Modulation of the immune response and tumor growth by activated Ras

Leukemia

Volumn 13, Issue 4, 1999, Pages 502-513

  Weijzen, S ^a   Velders, M P ^a   Kast, W M ^a  

^a LOYOLA UNIVERSITY HEALTH SYSTEM   (United States)

Author keywords

Immune escape; Leukemia; Metastatic potential; Ras; Tumor growth enhancement

Indexed keywords

2 [[2 [[2 [(2 AMINO 3 MERCAPTOPROPYL)AMINO] 3 METHYLPENTYL]OXY] 1 OXO 3 PHENYLPROPYL]AMINO] 4 (METHYLSULFONYL)BUTANOIC ACID ISOPROPYL ESTER; ANTINEOPLASTIC AGENT; CELL ADHESION MOLECULE; COMPLEMENTARY DNA; CYTOKINE; CYTOKINE RECEPTOR; DOXORUBICIN; ENZYME; GROWTH FACTOR; GROWTH FACTOR RECEPTOR; MAJOR HISTOCOMPATIBILITY ANTIGEN; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEINASE; RAS PROTEIN; TUMOR ANTIGEN;

ACUTE GRANULOCYTIC LEUKEMIA; BREAST CANCER; CANCER IMMUNOTHERAPY; HUMAN; IMMUNOMODULATION; MAJOR HISTOCOMPATIBILITY COMPLEX; METASTASIS POTENTIAL; MUTATION RATE; ONCOGENE RAS; PANCREAS CANCER; PRIORITY JOURNAL; PROGNOSIS; REOVIRUS; REVIEW; T LYMPHOCYTE ACTIVATION; TUMOR GROWTH; TUMOR IMMUNOLOGY;

EID: 0032937404     PISSN: 08876924     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.leu.2401367     Document Type: Review

References (107)

1. Bos JL. Ras oncogenes in human cancer: a review. Cancer Res 1989; 49: 4682-4689.
2. Padua RA, Guinn BA, Al-Sabah AI, Smith M, Taylor C, Pettersson T, Ridge S, Carter G, White D, Oscier D, Chevert S, West R. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia 1998; 12: 887-892.
3. De Souza Fernandez T, Menezes de Souza J, Macedo Silva ML, Tabak D, Abdelhay E. Correlation of N-ras point mutations with specific chromosomal abnormalities in primary myebdysplastic syndrome. Leukemia Res 1998; 22: 125-134.
4. De Melo MB, Lorand-Metze I, Lima CS, Saad ST, Costa FF. N-ras gene point mutations in Brazilian acute myelogenous leukemia patients correlate with a poor prognosis. Leuk Lymphoma 1997; 24: 309-317.
5. Wang JC, Chen C. N-Ras oncogene mutations in patients with agnogenic myeloid metaplasia in leukemic transformation. Leukemia Res 1998; 22: 639-643.
6. Sheng XM, Kawamura M, Ohnishi H, Ida K, Hanada R, Kojima S, Kobayashi M, Bessho F, Yanagisawa M, Hayashi Y. Mutations of the RAS genes in childhood acute myeloid leukemia, myelodysplastic syndrome and juvenile chronic myelocytic leukemia. Leukemia Res 1997; 21: 697-701.
7. Misawa S, Horiike S, Kaneko H, Kashima K. Genetic aberrations in the development and subsequent progression of myelodysplastic syndrome. Leukemia 1997; 11 (Suppl. 3): 533-535.
8. Solana R, Romero J, Alonso C, Pena J. MHC class I antigen expression is inversely related with tumor malignancy and ras oncogene product (pilras) levels in human breast tumors. Inv Met 1992; 12: 210-217.
9. Benhatter J, Losi L, Chaubert P, Givel JC, Costa J. Prognostic significance of K-ras mutations in colorectal cancer. Gastroent 1993; 104: 1044-1048.
10. Slebos RJ, Kibbelaar RE, Dalesio O, Kooistra A, Stam J, Meijer CJ, Wagenaar SS, Vanderschueren RG, Van Zandwijk N, Mooi WJ, Bos JL, Rodenhuis S. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. New Engl J Med 1990; 323: 561-565.
11. Stahel RA. Antigens, receptors and dominant oncogenes and the prognosis of non-small cell lung cancer. Lung Cancer 1994; 11 (Suppl. 3): S31-S38.
12. Wang Y, Lee H, Chen S, Yang S, Chen C. Analysis of K-ras gene mutations in lung carcinomas: correlation with gender, histological subtypes, and clinical outcome. J Cancer Res Clin Oncol 1998; 124: 517-522.
13. Baitsch D, Bastian D, Barth P, Schudy A, Nies C, Kisker O, Wagner H, Rothmund M. K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas. Ann Surg 1998; 228: 79-86.
14. Friess H, Berberat P, Schilling M, Kunz J, Korc M, Buchler MW. Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors. J Mol Med 1996; 74: 35-42.
15. Iniesta P, de Juan C, Caldes T, Vega F, Lopez J, Frenandez C, Sanchez A, Torres A, Balibrea J, Benito M. Genetic abnormalities and microsatellite instability in colorectal cancer. Cancer Det Prev 1998; 22: 383-395.
16. Kressner U, Bjorheim J, Westring S, Wahlberg SS, Pahlman L, Glimelius B, Lindmark G, Lindblom A, Borresen-Dale A. Ki-ras mutations and prognosis in colorectal cancer. Eur J Cancer 1998; 34: 518-521.
17. Leon J, Guerrero I, Pellicer A. Differential expression of the ras gene family in mice. Mol Cell Biol 1987; 7: 1535-1540.
18. Lowy DR, Willumsen BM. Function and regulation of ras. Ann Rev Biochem 1993; 62: 851-891.
19. Wittinghofer A, Scheffzek K, Ahmadian MR. The interaction of Ras with GTPase-activating proteins. FEBS Lett 1997; 410: 63-67.
20. Prendergast GC, Gibbs JB. Ras regulatory interactions: novel targets for anti-cancer intervention? Bioessays 1994; 16: 187-191.
21. Gomez J, Martinez C, Fernandez B, Garcia A, Rebollo A. Ras activation leads to cell proliferation or apoptotic cell death upon interleukin-2 stimulation or lymphokine deprivation, respectively. Eur J Immunol 1997; 27: 1610-1618.
22. Clark GJ, Der CJ. Aberrant function of the Ras signal transduction pathway in human breast cancer. Br Cancer Res Trt 1995; 35: 133-144.
23. Rommel C, Hafen E. Ras-a versatile cellular switch. Curr Opin Genet Dev 1998; 8: 412-418.
24. Hall A. A biochemical function for ras - at last. Science 1994; 264: 1413-1414.
25. Chen CY, Liou J, Forman LW, Faller DV. Differential regulation of discrete apoptotic pathways by Ras. J Biol Chem 1998; 273: 16700-16709.
26. Toi M, Hamada Y, Nakamura T, Mukaida H, Suehiro S, Wada T, Toge T, Niimoto M, Hattori T. Immunocytochemical and biochemical analysis of epidermal growth factor receptor expression in human breast cancer tissues: relationship to estrogen receptor and lymphatic invasion. Int J Cancer 1989; 43: 220-225.
27. Basu TN, Gutmann DH, Fletcher JA, Glover TW, Collins FS, Downward J. Aberrant regulation of ras proteins in malignant tumour cells from type 1 neurofibromatosis patients. Nature 1992; 356: 713-715.
28. Stiller CA, Chessells JM, Fitchett M. Neurofibromatosis and childhood leukemia/lymphoma: a population-based UKCCSG study. Br J Cancer 1994; 70: 969-972.
29. Satoh T, Fantl WJ, Escobedo JA, Williams LT, Kaziro Y. Platelet-derived growth factor receptor mediates activation of ras through different signaling pathways in different cell types. Mol Cell Biol 1993; 13: 3706-3713.
30. Sanchez-Garcia I, Martin-Zanca D. Regulation of Bcl-2 gene expression by BCR-ABL is mediated by Ras. J Mol Biol 1997; 267: 225-228.
31. Neefjes JJ, Momburg F. Cell biology of antigen presentation. Curr Opin Immunol 1993; 5: 27-34.
32. + T lymphocytes against tumor cells bearing mutated epitopes of K-ras p21. Eur J Immunol 1995; 25: 2588-2597.
33. Cheever MA, Chen W, Disis ML, Takahashi M, Peace DJ. T-cell immunity to oncogenic proteins including mutated ras and chimeric bcr-abl. Ann NY Acad Sci 1993; 690: 101-112.
34. Peace DJ, Chen W, Nelson H, Cheever MA. T cell recognition of transforming proteins encoded by mutated ras proto-oncogenes. J Immunol 1991; 146: 2059-2065.
35. Skipper J, Stauss HJ. Identification of two cytotoxic T lymphocyte-recognized epitopes in the Ras protein. J Exp Med 1993; 177: 1493-1498.
36. + T cell responses. Eur J Immunol 1996; 26: 435-443.
37. Peace DJ, Smith JW, Chen W, You SG, Cosand WL, Blake J, Cheever MA. Lysis of ras oncogene-transformed cells by specific cytotoxic T lymphocytes elicited by primary in vitro immunization with mutated ras peptide. J Exp Med 1994; 179: 473-479.
38. Fenton RG, Taub DD, Kwak LW, Smith MR, Longo DL. Cytotoxic T-cell response and in vivo protection against tumor cells harboring activated ras proto-oncogenes. J Natl Cancer Inst 1993; 85: 1294-1302.
39. Abrams SI, Hand PH, Tsang KY, Schlom J. Mutant ras epitopes as targets for cancer vaccines. Semin Oncol 1996; 23: 118-134.
40. + T-cell immunity to mutated ras protein in pancreatic and colon cancer patients. Cancer Res 1995; 55: 2984-2987.
41. Jung S, Schluesener HJ. Human T lymphocytes recognize a peptide of single point-mutated oncogenic ras proteins. J Exp Med 1991; 173: 273-276.
42. Gedde-Dahl T 3rd, Eriksen JA, Thorsby E, Gaudernack G. T-cell responses against products of oncogenes: generation and characterization of human T cell clones specific for p21 ras-derived synthetic peptides. Hum Immunol 1992; 33: 266-274.
43. Fossum B, Gedde-Dahl T 3rd, Hansen T, Eriksen JA, Thorsby E, Gaudernack G. Overlapping epitopes encompassing a point mutation (12 Gly → Arg) in p21 ras can be recognized by HLA-DR, -DP and -DQ restricted T cells. Eur J Immunol 1993; 23: 2687-2691.
44. Tsang KY, Nieroda CA, DeFilippi R, Chung YK, Yamaue H, Greiner JW, Schlom J. Induction of human cytotoxic T cell lines directed against point-mutated p21 ras-derived synthetic peptides. Vaccine Res 1994; 3: 183-193.
45. Van Elsas A, Nijman HW, Van der Minne CE, Mourer JS, Kast WM, Melief CJM, Schrier PI. Induction and characterization of cytotoxic T-lymphocytes recognizing a mutated p21 ras peptide presented by HLA-A*0201. Int J Cancer 1995; 61: 389-396.
46. + T cells from a patient with colon carcinoma, specific for a mutant p21-Ras-derived peptide (Gly13 → Asp), are cytotoxic towards a carcinoma cell line harbouring the same mutation. Cancer Immunol Immunother 1995; 40: 165-172.
47. Versteeg R, Noordermeer IA, Kruse-Wolters M, Ruiter DJ, Schrier PI. c-myc down-regulates class I HLA expression in human melanomas. EMBO J 1988; 7: 1023-1029.
48. Bernards R, Dessain SK, Weinberg RA. N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell 1986; 47: 667-674.
49. Lohmann S, Wollscheid U, Huber C, Seliger B. Multiple levels of MHC class I down-regulation by ras oncogenes. Scand J Immunol 1996; 43: 537-544.
50. Testorelli C, Bussini S, De Filippi R, Marelli O, Orlando L, Greiner JW, Grohmann U, Tentori L, Giuliani A, Bonmassar E, Graziani G. Dacarbazine-induced immunogenicity of a murine leukemia is attenuated in cells transfected with mutated K-ras gene. J Exp Clin Cancer Res 1997; 16: 15-22.
51. Ehrlich T, Wishniak O, Isakov N, Cohen O, Segal S, Rager-Zisman B, Gopas J. The effect of H-ras expression on tumorigenicity and immunogenicity of Balb/c 3T3 fibroblasts. Immunol Lett 1993; 39: 3-8.
52. Van Elsas A, Van Deursen E, Wielders R, Van den Berg-Bakker CA, Schrier PI. ras oncogene activation does not induce sensitivity to natural killer cell-mediated lysis in human melanoma. J Invest Dermatol 1994; 103 (Suppl.): 117S-121S.
53. Toes REM, Offringa R, Blom RJJ, Brandt RMP, Van der Eb AJ, Melief CJM, Kast WM. An adenovirus type 5 early region 1B-encoded CTL epitope-mediating tumor eradication by CTL clones is down-modulated by an activated ras oncogene. J Immunol 1995; 154: 3396-3405.
54. Offringa R, Feltkamp MCW, Voordouw AC, Lowik C, Van der Eb AJ, Melief CJM, Kast WM. Cells transformed by adenovirus type 5 E1A and activated ras evade destruction by T-cell immunity. Thesis, Leiden University, The Netherlands, 1991; 131-147.
55. Fernandez A, Chen PW, Aggarwal BB, Ananthaswamy HN. Resistance of Ha-ras oncogene-induced progresser tumor variants to tumor necrosis factor and interferon-γ. Lymph Cyt Res 1992; 11: 79-85.
56. Fenton RG, Hixon JA, Wright PW, Brooks AD, Sayers TJ. Inhibition of Fas(CD95) expression and Fas-mediated apoptosis by oncogenic ras. Cancer Res 1998; 58: 3391-3400.
57. Castelli C, Sensi M, Lupetti R, Mortarini R, Panceri P, Anichini A, Parmiani G. Expression of interleukin 1α, interleukin 6, and tumor necrosis factor a genes in human melanoma clones is associated with that of mutated N-RAS oncogene. Cancer Res 1994; 54: 4785-4790.
58. Demetri GD, Ernst TJ, Pratt ES, Zenzie BW, Rheinwald JG, Griffin JD. Expression of ras oncogenes in cultured human cells alters the transcriptional and posttranscriptional regulation of cytokine genes. J Clin Invest 1990; 86: 1261-1269.
59. Hoelzer D, Seipelt G. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in the treatment of myeloid leukemia. Curr Opin Hematol 1995; 2: 196-203.
60. Samanci A, Qing Y, Fagerberg J, Strigard K, Smith G, Ruden U, Wahren B, Mellstedt H. Pharmacological administration of granulocyte/macrophage colony-stimulating factor is of significant importance for the induction of a strong humoral and cellular response in patients immunized with recombinant carcinoembryonic antigen. Cancer Immunol Immunother 1998; 47: 131-142.
61. Nagai E, Ogawa T, Kielian T, Ikubo A, Suzuki T. Irradiated tumor cells adenovirally engineered to secrete granulocyte/macrophage colony-stimulating factor establish antitumor immunity and eliminate pre-existing tumors in syngeneic mice. Cancer Immunol Immunother 1998; 47: 72-80.
62. Jager E, Ringhoffer M, Dienes H-P, Arand M, Karbach J, Jager D, Ilsemann C, Hagedorn M, Oesch F, Knuth A. Granulocyte-macrophage colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 1996; 67: 54-62.
63. Bollag G, Clapp DW, Shin S, Adler F, Zhang YY, Thompson P, Lange BJ, Freedman MH, McCormick F, Jacks T, Shannon K. Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells. Nature Gen 1996; 12: 144-148.
64. Largaespada DA, Brannan CI, Jerkins NA, Copeland NG. NF1 deficiency causes Ras-mediated granulocyte/macrophage colony stimulating factor hypersensitivity and chronic myeloid leukaemia. Nature Gen 1996; 12: 137-143.
65. White FC, Benehacene A, Scheele JS, Kamps M. VEGF mRNA is stabilized by ras and tyrosine kinase oncogenes, as well as by UV radiation - evidence for divergent stabilization pathways. Growth Factors 1997; 14: 199-212.
66. Larcher F, Robles Al, Duran H, Murillas R, Quintanilla M, Cano A, Conti CJ, Jorcano JL. Up-regulation of vascular endothelial growth factor/vascular permeability factor in mouse skin carcinogenesis correlates with malignant progression state and activated H-ras expression levels. Cancer Res 1996; 56: 5391-5396.
67. Endo K, Borer CH, Tsujimoto Y. Modulation of LFA-1 surface antigen expression by activated H-ras oncogene in EBV-infected human B-lymphoblast cells. Oncogene 1991; 6: 1391-1396.
68. Roosien FF, De Kuiper PE, De Rijk D, Roos E. Invasive and metastatic capacity of revertants of LFA-1-deficient mutant T-cell hybridomas. Cancer Res 1990; 50: 3509-3513.
69. Springer TA. Adhesion receptors of the immune system. Nature 1990; 346: 425-434.
70. Behrend El, Craig AM, Wilson SM, Denhardt DT, Chambers AF. Reduced malignancy of ras-transformed NIH 3T3 cells expressing antisense osteopontin RNA. Cancer Res 1994; 54: 832-837.
71. Achkar C, Gong QM, Frankfater A, Bajkowski AS. Differences in targeting and secretion of cathepsins B and L by BALB/3T3 fibroblasts and Moloney murine sarcoma virus-transformed BALB/3T3 fibroblasts. J Biol Chem 1990; 265: 13650-13654.
72. Chambers AF, Colella R, Denhardt DT, Wilson SM. Increased expression of cathepsins L and B and decreased activity of their inhibitors in metastatic, ras-transformed NIH 3T3 cells. Mol Carc 1992; 5: 238-245.
73. Yan Z, Deng X, Chen M, Xu Y, Ahram M, Sloane BF, Friedman E. Oncogenic c-Ki-ras but not oncogenic c-Ha-ras up-regulates CEA expression and disrupts basolateral polarity in colon epithelial cells. J Biol Chem 1997; 272: 27902-27907.
74. Donatien PD, Diment SL, Boissy RE, Orlow SJ. Melanosomal and lysosomal alterations in murine melanocytes following transfection with the v-rasHa oncogene. Int J Cancer 1996; 66: 557-563.
75. Kim K, Cai J, Shuja S, Kuo T, Murnane MJ. Presence of activated ras correlates with increased cysteine proteinase activities in human colorectal carcinomas. Int J Cancer 1998; 79: 324-333.
76. Gjertsen MK, Bakka A, Breivik J, Saeterdal I, Solheim BG, Soreide O, Thorsby E, Gaudernack G. Vaccination with mutant ras peptides and induction of T-cell responsiveness in pancreatic carcinoma patients carrying the corresponding RAS mutation. Lancet 1995; 346: 1399-1400.
77. + T lymphocytes, generated by mutant p21-ras (12val) peptide vaccination of a patient recognize 12val-dependent nested epitopes present within the vaccine peptide and kill autologous tumour cells carrying this mutation. Int J Cancer 1997; 72: 784-790.
78. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstruction of cellular immunity against CMV in recipients of allogeneic bone marrow by adoptive transfer of T cell clones from the donor. New Engl J Med 1995; 333: 1038-1044.
79. Abrams SI, Khleif SN, Bergmannleitner ES, Kantor JA, Chung Y, Hamilton JM, Schlom J. Generation of stable CD4(+) and CD8(+) T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12. Cell Immunol 1997; 182: 137-151.
80. + T lymphocyte neo-epitope created by a ras codon 12 mutation which is restricted by the HLA-A2 allele. Cell Immunol 1998; 187: 103-116.
81. Gjertsen MK, Gaudernack G. Mutated ras peptides as vaccines in immunotherapy of cancer. Vox Sang 1998; 74 (Suppl. 2): 489-495.
82. Cella M, Sallusto F, Lanzavecchia A. Origin, maturation and antigen presenting function of dendritic cells. Curr Opin Immunol 1997; 9: 10-16.
83. Toes REM, Blom RJJ, Offringa R, Kast WM, Melief CJM. Enhanced tumor outgrowth after peptide vaccination. Functional deletion of tumor-specific CTL induced by peptide vaccination can lead to the inability to reject tumors. J Immunol 1996; 156: 3911-3918.
84. Toes REM, Offringa R, Blom RJJ, Melief CJM, Kast WM. Peptide vaccination can lead to enhance tumor growth through specific T-cell tolerance induction. Proc Natl Acad Sci USA 1996; 93: 7855-7860.
85. Toes REM, Van der Voort EIH, Schoenberger SP, Drijfhout JW, Van Bloois L, Storm G, Kast WM, Offringa R, Melief CJM. Enhancement of tumor outgrowth through CTL tolerization after peptide vaccination is avoided by peptide presentation on dendritic cells. J Immunol 1998; 160: 4449-4456.
86. Jansen B, Schlagbauer-Wadl H, Eichler HG, Wolff K, Van Elsas A, Schrier PI, Pehamberger H. Activated N-ras contributes to the chemoresistance of human melanoma in severe combined immunodeficiency (SCID) mice by blocking apoptosis. Cancer Res 1997; 57: 362-365.
87. Perrin D, Halazy S, Hill BT. Inhibitors of the Ras signal transduction pathway as potential antitumour agents. J Enzyme Inhibition 1996; 11: 77-95.
88. Gibbs JB, Oliff A, Kohl NE. Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic. Cell 1994; 77: 175-178.
89. Qian Y, Sebti SM, Hamilton AD. Farnesyltransferase as a target for anticancer drug design. Biopolymers 1997; 43: 25-41.
90. Kohl NE, Omer CA, Conner MW, Anthony NJ, Davide JP, deSolms SJ, Giuliani EA, Gomez RP, Graham SL, Hamilton K, Gibbs J. Inhibition of famesyltransferase induces regression of mammary and salivary carcinomas in ras transgenic mice. Nature Med 1995; 1: 792-797.
91. Cox AD, Der CJ. Farnesyltransferase inhibitors and cancer treatment: targeting simply Ras? Biochim Biophys Acta 1997; 1333: F51-71.
92. Mangues R, Corral T, Kohl NE, Symmans WF, Lu S, Malumbres M, Gibbs JB, Oliff A, Pellicer A. Antitumor effect of a farnesyl protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res 1998; 58: 1253-1259.
93. Van N, Ricca C, Fletcher J, Glover T, Seizinger BR, Manne V. Farnesyltransferase inhibitors block the neurofibromatosis type I (NF1) malignant phenotype. Cancer Res 1995; 55: 3569-3575.
94. Prendergast GC, Davide JP, Lebowitz PF, Wechsler-Reya R, Kohl NE. Resistance of a variant ras-transformed cell line to phenotypic reversion by farnesyl transferase inhibitors. Cancer Res 1996; 56: 2626-2632.
95. Mukhopadhyay T, Tainsky M, Cavender AC, Roth JA. Specific inhibition of K-ras expression and tumorigenicity of lung cancer cells by antisense RNA. Cancer Res 1991; 51: 1744-1748.
96. Zhang Y, Mukhopadhyay T, Donehower LA, Georges RN, Roth JA. Retroviral vector-mediated transduction of K-ras antisense RNA into human lung cancer cells inhibits expression of the malignant phenotype. Hum Gene Ther 1993; 4: 451-460.
97. Alemany R, Ruan S, Kataoka M, Koch PE, Mukhopadhyay T, Cristiano RJ, Roth JA, Zhang WW. Growth inhibitory effect of anti-K-ras adenovirus on lung cancer cells. Cancer Gene Ther 1996; 3: 296-301.
98. Aoki K, Yoshida T, Sugimura T, Terada M. Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity. Cancer Res 1995; 55: 3810-3816.
99. Cochet O, Kenigsberg M, Delumeau I, Virone-Oddos A, Multon M, Fridman WH, Schweighoffer F, Teillaud J, Tocque B, Intracellular expression of an antibody fragment-neutralizing p21 ras promotes tumor regression. Cancer Res 1998; 58: 1170-1176.
100. Coffey MS, Strong JE, Forsyth PA, Lee PWK. Reovirus therapy for tumors with activated Ras pathway. Science 1998; 282: 1332-1334.
101. Raquette RL, Landaw EM, Pierre RV, Kahan J, Lubbert M, Lazcano O, Isaac G, McCormick F, Koeffler HP. N-ras mutations are associated with poor prognosis and increased risk of leukemia in myelodysplastic syndrome. Blood 1993; 82: 590-599.
102. Constantinidou M, Chalevelakis G, Economopoulos T, Koffa M, Liloglou T, Anastassiou C, Yalouris A, Spandidos DA, Raptis S. Codon 12 ras mutations in patients with myelodysplastic syndrome: incidence and prognostic value. Ann Hematol 1997; 74: 11-14.
103. Fengru L, Suyun L, Jinhai R, Junping W, Shirong X, Runsheng L, Ergu Y. Correlated flow cytometric analysis of H-ras p21 and DNA ploidy in acute myelogenous leukemia. J Tongji Med University 1996; 16: 75-77.
104. Radich JP, Kopecky KJ, Willman CL, Weick J, Head D, Appelbaum F, Collins SJ. N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. Blood 1990; 76: 801-807.
105. Al-Mulla F, Going J, Sowden ETHH, Winter A, Pickford IR, Birnie GD. Heterogeneity of mutant versus wild-type Ki-ras in primary and metastatic colorectal carcinomas, and association of codon-12 valine with early mortality. J Path 1998; 185: 130-138.
106. Ahnen DJ, Feigl P, Quan G, Fenoglio-Preiser C, Lovato LC, Bunn PA Jr, Stemmerman G, Wells JD, MacDonald JS, Meyskens FL, Jr. Ki-ras mutation and p53 overexpression predict the clinical behavior of colorectal cancer: a Southwest Oncology Group study. Cancer Res 1998; 58: 1149-1158.
107. Mitsudomi T, Steinberg SM, Oie HK, Mulshine JL, Phelps R, Viallet J, Pass HI, Minna JD, Gazdar AF. ras gene mutations in non-small cell lung cancers are associated with shortened survival irrespective of treatment intent. Cancer Res 1991; 51: 4999-5002.