Antisense therapeuticsS Agrawal
Hybridon Inc, Cambridge, MA 02139, USA
Curr Opin Chem Biol 2:519-28. 1998
..Questions regarding the specificity of action and side effects of antisense phosphorothioate oligonucleotides have arisen simultaneously...
Antisense and/or immunostimulatory oligonucleotide therapeuticsS Agrawal
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Curr Cancer Drug Targets 1:197-209. 2001
....
GEM 231, a second-generation antisense agent complementary to protein kinase A RIalpha subunit, potentiates antitumor activity of irinotecan in human colon, pancreas, prostate and lung cancer xenograftsSudhir Agrawal
Hybridon, Inc, Cambridge, MA 02139, USA
Int J Oncol 21:65-72. 2002
..These results suggest that the use of irinotecan in combination with GEM 231 may increase the therapeutic index of irinotecan in cancer patients...
Modulation of Toll-like Receptor 9 Responses through Synthetic Immunostimulatory Motifs of DNASudhir Agrawal
Hybridon, Inc, Cambridge, Massuchusetts 02139, USA
Ann N Y Acad Sci 1002:30-42. 2003
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Role of Toll-like receptors in antisense and siRNA [corrected]Sudhir Agrawal
Hybridon, Inc, 345 Vassar Street, Cambridge, Massachusetts 02139, USA
Nat Biotechnol 22:1533-7. 2004
..Do antisense and siRNA agents work as ligands for Toll-like receptors (TLRs), a family of pathogen-associated, molecular pattern recognition receptors?..
Medicinal chemistry and therapeutic potential of CpG DNASudhir Agrawal
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02137, USA
Trends Mol Med 8:114-21. 2002
..This article reviews recent progress in understanding the effects of CpG DNA, the medicinal chemistry of CpG DNA, and its possible therapeutic applications...
Antisense therapeutics: is it as simple as complementary base recognition?S Agrawal
Hybridon, 155 Fortune Boulevard, Milford, MA 01757, USA
Mol Med Today 6:72-81. 2000
..Here, we discuss different mechanisms of action of oligonucleotides and the possible ways of minimizing non-antisense-related [corrected] effects to improve their specificity...
Importance of nucleotide sequence and chemical modifications of antisense oligonucleotidesS Agrawal
Hybridon, Inc, Milford, MA 01757, USA
Biochim Biophys Acta 1489:53-68. 1999
....
Potentiation of antitumor activity of irinotecan by chemically modified oligonucleotidesS Agrawal
Hybridon, Inc, Cambridge, MA 02139, USA
Int J Oncol 18:1061-9. 2001
..The use of chemically modified oligonucleotides together with irinotecan may increase the therapeutic index of irinotecan in cancer patients and continued development of such agents should be considered...
Immunomodulatory oligonucleotides containing a cytosine-phosphate-2'-deoxy-7-deazaguanosine motif as potent toll-like receptor 9 agonistsEkambar R Kandimalla
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 102:6925-30. 2005
..These results suggest that IMOs induce strong and rapid immunostimulation and that the CpR dinucleotide is recognized by TLR9, leading to immune-cell activation and cytokine secretion in vitro and in vivo...
Divergent synthetic nucleotide motif recognition pattern: design and development of potent immunomodulatory oligodeoxyribonucleotide agents with distinct cytokine induction profilesEkambar R Kandimalla
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Nucleic Acids Res 31:2393-400. 2003
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Requirement of nucleobase proximal to CpG dinucleotide for immunostimulatory activity of synthetic CpG DNADong Yu
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Bioorg Med Chem 11:459-64. 2003
..It was found that 'GXCGTT' motif has an intermediate immunostimulatory activity between those of 'GACGTT' and 'GTCGTT' in the mouse cells...
A dinucleotide motif in oligonucleotides shows potent immunomodulatory activity and overrides species-specific recognition observed with CpG motifEkambar R Kandimalla
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 100:14303-8. 2003
....
Oral administration of a synthetic agonist of Toll-like receptor 9 potently modulates peanut-induced allergy in miceFu Gang Zhu
Idera Pharmaceuticals, Inc, Cambridge, Mass, USA
J Allergy Clin Immunol 120:631-7. 2007
..Agonists of Toll-like receptor 9 have been shown to induce potent T(H)1-type immune responses and prevent and reverse ovalbumin-induced T(H)2-dominant allergic asthma in mice...
Toll-like receptor 7 selective synthetic oligoribonucleotide agonists: synthesis and structure-activity relationship studiesTao Lan
Idera Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
J Med Chem 52:6871-9. 2009
..In conclusion, we have designed and synthesized novel SIMRA compounds that selectively act as agonists of TLR7...
Agonists of Toll-like receptor 9 containing synthetic dinucleotide motifsDong Yu
Idera Pharmaceuticals, Inc, 167 Sidney Street, Cambridge, Massachusetts 02139, USA
J Med Chem 50:6411-8. 2007
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Immunopharmacological and antitumor effects of second-generation immunomodulatory oligonucleotides containing synthetic CpR motifsDaqing Wang
Hybridon, Inc, Cambridge, MA 02139, USA
Int J Oncol 24:901-8. 2004
..IMO treatment resulted in the development of tumor-specific memory immune responses. No treatment-related toxicity was observed in mice at the doses and treatment schedules studied...
Novel oligodeoxynucleotide agonists of TLR9 containing N3-Me-dC or N1-Me-dG modificationsMallikarjuna Reddy Putta
Idera Pharmaceuticals, Inc. 345 Vassar Street, Cambridge, MA 02139, USA
Nucleic Acids Res 34:3231-8. 2006
..These are the first studies elucidating the role of N3-position of cytosine and N1-position of guanine in a CpG motif for TLR9 activation and immune stimulation...
CpG penta- and hexadeoxyribonucleotides as potent immunomodulatory agentsLakshmi Bhagat
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Biochem Biophys Res Commun 300:853-61. 2003
..Short-immunomer also inhibits growth of MCF-7 human tumor xenograft in nude mice. This is the first report of activity with such short DNA sequences and also of sequences lacking hexameric motifs proposed in earlier studies...
Design, synthesis, and immunostimulatory properties of CpG DNAs containing alkyl-linker substitutions: role of nucleosides in the flanking sequencesDong Yu
Hybridon, Inc, 345 Vassar Street, Cambridge, Massachusetts 02139, USA
J Med Chem 45:4540-8. 2002
..Substitution of deoxyribonucleosides with a C3 or C4 alkyl-linker was found to be optimal for potentiating immunostimulatory activity...
Oligodeoxynucleotides containing synthetic immunostimulatory motifs augment potent Th1 immune responses to HBsAg in miceYukui Li
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139-4818, United States
Int Immunopharmacol 5:981-91. 2005
..2 microg. These data demonstrate that IMOs enhance the immunogenicity of HBsAg through potent Th1 immune responses, which may allow lower doses of antigen in vaccination...
Modifications incorporated in CpG motifs of oligodeoxynucleotides lead to antagonist activity of toll-like receptors 7 and 9Dong Yu
Idera Pharmaceuticals, Inc, 167 Sidney Street, Cambridge, MA 02139, USA
J Med Chem 52:5108-14. 2009
..These types of modifications are commonly employed in antisense sequences and thereby may affect the intended mechanism of action...
Impact of secondary structure of toll-like receptor 9 agonists on interferon alpha inductionDong Yu
Idera Pharmaceuticals, 167 Sidney Street, Cambridge, MA 02139, USA
Antimicrob Agents Chemother 52:4320-5. 2008
..Taken together, the present results suggest that oligonucleotide-based agonists of TLR9 that form intermolecular duplexes induce potent immune responses in vivo...
Secondary structures in CpG oligonucleotides affect immunostimulatory activityEkambar R Kandimalla
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139-4818, USA
Biochem Biophys Res Commun 306:948-53. 2003
..These results may also provide insights to place CpG motifs appropriately in DNA vaccines to induce additional Th1 type responses...
Stabilized immune modulatory RNA compounds as agonists of Toll-like receptors 7 and 8Tao Lan
Idera Pharmaceuticals, Inc, 167 Sidney Street, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 104:13750-5. 2007
..This is a comprehensive study of RNA-based compounds containing structures and synthetic stimulatory motifs in mouse, monkey, and human systems without using lipid carriers...
Modulation of ovalbumin-induced Th2 responses by second-generation immunomodulatory oligonucleotides in miceFu-Gang Zhu
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Int Immunopharmacol 4:851-62. 2004
..These data demonstrate that IMOs prevent antigen-induced Th2 immune responses when co-administered to mice during OVA sensitization and that IMOs reverse established allergic responses induced by OVA...
Antitumor activity and immune response induction of a dual agonist of Toll-like receptors 7 and 8Daqing Wang
Idera Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
Mol Cancer Ther 9:1788-97. 2010
..CL25 pulmonary metastasis model. These studies show that the dual TLR7/8 agonist induced Th1-type immune responses and potent antitumor activity in mice via TLR7 and through the MyD88-dependent pathway...
Oral administration of second-generation immunomodulatory oligonucleotides induces mucosal Th1 immune responses and adjuvant activityDaqing Wang
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Vaccine 23:2614-22. 2005
..IMOs may prove to be effective oral adjuvants, able to promote strong systemic and mucosal immune responses to oral vaccines and antigens for therapeutic and prophylactic applications...
'Immunomers'--novel 3'-3'-linked CpG oligodeoxyribonucleotides as potent immunomodulatory agentsDong Yu
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Nucleic Acids Res 30:4460-9. 2002
..These results suggest that immunomers have several advantages over conventional linear CpG DNAs for immunomodulatory activity studies...
Conjugation of ligands at the 5'-end of CpG DNA affects immunostimulatory activityEkambar R Kandimalla
Hybridon, Inc, 345 Vassar Street, Cambridge, Massachusetts 02139, USA
Bioconjug Chem 13:966-74. 2002
..These results suggest that for optimal immunostimulatory activity, ligands should not be attached at the 5'-end of the CpG DNA...
Synthesis and immunological activities of novel Toll-like receptor 7 and 8 agonistsEkambar R Kandimalla
Idera Pharmaceuticals, Inc, Cambridge, MA 02139, United States
Cell Immunol 270:126-34. 2011
..In conclusion, we have designed and synthesized novel ORNs with varying sequence compositions and chemical modifications, which selectively act as agonists of TLR8 or dual agonists of TLR7 and TLR8...
Potent CpG oligonucleotides containing phosphodiester linkages: in vitro and in vivo immunostimulatory propertiesDong Yu
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Biochem Biophys Res Commun 297:83-90. 2002
..PO-immunomers activated NF-kappa B and induced cytokine secretion in J774 cell cultures. In addition, PO-immunomers showed antitumor activity in nude mice bearing human breast (MCF-7) and prostate (DU145) cancer xenografts...
Synthetic oligoribonucleotides-containing secondary structures act as agonists of Toll-like receptors 7 and 8Tao Lan
Idera Pharmaceuticals, Inc, 167 Sidney Street, Cambridge, MA 02139, USA
Biochem Biophys Res Commun 386:443-8. 2009
..These results suggest that secondary structures in ORN provide nuclease stability and lead to stimulation of immune responses through TLR8 as well as TLR7 depending on the presence of specific nucleotide motifs...
Oligodeoxyribonucleotide-based antagonists for Toll-like receptors 7 and 9Daqing Wang
Idera Pharmaceuticals, Inc, 167 Sidney Street, Cambridge, Massachusetts 02139, USA
J Med Chem 52:551-8. 2009
..Antagonists may be suitable candidates for treating inflammatory and autoimmune diseases where inappropriate or uncontrolled TLR activation has been implicated...
Novel oligonucleotides containing two 3'-ends complementary to target mRNA show optimal gene-silencing activityLakshmi Bhagat
Idera Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, United States
J Med Chem 54:3027-36. 2011
..These results suggest that GSOs are novel agents for gene silencing that can be delivered systemically with broader applicability...
Peptide conjugation at the 5'-end of oligodeoxynucleotides abrogates toll-like receptor 9-mediated immune stimulatory activityMallikarjuna Reddy Putta
Idera Pharmaceuticals, Inc, Cambridge, Massachusetts 02139, USA
Bioconjug Chem 21:39-45. 2010
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Synthetic oligoribonucleotides containing arabinonucleotides act as agonists of TLR7 and 8Tao Lan
Idera Pharmaceuticals, Inc, 167 Sidney Street, Cambridge, MA 02139, United States
Bioorg Med Chem Lett 19:2044-7. 2009
..In human PBMC and pDC assays, SIMRA compounds containing arabinonucleotides induced Th1-type cytokine profiles. These results suggest that SIMRA compounds containing arabinonucleotides act as agonists of TLR7 and TLR8...
Towards optimal design of second-generation immunomodulatory oligonucleotidesEkambar R Kandimalla
Hybridon Inc, Cambridge, MA 02139, USA
Curr Opin Mol Ther 4:122-9. 2002
..In addition, we describe the design of second-generation CpG DNA agents, and clinical applications of first-generation agents...
Self-stabilized CpG DNAs optimally activate human B cells and plasmacytoid dendritic cellsYan-Ping Cong
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Biochem Biophys Res Commun 310:1133-9. 2003
..Further modifications of the hairpin duplex region with a mixture of oligodeoxynucleotides and oligo-2'-O-methylribonucleotides in a heteroduplex formation permitted activation of both human B cells and pDCs...
Immunostimulatory properties of phosphorothioate CpG DNA containing both 3'-5'- and 2'-5'-internucleotide linkagesDong Yu
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Nucleic Acids Res 30:1613-9. 2002
..These results suggest that site-specific incorporation of 3'-deoxynucleotides in CpG DNA modulates immunostimulatory properties...
Chemistry of CpG DNAEkambar R Kandimalla
Hybridon, Inc, Cambridge, Massachusetts, USA
Curr Protoc Nucleic Acid Chem . 2003
..This unit discusses the receptors that recognize CpG motifs and important aspects of the sequence context of CpG motifs to the end of understanding and designing CpG DNA for therapeutic purposes...
Hybridization-based fluorescence assay allows quantitation of single-stranded oligodeoxynucleotides in low nanomolar rangeEkambar R Kandimalla
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Anal Biochem 328:93-5. 2004
Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkagesD Yu
Hybridon Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Bioorg Med Chem 9:2803-8. 2001
..These results have significance in understanding CpG oligonucleotide-receptor interactions and the development of potent immunomodulatory agents...
Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationshipsE R Kandimalla
Hybridon, Inc, Cambridge, MA 02139, USA
Bioorg Med Chem 9:807-13. 2001
..These studies suggest that it is possible to develop YpG- and CpR-motifs as an alternative to CpG-motifs in PS-oligos for immunostimulatory studies...
Modulation of immunostimulatory activity of CpG oligonucleotides by site-specific deletion of nucleobasesD Yu
Hybridon, Inc, 345 Vassar Street, Cambridge, MA 02139, USA
Bioorg Med Chem Lett 11:2263-7. 2001
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Synthetic agonists of Toll-like receptors 7, 8 and 9S Agrawal
Idera Pharmaceuticals, 167 Sidney Street, Cambridge, MA 02139, USA
Biochem Soc Trans 35:1461-7. 2007
..A second candidate, IMO-2125, is also a TLR9 agonist that has been shown to induce high and sustained levels of IFN (interferon) in non-human primates and is being evaluated in HepC-infected human subjects...
Anti-tumor efficacy of a novel antisense anti-MDM2 mixed-backbone oligonucleotide in human colon cancer models: p53-dependent and p53-independent mechanismsHui Wang
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA
Mol Med 8:185-99. 2002
..This study should provide a basis for future development of anti-MDM2 antisense oligonucleotides as cancer therapeutic agents used alone or in combination with conventional chemotherapeutics...
Chemotherapy and chemosensitization of non-small cell lung cancer with a novel immunomodulatory oligonucleotide targeting Toll-like receptor 9Hui Wang
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294-0019, USA
Mol Cancer Ther 5:1585-92. 2006
..The present study provides a rationale for developing the immunomodulatory oligonucleotide for lung cancer therapy...
Immunomodulatory oligonucleotides as novel therapy for breast cancer: pharmacokinetics, in vitro and in vivo anticancer activity, and potentiation of antibody therapyHui Wang
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, 113 Volker Hall, 35294, USA
Mol Cancer Ther 5:2106-14. 2006
..Based on the present results, we believe that the IMO is a good candidate for clinical development for breast cancer therapy used either alone or in combination with conventional cancer therapeutic agents...
Experimental therapy of human prostate cancer by inhibiting MDM2 expression with novel mixed-backbone antisense oligonucleotides: in vitro and in vivo activities and mechanismsHui Wang
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA
Prostate 54:194-205. 2003
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TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenograftsVincenzo Damiano
Departments of Endocrinologia e Oncologia Molecolare e Clinica, Universita di Napoli Federico II, 80131 Napoli, Italy
Proc Natl Acad Sci U S A 104:12468-73. 2007
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Antisense-MDM2 sensitizes LNCaP prostate cancer cells to androgen deprivation, radiation, and the combination in vivoRadka Stoyanova
Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
Int J Radiat Oncol Biol Phys 68:1151-60. 2007
..To test the effects of antisense (AS)-MDM2 alone and with androgen deprivation (AD), radiotherapy (RT), and AD + RT on wild-type LNCaP cells in an orthotopic in vivo model...
Antisense anti-MDM2 mixed-backbone oligonucleotides enhance therapeutic efficacy of topoisomerase I inhibitor irinotecan in nude mice bearing human cancer xenografts: In vivo activity and mechanismsHui Wang
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Int J Oncol 20:745-52. 2002
..These results suggest that oligonucleotides have a role in irinotecan metabolism and action, providing a basis for future development of antisense oligonucleotides as a sensitizer for irinotecan-based therapy...
Novel toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitorsVincenzo Damiano
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Istituto di Anatomia Patologica, and Dipartimento di Biologia e Patologia Cellulare e Molecolare, , Via S. Pansini 5, 80131 Naples, Italy
Clin Cancer Res 12:577-83. 2006
..Moreover, this therapeutic strategy could be translated in patients affected by colorectal cancer...
Application of XIAP antisense to cancer and other proliferative disorders: development of AEG35156/ GEM640Eric C LaCasse
Aegera Therapeutics Inc, Montreal, Quebec, Canada H3E 1A8
Ann N Y Acad Sci 1058:215-34. 2005
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Novel MDM2 p53-independent functions identified through RNA silencing technologiesZhuo Zhang
Department of Pharmacology and Toxicology and Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
Ann N Y Acad Sci 1058:205-14. 2005
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Antisense oligonucleotide targeted to RIalpha subunit of cAMP-dependent protein kinase (GEM231) enhances therapeutic effectiveness of cancer chemotherapeutic agent irinotecan in nude mice bearing human cancer xenografts: in vivo synergistic activity, pharHui Wang
Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA
Int J Oncol 21:73-80. 2002
..These results suggest that GEM231 have a role in irinotecan metabolism and its antitumor activity, providing a basis for future development of this oligonucleotide as a chemosensitizer for irinotecan-based therapy...
Antisense anti-MDM2 oligonucleotides as a novel approach to the treatment of glioblastoma multiformeGautam Prasad
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 35294-0019, USA
Anticancer Res 22:107-16. 2002
..In conclusion, inhibiting MDM2 expression could be a novel pharmacological approach to glioblastoma therapy...
Radiosensitization by antisense anti-MDM2 mixed-backbone oligonucleotide in in vitro and in vivo human cancer modelsZhuo Zhang
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA
Clin Cancer Res 10:1263-73. 2004
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Combined targeting of epidermal growth factor receptor and MDM2 by gefitinib and antisense MDM2 cooperatively inhibit hormone-independent prostate cancerRoberto Bianco
Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, , Naples, Italy
Clin Cancer Res 10:4858-64. 2004
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Protein kinase A RIalpha antisense inhibition of PC3M prostate cancer cell growth: Bcl-2 hyperphosphorylation, Bax up-regulation, and Bad-hypophosphorylationYee Sook Cho
Cellular Biochemistry Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute NIH, Bethesda, MD 20892 1750, USA
Clin Cancer Res 8:607-14. 2002
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Novel antisense anti-MDM2 mixed-backbone oligonucleotides: proof of principle, in vitro and in vivo activities, and mechanismsRuiwen Zhang
Departments of Pharmacology and Toxicology, Division of Clinical Pharmacology, Comprehensive Cancer Center, and Gene Therapy Center, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294, USA
Curr Cancer Drug Targets 5:43-9. 2005
..These results provide a basis for clinical evaluation of antisense anti-MDM2 oligonucleotides as chemosensitizers and radiosensitizers. In addition, the MBO has been successfully used to identify novel functions of MDM2...
Antisense MDM2 enhances the response of androgen insensitive human prostate cancer cells to androgen deprivation in vitro and in vivoZhaomei Mu
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Prostate 68:599-609. 2008
..In this study, we investigated the effects of AS-MDM2 combined with AD on androgen resistant LNCaP (LNCaP-Res) and moderately androgen resistant bcl-2 overexpressing LNCaP (LNCaP-BST) cells...
Thermal stress-induced HSP70 mediates protection against intrapancreatic trypsinogen activation and acute pancreatitis in ratsLakshmi Bhagat
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
Gastroenterology 122:156-65. 2002
..The worsening of pancreatitis, which occurs when non-thermally stressed animals are given AS-HSP70 before cerulein, suggests that cerulein-induced HSP70 expression in nontreated animals acts to limit the severity of pancreatitis...
Loss of XIAP protein expression by RNAi and antisense approaches sensitizes cancer cells to functionally diverse chemotherapeuticsDan C McManus
Aegera Oncology Inc, University of Ottawa and Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada K1H 8L1
Oncogene 23:8105-17. 2004
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Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosisEric C LaCasse
Aegera Therapeutics, Inc, Montreal, Quebec, Canada
Clin Cancer Res 12:5231-41. 2006
..AEG35156 is presently under clinical assessment in multiple phase I trials in cancer patients as a single agent and in combination with docetaxel in solid tumors or cytarabine/idarubicin in leukemia...
Immune modulatory oligonucleotides in the prevention and treatment of OVA-induced eustachian tube dysfunction in ratsDeidra A Blanks
Department of Otolaryngology Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Otolaryngol Head Neck Surg 137:321-6. 2007
..Otitis media with effusion (OME) is often associated with allergies. Immune modulatory oligonucleotides (IMO) mediate allergic inflammation and may therefore be efficacious in the treatment of airway inflammation...
CRIPTO-1: a novel target for therapeutic intervention in human carcinomaNicola Normanno
Department of Experimental Oncology, INT Fondazione Pascale, Via Mariano Semmola, I 80131 Naples, Italy
Int J Oncol 25:1013-20. 2004
..Taken together, these data strongly suggest that CR-1 might represent a novel target for therapeutic intervention in different carcinoma types...
Impact of site-specific nucleobase deletions on the arthritogenicity of DNAJan L Bjersing
Department of Rheumatology and Inflammation Research, University of Goteborg, Goteborg, Sweden
Inflammation 28:159-68. 2004
..This study indicates that specific structural elements within the ODN sequence but outside the CpG motif, modulate the immunostimulatory properties of CpG ODNs...
Novel immunomodulatory oligonucleotides prevent development of allergic airway inflammation and airway hyperresponsiveness in asthmaDevendra K Agrawal
Medical Microbiology and Immunology and Biomedical Sciences, Center for Allergy, Asthma and Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA
Int Immunopharmacol 4:127-38. 2004
..These data suggest that the treatment with these novel IMOs prevents OVA-induced allergic airway inflammation and AHR in asthma in the mouse and may provide a useful agent in the treatment of human asthma...
Chemosensitization and radiosensitization of human cancer by antisense anti-MDM2 oligonucleotides: in vitro and in vivo activities and mechanismsHui Wang
Departments of Pharmacology and Toxicology, Division of Clinical Pharmacology, Comprehensive Cancer Center, and Gene Therapy Center, University of Alabama at Birmingham, Alabama 35294-0019, USA
Ann N Y Acad Sci 1002:217-35. 2003
..These results provide a basis for clinical evaluation of antisense anti-MDM2 oligonucleotides as chemosensitizer and radiosensitizer...
Antisense MDM2 sensitizes prostate cancer cells to androgen deprivation, radiation, and the combinationZhaomei Mu
Department of Radiation Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
Int J Radiat Oncol Biol Phys 58:336-43. 2004
..CONCLUSION: AS sensitizes cells to AD, RT, and AD+RT and shows promise in the treatment of the full range of patients with prostate cancer. AS has the potential to sensitize the primary tumor to AD+RT and metastasis to AD...
Antisense MDM2 oligonucleotides restore the apoptotic response of prostate cancer cells to androgen deprivationZhaomei Mu
Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
Prostate 60:187-96. 2004
..Antisense MDM2 has broad potential as a therapeutic agent to sensitize prostate cancer cells to AD therapy by enhancing apoptotic cell death...
Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathwayZhuo Zhang
Department of Pharmacology and Toxicology and Division of Clinical Pharmacology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Oncogene 24:7238-47. 2005
..More knowledge about the MDM2-E2F1 interaction may be helpful in developing novel anticancer therapies...
Immunization with gp120-depleted whole killed HIV immunogen and a second-generation CpG DNA elicits strong HIV-specific responses in miceDaria Trabattoni
Chair of Immunology, DISP LITA Vialba, Via GB Grassi 74, 20157 Milano, Italy
Vaccine 24:1470-7. 2006
..The immune enhancing effects of HYB2055 adjuvant were dose-dependent. These findings warrant clinical evaluation of the HIV-1 immunogen/HYB2055 candidate as a therapeutic vaccine for HIV-1 infected patients...
A safety study of a mixed-backbone oligonucleotide (GEM231) targeting the type I regulatory subunit alpha of protein kinase A using a continuous infusion schedule in patients with refractory solid tumorsSanjay Goel
Einstein Comprehensive Cancer Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Clin Cancer Res 9:4069-76. 2003
..Alternative dosing schedules should include intermittent administration to minimize cumulative toxicity. Additional studies using intermittent continuous infusion schedules of GEM231 are warranted...
The role of immunomodulatory oligonucleotides in prevention of OVA-induced Eustachian tube dysfunctionCharles S Ebert
Department of Otolaryngology Head and Neck Surgery, CB 7070, G0412 Neurosciences Hospital, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7070, United States
Int J Pediatr Otorhinolaryngol 70:2019-26. 2006
..To evaluate the potential role of immunomodulatory oligonucleotides (IMO) in the prevention of OVA-induced Eustachian tube dysfunction (ETD) in a rat model...
Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapyZhuo Zhang
Department of Pharmacology and Toxicology and Comprehensive Cancer Center, University of Alabama at Birmingham, VH 113, 1670 University Boulevard, Birmingham, AL 35294, USA
Proc Natl Acad Sci U S A 100:11636-41. 2003
..MDM2 inhibitors such as second-generation antisense oligonucleotides have a broad spectrum of antitumor activities in human cancers regardless of p53 status, providing novel approaches to therapy of human prostate cancer...
Was induction of HIV-1 through TLR9?Sudhir Agrawal
J Immunol 171:1621; author reply 1621-2. 2003
Immune modulatory oligonucleotides in prevention of nasal allergen-induced Eustachian tube dysfunction in ratsCharles S Ebert
Department of Otolaryngology Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
Otolaryngol Head Neck Surg 137:250-5. 2007
..Develop a model of nasal allergen-induced Eustachian tube dysfunction (ETD) in a rat and investigate the role of immune modulatory oligonucleotides (IMOs) in the prevention of nasal allergen-induced ETD...
Induction of immune activation by a novel immunomodulatory oligonucleotide without thymocyte apoptosisWeiwen Jiang
Division of Rheumatology and Department of Immunology, Duke University Medical Center, Durham, NC, USA
Biochem Biophys Res Commun 318:60-6. 2004
..The levels of corticosterone induced by HYB2048 were also significantly lower than those induced by LPS. This pattern of activation could distinguish CpG DNA from LPS in its effects on the immune system...