Lung Cancer

  • Francis P. Worden
  • Gregory P. Kalemkerian
Part of the Cancer Treatment and Research book series (CTAR, volume 106)


Lung cancer is the most frequently diagnosed cancer in the world. In the United States alone, 164,100 new cases will be diagnosed and 156,900 people will die from lung cancer in the year 2000 (1). Since the early 1950’s, lung cancer has been the leading cause of cancer-related mortality among American men, and has recently surpassed breast cancer to become the leading cause of cancer-related mortality in American women (2). Between 1990 and 1996, overall lung cancer incidence and mortality rates in American men have decreased by 2.6% and 1.6% per year, respectively (1). In contrast, lung cancer incidence and mortality rates in women have just recently shown evidence of stabilization, while the absolute number of annual lung cancer deaths in women continues to rise.


Lung Cancer Natl Cancer Inst Bronchial Epithelial Cell Environmental Tobacco Smoke Lung Cancer Risk 
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.
    Greenlee R, Taylor M, Bolden S, Wingo P. Cancer Statistics, 2000. CA Cancer J Clin 2000; 50:7–33.PubMedGoogle Scholar
  2. 2.
    Wingo P, Ries L, Giovino Get al.Annual report to the nation on the status of cancer 19731996, with a special section on lung cancer and tobacco smoking. J Natl Cancer Inst 1999; 91:675–690.PubMedGoogle Scholar
  3. 3.
    Loeb L, Emster V, Warner Ket al.Smoking and lung cancer: an overview. Cancer Res 1984; 44:5940–58.PubMedGoogle Scholar
  4. 4.
    Garfinkel L. Trends in cigarette smoking in the United States. Prevent Med 1997; 26:447–50.Google Scholar
  5. 5.
    U.S. Department of Health and Human Services. The health benefits of smoking cessation: a report of the Surgeon General. DHHS Publication CDC90–8416. Washington, DC, U.S. Government Printing Office, 1990.Google Scholar
  6. 6.
    Moldeus P, Cotgreave IA, Berggren M. Lung protection by thiol-containing antioxidant: Nacetylcysteine. Respiration 1986; 50:31–43.Google Scholar
  7. 7.
    Church DF, Pryor WA. Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 1985: 64:111–26.PubMedGoogle Scholar
  8. 8.
    Wald NJ, Boreham J, Bailey A, Ritchie C, Haddow JE, Knight G. Urinary cotinine as marker of breathing other people’s tobacco smoke. Lancet. 1984; i:230–1.Google Scholar
  9. 9.
    Wald N, Ritchie C. Validation of studies on lung cancer in non-smokers married to smokers (letter). Lancet 1984; i ;1067.Google Scholar
  10. 10.
    Law MR, Hackshaw AK. Environmental tobacco smoke. Br Med Bull 1996; 52:22–34.PubMedGoogle Scholar
  11. 11.
    Wald NJ, Nanchahal K, Thompson SG, Cuckle HS. Does breathing other people’s tobacco smoke cause lung cancer? Brit Med J 1986; 293:1217–22.Google Scholar
  12. 12.
    Boffetta P, Agudo A, Ahrens Wet al.Multicenter case-control study of exposure to environmental tobacco smoke and lung cancer in Europe. J Natl Cancer Inst 1998; 90:1440–50.PubMedGoogle Scholar
  13. 13.
    Sockrider M. The respiratory effects of passive tobacco smoking. Current Opin Pulm Med 1996; 2:129–33.Google Scholar
  14. 14.
    Matanoski G, Kanchanaraksa S, Lantry Det al.Characteristics of nonsmoking women in NHANES I and NHANES I epidemiologic follow-up study with exposure to spouses who smoke. Am J Epidemiol 1995; 142:149–57.PubMedGoogle Scholar
  15. 15.
    Lee PN. Difficulties in assessing the relationship between passive smoking and lung cancer. Statist Methods Med Res 1998; 7:137–63.Google Scholar
  16. 16.
    Skillrud DM, Offord KP, Miller RD. Higher risk of lung cancer in chronic obstructive pulmonary disease: a prospective, matched, controlled study. Ann Int Med 1986; 105:503–7.PubMedGoogle Scholar
  17. 17.
    Aguayo SM. Determinants of susceptibility to cigarette smoke: potential roles for neuroendocrine cells and neuropeptides in airway inflammation, airway wall remodelling, and chronic airflow obstruction. Am J Respir Crit Care Med 1994; 149:1692–8.PubMedGoogle Scholar
  18. 18.
    Gosney JR, Sissons M, Allibone al.Pulmonary endocrine cells in chronic bronchitis and emphysema. J Pathol 1989; 147:127–33.Google Scholar
  19. 19.
    Aguayo SM, Miller YE, King TE. Idiopathic hyperplasia of pulmonary neuroendocrine cells. N Engl J Med 1993; 328:581–2.Google Scholar
  20. 20.
    Licciardello JT, Spitz MR, Hong WK. Multiple primary cancer in patients with cancer of the head and neck: second cancers of the head and neck, esophagus and lung. Int J Radiat Oncol Biol Phys 1989; 17:467–76.PubMedGoogle Scholar
  21. 21.
    Lippman SM, Hong WK. Second malignant tumors in head and neck squamous cell carcinoma: the overshadowing threat for patients with early-stage disease. Int Radiat Oncol Biol Phys 1989; 17:691–4.Google Scholar
  22. 22.
    Cooper JS, Pajak TF, Rubin Pet al.Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications for chemoprevention based on the RTOG experience. Int J Radiat Oncol 1989; 17:449–56.Google Scholar
  23. 23.
    Sagman U, Lishner M, Maki Eet al.Second primary malignancies following diagnosis of small cell lung cancer. J Clin Oncol 1992; 10:1525–33.PubMedGoogle Scholar
  24. 24.
    Heyne KH, Lippman SM, Lee JJet al.The incidence of second primary tumors in long-term survivors of small cell lung cancer. J Clin Oncol 1992; 10:1519–24.PubMedGoogle Scholar
  25. 25.
    Johnson BE. Second lung cancers in patients after treatment for an initial lung cancer. J Natl Cancer Inst 1998; 90:1335–45.PubMedGoogle Scholar
  26. 26.
    Samet JM. “Radon.” In:Epidemiology of Lung Cancer JM Sameted. New York: Marcel Dekker, 1994; 219–43.Google Scholar
  27. 27.
    Committee of the National Research Council on the Biologic Effects of Ionizing Radiation (BEIR-IV). Health risks of radon and other internally deposited alpha-emitters. Washington, DC: National Academy Press, 1988.Google Scholar
  28. 28.
    Harley NH. “Radon and daughters.” In:Environmental Toxicants - Human Exposures and Their Health Effects M Lippmanned. New York: Van Nostrand Reinhold, 1992; 520–42.Google Scholar
  29. 29.
    United States Environmental Protection Agency. Respiratory health effects of passive smoking: lung cancer and other disorders. Publication EPA/600/6–0/006F. Washington, DC: EPA, 1992.Google Scholar
  30. 30.
    Lubin JH, Boice JD, Edling Cet al.Lung cancer in radon-exposed miners and estimation of risk from indoor exposure. J Natl Cancer Inst 1995; 87:817–27.PubMedGoogle Scholar
  31. 31.
    Tokhata GK, Lilienfeld AM. Familial aggregation of lung cancer in humans. J Nati Cancer Inst 1963; 30:289–312.Google Scholar
  32. 32.
    Tokuhata GK, Lilienfeld AM. Familial aggregation of lung cancer among hospital patients. Public Health Rep 1963; 78:277–83.PubMedGoogle Scholar
  33. 33.
    Kunitoh H, Sekine I, Kubota Ket al.Histologic types of lung carcinoma and related family history of anatomic sites and histologic types of cancers. Cancer 1999; 87:1182–8.Google Scholar
  34. 34.
    Osann KE. Lung cancer in women: the importance of smoking, family history of cancer, and medical history of respiratory disease. Cancer Res 1991; 51:4893–7.PubMedGoogle Scholar
  35. 35.
    Wu AH, Fontham ET, Reynolds Pet al.Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States. Am J Epidemiol 1996; 143:535–42.PubMedGoogle Scholar
  36. 36.
    Ambrosone CB, Rao U, Michalek AM, Cummings KM, Mettlin CJ. Lung cancer histologic types and family history of cancer. Analysis of histologic subtypes of 872 patients with primary lung cancer. Cancer 1993; 72:1192–8.PubMedGoogle Scholar
  37. 37.
    Sellers TA, Bailey-Wilson J, Elston RCet al.Evidence for Mendelian inheritance in the pathogenesis of lung cancer. J Natl Cancer Inst 1990; 82:1272–9.PubMedGoogle Scholar
  38. 38.
    Karki NT, Pokela R, Nuutinen L, Pelkonen O. Aryl hydrocarbon hydroxylase in lymphocytes and lung tissue from lung cancer patients and controls. Int.1 Cancer 1987; 39:56570.Google Scholar
  39. 39.
    Hirvonen A. Genetic factors in individual responses to environmental exposures. J Occup Environ Med 1995; 37:37–43.PubMedGoogle Scholar
  40. 40.
    Raunio H, Husgafvel-Pursianen K, Anttila Set al.Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility - a review. Gene 1995; 159:113–21.PubMedGoogle Scholar
  41. 41.
    Ziegler RG, Mayne ST, Swanson CA. Nutrition and lung cancer. Cancer Causes Control 1996; 7:157–177.PubMedGoogle Scholar
  42. 42.
    Samet JM. “Lung Cancer.” In: P Greenwald, BS Kramer, DL Weed, eds.Cancer Prevention and Control.New York: Marcel Dekker, 1995; 561–83.Google Scholar
  43. 43.
    Willet WC, MacMahon B, Diet and cancer - an overview. N Engl J Med 1984; 310:697–703.Google Scholar
  44. 44.
    Pastorino U. “Chemoprevention of Lung Cancer in High-Risk Individuals.” In:Comprehensive Textbook of Thoracic OncologyJAisnerRArriagadaMGreenNMartiniMPerry, eds. Baltimore:Williams &Wilkens, 1996;1053–79.Google Scholar
  45. 45.
    Peto R, Doll R, Buckley JD, Sporn MB. Can dietary 13-carotene materially reduce human cancer rates? Nature 1981; 290:201–9.PubMedGoogle Scholar
  46. 46.
    Sabichi AL, Birrer MJ. The molecular biology of lung cancer: application to early detection and prevention. Oncology 1993; 7:19–26.PubMedGoogle Scholar
  47. 47.
    Birrer MJ, Alani R, Cuttitta Fet al.Early events in the neoplastic transformation of respiratory epithelium. J Natl Cancer Inst Monogr 1992; 13:31–7.PubMedGoogle Scholar
  48. 48.
    Shaw GL. “Carcinogenesis and lung cancer prevention.” In:Biology of Lung Cancer MA Kane PA Bunneds. New York: Marcel Dekker, 1998; 99–117.Google Scholar
  49. 49.
    Cairns J. The origin of human cancers. Nature 1981; 289:353–7.PubMedGoogle Scholar
  50. 50.
    Van Duuren BL, Goldschmidt BM. Co-carcinogenic tumor-promoting agents in tobacco carcinogenesis. J Natl Cancer Inst 1976; 56:1237–42.PubMedGoogle Scholar
  51. 51.
    Huncharek M. Changing risk groups for malignant mesoth el i oma. Cancer 1992; 69:2704–11.PubMedGoogle Scholar
  52. 52.
    Barbacid M.rasgenes. Ann Rev Biochem 1987; 56:799–827.Google Scholar
  53. 53.
    Slebos RJ, Kibbelaar RE, Dalesio 0et al.K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 1990; 323:561–65.PubMedGoogle Scholar
  54. 54.
    Rodenhuis S, Slebos RJ. Clinical significance of ras oncogene mutations in non-small cell lung cancer. Lung Cancer 1992; 52 (suppl):2665s-9s.Google Scholar
  55. 55.
    Slebos R, Rodenhuis S. The ras gene family in human non-small cell lung cancer. J Natl Cancer Inst Monogr 1992; 13:23–9.PubMedGoogle Scholar
  56. 56.
    Rosell R, Li S, Skacel Zet al.Prognostic impact of mutated k-ras gene in surgically resected non-small cell lung cancer patients. Oncogene 1993; 8:2407–12.PubMedGoogle Scholar
  57. 57.
    Mitsudomi T, Steinberg SM, Oie Het al.Ras gene mutations in non-small cell lung cancers are associated with shortened survival irrespective of treatment intent. Cancer Res 1991; 51:4999–5002.PubMedGoogle Scholar
  58. 58.
    Keohavong P, DeMichele MA, Melacrinos ACet al.Detection of k-ras mutations in lung carcinomas: relationship to prognosis. Clin Cancer Res 1996; 2:411–8.PubMedGoogle Scholar
  59. 59.
    Prins J, De Vries E, Mulder N. The myc family of oncogenes and their presence and importance in small-cell lung carcinoma and other tumour types. Anticancer Res 1993; 13:1373–85.Google Scholar
  60. 60.
    Shivaishi M, Nogochi M, Shimosato Yet al.Amplification of proto-onocogenes in surgical specimens of human lung cancer. Cancer Res 1989; 49:6474–79.Google Scholar
  61. 61.
    Takahashi T, Obata Y, Sekido Y, et al. Expression and amplification of myc gene family in small cell lung cancer and its relation to biological characteristics. Cancer Res 1989; 49:2683–88.Google Scholar
  62. 62.
    Johnson B, Ihde D, Makuch R, et al. myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course. J Clin Invest 1987; 79:1629–34.PubMedGoogle Scholar
  63. 63.
    Brennen J, O’Connor T, Makuch RW, et al.mycfamily DNA amplification in 107 tumors and tumor cell lines from patients with small-cell lung ca treated with different combination chemo regimens. Cancer Res 1991; 51:1708–12.Google Scholar
  64. 64.
    Stern DF, Heffernan PA, Weinberg RA. A product of the neu proto-oncogene, is a receptor like protein associated with tyrosine kinase activity, p185. Mol Cell Biol 1986; 6:1729–40.PubMedGoogle Scholar
  65. 65.
    Noguchi M, Murakami M, Bennett Wet al.Biological consequences of overexpression of a transfected c-erb-2 gene in immortalized human bronchial epithelial cells. Cancer Res 1993; 53: 2035–43.PubMedGoogle Scholar
  66. 66.
    Kern JA, Schwartz DA, Nordberg JEet al.P185neuexpression in human lung adenocarcinomas predicts shortened survival. Cancer Res 1990; 50:5184–91.PubMedGoogle Scholar
  67. 67.
    Shi D, He G, Cao Set al.Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. Mol Carcinogenesis 1992; 5:213–18.Google Scholar
  68. 68.
    Sidransky D, Hollstein M. Clinical implication of the p53 gene. Ann Rev Med 1996; 47:285–301.PubMedGoogle Scholar
  69. 69.
    Chiba I, Takahashi T, Nau Met al.Mutations in the p53 gene are frequent in primary, resected non small cell lung cancer. Oncogene 1990; 5:1603–10.PubMedGoogle Scholar
  70. 70.
    D’Amico D, Carbone D, Mitsudomi Tet al.High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene 1992; 7:339–46.PubMedGoogle Scholar
  71. 71.
    Denissenko MF, Pao A, Tang MS, Pfeifer GP. Preferential formation of benzo(a)pyrene adducts at lung cancer mutational hotspots inp53.Science 1996: 274:430–2.PubMedGoogle Scholar
  72. 72.
    Quinlan DC, Davidson AG, Summers CLetal.Accumulation of p53 protein correlates with a poor prognosis in human cancer. Cancer Res 1992; 52:4828–31.PubMedGoogle Scholar
  73. 73.
    Fujino M, Dosaka-Akita H, Harada Met al.Prognostic significance of p53 and ras p21 expression in nonsmall cell lung cancer. Cancer 1995; 76:2457–63.PubMedGoogle Scholar
  74. 74.
    Mitsudomi T, Lam S, Shirakusa Tet al.Detection and sequencing of p53 gene mutations in bronchial biopsy samples in patients with lung cancer. Chest 1993; 104:362–5.PubMedGoogle Scholar
  75. 75.
    Lee J, Yoon A, Kalapurakal Set al.Expression of p53 oncoprotein in non-small cell lung cancer: a favorable prognostic factor. J Clin Oncol 1995; 13:1893–1903.PubMedGoogle Scholar
  76. 76.
    Ewen ME. The cell cycle and the retinoblastoma protein family. Cancer Metast Rev 1994; 13:45–66.Google Scholar
  77. 77.
    Harbour JW, Lai SL, Whang-Peng Jet al.Abnormalities in structure and expression of the human retinoblastoma gene in small cell lung cancer. Science 1988; 241:353–7.PubMedGoogle Scholar
  78. 78.
    Shimizu E, Coxon A, Otterson Get al.RB protein status and clinical correlation from 171 cell lines representing lung cancer, extrapulnionary small cell carcinoma, and mesothelioma. Oncogene 1994; 9:2441–8.PubMedGoogle Scholar
  79. 79.
    Xu H, Hu S, Cagle Pet al.Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas. Cancer Res 1991; 51:2753–59.Google Scholar
  80. 80.
    Xu HJ, Quinlan DC, Davidson AGet al.Altered retinoblastoma protein expression and prognosis in early stage non-small cell lung carcinoma. J Natl Cancer Inst 1994; 86:695–99.PubMedGoogle Scholar
  81. 81.
    Lee JS, Kalapurakal S, Ro JY, Hong WK. Prognostic significance of retinoblastoma protein expression in non-small cell lung cancer. Proc Am Assoc Cancer Res 1995; 36:3787.Google Scholar
  82. 82.
    Hibi K, Takahashi T, Yamakawa Wet al.Three distinct regions involved in 3p deletion in human lung cancer. Oncogene 1992; 7:445–9.PubMedGoogle Scholar
  83. 83.
    Hung J, Kishimoto Y, Sugio Ket al.Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA 1995; 273:558–63.PubMedGoogle Scholar
  84. 84.
    Linnolia RI, Jensen SM, Laskin E, Buchhagen DL. Frequent alterations of chromosome 3p in the peripheral lung during pulmonary carcinogenesis in man. Proc Am Assoc Cancer Res 1995; 36:130.Google Scholar
  85. 85.
    Thiberville L, Payne P, VielkindsJ et al.Evidence of cumulative gene losses with progression of premalignant epithelial lesions to carcinoma of the bronchus. Cancer Res 1995; 55:5133–9.PubMedGoogle Scholar
  86. 86.
    Siegfried JM, Birrer MJ, Cuttitta K. “Detection of growth factor effects and expression in normal and neoplastic human bronchial cells.” In:Transformation of Human Epithelial Cells: Molecular Oncogenic Mechanisms Milo GEet al., eds. Boca Raton: CRC Press, 1992; 13–29.Google Scholar
  87. 87.
    Carpenter G, Zendegui JG. Epidermal growth factors for normal human bronchial epithelial cells. Exp Cell Res 1981; 41:3538–42.Google Scholar
  88. 88.
    Cuttitta F, Carney DN, Mulshine JLet al.Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 1985; 316:823–6.PubMedGoogle Scholar
  89. 89.
    Aguayo SM, Kane M, King TE. Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers. J Clin Invest 1989; 84:1105–13.PubMedGoogle Scholar
  90. 90.
    Shaw GL, Mulshine JL. “General strategies for early detection: new ideas and future directions.” In:Lung Cancer - Principles and Practice HI Pass JB Mitchell DH Johnson AT Turrisieds. Philadelphia: Lippincott-Raven, 1996. 329–40.Google Scholar
  91. 91.
    Kurie JM, Shin HJ, Lee JSet al.Increased epidermal growth factor receptor expression in metaplastic bronchial epithelium. Clin Cancer Res 1996; 2:1787–93.PubMedGoogle Scholar
  92. 92.
    Rusch V, Klimstra D, Venkatraman E. Pisters PW, Lagenfeld J, Dmitrovsky E. Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res 1997; 3:515–22.PubMedGoogle Scholar
  93. 93.
    Slaughter DP, Southwick HW, Smejkal W. Field cancerization of oral stratified squamous epithelium: clinical implications of multicentric origin. Cancer 1953; 6:963–8.PubMedGoogle Scholar
  94. 94.
    Auerbach O, Patrick TG, Stout AP, et al. The anatomical approach to the study of smoking and bronchogenic carcinoma: a preliminary report of forty-one cases. Cancer 1956; 9:76–83.PubMedGoogle Scholar
  95. 95.
    Auerbach O Gere B Forman JBet al.Changes in the bronchial epithelium in relation to smoking and cancer of the lung. N Engl J Med 1957; 256:97–104.PubMedGoogle Scholar
  96. 96.
    Auerbach O, Stout AP, Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking and cancer and in relation to lung cancer. N Engl J Med 1961; 265:253–67.PubMedGoogle Scholar
  97. 97.
    Smith Al Hung J Walker Let al.Extensive areas of aneuploidy are present in the respiratory epithelium of lung cancer patients. Br J Cancer 1996; 73:203–9.PubMedGoogle Scholar
  98. 98.
    Keith RL, Miller YE, Gemmill, RMet al.Angiogenic squamous dysplasia in bronchi of individuals at high risk for lung cancer. Clin Cancer Res 2000; 6:1616–25.PubMedGoogle Scholar
  99. 99.
    .Sudaresan V, Ganly P, Haselton Pet al.P53 and chromosome 3 abnormalities, characteristic of malignant lung tumours, are detectable in preinvasive lesions of the bronchus. Oncogene 1992;7:1989-97. Google Scholar
  100. 100.
    Hung J, Kishimoto Y, Sugio Ket al.Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung cancer. JAMA 1995; 273:558–63.PubMedGoogle Scholar
  101. 101.
    Miozzo M, Sozzi G, Musso Ket al.Microsatellite alterations in bronchial and sputum specimens of lung cancer patients. Cancer Res 1996; 56:2285–8.PubMedGoogle Scholar
  102. 102.
    Maollee JS, Kurie JMet al.Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst 1997; 89:857–62.Google Scholar
  103. 103.
    Wistuba II, Lam S, Behrens Cet al.Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 1997; 89:1366–73.PubMedGoogle Scholar
  104. 104.
    Sozzi G, Miozzo M, Tagliabue Eet al.Cytogenetic abnormalities and overexpression of receptors for growth normal bronchial epithelium and tumor samples of lung cancer patients. Cancer Res 1991; 51:400–4.PubMedGoogle Scholar
  105. 105.
    Rusch V, Klimstra D, Linkov I Dmitrovsky E.Aberrant expression ofp53 or the epidermal growth factor receptor is frequent in early bronchial neoplasia, and coexpression precedes squamous cell carcinoma development. Cancer Res 1995; 55:1365–72.Google Scholar
  106. 106.
    Vermylen P, Roufosse C, Ninane V, Sculier JP. Biology of pulmonary preneoplastic lesions. Cancer Treat Rev 1997; 23:241–62.PubMedGoogle Scholar
  107. 107.
    Westra WH, Baas IO, Hruban RH, et al. K-ras oncogene activation in atypical alveolar hyperplasia of the human lung. Cancer Res 1996; 56:2224–8.PubMedGoogle Scholar
  108. 108.
    Lippman SM, Kessler JF, Meyskens FL. Retinoids as preventive preventive and therapeutic anticancer agents (part II). Cancer Treat Rep 1987; 71:493–515.PubMedGoogle Scholar
  109. 109.
    Bertram JS, Kolonel LN, Meyskens FL. Rationale and strategies for chemoprevention of cancer in humans. Cancer Res 1987; 47:3012–31.PubMedGoogle Scholar
  110. 110.
    Kelloff G, Boone CW, Steele VEet al.Progress in cancer chemoprevention: perspectives on agent selection and short-term clinical intervention trials. Cancer Res 1994; 54(suppl):2015 s245.Google Scholar
  111. 111.
    Mangelsdorf DJ Umesono K, Evans R. “The Retinoid Receptors.” In:The Retinoids2nd editionMB Sporn AB Roberts DS Goodmaneds. New York: Raven Press, 1994; 319–49.Google Scholar
  112. 112.
    Wolbach SB, Howe PR, Tissue changes following deprivation of fat soluble A vitamin. J Exp Med 1925; 42:753–77.PubMedGoogle Scholar
  113. 113.
    Goodman DS. Vitamin A and retinoids in health and disease. N Engl J Med 1984; 310:1023–31.PubMedGoogle Scholar
  114. 114.
    Houle B, Rochette-Egly C, Bradley WEC. Tumor-suppressive effect of the retinoic acid receptor beta in human epidermoid lung cancer cells. Proc Natl Acad Sci USA 1993; 90:985–9.PubMedGoogle Scholar
  115. 115.
    Lotan R. Retinoids and chemoprevention of aerodigestive tract cancer. Cancer Metast Rev 1997; 16:349–56.Google Scholar
  116. 116.
    Xu XC, Sozzi G, Lee JSet al.Suppression of retinoic acid receptor p in non-small cell lung cancer in vivo: implications for lung cancer development. J Natl Cancer Inst 1997; 89:624–9.Google Scholar
  117. 117.
    Kim YH, Dohi DF, Han GRet al.Retinoid refractoriness occurs during lung carcinogenesis despite functional retinoid receptors. Cancer Res 1995; 55:5603–10.PubMedGoogle Scholar
  118. 118.
    Lotan R, Xu XC, Lippman SMet al.Suppression of retinoic acid receptor-I3 in premalignant oral lesions and its up-regulation by isotretinoin. N Engl J Med 1995; 332:1405–10.PubMedGoogle Scholar
  119. 119.
    Hong WK, Itri LM. “Retinoids and human cancers.” In:The Retinoids2nd editionMB Sporn AB Roberts DS Goodmaneds. NewYork: Raven Press, 1994:597–630.Google Scholar
  120. 120.
    Lee JS, Lippman SM, Benner SEet al.Randomized placebo-controlled trial of isotrentinoin in chemoprevention of bronchial squamous metaplasia. J Clin Oncol 1994; 12:937–45.Google Scholar
  121. 121.
    Xu XC, Lee JS, Lee JJet al.Nuclear retinoid acid receptor beta in bronchial epithelium of smokers before and during chemoprevention. J Natl Cancer Inst 1999; 91:1317–21.PubMedGoogle Scholar
  122. 122.
    Ayoub J, Jean-Francois R, Cormier Yet al.Placebo-controlled trial of 13-cis-retinoic acid activity on retinoic acid receptor-I3 expression in a population at high risk: implications for chemoprevention of lung cancer. J Clin Oncol 1999; 11:3546–52.Google Scholar
  123. 123.
    Bauernfiend JC. The safe use of vitamin A: a report of the International Vitamin A Consultative Group. Washington, DC: The Nutrition Foundation, 1980.Google Scholar
  124. 124.
    Bendich A, Langseth L. Safety of vitamin A. Am J Clin Nutr 1989; 49:358–71.PubMedGoogle Scholar
  125. 125.
    Formelli F, Clerici M, Campa Tet al.Five-year administration of fenretinide: pharmacokinetics and effects on plasma retinol concentrations. J Clin Oncol 1993; 11:2036–42.PubMedGoogle Scholar
  126. 126.
    Cobleigh MA, Dowlatshahi K, Deutsch TAet al.Phase 1/II trial of tamoxifen with or without fenretinide, an analog of vitamin A, in women with metastatic breast cancer. J Clin Oncol 1993; 11:474–7.PubMedGoogle Scholar
  127. 127.
    Costa A, Malone W, Perloff Met al.Tolerability of the synthetic retinoid fenretinide. Eur J Cancer Clin Oncol 1989; 25:805–8.PubMedGoogle Scholar
  128. 128.
    Naik HR, Kalemkerian G, Pienta KJ. 4-Hydroxyphenylretinamide in the chemoprevention of cancer. Adv Pharmacol 1995; 33:315–47.PubMedGoogle Scholar
  129. 129.
    Kalemkerian GP, Slusher R, Ramalingam Set al.Growth inhibition and induction of apoptosis by fenretinide in small cell lung cancer cell lines. J Natl Cancer Inst 1995; 87:1674–80.PubMedGoogle Scholar
  130. 130.
    Zou CP, Kurie JM, Lotan D, Zou CC, Hong WK, Lotan R. Higher potency of N-(4- hydroxyphenyl)retinatnide than all-trans-retinoic acid in induction of apoptosis in non-small cell lung cancer cell lines. Clin Cancer Res 1998; 4:1345–55.PubMedGoogle Scholar
  131. 131.
    Sun SY, Li W, Yue P, Lippman SM, Hong WK, Lotan R. Mediation of N-(4- hydroxyphenyl) retinamide-induced apoptosis in human cancer cells by different mechanisms. Cancer Res 1999; 59:2493–8.PubMedGoogle Scholar
  132. 132.
    Dimitrov NV, Boone CW, Hay MBet al.Plasma P–carotene levels –kinetice patterns during administration of various doses of ß–carotene. J Nutr Growth Cancer 1987; 3:227–37.Google Scholar
  133. 133.
    Burton GW, Ingold KU. ß–carotene–an unusual type of lipid antioxidant. Science 1984: 224:569–73.PubMedGoogle Scholar
  134. 134.
    The a-Tocopherol, P-Carotene Cancer Prevention Study Group. The effects of vitamin E and I3-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994; 330:1029–35.Google Scholar
  135. 135.
    Omenn GS, Goodman GE, Thomquist MDet al.Effects of P-carotene and vitamin A on lung cancer and cardiovascular disease. N Eng J Med 1996; 334:1150–5.Google Scholar
  136. 136.
    Xu MJ, Plezia PM, Alberts DSet al.Reduction in plasma or skin a-tocopherol concentration with long-term oral administration of I3-carotene in humans and mice. J Natl Cancer Inst 1992; 84:1559–65.PubMedGoogle Scholar
  137. 137.
    .Paolini M, Cantelli-Forti G, Perocco P, et al.Co-carcinogenic effect of 13-carotene. Nature 1999; 29:760–1.Google Scholar
  138. 138.
    Vane RJ, Botting RM. Mechanism of action of aspirin-like drugs. Semin Arthritis Rheum. 1997; 26:2–10.PubMedGoogle Scholar
  139. 139.
    . Williams CS, DuBois RN. Prostaglandin endoperoxide H synthase: why two isoforms? Am J Physiol 1996; 270:6393–400.Google Scholar
  140. 140.
    Wolff H, Saukkonen K, Antila Set al.Expression of cyclooxygenase-2 in human lung carcinoma. Cancer Res 1998; 58:4997–5001.PubMedGoogle Scholar
  141. 141.
    Thun MJ. Aspirin, NSAIDs, and digestive tract cancers. Cancer Metast Rev 1994; 13:26977.Google Scholar
  142. 142.
    Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiol 1994; 5:138–46.Google Scholar
  143. 143.
    Duperron C, Castonguay A. Chemopreventive efficacies of aspirin and suldindac against lung tumorigenesis in A/J mice. Carcinogenesis 1993; 14:1975–7.Google Scholar
  144. 144.
    Jalbert G, Castonyguay A. Effects of NSAIDs on NNK-induced pulmonary and gastric tumorigenesis in A/J mice. Cancer Letter 1992; 66:21–8.Google Scholar
  145. 145.
    Malkinson AM, Koski KM, Dwyer-Nield LDet al.Inhibition of 4-(methylnitrosamino)-1- (3-pyridy1)-1-butanone (NNK)- induced mouse lung tumor formatin by FGN-1 (sulindac sulfone). Carcinogenesis 1998; 19:1353–6.PubMedGoogle Scholar
  146. 146.
    Bilodeau JF, Wang M, Chung FL, Castonguay A. Effects of nonsteroidal antiinflammatory drugs on oxidative pathways in A/J mice. Free Rad Biol Med 1995; 18:47–54.PubMedGoogle Scholar
  147. 147.
    Jalbert G, Castonguay A. Effects of NSAIDs on NNK-induced pulmonary and gastric tumorigenesis in A/J mice. Cancer Letter 1992; 66:21–8.Google Scholar
  148. 148.
    Rioux N, Castonguay A. Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Cancer Res 1998; 58:5354–60.PubMedGoogle Scholar
  149. 149.
    Webb WR. Clinical evaluation of a new mucolytic agent acetylcysteine. J Thorac Cardiovasc Surg 1962; 44:330–43.PubMedGoogle Scholar
  150. 150.
    Tedeschi M, Bohm S, Di Re Fet al.Glutathione and detoxification. Cancer Treat Rev 1990; 17:203–8.PubMedGoogle Scholar
  151. 151.
    DeFlora S, Bennicelli C, Zannacchi Pet al.In vitro effects of N-acetylcysteine on the mutagenecity of direct-acting compounds and procarcinogens. Carcinogenesis 1984; 5:505–10.Google Scholar
  152. 152.
    DeFlora S, Izzotti A, D’Agostini Fet al.Antioxidant activity and other mechanisms of thiols involved in chemoprevention of mutation and cancer. Am J Med 1991; 91:122S–30S.Google Scholar
  153. 153.
    Meister A, Anderson M. Glutathione. Ann Rev Biochem 1983; 52:711–60.PubMedGoogle Scholar
  154. 154.
    de Vries N, van Zandwijk N, Pastorino U. Chemoprevention of head and neck and lung (pre)cancer. Rec Results Cancer Res 1999; 151:20–5.Google Scholar
  155. 155.
    de Vries N, van Zandwijk N, Pastorino U. The EUROSCAN study. Br J Cancer 1991; 64:985–9.PubMedGoogle Scholar
  156. 156.
    Van Zandwijk N, Pastorino U, de Vries N, Dalesio 0, Van Tinteren H. Randomized trial of chemoprevention with vitamin A and N-acetylcysteine in patients with cancer of the upper and lower airways: the Euroscan study. Proc Am Soc Clin Oncol 1999; 18:464a.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Francis P. Worden
  • Gregory P. Kalemkerian

There are no affiliations available

Personalised recommendations