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REQUEST MORE AT ADINFONOW.ORG Swiss firm Basilea for the development of a broad-spectrum cephalosporin. Even a modest revival in antibiotics R&D from big pharma could help fertilize drug discovery efforts in the industry. “A lot of the work and the new creative stuff we’re beginning to explore in the natural product area involves partnering with others who bring something to the table,” Miller says. Smaller companies may have access to new sample sources or cuttingedge technology, while Pfizer brings the chemistry and microbiology infrastructure to the collaboration. Miller is concerned that the lack of interest in the field might impede collaboration that can lead to advances. “Competition is really good,” he says. “We get ideas from each other, and when there are fewer companies, there are fewer sources of ideas For Excellence in Organic Chemistry • Medicinal Chemistry and Drug Discovery • Custom Synthesis (milligrams to kilograms) • Hit-to-Lead Optimization • Natural Product Isolation Servicing the Bio-Pharma Industry since 1986 240 Salem Street Woburn, MA 01801 Phone: (781) 932-4142 Fax: (781) 933-6695 Email: organix@organixinc.com www.organixinc.com COVER STORY “Antibiotics are different than other drugs. They uniquely depreciate because of Darwinian selection principles.” and less cross-fertilization of scientists moving around.” TO SPUR COLLABORATION and competition, some researchers say, government needs to do more to recognize the pitfalls of the antibiotics business. They say one way of encouraging investment in R&D would be to create new incentives, such as extending the patent lives of molecules that may have sat on laboratory shelves for years. “Antibiotics are different than other drugs,” Cubist’s Eisenstein says. “They uniquely depreciate because of Darwinian selection principles.” In diseases such as cancer, he points out, any resistance that develops is contained within the patient; the drug is still effective for the rest of the population with the disease. But with antibiotics, that resistant WWW.CEN-ONLINE.ORG 20 APRIL 14, 2008 strain can spread to the general population. “There are cases that a drug has not even been approved but already developed resistance,” Optimer’s Chang notes. When a drug has a limited life span, its commercial potential is compromised. “Where is the incentive?” he asks. Furthermore, in an attempt to delay the cycle of resistance, physicians tend to hold off on prescribing the newest drugs, using them only in the sickest patients stricken by the most severe organisms, Eisenstein says. But keeping the newest antibiotics as a last line of defense “paradoxically kills the supply,” he argues. Companies aren’t eager to refill the pipeline if they don’t stand to make money on new products. Some incentives are necessary, scientists say, because bugs continue to learn new ways of evading the current arsenal of drugs. “Sixty years ago, the leading causes of serious infections were Pneumococcus and S. aureus. Today, it’s still the same problems,” Harvard’s Moellering says. “Meanwhile, they’ve become more resistant to antimicrobials, and we haven’t done much at all to decrease the prevalence of those infections.” ■ REQUEST MORE AT ADINFONOW.ORG
Mammary Gland and Breast Cancer Proteomics Volume 7, Issue 4 • April 2008 Guest Editors: Sam Hanash, Fred Hutchinson Cancer Research Center and Serhiy Souchelnytskyi, Karolinska Institute Biomics Center (Sweden) Targeting Therapy for Breast Carcinoma by ATP Synthase Inhibitor Aurovertin B Tsui-Chin Huang, Hsin-Yi Chang, Chun-Hua Hsu, Wen-Hung Kuo, King-Jen Chang, and Hsueh-Fen Juan Combined Experimental and Statistical Strategy for Mass Spectrometry Based Serum Protein Profiling for Diagnosis of Breast Cancer: A Case-Control Study Anne K. Callesen, Werner Vach, Per E. Jørgensen, Søren Cold, Qihua Tan, René dePont Christensen, Ole Mogensen, Torben A. Kruse, Ole N. Jensen, and Jonna S. Madsen Proteome Profiling of Breast Tumors by Gel Electrophoresis and Nanoscale Electrospray Ionization Mass Spectrometry Louise Alldridge, Gergana Metodieva, Christina Greenwood, Khalid Al-Janabi, Laura Thwaites, Paul Sauven, and Metodi Metodiev Targeted Glycoproteomic Identification of Biomarkers for Human Breast Carcinoma Karen L. Abbott, Kazuhiro Aoki, Jae-Min Lim, Mindy Porterfield, Rachelle Johnson, Ruth M. O’Regan, Lance Wells, Michael Tiemeyer, and Michael Pierce Multiplexed Cell Signaling Analysis of Human Breast Cancer Applications for Personalized Therapy Julia D. Wulfkuhle, Runa Speer, Mariaelena Pierobon, Julie Laird, Virginia Espina, Jianghong Deng, Enzo Mammano, Sherry X. Yang, Sandra M. Swain, Donato Nitti, Laura J. Esserman, Claudio Belluco, Lance A. Liotta, and Emanuel F. Petricoin III Novel Breast Cancer Biomarkers Identified by Integrative Proteomic and Gene Expression Mapping Keli Ou, Kun Yu, Djohan Kesuma, Michelle Hooi, Ning Huang, Wei Chen, Suet Ying Lee, Xin Pei Goh, Lay keng Tan, Jia Liu, Sou Yen Soon, Suhaimi Bin Abdul Rashid, Thomas C. Putti, Hiroyuki Jikuya, Tetsuo Ichikawa, Osamu Nishimura, Manuel Salto-Tellez, and Patrick Tan New Protein Clustering of Breast Cancer Tissue Proteomics Using Actin Content as a Cellularity Indicator Ida Pucci-Minafra, Patrizia Cancemi, Nadia Ninfa Albanese, Gianluca Di Cara, Maria Rita Marabeti, Antonio Marrazzo, and Salvatore Minafra Special Issue “Currently, researchers are implementing numerous proteomics approaches that target the mammary gland and its associated pathologies. This special issue of JPR provides a snapshot of the progress in the field and a window on the various strategies being pursued to tackle the challenges at hand, which stem from the complexity of these tissues and the extensive heterogeneity inherent in diseases of the mammary gland.” —Sam Hanash and Serhiy Souchelnytskyi Mammary Gland and Breast Cancer Proteomics Papers from Volume 7, Issue 4 —————————————— Articles —————————————— Application of Protein Microarrays for Multiplexed Detection of Antibodies to Tumor Antigens in Breast Cancer Karen S. Anderson, Niroshan Ramachandran, Jessica Wong, Jacob V. Raphael, Eugenie Hainsworth, Gokhan Demirkan, Daniel Cramer, Dina Aronzon, F. Stephen Hodi, Lyndsay Harris, Tanya Logvinenko, and Joshua LaBaer Evaluation of Data-Dependent versus Targeted Shotgun Proteomic Approaches for Monitoring Transcription Factor Expression in Breast Cancer Charanjit Sandhu, Johannes A. Hewel, Gwenael Badis, Shaheynoor Talukder, Jian Liu, Timothy R. Hughes, and Andrew Emili Plasma Proteome Profiling of a Mouse Model of Breast Cancer Identifies a Set of Up-Regulated Proteins in Common with Human Breast Cancer Cells Sharon J. Pitteri, Vitor M. Faca, Karen S. Kelly-Spratt, A. Erik Kasarda, Hong Wang, Qing Zhang, Lisa Newcomb, Alexei Krasnoselsky, Sophie Paczesny, Gina Choi, Matthew Fitzgibbon, Martin W. McIntosh, Christopher J. Kemp, and Samir M. Hanash Identification of Breast Cancer Peptide Epitopes Presented by HLA-A*0201 Oriana E. Hawkins, Rodney S. VanGundy, Annette M. Eckerd, Wilfried Bardet, Rico Buchli, Jon A. Weidanz, and William H. Hildebrand Differentiating Proteomic Biomarkers in Breast Cancer by Laser Capture Microdissection and MALDI MS Melinda E. Sanders, Eduardo C. Dias, Baogang J. Xu, James A. Mobley, Dean Billheimer, Heinrich Roder, Julia Grigorieva, Mitchell Dowsett, Carlos L. Arteaga, and Richard M. Caprioli Proteomic Analysis of Microsomes from Lactating Bovine Mammary Gland Lifeng Peng, Pisana Rawson, Danyl McLauchlan, Klaus Lehnert, Russell Snell, and T. William Jordan A Proteomic Analysis of the Plasma Glycoproteins of a MCF-7 Mouse Xenograft: A Model System for the Detection of Tumor Markers Christina I. Orazine, Marina Hincapie, William S. Hancock, Maureen Hattersley, and Jeff H. Hanke —————————————— Reviews —————————————— Breast Tumor Microenvironment: Proteomics Highlights the Treatments Targeting Secretome Shui-Tein Chen, Tai-Long Pan, Hsueh-Fen Juan, Tai-Yuan Chen, Yih-Shyan Lin, and Chun-Ming Huang Humoral Immunity Directed against Tumor-Associated Antigens as Potential Biomarkers for the Early Diagnosis of Cancer Hailing Lu, Vivian Goodell, and Mary L. Disis Proteomics of Breast Cancer: The Quest for Markers and Therapeutic Targets Hubert Hondermarck, Christophe Tastet, Ikram El Yazidi-Belkoura, Robert-Alain Toillon, and Xuefen Le Bourhis Reproducibility of Mass Spectrometry Based Protein Profiles for Diagnosis of Breast Cancer across Clinical Studies: A Systematic Review Anne K. Callesen, Werner Vach, Per E. Jørgensen, Søren Cold, Ole Mogensen, Torben A. Kruse, Ole N. Jensen, and Jonna S. Madsen For a complete listing of all JPR Special Issues, go to http://pubs.acs.org/JPR
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