Skip to main content
NCBI home page
Sarcoma logoLink to Sarcoma
. 2002 Mar;6(1):27–42. doi: 10.1080/13577140220127530

Molecular Approaches to Sarcoma Therapy

R J Olsen 1, S R Tarantolo 2, S H Hinrichs 1,✉
PMCID: PMC2395489  PMID: 18521343

Abstract

Soft tissue sarcomas comprise a heterogeneous group of aggressive tumors that have a relatively poor prognosis. Although conventional therapeutic regimens can effectively cytoreduce the overall tumor mass, they fail to consistently achieve a curative outcome. Alternative gene-based approaches that counteract the underlying neoplastic process by eliminating the clonal aberrations that potentiate malignant behavior have been proposed. As compared to the accumulation of gene alterations associated with epithelial carcinomas, sarcomas are frequently characterized by the unique presence of a single chromosomal translocation in each histological subtype. Similar to the Philadelphia chromosome associated with CML, these clonal abnormalities result in the fusion of two independent unrelated genes to generate a unique chimeric protein that displays aberrant activity believed to initiate cellular transformation. Secondary gene mutations may provide an additional growth advantage that further contributes to malignant progression. The recent clinical success of the tyrosine kinase inhibitor, STI571, suggests that therapeutic approaches specifically directed against essential survival factors in sarcoma cells may be effective. This review summarizes published approaches targeting a specific molecular mechanism associated with sarcomagenesis. The strategy and significance of published translational studies in six distinct areas are presented. These include: (1) the disruption of chimeric transcription factor activity; (2) inhibition of growth stimulatory post-translational modifications; (3) restoration of tumor suppressor function; (4) interference with angiogenesis; (5) induction of apoptotic pathways; and (6) introduction of toxic gene products. The potential for improving outcomes in sarcoma patients and the conceptual obstacles to be overcome are discussed.

Full Text

The Full Text of this article is available as a PDF (291.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Afford S., Randhawa S. Apoptosis. Mol Pathol. 2000 Apr;53(2):55–63. doi: 10.1136/mp.53.2.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aman P. Fusion genes in solid tumors. Semin Cancer Biol. 1999 Aug;9(4):303–318. doi: 10.1006/scbi.1999.0130. [DOI] [PubMed] [Google Scholar]
  3. Antelman D., Perry S., Hollingsworth R., Gregory R. J., Driscoll B., Fung Y. K., Bookstein R. Engineered mutants of pRB with improved growth suppression potential. Oncogene. 1997 Dec 4;15(23):2855–2866. doi: 10.1038/sj.onc.1201465. [DOI] [PubMed] [Google Scholar]
  4. Aoki K., Akyürek L. M., San H., Leung K., Parmacek M. S., Nabel E. G., Nabel G. J. Restricted expression of an adenoviral vector encoding Fas ligand (CD95L) enhances safety for cancer gene therapy. Mol Ther. 2000 Jun;1(6):555–565. doi: 10.1006/mthe.2000.0076. [DOI] [PubMed] [Google Scholar]
  5. Aramburu-González J. A., Rodríguez-Justo M., Jiménez-Reyes J., Santonja C. A case of soft tissue mesenchymal chondrosarcoma metastatic to skin, clinically mimicking keratoacanthoma. Am J Dermatopathol. 1999 Aug;21(4):392–394. doi: 10.1097/00000372-199908000-00016. [DOI] [PubMed] [Google Scholar]
  6. Bais C., Santomasso B., Coso O., Arvanitakis L., Raaka E. G., Gutkind J. S., Asch A. S., Cesarman E., Gershengorn M. C., Mesri E. A. G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator. Nature. 1998 Jan 1;391(6662):86–89. doi: 10.1038/34193. [DOI] [PubMed] [Google Scholar]
  7. Barrios C., Castresana J. S., Ruiz J., Kreicbergs A. Amplification of the c-myc proto-oncogene in soft tissue sarcomas. Oncology. 1994 Jan-Feb;51(1):13–17. doi: 10.1159/000227302. [DOI] [PubMed] [Google Scholar]
  8. Bennicelli J. L., Barr F. G. Genetics and the biologic basis of sarcomas. Curr Opin Oncol. 1999 Jul;11(4):267–274. doi: 10.1097/00001622-199907000-00006. [DOI] [PubMed] [Google Scholar]
  9. Bernard G., Breittmayer J. P., de Matteis M., Trampont P., Hofman P., Senik A., Bernard A. Apoptosis of immature thymocytes mediated by E2/CD99. J Immunol. 1997 Mar 15;158(6):2543–2550. [PubMed] [Google Scholar]
  10. Bernasconi M., Remppis A., Fredericks W. J., Rauscher F. J., 3rd, Schäfer B. W. Induction of apoptosis in rhabdomyosarcoma cells through down-regulation of PAX proteins. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13164–13169. doi: 10.1073/pnas.93.23.13164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Black A. R., Azizkhan-Clifford J. Regulation of E2F: a family of transcription factors involved in proliferation control. Gene. 1999 Sep 17;237(2):281–302. doi: 10.1016/s0378-1119(99)00305-4. [DOI] [PubMed] [Google Scholar]
  12. Bosilevac J. M., Gilchrist C. A., Jankowski P. E., Paul S., Rees A. R., Hinrichs S. H. Inhibition of activating transcription factor 1- and cAMP-responsive element-binding protein-activated transcription by an intracellular single chain Fv fragment. J Biol Chem. 1998 Jul 3;273(27):16874–16879. doi: 10.1074/jbc.273.27.16874. [DOI] [PubMed] [Google Scholar]
  13. Bosilevac J. M., Olsen R. J., Bridge J. A., Hinrichs S. H. Tumor cell viability in clear cell sarcoma requires DNA binding activity of the EWS/ATF1 fusion protein. J Biol Chem. 1999 Dec 3;274(49):34811–34818. doi: 10.1074/jbc.274.49.34811. [DOI] [PubMed] [Google Scholar]
  14. Bougeret C., Virone-Oddos A., Adeline E., Lacroix F., Lefranc C., Ferrero L., Huet T. Cancer gene therapy mediated by CTS1, a p53 derivative: advantage over wild-type p53 in growth inhibition of human tumors overexpressing MDM2. Cancer Gene Ther. 2000 May;7(5):789–798. doi: 10.1038/sj.cgt.7700163. [DOI] [PubMed] [Google Scholar]
  15. Brekken R. A., Overholser J. P., Stastny V. A., Waltenberger J., Minna J. D., Thorpe P. E. Selective inhibition of vascular endothelial growth factor (VEGF) receptor 2 (KDR/Flk-1) activity by a monoclonal anti-VEGF antibody blocks tumor growth in mice. Cancer Res. 2000 Sep 15;60(18):5117–5124. [PubMed] [Google Scholar]
  16. Bridge J. A., Borek D. A., Neff J. R., Huntrakoon M. Chromosomal abnormalities in clear cell sarcoma. Implications for histogenesis. Am J Clin Pathol. 1990 Jan;93(1):26–31. doi: 10.1093/ajcp/93.1.26. [DOI] [PubMed] [Google Scholar]
  17. Bridge J. A. Cytogenetics and experimental models. Curr Opin Oncol. 1996 Jul;8(4):284–288. doi: 10.1097/00001622-199607000-00004. [DOI] [PubMed] [Google Scholar]
  18. Bridge J. A., Sreekantaiah C., Neff J. R., Sandberg A. A. Cytogenetic findings in clear cell sarcoma of tendons and aponeuroses. Malignant melanoma of soft parts. Cancer Genet Cytogenet. 1991 Mar;52(1):101–106. doi: 10.1016/0165-4608(91)90059-4. [DOI] [PubMed] [Google Scholar]
  19. Brooks P. C., Montgomery A. M., Rosenfeld M., Reisfeld R. A., Hu T., Klier G., Cheresh D. A. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994 Dec 30;79(7):1157–1164. doi: 10.1016/0092-8674(94)90007-8. [DOI] [PubMed] [Google Scholar]
  20. Brown A. D., Lopez-Terrada D., Denny C., Lee K. A. Promoters containing ATF-binding sites are de-regulated in cells that express the EWS/ATF1 oncogene. Oncogene. 1995 May 4;10(9):1749–1756. [PubMed] [Google Scholar]
  21. Cahlin C., Gelin J., Delbro D., Lönnroth C., Doi C., Lundholm K. Effect of cyclooxygenase and nitric oxide synthase inhibitors on tumor growth in mouse tumor models with and without cancer cachexia related to prostanoids. Cancer Res. 2000 Mar 15;60(6):1742–1749. [PubMed] [Google Scholar]
  22. Candotti F., Agbaria R., Mullen C. A., Touraine R., Balzarini J., Johns D. G., Blaese R. M. Use of a herpes thymidine kinase/neomycin phosphotransferase chimeric gene for metabolic suicide gene transfer. Cancer Gene Ther. 2000 Apr;7(4):574–580. doi: 10.1038/sj.cgt.7700153. [DOI] [PubMed] [Google Scholar]
  23. Carmeliet P., Jain R. K. Angiogenesis in cancer and other diseases. Nature. 2000 Sep 14;407(6801):249–257. doi: 10.1038/35025220. [DOI] [PubMed] [Google Scholar]
  24. Caron de Fromentel C., Gruel N., Venot C., Debussche L., Conseiller E., Dureuil C., Teillaud J. L., Tocque B., Bracco L. Restoration of transcriptional activity of p53 mutants in human tumour cells by intracellular expression of anti-p53 single chain Fv fragments. Oncogene. 1999 Jan 14;18(2):551–557. doi: 10.1038/sj.onc.1202338. [DOI] [PubMed] [Google Scholar]
  25. Carter S. K. Clinical strategy for the development of angiogenesis inhibitors. Oncologist. 2000;5 (Suppl 1):51–54. doi: 10.1634/theoncologist.5-suppl_1-51. [DOI] [PubMed] [Google Scholar]
  26. Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865–1869. doi: 10.1126/science.7997879. [DOI] [PubMed] [Google Scholar]
  27. Chen F., Castranova V., Shi X., Demers L. M. New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem. 1999 Jan;45(1):7–17. [PubMed] [Google Scholar]
  28. Chen J., Wu X., Lin J., Levine A. J. mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol Cell Biol. 1996 May;16(5):2445–2452. doi: 10.1128/mcb.16.5.2445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Clark J., Rocques P. J., Crew A. J., Gill S., Shipley J., Chan A. M., Gusterson B. A., Cooper C. S. Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet. 1994 Aug;7(4):502–508. doi: 10.1038/ng0894-502. [DOI] [PubMed] [Google Scholar]
  30. Coiffier B., Haioun C., Ketterer N., Engert A., Tilly H., Ma D., Johnson P., Lister A., Feuring-Buske M., Radford J. A. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998 Sep 15;92(6):1927–1932. [PubMed] [Google Scholar]
  31. Coindre J. M., Terrier P., Bui N. B., Bonichon F., Collin F., Le Doussal V., Mandard A. M., Vilain M. O., Jacquemier J., Duplay H. Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol. 1996 Mar;14(3):869–877. doi: 10.1200/JCO.1996.14.3.869. [DOI] [PubMed] [Google Scholar]
  32. Colcher D., Minelli M. F., Roselli M., Muraro R., Simpson-Milenic D., Schlom J. Radioimmunolocalization of human carcinoma xenografts with B72.3 second generation monoclonal antibodies. Cancer Res. 1988 Aug 15;48(16):4597–4603. [PubMed] [Google Scholar]
  33. Crozat A., Aman P., Mandahl N., Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993 Jun 17;363(6430):640–644. doi: 10.1038/363640a0. [DOI] [PubMed] [Google Scholar]
  34. Danks M. K., Morton C. L., Pawlik C. A., Potter P. M. Overexpression of a rabbit liver carboxylesterase sensitizes human tumor cells to CPT-11. Cancer Res. 1998 Jan 1;58(1):20–22. [PubMed] [Google Scholar]
  35. De Chiara A., T'Ang A., Triche T. J. Expression of the retinoblastoma susceptibility gene in childhood rhabdomyosarcomas. J Natl Cancer Inst. 1993 Jan 20;85(2):152–157. doi: 10.1093/jnci/85.2.152. [DOI] [PubMed] [Google Scholar]
  36. Devaney K., Abbondanzo S. L., Shekitka K. M., Wolov R. B., Sweet D. E. MIC2 detection in tumors of bone and adjacent soft tissues. Clin Orthop Relat Res. 1995 Jan;(310):176–187. [PubMed] [Google Scholar]
  37. Dworzak M. N., Fritsch G., Fleischer C., Printz D., Fröschl G., Buchinger P., Mann G., Gadner H. CD99 (MIC2) expression in paediatric B-lineage leukaemia/lymphoma reflects maturation-associated patterns of normal B-lymphopoiesis. Br J Haematol. 1999 Jun;105(3):690–695. doi: 10.1046/j.1365-2141.1999.01426.x. [DOI] [PubMed] [Google Scholar]
  38. Eatock M. M., Schätzlein A., Kaye S. B. Tumour vasculature as a target for anticancer therapy. Cancer Treat Rev. 2000 Jun;26(3):191–204. doi: 10.1053/ctrv.1999.0158. [DOI] [PubMed] [Google Scholar]
  39. Eck S. L., Alavi J. B., Alavi A., Davis A., Hackney D., Judy K., Mollman J., Phillips P. C., Wheeldon E. B., Wilson J. M. Treatment of advanced CNS malignancies with the recombinant adenovirus H5.010RSVTK: a phase I trial. Hum Gene Ther. 1996 Aug 1;7(12):1465–1482. doi: 10.1089/hum.1996.7.12-1465. [DOI] [PubMed] [Google Scholar]
  40. Eggermont A. M., Schraffordt Koops H., Klausner J. M., Kroon B. B., Schlag P. M., Liénard D., van Geel A. N., Hoekstra H. J., Meller I., Nieweg O. E. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience. Ann Surg. 1996 Dec;224(6):756–765. doi: 10.1097/00000658-199612000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Eisenhauer E. A. From the molecule to the clinic--inhibiting HER2 to treat breast cancer. N Engl J Med. 2001 Mar 15;344(11):841–842. doi: 10.1056/NEJM200103153441110. [DOI] [PubMed] [Google Scholar]
  42. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  43. Feig B. W., Lu X., Hunt K. K., Shan Q., Yu D., Pollock R., Chiao P. Inhibition of the transcription factor nuclear factor-kappa B by adenoviral-mediated expression of I kappa B alpha M results in tumor cell death. Surgery. 1999 Aug;126(2):399–405. [PubMed] [Google Scholar]
  44. Fisher C. Synovial sarcoma. Ann Diagn Pathol. 1998 Dec;2(6):401–421. doi: 10.1016/s1092-9134(98)80042-7. [DOI] [PubMed] [Google Scholar]
  45. Folkman J. Angiogenesis and angiogenesis inhibition: an overview. EXS. 1997;79:1–8. doi: 10.1007/978-3-0348-9006-9_1. [DOI] [PubMed] [Google Scholar]
  46. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995 Jan;1(1):27–31. doi: 10.1038/nm0195-27. [DOI] [PubMed] [Google Scholar]
  47. Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med. 1971 Nov 18;285(21):1182–1186. doi: 10.1056/NEJM197111182852108. [DOI] [PubMed] [Google Scholar]
  48. Forus A., Flørenes V. A., Maelandsmo G. M., Fodstad O., Myklebost O. The protooncogene CHOP/GADD153, involved in growth arrest and DNA damage response, is amplified in a subset of human sarcomas. Cancer Genet Cytogenet. 1994 Dec;78(2):165–171. doi: 10.1016/0165-4608(94)90085-x. [DOI] [PubMed] [Google Scholar]
  49. Fredericks W. J., Ayyanathan K., Herlyn M., Friedman J. R., Rauscher F. J., 3rd An engineered PAX3-KRAB transcriptional repressor inhibits the malignant phenotype of alveolar rhabdomyosarcoma cells harboring the endogenous PAX3-FKHR oncogene. Mol Cell Biol. 2000 Jul;20(14):5019–5031. doi: 10.1128/mcb.20.14.5019-5031.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Fredericks W. J., Ayyanathan K., Rauscher F. J., 3rd Regulating the neoplastic phenotype using engineered transcriptional repressors. Cancer Lett. 2001 Jan;162 (Suppl):S23–S32. doi: 10.1016/s0304-3835(00)00649-2. [DOI] [PubMed] [Google Scholar]
  51. Gabrilovich D. I., Ishida T., Nadaf S., Ohm J. E., Carbone D. P. Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clin Cancer Res. 1999 Oct;5(10):2963–2970. [PubMed] [Google Scholar]
  52. Gazit G., Hung G., Chen X., Anderson W. F., Lee A. S. Use of the glucose starvation-inducible glucose-regulated protein 78 promoter in suicide gene therapy of murine fibrosarcoma. Cancer Res. 1999 Jul 1;59(13):3100–3106. [PubMed] [Google Scholar]
  53. Gibson A. A., Harwood F. G., Tillman D. M., Houghton J. A. Selective sensitization to DNA-damaging agents in a human rhabdomyosarcoma cell line with inducible wild-type p53 overexpression. Clin Cancer Res. 1998 Jan;4(1):145–152. [PubMed] [Google Scholar]
  54. Girnita L., Wang M., Xie Y., Nilsson G., Dricu A., Wejde J., Larsson O. Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1 receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic implications. Anticancer Drug Des. 2000 Feb;15(1):67–72. [PubMed] [Google Scholar]
  55. Goel A., Colcher D., Baranowska-Kortylewicz J., Augustine S., Booth B. J., Pavlinkova G., Batra S. K. Genetically engineered tetravalent single-chain Fv of the pancarcinoma monoclonal antibody CC49: improved biodistribution and potential for therapeutic application. Cancer Res. 2000 Dec 15;60(24):6964–6971. [PubMed] [Google Scholar]
  56. Goldfarb M. Functions of fibroblast growth factors in vertebrate development. Cytokine Growth Factor Rev. 1996 Dec;7(4):311–325. doi: 10.1016/s1359-6101(96)00039-1. [DOI] [PubMed] [Google Scholar]
  57. Goldman J. M., Melo J. V. Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001 Apr 5;344(14):1084–1086. doi: 10.1056/NEJM200104053441409. [DOI] [PubMed] [Google Scholar]
  58. Goletz T. J., Mackall C. L., Berzofsky J. A., Helman L. J. Molecular alterations in pediatric sarcomas: potential targets for immunotherapy. Sarcoma. 1998;2(2):77–87. doi: 10.1080/13577149878037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Gortzak E., Azzarelli A., Buesa J., Bramwell V. H., van Coevorden F., van Geel A. N., Ezzat A., Santoro A., Oosterhuis J. W., van Glabbeke M. A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma. Eur J Cancer. 2001 Jun;37(9):1096–1103. doi: 10.1016/s0959-8049(01)00083-1. [DOI] [PubMed] [Google Scholar]
  60. Greco A., Roccato E., Miranda C., Cleris L., Formelli F., Pierotti M. A. Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer. 2001 May 1;92(3):354–360. doi: 10.1002/ijc.1190. [DOI] [PubMed] [Google Scholar]
  61. Gutheil J. C., Campbell T. N., Pierce P. R., Watkins J. D., Huse W. D., Bodkin D. J., Cheresh D. A. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res. 2000 Aug;6(8):3056–3061. [PubMed] [Google Scholar]
  62. Hahn J. H., Kim M. K., Choi E. Y., Kim S. H., Sohn H. W., Ham D. I., Chung D. H., Kim T. J., Lee W. J., Park C. K. CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion. J Immunol. 1997 Sep 1;159(5):2250–2258. [PubMed] [Google Scholar]
  63. Hainaut P., Soussi T., Shomer B., Hollstein M., Greenblatt M., Hovig E., Harris C. C., Montesano R. Database of p53 gene somatic mutations in human tumors and cell lines: updated compilation and future prospects. Nucleic Acids Res. 1997 Jan 1;25(1):151–157. doi: 10.1093/nar/25.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Hamada T., Komiya S., Yano H., Zenmyo M., Hiraoka K., Inoue A., Morimatsu M. Modulation of fas-mediated apoptosis in osteosarcoma cell lines. Int J Oncol. 1999 Dec;15(6):1125–1131. doi: 10.3892/ijo.15.6.1125. [DOI] [PubMed] [Google Scholar]
  65. Hasegawa T., Seki K., Ono K., Hirohashi S. Angiomatoid (malignant) fibrous histiocytoma: a peculiar low-grade tumor showing immunophenotypic heterogeneity and ultrastructural variations. Pathol Int. 2000 Sep;50(9):731–738. doi: 10.1046/j.1440-1827.2000.01112.x. [DOI] [PubMed] [Google Scholar]
  66. Hieken T. J., Das Gupta T. K. Mutant p53 expression: a marker of diminished survival in well-differentiated soft tissue sarcoma. Clin Cancer Res. 1996 Aug;2(8):1391–1395. [PubMed] [Google Scholar]
  67. Higgins K. A., Perez J. R., Coleman T. A., Dorshkind K., McComas W. A., Sarmiento U. M., Rosen C. A., Narayanan R. Antisense inhibition of the p65 subunit of NF-kappa B blocks tumorigenicity and causes tumor regression. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9901–9905. doi: 10.1073/pnas.90.21.9901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Hirota S., Isozaki K., Moriyama Y., Hashimoto K., Nishida T., Ishiguro S., Kawano K., Hanada M., Kurata A., Takeda M. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998 Jan 23;279(5350):577–580. doi: 10.1126/science.279.5350.577. [DOI] [PubMed] [Google Scholar]
  69. Hunt K. K., Feig B. W. Preclinical experimental therapeutic approaches in soft tissue sarcoma. Semin Surg Oncol. 1999 Jul-Aug;17(1):78–82. doi: 10.1002/(sici)1098-2388(199907/08)17:1<78::aid-ssu10>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  70. Hunter T., Karin M. The regulation of transcription by phosphorylation. Cell. 1992 Aug 7;70(3):375–387. doi: 10.1016/0092-8674(92)90162-6. [DOI] [PubMed] [Google Scholar]
  71. Hunter T. Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 1995 Jan 27;80(2):225–236. doi: 10.1016/0092-8674(95)90405-0. [DOI] [PubMed] [Google Scholar]
  72. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  73. Jiang H., Karnezis A. N., Tao M., Guida P. M., Zhu L. pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels. Oncogene. 2000 Aug 10;19(34):3878–3887. doi: 10.1038/sj.onc.1203722. [DOI] [PubMed] [Google Scholar]
  74. Joensuu H., Roberts P. J., Sarlomo-Rikala M., Andersson L. C., Tervahartiala P., Tuveson D., Silberman S., Capdeville R., Dimitrijevic S., Druker B. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001 Apr 5;344(14):1052–1056. doi: 10.1056/NEJM200104053441404. [DOI] [PubMed] [Google Scholar]
  75. Karpeh M. S., Brennan M. F., Cance W. G., Woodruff J. M., Pollack D., Casper E. S., Dudas M. E., Latres E., Drobnjak M., Cordon-Cardo C. Altered patterns of retinoblastoma gene product expression in adult soft-tissue sarcomas. Br J Cancer. 1995 Oct;72(4):986–991. doi: 10.1038/bjc.1995.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Kawai A., Woodruff J., Healey J. H., Brennan M. F., Antonescu C. R., Ladanyi M. SYT-SSX gene fusion as a determinant of morphology and prognosis in synovial sarcoma. N Engl J Med. 1998 Jan 15;338(3):153–160. doi: 10.1056/NEJM199801153380303. [DOI] [PubMed] [Google Scholar]
  77. Kim D. H., Sohn J. H., Lee M. C., Lee G., Yoon G. S., Hashimoto H., Sonobe H., Ro J. Y. Primary synovial sarcoma of the kidney. Am J Surg Pathol. 2000 Aug;24(8):1097–1104. doi: 10.1097/00000478-200008000-00007. [DOI] [PubMed] [Google Scholar]
  78. Kim J., Pelletier J. Molecular genetics of chromosome translocations involving EWS and related family members. Physiol Genomics. 1999 Nov 11;1(3):127–138. doi: 10.1152/physiolgenomics.1999.1.3.127. [DOI] [PubMed] [Google Scholar]
  79. Kishi K., Petersen S., Petersen C., Hunter N., Mason K., Masferrer J. L., Tofilon P. J., Milas L. Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. Cancer Res. 2000 Mar 1;60(5):1326–1331. [PubMed] [Google Scholar]
  80. Ko S. C., Cheon J., Kao C., Gotoh A., Shirakawa T., Sikes R. A., Karsenty G., Chung L. W. Osteocalcin promoter-based toxic gene therapy for the treatment of osteosarcoma in experimental models. Cancer Res. 1996 Oct 15;56(20):4614–4619. [PubMed] [Google Scholar]
  81. Kobet E., Zeng X., Zhu Y., Keller D., Lu H. MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12547–12552. doi: 10.1073/pnas.97.23.12547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Kontny H. U., Lehrnbecher T. M., Chanock S. J., Mackall C. L. Simultaneous expression of Fas and nonfunctional Fas ligand in Ewing's sarcoma. Cancer Res. 1998 Dec 15;58(24):5842–5849. [PubMed] [Google Scholar]
  83. Kottaridis P. D., Milligan D. W., Chopra R., Chakraverty R. K., Chakrabarti S., Robinson S., Peggs K., Verfuerth S., Pettengell R., Marsh J. C. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood. 2000 Oct 1;96(7):2419–2425. [PubMed] [Google Scholar]
  84. Kovar H., Aryee D. N., Jug G., Henöckl C., Schemper M., Delattre O., Thomas G., Gadner H. EWS/FLI-1 antagonists induce growth inhibition of Ewing tumor cells in vitro. Cell Growth Differ. 1996 Apr;7(4):429–437. [PubMed] [Google Scholar]
  85. Kovar H., Aryee D., Zoubek A. The Ewing family of tumors and the search for the Achilles' heel. Curr Opin Oncol. 1999 Jul;11(4):275–284. doi: 10.1097/00001622-199907000-00007. [DOI] [PubMed] [Google Scholar]
  86. Kovar H. Progress in the molecular biology of ewing tumors. Sarcoma. 1998;2(1):3–17. doi: 10.1080/13577149878109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Kuroda M., Ishida T., Takanashi M., Satoh M., Machinami R., Watanabe T. Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes by TLS/FUS-CHOP type II chimeric protein. Am J Pathol. 1997 Sep;151(3):735–744. [PMC free article] [PubMed] [Google Scholar]
  88. Kushner B. H., LaQuaglia M. P., Cheung N. K., Kramer K., Hamelin A. C., Gerald W. L., Ladanyi M. Clinically critical impact of molecular genetic studies in pediatric solid tumors. Med Pediatr Oncol. 1999 Dec;33(6):530–535. doi: 10.1002/(sici)1096-911x(199912)33:6<530::aid-mpo2>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  89. Köhler G., Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975 Aug 7;256(5517):495–497. doi: 10.1038/256495a0. [DOI] [PubMed] [Google Scholar]
  90. Ladanyi M., Bridge J. A. Contribution of molecular genetic data to the classification of sarcomas. Hum Pathol. 2000 May;31(5):532–538. doi: 10.1053/hp.2000.6706. [DOI] [PubMed] [Google Scholar]
  91. Lambert G., Bertrand J. R., Fattal E., Subra F., Pinto-Alphandary H., Malvy C., Auclair C., Couvreur P. EWS fli-1 antisense nanocapsules inhibits ewing sarcoma-related tumor in mice. Biochem Biophys Res Commun. 2000 Dec 20;279(2):401–406. doi: 10.1006/bbrc.2000.3963. [DOI] [PubMed] [Google Scholar]
  92. Latres E., Drobnjak M., Pollack D., Oliva M. R., Ramos M., Karpeh M., Woodruff J. M., Cordon-Cardo C. Chromosome 17 abnormalities and TP53 mutations in adult soft tissue sarcomas. Am J Pathol. 1994 Aug;145(2):345–355. [PMC free article] [PubMed] [Google Scholar]
  93. Lessnick S. L., Braun B. S., Denny C. T., May W. A. Multiple domains mediate transformation by the Ewing's sarcoma EWS/FLI-1 fusion gene. Oncogene. 1995 Feb 2;10(3):423–431. [PubMed] [Google Scholar]
  94. Lewis J. J., Brennan M. F. Soft tissue sarcomas. Curr Probl Surg. 1996 Oct;33(10):817–872. [PubMed] [Google Scholar]
  95. Li F. P., Fraumeni J. F., Jr Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome? Ann Intern Med. 1969 Oct;71(4):747–752. doi: 10.7326/0003-4819-71-4-747. [DOI] [PubMed] [Google Scholar]
  96. Li P., Yuan M., Xia H. [Experimental study of the therapeutic effects of an anti-endothelial cell monoclonal antibody BVE-1 for solid tumor xenograft in nude mice]. Zhonghua Zhong Liu Za Zhi. 1998 Jul;20(4):280–283. [PubMed] [Google Scholar]
  97. Lin P. P., Brody R. I., Hamelin A. C., Bradner J. E., Healey J. H., Ladanyi M. Differential transactivation by alternative EWS-FLI1 fusion proteins correlates with clinical heterogeneity in Ewing's sarcoma. Cancer Res. 1999 Apr 1;59(7):1428–1432. [PubMed] [Google Scholar]
  98. Linehan D. C., Bowne W. B., Lewis J. J. Immunotherapeutic approaches to sarcoma. Semin Surg Oncol. 1999 Jul-Aug;17(1):72–77. doi: 10.1002/(sici)1098-2388(199907/08)17:1<72::aid-ssu9>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  99. Mackall C., Berzofsky J., Helman L. J. Targeting tumor specific translocations in sarcomas in pediatric patients for immunotherapy. Clin Orthop Relat Res. 2000 Apr;(373):25–31. doi: 10.1097/00003086-200004000-00005. [DOI] [PubMed] [Google Scholar]
  100. Marconi P., Tamura M., Moriuchi S., Krisky D. M., Niranjan A., Goins W. F., Cohen J. B., Glorioso J. C. Connexin 43-enhanced suicide gene therapy using herpesviral vectors. Mol Ther. 2000 Jan;1(1):71–81. doi: 10.1006/mthe.1999.0008. [DOI] [PubMed] [Google Scholar]
  101. Massuda E. S., Dunphy E. J., Redman R. A., Schreiber J. J., Nauta L. E., Barr F. G., Maxwell I. H., Cripe T. P. Regulated expression of the diphtheria toxin A chain by a tumor-specific chimeric transcription factor results in selective toxicity for alveolar rhabdomyosarcoma cells. Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14701–14706. doi: 10.1073/pnas.94.26.14701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. May W. A., Gishizky M. L., Lessnick S. L., Lunsford L. B., Lewis B. C., Delattre O., Zucman J., Thomas G., Denny C. T. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FLI1 for transformation. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5752–5756. doi: 10.1073/pnas.90.12.5752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Mendel D. B., Schreck R. E., West D. C., Li G., Strawn L. M., Tanciongco S. S., Vasile S., Shawver L. K., Cherrington J. M. The angiogenesis inhibitor SU5416 has long-lasting effects on vascular endothelial growth factor receptor phosphorylation and function. Clin Cancer Res. 2000 Dec;6(12):4848–4858. [PubMed] [Google Scholar]
  104. Meye A., Würl P., Bache M., Bartel F., Grünbaum U., Mansa-ard J., Schmidt H., Taubert H. Colony formation of soft tissue sarcoma cells is inhibited by lipid-mediated antisense oligodeoxynucleotides targeting the human mdm2 oncogene. Cancer Lett. 2000 Feb 28;149(1-2):181–188. doi: 10.1016/s0304-3835(99)00356-0. [DOI] [PubMed] [Google Scholar]
  105. Milas M., Yu D., Lang A., Ge T., Feig B., El-Naggar A. K., Pollock R. E. Adenovirus-mediated p53 gene therapy inhibits human sarcoma tumorigenicity. Cancer Gene Ther. 2000 Mar;7(3):422–429. doi: 10.1038/sj.cgt.7700141. [DOI] [PubMed] [Google Scholar]
  106. Mizuguchi H., Nakanishi M., Nakanishi T., Nakagawa T., Nakagawa S., Mayumi T. Application of fusogenic liposomes containing fragment A of diphtheria toxin to cancer therapy. Br J Cancer. 1996 Feb;73(4):472–476. doi: 10.1038/bjc.1996.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Mizuguchi H., Nakanishi T., Nakanishi M., Nakagawa T., Nakagawa S., Mayumi T. Intratumor administration of fusogenic liposomes containing fragment A of diphtheria toxin suppresses tumor growth. Cancer Lett. 1996 Feb 27;100(1-2):63–69. doi: 10.1016/0304-3835(95)04081-1. [DOI] [PubMed] [Google Scholar]
  108. Montaner S., Sodhi A., Pece S., Mesri E. A., Gutkind J. S. The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B. Cancer Res. 2001 Mar 15;61(6):2641–2648. [PubMed] [Google Scholar]
  109. Moore P. S., Chang Y. Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med. 1995 May 4;332(18):1181–1185. doi: 10.1056/NEJM199505043321801. [DOI] [PubMed] [Google Scholar]
  110. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  111. Nakashima T., Hudson J. M., Clayman G. L. Antisense inhibition of vascular endothelial growth factor in human head and neck squamous cell carcinoma. Head Neck. 2000 Aug;22(5):483–488. doi: 10.1002/1097-0347(200008)22:5<483::aid-hed7>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  112. Niculescu-Duvaz I. Technology evaluation: gemtuzumab ozogamicin, Celltech Group. Curr Opin Mol Ther. 2000 Dec;2(6):691–696. [PubMed] [Google Scholar]
  113. Oku T., Tjuvajev J. G., Miyagawa T., Sasajima T., Joshi A., Joshi R., Finn R., Claffey K. P., Blasberg R. G. Tumor growth modulation by sense and antisense vascular endothelial growth factor gene expression: effects on angiogenesis, vascular permeability, blood volume, blood flow, fluorodeoxyglucose uptake, and proliferation of human melanoma intracerebral xenografts. Cancer Res. 1998 Sep 15;58(18):4185–4192. [PubMed] [Google Scholar]
  114. Olsen R. J., Hinrichs S. H. Phosphorylation of the EWS IQ domain regulates transcriptional activity of the EWS/ATF1 and EWS/FLI1 fusion proteins. Oncogene. 2001 Mar 29;20(14):1756–1764. doi: 10.1038/sj.onc.1204268. [DOI] [PubMed] [Google Scholar]
  115. Ordi J., de Alava E., Torné A., Mellado B., Pardo-Mindan J., Iglesias X., Cardesa A. Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript. Am J Surg Pathol. 1998 Aug;22(8):1026–1032. doi: 10.1097/00000478-199808000-00014. [DOI] [PubMed] [Google Scholar]
  116. Ouchida M., Ohno T., Fujimura Y., Rao V. N., Reddy E. S. Loss of tumorigenicity of Ewing's sarcoma cells expressing antisense RNA to EWS-fusion transcripts. Oncogene. 1995 Sep 21;11(6):1049–1054. [PubMed] [Google Scholar]
  117. Parasuraman S., Rao B. N., Bodner S., Cain A., Pratt C. B., Merchant T. E., Pappo A. S. Clear cell sarcoma of soft tissues in children and young adults: the St. Jude Children's Research Hospital experience. Pediatr Hematol Oncol. 1999 Nov-Dec;16(6):539–544. doi: 10.1080/088800199276831. [DOI] [PubMed] [Google Scholar]
  118. Patel S. R., Benjamin R. S. New chemotherapeutic strategies for soft tissue sarcomas. Semin Surg Oncol. 1999 Jul-Aug;17(1):47–51. doi: 10.1002/(sici)1098-2388(199907/08)17:1<47::aid-ssu6>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  119. Pawlik C. A., Iyengar R. V., Krull E. J., Mason S. E., Khanna R., Harris L. C., Potter P. M., Danks M. K., Guichard S. M. Use of the ornithine decarboxylase promoter to achieve N-MYC-mediated overexpression of a rabbit carboxylesterase to sensitize neuroblastoma cells to CPT-11. Mol Ther. 2000 May;1(5 Pt 1):457–463. doi: 10.1006/mthe.2000.0064. [DOI] [PubMed] [Google Scholar]
  120. Pisters P. W., Harrison L. B., Leung D. H., Woodruff J. M., Casper E. S., Brennan M. F. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol. 1996 Mar;14(3):859–868. doi: 10.1200/JCO.1996.14.3.859. [DOI] [PubMed] [Google Scholar]
  121. Pisters P. W., Leung D. H., Woodruff J., Shi W., Brennan M. F. Analysis of prognostic factors in 1,041 patients with localized soft tissue sarcomas of the extremities. J Clin Oncol. 1996 May;14(5):1679–1689. doi: 10.1200/JCO.1996.14.5.1679. [DOI] [PubMed] [Google Scholar]
  122. Pollock J. D., Rane S. G. p21ras signaling is necessary but not sufficient to mediate neurotrophin induction of calcium channels in PC12 cells. J Biol Chem. 1996 Apr 5;271(14):8008–8014. doi: 10.1074/jbc.271.14.8008. [DOI] [PubMed] [Google Scholar]
  123. Pollock R., Lang A., Ge T., Sun D., Tan M., Yu D. Wild-type p53 and a p53 temperature-sensitive mutant suppress human soft tissue sarcoma by enhancing cell cycle control. Clin Cancer Res. 1998 Aug;4(8):1985–1994. [PubMed] [Google Scholar]
  124. Rodwell J. D. Engineering monoclonal antibodies. Nature. 1989 Nov 2;342(6245):99–100. doi: 10.1038/342099a0. [DOI] [PubMed] [Google Scholar]
  125. Roth J. A. Restoration of tumour suppressor gene expression for cancer. Forum (Genova) 1998 Oct-Dec;8(4):368–376. [PubMed] [Google Scholar]
  126. Roth J. A., Swisher S. G., Meyn R. E. p53 tumor suppressor gene therapy for cancer. Oncology (Williston Park) 1999 Oct;13(10 Suppl 5):148–154. [PubMed] [Google Scholar]
  127. Sassone-Corsi P. Coupling gene expression to cAMP signalling: role of CREB and CREM. Int J Biochem Cell Biol. 1998 Jan;30(1):27–38. doi: 10.1016/s1357-2725(97)00093-9. [DOI] [PubMed] [Google Scholar]
  128. Schneider-Stock R., Walter H., Radig K., Rys J., Bosse A., Kuhnen C., Hoang-Vu C., Roessner A. MDM2 amplification and loss of heterozygosity at Rb and p53 genes: no simultaneous alterations in the oncogenesis of liposarcomas. J Cancer Res Clin Oncol. 1998;124(10):532–540. doi: 10.1007/s004320050211. [DOI] [PubMed] [Google Scholar]
  129. Scotlandi K., Baldini N., Cerisano V., Manara M. C., Benini S., Serra M., Lollini P. L., Nanni P., Nicoletti G., Bernard G. CD99 engagement: an effective therapeutic strategy for Ewing tumors. Cancer Res. 2000 Sep 15;60(18):5134–5142. [PubMed] [Google Scholar]
  130. Shand N., Weber F., Mariani L., Bernstein M., Gianella-Borradori A., Long Z., Sorensen A. G., Barbier N. A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group. Hum Gene Ther. 1999 Sep 20;10(14):2325–2335. doi: 10.1089/10430349950016979. [DOI] [PubMed] [Google Scholar]
  131. Singer S. New diagnostic modalities in soft tissue sarcoma. Semin Surg Oncol. 1999 Jul-Aug;17(1):11–22. doi: 10.1002/(sici)1098-2388(199907/08)17:1<11::aid-ssu3>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  132. Skapek S. X., Shaffer L. G., Barker J. A. Cytogenetics and the biological basis of sarcomas. Curr Opin Oncol. 1998 Jul;10(4):318–325. doi: 10.1097/00001622-199807000-00008. [DOI] [PubMed] [Google Scholar]
  133. Sodhi A., Montaner S., Patel V., Zohar M., Bais C., Mesri E. A., Gutkind J. S. The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha. Cancer Res. 2000 Sep 1;60(17):4873–4880. [PubMed] [Google Scholar]
  134. Sohn H. W., Choi E. Y., Kim S. H., Lee I. S., Chung D. H., Sung U. A., Hwang D. H., Cho S. S., Jun B. H., Jang J. J. Engagement of CD99 induces apoptosis through a calcineurin-independent pathway in Ewing's sarcoma cells. Am J Pathol. 1998 Dec;153(6):1937–1945. doi: 10.1016/S0002-9440(10)65707-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  135. Sonenshein G. E. Rel/NF-kappa B transcription factors and the control of apoptosis. Semin Cancer Biol. 1997 Apr;8(2):113–119. doi: 10.1006/scbi.1997.0062. [DOI] [PubMed] [Google Scholar]
  136. Springer M. L., Kraft P. E., Blau H. M. Inhibition of solid tumor growth by Fas ligand-expressing myoblasts. Somat Cell Mol Genet. 1998 Sep;24(5):281–289. doi: 10.1023/b:scam.0000007131.09916.46. [DOI] [PubMed] [Google Scholar]
  137. Stephenson J. Researchers buoyed by promise of targeted leukemia therapy. JAMA. 2000 Jan 19;283(3):317–321. [PubMed] [Google Scholar]
  138. Sturla L. M., Westwood G., Selby P. J., Lewis I. J., Burchill S. A. Induction of cell death by basic fibroblast growth factor in Ewing's sarcoma. Cancer Res. 2000 Nov 1;60(21):6160–6170. [PubMed] [Google Scholar]
  139. Takebayashi H., Oida H., Fujisawa K., Yamaguchi M., Hikida T., Fukumoto M., Narumiya S., Kakizuka A. Hormone-induced apoptosis by Fas-nuclear receptor fusion proteins: novel biological tools for controlling apoptosis in vivo. Cancer Res. 1996 Sep 15;56(18):4164–4170. [PubMed] [Google Scholar]
  140. Tallman M. S., Andersen J. W., Schiffer C. A., Appelbaum F. R., Feusner J. H., Ogden A., Shepherd L., Rowe J. M., François C., Larson R. S. Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome. Blood. 2000 Jan 1;95(1):90–95. [PubMed] [Google Scholar]
  141. Tallman M. S., Andersen J. W., Schiffer C. A., Appelbaum F. R., Feusner J. H., Ogden A., Shepherd L., Willman C., Bloomfield C. D., Rowe J. M. All-trans-retinoic acid in acute promyelocytic leukemia. N Engl J Med. 1997 Oct 9;337(15):1021–1028. doi: 10.1056/NEJM199710093371501. [DOI] [PubMed] [Google Scholar]
  142. Tanaka K., Iwakuma T., Harimaya K., Sato H., Iwamoto Y. EWS-Fli1 antisense oligodeoxynucleotide inhibits proliferation of human Ewing's sarcoma and primitive neuroectodermal tumor cells. J Clin Invest. 1997 Jan 15;99(2):239–247. doi: 10.1172/JCI119152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  143. Taubert H., Meye A., Würl P. Soft tissue sarcomas and p53 mutations. Mol Med. 1998 Jun;4(6):365–372. [PMC free article] [PubMed] [Google Scholar]
  144. The Nobel lectures in immunology. The Nobel prize for physiology or medicine, 1908, awarded to Elie Metchnikoff & Paul Ehrlich "in recognition of their work on immunity". Scand J Immunol. 1990 Jan;31(1):1–13. [PubMed] [Google Scholar]
  145. Tierney J. F., Mosseri V., Stewart L. A., Souhami R. L., Parmar M. K. Adjuvant chemotherapy for soft-tissue sarcoma: review and meta-analysis of the published results of randomised clinical trials. Br J Cancer. 1995 Aug;72(2):469–475. doi: 10.1038/bjc.1995.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Tobar A., Avigad S., Zoldan M., Mor C., Goshen Y., Zaizov R. Clinical relevance of molecular diagnosis in childhood rhabdomyosarcoma. Diagn Mol Pathol. 2000 Mar;9(1):9–13. doi: 10.1097/00019606-200003000-00002. [DOI] [PubMed] [Google Scholar]
  147. Toguchida J., Yamaguchi T., Ritchie B., Beauchamp R. L., Dayton S. H., Herrera G. E., Yamamuro T., Kotoura Y., Sasaki M. S., Little J. B. Mutation spectrum of the p53 gene in bone and soft tissue sarcomas. Cancer Res. 1992 Nov 15;52(22):6194–6199. [PubMed] [Google Scholar]
  148. Toretsky J. A., Connell Y., Neckers L., Bhat N. K. Inhibition of EWS-FLI-1 fusion protein with antisense oligodeoxynucleotides. J Neurooncol. 1997 Jan;31(1-2):9–16. doi: 10.1023/a:1005716926800. [DOI] [PubMed] [Google Scholar]
  149. Toretsky J. A., Thakar M., Eskenazi A. E., Frantz C. N. Phosphoinositide 3-hydroxide kinase blockade enhances apoptosis in the Ewing's sarcoma family of tumors. Cancer Res. 1999 Nov 15;59(22):5745–5750. [PubMed] [Google Scholar]
  150. Tsuchiya H., Yamamoto N., Asada N., Terasaki T., Kanazawa Y., Takanaka T., Nishijima H., Tomita K. Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade soft tissue sarcoma. Anticancer Res. 2000 May-Jun;20(3B):2137–2143. [PubMed] [Google Scholar]
  151. Uchida A., Seto M., Hashimoto N., Araki N. Molecular diagnosis and gene therapy in musculoskeletal tumors. J Orthop Sci. 2000;5(4):418–423. doi: 10.1007/pl00021460. [DOI] [PubMed] [Google Scholar]
  152. Uherek C., Wels W. DNA-carrier proteins for targeted gene delivery. Adv Drug Deliv Rev. 2000 Nov 15;44(2-3):153–166. doi: 10.1016/s0169-409x(00)00092-2. [DOI] [PubMed] [Google Scholar]
  153. Van Valen F., Fulda S., Truckenbrod B., Eckervogt V., Sonnemann J., Hillmann A., Rödl R., Hoffmann C., Winkelmann W., Schäfer L. Apoptotic responsiveness of the Ewing's sarcoma family of tumours to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). Int J Cancer. 2000 Oct 15;88(2):252–259. doi: 10.1002/1097-0215(20001015)88:2<252::aid-ijc17>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  154. Villunger A., Strasser A. Does "death receptor" signaling play a role in tumorigenesis and cancer therapy? Oncol Res. 1998;10(11-12):541–550. [PubMed] [Google Scholar]
  155. Vitaliti A., Wittmer M., Steiner R., Wyder L., Neri D., Klemenz R. Inhibition of tumor angiogenesis by a single-chain antibody directed against vascular endothelial growth factor. Cancer Res. 2000 Aug 15;60(16):4311–4314. [PubMed] [Google Scholar]
  156. Wang C. Y., Mayo M. W., Baldwin A. S., Jr TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science. 1996 Nov 1;274(5288):784–787. doi: 10.1126/science.274.5288.784. [DOI] [PubMed] [Google Scholar]
  157. Wang M., Xie Y., Girnita L., Nilsson G., Dricu A., Wejde J., Larsson O. Regulatory role of mevalonate and N-linked glycosylation in proliferation and expression of the EWS/FLI-1 fusion protein in Ewing's sarcoma cells. Exp Cell Res. 1999 Jan 10;246(1):38–46. doi: 10.1006/excr.1998.4280. [DOI] [PubMed] [Google Scholar]
  158. Ward E. S., Güssow D., Griffiths A. D., Jones P. T., Winter G. Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature. 1989 Oct 12;341(6242):544–546. doi: 10.1038/341544a0. [DOI] [PubMed] [Google Scholar]
  159. Watanabe T., Sullenger B. A. Induction of wild-type p53 activity in human cancer cells by ribozymes that repair mutant p53 transcripts. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8490–8494. doi: 10.1073/pnas.150104097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  160. Wei G., Antonescu C. R., de Alava E., Leung D., Huvos A. G., Meyers P. A., Healey J. H., Ladanyi M. Prognostic impact of INK4A deletion in Ewing sarcoma. Cancer. 2000 Aug 15;89(4):793–799. doi: 10.1002/1097-0142(20000815)89:4<793::aid-cncr11>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  161. Wick M. R. Immunohistology of neuroendocrine and neuroectodermal tumors. Semin Diagn Pathol. 2000 Aug;17(3):194–203. [PubMed] [Google Scholar]
  162. Wörn A., Plückthun A. Stability engineering of antibody single-chain Fv fragments. J Mol Biol. 2001 Feb 2;305(5):989–1010. doi: 10.1006/jmbi.2000.4265. [DOI] [PubMed] [Google Scholar]
  163. Würl P., Meye A., Lautenschläger C., Schmidt H., Bache M., Kalthoff H., Schönfelder M., Rath F. W., Taubert H. Clinical relevance of pRb and p53 co-overexpression in soft tissue sarcomas. Cancer Lett. 1999 May 24;139(2):159–165. doi: 10.1016/s0304-3835(99)00034-8. [DOI] [PubMed] [Google Scholar]
  164. Yancopoulos G. D., Davis S., Gale N. W., Rudge J. S., Wiegand S. J., Holash J. Vascular-specific growth factors and blood vessel formation. Nature. 2000 Sep 14;407(6801):242–248. doi: 10.1038/35025215. [DOI] [PubMed] [Google Scholar]
  165. Yap D. B., Hsieh J. K., Chan F. S., Lu X. mdm2: a bridge over the two tumour suppressors, p53 and Rb. Oncogene. 1999 Dec 13;18(53):7681–7689. doi: 10.1038/sj.onc.1202954. [DOI] [PubMed] [Google Scholar]
  166. Yi H., Fujimura Y., Ouchida M., Prasad D. D., Rao V. N., Reddy E. S. Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias. Oncogene. 1997 Mar 20;14(11):1259–1268. doi: 10.1038/sj.onc.1201099. [DOI] [PubMed] [Google Scholar]
  167. Yokota T., Milenic D. E., Whitlow M., Schlom J. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res. 1992 Jun 15;52(12):3402–3408. [PubMed] [Google Scholar]
  168. Yuyama Y., Tsujimoto M., Fujimoto Y., Oku N. Potential usage of thermosensitive liposomes for site-specific delivery of cytokines. Cancer Lett. 2000 Jul 3;155(1):71–77. doi: 10.1016/s0304-3835(00)00410-9. [DOI] [PubMed] [Google Scholar]
  169. Zhang L., Yu D., Hu M., Xiong S., Lang A., Ellis L. M., Pollock R. E. Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial sarcoma by transcriptional suppression of vascular endothelial growth factor expression. Cancer Res. 2000 Jul 1;60(13):3655–3661. [PubMed] [Google Scholar]
  170. Zoubek A., Dockhorn-Dworniczak B., Delattre O., Christiansen H., Niggli F., Gatterer-Menz I., Smith T. L., Jürgens H., Gadner H., Kovar H. Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J Clin Oncol. 1996 Apr;14(4):1245–1251. doi: 10.1200/JCO.1996.14.4.1245. [DOI] [PubMed] [Google Scholar]
  171. de Alava E., Antonescu C. R., Panizo A., Leung D., Meyers P. A., Huvos A. G., Pardo-Mindán F. J., Healey J. H., Ladanyi M. Prognostic impact of P53 status in Ewing sarcoma. Cancer. 2000 Aug 15;89(4):783–792. [PubMed] [Google Scholar]
  172. de Alava E., Gerald W. L. Molecular biology of the Ewing's sarcoma/primitive neuroectodermal tumor family. J Clin Oncol. 2000 Jan;18(1):204–213. doi: 10.1200/JCO.2000.18.1.204. [DOI] [PubMed] [Google Scholar]
  173. de Alava E., Kawai A., Healey J. H., Fligman I., Meyers P. A., Huvos A. G., Gerald W. L., Jhanwar S. C., Argani P., Antonescu C. R. EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol. 1998 Apr;16(4):1248–1255. doi: 10.1200/JCO.1998.16.4.1248. [DOI] [PubMed] [Google Scholar]
  174. van Geel A. N., Pastorino U., Jauch K. W., Judson I. R., van Coevorden F., Buesa J. M., Nielsen O. S., Boudinet A., Tursz T., Schmitz P. I. Surgical treatment of lung metastases: The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Cancer. 1996 Feb 15;77(4):675–682. doi: 10.1002/(sici)1097-0142(19960215)77:4<675::aid-cncr13>3.3.co;2-h. [DOI] [PubMed] [Google Scholar]

Articles from Sarcoma are provided here courtesy of Wiley

RESOURCES