A5038833981- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cell death mechanisms and regulation
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- RNA regulation and disease
- Cytokine Signaling Pathways and Interactions
- Virus-based gene therapy research
- Cancer-related Molecular Pathways
- Inorganic and Organometallic Chemistry
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Reactions
- T-cell and Retrovirus Studies
- Cytomegalovirus and herpesvirus research
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Protein Kinase Regulation and GTPase Signaling
- Retinoids in leukemia and cellular processes
- Immunotherapy and Immune Responses
University of Freiburg
2024
City Of Hope National Medical Center
2009-2018
City of Hope
2009-2018
Albert Einstein College of Medicine
2003-2014
Montefiore Medical Center
2003-2009
Yeshiva University
1982-2006
Columbia University
1995-2004
Immunovaccine (Canada)
2004
Centrum Badań Molekularnych i Makromolekularnych Polskiej Akademii Nauk
2001
Polish Academy of Sciences
2001
Addition of antisense oligonucleotides to cell cultures has been used specifically inhibit gene expression. We have investigated the mechanism by which enter living cells. These compounds are taken up cells in a saturable, size-dependent manner compatible with receptor-mediated endocytosis. Polynucleotides any length competitive inhibitors oligomer transport, providing they possess 5'-phosphate moiety. Using oligo(dT)-cellulose for affinity purification, we identified an 80-kDa surface...
We have recently shown that phosphorothioate (PS) oligodeoxynucleotide (ODN) analogs, unlike their normal congeners, exhibit significant anti-HIV activity (Matsukura et al., (1987) Proc. Natl. Acad. Sci. USA 84, 7706-7710). now report the syntheses, melting temperatures (Tm), and nuclease susceptibilities of a series ODN analogs. These include all-PS duplexes, duplexes with one chain other either all-PS, or end-capped several PS groups at both 3' 5' ends. The DNase S-ODNs are much less than...
We administered suramin, an anti-parasitic drug and reverse transcriptase inhibitor, to 15 patients with metastatic cancer. This compound is known inhibit the binding of growth factors (eg, epidermal factor [EGF], platelet-derived [PDGF], tumor factor-beta [TGF-beta]) their receptors thus antagonize ability these stimulate cells in vitro. There were no complete responses (CRs), four partial (PRs) (two ten adrenal cortex, one renal, adult T-cell leukemia-lymphoma [HTLV-1]), two minimal (MRs)...
For the past 15-20 years, intracellular delivery and silencing activity of oligodeoxynucleotides have been essentially completely dependent on use a technology (e.g. lipofection). We developed method (called 'gymnosis') that does not require any transfection reagent or additives to serum whatsoever, but rather takes advantage normal growth properties cells in tissue culture order promote productive oligonucleotide uptake. This robust permits sequence-specific multiple targets large number...
In this report, we demonstrate the sequence-specific suppression of viral expression in T cells chronically infected with human immunodeficiency virus 1 (HIV-1), using antisense phosphorothioate oligodeoxynucleotides. As a target for intervention, used HIV-1 gene rev, which is essential replication and regulates virion proteins, part, by affecting splicing mRNA. A oligomer complementary to initiation sequence rev had significant selective inhibitory effect on production several proteins...
We have studied the translation of rabbit globin mRNA in cell free systems (reticulocyte lysate and wheat germ extract) microinjected Xenopus oocytes presence anti-sense oligodeoxynucleotides. Results obtained with unmodified all-oxygen compounds were compared those when phosphorothioate or α-DNA was used. In system a 17-mer sequence targeted to coding region β-globin specifically inhibitory either phosphodiester oligonucleotide its analogue contrast no effect observed α-oligomer. These...
Suramin is known to inhibit the growth of malignant prostate carcinoma cells in vitro. This led us evaluate effectiveness suramin treatment 38 patients with refractory hormone therapy.Suramin was administered by continuous infusion at a rate designed reach peak 300 micrograms/mL end 14 days. Patients were given 8 weeks recover from any toxicity before beginning second cycle. Subsequent cycles same manner except starting dose 280 mg/m2.In 17 measurable soft tissue disease, three had complete...
Suramin, a polysulfonated naphthylurea, has anti-reverse transcriptase and anti-proliferative activities inhibits the binding of various growth factors to their cell surface receptors. This drug is used in treatment acquired immunodeficiency syndrome several types cancers. Increased levels circulating glycosaminoglycans have been observed suramin-treated cancer patients, suggesting that it may inhibit glycosaminoglycan catabolism. Melanoma-derived heparanase, heparan sulfate-specific...
Antisense oligonucleotide biotechnology, at least in theory, provides a specific, rapid, and potentially high-throughput method for inhibiting gene expression exploring function. Over the past decade, plethora of experiments has been submitted, lesser number published, employing this approach to mRNA level. The specificity antisense stems, course, from (or, “information content”) Watson-Crick base pair interaction. The fact that oligonucleotides carry significant information addition...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDynamics of the internalization phosphodiester oligodeoxynucleotides in HL60 cellsC. A. Stein, John L. Tonkinson, Li Ming Zhang, Leonid Yakubov, James Gervasoni, Robert Taub, and Susan RotenbergCite this: Biochemistry 1993, 32, 18, 4855–4861Publication Date (Print):May 11, 1993Publication History Published online1 May 2002Published inissue 11 1993https://pubs.acs.org/doi/10.1021/bi00069a022https://doi.org/10.1021/bi00069a022research-articleACS...
Modified analogues of antisense oligodeoxynucleotides (ODNs), particularly phosphorothioates ([S]ODNs), have been extensively used to inhibit gene expression. The potential sequence specificity oligomers makes them attractive as molecular drugs for human diseases. use [S]ODNs expression has complicated by frequent nonspecific effects. In this study we show in diverse cell types that [S]ODNs, independent their base sequence, mediated the induction an Sp1 nuclear transcription factor....
We report the development of a severe polyneuropathy in 4 38 patients who were receiving parenteral suramin therapy for treatment various underlying malignancies. In 2 these patients, neuropathy progressed to generalized flaccid paralysis with bulbar and respiratory involvement, requiring endotracheal intubation ICU monitoring. EMG nerve conduction studies showed evidence block, suggestive demyelinating polyneuropathy. After several weeks, both improved clinically. The other developed...
Recent studies have suggested that loss of heterozygosity at loci on the short arm human chromosome 11 (11p) may be important in pathogenesis benign and malignant adrenal cortical tumors. To test this concept, adrenocortical carcinomas from nine patients lesions eight were tested for alleles chromosomes 11, 13, 17. All with carcinoma whose normal somatic tissues heterozygous a locus 17p had lost tumor. Four six who one or more 11p Three showed 13q Loss 11p, 13q, was observed primary tumors...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTLong-range intervalence electron tunneling through fully saturated systemsC. A. Stein, Nita Lewis, and Gunther SeitzCite this: J. Am. Chem. Soc. 1982, 104, 9, 2596–2599Publication Date (Print):May 1, 1982Publication History Published online1 May 2002Published inissue 1 1982https://pubs.acs.org/doi/10.1021/ja00373a043https://doi.org/10.1021/ja00373a043research-articleACS PublicationsRequest reuse permissionsArticle...
Antisense oligonucleotides (ASOs) are known to trigger mRNA degradation in the nucleus via an RNase H-dependent mechanism. We have now identified a putative cytoplasmic mechanism through which ASO gapmers silence their targets when transfected or delivered gymnotically (i.e. absence of any transfection reagent). shown that can interact with Ago-2 PAZ domain and localize into GW-182 mRNA-degradation bodies (GW-bodies). The products targeted mRNA, however, not generated by Ago-2-directed...
Antisense oligodeoxynucleotides offer potential as therapeutic agents to inhibit gene expression. Recent evidence indicates that designed target specific nucleic acid sequences can interact nonspecifically with proteins. This report describes the interactive capabilities of phosphorothioate defined sequence and length two essential protein tyrosine receptors, flk-1 epidermal growth factor receptor (EGFR), their effects on signaling in a transfected tumor cell line, respectively....