4,342 research outputs found
Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia
No full textXiaoyan Wu,1 Lin Wang,1 Yining Qiu,1 Bingyu Zhang,1 Zhenhua Hu,2 Runming Jin1 1Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Pharmacy, Shanghai Jiao Tong University, Shanghai, China Abstract: T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. Keywords: T cell acute lymphoblastic leukemia, IRAK1/4 inhibitor, ABT-737, Box-Behnken design and response surface methodology, PEG-PLG
Hydrobiologische untersuchungen, [Abt.] II-III,
No full textCaption title.[Abt.] II. Die abhängigkeit der produktivität nordostdeutscher seen von ihrer sohlenform. [Abt.] III. Die häusigeren planktonwesen nordostdeutscher seen.Mode of access: Internet
bruder Chunrat der abt von Raitenhaſlach - 1289.
No full textAbt Konrad von Raitenhaßlach beurkundet, daß er den Streit zwischen seinen Brüdern Heinrich und Otto einerseits und Konrad von Pernungsheim, dem Ehemann seiner Schwestertochter, andrerseits wegen einer Hube zu Pößmoos, nach dem beide Parteien ihm die Schlichtung übertragen hatten, wie folgt, geschlichtet habe. Die Brüder Heinrich und Otto sollen unbestritten lastenfrei die eine Hälfte der Hube haben und der anderen Hälfte (Konrads von Pernungsheim und seiner Ehefrau Diemut der Schwestertochter Abt Konrads) rᷝbehalter [vgl. Spiegel deutscher Leute hg. J. Ficker (Innsbruck 1859) ¶ 55 S. 63 Schwabenspiegel hg. F. L. A. Freiherr von Laßberg (Tübingen 1840) ¶ 59 S. 29 = hg. W. Wackernagel (Zürich und Frauenfeld 1840) ¶ 52. S. 49, 6] sein bis zu »ihr beider⟨ Tod. Gewinnen Konrad von Pernungsheim und seine Ehefrau Kinder, die Lehen haben können [d. h. Söhne sind], so sollen diese die Hube mit ihnen [den Brüdern Heinrich und Otto] gemeinsam haben. Gewinnt Konrad von Pernungsheim aber nur Töchter, so sollen die Brüder Heinrich und Otto oder deren beider Kinder [d. h. Söhne] nach deren Tode rᷝbehalter der Töchter sein. Gewinnt der Pernungsheimer weder Söhne noch Töchter, so soll die halbe Hube ihm doch gehören bis zu seinem Tod. --{'name': 'BAdW', 'uri': 'badw.png'
ABT-888 restores sensitivity in temozolomide resistant glioma cells and xenografts
No full textBackgroundTemozolomide (TMZ) is active against glioblastomas (GBM) in which the O6-methylguanine-DNA methyltransferase (MGMT) gene is silenced. However, even in responsive cases, its beneficial effect is undermined by the emergence of drug resistance. Here, we tested whether inhibition of poly (ADP-ribose) polymerase-1 and -2 (PARP) enhanced the effectiveness of TMZ.MethodsUsing patient derived brain tumor initiating cells (BTICs) and orthotopic xenografts as models of newly diagnosed and recurrent high-grade glioma, we assessed the effects of TMZ, ABT-888, and the combination of TMZ and ABT-888 on the viability of BTICs and survival of tumor-bearing mice. We also studied DNA damage repair, checkpoint protein phosphorylation, and DNA replication in mismatch repair (MMR) deficient cells treated with TMZ and TMZ plus ABT-888.ResultsCells and xenografts derived from newly diagnosed MGMT methylated high-grade gliomas were sensitive to TMZ while those derived from unmethylated and recurrent gliomas were typically resistant. ABT-888 had no effect on the viability of BTICs or tumor bearing mice, but co-treatment with TMZ restored sensitivity in resistant cells and xenografts from newly diagnosed unmethylated gliomas and recurrent gliomas with MSH6 mutations. In contrast, the addition of ABT-888 to TMZ had little sensitizing effect on cells and xenografts derived from newly diagnosed methylated gliomas. In a model of acquired TMZ resistance mediated by loss of MMR gene MSH6, re-sensitization to TMZ by ABT-888 was accompanied by persistent DNA strand breaks, re-engagement of checkpoint kinase signaling, and interruption of DNA synthesis.ConclusionIn laboratory models, the addition of ABT-888 to TMZ overcame resistance to TMZ.</div
An adenosine kinase inhibitor, ABT-702, inhibits spinal nociceptive transmission by adenosine release via equilibrative nucleoside transporters in rat
No full textAdenosine kinase (AK) inhibitor is a potential candidate for controlling pain, but some AK inhibitors have problems of adverse effects such as motor impairment. ABT-702, a non-nucleoside AK inhibitor, shows analgesic effect in animal models of pain. Here, we investigated the effects of ABT-702 on synaptic transmission via nociceptive and motor reflex pathways in the isolated spinal cord of neonatal rats. The release of adenosine from the spinal cord was measured by HPLC. ABT-702 inhibited slow ventral root potentials (sVRPs) in the nociceptive pathway more potently than monosynaptic reflex potentials (MSRs) in the motor reflex pathway. The inhibitory effects of ABT-702 were mimicked by exogenously applied adenosine, blocked by 8CPT (8-cyclopentyl-1,3-dipropylxanthine), an adenosine A(1) receptor antagonist, and augmented by EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), an adenosine deaminase (ADA) inhibitor. Equilibrative nucleoside transporter (ENT) inhibitors reversed the effects of ABT-702, but not those of adenosine. ABT-702 released adenosine from the spinal cord, an effect that was also reversed by ENT inhibitors. The ABT-702-facilitated release of adenosine by way of ENTs inhibits nociceptive pathways more potently than motor reflex pathways in the spinal cord via activation of A1 receptors. This feature is expected to lead to good analgesic effects, but, caution may be required for the use of AK inhibitors in the case of ADA dysfunction or a combination with ENT inhibitors. (C) 2015 Elsevier Ltd. All rights reserved
Petrus von Leoben, Abt von St. Lambrecht
No full textHl. Lambert in ganzer
Figur stehend in einem gotischen Architekturbaldachin, im
bischöflichen Ornat mit Mitra und Stab in der Linken, die Rechte ist
segnend erhoben. Darunter in einer Nische verkleinert der Abt in
ganzer Figur im Ornat mit Mitra und Stab in der Rechten. Beiderseits
der Nische je ein Wappen, r. vermeintliches Papstwappen
(Exemptionsanspruch!), l. Stiftswappen (L), darunter Blumen
Data Supplement from Cell and Molecular Determinants of <i>In Vivo</i> Efficacy of the BH3 Mimetic ABT-263 against Pediatric Acute Lymphoblastic Leukemia Xenografts
No full textSupplementary Tables S5-S8. Complete summary of in vivo single-agent ABT-263 responses of individual mice; S7. In vivo efficacy of combining ABT-263 with vincristine (VCR), dexamethasone (DEX) or L-asparaginase (L-ASN) against pediatric ALL Xenografts; S8. Complete summary of in vivo responses of ABT-263 combined with vincristine (VCR), dexamethasone (DEX) or L-asparaginase (L-ASN) of individual mice</p
Ludw. Freih. v. Pastor, Gesehichte der Päpste seit dem Ausgang des Mittelalters. XIV Bd. : Gesehichte der Päpste im Zeitalter des furstlichen Absolutismus, von der Wahl Innozenz XX bis zum Tode Innozenz XII (1644-1700). 1e Abt. Innozenz X, Alexander VII, Klemens IX und X (1644-1676). 2e Abt. Innozenz XI, Alexander VIII, Innozenz XII (1676-1700)
No full textMarchal L. Ludw. Freih. v. Pastor, Gesehichte der Päpste seit dem Ausgang des Mittelalters. XIV Bd. : Gesehichte der Päpste im Zeitalter des furstlichen Absolutismus, von der Wahl Innozenz XX bis zum Tode Innozenz XII (1644-1700). 1e Abt. Innozenz X, Alexander VII, Klemens IX und X (1644-1676). 2e Abt. Innozenz XI, Alexander VIII, Innozenz XII (1676-1700). In: Revue des Sciences Religieuses, tome 11, fascicule 3, 1931. pp. 488-492
J. v. Uexküll: Im Kampfe um die Tierseele. Sep.-Abdr. aus Ergebnisse der Physiologie, II. Abt., hrsg. von L. Asher u. K. Spiro. Wiesbaden, Bergmann, 1902. 24 S.
No full textJ. V. UEXKÜLL: IM KAMPFE UM DIE TIERSEELE. SEP.-ABDR. AUS ERGEBNISSE DER PHYSIOLOGIE, II. ABT., HRSG. VON L. ASHER U. K. SPIRO. WIESBADEN, BERGMANN, 1902. 24 S.
Zeitschrift für Psychologie und Physiologie der Sinnesorgane (-)
Zeitschrift für Psychologie und Physiologie der Sinnesorgane (33) (a0001)
J. v. Uexküll: Im Kampfe um die Tierseele. Sep.-Abdr. aus Ergebnisse der Physiologie, II. Abt., hrsg. von L. Asher u. K. Spiro. Wiesbaden, Bergmann, 1902. 24 S. (33) (p0472
Ludw. Freih. v. Pastor, Gesehichte der Päpste seit dem Ausgang des Mittelalters. XIV Bd. : Gesehichte der Päpste im Zeitalter des furstlichen Absolutismus, von der Wahl Innozenz XX bis zum Tode Innozenz XII (1644-1700). 1e Abt. Innozenz X, Alexander VII, Klemens IX und X (1644-1676). 2e Abt. Innozenz XI, Alexander VIII, Innozenz XII (1676-1700)
No full textMarchal L. Ludw. Freih. v. Pastor, Gesehichte der Päpste seit dem Ausgang des Mittelalters. XIV Bd. : Gesehichte der Päpste im Zeitalter des furstlichen Absolutismus, von der Wahl Innozenz XX bis zum Tode Innozenz XII (1644-1700). 1e Abt. Innozenz X, Alexander VII, Klemens IX und X (1644-1676). 2e Abt. Innozenz XI, Alexander VIII, Innozenz XII (1676-1700). In: Revue des Sciences Religieuses, tome 11, fascicule 3, 1931. pp. 488-492
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