Pharmacokinetics, toxicity, and efficacy of ends-modified raf antisense oligodeoxyribonucleotide encapsulated in a novel cationic liposome

Clinical Cancer Research

Volumn 8, Issue 11, 2002, Pages 3611-3621

  Gokhale, Prafulla C ^a   Zhang, Chuanbo ^a   Newsome, Joseph T ^a   Pei, Jin ^a   Ahmad, Imran ^a   Rahman, Aquilur ^a   Dritschilo, Anatoly ^a   Kasid, Usha N ^a  

^a GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; ALTERNATIVE COMPLEMENT PATHWAY C3 C5 CONVERTASE; ANTINEOPLASTIC AGENT; ANTISENSE OLIGODEOXYNUCLEOTIDE; ASPARTATE AMINOTRANSFERASE; CATION; COMPLEMENT COMPONENT C3A; LIPOSOME; LIVER ENZYME; RAF PROTEIN; ANTISENSE OLIGONUCLEOTIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; DRUG HALF LIFE; DRUG STABILITY; HEMOLYSIS; HISTOPATHOLOGY; HUMAN; HUMAN CELL; MONKEY; NONHUMAN; PRIORITY JOURNAL; PROSTATE TUMOR; PROTEIN EXPRESSION; PROTEIN FUNCTION; RABBIT; TOXICITY TESTING; ANIMAL; BAGG ALBINO MOUSE; CELL CULTURE; CELL DIVISION; CELL SURVIVAL; FEMALE; GENETICS; MACACA; MALE; METABOLISM; MOUSE; NUDE MOUSE; TEMPERATURE; TIME;

ANIMALS; CATIONS; CELL DIVISION; CELL SURVIVAL; FEMALE; HUMANS; LIPOSOMES; MACACA FASCICULARIS; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; OLIGONUCLEOTIDES, ANTISENSE; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-RAF; RABBITS; TEMPERATURE; TIME FACTORS; TUMOR CELLS, CULTURED;

EID: 0036848796     PISSN: 10780432     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (70)

1. Kolch, W., Heidecker, G., Lloyd, P., and Rapp, U. R. Raf-1 protein kinase is required for growth of induced NIH/3T3 cells. Nature (Lond.), 349: 426-428, 1991.
2. Kasid, U., Pfeifer, A., Brennan, T., Beckett, M., Weichselbaum, R. R., Dritschilo, A., and Mark, G. E. Effect of antisense c-raf-1 on tumorigenicity and radiation sensitivity of a human squamous carcinoma. Science (Wash. DC), 243: 1354-1356, 1989.
3. Kasid, U., Suy, S., Dent, P., Ray, S., Whiteside, T. L., and Sturgill, T. W. Activation of Raf by ionizing radiation. Nature (Lond.), 382: 813-816, 1996.
4. Morrison, D. K., and Cutler, R. E., Jr. The complexity of Raf-1 regulation. Curr. Opin. Cell Biol., 9: 174-179, 1997.
5. Kolch, W. Meaningful relationships: The regulation of Ras/Raf/MEK/ ERK pathway by protein interactions. Biochem. J., 351: 289-305, 2000.
6. Podar, K., Tai, Y., Davies, F. E., Lentzsch, S., Sattler, M., Hideshima, T., Lin, B. K., Gupta, D., Shima, Y., Chauhan, D., Mitsiades, C., Raje, N., Richardson, P., and Anderson, K. C. Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration. Blood, 98: 428-435, 2001.
7. Kasid, U., and Suy, S. Stress-responsive signal transduction: Emerging concepts and biological significance. In: C. S. Potten, C. Booth, and J. Wilson (eds.), Apoptosis Genes, pp. 85-118. Norwell, MA: Kluwer Academic Publishers, 1998.
8. Garrington, T. P., and Johnson, G. L. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr. Opin. Cell Biol., 11: 211-218, 1999.
9. ARF. Cell, 103: 321-330, 2000.
10. Wang, H. G., Rapp, U. R., and Reed, J. Bcl-2 targets the protein kinase Raf-1 to mitochondria. Cell, 87: 629-638, 1996.
11. Zhong, J., Troppmair, J., and Rapp, U. R. Independent control of cell survival by Raf-1 and Bcl-2 at the mitochondria. Oncogene, 20: 4807-4816, 2001.
12. Gise, A. V., Lorenz, P., Wellbrock, C., Hemmings, B., Berberich-Siebelt, F., Rapp, U. R., and Troppmair, J. Apoptosis suppression by Raf-1 and MEK1 requires MEK and phosphatidylinositol 3 kinase dependent signals. Mol. Cell. Biol., 21: 2324-2336, 2001.
13. Mikula, M., Schreiber, M., Husak, Z., Kucerova, L., Rüth, J., Wieser, R., Zatloukal, K., Beug, H., Wagner, E. F., and Baccarini, M. Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene. EMBO J., 20: 1952-1962, 2001.
14. Chen, J., Fujii, K., Zhang, L., Roberts, T., and Fu, H. Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism. Proc. Natl. Acad. Sci. USA. 98: 7783-7788, 2001.
15. Wang, S., Ghosh, R. N., and Chellappan, S. P. Raf-1 physically interacts with Rb and regulates its functions: A link between mitogenic signaling and cell cycle regulation. Mol. Cell. Biol., 18: 7487-7498, 1998.
16. Janosch, P., Kieser, A., Eulitz, M., Lovric, J., Sauer, G., Reichert, M., Gounari, F., Buescher, D., Baccarini, M., Mischak, H., and Kolch, W. The Raf-1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments. FASEB J., 14: 2008-2021, 2000.
17. Broustas, C. G., Grammatikakis, N., Eto, M., Dent, P., Brautigan, D. L., and Kasid, U. Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity. J. Biol. Chem., 277: 3053-3059, 2002.
18. Patel, S., Wang, F-H., Whiteside, T. L., and Kasid, U. Constitutive modulation of Raf-1 protein kinase is associated with differential gene expression of several known and unknown genes. Mol. Med., 3: 674-685, 1997.
19. Schulze, A., Lehmann, K., Jefferies, H. B. J., McMahon, M., and Downward, J. Analysis of the transcriptional program induced by Raf in epithelial cells. Genes Dev., 15: 981-994, 2001.
20. Monia, B. P., Johnston, J. F., Geiger, T., Muller, M., and Fabbro, D. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase. Nat. Med., 2: 668-675, 1996.
21. Pfeifer, A., Mark, G., Leung, S., Dougherty, M., Spillare, E., and Kasid, U. Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung-carcinoma. Biochem. Biophys. Res. Commun., 252: 481-486, 1998.
22. Rasouli-Nia, A., Liu, D., Perdue, S., and Britten, R. A. High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced cytotoxicity. Clin. Cancer Res., 4: 1111-1116, 1998.
23. Crooke, S. T. Therapeutic applications of oligonucleotides. Annu. Rev. Pharmacol. Toxicol., 32: 329-376, 1992.
24. Agrawal, S. Factors affecting the specificity and mechanisms of action of antisense oligonucleotide. Antisense Nucleic Acid Drug Dev., 9: 371-375, 1999.
25. Koller, E., Gaarde, W. A., and Monia, B. P. Elucidating cell signaling mechanisms using antisense technology. Trends Pharmacol. Sci., 21: 142-148, 2000.
26. Monia, B. P., Holmlund, J., and Dorr, A. F. Antisense approaches for the treatment of cancer. Cancer Investig., 18: 635-650, 2000.
27. Lebedeva, I., and Stein, C. A. Antisense oligonucleotides: Promise and reality. Annu. Rev. Pharmacol. Toxicol., 41: 403-419, 2001.
28. Stein, C. A. The experimental use of antisense oligonucleotides: A guide for the perplexed. J. Clin. Investig., 108: 641-644, 2001.
29. Soldatenkov, V. A., Dritschilo, A., Wang, F-H., Olah Z., Anderson, W. B., and Kasid, U. Inhibition of Raf-1 protein kinase by antisense phosphorothioate oligodeoxyribonucleotide is associated with sensitization of human laryngeal squamous carcinoma cells to gamma radiation. Cancer J. Sci. Am., 3: 13-20, 1997.
30. McPhillips, F., Mullen, P., Monia, B. P., Ritchie, A. A., Dorr, F. A., Smyth, J. F., and Langdon, S. P. Association of c-Raf expression with survival and its targeting with antisense oligonucleotides in ovarian cancer. Br. J. Cancer, 85: 1753-1758, 2001.
31. Lau, Q. C., Brusselbach, S., and Müller, R. Abrogation of c-Raf expression induces apoptosis in tumor cells. Oncogene, 16: 1899-1902, 1998.
32. Rahman, A., White, G., More, N., and Schein, P. S. Pharmacological, toxicological, and therapeutic evaluation in mice of doxorubicin entrapped in cardiolipin liposomes. Cancer Res., 45: 796-803, 1985.
33. Gokhale, P. C., Radhakrishnan, B., Husain, S. R., Abernethy, D. R., Sacher, R., Dritschilo, A., and Rahman, A. An improved method of encapsulation of doxorubicin in liposomes: Pharmacological, toxicological, and therapeutic evaluation. Br. J. Cancer, 74: 43-48, 1996.
34. Gokhale, P. C., Pei, J., Zhang, C., Ahmad, I., Rahman, A., and Kasid, U. Improved safety, pharmacokinetics, and therapeutic efficacy profiles of a novel liposomal formulation of mitoxantrone. Anticancer Res., 21: 3313-3322, 2001.
35. Fishman, M., Strauss, L., Pei, J., Gokhale, P., Zhang, C., LoRusso, P., Kraut, E., Fleming, C., Ahmad, A., Zhang, A., Khan, S., and Kasid, U. Liposome-encapsulated mitoxantrone (LEM): Pharmacokinetic and Phase I studies. Proc. Am. Soc. Clin. Oncol. Annu. Meet., 21: 84b, 2002.
36. Moreira, J. N., Hansen, C. B., Gaspar, R., and Allen, T. M. A growth factor antagonist as a targeting agent for sterically stabilized liposomes in human small cell lung cancer. Biochim. Biophys. Acta, 1514: 303-317, 2001.
37. Garcia-Chaumont, C., Seksek, O., Grzybowska, J., Borowski, E., and Bolard, J. Delivery systems for antisense oligonucleotides. In: D. Shugar (ed.), Pharmacol. Ther., 87: 255-277, 2000.
38. Leonetti, C., Biroccio, A., Benassi, B., Stringaro, A., Stoppacciaro, A., Semple, S. C., and Zupi, G. Encapsulation of c-myc antisense oligodeoxynucleotides in lipid particles improves antitumoral efficacy in vivo in a human melanoma line. Cancer Gene Ther., 8: 459-468, 2001.
39. 2 targeted immunoliposomes: Antitumor effects. J. Natl. Cancer Inst. (Bethesda), 92: 253-261, 2000.
40. Tari, A. M., Stephens, C., Rosenblum, M., and Lopez-Berestein, G. Pharmacokinetics, tissue distribution, and safety of P-ethoxy oligonucleofides incorporated in liposomes. J. Liposome Res., 8: 251-264, 1998.
41. Islam, A., Handley, S. L., Thompson, K. S. J., and Akhtar, S. Studies on uptake, sub-cellular trafficking and efflux of antisense oligodeoxynucleotides in glioma cells using self-assembling cationic lipoplexes as delivery systems. J. Drug Targeting, 7: 373-382, 2000.
42. De Oliveira, M. C., Boutet, V., Fattal, E., Boquet, D., Grognet, J., Couvreur, P., and Deverre, J-R. Improvement of in vivo stability of phosphodiester oligonucleotide using anionic liposomes in mice. Life Sci., 67: 1625-1637, 2000.
43. Gokhale, P. C., Soldatenkov, V., Wang, F-H., Rahman, A., Dritschilo, A., and Kasid, U. Antisense raf oligodeoxyribonucleotide is protected by liposomal encapsulation and inhibits Raf-1 protein expression in vitro and in vivo: Implications for gene therapy of radioresistant cancer. Gene Ther., 4: 1289-1299, 1997.
44. Gokhale, P. C., McRae, D., Monia, B. P., Bagg, A., Rahman, A., Dritschilo, A., and Kasid, U. Antisense raf oligodeoxyribonucleotide is a radiosensitizer in vivo. Antisense Nucleic Acid Drug Dev., 9: 191-201, 1999.
45. Suy, S., Anderson, W. B., Dent, P., Chang, E., and Kasid, U. Association of Grb2 with Sos and Ras with Raf-1 upon gamma irradiation of breast cancer cells. Oncogene, 15: 53-61, 1997.
46. Weinstein-Oppenheimer, C. R., Blalock, W. L., Steelman, L. S., Chang, F., and McCubrey, J. A. The Raf signal transduction cascade as a target for chemotherapeutic intervention in growth factor-responsive tumors. In: J. G. Cory (ed.), Pharmacol. Ther., 88: 229-279, 2000.
47. Awada, A., Hendlisz, A., Gil, T., Bleiberg, H., Bartholomeus, S., De Valeriola, D., Dewitte, M., Coppieters, S., Moeller, J., De Becker, D., Meert, A., and Piccart, M. A clinical, pharmacokinetic and pharmacodynamic Phase I study of the raf kinase inhibitor BAY 43-9006 in patients with advanced solid cancers. Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications. 569: 116, 2001.
48. Zeng, J., Nheu, T., Zorzet, A., Catimel, B., Nice, E., Maruta, H., Burgess, A. W., and Treutlein, H. R. Design of inhibitors of Ras-Raf interaction using a computational combination algorithm. Protein Eng., 14: 39-45, 2001.
49. Rudin, C. M., Holmlund, J., Fleming, G. F., Mani, S., Stadler, W. M., Schumm, P., Monia, B. P., Johnston, J. F., Geary, R., Yu, R. Z., Kwoh, T. J., Dorr, F. A., and Ratain, M. J. Phase I trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. Clin. Cancer Res., 7: 1214-1220, 2001.
50. Valerie, K. Viral vectors for gene delivery. In: S. Wu-Pong and Y. Rojanasakul (eds.), Biopharmaceutical Drug Design and Development, pp. 69-142. Totowa, NJ: Humana Press, Inc., 1999.
51. 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: 2941-2952, 1999.
52. Shibata, T., Giaccia, A. J., and Brown, J. M. Development of a hypoxia-responsive vector for tumor-specific gene delivery. Gene Ther., 7: 493-498, 2000.
53. Roth, J. A., Grammer, S. F., Swisher, S. G., Komaki, R., Nemunaitis, J., Merritt, J., Fujiwara, T., and Meyn, R. E., Jr. Gene therapy approaches for the management of non-small cell lung cancer. Semin. Oncol., 28: 50-56, 2001.
54. Henry, S. P., Giclas, P. C., Leeds, J., Pangburn, M., Auletta, C., Levin, A. A., and Kornbrust, D. J. Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: Potential mechanism of action. J. Pharmacol. Exp. Ther., 281: 810-816, 1997.
55. Hall, E. J. Radiobiology for the Radiologist, Ed. 5, pp. 5-17. Philadelphia: Lippincott, 2000.
56. Khodarev, N. N., Park, J. O., Yu, J., Gupta, N., Nodzenski, E., Roizman, B., and Weichselbaum, R. R. Dose-dependent and independent temporal patterns of gene response to ionizing radiation in normal and tumor cells and tumor xenografts. Proc. Natl. Acad. Sci. USA, 98: 12665-12670, 2001.
57. Hollander, M. C., Sheikh, M. S., Bulavin, D. V., Lundgren, K., Augeri-Henmueller, L., Shehee, R., Molinaro, T. A., Kim, K. E., Tolosa, E., Ashwell, J. D., Rosenberg, M. P., Zhan, Q., Fernandez-Salguero, P. M., Morgan, W. F., Deng, C. X., and Fornace, A. J., Jr. Genomic instability in Gadd45a-deficient mice. Nat. Genet., 23: 176-184, 1999.
58. Jones, H. A., Hahn, S. M., Bernhard, E., and McKenna, W. G. Ras inhibitors and radiation therapy. Semin. Radiat. Oncol., 11: 328-337, 2001.
59. Kastan, M. B. Molecular determinants of sensitivity to antitumor agents. Biochim. Biophys. Acta, 1424: R37-R42, 1999.
60. Brown, J. M., and Giaccia, A. J. The unique physiology of solid tumors: Opportunities (and problems) for cancer therapy. Cancer Res., 58: 1408-1416, 1998.
61. Poggi, M. M., Coleman, N., and Mitchell, J. B. Sensitizers and protectors of radiation and chemotherapy. Curr. Prob. Cancer, 25: 329-412, 2001.
62. Teicher, B. A. A systems approach to cancer therapy. Cancer Metastasis Rev., 15: 247-272, 1996.
63. Mewani, R., Tang, W., Rahman, A., Dritschilo, A., Ahmad, I., Kasid, U., and Gokhale, P. C. Enhanced antitumor activity of liposome-entrapped antisense raf oligonucleotide (LErafAON) in combination with chemotherapeutic agents. Proc. Am. Assoc. Cancer Res., 43: 577, 2002.
64. Pei, J., Zhang, C., Gokhale, P. C., Rahman, A., Dritschilo, A., Ahmad, I., and Kasid, U. Antitumor activity of a combination of liposomal antisense raf oligodeoxyribonucleotide (LErafAON) and chemotherapeutic drug cisplatin, mitoxantrone or epirubicin. Proc. Am. Assoc. Cancer Res., 43: 413, 2002.
65. Pei, J., Zhang, C., Gokhale, P. C., Rahman, A., Dritschilo, A. Ahmad, I., and Kasid, U. Enhanced effects of a novel liposome-based antisense raf oligodeoxyribonucleotide (LErafAON) in combination with taxotere or gemcitabine. Abstract No. 10, First International Congress on Targeted Therapies, Washington, DC, 2002.
66. Dritschilo, A., Huang, C., Strauss, L., Fleming, C., Rahman, A., Rudin, C., Collins, B., Marshall, J., Singh, A., Zhang, C., Kumar, D., Gokhale, P., and Kasid, U. Liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) in patients with advanced solid tumors: Phase I study of daily infusion during radiation therapy. Proc. Am. Soc. Clin. Oncol. Annu. Meet., 21: 28a, 2002.
67. Rudin, C., Bertucci, D., Strauss, L., Fleming, C., Kindler, H., Fleming, G., Zhang, C., Kumar, D., Gokhale, P., Kasid, U., and Ratain, M. Liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) in patients with advanced solid tumors: Phase I study of weekly infusion. Proc. Am. Soc. Clin. Oncol. Annu. Meet., 21: 9b, 2002.
68. th EORTC-NCI-AACR Symposium on "Molecular Targets and Cancer Therapeutics," 2002.
69. Dritschilo, A., Huang, C., Strauss, L., Fleming, C., Rahman, A., Rudin, C., Collins, B., Marshall, J., Singh, A., Zhang, C., Kumar, D., Gokhale, P, and Kasid, U. Liposome-encapsulated c-raf antisense oligodeoxynucleotide (LErafAON) in patients with advanced solid tumors: Phase I study of daily infusion during radiation therapy. Pharmacotherapy (in press), 2002.
70. Park, Y. G., Nesterova, M., Agrawal, S., and Cho-Chung, Y. S. Dual blockade of cyclic AMP response element- (CRE) and AP-1-directed transcription by CRE-transcription factor decoy oligonucleotide: Gene-specific inhibition of tumor growth. J. Biol. Chem., 274: 1573-1580, 1999.