Papers by Martin Hildebrandt
Monitoring of Tumor Cell Purging After Highly Efficient Immunomagnetic Selection of CD34 Cells From Leukapheresis Products in Breast Cancer Patients: Comparison of Immunocytochemical Tumor Cell Staining and Reverse Transcriptase–Polymerase Chain Reaction
Blood, 1997
We studied the efficiency of indirect tumor cell purging via enrichment of CD34+ hematopoietic pr... more We studied the efficiency of indirect tumor cell purging via enrichment of CD34+ hematopoietic progenitor cells from leukapheresis products (LP) in breast cancer patients based on immunomagnetic selection of CD34+ cells. Detection of tumor cells was made by immunocytochemical staining. In addition, we evaluated the capacity of cytokeratin 19 (CK19)- and a novel epidermal growth factor receptor (EGF-R)-specific reverse transcriptase-polymerase chain reaction (RT-PCR) for monitoring tumor cell depletion. LP from 13 breast cancer patients were analyzed. Twenty-three CD34 selection procedures were performed. A median of 1.4 x 10(10) total nucleated cells ([TNC] range, 0.88 to 3.5 x 10(10)) with a median CD34 purity of 2.5% (range, 0.4% to 6.3%) were entered into the selection procedure. Immunomagnetic CD34 enrichment resulted in a median purity of 83.3% (range, 45% to 95.4%) and a median recovery of 73.2% (range, 22% to 95%). Retransfusion of CD34-selected cells after high-dose chemotherapy resulted in a rapid and sustained hematologic recovery, reaching an absolute neutrophil count of 500/microL at day +10 and platelet count of 20,000/microL at day +11. Tumor cell depletion was quantified by immunocytochemical detection of CK19-positive cells. By this method, a median tumor cell depletion of 1.9 log (range, 0.7 to > 3 log) could be demonstrated. Immunocytochemical detection of tumor cells was more sensitive than RT-PCR, yielding positive results in 81% of LP (17 to 21) versus 58% positive LP (10 of 17). However, EGF-R-based RT-PCR was much more sensitive than CK19-based RT-PCR (10 of 17 v 1 of 17). Despite highly efficient CD34 selection, tumor cells were still detectable after CD34 enrichment using immunocytochemistry and EGF-R-specific RT-PCR. Thus, this novel EGF-R-specific RT-PCR appears to be of value as an additional method to detect contaminating breast cancer cells within LP.
Mapara, MY, Körner, IJ, Hildebrandt, M, Bargou, R, Krahl, D, Reichardt, P & Dörken, B. Monitoring of tumor cell purging after highly enriched efficient immunomagnetic selection of CD34 cells from leukapheresis products in breast cancer patients: Comparison of immunocytochemical tumor cell stainin...
Blood
ABSTRACT
Hildebrandt, M, Mapara, MY, Korner, IJ, Bargou, RC, Moldenhauer, G & Dorken, B. Reverse transcriptase-polymerase chain reaction (RT-PCR)-controlled immunomagnetic purging of breast cancer cells using the magnetic cell separation (MACS) system: a sensitive method for monitoring purging efficiency....
Experimental Hematology
ABSTRACT
The Dictyostelium discoideum EB4 gene product and a truncated mutant form of the protein are localized in prespore vesicles but absent from mature spores
Developmental Biology
Using polyclonal antibodies directed against two different parts of the predicted Dictyostelium p... more Using polyclonal antibodies directed against two different parts of the predicted Dictyostelium prespore protein EB4-PSV, we have investigated the regulation and localization of its 58-kDa gene product in wild-type cells and a 31-kDa truncated form in the gene disruption transformant A3. In both strains, the protein is synthesized during aggregation and is found in the membrane fraction of prespore vesicles (PSV). In contrast to other PSV proteins, the EB4 gene product is not found in mature spores.
Single-frequency photonic crystal fiber amplifier with 148 W output power - art. no. 64531J
Proceedings of SPIE - The International Society for Optical Engineering
A high-power, single-frequency, ytterbium doped photonic crystal fiber amplifier using a Nd:YAG n... more A high-power, single-frequency, ytterbium doped photonic crystal fiber amplifier using a Nd:YAG non-planar ring oscillator seed source is reported. The system delivers up to 148 W of output power and a slope efficiency of 76% with respect to the launched pump power. At maximum output power the amplified spontaneous emission was suppressed by more than 40 dB and a polarization extinction ratio of 28 dB was obtained. Single transverse-mode operation with M2 values better than 1.2 was measured by a standard method. To investigate the real overlap of the photonic crystal fiber transverse-mode with the Gaussian fundamental-mode, sensitive beam quality measurements with a Fabry-Perot ring-cavity premode cleaner will be presented.
best practice onkologie, 2010
Interessenkonflikte und Arzneimittelstudien – Einfluss der pharmazeutischen Industrie und daraus resultierende Gefahren für die Integrität der medizinischen Wissenschaft
Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen, 2009
ABSTRACT Numerous studies have addressed the subject of the extent and consequences of financial ... more ABSTRACT Numerous studies have addressed the subject of the extent and consequences of financial ties between pharmaceutical companies, academic institutions and clinical researchers. Based on these reports, guidelines for the management of conflicts of interest have been developed which give priority to the patients’ welfare on all levels of interaction between doctors and industrial sponsors. The declaration of potential conflicts of interest and strict adherence to guidelines are mandatory to retain the physicians’ credibility, reputation, and professional autonomy. Enhanced transparency in the conduct and analysis of clinical trials should be regarded as a valuable tool to uncover and avoid undue influence on clinical trials and derived prescription recommendations.
[Conflicts of interest and clinical drug trials -- impact of the pharmaceutical industry and the impingement on the integrity of medical science]
Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen, 2009
Numerous studies have addressed the subject of the extent and consequences of financial ties betw... more Numerous studies have addressed the subject of the extent and consequences of financial ties between pharmaceutical companies, academic institutions and clinical researchers. Based on these reports, guidelines for the management of conflicts of interest have been developed which give priority to the patients' welfare on all levels of interaction between doctors and industrial sponsors. The declaration of potential conflicts of interest and strict adherence to guidelines are mandatory to retain the physicians' credibility, reputation, and professional autonomy. Enhanced transparency in the conduct and analysis of clinical trials should be regarded as a valuable tool to uncover and avoid undue influence on clinical trials and derived prescription recommendations.
Mechanisms of gene regulation by endogenous and artificially introduced antisense RNA
Biochemical Society transactions, 1992
Developmental regulation of antisense-mediated gene silencing in Dictyostelium
Antisense research and development, 1994
In Dictyostelium, the expression of antisense transcripts has been successfully used to reduce or... more In Dictyostelium, the expression of antisense transcripts has been successfully used to reduce or eliminate gene expression. In most cases this occurs on the level of RNA stability resulting in a loss of both sense and antisense transcript accumulation. We here show that the antisense effect is regulated during the developmental cycle, i.e., in certain developmental stages and under certain developmental conditions, complementary RNAs appear not to interact with each other, resulting in a failure to abolish expression of the gene of interest. We find that this is not only the case with artificially introduced antisense constructs but also with the endogenous, antisense-regulated PSV-A gene. Our data demonstrate that antisense-mediated gene silencing is conferred by a biochemical machinery that is subject to regulation in vivo. The results provide a basis to better understand this machinery and to dissect the components. They may also explain the failure of some antisense experiments...
The Dictyostelium discoideum EB4 gene product and a truncated mutant form of the protein are localized in prespore vesicles but absent from mature spores
Using polyclonal antibodies directed against two different parts of the predicted Dictyostelium p... more Using polyclonal antibodies directed against two different parts of the predicted Dictyostelium prespore protein EB4-PSV, we have investigated the regulation and localization of its 58-kDa gene product in wild-type cells and a 31-kDa truncated form in the gene disruption transformant A3. In both strains, the protein is synthesized during aggregation and is found in the membrane fraction of prespore vesicles (PSV). In contrast to other PSV proteins, the EB4 gene product is not found in mature spores.
Regulation of advanced therapy medicinal products will affect the practice of haematopoietic SCT in the near future: a perspective from the EBMT cell-processing committee
Bone Marrow Transplantation, 2014
Nucleoside Diphosphate Kinase: an Old Enzyme with New Functions?
Advances in Experimental Medicine and Biology, 1994
Mode Selection in High-Power Single-Frequency Lasers
Frontiers in Optics 2007/Laser Science XXIII/Organic Materials and Devices for Displays and Energy Conversion, 2007
ABSTRACT We report on mode selection methods in high-power single-frequency laser systems for gra... more ABSTRACT We report on mode selection methods in high-power single-frequency laser systems for gravitational wave detection. That covers transversal selection in oscillators via resonator design as well as longitudinal by injection locking and different amplification schemes.
The puzzling situation of hospital exemption for advanced therapy medicinal products in Europe and stakeholders' concerns
Cytotherapy, 2014
Evolution of SBS gain spectra in high-power single-frequency ytterbium doped fiber amplifiers
… Science. CLEO/ …, 2008
We present theoretical modelling and experimental heterodyne measurements of spontaneous and stim... more We present theoretical modelling and experimental heterodyne measurements of spontaneous and stimulated Brillouin scattering gain spectra from a single-frequency ytterbium doped fiber amplifier system delivering 130 W of output power.
Detection and simulation of thermally induced deformation of Brillouin scattering spectra in a high-power PCF amplifier
… Conference. CLEO …, 2009
A growing demand for narrow-linewidth laser sources with high average output power for scientific... more A growing demand for narrow-linewidth laser sources with high average output power for scientific, industrial and military applications has pushed the development of ytterbium doped large mode-area (LMA) fiber amplifiers to more than 400 W of output ...
Combined Positive/Negative Selection in Stem Cell Transplantation: Perspectives in Graft Engineering
Transfusion Medicine and Hemotherapy, 1999
ABSTRACT
PBPC mobilization with paclitaxel, ifosfamide, and G-CSF with or without amifostine: results of a prospective randomized trial
Transfusion, 2001
The impact of amifostine on PBPC mobilization with paclitaxel and ifosfamide plus G-CSF was asses... more The impact of amifostine on PBPC mobilization with paclitaxel and ifosfamide plus G-CSF was assessed. Forty patients with a median age of 34 years (range, 19-53) who had germ cell tumor were evaluated for high-dose chemotherapy. Patients were randomly assigned to receive either a single 500-mg dose of amifostine (Group A, n = 20) or no amifostine (Group B, n = 20) before mobilization chemotherapy with paclitaxel (175 mg/m(2)) given over 3 hours and ifosfamide (5 g/m(2)) given over 24 hours (TI) on Day 1. G-CSF at 10 microg per kg per day was given subsequent to TI with or without amifostine from Day 3 until the end of leukapheresis procedures. In 2 (10%) of 20 patients receiving amifostine and 3 (15%) of 20 patients not receiving it, no PBPC separation was performed because of mobilization failure. No significant differences were observed in the study arms with regard to the time from chemotherapy until first PBPC collection or the number of apheresis procedures needed to harvest more than 2.5 x 10(6) CD34+ cells per kg. Furthermore, leukapheresis procedures yielded comparable doses of CD34+ cells per kg (3.4 x 10(6) vs. 3.6 x 10(6); p = 0.82), MNCs per kg (2.7 x 10(8) vs. 2.6 x 10(8); p = 0.18), and CFU-GM per kg (15.9 x 10(4) vs. 19.3 x 10(4); p = 0.20). Patients in Group A had higher numbers of circulating CD34+ cells on Day 10 (103.0/microL vs. 46.8/microL; p = 0.10) and on Day 11 (63.0/microL vs.14.3/microL; p = 0.04) than did patients in Group B. Administration of a single dose of amifostine before chemotherapy with TI mobilized higher numbers of CD34 cells in the circulation, but did not enhance the overall collection efficiency in the present trial.
A human NDP-kinase B specifically binds single-stranded poly-pyrimidine sequences
Nucleic Acids Research, 1995
Recently, a DNA binding protein 'PUF' was purified that binds to a poly-pyrimidin... more Recently, a DNA binding protein 'PUF' was purified that binds to a poly-pyrimidine rich element in the human c-myc promoter. Cloning of the corresponding gene surprisingly identified this putative transcription factor as isoform B of the enzyme nucleoside diphosphate kinase (NDPK-B) [Postel et al. (1993) Science, 261, 478-480], the product of the potential metastasis suppressor gene nm23-H2. Using different recombinant NDP kinases, we demonstrate by electrophoretic mobility shift analysis (EMSA) that the NDP kinase DNA binding properties are predominantly observed with human isoform B. Unlike typical DNA binding proteins that are involved in transcriptional regulation, binding occurs to single-stranded DNA rather than to a double-stranded oligonucleotide. As a consequence, complexes of single-stranded DNA and NDPK-B are generated from double-stranded oligonucleotide hybrids in an ATP independent manner. In addition to the c-myc element, NDPK-B is binding in vitro to a variety of poly-pyrimidine rich sequences including dC or dT homo-oligomers, (CT)n dinucleotide repeats, the initiator region of the Adenovirus major late promoter and even poly-pyrimidine rich RNAs. The possible consequences of these findings in understanding the multiple roles of NDP kinase are discussed.
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Papers by Martin Hildebrandt