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- Towards computational prediction of microRNA function and activity
- An alignment-free method to identify candidate orthologous enhancers in multiple Drosophila genomes
- Genome-wide functional element detection using pairwise statistical alignment outperforms multi-genome footprinting techniques
- Mining metabolic pathways through gene expression
- Integration of pathway knowledge into a weighted recursive feature elimination approach for cancer patients risk stratification
- Identifying compositionally homogeneous and nonhomogeneous domains within the human genome using a novel segmentation algorithm
- A Poisson model for random multigraphs
- A Bayesian approach using covariance of SNP data to detect differences in linkage disequilibrium patterns between groups
- Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor
- Over-optimism in bioinformatics: an illustration
Nucleic Acids Research
- Identifying compositionally homogeneous and nonhomogeneous domains within the human genome using a novel segmentation algorithm
- A flexible and efficient template format for circular consensus sequencing and SNP detection
- Towards computational prediction of microRNA function and activity
- Zinc-finger nuclease-driven targeted integration into mammalian genomes using donors with limited chromosomal homology
- The synthetic integron: an in vivo genetic shuffling device
Bioinformatics
- Semi-supervised multi-task learning for predicting interactions between HIV-1 and human proteins
- Detecting host factors involved in virus infection by observing the clustering of infected cells in siRNA screening images
- Mass spectrometry data processing using zero-crossing lines in multi-scale of Gaussian derivative wavelet
- Author Index
- Utopia documents: linking scholarly literature with research data
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Cancer
Her 2 in 1
Mark J. Smyth, John Stagg. In this issue of Cancer Cell, Park et al. demonstrate that anti-erbB2 antibody primes adaptive immunity for increased tumor clearance and suggest that chemotherapy may in fact interfere wit....
MEKing Retinoids Work Better
Yaël P. Mossé, John M. Maris. Retinoids can induce terminal differentiation in a subset of neuronal cancer cells, but what determines response has been unclear. In a recent issue of Cell, Hölzel and colleagues show that....
EZH2 Mutations: Mutating the Epigenetic Machinery in Myeloid Malignancies
Omar Abdel-Wahab, Ross L. Levine. Two recent studies identified loss-of-function mutations in the histone H3 methyltransferase EZH2 in myelodysplastic syndromes and myeloproliferative neoplasms, provided further demonstration of m....
SIK2 Is a Centrosome Kinase Required for Bipolar Mitotic Spindle Formation that Provides a Potential Target for Therapy in Ovarian Cancer
Ahmed Ashour Ahmed, Zhen Lu, Nicholas B. Jennings, Dariush Etemadmoghadam, Luisa Capalbo, Rodrigo O. Jacamo, Nuno Barbosa-Morais, Xiao-Feng Le, Pablo Vivas-Mejia, Gabriel Lopez-Berestein, Geoffrey Grandjean, Geoffrey Bartholomeusz, Warren Liao, Michael Andreeff, David Bowtell, David M. Glover, Anil K. Sood, Robert C. Bast. Regulators of mitosis have been successfully targeted to enhance response to taxane chemotherapy. Here, we show that the salt inducible kinase 2 (SIK2) localizes at the centrosome, plays a key rol....
Che-1 Promotes Tumor Cell Survival by Sustaining Mutant p53 Transcription and Inhibiting DNA Damage Response Activation
Tiziana Bruno, Agata Desantis, Gianluca Bossi, Silvia Di Agostino, Cristina Sorino, Francesca De Nicola, Simona Iezzi, Annapaola Franchitto, Barbara Benassi, Sergio Galanti, Francesca La Rosa, Aristide Floridi, Alfonso Bellacosa, Claudio Passananti, Giovanni Blandino, Maurizio Fanciulli. Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che....
Ink4a/Arf and Oncogene-Induced Senescence Prevent Tumor Progression during Alternative Colorectal Tumorigenesis
Moritz Bennecke, Lydia Kriegl, Monther Bajbouj, Kristin Retzlaff, Sylvie Robine, Andreas Jung, Melek C. Arkan, Thomas Kirchner, Florian R. Greten. Colonic cancers with a serrated morphology have been proposed to comprise a molecularly distinct tumor entity following an alternative pathway of genetic alterations independently of APC mu....
Phosphorylation by Casein Kinase I Promotes the Turnover of the Mdm2 Oncoprotein via the SCFβ-TRCP Ubiquitin Ligase
Hiroyuki Inuzuka, Alan Tseng, Daming Gao, Bo Zhai, Qing Zhang, Shavali Shaik, Lixin Wan, Xiaolu L. Ang, Caroline Mock, Haoqiang Yin, Jayne M. Stommel, Steven Gygi, Galit Lahav, John Asara, Zhi-Xiong Jim Xiao, William G. Kaelin, J. Wade Harper, Wenyi Wei. Mdm2 is the major negative regulator of the p53 pathway. Here, we report that Mdm2 is rapidly degraded after DNA damage and that phosphorylation of Mdm2 by casein kinase I (CKI) at multiple sites ....
The Therapeutic Effect of Anti-HER2/neu Antibody Depends on Both Innate and Adaptive Immunity
SaeGwang Park, Zhujun Jiang, Eric D. Mortenson, Liufu Deng, Olga Radkevich-Brown, Xuanming Yang, Husain Sattar, Yang Wang, Nicholas K. Brown, Mark Greene, Yang Liu, Jie Tang, Shengdian Wang, Yang-Xin Fu. Anti-HER2/neu antibody therapy is reported to mediate tumor regression by interrupting oncogenic signals and/or inducing FcR-mediated cytotoxicity. Here, we demonstrate that the mechanisms of tumo....
Double Antiangiogenic Protein, DAAP, Targeting VEGF-A and Angiopoietins in Tumor Angiogenesis, Metastasis, and Vascular Leakage
Young Jun Koh, Hak-Zoo Kim, Seong-Ik Hwang, Jeung Eun Lee, Nuri Oh, Keehoon Jung, Minah Kim, Kyung Eun Kim, Homin Kim, Nam-Kyu Lim, Choon-Ju Jeon, Gyun Min Lee, Byeong Hwa Jeon, Do-Hyun Nam, Hoon Ki Sung, Andras Nagy, Ook Joon Yoo, Gou Young Koh. Two vascular growth factor families, VEGF and the angiopoietins, play critical and coordinate roles in tumor progression and metastasis. A single inhibitor targeting both VEGF and angiopoietins is....
Regulation of Tumor Angiogenesis by EZH2
Chunhua Lu, Hee Dong Han, Lingegowda S. Mangala, Rouba Ali-Fehmi, Christopher S. Newton, Laurent Ozbun, Guillermo N. Armaiz-Pena, Wei Hu, Rebecca L. Stone, Adnan Munkarah, Murali K. Ravoori, Mian M.K. Shahzad, Jeong-Won Lee, Edna Mora, Robert R. Langley, Amy R. Carroll, Koji Matsuo, Whitney A. Spannuth, Rosemarie Schmandt, Nicholas B. Jennings, Blake W. Goodman, Robert B. Jaffe, Alpa M. Nick, Hye Sun Kim, Eylem Ozturk Guven, Ya-Huey Chen, Long-Yuan Li, Ming-Chuan Hsu, Robert L. Coleman, George A. Calin, Emir B. Denkbas, Jae Yun Lim, Ju-Seog Lee, Vikas Kundra, Michael J. Birrer, Mien-Chie Hung, Gabriel Lopez-Berestein, Anil K. Sood. Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either ....
A Centrosome Kinase Modulates Antitumor Drug Sensitivity
Jeffrey L. Salisbury. In this issue of Cancer Cell, Ahmed and coworkers identify SIK2 as a centrosome kinase and show that it controls the localization of the centriole linker protein C-Nap1. Interference with S....
The Molecular Biology of Myeloproliferative Disorders
Jerald Radich. The myeloproliferative disorders (MPDs) are a spectrum of clonal disorders of the hematopoietic system. The discovery of activating mutations of the tyrosine kinase JAK2 in polycythemia vera, esse....
Testimony from the Bedside: From Coley's Toxins to Targeted Immunotherapy
Jin Mo Park, David E. Fisher. A new clinical study reported in the New England Journal of Medicine unveils the long-awaited outcome of anti-CTLA-4 therapy for melanoma. It provides grounds for continued enthusiasm for c....
Siah2-Dependent Concerted Activity of HIF and FoxA2 Regulates Formation of Neuroendocrine Phenotype and Neuroendocrine Prostate Tumors
Jianfei Qi, Koh Nakayama, Robert D. Cardiff, Alexander D. Borowsky, Karen Kaul, Roy Williams, Stan Krajewski, Dan Mercola, Philip M. Carpenter, David Bowtell, Ze'ev A. Ronai. Neuroendocrine (NE) phenotype, seen in >30% of prostate adenocarcinomas (PCa), and NE prostate tumors are implicated in aggressive prostate cancer. Formation of NE prostate tumors in the TRA....
4E-BP1 Is a Key Effector of the Oncogenic Activation of the AKT and ERK Signaling Pathways that Integrates Their Function in Tumors
Qing-Bai She, Ensar Halilovic, Qing Ye, Wei Zhen, Senji Shirasawa, Takehiko Sasazuki, David B. Solit, Neal Rosen. PIK3CA and PTEN alterations are common in human cancer, but only a fraction of such tumors are dependent upon AKT signaling. AKT independence is associated with redundant activation ....
PCBP1 Suppresses the Translation of Metastasis-Associated PRL-3 Phosphatase
Haihe Wang, Leah A. Vardy, Cheng Peow Tan, Jia Min Loo, Ke Guo, Jie Li, Seng Gee Lim, Jianbiao Zhou, Wee Joo Chng, Siok Bian Ng, Hui Xiang Li, Qi Zeng. Overexpression of phosphatase of regenerating liver (PRL)-3 is associated with the progression of diverse human cancers. We show that the overexpression of PRL-3 protein is not directly associated....
A Synthetic Lethal Interaction between K-Ras Oncogenes and Cdk4 Unveils a Therapeutic Strategy for Non-small Cell Lung Carcinoma
Marta Puyol, Alberto Martín, Pierre Dubus, Francisca Mulero, Pilar Pizcueta, Gulfaraz Khan, Carmen Guerra, David Santamaría, Mariano Barbacid. We have unveiled a synthetic lethal interaction between K-Ras oncogenes and Cdk4 in a mouse tumor model that closely recapitulates human non-small cell lung carcinoma (NSCLC). Ablati....
Wnt/Ca2+/NFAT Signaling Maintains Survival of Ph+ Leukemia Cells upon Inhibition of Bcr-Abl
Mark A. Gregory, Tzu L. Phang, Paolo Neviani, Francesca Alvarez-Calderon, Christopher A. Eide, Thomas O'Hare, Vadym Zaberezhnyy, Richard T. Williams, Brian J. Druker, Danilo Perrotti, James DeGregori. Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to eradicate Bcr-Abl+ leukemia cells. To identify genes ....
PML/RARA Oxidation and Arsenic Binding Initiate the Antileukemia Response of As2O3
Marion Jeanne, Valérie Lallemand-Breitenbach, Omar Ferhi, Marcel Koken, Morgane Le Bras, Stéphanie Duffort, Laurent Peres, Caroline Berthier, Hassane Soilihi, Brian Raught, Hugues de Thé. As2O3 cures acute promyelocytic leukemia (APL) by initiating PML/RARA oncoprotein degradation, through sumoylation of its PML moiety. However, how As2O3....
Integrative Genomic Profiling of Human Prostate Cancer
Barry S. Taylor, Nikolaus Schultz, Haley Hieronymus, Anuradha Gopalan, Yonghong Xiao, Brett S. Carver, Vivek K. Arora, Poorvi Kaushik, Ethan Cerami, Boris Reva, Yevgeniy Antipin, Nicholas Mitsiades, Thomas Landers, Igor Dolgalev, John E. Major, Manda Wilson, Nicholas D. Socci, Alex E. Lash, Adriana Heguy, James A. Eastham, Howard I. Scher, Victor E. Reuter, Peter T. Scardino, Chris Sander, Charles L. Sawyers, William L. Gerald. Annotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focu....