Growth regulation of human neuroblastoma

  • Osama M. El-Badry
  • Mark A. Israel
Part of the Cancer Treatment and Research book series (CTAR, volume 63)


Neuroblastoma is a highly malignant tumor of infants and children. It typically occurs before the age of 5 years and accounts for up to 50% of all malignancies among infants [for review see 1,2]. A significant fraction of cases are identified neonatally, indicating that the tumor can arise during fetal life and may represent a disorder of normal development [3]. These tumors arise in sympathetic neuroblasts that originate in the neural crest and are destined to become chromaffin or neuronal tissues of the peripheral nervous system [4]. Sixty-five percent of neuroblastomas occur in the abdomen, where adrenal medullary tumors account for 40% of these tumors [1,2]. Approximately 50% of infants and 70% of older children with neuroblastomas have evidence of tumor spread beyond the primary location to metastatic sites, including the lymph nodes, bone, bone marrow, liver, and skin, at the time they first come to medical attention [1]. In children under 1 year of age, a special presentation of disseminated neuroblastoma, which is most clearly distinguished from the more common presentation of advanced-stage neuroblastoma in that it does not involve lytic lesions of the bone, has been recognized [5, 6, 7, 8]. This group, designated stage IVs, includes approximately 17% of neuroblastoma tumors arising in children under the age of 1 year. Remarkably these tumors regress without therapy, while those of older patients or of young children with metastatic disease to bone have a very poor prognosis [1].


Neuroblastoma Cell Neuroblastoma Cell Line Human Neuroblastoma Cell Human Neuroblastoma Cell Line Neuroblastoma Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Pizzo PA, Miser JS, Cassady JR, Filler RM: Solid tumors of childhood. In: Cancer: Principles and Practices of Oncology 2. DeVita VT, Jr., Hellman S, Rosenberg SA (eds): JB Lipincott, Philadelphia, 1985, pp 1511–1574.Google Scholar
  2. 2.
    Triche TJ, Cavazzana AO: Pathology in pediatric oncology. In: Pizzo PA, Poplack DG (eds): Principles and Practices of Pcdiatric Oncology. JB Lippincott, Philadelphia, 1989, pp 93–125.Google Scholar
  3. 3.
    Knudson AG Jr., Strong LC: Mutation and cancer: Neuroblastoma and pheochromo-cytoma. Am J Human Genet 24:514–532, 1972.Google Scholar
  4. 4.
    Israel MA: The evolution of clinical molecular genetics: Neuroblastoma as a model tumor. Am J Pediatr Hematol Oncol 8:163–172, 1986.PubMedGoogle Scholar
  5. 5.
    Evans AE, Gerson J, Schnaufer L: Spontaneous regression of neuroblastoma. Natl Cancer Inst Monogr 44:49–54, 1976.PubMedGoogle Scholar
  6. 6.
    Everson TC, Cole WH: Spontaneous regression of cancer. WB Saunders, Philadelphia, 1966, pp 11-87.Google Scholar
  7. 7.
    Knudson AG Jr., Meadows AT: Regression of neuroblastoma IV-S: A genetic hypothesis. N Engl J Med 302:1254–1256, 1980.PubMedGoogle Scholar
  8. 8.
    Brodeur GM, Seeger RC, Barrett A, et al.: International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma. J Clin Oncol 6:1874–1881, 1988.PubMedGoogle Scholar
  9. 9.
    Whang-Peng J, Triche TJ, Knutsen T, et al.: Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet 21:185–208, 1986.PubMedGoogle Scholar
  10. 10.
    Triche TJ: Neuroblastoma and other childhood neural tumors: A review. Pediatr Pathol 10:175–193, 1990.PubMedGoogle Scholar
  11. 11.
    Ikeda I, Ishizaka Y, Tahira T, et al.: Specific expression of the ret proto-oncogene in human neuroblastoma cell lines. Oncogene 5:1291–1296, 1990.PubMedGoogle Scholar
  12. 12.
    Nagao M, Ishizaka Y, Nakagawara A, et al.: Expression of ret proto-oncogene in human neuroblastomas. Jpn J Cancer Res 81:309–312, 1990.PubMedGoogle Scholar
  13. 13.
    Vecchio G, Cavazzana AO, Triche TJ, et al.: Expression of the dbl proto-oncogene in Ewing’s sarcomas. Oncogene 4:897–900, 1989.PubMedGoogle Scholar
  14. 14.
    Cox D, Yuncken C, Spriggs A: Minute chromatin bodies in malignant tumours of childhood. Lancet 2:55, 1965.Google Scholar
  15. 15.
    Biedler JL, Helson L, Spengler BA: Morphology and growth, tumorigenicity, and cytogenetics of human neuroblastoma cells in continuous culture. Cancer Res 33:2643–2652, 1973.PubMedGoogle Scholar
  16. 16.
    Biedler JL, Ross RA, Shanske S, et al.: Human neuroblastoma cytogenetics: Search for significance of homogeneously staining regions and double minute chromosomes. Prog Clin Biol Res 12:81–96, 1980.Google Scholar
  17. 17.
    Biedler JL, Meyers MB, Spengler BA: Homogeneously staining regions and double minute chromosomes: Prevalent cytogenetic abnormalities of human neuroblastoma cells. Adv Cell Neurobiol 4:267–307, 1983.Google Scholar
  18. 18.
    Brodeur GM, Sekhon GS, Goldstein MN: Chromosomal aberrations in human neuroblastomas. Cancer 40:2256–2263, 1977.PubMedGoogle Scholar
  19. 19.
    Brodeur GM, Green AA, Hayes FA, et al.: Cytogenetic features of human neuroblastomas and cell lines. Cancer Res 41:4678–4686, 1981.PubMedGoogle Scholar
  20. 20.
    Gilbert F, Feder M, Balaban G, et al.: Human neuroblastoma and abnormalities of chromosomes 1 and 17. Cancer Res 44:5444–5449, 1984.PubMedGoogle Scholar
  21. 21.
    Montgomery KT, Biedler JL, Spengler BA, et al.: Specific DNA sequence amplification in human neuroblastoma cells. Proc Natl Acad Sci USA 80:5724–5728, 1983.PubMedGoogle Scholar
  22. 22.
    Franke F, Rudolph B, Christiansen H, et al.: Tumour karyotype may be important in the prognosis of human neuroblastoma. J Cancer Res Clin Oncol 111:266–272, 1986.PubMedGoogle Scholar
  23. 23.
    Christiansen H, Lampert F: Tumour karyotype discriminates between good and bad prognostic outcome in neuroblastoma. Br J Cancer 57:121–126, 1988.PubMedGoogle Scholar
  24. 24.
    Biedler JL, Spengler BA: Metaphase chromosome anomaly: Association with drug resistance and cell-specific products. Science 191:185–187, 1976.PubMedGoogle Scholar
  25. 25.
    Alitalo K, Schwab M, Lin CC, et al.: Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci USA 80:1707–1711, 1983.PubMedGoogle Scholar
  26. 26.
    Little CD, Nau MM, Carney DN, et al.: Amplification and expression of the c-myc oncogene in human lung cancer cell lines. Nature 306:194–196, 1983.PubMedGoogle Scholar
  27. 27.
    Gilbert F, Balaban G, Breg WR, et al.: Homogeneously staining region in a retinoblastoma cell line: Relevance to tumor initiation and progression. J Natl Caner Inst 67:301–306, 1981.Google Scholar
  28. 28.
    Kohl NE, Kanda N, Schreck RR, et al.: Transposition and amplification of oncogene-related sequences in human neuroblastoma. Cell 35:359–367, 1983.PubMedGoogle Scholar
  29. 29.
    Schwab M, Alitalo K, Klempnauer KH, et al.: Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature 305:245–248, 1983.PubMedGoogle Scholar
  30. 30.
    Schwab M, Ellison J, Busch M, et al.: Enhanced expression of the human gene N-myc consequent to amplification of DNA may contribute to malignant progression of neuroblastoma. Proc Natl Acad Sci USA 81:4940–4944, 1984.PubMedGoogle Scholar
  31. 31.
    Brodeur GM, Seeger RC, Schwab M, et al.: Amplification of N-myc sequences in primary human neuroblastomas: Correlation with advanced disease stage. Prog Clin Biol Res 175:105–113, 1985.PubMedGoogle Scholar
  32. 32.
    Brodeur GM, Seeger RC: Gene amplification in human neuroblastomas: Basic mechanisms and clinical implications. Cancer Genet Cytogenet 19:101–111, 1986.PubMedGoogle Scholar
  33. 33.
    Shiloh Y, Korf B, Kohn NE, et al.: Amplifications and rearrangement of DNA sequences from the chromosomal region 2p24 in human neuroblastoma. Cancer Res 46:5297–5301, 1986.PubMedGoogle Scholar
  34. 34.
    Suzuki T, Yokota J, Mugishima H, et al.: Frequent loss of heterozygosity on chromosome 14q in neuroblastoma. Cancer Res 49:1095–1098, 1989.PubMedGoogle Scholar
  35. 35.
    Srivatsan ES, Venugopal M, Seeger RC: Loss of heterozygosity for alleles on chromosomes llq and 14q in neuroblastoma. Prog Clin Biol Res 366:91–98, 1991.PubMedGoogle Scholar
  36. 36.
    Gilbert F, Balaban G, Moorhead P, et al.: Abnormalities of chromosomes lp in human neuroblastoma tumors and cell lines. Cancer Genet Cytogenet 7:33–42, 1982.PubMedGoogle Scholar
  37. 37.
    Schwab M: Is there a neuroblastoma anti-oncogene? Prog Clin Biol Res 366:1–10, 1991.PubMedGoogle Scholar
  38. 38.
    Mitlamn F: Catalog of Chromosome Aberrations in Cancer. Prog Top Cytogenet, 2nd ed., Vol. 5, Alan R. Liss, New York, 1985.Google Scholar
  39. 39.
    Hunt JD, Tereba AT: Molecular evaluation of abnormalities of the short arm of chromosome 1 in neuroblastoma. Genes Chromosomes Cancer 2:137–146, 1990.PubMedGoogle Scholar
  40. 40.
    Knudson AG Jr., Meadows AT: Developmental genetics of neuroblastoma. J Natl Cancer Inst 57:675–681, 1976.PubMedGoogle Scholar
  41. 41.
    Pasquale SR, Jones GR, Doersen C-J, et al.: Tumorigenicity and oncogene expression in pediatric cancers. Cancer Res 47:2715–2719, 1988.Google Scholar
  42. 42.
    Atkin NB: Chromosome 1 aberrations in cancer. Cancer Genet Cytogenet 21:279–285, 1986.PubMedGoogle Scholar
  43. 43.
    Fong CT, Dracopoli NC, White PS, et al.: Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: Correlation with N-myc amplification. Proc Natl Acad Sci USA 86:3753–3757, 1989.PubMedGoogle Scholar
  44. 44.
    Martinsson T, Weith A, Cziepluch C, et al.: Chromosome 1 deletions in human neuroblastomas: Generation and fine mapping of microclones from the distal lp region. Genes Chromosomes Cancer 1:67–78, 1989.PubMedGoogle Scholar
  45. 45.
    Weith A, Martinsson T, Cziepluch C, et al.: Neuroblastoma consensus deletion maps to chromosome Ip36.1-2. Genes Chromosomes Cancer 1:159–166, 1989.PubMedGoogle Scholar
  46. 46.
    Look AT, Hayes FA, Nitschke R, et al.: Cellular DNA content as a predictor of response to chemotherapy in infants with unresectable neuroblastoma. N Engl J Med 311:231–235, 1984.PubMedGoogle Scholar
  47. 47.
    Hayashi Y, Hanada R, Yamamoto K, et al.: Chromosome findings and prognosis in neuroblastoma [letter]. Cancer Genet Cytogenet 29:175–177, 1987.PubMedGoogle Scholar
  48. 48.
    Hayashi Y, Inaba T, Hanada R, et al.: Chromosome findings and prognosis in 15 patients with neuroblastoma found by VMA mass screening. J Pediatr 112:567–571, 1988.PubMedGoogle Scholar
  49. 49.
    Hayashi Y, Kanda N, Inaba T, et al.: Cytogenetic findings and prognosis in neuroblastoma with emphasis on marker chromosome 1. Cancer 63:126–132, 1989.PubMedGoogle Scholar
  50. 50.
    Kaneko Y, Kanda N, Maseki N, et al.: Different karyotypic patterns in early and advanced stage neuroblastomas. Cancer Res 47:311–318, 1987.PubMedGoogle Scholar
  51. 51.
    Oppedal BR, Storm MI, Lie SO, et al.: Prognostic factors in neuroblastoma. Clinical, histopathologic, and immunohistochemical features and DNA ploidy in relation to prognosis. Cancer 62:772–780, 1988.PubMedGoogle Scholar
  52. 52.
    Bourhis J, DeVathaire F, Wilson GD, et al.: Combined analysis of DNA ploidy index and N-myc genomic content in neuroblastoma. Cancer Res 51:33–36, 1991.PubMedGoogle Scholar
  53. 53.
    Dominici C, Negroni A, Romeo A, et al.: Association of near-diploid DNA content and N-myc amplification in neuroblastomas. Clin Exp Metastasis 7:201–211, 1989.PubMedGoogle Scholar
  54. 54.
    Bishop JM: Molecular themes in oncogenesis. Cell 64:235–248, 1991.PubMedGoogle Scholar
  55. 55.
    Takahashi M, Cooper GM: Ret transforming gene encodes a fusion protein homologous to tyrosine kinases. Mol Cell Biol 7:1378–1385, 1987.PubMedGoogle Scholar
  56. 56.
    Tahira T, Ishizaka Y, Itoh F, et al.: Characterization of ret proto-oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line. Oncogene 5:97–102, 1990.PubMedGoogle Scholar
  57. 57.
    Ishizaka Y, Ochiai M, Tahira T, et al.: Activation of the ret-II oncogene products differing in carboxy-termini due to alternative splicing. Oncogene 4:789–794, 1989.PubMedGoogle Scholar
  58. 58.
    Tahira T, Ishizaka Y, Sugimura T, et al.: Expression of proto-ret mRNA in embryonic and adult rat tissues. Biochem Biophys Res Commun 153:1290–1295, 1988.PubMedGoogle Scholar
  59. 59.
    Hunter T, Sefton BM: Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci USA 77:1311–1315, 1980.PubMedGoogle Scholar
  60. 60.
    Collett MS, Purchio AF, Erikson RL.: Avian sarcoma virus-transforming protein, pp60c-src shows protein kinase activity for tyrosine. Nature 285:167–169, 1980.PubMedGoogle Scholar
  61. 61.
    Burgge JS, Cotton PC, Queral AE, et al.: Neurons express high levels of a structurally modified activated form of pp60c-src. Nature 316:554–557, 1985.Google Scholar
  62. 62.
    Parsons SJ, Creutz CE.: pp60c-src activity detected in the chromaffin granule membrane. Biochem Biophys Res Commun 134:736–742, 1986.PubMedGoogle Scholar
  63. 63.
    Golden A, Nemeth SP, Brugge JS: Blood platelets express high levels of the pp60c-src specific tyrosine kinase activity. Proc Natl Acad Sci USA 83:852–856, 1986.PubMedGoogle Scholar
  64. 64.
    Mellstrom K, Bjelfman C, Hammerling U, et al.: Expression of c-src in cultured human neuroblastoma and small cell lung carcinoma cell lines correlates with neurocrine differentiation. Mol Cell Biol 7:4178–4184, 1987.PubMedGoogle Scholar
  65. 65.
    Bolen JB, Veillette A, Schwartz AM, et al.: Activation of pp60c-src protein kinase activity in human colon carcinoma. Proc Natl Acad Sci USA 84:2251–2255, 1987.PubMedGoogle Scholar
  66. 66.
    Cartwright CA, Kamps MP, Meisler AI, et al.: pp60c-src activation in human colon carcinoma. J Clin Invest 83:2025–2033, 1989.PubMedGoogle Scholar
  67. 67.
    Rosen N, Bolen JB, Schwartz AM, et al.: Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. J Biol Chem 261:13754–13759, 1986.PubMedGoogle Scholar
  68. 68.
    Jocobs C, Rubsamen H: Expression of pp60c-src protein kinase in adult and fetal human tissue: High activities in some sarcomas and mammary carcinomas. Cancer Res 43:1696–1702, 1983.Google Scholar
  69. 69.
    Bolen JB, Rosen N, Israel MA: Increased pp60c-src tyrosyl kinase activity in human neuroblastomas is associated with amino-terminal tyrosine phosphorylation of the src gene product. Proc Natl Acad Sci USA 82:7275–7279, 1985.PubMedGoogle Scholar
  70. 70.
    O’Shaughnessy J, DeSeau V, Amini S, et al.: Analysis of the src gene product structure, abundance, and protein kinase activity in human neuroblastoma and glioblastoma cells. Oncogene Res 2:1–18, 1987.Google Scholar
  71. 71.
    Pyper JM, Bolen JP: Identification of a novel neuronal c-src exon expressed in human brain. Mol Cell Biol 10:2035–2040, 1990.PubMedGoogle Scholar
  72. 72.
    LeBeau JM, Wiestler OD, Walter G: An altered form of pp60c-src is expressed primarily in the central nervous system. Mol Cell Biol 7:4115–4117, 1987.Google Scholar
  73. 73.
    Bjelfman C, Hedborg F, Johansson I, et al.: Expression of the neuronal form of pp60c-src in neuroblastoma in relation to clinical stage and prognosis. Cancer Res 50:6908–6914, 1990.PubMedGoogle Scholar
  74. 74.
    Matsunaga T, Takahashi H, Ohnuma N, et al.: Expression of N-myc and c-src protooncogenes correlating to the undifferentiated phenotype and prognosis of primary neuroblastomas. Cancer Res 51:3148–3152, 1991.PubMedGoogle Scholar
  75. 75.
    Feramisco JR, Gross M, Kamata T, et al.: Microinjection of the oncogene form of the human Ha-ras (T-24) protein results in rapid proliferation of quiescent cells. Cell 38: 109–117, 1984.PubMedGoogle Scholar
  76. 76.
    Mulcahy LS, Smith MR, Stacy DW: Requirement for ras protooncogene function during serum stimulate growth of NIH3T3 cells. Nature 313:241–243, 1985.PubMedGoogle Scholar
  77. 77.
    Hurley JB, Simon MI, Teplow DB, et al.: Homologies between signal transducing G proteins and ras gene products. Science 226:860–862, 1984.PubMedGoogle Scholar
  78. 78.
    Birchmeier C, Broek D, Wigler M: Ras proteins can induce miosis in xenopus oocytes. Cell 43:615–621, 1985.PubMedGoogle Scholar
  79. 79.
    Tanaka T, Slamon DJ, Shimoda H, et al.: Expression of Ha-ras oncogene products in human neuroblastomas and the significant correlation with a patient’s prognosis. Cancer Res 48:1030–1034, 1988.PubMedGoogle Scholar
  80. 80.
    Tanaka T: Tumor markers — personal experience. Ha-ras P21 in neuroblastoma: A new marker associating to patient’s prognosis. Gan To Kagaku Ryoho 18:143–150, 1991.PubMedGoogle Scholar
  81. 81.
    Tanaka T, Ida N, Shimoda H, et al.: Organ specific expression of ras oncoproteins during growth and development of the rat. Mol Cell Biochem 70:97–104, 1986.PubMedGoogle Scholar
  82. 82.
    Noda M, Ko M, Ogura A, et al.: Sarcoma viruses carrying ras oncogenes induce differentiation-associated properties in neural cell line. Nature 318:73–75, 1985.PubMedGoogle Scholar
  83. 83.
    Bar-Sagi D, Feramisco JR: Microinjection of the ras oncogene protein into PC12 cells induce morphological differentiation. Cell 42:841–848, 1985.PubMedGoogle Scholar
  84. 84.
    Hagag N, Halegoua S, Viola M: Inhibition of growth factor-induced differentiation of PC12 cells by microinjection of antibody to ras p21. Nature 319:680–682, 1986.PubMedGoogle Scholar
  85. 85.
    Moley JF, Brother MB, Wells SA, et al.: Low frequency of ras gene mutations in neuroblastomas, pheochromocytomas, and medullary thyroid cancers. Cancer Res 51:1596–1599, 1991.PubMedGoogle Scholar
  86. 86.
    Dalla-Favera R, Wong-Staal F, Gallo RC: onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary cells of the same patient. Nature 299:61–63, 1982.PubMedGoogle Scholar
  87. 87.
    Schwab M, Varmus HE, Bishop JM: Human N-myc contributes to neoplastic transformation of mammalian cells in culture. Nature 316:160–162, 1985.PubMedGoogle Scholar
  88. 88.
    Yancopoulos GD, Nisen PD, Tesfaye A, et al.: N-myc can cooperate with ras to transform normal cells in culture. Proc Natl Acad Sci USA 82:5455–5459, 1985.PubMedGoogle Scholar
  89. 89.
    Brodeur GM, Seeger RC, Schwab M, et al.: Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224:1121–1124, 1984.PubMedGoogle Scholar
  90. 90.
    Seeger RC, Brodeur GM, Sather H, et al.: Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas. N Engl J Med 313:1111–1116, 1985.PubMedGoogle Scholar
  91. 91.
    Nakagawara A, Ikeda K, Yokoyama T, et al.: Surgical aspects of N-myc amplification in relation to disease stage and histologie types in human neuroblastomas. Cancer 60: 820–826, 1987.PubMedGoogle Scholar
  92. 92.
    Tsuda T, Obara M, Hirano H, et al.: Analysis of N-myc amplification in relation to disease stage and histologie types in human neuroblastomas. Cancer 60:820–826, 1987.PubMedGoogle Scholar
  93. 93.
    Tsuda H, Shimosato Y, Upton MP, et al.: Retrospective study on amplification of N-myc and c-myc genes in pediatrie solid tumors and its association with prognosis and tumor differentiation. Lab Invest 59:321–327, 1988.PubMedGoogle Scholar
  94. 94.
    Nakagawara A, Ikeda K, et al.: N-myc oncogene amplification and prognostic factors of neuroblastoma in children. J Pediatr Surg 22:895–898, 1987.PubMedGoogle Scholar
  95. 95.
    Nakagawara A, Ikeda K, Yokoyama T, et al.: Surgical aspects of N-myc oncogene amplification of neuroblastoma. Surgery 104:34–39, 1988.PubMedGoogle Scholar
  96. 96.
    Nakagawara A, Ikeda K: N-myc oncogene amplification and catecholamine metabolism in children with neuroblastoma. Lancet 1:559, 1987.PubMedGoogle Scholar
  97. 97.
    Phillips WS, Stafford PW, Duvol-Arnold B, et al.: Neuroblastoma and the clinical significance of N-myc oncogene amplification. Surg Gynecol Obstet 172:73–80, 1991.PubMedGoogle Scholar
  98. 98.
    Brodeur GM, Seeger RC, Sather H, et al.: Clinical implications of oncogene activation in human neuroblastomas. Cancer 58 (Suppl. 2):541–545, 1986.PubMedGoogle Scholar
  99. 99.
    Tonini GP, Verdona G, DeBernardi B, et al.: N-myc oncogene amplification in a patient with IV-S neuroblastoma. Am J Pediatr Hematol Oncol 9:8–10, 1987.PubMedGoogle Scholar
  100. 100.
    Cohn SL, Herst CV, Maurer HS, et al.: N-myc amplification in an infant with stage IVs neuroblastoma. J Clin Oncol 5:1441–1444, 1987.PubMedGoogle Scholar
  101. 101.
    Carlsen NLT, Christensen IJ, Schroeder H, et al.: Prognostic value of different staging systems in neuroblastomas and completeness of tumour excision. Arch Dis Child 61: 832–842, 1986.PubMedGoogle Scholar
  102. 102.
    Garvin J Jr., Bendit I, Nisen PD: N-myc oncogene expression and amplification in metastatic lesions of stage IV-S neuroblastoma. Cancer 65:2572–2575, 1990.PubMedGoogle Scholar
  103. 103.
    Nakagawara A, Sasazuki T, Akiyama H, et al.: N-myc oncogene and stage IV-S neuroblastoma. Cancer 65:1960–1967, 1990.PubMedGoogle Scholar
  104. 104.
    Michitsch R, Biedler JL, Melera P: Modulation of N-myc expression, but not tumorigenicity accompanies phenotypic conversion of neuroblastoma cells in prolonged culture. Prog Clin Biol Res 271:103–120, 1988.PubMedGoogle Scholar
  105. 105.
    Slamon DJ, Boone TC, Seeger RC, et al.: Identification and characterization of the protein encoded by the human N-myc oncogene. Science 232:768–772, 1986.PubMedGoogle Scholar
  106. 106.
    Ramsey G, Stanton L, Schwab M, et al.: Human proto-oncogene N-myc encodes nuclear proteins that bind DNA. Mol Cell Biol 6:4450–4467, 1986.Google Scholar
  107. 107.
    Seeger RC, Wada R, Brodeur GM, et al.: Expression of N-myc by neuroblastomas with one or multiple copies of the oncogene. Prog Clin Biol Res 271:41–49, 1988.PubMedGoogle Scholar
  108. 108.
    Kohl NE, Gee CE, Alt FW: Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science 226:1335–1337, 1984.PubMedGoogle Scholar
  109. 109.
    Schwab M, Varmus H, Bishop J, et al.: Chromosome localization in normal human cells and neuroblastomas of a gene related to c-myc. Nature 308:288–291, 1984.PubMedGoogle Scholar
  110. 110.
    Alt F, DePinho R, Zimmerman K, et al.: The human myc gene family. Cold Spring Harbor Symp Quant Biol 51:931–941, 1986.PubMedGoogle Scholar
  111. 111.
    Zimmerman K, Yancopoulos G, Collum R, et al.: Differential expression of myc family genes during murine development. Nature 319:780–783, 1986.PubMedGoogle Scholar
  112. 112.
    Hirvonen H, Sandberg M, Kalimo H, et al.: The N-myc proto-oncogene and IGF-II growth factor mRNAs are expressed by distinct cells in human fetal kidney and brain. J Cell Biol 108:1093–1104, 1989.PubMedGoogle Scholar
  113. 113.
    Grady EF, Schwab M, Rosenau W: Expression of N-myc and c-src during the development of fetal human brain. Cancer Res 47:2931–2936, 1987.PubMedGoogle Scholar
  114. 114.
    Dildrop R, Zimmerman KD, DePinho R, et al.: Differential expression of myc family genes during development: Normal and deregulated N-myc expression in transgenic mice. Curr Top Microbiol Immunol 141:100–109, 1988.PubMedGoogle Scholar
  115. 115.
    Dildrop R, Ma A, Zimmerman KD, et al.: IgH enhancer-mediated deregulation of N-myc gene expression in transgenic mice: Generation of lymphoid neoplasias that lack c-myc expression. EMBO J 8:1121–1128, 1989.PubMedGoogle Scholar
  116. 116.
    Dildrop R, Zimmerman KD, Yancopoulos G, et al.: Differential expression of myc-family genes during development: Normal and deregulated N-myc expression in transgenic mice. Curr Top Microbiol Immunol 51:931–941, 1986.Google Scholar
  117. 117.
    Lee WH, Murphree AC, Benedict WF: Expression and amplification of the NMYC gene in primary retinoblastoma. Nature 309:458–460, 1984.PubMedGoogle Scholar
  118. 118.
    Nau M, Brooks B, Carney D, et al.: Human small-cell lung cancers show amplification and expression of the N-myc gene. Proc Natl Acad Sci USA 83:1092–1096, 1986.PubMedGoogle Scholar
  119. 119.
    Rosolen A, Whitesell L, Ikegaki N, et al.: Antisense inhibition of single copy N-myc expression results in decreased cell growth without reduction of c-myc protein in a neuroepithelioma cell line. Cancer Res 50:6316–6322, 1990.PubMedGoogle Scholar
  120. 120.
    Schweigerer L, Breit S, Wenzel A, et al.: Augmented MYCN expression advances the malignant phenotype of human neuroblastoma cells: Evidence for induction of autocrine growth factor activity. Cancer Res 50:4411–4416, 1990.PubMedGoogle Scholar
  121. 121.
    Rosen N, Reynolds C, Thiele C, et al.: Increased N-myc expression following progressive growth of human neuroblastoma. Cancer Res 46:4139–4142, 1986.PubMedGoogle Scholar
  122. 122.
    Berman SA, Bursztajn S, Kinnard R, et al.: Increased N-MYC mRNA expression associated with dibutyryl cyclic AMP induced neuroblastoma differentiation. J Neurogenet 6:75–86, 1989.PubMedGoogle Scholar
  123. 123.
    Thiele CJ, Israel MA: Regulation of N-myc expression is a critical event controlling the ability of human neuroblasts to differentiate. Exp Cell Biol 56:321–333, 1988.PubMedGoogle Scholar
  124. 124.
    Zimmerman K, Alt FW: Expression and function of myc family genes. Crit Rev Oncog 2:75–95, 1990.PubMedGoogle Scholar
  125. 125.
    Thiele CJ, Reynolds CP, Israel MA: Decreased expression of N-myc precedes retinoic acid-induced morphological differentiation of human neuroblastoma. Nature 313:404–406, 1985.PubMedGoogle Scholar
  126. 126.
    Amatruda TT, III, Sidell N, Ranyard J, et al.: Retinoic acid treatment of human neuroblastoma cells is associated with decreased N-myc expression. Biochem Biophys Res Commun 126:1189–1195, 1985.PubMedGoogle Scholar
  127. 127.
    Horii Y, Sugimoto T, Swada T, et al.: Differential expression of N-myc and c-src protooncogenes during neuronal and schwannian differentiation of human neuroblastoma cells. Int J Cancer 43:305–309, 1989.PubMedGoogle Scholar
  128. 128.
    Cornaglia-Ferraris P, Tonini GP: Letter to the editor. Am J Pediatr Hematol Oncol 10:182–183, 1988.Google Scholar
  129. 129.
    Festinstein H, Schmidt W: Variation in MHC antigenic profiles of tumor cells and its biologic effects. Immunol Rev 60:85–127, 1981.Google Scholar
  130. 130.
    Katzav S, de Baetselier P, Tartakowsky B, et al.: Alterations in major histocompatibility complex phenotypes of mouse cloned T10 sarcoma cells; association with shifts from nonmetastatic to metastatic cells. J Natl Cancer Inst 71:317–324, 1983.PubMedGoogle Scholar
  131. 131.
    Schmidt W, Atfield G, Festenstein H: Loss of H-2 gene products from AKR spontaneous leukemias. Immunogenetics 8:311, 1979.Google Scholar
  132. 132.
    Schrier PI, Bernards R, Vaessen MJ, et al.: Expression of class I major histocompatibility antigen switched off by highly oncogenic adenovirus 12 in transformed rat cells. Nature 305:771–775, 1983.PubMedGoogle Scholar
  133. 133.
    Hui K, Grosveld F, Festinstein H: Rejection of transplantable AKR leukemia cells following MHC DNA-mediated cell transformation. Nature 311:750–752, 1984.PubMedGoogle Scholar
  134. 134.
    Tanaka K, Isselbacher K, Khoury G, et al.: Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science 228:26–30, 1985.PubMedGoogle Scholar
  135. 135.
    Wallich R, Bulbue M, Hammerling G, et al.: Albrogation of metastatic properties of tumor cells by ‘de novo’ expression of H-2K antigens following H-2 gene transfection. Nature 315:301–305, 1985.PubMedGoogle Scholar
  136. 136.
    Salerno C, Crepaldi T, Savoia P, et al.: Expression of HLA class I antigens in human tumors and their involvement in tumor growth. Res Clin Lab 20:85–93, 1990.Google Scholar
  137. 137.
    Lampson LA, Fisher CA, Whelan JP: Striking paucity of HLA-A, B, C and B2-microglobulin on human neuroblastoma cell lines. J Immunol 130:2471–2478, 1983.PubMedGoogle Scholar
  138. 138.
    Favrot MC, Combaret V, Goillot E, et al.: Expression of leucocyte adhesion molecules on 66 clinical neuroblastoma specimens. Int J Cancer 48:502–510, 1991.PubMedGoogle Scholar
  139. 139.
    Dausset J: The major histocompatibility complex in man. Science 213:1469–1474, 1981.PubMedGoogle Scholar
  140. 140.
    Main EK, Lampson LA, Hart MK, et al.: Human neuroblastoma cells are susceptible to lysis of natural killer cells but not by cytotoxic T lymphocytes. J Immunol 135:242–246, 1985.PubMedGoogle Scholar
  141. 141.
    Lampson LA: Biological significance of HLA-A, B, C expression in neuroblastoma and related cell lines. Prog Clin Biol Res 271:409–420, 1988.PubMedGoogle Scholar
  142. 142.
    Cooper MJ, Huchins GM, Cohen PS, et al.: Human neuroblastoma tumors correspond to the arrested differentiation of chromaffin adrenal medullary neuroblasts. Cell Growth Differ 1:149–159, 1990.PubMedGoogle Scholar
  143. 143.
    Lampson LA, Fisher CA: Weak HLA and beta 2-microglobulin expression of neuronal cell lines can be modulated by interferon. Proc Natl Acad Sci USA 81:6476–6480, 1984.PubMedGoogle Scholar
  144. 144.
    Houghton AN, Thomson TM, Gross D, et al.: Surface antigens of melanoma and melanocytes. Specificity of induction of la antigens by human gamma-interferon. J Exp Med 160:255–269, 1984.PubMedGoogle Scholar
  145. 145.
    Gross N, Beck D, Favre S, et al.: In vitro antigenic modulation of human neuroblastoma cells induced by IFN-gamma, retinoic acid and dibutyryl cyclic AMP. Int J Cancer 39:521–529, 1987.PubMedGoogle Scholar
  146. 146.
    Sugimoto T, Horii Y, Hino T, et al.: Differential susceptibility of HLA class II antigens induced by gamma-interferon in human neuroblastoma cell lines. Cancer Res 49: 1824–1828, 1989.PubMedGoogle Scholar
  147. 147.
    Gross N, Beck D, Favre S: In vitro modulation and relationship between N-myc and HLA class I RNA steady-state levels in human neuroblastoma cells. Cancer Res 50:7532–7536, 1990.PubMedGoogle Scholar
  148. 148.
    Evans A, Main E, Zier K, et al.: The effects of gamma interferon on the natural killer and tumor cells of children with neuroblastoma. Cancer 64:1383–1387, 1989.PubMedGoogle Scholar
  149. 149.
    Reynolds CP, Tomayko MM, Donner L, et al.: Biological classification of cell lines derived from human extra-cranial neural tumors. Prog Clin Biol Res 271:291–306, 1988.PubMedGoogle Scholar
  150. 150.
    Bernards R, Dessain SK, Weinberg RA: N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell 47:667–674, 1986.PubMedGoogle Scholar
  151. 151.
    Versteeg R, Noordermeer I, Kruse-Wolters M, et al.: c-myc down-regulates class I HLA expression in human melanomas. EMBO J 7:1023–1029, 1988.PubMedGoogle Scholar
  152. 152.
    Versteeg R, van der Minne C, Plomp A, et al.: N-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells. Molec Cell Biol 10:5416–5423, 1990.PubMedGoogle Scholar
  153. 153.
    Feltner DE, Cooper M, Weber J, et al.: Expression of class-I histocompatibility antigens in neuro-ectodermal tumors is independent of the expression of a transfected neuroblastoma myc gene. J Immunol 143:4292–4299, 1989.PubMedGoogle Scholar
  154. 154.
    Sporn MB, Roberts AB: Autocrine growth factors and cancer. Nature 313:745–747, 1985.PubMedGoogle Scholar
  155. 155.
    Cuttitta F, Carney DN, Mulshine J, et al.: Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 316:823–826, 1985.PubMedGoogle Scholar
  156. 156.
    Schwab G, Siegall CB, Aarden LA, et al.: Characterization of an interlukin-6-mediated autocrine growth loop in the human multiple myeloma cell line, U266. Blood 77:587–593, 1991.PubMedGoogle Scholar
  157. 157.
    El-Badry OM, Minniti C, Kohn EC, et al.: Insulin-like growth factor II acts as an autocrine growth and motility factor in human rhabdomyosarcoma tumors. Cell Growth Differ 1:325–331, 1990.PubMedGoogle Scholar
  158. 158.
    Yee D, Cullen KJ, Paik S, et al.: Insulin-like growth factor II mRNA expression in human breast cancer. Cancer Res 48:6691–6696, 1988.PubMedGoogle Scholar
  159. 159.
    Yee D, Paik S, Lebovic GS, et al.: Analysis of insulin-like growth factor I gene expression in malignancy: Evidence for a paracrine role in human breast cancer. Mol Endocrinol 3:509–517, 1989.PubMedGoogle Scholar
  160. 160.
    Ross RA, Spengler BA, Biedler JL: Coordinate morphological and biochemical interconversion of human neuroblastoma cells. J Natl Cancer Inst 71:741–747, 1983.PubMedGoogle Scholar
  161. 161.
    Ciccarone V, Spengler B, Meyers M, et al.: Phenotypic diversification in human neuroblastoma cells: Expression of distinct neural crest lineages. Cancer Res 49:219–225, 1989.PubMedGoogle Scholar
  162. 162.
    Rettig W, Spengler B, Chesa P, et al.: Coordinate changes in neuronal phenotype and surface antigen expression in human neuroblastoma cell variants. Cancer Res 47: 1383–1389, 1987.PubMedGoogle Scholar
  163. 163.
    Bossart E, Conti G: Epidermal growth factor stimulates colony formation and non-neuronal marker protein expression by human neuroblastoma in methylcellulose culture. Anticancer Res 9:1497–1504, 1989.PubMedGoogle Scholar
  164. 164.
    Suardet L, Gross N, Gaide A-C, et al.: Epidermal growth factor responsiveness of a new human neuroblastoma cell line. Int J Cancer 44:661–668, 1989.PubMedGoogle Scholar
  165. 165.
    Ludecke G, Unsicker K: Mitogenic effects of neurotrophic factors on human neuroblastoma IMR 32 cells. Cancer 65:2270–2277, 1990.PubMedGoogle Scholar
  166. 166.
    El-Badry OM, Romanus JA, Helman LJ, et al.: Autonomous growth of a human neuroblastoma cell line is mediated by insulin-like growth factor II. J Clin Invest 84: 829–839, 1989.PubMedGoogle Scholar
  167. 167.
    El-Badry OM, Helman LJ, Chatten J, et al.: Insulin-like growth factor II-mediated proliferation of human neuroblastoma. J Clin Invest 87:648–657, 1991.PubMedGoogle Scholar
  168. 168.
    El-Badry OM, Meyers MB, Spengler BA, et al.: Medium conditioned by human neuroblastoma BE(2)-C cells contains an autocrine/paracrine acting growth factor with properties similar to insulin-like growth factor II. Prog Clin Biol Res 366:257–266, 1991.PubMedGoogle Scholar
  169. 169.
    El-Badry OM: Insulin-like growth factor II gene expression in human neuroblastoma. Prog Clin Biol Res 366:249–256, 1991.PubMedGoogle Scholar
  170. 170.
    Van Wyk JJ, Graves DC, Casella SJ, et al.: Evidence from monoclonal antibody studies that insulin stimulated deoxyribonucleic acid synthesis through the type I somatomedin receptor. J Clin Endocrinol Metab 61:639–643, 1985.PubMedGoogle Scholar
  171. 171.
    Flier SJ, Usher P, Moses AC: Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I and insulin in human skin fibroblasts. Proc Natl Acad Sci USA 83:664–668, 1986.PubMedGoogle Scholar
  172. 172.
    Furlanetto RW, DiCarlo JN, Wisehart C: The type II insulin-like growth factor receptor does not mediate deoxyribonucleic acid synthesis in human fibroblasts. J Clin Endocrinol Metab 64:1142–1149, 1987.PubMedGoogle Scholar
  173. 173.
    Ota AW, Wilson GL, Spilberg O, et al.: Functional insulin-like growth factor I (IGF-I) receptors are expressed by neural derived continuous cell lines. Endocrinology 122:145–152, 1988.PubMedGoogle Scholar
  174. 174.
    Ota AW, Wilson GL, LeRoith D: Insulin-like growth factor I receptors on mouse neuroblastoma cells: Two B subunits are derived from differences in glycosylation. Eur J Biochem 174:521–530, 1988.PubMedGoogle Scholar
  175. 175.
    Sturm MA, Conover CA, Pham H, et al.: Insulin-like growth factors and receptors and binding protein in rat neuroblastoma cells. Endocrinology 124:388–396, 1989.PubMedGoogle Scholar
  176. 176.
    Mattsson MEK, Hammerling U, Mohall E, et al.: Mitogenically uncoupled insulin and IGF-I receptors of differentiated human neuroblastoma cells are functional and mediate ligand-induced signals. Growth Factors 2:251–265, 1990.PubMedGoogle Scholar
  177. 177.
    Chelmicka-Schorr E, Checinski ME, Arnason BGW: PC12 pheochromocytoma and sympathetic nervous system derived trophic factors augment growth of neuroblastoma. Eur J Cancer Clin Oncol 25:1057–1059, 1989.PubMedGoogle Scholar
  178. 178.
    Chelmicka-Schorr E, Checinski ME: Sympathetic nervous system derived trophic factor augments growth of human neuroblastoma in vitro. Eur J Cancer Clin Oncol 25:393–394, 1989.PubMedGoogle Scholar
  179. 179.
    Brown AL, Graham EE, Nissley SP, et al.: Developmental regulation of insulin-like growth factor II mRNA in different rat tissues. J Biol Chem 261:13144–13150, 1986.PubMedGoogle Scholar
  180. 180.
    Levinovitz A, Norstedt G: Developmental and steroid hormonal regulation of insulin-like growth factor II expression. Mol Endocrinol 3:797–804, 1989.PubMedGoogle Scholar
  181. 181.
    Scott J, Cowell JJ, Robertson ME, et al.: Insulin-like growth factor-II gene expression in Wilms’ tumor and embryonic tissues. Nature 317:260–262, 1985.PubMedGoogle Scholar
  182. 182.
    van Dijk JP, Tanswell AK, Challis JRG: Insulin-like growth factor (IGF)-II and insulin, but not IGF-I are mitogenic for fetal rat adrenal cells in vitro. J Endocrinol 119:509–516, 1988.PubMedGoogle Scholar
  183. 183.
    Froesch ER, Shmid C, Schwander J, et al.: Actions of insulin-like growth factors. Annu Rev Physiol 47:443–467, 1985.PubMedGoogle Scholar
  184. 184.
    Sara VR, Hall K, Misaki M, et al.: Ontogenesis of somatomedin and insulin receptors in the human fetus. J Clin Invest 71:1084–1094, 1983.PubMedGoogle Scholar
  185. 185.
    Shigematsu KM, Niwa M, Kurihara M, et al.: Receptor autoradiographic localization of insulin-like growth factor-I (IGF-I) binding sites in human fetal and adult adrenal glands. Life Sci 45:383–389, 1989.PubMedGoogle Scholar
  186. 186.
    Pillion DJ, Yang M, Grizzle WE: Distribution of receptors for insulin and insulin-like growth factor I (Somatomedin C) in the adrenal gland. Biochem Biophys Res Commun 154:138–145, 1988.PubMedGoogle Scholar
  187. 187.
    Furlanetto RW, Underwood LE, Van Wyk JJ, et al.: Estimation of somatomedin-C levels in normals and patients with pituitary disease by radioimmunoassay. J Clin Invest 60: 648–657, 1977.PubMedGoogle Scholar
  188. 188.
    Schoenle E, Zapf J, Humbel RE, et al.: Insulin-like growth factor I stimulates growth in hypophysectomized rats. Nature 296:252–253, 1982.PubMedGoogle Scholar
  189. 189.
    Han VKM, D’Ercole AJ, Lund PK: Cellular localization of somatomedin (insulin-like growth factor) messenger RNA in the human fetus. Science 236:193–197, 1987.PubMedGoogle Scholar
  190. 190.
    Gray A, Tarn AW, Dull TJ, et al.: Tissue-specific and developmentally regulated transcription of the insulin-like growth factor 2 gene. DNA 6:283–295, 1987.PubMedGoogle Scholar
  191. 191.
    Voutilainen R, Miller WL: Developmental and hormonal regulation of mRNAs for insulin-like growth factor II and steroidogenic enzymes in human fetal adrenals and gonads. DNA 7:9–15, 1988.PubMedGoogle Scholar
  192. 192.
    Brice AL, Cheetham JE, Bolton VN, et al.: Temporal changes in the expression of the insulin-like growth factor II gene associated with tissue maturation in the human fetus. Development 106:543–554, 1989.PubMedGoogle Scholar
  193. 193.
    Crowder RE: The development of the adrenal gland in man, with special reference to the origin and ultimate location of cell types and evidence in favour of the ‘cell migration theory.’ Contrib Embryol 36:195–210, 1957.Google Scholar
  194. 194.
    Turkei SB, Itabashi HH: The natural history of neuroblastic cells in the fetal adrenal gland. Am J Pathol 76:225–244, 1974.Google Scholar
  195. 195.
    Han VKM, Lund PK, Lee DC: Expression of somatomedin/insulin-like growth factor messenger ribonucleic acids in the human fetus: Identification, characterization, and tissue distribution. Clin Endocrinol Metab 66:422–429, 1988.Google Scholar
  196. 196.
    Suzuki T, Iwafuchi M, Yanaihara C, et al.: IGF-II-like immunoreactivity in human tissues, neuroendocrine tumors, and PC12 cells. Diabetes Res Clin Pract 7:S21–S27, 1989.PubMedGoogle Scholar
  197. 197.
    Rom WN, Basset P, Fells GA, et al.: Alveolar macrophages release an insulin-like growth factor I-type molecule. J Clin Invest 82:1685–1693, 1988.PubMedGoogle Scholar
  198. 198.
    Karey KP, Sirbasku DA: Human platelet-derived mitogens. II. Subcellular localization of insulinlike growth factor I to the alpha-granule and release in response to thrombin. Blood 74:1093–1100, 1989.Google Scholar
  199. 199.
    Merimee TJ, Grant MB, Broder CM, et al.: Insulin-like growth factor secretion by human B-lymphocytes: A comparison of cells from normal and pygmy subjects. J Clin Endocrinol Metab 69:978–984, 1989.PubMedGoogle Scholar
  200. 200.
    Mohan S, Jennings JC, Linkhart TA, et al.: Primary structure of human skeletal growth factor: Homology with human insulin-like growth factor-II. Biochim Biophys Acta 966: 44–55, 1988.PubMedGoogle Scholar
  201. 201.
    Frolik CA, Ellis LF, Williams DC: Isolation and characterization of insulin-like growth factor-II from human bone. Biochem Biophys Res Commun 151:1011–1018, 1988.PubMedGoogle Scholar
  202. 202.
    Stracke ML, Engel JD, Wilson LW, et al.: The type I IGF receptor is a motility receptor in human melanoma cells. J Biol Chem 264:21544–21549, 1989.PubMedGoogle Scholar
  203. 203.
    Thiele CJ, McKeon C, Triche TJ, et al.: Differential protooncogene expression characterizes histopathologically indistinguishable tumors of the peripheral nervous system. J Clin Invest 80:804–811, 1987.PubMedGoogle Scholar
  204. 204.
    Brodeur GM, Hayes FA, Green AA, et al.: Consistent N-myc copy number in simultaneous or consecutive neuroblastoma samples from sixty individual patients. Cancer Res 47:4248–4253, 1987.PubMedGoogle Scholar
  205. 205.
    Kaplan E, Meier P: Non-parametric estimation from incomplete observations. J Am Stat Assoc 53:457–481, 1958.Google Scholar
  206. 206.
    Mentel N: Evaluation of survival data and two new rank order statistics arising in its consideration. Canc Chem Rep 50:163–170, 1966.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Osama M. El-Badry
  • Mark A. Israel

There are no affiliations available

Personalised recommendations