Antisense and therapeutic oligonucleotides: toward a gene-targeting cancer clinic

Bibliography

• PATERSON BM, ROBERTS BE, KUFF EL: Structural gene identification and mapping by DNA. mRNA hybrid-arrested cell-free translation. Proc. Natl. Acad. ScL USA (1977) 74:4370–4374.
   PubMed Web of Science ®Google Scholar
• •The first report that single-stranded DNA could be used to inhibit gene expression.
   Google Scholar
• ZAMECNIK P, STEPHENSON M: Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligo deoxynucleo tide. Proc. Natl. Acad. ScL USA (1978) 75:280–284.
   PubMed Web of Science ®Google Scholar
• ••The first report that an antisense ODN can inhibit geneexpression and cell transformation.
   Google Scholar
• MIZUNO T, CHOU MY, INOUYE M: A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA). Proc. Natl. Acad. ScL USA (1984) 81:1966–1970.
   PubMed Web of Science ®Google Scholar
• HEYWOOD SM: tcRNA as a naturally occurringantisense RNA in eukaryotes. Nucl. Acids Res. (1986) 14:6771–6772.
   PubMed Web of Science ®Google Scholar
• NESTEROVA M, CHO-CHUNG YS: A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth. Nature Med. (1995) 1:528–533.
   PubMed Web of Science ®Google Scholar
• ••The first report that antisense technology can be used toinhibit protein kinase A-mediated cell growth and cell transformation.
   Google Scholar
• SZCZYLIK C, SKORSKI T, NICOLAIDES NC et al.: Selective inhibition of leukemia cell proliferation by BCR-ABL antisense oligodeoxynucleotides. Science (1991) 253:562–565.
   PubMed Web of Science ®Google Scholar
• ••The first report that antisense technology can be used toinhibit cell proliferation in myelogenous leukaemia cells.
   Google Scholar
• WU AG, JOSHI SS, CHAN WC et al: Effects of BCR-ABL antisen se oligonucleotides (AS-ODN) on human chronic myeloid leukemic cells: AS-ODN as effective purging agents. Leuk. Lymphoma (1995) 20:67–76.
   PubMed Web of Science ®Google Scholar
• PARK YG, NESTEROVA M, AGRAWAL S, CHO-CHUNG YS: Dual blockade of cyclic AMP response element- (CRE) and AP-1 -directed transcription by CRE-transcription factor decoy oligonucleotide. J. Biol. Chem. (1999) 274:1573–1580.
   PubMed Web of Science ®Google Scholar
• ••The first report of a transcription factor decoy oligonucleo-tide that could block cyclic AMP-mediated signaling and inhibit cell growth in a tumor cell-specific manner.
   Google Scholar
• NISHIDA E, GOTOH Y: The MAP kinase cascade isessential for diverse signal transduction pathways. Trends Biochem. ScL (1993) 18:128–131.
   PubMed Web of Science ®Google Scholar
• DAUM G, EISENMANN-TAPPE I, FRIES HVV et al: The insand outs of Raf kinases. Trends Biochem. ScL (1994) 19:474–480.
   PubMed Web of Science ®Google Scholar
• •A mini-review.
   Google Scholar
• MONIA BP, HOHNSTON JF, GEIGER T et al.: Antitumor activity of a phosphorothioate antisense oligode-oxynucleotide targeted against C-raf kinase. Nature Med. (1996) 2:668–675.
   PubMed Web of Science ®Google Scholar
• •The first report of antisense technology directed against C-raf.
   Google Scholar
• ODWYER PJ, STEVENSON JP, GALLAGHER M et al.: c-raf-1 depletion and tumor responses in patients treated with the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A). Clin. Cancer Res. (1999) 5:3977–3982.
   Google Scholar
• KHOSRAVI-FAR R, DER CJ: The ras signal transduction pathway. Cancer Met. Rev. (1994) 13:67–89.
   PubMed Web of Science ®Google Scholar
• •A thorough review.
   Google Scholar
• WHITE MA, NICOLETTE C, MINDEN A et al.: Multiple ras functions can contribute to mammalian cell transfor-mation. Cell (1995) 80:533–541.
   PubMed Web of Science ®Google Scholar
• BOS JL: P21 Ras: an oncoprotein functioning in growth factor-induced signal transduction. Eur. J Cancer (1995) 31A:1051–1054.
   Google Scholar
• BOS J: ras oncogenes in human cancer: a review. Cancer Res. (1989) 49:4682–4689.
   PubMed Web of Science ®Google Scholar
• LIAO Y, TANG Z-Y, YE S-L et al.: Modulation of apoptosis, tumorigenesity and metastatic potential with antisense H-ras oligo deoxynueleotides in a high metastatic tumor model of hepatoma: LCI-D20. Hepato-gastroenterology (2000) 47:365–370.
   Google Scholar
• GRAY GD, HERNANDEZ OM, HEBEL D et al.: Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogenes in nude mice. Cancer Res. (1993) 53:577–580.
   PubMed Web of Science ®Google Scholar
• DANG CV: c-Myc target genes involved in cell growth, apoptosis and metabolism. Mol. Cell. Biol. (1999) 19:1–11.
   PubMed Web of Science ®Google Scholar
• NESBIT CE, TERSAK JM, PROCHOWNIK EV: Myc oncogenes and human neoplastic disease. Oncogene (1999) 18:3004–3016.
   PubMed Web of Science ®Google Scholar
• SPENCER CA, GROUDINE M: Control of c-myc regula-tion in normal and neoplastic cells. Adv. Cancer Res. (1991) 56:1–48.
   PubMed Web of Science ®Google Scholar
• HOLT JT, REDNER RL, NIENHUIS AW: An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentia-tion. Mol. Cell. Biol. (1988) 8:963–973.
   PubMed Web of Science ®Google Scholar
• WICKSTROM EL, BACON TA, GONZALEZ A et al.: Humanpromyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA. Proc. NatL Acad. Sci. USA (1988) 85:1028–1032.
   PubMed Web of Science ®Google Scholar
• McMANAWAY ME, NECKERS LM, LOKE SL et al.: Tumour-specific inhibition of lymphoma growth by antisense oligodeoxynucleotide. Lancet (1990) 335:808–811.
   PubMed Web of Science ®Google Scholar
• KIMURA S, MAEKAWA T, HIRAKAWA K et al.: Alterations of c-myc expression by antisense oligodeoxynucleo-tides enhance the induction of apoptosis in HL-60 cells. Cancer Res. (1995) 55:1379–1384.
   PubMed Web of Science ®Google Scholar
• SAWYERS CL, CALLAHAN W, WITTE ON: Dominant negative MYC blocks transformation by ABL oncogenes. Cell (1992) 70:901–910.
   PubMed Web of Science ®Google Scholar
• BOURGEADE MF, DEFACHELLES AS, CAYRE YE: Myc isessential for transformation by TEL/platelet-derived growth factor receptor beta (PDGERbeta). Blood (1998) 91:3333–3339.
   Google Scholar
• SHI Y, GLYNN JM, GUILBERT LJ et al.: Role for c-myc in activation-induced apoptotic cell death in T cell hybridomas. Science (1992) 257:212–214.
   PubMed Web of Science ®Google Scholar
• WYLLIE AH, ROSE KA, MORRIS RG et al.: Rodent fibroblast tumours expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression. Br. J Cancer (1987) 56:251–259.
   PubMed Web of Science ®Google Scholar
• EVAN GI, WYLLIE AH, GILBERT CS et al.: Induction of apoptosis in fibroblasts by c-myc protein. Cell (1992) 69:119–128.
   PubMed Web of Science ®Google Scholar
• COLLINS S, GROUDINE M: Amplification of endogenousmyc-related DNA sequences in human myeloid leukemia cell line. Nature (1982) 298:679–681.
   PubMed Web of Science ®Google Scholar
• DEAN NM, MCKAY R, MIRAGLIA L et al.: Inhibition ofgrowth of human tumor cell lines in nude mice by an antisense oligonucleotide inhibitor of protein kinase C-alpha expression. Cancer Res. (1996) 56:3499–3507.
   PubMed Web of Science ®Google Scholar
• •The first report that antisense technology directed against the gene encoding protein kinase C could inhibit tumour growth.
   Google Scholar
• DLUGOSZ AA, CHENG C, WILLIAMS EK et al: Alterations in murine keratinocyte differentiation induced by activated rasil' genes are mediated by protein kinase C-a. Cancer Res. (1994) 6413–6420.
   Google Scholar
• HENRY SP, TAYLOR J, MIDGLEY L et al: Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleo-tide, in a 4-week study in CD-1 mice. Antisense Nucleic Acid Drug Dev. (1997) 7:473–481.
   PubMedGoogle Scholar
• HENRY SP, MONTEITH D, BENNETT F et al.: Toxico-logical and pharmacokinetic properties of chemically modified antisense oligonucleotide inhibitors of PKC-alp h a and C-raf kin as e. AntiCancer Drug Des. (1997) 12:409–420.
   PubMedGoogle Scholar
• HENRY SP, GRILLONE LR, ORR JL et al.: Comparison of the toxicity profiles of ISIS 1082 and ISIS 2105, phosphorothioate oligonucleotides, following subacute intradermal administration in Sprague-Dawley rats. Toxicology (1997) 116:77–88.
   PubMed Web of Science ®Google Scholar
• HENRY SP, MONTEITH D, LEVIN AA: Antisense oligonu-cleotide inhibitors for the treatment of cancer: II. Toxicological properties of phosphorothioate oligodeoxynucleotides. AntiCancer Drug Des. (1997) 12:395–408.
   PubMedGoogle Scholar
• HENRY SP, GICLAS PC, LEEDS JM et al.: Activation of thealternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action. J. Pharmacol. Exp. Ther. (1997) 281 :810–816.
   PubMed Web of Science ®Google Scholar
• GALBRAITH WM, HOBSON WC, GICLAS PC et al.: Complement activation and hemodynamic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey. Antisense Res. Dev. (1994) 4:201–206.
   PubMedGoogle Scholar
• NEMUNAITIS J, HOLMLUND JT, KRAYNAK M et al: Phase I evaluation of ISIS 3521, an antisense oligodeoxynu-cleotide to protein kinase c-alpha, in patients with advanced cancer. J Clin. Oncol (1999) i7:3586–3595.
   Google Scholar
• YUEN AR, HALSEY J, FISHER GA et al.: Phase I study of an antisense oligonucleotide to protein kinase c-a (ISIS 3521 /CGP 64128A) in patients with cancer. Clin. Cancer Res. (1999) 5:3357–3363.
   PubMed Web of Science ®Google Scholar
• ••One of the first clinical trials in which antisense technologyagainst protein kinase Ca exhibited a clinical response.
   Google Scholar
• CHO-CHUNG YS, CLAIR T: The regulatory subunit of cAMP-dependent protein kinase as a target for chemotherapy of cancer and other cellular dysfunctional-related diseases. Pharmacol Ther. (1993) 60:265–288.
   PubMed Web of Science ®Google Scholar
• •A thorough review.
   Google Scholar
• TORTORA G, PEPE S, BIANCO C. et al.: The RI4 subunit of protein kinase A controls serum dependency and entry into cell cycle of human mammary epithelial cells. Oncogene (1994) 9:3233–3240.
   Google Scholar
• •One of the first reports of the importance of the regulatory subunit of protein kinase A in the cell cycle.
   Google Scholar
• CIARDIELLO F, TORTORA G: Interactions between the epidermal growth factor receptor and Type I protein kinase A: biological significance and therapeutic implications. Clin. Cancer Res. (1998) 4:821–828.
   PubMed Web of Science ®Google Scholar
• TORTORA G, DAMIANO V, BIANCO C et al.: The subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor. Oncogene (1997) 14:923–928.
   PubMed Web of Science ®Google Scholar
• ••The first report of the mechanism of action for the regulatorysubunit of protein kinase.
   Google Scholar
• BRADBURY AW, CARTER DC, MILLER RW et al.: Protein kinase A (PK-A) regulatory subunit expression in colorectal cancer and related mucosa. Br. J Cancer (1994) 69:738–742.
   PubMedGoogle Scholar
• MILLER WR, WATSON DMA, CHETTY JW, ELTON RA: Tumor cyclic AMP binding proteins: an independent prognostic factor for disease recurrence and survival in breast cancer. Breast Cancer Res. Treat. (1993) 26:89–94.
   Google Scholar
• SIMPSON JBB, RAMAGE AD, HULME MJ et al.: Cyclic adenosine 3',5'-monophosphate-binding proteins in human ovarian cancer: correlations with clinicopa-thology features. Clin. Cancer Res. (1996) 2:201–206.
   Google Scholar
• MCDAID HM, CAIRNS MT, ATKINSON RJ et al.: Increased expression of the RI subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer. Br. J Cancer (1999) 79:933–939.
   PubMed Web of Science ®Google Scholar
• TORTORA G, YOKOZAKI H, PEPE S et al.: Differentiation of HL-60 leukemia by Type I regulatory subunit antisense oligodeoxynucleotide of c-AMP-dependent protein kinase. Proc. Natl. Acad. ScL (1991) 88:2011–2015.
   PubMed Web of Science ®Google Scholar
• ••The first report that antisense technology directed againstprotein kinase A inhibited cell growth and induced cell differentiation.
   Google Scholar
• YOKOZAKI H, BUDILLON A, TORORA G et al.: An antisense oligodeoxynucleotide that depletes RIa subunit of cyclic AMP-dependent protein kinase induces growth inhibition in human cancer cells. Cancer Res. (1993) 53:868–872.
   PubMed Web of Science ®Google Scholar
• •The first report that antisense technology directed against protein kinase A inhibited cell growth and induced changes in cell morphology in cancer cells of various epithelial cell types.
   Google Scholar
• CHO-CHUNG YS, NESTEROVA M, KONDRASHIN A et al.: Antisense-protein kin ase A: a single-gene-based therapeutic approach. Antisense Nucl. Acid Drug Dev. (1997) 7:217–223.
   PubMedGoogle Scholar
• NESTEROVA M, NOGUCHI K, PARK YG et al.: Compensa- tory stabilization of RII0 protein, cell cycle deregula-tion and growth arrest in colon and prostate carcinoma cells by antisense-directed down- regula-tion of protein kinase A RIa protein. Clin. Cancer Res. (2000) [In Press].
   Google Scholar
• •First report that antisense oligonucleotides directed against the regulatory subunit of one protein kinase A isoform ultimately led to the stabilisation of another isoform.
   Google Scholar
• SRIVASTAVA RK, SRIVASTAVA AR, SETH P et al.: Growth arrest and induction of apoptosis in breast cancer cells by antisense depletion of protein kinase A-RIa subunit: p53-independent mechanism of action. MM. Cell Biochem. (1999) 195:25–36.
   Google Scholar
• ALPER O, HACKER NF, CHO-CHUNG YS: Protein kinase A-RIa subunit-directed antisense inhibition of ovarian cancer cell growth: crosstalk with tyrosine kinase signaling pathway. Oncogene (1999) 18:4999–5004.
   PubMed Web of Science ®Google Scholar
• •One of the first suggestions of a mechanism by which antisense technology directed against protein kinase A inhibited tumour cell growth.
   Google Scholar
• NESTEROVA M, CHO-CHUNG YS: Oligonucleotide sequence-specific inhibition of gene expression, tumor growth inhibition and modulation of cAMP-signaling by an RNA-DNA hybrid antisense targeted to protein kinase A RIa subunit. Antisense Nucl. Acid Drug Devel. (2000): [In Press].
   Google Scholar
• •One of the first suggestions of a mechanism by which antisense technology directed against protein kinase A inhibited tumour cell growth.
   Google Scholar
• AKHTAR S, AGRAWAL S: In vivo studies with antisense oligonucleotides. Trends Pharmacol Sci. (1997) 18:12–18.
   PubMed Web of Science ®Google Scholar
• AGRAWAL S, ZHANG R: Antisense therapeutics. CUIT. Opin. Chem. Biol. (1998) 2:519–528.
   PubMed Web of Science ®Google Scholar
• •A thorough review.
   Google Scholar
• AGRAWAL S, ZHANG R. Pharmacokinetics and bioavail-ability of oligonucleotides following oral and colorectal administration in experimental animals. In: Antisense Research and Application, Handbook of Experi-mental Pharmacology. ST Crooke (Ed.), Springer, Berlin (1998):525–543.
   Google Scholar
• ZHANG R, ZENG XF, BOWMAN JD, AGRAWAL S: Growth inhibition of human lung cancer A549 xenografts in nude mice following oral administration of mixed-backbone oligonucleotides targeted at protein kinase A. Proc. Am. Assoc. Cancer Res. (1998) 39:3522.
   Google Scholar
• •One of the first reports of the potential for mixed backbone oligonucleotides in inhibiting tumour cell growth with fewer toxic effects.
   Google Scholar
• TORTORA G, BIANCO R, DAMIANO V et al.: Oral antisense that targets protein kinase Acooperates with taxol and inhibits tumor growth, angiogenesis and growth factor production. Clin. Cancer Res. (2000) 6:2506–2512.
   Google Scholar
• CHEN H, MARSHALL J, NESS E etal.: A safety and pharma- cokinetic study of a mixed-backbone oligonucleotide (GEM231) targeting the Type I protein kinase A by two-hour infusions in patients with refractory solid tumors. Clin. Cancer Res. (2000) 6:1259–1266.
   Google Scholar
• •The first phase I study of mixed backbone oligonucleotides directed against protein kinase A.
   Google Scholar
• SALOMON, DS, BRANDT R, CIARDIELLO F, NORMANNO N: Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol Hematol. (1995) 19:183–232.
   PubMed Web of Science ®Google Scholar
• •A thorough review.
   Google Scholar
• PANICO L, D'ANTONIO A, SALVATORE G et al.: Differen-tial immunohistochemical detection of transforming growth factor a, amphireg-ulin and CRIPTO in human normal and malignant breast tissues. Int. J Cancer. (1996) 65:51–56.
   Google Scholar
• SCHIFFER D: Classification and biology of astrocytic gliomas. Forum Trends Exp. Clin. Med. (1998) 8:244–255.
   Google Scholar
• STOLL SW, BENEDICT M, MITRA R et al.: EGF receptor signaling inhibits keratinocyte apoptosis: evidence for mediation by Bc1-X(L). Oncogene (1998) 16:1493–1499.
   PubMedGoogle Scholar
• PREWETT M, ROCKWELL P, ROSE C, GOLDSTEIN NI: Anti-tumor and cell cycle responses in KB cells treated with a chimeric anti-EGFR monoclonal antibody in combination with cisplatin. Int. J. Oncol. (1996) 9:217–224.
   PubMed Web of Science ®Google Scholar
• TIAN XX, LAM PYP, CHAN J et al.: Antisense epidermal growth factor receptor transfection impairs the prolif-eration ability of glioblastoma U87 cells. Neuropathol Appl. Neurobiol (1998) 24:389–396.
   Google Scholar
• HEY, XENG Q, DRENNING SD et al.: Inhibition of human squamous cell carcinoma growth in vivoby epidermal growth factor receptor antisense RNA transcribed from the U6 promoter. J. Natl. Cancer Inst. (1998) 90:1080–1087.
   PubMed Web of Science ®Google Scholar
• BASERGA R, HONGO A, RUBINI M et al.: The IGF-I receptor in cell growth, transformation and apoptosis. Biochim. Biophys. Acta (1997) 1332:105–126.
   PubMed Web of Science ®Google Scholar
• KALEKO M, RUTTER WG, MILLE AD: Overexpression of the human insulin-like growth Factor I receptor promotes ligand-independent neoplastic transforma-tion. Mol. Cell. Biol. (1990) 10:464–473.
   PubMed Web of Science ®Google Scholar
• RESNICOFF M, ABRAHAM D, YUTANAWIBOONCHAI W et al.: The insulin-like growth Factor I receptor protects tumor cells from apoptosis in viva Cancer Res. (1995) 55:2463–2469.
   Google Scholar
• BURFEIND P, CHERNICKY CL, RININSLAND F et al.:Antisense RNA to the Type I insulin-like growth factor receptor suppresses tumor growth and prevents invasion by rat prostate cancer cells in viva Proc. Natl. Acad. Sci. USA (1996) 93:7263–7268.
   PubMed Web of Science ®Google Scholar
• GERWINS P, BLANK JL, JOHNSON GL: Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway. J. Biol. Chem. (1997) 272:8288–8295.
   PubMedGoogle Scholar
• FOLTZ IN, GERL RE, WIELER JS et al: Human mitogen-activated protein kinase kinase 7 (MKK7) is highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environ-mental stresses and physiological stimuli. J Biol. Chem. (1998) 273:9344–9351.
   PubMedGoogle Scholar
• XU S, COBB MH: MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases. Biol. Chem. (1997) 272:32056–32060.
   Google Scholar
• GUPTA S, BARRETT T, WHITMARSH AJ et al: Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J (1996) 15:2760–2770.
   PubMed Web of Science ®Google Scholar
• SMEAL T, BINETRUY B, MERCOLA D et al.: On cogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73. Nature (1991) 354:494–496.
   PubMed Web of Science ®Google Scholar
• BOST F, McKAY R, BOST M et al: The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung car cinoma cells. Mol. Cell. Biol. (1999) 19:1938–1949.
   Google Scholar
• RIDLEY AJ: Rho: theme and variations. Current Biol. (1996) 6:1256–1264.
   Google Scholar
• •A thorough review.
   Google Scholar
• HILL CS, WYNNE J, TREISMAN R: The rho family GTPases RhoA, Rac1 and Cdc42Hs regulate transcriptional activation by SRF. Cell (1995) 81:1159–1170.
   PubMed Web of Science ®Google Scholar
• COSO OA, CHIARIELLO M, YU J-C et al.: The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signalling pathway. Cell (1995) 81:1137–1146.
   PubMed Web of Science ®Google Scholar
• TSUJIMOTO Y, CROCE CM: Analysis of the structure, transcripts and protein products of bc1-2, the gene involved in human follicular lymphoma. Proc. Natl. Acad. ScL USA (1986) 83:5214–5218.
   PubMed Web of Science ®Google Scholar
• MCDONNELL TJ, TRONCOSO P, BRISBY SM et al: Expres-sion of the protooncogene Bc1-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. (1992) 52:6940–6944.
   PubMed Web of Science ®Google Scholar
• RAFFO AJ, PERLMAN H, CHEN MW et al.: Overexpression of bc1-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo. Cancer Res. (1995) 55:4438–4445.
   PubMed Web of Science ®Google Scholar
• MCCONKEY DJ, GREENE G, PETTAWAY CA: Apoptosis resistance increases with metastatic potential in cells of the human ENCaP prostate carcinoma line. Cancer Res. (1996) 56:5594–5599.
   PubMedGoogle Scholar
• WATERS J, WEBB A, CUNNINGHAM D et al.: Phase I clinical and pharmacokinetic study of Bc1-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J. Clin. Oncol (2000) 1 8:1812–1823.
   Google Scholar
• •The first phase I study of antisense oligonucleotides directed against bc1–2.
   Google Scholar
• REED JC: Bc1-2 and the regulation of programmed cell death. J. Cell Biol. (1994) 124:1–6.
   PubMed Web of Science ®Google Scholar
• JANSEN B, SCHLAGBAUER-WADL H, BROWN BD et al.: Bc1-2 antisense therapy chemosensitizes human melanoma in SCID mice. Nature Med. (1998) 4:232–234.
   PubMed Web of Science ®Google Scholar
• •The first evidence that antisense oligonucleotides against bc1–2 may render cells susceptible to agents that induce apoptosis.
   Google Scholar
• FAKHARZADEH SS, TRUSKO SP, GEORGE DL: Tumori-genic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J (1991) 10:1565–1569.
   PubMed Web of Science ®Google Scholar
• MOMAND J, ZAMBETTI GP, OLSON DC et al: The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell (1992) 69:1237–1245.
   PubMed Web of Science ®Google Scholar
• OLINER JD, PIETENPOL JA, THIAGALINGAM S et al.: Oncoprotein Mdm2 conceals the activation domain of tumour suppressor p53. Nature (1993) 362:857–860.
   PubMed Web of Science ®Google Scholar
• HAUPT Y, MAYA R, KAZAZ A, OREN M: Mdm2 promotes the rapid degradation of p 53. Nature (1997) 387:296–299.
   PubMed Web of Science ®Google Scholar
• KUBBUTAT MHG, JONES SN, VOUSDEN KH: Regulation of p53 stability by Mdm2. Nature (1997) 387:299–303.
   Google Scholar
• WU X, BAYLE JH, OLSON D, LEVINE AJ: The p53-Mdm-2 autoregulatory feedback loop. Genes Dev. (1993) 7:1126–1132.
   PubMed Web of Science ®Google Scholar
• QUESNEL B, PREUDHOMME C, OSCIER D et al.: Over-expression of the Mdm2 gene is found in some cases of haematological malignancies. Br. J Haematol (1994) 88:415–418.
   PubMed Web of Science ®Google Scholar
• SUZUKI A, TOT M, YAMAMOTO Y et al.: Role of Mdm2 overexpression in doxorubicin resistance of breast carcinoma. Jpn. J. Cancer Res. (1998) 89:221–227.
   PubMedGoogle Scholar
• KHWAJA A, RODRIGUEZ-VICIANA P, WENNSTROM S et al.: Matrix adhesion and ras transformation both activate a phosphionositide 3-0H kinase and protein kinase B/Akt cellular survival pathway. EMBO J (1997) 16:2783–2793.
   PubMed Web of Science ®Google Scholar
• DUDEK H, DATTA SR, FRANKE TF et al.: Regulation ofneuronal survival by the serine-threonine protein kinase Akt. Science (1997) 275:661–665.
   PubMed Web of Science ®Google Scholar
• KAUFFMANN-ZEH A, RODRIGUEZ-VICIANA P, ULRICH E et al.: Suppression of c-Myc-induced apoptosis by ras signalling through PI (3) K and PKB. Nature (1997) 385:544–548.
   PubMed Web of Science ®Google Scholar
• KENNEDY SG, WAGNER AJ, CONEN SD et al: The PI 3 -kinase/Akt signalling pathway delivers an anti-apoptotic signal. Genes Dev. (1997) 11:701–713.
   PubMed Web of Science ®Google Scholar
• DATTA SR, DUDEK H, TAO X et al: Aktphosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell (1997) 91:231–241.
   PubMed Web of Science ®Google Scholar
• MARTE BM, DOWNWARD J: PKB/Akt. Connecting phosphoinositide 3-kinase to cell survival and beyond. Trends Biochem. ScL (1997) 22:355–358.
   Google Scholar
• CHENG JQ, GODWIN AK, BELLACOSA A et al.: AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc. Nati Acad ScL USA (1992) 89:9267–9271.
   PubMed Web of Science ®Google Scholar
• STAAL SP: Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2, amplification of AKT1 in a primary human gastric adenocarcinoma. Proc. Nati Acad. ScL USA (1987) 89:9267–9271.
   Google Scholar
• HOPKIN K: A surprising function for the PTEN tumor suppressor. Science (1998) 282:1027–1030.
   PubMedGoogle Scholar
• WALKER KS, DEAK M, PATERSON A et al.: Activation of protein kinase Bp and ryisoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro. Comparison with protein kinase B a. Biochem. J. (1998) 331:299–308.
   Google Scholar
• MASURE S, HAEFNER B, WESSELINK J-J et al.: Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3. Eur. J. Biochem. (1999) 265:353–360.
   Google Scholar
• COHEN P, HOLMES CFB, TSUKITANI Y: Okadaic acid: a new probe for the study of cellular regulation. Trends Biochem. ScL (1990) 15:98–102.
   Google Scholar
• HONKANEN RE: Cantharidin, another natural toxin that inhibits the activity of serine/threonine protein phosphatases types 1 and 2A. FEBS Lett. (1993) 330:283–286.
   Google Scholar
• WALSH AH, CHENG A, HONKANEN RE: Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A. FEBS Lett. (1997) 416:230–234.
   PubMed Web of Science ®Google Scholar
• CHENG A, BALCZON R, ZUO Z et al: Fostriecin-mediated G2-M-phase growth arrest correlates with abnormal centrosome replication, the formation of aberrant mitotic spindles and the inhibition of serine-treonine protein phosphatase activity. Cancer Res. (1998) 58:3611–3619.
   Google Scholar
• CHENG A, DEAN NM, HONKANEN RE: Serine/threonine protein phosphatase Type ty1 is required for the completion of cytokinesis in human A549 lung carcinoma cells. j Biol. Chem. (2000) 275:1846–1854.
   PubMed Web of Science ®Google Scholar
• ANDERSON CW, LEES-MILLER SP: The nuclear serine/threonine protein kinase DNA-PK. Crit. Rev. Eukary. Gene Expr. (1992) 2:283–314.
   PubMedGoogle Scholar
• GOTTLIEB TM, JACKSON SP: The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell (1993) 72:131–142.
   PubMed Web of Science ®Google Scholar
• JACKSON SP, JEGGO PA: DNA double-strand break repair and V(D)J recombination: involvement of DNA-PK. Trends Biochem. ScL (1995) 20:412–415.
   PubMed Web of Science ®Google Scholar
• WEAVER DT: What to do at an end: DNA double-strand-break repair. Trends Genet. (1995) 11:388–392.
   PubMedGoogle Scholar
• JACKSON SP, MACDONALD JJ, LEES-MILLER R: GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinase. Cell (1990) 63:155–165.
   PubMed Web of Science ®Google Scholar
• BHATTACHARYA S, RAMCHANDANI S, CERVONI N, SZYF M: A mammalian protein with specific demethylase activity for mCpG DNA. Nature (1999) 397:579–583.
   PubMed Web of Science ®Google Scholar
• CERVONI N, BHATTACHARYA S, SZYF M: DNA demethy-lase is a processive enzyme. J Biol. Chem. (1999) 274:8363–8366.
   PubMedGoogle Scholar
• ARAUJO FD, KNOX JD, SZYF M et al: Concurrent replica-tion and methylation at mammalian origins of replica-tion. Mol. Cell. Biol. (1998) 18:3475–3482.
   PubMedGoogle Scholar
• SZYF M, BOZOVIC V, TANIGAWA G: Growth regulation of mouse DNA methyltransferase gene expression. J Biol. Chem. (1991) 266:10027–10030.
   PubMed Web of Science ®Google Scholar
• SZYF M: DNA methylation properties: consequences for pharmacology. Trends Pharmacol Sci. (1994) 7:233–238.
   Google Scholar
• WU J, ISSA JP, HERMAN J et al.: Expression of an exogenous eukaryotic DNA methyltransferase gene induces transformation of N1H 313 cells. Proc. Nati Acad. ScL USA (1993) 90:8891–8895.
   PubMed Web of Science ®Google Scholar
• MACLEOD AR, SZYF M: Expression of antisense to DNA methyltransferase mRNA induces DNA demethylation and inhibits tumorigenesis. J. Biol. Chem. (1995) 270:8037–8043.
   PubMed Web of Science ®Google Scholar
• •First report of antisense technology directed against DNA methyltransferase.
   Google Scholar
• LAIRD PW, JACKSONGRUSBY L, FAZELI A et al:Suppres-sion of intestinal neoplasia by DNA hypomethylation. Cell (1995) 81:197–205.
   PubMed Web of Science ®Google Scholar
• RAMCHANDANI S, MACLEOD AR, PINARD M eta].: Inhibi-tion of tumorigenesis by a cytosine-DNA, methyltrans-ferase, antisense oligodeoxynucleotide. Proc. Natl. Acad. ScL USA (1997) 94:684–689.
   Google Scholar
• MILUTINOVIC S, KNOX JD, SZYF M: DNA methyltransfe-rase inhibition induces the transcription of the tumor p2iWAF1 /CIP1 dil. J. suppressorBiol. Chem. (2000) 275:6353–6359.
   Google Scholar
• LEUNG DW, CACHIANES G, KUANG W et al.: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science (1989) 246:1306–1309.
   PubMed Web of Science ®Google Scholar
• FERRARA N, HENZEL WJ: Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem. Biophys. Res. Commun. (1989) 1 61:851–858.
   Google Scholar
• TISHER E, MITCHELL R, HARTMANN T et al.: The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J. Biol. Chem. (1991) 266:11947–11954.
   Google Scholar
• DVORAK HF, SIOUSSAT TM, BROWN LF et al.: Distribu-tion of vascular permeability factor (vascular endothe-lial growth factor) in tumors: concentration in tumor blood vessels. J. Exp. Med. (1991) 174:1275–1278.
   PubMed Web of Science ®Google Scholar
• KECK PJ, HAUSER SD, KRIVI G et al.: Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science (1989) 246:1309–1312.
   PubMed Web of Science ®Google Scholar
• FERRARA N, HOUCK K, JAKEMAN L, LEUNG DW: Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr. Rev. (1992) 13:18–32.
   PubMed Web of Science ®Google Scholar
• WEINDEL K, MARME D, WEICH HA: AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. Biochem. Biophys. Res. Commun. (1992) 183:1167–1174.
   PubMed Web of Science ®Google Scholar
• MASOOD R, CAI J, ZHENG T et al.: Vascular endothelial growth factor/vascular permeability factor is an autocrine growth factor for AIDS-Kaposi sarcoma. Proc. Natl. Acad. ScL USA (1997) 94:979–984.
   PubMed Web of Science ®Google Scholar
• MAHER LI WOLD B, DERVAN PB: Inhibition of DNA binding proteins by oligonucleotide-directed triple helix formation. Science (1989) 245:725–730.
   Google Scholar
• •First report of the inhibition of transcription factor-enhancer binding through oligonucleotide-mediated triplex formation.
   Google Scholar
• CATAPANO CV, MCGUFFIE EM, PACHECO D, CARBONE GMRD: Inhibition of gene expression and cell prolif-eration by triple helix-forming oligonucleotides directed to the c-myc gene. Biochemistry (2000) 39:5126–5138.
   Google Scholar
• BIELINSKA A, SHIVDASSANI RA, ZHANG L, NABEL GJ: Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science (1990) 250:997–1000.
   PubMed Web of Science ®Google Scholar
• ••One of the first reports of transcription factor decoy oligonu-cleotides with modified phosphodiester bonds.
   Google Scholar
• MORISHITA R, GIBBONS GH, HORIUCHI M et al.: A novel molecular strategy using Cis element 'decoy' of F2F binding site inhibits smooth muscle proliferation in vivo. Proc. Natl. Acad. ScL USA (1995) 92:5855–5859.
   PubMed Web of Science ®Google Scholar
• •One of the first reports that transcription factor decoy oligonucleotides can inhibit cell proliferation.
   Google Scholar
• ZON G: Oligonucleotide analogues as potential chemotherapeutic agents. Pharm. Res. (1988) 5:539–549.
   PubMed Web of Science ®Google Scholar
• •A thorough review.
   Google Scholar
• AGRAWAL S, JIANG Z, ZHAO Q et al: Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: in vitro and in Vivo studies. Proc. Natl. Acad. Sci. USA (1997) 94:2620–2625.
   PubMed Web of Science ®Google Scholar
• •First report of second-generation mixed backbone oligonucleotides.
   Google Scholar
• CROOKE ST: Therapeutic applications of oligonucleo-tides. Ann. Rev. Pharmacol. Toxicol. (1992) 32:329–376.
   PubMed Web of Science ®Google Scholar
• •A thorough review.
   Google Scholar
• NABEL G, BALTIMORE D: An inducible transcription factor activates expression of human immunodefi-ciency virus in T cells. Nature (1987) 326:711–713.
   PubMed Web of Science ®Google Scholar
• LENARDO M, PIERCE JW, BALTIMORE D: Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science (1987) 236:1573–1577.
   PubMed Web of Science ®Google Scholar
• BAEUERLE PA, BALTIMORE D: The physiology of the NF-KB transcription factor. Mol. Aspects Cell Regul. (1991) 6:409–432.
   Google Scholar
• BOURS V, DEJARDIN E, GOUJON-LETAWE F et al: The NF-KB transcription factor and cancer: high expres-sion of NF-KB- and IKB-related proteins in tumor cell Biochem. Pharmacol. (1994) 47:145–149.
   Google Scholar
• HIMES SR, COLES LS, KATSIKEROS R et al: HTLV-1 tax activation of the GM-CSF and G-CSF promoters requires the interaction of NF-KB with other transcrip-tion factor families. Oncogene (1993) 8:3189–3197.
   PubMed Web of Science ®Google Scholar
• DUNN SM, COLES LS, LANG RK et al: Requirement for nuclear factor (NF)-KB p65 and NF-interleukin-6 binding elements in the tumor necrosis factor response region of the granulocyte colony-stimulating factor promoter. Blood (1994) 83:2469–2479.
   Google Scholar
• SHARMA HW, PEREZ JR, HIGGINS-SOCHASKI KA et al.: Transcription factor decoy approach to decipher the role of NF-KB in oncogenesis. AntiCancer Res. (1996) 16:61–69.
   Google Scholar
• SHARMA HVV, NARAYANAN R: The NF-KB transcription factor in on cogen esis. AntiCancerRes. (1996) 16:589–596.
   Google Scholar
• ROESLER WJ, VANDENBARK GR, HANSON RW: Cyclic AMP and the induction of eukaryotic gene transcrip-tion. J. Biol. Chem. (1988) 263:9063–9066.
   PubMed Web of Science ®Google Scholar
• •A mini-review.
   Google Scholar
• LEE YN, PARK YG, CHOI YH et al.: CRE-transcription factor decoy oligonucleotide inhibition of MCF-7 breast cancer cells: cross-talk with p53 signaling pathway. Biochem. (2000) 39:4863–4868.
   Google Scholar
• KWOK RPS, LUNDBLAD JR, CHRIVIA JC et al.: Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature (1994) 370:223–226.
   Google Scholar
• ARIAS J, ALBERTS AS, BRINDLE P et al.: Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature (1994) 370:226–229.
   PubMed Web of Science ®Google Scholar
• AGADIR A, SHEALY YF, HILL DL et al.: Retinyl methyl ether down-regulates activator protein 1 transcrip-tional activation in breast cancer cells. Cancer Res. (1997) 57:3444–3450.
   PubMedGoogle Scholar
• NILSSON M, FORD J, BOHM S et al: Characterization of a nuclear factor that binds juxtaposed with ATF3 /Jun on a composite response element specifically mediating induced transcription in response to an epidermal growth factor /Ras /Raf signaling pathway. Cell Growth Differ. (1997) 8:913–920.
   Google Scholar
• SUN P, ENSLEN H, MYUNG PS, MAURER RA: Differential activation of CREB by Ca2±/calmodulin-dependent protein kinases Type II and Type IVinvolves phospho-rylation of a site that negatively regulates activity. Genes Dev. (1994) 8:2527–2539.
   PubMed Web of Science ®Google Scholar
• XING J, GINTY DD, GREENBERG ME: Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science (1996) 273:959–963.
   PubMed Web of Science ®Google Scholar
• GONZALEZ GA, MONTMINY MR: Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell (1989) 59:675–680.
   PubMed Web of Science ®Google Scholar
• SHENG M, THOMSON MA, GREENBERG ME: CREB: A Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science (1991) 252:1427–1430.
   PubMed Web of Science ®Google Scholar
• GINTY DD, BONNI A, GREENBERG ME: Nerve growth factor activates a ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell (1994) 77:713–725.
   PubMedGoogle Scholar
• WILLIAMS JS, ANDRISANI OM: The hepatitis B virus X protein targets the basic region-leucine zipper domain of CREB. Proc. Natl. Acad. ScL USA (1995) 92:3819–3823.
   PubMed Web of Science ®Google Scholar
• LUNDBLAD JR, KWOK RPS, LAURANCE ME et al.: The human T-cell leukemia virus-1 transcriptional activator tax enhances cAMP-responsive element-binding protein (CREB) binding activity through interactions with the DNA minor groove. J. Biol. Chem. (1998) 273:19251–19259.
   Google Scholar