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Table of Contents

Breaking Advances

  • Breaking Advances
    Highlights from Recent Cancer Literature
    Cancer Res April 15 2011 71 (8) 2807-2808;

Reviews

  • Reviews
    The Two Faces of Capsaicin
    Ann M. Bode and Zigang Dong
    Cancer Res April 15 2011 71 (8) 2809-2814; DOI:10.1158/0008-5472.CAN-10-3756

  • Reviews
    Transcriptional Control of Cellular Metabolism by mTOR Signaling
    Jessica L. Yecies and Brendan D. Manning
    Cancer Res April 15 2011 71 (8) 2815-2820; DOI:10.1158/0008-5472.CAN-10-4158

Priority Report

  • Priority Report
    CREB Is a Novel Nuclear Target of PTEN Phosphatase
    Tingting Gu, Zhong Zhang, Jianli Wang, Junyi Guo, Wen Hong Shen and Yuxin Yin
    Cancer Res April 15 2011 71 (8) 2821-2825; DOI:10.1158/0008-5472.CAN-10-3399

    This study offers important insights into the function of the PTEN phosphatase in the nucleus, where this important tumor suppressor appears to act to suppress cancer in addition to its well-described roles in the cytoplasm.

Integrated Systems and Technologies

  • Integrated Systems and Technologies | Free Article
    Mathematical Modeling Predicts Synergistic Antitumor Effects of Combining a Macrophage-Based, Hypoxia-Targeted Gene Therapy with Chemotherapy
    Markus R. Owen, I. Johanna Stamper, Munitta Muthana, Giles W. Richardson, Jon Dobson, Claire E. Lewis and Helen M. Byrne
    Cancer Res April 15 2011 71 (8) 2826-2837; DOI:10.1158/0008-5472.CAN-10-2834

    This study uses multiscale mathematical modeling to study how hypoxic tumor cells can be attacked most effectively, using a proposed cell-based therapy that takes advantage of several targeting principles.

  • Integrated Systems and Technologies | Free Article
    A Multicellular Basis for the Origination of Blast Crisis in Chronic Myeloid Leukemia
    Rainer K. Sachs, Kerstin Johnsson, Philip Hahnfeldt, Janet Luo, Allen Chen and Lynn Hlatky
    Cancer Res April 15 2011 71 (8) 2838-2847; DOI:10.1158/0008-5472.CAN-10-4600

    A comprehensive mechanistic mathematical model gives evidence that the main driving mechanism for CML blast crisis origination is interaction between leukemic and normal cells.

Microenvironment and Immunology

  • Microenvironment and Immunology
    A Critical Role for GRP78/BiP in the Tumor Microenvironment for Neovascularization during Tumor Growth and Metastasis
    Dezheng Dong, Christopher Stapleton, Biquan Luo, Shigang Xiong, Wei Ye, Yi Zhang, Niyati Jhaveri, Genyuan Zhu, Risheng Ye, Zhi Liu, Kevin W. Bruhn, Noah Craft, Susan Groshen, Florence M. Hofman and Amy S. Lee
    Cancer Res April 15 2011 71 (8) 2848-2857; DOI:10.1158/0008-5472.CAN-10-3151

    Endothelial cell specific knockout illustrates a critical role for a stress chaperone in the tumor microenvironment, extending its known role in tumor cells and deepening its significance to therapeutic and imaging applications.

  • Microenvironment and Immunology
    Enhanced Efficacy of Therapeutic Cancer Vaccines Produced by Co-Treatment with Mycobacterium tuberculosis Heparin-Binding Hemagglutinin, a Novel TLR4 Agonist
    In Duk Jung, Soo Kyung Jeong, Chang-Min Lee, Kyung Tae Noh, Deok Rim Heo, Yong Kyoo Shin, Cheol-Heui Yun, Won-Jung Koh, Shizuo Akira, Jake Whang, Hwa-Jung Kim, Won Sun Park, Sung Jae Shin and Yeong-Min Park
    Cancer Res April 15 2011 71 (8) 2858-2870; DOI:10.1158/0008-5472.CAN-10-3487

    This study offers a clear rationale for the development of a powerful new vaccine adjuvant for dendritic cell-based immunotherapies, an emerging area of cancer therapy with the first FDA-approved product appearing in 2010.

  • Microenvironment and Immunology
    In vivo Inhibition of Human CD19-Targeted Effector T Cells by Natural T Regulatory Cells in a Xenotransplant Murine Model of B Cell Malignancy
    James C. Lee, Erik Hayman, Hollie J. Pegram, Elmer Santos, Glenn Heller, Michel Sadelain and Renier Brentjens
    Cancer Res April 15 2011 71 (8) 2871-2881; DOI:10.1158/0008-5472.CAN-10-0552

    Successful application of adoptive therapy of cancer using autologous T cells genetically targeted to tumor associated antigens is dependent upon prior depletion of tumor infiltrating regulatory T cells.

  • Microenvironment and Immunology
    IRF8 Regulates Acid Ceramidase Expression to Mediate Apoptosis and Suppresses Myelogeneous Leukemia
    Xiaolin Hu, Dafeng Yang, Mary Zimmerman, Feiyan Liu, Jine Yang, Swati Kannan, Andreas Burchert, Zdzislaw Szulc, Alicja Bielawska, Keiko Ozato, Kapil Bhalla and Kebin Liu
    Cancer Res April 15 2011 71 (8) 2882-2891; DOI:10.1158/0008-5472.CAN-10-2493

    Findings define how a critical tumor suppressor gene becomes attenuated in chronic myeloid leukemia, and how this attenuation leads to apoptotic resistance and disease progression.

  • Microenvironment and Immunology
    CD73-Deficient Mice Have Increased Antitumor Immunity and Are Resistant to Experimental Metastasis
    John Stagg, Upulie Divisekera, Helene Duret, Tim Sparwasser, Michele W.L. Teng, Phillip K. Darcy and Mark J. Smyth
    Cancer Res April 15 2011 71 (8) 2892-2900; DOI:10.1158/0008-5472.CAN-10-4246

    Findings offer preclinical proof-of-concept for therapeutic targeting of a important cell surface-based driver of immune escape in cancer, perhaps involved in many types of human cancer.

Molecular and Cellular Pathobiology

  • Molecular and Cellular Pathobiology
    FLT3-Mediated p38–MAPK Activation Participates in the Control of Megakaryopoiesis in Primary Myelofibrosis
    Christophe Desterke, Chrystele Bilhou-Nabéra, Bernadette Guerton, Christophe Martinaud, Carole Tonetti, Denis Clay, Paola Guglielmelli, Alessandro Vannucchi, Dominique Bordessoule, Hans Hasselbalch, Brigitte Dupriez, Nassima Benzoubir, Marie-Françoise Bourgeade, Olivier Pierre-Louis, Vladimir Lazar, William Vainchenker, Annelise Bennaceur-Griscelli, Heinz Gisslinger, Stéphane Giraudier and Marie-Caroline Le Bousse-Kerdilès
    Cancer Res April 15 2011 71 (8) 2901-2915; DOI:10.1158/0008-5472.CAN-10-1731

    Findings advance understanding of the pathophysiology of primary myelofibrosis, a bone marrow–derived disease, and suggest applications for drugs that target a key megakaryocytic signaling pathway as a new strategy to evaluate for treating this disease.

  • Molecular and Cellular Pathobiology
    DLC1 Interaction with S100A10 Mediates Inhibition of In Vitro Cell Invasion and Tumorigenicity of Lung Cancer Cells through a RhoGAP-Independent Mechanism
    Xuyu Yang, Nicholas C. Popescu and Drazen B. Zimonjic
    Cancer Res April 15 2011 71 (8) 2916-2925; DOI:10.1158/0008-5472.CAN-10-2158

    Findings reveal a mechanism through which plasminogen activator-dependent conversion of plasminogen to plasmin is attenuated, reducing tumor cell capacity for invasion and metastasis in the tumor microenvironment.

  • Molecular and Cellular Pathobiology
    MicroRNA-301 Mediates Proliferation and Invasion in Human Breast Cancer
    Wei Shi, Kate Gerster, Nehad M. Alajez, Jasmine Tsang, Levi Waldron, Melania Pintilie, Angela B. Hui, Jenna Sykes, Christine P'ng, Naomi Miller, David McCready, Anthony Fyles and Fei-Fei Liu
    Cancer Res April 15 2011 71 (8) 2926-2937; DOI:10.1158/0008-5472.CAN-10-3369

    This study establishes a novel nodal oncomiR in breast cancer that acts through several pathways to promote metastatic tumor progression.

  • Molecular and Cellular Pathobiology
    The Neuronal Differentiation Factor NeuroD1 Downregulates the Neuronal Repellent Factor Slit2 Expression and Promotes Cell Motility and Tumor Formation of Neuroblastoma
    Peng Huang, Satoshi Kishida, Dongliang Cao, Yuko Murakami-Tonami, Ping Mu, Masato Nakaguro, Naoshi Koide, Ichiro Takeuchi, Akira Onishi and Kenji Kadomatsu
    Cancer Res April 15 2011 71 (8) 2938-2948; DOI:10.1158/0008-5472.CAN-10-3524

    Findings establish the critical role of a neuronal differentiation factor in neuroblastoma and its functional relationship with a neuronal repellent factor.

  • Molecular and Cellular Pathobiology
    Overexpression of a Novel Activator of PAK4, the CDK5 Kinase–Associated Protein CDK5RAP3, Promotes Hepatocellular Carcinoma Metastasis
    Grace Wing-Yan Mak, Mandy Man-Lok Chan, Veronica Yee-Law Leong, Joyce Man-Fong Lee, Tai-On Yau, Irene Oi-Lin Ng and Yick-Pang Ching
    Cancer Res April 15 2011 71 (8) 2949-2958; DOI:10.1158/0008-5472.CAN-10-4046

    A gene implicated in cancer progression proves to directly support metastasis by activating a PAK kinase implicated in invasive cell motility.

  • Molecular and Cellular Pathobiology
    Functional Cooperation of RKTG with p53 in Tumorigenesis and Epithelial–Mesenchymal Transition
    Yuhui Jiang, Xiaoduo Xie, Zhigang Li, Zheng Wang, Yixuan Zhang, Zhiqiang Ling, Yi Pan, Zhenzhen Wang and Yan Chen
    Cancer Res April 15 2011 71 (8) 2959-2968; DOI:10.1158/0008-5472.CAN-10-4077

    A novel tumor suppressor collaborates with p53 in tumor formation and epithelial-mesenchymal transition.

  • Molecular and Cellular Pathobiology
    Cytoplasmic CUL9/PARC Ubiquitin Ligase Is a Tumor Suppressor and Promotes p53-Dependent Apoptosis
    Xin-Hai Pei, Feng Bai, Zhijun Li, Matthew D. Smith, Gabrielle Whitewolf, Ran Jin and Yue Xiong
    Cancer Res April 15 2011 71 (8) 2969-2977; DOI:10.1158/0008-5472.CAN-10-4300

    This study identifies a potential p53 activating E3 ligase located in the cytoplasm that functions as a tumor suppressor.

  • Molecular and Cellular Pathobiology
    Frequent Truncating Mutation of TFAM Induces Mitochondrial DNA Depletion and Apoptotic Resistance in Microsatellite-Unstable Colorectal Cancer
    Jianhui Guo, Li Zheng, Wenyong Liu, Xianshu Wang, Zemin Wang, Zehua Wang, Amy J. French, Dongchon Kang, Lin Chen, Stephen N. Thibodeau and Wanguo Liu
    Cancer Res April 15 2011 71 (8) 2978-2987; DOI:10.1158/0008-5472.CAN-10-3482

    A class of mutations that lead to mitochondrial DNA depletion and apoptotic resistance may be important drivers of tumorigenesis in most microsatellite-unstable colorectal cancers.

  • Molecular and Cellular Pathobiology
    Genome-Wide DNA Methylation Profiling of CpG Islands in Breast Cancer Identifies Novel Genes Associated with Tumorigenicity
    Victoria K. Hill, Christopher Ricketts, Ivan Bieche, Sophie Vacher, Dean Gentle, Cheryl Lewis, Eamonn R. Maher and Farida Latif
    Cancer Res April 15 2011 71 (8) 2988-2999; DOI:10.1158/0008-5472.CAN-10-4026

    A genome-wide study of DNA methylation patterns suggests clinically useful theranostic markers in breast cancer, as well as new candidate pathways in etiology, progression, and therapy.

Prevention and Epidemiology

  • Prevention and Epidemiology
    Comprehensive Pathway-Based Association Study of DNA Repair Gene Variants and the Risk of Nasopharyngeal Carcinoma
    Hai-De Qin, Yin Yao Shugart, Jin-Xin Bei, Qing-Hua Pan, Lina Chen, Qi-Sheng Feng, Li-Zhen Chen, Wei Huang, Jian Jun Liu, Timothy J. Jorgensen, Yi-Xin Zeng and Wei-Hua Jia
    Cancer Res April 15 2011 71 (8) 3000-3008; DOI:10.1158/0008-5472.CAN-10-0469

    Findings support the notion that RAD51L1 and other DNA repair genes play a role in the etilogy and development of nasopharyngeal carcinoma.

  • Prevention and Epidemiology
    Lung Cancer Diagnosis from Proteomic Analysis of Preinvasive Lesions
    S.M. Jamshedur Rahman, Adriana L. Gonzalez, Ming Li, Erin H. Seeley, Lisa J. Zimmerman, Xueqiong J. Zhang, M. Lisa Manier, Sandra J. Olson, Ronak N. Shah, Alison N. Miller, Joe B. Putnam, York E. Miller, Wilbur A. Franklin, William J. Blot, David P. Carbone, Yu Shyr, Richard M. Caprioli and Pierre P. Massion
    Cancer Res April 15 2011 71 (8) 3009-3017; DOI:10.1158/0008-5472.CAN-10-2510

    This study reports a simple proteomic signature in bronchial specimens as a quantitative tool for the diagnostic assessment of lung cancer beyond qualitative histology methods.

Therapeutics, Targets, and Chemical Biology

  • Therapeutics, Targets, and Chemical Biology
    High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation
    Taher Nassar, Suha Attili-Qadri, Oshrat Harush-Frenkel, Shimon Farber, Shimon Lecht, Philip Lazarovici and Simon Benita
    Cancer Res April 15 2011 71 (8) 3018-3028; DOI:10.1158/0008-5472.CAN-10-3118

    An oral nanocarrier of docetaxel favors lymphatic uptake in preclinical studies, potentially stimulating clinical studies that could allow docetaxel chemotherapy to be switched from intravenous to oral delivery in patients.

  • Therapeutics, Targets, and Chemical Biology
    Sildenafil Reverses ABCB1- and ABCG2-Mediated Chemotherapeutic Drug Resistance
    Zhi Shi, Amit K. Tiwari, Suneet Shukla, Robert W. Robey, Satyakam Singh, In-Wha Kim, Susan E. Bates, Xingxiang Peng, Ioana Abraham, Suresh V. Ambudkar, Tanaji T. Talele, Li-Wu Fu and Zhe-Sheng Chen
    Cancer Res April 15 2011 71 (8) 3029-3041; DOI:10.1158/0008-5472.CAN-10-3820

    A drug used widely to treat erectile dysfunction in men is found to abrogate two common mechanisms of chemotherapeutic drug resistance, with immediate potential applications to improve the treatment of many advanced cancers.

  • Therapeutics, Targets, and Chemical Biology
    Inhibition of NEDD8-Activating Enzyme Induces Rereplication and Apoptosis in Human Tumor Cells Consistent with Deregulating CDT1 Turnover
    Michael A. Milhollen, Usha Narayanan, Teresa A. Soucy, Petter O. Veiby, Peter G. Smith and Benjamin Amidon
    Cancer Res April 15 2011 71 (8) 3042-3051; DOI:10.1158/0008-5472.CAN-10-2122

    DNA re-replication elicited in cancer cells by a small molecule inhibitor currently in Phase I trials creates an unrecoverable cellular insult, with implications for gaining deeper understanding of a unique therapeutic mechanism of cytotoxicity in cancer treatment.

  • Therapeutics, Targets, and Chemical Biology
    PDK1 Attenuation Fails to Prevent Tumor Formation in PTEN-Deficient Transgenic Mouse Models
    Katharine Ellwood-Yen, Heike Keilhack, Kaiko Kunii, Brian Dolinski, Yamicia Connor, Kun Hu, Kumiko Nagashima, Erin O'Hare, Yusuf Erkul, Alessandra Di Bacco, Diana Gargano, Nirah H. Shomer, Minilik Angagaw, Erica Leccese, Paula Andrade, Melissa Hurd, Myung K. Shin, Thomas F. Vogt, Alan Northrup, Ekaterina V. Bobkova, Shailaja Kasibhatla, Roderick T. Bronson, Martin L. Scott, Giulio Draetta, Victoria Richon, Nancy Kohl, Peter Blume-Jensen, Jannik N. Andersen and Manfred Kraus
    Cancer Res April 15 2011 71 (8) 3052-3065; DOI:10.1158/0008-5472.CAN-10-2282

    This study employed a novel RNAi approach useful for context-dependent target validation in vivo, applying it to demonstrate that the protein kinase PDK1 is not a rate limiting factor for PI3K-pathway activation or tumor formation in PTEN-deficient mouse models.

Tumor and Stem Cell Biology

  • Tumor and Stem Cell Biology
    Frizzled 4 Regulates Stemness and Invasiveness of Migrating Glioma Cells Established by Serial Intracranial Transplantation
    Xun Jin, Hee-Young Jeon, Kyeung Min Joo, Jun-Kyum Kim, Juyoun Jin, Sung Hak Kim, Bong Gu Kang, Samuel Beck, Se Jeong Lee, Joong Kyu Kim, Ae-Kyung Park, Woong-Yang Park, Yun-Jaie Choi, Do-Hyun Nam and Hyunggee Kim
    Cancer Res April 15 2011 71 (8) 3066-3075; DOI:10.1158/0008-5472.CAN-10-1495

    Findings define an important role in glioma recurrence and poor prognosis for a G-protein coupled receptor that is part of the Wnt signaling family governing stemness and invasiveness of glioma stem cells.

  • Tumor and Stem Cell Biology
    FOXQ1 Regulates Epithelial-Mesenchymal Transition in Human Cancers
    Yuanyuan Qiao, Xia Jiang, Shuet Theng Lee, R.K. Murthy Karuturi, Shing Chuan Hooi and Qiang Yu
    Cancer Res April 15 2011 71 (8) 3076-3086; DOI:10.1158/0008-5472.CAN-10-2787

    Findings identify a member of the FOXO family of transcription factors as a critical regulator of EMT, stem cell properties, and chemotherapeutic resistance in cancer cells.

  • Tumor and Stem Cell Biology
    EMT and Stem Cell–Like Properties Associated with miR-205 and miR-200 Epigenetic Silencing Are Early Manifestations during Carcinogen-Induced Transformation of Human Lung Epithelial Cells
    Carmen S. Tellez, Daniel E. Juri, Kieu Do, Amanda M. Bernauer, Cindy L. Thomas, Leah A. Damiani, Mathewos Tessema, Shuguang Leng and Steven A. Belinsky
    Cancer Res April 15 2011 71 (8) 3087-3097; DOI:10.1158/0008-5472.CAN-10-3035

    This study extends present concepts of how EMT contributes to cancer progression by showing that it can also contribute to cancer initiation, by promoting clonal expansion and stem-like properties in premalignant lung epithelial cells.

  • Tumor and Stem Cell Biology
    Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth
    Gianluca Civenni, Anne Walter, Nikita Kobert, Daniela Mihic-Probst, Marie Zipser, Benedetta Belloni, Burkhardt Seifert, Holger Moch, Reinhard Dummer, Maries van den Broek and Lukas Sommer
    Cancer Res April 15 2011 71 (8) 3098-3109; DOI:10.1158/0008-5472.CAN-10-3997

    Using immunocompetent mouse models and methodologies to better preserve cell surface epitopes allowed the identification of a melanoma stem cell marker associated with metastatic disease.

  • Tumor and Stem Cell Biology
    Hypoxia Predicts Aggressive Growth and Spontaneous Metastasis Formation from Orthotopically Grown Primary Xenografts of Human Pancreatic Cancer
    Qing Chang, Igor Jurisica, Trevor Do and David W. Hedley
    Cancer Res April 15 2011 71 (8) 3110-3120; DOI:10.1158/0008-5472.CAN-10-4049

    Results offer experimental proof of the expected powerful effects of hypoxia on the progression of early stage pancreatic cancer, with potential to target these effects therapeutically.

  • Tumor and Stem Cell Biology
    Deletion of the Proline-Rich Region of the Murine Metastasis Susceptibility Gene Brd4 Promotes Epithelial-to-Mesenchymal Transition- and Stem Cell-Like Conversion
    Jude Alsarraj, Renard C. Walker, Joshua D. Webster, Thomas R. Geiger, Nigel P.S. Crawford, R. Mark Simpson, Keiko Ozato and Kent W. Hunter
    Cancer Res April 15 2011 71 (8) 3121-3131; DOI:10.1158/0008-5472.CAN-10-4417

    Findings suggest how an important metastasis susceptibility gene may predispose tumor cells to convert to more de-differentiated or primitive states that are metastatically aggressive.

  • Tumor and Stem Cell Biology
    Ror1 Is a Pseudokinase That Is Crucial for Met-Driven Tumorigenesis
    Alessandra Gentile, Luca Lazzari, Silvia Benvenuti, Livio Trusolino and Paolo M. Comoglio
    Cancer Res April 15 2011 71 (8) 3132-3141; DOI:10.1158/0008-5472.CAN-10-2662

    An uncharacterized member of the human kinome is revealed to be a pseudokinase that acts downstream of the MET oncoprotein, the activation of which mediates powerful effects on the progression of many types of human cancer.

  • Tumor and Stem Cell Biology
    CAMTA1, a 1p36 Tumor Suppressor Candidate, Inhibits Growth and Activates Differentiation Programs in Neuroblastoma Cells
    Kai-Oliver Henrich, Tobias Bauer, Johannes Schulte, Volker Ehemann, Hedwig Deubzer, Sina Gogolin, Daniel Muth, Matthias Fischer, Axel Benner, Rainer König, Manfred Schwab and Frank Westermann
    Cancer Res April 15 2011 71 (8) 3142-3151; DOI:10.1158/0008-5472.CAN-10-3014

    Findings define properties of a gene involved in neuronal differentiation that support its assignment as a 1p36 tumor suppressor gene in neuroblastoma.

  • Tumor and Stem Cell Biology
    Cancer-Associated Loss-of-Function Mutations Implicate DAPK3 as a Tumor‐Suppressing Kinase
    John Brognard, You-Wei Zhang, Lorena A. Puto and Tony Hunter
    Cancer Res April 15 2011 71 (8) 3152-3161; DOI:10.1158/0008-5472.CAN-10-3543

    There has been a recent flood of cancer kinome sequence data, but the functional consequences of the reported protein kinase mutations have been inferred largely through statistical approaches, and our studies represent a critical first step in assessing the functional relevance of putative driver mutations experimentally.

  • Tumor and Stem Cell Biology
    Serglycin Is a Theranostic Target in Nasopharyngeal Carcinoma that Promotes Metastasis
    Xin-Jian Li, Choon Kiat Ong, Yun Cao, Yan-Qun Xiang, Jian-Yong Shao, Aikseng Ooi, Li-Xia Peng, Wen-Hua Lu, Zhongfa Zhang, David Petillo, Li Qin, Ying-Na Bao, Fang-Jing Zheng, Claramae Shulyn Chia, N. Gopalakrishna Iyer, Tie-Bang Kang, Yi-Xin Zeng, Khee Chee Soo, Jeffrey M. Trent, Bin Tean Teh and Chao-Nan Qian
    Cancer Res April 15 2011 71 (8) 3162-3172; DOI:10.1158/0008-5472.CAN-10-3557

    Findings of this extensive study define a functionally important extracellular theranostic marker of metastasis in nasopharengeal carcinoma, a common deadly cancer in Asia.

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Cancer Research: 71 (8)
April 2011
Volume 71, Issue 8
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Issue Highlights

  • CD73-Deficient Mice Have Increased Antitumor Immunity and Are Resistant to Experimental Metastasis
  • Sildenafil Reverses ABCB1- and ABCG2-Mediated Chemotherapeutic Drug Resistance
  • PDK1 Attenuation Fails to Prevent Tumor Formation in PTEN-Deficient Transgenic Mouse Models

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  • Priority Report
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  • Tumor and Stem Cell Biology
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Cancer Research Online ISSN: 1538-7445
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