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Registros recuperados: 382
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Endothelial Massive Calcium Accumulation Death (MCAD): Mechanism, Target, and Predictive Biomarker for Anti-Angiogenic Therapy 17
Larry Weisenthal.
We cultured human umbilical vein endothelial cells with bevacizumab, with tyrosine kinase inhibitors known to be AA, and with traditional cytotoxic drugs. The images below show that, in the presence of physiological saline and non-favorable culture conditions, the vast majority of the endothelial cells undergo a "non-specific" type of cell death (NSCD), not associated with calcium accumulation, but with loss of cell membrane integrity, allowing uptake of the Fast Green dye, staining these dead dells a pale blue green. In the presence of known AA agents (e.g. bevacizumab, some TK inhibitors) a large percentage of the endothelial cells undergo death associated with massive calcium accumulation (MCAD), with these cells staining...
Tipo: Poster Palavras-chave: Cancer; Molecular Cell Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6647/version/1
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Ligand Based Virtual Screening to Design Novel Human MEK1 Protein Inhibitors for Potential Development of Drugs Against Melanoma 17
Vijayasree Potluri; Dibyabhaba Pradhan; Amineni Umamaheswari.
The Ras-dependent Raf/MEK/ERK signaling pathway is a major regulator of cell proliferation and survival. Hyper activation of the pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or mutations in RAF (V600E). MEK1 is dual-specificity tyrosine/threonine protein kinases found in the pathway. The RAF mutation (present in 50% of melanomas) have been shown to be highly dependent on MEK1 activity and also MEK1 is the only acknowledged activator of ERK, making them attractive targets for therapeutic intervention. In view of its importance, identification of potent inhibitor against MEK1 may be valuable to design effective drugs against melanoma. Inhibitors for human MEK1 reported till dates have...
Tipo: Poster Palavras-chave: Cancer; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4901/version/1
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Open Biomedical Ontologies Applied to Prostate Cancer 17
James A. Overton; Cesare Romagnoli; Rethy Chhem.
This paper surveys preliminary results from the Interdisciplinary Prostate Ontology Project (IPOP), in which ontologies from the Open Biomedical Ontologies (OBO) library have been used to annotate clinical reports about prostate cancer. First we discuss why we rejected several controlled vocabularies, including SNOMED, DICOM, and RadLex, preferring instead to use the OBO library. We then briefly describe the database-backed website we have created around the relevant OBO ontologies, and provide excerpts of reports from radiology, surgery, and pathology which we have hyperlinked to the ontology terms. This method allows us to discover which relevant terms exist in the OBO library, and which do not. The final section of this paper discusses these gaps in the...
Tipo: Manuscript Palavras-chave: Cancer; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3570/version/1
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Motif analysis of amphioxus, lamprey and invertebrate estrogen receptors and amphioxus and human estrogen-related receptors: Towards a better understanding of estrogen receptor evolution 17
Michael E. Baker; Charlie Chandsawangbhuwana.
*Background.* The origins of steroid-dependent regulation of the vertebrate estrogen receptor (ER) are poorly understood. Genes with statistically significant sequence similarity to vertebrate ERs have been found in lamprey, a basal vertebrate, and amphioxus, a basal chordate. Motif analysis of these sequences provides an opportunity to investigate early events in the evolution of the ER.
*Results.* We used artificial intelligence-based software to construct twelve motifs specific to the estrogen-binding domain of ER[alpha] and ER[beta] in land vertebrates and teleosts. We mapped these ER-specific motifs onto the sequences of lamprey, amphioxus, invertebrate and selected vertebrate ERs and amphioxus and human estrogen-related receptor...
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology; Ecology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1542/version/1
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PathExpand: Extending biological pathways using molecular interaction networks 17
Enrico Glaab; Anais Baudot; Natalio Krasnogor; Alfonso Valencia.
We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyze their enrichment in cancer mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes.
Tipo: Presentation Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/5639/version/1
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Antibody-antigen interactions: What is the required time to equilibrium? 17
Karl Andersson; Hanna Björkelund; Magnus Malmqvist.
The use of antibodies is widespread in many areas including in-vivo and in-vitro diagnostics, quantitative analysis in research laboratories and as therapeutic substances. Since the methods for generation of antibodies has improved and regularly results in high-affinity interactions, the standard assays used for quantification of the interaction properties should be revisited because they do not necessarily produce accurate results. Here we show that in several cases, the affinity determination of strongly binding antibodies will be inherently difficult when using standard procedures, due to impractically long incubation times. Real-time kinetic analysis is often the only realistic alternative for affinity determination.
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Microbiology.
Ano: 2010 URL: http://precedings.nature.com/documents/5218/version/1
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Structure and function prediction of human homologue hABH5 of _E. coli_ ALKB5 using in silico approach 17
shankaracharya shankaracharya; Saibal Das; Ambarish Sharan Vidyarthi.
Newly discovered human homologues of ALKB protein have shown the activity of DNA damaging drugs, used for cancer therapy. Little is known about the structure and function of hABH5, one of the members of this superfamily. Therefore, in the present study we intend to predict its structure and function using various bioinformatics tools. Modeling was done with modeler 9v7 to predict the 3D structure of the hABH5 protein. 3-D model of hABH5, ALKBH5.B99990005.pdb was predicted and evaluated. Validation results showed 96.8% residues in favor and an additional allowed region of the Ramachandran plot. Ligand binding residues prediction showed four ligand clusters, having 25 ligands in cluster 1. Importantly, conserved pattern of Pro158-X-Asp160-Xn-His266 in the...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Molecular Cell Biology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/5597/version/1
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Cancer and the social induction of aging 17
Rodrick Wallace; Deborah Wallace.
Age has long been known as the primary population 'risk factor' for cancer. We suggest that the observed disparities in hormonal cancers by ethnicity, gender, and other indices of social structure and power relationships, imply a differential aging by psychosocial and environmental exposures, in the context of cross-generational epigenetic heritage. A relatively simple model of malignancy regulation illuminates the cellular root of induced aging, and explains the decline in cancer rate with extreme old age via telomere shortening. We find that the multifactorial determinants of the disorder cannot be effectively addressed by 'small molecule' interventions at the individual level, but must involve comprehensive prevention...
Tipo: Manuscript Palavras-chave: Cancer; Immunology; Pharmacology; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6146/version/1
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A theory for the tissue specificity of BRCA1/2 related and other hereditary cancers 17
Bernard Friedenson.
Women who inherit a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. All these suggestions share the assumption that some disabled function of normal tumor suppressor genes leads to a tissue specific cancer response. Here the idea is proposed and tested that major determinants of where BRCA1/2 hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to an inflammatory process...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Immunology; Pharmacology.
Ano: 2010 URL: http://precedings.nature.com/documents/4881/version/1
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Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells 17
Cheng-Ta Yang; Jhy-Ming Li; Hsu-Huei Weng; Ya-Chin Li; Miao-Fen Chen.
Expression of survivin has been reported to be correlated with shorter survival in patients with non-small cell lung cancer (NSCLC), and overexpression of survivin may lead to radioresistance in various human cancers. In this study, we inhibited survivin expression by using an adenoviral vector (AdsiSurvivin)-mediated RNAi to elucidate the combined effect of survivin-targeting gene therapy and radiotherapy on the NSCLC cells. Our data revealed that AdsiSurvivin exerted survivin gene silencing, induced apoptosis, and significantly attenuated the growth potential in NSCLC cells within 72 hours after infection. The combined treatment modalities with AdsiSurvivin infection and radiation were significantly more potent on cell-growth inhibition than monotherapy....
Tipo: Manuscript Palavras-chave: Cancer; Molecular Cell Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/2589/version/1
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Analysis of Cancer Omics Data In A Semantic Web Framework 17
Matthew Holford; James P. McCusker; Kei Cheung; Michael Krauthammer.
Our work concerns the elucidation of the cancer (epi)genome, transcriptome and proteome to better understand the complex interplay between a cancel cell's molecular state and its response to anti-cancer therapy. To study the problem, we have previously focused on data warehousing technologies and statistical data integration. In this paper, we present recent work on extending our analytical capabilities using Semantic Web technology. A key new component presented here is a SPARQL endpoint to our existing data warehouse. This endpoint allows the merging of observed quantitative data with existing data from semantic knowledge sources such as Gene Ontology (GO). We show how such variegated quantitative and functional data can be integrated and...
Tipo: Presentation Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/5391/version/1
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Limiting effect of diazepam on Lewis lung carcinoma metastasis in anxious male mice 17
Vasily N. Kaledin; Svetlana I. Ilnitskaya; Valery P. Nikolin; Nelly A. Popova; Dmitry A. Smagin; Natalia N. Kudryavtseva.
_Aim:_ It has been shown previously that chronic social defeat stress produces development of strong anxiety and increases intensity of experimental metastasis in the losers in comparison with the control mice. The question was: is it possible to decrease the number of metastases in the losers by chronic or acute diazepam treatment. _Materials and Methods._ Sensory contact model was used for generating male mice with repeated experience of social defeats or victories in daily agonistic interactions. Lewis Lung Carcinoma cells (LLC) were injected into the tail vein of animals after 10 days of agonistic interactions. Then mice were treated acutely or chronically (7 days) with diazepam (1 mg/kg, i.p). Number of metastases in the lung was calculated in 16 days...
Tipo: Manuscript Palavras-chave: Cancer; Neuroscience; Pharmacology.
Ano: 2009 URL: http://precedings.nature.com/documents/2748/version/1
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PSA Dynamics traditionally evaluated with an inadequate formula 17
Hans-Jürg Gerber.
The PSA doubling time is usually calculated from measured PSA values with an inadequate formula that tacitly assumes the absence of that process, which it is supposed to reveal. We present a modified calculational procedure which is optimized to unveil a weak second exponential process in the presence of a strong first one, using early screening data. The notion of Break Even Time (BET) indicates the stages of the processes.
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2009 URL: http://precedings.nature.com/documents/3930/version/1
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Modeling miRNA regulation in signaling networks: miR-34a regulation of the p53/Sirt1 module 17
Xin Lai.
Micro RNAs are a family of small regulatory RNAs whose function is to regulate the activity and stability of specific messenger RNA targets through post-translational regulatory mechanisms. We studied a signaling module composed by p53, Sirt1 and the small regulatory miRNA, miR-34a, based on the integration of experimental evidence and quantitative data, with mathematical modeling. We further used the model to investigate different possible designs of the silencing mechanisms exerted by miR-34a on Sirt1, and to simulate the dynamics of the system under pathological conditions of deregulation of its components. 

Tipo: Poster Palavras-chave: Cancer; Molecular Cell Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/5123/version/1
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Structure-based design of novel pyrazoles as aurora kinase A inhibitors. 17
Mohane Coumar; Paritosh Shukla; Ajay Kumar Dixit; Jiun-Shyang Leou; John T. A. Hsu; Su-Ying Wu; Hsing-Pang Hsieh.
Inhibition of Aurora kinase, a member of serine/threonine kinase involved in the regulation of cell division is emerging as a new molecular targeted cancer treatment option. Three isoforms of Aurora kinase, A, B and C are known. Both Aurora A and B are over expressed in many human cancers and are linked to chromosome instability, oncogenic transformation, tumour progression and development of chemoresistance. Inhibitors of Aurora kinase, regardless of their kinase specificity spectrum have shown to promote cancer cell death by induction of apoptosis and mitotic catastrophe. Based on the current success of Aurora kinase inhibitors in the development of kinase-based cancer therapy, we have initiated a structure-based virtual screening for the identification...
Tipo: Poster Palavras-chave: Biotechnology; Cancer; Chemistry.
Ano: 2009 URL: http://precedings.nature.com/documents/2769/version/1
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Cancer invasion associated gene expression signature is present in differentially expressed genes in the reprogramming of fibroblasts into stem cells 17
Wei-yi Cheng; Hoon Kim; Jessica Kandel; Dimitris Anastassiou.
Tumors become invasive by penetrating adjacent connective tissue, but the underlying biological mechanisms remain obscure. We recently identified a precise gene expression signature of fibroblastic origin associated with cancer invasion, the first step of the metastatic cascade. The signature contains many coordinately overexpressed genes, prominent among which are COL11A1, THBS2 and INHBA. Here we show that there is a striking similarity between the set of expressed genes in this metastasis-associated fibroblastic (MAF) signature and the set of genes that are downregulated when fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs). Because it is known that fibroblast reprogramming involves a mesenchymal epithelial transition (MET), the...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Developmental Biology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/5924/version/1
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Method of Detecting and Targeting Mutations in Cancer 17
Byard Edwards.
While there are many differences between tumor and non-tumor cells, the basic underlying distinction is in the DNA. Tumor cells harbor mutations, at least some of which are not present in non-tumor cells. Thus, a method of directly targeting cells containing specific mutations has potential for detection or treatment of cancer without the toxicity associated with more indirect approaches. Also, as mutations are a necessary component of malignancy, such a method is potentially applicable to all tumors. 

I propose a method by which several recently developed techniques can be utilized in a novel way to accomplish the goal of directly targeting mutations for cancer detection and therapy. The model can be summarized as...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2007 URL: http://precedings.nature.com/documents/1314/version/1
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Berberine induces caspase-independent cell death in colon tumor cells through activation of apoptosis-inducing factor 17
Lihong Wang; Liping Liu; Yan Shi; Hamwei Cao; Rupesh Chaturvedi; Tianhui Hu; Keith Wilson; D. Brent Polk; Fang Yan.
Berberine, an isoquinoline alkaloid derived from plants, is a traditional medicine for treating bacterial diarrhea and intestinal parasite infections. Although berberine has recently been shown to suppress growth of several tumor cell lines, information regarding the effect of berberine on colon tumor growth is limited. Here, we investigated the mechanisms underlying the effects of berberine on regulating the fate of colon tumor cells, specifically the immorto Min mouse colonic epithelial (IMCE) cells carrying the Apcmin mutation, and of normal colon epithelial cells, namely young adult mouse colon (YAMC) epithelial cells. Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2011 URL: http://precedings.nature.com/documents/6438/version/1
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Requirement of RIZ1 for cancer prevention by methyl-balanced diet 17
Wenyun Zhou; Sergio Alonso; Daisaku Takai; Shelly C. Lu; Fumiichiro Yamamoto; Manuel Perucho; Shi Huang.
The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics.
Ano: 2008 URL: http://precedings.nature.com/documents/1732/version/1
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A Linguistic Approach to Aligning Representations of Human Anatomy and Radiology 17
Pinar Wennerberg; Manuel Möller; Sonja Zillner.
To realize applications such as semantic medical image search different domain ontologies are necessary that provide complementary knowledge about human anatomy and radiology. Consequently, integration of these different but nevertheless related types of medical knowledge from disparate domain ontologies becomes necessary. Ontology alignment is one way to achieve this objective. Our approach for aligning medical ontologies has three aspects: (a) linguistic-based, (b) corpus-based, and (c) dialogue-based. We briefly report on the linguistic alignment (i.e. the first aspect) using an ontology on human anatomy and a terminology on radiology
Tipo: Manuscript Palavras-chave: Cancer; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3521/version/1
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