ArticleProceedings of the National Academy of Sciences of the United States of America1999
Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIalpha subunit of protein kinase A after oral administration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 133 citations in OpenAlex.
- A phase I safety and dose escalation trial of docetaxel combined with GEM231, a second generation antisense oligonucleotide targeting protein kinase A R1alpha in patients with advanced solid cancers.Investigational new drugs · 2006Trial
- From a Concept on a Chalkboard to Gapmer Antisense.ACS omega · 2026Article
- Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease.Life (Basel, Switzerland) · 2025Review
- Oligonucleotide Formulations Prepared by High-Speed Electrospinning: Maximizing Loading and Exploring Downstream Processability.Pharmaceutics · 2023Article
- The Evolution of Antisense Oligonucleotide Chemistry-A Personal Journey.Biomedicines · 2021Review
- Targeting protein kinase A in cancer therapy: an update.EXCLI journal · 2014Review
- Preclinical evaluation of anticancer efficacy and pharmacological properties of FBA-TPQ, a novel synthetic makaluvamine analog.Marine drugs · 2012Article
- FKBP5 as a selection biomarker for gemcitabine and Akt inhibitors in treatment of pancreatic cancer.PloS one · 2012Article
- Pharmacokinetics and tissue distribution of 25-hydroxyprotopanaxadiol, an anti-cancer compound isolated from Panax ginseng, in athymic mice bearing xenografts of human pancreatic tumors.European journal of drug metabolism and pharmacokinetics · 2011Article
- A new mixed-backbone oligonucleotide against glucosylceramide synthase sensitizes multidrug-resistant tumors to apoptosis.PloS one · 2009Article
- Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy.Journal of cellular and molecular medicine · 2009Article
- In vitro and in vivo anticancer activity of novel synthetic makaluvamine analogues.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Article
- Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells.BMC medical genomics · 2008Article
- 20(S)-25-methoxyl-dammarane-3beta, 12beta, 20-triol, a novel natural product for prostate cancer therapy: activity in vitro and in vivo and mechanisms of action.British journal of cancer · 2008Article
- Antisense therapy in clinical oncology: preclinical and clinical experiences.Molecular biotechnology · 2006Review
- The future of antisense oligonucleotides in the treatment of respiratory diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2006Review
- Protein kinase A isozyme switching: eliciting differential cAMP signaling and tumor reversion.Oncogene · 2004Article
- Antisense therapy targeting MDM2 oncogene in prostate cancer: Effects on proliferation, apoptosis, multiple gene expression, and chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2003Article
- Review
- Antisense oligonucleotide therapy for urologic tumors.Current urology reports · 2003Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of the RIalpha subunit of cAMP-dependent protein kinase (PKA) has been demonstrated in various human cancers. PKA has been suggested as a potential target for cancer therapy. The goal of the present study was to evaluate an anti-PKA antisense oligonucleotide (mixed-backbone oligonucleotide) as a therapeutic approach to human cancer treatment. The identified oligonucleotide inhibited the growth of cell lines of human colon cancer (LS174T, DLD-1), leukemia (HL-60), breast cancer (MCF-7, MDA-MB-468), and lung cancer (A549) in a time-, concentration-, and sequence-dependent manner. In a dose-dependent manner, the oligonucleotide displayed in vivo antitumor activity in severe combined immunodeficient and nude mice bearing xenografts of human cancers of the colon (LS174T), breast (MDA-MB-468), and lung (A549). The routes of drug administration were intraperitoneal and oral. Synergistic effects were found when the antisense oligonucleotide was used in combination with the cancer chemotherapeutic agent cisplatin. The pharmacokinetics of the oligonucleotide after oral administration of (35)S-labeled oligonucleotide into tumor-bearing mice indicated an accumulation and retention of the oligonucleotide in tumor tissue. This study further provides a basis for clinical studies of the antisense oligonucleotide targeted to the RIalpha subunit of PKA (GEM 231) as a cancer therapeutic agent used alone or in combination with conventional chemotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.