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1. Abstract OT1-19-01: A Single Arm Phase 2 Study of Peri-Operative Checkpoint-Mediated Immune Therapy and Cryoablation in Women with Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer

Author

Heather McArthur, Elizabeth Comen, Yolanda Bryce, Stephen Solomon, Jorge Henrique Santos Leal, Christina DiLauro Abaya, Cristal Martinez, Reva Basho, Dorothy Park, Philomena McAndrew, Brigid Larkin, William Mills, David B. Page, Staci Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha Reddy, Meredith Carter, Sujata Patil, and Larry Norton

Subjects
Cancer Research, Oncology
Abstract

Background: Local tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with immune checkpoint inhibition (ICI)-augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this phase 2 study, we evaluate the disease specific impact of peri-op ICI in women with residual triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC), a subset at high risk of early relapse. Methods: Eligible pts are ≥18y, with ER < 10%, PR < 10%, HER2 negative (per ASCO/CAP definition), ≥ 1.0 cm, residual operable disease after taxane-based NAC. Approximately 80 pts will be enrolled and treated with ipi/nivo/cryo followed by breast surgery and adjuvant nivo across multiple institutions. Pts undergo percutaneous, image-guided cryo with concurrent research core biopsy 7-10 days prior to surgery and will receive ipi (1mg/kg IV) with nivo (240mg IV) 1 to 5 days prior to cryo. After surgery, pts will receive 3 additional doses of nivo at 240mg IV Q2 weeks. Adjuvant capecitabine is recommended for all patients per local standard-of-care. Patients will be stratified by NAC platinum administration, NAC anthracycline administration, and clinical nodal status (positive versus negative). The primary endpoint is 3-year Event Free Survival (EFS). Secondary endpoints include Invasive Disease-Free Survival (IDFS), Distant Disease-Free Survival (DDFS), overall survival (OS) and safety. Exploratory correlative studies will be performed on tumor and serum to characterize the immunologic impact of the intervention and to explore predictors of efficacy and toxicity. Funding sources: Susan G. Komen, ASCO Conquer Cancer Foundation, Breast Cancer Research Foundation, Bristol-Myers Squibb, BTG International Ltd. NCT03546686 Citation Format: Heather McArthur, Elizabeth Comen, Yolanda Bryce, Stephen Solomon, Jorge Henrique Santos Leal, Christina DiLauro Abaya, Cristal Martinez, Reva Basho, Dorothy Park, Philomena McAndrew, Brigid Larkin, William Mills, David B. Page, Staci Mellinger, Nicole Fredrich, Nicole Moxon, Sangeetha Reddy, Meredith Carter, Sujata Patil, Larry Norton. A Single Arm Phase 2 Study of Peri-Operative Checkpoint-Mediated Immune Therapy and Cryoablation in Women with Hormone Receptor-Negative, HER2-Negative Early Stage/Resectable Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-19-01.

Published
2023
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2. Supplementary Table 1 from Deep Sequencing of T-cell Receptor DNA as a Biomarker of Clonally Expanded TILs in Breast Cancer after Immunotherapy

Author

Heather L. McArthur, Larry Norton, Clifford Hudis, Jedd D. Wolchok, James P. Allison, Sujata Patil, Harlan Robins, Olivier Elemento, Virgilio Sacchini, Monica Morrow, Edi Brogi, Elizabeth Morris, Majid Maybody, Janice Sung, Adi Diab, Christopher Comstock, Phillip Wong, Zhiwan Dong, Stephen Solomon, Ryan Emerson, Jeremy C. Durack, Y Hanna Wen, David Redmond, Jianda Yuan, and David B. Page

Abstract

Supplementary Table 1: TCRB sequencing sample IDs

Published
2023
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3. Figure S2 from Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair–proficient Metastatic Colorectal Cancer

Author

Leonard B. Saltz, Christopher H. Crane, Nancy Kemeny, Yoshiya Yamada, Stephen Solomon, Joseph Erinjeri, Marinela Capanu, Joanne F. Chou, Krishna Juluru, Travis J. Hollmann, Efsevia Vakiani, Taha Merghoub, Phillip Wong, Pallavi Vedantam, Aliya Holland, Matthew J. Adamow, Martinique Ogle, Mark L. Solter, Pamela Vaiskauskas, Kathleen C. Mcauliffe, Ghassan K. Abou-Alfa, David Faleck, Louise C. Connell, Rona Yaeger, Karuna Ganesh, Anna M. Varghese, Zsofia K. Stadler, Paul B. Romesser, Martin R. Weiser, T. Jonathan Yang, John Cuaron, Diane Reidy-Lagunes, Danny N. Khalil, Andreas Rimner, Abraham J. Wu, Geoffrey Ku, Andrea Cercek, and Neil H. Segal

Abstract

Flow dot plots

Published
2023
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4. Data from Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair–proficient Metastatic Colorectal Cancer

Author

Leonard B. Saltz, Christopher H. Crane, Nancy Kemeny, Yoshiya Yamada, Stephen Solomon, Joseph Erinjeri, Marinela Capanu, Joanne F. Chou, Krishna Juluru, Travis J. Hollmann, Efsevia Vakiani, Taha Merghoub, Phillip Wong, Pallavi Vedantam, Aliya Holland, Matthew J. Adamow, Martinique Ogle, Mark L. Solter, Pamela Vaiskauskas, Kathleen C. Mcauliffe, Ghassan K. Abou-Alfa, David Faleck, Louise C. Connell, Rona Yaeger, Karuna Ganesh, Anna M. Varghese, Zsofia K. Stadler, Paul B. Romesser, Martin R. Weiser, T. Jonathan Yang, John Cuaron, Diane Reidy-Lagunes, Danny N. Khalil, Andreas Rimner, Abraham J. Wu, Geoffrey Ku, Andrea Cercek, and Neil H. Segal

Abstract

Purpose:Immune checkpoint inhibition (ICI) alone is not active in mismatch repair–proficient (MMR-P) metastatic colorectal cancer (mCRC), nor does radiotherapy alone result in objective systemic benefit. However, combined radiotherapy plus ICI can induce systemic antitumor immunity in preclinical and clinical models.Patients and Methods:In this single-center, phase II study, patients with chemotherapy-refractory MMR-P mCRC received durvalumab 1,500 mg plus tremelimumab 75 mg every 4 weeks plus radiotherapy. The primary endpoint was objective response rate (ORR) in nonirradiated lesions. Treatment and efficacy were correlated with peripheral immune cell profiles.Results:We enrolled 24 patients, and report outcomes after a median follow-up of 21.8 (range: 15.9–26.3) months. The ORR was 8.3% (2 patients) [95% confidence interval (CI), 1.0–27.0]. The median progression-free survival was 1.8 (95% CI, 1.7–1.9) months, median overall survival was 11.4 (95% CI, 10.1–17.4) months. Twenty five percent of patients (n = 6) had treatment-related grade 3–4 adverse events. We observed increased circulating CD8+ T lymphocyte activation, differentiation, and proliferation in patients with objective response.Conclusions:This combination of radiotherapy plus ICI study did not meet the prespecified endpoint criteria to be considered worthwhile for further study. However, rare instances of systemic immune augmentation and regression in nonirradiated lesions were observed (an abscopal response). Combination durvalumab and tremelimumab plus radiotherapy is feasible in MMR-P mCRC with a manageable safety profile. Further studies of novel immunotherapy combinations, and identification of biomarkers predictive of abscopal response are warranted.

Published
2023
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5. Table S1 from Phase II Single-arm Study of Durvalumab and Tremelimumab with Concurrent Radiotherapy in Patients with Mismatch Repair–proficient Metastatic Colorectal Cancer

Author

Leonard B. Saltz, Christopher H. Crane, Nancy Kemeny, Yoshiya Yamada, Stephen Solomon, Joseph Erinjeri, Marinela Capanu, Joanne F. Chou, Krishna Juluru, Travis J. Hollmann, Efsevia Vakiani, Taha Merghoub, Phillip Wong, Pallavi Vedantam, Aliya Holland, Matthew J. Adamow, Martinique Ogle, Mark L. Solter, Pamela Vaiskauskas, Kathleen C. Mcauliffe, Ghassan K. Abou-Alfa, David Faleck, Louise C. Connell, Rona Yaeger, Karuna Ganesh, Anna M. Varghese, Zsofia K. Stadler, Paul B. Romesser, Martin R. Weiser, T. Jonathan Yang, John Cuaron, Diane Reidy-Lagunes, Danny N. Khalil, Andreas Rimner, Abraham J. Wu, Geoffrey Ku, Andrea Cercek, and Neil H. Segal

Abstract

Radiation treatment summary

Published
2023
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7. Cave radon exposure, dose, dynamics and mitigation

Author

Robert Blackley, Chris L. Waring, Stephen Solomon, Andrew Yule, Andy Baker, Sylvester Werczynski, Stephen Long, and Stuart Hankin

Subjects
geography, geography.geographical_feature_category, Cave, Environmental science, Atmospheric sciences, Earth-Surface Processes, Radon exposure
Abstract

Many caves around the world have very high concentrations of naturally occurring 222Rn that may vary dramatically with seasonal and diurnal patterns. For most caves with a variable seasonal or diurnal pattern, 222Rn concentration is driven by bi-directional convective ventilation, which responds to external temperature contrast with cave temperature. Cavers and cave workers exposed to high 222Rn have an increased risk of contracting lung cancer. The International Commission on Radiological Protection (ICRP) has re-evaluated its estimates of lung cancer risk from inhalation of radon progeny (ICRP 115) and for cave workers the risk may now (ICRP 137) be 4–6 times higher than previously recognized. Cave Guides working underground in caves with annual average 222Rn activity > 1,000 Bq/m3 and default ICRP assumptions (2,000 workplace hours per year, equilibrium factor F = 0.4, dose conversion factor DCF = 14 µSv/(kBq h m-3) could now receive a dose of > 20 mSv/y. Using multiple gas tracers (d13 C--CO2, Rn and N2O), linked weather, source gas flux chambers, and convective air flow measurements a previous study unequivocally identified the external soil above Chifley Cave as the source of cave 222Rn. If the source of 222Rn is external to the cave, a strategy to lower cave 222Rn by passively decreasing summer pattern convective ventilation, which draws 222Rn into caves, is possible without harming the cave environment. A small net annual average temperature difference (warmer cave air) due to geothermal heat flux produces a large net annual volumetric air flow bias (2–5:1) favoring a winter ventilation pattern that flushes Rn from caves with ambient air. Rapid anthropogenic climate change over decades may heat the average annual external temperature relative to the cave temperature that is stabilized by the thermal inertia of the large rock mass. Relative external temperature increases due to climate change (Jenolan Caves, 2008–2018, 0.17°C) reduces the winter pattern air flow bias and increases Rn concentration in caves.

Published
2021
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8. REASSESSMENT OF INHALATION DOSES TO WORKERS IN AUSTRALIAN SHOW CAVES

Author

Stephen Solomon

Subjects
chemistry.chemical_element, Radon, Radiation Dosage, Risk Assessment, Radiation Protection, Cave, Radiation Monitoring, Occupational Exposure, Environmental health, Reference level, Administration, Inhalation, Humans, Radiology, Nuclear Medicine and imaging, Radiometry, geography, Radiation, geography.geographical_feature_category, Radiological and Ultrasound Technology, business.industry, Australia, Public Health, Environmental and Occupational Health, General Medicine, humanities, respiratory tract diseases, Caves, chemistry, Air Pollutants, Radioactive, Radon Progeny, Environmental science, Radiation protection, business, Dose conversion
Abstract

Exposure to radon in show caves is an existing exposure situation. A survey of radon levels in underground show caves around Australia, carried out in 1994, found that most of the show caves located in South-Eastern Australia had yearly average radon levels exceeding the Australian radon reference level of 1000 Bq m−3. At the time of the original survey, the radiation doses from exposure to radon progeny of the tour guides in these caves were estimated using the epidemiologically based dose conversion factors and all dose were assessed to be less than 10 mSv per year. In February 2018, the International Commission for Radiological Protection (ICRP) published updated radon and radon progeny dose conversion factors (DCF) applicable to worker exposure to radon in show caves. These updated DCF values are based on dosimetric modelling and are sensitive to the radon progeny activity size distribution. The recommended DCF values are up to a factor four times higher than the previous ICRP recommendations. The ICRP has published data that allows for the estimation of site-specific radon progeny dose coefficients if required. A reassessment of the radiation doses to workers in Australian show caves has been made using these updated ICRP DCF values and the historical measurements of radon progeny activity size distributions in Australian show caves. Using the site-specific DCF values, it is estimated that 15% of the workers exceeded 10 mSv y−1 and 6% exceeded 20 mSv y−1. Although the total number of show cave workers in Australia is very small, the updated radon progeny dose estimates are a significant radiation protection issue for the affected individuals and their employers.

Published
2019
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9. Managing Internal Radiation Contamination Following an Emergency: Identification of Gaps and Priorities

Author

Stephen Solomon, Arlene Alves dos Reis, George Etherington, Osamu Kurihara, Florence Menetrier, Maria Antonia Lopez, Armin Ansari, Jiangfeng Zhang, Jean-René Jourdain, Zhanat Carr, Chunsheng Li, Boris Kukhta, Centers for Disease Control and Prevention (CDC), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Australian Radiation Protection and Nuclear Safety Agency, and Chinese Center for Disease Control and Prevention

Subjects
Fukushima Nuclear Accident, [SDV]Life Sciences [q-bio], Brachytherapy, Poison control, Chernobyl Nuclear Accident, Suicide prevention, Occupational safety and health, 030218 nuclear medicine & medical imaging, 0302 clinical medicine, Medicine, Program Development, Child, Radiation, Radiological and Ultrasound Technology, Data Collection, General Medicine, Environmental exposure, 3. Good health, Child, Preschool, 030220 oncology & carcinogenesis, Radiological weapon, Radiation monitoring, Biological Assay, Medical emergency, Radioactive Hazard Release, Risk, Adolescent, education, Disaster Planning, Guidelines as Topic, Radiation Dosage, World Health Organization, Article, 03 medical and health sciences, Radiation Protection, Radiation Monitoring, Environmental health, Humans, Radiology, Nuclear Medicine and imaging, business.industry, Infant, Newborn, Public Health, Environmental and Occupational Health, Infant, Environmental Exposure, medicine.disease, 13. Climate action, Emergencies, business
Abstract

Following a radiological or nuclear emergency, first responders and the public may become internally contaminated with radioactive materials, as demonstrated during the Goiânia, Chernobyl and Fukushima accidents. Timely monitoring of the affected populations for potential internal contamination, assessment of radiation dose and the provision of necessary medical treatment are required to minimize the health risks from the contamination. This paper summarizes the guidelines and tools that have been developed, and identifies the gaps and priorities for future projects.© World Health Organisation 2016. All rights reserved. The World Health Organization has granted Oxford University Press permission for the reproduction of this article. Language: en

Published
2016
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10. Technical Note: Scintillation well counters and particle counting digital autoradiography devices can be used to detect activities associated with genomic profiling adequacy of biopsy specimens obtained after a low activity

Author

Assen S, Kirov, Louise M, Fanchon, Daniel, Seiter, Christian, Czmielewski, James, Russell, Snjezana, Dogan, Sean, Carlin, Katja, Pinker-Domenig, Ellen, Yorke, C Ross, Schmidtlein, Vitaly, Boyko, Sho, Fujisawa, Katia, Manova-Todorova, Pat, Zanzonico, Lawrence, Dauer, Joseph O, Deasy, John L, Humm, and Stephen, Solomon

Subjects
Image-Guided Biopsy, Fluorodeoxyglucose F18, Positron Emission Tomography Computed Tomography, Autoradiography, Feasibility Studies, Humans, Scintillation Counting, Biological Transport, Genomics, HT29 Cells, Article, Injections
Abstract

PURPOSE: Genomic profiling of biopsied tissue is the basis for precision cancer therapy. However biopsied materials may not contain sufficient amounts of tumor deoxyribonucleonic acid needed for the analysis. We propose a method to determine the adequacy of specimens for performing genomic profiling by quantifying their metabolic activity. METHODS: We estimated the average density of tumor cells in biopsy specimens needed to successfully perform genomic analysis following the Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) protocol from the minimum amount of deoxyribonucleonic acid needed and the volume of tissue typically used for analysis. The average (18)F-FDG uptake per cell was assessed by incubating H29 adenocarcinoma tumor cells in (18)F-FDG containing solution and then measuring their activity with a scintillation well counter. Consequently we evaluated the response of two devices around the minimum expected activities which would indicate genomic profiling adequacy of biopsy specimens obtained under (18)F-FDG PET/CT guidance. Surrogate samples obtained using 18G core needle biopsies of gels containing either (18)F-FDG loaded cells in the expected concentrations or the corresponding activity were measured using autoradiography and a scintillation well counter. Autoradiography was performed using a CCD based device with real time image display, as well as with digital autoradiography imaging plates following a 30 min off-line protocol for specimen activity determination against previously established calibration. RESULTS: Cell incubation experiments and estimates obtained from quantitative autoradiography of biopsy specimens (QABS) indicate that specimens acquired under (18)F-FDG PET/CT guidance that contained the minimum amount of cells needed for genomic profiling would have an average activity concentration in the range of about 3 to about 9 kBq/mL. When exposed to specimens with similar activity concentration, both a CCD based autoradiography device and a scintillation well counter produced signals with sufficient signal-to-background ratio for specimen genomic adequacy identification in less than 10 min, which is short enough to allow procedure guidance. CONCLUSION: Scintillation well counter measurements and CCD based autoradiography have adequate sensitivity to detect the tumor burden needed for genomic profiling during (18)F-FDG PET/CT guided 18G core needle biopsies of liver adenocarcinoma metastases.

Published
2017

11. 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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12. 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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13. Evaluation of radioxenon releases in Australia using atmospheric dispersion modelling tools

Author

Rick Tinker, Stephen Solomon, Marcus Grzechnik, Paul R.J. Saey, Emmy Hoffmann, and Blake Orr

Subjects
Meteorology, Atmosphere, Health, Toxicology and Mutagenesis, Australia, Monitoring system, General Medicine, Atmospheric dispersion modeling, Models, Theoretical, Pollution, Air Pollutants, Radioactive, Environmental Chemistry, Environmental science, Nuclear science, Waste Management and Disposal, Xenon Radioisotopes
Abstract

The origin of a series of atmospheric radioxenon events detected at the Comprehensive Test Ban Treaty Organisation (CTBTO) International Monitoring System site in Melbourne, Australia, between November 2008 and February 2009 was investigated. Backward tracking analyses indicated that the events were consistent with releases associated with hot commission testing of the Australian Nuclear Science Technology Organisation (ANSTO) radiopharmaceutical production facility in Sydney, Australia. Forward dispersion analyses were used to estimate release magnitudes and transport times. The estimated 133Xe release magnitude of the largest event (between 0.2 and 34 TBq over a 2 d window), was in close agreement with the stack emission releases estimated by the facility for this time period (between 0.5 and 2 TBq). Modelling of irradiation conditions and theoretical radioxenon emission rates were undertaken and provided further evidence that the Melbourne detections originated from this radiopharmaceutical production facility. These findings do not have public health implications. This is the first comprehensive study of atmospheric radioxenon measurements and releases in Australia.

Published
2009

14. Disclosing electronic data

Author

Stephen, Solomon

Subjects
Medical Records Systems, Computerized, Humans, Disclosure, Residential Facilities, United States
Published
2008

15. A phase I/IIA trial of continuous five-day infusion of squalamine lactate (MSI-1256F) plus carboplatin and paclitaxel in patients with advanced non-small cell lung cancer

Author

Roy S, Herbst, Lisa A, Hammond, David P, Carbone, Hai T, Tran, Kenneth J, Holroyd, Avinash, Desai, Jon I, Williams, B Nebiyou, Bekele, Howard, Hait, Victoria, Allgood, Stephen, Solomon, and Joan H, Schiller

Subjects
Adult, Aged, 80 and over, Male, Lung Neoplasms, Time Factors, Paclitaxel, Patient Selection, Angiogenesis Inhibitors, Middle Aged, Survival Analysis, Disease-Free Survival, Carboplatin, Pleural Effusion, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Lactates, Humans, Female, Infusions, Intravenous, Cholestanols, Aged, Neoplasm Staging
Abstract

Squalamine is an antitumor agent that has been shown to have antiangiogenic activity in animal models. This Phase I/IIA study was designed to assess the safety, clinical response, and pharmacokinetics of squalamine when administered as a 5-day continuous infusion in conjunction with standard chemotherapy every 3 weeks in patients with stage IIIB (pleural effusion) or stage IV non-small cell lung cancer.Patients with chemotherapy-naive non-small cell lung cancer were treated with escalating doses of squalamine in combination with standard doses of paclitaxel and carboplatin. Paclitaxel and carboplatin were administered on day 1, followed by squalamine as a continuous infusion on days 1-5, every 21 days.A total of 45 patients were enrolled (18 patients in the Phase I dose escalation arm and 27 in the Phase IIA arm). The starting dose of squalamine was 100 mg/m(2)/day and escalated to 400 mg/m(2)/day; two of three patients at 400 mg/m(2)/day had dose-limiting toxicity that included grade 3/4 arthralgia, myalgia, and neutropenia. On the basis of safety and toxicity, 300 mg/m(2)/day was selected as the Phase II dose of squalamine in this combination regimen. An additional 27 patients (a total of 33) were enrolled according to the protocol treatment schema at 300 mg/m(2)/day. There was no pharmacokinetic evidence of drug interactions for the combination of squalamine, carboplatin, and paclitaxel. Forty-three patients were evaluable for response. Partial tumor responses were observed in 12 (28%) of these patients; an additional 8 evaluable patients (19%) were reported to have stable disease. For all of the patients treated, the median survival was 10.0 months; and 1-year survival was 40%.The combination of squalamine given continuously daily for 5 days, with paclitaxel and carboplatin given on day 1, is well tolerated. Patient survival data and the safety profile of this drug combination suggests that the use of squalamine given at its maximum tolerated dose with cytotoxic chemotherapy should be explored further as a potentially effective therapeutic strategy for patients with stage IIIB or IV non-small cell lung cancer.

Published
2003

17. Elevated urinary excretion of beta-aminoisobutyric acid and exposure to inorganic lead

Author

B A Frank Buschman, Stephen Solomon, Opendra K. Sharma, Ernest Borek, Alf Fischbein, and Walter R. Farkas

Subjects
Adult, Male, medicine.medical_specialty, Aminoisobutyric Acids, Urinary system, Protoporphyrins, Urine, Toxicology, chemistry.chemical_compound, Internal medicine, medicine, Environmental Chemistry, Animals, Humans, General Environmental Science, biology, Public Health, Environmental and Occupational Health, RNA, Callithrix, biology.organism_classification, Thymine, Lead Poisoning, Occupational Diseases, Endocrinology, chemistry, Lead acetate, Toxicity, Metallurgy, DNA
Abstract

beta-Aminoisobutyric acid (beta-AIB), a normal degradation product of thymine, a constituent of DNA and, to a lesser extent, of transfer RNA, is excreted in low levels in human urine. We found that a group of iron workers occupationally exposed to inorganic lead excreted high levels of urinary beta-AIB. Elevated urinary excretion of beta-AIB was also observed in marmosets, Callithrix jacchus, that received lead acetate in drinking water. Our results suggest that increased urinary excretion of beta-AIB could stem from damage to DNA on exposure to lead.

Published
1987

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