells expressing CD161 in cancer patients.
Iliopoulou EG, Karamouzis MV, Missitzis I, Ardavanis A, Sotiriadou NN, Baxevanis CN, Rigatos G, Papamichail M, Perez SA.
Clin Cancer Res. 2006 Dec 1;12(23):6901-9.

Ii-Key/HER-2/neu(776-790) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER-2/neu+ tumors.
Sotiriadou NN, Kallinteris NL, Gritzapis AD, Voutsas IF, Papamichail M, von Hofe E, Humphreys RE, Pavlis T, Perez SA, Baxevanis CN.
Cancer Immunol Immunother. 2007 May;56(5):601-13.

Characterization of a novel cell penetrating peptide derived from Bag-1 protein.
Niarchos DK, Perez SA, Papamichail M.
Peptides. 2006 Nov;27(11):2661-9.

Vaccination with human HER-2/neu (435-443) CTL peptide induces effective antitumor immunity against HER-2/neu-expressing tumor cells in vivo.
Gritzapis AD, Mahaira LG, Perez SA, Cacoullos NT, Papamichail M, Baxevanis CN.
Cancer Res. 2006 May 15;66(10):5452-60.

Cell culture medium composition and translational adult bone marrow-derived stem cell research.
Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M.
Stem Cells. 2006 May;24(5):1409-10.

Fifth European progress in vaccination against cancer conference, PIVAC 5.
Cavallo F, Baxevanis CN.
Cancer Immunol Immunother. 2006 Jul;55(7):884-90.

Growth inhibition of breast cancer cell lines overexpressing Her2/neu by a novel internalized fully human Fab antibody fragment.
Belimezi MM, Papanastassiou D, Merkouri E, Baxevanis CN, Mamalaki A.
Cancer Immunol Immunother. 2006 Sep;55(9):1091-9.

Effect of IL-21 on NK cells derived from different umbilical cord blood populations.
Perez SA, Mahaira LG, Sotiropoulou PA, Gritzapis AD, Iliopoulou EG, Niarchos DK, Cacoullos NT, Kavalakis YG, Antsaklis AI, Sotiriadou NN, Baxevanis CN, Papamichail M.
Int Immunol. 2006 Jan;18(1):49-58.

Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells.
Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M.
Stem Cells. 2006 Feb;24(2):462-71.

Interactions between human mesenchymal stem cells and natural killer cells.
Sotiropoulou PA, Perez SA, Gritzapis AD, Baxevanis CN, Papamichail M.
Stem Cells. 2006 Jan;24(1):74-85.

 

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