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Molecular oncology in pancreatic cancer

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Abstract

Cancer of the pancreas still has a very poor prognosis despite improved diagnostic methods and therapeutic regimens. The reasons for the aggressiveness of this cancer are not known, and the molecular mechanisms that govern the growth of pancreatic cancer cells are still not clearly defined. During the past two decades the development of new molecular biological techniques has offered new perspectives for a better understanding of pancreatic cancer. Tumor markers such as CA19-9 and CEA are used for diagnosis and for following the postoperative course of cancer patients. Characterization of pancreatic cancer cells using several molecular biological techniques has revealed overexpression or altered expression of growth factors and adhesion molecules, implying altered cell-cell and growth-regulatory interactions. In pancreatic cancer mutations in oncogenes and tumor suppressor genes are frequently detected in p53 and K-ras. This article reviews the possible molecular approaches for diagnosis, prognosis, or even therapy of pancreatic cancer.

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Abbreviations

ECM :

Extracellular matrix

EGF :

Epidermal growth factor

aFGF :

Acidic fibroblast growth factor

bFGF :

Basic fibroblast growth factor

TGF :

Transforming growth factor

References

  1. Gudjonsson B (1987) Cancer of the pancreas: 50 years of surgery. Cancer 60:2284–2303

    CAS  PubMed  Google Scholar 

  2. Beger HG, Büchler M, Friess H (1994) Chirurgische Ergebnisse und Indikation zu adjuvanten Maßnahmen beim Pankreaskarzinom. Chirurg 65:246–252

    CAS  PubMed  Google Scholar 

  3. Hollywood DP, Barton CM (1993) Oncogenes and tumor suppressor genes. In: Lemoine NR, Neoptolemos JP, Cooke T (eds) Cancer: a molecular approach. Blackwell Scientific, Oxford, pp 2–41

    Google Scholar 

  4. Safi F, Beger HG, Bittner R, Büchler M, Krautzberger W (1986) CA19–9 and pancreatic adenocarcinoma. Cancer 57:779–783

    Google Scholar 

  5. Pleskow DK, Berger HJ, Gyves J, Allen E, McLean A, Podosky K (1989) Evaluation of a serologic marker, CA19–9, in the diagnosis of pancreatic cancer. Ann Intern Med 110:704–709

    Google Scholar 

  6. Safi F, Roscher R, Beger HG (1989) Tumor markers in pancreatic cancer. Sensitivity and specificity of CA 19–9. Hepatogastroenterology 36:419–423

    Google Scholar 

  7. Kübel R, Büchler M, Bosslet K, Baczaco K, Beger HG (1987) Immunohistochemical analysis of new monoclonal antibodies for pancreatic carcinoma associated antigens. In: Klapdor R (ed) New tumor markers and their monoclonal antibodies. Thieme. Stuttgart, pp. 354–358

    Google Scholar 

  8. Longenecker BM, Willans DJ, MacLean GD, Selvaraj S, Suesh MR, Noujaim AA (1987) Monoclonal antibodies and synthetic tumor-associated glycoconjugates in the study of expression of Thomsen-Friedenreich-like and Tn-like antigens to human cancers. J Natl Cancer Inst 78:489–496

    Google Scholar 

  9. Friess H, Buchler M, Auerbach B, Weber A, Malfertheiner P, Hammer K, Madry N, Greiner S, Bosslet K, Beger HG (1993) CA 494- a new tumor marker for the diagnosis of pancreatic cancer. Int J Cancer 53:759–763

    Google Scholar 

  10. Podolsky K, McPhee MS, Alpert E, Warshaw AL, Isselbacher KJ (1981) Galactosyltransferase isoenzyme II in the detection of pancreatic cancer: comparison with radiologic, endoscopic and serologic tests. N Eng J Med 304. 1313–1317

    Google Scholar 

  11. Russo AJ, Douglass HO, Leveson SH, Howell JH, Holyoke ED, Harvey SR, Chu TM, Goldrosen MH (1978) Evaluation of microleukocyte adherence inhibition assay as an immunodiagnostic test for pancreatic cancer. Cancer Res 38:2023–2039

    Google Scholar 

  12. Gelder FB, Reese CJ, Moossa AR, Hall T, Hunter R (1978) Purification, partial characterization and clinical evaluation of a pancreatic oncofetal antigen. Cancer Res 38:313–324

    Google Scholar 

  13. Warshaw AL, Lee KH, Wood WC, Cohen AM (1980) Sensitivity and specificity of serum ribonuclease in the diagnosis of pancreatic cancer. Am J Surg 139:27–32

    Google Scholar 

  14. Yamanaka Y, Friess H, Kobrin MS, Buchler M, Beger HG, Korc M (1993) Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 13:565–569

    CAS  PubMed  Google Scholar 

  15. Hall PA, Hughes CM, Staddon SL, Richman PL, Gullick WJ, Lemoine NR (1990) The c-erbB-2 proto-oncogene in human pancreatic cancer. J Pathol 161:195–200

    Google Scholar 

  16. Lemoine NR, Lobresco M, Leung H, Barton C, Hughes CM, Prigent SA, Gullick WJ, Kloppel G (1992) The erbB-3 gene in human pancreatic cancer. J Pathol 168:269–273

    Google Scholar 

  17. Korc M, Meltzer P, Trent J (1986) Enhanced expression of epidermal growth factor receptor correlates with alterations of chromosome 7 in human pancreatic cancer. Proc Natl Acad Sci U S A 83:5141–5144

    Google Scholar 

  18. Lemoine NR, Hughes CM, Barton CM, Poulsom R, Jeffery RE, Klöppel G, Hall PA, Gullick WJ (1992) The epidermal growth factor receptor in human pancreatic cancer. J Pathol 166:7–12

    CAS  PubMed  Google Scholar 

  19. Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H (1984) Expression of epidermal growth factor receptors in human brain tumors. Cancer Res 44:753–760

    Google Scholar 

  20. Ro J, North SM, Gallick GE, Hortobagyi GN, Guttermann JU, Blick M (1987) Amplified and overexpressed epidermal growth factor receptor gene in uncultured primary breast carcinoma. Cancer Res 48:161–164

    Google Scholar 

  21. Sainsbury JRC, Sherbet GV, Fardon JR, Harris AL (1985) Epidermal-growth-factor-receptors in human brain tumors. Lancet I:364–366

    Google Scholar 

  22. Neal DE, Bennett MK, Hall RR, Marsch C, Abel PD, Sainsbury JRC, Harris AL (1985) Epidermal-growth-factor-receptors in human bladder cancer: comparison of invasive and superficial tumors. Lancet I:366–368

    Google Scholar 

  23. Watanabe S, Lazar SE, Sporn MB (1987) Transformation of normal rat kidney (NRK) cells by an infectious retrovirus carrying a synthetic rat type alpha transforming growth factor gene. Proc Natl Acad Sci USA 84:1258–1262

    Google Scholar 

  24. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchler M, Beger HG (1992) Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 90:1352–1360

    Google Scholar 

  25. Barton CM, Hall PA, Hughes CM, Gullick WJ, Lemoine NR (1991) Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J Pathol 163:111–116

    Google Scholar 

  26. Smith JJ, Derynck R, Korc M (1987) Production of transforming growth factor a in human pancreatic cancer cells, evidence for a superagonist autocrine cycle. Proc Natl Acad Sci USA 84:7567–7570

    Google Scholar 

  27. Massague J (1990) The transforming growth factor family. Annu Rev Cell Biol 6:597–641

    CAS  PubMed  Google Scholar 

  28. Sporn MB, Roberts AB (1992) Transforming growth factor: recent progress and new challenges. J Cell Biol 119:1017–1021

    Article  CAS  PubMed  Google Scholar 

  29. Baldwin RL, Korc M (1993) Growth inhibition of human pancreatic carcinoma cells by transforming growth factor-b. Growth Factors 8:23–34

    Google Scholar 

  30. Yamanaka Y, Friess H, Buchler M, Beger HG, Gold LI, Korc M (1993) Synthesis and expression of transforming growth factor beta-1, beta-2, and beta-3 in the endocrine and exocrine pancreas. Diabetes 42:746–756

    Google Scholar 

  31. Friess H, Yamanaka Y, Buchler M, Ebert M, Beger HG, Gold LI, Korc M (1993) Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 105:1846–1856

    CAS  PubMed  Google Scholar 

  32. Friess H, Yamanaka Y, Büchler M, Beger HG, Kobrin MS, Baldwin RL, Korc M (1993) Enhanced expression of the type II transforming growth factor b receptor in human pancreatic cancer cells without alterations of type III receptor expression. Cancer Res 53:2704–2707

    CAS  PubMed  Google Scholar 

  33. Klagsbrun M (1989) The fibroblast growth factor family: structural and biological properties. Prog Growth Factor Res 1:207–235

    Google Scholar 

  34. Gospodarowicz D, Neufeld G, Schweigerer L (1986) Molecular and biological characterization of fibroblast growth factor, an angiogenic factor which also controls the proliferation and differentiation of mesoderm and neuroectoderm derived cells. Cell Differen 19:1–17

    Google Scholar 

  35. Gonzales AM, Buscaglia M, Fox R, Isacchi A, Sarmientos P, Farris J, Ong M, Martineau D, Lappi DA, Baird A (1992) Basic fibroblast growth factor in Dupuytren's contracture. Am J Pathol 141:661–671

    Google Scholar 

  36. Mori H, Maki M, Oishi K, Jaye M, Igarashi K, Yoshida O, Hatanaku M (1990) Increased expression of genes for basic fibroblast growth factor and transforming growth factor type b2 in human benign prostatic hyperplasia. Prostate 16:71–80

    Google Scholar 

  37. Friess H, Yamanaka Y, Buchler M, Beger HG, Do DA, Kobrin MS, Korc M (1994) Increased expression of acidic and basic fibroblast growth factors in chronic pancreatitis. Am J Pathol 144:117–128

    Google Scholar 

  38. Takahashi JA, Mod H, Fukumoto M, Igarashi M, Jaye M, Oda Y, Kikuchi H, Hatanaka M (1990) Gene expression of fibroblast growth factors in human gliomas and meningeomas. Demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues. Proc Natl Acad Sci USA 87:5710–5714

    Google Scholar 

  39. Yamanaka Y, Friess H, Buchler M, Beger HG, Uchida E, Onda M, Kobrin MS, Korc M (1993) Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res 53:5289–5296

    Google Scholar 

  40. Der CJ, Cox AD (1991) Isoprenoid modification and plasma membrane association: critical factors for ras oncogenicity. Cancer Cells 3:331–339

    Google Scholar 

  41. Almoguera C, Shibta D, Forrester K, Martin J, Arnheim N, Perucho, M (1988) Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–554

    CAS  PubMed  Google Scholar 

  42. Lemoine NR, Jain S, Hughes CM, Staddon SL, Maillet B, Hall PA, Klöppel G (1992) Ki-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology 102:230–236

    Google Scholar 

  43. DiGiuseppe JA, Hruban RH, Offerhaus GJ, Clement MJ, Van den Berg FM, Cameron JL, Van Mansfeld AD (1994) Detection of K-ras mutations in mucinous pancreatic duct hyperplasia from a patient with a family history of pancreatic carcinoma. Am J Pathol 144:889–895

    Google Scholar 

  44. Grünewald K, Lyons J, Fröhlich A, Feichtinger H, Weger RA, Schwab G, Janssen JWG, Bartram CR (1989) High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer 43:1037–1041

    Google Scholar 

  45. Hruban RH, van Mansfeld ADM, Offerhaus GJA, van Weering DK, Allison DC, Goodman SN, Kensler TW, Bose KK, Cameron JL, Bos JL (1993) K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization. Am J Pathol 143:545–554

    Google Scholar 

  46. Motojima K, Urano T, Nagata Y, Shiku H, Tsunoda T, Kanematsu T (1991) Mutations in the Kirsten-ras oncogene are common but lack correlation with prognosis and tumor stage in human pancreatic carcinoma. Am J Gastroenterol 86:1784–1788

    CAS  PubMed  Google Scholar 

  47. Schaeffer BK, Glasner S, Kuhlmann E, Myles JL, Longnecker DS (1994) Mutated c-K-ras in small pancreatic adenocarcinomas. Pancreas 9:161–165

    Google Scholar 

  48. Pellegata NS, Sessa F, Renault B, Bonato M, Leone BE, Solcia E, Ranzani GN (1994) K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions. Cancer Res 54:1556–1560

    Google Scholar 

  49. Kloppel G (1994) Gene changes and pancreatic carcinoma: the significance of K-ras. Dig Surg I 1:164–169

    Google Scholar 

  50. Barton CM, Staddon SL, Hughes CM, Hall PA, O'Sullivan C, Kloppel G, Theis B, Russell RCG, Neoptolemos J, Williamson RCN, Lane DP, Lemoine NR (1991) Abnormalities of the p53 tumor suppressor gene in human pancreatic cancer. Br J Cancer 64:1076–1082

    CAS  PubMed  Google Scholar 

  51. Ruggeri B, Zhang SY, Caamano J, DiRado M, Flynn SD, Klein-Szanto AJP (1992) Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor suppressor genes. Oncogene 7:1503–151 1

    Google Scholar 

  52. Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Buchler M, Beger HG, Korc M (1993) p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Lett 69:151–160

    Google Scholar 

  53. Kalthoff H, Schmiegel W, Roeder C, Kasche D, Schmidt A, Lauer G, Thiele HG, Honold G, Pantel K, Riethmüller G, Scherer E, Maner J, Deppert W (1993) p53 and K-RAS alterations in pancreatic epithelial cell lesions. Oncogene 8:289–298

    CAS  PubMed  Google Scholar 

  54. Scarpa A, Capelli P, Mukai K, Zamboni G, Oda T, Lacono C, Hirohashi S (1993) Pancreatic adenocarcinomas frequently show p53 gene mutations. Am J Pathol 142:1534–1543

    Google Scholar 

  55. Zhang SY, Ruggeri B, Agarwal P, Sorling AF, Obara T, Ura H, Namiki M, Klein-Szanto AJP (1994) Immunohistochemical analysis of p53 expression in human pancreatic carcinomas. Arch Pathol I 18:150–154

    Google Scholar 

  56. DiGiuseppe JA, Hruban RH, Goodman SN, Polak M, Van den Berg FM, Allison DC, Cameron JL, Offerhaus GJA (1994) Overexpression of p53 protein in adenocarcinoma of the pancreas. Am J Clin Pathol 101:684–688

    Google Scholar 

  57. Boschmann CR, Stryker S, Reddy JK, Ras MS (1994) Expression of p53 protein in precursor lesions and adenocarcinoma of the human pancreas. Am J Pathol 145:1291–1295

    Google Scholar 

  58. Caldas C, Hahn SA, da Costa LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE (1994) Frequent somatic mutations and homozygous deletions of the p16 (MTSI) gene in pancreatic adenocarcinoma. Nat Genet 8:27–32

    Google Scholar 

  59. Liu Q, Yan YX, McClure M, Natagawa H, Fujimura F, Rustgi AK (1995) MTSI (CDKN2) tumor suppressor gene deletions are a frequent event in esophagus squamous cancer and pancreatic adenocarcinoma cell lines. Oncogene 10:619–622

    Google Scholar 

  60. Barton CM, McKie AB, Hogg A, Bia B, Elia G, Phillips SMA, Ding SF, Lemoine NR (1995) Abnormalities of the RBIand DCC tumour suppressor genes are uncommon in humanpancreatic adenocarcinoma. Mol Carcinogen (in press)

  61. McKie AB, Filipe MI, Lemoine NR (1993) Abnormalities affecting the APC and DCC tumour suppressor gene loci on chromosome 5q occur frequently in gastric cancer but not in pancreatic cancer. Int J Cancer 55:598–603

    Google Scholar 

  62. Scupoli MT, Zamboni G, Achille A, Bogina G, Capalli P, Lemoine NR, Accolla RS, Scarpa A (1995) APC gene mutations frequently occur in ampullary tumors but not in exocrine pancreatic cancer. Am J Pathol (in press)

  63. Caron de Fromentel C, Soussi T (1992) TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer 4:1–15

    Google Scholar 

  64. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991) p53 mutations in human cancer. Science 253:49–53

    CAS  PubMed  Google Scholar 

  65. Levine AJ, Momand J Finlay CA (1991) The p53 tumour suppressor gene. Nature 351:453–456

    Google Scholar 

  66. Finlay CA, Hinds PW, Tan T-H, Eliyahu D, Oren M, Levine AJ (1988) Activating mutations for transformation by p53 produce a gene product that forms a hsc70-p53 complex with an altered half life. Mol Cell Biol 8:531–539

    Google Scholar 

  67. Hinds PW, Finlay CA, Frey AB, Levine AJ (1987) Immunological evidence for the association of p53 with a heat shock protein, hsc70, in p53-plus-ras-transformed cell lines. Mol Cell Biol 7:2863–2869

    Google Scholar 

  68. Kinzler KW, Vogelstein B (1994) Cancer therapy meets p53. N Eng J Med 331:49

    Google Scholar 

  69. Lowe SW, Ruby HE, Jacks T, Housman DE (1993) p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74:957–967

    Google Scholar 

  70. Harris CC, Hollstein M (1993) Clinical implications of the p53 tumor-suppressor gene. N Eng J Med 329:1318–1327

    Google Scholar 

  71. Volkmann M, Müller M, Hofmann WJ, Meyer M, Hagelstein J, Räth U, Kommerell B, Zentgraf, H Galle PR (1993) The humoral immune response to p53 in patients with hepatocellular carcinoma is specific for malignancy and independent of the alpha-fetoprotein status. Hepatology 18:559–565

    Google Scholar 

  72. Schlichtholz B, Legros Y, Gillet D, Gaillard C, Marty M, Lane D, Calvo F, Soussi T (1992) 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

    Google Scholar 

  73. Labrecque S, Naor N, Thomson D, Matlashewski G (1993) Analysis of the anti-p53 antibody response in cancer patients. Cancer Res 53:3468–3471

    Google Scholar 

  74. Gansauge S, Gansauge F, Negri G, Galle P, Link KH, Poch B, Beger HG (1994) p53-autoantibodies in diseases of the pancreatico-biliary system. Pancreas 9:788

    Google Scholar 

  75. Rouslahti E (1991) Integrins. J Clin Invest 87:1–5

    Google Scholar 

  76. Arnaout B (1990) Structure and function of the leukocyte adhesion molecules CD I I/CD 1 8. Blood 75:1037–1050

    Google Scholar 

  77. Waes CV, Kozarsky KF, Warren AB, Kidd L, Paugh D, Liebert M, Carey TE (1991) The A9 antigen associated with aggressive human squamous carcinoma is structurally and functionally similar to the newly defined integrin a6b4. Cancer Res 51:2395–2402

    Google Scholar 

  78. Lehmann M, Rabenandresana C, Tamura R, Lissitzky JC, Quaranta V, Pichon J Marvaldi J (1994) A monoclonal antibody inhibits adhesion to fibronectin and vitronectin of a colon carcinoma cell line and recognizes the integrins αvβ3, αvβ5, and αvβ6. Cancer Res 54:2102–2107

    Google Scholar 

  79. Abrahamson DR (1986) Recent studies on the structure and pathology of basement membranes. J Pathol 149:257–278

    Google Scholar 

  80. D'Ardenne AJ, Burns J, Sykes BC, Kirkpatric P (1983) Comparative distribution of fibronectin and type III collagen in normal human tissues. J Pathol 141:55–69

    Google Scholar 

  81. Preissner KT (1991) Structure and biological role of vitronectin. Annu Rev Cell Biol 7:275–310

    CAS  PubMed  Google Scholar 

  82. Liottta LA (1986) Tumor invasion and metastases — role of the extracellular matrix: Rhoads Memorial Award Lecture. Cancer Res 46:1–7

    Google Scholar 

  83. Shimoyama S, Gansauge F, Gansauge S, Oohara T, Beger HG (1995) Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison to normal pancreas. Int J Pancreatol (in press)

  84. Johnston PG, Lenz HJ, Leichman CG, Dananberg KD, Allegra CJ, Danenberg PV, Leichman L (1995) Thymidilate synthase gene and protein expression correlate and are associated with response to 5-fluorouracil in human colorectal and gastric tumors. Cancer Res 55:1407–5105

    CAS  PubMed  Google Scholar 

  85. Dohner H, Fischer K, Bentz M, Hansen K, Benner A, Cabot G, Diehl D, Schlenk R, Coy J, Stilgenbauer S (1995) p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias. Blood 85:1580–1589

    Google Scholar 

  86. Wattel E, Preudhomme C, Hecquet B, Vanrumbeke M, Quesnel B, Dervite I, Morel P, Fenaux P (1994) p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 84:3148–3157

    Google Scholar 

  87. Van der Zee AG, Hollema H, Suurmeijer AJ, Krans M, Sluiter WJ, Willemse PH, Aalders JG, de Vries EG (1995) Value of P-glycoprotein, glutathione 5-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. J Clin Oncol 13:70–78

    Google Scholar 

  88. Jacquemier J, Penault-Llorca F, Viens P, Houvenaeghel G, Hassoun J, Torrente M, Adelaide J, Birnbaum D (1994) Breast cancer response to adjuvant chemotherapy in correlation with erbB2 and p53 expression. Anticancer Res 14:2773–2778

    Google Scholar 

  89. Niwa K, Itoh M, Murase T, Morishita S, Itoh N, Mori H, Taaya T (1994) Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance. Br J Cancer 70:1191–1197

    Google Scholar 

  90. Lemoine NR (1994) Genetic intervention for therapy and prevention of pancreatic cancer Dig Surg I 1:170–177

    Google Scholar 

  91. Huang HJ, Yee JK, Shew JY, Chen PL, Bookstein R, Friedmann T, Lee EY, Lee WH (1988) Suppression of the neoplastic phenotype by replacement of the RB gene in human cancer cells. Science 242:1563–1566

    Google Scholar 

  92. Bookstein R, Shew JY, Chen PL, Scully P, Lee WH (1990) Suppression of tumorigenicity of human prostate carcinoma cells by replacing a mutated RB gene. Science 247:712–715

    Google Scholar 

  93. Tanaka K, Oshimura M, Kikuchi R, Seki M, Hayashi T, Miyaki M (1991) Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 5 or 18. Nature 349:340–342

    Google Scholar 

  94. Baker SJ, Markowitz S, Fearon ER, Willson JKV, Vogelstein B (1990) Suppression of human colorectal carcinoma cell growth by wild-type p53. Science 249:912–915

    Google Scholar 

  95. Carter G, Lemoine NR (1993) Antisense technology for cancer therapy: does it make sense? Br J Cancer 67:869–876

    Google Scholar 

  96. Nellen W, Lichtenstein C (1993) What makes an mRNA antisense-itive? Trends Biol Sci 18:419–423

    Google Scholar 

  97. Prins J, DeVries E, Mulder N (1993) Antisense of oligonucleotides and the inhibition of oncogene expression. Clin Oncol 5:245–252

    Google Scholar 

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Gansauge, S., Gansauge, F. & Beger, H.G. Molecular oncology in pancreatic cancer. J Mol Med 74, 313–320 (1996). https://doi.org/10.1007/BF00207508

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