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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Feb 15;91(4):1198–1205. doi: 10.1073/pnas.91.4.1198

Cytokine therapeutics: lessons from interferon alpha.

J U Gutterman 1
PMCID: PMC43124  PMID: 8108387

Abstract

Cytokines are soluble proteins that allow for communication between cells and the external environment. Interferon (IFN) alpha, the first cytokine to be produced by recombinant DNA technology, has emerged as an important regulator of growth and differentiation, affecting cellular communication and signal transduction pathways as well as immunological control. This review focuses on the biological and clinical activities of the cytokine. Originally discovered as an antiviral substance, the efficacy of IFN-alpha in malignant, viral, immunological, angiogenic, inflammatory, and fibrotic diseases suggests a spectrum of interrelated pathophysiologies. The principles learned from in vivo studies will be discussed, particularly hairy cell leukemia, chronic myelogenous leukemia, certain angiogenic diseases, and hepatitis. After the surprising discovery of activity in a rare B-cell neoplasm, IFN-alpha emerged as a prototypic tumor suppressor protein that represses the clinical tumorigenic phenotype in some malignancies capable of differentiation. Regulatory agencies throughout the world have approved IFN-alpha for treatment of 13 malignant and viral disorders. The principles established with this cytokine serve as a paradigm for future development of natural proteins for human disease.

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Selected References

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  1. Adams F., Quesada J. R., Gutterman J. U. Neuropsychiatric manifestations of human leukocyte interferon therapy in patients with cancer. JAMA. 1984 Aug 17;252(7):938–941. [PubMed] [Google Scholar]
  2. Alldridge L. C., O'Farrell M. K., Dealtry G. B. Interferon beta increases expression of vimentin at the messenger RNA and protein levels in differentiated embryonal carcinoma (PSMB) cells. Exp Cell Res. 1989 Dec;185(2):387–393. doi: 10.1016/0014-4827(89)90308-x. [DOI] [PubMed] [Google Scholar]
  3. Aman M. J., Rudolf G., Goldschmitt J., Aulitzky W. E., Lam C., Huber C., Peschel C. Type-I interferons are potent inhibitors of interleukin-8 production in hematopoietic and bone marrow stromal cells. Blood. 1993 Oct 15;82(8):2371–2378. [PubMed] [Google Scholar]
  4. Antonelli G., Currenti M., Turriziani O., Dianzani F. Neutralizing antibodies to interferon-alpha: relative frequency in patients treated with different interferon preparations. J Infect Dis. 1991 Apr;163(4):882–885. doi: 10.1093/infdis/163.4.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Antoniades H. N. Linking cellular injury to gene expression and human proliferative disorders: examples with the PDGF genes. Mol Carcinog. 1992;6(3):175–181. doi: 10.1002/mc.2940060302. [DOI] [PubMed] [Google Scholar]
  6. Arnason B. G. Interferon beta in multiple sclerosis. Neurology. 1993 Apr;43(4):641–643. doi: 10.1212/wnl.43.4.641. [DOI] [PubMed] [Google Scholar]
  7. Baltimore D. The Gerhard Domagk Lecture. Transcription factors in lymphoid development. Ann N Y Acad Sci. 1993 Jun 23;685:420–428. doi: 10.1111/j.1749-6632.1993.tb35901.x. [DOI] [PubMed] [Google Scholar]
  8. Barillari G., Gendelman R., Gallo R. C., Ensoli B. The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7941–7945. doi: 10.1073/pnas.90.17.7941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Barnhill R. L., Levy M. A. Regressing thin cutaneous malignant melanomas (< or = 1.0 mm) are associated with angiogenesis. Am J Pathol. 1993 Jul;143(1):99–104. [PMC free article] [PubMed] [Google Scholar]
  10. Baron S., Tyring S. K., Fleischmann W. R., Jr, Coppenhaver D. H., Niesel D. W., Klimpel G. R., Stanton G. J., Hughes T. K. The interferons. Mechanisms of action and clinical applications. JAMA. 1991 Sep 11;266(10):1375–1383. doi: 10.1001/jama.266.10.1375. [DOI] [PubMed] [Google Scholar]
  11. Beloqui O., Prieto J., Suárez M., Gil B., Qian C. H., García N., Civeira M. P. N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. J Interferon Res. 1993 Aug;13(4):279–282. doi: 10.1089/jir.1993.13.279. [DOI] [PubMed] [Google Scholar]
  12. Bernhagen J., Calandra T., Mitchell R. A., Martin S. B., Tracey K. J., Voelter W., Manogue K. R., Cerami A., Bucala R. MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature. 1993 Oct 21;365(6448):756–759. doi: 10.1038/365756a0. [DOI] [PubMed] [Google Scholar]
  13. Bishop J. M. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. doi: 10.1016/0092-8674(91)90636-d. [DOI] [PubMed] [Google Scholar]
  14. Blau H. M. Differentiation requires continuous active control. Annu Rev Biochem. 1992;61:1213–1230. doi: 10.1146/annurev.bi.61.070192.010025. [DOI] [PubMed] [Google Scholar]
  15. Bloom B. R. The power of negative thinking. J Clin Invest. 1993 Apr;91(4):1265–1266. doi: 10.1172/JCI116322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bocci V. Roles of interferon produced in physiological conditions. A speculative review. Immunology. 1988 May;64(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  17. Bocci V. What roles have anti-interferon antibodies in physiology and pathology? Ric Clin Lab. 1991 Jan-Mar;21(1):79–84. doi: 10.1007/BF02919115. [DOI] [PubMed] [Google Scholar]
  18. Bourinbaiar A. S., Nagorny R. Inhibitory effect of natural interferon alpha on human immunodeficiency virus type 1 transmission from epithelial cells to lymphocytes in vitro. Eur J Pharmacol. 1993 Jan 5;230(1):15–22. doi: 10.1016/0014-2999(93)90404-6. [DOI] [PubMed] [Google Scholar]
  19. Brugge J. S. New intracellular targets for therapeutic drug design. Science. 1993 May 14;260(5110):918–919. doi: 10.1126/science.8388123. [DOI] [PubMed] [Google Scholar]
  20. Calabretta B., Battini R., Kaczmarek L., de Riel J. K., Baserga R. Molecular cloning of the cDNA for a growth factor-inducible gene with strong homology to S-100, a calcium-binding protein. J Biol Chem. 1986 Sep 25;261(27):12628–12632. [PubMed] [Google Scholar]
  21. Cantley L. C., Auger K. R., Carpenter C., Duckworth B., Graziani A., Kapeller R., Soltoff S. Oncogenes and signal transduction. Cell. 1991 Jan 25;64(2):281–302. doi: 10.1016/0092-8674(91)90639-g. [DOI] [PubMed] [Google Scholar]
  22. Castilla A., Prieto J., Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. N Engl J Med. 1991 Apr 4;324(14):933–940. doi: 10.1056/NEJM199104043241401. [DOI] [PubMed] [Google Scholar]
  23. Chany C. Mechanism of homeostatic regulation of tissue growth and reversion of transformed cells to nonmalignancy: a yin-yang problem. J Interferon Res. 1990 Oct;10(5):453–459. doi: 10.1089/jir.1990.10.453. [DOI] [PubMed] [Google Scholar]
  24. Cheng K. C., Loeb L. A. Genomic instability and tumor progression: mechanistic considerations. Adv Cancer Res. 1993;60:121–156. doi: 10.1016/s0065-230x(08)60824-6. [DOI] [PubMed] [Google Scholar]
  25. Clark W. H. Tumour progression and the nature of cancer. Br J Cancer. 1991 Oct;64(4):631–644. doi: 10.1038/bjc.1991.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Clarkson B., Strife A. Linkage of proliferative and maturational abnormalities in chronic myelogenous leukemia and relevance to treatment. Leukemia. 1993 Nov;7(11):1683–1721. [PubMed] [Google Scholar]
  27. Clerici M., Lucey D. R., Berzofsky J. A., Pinto L. A., Wynn T. A., Blatt S. P., Dolan M. J., Hendrix C. W., Wolf S. F., Shearer G. M. Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro. Science. 1993 Dec 10;262(5140):1721–1724. doi: 10.1126/science.7903123. [DOI] [PubMed] [Google Scholar]
  28. Constantoulakis P., Campbell M., Felber B. K., Nasioulas G., Afonina E., Pavlakis G. N. Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene. Science. 1993 Feb 26;259(5099):1314–1318. doi: 10.1126/science.7680491. [DOI] [PubMed] [Google Scholar]
  29. Contente S., Kenyon K., Rimoldi D., Friedman R. M. Expression of gene rrg is associated with reversion of NIH 3T3 transformed by LTR-c-H-ras. Science. 1990 Aug 17;249(4970):796–798. doi: 10.1126/science.1697103. [DOI] [PubMed] [Google Scholar]
  30. De Panfilis G., Manara G. C., Ferrari C., Torresani C. Adhesion molecules on the plasma membrane of epidermal cells. III. Keratinocytes and Langerhans cells constitutively express the lymphocyte function-associated antigen 3. J Invest Dermatol. 1991 Apr;96(4):512–517. doi: 10.1111/1523-1747.ep12470220. [DOI] [PubMed] [Google Scholar]
  31. Del Sal G., Ruaro M. E., Philipson L., Schneider C. The growth arrest-specific gene, gas1, is involved in growth suppression. Cell. 1992 Aug 21;70(4):595–607. doi: 10.1016/0092-8674(92)90429-g. [DOI] [PubMed] [Google Scholar]
  32. Dhingra K., Kurzrock R., Kantarjian H., Baine R., Eastman P. S., Ku S., Gutterman J. U., Talpaz M. Minimal residual disease in interferon-treated chronic myelogenous leukemia: results and pitfalls of analysis based on polymerase chain reaction. Leukemia. 1992 Aug;6(8):754–760. [PubMed] [Google Scholar]
  33. Dianzani F. Interferon treatments: how to use an endogenous system as a therapeutic agent. J Interferon Res. 1992 May;Spec No:109–118. doi: 10.1089/jir.1992.1992.109. [DOI] [PubMed] [Google Scholar]
  34. Dowding C., Guo A. P., Osterholz J., Siczkowski M., Goldman J., Gordon M. Interferon-alpha overrides the deficient adhesion of chronic myeloid leukemia primitive progenitor cells to bone marrow stromal cells. Blood. 1991 Jul 15;78(2):499–505. [PubMed] [Google Scholar]
  35. Dvorak H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986 Dec 25;315(26):1650–1659. doi: 10.1056/NEJM198612253152606. [DOI] [PubMed] [Google Scholar]
  36. Eaves C. J., Cashman J. D., Zoumbos N. C., Barnett M. J., Eaves A. C. Biological strategies for the selective manipulation of normal and leukemic stem cells. Stem Cells. 1993 Oct;11 (Suppl 3):109–121. doi: 10.1002/stem.5530110924. [DOI] [PubMed] [Google Scholar]
  37. Estrov Z., Kurzrock R., Wetzler M., Kantarjian H., Blake M., Harris D., Gutterman J. U., Talpaz M. Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity. Blood. 1991 Sep 15;78(6):1476–1484. [PubMed] [Google Scholar]
  38. Evans H. J. Molecular genetic aspects of human cancers: the 1993 Frank Rose Lecture. Br J Cancer. 1993 Dec;68(6):1051–1060. doi: 10.1038/bjc.1993.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Evans S. S., Collea R. P., Appenheimer M. M., Gollnick S. O. Interferon-alpha induces the expression of the L-selectin homing receptor in human B lymphoid cells. J Cell Biol. 1993 Dec;123(6 Pt 2):1889–1898. doi: 10.1083/jcb.123.6.1889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Evans S. S., Wang W. C., Gregorio C. C., Han T., Repasky E. A. Interferon-alpha alters spectrin organization in normal and leukemic human B lymphocytes. Blood. 1993 Feb 1;81(3):759–766. [PubMed] [Google Scholar]
  41. Fabra A., Nakajima M., Bucana C. D., Fidler I. J. Modulation of the invasive phenotype of human colon carcinoma cells by organ specific fibroblasts of nude mice. Differentiation. 1992 Dec;52(1):101–110. doi: 10.1111/j.1432-0436.1992.tb00504.x. [DOI] [PubMed] [Google Scholar]
  42. Farber E., Rubin H. Cellular adaptation in the origin and development of cancer. Cancer Res. 1991 Jun 1;51(11):2751–2761. [PubMed] [Google Scholar]
  43. Farci P., Mandas A., Coiana A., Lai M. E., Desmet V., Van Eyken P., Gibo Y., Caruso L., Scaccabarozzi S., Criscuolo D. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med. 1994 Jan 13;330(2):88–94. doi: 10.1056/NEJM199401133300202. [DOI] [PubMed] [Google Scholar]
  44. Fischer D. G., Tal N., Novick D., Barak S., Rubinstein M. An antiviral soluble form of the LDL receptor induced by interferon. Science. 1993 Oct 8;262(5131):250–253. doi: 10.1126/science.8211145. [DOI] [PubMed] [Google Scholar]
  45. Folkman J., Ingber D. Inhibition of angiogenesis. Semin Cancer Biol. 1992 Apr;3(2):89–96. [PubMed] [Google Scholar]
  46. Folkman J., Shing Y. Angiogenesis. J Biol Chem. 1992 Jun 5;267(16):10931–10934. [PubMed] [Google Scholar]
  47. Foster G. R., Thomas H. C. Recent advances in the molecular biology of hepatitis B virus: mutant virus and the host response. Gut. 1993 Jan;34(1):1–3. doi: 10.1136/gut.34.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Francis M. L., Meltzer M. S., Gendelman H. E. Interferons in the persistence, pathogenesis, and treatment of HIV infection. AIDS Res Hum Retroviruses. 1992 Feb;8(2):199–207. doi: 10.1089/aid.1992.8.199. [DOI] [PubMed] [Google Scholar]
  49. Gaspari A. A., Fleisher T. A., Kraemer K. H. Impaired interferon production and natural killer cell activation in patients with the skin cancer-prone disorder, xeroderma pigmentosum. J Clin Invest. 1993 Sep;92(3):1135–1142. doi: 10.1172/JCI116682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Genot E. Interferon alpha and intracytoplasmic free calcium in hairy cell leukemia cells. Leuk Lymphoma. 1994 Feb;12(5-6):373–381. doi: 10.3109/10428199409073778. [DOI] [PubMed] [Google Scholar]
  51. Gillies M., Su T., Sarossy M., Hollows F. Interferon-alpha 2b inhibits proliferation of human Tenon's capsule fibroblasts. Graefes Arch Clin Exp Ophthalmol. 1993 Feb;231(2):118–121. doi: 10.1007/BF00920225. [DOI] [PubMed] [Google Scholar]
  52. Gishizky M. L., Johnson-White J., Witte O. N. Efficient transplantation of BCR-ABL-induced chronic myelogenous leukemia-like syndrome in mice. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3755–3759. doi: 10.1073/pnas.90.8.3755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Gooding L. R. Virus proteins that counteract host immune defenses. Cell. 1992 Oct 2;71(1):5–7. doi: 10.1016/0092-8674(92)90259-f. [DOI] [PubMed] [Google Scholar]
  54. Grunwald G. B. The structural and functional analysis of cadherin calcium-dependent cell adhesion molecules. Curr Opin Cell Biol. 1993 Oct;5(5):797–805. doi: 10.1016/0955-0674(93)90028-o. [DOI] [PubMed] [Google Scholar]
  55. Gutterman J. U., Blumenschein G. R., Alexanian R., Yap H. Y., Buzdar A. U., Cabanillas F., Hortobagyi G. N., Hersh E. M., Rasmussen S. L., Harmon M. Leukocyte interferon-induced tumor regression in human metastatic breast cancer, multiple myeloma, and malignant lymphoma. Ann Intern Med. 1980 Sep;93(3):399–406. doi: 10.7326/0003-4819-93-3-399. [DOI] [PubMed] [Google Scholar]
  56. Gutterman J. U., Fine S., Quesada J., Horning S. J., Levine J. F., Alexanian R., Bernhardt L., Kramer M., Spiegel H., Colburn W. Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients. Ann Intern Med. 1982 May;96(5):549–556. doi: 10.7326/0003-4819-96-5-549. [DOI] [PubMed] [Google Scholar]
  57. Hajjar D. P., Pomerantz K. B. Signal transduction in atherosclerosis: integration of cytokines and the eicosanoid network. FASEB J. 1992 Aug;6(11):2933–2941. doi: 10.1096/fasebj.6.11.1644257. [DOI] [PubMed] [Google Scholar]
  58. Haralson M. A. Extracellular matrix and growth factors: an integrated interplay controlling tissue repair and progression to disease. Lab Invest. 1993 Oct;69(4):369–372. [PubMed] [Google Scholar]
  59. Harris H. The role of differentiation in the suppression of malignancy. J Cell Sci. 1990 Sep;97(Pt 1):5–10. doi: 10.1242/jcs.97.1.5. [DOI] [PubMed] [Google Scholar]
  60. Henco K., Brosius J., Fujisawa A., Fujisawa J. I., Haynes J. R., Hochstadt J., Kovacic T., Pasek M., Schamböck A., Schmid J. Structural relationship of human interferon alpha genes and pseudogenes. J Mol Biol. 1985 Sep 20;185(2):227–260. doi: 10.1016/0022-2836(85)90401-2. [DOI] [PubMed] [Google Scholar]
  61. Hoofnagle J. H., Di Bisceglie A. M., Shindo M. Antiviral therapy of hepatitis C--present and future. J Hepatol. 1993;17 (Suppl 3):S130–S136. doi: 10.1016/s0168-8278(05)80438-6. [DOI] [PubMed] [Google Scholar]
  62. Huang S., Hendriks W., Althage A., Hemmi S., Bluethmann H., Kamijo R., Vilcek J., Zinkernagel R. M., Aguet M. Immune response in mice that lack the interferon-gamma receptor. Science. 1993 Mar 19;259(5102):1742–1745. doi: 10.1126/science.8456301. [DOI] [PubMed] [Google Scholar]
  63. Hunter T. Braking the cycle. Cell. 1993 Dec 3;75(5):839–841. doi: 10.1016/0092-8674(93)90528-x. [DOI] [PubMed] [Google Scholar]
  64. Ingber D. E. Extracellular matrix as a solid-state regulator in angiogenesis: identification of new targets for anti-cancer therapy. Semin Cancer Biol. 1992 Apr;3(2):57–63. [PubMed] [Google Scholar]
  65. Jones P. L., Schmidhauser C., Bissell M. J. Regulation of gene expression and cell function by extracellular matrix. Crit Rev Eukaryot Gene Expr. 1993;3(2):137–154. [PubMed] [Google Scholar]
  66. Juliano R. L., Varner J. A. Adhesion molecules in cancer: the role of integrins. Curr Opin Cell Biol. 1993 Oct;5(5):812–818. doi: 10.1016/0955-0674(93)90030-t. [DOI] [PubMed] [Google Scholar]
  67. Kaplan E. H., Leslie W. T. Cutaneous T-cell lymphomas. Curr Opin Oncol. 1993 Sep;5(5):812–818. doi: 10.1097/00001622-199309000-00007. [DOI] [PubMed] [Google Scholar]
  68. Kaye K. M., Izumi K. M., Kieff E. Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9150–9154. doi: 10.1073/pnas.90.19.9150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Keating A. Investigation of bcr-abl transcription by Ph-positive chronic myeloid leukemia progenitors. Stem Cells. 1993 Oct;11 (Suppl 3):31–33. doi: 10.1002/stem.5530110910. [DOI] [PubMed] [Google Scholar]
  70. Klagsbrun M., Soker S. VEGF/VPF: the angiogenesis factor found? Curr Biol. 1993 Oct 1;3(10):699–702. doi: 10.1016/0960-9822(93)90073-w. [DOI] [PubMed] [Google Scholar]
  71. Klein G., Boon T. Tumor immunology: present perspectives. Curr Opin Immunol. 1993 Oct;5(5):687–692. doi: 10.1016/0952-7915(93)90122-9. [DOI] [PubMed] [Google Scholar]
  72. Klein G. Genes that can antagonize tumor development. FASEB J. 1993 Jul;7(10):821–825. doi: 10.1096/fasebj.7.10.8344481. [DOI] [PubMed] [Google Scholar]
  73. Klein G., Klein E. Conditioned tumorigenicity of activated oncogenes. Cancer Res. 1986 Jul;46(7):3211–3224. [PubMed] [Google Scholar]
  74. Knudson A. G. Antioncogenes and human cancer. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10914–10921. doi: 10.1073/pnas.90.23.10914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Knudson A. G. Stem cell regulation, tissue ontogeny, and oncogenic events. Semin Cancer Biol. 1992 Jun;3(3):99–106. [PubMed] [Google Scholar]
  76. Kovacs E. J. Fibrogenic cytokines: the role of immune mediators in the development of scar tissue. Immunol Today. 1991 Jan;12(1):17–23. doi: 10.1016/0167-5699(91)90107-5. [DOI] [PubMed] [Google Scholar]
  77. Kurzrock R., Gutterman J. U., Talpaz M. The molecular genetics of Philadelphia chromosome-positive leukemias. N Engl J Med. 1988 Oct 13;319(15):990–998. doi: 10.1056/NEJM198810133191506. [DOI] [PubMed] [Google Scholar]
  78. Lane H. C., Davey V., Kovacs J. A., Feinberg J., Metcalf J. A., Herpin B., Walker R., Deyton L., Davey R. T., Jr, Falloon J. Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial. Ann Intern Med. 1990 Jun 1;112(11):805–811. doi: 10.7326/0003-4819-112-11-805. [DOI] [PubMed] [Google Scholar]
  79. Lee S. W., Tomasetto C., Sager R. Positive selection of candidate tumor-suppressor genes by subtractive hybridization. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2825–2829. doi: 10.1073/pnas.88.7.2825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Lengyel P. Tumor-suppressor genes: news about the interferon connection. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5893–5895. doi: 10.1073/pnas.90.13.5893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Lepe-Zuniga J. L., Quesada J. R., Baron S., Reuben J., Gutterman J. U. Alpha interferon production in patients with hairy cell leukemia: correlations with disease activity and remission status. Hematol Pathol. 1987;1(3):157–165. [PubMed] [Google Scholar]
  82. Liddle C. Interferon treatment of hepatitis C: is it virological cure? J Gastroenterol Hepatol. 1993 May-Jun;8(3):209–211. doi: 10.1111/j.1440-1746.1993.tb01187.x. [DOI] [PubMed] [Google Scholar]
  83. Lippman S. M., Kavanagh J. J., Paredes-Espinoza M., Delgadillo-Madrueño F., Paredes-Casillas P., Hong W. K., Holdener E., Krakoff I. H. 13-cis-retinoic acid plus interferon alpha-2a: highly active systemic therapy for squamous cell carcinoma of the cervix. J Natl Cancer Inst. 1992 Feb 19;84(4):241–245. doi: 10.1093/jnci/84.4.241. [DOI] [PubMed] [Google Scholar]
  84. Lippman S. M., Parkinson D. R., Itri L. M., Weber R. S., Schantz S. P., Ota D. M., Schusterman M. A., Krakoff I. H., Gutterman J. U., Hong W. K. 13-cis-retinoic acid and interferon alpha-2a: effective combination therapy for advanced squamous cell carcinoma of the skin. J Natl Cancer Inst. 1992 Feb 19;84(4):235–241. doi: 10.1093/jnci/84.4.235. [DOI] [PubMed] [Google Scholar]
  85. Lowe S. W., Ruley H. E., Jacks T., Housman D. E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell. 1993 Sep 24;74(6):957–967. doi: 10.1016/0092-8674(93)90719-7. [DOI] [PubMed] [Google Scholar]
  86. Lu C., Kerbel R. S. Interleukin-6 undergoes transition from paracrine growth inhibitor to autocrine stimulator during human melanoma progression. J Cell Biol. 1993 Mar;120(5):1281–1288. doi: 10.1083/jcb.120.5.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Lu K. P., Means A. R. Regulation of the cell cycle by calcium and calmodulin. Endocr Rev. 1993 Feb;14(1):40–58. doi: 10.1210/edrv-14-1-40. [DOI] [PubMed] [Google Scholar]
  88. Luna E. J., Hitt A. L. Cytoskeleton--plasma membrane interactions. Science. 1992 Nov 6;258(5084):955–964. doi: 10.1126/science.1439807. [DOI] [PubMed] [Google Scholar]
  89. Lynch S. A., Brugge J. S., Fromowitz F., Glantz L., Wang P., Caruso R., Viola M. V. Increased expression of the src proto-oncogene in hairy cell leukemia and a subgroup of B-cell lymphomas. Leukemia. 1993 Sep;7(9):1416–1422. [PubMed] [Google Scholar]
  90. Mandelli F., Avvisati G., Amadori S., Boccadoro M., Gernone A., Lauta V. M., Marmont F., Petrucci M. T., Tribalto M., Vegna M. L. Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. N Engl J Med. 1990 May 17;322(20):1430–1434. doi: 10.1056/NEJM199005173222005. [DOI] [PubMed] [Google Scholar]
  91. Masucci M. G. Viral immunopathology of human tumors. Curr Opin Immunol. 1993 Oct;5(5):693–700. doi: 10.1016/0952-7915(93)90123-a. [DOI] [PubMed] [Google Scholar]
  92. Matsuyama T., Kimura T., Kitagawa M., Pfeffer K., Kawakami T., Watanabe N., Kündig T. M., Amakawa R., Kishihara K., Wakeham A. Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development. Cell. 1993 Oct 8;75(1):83–97. [PubMed] [Google Scholar]
  93. Mayer R. J., Arnold J., László L., Landon M., Lowe J. Ubiquitin in health and disease. Biochim Biophys Acta. 1991 Jun 13;1089(2):141–157. doi: 10.1016/0167-4781(91)90002-4. [DOI] [PubMed] [Google Scholar]
  94. McCauley R. L., Chopra V., Li Y. Y., Herndon D. N., Robson M. C. Altered cytokine production in black patients with keloids. J Clin Immunol. 1992 Jul;12(4):300–308. doi: 10.1007/BF00918154. [DOI] [PubMed] [Google Scholar]
  95. McLaughlin P., Cabanillas F., Hagemeister F. B., Swan F., Jr, Romaguera J. E., Taylor S., Rodriguez M. A., Velasquez W. S., Redman J. R., Gutterman J. U. CHOP-Bleo plus interferon for stage IV low-grade lymphoma. Ann Oncol. 1993 Mar;4(3):205–211. doi: 10.1093/oxfordjournals.annonc.a058457. [DOI] [PubMed] [Google Scholar]
  96. McWhirter J. R., Wang J. Y. An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias. EMBO J. 1993 Apr;12(4):1533–1546. doi: 10.1002/j.1460-2075.1993.tb05797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Melamed D., Tiefenbrun N., Yarden A., Kimchi A. Interferons and interleukin-6 suppress the DNA-binding activity of E2F in growth-sensitive hematopoietic cells. Mol Cell Biol. 1993 Sep;13(9):5255–5265. doi: 10.1128/mcb.13.9.5255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Melief C. J., Kast W. M. Potential immunogenicity of oncogene and tumor suppressor gene products. Curr Opin Immunol. 1993 Oct;5(5):709–713. doi: 10.1016/0952-7915(93)90125-c. [DOI] [PubMed] [Google Scholar]
  99. Mesnil M., Yamasaki H. Cell-cell communication and growth control of normal and cancer cells: evidence and hypothesis. Mol Carcinog. 1993;7(1):14–17. doi: 10.1002/mc.2940070103. [DOI] [PubMed] [Google Scholar]
  100. Metcalf D. The roles of stem cell self-renewal and autocrine growth factor production in the biology of myeloid leukemia. Cancer Res. 1989 May 1;49(9):2305–2311. [PubMed] [Google Scholar]
  101. Minutello M. A., Pileri P., Unutmaz D., Censini S., Kuo G., Houghton M., Brunetto M. R., Bonino F., Abrignani S. Compartmentalization of T lymphocytes to the site of disease: intrahepatic CD4+ T cells specific for the protein NS4 of hepatitis C virus in patients with chronic hepatitis C. J Exp Med. 1993 Jul 1;178(1):17–25. doi: 10.1084/jem.178.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Montminy M. Trying on a new pair of SH2s. Science. 1993 Sep 24;261(5129):1694–1695. doi: 10.1126/science.8397444. [DOI] [PubMed] [Google Scholar]
  103. Morse S. S. Emerging viruses: defining the rules for viral traffic. Perspect Biol Med. 1991 Spring;34(3):387–409. doi: 10.1353/pbm.1991.0038. [DOI] [PubMed] [Google Scholar]
  104. Moses M. A., Langer R. Inhibitors of angiogenesis. Biotechnology (N Y) 1991 Jul;9(7):630–634. doi: 10.1038/nbt0791-630. [DOI] [PubMed] [Google Scholar]
  105. Mozes E., Kohn L. D., Hakim F., Singer D. S. Resistance of MHC class I-deficient mice to experimental systemic lupus erythematosus. Science. 1993 Jul 2;261(5117):91–93. doi: 10.1126/science.8316860. [DOI] [PubMed] [Google Scholar]
  106. Murphy J. S., Tamm I. Effects of interferon-beta on the translocation rate and stationary time in human fibroblasts in culture. Cell Motil Cytoskeleton. 1991;19(2):99–108. doi: 10.1002/cm.970190205. [DOI] [PubMed] [Google Scholar]
  107. Nachmias V. T. Small actin-binding proteins: the beta-thymosin family. Curr Opin Cell Biol. 1993 Feb;5(1):56–62. doi: 10.1016/s0955-0674(05)80008-0. [DOI] [PubMed] [Google Scholar]
  108. Naeim F., Hoon D. S., Cheng L., Herschman H., Cochran A., Jr Reactivity of neoplastic cells of hairy cell leukemia with antisera to S-100 protein. Am J Clin Pathol. 1987 Jul;88(1):86–91. doi: 10.1093/ajcp/88.1.86. [DOI] [PubMed] [Google Scholar]
  109. Nathan C., Sporn M. Cytokines in context. J Cell Biol. 1991 Jun;113(5):981–986. doi: 10.1083/jcb.113.5.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Nguyen M., Watanabe H., Budson A. E., Richie J. P., Folkman J. Elevated levels of the angiogenic peptide basic fibroblast growth factor in urine of bladder cancer patients. J Natl Cancer Inst. 1993 Feb 3;85(3):241–242. doi: 10.1093/jnci/85.3.241. [DOI] [PubMed] [Google Scholar]
  111. Noda M. Mechanisms of reversion. FASEB J. 1993 Jul;7(10):834–840. doi: 10.1096/fasebj.7.10.8344483. [DOI] [PubMed] [Google Scholar]
  112. Oberg K. The action of interferon alpha on human carcinoid tumours. Semin Cancer Biol. 1992 Feb;3(1):35–41. [PubMed] [Google Scholar]
  113. Oldstone M. B. Rous-Whipple Award Lecture. Viruses and diseases of the twenty-first century. Am J Pathol. 1993 Nov;143(5):1241–1249. [PMC free article] [PubMed] [Google Scholar]
  114. Ozer H., George S. L., Schiffer C. A., Rao K., Rao P. N., Wurster-Hill D. H., Arthur D. D., Powell B., Gottlieb A., Peterson B. A. Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583. Blood. 1993 Nov 15;82(10):2975–2984. [PubMed] [Google Scholar]
  115. Parronchi P., De Carli M., Manetti R., Simonelli C., Sampognaro S., Piccinni M. P., Macchia D., Maggi E., Del Prete G., Romagnani S. IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J Immunol. 1992 Nov 1;149(9):2977–2983. [PubMed] [Google Scholar]
  116. Patterson P. H., Nawa H. Neuronal differentiation factors/cytokines and synaptic plasticity. Cell. 1993 Jan;72 (Suppl):123–137. doi: 10.1016/s0092-8674(05)80032-7. [DOI] [PubMed] [Google Scholar]
  117. Pendergast A. M., Quilliam L. A., Cripe L. D., Bassing C. H., Dai Z., Li N., Batzer A., Rabun K. M., Der C. J., Schlessinger J. BCR-ABL-induced oncogenesis is mediated by direct interaction with the SH2 domain of the GRB-2 adaptor protein. Cell. 1993 Oct 8;75(1):175–185. [PubMed] [Google Scholar]
  118. Perrillo R. P. Interferon in the management of chronic hepatitis B. Dig Dis Sci. 1993 Apr;38(4):577–593. doi: 10.1007/BF01316785. [DOI] [PubMed] [Google Scholar]
  119. Pestka S., Langer J. A., Zoon K. C., Samuel C. E. Interferons and their actions. Annu Rev Biochem. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  120. Peters K., Vejlsgaard G. L. Basal cell and squamous cell carcinoma and Kaposi's sarcoma. Curr Opin Oncol. 1992 Apr;4(2):380–385. doi: 10.1097/00001622-199204000-00021. [DOI] [PubMed] [Google Scholar]
  121. Pienta K. J., Getzenberg R. H., Coffey D. S. Cell structure and DNA organization. Crit Rev Eukaryot Gene Expr. 1991;1(4):355–385. [PubMed] [Google Scholar]
  122. Platanias L. C., Pfeffer L. M., Cruciani R., Colamonici O. R. Characterization of the alpha subunit of the IFN-alpha receptor. Evidence of N- and O-linked glycosylation and association with other surface proteins. J Immunol. 1993 Apr 15;150(8 Pt 1):3382–3388. [PubMed] [Google Scholar]
  123. Poli G., Orenstein J. M., Kinter A., Folks T. M., Fauci A. S. Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science. 1989 May 5;244(4904):575–577. doi: 10.1126/science.2470148. [DOI] [PubMed] [Google Scholar]
  124. Powrie F., Coffman R. L. Cytokine regulation of T-cell function: potential for therapeutic intervention. Trends Pharmacol Sci. 1993 May;14(5):164–168. doi: 10.1016/0165-6147(93)90202-u. [DOI] [PubMed] [Google Scholar]
  125. Prehn R. T. Many growth factors may not be growth factors. Cancer Res. 1992 Feb 1;52(3):501–507. [PubMed] [Google Scholar]
  126. Prendergast G. C., Gibbs J. B. Pathways of Ras function: connections to the actin cytoskeleton. Adv Cancer Res. 1993;62:19–64. doi: 10.1016/s0065-230x(08)60314-0. [DOI] [PubMed] [Google Scholar]
  127. Preston-Martin S., Pike M. C., Ross R. K., Jones P. A., Henderson B. E. Increased cell division as a cause of human cancer. Cancer Res. 1990 Dec 1;50(23):7415–7421. [PubMed] [Google Scholar]
  128. Puck T. T., Krystosek A. Reverse transformation, genome exposure, and cancer. Adv Cancer Res. 1993;62:125–151. doi: 10.1016/s0065-230x(08)60317-6. [DOI] [PubMed] [Google Scholar]
  129. Quesada J. R., Alexanian R., Hawkins M., Barlogie B., Borden E., Itri L., Gutterman J. U. Treatment of multiple myeloma with recombinant alpha-interferon. Blood. 1986 Feb;67(2):275–278. [PubMed] [Google Scholar]
  130. Quesada J. R., Gutterman J. U. Psoriasis and alpha-interferon. Lancet. 1986 Jun 28;1(8496):1466–1468. doi: 10.1016/s0140-6736(86)91502-3. [DOI] [PubMed] [Google Scholar]
  131. Quesada J. R., Hersh E. M., Manning J., Reuben J., Keating M., Schnipper E., Itri L., Gutterman J. U. Treatment of hairy cell leukemia with recombinant alpha-interferon. Blood. 1986 Aug;68(2):493–497. [PubMed] [Google Scholar]
  132. Quesada J. R., Reuben J., Manning J. T., Hersh E. M., Gutterman J. U. Alpha interferon for induction of remission in hairy-cell leukemia. N Engl J Med. 1984 Jan 5;310(1):15–18. doi: 10.1056/NEJM198401053100104. [DOI] [PubMed] [Google Scholar]
  133. Quesada J. R., Talpaz M., Rios A., Kurzrock R., Gutterman J. U. Clinical toxicity of interferons in cancer patients: a review. J Clin Oncol. 1986 Feb;4(2):234–243. doi: 10.1200/JCO.1986.4.2.234. [DOI] [PubMed] [Google Scholar]
  134. Rabbitts T. H. Translocations, master genes, and differences between the origins of acute and chronic leukemias. Cell. 1991 Nov 15;67(4):641–644. doi: 10.1016/0092-8674(91)90057-6. [DOI] [PubMed] [Google Scholar]
  135. Raff M. C. Social controls on cell survival and cell death. Nature. 1992 Apr 2;356(6368):397–400. doi: 10.1038/356397a0. [DOI] [PubMed] [Google Scholar]
  136. Rastinejad F., Conboy M. J., Rando T. A., Blau H. M. Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin. Cell. 1993 Dec 17;75(6):1107–1117. doi: 10.1016/0092-8674(93)90320-p. [DOI] [PubMed] [Google Scholar]
  137. Reichlin S. Neuroendocrine-immune interactions. N Engl J Med. 1993 Oct 21;329(17):1246–1253. doi: 10.1056/NEJM199310213291708. [DOI] [PubMed] [Google Scholar]
  138. Rich B. E., Campos-Torres J., Tepper R. I., Moreadith R. W., Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J Exp Med. 1993 Feb 1;177(2):305–316. doi: 10.1084/jem.177.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  139. Romagnani S. Induction of TH1 and TH2 responses: a key role for the 'natural' immune response? Immunol Today. 1992 Oct;13(10):379–381. doi: 10.1016/0167-5699(92)90083-J. [DOI] [PubMed] [Google Scholar]
  140. Ross C., Tingsgaard P., Jørgensen H., Vejlsgaard G. L. Interferon treatment of cutaneous T-cell lymphoma. Eur J Haematol. 1993 Aug;51(2):63–72. doi: 10.1111/j.1600-0609.1993.tb01595.x. [DOI] [PubMed] [Google Scholar]
  141. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
  142. Sager R., Anisowicz A., Neveu M., Liang P., Sotiropoulou G. Identification by differential display of alpha 6 integrin as a candidate tumor suppressor gene. FASEB J. 1993 Jul;7(10):964–970. doi: 10.1096/fasebj.7.10.8344495. [DOI] [PubMed] [Google Scholar]
  143. Sager R. Tumor suppressor genes: the puzzle and the promise. Science. 1989 Dec 15;246(4936):1406–1412. doi: 10.1126/science.2574499. [DOI] [PubMed] [Google Scholar]
  144. Schulman H. The multifunctional Ca2+/calmodulin-dependent protein kinases. Curr Opin Cell Biol. 1993 Apr;5(2):247–253. doi: 10.1016/0955-0674(93)90111-3. [DOI] [PubMed] [Google Scholar]
  145. Sen G. C., Lengyel P. The interferon system. A bird's eye view of its biochemistry. J Biol Chem. 1992 Mar 15;267(8):5017–5020. [PubMed] [Google Scholar]
  146. Sen G. C., Ransohoff R. M. Interferon-induced antiviral actions and their regulation. Adv Virus Res. 1993;42:57–102. doi: 10.1016/s0065-3527(08)60083-4. [DOI] [PubMed] [Google Scholar]
  147. Shan B., Vazquez E., Lewis J. A. Interferon selectively inhibits the expression of mitochondrial genes: a novel pathway for interferon-mediated responses. EMBO J. 1990 Dec;9(13):4307–4314. doi: 10.1002/j.1460-2075.1990.tb07879.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  148. Shih I. M., Herlyn M. Role of growth factors and their receptors in the development and progression of melanoma. J Invest Dermatol. 1993 Feb;100(2 Suppl):196S–203S. [PubMed] [Google Scholar]
  149. Shoeman R. L., Höner B., Mothes E., Traub P. Potential role of the viral protease in human immunodeficiency virus type 1 associated pathogenesis. Med Hypotheses. 1992 Mar;37(3):137–150. doi: 10.1016/0306-9877(92)90071-j. [DOI] [PubMed] [Google Scholar]
  150. Skolnick M. H., Cannon-Albright L. A., Goldgar D. E., Ward J. H., Marshall C. J., Schumann G. B., Hogle H., McWhorter W. P., Wright E. C., Tran T. D. Inheritance of proliferative breast disease in breast cancer kindreds. Science. 1990 Dec 21;250(4988):1715–1720. doi: 10.1126/science.2270486. [DOI] [PubMed] [Google Scholar]
  151. Skurkovich S., Skurkovich B., Bellanti J. A. A disturbance of interferon synthesis with the hyperproduction of unusual kinds of interferon can trigger autoimmune disease and play a pathogenetic role in AIDS: the removal of these interferons can be therapeutic. Med Hypotheses. 1993 Aug;41(2):177–185. doi: 10.1016/0306-9877(93)90066-y. [DOI] [PubMed] [Google Scholar]
  152. Smalley R. V., Andersen J. W., Hawkins M. J., Bhide V., O'Connell M. J., Oken M. M., Borden E. C. Interferon alfa combined with cytotoxic chemotherapy for patients with non-Hodgkin's lymphoma. N Engl J Med. 1992 Nov 5;327(19):1336–1341. doi: 10.1056/NEJM199211053271902. [DOI] [PubMed] [Google Scholar]
  153. Solal-Celigny P., Lepage E., Brousse N., Reyes F., Haioun C., Leporrier M., Peuchmaur M., Bosly A., Parlier Y., Brice P. Recombinant interferon alfa-2b combined with a regimen containing doxorubicin in patients with advanced follicular lymphoma. Groupe d'Etude des Lymphomes de l'Adulte. N Engl J Med. 1993 Nov 25;329(22):1608–1614. doi: 10.1056/NEJM199311253292203. [DOI] [PubMed] [Google Scholar]
  154. Sonenberg N. Translation factors as effectors of cell growth and tumorigenesis. Curr Opin Cell Biol. 1993 Dec;5(6):955–960. doi: 10.1016/0955-0674(93)90076-3. [DOI] [PubMed] [Google Scholar]
  155. Sporn M. B. Carcinogenesis and cancer: different perspectives on the same disease. Cancer Res. 1991 Dec 1;51(23 Pt 1):6215–6218. [PubMed] [Google Scholar]
  156. Sporn M. B., Roberts A. B. Autocrine secretion--10 years later. Ann Intern Med. 1992 Sep 1;117(5):408–414. doi: 10.7326/0003-4819-117-5-408. [DOI] [PubMed] [Google Scholar]
  157. Sporn M. B., Roberts A. B. TGF-beta: problems and prospects. Cell Regul. 1990 Nov;1(12):875–882. doi: 10.1091/mbc.1.12.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  158. Srivastava P. K. Peptide-binding heat shock proteins in the endoplasmic reticulum: role in immune response to cancer and in antigen presentation. Adv Cancer Res. 1993;62:153–177. doi: 10.1016/s0065-230x(08)60318-8. [DOI] [PubMed] [Google Scholar]
  159. Stanley L. A., Adams D. J., Balkwill F. R., Griffin D., Wolf C. R. Differential effects of recombinant interferon alpha on constitutive and inducible cytochrome P450 isozymes in mouse liver. Biochem Pharmacol. 1991 Jul 5;42(2):311–320. doi: 10.1016/0006-2952(91)90718-k. [DOI] [PubMed] [Google Scholar]
  160. Stewart T. A., Hultgren B., Huang X., Pitts-Meek S., Hully J., MacLachlan N. J. Induction of type I diabetes by interferon-alpha in transgenic mice. Science. 1993 Jun 25;260(5116):1942–1946. doi: 10.1126/science.8100367. [DOI] [PubMed] [Google Scholar]
  161. Strander H., Bauer H. C., Brosjö O., Kreicbergs A., Lindholm J., Nilsonne U., Silfverswärd C., Szamosi A. Adjuvant interferon treatment in human osteosarcoma. Cancer Treat Res. 1993;62:29–32. doi: 10.1007/978-1-4615-3518-8_5. [DOI] [PubMed] [Google Scholar]
  162. Strander H. Interferon treatment of human neoplasia. Adv Cancer Res. 1986;46:1–265. [PubMed] [Google Scholar]
  163. Strober W., Ehrhardt R. O. Chronic intestinal inflammation: an unexpected outcome in cytokine or T cell receptor mutant mice. Cell. 1993 Oct 22;75(2):203–205. doi: 10.1016/0092-8674(93)80062-j. [DOI] [PubMed] [Google Scholar]
  164. Takada N., Takase S., Takada A. Effects of genotypes of hepatitis C virus on interferon treatment for chronic type C hepatitis. Gastroenterol Jpn. 1993 Apr;28(2):268–275. doi: 10.1007/BF02779230. [DOI] [PubMed] [Google Scholar]
  165. Takeichi M. Cadherins in cancer: implications for invasion and metastasis. Curr Opin Cell Biol. 1993 Oct;5(5):806–811. doi: 10.1016/0955-0674(93)90029-p. [DOI] [PubMed] [Google Scholar]
  166. Talpaz M., Kantarjian H. M., McCredie K., Trujillo J. M., Keating M. J., Gutterman J. U. Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia. N Engl J Med. 1986 Apr 24;314(17):1065–1069. doi: 10.1056/NEJM198604243141701. [DOI] [PubMed] [Google Scholar]
  167. Talpaz M., Kantarjian H., Kurzrock R., Trujillo J. M., Gutterman J. U. Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia. Philadelphia chromosome-positive patients. Ann Intern Med. 1991 Apr 1;114(7):532–538. doi: 10.7326/0003-4819-114-7-532. [DOI] [PubMed] [Google Scholar]
  168. Talpaz M., Mavligit G., Keating M., Walters R. S., Gutterman J. U. Human leukocyte interferon to control thrombocytosis in chronic myelogenous leukemia. Ann Intern Med. 1983 Dec;99(6):789–792. doi: 10.7326/0003-4819-99-6-789. [DOI] [PubMed] [Google Scholar]
  169. Tamm I., Lin S. L., Pfeffer L. M., Sehgal P. B. Interferons alpha and beta as cellular regulatory molecules. Interferon. 1987;9:13–74. [PubMed] [Google Scholar]
  170. Tanaka N., Kawakami T., Taniguchi T. Recognition DNA sequences of interferon regulatory factor 1 (IRF-1) and IRF-2, regulators of cell growth and the interferon system. Mol Cell Biol. 1993 Aug;13(8):4531–4538. doi: 10.1128/mcb.13.8.4531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  171. Temin H. M. Evolution of cancer genes as a mutation-driven process. Cancer Res. 1988 Apr 1;48(7):1697–1701. [PubMed] [Google Scholar]
  172. Tilg H., Mier J. W., Vogel W., Aulitzky W. E., Wiedermann C. J., Vannier E., Huber C., Dinarello C. A. Induction of circulating IL-1 receptor antagonist by IFN treatment. J Immunol. 1993 May 15;150(10):4687–4692. [PubMed] [Google Scholar]
  173. Todd J. A., Steinman L. The environment strikes back. Curr Opin Immunol. 1993 Dec;5(6):863–865. doi: 10.1016/0952-7915(93)90097-c. [DOI] [PubMed] [Google Scholar]
  174. Tsukita S., Itoh M., Nagafuchi A., Yonemura S., Tsukita S. Submembranous junctional plaque proteins include potential tumor suppressor molecules. J Cell Biol. 1993 Dec;123(5):1049–1053. doi: 10.1083/jcb.123.5.1049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  175. Tzung S. P., Mahl T. C., Lance P., Andersen V., Cohen S. A. Interferon-alpha prevents endotoxin-induced mortality in mice. Eur J Immunol. 1992 Dec;22(12):3097–3101. doi: 10.1002/eji.1830221211. [DOI] [PubMed] [Google Scholar]
  176. Upadhyaya G., Guba S. C., Sih S. A., Feinberg A. P., Talpaz M., Kantarjian H. M., Deisseroth A. B., Emerson S. G. Interferon-alpha restores the deficient expression of the cytoadhesion molecule lymphocyte function antigen-3 by chronic myelogenous leukemia progenitor cells. J Clin Invest. 1991 Dec;88(6):2131–2136. doi: 10.1172/JCI115543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  177. Uyemura K., Yamamura M., Fivenson D. F., Modlin R. L., Nickoloff B. J. The cytokine network in lesional and lesion-free psoriatic skin is characterized by a T-helper type 1 cell-mediated response. J Invest Dermatol. 1993 Nov;101(5):701–705. doi: 10.1111/1523-1747.ep12371679. [DOI] [PubMed] [Google Scholar]
  178. Vedantham S., Gamliel H., Golomb H. M. Mechanism of interferon action in hairy cell leukemia: a model of effective cancer biotherapy. Cancer Res. 1992 Mar 1;52(5):1056–1066. [PubMed] [Google Scholar]
  179. Verma A., Hirsch D. J., Glatt C. E., Ronnett G. V., Snyder S. H. Carbon monoxide: a putative neural messenger. Science. 1993 Jan 15;259(5093):381–384. doi: 10.1126/science.7678352. [DOI] [PubMed] [Google Scholar]
  180. Verma D. S., Spitzer G., Gutterman J. U., Zander A. R., McCredie K. B., Dicke K. A. Human leukocyte interferon preparation blocks granulopoietic differentiation. Blood. 1979 Dec;54(6):1423–1427. [PubMed] [Google Scholar]
  181. Wang C., Constantinescu S. N., MacEwan D. J., Strulovici B., Dekker L. V., Parker P. J., Pfeffer L. M. Interferon alpha induces protein kinase C-epsilon (PKC-epsilon) gene expression and a 4.7-kb PKC-epsilon-related transcript. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):6944–6948. doi: 10.1073/pnas.90.15.6944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  182. Weinberg R. Tumor suppressor genes. Neuron. 1993 Aug;11(2):191–196. doi: 10.1016/0896-6273(93)90177-s. [DOI] [PubMed] [Google Scholar]
  183. Weissman I. L. The whole body view. Curr Biol. 1993 Nov 1;3(11):766–769. doi: 10.1016/0960-9822(93)90026-k. [DOI] [PubMed] [Google Scholar]
  184. Willman C. L., Sever C. E., Pallavicini M. G., Harada H., Tanaka N., Slovak M. L., Yamamoto H., Harada K., Meeker T. C., List A. F. Deletion of IRF-1, mapping to chromosome 5q31.1, in human leukemia and preleukemic myelodysplasia. Science. 1993 Feb 12;259(5097):968–971. doi: 10.1126/science.8438156. [DOI] [PubMed] [Google Scholar]
  185. Windle M., Mondul T., Whitney R. B., Cummings K. M., Stadler I., Chadha K. C. A discriminant function analysis of various interferon parameters among alcoholics and heavy smokers. Drug Alcohol Depend. 1993 Jan;31(2):139–147. doi: 10.1016/0376-8716(93)90066-y. [DOI] [PubMed] [Google Scholar]
  186. Workman P. Introduction: new anticancer drug design and discovery based on advances in molecular oncology. Semin Cancer Biol. 1992 Dec;3(6):329–333. [PubMed] [Google Scholar]
  187. Wyllie A. H. Apoptosis (the 1992 Frank Rose Memorial Lecture). Br J Cancer. 1993 Feb;67(2):205–208. doi: 10.1038/bjc.1993.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  188. Yamamura M., Modlin R. L., Ohmen J. D., Moy R. L. Local expression of antiinflammatory cytokines in cancer. J Clin Invest. 1993 Mar;91(3):1005–1010. doi: 10.1172/JCI116256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  189. Zeng F. Y., Weiser W. Y., Kratzin H., Stahl B., Karas M., Gabius H. J. The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor. Arch Biochem Biophys. 1993 May 15;303(1):74–80. doi: 10.1006/abbi.1993.1257. [DOI] [PubMed] [Google Scholar]
  190. Zhuo M., Small S. A., Kandel E. R., Hawkins R. D. Nitric oxide and carbon monoxide produce activity-dependent long-term synaptic enhancement in hippocampus. Science. 1993 Jun 25;260(5116):1946–1950. doi: 10.1126/science.8100368. [DOI] [PubMed] [Google Scholar]
  191. Ziegler-Heitbrock H. W., Schlag R., Flieger D., Thiel E. Favorable response of early stage B CLL patients to treatment with IFN-alpha 2. Blood. 1989 May 1;73(6):1426–1430. [PubMed] [Google Scholar]
  192. Zinkernagel R. M., Pircher H. P., Ohashi P., Oehen S., Odermatt B., Mak T., Arnheiter H., Bürki K., Hengartner H. T and B cell tolerance and responses to viral antigens in transgenic mice: implications for the pathogenesis of autoimmune versus immunopathological disease. Immunol Rev. 1991 Aug;122:133–171. doi: 10.1111/j.1600-065x.1991.tb00601.x. [DOI] [PubMed] [Google Scholar]

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