Effects of a synthetic PEG-ylated Tie-2 agonist peptide on endotoxemic lung injury and mortality.

Yu-Qing Zhou, Su-Ning Zhu, F Stuart Foster, Myron I Cybulsky, R Mark Henkelman, Narges K Tafreshi, Marilyn M Bui, Kellsey Bishop, Mark C Lloyd, Steven a Enkemann, Alexis S Lopez, Dominique Abrahams, Bradford W Carter, Josef Vagner, Stephen R Grobmyer, Stephen R Gobmyer, Robert J Gillies, David L Morse, Fúlvia D Marques, Anderson J Ferreira, Rubén D M Sinisterra, Bruno a Jacoby, Frederico B Sousa, Marcelo V Caliari, Gerluza a B Silva, Marcos B Melo, Ana P Nadu, Leandro E Souza, Maria C C Irigoyen, Alvair P Almeida, Robson a S Santos, Xi Wang, Madhavi Bathina, John Lynch, Brian Koss, Christopher Calabrese, Sharon Frase, John D Schuetz, Jerold E Rehg, Joseph T Opferman, James Mehi, Marc Lukacs, Desmond Hirson, Chris White, Chris Chaggares, Andrew Needles, Andreas Blana, Sven Kaese, Lisa Fortmüller, Sandra Laakmann, Dierk Damke, Kelly van Bragt, Jens Eckstein, Ilaria Piccini, Uwe Kirchhefer, Stanley Nattel, Günter Breithardt, Peter Carmeliet, Edward Carmeliet, Ulrich Schotten, Sander Verheule, Paulus Kirchhof, Larissa Fabritz, Sascha David, Chandra C Ghosh, Philipp Kümpers, Nelli Shushakova, Paul Van Slyke, Eliyahu V Khankin, S Ananth Karumanchi, Dan Dumont, Samir M Parikh, Atta Behfar, Satsuki Yamada, Ruben Crespo-Diaz, Jonathan J Nesbitt, Lois a Rowe, Carmen Perez-Terzic, Vinciane Gaussin, Christian Homsy, Jozef Bartunek, Andre Terzic, Daniela Carnevale, Giuseppe Cifelli, Giada Mascio, Michele Madonna, Mauro Sbroggiò, Cinzia Perrino, Maria Grazia Persico, Giacomo Frati, Giuseppe Lembo, Mattia Quattrocelli, Stefania Crippa, Celeste Montecchiani, Jordi Camps, Antonia Icaro Cornaglia, Luisa Boldrin, Jennifer Morgan, Alberto Calligaro, Andrea Casasco, Aldo Orlacchio, Rik Gijsbers, Jan D'Hooge, Jaan Toelen, Stefan Janssens, Maurilio Sampaolesi, Risto Kerkelä, Sara Karsikas, Zoltan Szabo, Raisa Serpi, Johanna Magga, Erhe Gao, Kari Alitalo, Andrey Anisimov, Raija Sormunen, Ilkka Pietilä, Laura Vainio, Walter J Koch, Kari I Kivirikko, Johanna Myllyharju, Peppi Koivunen, Hedi Razavi, Shahrzad Y Zarafshar, Hirofumi Sawada, Charles a Taylor, Jeffrey a Feinstein, Jordan D Miller, Robert M Weiss, Donald D Heistad, Kelly Van Bragt, Hadas Bar-Joseph, Irit Ben-Aharon, Moran Tzabari, Galia Tsarfaty, Salomon M Stemmer, Ruth Shalgi
American journal of physiology. Lung cellular and molecular physiology2011
PURPOSE: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. EXPERIMENTAL DESIGN: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. RESULTS: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. CONCLUSION: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities.
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