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12 results on '"Petros Mouratidis"'

1. Histological characterization of HIFU lesions

Author

Ian Rivens, Chaturika Jayadewa, Petros Mouratidis, and Gail ter Haar

Subjects
High intensity focused ultrasound surgery, HIFU, FUS, liver histology, acoustic cavitation, thermal and boiling damage, Medical technology, R855-855.5
Abstract

Background: High intensity focused ultrasound (HIFU) can destroy tissue by thermal ablation which may be accompanied by acoustic cavitation and/or tissue water boiling, but the biological and histological effects of these treatments have not been fully documented. Here, detailed histological analysis over time using well characterized HIFU exposures in in vivo rat livers is described.Methods: Exposures used invoked either (i) thermal, with acoustic cavitation and/or tissue water boiling or (ii) predominantly thermal damage. Cavitation activity was detected using both active and passive methods. Histological assessment involved hematoxylin and eosin (H&E), picrosirius red and immunohistochemical staining.Results: Distinct concentric damage regions were identified after HIFU exposures. The outermost ring showed a red H&E-stained rim that was characterized by hemorrhage. The adjacent inner band appeared white due to increased extracellular spaces. The morphology of the next zone depended on the exposure. Where there was no tissue acoustic cavitation/water boiling, this was the lesion center, in which heat-fixed cells were seen. Where acoustic cavitation/boiling occurred, a centermost zone with irregular holes up to several hundred microns across was seen. Cleaved caspase-3 and Hsp70 staining in the periphery of both types of HIFU exposures was seen within the outermost ring of hemorrhage, where an inflammatory response was also observed. By day 7, a distinct acellular region in the center of the HIFU lesions had been created.Conclusions: These results identify the morphological effects and elucidate the similarities and differences of HIFU-induced thermal lesions in the presence or absence of acoustic cavitation/tissue water boiling.

Published
2024
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2. Complementary techniques for the reliable characterisation of tissue samples: A case study on pancreatic tumours analysed by means of X-ray fluorescence analysis and IR spectroscopy.

Author

Katja Frenzel, Yves Kayser, Andrea Hornemann, Bernd Kästner, Arne Hoehl, Petros Mouratidis, Ian Rivens, Gail Ter Haar, and Burkhard Beckhoff

Subjects
Medicine, Science
Abstract

An improvement in the reliability and comparability of tissue characterization results is crucial for enabling further progress in cancer detection and the assessment of therapeutic effects. This can only be achieved by integrating quantitative methods into well-established qualitative characterization routines. This case study presents a hybrid metrological approach for tissue characterisation including vibrational Fourier Transform InfraRed (FTIR) spectroscopy and traceable reference-free X-Ray Fluorescence analysis (XRF). Through the combination of spatially resolved qualitative molecular information with quantitative elemental concentrations an all-encompassing sample characterisation can be provided. The study was performed on tissue sections of syngeneic murine pancreatic ductal adenocarcinoma KPC (KrasG12D/+; Trp53R172H/+; Pdx-1-Cre) tumours ex-vivo. Sections from healthy pancreatic tissues, sham-exposed tumours and tumours subjected to low dose radiotherapy treatment (2 Gray and 6 Gray) were analysed using both methods. Additional sample integrity studies using Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy at the carbon and nitrogen K-edges were performed to assess the effect of sample aging and XRF investigations on the samples. Results showed an increase in the concentrations of elemental biomarkers, including S, K and amide I structures in malignant pancreatic tissue compared to healthy pancreatic tissue. The exposure of tumours to 6 Gy radiation decreases the levels of these elements towards a phenotype seen in the healthy pancreas. A protocol for hybrid investigations is presented, with emphasis on the sample preparation, minimizing the impact of consecutive applied methods on their measurands, and ensuring the compatibility and reliability of achieved results. The study demonstrates the cancer recognition capabilities, and the sensitivity for low dosage radiotherapy treatment monitoring for each method individually and assesses the potential of combining molecular fingerprinting with non-destructive quantitative elemental information for tissue sample characterization.

Published
2024
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3. HSP90 inhibition acts synergistically with heat to induce a pro-immunogenic form of cell death in colon cancer cells

Author

Gail ter Haar and Petros Mouratidis

Subjects
Hyperthermia, Cancer Research, Programmed cell death, Physiology, Colorectal cancer, Cell, Thermal ablation, thermal dose, Apoptosis, thermal ablation, Cell Line, Tumor, Physiology (medical), Heat shock protein, Medical technology, medicine, Humans, HSP90 Heat-Shock Proteins, R855-855.5, nvp-auy922, biology, Chemistry, hsp90 inhibition, biochemical phenomena, metabolism, and nutrition, HCT116 Cells, hyperthermia, medicine.disease, Hsp90, digestive system diseases, medicine.anatomical_structure, Colonic Neoplasms, heat shock proteins, Cancer cell, biology.protein, Cancer research
Abstract

Background Sub-ablative heat induces pleiotropic biological effects in cancer cells, activating programmed cell death or survival processes. These processes decide the fate of the heated cell. This study investigates these and assesses whether heat, in combination with HSP90 inhibition, augments cell death and induces a pro-immune phenotype in these cells. Methods HCT116 and HT29 cells were subjected to thermal doses (TID) of 60 and 120CEM43 using a PCR thermal cycler. HSP90 was inhibited with NVP-AUY922. Viability was assessed using the MTT assay. Cellular ATP and HSP70 release were assessed using ATP and Enzyme-linked Immunosorbent assays, respectively. Flow cytometry and immunoblotting were used to study the regulation of biomarkers associated with the heat shock response, the cell cycle, and immunogenic and programmed cell death. Results Exposure of HCT116 and HT29 cells to TIDs of 60 and 120CEM43 decreased their viability. In addition, treatment with 120CEM43 increased intracellular HSP70 and the percentage of HCT116/HT29 cells in the G2/M cell cycle phase, ATP release and Calreticulin/HSP70/HSP90 exposure in the plasma membrane, while downregulating CD47 compared to sham-exposed cells. When combined with NVP-AUY922, treatment of HCT116/HT29 cells with 120CEM43 resulted in a synergistic decrease of cell viability associated with the induction of apoptosis. Also, the combined treatments increased Calreticulin exposure, CD47 downregulation, and HSP70 release compared to the sham-exposed cells. Conclusion Sub-ablative heating can act synergistically with the clinically relevant HSP90 inhibitor NVP-AUY922 to induce a pro-immunogenic form of cell death in colon cancer cells.

Published
2021
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4. Holographic Focused Ultrasound Hyperthermia System for Uniform Simultaneous Thermal Exposure of Multiple Tumor Spheroids

Author

Diana Andrés, Ian Rivens, Petros Mouratidis, Noé Jiménez, Francisco Camarena, and Gail ter Haar

Subjects
Cancer Research, Oncology, acoustic holograms, acoustic lenses, ultrasound hyperthermia, tumor spheroids, thermal dose
Abstract

Hyperthermia is currently used to treat cancer due to its ability to radio- and chemo-sensitize and to stimulate the immune response. While ultrasound is non-ionizing and can induce hyperthermia deep within the body non-invasively, achieving uniform and volumetric hyperthermia is challenging. This work presents a novel focused ultrasound hyperthermia system based on 3D-printed acoustic holograms combined with a high-intensity focused ultrasound (HIFU) transducer to produce a uniform iso-thermal dose in multiple targets. The system is designed with the aim of treating several 3D cell aggregates contained in an International Electrotechnical Commission (IEC) tissue-mimicking phantom with multiple wells, each holding a single tumor spheroid, with real-time temperature and thermal dose monitoring. System performance was validated using acoustic and thermal methods, ultimately yielding thermal doses in three wells that differed by less than 4%. The system was tested in vitro for delivery of thermal doses of 0–120 cumulative equivalent minutes at 43 °C (CEM43) to spheroids of U87-MG glioma cells. The effects of ultrasound-induced heating on the growth of these spheroids were compared with heating using a polymerase chain reaction (PCR) thermocycler. Results showed that exposing U87-MG spheroids to an ultrasound-induced thermal dose of 120 CEM43 shrank them by 15% and decreased their growth and metabolic activity more than seen in those exposed to a thermocycler-induced heating. This low-cost approach of modifying a HIFU transducer to deliver ultrasound hyperthermia opens new avenues for accurately controlling thermal dose delivery to complex therapeutic targets using tailored acoustic holograms. Spheroid data show that thermal and non-thermal mechanisms are implicated in the response of cancer cells to non-ablative ultrasound heating.

Published
2023
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5. Pulsed focused ultrasound can improve the anti-cancer effects of immune checkpoint inhibitors in murine pancreatic cancer

Author

Elizabeth E Repasky, Gail ter Haar, Marcia Costa, Petros Mouratidis, and I. Rivens

Subjects
0301 basic medicine, medicine.medical_treatment, pancreatic cancer, Biomedical Engineering, Biophysics, Bioengineering, CD8-Positive T-Lymphocytes, Biochemistry, immune checkpoint inhibitors, Biomaterials, Mice, 03 medical and health sciences, 0302 clinical medicine, Immune system, Pancreatic cancer, medicine, Animals, Humans, Pancreas, Research Articles, business.industry, Ultrasound, Cancer, FOXP3, Life Sciences–Physics interface, Immunotherapy, pulsed high-intensity focused ultrasound, medicine.disease, Pancreatic Neoplasms, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research, focused ultrasound, High-Intensity Focused Ultrasound Ablation, immunotherapy, business, CD8, Biotechnology
Abstract

Pulsed high-intensity focused ultrasound (pHIFU) uses acoustic pressure to physically disrupt tumours. The aim of this study was to investigate whether pHIFU can be used in combination with immune checkpoint inhibitors (ICIs) to enhance survival of tumour-bearing animals. Murine orthotopic pancreatic KPC tumours were exposed both to a grid of pHIFU lesions (peak negative pressure = 17 MPa, frequency = 1.5 MHz, duty cycle = 1%, 1 pulse s−1, duration = 25 s) and to anti-CTLA-4/anti-PD-1 antibodies. Acoustic cavitation was detected using a weakly focused passive sensor. Tumour dimensions were measured with B-mode ultrasound before treatment and with callipers post-mortem. Immune cell subtypes were quantified with immunohistochemistry and flow cytometry. pHIFU treatment of pancreatic tumours resulted in detectable acoustic cavitation and increased infiltration of CD8+T cells in the tumours of pHIFU and pHIFU + ICI-treated subjects compared with sham-exposed subjects. Survival of subjects treated with pHIFU + ICI was extended relative to both control untreated subjects and those treated with either pHIFU or ICI alone. Subjects treated with pHIFU + ICI had increased levels of CD8+IFNγ+T cells, increased ratios of CD8+IFNγ+to CD3+CD4+FoxP3+and CD11b+Ly6G+cells, and decreased CD11chighcells in their tumours compared with controls. These results provide evidence that pHIFU combined with ICI may have potential for use in pancreatic cancer therapy.

Published
2021
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6. 'Relationship between thermal dose and cell death for 'rapid' ablative and 'slow' hyperthermic heating'

Author

I. Rivens, Gail ter Haar, Richard Symonds-Tayler, Petros Mouratidis, and John Civale

Subjects
Hyperthermia, Cancer Research, Programmed cell death, lcsh:Medical technology, Physiology, Thermal ablation, thermal dose, 030218 nuclear medicine & medical imaging, Heating, 03 medical and health sciences, symbols.namesake, thermal ablation, 0302 clinical medicine, Physiology (medical), Ablative case, medicine, Dosimetry, Humans, Viability assay, Arrhenius equation, Cell Death, Chemistry, business.industry, arrhenius, Hyperthermia, Induced, medicine.disease, hyperthermia, lcsh:R855-855.5, 030220 oncology & carcinogenesis, symbols, heat, Thermal dose, Nuclear medicine, business
Abstract

Aim: Thermal isoeffective dose (TID) has not been convincingly validated for application to predict biological effects from rapid thermal ablation (e.g., using >55 °C). This study compares the classical method of quantifying TID (derived from hyperthermia data) with a temperature-adjusted method based on the Arrhenius model for predicting cell survival in vitro, after either ‘rapid’ ablative or ‘slow’ hyperthermic exposures. Methods: MTT assay viability data was obtained from two human colon cancer cell lines, (HCT116, HT29), subjected to a range of TIDs (120–720 CEM43) using a thermal cycler for hyperthermic (>2 minutes, 55 °C). TID was initially estimated using a constant RCEM>43°C=0.5, and subsequently using RCEM(T), derived from temperature dependent cell survival (injury rate) Arrhenius analysis. Results: ‘Slow’ and ‘rapid’ exposures resulted in cell survival and significant regrowth (both cell lines) 10 days post-treatment for 240 CEM43 (RCEM>43°C=0.5), while 340-550 CEM43 (RCEM>43°C =0.5) delivered using ‘rapid’ exposures showed 12 ± 6% viability and ‘slow’ exposures resulted in undetectable viability. Arrhenius analysis of experimental data (activation energy ΔE = 5.78 ± 0.04 × 105 J mole−1, frequency factor A = 3.27 ± 11 × 1091 sec−1) yielded RCEM=0.42 * e0.0041*T which better-predicted cell survival than using R CEM> 43°C=0.5. Conclusions: TID calculated using an RCEM(T) informed by Arrhenius kinetic parameters provided a more consistent, heating strategy independent, predictor of cell viability, improving dosimetry of ablative thermal exposures. Cell viability was only undetectable above 305 ± 10 CEM43 using this revised measure.

Published
2019

7. International Society for Therapeutic Ultrasound Conference 2016

Author

Brian Fowlkes, Pejman Ghanouni, Narendra Sanghvi, Constantin Coussios, Paul C. Lyon, Michael Gray, Christophoros Mannaris, Marie de Saint Victor, Eleanor Stride, Robin Cleveland, Robert Carlisle, Feng Wu, Mark Middleton, Fergus Gleeson, Jean-Franҫois Aubry, Kim Butts Pauly, Chrit Moonen, Jacob Vortman, Shirley Sharabi, Dianne Daniels, David Last, David Guez, Yoav Levy, Alexander Volovick, Javier Grinfeld, Itay Rachmilevich, Talia Amar, Zion Zibly, Yael Mardor, Sagi Harnof, Michael Plaksin, Yoni Weissler, Shy Shoham, Eitan Kimmel, Omer Naor, Nairouz Farah, Dong-Guk Paeng, Zhiyuan Xu, John Snell, Anders H. Quigg, Matthew Eames, Changzhu Jin, Ashli C. Everstine, Jason P. Sheehan, Beatriz S. Lopes, Neal Kassell, Thomas Looi, Vera Khokhlova, Charles Mougenot, Kullervo Hynynen, James Drake, Michael Slayton, Richard C. Amodei, Keegan Compton, Ashley McNelly, Daniel Latt, John Kearney, David Melodelima, Aurelien Dupre, Yao Chen, David Perol, Jeremy Vincenot, Jean-Yves Chapelon, Michel Rivoire, Wei Guo, Guoxin Ren, Guofeng Shen, Michael Neidrauer, Leonid Zubkov, Michael S. Weingarten, David J. Margolis, Peter A. Lewin, Nathan McDannold, Jonathan Sutton, Natalia Vykhodtseva, Margaret Livingstone, Thiele Kobus, Yong-Zhi Zhang, Michael Schwartz, Yuexi Huang, Nir Lipsman, Jennifer Jain, Martin Chapman, Tejas Sankar, Andres Lozano, Robert Yeung, Christakis Damianou, Nikolaos Papadopoulos, Omer Brokman, Eyal Zadicario, Ori Brenner, David Castel, Shih-Ying Wu, Julien Grondin, Wenlan Zheng, Marc Heidmann, Maria Eleni Karakatsani, Carlos J. Sierra Sánchez, Vincent Ferrera, Elisa E. Konofagou, Marinos Yiannakou, HongSeok Cho, Hwayoun Lee, Mun Han, Jong-Ryul Choi, Taekwan Lee, Sanghyun Ahn, Yongmin Chang, Juyoung Park, Nicholas Ellens, Ari Partanen, Keyvan Farahani, Raag Airan, Alexandre Carpentier, Michael Canney, Alexandre Vignot, Cyril Lafon, Jean-yves Delattre, Ahmed Idbaih, Henrik Odéen, Bradley Bolster, Eun Kee Jeong, Dennis L. Parker, Pooja Gaur, Xue Feng, Samuel Fielden, Craig Meyer, Beat Werner, William Grissom, Michael Marx, Hans Weber, Valentina Taviani, Brian Hargreaves, Jun Tanaka, Kentaro Kikuchi, Ayumu Ishijima, Takashi Azuma, Kosuke Minamihata, Satoshi Yamaguchi, Teruyuki Nagamune, Ichiro Sakuma, Shu Takagi, Mathieu D. Santin, Laurent Marsac, Guillaume Maimbourg, Morgane Monfort, Benoit Larrat, Chantal François, Stéphane Lehéricy, Mickael Tanter, Gesthimani Samiotaki, Shutao Wang, Camilo Acosta, Eliza R. Feinberg, Zsofia I. Kovacs, Tsang-Wei Tu, Georgios Z. Papadakis, William C. Reid, Dima A. Hammoud, Joseph A. Frank, Zsofia i. Kovacs, Saejeong Kim, Neekita Jikaria, Michele Bresler, Farhan Qureshi, Jingjing Xia, Po-Shiang Tsui, Hao-Li Liu, Juan C. Plata, Bragi Sveinsson, Vasant A. Salgaonkar, Matthew Adams, Chris Diederich, Eugene Ozhinsky, Matthew D. Bucknor, Viola Rieke, Andrew Mikhail, Lauren Severance, Ayele H. Negussie, Bradford Wood, Martijn de Greef, Gerald Schubert, Mario Ries, Megan E. Poorman, Mary Dockery, Vandiver Chaplin, Stephanie O. Dudzinski, Ryan Spears, Charles Caskey, Todd Giorgio, Marcia M. Costa, Efthymia Papaevangelou, Anant Shah, Ian Rivens, Carol Box, Jeff Bamber, Gail ter Haar, Scott R. Burks, Matthew Nagle, Ben Nguyen, Blerta Milo, Nhan M. Le, Shaozhen Song, Kanheng Zhou, Ghulam Nabi, Zhihong Huang, Shmuel Ben-Ezra, Shani Rosen, Senay Mihcin, Jan Strehlow, Ioannis Karakitsios, Nhan Le, Michael Schwenke, Daniel Demedts, Paul Prentice, Sabrina Haase, Tobias Preusser, Andreas Melzer, Jean-Louis Mestas, Kamel Chettab, Gustavo Stadthagen Gomez, Charles Dumontet, Bettina Werle, Fabrice Marquet, Pierre Bour, Fanny Vaillant, Sana Amraoui, Rémi Dubois, Philippe Ritter, Michel Haïssaguerre, Mélèze Hocini, Olivier Bernus, Bruno Quesson, Amit Livneh, Dan Adam, Justine Robin, Bastien Arnal, Mathias Fink, Mathieu Pernot, Tatiana D. Khokhlova, George R. Schade, Yak-Nam Wang, Wayne Kreider, Julianna Simon, Frank Starr, Maria Karzova, Adam Maxwell, Michael R. Bailey, Jonathan E. Lundt, Steven P. Allen, Jonathan R. Sukovich, Timothy Hall, Zhen Xu, Philip May, Daniel W. Lin, Charlotte Constans, Thomas Deffieux, Jean-Francois Aubry, Eun-Joo Park, Yun Deok Ahn, Soo Yeon Kang, Dong-Hyuk Park, Jae Young Lee, J. Vidal-Jove, E. Perich, A. Ruiz, A. Jaen, N. Eres, M. Alvarez del Castillo, Rachel Myers, James Kwan, Christian Coviello, Cliff Rowe, Calum Crake, Sean Finn, Edward Jackson, Antonios Pouliopoulos, Caiqin Li, Marc Tinguely, Meng-Xing Tang, Valeria Garbin, James J. Choi, Lisa Folkes, Michael Stratford, Sandra Nwokeoha, Tong Li, Navid Farr, Samantha D’Andrea, Kayla Gravelle, Hong Chen, Donghoon Lee, Joo Ha Hwang, Sophie Tardoski, Jacqueline Ngo, Evelyne Gineyts, Jean-Pau Roux, Philippe Clézardin, Allegra Conti, Rémi Magnin, Matthieu Gerstenmayer, François Lux, Olivier Tillement, Sébastien Mériaux, Stefania Della Penna, Gian Luca Romani, Erik Dumont, Tao Sun, Chanikarn Power, Eric Miller, Oleg Sapozhnikov, Sergey Tsysar, Petr V. Yuldashev, Victor Svet, Dongli Li, Antonio Pellegrino, Nik Petrinic, Clive Siviour, Antoine Jerusalem, Peter V. Yuldashev, Bryan W. Cunitz, Barbrina Dunmire, Claude Inserra, Matthieu Guedra, Cyril Mauger, Bruno Gilles, Maxim Solovchuk, Tony W. H. Sheu, Marc Thiriet, Yufeng Zhou, Esra Neufeld, Christian Baumgartner, Davnah Payne, Adamos Kyriakou, Niels Kuster, Xu Xiao, Helen McLeod, Christopher Dillon, Allison Payne, Vera A. Khokhova, Ilya Sinilshchikov, Yulia Andriyakhina, Andrey Rybyanets, Natalia Shvetsova, Alex Berkovich, Igor Shvetsov, Caroline J. Shaw, John Civale, Dino Giussani, Christoph Lees, Valery Ozenne, Solenn Toupin, Vasant Salgaonkar, Elena Kaye, Sebastien Monette, Majid Maybody, Govindarajan Srimathveeravalli, Stephen Solomon, Amitabh Gulati, Mario Bezzi, Jürgen W. Jenne, Thomas Lango, Michael Müller, Giora Sat, Christine Tanner, Stephan Zangos, Matthias Günther, Au Hoang Dinh, Emilie Niaf, Flavie Bratan, Nicolas Guillen, Rémi Souchon, Carole Lartizien, Sebastien Crouzet, Olivier Rouviere, Yang Han, Thomas Payen, Carmine Palermo, Steve Sastra, Kenneth Olive, Johanna M. van Breugel, Maurice A. van den Bosch, Benjamin Fellah, Denis Le Bihan, Luis Hernandez-Garcia, Charles A. Cain, Erasmia Lyka, Delphine Elbes, Chunhui Li, Satoshi Tamano, Hayato Jimbo, Shin Yoshizawa, Keisuke Fujiwara, Kazunori Itani, Shin-ichiro Umemura, Dan Stoianovici, Zulfadhli Zaini, Ryo Takagi, Shenyan Zong, Ron Watkins, Aurea Pascal-Tenorio, Peter Jones, Kim Butts-Pauly, Donna Bouley, Yazhu Chen, Chung-Yin Lin, Han-Yi Hsieh, Kuo-Chen Wei, Camille Garnier, Gilles Renault, Reza Seifabadi, Emmanuel Wilson, Avinash Eranki, Peter Kim, Dennis Lübke, Peter Huber, Joachim Georgii, Caroline V. Dresky, Julian Haller, Pavel Yarmolenko, Karun Sharma, Haydar Celik, Guofeng Li, Weibao Qiu, Hairong Zheng, Meng-Yen Tsai, Po-Chun Chu, Taylor Webb, Urvi Vyas, Matthew Walker, Jidan Zhong, Adam C. Waspe, Mojgan Hodaie, Feng-Yi Yang, Sin-Luo Huang, Yuval Zur, Benny Assif, Christian Aurup, Hermes Kamimura, Antonio A. Carneiro, Sven Rothlübbers, Julia Schwaab, Graeme Houston, Haim Azhari, Noam Weiss, Jacob Sosna, S. Nahum Goldberg, Victor Barrere, Kee W. Jang, Bobbi Lewis, Xiaotong Wang, Visa Suomi, David Edwards, Zahary Larrabee, Arik Hananel, Boaz Rafaely, Rasha Elaimy Debbiny, Carmel Zeltser Dekel, Michael Assa, George Menikou, Petros Mouratidis, José A. Pineda-Pardo, Marta Del Álamo de Pedro, Raul Martinez, Frida Hernandez, Silvia Casas, Carlos Oliver, Patricia Pastor, Lidia Vela, Jose Obeso, Paul Greillier, Ali Zorgani, Stefan Catheline, Vyacheslav Solovov, Michael O. Vozdvizhenskiy, Andrew E. Orlov, Chueh-Hung Wu, Ming-Kuan Sun, Tiffany T. Shih, Wen-Shiang Chen, Fabrice Prieur, Arnaud Pillon, Valerie Cartron, Patrick Cebe, Nathalie Chansard, Maxime Lafond, Pauline Muleki Seya, Jean-Christophe Bera, Tanguy Boissenot, Elias Fattal, Alexandre Bordat, Helene Chacun, Claire Guetin, Nicolas Tsapis, Kazuo Maruyama, Johan Unga, Ryo Suzuki, Cécile Fant, Bernadette Rogez, Mercy Afadzi, Ola Finneng Myhre, Siri Vea, Astrid Bjørkøy, Petros Tesfamichael Yemane, Annemieke van Wamel, Sigrid Berg, Rune Hansen, Bjørn Angelsen, and Catharina Davies

Subjects
0301 basic medicine, medicine.medical_specialty, Therapeutic ultrasound, business.industry, Tel aviv, medicine.medical_treatment, 02 engineering and technology, 021001 nanoscience & nanotechnology, 03 medical and health sciences, 030104 developmental biology, Ophthalmology, medicine, Radiology, Nuclear Medicine and imaging, Medical physics, 0210 nano-technology, business
Published
2017
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8. 5th International Symposium on Focused Ultrasound

Author

Menashe Zaaroor, Alon Sinai, Dorit Goldsher, Ayelet Eran, Maria Nassar, Ilana Schlesinger, Jonathon Parker, Vinod Ravikumar, Pejman Ghanouni, Sherman Stein, Casey Halpern, Vibhor Krishna, Amelia Hargrove, Punit Agrawal, Barbara Changizi, Eric Bourekas, Michael Knopp, Ali Rezai, Brian Mead, Namho Kim, Panagiotis Mastorakos, Jung Soo Suk, Wilson Miller, Alexander Klibanov, Justin Hanes, Richard Price, Shutao Wang, Oluyemi Olumolade, Tara Kugelman, Vernice Jackson-Lewis, Maria Eleni Karakatsani, Yang Han, Serge Przedborski, Elisa Konofagou, Kullervo Hynynen, Isabelle Aubert, Gerhard Leinenga, Rebecca Nisbet, Robert Hatch, Anneke Van der Jeugd, Harrison Evans, Jürgen Götz, Ann Van der Jeugd, Paul Fishman, Paul Yarowsky, Victor Frenkel, Shen Wei-Bin, Ben Nguyen, Carlos Sierra Sanchez, Camilo Acosta, Cherry Chen, Shih-Ying Wu, Muna Aryal, Iason T. Papademetriou, Yong-Zhi Zhang, Chanikarn Power, Nathan McDannold, Tyrone Porter, Zsofia Kovacs, Saejeong Kim, Neekita Jikaria, Farhan Qureshi, Michele Bresler, Joseph Frank, Henrik Odéen, George Chiou, John Snell, Nick Todd, Bruno Madore, Dennis Parker, Kim Butts Pauly, Mike Marx, Sumeeth Jonathan, William Grissom, Costas Arvanitis, Gregory Clement, Joshua de Bever, Allison Payne, Douglas Christensen, Guillaume Maimbourg, Mathieu David Santin, Alexandre Houdouin, Stéphane Lehericy, Mickael Tanter, Jean Francois Aubry, Christian Federau, Beat Werner, Dong-Guk Paeng, Zhiyuan Xu, Anders Quigg, Matt Eames, Changzhu Jin, Ashli Everstine, Jason Sheehan, M. Beatriz Lopes, Neal Kassell, James Drake, Karl Price, Lior Lustgarten, Vivian Sin, Charles Mougenot, Elizabeth Donner, Emily Tam, Mojgan Hodaie, Adam Waspe, Thomas Looi, Samuel Pichardo, Wonhye Lee, Yong An Chung, Yujin Jung, In-Uk Song, Seung-Schik Yoo, Hyun-Chul Kim, Jong-Hwan Lee, Charles Caskey, Wolf Zinke, Josh Cosman, Jillian Shuman, Jeffrey Schall, Christian Aurup, Hong Chen, Hermes Kamimura, Antonio Carneiro, Tao Sun, Navid Nazai, Sam Patz, Margaret Livingstone, Todd Mainprize, Yuexi Huang, Ryan Alkins, Martin Chapman, James Perry, Nir Lipsman, Allison Bethune, Arjun Sahgal, Maureen Trudeau, Hao-Li Liu, Po-Hung Hsu, Kuo-Chen Wei, Jonathan Sutton, Phillip Alexander, Eric Miller, Thiele Kobus, Alexandre Carpentier, Michael Canney, Alexandre Vignot, Kevin Beccaria, Delphine Leclercq, Cyril Lafon, Jean Yves Chapelon, Khe Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih, David Moore, Alexis Xu, Paul Schmitt, Jessica Foley, Jonathan Sukovich, Charles Cain, Aditya Pandey, Neeraj Chaudhary, Sandra Camelo-Piragua, Steven Allen, Jon Cannata, Dejan Teofilovic, Jim Bertolina, Timothy Hall, Zhen Xu, Julien Grondin, Vincent Ferrera, Gail ter Haar, Petros Mouratidis, Elizabeth Repasky, Kelsie Timbie, Lena Badr, Benjamin Campbell, John McMichael, Andrew Buckner, Jessica Prince, Aaron Stevens, Timothy Bullock, Karin Skalina, Chandan Guha, Franco Orsi, Guido Bonomo, Paolo Della Vigna, Giovanni Mauri, Gianluca Varano, George Schade, Yak-Nam Wang, Venu Pillarisetty, Joo Ha Hwang, Vera Khokhlova, Michael Bailey, Tatiana Khokhlova, Ilya Sinilshchikov, Petr Yuldashev, Yulia Andriyakhina, Wayne Kreider, Adam Maxwell, Oleg Sapozhnikov, Ari Partanen, Jonathan Lundt, Tobias Preusser, Sabrina Haase, Mario Bezzi, Jürgen Jenne, Thomas Langø, Massimo Midiri, Michael Mueller, Giora Sat, Christine Tanner, Stephan Zangos, Matthias Guenther, Andreas Melzer, Arianna Menciassi, Selene Tognarelli, Andrea Cafarelli, Alessandro Diodato, Gastone Ciuti, Sven Rothluebbers, Julia Schwaab, Jan Strehlow, Senay Mihcin, Steffen Tretbar, Thomas Payen, Carmine Palermo, Steve Sastra, Kenneth Olive, Matthew Adams, Vasant Salgaonkar, Serena Scott, Graham Sommer, Chris Diederich, Joan Vidal-Jove, Eloi Perich, Antonio Ruiz, Manuela Velat, David Melodelima, Aurelien Dupre, Jeremy Vincenot, Chen Yao, David Perol, Michel Rivoire, Samantha Tucci, Lisa Mahakian, Brett Fite, Elizabeth Ingham, Sarah Tam, Chang-il Hwang, David Tuveson, Katherine Ferrara, Stephen Scionti, Lili Chen, Dusica Cvetkovic, Xiaoming Chen, Roohi Gupta, Bin Wang, Charlie Ma, Kenneth Bader, Kevin Haworth, Christy Holland, Narendra Sanghvi, Roy Carlson, Wohsing Chen, Christian Chaussy, Stefan Thueroff, Claudio Cesana, Carlo Bellorofonte, Qingguo Wang, Han Wang, Shengping Wang, Junhai Zhang, Alberto Bazzocchi, Alessandro Napoli, Robert Staruch, Chenchen Bing, Sumbul Shaikh, Joris Nofiele, Debra Szczepanski, Michelle Wodzak Staruch, Noelle Williams, Theodore Laetsch, Rajiv Chopra, Jarrett Rosenberg, Rachelle Bitton, Suzanne LeBlang, Joshua Meyer, Mark Hurwitz, Pavel Yarmolenko, Haydar Celik, Avinash Eranki, Viktoriya Beskin, Domiciano Santos, Janish Patel, Matthew Oetgen, AeRang Kim, Peter Kim, Karun Sharma, Alexander Chisholm, Dionne Aleman, Roberto Scipione, Michael Temple, Joao Guilherme Amaral, Ruby Endre, Maria Lamberti-Pasculli, Joost de Ruiter, Fiona Campbell, Jennifer Stimec, Samit Gupta, Manoj Singh, Sevan Hopyan, Gregory Czarnota, David Brenin, Carrie Rochman, Roussanka Kovatcheva, Jordan Vlahov, Katja Zaletel, Julian Stoinov, Matthew Bucknor, Viola Rieke, Jenny Shim, Korgun Koral, Brian Lang, Carlos Wong, Heather Lam, Alexander Shinkov, Jim Hu, Xi Zhang, Jonathan Macoskey, Kimberly Ives, Gabe Owens, Hitinder Gurm, Jiaqi Shi, Matthew Pizzuto, Christopher Dillon, Ivy Christofferson, Elaine Hilas, Jill Shea, Paul Greillier, Bénédicte Ankou, Francis Bessière, Ali Zorgani, Mathieu Pioche, Wojciech Kwiecinski, Julie Magat, Sandrine Melot-Dusseau, Romain Lacoste, Bruno Quesson, Mathieu Pernot, Stefan Catheline, Philippe Chevalier, Fabrice Marquet, Pierre Bour, Fanny Vaillant, Sana Amraoui, Rémi Dubois, Philippe Ritter, Michel Haïssaguerre, Mélèze Hocini, Olivier Bernus, Pamela Tebebi, Scott Burks, Blerta Milo, Michael Gertner, Jimin Zhang, Andrew Wong, Yu Liu, Azadeh Kheirolomoom, Jai Seo, Katherine Watson, Hua Zhang, Josquin Foiret, Alexander Borowsky, Doudou Xu, Maya Thanou, Miguell Centelles, Mike Wright, Maral Amrahli, Po-Wah So, Wladyslaw Gedroyc, Esther Kneepkens, Edwin Heijman, Jochen Keupp, Steffen Weiss, Klaas Nicolay, Holger Grüll, Matthew Nagle, Anastasia V. Nikolaeva, Marina E. Terzi, Sergey A. Tsysar, Bryan Cunitz, Pierre Mourad, Matthew Downs, Georgiana Yang, Qi Wang, Johnny Chen, Justin Farry, Adam Dixon, Zhongmin Du, Ali Dhanaliwala, John Hossack, Ashish Ranjan, Danny Maples, Rachel Wardlow, Jerry Malayer, Akhilesh Ramachandran, Hirofumi Namba, Motohiro Kawasaki, Masashi Izumi, Katsuhito Kiyasu, Ryuichi Takemasa, Masahiko Ikeuchi, Takahiro Ushida, Calum Crake, Satya V. V. N. Kothapalli, Wan Leighton, Zhaorui Wang, H. Michael Gach, William Straube, Michael Altman, Young-sun Kim, Hyo Keun Lim, Hyunchul Rhim, Johanna van Breugel, Manon Braat, Chrit Moonen, Maurice van den Bosch, Mario Ries, Cristina Marrocchio, Susan Dababou, Jae Young Lee, Hyun Hoon Chung, Soo Yeon Kang, Kook Jin Kang, Keon Ho Son, Dandan Zhang, Juan Plata, Peter Jones, Aurea Pascal-Tenorio, Donna Bouley, Aaron Bond, Robert Dallapiazza, Diane Huss, Amy Warren, Scott Sperling, Ryder Gwinn, Binit Shah, W. Jeff Elias, Colleen Curley, Ying Zhang, Karina Negron, Roger Abounader, Gesthimani Samiotaki, Tsang-Wei Tu, Georgios Papadakis, Dima Hammoud, Matthew Silvestrini, Frank Wolfram, Daniel Güllmar, Juergen Reichenbach, Denis Hofmann, Joachim Böttcher, Harald Schubert, Thomas G. Lesser, Scott Almquist, Francisco Camarena, Sergio Jiménez-Gambín, Noé Jiménez, Jin Woo Chang, Vandiver Chaplin, Rebekah Griesenauer, Michael Miga, Nicholas Ellens, Raag Airan, Alfredo Quinones-Hinojosa, Keyvan Farahani, Xue Feng, Samuel Fielden, Li Zhao, Max Wintermark, Craig Meyer, Sijia Guo, Xin Lu, Jiachen Zhuo, Su Xu, Rao Gullapalli, Dheeraj Gandhi, Omer Brokman, Hongchae Baek, Hyungmin Kim, Steven Leung, Taylor Webb, Natalia Vykhodtseva, Thai-Son Nguyen, Chang Kyu Park, Sang Man Park, Na Young Jung, Min Soo Kim, Won Seok Chang, Hyun Ho Jung, Michael Plaksin, Yoni Weissler, Shy Shoham, Eitan Kimmel, Pavel B. Rosnitskiy, Steve Krupa, Eilon Hazan, Omer Naor, Yoav Levy, Noam Maimon, Inbar Brosh, Itamar Kahn, Jessica Cahill, Elodie Constanciel Colas, Adrian Wydra, Roman Maev, Amirah Aly, Ozge Sesenoglu-Laird, Linas Padegimas, Mark Cooper, Barbara Waszczak, Seruz Tehrani, Craig Slingluff, James Larner, Kumari Andarawewa, Eugene Ozhinsky, Rutwik Shah, Roland Krug, Roel Deckers, Sabine Linn, Britt Suelmann, Arjen Witkamp, Paul Vaessen, Paul van Diest, Lambertus W. Bartels, Clemens Bos, Nicolas Borys, Gert Storm, Elsken Van der Wall, Navid Farr, Moez Alnazeer, Prateek Katti, Bradford Wood, Alexis Farrer, Cyril Ferrer, Baudouin Denis de Senneville, Marijn van Stralen, Jingfei Liu, J. Kent Leach, Stephan Zidowitz, Hsin-Lun Lee, Fang-Chi Hsu, Chia-Chun Kuo, Shiu-Chen Jeng, Tung-Ho Chen, Nai-Yi Yang, Jeng-Fong Chiou, Yi-tzu Kao, Chia-Hsin Pan, Jing-Fu Wu, Yi-Chieh Tsai, Sara Johnson, Dawei Li, Ye He, Ioannis Karakitsios, Michael Schwenke, Daniel Demedts, Xu Xiao, Ian Cavin, Emilee Minalga, Robb Merrill, Rock Hadley, Pascal Ramaekers, Martijn de Greef, Kian Shahriari, Mohammad Hossein Parvizi, Kiana Asadnia, Marzieh Chamanara, Seyed Kamran Kamrava, Hamid Reza Chabok, Ruben Stein, Sébastien Muller, Jeremy Tan, Cornel Zachiu, Hans-Peter Erasmus, Glen Van Arsdell, Lee Benson, Kee W. Jang, Mary Angstadt, Bobbi Lewis, Hailey McLean, Martijn Hoogenboom, Dylan Eikelenboom, Martijn den Brok, Pieter Wesseling, Arend Heerschap, Jurgen Fütterer, Gosse Adema, Kevin Wang, Pei Zhong, Joyce Joy, Helen McLeod, Harry Kim, Matthew Lewis, Arda Ozilgen, Peter Zahos, Dezba Coughlin, Xinyan Tang, Jeff Lotz, Kathleen Jedruszczuk, Amitabh Gulati, Stephen Solomon, Elena Kaye, John Mugler, Gaetano Barbato, Gian Luca Scoarughi, Cristiano Corso, Alessandro Gorgone, Ilaria Giuseppina Migliore, Zachary Larrabee, Arik Hananel, Jean-Francois Aubry, Ayele Negussie, Emmanuel Wilson, Reza Seifabadi, Hyungwon Moon, Jeeun Kang, Changbeom Sim, Jin Ho Chang, Hyuncheol Kim, Hak Jong Lee, Noboru Sasaki, Mitsuyoshi Takiguchi, Lukas Sebeke, Xi Luo, Bram de Jager, Maurice Heemels, Christopher Abraham, Laura Curiel, Rémi Berriet, Margit Janát-Amsbury, Joseph Corea, Patrick Peiyong Ye, Ana Clauda Arias, Micheal Lustig, and Bryant Svedin

Subjects
Pathology, medicine.medical_specialty, business.industry, Blood–brain barrier, Focused ultrasound, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Disease therapy, 0302 clinical medicine, medicine.anatomical_structure, medicine, Radiology, Nuclear Medicine and imaging, business, 030217 neurology & neurosurgery
Published
2016
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9. Abstract 2760: Therapeutic ultrasound increases CD8+ lymphocyte infiltration of pancreatic tumors

Author

Petros Mouratidis and Gail ter Haar

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Therapeutic ultrasound, business.industry, medicine.medical_treatment, Ultrasound, Immunotherapy, medicine.disease, Immune system, Oncology, Pancreatic tumor, Pancreatic cancer, Cancer cell, medicine, business, Infiltration (medical)
Abstract

Objectives: The clinical benefit of immunotherapy has not yet been realized in pancreatic cancer, which is characterized by a low antigenicity and dense stroma profile. Focused ultrasound can be used in the treatment of solid tumors, either by inducing necrosis (using ablative temperatures), or by creating cavitation which results in mechanical disruption of the stroma surrounding cancer cells. Both processes may increase the immunogenicity of tumors, and there is anecdotal clinical evidence to that effect. In a pre-clinical study, orthotopic pancreatic tumors have been subjected to a number of different ultrasound exposure regimes (both thermal & cavitational) to explore whether increased T cell infiltration and immune cell activity in the tumor can be induced. Methods: Syngeneic orthotopic pancreatic KPC tumors (KrasLSL.G12D/+; p53R172H/+; PdxCre tg/+) were grown in murine C57BL/6 subjects (> 12 weeks old). Tumor growth was monitored using imaging ultrasound. Tumors were exposed to ultrasound using the Alpinion VIFU 2000 Therapeutic Ultrasound system, with exposure parameters designed to result in either heating (power = 65 W, exposure duration = 2 seconds, duty cycle = 100 %, 6 repeats) or cavitation (power = 200 W, duty cycle = 1 %, pulse repetition frequency = 1, 60 repeats) in the target tissue. Cavitation was detected using a passive, weakly focused, broadband (0.1 to 20 MHz) sensor. The effect of ultrasound on the viability of tumor cells, and their extracellular matrix, was investigated using histology of formalin-fixed, paraffin-embedded control and treated tumors. Immunohistochemical analysis of CD4+ and CD8+ cells in the tumor, and flow cytometry of the blood and spleen, were used. Results: Therapeutic ultrasound treatments resulted in cell and collagen depleted regions inside the tumor. Significant broadband signal (suggestive of cavitation) was seen only in the ‘cavitation' ultrasound exposures. Skin damage, where seen, was limited. Within a week of therapeutic ultrasound exposures a) an increase in the infiltration of CD8+ cells in the tumor volume, b) an increase in the percentage of the tumor area covered by CD8+ cells, c) an increase in the ratio of the percentage of the tumor area covered by CD8+ cells to that covered by CD4+ cells, and d) a decrease in the percentage of the tumor area covered by CD4+ cells were seen. Immune system regulation was also evident in the blood and spleen of treated subjects. Conclusions: Therapeutic ultrasound exposure parameters that could regulate the immune response of subjects carrying orthotopic pancreatic tumors have been identified. These results provide a rationale for the use of Therapeutic ultrasound in combination with current immunotherapeutic approaches to improve the control of pancreatic tumor growth. Citation Format: Petros Mouratidis, Gail ter Haar. Therapeutic ultrasound increases CD8+ lymphocyte infiltration of pancreatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2760.

Published
2018
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10. A study of thermal dose-induced autophagy, apoptosis and necroptosis in colon cancer cells

Author

Petros Mouratidis, Ian Rivens, and Gail ter Haar

Subjects
Cancer Research, Programmed cell death, Physiology, Necroptosis, Autophagy, Apoptosis, Biology, Cell biology, Survival Rate, Necrosis, Physiology (medical), Cell Line, Tumor, Cancer cell, Colonic Neoplasms, Cytotoxic T cell, Humans, MTT assay, Viability assay
Abstract

The pleiotropic effects of heat on cancer cells have been well documented. The biological effects seen depend on the temperature applied, and the heating duration. In this study we investigate the cytotoxic effects of heat on colon cancer cells and determine how different cell death processes such as autophagy, apoptosis and necroptosis play a role in cell response.The thermal dose concept was used to provide a parameter that will allow comparison of different thermal treatments. Two human colon cancer cell lines, HCT116 and HT29, were subjected to ablative temperatures using a polymerase chain reaction thermal cycler. Temperature was recorded using thermocouples. Cell viability was assessed using the MTT assay. Induction of apoptosis was estimated using an enzyme-linked immunosorbent assay that detects cleaved cytoplasmic nucleosomes. Protein regulation was determined using immunoblotting. The percentage of cells undergoing apoptosis and autophagy was determined with annexin V/propidium iodide staining and a cationic amphiphilic tracer using fluorescence-activated cell sorting analysis.Exposure of colon cancer cells to ablative thermal doses results in decreased cell viability. The cytotoxic effect of heat is associated with induction of apoptosis and autophagy, the amount depending on both the thermal dose applied and on the time elapsed after treatment. Autophagy induction is mainly seen in live cells. RIPK3 protein levels are increased after exposure of cells to heat. A necroptosis inhibitor does not affect cell viability.Autophagy, apoptosis and necroptosis are associated with the response of these cancer cell lines to supra-normal temperatures.

Published
2015

11. The Immunological Effects of Therapeutic Ultrasound

Author

Gail ter Haar and Petros Mouratidis

Subjects
medicine.medical_specialty, Acoustics and Ultrasonics, Radiological and Ultrasound Technology, Therapeutic ultrasound, business.industry, medicine.medical_treatment, Biophysics, medicine, Radiology, Nuclear Medicine and imaging, Radiology, business
Published
2017
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12. Abstract 3611: An investigation of thermal dose as a parameter to model the thermal effects of high intensity focused ultrasound in cancer therapy

Author

Gail ter Haar and Petros Mouratidis

Subjects
Cancer Research, Programmed cell death, Pathology, medicine.medical_specialty, Chemistry, Necroptosis, Cell cycle, chemistry.chemical_compound, Oncology, Apoptosis, Cancer cell, Cancer research, medicine, Viability assay, Propidium iodide, Heat shock
Abstract

Objectives: High Intensity Focused Ultrasound (HIFU) is a non-invasive technique for treating solid tumours by exposing target tissue to ablative temperatures, resulting in necrotic cell death. Progression of HIFU as a mainstream treatment option is hampered by lack of measurable dosimetric standards. Thermal dose (TD) is a parameter that can be used to describe HIFU treatments in the clinic and suggests that, above a reference temperature, for every 1°C increase in temperature, treatment time should be halved to achieve the same thermal damage. In our study we investigated whether TD can be used to describe the biological effect for a range of different thermal exposures. The activation of distinct programmed cell death processes in response to heat was determined. Methods: Two human colon cancer cell lines, HCT116 and HT29, were exposed to heat using a thermal cycler for long duration treatments, or using a pre-heated water bath for short duration treatments. Temperature was recorded using thermocouples. Cell viability was assessed using the MTT assay. Induction of apoptosis was estimated using an ELISA assay to detect cleaved cytoplasmic nucleosomes and using annexin V / propidium iodide (PI) staining to determine phosphatidylserine exposure to the outer side of the plasma membrane. Induction of autophagy was determined using immunoblotting with an antibody against LC3II, and using a fluorescent cationic amphiphillic tracer to detect autophagosomes. Necroptosis and basic heat shock response was determined by western blotting using antibodies against RIPK3 and Hsp70 respectively. The percentage of cells at different stages of the cell cycle was estimated by staining DNA with PI. Results: Exposure of cancer cells to TDs of 60 to 240 minutes resulted in decreased viability that depended on the TD applied and on time elapsed after treatment. This effect was associated with induction of apoptosis, autophagy and necroptosis. Autophagy induction was correlated with live cells. The percentage of cells undergoing each form of cell death was estimated at different time points up to 48 hours after treatment. A transient increase in the percentage of cells in the G1 phase of the cell cycle and activation of heat shock protein expression were associated with the response of cells to heat. Reduction in cell viability observed after exposure of cancer cells to TDs between 300 minutes and 1000 minutes depended on the method and duration of thermal exposure. Conclusions: TD induced pleiotropic biological effects such as increased cytotoxicity and activation of distinct programmed cell death processes in colon cancer cells. The method of heat delivery was shown to play an important role on the outcome of the thermal treatment suggesting limitations for the use of the TD parameter as a dosimetric standard in the clinic. Citation Format: Petros Mouratidis, Gail ter Haar. An investigation of thermal dose as a parameter to model the thermal effects of high intensity focused ultrasound in cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3611. doi:10.1158/1538-7445.AM2015-3611

Published
2015
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