Reference

Reversal of multidrug resistance by tacrolimus hydrate

Reversal of multidrug resistance by tacrolimus hydrate. Wu, Jianghong; Furusawa, Shinobu; Nakano, Shinya; Takahashi, Miki; Chiba, Hiroaki; Takayanagi, Motoaki; Takayanagi, Yoshio; Sasaki, Ken-Ichi (Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy, Sendai, Japan). Methods and Findings in Experimental and Clinical Pharmacology, 18(10), 651-658 (English) 1996 Prous. CODEN: MFEPDX. ISSN: 0379-0355. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Tacrolimus hydrate, a potent immunosuppressant produced by Streptomyces tsukubaensis, was examd. for its effect on epirubicin activity in multidrug-resistant P388 leukemia (P388/R) cells overexpressing P-glycoprotein and the parent (P388/S) cells. In the absence of modulator, the 50% inhibitory concn. for epirubicin after 48-h incubation, detd. using a microculture tetrazolium assay, was 0.8mg/mL in P388/R cells and 0.009 mg/mL in P388/S cells. P388/R cells demonstrated a 90-fold redn. in sensitivity to epirubicin. Tacrolimus hydrate (1 and 10 mM) markedly enhanced epirubicin cytotoxicity by 4.2- and 26.7-fold for P388/R cells. A significant increase in LDH release from cells by tacrolimus hydrate was also obsd. in P388/R cells treated with epirubicin. Tacrolimus hydrate had a marked effect on epirubicin-induced G2/M blockade in the resistant cells. Both tacrolimus hydrate and cyclosporin A dramatically increased the accumulation of epirubicin by the resistant cells, while these compds.In this experiment, several chemicals are used like 109581-93-3 and 59865-13-3 had no effect on epirubicin accumulation in the parent cells. Thus, tacrolimus hydrate is able to down-modulate P-glycoprotein-assocd. resistance through inhibition of P-glycoprotein function, suggesting that the drug may be a candidate for killing drug-resistant tumor cells. .

Long-term therapeutic efficacy and safety of low-dose tacrolimus (FK506) for myasthenia gravis

All Rights Reserved. Long-term therapeutic efficacy and safety of low-dose tacrolimus (FK506) for myasthenia gravis. Tada, Masayoshi; Shimohata, Takayoshi; Tada, Mari; Oyake, Mutsuo; Igarashi, Shuichi; Onodera, Osamu; Naruse, Satoshi; Tanaka, Keiko; Tsuji, Shoji; Nishizawa, Masatoyo (Department of Neurology, Resource Branch for Brain Disease Research, Brain Research Institute, Niigata University 1-757 Asahi-machi-dori Niigata, Niigata 951-8585, Japan). Journal of the Neurological Sciences, 247(1), 17-20 (English) 2006 Elsevier B.V. CODEN: JNSCAG. ISSN: 0022-510X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 Objective: To elucidate the long-term therapeutic efficacy and safety of low-dose FK506 (tacrolimus) in patients with myasthenia gravis (MG). Patients and methods: We treated nine patients with MG (all women: age range: 35-83 years (mean: 51.1 years); MGFA classification: 4 type IIa, 4 type IIb, and 1 type IVb patients) with FK506 for more than 24 mo (observation period: 24-46 mo). All the patients had undergone extended thymectomy before FK506 treatment; two patients (22.2%) had noninvasive thymoma and six (66.7%) had thymic hyperplasia. We evaluated total Quant. MG (Q-MG) score, anti-acetylcholine receptor (AChR) antibody titer in the blood, interleukin 2 (IL-2) prodn. 109581-93-3 and 50-24-8 which are cas registry numbers are also used here. in peripheral blood mononuclear cells (PBMCs), administration dosage of prednisolone (PSL), and adverse effects of FK506. Results: A redn. in steroid dosage of 50% without worsening of the symptoms was obsd. 1 yr after FK506 administration in three out of six steroid-dependent MG patients (50.0%). The total Q-MG scores (range: 0-39 points) at 6 mo and 1 yr after FK506 administration improved by 3 points or more in six (66.7%) and seven (77.8%) out of nine patients, resp. The efficacy of FK506 was maintained for more than 2 years. Although adverse effects were obsd. in three patients (33.3%), these were not serious. Conclusions: Our study indicates that low-dose FK506 treatment may be efficacious not only in controlling intractable myasthenic symptoms, but also in reducing steroid dosage, and that FK506 is safe as an adjunctive drug to PSL for MG treatment for a max. of 3 years. .