TY  - JOUR
A1  - Sinn, Stefan
A1  - Eichler, Mirjam
A1  - Müller, Lothar
A1  - Bünger, Daniel
A1  - Groll, Jüergen
A1  - Ziemer, Gerhard
A1  - Rupp, Frank
A1  - Northoff, Hinnak
A1  - Geis-Gerstorfer, Jürgen
A1  - Gehring, Frank K.
A1  - Wendel, Hans P.
T1  - NCO-sP(EO-stat-PO) Coatings on Gold Sensors-a QCM Study of Hemocompatibility
JF  - Sensors
N2  - The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide-polypropylene oxide co-polymers NCO-sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM) sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP), followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM) was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules.
KW  - self-assembled monolayers
KW  - 316L stainless-steel
KW  - protein adsorption
KW  - poly(ethylene glycol)
KW  - platelet-adhesion
KW  - blood-plasma
KW  - surfaces
KW  - biosensor
KW  - cell self-assembled monolayers
KW  - cell coagulation
KW  - surface coating
KW  - biosensors
KW  - hemocompatibility
KW  - QCM
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141110
VL  - 11
IS  - 5
ER  - 
TY  - JOUR
A1  - Proetel, Ulrike
A1  - Pletsch, Nadine
A1  - Lauseker, Michael
A1  - Müller, Martin C.
A1  - Hanfstein, Benjamin
A1  - Krause, Stefan W.
A1  - Kalmanti, Lida
A1  - Schreiber, Annette
A1  - Heim, Dominik
A1  - Baerlocher, Gabriela M.
A1  - Hofmann, Wolf-Karsten
A1  - Lange, Elisabeth
A1  - Einsele, Hermann
A1  - Wernli, Martin
A1  - Kremers, Stephan
A1  - Schlag, Rudolf
A1  - Müller, Lothar
A1  - Hänel, Mathias
A1  - Link, Hartmut
A1  - Hertenstein, Bernd
A1  - Pfirrmann, Markus
A1  - Hochhaus, Andreas
A1  - Hasford, Joerg
A1  - Hehlmann, Rüdiger
A1  - Saußele, Susanne
T1  - Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV
JF  - Annals of Hematology
N2  - The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
KW  - chronic myeloid leukemia
KW  - older patients
KW  - different imatinib dose regimens
KW  - early applied higher imatinib dosages
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121574
SN  - 0939-5555
VL  - 93
IS  - 7
ER  - 
TY  - JOUR
A1  - Mc Laughlin, Anna M.
A1  - Schmulenson, Eduard
A1  - Teplytska, Olga
A1  - Zimmermann, Sebastian
A1  - Opitz, Patrick
A1  - Groenland, Stefanie L.
A1  - Huitema, Alwin D. R.
A1  - Steeghs, Neeltje
A1  - Müller, Lothar
A1  - Fuxius, Stefan
A1  - Illerhaus, Gerald
A1  - Joerger, Markus
A1  - Mayer, Frank
A1  - Fuhr, Uwe
A1  - Holdenrieder, Stefan
A1  - Hempel, Georg
A1  - Scherf-Clavel, Oliver
A1  - Jaehde, Ulrich
A1  - Kloft, Charlotte
T1  - Developing a nationwide infrastructure for therapeutic drug monitoring of targeted oral anticancer drugs: the ON-TARGET study protocol
JF  - Cancers
N2  - Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.
KW  - therapeutic drug monitoring
KW  - oral anticancer drugs
KW  - renal cell carcinoma
KW  - volumetric absorptive microsampling
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252196
SN  - 2072-6694
VL  - 13
IS  - 24
ER  -