Timothy G. Geiser
Applied Biosystems
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Featured researches published by Timothy G. Geiser.
British Journal of Cancer | 1996
D. Del Bufalo; Carla Cucco; Carlo Leonetti; Gennaro Citro; Igea D'Agnano; M. Benassi; Timothy G. Geiser; Gerald Zon; Bruno Calabretta; Gabriella Zupi
We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs.
Leukemia | 1997
P. De Fabritiis; Tomasz Skorski; M. S. De Propris; Marco G. Paggi; Margaret Nieborowska-Skorska; Alessandro Lisci; S. Buffolino; K. Campbell; Timothy G. Geiser; Bruno Calabretta
We studied the effect of phosphorothioate oligodeoxynucleotides ([S]ODNs) complementary to the bcr-abl junction on cells taken at diagnosis from 41 patients with Philadelphia-positive chronic myelogenous leukaemia (CML). Experiments included the evaluation of the anti-leukaemic effect of 16- and 26-mer antisense [S]ODNs on both mononuclear and CD34+ cells, evaluation of incubation time and correlation of colony growth inhibition with the down-regulation of p210bcr-abl. At the same time, the uptake of [S]ODNs by mononuclear and purified CD34+ cell populations and the cross-hybridization of 26- and 16-mer [S]ODNs with the complementary sequences were evaluated. After incubation for 120 h with 26-mer antisense [S]ODNs on mononuclear cells, overall mean colony recovery was 41.9% of the untreated control samples; in particular, a significant reduction in colony formation was observed in 22 of the 35 cases tested. The effect of 26-mer ODNs on CD34+ cells was comparable to that observed on mononuclear cells in terms of colony inhibition; however, a higher proportion of cases showed a significant inhibition of colony formation. In comparison with the 26-mer antisense [S]ODNs, the anti-leukaemic effect of the 16-mer antisense [S]ODNs was less evident on mononuclear cells and comparable on CD34+ cells; however, a more specific effect was evident on both target cells. Hybridization experiments confirmed a partial cross-reactivity when the 26-mer ODNs were hybridized with their complementary sequence; this did not occur when 16-mer ODNs were similarly tested. Experiments aimed at evaluating the effect of the incubation time showed a significant increase in anti-leukaemic effect after a 120 h incubation period compared to that measured after a 24 h incubation period; this was parallelled by a progressive increase in the intracellular concentrations of [S]ODNs from day 1 to day 5. The accumulation of [S]ODNs correlated with a marked down-regulation of p210bcr-abl levels which was first detectable after 72 h of treatment. The down-regulation of p210bcr-abl levels following treatment with [S]ODNs showed a correlation between the effect of antisense [S]ODNs on leukaemic colony formation and protein expression. These studies confirm that, under optimal conditions of target cell culture and ODN size, antisense [S]ODNs complementary to the bcr-abl junction have specific anti-leukaemic effects.
Tetrahedron Letters | 1990
Victoria L. Boyd; David H. Hawke; Timothy G. Geiser
Abstract Woodwards Reagent K was used to activate the carboxyl group of protected amino acids. Subsequent reaction with trimethylsilylisothiocyanate consistently resulted in high yields of the 1-NFmoc-2-thiohydantoins. The protecting group(s) were readily removed with piperidine and TFA and the final thiohydantoin products were recovered in pure form after chromatography and crystallization. These especially mild conditions provide an improved synthetic route to the thiohydantoins, especially for the amino acids bearing sensitive side-chain groups.
Nucleosides, Nucleotides & Nucleic Acids | 1989
Alex Andrus; Timothy G. Geiser; Gerald Zon
Abstract Nudease-resistant oligonucleotides (11 to 28-mers) containing stereorandom phosphorothioate linkages have been recently reported to exhibit potent anti-HIV III effects and sequence-specific inhibition of protein synthesis. Relatively large amounts (100 mg 1g) of these analogues. which are needed for further biological testing and initial pharmacokinetic and pre-clinical studies, were readily obtained by automated hydrogen phosphonate chemistry followed by reversed-phase HPLC and further processing. This chemistry features 1 -adamanetanecarbonyl chloride as the activator, capping with isopropyl phosphite, and more complete sulfurization in only one-step following chain assembly. An automated, quantitative. picomole method for analysis of the analogues in blood samples has been developed.
Archive | 1984
John Bridgham; Timothy G. Geiser; Michael W. Hunkapiller; Stephen B. H. Kent; Mark P. Marriott; Paul Oliver Ramstad; Eric S. Nordman
Archive | 2014
Charles S. Vann; Debjyoti Banerjee; Timothy G. Geiser; James C. Nurse; Nigel P. Beard
Leukemia | 1995
de Fabritis P; S. Amadori; Maria Concetta Petti; Marco Mancini; Enrico Montefusco; Picardi A; Timothy G. Geiser; K. Campbell; Bruno Calabretta; Franco Mandelli
Archive | 1987
John Bridgham; Timothy G. Geiser; Michael W. Hunkapiller; Stephen B. H. Kent; Mark P. Marriott; Paul Oliver Ramstad; Eric S. Nordman
Antisense & Nucleic Acid Drug Development | 1999
Scott D. Putney; Josiah Brown; Carla Cucco; Rino Lee; Tomasz Skorski; Carlo Leonetti; Timothy G. Geiser; Bruno Calabretta; Gabriella Zupi; Gerald Zon
Archive | 1992
John Bridgham; Timothy G. Geiser; Michael W. Hunkapiller; Stephen B. H. Kent; Mark P. Marplott; Paul Oliver Ramstad