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  • 1
    Publication Date: 2015-09-16
    Description: Purpose: Natural killer (NK) cells may play an important role in the immune response to multiple myeloma; however, multiple myeloma cells express killer immunoglobulin-like receptor (KIR) ligands to prevent NK cell cytotoxicity. Lenalidomide can expand and activate NK cells in parallel with its direct effects against multiple myeloma; however, dexamethasone may impair these favorable immunomodulatory properties. IPH2101, a first-in-class antiinhibitory KIR antibody, has acceptable safety and tolerability in multiple myeloma as a single agent. The present work sought to characterize lenalidomide and IPH2101 as a novel, steroid-sparing, dual immune therapy for multiple myeloma. Experimental Design: A phase I trial enrolled 15 patients in three cohorts. Lenalidomide was administered per os at 10 mg on cohort 1 and 25 mg on cohorts 2 and 3 days 1 to 21 on a 28-day cycle with IPH2101 given intravenously on day 1 of each cycle at 0.2 mg/kg in cohort 1, 1 mg/kg in cohort 2, and 2 mg/kg in cohort 3. No corticosteroids were utilized. The primary endpoint was safety, and secondary endpoints included clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD). Results: The biologic endpoint of full KIR occupancy was achieved across the IPH2101 dosing interval. PD and PK of IPH2101 with lenalidomide were similar to data from a prior single-agent IPH2101 trial. Five serious adverse events (SAE) were reported. Five objective responses occurred. No autoimmunity was seen. Conclusions: These findings suggest that lenalidomide in combination with antiinhibitory KIR therapy warrants further investigation in multiple myeloma as a steroid-sparing, dual immune therapy. This trial was registered at www.clinicaltrials.gov (reference: NCT01217203). Clin Cancer Res; 21(18); 4055–61. ©2015 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 2
    Publication Date: 2015-02-27
    Description: Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30 + NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.
    Keywords: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2013-07-26
    Description: Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease. Nonetheless, outcomes are suboptimal for patients failing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We performed a multi-center phase II trial investigating the safety and efficacy of ofatumumab, a monoclonal antibody against CD20, combined with ICE or DHAP second-line therapy in patients with relapsed or refractory DLBCL, grade 3b follicular lymphoma, or transformed follicular lymphoma. Sixty-one patients were treated with either ofatumumab-ICE (35) or ofatumumab-DHAP (26). The overall response rate (ORR) was 61%, and the complete response (CR) rate was 37%. In patients with 2 or 3 adverse risk factors according to the second-line, age-adjusted, international prognostic index, the ORR was 59% and CR 31%, and in patients with early-relapsing or primary refractory disease, the ORR was 55% and CR 30%. Toxicity was largely hematologic, and stem cell mobilization was successful in 43 of 45 patients. Substitution of ofatumumab for rituximab in standard second-line regimens following failure of R-CHOP is a promising approach. This trial was registered at www.clinicaltrials.gov as NCT00823719.
    Keywords: Free Research Articles, Lymphoid Neoplasia, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 259 (1976), S. 129-130 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Bone marrow cells in untreated acute myelogenous leukaemia (AML) show abnormal growth in vitro in the Robinson assay6. Characteristically, there is near total failure of colony formation; predominantly clusters are formed containing 20 cells or less7'8. Because such poor proliferation in vitro ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of wildlife research 26 (1980), S. 11-22 
    ISSN: 1439-0574
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Description / Table of Contents: Summary 1. Inquiries made in Lower Austria during two consecutive breeding periods and on two fixed days between (November, January) provided data about disperion pattern and breeding success of the Common Buzzard in different landscapes on a basis of average (1977) and high (1978) density of the Common Vole. 2. During all seasons the local population density is determined by the distribution of woods and open countryside and by the density of the Common Vole. In sparesly wooded areas woods can be densely populated by relatively many breeding-pairs, but their number is limited by the prevailing density of the Common Vole which has an influence on the extent of the Buzzard's individual cruising radius. In woodland habitats the presence of the Common Buzzard depends on the availability of suitably large open areas sufficiently rich in prey. During winter, the snow cover can cause the population to fluctuate, although the influence of the habitat on the local population density continues even during these periods. 3. The siting of eyries affects the difficulty of procuring prey. A poor supply of prey necessitates the eyrie being built near the edge of the woodland. 4. Eyries near the edge of the woodland and eyries in deciduous trees seem to be unfavourable for buzzards breeding early in the year. Microclimatic circumstances could play a role in this. 5. Breeding succes is determined by the efficiency of procuring food and the place of the eyrie with regard to the cruising radius. 6. The population of Common Buzzard which was studied is functioning successfully as regards self-regulation.
    Abstract: Resumé 1. Des enquêtes réalisées en Basse-Autriche au cours de deux périodes successives de couvaison et de deux journées intermédaires (novembre, janvier) ont permis de recueillir des données sur le mode de dispersion et sur les succès de l'élevage chez la Buse variable (Buteo buteo) dans différents sites et lors d'années avec densités moyennes de souris (1977) et fortes densités de souris (1978). 2. En toutes saisons les densités locales sont déterminées par la répartition „forêt-paysage ouvert“ et par l'abondance des souris. Dans des régions à faible taux de boisement la densité des couples nicheurs peut être relativement élevée, leur nombre étant cependant limité par le rayon d'action individuel, lequel est déterminé par l'abondance des souris. Dans les régions forestières, la densité de la Buse dépend de la présence de surfaces dégagées plus étendues et également plus riches en proies. Au cours de la mauvaise saison, l'enneigement peut déterminer des variations d'effectifs mais l'influence de la configuration du paysage sur les densités de population locales ne disparait pas pour autant. 3. La situation des aires de nidification est une question d'efficacité de la prédation. Une efficacité prédatrice moindre amène les oiseaux à installer leurs aires en bordure de la forêt. 4. Des aires installées en bordure de la forêt ou encore dans des feuillus constituent de toute évidence des situations défavorables pour la Buse, dont la période de nidification est précoce. A cet égard, des facteurs de micro-climat pouraient jouer un rôle. 5. Le succès de l'élevage des jeunes est déterminé par l'efficacité de l'approvisionnement alimentaire et par la situation de l'aire en relation avec le rayon d'action. 6. La population des buses étudiée ici se trouve dans une phase d'auto-régulation effective.
    Notes: Zusammenfassung 1. In Niederösterreich durchgeführte Erhebungen in zwei aufeinanderfolgenden Brutperioden und an zwei dazwischenliegenden Stichtagen (November, Januar) haben Unterlagen über Dispersionsmuster und Aufzuchterfolge beim Mäusebussard(Buteo buteo) in verschiedenen Landschaftssituationen bei durchschnittlichen (1977) und hohen (1978) Feldmausdichten erbracht. 2. Zu allen Jahreszeiten sind die lokalen Siedlungsdichten durch die Verteilung von Wald und offener Landschaft und durch das herrschende Feldmausangebot bestimmt. In waldarmen Gebieten können Waldflächen von relativ vielen Brutpaaren besiedelt werden, ihre Zahl ist aber durch die von der herrschenden Feldmausdichte beeinflußte Ausdehnung der individuellen Aktionsräume limitiert. In Waldlandschaften ist das Vorkommen von Mäusebussarden vom Vorhandensein entsprechend großer und ausreichend beutereicher offener Flächen abhängig. Im Winterhalbjahr kann Schneebedeckung Bestandsverschiebungen bedingen, der Einfluß der Landschaftssituation auf die lokalen Siedlungsdichten bleibt aber auch in diesen Perioden erhalten. 3. Die Lage der Horststandorte ist eine Frage der Effizienz der Beutebeschaffung. Geringe Fangeffizienzen erzwingen waldrandnahe Horststandorte. 4. Waldrandnahe Horststandorte und Horste in Laubbäumen sind für den jahreszeitlich früh brütenden Mäusebussard offensichtlich ungünstig. Mikroklimatische Faktoren können dabei eine Rolle spielen. 5. Der Aufzuchterfolg wird durch die Effizienz der Nahrungsbeschaffung und durch die Situation des Horststandortes in bezug zum Aktionsraum bestimmt. 6. Die untersuchte Population des Mäusebussards befindet sich im Stadium einer funktionierenden Selbstregulation.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Langenbeck's archives of surgery 323 (1968), S. 56-65 
    ISSN: 1435-2451
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Nach einigen Vorbemerkungen zur Entwicklungsgeschichte und zur Nomenklatur der Nabelschnurbrüche werden die operativen und konservativen Behandlungsmethoden aus der Literatur zitiert und besprochen. Aus den Jahren 1949 bis 1965 werden 380 beschriebene, teils operativ, teils konservativ behandelte Fälle zusammengestellt. Beschreibung eines Falles mit Operationsverfahren unter Verwendung eines lyophilisierten Duratransplantates.
    Notes: Summary After some preliminary remarks about the embryology and nomenclature of omphalocele, the surgical and conservative methods of treatment are reviewed and discussed. 380 partly surgical and partly conservative treated cases, published between 1949 and 1965 are compiled. One case operated by using a duramater-homograft is described.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Archives of gynecology and obstetrics 238 (1985), S. 661-662 
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Die Zugabe von Medroxyprogesteron-Acetat (MPA) hatte keinen signifikanten Einfluß auf menschliche Knochenmarkszellen, die in vitro mit Adriamycin oder Cisplatin behandelt wurden. Dies deutet darauf hin, daß der klinisch beobachtete myeloprotektive Effekt von MPA bei Patienten, welche MPA plus Zytostatika erhielten, nicht durch einen direkten Wirkungsmechanismus auf Knochenmarkszellen erklärt werden kann.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Cancer Genetics and Cytogenetics 28 (1987), S. 42 
    ISSN: 0165-4608
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1335
    Keywords: Drug sensitivity testing ; Bone marrow cells ; Human tumor colony-forming assay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We investigated the responsiveness of human normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) continuously exposed in vitro to 1 of 12 anticancer drugs. All drugs except bleomycin showed a simple negative exponential dosesurvival curve. The in vitro toxicity of drugs in GM-CFUC did not always correlate with the relative myelosuppressive potency observed in vivo. In addition, tumor specimens from 38 patients mainly with ovarian cancer were cultured in a human tumor colony-forming assay and continuously exposed to drugs at low, intermediate, and high concentrations capable of killing 40%, 78%, and 99% of GM-CFUC, respectively. The most active drugs were cis-platinum, velban, 5-fluorouracil, and 5-fluoro-ara-AMP. Dosesurvival curves of bone marrow progenitor cells may serve as an in vitro reference system for selecting appropriate drug concentrations of myelosuppressive drugs in drug-sensitivity assays of human tumors.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-7217
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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