Chapter 10 : Progress in the Molecular Medicine of Cancer

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Cancer is a formidable challenge, and one should have no illusions that major breakthroughs in the prevention, diagnosis, and treatment of the disease will come easily. Nevertheless, several converging lines of research are providing exciting new opportunities for clinical application. Some of these areas are summarized in this chapter. The goal is to identify a few areas in which the molecular foundations of oncology are supporting ideas that are likely to have clinical ramifications in the near future. The molecular dissection of colon cancer continues to provide new insights into the cascade of genetic events that lead to full-blown malignant transformation. Microsatellite alterations are associated with small-cell lung cancer, head and neck tumors, bladder cancer, and most likely other tumors as well. Diseases targeted for innovative trials of cytokine gene-transfected tumor cells include breast, ovarian, renal, and colon cancers, and development of their use against melanoma continues. The suicide vector model serves as one template for further development in other cancers as well, especially those compartmentalized in relatively sequestered sites, e.g., intraperitoneal ovarian cancer or primary central nervous system lymphoma, an opportunistic cancer associated with AIDS. Molecular medicine continues to uncover the broad principles that govern the interplay between internal and external factors that modulate net gene expression and cellular function for many cell types. If the tradition of excellence and the balance between creativity and scientific rigor exemplified by the work of Howard Temin is maintained, progress against cancer is assuredly made.

Citation: Broder S. 1995. Progress in the Molecular Medicine of Cancer, p 129-152. In Cooper G, Temin R, Sugden B (ed), The DNA Provirus. ASM Press, Washington, DC. doi: 10.1128/9781555818302.ch10

Key Concept Ranking

Memory B Cell
Tumor Necrosis Factor
Major Histocompatibility Complex
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1. Aaltonen, L. A.,, P. Peltomaki,, F. S. Leach,, P. Sistonen,, L. Pylkkanen,, J. P. Mecklin,, H. Jarvinen,, S. M. Powell,, J. Jen,, S. R. Hamilton,, G. M. Petersen,, K. W. Kinzler,, B. Vogelstein,, and A. D. L. Chapelle. 1993. Clues to the pathogenesis of familial colorectal cancer. Science 260:812816.
2. Asher, A. L.,, J. J. Mule,, A. Kasid,, N. P. Restifo,, J. C. Salo,, C. M. Reichert,, G. Jaffe,, B. Fendly,, M. Kreigler,, and S. A. Rosenberg. 1991. Murine tumor cells transduced with the gene for tumor necrosis factor-alpha. J. Immunol. 146:3227.
3. Bayever, E.,, K. M. Haines,, P. L. Iversen,, R. W. Ruddon,, S. J. Pirruccello,, C. P. Mountjoy,, M. A. Arneson,, and L. J. Smith. Selective cytotoxicity to human myeloblasts produced by oligodeox-yribonucleotides directed to p53 nucleotide sequences. Leukemia Lymphoma, in press.
4. Bayever, E.,, P. L. Iversen,, M. R. Bishop,, J. G. Sharp,, H. K. Tewary,, M. A. Arneson,, S. J. Pirruccello,, R. R. Ruddon,, A. Kessinger,, G. Zon,, and J. O. Armitage. Systemic administration of a phosphorothioate oligonucleotide with a sequence complementary to p53 for acute myelogenous leukemia and myelodysplastic syndrome: initial results of a phase I trial. Antisense Res. Dev., in press.
5. Bhalla, K.,, C. Tang,, A. M. Ibrado,, S. Grant,, E. Tourkina,, C. Holladay,, M. Hughes,, M. E. Mahoney,, and Y. Huang. 1992. Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein (pIXY 321) enhances high-dose ara-C-induced programmed cell death or apoptosis in human myeloid leukemia cells. Blood 80:28832890.
6. Biondi, A.,, A. Rambaldi,, M. Alcalay,, P. P. Pandolfi,, F. Lo Coco,, D. Diverio,, V. Rossi,, A. Mencarel-li,, D. L. Longo,, D. Zangrilli,, G. Masera,, T. Barbui,, F. Mandelli,, F. Grignani,, and P. G. Pelicci. 1991. RAR-α gene rearrangements as a genetic marker for diagnosis and monitoring in acute promyelocytic leukemia. Blood 77:14181422.
7. Bissonette, R. P.,, F. Echeverri,, A. Mahboubi,, and D. R. Green. 1992. Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature (London) 359:552554.
8. Bodley, A. L.,, and L. F. Liu. 1988. Topoisomerases as novel targets for cancer chemotherapy. Bio/Technology 6:13151319.
9. Boulikas, T. 1991. Relation between carcinogenesis, chromatin structure and poly(ADP-ribosyla-tion). Anticancer Res. 11:489528.
10. Cannon-Albright, L. A.,, D. E. Goldgar,, L. J. Meyer,, C. M. Lewis,, D. E. Anderson,, J. W. Fountain,, M. E. Hegi,, R. W. Wiseman,, E. M. Petty,, A. E. Bale,, O. I. Olopade,, M. O. Diaz,, D. J. Kwiatkowski,, M. W. Piepkorn,, J. J. Zone,, and M. H. Skolnick. 1992. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science 258:11481152.
11. Carson, D. A.,, and J. M. Ribeiro. 1993. Apoptosis and disease. Lancet 341:12511254.
12. Castaigne, S.,, N. Bailitrand,, H. de Thé,, A. Dejean,, L. Degos,, and C. A. Chomienne. 1992. PML/ retinoic acid polymerase chain reaction in acute promyelocytic leukemia. Blood 79:31103115.
13. Cerretti, D. P.,, C. J. Kozlosky,, B. Mosley,, N. Nelson,, K. Van Ness,, T. A. Greenstreet,, C. J. March,, S. R. Kronheim,, T. Druck,, L. A. Cannizzaro,, K. Huebner,, and R. A. Black. 1992. Molecular cloning of the interleukin-1/3 converting enzyme. Science 256:97100.
14. Chen, C.-S.,, P. H. B. Sorensen,, P. H. Domer,, G. H. Reaman,, S. J. Korsmeyer,, N. A. Heerema,, G. D. Hammond,, and J. H. Kersey. 1993. Molecular rearrangements on chromosome 1 lq23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome. Blood 81:23862393.
15. Cherny, D. Y.,, B. P. Belotserkovskii,, M. D. Frank-Kamenetskii,, M. Egholm,, O. Buchardt,, R. H. Berg,, and P. E. Nielsen. 1993. DNA unwinding upon strand-displacement binding of a thymine-substituted polyamide to double-stranded DNA. Proc. Natl. Acad. Sci. USA 90:16671670.
16. Chiron, M.,, C. Demur,, V. Pierson,, J. P. Jaffrezou,, C. Muller,, S. Saivin,, C. Bordier,, C. Bousquet,, N. Dastugue,, and G. Laurent. 1992. Sensitivity of fresh acute myeloid leukemia cells to etoposide: relationship with cell growth characteristics and DNA single-strand breaks. Blood 80:13071315.
17. Cimino, G.,, D. T. Moir,, O. Canaani,, K. Williams,, W. M. Crist,, S. Katzav,, L. Cannizzaro,, B. Lange,, P. C. Nowell,, C. M. Croce,, and E. Canaani. 1991. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23),t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res. 51:67126714.
18. Clarke, A. R.,, C. A. Purdie,, D. J. Harrison,, R. G. Morris,, C. C. Bird,, M. L. Hooper,, and A. H. Wyllie. 1993. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature (London) 362:849852.
19. Culver, K. W.,, Z. Ram,, S. Wallbridge,, H. Ishii,, E. H. Oldfield,, and R. M. Blaese. 1992. In vivo gene transfer with retroviral vector-producer for treatment of experimental brain tumors. Science 256:15501552.
20. Daley, G. Q.,, R. A. Van Etten,, and D. Baltimore. 1990. Induction of chronic myelogenous leukemia in mice by the P210 bcr/abl gene of the Philadelphia chromosome. Science 247:824830.
21. D'Amico, D.,, D. Carbone,, T. Mitsudomi,, M. Nau,, J. Fedorko,, E. Russell,, B. Johnson,, D. Buchha-gen,, S. Bodner,, R. Phelps,, A. Gazdar,, and J. D. Minna. 1992. High frequency of somatically acquired p53 mutations in small-cell lung cancer cell lines and tumors. Oncogene 7:339346.
22. Delattre, O.,, J. Zucman,, B. Plougastel,, C. Desmaze,, T. Melot,, M. Peter,, H. Kovar,, I. Joubert,, P. de Jong,, G. Rouleau,, A. Aurias,, and G. Thomas. 1992. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature (London) 359:162165.
23. Djabali, M.,, L. Selleri,, P. Parry,, M. Bower,, B. D. Young,, and G. A. Evans. 1992. A trithorax-like gene is interrupted by chromosome 1 lq23 translocations in acute leukaemias. Nature Genet. 2:113118.
24. Donehower, L. A.,, M. Harvey,, B. L. Slagle,, M. J. McArthur,, C. A. Motgomery, Jr.,, J. S. Butel,, and A. Bradley. 1992. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature (London) 356:215221.
25. Dranoff, G.,, E. Jaffee,, A. Lazenby,, P. Golumbek,, H. Levitsky,, K. Brose,, V. Jackson,, H. Hamada,, D. Pardoll,, and R. C. Mulligan. 1993. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent-specific, and long-lasting anti-tumor immunity. Proc. Natl. Acad. Sci. USA 90:35393543.
26. Epstein, R. J. 1990. Drug-induced DNA damage and tumor chemosensitivity. J. Clin. Oncol. 8:20622084.
27. Evan, G. I.,, A. H. Wyllie,, C. S. Gilbert,, T. D. Littlewood,, H. Land,, M. Brooks,, C. M. Waters,, L. Z. Penn,, and D. C. Hancock. 1992. Induction of apoptosis in fibroblasts by c-Myc protein. Cell 69:119128.
28. Fanidi, A.,, E. A. Harrington,, and G. I. Evan. 1992. Cooperative interaction between c-myc and bcl-2 proto-oncogenes. Nature (London) 359:554556.
29. Futreal, P. A.,, Q. Liu,, D. Shattuck-Eidens,, C. Cochran,, K. Harshman,, S. Tavtigian,, L. M. Bennett,, A. Haugen-Strano,, J. Swensen,, Y. Miki,, K. Eddington,, M. McClure,, C. Frye,, J. Weaver-Feldhaus,, W. Ding,, Z. Gholami,, P. Soderkvist,, L. Terry,, S. Jhanwar,, A. Berchuck,, J. D. Iglehart,, J. Marks,, D. G. Ballinger,, J. C. Barrett,, M. H. Skolnick,, A. Kamb,, and R. Wiseman. BRCA1 mutations in primary breast and ovarian carcinomas. Science 266:120122.
30. Gaidano, G.,, P. Ballerini,, J. Z. Gong,, G. Inghirami,, A. Neri,, E. W. Newcomb,, I. T. Magrath,, D. M. Knowles,, and R. Dalla-Favera. 1991. p53 mutations in human lymphoid malignancies: association with Burkitt lymphoma and chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. USA 88:54135417.
31. Garcia, I.,, I. Martinou,, Y. Tsujimoto,, and J.-C. Martinou. 1992. Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. Science 258:302304.
32. Gatti, R. A.,, E. Boder,, H. V. Vinters,, R. S. Sparkes,, A. Norman,, and K. Lange. 1991. Ataxia-telangiectasia: an interdisciplinary approach to pathogenesis. Medicine 70:99117.
33. Goddard, A. D.,, J. Borrow,, P. S. Freemont,, and E. Solomon. 1991. Characterization of a zinc finger gene disrupted by t(15;17) in acute promyelocytic leukemia. Science 254:13711374.
34. Golumbek, P. T.,, A. J. Lazenby,, H. I. Levitsky,, L. M. Jaffee,, H. Karasuvama,, M. Baker,, and D. M. Pardoll. 1991. Treatment of established renal cell cancer by tumor cells engineered to secrete interleukin-4. Science 254:713.
35. Groden, J.,, A. Thliveris,, W. Samowitz,, M. Carlson,, L. Gelbert,, H. Albertson,, G. Joslyn,, J. Stevens,, L. Spirio,, M. Robertson,, L. Sargeant,, K. Krapcho,, E. Wolff,, R. Burt,, J. P. Hughes,, J. Warrington,, J. McPherson,, J. Wasmuth,, D. Le Paslier,, H. Abderrahim,, D. Cohen,, M. Leppert,, and R. White. 1991. Identification and characterization of the familial adenomatous polyposis coli gene. Cell 66:589600.
36. Gu, Y.,, T. Nakamura,, H. Alder,, R. Prasad,, O. Canaani,, G. Cimino,, C. M. Croce,, and E. Canaani. 1992. The t(4;ll) chromosome translocation of human acute leukemias fuses the ALL-l gene, related to drosophila trithorax, to the AF-4 gene. Cell 71:701708.
37. Gupta, R. K.,, J. S. Whelan,, T. A. Lister,, B. D. Young,, and J. G. Bodmer. 1992. Direct sequence analysis of the t(14;18) chromosomal translocation in Hodgkin's disease. Blood 79:20842088.
38. Hancock, S. L.,, M. A. Tucker,, and R. T. Hoppe. 1993. Breast cancer after treatment of Hodgkin's disease. J. Natl. Cancer Inst. 85:2531.
39. Hanvey, J. C.,, N. J. Peffer,, J. E. Bisi,, S. A. Thomson,, R. Cadilla,, J. A. Josey,, D. J. Ricca,, C. F. Hassman,, M. A. Bonham,, K. G. Au,, S. G. Carter,, D. A. Bruckenstein,, A. L. Boyd,, S. A. Noble,, and L. E. Babiss. 1992. Antisense and antigene properties of peptide nucleic acids. Science 258:14811485.
40. Harding, F. A.,, and J. P. Allison. 1993. CD28-B7 interactions allow the induction of CD8 cytotoxic T lymphocytes in the absence of exogenous help. J. Exp. Med. 177:17911796.
41. Helene, C. 1991. Rational design of sequence-specific oncogene inhibitors based on antisense and antigene oligonucleotides. Eur. J. Cancer 27:14661471.
42. Herskowitz, I. 1987. Functional inactivation of genes by dominant negative mutations. Nature (London) 329:219222.
43. Hollstein, M.,, D. Sidransky,, B. Vogelstein,, and C. C. Harris. 1991. p53 mutations in human cancers. Science 253:4953.
44. Howell, A.,, D. J. Dodwell,, H. Anderson,, and J. Redford. 1992. Response after withdrawal of tamoxifen and progestogens in advanced breast cancer. Ann. Oncol. 3:611617.
45. Hunger, S. P.,, D. C. Tkachuk,, M. D. Amylon,, M. P. Link,, A. J. Carroll,, J. L. Welborn,, C. L. Willman,, and M. L. Cleary. 1993. HRX involvement in de novo and secondary leukemias with diverse chromosome llq23 abnormalities. Blood 81:31973203.
46. Jaffee, E. M.,, G. Dranoff,, L. K. Cohen,, K. M. Hauda,, S. Clift,, F. F. Marshall,, R. C. Mulligan,, and D. M. Pardoll. 1993. High efficiency gene transfer into primary human tumor explants without cell selection. Cancer Res. 53:22212226.
47. James, G. L.,, J. L. Goldstein,, M. S. Brown,, T. E. Rawson,, T. C. Somers,, R. S. McDowell,, C. W. Crowley,, B. K. Lucas,, A. D. Levinson,, and J. D. Marsters, Jr. 1993. Benzodiazepine peptidomimetics: potent inhibitors of ras farnesylation in animal cells. Science 260:19371942.
48. Jiang, S.-Y.,, S. M. Langan-Fahey,, A. L. Stella,, R. McCague,, and V. C. Jordan. 1992. Point mutation of estrogen receptor (ER) in the ligand-binding domain of antiestrogens in ER-negative breast cancer cells stably expressing complementary DNAs for ER. Mol. Endocrinol. 6: 21672174.
49. Kaneko, Y.,, N. Maseki,, N. Takasaki,, M. Sakuria,, Y. Hayashi,, S. Nakazawa,, T. Mori,, M. Sakurai,, T. Takeda,, T. Shikano,, and Y. Hiyoshi. 1986. Clinical and hematologic characteristics in acute leukemia with 11q23 translocations. Blood 67:484491.
50. Kastan, M. B.,, O. Onyekwere,, D. Sidransky,, B. Vogelstein,, and R. W. Craig. 1991. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51:63046311.
51. Kastan, M. B.,, Q. Zhan,, W. S. El-Deiry,, F. Carrier,, T. Jacks,, W. V. Walsh,, B. S. Plunkett,, B. Vogelstein,, and A. J. Fornace, Jr. 1992. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 71:587597.
52. Kelly, W. K.,, and H. I. Scher. 1993. Prostate specific antigen decline after antiandrogen withdrawal. J. Urol. 149:607609.
53. Khosvari-Far, R.,, A. D. Cox,, K. Kato,, and C. J. Der. 1992. Protein prenylation: key to ras function and cancer intervention? Cell Growth Diff. 3:461469.
54. Kinzler, K. W.,, M. C. Nilbert,, L.-K. Su,, B. Vogelstein,, T. M. Bryan,, D. B. Levy,, K. J. Smith,, A. C. Preisinger,, P. Hedge,, D. McKechnie,, R. Finniear,, A. Markham,, J. Groffen,, M. S. Boguski,, S. F. Altschul,, A. Horii,, H. Ando,, Y. Miyoshi,, Y. Miki,, I. Nishisho,, and Y. Nakamura. 1991. Identification of FAP locus genes from chromosome 5q21. Science 253:661665.
55. Kohl, N. E.,, S. D. Mosser,, S. J. deSolms,, E. A. Giuliani,, D. L. Pompliano,, S. L. Graham,, R. L. Smith,, E. M. Scolnick,, A. Oliff,, and J. B. Gibbs. 1993. Selective inhibition of ras-dependent transformation by a farnesyltransferase inhibitor. Science 260:19341937.
56. Korsmeyer, S. J. 1992. Bcl-2 initiates a new category of oncogenes: regulators of cell death. Blood 80:879886.
57. Kuerbitz, S. J.,, B. S. Plunkett,, W. V. Walsh,, and M. B. Kastan. 1992. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc. Natl. Acad. Sci. USA 89:74917495.
58. Levine, A. J.,, J. Momand,, and C. A. Finlay. 1991. The p53 tumour suppressor gene. Nature (London) 351:453455.
59. Lowe, S. W.,, E. M. Schmitt,, S. W. Smith,, B. A. Osborne,, and T. Jacks. 1993. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature (London) 362:847849.
60. Malkin, D.,, F. P. Li,, L. C. Strong,, J. F. Fraumeni, Jr.,, C. E. Nelson,, D. H. Kim,, J. Kassel,, M. A. Gryka,, F. Z. Bischoff,, M. A. Tainsky,, and S. H. Friend. 1990. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:12331238.
61. Mao, L.,, D. J. Lee,, M. S. Tockman,, Y. S. Erozan,, F. Askin,, and D. Sidransky. 1994. Microsatellite alterations as clonal markers for the detection of human cancer. Proc. Natl. Acad. Sci. USA 91: 98719875.
62. Martiat, P.,, P. Lewalle,, A. S. Taj,, M. Phillipe,, Y. Larondelle,, J. L. Vaerman,, C. Wildmann,, J. M. Goldman,, and J. L. Michaux. 1993. Retrovirally transduced antisense sequences stably suppress P210 BCR-ABL expression and inhibit the proliferation of BCR/ABL-containing cell lines. Blood 81:502509.
63. Marx, J. 1993. Cell death studies yield cancer clues. Science 259:760761.
64. Miki, Y.,, J. Swensen,, D. Shattuck-Eidens,, P. A. Futreal,, K. Harshman,, S. Tavtigian,, Q. Liu,, C. Cochran,, L. M. Bennett,, W. Ding,, R. Bell,, J. Rosenthal,, C. Hussey,, T. Tran,, M. McClure,, C. Frye,, T. Hattier,, R. Phelps,, A. Haugen-Strano,, H. Katcher,, K. Yakumo,, Z. Gholami,, D. Shaffer,, S. Stone,, S. Bayer,, C. Wray,, R. Bogden,, P. Dayananth,, J. Ward,, P. Tonin,, S. Narod,, P. K. Bristow,, F. H. Norris,, L. Helvering,, P. Morrison,, P. Rosteck,, M. Lai,, J. C. Barrett,, C. Lewis,, S. Neuhausen,, L. Cannon-Albright,, D. Goldgar,, R. Wiseman,, A. Kamb,, and M. H. Skolnick. 1994. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266: 6671.
65. Miller, A. D. 1992. Human gene therapy comes of age. Nature (London) 357:455460.
66. Miyashita, T.,, and J. C. Reed. 1993. Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood 81:151157.
67. Morgan, G. J.,, F. Cotter,, F. E. Katz,, S. A. Ridge,, P. Domer,, S. Korsmeyer,, and L. M. Wiedemann. 1992. Breakpoints at llq23 in infant leukemias with the t(11;19) (q23;p13) are clustered. Blood 80:21722175.
68. Morrissey, J.,, D. C. Tkachuk,, A. Milatovich,, U. Francke,, M. Link,, and M. L. Cleary. 1993. A serine/proline-rich protein is fused to HRX in t(4;11) acute leukemias. Blood 81:11241131.
69. Mullen, C. A.,, M. Kilstrup,, and R. M. Blaese. 1992. Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine: a negative selection system. Proc. Natl. Acad. Sci. USA 89:3337.
69a.. Myers, C. Personal communication.
70. Nichols, J.,, and S. D. Nimer. 1992. Transcription factors, translocations, and leukemia. Blood 80:29532963.
71. Nicolaides, N. C,., N. Papadopoulos,, B. Liu,, Y. F. Wei,, K. C. Carter,, S. M. Ruben,, C. A. Rosen,, W. A. Haseltine,, R. D. Fleischmann,, C. M. Fraser,, M. D. Adams,, J. C. Venter,, M. G. Dunlop,, S. R. Hamilton,, G. M. Petersen,, A. de la Chapelle,, B. Vogelstein,, and K. W. Kinzler. 1994. Mutations of two PMS homologues in hereditary nonpolyposis colon cancer. Nature (London) 371:7580.
72. Nishisho, I.,, Y. Nakamura,, Y. Miyoshi,, Y. Miki,, H. Ando,, A. Horii,, K. Koyama,, J. Utsunomiya,, S. Baba,, P. Hedge,, A. Markham,, A. J. Krush,, G. Petersen,, S. R. Hamilton,, M. C. Nilbert,, S. B. Levy,, T. M. Bryan,, A. C. Preisinger,, K. J. Smith,, L.-K. Su,, K. W. Kinzler,, and B. Vogelstein. 1991. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253: 665669.
73. Pedersen-Bjergaard, J.,, T. C. Sigsgaard,, D. Nielson,, S. B. Gjedde,, P. Philip,, M. Hansen,, S. O. Larsen,, M. Rorth,, H. Mouridsen,, and P. Dombernowsky. 1992. Acute monocytic or myelomono-cytic leukemia with balanced chromosome translocation to band 11q23 after therapy with 4-epi-doxorubicin and cisplatin or cyclophosphamide for breast cancer. J. Clin. Oncol. 10: 14441451.
74. Peltomaki, P.,, L. A. Aaltonen,, P. Sistonen,, L. Pylkkanenm,, J. P. Mecklin,, H. Jarvinen,, J. S. Green,, J. R. Jass,, J. L. Weber,, F. S. Leach,, G. M. Petersen,, S. R. Hamilton,, A. D. L. Chapelle,, and B. Vogelstein. 1993. Genetic mapping of a locus predisposing to human colorectal cancer. Science 260:810812.
75. Prakash, G.,, and E. T. Kool. 1991. Molecular recognition by circular oligodeoxynucleotides. Strong binding of single-stranded DNA and RNA. J. Chem. Soc. Chem. Commun. 1991:11611163.
76. Pui, C.-H.,, R. C. Ribeiro,, M. L. Hancock,, G. K. Riveria,, W. E. Evans,, S. C. Raimondi,, D. R. Head,, F. G. Behm,, M. H. Mahmoud,, J. T. Sandlund,, and W. M. Crist. 1991. Acute myeloid leukemia in children treated with epipodophyllotoxins for acute lymphoblastic leukemia. N. Engl. J. Med. 325:16821687.
77. Rabizadeh, S.,, J. Oh,, L. Zhong,, J. Yang,, C. M. Bitler,, L. L. Butcher,, and D. E. Bredesen. 1993. Induction of apoptosis by the low-affinity NGF receptor. Science 261:345348.
78. Raimondi, S. C.,, S. C. Peiper,, G. R. Kitchingman,, F. G. Behm,, D. L. Williams,, M. L. Hancock,, and J. Mirro, Jr. 1989. Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23. Blood 73:16271634.
79. Ratajczak, M. Z.,, N. Hijiya,, L. Catani,, K. DeRiel,, S. M. Luger,, P. McGlave,, and A. Gewirtz. 1992. Acute- and chronic-phase chronic myelogenous leukemia colony-forming units are highly sensitive to the growth inhibitory effects of c-myb antisense oligodeoxynucleotides. Blood 79:19561961.
80. Ratajczak, M. Z.,, J. A. Kant,, S. M. Luger,, N. Hijiya,, J. Zhang,, G. Zon,, and A. M. Gewirtz. 1992. In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. Proc. Natl. Acad. Sci. USA 89:1182311827.
81. Roberston, L. E.,, S. Chubb,, R. E. Meyn,, M. Story,, R. Ford,, W. N. Hittleman,, and W. Plunkett. 1993. Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2' -deoxy-adenosine and 9-b-D-arabinosyl-2-fluoradenine. Blood 81:143150.
82. Rosenberg, S. A.,, P. Aebersold,, K. Cornetta,, A. Kasid,, R. A. Morgan,, R. Moen,, E. M. Karson,, M. T. Lotze,, J. C. Yang,, S. L. Topalian,, M. J. Merino,, K. Culver,, A. D. Miller,, R. M. Blaese,, and W. F. Anderson. 1990. Gene transfer into humans—immunotherapy of patients with advanced melanoma, using tumor-infiltrating lymphocytes modified by retroviral gene transduction. N. Engl. J. Med. 323:570578.
83. Rubin, C. M.,, D. C. Arthur,, W. G. Woods,, B. J. Lange,, P. C. Nowell,, J. D. Rowley,, J. Nachman,, B. Bostrom,, E. S. Baum,, C. R. Suarez,, N. R. Shah,, E. Morgan,, H. S. Maurer,, S. E. McKenzie,, R. A. Larson,, and M. M. Le Beau. 1991. Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy. Blood 78:29822988.
84. Sachs, L.,, and J. Lotem. 1993. Control of programmed cell death in normal and leukemic cells: new implications for therapy. Blood 82:1521.
85. Sandoval, C.,, C. H. Pui,, L. C. Bowman,, D. Heaton,, C. A. Hurwitz,, S. C. Raimondi,, F. G. Behm,, and D. R. Head. 1993. Secondary acute myeloid leukemia in children previously treated with alkylating agents, intercalating topoisomerase II inhibitors, and irradiation. J. Clin. Oncol. 11: 10391045.
86. Satoh, M. S.,, and T. Lindahl. 1992. Role of poly(ADP-ribose) formation in DNA repair. Nature (London) 356:356358.
87. Sawyers, C. L.,, W. Callahan,, and O. N. Witte. 1992. Dominant negative MYC blocks transformation by ABL oncogenes. Cell70:901910.
88. Scher, H.,, T. Curley,, S. Yeh,, J. M. Iversen,, M. O'Dell,, and S. M. Larson. 1992. Therapeutic alternatives for hormone-refractory prostatic cancer. Semin. Urol. 10:5564.
89. Shi, Y.,, J. M. Glynn,, L. J. Guilbert,, T. G. Cotter,, R. P. Bissonette,, and D. R. Green. 1992. Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science 257:212214.
89a.. Simons, J. W.,, E. M. Jaffee,, and D. M. Pardoll. Personal communication.
90. Slichenmeyer, W. J.,, E. K. Rowinsky,, R. C. Donehower,, and S. H. Kaufmann. 1993. The current status of camptothecin analogues as antitumor agents. J. Natl. Cancer Inst. 85:27.
91. Stetler-Stevenson, M. 1992. The t( 14; 18) translocation in Hodgkin's disease. J. Natl. Cancer Inst. 84:17701771.
92. Swift, M. Ionizing radiation, breast cancer, and ataxia-telangiectasia. J. Natl. Cancer Inst., in press.
93. Swift, M.,, D. Morrell,, R. B. Massey,, and C. L. Chase. 1991. Incidence of cancer in 161 families affected by ataxia-telangiectasia. N. Engl. J. Med. 325:18311836.
94. Szczylik, C.,, T. Skorski,, N. C. Nicolaides,, L. Manzella,, L. Malaguarnera,, D. Venturelli,, A. M. Gewirtz,, and B. Calabretta. 1991. Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. Science 253:562565.
95. Thibodeau, S. N.,, G. Bren,, and D. Schaid. 1993. Microsatellite instability in cancer of the proximal colon. Science 260:816819.
96. Thompson, L. 1992. At age 2, gene therapy enters a growth phase. Science 258:744746.
97. Thornberry, N. A.,, H. G. Bull,, J. R. Calaycay,, K. T. Chapman,, A. D. Howard,, M. J. Kostura,, D. K. Miller,, S. M. Molineaux,, J. R. Weidner,, J. Aunins,, K. O. Elliston,, J. M. Ayala,, F. J. Casano,, J. Chin,, G. J.-F. Ding,, L. A. Egger,, E. P. Gaffney,, G. Limjuco,, O. C. Palyha,, S. M. Raju,, A. M. Rolando,, J. P. Salley,, T.-T. Yamin,, T. D. Lee,, J. E. Shively,, M. MacCross,, R. A. Mumford,, J. A. Schmidt,, and M. J. Toccil. 1992. A novel heterodimeric cysteine protease is required for interleukin-1/3 processing in monocytes. Nature (London) 356:768774.
98. Tkachuk, D. C.,, S. Kohler,, and M. L. Cleary. 1992. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 71:691700.
99. Townsend, S. E.,, and J. P. Allison. 1993. Tumor rejection after direct costimulation of CD8 T cells by B7-transfected melanoma cells. Science 259:368370.
100. Trojan, J.,, T. R. Johnson,, S. D. Rudin,, J. Ilan,, M. L. Tykocinski,, and J. Ilan. 1993. Treatment and prevention of rat glioblastoma by immunogenic C6 cells expressing antisense insulin-like growth factor I RNA. Science 259:9496.
101. Vaux, D. L.,, I. L. Weissman,, and S. K. Kim. 1992. Prevention of programmed cell death in Caenorhabditis elegans by human bcl-2. Science 258:19551957.
102. Vogelstein, B.,, E. R. Fearon,, S. R. Hamilton,, S. E. Kern,, A. C. Preisinger,, M. Leppert,, Y. Nakamura,, R. White,, A. M. M. Smits,, and J. L. Bos. 1988. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319:525532.
103. Waldmann, T. A.,, J. Misiti,, D. L. Nelson,, and K. H. Kraemer. 1983. Ataxia-telangiectasia: a multisystem hereditary disease with immunodeficiency, impaired organ maturation, x-ray hypersensitivity, and a high incidence of neoplasia. Ann. Intern. Med. 99:367379.
104. Yahalom, J.,, J. A. Petrek,, P. W. Biddinger,, S. Kessler,, D. D. Dershaw,, B. McCormick,, M. P. Osborne,, D. A. Kinne,, and P. P. Rosen. 1992. Breast cancer in patients irradiated for Hodgkin's disease: a clinical and pathologic analysis of 45 events in 37 patients. J. Clin. Oncol. 10:16741681.
105. Yonisch-Rouach, E.,, D. Resnitzky,, J. Lotem,, L. Sachs,, A. Kimchi,, and M. Oren. 1991. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature (London) 352:345347.

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