[Berliini] [Olympisches Dorf, den] 4/8 36

Kirje 4.8.1936

A multicenter phase II study (SAKK 36/06) of single-agent everolimus (RAD001) in patients with relapsed or refractory mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and is in most cases an incurable disease. It is characterized by the translocation t(11;14) leading to Cyclin D1 over-expression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) threonine kinase and can be effectively blocked by mTOR inhibitors. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus in a prospective, multicentre trial in patients with relapsed or refractory MCL (NCT00516412).Methods: Eligible patients with confirmed relapsed or refractory MCL received everolimus 10 mg for 28 days (one cycle) for a total of 6 cycles or until disease progression. The primary endpoint was the best objective response (OR) with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints.Results: A total of 36 patients with 35 evaluable patients at a median age of 69 years (range 40 to 85 years) from 19 centers were enrolled between August 2007 and January 2010. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade 3 or higher. The OR rate was 20% (95% CI: 8-37%) with 2 complete remissions (CR) and 5 partial response (PR), stable disease (SD) 48% and progression disease (PD) 28%. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Three patients achieved a lasting complete molecular response when assessed in the peripheral blood.Conclusion: This study demonstrates that single agent everolimus is well tolerated and has anti-lymphoma activity including lasting molecular responses. Further studies of everolimus either in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.

Helsinki 8/7 36

Kirje 8.7.1936

Pièces diverses concernant principalement l'histoire de TULLE.

Contient : Notice historique sur l'église de Tulle, sans indication d'auteur, avec listes de dignitaires, pièces, etc ; « Index beneficiorum spectantium ad collationem episcopi Tutellensis, » de la main de Baluze ; « Extrait du departement fait pour raison du restablissement du siege de Tulle » (id.) ; Factum pour Monseigneur l'évêque de Tulle, contre l'évêque de Cahors ; imprimé in-fol., s. d ; Arrest du Conseil pour Messieurs de l'Eglise cathédrale de Tulle (24 mai 1647) ; imprimé in-4° ; Extrait des registres du Conseil d'Etat, relatif au procès entre le chapitre de Tulle et Antoine Lesteyrie (8 mai 1666) ; imprimé in-4° ; Extrait des registres du Grand Conseil, relatif à la même affaire (8 mai 1666) : imprimé in-4° ; Notes sur diverses traditions relatives à saint Etienne d'Obazine ; Lettre de Leguy au Dr Baluze (Gimel, 11 juin [16]87) ; Vie de saint Domene, en français ; Autre exemplaire de la même vie ; « Vita sancti Dominii, ex veteri codice ms. » ; Extraits d'un missel manuscrit de Limoges, relatifs au même saint ; Lettre de M. de Lentilhac à Baluze (Gimel, 11 juin 1687) ; Notes relatives à saint Domene et à son culte, envoyées de Gimel à Baluze ; Lettre de Baluze à M. Gerard, chanoine de Sarlat (Tulle, 29 mars 1855) ; copie ; Diplôme de Pépin d'Aquitaine (1er février 836), tiré des archives de Moissac ; Lettre de M. Salvary à Baluze (Tulle, 11 mars 1651) ; Deux feuillets d'un ms. du XIIe s., contenant le début de la vie de saint Chaffre (Bibl. hag. lat., n° 8102) ; Lettre d'Humbert [Ancelin], évêque de Tulle, à Baluze (Tulle, 17 avril 1701) ; Lettre d'A. Levaillant à Baluze (Paris, 9 septembre 1702) ; Liste des évêques de Tulle jusqu'à Humbert Ancelin ; Inventaire de bulles concernant l'évêché de Tulle ; Accord entre Guillaume, seigneur de Gimel, et Pierre Foucher, seigneur de Saint-Pardoux (1310) ; « Enqueste de la noblesse de feu M. Christophle de l'Estang, evesque de Carcassonne » (1er mai 1617) ; Lettre non signée, adressée à Baluze (Tulle, 21 décembre 1684) ; Notes sur la famille de Lagarde ; « Sur les conquestes de Monseigneur le Dauphin, de Philisbourg » (Noël 1688) ; pièce de vers par M. Courreze, prêtre de Tulle ; Conversion à la foi catholique... de Monsieur de Meillars, par le R. P. Pierre Léan ; imprimé de 16 pages in-4°, Tulle, 1651 (Cf. Sommervogel, Bibl. de la Compagnie de Jésus, t. IV, col. 1620) ; La sainte Lunade de saint-Jean-Baptiste, par un prêtre de Tulle [A. Beril] ; imprimé de 36 pages in-4°, Tulle, 1680 ; Lettre d'A. Beril, curé de Saint-Salvadour [à Baluze] (26 septembre 1680) ; Catalogus abbatum et episcoporum Tutellensium, par Baluze ; placard imprimé, Tulle, 1654 (six exemplaires)

Comparative effects of GLP-1-(7-36) amide, oxyntomodulin and glucagon on rabbit gastric parietal cell function.

We have investigated in vitro, the effects of glucagon-like peptide-1-(7-36) amide (GLP-1-(7-36) amide), oxyntomodulin and glucagon on two rabbit parietal cell-enriched fractions (F3, F3n), with parietal cell contents of 60% and 88%, respectively. Histamine (10(-5) M) stimulated [14C]aminopyrine accumulation to an amount of 850% in excess of the basal level, whereas GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-6) M) induced increases of 50% and 30%, respectively. With a histamine concentration of 10(-6) M, [14C]aminopyrine accumulation was stimulated to 498% in excess of the basal level; GLP-1-(7-36) amide (10(-7) M) and oxyntomodulin (10(-7) M) induced increases of 18% and 15%, respectively. With these parameters, oxyntomodulin[19-37] and glucagon were without effect. Specific binding of [125I]GLP-1-(7-36) amide to parietal cell plasma membranes was inhibited dose-dependently by GLP-1-(7-36) amide, oxyntomodulin and glucagon with inhibitory concentrations of 0.25 nM, 65 nM and 800 nM, respectively. No specific binding of [125I]oxyntomodulin or [125I]glucagon was detectable. GLP-1-(7-36) amide receptor mRNA was only detected in parietal cell-enriched fractions. GLP-1-(7-36) amide, oxyntomodulin and glucagon stimulated parietal cell cAMP production to similar maximal levels with median values close to 0.28 nM, 10.5 nM and 331.7 nM, whereas oxyntomodulin[19-37] had no effect. The maximal cAMP production induced by GLP-1-(7-36) amide, oxyntomodulin or glucagon was additive to that induced by histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Footnotes, January-March 2011, Vol.36, no.1-3

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