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Effective Induction (effective + induction)
Selected AbstractsAntisense oligodeoxynucleotide therapy targeting clusterin gene for prostate cancer: Vancouver experience from discovery to clinicINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2005HIDEAKI MIYAKE Abstract Background The objective of this study was to review our experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy for prostate cancer targeting antiapoptotic gene, clusterin. Methods We initially summarized our data demonstrating that clusterin could be an optimal therapeutic target for prostate cancer, then presented the process of developing AS ODN therapy using several preclinical animal models. Finally, the preliminary data of the recently completed phase I clinical trial using AS clusterin ODN as well as the future prospects of this therapy are discussed. Results Expression of clusterin was highly up-regulated after androgen withdrawal and during progression to androgen-independence, but low or absent in untreated tissues in both prostate cancer animal model systems and human clinical specimens. Introduction of the clusterin gene into human prostate cancer cells confers resistance to several therapeutic stimuli, including androgen ablation, chemotherapy and radiation. AS ODN targeting the translation initiation site of the clusterin gene markedly inhibited clusterin expression in prostate cancer cells in a dose-dependent and sequence-specific manner. Systemic treatment with AS clusterin ODN enhanced the effects of several conventional therapies through the effective induction of apoptosis in prostate cancer xenograft models. Based on these findings, a phase I clinical trial was completed using AS clusterin ODN incorporating 2,-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), showing up to 90% suppression of clusterin in prostate cancer. Conclusions The data described above identified clusterin as an antiapoptotic gene up-regulated in an adaptive cell survival manner following various cell death triggers that helps confer a phenotype resistant to therapeutic stimuli. Inhibition of clusterin expression using AS ODN technology enhances apoptosis induced by several conventional treatments, resulting in the delay of AI progression and improved survival. Clinical trials using AS ODN confirm potent suppression of clusterin expression and phase II studies will begin in early 2005. [source] More effective induction of spawning with long-acting GnRH agonist in the shi drum, Umbrina cirrosa L. (Sciaenidae, Teleostei), a valuable candidate for Mediterranean maricultureJOURNAL OF APPLIED ICHTHYOLOGY, Issue 3 2002A. Barbaro Three experiments of spawning induction in shi drum, Umbrina cirrosa L., were performed in six different commercial Italian hatcheries from May to August (water temperatures: 19,29 °C; salinity: 21,37 p.p.t.). In the first experiment, 119 females (1,4.7 kg), subdivided into 29 lots, were injected with a single dose (2, 5, 8, 10, 15 and 20 ,g kg,1 body weight) of short-acting gonadotropin- releasing hormone agonist (GnRHa-S), des-Gly10,[D-Ala6]-LH-RH ethylamide. In the other two experiments, 85 females (0.7,5.8 kg), subdivided into 22 and four lots, were treated with one (40 or 80 ,g kg,1) or three doses (40 ,g kg,1) of long-acting GnRHa (GnRHa-L), respectively. GnRHa-S stimulated spawning in 69% of the 29 treated lots; the number of eggs laid reached a maximum of 130 000 and a weighted mean of 29 200 total eggs kg,1. GnRHa-L elicited a spawning response in 95% of the 22 one-dose treated lots; the number of laid eggs was higher than with GnRHa-S, reaching a maximum of 213 100 and a weighted mean of 59 400 total eggs kg,1. The yield of developing embryos in 67% of the single GnRHa-L treatments was higher (sometimes up to three times) than with GnRHa-S. Triple treatments of the four lots of females with GnRHa-L always resulted in spawning responses; the best result corresponded to a number of total laid eggs of 358 900 eggs kg,1 with a yield of 177 300 developing embryos. [source] The use of propofol and remifentanil for the anaesthetic management of a super-obese patientANAESTHESIA, Issue 8 2007L. La Colla Summary Morbid obesity is defined as body mass index (BMI) >,35 kg.m,2, and super-obesity as BMI >,55 kg.m,2. We report the case of a 290-kg super-obese patient scheduled for open bariatric surgery. A propofol-remifentanil TCI (target controlled infusion) was chosen as the anaesthetic technique both for sedation during awake fibreoptic nasotracheal intubation and for maintenance of anaesthesia during surgery. Servin's weight correction formula was used for propofol. Arterial blood samples were taken at fixed time points to assess the predictive performance of the TCI system. A significant difference between measured and predicted plasma propofol concentrations was found. After performing a computer simulation, we found that predictive performance would have improved significantly if we had used an unadjusted pharmacokinetic set. However, in conclusion (despite the differences between measured and predicted plasma propofol concentrations), the use of a propofol-remifentanil TCI technique both for sedation during awake fibreoptic intubation and for Bispectral Index-guided propofol-remifentanil anaesthesia resulted in a rapid and effective induction, and operative stability and a rapid emergence, allowing rapid extubation in the operating room and an uneventful recovery. [source] Chiral interaction in peptide molecules: Effects of chiral peptide species on helix-sense induction in an N-terminal-free achiral peptideBIOPOLYMERS, Issue 5 2006Yoshihito Inai Abstract Noncovalent chiral domino effect (NCDE) has been proposed as terminal-specific interaction upon a 310 -helical peptide chain, of which the helix sense is manipulated by an external chiral stimulus (mainly amino acid derivatives) operating on the N-terminus (Inai, Y., et al. J Am Chem Soc 2000, 122, 11731,11732; ibid., 2002, 124, 2466,2473; ibid., 2003, 125, 8151,8162). We have investigated here a helix-sense induction in an optically inactive N-terminal-free nonapeptide (1) through the screening of several peptide species that differ in chiral sequence, chain length, and C-terminal group. Helix-sense induction in peptide 1 depends largely on both the C-terminal chirality and carboxyl group in the external peptide, in which N-carbonyl-blocked amino acids, "monopeptide acids," should be the minimum requirement for effective induction. N-Protected mono- to tetrapeptides of L -Leu residue commonly induce a right-handed helix. NMR study and theoretical computation reveal that the N-terminal segment of peptide 1 binds the N-protected dipeptide molecule through multipoint coordination to induce a right-handed helix preferentially. The present findings not only will improve our understanding of the chiral roles in peptide or protein helical termini, but also might demonstrate potential applications to chirality-responsive materials based on peptide helical fragments. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 471,481, 2006 This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] | ||||||||||