Clinical significance of p53 in non-small cell lung cancer (Review)

Oncology Reports

Volumn 6, Issue 1, 1999, Pages 19-28

  Komiya, Takefumi ^a,b   Hirashima, Tomonori ^a   Kawase, Ichiro ^a  

^a OSAKA PREFECTURAL MEDICAL CENTER FOR RESPIRATORY AND ALLERGIC DISEASES   (Japan)

^b KINKI UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Non small cell lung cancer; p53; Prognosis

Indexed keywords

PROTEIN P53; TUMOR MARKER; TUMOR PROTEIN;

APOPTOSIS; CELL CULTURE; CHROMOSOME 17; CLINICAL TRIAL; EXON; GENE DELETION; GENE EXPRESSION REGULATION; GENE THERAPY; GENETICS; HUMAN; LUNG NON SMALL CELL CANCER; LUNG TUMOR; MORTALITY; MULTICENTER STUDY; PATHOLOGY; POINT MUTATION; PROGNOSIS; PROSPECTIVE STUDY; RADIATION DOSE; RADIATION EXPOSURE; REVIEW; SINGLE STRAND CONFORMATION POLYMORPHISM; TUMOR SUPPRESSOR GENE;

APOPTOSIS; CARCINOMA, NON-SMALL-CELL LUNG; CHROMOSOMES, HUMAN, PAIR 17; CLINICAL TRIALS; EXONS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE THERAPY; GENES, P53; HUMANS; LUNG NEOPLASMS; MULTICENTER STUDIES; NEOPLASM PROTEINS; POINT MUTATION; POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL; PROGNOSIS; PROSPECTIVE STUDIES; RADIATION TOLERANCE; SEQUENCE DELETION; TUMOR CELLS, CULTURED; TUMOR MARKERS, BIOLOGICAL; TUMOR SUPPRESSOR PROTEIN P53;

EID: 0032616203     PISSN: 1021335X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (119)

1. Fearon ER and Vogelstein B: A genetic model for colorectal tumorigenesis. Cell 61: 759-767, 1990.
2. Bishop JM: The molecular genetics of cancer. Science 235: 305-311, 1987.
3. Chang F, Syrjanen S and Syrjanen K: Implications of the p53 tumor-suppressor gene in clinical oncology. J Clin Oncol 13: 1009-1022, 1995.
4. Lane DP and Crawford LV: T antigen is bound to a host protein in SV40-transformed cells. Nature 278: 261-263, 1979.
5. Linzer DI and Levine AJ: Characterization of a 54 kDa cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17: 43-52, 1979.
6. Parada LF, Land H, Weinberg RA, Wolf D and Rotter V: Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation. Nature 312: 649-651, 1984.
7. Hinds P, Finlay C and Levine AJ: Mutation is required to activate the p53 gene for cooperation with the ras oncogene and transformation. J Virol 63: 739-746, 1989.
8. Takahashi T, Carbone D, Takahashi T, Nau MM, Hida T, Linnoila I, Ueda R and Minna JD: Wild-type but not mutant p53 suppresses the growth of human lung cancer cells bearing multiple genetic Tesions. Cancer Res 52: 2340-2343, 1992.
9. Hollstein M, Sidransky D, Vogelstein B and Harris CC: p53 mutations in human cancers. Science 253: 49-53, 1991.
10. Levine AJ, Momand J and Finlay CA: The p53 tumour suppressor gene. Nature 351: 453-456, 1991.
11. McBride OW, Merry D and Givol D: The gene for human p53 cellular tumor antisen is located on chromosome 17 short arm (17p13). Proc Natl Acad Sci USA 83: 130-134, 1986.
12. Miller C, Mohandas T, Wolf D, Prokocimer M, Rotter V and Koeffler HP: Human p53 gene localized to short arm of chromosome 17, Nature 319: 783-784, 1986.
13. Soussi T, Caron de Fromentel C and May P: Structural aspects of the p53 protein in relation to gene evolution. Oncogene 5: 945-952, 1990.
14. Vogelstein B and Kinzler KW: p53 function and dysfunction. Cell 70: 523-526, 1992.
15. Fields S and Jang SK: Presence of a potent transcription activating sequence in the p53 protein. Science 249: 1046-1049, 1990.
16. Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ: The p21 Cdk-interacting protein Cip1 is a potent inhibitor of GI cyclin-dependent kinases. Cell 75, 805-816, 1993.
17. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817-825, 1993.
18. El-Deiry WS, Tokino T, Waldman T, Oliner JD, Velculescu VE, Burrell M, Hill DE, Healy E, Rees JL, Hamilton SR, et al: Topological control of p21WAF1/CIP1 expression in normal and neoplastic tissues. Cancer Res 55: 2910-2919, 1995.
19. Wu X, Bayle JH, Olson D and Levine AJ: The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7: 1126-1132, 1993.
20. Barak Y, Juven T, Haffner R and Oren M. mdm2 expression is induced by wild-type p53 activity. EMBO J 12: 461-468, 1993.
21. Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B and Fornace AJ Jr: A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71: 587-597, 1992.
22. Miyashita T and Reed JC: Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80: 293-299, 1995.
23. Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C and Vogelstein B: Identification of p53 as a sequence-specific DNA-binding protein. Science 252: 1708-1711, 1991.
24. Lane DP: Cancer. p53, guardian of the genome. Nature 358: 15-16, 1992.
25. Soussi T, Legros Y, Lubin R, Ory K and Schlichtholz B: Multifactorial analysis of p53 alteration in human cancer: a review. Int J Cancer 57: 1-9, 1994.
26. Koshland DE Jr: Molecule of the year (editorial). Science 262: 1953, 1993.
27. Cluba I, Takahashi T, Nau MM, D'Amico D, Curiel DT, Mitsudomi T, Buchhagen DL, Carbone D, Piantadosi S, Koga H, et al: Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. Oncogene 5: 1603-1610, 1990.
28. Mitsudomi T, Steinberg SM, Nau MM, Carbone D, D'Amico D, Bodner S, Oie HK, Linnoila RI, Mulshine JL, Minna JD, et al: p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene 7: 171-180, 1992.
29. Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M, Levitt M, Pass H, Gazdar AF and Minna JD: p53: a frequent target for genetic abnormalities in lung cancer. Science 246: 491-494, T989.
30. Chang F, Syrjanen S, Tervahauta A and Syrjanen K: Tumourigenesis associated with the p53 tumour suppressor gene. Br J Cancer 68: 653-661, 1993.
31. Carbone D and Kratzke R: RB1 and p53 genes. In: Lung Cancer, Principles and Practice. 1st edition. Pass HI, Mitchell JB, Johnson DH and Turrisi AT (eds). Lippincott-Raven Publishers, Philadelphia, pp107-121, 1996.
32. Baker SJ, Preisinger AC, Jessup JM, Paraskeva C, Markowitz S, Willson JK, Hamilton S and Vogelstein B: p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis. Cancer Res 50: 7717-7722, 1990.
33. Greenblatt MS, Bennett WP, Hollstein M and Harris CC: Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855-4878, 1994.
34. Jones PA, Buckley JD, Henderson BE, Ross RK and Pike MC: From gene to carcinogen: a rapidly evolving field in molecular epidemiology. Cancer Res 51: 3617-3620, 1991.
35. Harris CC: Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res 51: 5023s-5044s, 1991.
36. Ruggeri B, DiRado M, Zhang SY, Bauer B, Goodrow T and Klein-Szanto AJ: Benzo[a]pyrene-induced murine skin tumors exhibit frequent and characteristic G to T mutations in the p53 gene. Proc Natl Acad Sci USA 90: 1013-1017, 1993.
37. Orita M, Suzuki Y, Sekiya T and Hayashi K: Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. Genomics 5: 874-879, 1989
38. Orita M, Iwahana H, Kanazawa H, Hayashi K and Sekiya T: Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc Natl Acad Sci USA 86: 2766-2770, 1989.
39. Top B: A simple method to attach a universal 50-bp GC-clamp to PCR fragments used for mutation analysis by DGGE PCR Methods Appl 2: 83-85, 1992.
40. Harvey DM and Levine AJ: p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev 5: 2375-2385, 1991.
41. Bartek J, Bartkova J, Vojtesek B, Staskova Z, Lukas J, Rejthar A, Kovarik J, Midgley CA, Gannon JV and Lane DP: Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies. Oncogene 6: 1699-1703, 1991.
42. Brambilla E, Negoescu A, Gazzeri S, Lantuejoul S, Moro D, Brambilla C and Coll JL: Apoptosis-related factors p53, Bc12, and Bax in neuroendocrine lung tumors. Am J Pathol 149: 1941-1952,1996.
43. Carbone DP, Mitsudomi T, Chiba I, Piantadosi S, Rusch V, Nowak JA, McIntire D, Slamon D, Gazdar A and Minna J: p53 immunostaining positivity is associated with reduced survival and is imperfectly correlated with gene mutations in resected non-small cell lung cancer. A preliminary report of LCSG 871. Chest 106: 377S-381S, 1994.
44. Bodner SM, Minna JD, Jensen SM, D'Amico D, Carbone D, Mittudomi T, Fedorko J, Buchhagen DL, Nau MM, Gazdar AF, et al: Expression of mutant p53 proteins in lung cancer correlates with the class of p53 gene mutation. Oncogene 7: 743-749, 1992.
45. Nishio M, Koshikawa T, Kuroishi T, Suyama M, Uchida K, Takagi Y, Washimi O, Sugiura T, Ariyoshi Y, Takahashi T and Ueda R: Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers. J Clin Oncol 14: 497-502, 1996.
46. Legros Y, Lacabanne V, D'Agay MF, Larsen CJ, Pla M and Soussi T: Production of human p53 specific monoclonal antibodies and their use in immunohistochemical studies of tumor cells. Bull Cancer 80: 102-110, 1993.
47. Lee JS, Yoon A, Kalapurakal SK, Ro JY, Lee JJ, Tu N, Hittelman WN and Hong WK: Expression of p53 oncoprotein in non-small-cell lung cancer: a favorable prognostic factor. J Clin Oncol 13: 1893-1903, 1995.
48. Vojtesek B, Bartek J, Midgley CA and Lane DP: An immunochemical analysis of the human nuclear phosphoprotein p53. New monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151: 237-244, 1992.
49. Cattoretti G, Pileri S, Parravicini C, Backer MH, Poggi S, Bifulco C, Key G, D'Amato L, Sabattini E, Feudale E, et al: Antigen unmasking on formalin-fixed, paraffin-embedded tissue sections. J Pathol 171: 83-98, 1993.
50. Crawford LV, Pim DC and Bulbrook RD: Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer 30: 403-408, 1982.
51. Lubin R, Schlichtholz B, Bengoufa D, Zalcman G, Tredaniel J, Hirsch A, de Fromentel CC, Preudhomme C, Fenaux P, Fournier G, et al: Analysis of p53 antibodies in patients with various cancers define B-cell epitopes of human p53: distribution on primary structure and exposure on protein surface. Cancer Res 53: 5872-5876, 1993.
52. Winter SF, Minna JD, Johnson BE, Takahashi T, Gazdar AF and Carbone DP: Development of antibodies against p53 in lung cancer patients appears to be dependent on the type of p53 mutation. Cancer Res 52: 4168-4174, 1992.
53. Schlichtholz B, Legros Y, Gillet D, Gaillard C, Marty M, Lane D, Calvo F and Soussi T: The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res 52: 6380-6384, 1992.
54. Wild CP, Ridanpaa M, Anttila S, Lubin R, Soussi T, Husgafvel-Pursiainen K and Vainio H. p53 antibodies in the sera of lung cancer patients: comparison with p53 mutation in the tumour tissue. Int J Cancer 64: 176-181, 1995.
55. Marxsen J, Schmiegel W, Roder C, Harder R, Juhl H, HenneBruns D, Kremer B and Kalthoff H: Detection of the anti-p53 antibody response in malignant and benign pancreatic disease. Br J Cancer 70: 1031-1034, 1994.
56. Komiya T, Hirashima T, Takada M, Masuda N, Yasumitsu T, Nakagawa K, Hosono Y, Kikui M, Tsuji S, Fukuoka M and Kawase I: Prognostic significance of serum p53 antibodies in squamous cell carcinoma of the lung. Anticancer Res 17: 3721-3724, 1997.
57. Mitsudomi T, Oyama T, Kusano T, Osaki T, Nakanishi R and Shirakusa T: Mutations of the p53 gene as a predictor of poor prognosis in patients with non-small-cell lung cancer. J Natl Cancer Inst 85: 2018-2023, 1993.
58. Horio Y, Takahashi T, Kuroishi T, Hibi K, Suyama M, Niimi T, Shimokata K, Yamakawa K, Nakamura Y, Ueda R, et al: Prognostic significance of p53 mutations and 3p deletions in primary resected non-small cell lung cancer. Cancer Res 53: 1-4, 1993.
59. Isobe T, Hiyama K, Yoshida Y, Fujiwara Y and Yamakido M: Prognostic significance of p53 and ras gene abnormalities in lung adenocarcinoma patients with stage I disease after curative resection. Jpn J Cancer Res 85: 1240-1246, 1994.
60. Top B, Mooi WJ, Klaver SG, Boerrigter L, Wisman P, Elbers HR, Visser S and Rodenhuis S: Comparative analysis of p53 gene mutations and protein accumulation in human non-small-cell lung cancer. Int J Cancer 64: 83-91, 1995.
61. Fukuyama Y, Mitsudomi T, Sugio K, Ishida T, Akazawa K and Sugimachi K: K-ras and p53 mutations are an independent unfavourable prognostic indicator in patients with non-small-cell lung cancer. Br J Cancer 75: 1125-1130, 1997.
62. Ohno A, Hirashima T, Kubo A, Masuda N, Takada M, Fujiwara H, Yasumitsu T, Kikui M, Fukuoka M and Nakagawa K: p53 status is associated with a favorable prognosis in patients with stage I-IIIa non-small cell lung cancer. Int J Oncol 10: 521-528, 1997.
63. Vega FJ, Iniesta P, Caldes T, Sanchez A, Lopez JA, de Juan C, Diaz-Rubio E, Torres A, Balibrea JL and Benito M: p53 exon 5 mutations as a prognostic indicator of shortened survival in nonsmall-cell lung cancer. Br J Cancer 76: 44-51, 1997.
64. Quinlan DC, Davidson AG, Summers CL, Warden HE and Doshi HM: Accumulation of p53 protein correlates with a poor prognosis in human lung cancer. Cancer Res 52: 4828-4831, 1992.
65. McLaren R, Kuzu I, Dunnill M, Harris A, Lane D and Gatter KC: The relationship of p53 immunostaining to survival in carcinoma of the lung. Br J Cancer 66: 735-738, 1992.
66. Brambilla E, Gazzeri S, Moro D, Caron de Fromentel C, Gouyer V, Jacrot M, Brambilla C: Immunohistochemical study of p53 in human king carcinomas. Am J Pathol 143: 199-210, 1993.
67. Morkve O, Halvorsen OJ, Skjaerven R, Stangeland L, Gulsvik A and Laerum OD: Prognostic significance of p53 protein expression and DNA ploidy in surgically treated non-small cell lung carcinomas. Anticancer Res 13: 571-578, 1993.
68. Ebina M, Steinberg SM, Mulshine JL and Linnoila RI: Relationship of p53 overexpression and up-regulation of proliferating cell nuclear antigen with the clinical course of nonsmall cell lung cancer. Cancer Res 54: 2496-2503, 1994.
69. Volm M and Mattern J: Immunohistochemical detection of p53 in non-small-cell lung cancer. J Natl Cancer Inst 86: 1249, 1994.
70. Passlick B, Izbicki JR, Haussinger K, Thetter O and Pantel K: Immunohistochemical detection of P53 protein is not associated with a poor prognosis in non-small-cell lung cancer. J Thorac Cardiovasc Surg 109: 1205-1211, 1995.
71. Fujino M, Dosaka-Akita H, Harada M, Hiroumi H, Kinoshita I, Akie K and Kawakami Y: Prognostic significance of p53 and ras p21 expression in non-small cell lung cancer. Cancer 76: 2457-2463, 1995.
72. Harpole D Jr, Herndon JN, Wolfe WG, Iglehart JD and Marks JR: A prognostic model of recurrence and death in stage I non-small cell lung cancer utilizing presentation, histopathology, and oncoprotein expression. Cancer Res 55: 51-56, 1995.
73. Tormanen U, Eerola AK, Rainio P, Vahakangas K, Soini Y, Sormunen R, Bloigu R, Lehto VP and Paakko P: Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. Cancer Res 55: 5595-5602, 1995.
74. Langendijk JA, Thunnissen FB, Lamers RJ, de Jong JM, ten Velde GP and Wouters EF: The prognostic significance of accumulation of p53 protein in stage III non-small cell lung cancer treated by radiotherapy. Radiother Oncol 36: 218-224, 1995.
75. Fontanini G, Vignati S, Lucchi M, Mussi A, Calcinai A, Boldrini L, Chine S, Silvestri V, Angeletti CA, Basolo F and Bevilacqua G: Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression. Br J Cancer 75: 1295-1301, 1997.
76. Kwa HB, Michalides RJ, Dijkman JH and Mooi WJ: The prognostic value of NCAM, p53 and cyclin Dl in resected nonsmall cell lung cancer. Lung Cancer 14: 207-217, 1996.
77. Ohsaki Y, Toyoshima E, Fujiuchi S, Matsui H, Hirata S, Miyokawa N, Kubo Y and Kikuchi K: bcl-2 and p53 protein expression in non-small cell lung cancers: correlation with survival time. Clin Cancer Res 2: 915-920, 1996.
78. Costa A, Silvestrini R, Mochen C, Lequaglie C, Boracchi P, Faranda A, Vessecchia G and Ravasi G: P53 expression, DNA ploidy and S-phase cell fraction in operable locally advanced non-small-cell lung cancer. Br J Cancer 73: 914-919, 1996.
79. Xu HJ, Cagle PT, Hu SX, Li J and Benedict WF: Altered retinoblastoma and p53 protein status in non-small cell carcinoma of the lung: potential synergistic effects on prognosis. Clin Cancer Res 2: 1169-1176, 1996.
80. Dalquen P, Sauter G, Torhorst J, Schultheiss E, Jordan P, Lehmann S, Soler M, Stulz P, Mihatsch MJ and Gudat F: Nuclear p53 overexpression is an independent prognostic parameter in node-negative non-small cell lung carcinoma. (Review). J Pathol 178: 3-58, 1996.
81. Ishida H, Irie K, Itoh T, Furukawa T and Tokunaga O: The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction. Cancer 80: 1034-1045, 1997.
82. Pastorino U, Andreola S, Tagliabue E, Pezzella F, Incarbone M, Sozzi G, Buyse M, Menard S, Pierotti M and Rilke F: Immunocytochemical markers in stage I lung cancer: relevance to prognosis. J Clin Oncol 15: 2858-2865, 1997.
83. Higashiyama M, Doi O, Kodama K, Yokouchi H, Kasugai T, Ishiguro S, Takami K, Nakayama T and Nishisho I: MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation. Br J Cancer 75: 1302-1308, 1997.
84. Apolinario RM, van der Valk P, de Jong JS, Deville W, van Ark-Otte J, Dingemans AM, van Mourik JC, Postmus PE, Pinedo HM and Giaccone G: Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small-cell lung cancer. J Clin Oncol 15: 2456-2466, 1997.
85. MacKinnon M, Kerr KM, King G, Kennedy MM, Cockburn JS and Jeffrey RR: p53, c-erbB-2 and nm23 expression have no prognostic significance in primary pulmonary adenocarcinoma. Eur J Cardiothorac Surg 11: 838-842, 1997.
86. Yu CJ, Shun CT, Yang PC, Lee YC, Shew JY, Kuo SH and Luh KT: Sialomucin expression is associated with erbB-2 oncoprotein overexpression, early recurrence, and cancer death in non-small-cell lung cancer. Am J Respir Crit Care Med 155: 1419-1427, 1997.
87. Lucchi M, Fontanini G, Mussi A, Vignati S, Ribechini A, Menconi GF, Bevilacqua G and Angeletti CA: Tumor angiogenesis and biologic markers in resected stage I NSCLC. Eur J Cardiothorac Surg 12: 535-541, 1997.
88. Quantin X, Pujol JL, Lehmann M, Simony J, Serre I and Michel FB: Immunohistochemical detection of p53 protein and prognosis of surgically resected non-small-cell lung cancer. Cancer Detect Prev 21: 418-425, 1997.
89. Bourhis J, Lubin R, Roche B, Koscielny S, Bosq J, Dubois I, Talbot M, Marandas P, Schwaab G, Wibault P, Luboinski B, Eschwege F and Soussi T: Analysis of p53 serum antibodies in patients with head and neck squamous cell carcinoma. J Natl Cancer Inst 88: 1228-1233, 1996.
90. Sozzi G, Miozzo M, Donghi R, Pilotti S, Cariani CT, Pastorino U, Della Porta G and Pierotti MA: Deletions of 17p and p53 mutations in preneoplastic lesions of the lung. Cancer Res 52: 6079-6082, 1992.
91. Sundaresan V, Ganly P, Hasleton P, Rudd R, Sinha G, Bleehen NM and Rabbitts P: p53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. Oncogene 7: 1989-1997, 1992.
92. Bennett WP, Colby TV, Travis WD, Borkowski A, Jones RT, Lane DP, Metcalf RA, Samet JM, Takeshima Y, Gu JR, et al: p53 protein accumulates frequently in early bronchial neoplasia. Cancer Res 53: 4817-4822, 1993.
93. Mao L, Hruban RH, Boyle JO, Tockman M and Sidransky D: Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res 54: 1634-1637, 1994.
94. Lubin R, Zalcman G, Bouchet L, Tredanel J, Legros Y, Cazals D, Hirsch A and Soussi T: Serum p53 antibodies as early markers of lung cancer. Nat Med 1: 701-702, 1995.
95. Noguchi M, Maezawa N, Nakanishi Y, Matsuno Y, Shimosato Y and Hirohashi S: Application of the p53 gene mutation pattern for differential diagnosis of primary versus metastatic lung carcinomas. Diagn Mol Pathol 2: 29-35, 1993.
96. Mitsudomi T, Yatabe Y, Koshikawa T, Hatooka S, Shinoda M, Suyama M, Sugiura T, Ogawa M and Takahashi T: Mutations of the P53 tumor suppressor gene as clonal marker for multiple primary lung cancers. J Thorac Cardiovasc Surg 114: 354-360, 1997.
97. Yang HK, Linnoila RI, Conrad NK, Krasna MJ, Aisner SC, Johnson BE and Kelley MJ: TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract. Int J Cancer 64: 229-233, 1995.
98. Martini N and Melamed MR: Multiple primary lung cancers. J Thorac Cardiovasc Surg 70: 606-612, 1975.
99. Reichel MB, Ohgaki H, Petersen I and Kleihues P: p53 mutations in primary human lung tumors and their metastases. Mol Carcinogen 9: 105-109, 1994.
100. Taniguchi Y, Gemma A, Takeda Y, Takenaka K, Niitani H, Kudoh S and Shimada T: Stability of p53 tumor suppressor gene mutations during the process of metastasis and during chemotherapy. Lung Cancer 14: 219-228, 1996.
101. Weinstein JN, Myers TG, O'Connor PM, Friend SH, Fornace Jr A, Kohn KW, Fojo T, Bates SE, Rubinstein LV, Anderson NL, Buolamwini JK, van Osdol WW, Monks AP, Scudiero DA, Sausville EA, Zaharcvitz DW, Bunow B, Viswanadhan VN, Johnson GS, Wittes RE and Paull KD: An information-intensive approach to the molecular pharmacology of cancer. Science 275: 343-349, 1997.
102. Fan S, El-Deiry WS, Bae I, Freeman J, Jondle D, Bhatia K, Fornace Jr AJ, Magrath I, Kohn KW and O'Connor PM: p53 gene mutations are associated with decreased sensitivity of human lymphoma cells to DNA damaging agents. Cancer Res 54: 5824-5830, 1994.
103. Fujiwara T, Grimm EA, Mukhopadhyay T, Zhang WW, Owen-Schaub LB and Roth JA: Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene. Cancer Res 54: 2287-2291, 1994.
104. Rusch V, Klimstra D, Venkatraman E, Oliver J, Martini N, Gralla R, Kris M and Dmitrovsky E: Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer. Cancer Res 55: 5038-5042, 1995.
105. Martini N, Kris MG, Flehinger BJ, Gralla RJ, Bains MS, Burt ME, Heelan R, McCormack PM, Pisters KM, Rigas JR, et al: Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients. Ann Thorac Surg 55: 1365-1373, 1993.
106. Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, Housman DE and Jacks T: p53 status and the efficacy of cancer therapy in vivo. Science 266: 807-810, 1994.
107. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B and Craig RW: Participation of p53 protein in the cellular response to DNA damage. Cancer Res 51: 6304-6311, 1991.
108. O'Connor PM, Jackman J, Jondle D, Bhatia K, Magrath I and Kohn KW: Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines. Cancer Res 53: 776-780, 1993.
109. Brachman DG, Beckett M, Graves D, Haraf D, Vokes E and Weichselbaum RR: p53 mutation does not correlate with radiosensitivity in 24 head and neck cancer cell lines. Cancer Res 53, 3667-3669, 1993.
110. Slichenmyer WJ, Nelson WG, Slebos RJ and Kastan MB: Loss of a p53-associated G1 checkpoint does not decrease cell survival following DNA damage. Cancer Res 53: 4164-4168, 1993.
111. Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, Carey RW, Frei EF and Green MR: A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stase III non-small-cell lung cancer. N Engl J Med 323: 940-945, 1990.
112. Lechevalier T, Arriagada R, Quoix E, Ruffie P, Martin M, Tarayre M, Lacombe-Terrier MJ, Douilland JY and Laplanche A: Radiotherapy alone versus combined chemotherapy and radiotherapy in non-resectable non-small-cell lung cancer: first analysis of a randomized trial in 353 patients. J Natl Cancer Inst 83: 417-423, 1991.
113. Sause WT, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran WJ, Byhardt RW, Turrisi AT, et al: Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst 87: 198-205, 1995.
114. Safran H, King T, Choy H, Gollerkeri A, Kwakwa H, Lopez F, Cole B, Myers J, Tarpey J and Rosmarin A: p53 mutations do not predict response to paclitaxel/radiation for non-small cell lung carcinoma. Cancer 78: 1203-1210, 1996.
115. Fujiwara T, Cai DW, Georges RN, Mukhopadhyay T, Grimm EA and Roth JA. Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model. J Natl Cancer Inst 86: 1458-1462, 1994
116. Fujiwara T, Grimm EA, Mukhopadhyay T, Cai DW, Owen-Schaub LB and Roth JA: A retroviral wild-type p53 expression vector penetrates human lung cancer spheroids and inhibits growth by inducing apoptosis. Cancer Res 53: 4129-4133, 1993.
117. Roth JA, Nguyen D, Lawrence DD, Kemp BL, Carrasco CH, Ferson DZ, Hong WK, Komaki R, Lee JJ, Nesbitt JC, Pisters KM, Putnam JB, Schea R, Shin DM, Walsh GL, Dolormente MM, Han CI, Martin FD, Yen N, Xu K, Stephens LC, McDonnell TJ, Mukhopadhyay T and Cai D: Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat Med 2: 985-991, 1996.
118. Nguyen D, Spitz FR, Yen N, Cristiano RJ and Roth JA: Gene therapy for lung cancer: enhancement of tumor suppression by a combination of sequential systemic cisplatin and adenovirus-mediated p53 gene transfer. J Thorac Cardiovasc Surg 112: 1372-1376, 1996.
119. Nielsen LL and Maneval DC: p53 tumor suppresor gene therapy for cancer. Cancer Gene Ther 5: 52-63, 1998.