993 resultados para 982.65


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Vorbesitzer: du Roullet

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Vorbesitzer: Eljāqīm Carmoly; Abraham Merzbacher

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Vorbesitzer: Bartholomaeusstift Frankfurt am Main

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Downregulation of the unfolded protein response mediates proteasome inhibitor resistance in Multiple Myeloma.The Human Immunodeficieny Virus protease inhibitor nelfinavir activates the unfolded protein response in vitro. We determined dose limiting toxicity and recommended dose for phase II of nelfinavir in combination with the proteasome inhibitor bortezomib. 12 patients with advanced hematological malignancies were treated with nelfinavir (2500 - 5000 mg/d p.o., d 1-14, 3+3 dose escalation) and bortezomib (1.3 mg/m2, d 1, 4, 8, 11; 21 day cycles). A run in phase with nelfinavir monotherapy allowed pharmakokinetic/pharmakodynamic assessment of nelfinavir in the presence or absence of concomittant bortezomib. Endpoints included dose limiting toxicity, activation of the unfolded protein response, proteasome activity, toxicity and response to trial treatment. Nelfinavir 2 x 2500 mg was the recommended phase II dose identified. Nelfinavir alone significantly upregulated expression of proteins related to the unfolded protein response in peripheral blood mononuclear cells and inhibited proteasome activity. Of 10 evaluable patients in the dose escalation cohort, 3 achieved a partial response, 4 stable disease for ≥ 2 cycles, while 3 had progressive disease as best response. In an exploratory extension cohort with 6 relapsed, bortezomib-refractory, lenalidomide-resistant myeloma patients treated at the recommended phase II dose, 3 reached a partial response, 2 a minor response and one progressive disease. The combination of nelfinavir with bortezomib is safe and shows promising signals for activity in advanced, bortezomib-refractory MM. Induction of the unfolded protein response by nelfinavir may overcome the biological features of proteasome inhibitor resistance. (Trial registration NCT01164709).

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Samuel Klein

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Bertha Badt

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Vorbesitzer: Dominikanerkloster Frankfurt am Main;

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veröffentlicht in: Schopenhauer, Arthur : Arthur Schopenhauers sämtliche Werke - München : Piper - Bd. 15 : Der Briefwechsel Arthur Schopenhauers ; 2 (1849 - 1860), Nr. 425

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u.a. Frankfurter Zeitung; Politik; Bildnis Schopenhauer;

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Vorbesitzer: Limburg (?)

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Die Neufoliierung erfolgte anhand des vollständigen Exemplares, es fehlen die Blätter 8, 56 - 58 und 107 - 108. Die fehlenden Blätter 56 - 58 wurden handschriftlich ergänzt, diese Ergänzungen sind als Bl. II - XI foliiert und befinden sich zwischen Bl. 55 und 59. Nach Bl. 9 befindet sich ein als Bl. 9a foliiertes leeres Blatt.