Advertisement

Letters in Peptide Science

, Volume 10, Issue 3–4, pp 191–214 | Cite as

Receptor-specific targeting with complementary peptide nucleic acids conjugated to peptide analogs and radionuclides

  • Eric Wickstrom
  • Mathew L. Thakur
  • Edward R. Sauter
Article

Abstract

Genomic sequencing makes it possible to identify all the genes of an organism, now including Homo sapiens. Yet measurement of the expression of each gene of interest still presents a dauntingprospect. Northern blots, RNase protection assays, as well as microarrays and related technologies permit measurement of gene expression in total RNA extracted from cultured cells or tissue samples. It would be most valuable, however, to quantitate gene expression noninvasively in living cells and tissues. Unfortunately,no reliable method has been available to measure levels of specificmRNAs in vivo. Peptide nucleic acids (PNAs) display superior ruggedness and hybridization properties as a diagnostic tool for gene expression, and could be used for this purpose. On the down side, they are negligibly internalized by normal or malignant cells in the absence of conjugated ligands. Nevertheless,we have observed that Tc-99m-peptides can delineate tumors, and PNA-peptides designed to bind to IGF-1 receptors on malignant cellsare taken up specifically and concentrated in nuclei. We have postulated that antisense Tc-99m-PNA-peptides will be taken up by human cancer cells, will hybridize to complementary mRNA targets, and will permit scintigraphic imaging of oncogene mRNAsin human cancer xenografts in a mouse model. The oncogenes cyclinD1, ERBB2, c-MYC, K-RAS, and tumor suppressor p53 are being probed initially. These experimentsprovide a proof-of-principle for noninvasive detection of oncogeneexpression in living cells and tissues. This scintigraphic imaging technique should be applicable to any particular gene of interest in a cell or tissue type with characteristic receptors.

antisense breast cancer chelators conjugates gene expression hybridization imaging non-invasive oligonucleotides oncogenes peptides radionuclides scintigraphy tumors 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adelaide, J., Monges, G., Derderian, C., Seitz, J. F. and Birnbaum, D., Oesophageal cancer and amplification of the human cyclin D gene CCND1/PRAD1. Br. J. Cancer, 71 (1995) 64.PubMedGoogle Scholar
  2. Agrawal, S., Antisense oligonucleotides: Towards clinical trials. Trends Biotech., 14 (1996a) 376.Google Scholar
  3. Agrawal, S., Antisense Therapeutics. Methods in Molecular Medi-cine J. M. Walker (Ed.), 10 Vols., Humana Press, Totowa NJ, 1996b.Google Scholar
  4. Agrawal, S., Jiang, Z., Zhao, Q., Shaw, D., Cai, Q., Roskey, A., Channavajjala, L., Saxinger, C. and Zhang, R., Mixed-backbone oligonucleotides as second generation antisense oli-gonucleotides: In vitroand in vivostudies. Proceedings of the National Academy of Sciences of the United States of America, 94 (1997) 2620.Google Scholar
  5. Albericio, F., Hammer, R.P., Garcia-Echeverria, C., Molins, M.A., Chang, J.L., Munson, M.C., Pons, M., Giralt, E. and Barany, G., Cyclization of disulfide-containing peptides in solid-phase synthesis. Int. J. Pept. Protein Res., 37 (1991) 402.PubMedGoogle Scholar
  6. Alimandi, M., Romano, A., Curia, M.C., Muraro, R., Fedi, P., Aaronson, S.A., Di Fiore, P.P. and Kraus, M.H., Cooperative signaling of ErbB3 and ErbB2 in neoplastic transformation and human mammary carcinomas. Oncogene, 10 (1995) 1813.PubMedGoogle Scholar
  7. Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N. and Perucho, M., Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell, 53 (1988) 549.CrossRefPubMedGoogle Scholar
  8. American Cancer Society, http://www3.cancer.org/cancerinfo, 2001.Google Scholar
  9. Andrews, D.W., Resnicoff, M., Flanders, A.E., Kenyon, L., Curtis, M., Merli, G., Baserga, R., Iliakis, G. and Aiken, R.D., Results of a pilot study involving the use of an antisense oligodeoxy-nucleotide directed against the insulin-like growth factor type I receptor in malignant astrocytomas. J. Clin. Oncol., 19 (2001) 2189.PubMedGoogle Scholar
  10. Aoki, K., Yoshida, T., Sugimura, T. and Terada, M., Liposome-mediated in vivogene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity. Cancer Res., 55 (1995) 3810.PubMedGoogle Scholar
  11. Aramini, J.M. and Germann, M.W., NMR studies of DNA duplexes containing alpha-anomeric nucleotides and polarity reversals. Biochem. Cell Biol 76 (1998) 403.PubMedGoogle Scholar
  12. Arany, I., Yen, A. and Tyring, S.K. p53, WAF1/CIP1 and mdm2 expression in skin lesions associated with human papillomavirus and human immunodeficiency virus. Anticancer Res., 17 (1997) 1281.PubMedGoogle Scholar
  13. Armengol, G., Knuutila, S., Lluis, F., Capella, G., Miro, R. and Caballin, M.R., DNA copy number changes and evaluation of MYC, IGF1R, and FES amplification in xenografts of pancreatic adenocarcinoma. Cancer Genet. Cytogenet., 116 (2000) 133.CrossRefPubMedGoogle Scholar
  14. Arnold, A., Kim, H.G., Gaz, R.D., Eddy, R.L., Fukushima, Y., Byers, M.G., Shows, T.B. and Kronenberg, H.M., Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in a parathyroid adenoma. J. Clin. Invest., 83 (1989) 2034.PubMedGoogle Scholar
  15. Bacon, T.A. and Wickstrom, E., Daily addition of an anti-c-myc DNA oligomer induces granulocytic differentiation of human promyelocytic leukemia HL-60 cells in both serum-containing and serum-free media. Oncogene Res., 6 (1991a) 21.PubMedGoogle Scholar
  16. Bacon, T.A. and Wickstrom, E., Walking along human c-myc mRNA with antisense oligodeoxynucleotides: Maximum effic-acy at the 5 cap region. Oncogene Res., 6 (1991b) 13.PubMedGoogle Scholar
  17. Bartkova, J., Lukas, J., Muller, H., Strauss, M., Gusterson, B. and Bartek, J., Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Cancer Res., 55 (1995) 949.PubMedGoogle Scholar
  18. Baserga, R., The insulin-like growth factor I receptor: A key to tumor growth? Cancer Res., 55 (1995) 249.PubMedGoogle Scholar
  19. Basu, S., Kolan, H.R., Thakur, M.L. and Wickstrom, E., Solid phase synthesis of a HYNIC-D-peptide-phosphorothioate oli-godeoxynucleotide conjugate from two arms of a polyethylene glycol-polystyrene support. J. Labeled Comp. Radiopharm., 37 (1995) 350.Google Scholar
  20. Basu, S. and Wickstrom, E., Solid phase synthesis of a D-peptide-phosphorothioate oligodeoxynucleotide conjugate from two arms of a polyethylene glycol-polystyrene support. Tetra-hedron Lett., 36 (1995) 4943.Google Scholar
  21. Basu, S. and Wickstrom, E., Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insulin-like growth factor 1 for increased cellular uptake. Bioconj. Chemistry, 8 (1997) 481.Google Scholar
  22. Bayever, E., Haines, K.M., Iversen, P.L., Ruddon, R.W., Pirruc-cello, S.J., Mountjoy, C.P., Arneson, M.A. and Smith, L.J., Selective cytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences. Leukemia Lymphoma, 12 (1994) 223.PubMedGoogle Scholar
  23. Belikova, A.M., Zarytova, V.F. and Grineva, N.I., Synthesis of ribonucleosides and diribonucleoside phosphates containing 2-chloroethylamine and nitrogen mustard residues. Tetrahedron Lett., 37 (1967) 3557.PubMedGoogle Scholar
  24. Bennett, C.F., Dean, N., Ecker, D.J. and Monia, B.P., Pharmacology of antisense therapeutic agents. In S. Agrawal (Ed.), Antisense Therapeutics, 10 Vols. Humana Press, Totowa NJ, 1996, pp. 13-46. (1996).Google Scholar
  25. Bertram, J., Killian, M., Brysch, W., Schlingensiepen, K.H. and Kneba, M., Reduction of erbB2 gene product in mamma carcinoma cell lines by erbB2 mRNA-specific and tyrosine kinase consensus phosphorothioate antisense oligonucleotides. Biochem. Biophys. Res. Commun., 200 (1994) 661.CrossRefPubMedGoogle Scholar
  26. Bièche, I., Laurendeau, I., Tozlu, S., Olivi, M., Vidaud, D., Lidereau, R. and Vidaud, M., Quantitation of MYC gene ex-pression in sporadic breast tumors with a real-time reverse transcription-PCR assay. Cancer Res., 59 (1999a) 2759.PubMedGoogle Scholar
  27. Bièche, I., Onody, P., Laurendeau, I., Olivi, M., Vidaud, D., Lidereau, R. and Vidaud, M., Real-time reverse transcription-PCR assay for future management of ERBB2-based clinical applications. Clin. Chem., 45 (1999b) 1148.PubMedGoogle Scholar
  28. Bishop, J.M., Molecular themes in oncogenesis. Cell, 64 (1991) 235.CrossRefPubMedGoogle Scholar
  29. Bishop, M.R., Jackson, J.D., Tarantolo, S.R., O'Kane-Murphy, B., Iversen, P.L., Bayever, E., Joshi, S.M., Sharp, J.G., Pierson, J.L., Warkentin, P.I., Armitage, J.O. and Kessinger, A., Ex vivotreatment of bone marrow with phosphorothioate oligonucleotide OL(1)p53 for autologous transplantation in acute myelogen-ous leukemia and myelodysplastic syndrome. J. Hematother., 6 (1997) 441.PubMedGoogle Scholar
  30. Blackwood, E.M. and Eisenman, R.N., Max: A helix-loop-helix zipper protein that forms a sequence-specific DNA-binding com-plex with Myc. Science, 251 (1991) 1211.PubMedGoogle Scholar
  31. Boffa, L.C., Scarfi, S., Mariani, M.R., Damonte, G., Allfrey, V.G., Benatti, U. and Morris, P.L., Dihydrotestosterone as a selective cellular/nuclear localization vector for anti-gene peptide nucleic acid in prostatic carcinoma cells (In Process Citation). Cancer Res., 60 (2000) 2258.PubMedGoogle Scholar
  32. Bonham, M.A., Brown, S., Boyd, A.L., Brown, P.H., Bruckenstein, D.A., Hanvey, J.C., Thomson, S.A., Pipe, A., Hassman, F., Bisi, J.E. et al.,An assessment of the antisense properties of RNase H-competent and steric-blocking oligomers. Nucl. Acids Res., 23 (1995) 1197.PubMedGoogle Scholar
  33. Broaddus, W.C., Liu, Y., Steele, L.L., Gillies, G.T., Lin, P.S., Loudon, W.G., Valerie, K., Schmidt-Ullrich, R.K. and Fillmore, H.L., Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction. J. Neurosurg., 91 (1999) 997.PubMedGoogle Scholar
  34. Brysch, W., Magal, E., Louis, J.C., Kunst, M., Klinger, I., Schlin-gensiepen, R. and Schlingensiepen, K.H., Inhibition of p185c-erbB-2 proto-oncogene expression by antisense oligodeoxynuc-leotides down-regulates p185-associated tyrosine-kinase activity and strongly inhibits mammary tumor-cell proliferation. Cancer Gene. Ther., 1 (1994) 99.PubMedGoogle Scholar
  35. Cobleigh, M.A., Vogel, C.L. and Tripathy, N.J. et al.,Efficacy and safety of Herceptin (humanized anti-human HER-2 antibody) as a single agent in 222 women with HER2 overexpression who relapsed following chemotherapy for metastatic breast cancer. Proc. Am. Soc. Clin. Oncol., 17 (1998) 97.Google Scholar
  36. Collins, J.F., Herman, P., Schuch, C. and Bagby Jr., G.C., c-myc antisense oligonucleotides inhibit the colony-forming capacity of Colo 320 colonic carcinoma cells. J. Clin. Invest., 89 (1992) 1523.PubMedGoogle Scholar
  37. Colomer, R., Lupu, R., Bacus, S.S. and Gelmann, E.P., erbB-2 antisense oligonucleotides inhibit the proliferation of breast car-cinoma cells with erbB-2 oncogene amplification. Br. J. Cancer, 70 (1994) 819.PubMedGoogle Scholar
  38. Daaka, Y. and Wickstrom, E., Target dependence of antisense oli-godeoxynucleotide inhibition of c-Ha-ras p21 expression and focus formation in T24-transformed NIH3T3 cells. Oncogene Res., 5 (1990) 267.PubMedGoogle Scholar
  39. Deng, C., Zhang, P., Harper, J.W., Elledge, S.J. and Leder, P., Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell, 82 (1995) 675.CrossRefPubMedGoogle Scholar
  40. Dong, M., Nio, Y., Tamura, K., Song, M.M., Guo, K.J., Guo, R.X. and Dong, Y.T., Ki-ras point mutation and p53 expression in human pancreatic cancer: A comparative study among Chinese, Japanese, and Western patients. Cancer Epidemiol. Biomarkers Prev., 9 (2000) 279.Google Scholar
  41. Downward, J., Riehl, R., Wu, L. and Weinberg, R.A., Identification of a nucleotide exchange-promoting activity for p21ras. Proc. Natl. Acad. Sci. USA, 87 (1990) 5998.PubMedGoogle Scholar
  42. Dugan, M.C., Dergham, S.T., Kucway, R., Singh, K., Biernat, L., Du, W., Vaitkevicius, V.K., Crissman, J.D. and Sarkar, F.H., HER-2/neu expression in pancreatic adenocarcinoma: Relation to tumor differentiation and survival. Pancreas, 14 (1997) 229.CrossRefPubMedGoogle Scholar
  43. Egholm, M., Buchardt, O., Christensen, L., Behrens, C., Freier, S.M., Driver, D.A., Berg, R.H., Kim, S.K., Norden, B. and Nielsen, P.E., PNA hybridizes to complementary oligonuc-leotides obeying the Watson-Crick hydrogen-bonding rules (see comments). Nature, 365 (1993) 566.CrossRefPubMedGoogle Scholar
  44. Eisenhut, M. and Haberkorn, U., [123I]VIP receptor scintigraphy in patients with pancreatic adenocarcinomas. Eur. J. Nucl. Med., 27 (2000) 1589.CrossRefPubMedGoogle Scholar
  45. Gansauge, S., Gansauge, F., Ramadani, M., Stobbe, H., Rau, B., Harada, N. and Beger, H.G., Overexpression of cyclin D1 in human pancreatic carcinoma is associated with poor prognosis. Cancer Res., 57 (1997) 1634.PubMedGoogle Scholar
  46. Georges, R.N., Mukhopadhyay, T., Zhang, Y., Yen, N. and Roth, J.A., Prevention of orthotopic human lung cancer growth by in-. tratracheal instillation of a retroviral antisense K-ras construct. Cancer Res., 53 (1993) 1743.PubMedGoogle Scholar
  47. Gibbs, J.B., Schaber, M.D., Allard, W.J., Sigal, I.S. and Scolnick, E.M., Purification of ras GTPase activating protein from bovine brain. Proc. Natl. Acad. Sci. USA, 85 (1988) 5026.PubMedGoogle Scholar
  48. Goldman, R., Levy, R.B., Peles, E. and Yarden, Y., Heterodi-merization of the erbB-1 and erbB-2 receptors in human breast carcinoma cells: A mechanism for receptor transregulation. Biochemistry, 29 (1990) 11024.CrossRefPubMedGoogle Scholar
  49. Good, L. and Nielsen, P.E., Progress in developing PNA as a gene-targeted drug. Antisense Nucleic Acid Drug Dev., 7 (1997) 431.PubMedGoogle Scholar
  50. Good, L. and Nielsen, P.E., Inhibition of translation and bacterial growth by peptide nucleic acid targeted to ribosomal RNA. Proc. Natl. Acad. Sci. USA, 95 (1998) 2073.CrossRefPubMedGoogle Scholar
  51. Goodrich, D.W. and Lee, W.-H., Molecular characterization of the retinoblastoma susceptibility gene. Biochim. Biophys. Acta, 1155 (1993) 43.PubMedGoogle Scholar
  52. Gray, G.D., Basu, S. and Wickstrom, E., Transformed and im-mortalized cellular uptake of oligodeoxynucleoside phosphoro-thioates, 3-alkylamino oligodeoxynucleotides, 2-O-methyl oli-goribonucleotides, oligodeoxynucleoside methylphosphonates, and peptide nucleic acids. Biochem. Pharmacol., 53 (1997a) 1465.Google Scholar
  53. Gray, G.D., Townsend, R., Hayasaka, H., Korngold, R. and Wickstrom, E., Immune cell involvement in anti-c-mycDNA prevention of tumor formation in a mouse model of Burkitt's lymphoma. Nucleosides Nucleotides, 16 (1997b) 1727.Google Scholar
  54. Gray, G.D. and Wickstrom, E., Rapid measurement of modified oligonucleotide levels in plasma samples with a fluorophore specific for single-stranded DNA. Antisense Nucl. Acid Drug Develop., 7 (1997) 133.Google Scholar
  55. Gurnani, M., Lipari, P., Dell, J., Shi, B. and Nielsen, L.L., Adenovirus-mediated p53 gene therapy has greater efficacy when combined with chemotherapy against human head and neck, ovarian, prostate, and breast cancer. Cancer Chemother. Pharmacol., 44 (1999) 143.CrossRefPubMedGoogle Scholar
  56. Hanvey, J.C., Peffer, N.J., Bisi, J.E., Thomson, S.A., Cadilla, R., Josey, J.A., Ricca, D.J., Hassman, C.F., Bonham, M.A., Au, K.G. et al.,Antisense and antigene properties of peptide nucleic acids. Science, 258 (1992) 1481.PubMedGoogle Scholar
  57. Heikkila, R., Schwab, G., Wickstrom, E., Loke, S.L., Pluznik, D.H., Watt, R. and Neckers, L.M., A c-myc antisense oligodeoxynuc-leotide inhibits entry into S phase but not progress from G0 to G1. Nature, 328 (1987) 445.CrossRefPubMedGoogle Scholar
  58. Helin, K. and Harlow, E., The retinoblastoma protein as a transcrip-tional repressor. Trends Cell Biol., 3 (1992) 43.Google Scholar
  59. Hinds, P.W., Dowdy, S.F., Eaton, E.N., Arnold, A. and Weinberg, R.A., Function of a human cyclin gene as an oncogene. Proc. Natl. Acad. Sci. USA, 91 (1994) 709.PubMedGoogle Scholar
  60. Ho, P.T., Ishiguro, K., Wickstrom, E. and Sartorelli, A.C., Non-sequence-specific inhibition of transferrin receptor expression in HL-60 leukemia cells by phosphorothioate oligodeoxynuc-leotides. Antisense Res. Develop., 1 (1991) 329.Google Scholar
  61. Holland, P.M., Abramson, R.D., Watson, R. and Gelfand, D.H., Detection of specific polymerase chain reaction product by util-izing the 5-3 exonuclease activity of Thermus aquaticus DNA polymerase. Proc. Natl. Acad. Sci. USA, 88 (1991) 7276.PubMedGoogle Scholar
  62. Huang, Y., Snyder, R., Kligshteyn, M. and Wickstrom, E., Preven-tion of tumor formation in a mouse model of Burkitt's lymphoma by 6 weeks of treatment with anti-c-myc DNA phosphorothioate. Mol. Med., 1 (1995) 647.PubMedGoogle Scholar
  63. Hughes, J., Astriab, A., Yoo, H., Alahari, S., Liang, E., Sergueev, D., Shaw, B.R. and Juliano, R.L., In vitrotransport and deliv-ery of antisense oligonucleotides (In Process Citation). Meth. Enzymol. 313 (2000) 342.PubMedGoogle Scholar
  64. Hustinx, R., Shiue, C.Y., Zhuang, H., McDonald, D., Lanuti, M., Lambright, E., Smith, J.G., Karp, J.S., Lu, P., Eck, S.L. and Alavi, A.A., Imaging in vivoherpes simplex virus thymidine kinase gene transfer and expression in tumors using positron emission tomography. J. Nucl. Med., 41 (2000) 264P.Google Scholar
  65. Jiang, W., Kahn, S.M., Zhou, P., Zhang, Y.J., Cacace, A.M., Infante, A.S., Doi, S., Santella, R.M. and Weinstein, I.B., Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression. Oncogene 8 (1993) 3447.PubMedGoogle Scholar
  66. Kashani-Sabet, M., Funato, T., Florenes, V.A., Fodstad, O. and Scanlon, K.J., Suppression of the neoplastic phenotype in vivoby an anti-ras ribozyme. Cancer Res., 54 (1994) 900.PubMedGoogle Scholar
  67. Kasuya, K., Watanabe, H., Nakasako, T., Ajioka, Y. and Koyanagi, Y., p53 protein overexpression and K-ras codon 12 mutation in pancreatic ductal carcinoma: Correlation with histologic factors. Pathol. Int., 47 (1997) 531.PubMedGoogle Scholar
  68. Kawada, M., Fukazawa, H., Mizuno, S. and Uehara, Y., Inhibition of anchorage-independent growth of ras-transformed cells on polyHEMA surface by antisense oligodeoxynucleotides directed against K-ras. Biochem. Biophys. Res. Commun., 231 (1997) 735.CrossRefPubMedGoogle Scholar
  69. Kennedy, M.M., Biddolph, S., Lucas, S.B., Howells, D.D., Picton, S., McGee, J.O., Silva, I., Uhlmann, V., Luttich, K. and O'Leary, J.J., Cyclin D1 expression and HHV8 in Kaposi sarcoma. J. Clin. Pathol., 52 (1999) 569.PubMedGoogle Scholar
  70. Kita, K., Saito, S., Morioka, C.Y. and Watanabe, A., Growth inhibition of human pancreatic cancer cell lines by anti-sense oligonucleotides specific to mutated K-ras genes. Int. J. Cancer, 80 (1999) 553.CrossRefPubMedGoogle Scholar
  71. Kokai, Y., Cohen, J.A., Drebin, J.A. and Greene, M.I., Stage-and tissue-specific expression of the neu oncogene in rat develop-ment. Proc. Natl. Acad. Sci. USA, 84 (1987) 8498.PubMedGoogle Scholar
  72. Kraus, M.H., Issing, W., Miki, T., Popescu, N.C. and Aaronson, S.A., Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: Evidence for overexpression in a subset of human mammary tumors. Proc. Natl. Acad. Sci. USA, 86 (1989) 9193.PubMedGoogle Scholar
  73. Krieg, A.M., Yi, A.K., Matson, S., Waldschmidt, T.J., Bishop, G.A., Teasdale, R., Koretzky, G.A. and Klinman, D.M., CpG motifs in bacterial DNA trigger direct B-cell activation. Nature, 374 (1995) 546.CrossRefPubMedGoogle Scholar
  74. Lal, R.B., Rudolph, D.L., Folks, T.M. and Hooper, W.C., Over expression of insulin-like growth factor receptor type-I in T-cell lines infected with human T-lymphotropic virus types-I and-II. Leuk. Res., 17 (1993) 31.CrossRefPubMedGoogle Scholar
  75. Leonetti, C., D'Agnano, I., Lozupone, F., Valentini, A., Geiser, T., Zon, G., Calabretta, B., Citro, G.C. and Zupi, G., Antitu-mor effect of c-myc antisense phosphorothioate oligodeoxynuc-leotides on human melanoma cells in vitroand and in mice [see comments]. J. Natl. Cancer Inst., 88 (1996) 419.PubMedGoogle Scholar
  76. Liu, X. and Pogo, B.G. Inhibition of erbB-2-positive breast can-cer cell growth by erbB-2 antisense oligonucleotides. Antisense Nucl. Acid Drug Dev., 6 (1996) 9.Google Scholar
  77. Lovec, H., Sewing, A., Lucibello, F.C., Muller, R. and Moroy, T., Oncogenic activity of cyclin D1 revealed through cooperation with Ha-ras: Link between cell cycle control and malignant transformation. Oncogene, 9 (1994) 323.PubMedGoogle Scholar
  78. Lowy, D.R. and Willumsen, B.M., Function and regulation of ras. Annu. Rev. Biochem., 62 (1993) 851.CrossRefPubMedGoogle Scholar
  79. Martin, K.J., Kritzman, B.M., Price, L.M., Koh, B., Kwan, C.P., Zhang, X., Mackay, A., O'Hare, M.J., Kaelin, C.M., Mutter,.212 G.L., Pardee, A.B. and Sager, R., Linking gene expression pat-terns to therapeutic groups in breast cancer (In Process Citation). Cancer Res., 60 (2000) 2232.PubMedGoogle Scholar
  80. Marwick, C., First 'antisense' drug will treat CMV retinitis (news). JAMA, 280 (1998) 871.PubMedGoogle Scholar
  81. Matsushime, H.D., Quelle, E., Shurtleff, S.A., Shibuya, M., Sherr, C.J. and Kato, J.-Y., D-type cyclin-dependent kinase activity in mammalian cells. Mol. Cell Biol., 14 (1994) 2066.PubMedGoogle Scholar
  82. McManaway, M.E., Neckers, L.M., Loke, S.L., al-Nasser, A.A., Redner, R.L., Shiramizu, B.T., Goldschmidts, W.L., Huber, B.E., Bhatia, K. and Magrath, I.T., Tumour-specific inhibition of lymphoma growth by an antisense oligodeoxynucleotide. Lancet, 335 (1990) 808.CrossRefPubMedGoogle Scholar
  83. Mier, W., Eritja, R., Mohammed, A., Haberkorn, U. and Eisen-hut, M., Preparation and evaluation of tumor-targeting peptide-oligonucleotide conjugates. Bioconjug. Chem., 11 (2000) 855.CrossRefPubMedGoogle Scholar
  84. Mier, W., Eritja, R., Mohammed, A., Haberkorn, U. and Eisenhut, M., Preparation and preclinical development of tumor-targeting peptide-PNA conjugates. J. Labelled Comp. Radiopharm., 42 (2001) 115P.Google Scholar
  85. Moberg, K.H., Logan, T.J., Tyndall, W.A. and Hall, D.J., Three distinct elements within the murine c-myc promoter are required for transcription. Oncogene, 7 (1992a) 411.PubMedGoogle Scholar
  86. Moberg, K.H., Tyndall, W.A. and Hall, D.J., Wild-type murine p53 represses transcription from the murine c-myc promoter in a human glial cell line. J. Cell Biochem., 49 (1992b) 208.CrossRefPubMedGoogle Scholar
  87. Monia, B.P., Lesnik, E.A., Gonzalez, C., Lima, W.F., McGee, D., Guinosso, C.J., Kawasaki, A.M., Cook, P.D. and Freier, S.M., Evaluation of 2-modified oligonucleotides containing 2-deoxy gaps as antisense inhibitors of gene expression. J. Biol. Chem., 268 (1993) 14514.PubMedGoogle Scholar
  88. Motokura, T. and Arnold, A., PRAD1/cyclin D1 proto-oncogene: Genomic organization, 5 DNA sequence, and sequence of a tumor-specific rearrangement breakpoint. Genes Chromosomes Cancer, 7 (1993) 89.PubMedGoogle Scholar
  89. Mukhopadhyay, T., Tainsky, M., Cavender, A.C. and Roth, J.A., Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. Cancer Res., 51 (1991) 1744.PubMedGoogle Scholar
  90. Namavari, M., Barrio, J.R., Toyokuni, T., Gambhir, S.S., Cherry, S.R., Herschman, H.R., Phelps, M.E. and Satyamurthy, N., Syn-thesis of 8-[(18)F]fluoroguanine derivatives: In vivoprobes for imaging gene expression with positron emission tomography., Nucl. Med. Biol., 27 (2000) 157.PubMedGoogle Scholar
  91. Nemunaitis, J., Swisher, S.G., Timmons, T., Connors, D., Mack, M., Doerksen, L., Weill, D., Wait, J., Lawrence, D.D., Kemp, B.L., Fossella, F., Glisson, B.S., Hong, W.K., Khuri, F.R., Kurie, J.M., Lee, J.J., Lee, J.S., Nguyen, D.M., Nesbitt, J.C., Perez-Soler, R., Pisters, K.M., Putnam, J.B., Richli, W.R., Shin, D.M., Walsh, G.L. and Merritt, J., Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer (In Process Citation).J. Clin. Oncol., 18 (2000) 609.PubMedGoogle Scholar
  92. Nevins, J.R., E2F; A link between the Rb tumor suppressor protein and viral oncogenesis. Science, 258 (1992) 424.PubMedGoogle Scholar
  93. Okada, F., Rak, J.W., Croix, B.S., Lieubeau, B., Kaya, M., Ron-cari, L., Shirasawa, S., Sasazuki, T. and Kerbel, R.S., Impact of oncogenes in tumor angiogenesis: mutant K-ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells. Proc. Natl. Acad. Sci. USA, 95 (1998) 3609.CrossRefPubMedGoogle Scholar
  94. Oliff, A., Farnesyltransferase inhibitors: Targeting the molecular basis of cancer. Biochim. Biophys. Acta, 1423 (1999) C19.Google Scholar
  95. Pallela, V.R., Thakur, M.L., Chakder, S. and Rattan, S., 99mTc-labeled vasoactive intestinal peptide receptor agonist: Functional studies. J. Nucl. Med., 40 (1999a) 352.PubMedGoogle Scholar
  96. Pallela, V.R., Thakur, M.L., Consigny, P.M., Rao, P.S., Vasileva-Belnikolavska, D. and Shi, R., Imaging thromboembolism with Tc-99m-labeled thrombospondin receptor analogs TP-1201 and TP-1300. Thromb. Res., 93 (1999b) 191.CrossRefPubMedGoogle Scholar
  97. Pietrzkowski, Z., Sell, C., Lammers, R., Ullrich, A. and Baserga, R., Roles of insulinlike growth factor 1 (IGF-1) and the IGF-1 receptor in epidermal growth factor-stimulated growth of 3T3 cells. Mol. Cell Biol., 12 (1992a) 3883.PubMedGoogle Scholar
  98. Pietrzkowski, Z., Wernicke, D., Porcu, P., Jameson, B.A. and Baserga, R., Inhibition of cellular proliferation by peptide ana-logues of insulin-like growth factor 1. Cancer Res., 52 (1992b) 6447.PubMedGoogle Scholar
  99. Pirollo, K.F., Hao, Z., Rait, A., Ho, C.W. and Chang, E.H., Evid-ence supporting a signal transduction pathway leading to the radiation-resistant phenotype in human tumor cells. Biochem. Biophys. Res. Commun., 230 (1997) 196.CrossRefPubMedGoogle Scholar
  100. Ponomarev, V., Dubrovin, M., Balatoni, J., Finn, R., Blasberg, R.G. and Tjuvajev, J.G., PET imaging of p53 gene expression in tumors. J. Nucl. Med., 41 (2000) 263P.Google Scholar
  101. Press, M.F., Pike, M.C., Chazin, V.R., Hung, G., Udove, J.A., Markowicz, M., Danyluk, J., Godolphin, W., Sliwkowski, M., Akita, R. et al.,Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res., 53 (1993) 4960.PubMedGoogle Scholar
  102. Qiao, Q., Ramadani, M., Gansauge, S., Gansauge, F., Leder, G. and Beger, H.G., Reduced membranous and ectopic cytoplasmic ex-pression of beta-catenin correlate with cyclin D1 overexpression and poor prognosis in pancreatic cancer. Int. J. Cancer, 95 (2001) 194.CrossRefPubMedGoogle Scholar
  103. Quelle, D.E., Ashmun, R.A., Shurtleff, S.A., Kato, J.Y., Bar-Sagi, D., Roussel, M.F. and Sherr, C.J., Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev., 7 (1993) 1559.PubMedGoogle Scholar
  104. Rait, V.K. and Shaw, B.R., Boranophosphates support the RNase H cleavage of polyribonucleotides [In Process Citation]. Antisense Nucl. Acid Drug Dev., 9 (1999) 53.Google Scholar
  105. Reubi, J.C., Neuropeptide receptors in health and disease: The mo-lecular basis for in vivoimaging (see comments). J. Nucl. Med., 36 (1995) 1825.PubMedGoogle Scholar
  106. Robinson, L.A., Smith, L.J., Fontaine, M.P., Kay, H.D., Mountjoy, C.P. and Pirruccello, S.J., c-myc antisense oligodeoxyribonuc-leotides inhibit proliferation of non-small cell lung cancer. Ann. Thorac. Surg., 60 (1995) 1583.CrossRefPubMedGoogle Scholar
  107. Ross, J.S. and Fletcher, J.A., The HER-2/neu oncogene in breast cancer: Prognostic factor, predictive factor, and target for ther-apy. Oncologist, 3 (1998) 237.PubMedGoogle Scholar
  108. Ru, K., Taub, M.L. and Wang, J.H., Specific inhibition of breast cancer cells by antisense poly-DNP-oligoribonucleotides and targeted apoptosis. Oncol. Res., 10 (1998) 389.PubMedGoogle Scholar
  109. Sauter, E.R., Cleveland, D., Trock, B., Ridge, J.A. and Klein-Szanto, A.J., p53 is overexpressed in fifty percent of pre-invasive lesions of head and neck epithelium. Carcinogenesis, 15 (1994) 2269.PubMedGoogle Scholar
  110. Sauter, E.R., Herlyn, M., Liu, S.C., Litwin, S. and Ridge, J.A., Prolonged response to antisense cyclin D1 in a human squamous cancer xenograft model. Clin. Cancer Res., 6 (2000) 654.Google Scholar
  111. Sauter, E.R., Keller, S.M., Erner, S. and Goldberg, M., HER-2/neu: A differentiation marker in adenocarcinoma of the esophagus. Cancer Lett., 75 (1993) 41.CrossRefPubMedGoogle Scholar
  112. Sauter, E.R., Nesbit, M., Litwin, S., Klein-Szanto, A.J., Cheffetz, S. and Herlyn, M., Antisense cyclin D1 induces apoptosis and tumor shrinkage in human squamous carcinomas (In Process Citation). Cancer Res., 59 (1999a) 4876.PubMedGoogle Scholar
  113. Sauter, E.R., Nesbit, M., Litwin, S., Klein-Szanto, A.J.P. and Herlyn, M., Combination gene therapy to treat human malignant melanoma. Proc. Am. Assoc. Cancer Res., 40 (1999b) 3951A.Google Scholar
  114. Sauter, E.R., Ridge, J.A., Litwin, S. and Langer, C.J., Pretreatment p53 protein expression correlates with decreased survival in pa-tients with end-stage head and neck cancer. Clin. Cancer Res., 1 (1995a) 1407.PubMedGoogle Scholar
  115. Sauter, E.R., Ridge, J.A., Trock, B., Cleveland, D., Whitley, K.V., Mohr, R.M. and Klein-Szanto, A., Overexpression of the p53 gene in primary and metastatic head and neck carcinomas. Laryngoscope, 105 (1995b) 653.PubMedGoogle Scholar
  116. Schechter, A.L., Hung, M.C., Vaidyanathan, L., Weinberg, R.A., Yang-Feng, T.L., Francke, U., Ullrich, A. and Coussens, L., The neu gene: An erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science, 229 (1985) 976.PubMedGoogle Scholar
  117. Seidman, A.D., Single-agent paclitaxel in the treatment of breast cancer: Phase I and II development. Semin. Oncol., 26 (1999) 14.PubMedGoogle Scholar
  118. Shaw, B.R., Sergueev, D., He, K., Porter, K., Summers, J., Sergueeva, Z. and Rait, V., Boranophosphate backbone: A mimic of phosphodiesters, phosphorothioates, and methyl phosphon-ates. Meth. Enzymol., 313 (2000) 226.PubMedGoogle Scholar
  119. Slamon, D., Leyland-Jones, B., Shak, S. et al.,Addition of Herceptin (humanized anti-human HER2 antibody) to first line chemotherapy for HER2 overexpressing metastatic brest cancer markedly increases anticancer activity: A randomized, multina-tional controlled phase III trial. Proc. Am. Soc. Clin. Oncol., 17 (1998) 98.Google Scholar
  120. Slamon, D.J., Clark, G.M., Wong, S.G., Levin, W.J., Ullrich, A. and McGuire, W.L., Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 235 (1987) 177.PubMedGoogle Scholar
  121. Smith, J.B. and Wickstrom, E., Antisense c-myc and immunostim-ulatory oligonucleotide inhibition of tumorigenesis in a murine B-cell lymphoma transplant model. J. Natl. Cancer Inst., 90 (1998) 1146.PubMedGoogle Scholar
  122. Smith, J.B. and Wickstrom, E., Preclinical antisense DNA therapy of cancer in mice. Meth. Enzymol., 314 (2000) 537.PubMedGoogle Scholar
  123. St. John, L.S., Sauter, E.R., Herlyn, M., Litwin, S. and Adler-Storthz, K., Endogeneous p53 gene status predicts response of human squamous cell carcinomas to wild-type p53. Cancer Gene Ther., (2000) in press.Google Scholar
  124. Stalteri, M.A. and Mather, S.J., In-vitrostudies on 99m-Tc-labeled HYNIC-conjugated oligonucleotides. Nucl. Med. Commun., 21 (2000) 374.CrossRefGoogle Scholar
  125. Tada, M., Omata, M., Kawai, S., Saisho, H., Ohto, M., Saiki, R.K. and Sninsky, J.J., Detection of ras gene mutations in pan-creatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res., 53 (1993) 2472.PubMedGoogle Scholar
  126. Tan, M.H. and Chu, T.M., Characterization of the tumorigenic and metastatic properties of a human pancreatic tumor cell line (AsPC-1) implanted orthotopically into nude mice. Tumour Biol., 6 (1985) 89.PubMedGoogle Scholar
  127. Tan, T.M., Kalisch, B.W., van de Sande, J.H., Ting, R.C. and Tan, Y.H., Biologic activity of oligonucleotides with polarity and ano-meric center reversal. Antisense Nucl. Acid Drug Dev., 8 (1998) 95.Google Scholar
  128. Thakur, M.L., Marcus, C.S., Saeed, S., Pallela, V., Minami, C., Diggles, L., Le Pham, H., Ahdoot, R. and Kalinowski, E.A., 99mTc-labeled vasoactive intestinal peptide analog for rapid localization of tumors in humans. J. Nucl. Med., 41 (2000a) 107.PubMedGoogle Scholar
  129. Thakur, M.L., Pallela, V.R., Consigny, P.M., Rao, P.S., Vessileva-Belnikolovska, D. and Shi, R., Imaging vascular thrombosis with 99mTc-labeled fibrin alpha-chain peptide. J. Nucl. Med., 41 (2000b) 161.PubMedGoogle Scholar
  130. Thissen, J.A., Gross, J.M., Subramanian, K., Meyer, T. and Casey, P.J., Prenylation-dependent association of Ki-Ras with micro-tubules. Evidence for a role in subcellular trafficking. J. Biol. Chem., 272 (1997) 30362.CrossRefPubMedGoogle Scholar
  131. Thor, A.D., Berry, D.A., Budman, D.R., Muss, H.B., Kute, T., Henderson, I.C., Barcos, M., Cirrincione, C., Edgerton, S., Allred, C., Norton, L. and Liu, E.T., erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer (see comments). J. Natl. Cancer Inst., 90 (1998) 1346.CrossRefPubMedGoogle Scholar
  132. Thor, A.D., Moore II, D.H., Edgerton, S.M., Kawasaki, E.S., Reih-saus, E., Lynch, H.T., Marcus, J.N., Schwartz, L., Chen, L.C., Mayall, B.H. et al.,Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J. Natl. Cancer Inst., 84 (1992) 845.PubMedGoogle Scholar
  133. Tian, X. and Wickstrom, E., Continuous solid-phase synthesis and disulfide cyclization of peptide-PNA-peptide chimeras. Organic Lett., 4 (2002) 4013.CrossRefGoogle Scholar
  134. Tong, Z., Singh, G. and Rainbow, A.J., The role of the p53 tumor suppressor in the response of human cells to photofrin-mediated photodynamic therapy (In Process Citation). Photochem. Photo-biol., 71 (2000) 201.Google Scholar
  135. Ullrich, A., Gray, A., Tam, A.W., Yang-Feng, T., Tsubokawa, M., Collins, C., Henzel, W., Le Bon, T., Kathuria, S., Chen, E. et al., Insulin-like growth factor I receptor primary structure: compar-ison with insulin receptor suggests structural determinants that define functional specificity. Embo J., 5 (1986) 2503.PubMedGoogle Scholar
  136. Ulsh, L.S. and Shih, T.Y., Metabolic turnover of human c-rasH p21 protein of E J. bladder carcinoma and its normal cellular and viral homologs. Mol. Cell Biol., 4 (1984) 1647.PubMedGoogle Scholar
  137. Vaughn, J.P., Iglehart, J.D., Demirdji, S., Davis, P., Babiss, L.E., Caruthers, M.H. and Marks, J.R., Antisense DNA downregu-lation of the ERBB2 oncogene measured by a flow cytometric assay. Proc. Natl. Acad. Sci. USA, 92 (1995) 8338.PubMedGoogle Scholar
  138. Vaughn, J.P., Stekler, J., Demirdji, S., Mills, J.K., Caruthers, M.H., Iglehart, J.D. and Marks, J.R., Inhibition of the erbB-2 tyrosine kinase receptor in breast cancer cells by phosphoromonothioate and phosphorodithioate antisense oligonucleotides. Nucl. Acids Res., 24 (1996) 4558.CrossRefPubMedGoogle Scholar
  139. Walder, R.Y. and Walder, J.A., Role of RNase H in hybrid-arrested translation by antisense oligonucleotides. Proc. Natl. Acad. Sci. USA, 85 (1988) 5011.PubMedGoogle Scholar
  140. Watson, P.H., Pon, R.T. and Shiu, R.P., Inhibition of c-myc expres-sion by phosphorothioate antisense oligonucleotide identifies a critical role for c-myc in the growth of human breast cancer. Cancer Res., 51 (1991) 3996.PubMedGoogle Scholar
  141. Wickstrom, E., Prospects for Antisense Nucleic Acid Therapy of Cancer and AIDS, Wiley-Liss, New York,1991.Google Scholar
  142. Wickstrom, E., Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, Marcel Dekker, New York,1998.Google Scholar
  143. Wickstrom, E., Bacon, T.A. and Wickstrom, E.L., Down-regulation of c-MYC antigen expression in lymphocytes of Emu-c-myc transgenic mice treated with anti-c-myc DNA methylphosphon-ates. Cancer Res., 52 (1992) 6741.PubMedGoogle Scholar
  144. Wickstrom, E., Simonet, W.S., Medlock, K. and Ruiz-Robles, I., Complementary oligonucleotide probe of vesicular stomatitis virus matrix protein mRNA secondary structure. Biophys. J., 49 (1986a) 15.Google Scholar
  145. Wickstrom, E. and Tyson, F.L., Oligonucleotides as Therapeutic Agents, London, 1997.Google Scholar
  146. Wickstrom, E.L., Bacon, T.A., Gonzalez, A., Freeman, D.L., Ly-man, G.H. and Wickstrom, E., Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhib-ited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. Proc. Natl. Acad. Sci. USA, 85 (1988) 1028.PubMedGoogle Scholar
  147. Wickstrom, E.L., Bacon, T.A., Gonzalez, A., Lyman, G.H. and Wickstrom, E., Anti-c-myc DNA increases differentiation and decreases colony formation by HL-60 cells. In VitroCell. De-velop. Biol., 25 (1989) 297.Google Scholar
  148. Wickstrom, E.L., Wickstrom, E., Lyman, G.H. and Freeman, D.L., HL60 cell proliferation inhibited by an anti-c-mycpentadec-adeoxynucleotide. Fed. Proc., 45 (1986b) 1708.Google Scholar
  149. Xu, L., Pirollo, K.F., Tang, W.H., Rait, A. and Chang, E.H., Transferrin-liposome-mediated systemic p53 gene therapy in combination with radiation results in regression of human head and neck cancer xenografts. Hum. Gene Ther., 10 (1999) 2941.CrossRefPubMedGoogle Scholar
  150. Yamaguchi, K., Chijiiwa, K., Noshiro, H., Torata, N., Kinoshita, M. and Tanaka, M., Ki-ras codon 12 point mutation and p53 muta-tion in pancreatic diseases. Hepatogastroenterology, 46 (1999) 2575.PubMedGoogle Scholar
  151. Yasuda, D., Iguchi, H., Ikeda, Y., Nishimura, S., Steeg, P., Misawa, T., Nasawa, H. and Kono, A., Possible association of nm23 gene expression and Ki-ras point mutations with metastatic potential in human pancreatic cancer-derived cell lines. Int. J. Oncol., 3 (1993) 641.Google Scholar
  152. Zamecnik, P.C. and Stephenson, M.L., Inhibition of Rous sar-coma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc. Natl. Acad. Sci. USA, 75 (1978) 280.PubMedGoogle Scholar
  153. Zhang, Y., Yu, D., Xia, W. and Hung, M.C., HER-2/neu-targeting cancer therapy via adenovirus-mediated E1A delivery in an animal model. Oncogene, 10 (1995) 1947.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Eric Wickstrom
    • 1
    • 2
    • 3
  • Mathew L. Thakur
    • 4
    • 5
    • 6
  • Edward R. Sauter
    • 7
  1. 1.Department of Biochemistry and Molecular PharmacologyThomas Jefferson UniversityPhiladelphiaU.S.A.
  2. 2.Department of Radiology, Kimmel Cancer CenterPhiladelphiaU.S.A. and
  3. 3.Cardeza Foundation for Hematologic Research, Thomas Jefferson UniversityPhiladelphiaU.S.A.;
  4. 4.Department of RadiologyThomas Jefferson UniversityPhiladelphiaU.S.A.
  5. 5.Department of RadiologyThomas Jefferson UniversityPhiladelphiaU.S.A. and
  6. 6.Department of Radiation OncologyThomas Jefferson UniversityPhiladelphiaU.S.A
  7. 7.Department of SurgeryUniversity of MissouriColumbiaU.S.A

Personalised recommendations