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52. A Five-Year report on the conception and establishment of the MSc Radiation Biology at the Technical University of Munich

Author

Kessel, Carmen, primary, Atkinson, Michael J., additional, Schmid, Thomas E., additional, Trott, Klaus, additional, Wilkens, Jan J., additional, Anastasov, Natasa, additional, Rosemann, Michael, additional, Azimzadeh, Omid, additional, Tapio, Soile, additional, Moertl, Simone, additional, Kulka, Ulrike M., additional, Abend, Michael, additional, Port, Matthias, additional, Beinke, Christina, additional, Mustafa, Mona, additional, Neff, Frauke, additional, Pfeiffer, Daniela, additional, Berberat, Pascal, additional, and Combs, Stephanie E., additional

Published
2020
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53. Early detection of radiation-induced lung damage with X-ray dark-field radiography in mice

Author

Burkhardt, Rico, primary, Gora, Thomas, additional, Fingerle, Alexander A., additional, Sauter, Andreas P., additional, Meurer, Felix, additional, Umkehrer, Stephan, additional, von Teuffenbach, Maximilian, additional, Kampfer, Severin, additional, Schilling, Daniela, additional, Feuchtinger, Annette, additional, Walch, Axel K., additional, Rummeny, Ernst, additional, Combs, Stephanie E., additional, Schmid, Thomas E., additional, Pfeiffer, Franz, additional, Wilkens, Jan J., additional, and Herzen, Julia, additional

Published
2020
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55. Technical and dosimetric realization of in vivo x‐ray microbeam irradiations at the Munich Compact Light Source

Author

Burger, Karin, primary, Urban, Theresa, additional, Dombrowsky, Annique C., additional, Dierolf, Martin, additional, Günther, Benedikt, additional, Bartzsch, Stefan, additional, Achterhold, Klaus, additional, Combs, Stephanie E., additional, Schmid, Thomas E., additional, Wilkens, Jan J., additional, and Pfeiffer, Franz, additional

Published
2020
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59. Proton pencil minibeam irradiation of an in-vivo mouse ear model spares healthy tissue dependent on beam size

Author

Sammer, Matthias, primary, Zahnbrecher, Esther, additional, Dobiasch, Sophie, additional, Girst, Stefanie, additional, Greubel, Christoph, additional, Ilicic, Katarina, additional, Reindl, Judith, additional, Schwarz, Benjamin, additional, Siebenwirth, Christian, additional, Walsh, Dietrich W. M., additional, Combs, Stephanie E., additional, Dollinger, Günther, additional, and Schmid, Thomas E., additional

Published
2019
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60. Cytosolic Hsp70 as a biomarker to predict clinical outcome in patients with glioblastoma

Author

Lämmer, Friederike, Delbridge, Claire, Würstle, Silvia, Neff, Frauke, Meyer, Bernhard, Schlegel, Jürgen, Kessel, Kerstin A., Schmid, Thomas E., Schilling, Daniela, and Combs, Stephanie E.

Subjects
Clinical Research Design, Science, Cancer Treatment, Research and Analysis Methods, Methylation, Biochemistry, Heat Shock Response, Mathematical and Statistical Techniques, Diagnostic Medicine, Medicine and Health Sciences, Blastomas, Statistical Methods, Immunohistochemistry Techniques, Neurological Tumors, Cellular Stress Responses, Statistics, Chemical Reactions, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, Prognosis, Survival Analysis, Histochemistry and Cytochemistry Techniques, Chemistry, Oncology, Neurology, Cell Processes, Research Design, Physical Sciences, Immunologic Techniques, Medicine, Biomarkers, Mathematics, Glioblastoma Multiforme, Research Article
Abstract

IntroductionThe major stress-inducible heat shock protein 70 (Hsp70) is induced after different stress stimuli. In tumors, elevated intracellular Hsp70 levels were associated on the one hand with radio- and chemotherapy resistance and on the other hand with a favorable outcome for patients. This study was undertaken to investigate cytosolic Hsp70 (cHsp70) as a potential biomarker for progression free (PFS) and overall survival (OS) in patients with primary glioblastomas (GBM).MethodsThe cHsp70 expression in tumor tissue of 60 patients diagnosed with primary GBM was analyzed by immunohistochemistry. The cHsp70 expression was correlated to the PFS and OS of the patients.ResultsA high cHsp70 expression was associated with a prolonged PFS (hazard ratio = 0.374, p = 0.001) and OS (hazard ratio = 0.416, p = 0.014) in GBM patients treated according to the standard Stupp protocol with surgery, radiotherapy and temozolomide.ConclusionsThese data suggest that the intracellular Hsp70 expression might serve as a prognostic marker in patients with primary GBM.

Published
2019

62. Utilizing Heat Shock Protein 70 (Hsp70) as a Tumor-Specific Blood Biomarker and for the Isolation of Circulating Tumor Cells (CTCs)

Author

Schmid, Thomas E. (Priv.-Doz. Dr.), Multhoff, Gabriele (Prof. Dr.), Breuninger, Stephanie, Schmid, Thomas E. (Priv.-Doz. Dr.), Multhoff, Gabriele (Prof. Dr.), and Breuninger, Stephanie

Abstract

Membrane-bound heat shock protein 70 (Hsp70) is an important and promising tumor biomarker that can be found on the surface of tumor cells, as well as in the blood of cancer patients. In this project, the unique monoclonal antibody cmHsp70.1, which detects the membrane-bound form of Hsp70, was used to develop an ELISA to detect Hsp70 in plasma and serum samples, as well as bead- or wire-based methods to capture circulating tumor cells from patient blood., Das membrangebundene Hitzeschockprotein 70 (Hsp70) ist ein bedeutender und vielversprechender Tumor-Biomarker, der sowohl auf der Oberfläche von Tumorzellen, als auch im Blut von Krebspatienten vorkommt. In diesem Projekt wurde der einzigartige monoklonale Antikörper cmHsp70.1, welcher die membrangebundene Form von Hsp70 bindet, dazu verwendet, einen ELISA zur Detektion von Hsp70 in Plasma- und Serumproben, sowie Bead- bzw. Draht-basierte Methoden zur Isolierung von zirkulierenden Tumorzellen aus dem Blut von Krebspatienten zu entwickeln.

Published
2019

63. Utilizing Heat Shock Protein 70 (Hsp70) as a Tumor-Specific Blood Biomarker and for the Isolation of Circulating Tumor Cells (CTCs)

Author

Multhoff, Gabriele (Prof. Dr.), Multhoff, Gabriele (Prof. Dr.);Schmid, Thomas E. (Priv.-Doz. Dr.), Breuninger, Stephanie, Multhoff, Gabriele (Prof. Dr.), Multhoff, Gabriele (Prof. Dr.);Schmid, Thomas E. (Priv.-Doz. Dr.), and Breuninger, Stephanie

Abstract

Membrane-bound heat shock protein 70 (Hsp70) is an important and promising tumor biomarker that can be found on the surface of tumor cells, as well as in the blood of cancer patients. In this project, the unique monoclonal antibody cmHsp70.1, which detects the membrane-bound form of Hsp70, was used to develop an ELISA to detect Hsp70 in plasma and serum samples, as well as bead- or wire-based methods to capture circulating tumor cells from patient blood., Das membrangebundene Hitzeschockprotein 70 (Hsp70) ist ein bedeutender und vielversprechender Tumor-Biomarker, der sowohl auf der Oberfläche von Tumorzellen, als auch im Blut von Krebspatienten vorkommt. In diesem Projekt wurde der einzigartige monoklonale Antikörper cmHsp70.1, welcher die membrangebundene Form von Hsp70 bindet, dazu verwendet, einen ELISA zur Detektion von Hsp70 in Plasma- und Serumproben, sowie Bead- bzw. Draht-basierte Methoden zur Isolierung von zirkulierenden Tumorzellen aus dem Blut von Krebspatienten zu entwickeln.

Published
2019

64. In Vitro Versuchsreihe zum Einfluss von Selen als Radikalfänger bei Mammakarzinomzellen

Author

Schmid, Thomas E. (Priv.-Doz. Dr.), Schmid, Thomas E. (Priv.-Doz. Dr.);Combs, Stephanie E. (Prof. Dr.), Herold, Birgit, Schmid, Thomas E. (Priv.-Doz. Dr.), Schmid, Thomas E. (Priv.-Doz. Dr.);Combs, Stephanie E. (Prof. Dr.), and Herold, Birgit

Abstract

Das Ziel der Studie war es herauszufinden ob Selen als Radikalfänger Brustkrebszellen vor Bestrahlung schützt. Dazu wurden drei Brustkrebszelllinien verwendet: MCF7, T47D, MDA-MB231. Die Apoptoseinduktion, die DNS-Doppelstrangbruchinduktion und das klonogene Zellüberleben wurden in vitro unter drei verschiedenen Selenkonzentrationen mit und ohne Bestrahlung gemessen. Die ersten beiden Tests zeigten keinen signifikanten Einfluss von Selen. Im Koloniebildungstest führte Selenzugabe zu erhöhtem Zellüberleben nach Bestrahlung und damit zu einem protektiven Effekt., The aim of this study was to investigate if selenium as radical scavenger has protective effects after irradiation of breast cancer cells. Three cell lines were used. MCF7, T47D, MDA-MB231. The rate of apoptosis, frequency of DNA double- strand breaks and clonogenic cell survival were measured in-vitro using three different selenium concentrations, with and without radiation. In the first two tests the selenium concentration showed no significant influences. In the clonogenic cell survival test after supplementation with selen leaded to higher cell survival after irradiation which demonstrated a protective effect.

Published
2016

65. DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage

Author

Ilicic, Katarina, Greubel, Christoph, Girst, Stefanie, Reindl, Judith, Sammer, Matthias, Schwarz, Benjamin, Siebenwirth, Christian, Walsh, Dietrich W. M., Schmid, Thomas E., Scholz, Michael, and Dollinger, Günther

Abstract

Scientific reports 8(1), 16063 (2018). doi:10.1038/s41598-018-34323-9, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Published
2018
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66. A proof of principle experiment for microbeam radiation therapy at the Munich compact light source

Author

Dombrowsky, Annique C., primary, Burger, Karin, additional, Porth, Ann-Kristin, additional, Stein, Marlon, additional, Dierolf, Martin, additional, Günther, Benedikt, additional, Achterhold, Klaus, additional, Gleich, Bernhard, additional, Feuchtinger, Annette, additional, Bartzsch, Stefan, additional, Beyreuther, Elke, additional, Combs, Stephanie E., additional, Pfeiffer, Franz, additional, Wilkens, Jan J., additional, and Schmid, Thomas E., additional

Published
2019
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67. Beam size limit for pencil minibeam radiotherapy determined from side effects in an in-vivo mouse ear model

Author

Sammer, Matthias, primary, Teiluf, Katharina, additional, Girst, Stefanie, additional, Greubel, Christoph, additional, Reindl, Judith, additional, Ilicic, Katarina, additional, Walsh, Dietrich W. M., additional, Aichler, Michaela, additional, Walch, Axel, additional, Combs, Stephanie E., additional, Wilkens, Jan J., additional, Dollinger, Günther, additional, and Schmid, Thomas E., additional

Published
2019
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68. Acute Skin Damage and Late Radiation-Induced Fibrosis and Inflammation in Murine Ears after High-Dose Irradiation

Author

Dombrowsky, Annique C., primary, Schauer, Jannis, additional, Sammer, Matthias, additional, Blutke, Andreas, additional, Walsh, Dietrich W. M., additional, Schwarz, Benjamin, additional, Bartzsch, Stefan, additional, Feuchtinger, Annette, additional, Reindl, Judith, additional, Combs, Stephanie E., additional, Dollinger, Günther, additional, and Schmid, Thomas E., additional

Published
2019
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70. Local inhibition of rRNA transcription without nucleolar segregation after targeted ion irradiation of the nucleolus

Author

Siebenwirth, Christian, primary, Greubel, Christoph, additional, Drexler, Guido A., additional, Reindl, Judith, additional, Walsh, Dietrich W. M., additional, Schwarz, Benjamin, additional, Sammer, Matthias, additional, Baur, Iris, additional, Pospiech, Helmut, additional, Schmid, Thomas E., additional, Dollinger, Günther, additional, and Friedl, Anna A., additional

Published
2019
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71. Survival of tumor cells after proton irradiation with ultra-high dose rates

Author

Belka Claus, Schmid Thomas E, Drexler Guido A, Greubel Christoph, Hable Volker, Auer Susanne, Dollinger Günther, and Friedl Anna A

Subjects
laser acceleration, proton therapy, dose rate effects, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Laser acceleration of protons and heavy ions may in the future be used in radiation therapy. Laser-driven particle beams are pulsed and ultra high dose rates of >109 Gy s-1may be achieved. Here we compare the radiobiological effects of pulsed and continuous proton beams. Methods The ion microbeam SNAKE at the Munich tandem accelerator was used to directly compare a pulsed and a continuous 20 MeV proton beam, which delivered a dose of 3 Gy to a HeLa cell monolayer within < 1 ns or 100 ms, respectively. Investigated endpoints were G2 phase cell cycle arrest, apoptosis, and colony formation. Results At 10 h after pulsed irradiation, the fraction of G2 cells was significantly lower than after irradiation with the continuous beam, while all other endpoints including colony formation were not significantly different. We determined the relative biological effectiveness (RBE) for pulsed and continuous proton beams relative to x-irradiation as 0.91 ± 0.26 and 0.86 ± 0.33 (mean and SD), respectively. Conclusions At the dose rates investigated here, which are expected to correspond to those in radiation therapy using laser-driven particles, the RBE of the pulsed and the (conventional) continuous irradiation mode do not differ significantly.

Published
2011
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72. A Five-Year report on the conception and establishment of the MSc Radiation Biology at the Technical University of Munich.

Author

Kessel, Carmen, Atkinson, Michael J., Schmid, Thomas E., Trott, Klaus, Wilkens, Jan J., Anastasov, Natasa, Rosemann, Michael, Azimzadeh, Omid, Tapio, Soile, Moertl, Simone, Kulka, Ulrike M., Abend, Michael, Port, Matthias, Beinke, Christina, Mustafa, Mona, Neff, Frauke, Pfeiffer, Daniela, Berberat, Pascal, and Combs, Stephanie E.

Subjects
RADIOBIOLOGY, VOCATIONAL guidance, UNDERGRADUATE education, CONCEPTION, UNDERGRADUATE programs, MEDICAL school graduates
Abstract

The MSc Radiation Biology course is a highly interdisciplinary degree program placing radiation biology at the interface between biology, medicine, and physics, as well as their associated technologies. The goal was to establish an internationally acknowledged program with diverse and heterogeneous student cohorts, who benefit from each other academically as well as culturally. We have completed a Five-Year evaluation of the program to assess our qualification profile and the further direction we want to take. We evaluated the student cohort's data from the last 5 years regarding gender, age, and nationality as well as the highest degree before applying and career path after graduation. Data shows a great diversity regarding nationalty as well as undergraduate background. Cohort sizes could be increased and future prospects mainly aimed to a PhD. Measures after regular quality meetings and students' feedback led to improving the curriculum and workload, teacher's training, and changes to examination regulations. After 5 years, statistics show that our expectations have been met exceedingly. All graduates had excellent career opportunities reflecting the necessity of this MSc and its topics. We are continuously working on improving the program and adapting the curriculum to the requirements in radiation sciences. The future vision includes an expansion of the program as well as undergraduate education opportunities in this field. [ABSTRACT FROM AUTHOR]

Published
2021
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73. Immunologische Phänomene lokaler Strahlentherapie

Author

Schmid, Thomas E. (Priv.-Doz. Dr.), Geinitz, Hans (Prof. Dr.), Knolle, Percy A. (Prof. Dr.), Sage, Eva Katharina, Schmid, Thomas E. (Priv.-Doz. Dr.), Geinitz, Hans (Prof. Dr.), Knolle, Percy A. (Prof. Dr.), and Sage, Eva Katharina

Abstract

Brustkrebs bei Frauen bzw. Prostatakarzinom beim Mann sind die jeweils häufigsten Tumorentitäten weltweit. Die perkutane Strahlentherapie spielt in der Tumorbehandlung in definitiver Form, in adjuvanter Form nach der Operation und/oder Chemotherapie sowie in der Rezidiv-Therapie eine wichtige Rolle. Ich habe im peripheren Blut von insgesamt 40 Brustkrebspatientinnen und ca. 35 Prostatakrebspatienten die Veränderung der Gesamtlymphozyten und ihrer Subgruppen vor, während und nach lokaler Strahlentherapie untersucht und verglichen., Breast cancer in women and prostate cancer in men are the most common cancer entities worldwide. Local radiotherapy forms one of the most important columns in cancer treatment. In first line, in form of adjuvant therapy after surgery and/or chemotherapy, or even in the therapy of tumor relapse. In this work I analyzed lymphocytes and their subpopulations in peripheral blood of 40 breast cancer patients and ca. 35 prostate cancer patients before, during and after local radiotherapy.

Published
2018

74. Immunologische Phänomene lokaler Strahlentherapie

Author

Geinitz, Hans (Prof. Dr.), Geinitz, Hans (Prof. Dr.);Schmid, Thomas E. (Priv.-Doz. Dr.);Knolle, Percy A. (Prof. Dr.), Sage, Eva Katharina, Geinitz, Hans (Prof. Dr.), Geinitz, Hans (Prof. Dr.);Schmid, Thomas E. (Priv.-Doz. Dr.);Knolle, Percy A. (Prof. Dr.), and Sage, Eva Katharina

Abstract

Brustkrebs bei Frauen bzw. Prostatakarzinom beim Mann sind die jeweils häufigsten Tumorentitäten weltweit. Die perkutane Strahlentherapie spielt in der Tumorbehandlung in definitiver Form, in adjuvanter Form nach der Operation und/oder Chemotherapie sowie in der Rezidiv-Therapie eine wichtige Rolle. Ich habe im peripheren Blut von insgesamt 40 Brustkrebspatientinnen und ca. 35 Prostatakrebspatienten die Veränderung der Gesamtlymphozyten und ihrer Subgruppen vor, während und nach lokaler Strahlentherapie untersucht und verglichen., Breast cancer in women and prostate cancer in men are the most common cancer entities worldwide. Local radiotherapy forms one of the most important columns in cancer treatment. In first line, in form of adjuvant therapy after surgery and/or chemotherapy, or even in the therapy of tumor relapse. In this work I analyzed lymphocytes and their subpopulations in peripheral blood of 40 breast cancer patients and ca. 35 prostate cancer patients before, during and after local radiotherapy.

Published
2018

75. Combination of Photon and Carbon Ion Irradiation with Targeted Therapy Substances Temsirolimus and Gemcitabine in Hepatocellular Carcinoma Cell Lines

Author

Dehne, Sarah, Fritz, Clarissa, Rieken, Stefan, Baris, Daniela, Brons, Stephan, Haberer, Thomas, Debus, Jürgen, Weber, Klaus-Josef, Schmid, Thomas E., Combs, Stephanie E., and Habermehl, Daniel

Subjects
carbon ion irradiation, Temsirolimus, combined modality treatment, Oncology, hepatocellular carcinoma, Gemcitabine
Abstract

Background This work investigates on putative cytotoxic effects in four different hepatocellular carcinoma (HCC) cell lines after irradiation with photons or carbon ions in combination with new targeted molecular therapy using either Temsirolimus (TEM) or Gemcitabine (GEM). Methods and materials The HCC cell lines HepG2, Hep3B, HuH7, and PLC were cultured and irradiated with photons or carbon ions at the Heidelberg Ion Beam Therapy Center using the raster-scanning method. For combination experiments, cell lines were first treated with Temsirolimus or GEM before irradiation. Cytotoxicity was measured by a clonogenic survival assay. The evaluation of the experiments and the obtained survival curves were based on the concept of additivity defined by Steel and Peckham. Results The results for the combination of carbon ions and both tested systemic substances TEM and GEM showed independent toxicities in all four cell lines. Supra-additive effects were observed in PLC cells for photon irradiation combined either with TEM or GEM and in HuH7 cells for the combination of photons with TEM. Conclusion Addition of targeted therapy substances Temsirolimus and GEM to photon irradiation showed additive cytotoxicity in HCC cell lines, whereas independent toxicities where reached by the combination of carbon ions to these substances. It can be assumed that combining 12C with systemic substances only has independent effects because heavy ions cause direct damage because of their high-LET character resulting in complex and clustered double-strand breaks. Nonetheless, further investigations are warranted in order to determine whether addition of systemic therapy allows a reduction of radiation doses in combination therapy. This could possibly lead to better responses and tolerances in patients with HCC.

Published
2017
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79. DNA damage interactions on both nanometer and micrometer scale determine overall cellular damage

Author

Friedrich, Thomas, primary, Ilicic, Katarina, additional, Greubel, Christoph, additional, Girst, Stefanie, additional, Reindl, Judith, additional, Sammer, Matthias, additional, Schwarz, Benjamin, additional, Siebenwirth, Christian, additional, Walsh, Dietrich W. M., additional, Schmid, Thomas E., additional, Scholz, Michael, additional, and Dollinger, Günther, additional

Published
2018
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81. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Gro

Author

Stangl, Stefan, primary, Tontcheva, Nikoletta, additional, Sievert, Wolfgang, additional, Shevtsov, Maxim, additional, Niu, Minli, additional, Schmid, Thomas E., additional, Pigorsch, Steffi, additional, Combs, Stephanie E., additional, Haller, Bernhard, additional, Balermpas, Panagiotis, additional, Rödel, Franz, additional, Rödel, Claus, additional, Fokas, Emmanouil, additional, Krause, Mechthild, additional, Linge, Annett, additional, Lohaus, Fabian, additional, Baumann, Michael, additional, Tinhofer, Inge, additional, Budach, Volker, additional, Stuschke, Martin, additional, Grosu, Anca-Ligia, additional, Abdollahi, Amir, additional, Debus, Jürgen, additional, Belka, Claus, additional, Maihöfer, Cornelius, additional, Mönnich, David, additional, Zips, Daniel, additional, and Multhoff, Gabriele, additional

Published
2017
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82. Heat shock protein 70 and tumor‐infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy : a multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

Author

Stangl, Stefan, Tontcheva, Nikoletta, Sievert, Wolfgang, Shevtsov, Maxim, Niu, Minli, Schmid, Thomas E., Pigorsch, Steffi, Combs, Stephanie, Haller, Bernhard, Balermpas, Panagiotis, Rödel, Franz, Rödel, Claus, Fokas, Emmanouil, Krause, Mechthild, Linge, Annett, Lohaus, Fabian, Baumann, Michael, Tinhofer, Inge, Budach, Volker, Stuschke, Martin, Grosu, Anca-Ligia, Abdollahi, Amir, Debus, Jürgen, Belka, Claus, Maihöfer, Cornelius, Mönnich, David, Zips, Daniel, Multhoff, Gabriele, Stangl, Stefan, Tontcheva, Nikoletta, Sievert, Wolfgang, Shevtsov, Maxim, Niu, Minli, Schmid, Thomas E., Pigorsch, Steffi, Combs, Stephanie, Haller, Bernhard, Balermpas, Panagiotis, Rödel, Franz, Rödel, Claus, Fokas, Emmanouil, Krause, Mechthild, Linge, Annett, Lohaus, Fabian, Baumann, Michael, Tinhofer, Inge, Budach, Volker, Stuschke, Martin, Grosu, Anca-Ligia, Abdollahi, Amir, Debus, Jürgen, Belka, Claus, Maihöfer, Cornelius, Mönnich, David, Zips, Daniel, and Multhoff, Gabriele

Abstract

Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.

Published
2017

83. Increased cell survival and cytogenetic integrity by spatial dose redistribution at a compact synchrotron X-ray source

Author

Burger, Karin, primary, Ilicic, Katarina, additional, Dierolf, Martin, additional, Günther, Benedikt, additional, Walsh, Dietrich W. M., additional, Schmid, Ernst, additional, Eggl, Elena, additional, Achterhold, Klaus, additional, Gleich, Bernhard, additional, Combs, Stephanie E., additional, Molls, Michael, additional, Schmid, Thomas E., additional, Pfeiffer, Franz, additional, and Wilkens, Jan J., additional

Published
2017
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84. Master of Science (MSc) Program in Radiation Biology: An Interdepartmental Course Bridging the Gap between Radiation-Related Preclinical and Clinical Disciplines to Prepare Next-Generation Medical Scientists

Author

Combs, Stephanie E., primary, Kessel, Carmen, additional, Wilkens, Jan J., additional, Multhoff, Gabriele, additional, Schmid, Thomas E., additional, Vaupel, Peter, additional, Trott, Klaus-Rüdiger, additional, Berberat, Pascal, additional, and Atkinson, Michael J., additional

Published
2017
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86. Microbeam radiation therapy at a laser-based compact synchrotron x-ray source

Author

Burger, Karin, primary, Ilicic, Katarina, additional, Hunger, Annique, additional, Dierolf, Martin, additional, Gunther, Benedikt, additional, Schmid, Ernst, additional, Walsh, Dietrich W. M., additional, Urban, Theresa, additional, Bartzsch, Stefan, additional, Radtke, Amira, additional, Eggl, Elena, additional, Achterhold, Klaus, additional, Gleich, Bernhard, additional, Combs, Stephanie E., additional, Molls, Michael, additional, Schmid, Thomas E., additional, Pfeiffer, Franz, additional, and Wilkens, Jan J., additional

Published
2017
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87. Live cell imaging of mitochondria following targeted irradiation in situ reveals rapid and highly localized loss of membrane potential

Author

Walsh, Dietrich W. M., primary, Siebenwirth, Christian, additional, Greubel, Christoph, additional, Ilicic, Katarina, additional, Reindl, Judith, additional, Girst, Stefanie, additional, Muggiolu, Giovanna, additional, Simon, Marina, additional, Barberet, Philippe, additional, Seznec, Hervé, additional, Zischka, Hans, additional, Multhoff, Gabriele, additional, Schmid, Thomas E., additional, and Dollinger, Guenther, additional

Published
2017
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88. Session 23: Radiation therapy III – Particle therapy II

Author

Dollinger, Günther, primary, Greubel, Christoph, additional, Reindl, Judith, additional, Girst, Stephanie, additional, Schwarz, Benjamin, additional, Siebenwirth, Christian, additional, Walsh, Dieter, additional, Ilicic, Katarina, additional, Multhoff, Gabriele, additional, Wilkens, Jan, additional, and Schmid, Thomas E., additional

Published
2017
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89. Hsp70 - a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck

Author

Gehrmann, Mathias, Specht, Hanno M, Bayer, Christine, Brandstetter, Markus, Chizzali, Barbara, Duma, Marciana, Breuninger, Stephanie, Hube, Kathrin, Lehnerer, Sophie, van Phi, Valerie, Sage, Eva, Schmid, Thomas E, Sedelmayr, Michael, Schilling, Daniela, Sievert, Wolfgang, Stangl, Stefan, and Multhoff, Gabriele

Subjects
ddc
Published
2013

91. Imaging of Hsp70-positive tumors with cmHsp70.1 antibody-conjugated gold nanoparticles

Author

Gehrmann,Mathias K, Kimm,Melanie A, Stangl,Stefan, Schmid,Thomas E, Noël,Peter B, Rummeny,Ernst J, Multhoff,Gabriele, Gehrmann,Mathias K, Kimm,Melanie A, Stangl,Stefan, Schmid,Thomas E, Noël,Peter B, Rummeny,Ernst J, and Multhoff,Gabriele

Abstract

Mathias K Gehrmann,1 Melanie A Kimm,2 Stefan Stangl,1 Thomas E Schmid,1 Peter B Noël,2 Ernst J Rummeny,2 Gabriele Multhoff11Department of Radiation Oncology, 2Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyAbstract: Real-time imaging of small tumors is still one of the challenges in cancer diagnosis, prognosis, and monitoring of clinical outcome. Targeting novel biomarkers that are selectively expressed on a large variety of different tumors but not normal cells has the potential to improve the imaging capacity of existing methods such as computed tomography. Herein, we present a novel technique using cmHsp70.1 monoclonal antibody-conjugated spherical gold nanoparticles for quantification of the targeted uptake of gold nanoparticles into membrane Hsp70-positive tumor cells. Upon binding, cmHsp70.1-conjugated gold nanoparticles but not nanoparticles coupled to an isotype-matched IgG1 antibody or empty nanoparticles are rapidly taken up by highly malignant Hsp70 membrane-positive mouse tumor cells. After 24 hours, the cmHsp70.1-conjugated gold nanoparticles are found to be enriched in the perinuclear region. Specificity for membrane Hsp70 was shown by using an Hsp70 knockout tumor cell system. Toxic side effects of the cmHsp70.1-conjugated nanoparticles are not observed at a concentration of 1–10 µg/mL. Experiments are ongoing to evaluate whether cmHsp70.1 antibody-conjugated gold nanoparticles are suitable for the detection of membrane-Hsp70-positive tumors in vivo.Keywords: heat shock protein 70, tumor biomarker, theranostics, multimodal CT, multispectral CT, k-edge

Published
2015

92. Heat shock protein 70 and tumor‐infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

Author

Stangl, Stefan, Tontcheva, Nikoletta, Sievert, Wolfgang, Shevtsov, Maxim, Niu, Minli, Schmid, Thomas E., Pigorsch, Steffi, Combs, Stephanie E., Haller, Bernhard, Balermpas, Panagiotis, Rödel, Franz, Rödel, Claus, Fokas, Emmanouil, Krause, Mechthild, Linge, Annett, Lohaus, Fabian, Baumann, Michael, Tinhofer, Inge, Budach, Volker, and Stuschke, Martin

Abstract

Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers. [ABSTRACT FROM AUTHOR]

Published
2018
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93. Role of membrane Hsp70 in radiation sensitivity of tumor cells

Author

Murakami, Naoya, primary, Kühnel, Annett, additional, Schmid, Thomas E., additional, Ilicic, Katarina, additional, Stangl, Stefan, additional, Braun, Isabella S., additional, Gehrmann, Mathias, additional, Molls, Michael, additional, Itami, Jun, additional, and Multhoff, Gabriele, additional

Published
2015
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94. Auswirkungen von definitiver und Salvage-Strahlentherapie auf die Verteilung von Lymphozytensubpopulationen bei Prostatakarzinompatienten.

Author

Sage, Eva, Schmid, Thomas, Geinitz, Hans, Gehrmann, Mathias, Sedelmayr, Michael, Duma, Marciana, Combs, Stephanie, Multhoff, Gabriele, Sage, Eva K, Schmid, Thomas E, Duma, Marciana N, and Combs, Stephanie E

Subjects
CANCER relapse, CLINICAL trials, COMPARATIVE studies, DOSE-response relationship (Radiation), LYMPHOCYTES, RESEARCH methodology, MEDICAL cooperation, PROSTATE tumors, RADIATION doses, RESEARCH, RESEARCH evaluation, EVALUATION research, TREATMENT effectiveness, SALVAGE therapy, LYMPHOCYTE count, PREVENTION
Abstract

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2017
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95. Combination of Photon and Carbon lon Irradiation with Targeted Therapy Substance Temsirolimus and Gemctabine in Hepatocelluar Carcinoma Cell Lines.

Author

Dehne, Sarah, Fritz, Clarissa, Rieken, Stefan, Baris, Daniela, Brons, Stephan, Haberer, Thomas, Debus, Jürgen, Weber, Klaus-Josef, Schmid, Thomas E., Combs, Stephanie E., and Habermehl, Daniel

Subjects
LIVER cancer, IRRADIATION
Abstract

Background: This work investigates on putative cytotoxic effects in four different hepatocellular carcinoma (HCC) cell lines after irradiation with photons or carbon ions in combination with new targeted molecular therapy using either Temsirolimus (TEM) or Gemcitabine (GEM). Methods and materials: The HCC cell lines HepG2, Hep3B, HuH7, and PLC were cultured and irradiated with photons or carbon ions at the Heidelberg Ion Beam Therapy Center using the raster-scanning method. For combination experiments, cell lines were first treated with Temsirolimus or GEM before irradiation. Cytotoxicity was measured by a clonogenic survival assay. The evaluation of the experiments and the obtained survival curves were based on the concept of additivity defined by Steel and Peckham. Results: The results for the combination of carbon ions and both tested systemic substances TEM and GEM showed independent toxicities in all four cell lines. Supra-additive effects were observed in PLC cells for photon irradiation combined either with TEM or GEM and in HuH7 cells for the combination of photons with TEM. Conclusion: Addition of targeted therapy substances Temsirolimus and GEM to photon irradiation showed additive cytotoxicity in HCC cell lines, whereas independent toxicities where reached by the combination of carbon ions to these substances. It can be assumed that combining 12C with systemic substances only has independent effects because heavy ions cause direct damage because of their high-LET character resulting in complex and clustered double-strand breaks. Nonetheless, further investigations are warranted in order to determine whether addition of systemic therapy allows a reduction of radiation doses in combination therapy. This could possibly lead to better responses and tolerances in patients with HCC. [ABSTRACT FROM AUTHOR]

Published
2017
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96. Hsp70 - a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck

Author

Gehrmann, Mathias, primary, Specht, Hanno M, additional, Bayer, Christine, additional, Brandstetter, Markus, additional, Chizzali, Barbara, additional, Duma, Marciana, additional, Breuninger, Stephanie, additional, Hube, Kathrin, additional, Lehnerer, Sophie, additional, van Phi, Valerie, additional, Sage, Eva, additional, Schmid, Thomas E, additional, Sedelmayr, Michael, additional, Schilling, Daniela, additional, Sievert, Wolfgang, additional, Stangl, Stefan, additional, and Multhoff, Gabriele, additional

Published
2014
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98. Stress Response Leading to Resistance in Glioblastoma--The Need for Innovative Radiotherapy (iRT) Concepts.

Author

Combs, Stephanie E., Schmid, Thomas E., Vaupel, Peter, and Multhoff, Gabriele

Abstract

Glioblastoma (GBM) is the most common and most aggressive malignant primary brain tumor in adults. In spite of multimodal therapy concepts, consisting of surgery, radiotherapy and chemotherapy, the median survival, merely 15-18 months, is still poor. Mechanisms for resistance of GBM to radio(chemo)therapy are not fully understood yet and due to the genetic heterogeneity within the tumor including radiation-resistant tumor stem cells, there are several factors leading to therapy failure. Recent research revealed that, hypoxia during radiation and miRNAs may adversely affect the therapeutic response to radiotherapy. Further molecular alterations and prognostic markers like the DNA-repair protein O6-methylguanine-DNA methyltransferase (MGMT), anti-apoptotic molecular chaperones, and/or the activity of aldehyde dehydrogenase 1 (ALDH1) have also been identified to play a role in the sensitivity to cytostatic agents. Latest approaches in the field of radiotherapy to use particle irradiation or dose escalation strategies including modern molecular imaging, however, need further evaluation with regard to long-term outcome. In this review we focus on current information about the mechanisms and markers that mediate resistance to radio(chemo)therapy, and discuss the opportunities of Innovative Radiotherapy (iRT) concepts to improve treatment options for GBM patients. [ABSTRACT FROM AUTHOR]

Published
2016
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100. A laser-driven nanosecond proton source for radiobiological studies

Author

Bin, Jianhui, primary, Allinger, Klaus, additional, Assmann, Walter, additional, Dollinger, Günther, additional, Drexler, Guido A., additional, Friedl, Anna A., additional, Habs, Dieter, additional, Hilz, Peter, additional, Hoerlein, Rainer, additional, Humble, Nicole, additional, Karsch, Stefan, additional, Khrennikov, Konstantin, additional, Kiefer, Daniel, additional, Krausz, Ferenc, additional, Ma, Wenjun, additional, Michalski, Dörte, additional, Molls, Michael, additional, Raith, Sebastian, additional, Reinhardt, Sabine, additional, Röper, Barbara, additional, Schmid, Thomas E., additional, Tajima, Toshiki, additional, Wenz, Johannes, additional, Zlobinskaya, Olga, additional, Schreiber, Joerg, additional, and Wilkens, Jan J., additional

Published
2012
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