The Harris Center serves as key hub for translational research - research programs focus on understanding pathways that contribute to tumor growth, identifying bio-markers and small molecule therapuetics
Ramnik Xavier, MD
Chordoma is a rare, slow-growing malignant tumor believed to arise from cellular remnants of the notochord. The treatment of chordomas is difficult. Wide surgical excision is desirable, but it is rarely feasible based on the anatomic location of the tumor at the base of the skull or the base of the spine.
Currently there are no effective drugs for chordoma, and there are no drugs currently approved to treat chordoma. Unlike with other types of sarcoma, there is no specific known tumor-suppressor gene or oncogene associated with chordoma.
There is a need, however, for understanding the molecular biology of chordoma. We have obtained a number of chordoma cell lines. Most importantly, the Massachusetts General Hospital Sarcoma Group has archived more than 150 cases of chordoma tissues and paraffin blocks in our tissue bank. DNA, RNA and protein samples from chordoma tumor tissues will be analyzed by CGH or SNP array, gene and protein expression profile with the hope of identification of chordoma susceptibility genes or pathways.
The new discoveries from these studies will identify potential tumor-suppressor genes and oncogenes, then proteins for testing in chordoma tissues. We plan to determine the efficacy of targeting mTOR, Stat3 expression in chordoma cells by small molecular compounds, siRNA and to evaluate its effect on chordoma cell growth, proliferation and apoptosis.
Our goal is to be able to identify new molecular targets, assess new therapeutics, and better characterize the prognosis of chordomas.
Recent Chordoma Studies
The following articles are a selection of publications from Harris Center researchers from 2000 to 2010, arranged in chronological order with the most recent at the top. Click on a title for the PubMed summary of the article.
Establishment and characterization of a novel chordoma cell line: CH22. Liu X, Nielsen GP, Rosenberg AE, Waterman PR, Yang W, Choy E, Sassi S, Yang S, Harmon DC, Yang C, Schwab JH, Kobayashi E, Mankin HJ, Xavier R, Weissleder R, Duan Z, Hornicek FJ. J Orthop Res. 2012 Apr 13. doi: 10.1002/jor.22113
Extended dermal apposition: a simple technique for the closure of irradiated perineal and sacral wounds. Hartzell TL, Medina M, Hornicek FJ, Austen WG Jr. Plast Reconstr Surg. 2011 Jun;127(6):170e-3e
Recurrent chromosomal copy number alterations in sporadic chordomas Le LP, Nielsen GP, Rosenberg AE, Thomas D, Batten JM, Deshpande V, Schwab J, Duan Z, Xavier RJ, Hornicek FJ, Iafrate AJ. PLoS One. 2011;6(5):e18846. Epub 2011 May 13
Nanoparticles: a promising modality in the treatment of sarcomas. Susa M, Milane L, Amiji MM, Hornicek FJ, Duan Z.Pharm Res. 2011 Feb;28(2):260-72. Epub 2010 May 27.
Proteomic profiling of chordoma. DeLaney TF, Duan Z, Hornicek FJ. J Surg Oncol. 2010 Dec 1;102(7):719. doi: 10.1002/jso.21766
Blockage of Stat3 With CDDO-Me Inhibits Tumor Cell Growth in Chordoma Yang C, Hornicek FJ, Wood KB, Schwab JH, Choy E, Mankin H, Duan Z. Spine 2010 Apr 9. [Epub ahead of print]PMID: 20386502 [PubMed - as supplied by publisher]
A novel target for treatment of chordoma: signal transducers and activators of transcription 3 Yang C, Schwab JH, Schoenfeld AJ, Hornicek FJ, Wood KB, Nielsen GP, Choy E, Mankin H, Duan Z. Mol Cancer Ther 2009 Sep;8(9):2597-605.
Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Schwab J, Antonescu C, Boland P, Healey J, Rosenberg A, Nielsen P, Iafrate J, Delaney T, Yoon S, Choy E, Harmon D, Raskin K, Yang C, Mankin H, Springfield D, Hornicek F, Duan Z. Anticancer Res. 2009 Jun;29(6):1867-71. PMID: 19528441 [PubMed - in process]
Aberrant hyperactivation of akt and Mammalian target of rapamycin complex 1 signaling in sporadic chordomas. Han S, Polizzano C, Nielsen GP, Hornicek FJ, Rosenberg AE, Ramesh V. Clin Cancer Res. 2009 Mar 15;15(6):1940-6. Epub 2009 Mar 10. PMID: 19276265
Combination short-course preoperative irradiation, surgical resection, and reduced-field high-dose postoperative irradiation in the treatment of tumors involving the bone. Wagner TD, Kobayashi W, Dean S, Goldberg SI, Kirsch DG, Suit HD, Hornicek FJ, Pedlow FX, Raskin KA, Springfield DS, Yoon SS, Gebhardt MC, Mankin HJ, Delaney TF. Int J Radiat Oncol Biol Phys. 2009 Jan 1;73(1):259-66. PMID: 19100921
Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas.
Chordoma and chondrosarcoma gene profile: implications for immunotherapy. Schwab JH, Boland PJ, Agaram NP, Socci ND, Guo T, O'Toole GC, Wang X, Ostroumov E, Hunter CJ, Block JA, Doty S, Ferrone S, Healey JH, Antonescu CR.
Cancer Immunol Immunother. 2009 Mar;58(3):339-49. Epub 2008 Jul 19.
The surgical pathology of notochordal remnants in adult intervertebral disks: a report of 3 cases.
Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De Maglio G, den Bakker MA, Di Francesco L, Kalil RK, Athanasou NA, O'Donnell P, McCarthy EF, Flanagan AM. Am J Surg Pathol. 2008 Apr;32(4):572-80. PMID: 18301055
Intraosseous benign notochord cell tumors (BNCT): further evidence supporting a relationship to chordoma. Deshpande V, Nielsen GP, Rosenthal DI, Rosenberg AE. Am J Surg Pathol. 2007 Oct;31(10):1573-7. PMID: 17895760
Clonality studies in sacral chordoma. Klingler L, Trammell R, Allan DG, Butler MG, Schwartz HS. Cancer Genet Cytogenet. 2006 Nov;171(1):68-71. PMID: 17074594
Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases.
Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor. Park L, Delaney TF, Liebsch NJ, Hornicek FJ, Goldberg S, Mankin H, Rosenberg AE, Rosenthal DI, Suit HD. Int J Radiat Oncol Biol Phys. 2006 Aug 1;65(5):1514-21. Epub 2006 Jun 6. PMID: 16757128
Sarcoma and skin radiation oncology. Nedea EA, DeLaney TF. Hematol Oncol Clin North Am. 2006 Apr;20(2):401-29. Review.
Corroboration of a familial chordoma locus on chromosome 7q and evidence of genetic heterogeneity using single nucleotide polymorphisms (SNPs). Yang XR, Beerman M, Bergen AW, Parry DM, Sheridan E, Liebsch NJ, Kelley MJ, Chanock S, Goldstein AM. Int J Cancer. 2005 Sep 1;116(3):487-91. PMID: 15818627
Spinal cord tolerance to high-dose fractionated 3D conformal proton-photon irradiation as evaluated by equivalent uniform dose and dose volume histogram analysis. Marucci L, Niemierko A, Liebsch NJ, Aboubaker F, Liu MC, Munzenrider JE. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):551-5. PMID: 15145175
Anterior spinal arthrodesis with structural cortical allografts and instrumentation for spine tumor surgery.Lewandrowski KU, Hecht AC, DeLaney TF, Chapman PA, Hornicek FJ, Pedlow FX. Spine (Phila Pa 1976). 2004 May 15;29(10):1150-8; discussion 1159. Review. PMID: 15131446
Clinical outcome in chordoma: utility of flow cytometry in DNA determination. Berven S, Zurakowski D, Mankin HJ, Gebhardt MC, Springfield DS, Hornicek FJ. Spine (Phila Pa 1976). 2002 Feb 15;27(4):374-9. PMID: 11840103
Chordoma periphericum: a case report. Nielsen GP, Mangham DC, Grimer RJ, Rosenberg AE. Am J Surg Pathol. 2001 Feb;25(2):263-7. PMID: 11176077
Role of onlay grafting with minimal internal fixation for occipitocervical fusion in oncologic patients. Sanpakit S, Mansfield TL, Liebsch J. J Spinal Disord. 2000 Oct;13(5):382-90. PMID: 11052346
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