Cancer and Metastasis Reviews

, Volume 15, Issue 1, pp 27–51 | Cite as

Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck

  • Peter G. Sacks


In vitro models are currently being used to study head and neck squamous cell carcinoma (HNSCC). Several hundred HNSCC cell lines have been established by various investigators and used to study a broad spectrum of questions related to head and neck cancer. The head and neck model with respect to multistage carcinogenesis is now complete. Several techniques exist for the culture of normal epithelial cells from the upper aerodigestive tract (UADT). The biology of these UADT cells (oral cavity, oropharynx, hypopharynx and larynx) is being studied. Successful culture of premalignant lesions (dysplastic mucosa, leukoplakia, erythroplakia) has resulted in establishment of a limited number of premalignant cell lines and cell cultures. HPV infection of normal oral epithelial cells for immortalization (∼ premalignant cells) coupled with transformation with carcinogens (malignant cells) has established an experimental model for progression. Two in vivo models for oral carcinogenesis, the 7,12 dimethylbenz(a)anthracene-induced hamster cheek pouch model and the 4-nitroquinoline-N-oxide rat oral model, have been established in culture. Thus, multistage carcinogenesis models have been established from both human tissues and animal models and include cultures of normal, premalignant and malignant cells. Culture techniques for growing dissociated primary tumor cells for short term experimental analysis are being used. The culture of normal or tumor tissue as organ/explant cultures allows for the maintenance of normal cell-cell and cell-matrix interactions, but limits experimentation since these cultures cannot be propagated. Several three dimensional model systems are being used to obtain this histological complexity but allow for experimentation. The ability to culture normal, premalignant and malignant cells coupled with the use of a variety of culture techniques, should allow for the continued growth and experimentation in head and neck cancer research.

Key words

epithelial cells squamous cell carcinoma premalignant cell culture in vitro 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Serrano M, Hannon G, Beach D: A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4. Nature (Lond) 366: 704–707, 1993Google Scholar
  2. 2.
    Kamb A, Gruis N, Feldhaus J, Liu Q, Harshman K, Tavtigian S, Stockert E, Day R, Johnson B, Skolnick M: A cell cycle regulator potentially involved in genesis of many tumor types. Science 264: 436–439, 1994Google Scholar
  3. 3.
    Nobori T, Miura K, Wu D, Lois A, Takabayashi K, Carson D: Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 368: 753–756, 1994Google Scholar
  4. 4.
    Zhang S-Y, Klein-Szanto AJP, Sauter ER, Shafarenko M, Mitsunaga S, Nobori T, Carson DA, Ridge JA, Goodrow TL: Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck. Cancer Res 54: 5050–5053, 1994Google Scholar
  5. 5.
    Lydiatt WM, Murty VVVS, Davidson BJ, Xu L, Dyomina K, Sacks PG, Schantz SP, Chaganti RSK: Homozygous deletions and loss of expression of the CDNK2 gene occur frequently in head and neck squamous cell carcinoma cell lines but infrequently in primary tumors. Genes Chrom Cancer 13: 94–98, 1995Google Scholar
  6. 6.
    Sacks PG, Parnes SM, Gallick GE, Mansouri Z, Lichtner R, Satya-Prakash KL, Pathak S, Parsons DF: Establishment and characterization of two new squamous cell carcinoma cell lines derived from tumors of the head and neck. Cancer Res 48: 2858–2866, 1988Google Scholar
  7. 7.
    Hong WK, Endicott J, Itri LM, Doos W, Batsakis JG, Bell R, Fofonoff S, Byers R, Atkinson EN, Vaughan CM, Toth BB, Kramer A, Dimery IW, Skipper P, Strong S: 13-cis-retinoic acid in the treatment of oral leukoplakia. New Eng J Med 315: 1501–1505, 1986Google Scholar
  8. 8.
    Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS, Byers RM, Schantz SP, Kramer AM, Lotan R, Peters LJ, Dimery IW, Brown BW, Goepfert H: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. New Eng J Med 323: 795–801, 1990Google Scholar
  9. 9.
    Carey TE: Establishment of epidermoid carcinoma cell lines. In: Wittes RE (ed) Head and Neck Cancer. John Wiley & Sons. New York, 1985, pp 287–314Google Scholar
  10. 10.
    Easty DM, Easty GC, Carter RL, Monaghan P, Butler LJ: Ten human carcinoma cell lines derived from squamous carcinoma of the head and neck. Brit J Cancer 43: 772–785, 1981Google Scholar
  11. 11.
    Krause CJ, Carey TE, Ott RW, Hurbis C, McClatchey KD, Regezi JA: Human squamous cell carcinoma. Establishment and characterization of new permanent cell lines. Arch Otolaryngol 107: 703–710, 1981Google Scholar
  12. 12.
    Rheinwald JG, Beckett MA: Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res 41: 1657–1663, 1981Google Scholar
  13. 13.
    Fearon ER, Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61: 759–767, 1990Google Scholar
  14. 14.
    Slaughter DP, Southwick HW, Smejkal W: ‘Field cancerization’ in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer 6: 963–968, 1953Google Scholar
  15. 15.
    Voravud N, Shin DM, Ro JY, Lee JS, Hong WK, Hittelman WN: Increased polysomies of chromosomes 7 and 17 during head and neck multistage tumorigenesis. Cancer Res 53: 2874–2883, 1993Google Scholar
  16. 16.
    Shin DM, Kim J, Ro JY, Hittelman J, Roth JA, Hong WK, Hittelman WN: Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 54: 321–326, 1994Google Scholar
  17. 17.
    Shin DM, Voravud N, Ro JY, Lee JS, Hong WK, Hittelman WN: Sequential upregulation of proliferating cell nuclear antigen in head and neck tumorigenesis: a potential biomarker. J Nat Cancer Inst 85: 971–978, 1993Google Scholar
  18. 18.
    Grandis JR, Tweardy DJ: Elevated levels of transforming growth factor α and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 53: 3579–3584, 1993Google Scholar
  19. 19.
    Shin DM, Ro JY, Hong WK, Hittelman WN: Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. Cancer Res 54: 3153–3159, 1994Google Scholar
  20. 20.
    Ogden GR, Lane EB, Hopwood DV, Chisholm DM: Evidence for field change in oral cancer based on cytokeratin expression. Brit J Cancer 67: 1324–1330, 1993Google Scholar
  21. 21.
    Xu XC, Ro JY, Lee JS, Shin DM, Hong WK, Lotan R: Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues. Cancer Res 54: 3580–3587, 1994Google Scholar
  22. 22.
    Rupniak HT, Rowlatt C, Lane EB, Steele JG, Trejdosiewicz LK, Laskiewicz B, Povey S, Hill BT: Characteristics of four new human cell lines derived from squamous cell carcinomas of the head and neck. J Nat Cancer Inst 75: 621–635, 1985Google Scholar
  23. 23.
    Baker SR: An in vivo model for squamous cell carcinoma of the head and neck. Laryng 95: 43–56, 1985Google Scholar
  24. 24.
    Prime SS, Nixon SVR, Crane IJ, Stone A, Matthews JB, Maitland NJ, Remnant L, Powell SK, Game SM, Scully C: The behaviour of human squamous cell carcinoma in cell culture. J Path 160: 259–269, 1990Google Scholar
  25. 25.
    Edington KG, Loughran OP, Berry IJ, Parkinson EK: Cellular immortality: a late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss. Mol Carcinogen 13: 254–265, 1995Google Scholar
  26. 26.
    Stamps AC, Gusterson BA, O'Hare MJ: Are tumours immortal? Eur J Cancer 28A: 1495–1500, 1992Google Scholar
  27. 27.
    Rheinwald JG, Green H: Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 6: 331–343, 1975Google Scholar
  28. 28.
    Tsao MC, Walthall BJ, Ham RJ: Clonal growth of normal human epidermal keratinocytes in a defined medium. J Cell Physiol 110: 219–229, 1982Google Scholar
  29. 29.
    Boyce ST, Ham RG: Calcium-regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture and serum-free serial culture. J Invest Dermatol 81: 33s-40s, 1983Google Scholar
  30. 30.
    MacCallum DK, Lillie JH, Jepsen A, Arenholt-Bindslev D: The culture of oral epithelium. Int Rev Cytol 109: 313–330, 1987Google Scholar
  31. 31.
    Southgate J, Williams HK, Trejdosiewicz LK, Hodges GM: Primary culture of human oral epithelial cells. Growth requirements and expression of differentiated characteristics. Lab Invest 56: 211–223, 1987Google Scholar
  32. 32.
    De Luca M, D'Anna F, Bondanza S, Franzi AT, Cancedda R: Human epithelial cells induce human melanocyte growth in vitro but only skin keratinocytes regulate its proper differentiation in the absence of dermis. J Cell Biol 107: 1919–1926, 1988Google Scholar
  33. 33.
    Lindberg K, Rheinwald JG: Three distinct keratinocyte subtypes identified in human oral epithelium by their patterns of keratin expression in culture and in xenografts. Diff 45: 230–241, 1990Google Scholar
  34. 34.
    Murrah VA, Gilchrist EP, Moyer MP: Morphologic and growth effects of tobacco-associated chemical carcinogens and smokeless tobacco extracts on human oral epithelial cells in culture. Oral Surg Oral Med Oral Path 75: 323–332, 1993Google Scholar
  35. 35.
    Rollins BJ, O'Connell TM, Bennett G, Burton LE, Stiles CD, Rheinwald JG: Environment-dependent growth inhibition of human epidermal keratinocytes by recombinant human transforming growth factor-beta. J Cell Physiol 139: 455–462, 1989Google Scholar
  36. 36.
    Sundqvist K, Liu Y, Arvidson K, Ormstad K, Nilsson L, Toftgård R, Grafström RC: Growth regulation of serumfree cultures of epithelial cells from normal human buccal mucosa. In Vitro Cell Dev Biol 27A: 562–568, 1991Google Scholar
  37. 37.
    Sundqvist K, Kulkarni P, Hybbinette SS, Bertolero F, Liu Y, Grafström RC: Serum-free growth and karyotype analyses of cultured normal and tumorous (SqCC/Y1) human buccal epithelial cells. Cancer Comm 3: 331–340, 1991Google Scholar
  38. 38.
    Oda D, Watson E: Human oral epithelial cell culture I. Improved conditions for reproducible culture in serum-free medium. In Vitro Cell Dev Biol 26: 589–595, 1990Google Scholar
  39. 39.
    Oda D, Dale BA, Bourekis G: Human oral epithelial cell culture II. Keratin expression in fetal and adult gingival cells. In Vitro Cell Dev Biol 26: 596–603, 1990Google Scholar
  40. 40.
    Kasperbauer JL, Neel HB, Scott RE: Proliferation and differentiation characteristics of normal human squamous mucosal cells of the upper aerodigestive tract. Ann Otol Rhinol Laryngol 99: 29–37, 1990Google Scholar
  41. 41.
    Rikimaru K, Toda H, Tachikawa N, Kamata N, Enomoto S: Growth of the malignant and nonmalignant human squamous cells in a protein-free defined medium. In Vitro Cell Dev Biol 26: 849–856, 1990Google Scholar
  42. 42.
    Steinberg BM, Abramson AL, Meade RD: Culture of human laryngeal papilloma cells in vitro. Otolaryngol Head Neck Surg 90: 728–735, 1982Google Scholar
  43. 43.
    Mendelsohn MG, Dilorenzo TP, Abramson AL, Steinberg BM: Retinoic acid regulates, in vitro, the two normal pathways of differentiation of human laryngeal keratinocytes. In Vitro Cell Dev Biol 27A: 137–141, 1991Google Scholar
  44. 44.
    Cowley GP, Smith JA, Gusterson BA: Increased EGF receptors on human squamous carcinoma cell lines. Brit J Cancer 53: 223–229, 1986Google Scholar
  45. 45.
    Hoffman HT, Subnani M, Cha M, Kidd L, Landman J, Tooley R, Carey TE: Calcium regulation of antigen expression on normal and malignant human squamous cells in vitro. Arch Otolaryngol Head Neck Surg 126: 299–303, 1990Google Scholar
  46. 46.
    Xu L, Sacks PG, Schantz SP: Comparison of conditions for the culture of normal human epithelia of the upper aerodigestive tract. Head & Neck 16: 478, 1994Google Scholar
  47. 47.
    Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafström RC: Cytotoxic and genotoxic effects of areca nutrelated compounds in cultured human buccal epithelial cells. Cancer Res 49: 5294–5298, 1989Google Scholar
  48. 48.
    Sundqvist K, Grafstrom RC: Effects of areca nut on growth, differentiation and formation of DNA damage in cultured human buccal epithelial cells. Int J Cancer 52: 305–310, 1992Google Scholar
  49. 49.
    Liu Y, Sundqvist K, Belinsky SA, Castonguay A, Tjalve H, Grafström RC: Metabolism and macromolecular interaction of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in cultured explants and epithelial cells of human buccal mucosa. Carcinogen 14: 2383–2388, 1993Google Scholar
  50. 50.
    Reppucci AD, DiLorenzo TP, Abramson AL, Steinberg BM: In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid. Otolaryngol Head Neck Surg 105: 528–532, 1991Google Scholar
  51. 51.
    DiLorenzo TP, Taichman LB, Steinberg BM: Replication and persistence of HPV DNA in cultured cells derived from laryngeal papillomas. Virology 186: 148–153, 1992Google Scholar
  52. 52.
    Vambutas A, DiLorenzo TP, Steinberg BM: Laryngeal papilloma cells have high levels of epidermal growth factor receptor and respond to epidermal growth factor by a decrease in epithelial differentiation. Cancer Res 53: 910–914, 1993Google Scholar
  53. 53.
    Park N-H, Min B-M, Li S-I, Huang MZ, Cherick HM, Doniger J: Immortalization of normal human oral keratinicytes with type 16 human papillomavirus. Carcinogen 12: 1627–1631, 1991Google Scholar
  54. 54.
    Crowe DL, Hu L, Gudas LJ, Rheinwald JG: Variable expression of retinoic acid receptor (RARβ) mRNA in human oral and epidermal keratinocytes: relation to keratin 19 expression and keratinization potential. Diff 48: 199–208, 1991Google Scholar
  55. 55.
    Chang SE, Foster S, Betts D, Marnock WE: DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non-malignant phenotype. Int J Cancer 52: 896–902, 1992Google Scholar
  56. 56.
    Burns JE, Clark LJ, Yeudall WA, Mitchell R, Mackenzie K, Chang SE, Parkinson EK: The p53 status of cultured human premalignant oral keratinocytes. Brit J Cancer 70: 591–595, 1995Google Scholar
  57. 57.
    Toma S, Albanese E, Palumbo R, Nicoló G, Morerio C, Mangiante PE, Bonatti S, Cancedda R, Santi L: In vitro effects of β-carotene on human oral keratinocytes from precancerous lesions and squamous carcinoma. Anti-Cancer Drugs 2: 581–589, 1991Google Scholar
  58. 58.
    Sacks PG, Hong WK, Hittelman WN: In vitro studies of the premalignant process: initial culture of oral premalignant lesions. Cancer Bull 43: 485–498, 1991Google Scholar
  59. 59.
    Edington KG, Berry IJ, O'Prey M, Burns JE, Clark LJ, Mitchell R, Robertson G, Soutar D, Coggins LW, Parkinson EK: In vitro analysis of multistage head and neck squamous cell carcinoma: defective terminal maturation is an early and ubiquitous event. In: Freshney IR (ed) Culture of Tumour Cells. Culture of Specialised Cells. Wiley-Liss, New York, 1995, in pressGoogle Scholar
  60. 60.
    Loughran O, Edington KG, Berry IJ, Clark LJ, Parkinson EK: Loss of heterozygosity of chromosome 9p21 is associated with the immortal phenotype of neoplastic human head and neck keratinocytes. Cancer Res 54: 5045–5049, 1994Google Scholar
  61. 61.
    Romani VG, Abramson AL, Steinberg BM: Laryngeal papilloma cells in culture have an altered cytoskeleton. Acta Oto-Laryngologica 103: 345–352, 1987Google Scholar
  62. 62.
    Steinberg BM, Meade R, Kalinowski S, Abramson AL: Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. Otolaryngol Head Neck Surg 116: 1167–1171, 1990Google Scholar
  63. 63.
    DiLorenzo TP, Steinberg BM: Laryngeal keratinocytes show variable inhibition of replication by TGF-beta. J Cell Sci 96: 115–119, 1990Google Scholar
  64. 64.
    Li SL, Kim MS, Cherrick HM, Doniger J, Park N-H: Sequential combined tumorigenic effect of HPV-16 and chemical carcinogens. Carcinogen 13: 1981–1987, 1992Google Scholar
  65. 65.
    Kim MS, Shin KH, Baek JH, Cherrick HM, Park N-H: HPV-16, tobacco-specific N-nitrosamine, and N-methyl-N'-nitro-N-nitrosoguanidine in oral carcinogenesis. Cancer Res 53: 4811–4816, 1993Google Scholar
  66. 66.
    Xu L, Davidson BJ, Murty VVVS, Li R-G, Sacks PG, Garin-Chesa P, Schantz SP, Chaganti RSK: TP53 gene mutations and CCND1 gene amplification in head and neck squamous cell carcinoma cell lines. Int J Cancer 59: 383–387, 1994Google Scholar
  67. 67.
    Carey TE: Head and neck tumor cell lines. In: Ray RJ, Park J-G, Gazdar A (ed) Atlas of Human Tumor Cell Lines. Academic Press, Inc., San Diego, 1994, pp 79–120Google Scholar
  68. 68.
    Schantz SP, Racz T, Ordonez NG, Terry N, Taylor DL, Bugis S, Sacks PG: Differential sensitivity of head and neck cancers to non-major histocompatibility-restricted killer cell activity. J Surg Res 48: 154–164, 1990Google Scholar
  69. 69.
    Cobleigh MA, Gallagher PA, Hill JH, Appelbaum EL, McGuire WP: Growth of human squamous head and neck cancer in vitro. Am J Pathol 115: 397–402, 1984Google Scholar
  70. 70.
    Rupniak HT, Hill BT: The poor cloning ability in agar of human tumour cells from biopsies of primary tumours. Cell Biol Int Rept 4: 479–486, 1980Google Scholar
  71. 71.
    Saito H, Ohtsubo T, Fujieda S, Tanigawa N: Chemosensitivity of head and neck cancer with the rapid thymidine incorporation assay and its clinical application. Eur Arch Oto-Rhino-Laryngol 249: 400–403, 1992Google Scholar
  72. 72.
    Brock WA, Baker FL, Peters LJ: Radiosensitivity of human head and neck squamous cell carcinomas in primary culture and its potential as a predictive assay of tumor radiocurability. Int J Rad Biol 56: 751–760, 1989Google Scholar
  73. 73.
    Girinsky T, Bernheim A, Lubin R, Tavakoli-Razavi T, Baker F, Janot F, Wibault P, Cosset J-M, Duvillard P, Duverger A, Fertil B: In vitro parameters and treatment outcome in head and neck cancers treated with surgery and/or radiation: cell characterization and correlations with local control and overall survival. Int J Rad Oncol Biol Phys 30: 789–794, 1994Google Scholar
  74. 74.
    Geara F, Girinski TA, Chavaudra N, Cosset JM, Dubray B, Brock WA, Malaise EP: Estimation of clonogenic cell fraction in primary cultures derived from human squamous cell carcinomas. Int J Radiat Oncol 21: 661–665, 1991Google Scholar
  75. 75.
    Jin Y, Mertens F, Jin C, Åkervall J, Wennerberg J, Gorunova L, Mandahl N, Heim S, Mitelman F: Nonrandom chromosome abnormalities in short-term cultured primary squamous cell carcinomas of the head and neck. Cancer Res 55: 3204–3210, 1995Google Scholar
  76. 76.
    Wang MB, Lichtenstein A, Mickel RA: Hierarchical immunosuppression of regional lymph nodes in patients with head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 105: 517–527, 1991Google Scholar
  77. 77.
    Eveson JW: Animal models of intra-oral chemical carcinogenesis: a review. J Oral Path 10: 129–146, 1981Google Scholar
  78. 78.
    Shklar G: Experimental oral pathology in the syrian hamster. Prog Exp Tumor Res 16: 518–538, 1972Google Scholar
  79. 79.
    Odukoya O, Schwartz J, Weichselbaum R, Shklar G: An epidermoid carcinoma cell line derived from hamster 7,12-dimethylbenz[a]anthracene-induced buccal pouch tumors. J Nat Cancer Inst 71: 1253–1264, 1983Google Scholar
  80. 80.
    Wong DTW: Amplification of c-erb B1 oncogene in chemically-induced oral carcinoma. Carcinogen 8: 1963–1965, 1987Google Scholar
  81. 81.
    Wong DTW, Gallagher GT, Gertz R, Chang ALC, Shklar G: Transforming growth factor α in chemically transformed hamster oral keratinocytes. Cancer Res 48: 3130–3134, 1988Google Scholar
  82. 82.
    Min BM, Kim K, Cherrick HM, Park N-H: Three cell lines from hamster buccal pouch tumors induced by topical 7,12-dimethylbenz(a)anthracene, alone or in conjunction with herpes simplex virus inoculation. In Vitro Cell Dev Biol 27A: 128–136, 1991Google Scholar
  83. 83.
    Polverini PJ, Solt DB: Effect of in vivo carcinogen exposure on colony formation and growth of hamster buccal pouch keratinocytes in culture. Lab Invest 54: 432–441, 1986Google Scholar
  84. 84.
    Polverini PJ, Solt DB: Expression of the angiogenic phenotype by a subpopulation of keratinocytes derived from 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium. Carcinogen 9: 117–122, 1988Google Scholar
  85. 85.
    Polverini PJ, Shimizu K, Solt DB: Control of angiogenic activity in carcinogen-initiated and neoplastic hamster pouch keratinocytes and their hybrid cells. J Oral Path 17: 522–527, 1988Google Scholar
  86. 86.
    Solt DB, Polverini PJ, Ray S, Fei Y, Biswas DK: Early neoplastic commitment of hamster buccal pouch epithelium exposed biweekly to 7,12-dimethylbenz[a]anthracene. Carcinogen 9: 2173–2177, 1988Google Scholar
  87. 87.
    Husain S, Fei Y, Roy S, Solt DB, Polverini PJ, Biswas DK: Sequential expression and cooperative interactions of c-Ha-ras and c-erbB genes in in vivo carcinogenesis. Proc Nat Acad Sci (Wash) 86: 1264–1268, 1989Google Scholar
  88. 88.
    Moroco JR, Solt DB, Polverini PJ: Sequential loss of suppressor genes for three specific functions during in vivo carcinogenesis. Lab Invest 63: 298–306, 1990Google Scholar
  89. 89.
    Hussong JW, Polverini PJ, Solt DB: Resistant keratinocytes in 7,12-dimethylbenz[a]anthracene initiated hamster buccal pouch epithelium. Carcinogen 12: 617–622, 1991Google Scholar
  90. 90.
    Steidler NE, Reade PC: Experimental induction of oral squamous cell carcinomas in mice with 4-nitroquinoline-1-oxide. Oral Surg Oral Med Oral Path 57: 524–531, 1984Google Scholar
  91. 91.
    Prime SS, Malamos D, Rosser TJ, Scully C: Oral epithelial atypia and acantholytic dyskeratosis in rats painted with 4-nitroquinoline N-oxide. J Oral Path 15: 280–283, 1986Google Scholar
  92. 92.
    Crane IJ, Luker J, Stone A, Scully C, Prime SS: Characterisation of malignant rat keratinocytes in culture following the induction of oral squamous cell carcinomas in vivo. Carcinogen 7: 1723–1727, 1986Google Scholar
  93. 93.
    Crane IJ, Rice SQJ, Luker J, de Gay L, Scully C, Prime SS: The expression of MHC antigens on cultured oral keratinocytes and relationship to malignancy. Brit J Exp Path 69: 749–758, 1988Google Scholar
  94. 94.
    Crane IJ, Luker J, de Gay L, Rice SQL, Scully C, Prime SS: Transformation of oral keratinocytes in vitro by 4-nitroquinoline N-oxide. Carcinogen 9: 2251–2256, 1988Google Scholar
  95. 95.
    Luker J, de Gay L, Crane IJ, Stone A, Scully C, Prime SS: The inter-relationship between anchorage independence and tumorigenicity in early cultures of oral keratinocytes. Virchow's Arch B Cell Pathol 54: 246–251, 1988Google Scholar
  96. 96.
    Crane IJ, Patel V, Scully C, Prime SS: Development of aneuploidy in experimental oral carcinogenesis. Carcinogen 12: 2375–2377, 1989Google Scholar
  97. 97.
    Game SM, Stone A, Scully C, Prime SS: Tumour progression in experimental oral carcinogenesis is associated with changes in EGF and TGF-β receptor expression and altered responses to these growth factors. Carcinogen 11: 965–973, 1990Google Scholar
  98. 98.
    Game SM, Stone A, Matthews JB, Scully C, Prime SS: Differentiation of malignant oral rat keratinocytes reflects changes in EGF and TGF-β receptor expression but not growth factor dependence. Carcinogen 12: 409–416, 1991Google Scholar
  99. 99.
    Yuspa SH, Morgan DL: Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature 293: 72–74, 1981Google Scholar
  100. 100.
    Yuspa SH: The pathogenesis of squamous cell cancer: Lessons learned from studies of skin carcinogenesis — Thirtythird G.H.A. Clowes Memorial Award Lecture. Cancer Res 54: 1178–1189, 1994Google Scholar
  101. 101.
    Aldaz CM, Conti CJ, Klein-Szanto AJP, Slaga T: Progressive dysplasia and aneuploidy are hallmarks of mouse skin papillomas: relevance to malignancy. Proc Nat Acad Sci (Wash) 84: 2029–2032, 1987Google Scholar
  102. 102.
    Dinesman A, Haughey B, Gates GA, Aufdemorte T, von Hoff DD: Development of a new in vivo model for head and neck cancer. Otolaryngol Head Neck Surg 103: 766–774, 1990Google Scholar
  103. 103.
    Sklizovic D, Sanger JR, Kindwall EP, Fink JG, Grunert BK, Campbell BH: Hyperbaric oxygen therapy and squamous cell carcinoma cell line growth. Head & Neck 15: 236–240, 1993Google Scholar
  104. 104.
    Shalinsky DR, Bischoff ED, Gregory ML, Gottardis MM, Hayes JS, Lamph WW, Heyman RA, Shirley MA, Cooke TA, Davies PJA, Thomazy V: Retinoid-induced suppression of squamous cell differentiation in human oral squamous cell carcinoma xenografts (line 1483) in athymic nude mice. Cancer Res 55: 3183–3191, 1995Google Scholar
  105. 105.
    von Dongen GAMS, Braakhuis BJM, Leyva A, Hendriks HR, Kipp BBA, Bagnay M, Snow GB: Anti-tumor and differentiation-inducing activity of N,N-dimethylformamide (DMF) in head-and-neck cancer xenografts. Int J Cancer 43: 285–292, 1989Google Scholar
  106. 106.
    Yoneda TY, Alsina MM, Watatani K, Bellot F, Schlessinger J, Mundy GR: Dependence on a human squamous carcinoma and associated paraneoplastic syndromes on the epidermal growth factor receptor pathway in nude mice. Cancer Res 51: 2438–2443, 1991Google Scholar
  107. 107.
    Sacchi M, Vitolo D, Sedlmayr P, Rabinowich H, Johnson JT, Herberman RB, Whiteside TL: Induction of tumor regression in experimental model of human head and neck cancer by human A-LAK cells and IL-2. Int J Cancer 47: 784–791, 1991Google Scholar
  108. 108.
    Clayman GL, El-Naggar AK, Roth JA, Zhang W-W, Goepfert H, Taylor DL, Liu T-J: In vivo molecular therapy with p53 adenovirus for microscopic residual head and neck squamous carcinoma. Cancer Res 55: 1–6, 1995Google Scholar
  109. 109.
    Freshney RI: Culture of animal cells. A manual of basic technique. In: Wiley-Liss, New York, 1987Google Scholar
  110. 110.
    Sacks M, Parnes SM, Price JC, Risemberg H, Goldstein JC, Marko M, Parsons DF: In vitro modulation of differentiation by calcium in organ cultures of human and murine epithelial tissue. In Vitro Cell Dev Biol 21: 99–107, 1985Google Scholar
  111. 111.
    Sacks PG, Wansor KJ, Parsons DF: Organ-cultured epithelial tissue as an in vitro model for invasion: quantification and high-voltage electron microscopy of tumor cell attachment. Cancer Res 44: 3063–3074, 1984Google Scholar
  112. 112.
    Read J, Watt FM: A model for in vitro studies of epidermal homeostasis: Proliferation and involucrin synthesis by cultured human keratinocytes during recovery after stripping off the suprabasal layers. J Invest Dermatol 90: 739–743, 1988Google Scholar
  113. 113.
    Browman GP, Kanclerz A, Booker L, Daya D, Archibald SD, Young JE, Goldsmith CH: Optimal conditions for immunohistochemical determination of the in vitro DNA synthesis labelling index with bromodeoxyuridine in head and neck cancer. Cell Prolif 24: 579–585, 1991Google Scholar
  114. 114.
    Vescio RA, Redfern CH, Nelson TJ, Ugoretz S, Stern PH, Hoffman RM: In vivo-like drug responses of human tumors growing in three-dimensional, gel-supported, primary culture. Proc Nat Acad Sci (Wash) 84: 5029–5033, 1987Google Scholar
  115. 115.
    Robbins KT, Varki NM, Storniolo AM, Hoffman H, Hoffman RM: Drug response of head and neck tumors in native-state histoculture. Arch Otolaryngol Head Neck Surg 117: 83–86, 1991Google Scholar
  116. 116.
    Robbins KT, Connors KM, Storniolo AM, Hanchett C, Hoffman RM: Sponge-gel supported histoculture drug-response assay for head and neck cancer. Correlations with clinical response to cisplatin. Arch Otolaryngol Head Neck Surg 120: 288–292, 1994Google Scholar
  117. 117.
    Castonguay A, Stoner GD, Schut HAI, Hecht SS: Metabolism of tobacco-specific N-nitrosamines by cultured human tissues. Proc Nat Acad Sci (Wash) 80: 6694–6697, 1983Google Scholar
  118. 118.
    Murphy SE, Heiblum R, Trushin N: Comparative metabolism of N′-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by cultured rat oral tissue and esophagus. Cancer Res 50: 4685–4691, 1990Google Scholar
  119. 119.
    Zaslav AL, Stamberg J, Steinberg BM, Lin YJ, Abramson A: Cytogenetic analysis of head and neck carcinomas. Genes Chrom Cancer 56: 181–187, 1991Google Scholar
  120. 120.
    Hoffman RM: Three-dimensional histoculture: origins and applications in cancer research. Cancer Cells 3: 86–92, 1991Google Scholar
  121. 121.
    Mueller-Klieser W: Multicellular spheroids. A review on cellular aggregates in cancer research. J Cancer Res Clin Oncol 113: 101–122, 1987Google Scholar
  122. 122.
    Sutherland RM: Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 240: 177–184, 1988Google Scholar
  123. 123.
    Sacks PG: Growth of head and neck squamous-cell carcinoma cell lines as multicell tumor spheroids. In: Wolf GT, Carey TE (eds) Head and Neck Oncology Research. Kugler and Ghedini, Berkeley, CA, 1988, pp 3–9Google Scholar
  124. 124.
    Sacks PG, Oke V, Vasey T, Lotan R: Retinoic acid inhibition of a head and neck multicellular tumor spheroid model. Head & Neck 11: 219–225, 1989Google Scholar
  125. 125.
    Sacks PG, Oke V, Amos B, Vasey T, Lotan R: Modulation of growth, differentiation, and glycoprotein synthesis by β-all-trans retinoic acid in a multicellular tumor spheroid model for squamous carcinoma of the head and neck. Int J Cancer 44: 926–933, 1989Google Scholar
  126. 126.
    Sacks PG, Oke V, Calkins DP, Vasey T, Terry NH: Effects of beta-all-trans retinoic acid on growth, proliferation, and cell death in a multicellular tumor spheroid model for squamous carcinomas. J Cell Physiol 144: 237–243, 1990Google Scholar
  127. 127.
    Sacks PG, Oke V, Mehta K: Antiproliferative effects of free and liposome-encapsulated retinoic acid in a squamous carcinoma model: monolayer cells and multicellular tumor spheroids. J Cancer Res Clin Oncol 118: 490–496, 1992Google Scholar
  128. 128.
    Parthasarathy R, Sacks PG, Harris D, Brock H, Mehta K: Interaction of liposome-associated retinoic acid with squamous carcinoma cells. Cancer Chemo Pharmacol 34: 527–534, 1994Google Scholar
  129. 129.
    Silberberg MB, Savage HE, Tang GC, Sacks PG, Alfano RR, Schantz SP: Detecting retinoic acid-induced biochemical alterations in squamous cell carcinoma using intrinsic fluorescence spectroscopy. Laryng 104: 278–282, 1994Google Scholar
  130. 130.
    Sacks PG, Racz T, Schantz SP, Rosenblum MG: Growth inhibition by interferon beta and gamma of MDA 886Ln monolayer cells and multicellular tumor spheroids. A differentiation therapy model for squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 120: 1267–1272, 1994Google Scholar
  131. 131.
    Sacks PG, Taylor DL, Racz T, Vasey T, Oke V, Schantz SP: A multicellular tumor spheroid model of cellular immunity against head and neck cancer. Cancer Immunol Immunother 32: 195–200, 1990Google Scholar
  132. 132.
    Vujanovic NL, Yasumura S, Hirabayashi H, Lin W-C, Watkins S, Herberman RB, Whiteside TL: Antitumor activities of subsets of human IL-2-activated natural killer cells in solid tissues. J Immunol 154: 281–289, 1995Google Scholar
  133. 133.
    Kohno N, Ohnuma T, Biller HF, Holland JF: Effects of cisplatin plus fluorouracil vs cisplatin plus cytarabine on head and neck squamous multicellular tumor spheroids. Head Neck Surg 114: 157–161, 1988Google Scholar
  134. 134.
    Kohno N, Ohnuma T, Kawaida M, Kawasaki K, Ichikawa G: Effects of folinic acid on 5-fluorouracil induced cell lethality with or without cisplatin against head and neck laryngeal squamous carcinoma multicellular tumor spheroids. Acta Oto-Laryngologica 112: 566–573, 1992Google Scholar
  135. 135.
    Kohno N, Ohnuma T, Truog P: Effects of hyaluronidase on doxorubicin penetration into squamous carcinoma multicellular tumor spheroids and its cell lethality. J Cancer Res Clin Oncol 120: 293–297, 1994Google Scholar
  136. 136.
    Stuschke M, Budach V, Budach W, Feldmann HJ, Sack H: Radioresponsiveness, sublethal damage repair and stem cell rate in spheroids from three human tumor lines: comparison with xenograft data. Int J Rad Oncol Biol Phys 24: 119–126, 1992Google Scholar
  137. 137.
    Schwachöfer JHM, Crooijmans RPMA, Hoogenhout J, Kal HB: The influence of once or twice daily irradiation regimens on growth of squamous cell carcinoma spheroids of different diameters. Anticancer Res 11: 1369–1372, 1991Google Scholar
  138. 138.
    Schwachöfer JHM, Crooijmans RPMA, Hoogenhout J, Kal HB, Theeuwes AGM: Effectiveness in inhibition of recovery of cell survival by cisplatin and carboplatin: influence of treatment sequence. Int J Rad Oncol Biol Phys 20: 1235–1241, 1991Google Scholar
  139. 139.
    Köpf-Maier P, Zimmermann B: Organoid reorganization of human tumors under in vitro conditions. Cell Tiss Res 264: 563–576, 1991Google Scholar
  140. 140.
    Köpf-Maier P: A new approach for realizing the ‘antioncogram’. Life Sci 50: 1711–1718, 1992Google Scholar
  141. 141.
    Köpf-Maier P, Kolon B: An organoid culture assay (OCA) for determining the drug sensitivity of human tumors. Int J Cancer 51: 99–107, 1992Google Scholar
  142. 142.
    Asselineau D, Bernard BA, Bailly C, Darmon M, Prunieras M: Human epidermis reconstructed by culture: Is it ‘normal’? J Invest Dermatol 86: 181–186, 1986Google Scholar
  143. 143.
    Kautsky MB, Fleckman P, Dale BA: Retinoic acid regulates oral epithelial differentiation by two mechanisms. J Invest Dermatol 104: 224–230, 1995Google Scholar
  144. 144.
    Boukamp P, Rupniak HTR, Fusenig NE: Environmental modulation of the expression of differentiation and malignancy in six squamous cell carcinoma cell lines. Cancer Res 45: 5582–5592, 1985Google Scholar
  145. 145.
    Regnier M, Desbas C, Bailly C, Darmon M: Differentiation of normal and tumoral human keratinocytes cultured on dermis: reconstruction of either normal or tumoral architecture. In Vitro Cell Dev Biol 24: 625–632, 1988Google Scholar
  146. 146.
    Choi Y, Fuchs E: TGF-β and retinoic acid: regulators of growth and modifiers of differentiation in human epidermis. Cell Reg 1: 791–809, 1990Google Scholar
  147. 147.
    Wu Y-J, Parker LM, Binder NE, Beckett MA, Sinard JH, Griffiths CT, Rheinwald JG: The mesothelial keratins: a new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia. Cell 31: 693–703, 1982Google Scholar
  148. 148.
    Reiss M, Pitman SW, Sartorelli AC: Modulation of the terminal differentiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid. J Nat Cancer Inst 74: 1015–1023, 1985Google Scholar
  149. 149.
    Hauser-Urfer IH, Stauffer J: Comparative chromosome analysis of nine squamous cell carcinoma lines from tumors of the head and neck. Cytogenet Cell Genet 39: 35–39, 1985Google Scholar
  150. 150.
    Gioanni J, Fischel J-L, Lambert J-C, Demard F, Mazeau C, Zanghellini E, Ettore F, Formento P, Chauvel P, Lalanne C-M, Courdi A: Two new human tumor cell lines derived from squamous cell carcinomas of the tongue: establishment, characterization and response to cytotoxic treatment. Eur J Cancer 24: 1445–1455, 1988Google Scholar
  151. 151.
    Meghji S, Sandy JR, Scutt AM, Harvey W, Carter RL, Harris M: Macromolecular osteolytic factor synthesised by squamous carcinoma cell lines from the head and neck in vitro is interleukin 1. Brit J Cancer 58: 17–21, 1988Google Scholar
  152. 152.
    Momose F, Araida T, Negishi A, Ichijo H, Shioda S, Sasaki S: Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med 18: 391–395, 1989Google Scholar
  153. 153.
    Nakano S, Nakayama M, Ichinose I, Mitsugi K, Nagafuchi S, Niho Y: Characterization of a newly established, TA-4-producing squamous carcinoma cell line derived from metastatic tongue carcinoma. Int J Cancer 44: 301–306, 1989Google Scholar
  154. 154.
    Tadokoro K, Ueda M, Ohshima T, Fujita K, Rikimaru K, Takahashi N, Enomoto S, Tsuchida N: Activation of oncogenes in human oral cancer cells: a novel codon 13 mutation of c-H-ras-1 and concurrent amplifications of c-erbB-1 and c-myc. Oncogene 4: 499–505, 1989Google Scholar
  155. 155.
    Crooijmans RPMA, Schwachöfer JHM, Hoogenhout J, Merkx G, Poels LG, Jap PHK, Ramaekers FCS, Mijnheere EP, Elprana D, Thomas CMG: Cell lines of human oral squamous-cell carcinomas retaining their differentiated phenotype. Int J Cancer 45: 945–951, 1990Google Scholar
  156. 156.
    Shuler C, Kurian P, French BT, Noyes I, Sital N, Hollering J, Trewyn RW, Schuller D, Milo GE: Noncorrelative c-myc and ras oncogene expression in squamous cell carcinoma cells with tumorigenic potential. Terat Carcin Mut 10: 53–65, 1990Google Scholar
  157. 157.
    Pekkola-Heino K, Kulmala J, Klemi P, Lakkala T, Aitasalo K, Joensuu H, Grenman R: Effects of radiation fractionation on four squamous cell carcinoma lines with dissimilar inherent radiation sensitivity. J Cancer Res Clin Oncol 117: 597–602, 1991Google Scholar
  158. 158.
    Rikimaru K, Tadokoro K, Yamamoto T, Enomoto S, Tsuchida N: Gene amplification and overexpression of epidermal growth factor in squamous cell carcinoma of the head and neck. Head & Neck 14: 8–13, 1992Google Scholar
  159. 159.
    Chew EC, King WWK, Hou HJ, Yam HF: Establishment and characterization of two new cell lines derived from squamous carcinoma of the tongue in Chinese patients. Anticancer Res 12: 1627–1634, 1992Google Scholar
  160. 160.
    Urade M, Ogura T, Mima T, Matsuya T: Establishment of human squamous carcinoma cell lines highly and minimally sensitive to bleomycin and analysis of factors involved in the sensitivity. Cancer 69: 2589–2597, 1992Google Scholar
  161. 161.
    Somers KD, Merrick MA, Lopez ME, Incognito LS, Schecter GL, Casey G: Frequent p53 mutations in head and neck cancer. Cancer Res 52: 5997–6000, 1992Google Scholar
  162. 162.
    Scher RL, Koch WM, Richtsmeier WJ: Induction of intercellular adhesion molecule (ICAM-1) on squamous cell carcinoma by interferon gamma. Arch Otolaryngol Head Neck Surg 119: 432–438, 1993Google Scholar
  163. 163.
    Cowan JM, Beckett MA, Weichselbaum RR: Chromosome changes characterizing in vitro response to radiation in human squamous cell carcinoma lines. Cancer Res 53: 5542–5547, 1993Google Scholar
  164. 164.
    Liu T-J, Zhang W-W, Taylor DT, Roth JA, Goepfert H, Clayman GL: Growth suppression of human head and neck cancer cells by the introduction of wild-type p53 gene via a recombinant adenovirus. Cancer Res 54: 3662–3667, 1994Google Scholar
  165. 165.
    Harada M, Miyata K, Wada T, Morita N, Sakamoto T: Establishment and characterization of a cell line (H-1) from squamous cell carcinoma of human gingiva-effect of temperature [in Japanese]. Human Cell 6: 29–35, 1993Google Scholar
  166. 166.
    Inagaki T, Matsuwari S, Takahashi R, Shimada K, Fujie K, Maeda S: Establishment of human oral-cancer cell lines (KOSC-2 and-3) carrying p53 and c-myc abnormalities by geneticin treatment. Int J Cancer 56: 301–308, 1994Google Scholar
  167. 167.
    Matsuo K, Ishibashi Y, Kobayashi I, Ozeki S, Ohishi M, Tange T, Hirata J, Kiyoshima T, Sakai H: New human oral squamous carcinoma cell line and its tumorigenic subline producting granulocyte colony-stimulating factor. Jap J Cancer Res 85: 1257–1262, 1994Google Scholar
  168. 168.
    Fukiage T, Chikamatsu K, Matsuoka H, Murakami H, Eura M, Masuyama K, Ishikawa T: Establishment of a human cell line from maxillary squamous cell carcinoma and its biological features as a stimulator for induction of cytotoxic T lymphocytes. Auris, Nasus, Larynx 21: 163–172, 1994Google Scholar
  169. 169.
    Osaki T, Tatemoto Y, Yoneda K, Yamamoto T: Tumorigenicity of cell lines established from oral squamous cell carcinoma and its metastatic lymph nodes. Oral Oncol Eur J Cancer Res 30B: 296–301, 1994Google Scholar
  170. 170.
    Pekkola-Heino K, Joensuu H, Klemi P, Grenman R: Relation of DNA ploidy and proliferation rate to radiation sensitivity in squamous carcinoma cell lines. Arch Otolaryngol Head Neck Surg 120: 750–754, 1994Google Scholar
  171. 171.
    Moore AW, Sabachewsky L, Toolan HW: Culture characteristics of four permanent lines of human cancer cells. Cancer Res 13: 598–605, 1955Google Scholar
  172. 172.
    Eagle H: Nutrition needs of mammalian cells in tissue culture. Science 122: 501–504, 1955Google Scholar
  173. 173.
    Moore GE, Sandberg AA: Studies of a human tumor cell line with a diploid karyotype. Cancer 17: 170–175, 1964Google Scholar
  174. 174.
    Rangan SR: A new cell line (FaDu) from hypopharyngeal carcinoma. Cancer 29: 117–121, 1972Google Scholar
  175. 175.
    Peterson WDJ, Stulberg CS, Simpson WF: A permanent heteroploid cell line with type B glucose-6-phosphate dehydrogenase. Proc Soc Exp Biol Med 136: 1187–1191, 1971Google Scholar
  176. 176.
    Okabe T, Sato N, Kondo Y, Asano S, Ohsawa N, Kosaka K, Ueyama Y: Establishment and characterization of a human cancer cell line that produces human colony stimulating factor. Cancer Res 38: 3910–3917, 1978Google Scholar
  177. 177.
    Zenner HP, Lehner W, Hermann IF: Establishment of carcinoma cell lines from larynx and submadibular gland. Arch Otorhinolaryngol 225: 269–277, 1979Google Scholar
  178. 178.
    Zenner HP, Hermann IF, Bremer W, Stahl-Mauge C: Head and neck carcinoma models: In vivo reproduction in athymic mice and in vitro culture. Acta Otolaryngol 96: 371–381, 1983Google Scholar
  179. 179.
    Carey TE, Kimmel KA, Schwartz DR, Richter DE, Baker SR, Krause CJ: Antibodies to human squamous cell carcinoma. Otolaryngol Head Neck Surg 91: 482–491, 1983Google Scholar
  180. 180.
    Weichselbaum RR, Dahlberg W, Beckett M, Karrison T, Miller D, Carl J, Ervin TJ: Radiation-resistant and repair-proficient human tumor cells may be associated with radio-therapy failure in head-and neck-patients. Proc Nat Acad Sci (Wash) 83: 2684–2688, 1986Google Scholar
  181. 181.
    Yanagawa T, Hayashi Y, Yoshida H, Yuri Y, Nagamine S, Bando T, Sato M: An adenoid squamous carcinoma-forming cell line established from an oral keratinizing squamous cell carcinoma expressing carcinoembryonic antigen. Am J Pathol 124: 496–509, 1986Google Scholar
  182. 182.
    Heo DS, Snyderman C, Gollin SM, Pan S, Walker E, Deka R, Barnes EL, Johnson JT, Heberman RB, Whiteside TL: Biology, cytogenetics, and sensitivity to immunologic effector cells of new head and neck squamous carcinoma cell lines. Cancer Res 49: 5167–5175, 1989Google Scholar
  183. 183.
    Komiyama S, Matsui K, Kudoh S, Nogae I, Kuratomi Y, Saburi Y, Asoh K-I, Kohno K, Kuwano M: Establishment of tumor cell lines from a patient with head and neck cancer and their different sensitivities to anti-cancer agents. Cancer 63: 675–681, 1989Google Scholar
  184. 184.
    Grenman R, Carey TE, McClatchey KD, Wagner JG, Pekkola-Heino K, Schwartz DR, Wolf GT, Lacivita LP, Ho L, Baker SR, Krause CJ, Lichter AS: In vitro radiation resistance among cell lines established from patients with squamous cell carcinoma of the head and neck. Cancer 67: 2741–2747, 1991Google Scholar
  185. 185.
    Easty DM, Easty GC, Baici A, Carter RL, Cederholm-Williams SA, Felix H, Gusterson B, Haemmerli G, Hauser-Urfer I, Heizmann CW, Mareel M, Stehrenberger B, Sträuli P: Biological studies of ten human squamous carcinoma cell lines: an overview. Eur J Cancer Clin Oncol 22: 617–634, 1986Google Scholar
  186. 186.
    Kamada N, Chida K, Rikimaru K, Horikoshi M, Enomoto S, Kuroki T: Growth-inhibitory effects of epidermal growth factor and overexpression of the receptors on human squamous cell carcinomas in culture. Cancer Res 46: 1648–1653, 1986Google Scholar
  187. 187.
    King I, Sartorelli AC: Epidermal growth factor receptor gene expression, protein kinase activity, and terminal differentiation of human malignant epidermal cells. Cancer Res 49: 5677–5681, 1989Google Scholar
  188. 188.
    Maxwell SA, Sacks PG, Gutterman JU, Gallick GE: Epidermal growth factor receptor protein-tyrosine kinase activity in human cell lines established from squamous carcinomas of the head and neck. Cancer Res 49: 1130–1137, 1989Google Scholar
  189. 189.
    Osaku M, Ueda M, Ando N, Shinozawa Y, Hirota N, Shimizu N, Abe O: Targeted killing of squamous carcinoma cells by a monoclonal antibody-peplomycin conjugate which recognizes the EGF receptor. Anticancer Res 11: 1951–1956, 1991Google Scholar
  190. 190.
    Kim JS, Steck PA, Gallick GE, Lee JS, Blick M, Hong WK, Lotan R: Suppression by retinoic acid of epidermal growth factor receptor autophosphorylation and glycosylation in cultured human head and neck squamous carcinoma cells. Mono J Natl Cancer Inst 13: 101–110, 1992Google Scholar
  191. 191.
    Komiyama S, Matsui K, Miyazaki H, Kudoh S, Mizoguchi H, Shimizu N: Heterogeneity in epidermal growth factor responsiveness and tumor growth of human maxillary cancer cell lines. Ann Otol Rhinol Laryngol 101: 519–524, 1992Google Scholar
  192. 192.
    Moroni MC, Willingham MC, Beguinot L: EGF-R antisense RNA blocks expression of the epidermal growth factor receptor and suppresses the transforming phenotype of a human carcinoma cell line. J Biol Chem 267: 2714–2722, 1992Google Scholar
  193. 193.
    Prime SS, Game SM, Matthews JB, Stone A, Donnelly MJ, Yeudall WA, Patel V, Sposto R, Silverthorne A, Scully C: Epidermal growth factor and transforming growth factor α characteristics of human oral carcinoma cell lines. Brit J Cancer 69: 8–15, 1994Google Scholar
  194. 194.
    Bujia J, Wustrow TP: Heterologous epidermal growth factor receptor (EGF-R) expression in larynx cancer cell lines: evidence for the existence of structurally modified receptors. Acta Oto-Laryngologica 113: 789–792, 1993Google Scholar
  195. 195.
    Stanton P, Richards S, Reeves J, Nikolic M, Edington K, Clark L, Robertson G, Souter D, Mitchell R, Hendler FJ, Cooke T, Parkinson EK, Ozanne BW: Epidermal growth factor receptor expression by human squamous cell carcinomas of the head and neck, cell lines and xenografts. Brit J Cancer 70: 427–433, 1994Google Scholar
  196. 196.
    Modjtahedi H, Eccles S, Sandle J, Box G, Titley J, Dean C: Differentiation or immune destruction: two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor. Cancer Res 54: 1695–1701, 1994Google Scholar
  197. 197.
    Bonner JA, Maihle NJ, Folven BS, Christiansen TJH, Spain K: The interaction of epidermal growth factor and radiation in human head and neck squamous cell carcinoma cell lines with vastly different radiosensitivities. Int J Rad Oncol Biol Phys 29: 243–247, 1994Google Scholar
  198. 198.
    Sturgis EM, Sacks PG, Masui H, Mendelsohn J, Schantz SP: Effects of antiepidermal growth factor receptor antibody 528 on the proliferation and differentiation of head and neck cancer. Otolaryngol Head Neck Surg 111: 633–643, 1994Google Scholar
  199. 199.
    Tatake RJ, Krishnan N, Rao RS, Fakih AR, Gangal SG: Lymphokine-activated killer-cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer. Int J Cancer 43: 560–566, 1989Google Scholar
  200. 200.
    Burkey BB, Omann GM, Wolf GT: Intracellular calcium changes associated with in vitro lymphokine-activated killer and natural killer cell cytotoxicity. Arch Otolaryngol Head Neck Surg 117: 1281–1286, 1991Google Scholar
  201. 201.
    Weidmann E, Sacchi M, Plaisance S, Heo DS, Yasumura S, Lin W-C, Johnson JT, Herberman RB, Azzarone B, Whiteside TL: Receptors for interleukin 2 on human squamous cell carcinoma cell lines and tumor in situ. Cancer Res 52: 5963–5970, 1992Google Scholar
  202. 202.
    Sacchi M, Klapan I, Johnson JT, Whiteside TL: Antiproliferative effects of cytokines on squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 117: 321–326, 1991Google Scholar
  203. 203.
    Rabinowich H, Vitolo D, Altarac S, Herberman RB, Whiteside TL: Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2-activated natural killer cells. J Immunol 149: 340–349, 1992Google Scholar
  204. 204.
    Rubin AL, Rice RH: Differential regulation by retinoic acid and calcium of transglutaminases in cultured neoplastic and normal human keratinocytes. Cancer Res 46: 2356–2361, 1986Google Scholar
  205. 205.
    Jetten AM, Kim JS, Sacks PG, Rearick JI, Lotan D, Hong WK, Lotan R: Inhibition of growth and squamous-cell differentiation markers in cultured human head and neck squamous carcinoma cells by beta-all-trans retinoic acid. Int J Cancer 45: 195–202, 1990Google Scholar
  206. 206.
    Hu L, Crowe DL, Rheinwald JG, Chambon P, Gudas LJ: Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res 51: 3972–3981, 1991Google Scholar
  207. 207.
    Sarkar R, Das SK: Characteristics of retinoid-induced adhesion in a cultured human oral carcinoma cell line. Neoplasma 39: 87–91, 1992Google Scholar
  208. 208.
    Zou C-P, Clifford JL, Xu X-C, Sacks PG, Chambon P, Hong WK, Lotan R: Modulation by retinoic acid (RA) of squamous cell differentiation, and nuclear RA receptors in human head and neck squamous cell carcinoma lines. Cancer Res 54: 5479–5487, 1994Google Scholar
  209. 209.
    Toma S, Monteghirfo S, Tasso P, Nicolo G, Spadini N, Palumbo R, Molina F: Antiproliferative and synergistic effect of interferon alpha-2a, retinoids and their association in established human cancer cell lines. Cancer Lett 82: 209–216, 1994Google Scholar
  210. 210.
    Sacks PG, Harris D, Chou T-C: Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a rationale for combination therapy with chemotherapeutic agents. Int J Cancer 61: 409–415, 1995Google Scholar
  211. 211.
    Osella P, Carlson A, Wyandt H, Milunsky A: Cytogenetic studies of eight squamous cell carcinomas of the head and neck. Deletion of 7q, a possible primary chromosomal event. Cancer Genet Cytogenet 59: 73–78, 1992Google Scholar
  212. 212.
    Patel V, Yeudall WA, Gardner A, Mutlu S, Scully C, Prime SS: Consistent chromosomal anomalies in keratinocyte cell lines derived from untreated malignant lesions of the oral cavity. Genes Chrom Cancer 7: 109–115, 1993Google Scholar
  213. 213.
    Van Dyke DL, Worsham MJ, Benninger MS, Krause CJ, Baker SR, Wolf GT, Drumheller T, Tilley BC, Carey TE: Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region. Genes Chrom Cancer 93: 192–206, 1994Google Scholar
  214. 214.
    Sreekantaiah C, Rao PH, Xu L, Sacks PG, Schantz SP, Chaganti RSK: Consistent chromosomal losses in head and neck squamous cell carcinoma cell lines. Genes Chrom Cancer 11: 29–39, 1994Google Scholar
  215. 215.
    Virolainen E, Carey TE, Wicha M, Krause CJ: Factors affecting the growth of head and neck squamous carcinoma cell lines. Otolaryngol Head Neck Surg 91: 126–135, 1983Google Scholar
  216. 216.
    Bijman JT, Wagener DJT, Graafsma SJ, Wessels JMC, van den Broek P: Modulation of proliferation of a human head and neck squamous carcinoma cell line (HN-1) by catecholamines and histamine. Anticancer Res 7: 147–150, 1987Google Scholar
  217. 217.
    Scott RE, Wilke MS, Wille JJJ, Pittelkow MR, Hsu BM, Kasperbauer JL: Human squamous carcinoma cells express complex defects in the control of proliferation and differentiation. Am J Pathol 133: 374–380, 1988Google Scholar
  218. 218.
    Wilke MS, Hsu BM, Wille JJJ, Pittelkow MR, Scott RE: Biologic mechanisms for the regulation of normal human keratinocyte proliferation and differentiation. Am J Pathol 131: 171–181, 1988Google Scholar
  219. 219.
    Violette SM, King I, Browning JL, Pepinsky RB, Wallner PB, Sartorelli AC: Role of lipocortin I in the glucocorticoid induction of the terminal differentiation of a human squamous carcinoma. J Cell Physiol 142: 70–77, 1990Google Scholar
  220. 220.
    Pillai S, Bikle DD, Mancianti ML, Hincenbergs M: Uncoupling of the calcium-sensing mechanism and differentiation in squamous carcinoma cell lines. Exp Cell Res 192: 567–573, 1991Google Scholar
  221. 221.
    Harari PM, Contreras L, Pickart MA, Ritter MA, Kinsella TJ: Modulation of proliferation kinetics in human squamous cell carcinomas of the head and neck. Arch Otolaryngol Head Neck Surg 119: 738–742, 1993Google Scholar
  222. 222.
    Sugiyama M, Speight PM, Prime SS, Watt FM: Comparison of integin expression and terminal differentiation capacity in cell lines derived from oral squamous cell carcinomas. Carcinogen 14: 2171–2176, 1993Google Scholar
  223. 223.
    Minn H, Clavo AC, Grenman R, Wahl RL: In vitro comparison of cell proliferation kinetics and uptake of tritiated fluorodeoxyglucose and L-methionine in squamous-cell carcinoma of the head and neck. J Nucl Med 36: 252–258, 1995Google Scholar
  224. 224.
    Kim K, Akoto-Amanfu E, Cherrick HM, Park N-H: Anchorage-independent growth and the expression of cellular proto-oncogenes in normal human epidermal keratinocytes and in human squamous cell carcinoma cell lines. Oral Surg Oral Med Oral Path 71: 303–311, 1991Google Scholar
  225. 225.
    Yin XY, Donovan-Peluso M, Whiteside TL, Johnson JT, Day R, Herberman RB, Locker J: Gene amplification and gene dosage in cell lines derived from squamous cell carcinoma of the head and neck. Genes Chrom Cancer 3: 443–454, 1991Google Scholar
  226. 226.
    Somers KD, Cartwright SL, Schechter GL: Amplification of the int-2 gene in human head and neck squamous cell carcinomas. Oncogene 5: 915–921, 1990Google Scholar
  227. 227.
    Kim MS, Li SL, Bertolami CN, Cherrick HM, Park N-H: State of p53, Rb and DCC tumor suppressor genes in human oral cancer cell lines. Anticancer Res 13: 1405–1413, 1993Google Scholar
  228. 228.
    Clark LJ, Edington K, Swan IRC, McLay KA, Newlands WJ, Wills LC, Young HA, Johnston PW, Mitchell R, Robertson G, Soutar D, Parkinson EK, Birnie GD: The absence of Harvey ras mutations during development and progression of squamous cell carcinomas of the head and neck. Brit J Cancer 68: 617–620, 1993Google Scholar
  229. 229.
    Yeudall WA, Torrance LK, Elsegood KA, Speight P, Scully C, Prime SS: Ras gene point mutation is a rare event in premalignant tissues and malignant cells and tissues from orla mucosal lesions. Oral Oncol Eur J Cancer Res 29B: 63–67, 1993Google Scholar
  230. 230.
    Patel BK, Kasid U: Nucleotide sequence analysis of c-raf-1 cDNA and promoter from a radiation-resistant human squamous carcinoma cell line: deletion within exon 17. Mol Carcinogen 8: 7–12, 1993Google Scholar
  231. 231.
    Brookes S, Lammie GA, Schuuring E, de Boer C, Michalides R, Dickson C, Peters G: Amplified region of chromosome band 11q13 in breast and squamous cell carcinomas encompasses three CpG islands telomeric of FGF3, including the expressed gene EMS1. Genes Chrom Cancer 6: 222–231, 1993Google Scholar
  232. 232.
    Min B-M, Baek J-H, Shin K-H, Gujuluva CN, Cherrick HM, Park N-H: Inactivation of the p53 gene by either mutation or HPV infection is extremely frequent in human oral squamous cell carcinoma cell lines. Oral Oncol Eur J Cancer Res 30B: 338–345, 1994Google Scholar
  233. 233.
    Brachman DG, Beckett M, Graves D, Haraf D, Vokes E, Weichselbaum RR: p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res 53: 3667–3669, 1993Google Scholar
  234. 234.
    Smeets MF, Mooren EH, Begg AC: Radiation-induced DNA damage and repair in radiosensitive and radioresistant human tumour cells measured by field inversion gel electrophoresis. Int J Rad Biol 63: 703–713, 1993Google Scholar
  235. 235.
    Weichselbaum RR, Hallahan DE, Beckett MA, Mauceri HJ, Lee H, Sukhatme VP, Kufe DW: Gene therapy targeted by radiation preferentially radiosensitizes tumor cells. Cancer Res 54: 4266–4269, 1994Google Scholar
  236. 236.
    Bellamy AS, Whelan RDH, Hill BT: Studies of variation in inherent sensitivities to radiation, 5-fluorouracil and methotrexate in a series of human and murine tumor cell lines in vitro. Int J Rad Oncol Biol Phys 10: 87–93, 1984Google Scholar
  237. 237.
    Lock RB, Hill BT: Differential patterns of anti-tumour drug responses and mechanisms of resistance in a series of independently-derived VP-16 resistant human tumour cells. Int J Cancer 42: 373–381, 1988Google Scholar
  238. 238.
    Morris G, Mistry JS, Jani JP, Sebti SM, Lazo JS: Cysteineproteinase inhibitors and bleomycin-sensitive and-resistant cells. Biochem Pharm 41: 1559–1566, 1991Google Scholar
  239. 239.
    Etienne MC, Bernard S, Fischel JL, Formento P, Gioanni J, Santini J, Demard F, Schneider M, Milano G: Dose reduction without loss of efficacy for 5-fluorouracil and cisplatin combined with folinic acid. In vitro study on head and neck carcinoma cell lines. Brit J Cancer 63: 372–377, 1991Google Scholar
  240. 240.
    Braakhuis BJM, Visser GW, Stringer I, Peters GJ: In vitro antiproliferative and metabolic activity of eight novel 5-fluorinated uracil nucleosides. Eur J Cancer 27: 250–253, 1991Google Scholar
  241. 241.
    Esaki T, Nakano S, Tatsumoto T, Kuroki-Migita M, Mitsugi K, Nakamura M, Niho Y: Inhibition by 5-fluorouracil of cis-diamminedichloroplatinum(II)-induced DNA interstrand cross-link removal in a HST-1 human squamous carcinoma cell line. Cancer Res 52: 6501–6506, 1992Google Scholar
  242. 242.
    Braakhuis BJM, Jansen G, Noordhuis P, Kegel A, Peters GJ: Importance of pharmacodynamics in the in vitro antiproliferative activity of the antifolates methotrexate and 10-ethy-10-deazaaminopterin against human head and neck squamous cell carcinoma. Biochem Pharm 46: 2155–2166, 1993Google Scholar
  243. 243.
    Hanson WG, Ferguson PJ: Differential methotrexate toxicity between two human oral squamous carcinoma cell lines. J Otolaryngol 22: 143–147, 1993Google Scholar
  244. 244.
    Haller J, Burgess R, Dawson D: Increased cytotoxicity of squamous cell carcinoma of the head and neck by combining cisplatin with VP-16 and ciproflocacin. Laryng 103: 1081–1083, 1993Google Scholar
  245. 245.
    Teicher BA, Schwartz JL, Holden SA, Ara G, Northey D: In vivo modulation of several anticancer agents by betacarotene. Cancer Chemo Pharmacol 34: 235–241, 1994Google Scholar
  246. 246.
    Yellin SA, Davidson BJ, Pinto JT, Sacks PG, Qiao C, Schantz SP: Relationship of glutathione and glutathione-S-transferase to cisplatin sensitivity in human head and neck squamous carcinoma cell lines. Cancer Lett 85: 223–232, 1994Google Scholar
  247. 247.
    Todd R, Donoff BR, Gertz R, Chang ALC, Chow P, Matossian K, McBride J, Chiang T, Gallagher GT, Wong DTW: TGF-α and EGF-receptor mRNAs in human oral cancers. Carcinogen 10: 1553–1556, 1989Google Scholar
  248. 248.
    Reiss M, Stash EB: High frequency of resistance of human squamous carcinoma cells to the anti-proliferative action of transforming growth factor-β. Cancer Commun 1990: 363–369, 1990Google Scholar
  249. 249.
    Reiss M, Stash EB, Vellucci VF, Zhou Z-L: Activation of the autocrine transforming growth factor α pathway in human squamous carcinoma cells. Cancer Res 51: 6254–6262, 1991Google Scholar
  250. 250.
    Prime SS, Matthews JB, Patel V, Game SM, Donnelly M, Stone A, Paterson IC, Sandy JR, Yeudall WA: TGF-beta receptor regulation mediates the response to exogenous ligand but is independent of the degree of cellular differentiation in human oral keratinocytes. Int J Cancer 56: 406–412, 1994Google Scholar
  251. 251.
    Garrigue-Antar L, Muñoz-Antonia T, Antonia SJ, Gesmonde J, Vellucci VF, Reiss M: Missense mutations of the transforming growth factor β type II receptor in human head and neck squamous carcinoma cells. Cancer Res 55: 3982–3987, 1995Google Scholar
  252. 252.
    Huang C-C, Blitzer A, Abramson M, Wu C-h: Collagenase and protease activities in head and neck tumors. Otolaryngol Head Neck Surg 88: 749–752, 1980Google Scholar
  253. 253.
    Tsao SW, Burman JF, Easty DM, Easty GC, Carter RL: Some mechanisms of local bone destruction by squamous carcinomas of the head and neck. Brit J Cancer 43: 392–401, 1981Google Scholar
  254. 254.
    Burman JF, Carter RL: Lysis of type-I collagen by squamous carcinomas of the head and neck. Int J Cancer 36: 109–116, 1985Google Scholar
  255. 255.
    Baici A, Sträuli P: Release of proteases by cultures of human cell lines derived from squamous carcinomas of the tongue and larynx. Expl Cell Biol 53: 213–219, 1985Google Scholar
  256. 256.
    Wenig BL, Steinberg BM, Sciubba JJ, gomes BC, Abramson AL: An organ culture system designed to study interaction of fetal rat calvaria with human head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg 88: 235–241, 1988Google Scholar
  257. 257.
    Clayman G, Wang SW, Nicolson GL, El-Naggar A, Mazar A, Henkin J, Blasi F, Goepfert H, Boyd DD: Regulation of urokinase-type plasminogen activator expression in squamous-cell carcinoma of the oral cavity. Int J Cancer 54: 1–8, 1993Google Scholar
  258. 258.
    Kawahara E, Okada Y, Nakanishi I, Iwata K, Kojima S, Kumagai S, Yamamoto E: The expression of invasive behavior of differentiated squamous carcinoma cell lines evaluated by an in vitro invasion model. Jap J Cancer Res 84: 409–418, 1993Google Scholar
  259. 259.
    Yabkowitz R, Mansfield PJ, Dixit VM, Suchard SJ: Motility of human carcinoma cells in response to thrombospondin: relationship to metastatic potential and thrombospondin structural domains. Cancer Res 53: 378–387, 1993Google Scholar
  260. 260.
    Kinsella AR, Bowie GL, Field JK, Jones AS: Expression of the cell-cell adhesion molecule E-cadherin in tongue carcinoma lines. J Laryngol Otol 108: 957–961, 1994Google Scholar
  261. 261.
    Ishisaki A, Oida S, Momose F, Amagasa T, Rikimaru K, Ichijo H, Sasaki S: Identification and chracterization of autocrine-motility-factor-like activity in oral squamous-cell-carcinoma cells. Int J Cancer 59: 783–788, 1994Google Scholar
  262. 262.
    Varani J, Dixit VM, Fligiel SEG, McKeever PE, Carey TE: Thrombospondin-induced attachment and spreading of human squamous carcinoma cells. Exp Cell Res 167: 376–390, 1986Google Scholar
  263. 263.
    Schuger L, Dixit VM, Carey TE, Varani J: Modulation of squamous carcinoma cell growth, morphology, adhesiveness and extracellular matrix production by interferon-γ and tumor necrosis factor-α. Pathobiology 58: 279–286, 1990Google Scholar
  264. 264.
    Schrijvers AHGJ, Gerretsen M, Fritz JM, van Walsum M, Quak JJ, Snow GB, van Dongen GAMS: Evidence for a role of the monoclonal antibody R48 defined antigen in cell-cell adhesion in squamous epithelia and head and neck squamous cell carcinoma. Exp Cell Res 196: 264–269, 1991Google Scholar
  265. 265.
    Mutlu S, Scully MS, Prime SS: Effect of IFN-γ on the expression of MHC class I and class II antigens in a human malignant oral epithelial cell line. J Oral Pathol Med 20: 218–221, 1991Google Scholar
  266. 266.
    Carey TE, Laurikainen L, Nair TS, Reinke TS, Coling DE, Wolf GT, Van Waes C, Liebert M, Marcelo C: Regulation of expression and phosphorylation of A9/alpha 6 beta 4 integrin in normal and neoplastic keratinocytes. Mono J Natl Cancer Inst 13: 75–86, 1992Google Scholar
  267. 267.
    Nielsen-Preiss SM, Quigley JP: Detection and characterization of low abundance cellular proteins that specifically increase u[on loss of the metastatic phenotype. J Biol Chem 51: 219–235, 1993Google Scholar
  268. 268.
    Pattaramalai S, Skubitz AP: Promotion of human oral squamous cell carcinoma adhesion in vitro by the carboxyterminal globular domain of laminin. Arch Oral Biol 39: 925–933, 1994Google Scholar
  269. 269.
    Steele C, Sacks PG, Adler-Storthz K, Shillitoe EJ: Effect on cancer cells of plasmids that express antisense RNA of human papillomavirus type 18. Cancer Res 52: 4706–4711, 1992Google Scholar
  270. 270.
    Steele C, Cowsert LM, Shillitoe EJ: Effects of human papillomavirus type 18-specific antisense oligonucleotides on the transformed phenotype of human carcinoma cell lines. Cancer Res 53: 2330–2337, 1993Google Scholar
  271. 271.
    Clayman GL, Trapnell BC, Mittereder N, Liu T-J, Eicher S, Zhang S, Shillitoe EJ: Transduction of normal and malignant oral epithelium by an adenovirus vector: The effect of dose and treatment time on transduction efficiency and tissue penetration. Cancer Gene Ther 2: 105–111, 1995Google Scholar
  272. 272.
    Latif F, Fivash M, Glenn G, Tory K, Orcutt ML, Hampsch K, Delisio J, Lerman M, Cowan J, Beckett M, Weichselbaum R: Chromosome 3p deletions in head and neck carcinomas: statistical ascertainment of allelic loss. Cancer Res 52: 1451–1456, 1992Google Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Peter G. Sacks
    • 1
  1. 1.Head & Neck Service, Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Memorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations