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Comments on Cultured Human Sarcoma Cells

Comments on Cultured Human Sarcoma Cells Human sarcoma cell populations maintained in culture reflect to the native tumor cells better if the culture retains those nonmalignant cells that comprised the tumor’s microenvironment in vivo [Hu M, et al. Characterization of 11 human sarcoma cell strains. Cancer 2002; 95: 1569–76] and thus provide paracrine growth factors and protection from apoptotic death to the tumor cells. Whereas sarcoma cell cultures obtained through meticulous efforts aimed at the elimination of all non-malignant cells of the tumor’s original microenvironment consist of subpopulations of tumor cells growing exclusively with the support of their own autocrine growth loops [Sinkovics JG, et al. Growth of human tumor cells in established cultures. In: Busch H, ed. Methods in Cancer Research. Vol 14. New York: Academic Press, 1978; 243–323]. It has been some 30 years since that, at the Section of transformed cells (KIRs; NKp30,44,46; NKG2D) Clinical Tumor Virology and Immunology, and subtypes of immune T cells (TIL) were Department of Medicine, The University of Texas separated; and perforins of lymphocyte origin and M.D. Anderson Hospital, we established over 50 death ligands and their receptors (TNFa;FasL! human tumor cell lines, amongthem 25 deriving FasR CD95) inducingextrinsic apoptosis were dis- from sarcomas. covered elsewhere. Furthermore nuclear clumping One purpose of the study was a search for causative and death of the lymphocytes attackingsarcoma cells retroviruses, since from the chicken through mice up also occurred: the ‘counterattack on lymphocytes’, 8,9 to some simian species causative sarcoma viruses while sarcoma cells remained intact (Fig. 1); these were isolated and identified. Filtered supernatant pictures were taken longbefore the discovery of the fluids of human sarcoma cell cultures occasionally Fas system. A third and main purpose of these studies caused ‘antigenic conversion’ (as shown by immuno- was the preparation of ‘viral oncolysates’ from some fluorescence stains) and ‘focus formation’ in cultures of these cell lines for active tumor-specific immu- 2 10 11,12 of human embryonic fibroblasts. These phenomena notherapy against sarcomas and melanoma. could not be propagated by passages and yielded no Our work as reported biannually in the institu- human sarcoma viral isolates, even though transmis- tional Research Report from 1960 to 1978 preceded sion EM pictures showed rare retroviral particles in the discovery of oncogenes whereby a retrovirus some of these cells. Some xenotropic murine retro- transduces a cellular protooncogene (for example viral particles showed up in cultured human sarcoma c-myc,c-sis,c-src, etc.) and thus gains oncogenicity; cells xenografted into nude mice. Another purpose and it was carried out in the absence of the as yet of the study was to test autologous and allogeneic undiscovered monoclonal antibodies for lympho- patient lymphocytes for cytotoxicity against cultured cyte subtyping. Decades have since gone by and we sarcoma cells and correlate these reactions with the still do not have an established human sarcoma 4,5 clinical course of the patients. Some spectacular vaccine to prevent potsurgical relapses and we do not interaction between sarcoma cells and lymphocytes effectively utilize immune lymphocytes for adoptive occurred and were photographed. Allogeneic large immunotherapy of metastatic disease. lymphocytes with granular cytoplasm lysed sarcoma We now know that our aim at establishinghuman cells; smaller autologous lymphocytes with thinner tumor cell lines was misdirected. When we forcefully rim of cytoplasm and compact nucleus caused and with great efforts separated tumor cells from 6–8 clumpingin the nuclei of sarcoma cells. These normal connective tissue cells that accompanied purely morphological observations gained their expla- them and changed media diligently, even on week- nations later when NK cells and their derivatives (LAK ends, we deprived our cultures of the as yet undis- cells) with their receptors recognizing malignantly covered paracrine growth factors and thus selected ISSN 1357-714X print/1369-1643  2003 Taylor & Francis Ltd DOI: 10.1080/13577140310001607301 76 J. G. Sinkovics Fig. 1. (a) Allogeneic large lymphocytes lyse the cytoplasm of two sarcoma cells. (b) Two autologous lymphocytes kill two melanoma cells by causing nuclear clumping. (c) Autologous lymphocytes attacking fibrosarcoma cell undergo nuclear clumping and die while sarcoma cell survives. J.G. Sinkovics, M.D. Anderson Hospital, Houston TX (1972–1974). Fig. 2. Kaposi sarcoma cell with budding retroviral particles that failed to react with commercial kits aimed at HTLV-I or HIV-1 structural proteins. F. Gyorkeyy and J.G. Sinkovics, VA Medical Center, Houston TX, 1983 (unpublished). out subpopulations of those tumor cells that were tumor; and now HHV-8), KS cells occasionally 15,16 growing with the support of their own autocrine displayed buddingretrovirus particles (Fig. 2). growth loops. We are now promotinga new workinghypothesis It was especially difficult to establish cell lines from that a retroviral dsDNA provirus deprived of env classical pre-AIDS Kaposi’s sarcoma (KS) tumors: gene (but occasionally capable of acquiring one) we continued to refresh the media of their primary exists in these cells inserted next to the int-bFGF cultures sometimes daily and did not use ‘condi- gene family, which is thus transactivated and tioned media’. In addition to herpesviruses (CMV; amplified to encode bFGF. When excess bFGF EBV in the B-lineage lymphocytes infiltrating the ligands are released and captured by their receptors Human sarcoma cells 77 6. Sinkovics JG. A reappraisal of cytotoxic lymphocytes as expressed by the same cells, an autocrine growth in human tumor immunology. In: Cory JG, loop is established. Szentivanyi A, ed. Cancer Biology and Therapeutics. The recent outstandingreport from the same The First Annual H. Lee Moffitt International institution recognizes the interaction whereby sub- Symposium. New York, London: Plenum Press, verted stromal cells serve the tumor cells with growth 1987; 225–53. 7. Sinkovics JG. Cytotoxic lymphocytes. Ann Clin Lab Sci factors of paracrine origin. This is a highly general- 12 1986; 16: 488–96. ized phenomenon and it is applicable to many 8. Sinkovics JG. Programmed cell death (apoptosis): its tumors other than sarcomas. For example, certain virological and immunological connections. Acta melanoma cells use the Fas ligand (L) as an Microbiol Hung 1991; 38: 321–34. autocrine-paracrine growth factor; neuroblastoma 9. Sinkovics JG. Malignant lymphoma arising from natural killer cells: report of the first case in 1970 cells are driven to grow by TNFa; lymphoma cells and newer developments in the FasL!FasR armed with FasL kill host immune T cells; and (CD95) system. Acta Microbiol Immunol Hung 1997; CLL cells are protected from apoptosis by IFNg or 44: 295–307. by stromal cell-derived factor-1 (SDF-1) released 10. Sinkovics JG, Plager C, Romero JJ. Immunology and from subverted fibroblast-like cells of the host. immunotherapy of patients with sarcomas. In: Crispen RG, ed. Immunotherapy of Solid Tumors. Philadelphia, While the c-sis-product PDGF and molecular PA: Franklin Institute Press, 1977; 211–9. mediators of neoangiogenesis (bFGF; VEGF and 11. Sinkovics JG, Plager C, McMurtrey M, Papadopoulos their receptors) are well recognized growth factors NE, et al. Adjuvant chemoimmunotherapy for malig- for sarcoma cells, SDF-1 has not as yet received the nant melanoma. In: Crispen RG, ed. Neoplasm attention it deserves. Immunity: Experimental and Clinical. Amsterdam, Oxford: Elsevier North-Holland, 1980; 481–519. 12. Sinkovics JG, Horvath JC. Vaccination against human References cancers. Int J Oncol 2000; 16: 81–96. 13. Sinkovics JG. Oncogenes and growth factors. Crit Rev 1. Sinkovics JG, Gyo¨rkey F, Kusyk C, Siciliano MJ. Immunol 1988; 8: 217–98. Growth of human tumor cells in established cultures. 14. Sinkovics JG, Dreesman G. Monoclonal antibodies of In: Busch H, ed. Methods in Cancer Research. Vol 14. hybridomas. Rev Infect Dis 1983; 5: 9–34. New York: Academic Press, 1978; 243–323. 15. Gyorkey F, Sinkovics JG, Melnick JL, Gyorkey P. 2. Sinkovics JG, Plager C, McMurtrey MJ, et al. Retroviruses in Kaposi sarcoma cells in AIDS. Immunotherapy of human sarcomas. In: Primary New Engl J Med 1984; 311: 1183–4. Management of Bone and Soft Tissue Tumors. Twenty- 16. Sinkovics JG, Horvath JC. Kaposi’s sarcoma: breeding first Annual Clinical Conference on Cancer, 1976, at ground of Herpesviridae. A tour de force over viral The University of Texas System Cancer Center M.D. evolution. Int J Oncol 1999; 14: 615–46. Anderson Hospital and Tumor Institute, Houston, 17. Hu M, Nicolson GL, Yu D, et al. Characterization TX. Chicago, IL: Year Book Medical Publishers, Inc. of 11 human sarcoma cell strains. Cancer 2002; 1977; 361–410. 95: 1569–76. 3. Gyorkey F, Sinkovics JG, Gyorkey P. Electron 18. Horvath JC, Horvath E, Sinkovics JG, et al. Human microscopic observations on structures resembling melanoma cells (HMC) eliminate autologous host myxovirus in human sarcomas. Cancer 1971; 27: FasRþ lymphocytes (Ly ) and escape apoptotic death (A) 1449–54. by utilizingthe FasL !FasR system as an autocrine 4. Sinkovics JG, Kay HD, Thota H. The evaluation of FasLþFasRþ growth loop (HMC ). 89th Annual Meeting. chemoimmunotherapy regimens by in vitro lympho- Proc Am Assoc Cancer Res 1998; 39: 584, #3971. cyte cytotoxicity directed to cultured human tumor 19. Goillot E, Combaret V, Ladenstein R, et al. Tumor cells. In: Bibliotheca Haematologica. Vol 43. Basel, necrosis factor as an autocrine growth factor for New York: S. Karger, 1976; 281–4. neuroblastoma. Cancer Res 1992; 52: 3194–200. 5. Sinkovics JG. Complete remissions lastingover three 20. Sinkovics JG, Horvath JC. Virological and immuno- years in adult patients treated for metastatic sarcoma. logical connotations of apoptotic and anti-apoptotic In: Crispen RG, ed. Tumor Progression. Amsterdam, forces in neoplasia. Int J Oncol 2001; 19: 473–88. New York: Elsevier North-Holland, 1980; 315–31. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Sarcoma Hindawi Publishing Corporation

Comments on Cultured Human Sarcoma Cells

Sinkovics, Joseph G.
Sarcoma , Volume 7 – Jan 1, 2003
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Hindawi Publishing Corporation
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Copyright © 2003 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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1357-714X
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1369-1643
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10.1080/13577140310001607301
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Abstract

Human sarcoma cell populations maintained in culture reflect to the native tumor cells better if the culture retains those nonmalignant cells that comprised the tumor’s microenvironment in vivo [Hu M, et al. Characterization of 11 human sarcoma cell strains. Cancer 2002; 95: 1569–76] and thus provide paracrine growth factors and protection from apoptotic death to the tumor cells. Whereas sarcoma cell cultures obtained through meticulous efforts aimed at the elimination of all non-malignant cells of the tumor’s original microenvironment consist of subpopulations of tumor cells growing exclusively with the support of their own autocrine growth loops [Sinkovics JG, et al. Growth of human tumor cells in established cultures. In: Busch H, ed. Methods in Cancer Research. Vol 14. New York: Academic Press, 1978; 243–323]. It has been some 30 years since that, at the Section of transformed cells (KIRs; NKp30,44,46; NKG2D) Clinical Tumor Virology and Immunology, and subtypes of immune T cells (TIL) were Department of Medicine, The University of Texas separated; and perforins of lymphocyte origin and M.D. Anderson Hospital, we established over 50 death ligands and their receptors (TNFa;FasL! human tumor cell lines, amongthem 25 deriving FasR CD95) inducingextrinsic apoptosis were dis- from sarcomas. covered elsewhere. Furthermore nuclear clumping One purpose of the study was a search for causative and death of the lymphocytes attackingsarcoma cells retroviruses, since from the chicken through mice up also occurred: the ‘counterattack on lymphocytes’, 8,9 to some simian species causative sarcoma viruses while sarcoma cells remained intact (Fig. 1); these were isolated and identified. Filtered supernatant pictures were taken longbefore the discovery of the fluids of human sarcoma cell cultures occasionally Fas system. A third and main purpose of these studies caused ‘antigenic conversion’ (as shown by immuno- was the preparation of ‘viral oncolysates’ from some fluorescence stains) and ‘focus formation’ in cultures of these cell lines for active tumor-specific immu- 2 10 11,12 of human embryonic fibroblasts. These phenomena notherapy against sarcomas and melanoma. could not be propagated by passages and yielded no Our work as reported biannually in the institu- human sarcoma viral isolates, even though transmis- tional Research Report from 1960 to 1978 preceded sion EM pictures showed rare retroviral particles in the discovery of oncogenes whereby a retrovirus some of these cells. Some xenotropic murine retro- transduces a cellular protooncogene (for example viral particles showed up in cultured human sarcoma c-myc,c-sis,c-src, etc.) and thus gains oncogenicity; cells xenografted into nude mice. Another purpose and it was carried out in the absence of the as yet of the study was to test autologous and allogeneic undiscovered monoclonal antibodies for lympho- patient lymphocytes for cytotoxicity against cultured cyte subtyping. Decades have since gone by and we sarcoma cells and correlate these reactions with the still do not have an established human sarcoma 4,5 clinical course of the patients. Some spectacular vaccine to prevent potsurgical relapses and we do not interaction between sarcoma cells and lymphocytes effectively utilize immune lymphocytes for adoptive occurred and were photographed. Allogeneic large immunotherapy of metastatic disease. lymphocytes with granular cytoplasm lysed sarcoma We now know that our aim at establishinghuman cells; smaller autologous lymphocytes with thinner tumor cell lines was misdirected. When we forcefully rim of cytoplasm and compact nucleus caused and with great efforts separated tumor cells from 6–8 clumpingin the nuclei of sarcoma cells. These normal connective tissue cells that accompanied purely morphological observations gained their expla- them and changed media diligently, even on week- nations later when NK cells and their derivatives (LAK ends, we deprived our cultures of the as yet undis- cells) with their receptors recognizing malignantly covered paracrine growth factors and thus selected ISSN 1357-714X print/1369-1643  2003 Taylor & Francis Ltd DOI: 10.1080/13577140310001607301 76 J. G. Sinkovics Fig. 1. (a) Allogeneic large lymphocytes lyse the cytoplasm of two sarcoma cells. (b) Two autologous lymphocytes kill two melanoma cells by causing nuclear clumping. (c) Autologous lymphocytes attacking fibrosarcoma cell undergo nuclear clumping and die while sarcoma cell survives. J.G. Sinkovics, M.D. Anderson Hospital, Houston TX (1972–1974). Fig. 2. Kaposi sarcoma cell with budding retroviral particles that failed to react with commercial kits aimed at HTLV-I or HIV-1 structural proteins. F. Gyorkeyy and J.G. Sinkovics, VA Medical Center, Houston TX, 1983 (unpublished). out subpopulations of those tumor cells that were tumor; and now HHV-8), KS cells occasionally 15,16 growing with the support of their own autocrine displayed buddingretrovirus particles (Fig. 2). growth loops. We are now promotinga new workinghypothesis It was especially difficult to establish cell lines from that a retroviral dsDNA provirus deprived of env classical pre-AIDS Kaposi’s sarcoma (KS) tumors: gene (but occasionally capable of acquiring one) we continued to refresh the media of their primary exists in these cells inserted next to the int-bFGF cultures sometimes daily and did not use ‘condi- gene family, which is thus transactivated and tioned media’. In addition to herpesviruses (CMV; amplified to encode bFGF. When excess bFGF EBV in the B-lineage lymphocytes infiltrating the ligands are released and captured by their receptors Human sarcoma cells 77 6. Sinkovics JG. A reappraisal of cytotoxic lymphocytes as expressed by the same cells, an autocrine growth in human tumor immunology. In: Cory JG, loop is established. Szentivanyi A, ed. Cancer Biology and Therapeutics. The recent outstandingreport from the same The First Annual H. Lee Moffitt International institution recognizes the interaction whereby sub- Symposium. New York, London: Plenum Press, verted stromal cells serve the tumor cells with growth 1987; 225–53. 7. Sinkovics JG. Cytotoxic lymphocytes. Ann Clin Lab Sci factors of paracrine origin. This is a highly general- 12 1986; 16: 488–96. ized phenomenon and it is applicable to many 8. Sinkovics JG. Programmed cell death (apoptosis): its tumors other than sarcomas. For example, certain virological and immunological connections. Acta melanoma cells use the Fas ligand (L) as an Microbiol Hung 1991; 38: 321–34. autocrine-paracrine growth factor; neuroblastoma 9. Sinkovics JG. Malignant lymphoma arising from natural killer cells: report of the first case in 1970 cells are driven to grow by TNFa; lymphoma cells and newer developments in the FasL!FasR armed with FasL kill host immune T cells; and (CD95) system. Acta Microbiol Immunol Hung 1997; CLL cells are protected from apoptosis by IFNg or 44: 295–307. by stromal cell-derived factor-1 (SDF-1) released 10. Sinkovics JG, Plager C, Romero JJ. Immunology and from subverted fibroblast-like cells of the host. immunotherapy of patients with sarcomas. In: Crispen RG, ed. Immunotherapy of Solid Tumors. Philadelphia, While the c-sis-product PDGF and molecular PA: Franklin Institute Press, 1977; 211–9. mediators of neoangiogenesis (bFGF; VEGF and 11. Sinkovics JG, Plager C, McMurtrey M, Papadopoulos their receptors) are well recognized growth factors NE, et al. Adjuvant chemoimmunotherapy for malig- for sarcoma cells, SDF-1 has not as yet received the nant melanoma. In: Crispen RG, ed. Neoplasm attention it deserves. Immunity: Experimental and Clinical. Amsterdam, Oxford: Elsevier North-Holland, 1980; 481–519. 12. Sinkovics JG, Horvath JC. Vaccination against human References cancers. Int J Oncol 2000; 16: 81–96. 13. Sinkovics JG. Oncogenes and growth factors. Crit Rev 1. Sinkovics JG, Gyo¨rkey F, Kusyk C, Siciliano MJ. Immunol 1988; 8: 217–98. Growth of human tumor cells in established cultures. 14. Sinkovics JG, Dreesman G. Monoclonal antibodies of In: Busch H, ed. Methods in Cancer Research. Vol 14. hybridomas. Rev Infect Dis 1983; 5: 9–34. New York: Academic Press, 1978; 243–323. 15. Gyorkey F, Sinkovics JG, Melnick JL, Gyorkey P. 2. Sinkovics JG, Plager C, McMurtrey MJ, et al. Retroviruses in Kaposi sarcoma cells in AIDS. Immunotherapy of human sarcomas. In: Primary New Engl J Med 1984; 311: 1183–4. Management of Bone and Soft Tissue Tumors. Twenty- 16. Sinkovics JG, Horvath JC. Kaposi’s sarcoma: breeding first Annual Clinical Conference on Cancer, 1976, at ground of Herpesviridae. A tour de force over viral The University of Texas System Cancer Center M.D. evolution. Int J Oncol 1999; 14: 615–46. Anderson Hospital and Tumor Institute, Houston, 17. Hu M, Nicolson GL, Yu D, et al. Characterization TX. Chicago, IL: Year Book Medical Publishers, Inc. of 11 human sarcoma cell strains. Cancer 2002; 1977; 361–410. 95: 1569–76. 3. Gyorkey F, Sinkovics JG, Gyorkey P. Electron 18. Horvath JC, Horvath E, Sinkovics JG, et al. Human microscopic observations on structures resembling melanoma cells (HMC) eliminate autologous host myxovirus in human sarcomas. Cancer 1971; 27: FasRþ lymphocytes (Ly ) and escape apoptotic death (A) 1449–54. by utilizingthe FasL !FasR system as an autocrine 4. Sinkovics JG, Kay HD, Thota H. The evaluation of FasLþFasRþ growth loop (HMC ). 89th Annual Meeting. chemoimmunotherapy regimens by in vitro lympho- Proc Am Assoc Cancer Res 1998; 39: 584, #3971. cyte cytotoxicity directed to cultured human tumor 19. Goillot E, Combaret V, Ladenstein R, et al. Tumor cells. In: Bibliotheca Haematologica. Vol 43. Basel, necrosis factor as an autocrine growth factor for New York: S. Karger, 1976; 281–4. neuroblastoma. Cancer Res 1992; 52: 3194–200. 5. Sinkovics JG. Complete remissions lastingover three 20. Sinkovics JG, Horvath JC. Virological and immuno- years in adult patients treated for metastatic sarcoma. logical connotations of apoptotic and anti-apoptotic In: Crispen RG, ed. Tumor Progression. Amsterdam, forces in neoplasia. Int J Oncol 2001; 19: 473–88. New York: Elsevier North-Holland, 1980; 315–31. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

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Sarcoma – Hindawi Publishing Corporation

Published: Jan 1, 2003

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