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Suppression of TNF-α induced NFκB activity by gallic acid and its semi-synthetic alkyl-gallates: Possible role in cancer chemoprevention Nature Precedings
Suaib Luqman; Mauro C. C. Morais; Tamara P. Kondratyuk; Maicon S. Petronio; Luis O. Regasini; Dulce H. S. Silva; Vanderlan S. Bolzani; Christiane P. Soares; John M. Pezzuto.
NFκB, a transcription factor, regulates the expression of a number of genes involved in carcinogenesis. Thus, agents that can suppress NFκB activation have the potential to suppress carcinogenesis. In the present investigation, gallic acid was isolated from Alchornea glandulosa (Euphorbiaceae) and eight semi-synthetic alkyl gallates were prepared from the reaction of the corresponding alcohols with gallic acid at 80oC for 48 h in good yields (70-97%). All the compounds were evaluated against TNF-α-induced NFκB activation with stable transfected 293/NFκB-Luc human embryonic kidney cells. Treatment of cells with gallic acid and the gallate esters (20 µg/ml) significantly reduced TNF-α...
Tipo: Poster Palavras-chave: Cancer; Chemistry; Molecular Cell Biology; Pharmacology.
Ano: 2012 URL: http://precedings.nature.com/documents/6922/version/1
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A randomised controlled trial of an intervention to promote early presentation of breast cancer in older women: effect on breast cancer awareness Nature Precedings
Louise Linsell; Lindsay J. L. Forbes; Marcia Kapari; Caroline Burgess; Lynne Omar; Lorraine Tucker; Amanda J. Ramirez.
There is virtually no evidence for the effectiveness of interventions to promote early presentation in breast cancer. We tested the efficacy of an intervention to equip older women with the knowledge, skills, confidence and motivation to detect symptoms and seek help promptly, with the aim of promoting early presentation with breast cancer symptoms. We randomised 867 women aged 67 to 70 attending for their final routine appointment on the UK NHS Breast Screening Programme to receive: a scripted ten-minute interaction with a radiographer plus a booklet; a booklet alone; or usual care. The primary outcome was whether or not a woman was breast cancer aware based on knowledge of breast cancer symptoms and age-related risk; and reported breast checking. At one...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2009 URL: http://precedings.nature.com/documents/3816/version/1
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Involvement of proteasome b1i subunit, LMP2, on uterine leiomyosarcma tumorigenesis Nature Precedings
Takuma Hayashi; Akiko Horiuchi; Ikuo Konishi.
Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone; however, the development of human uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic-biomarker, which distinguishes malignant human uterine LMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with human uterine LMS, in order to establish a clinical treatment method. Homozygous deficient mice for a proteasome...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2011 URL: http://precedings.nature.com/documents/6478/version/1
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Study Of Phenothiazine On p53 Core Domain Mutant Y220C: Finding The Anti-tumor Activity Of Phenothiazine Nature Precedings
Asif Husain Naqvi; Hardik H. Sheth; Vijay Kumar; Suchindran H S; Vivek Gupta.
The tumor suppressor protein p53 is a transcription factor that plays a key role in the prevention of cancer development. The p53 cancer mutation Y220C induces formation of a cavity on the protein's surface that can accommodate stabilizing small molecules. We have attempted with the help of virtual screening and molecular docking approach using Lamarckian Genetic Algorithm to elucidate the extent of specificity of p53 cancer mutation Y220C towards different class of Phenothiazines (an anti-cancer agent). 

The 393 residue p53 tumor suppressor protein exists in a dynamic equilibrium to form homotetramers. Each chain comprises several functional domains. The N terminal part of the protein consists of the...
Tipo: Presentation Palavras-chave: Cancer; Pharmacology; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6135/version/1
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Information homeostasis as a fundamental principle governing the cell division and death Nature Precedings
Arvind Kumar; Harinder P. Singh.
To express genetic information with minimal error is one of the key functions of a cell. Here we propose an information theory based phenomenological model for the expression of genetic information. Based on the model we propose, the concept of "information homeostasis" ensures that genetic information is expressed with minimal error. We suggest that together with energy homeostasis, information homeostasis is a fundamental working principle of a biological cell. This model proposes a novel explanation of why a cell divides and why it stops to divide and thus provides novel insight into oncogenesis and various neuro-degenerative diseases. Moreover, the model suggests a theoretical framework to understand cell division and death, beyond...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics.
Ano: 2011 URL: http://precedings.nature.com/documents/5940/version/1
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Regulation of Phosphatase Homologue of Tensin Protein Expression by Bone Morphogenetic Proteins in Prostate Epithelial Cells Nature Precedings
Travis Jerde; Zhong Wu; Dan Theodorescu; Wade Bushman.
Phosphatase homologue of tensin (PTEN) is the key endogenous inhibitor of phosphoinositide signaling and is the most commonly mutated gene in human prostate cancer. The bone morphogenetic proteins (BMPs) are secreted developmental signaling molecules known to promote differentiation in the prostate. BMP ligands have been shown to inhibit prostate cancer cell line proliferation and tumor growth and expression of BMPs, BMP ligands, receptors and signaling effectors are diminished in prostate cancer. A previous report in the colon led us to investigate the potential mechanistic relationship between PTEN and BMP signaling in prostate epithelial cells. We show here that BPM signaling positively regulates PTEN in normal and malignant prostate cells by increasing...
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4311/version/1
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Myosin II isoforms with separate but linked functions determine the fate of lamellipodia extension during cell spreading Nature Precedings
Venkaiah Betapudi.
Non-muscle myosin II role has been implicated in the extension of lamellipodia, a critical step in the initiation of directed cell migration, invasion and other cellular processes, but the mechanistic details are limited to driving retrograde actin filaments. The present study reveals distinct localization of myosin IIA and IIB with an unexpected opposite mechanical roles in mediating lamellipodia extension during spreading. Attachment of cells to matrix is impaired in the absence of either isoforms, but differential regulation of focal contacts formation occurs in myosin IIA^-^; and IIB^-^; cells. Spreading cells expressing both isoforms display an organized actin network consisting of retrograde filaments, arcs and central filaments. Loss of actin arcs...
Tipo: Manuscript Palavras-chave: Cancer; Microbiology; Molecular Cell Biology.
Ano: 2009 URL: http://precedings.nature.com/documents/2868/version/1
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QSAR and Docking Studies of Gallic Acid Derivatives for Anticancer and Immunomodulatory Activity Nature Precedings
Dharmendra Kumar Yadav; Feroz Khan; Arvind Singh Negi.
Immuno-modulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. In the present communication QSAR and molecular docking studies for immuno-modulatory activity of derivatives of gallic acid were performed. Molecular docking studies showed higher binding affinity with INFα-2, IL-6, and IL-4 receptors. Binding site residues indicate hydrogen bonds formation with gallic acid derivative compounds G-3, G-4, G-5, G-6, G-7 and G-10. Further screening through quantitative structure activity relationship model establishes the immuno-modulatory activity of the compounds G-4, G-7, G-9, G-10, G-12 and G-13. Activity was predicted through a robust statistical model, developed by forward feed multiple...
Tipo: Presentation Palavras-chave: Biotechnology; Cancer; Chemistry; Pharmacology; Bioinformatics; Plant Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6620/version/1
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Inflammation targets specific organs for cancer in carriers of BRCA1/2 pathway mutations Nature Precedings
Bernard Friedenson.
Women who inherit a defective BRCA1 or BRCA2 gene have risks for breast/ovarian cancer that are so high and apparently so selective that many mutation carriers choose to have the most likely targets for cancer surgically removed. Recent research has focused on better methods of treating such seemingly unavoidable hereditary cancers. Prevention has received much less attention so a positive test result for a cancer gene leaves carriers with very limited options. 
In order to prevent BRCA1/2 related cancers, it may be important to understand why they seem to occur only in certain characteristic organs. Results here show that mutations in a pathway depending on BRCA1/2 gene products magnify cancer risks from chronic infection and...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Immunology; Microbiology.
Ano: 2010 URL: http://precedings.nature.com/documents/4225/version/1
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Diagnostic robustness of DNA microarrays in the classification of acute leukemia Nature Precedings
Marie Loh; Adrian Mondry.
Countless statistical methods have been described for the analysis of DNA microarrays, and each yields distinct results. This raises the question whether DNA microarrays are robust diagnostic tools.

In order to address this issue, we compared five formally similar statistical tests for gene selection on a single data set derived from acute leukemia patients. Inter-test agreement of gene selection, of sample classification and with standard clinical diagnosis was calculated using Cohen's κ-score.

The inter-test agreement scores were 0.15 < κ < 0.68 for gene selection, and 0.60 < κ < 0.89 for sample classification....
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Genetics & Genomics; Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2007 URL: http://precedings.nature.com/documents/1056/version/1
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Cancer chemopreventive action of α-(-)-bisabolol, a sesquiterpene alcohol involves inhibition of cathepsin D and ornithine decarboxylase via tramping nitric oxide Nature Precedings
Suchita Srivastava; Suaib Luqman.
Terpenoids, traditionally used for cosmetic and medicinal purposes, are currently being explored as cancer chemopreventive as well as chemotherapeutic agent in clinical trials. α-(-)-bisabolol, a naturally occurring monocyclic sesquiterpene alcohol is a major component of essential oil of chamomile (Matricaria recutita L., Chamomilla recutita L., Matricaria chamomilla; Family Asteraceae). As substantiated previously, α-(-)-bisabolol is known to have antimicrobial, anti-irritant, anti-inflammatory and anti-allergic properties. It also affects cell viability and growth of various human and murine cell lines by either inducing apoptosis or suppressing Akt activation or down regulating expression of some genes implicated in carcinogenesis....
Tipo: Poster Palavras-chave: Cancer; Pharmacology.
Ano: 2012 URL: http://precedings.nature.com/documents/6902/version/1
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Lead identification and docking studies of metastatic protein human mitogen activated protein kinase kinase4 Nature Precedings
Harika Meduru; Dibyabhaba Pradhan; Manne Munikumar; Amineni Umamaheswari.
Human dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4) is a direct activator of MAP kinases in response to various environmental stresses or mitogenic stimuli. Upon phosphorylation, MAP2K4 has been shown to activate MAPK8, MAPK9 and MAPK14/p38 but not MAPK1/ERK2 or MAPK3/ERK1. Over expression of MAP2K4 causes carcinogenic effects, such as ovarian cancer, colorectal cancer, prostate cancer and pancreatic cancer. Our present study was carried out to design a potent drug molecule against MAP2K4 to control over expression. As there is no experimentally determined structure for MAP2K4, the homology modeling technique of Modeller9v7 was implemented to generate a MAP2K4 3D model based on the co-crystal structure of MAP2K6 (PDB ID: 3FME) with...
Tipo: Poster Palavras-chave: Cancer; Pharmacology; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/5457/version/1
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3D models of lamprey corticoid receptor complexed with 11-deoxycortisol and deoxycorticosterone Nature Precedings
Michael E. Baker; Kayla Y. Uh; Paiyuam Asnaashari.
The serum of Atlantic sea lamprey, a basal vertebrate, contains two corticosteroids, 11-deoxycortisol and deoxycorticosterone. Only 11-deoxycortisol has high affinity [Kd~3 nM] for the corticoid receptor [CR] in lamprey gill cytosol. To investigate the binding of 11-deoxycortisol to the CR, we constructed 3D models of lamprey CR complexed with 11-deoxycortisol and deoxycorticosterone. These 3D models reveal that Leu-220 and Met-299 in lamprey CR have contacts with the 17[alpha]-hydroxyl on 11-deoxycortisol. Lamprey CR is the ancestor of the mineralocorticoid receptor [MR] and glucocorticoid receptor [GR]. Unlike human MR and human GR, the 3D model of lamprey CR finds a van der Waals contact between Cys-227 in helix 3 and Met-264 in helix 5. Mutant...
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology; Pharmacology; Bioinformatics; Evolutionary Biology.
Ano: 2011 URL: http://precedings.nature.com/documents/6216/version/1
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NPO: Ontology for Cancer Nanotechnology Research Nature Precedings
Dennis Thomas; Rohit Pappu; Nathan Baker.
We present the design and development of NanoParticle Ontology (NPO). The ontology is implemented in the Ontology Web Language (OWL). The domain terms in NPO currently represent entities, which describe knowledge about physical, chemical, and functional properties of nanoparticles characterized in cancer nanotechnology research. The upper-level of NPO is formed using terms from the Basic Formal Ontology (BFO).
Tipo: Manuscript Palavras-chave: Cancer; Bioinformatics.
Ano: 2009 URL: http://precedings.nature.com/documents/3514/version/1
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Connecting Seed Lists of Mammalian Proteins Using Steiner Trees Nature Precedings
Amelia G. White; Avi Ma'ayan.
Multivariate experiments and genomics studies applied to mammalian cells often produce lists of genes or proteins altered under treatment/disease vs. control/normal conditions. Such lists can be identified in known protein-protein interaction networks to produce subnetworks that “connect” the genes or proteins from the lists. Such subnetworks are valuable for biologists since they can suggest regulatory mechanisms that are altered under different conditions. Often such subnetworks are overloaded with links and nodes resulting in connectivity diagrams that are illegible due to edge overlap. In this study, we attempt to address this problem by implementing an approximation to the Steiner Tree problem to connect seed lists of mammalian...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Molecular Cell Biology; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/1768/version/1
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Identification of small molecule inhibitor of cyclophilin-A using high throughput virtual screening and molecular docking Studies Nature Precedings
Pallapotu Navya; I Vani Priyadarshini; Amineni Umamaheswari.
The inhibitors of cyclophilin A (CyPA) have drawn a great deal of attention due to their promising potential as small-molecule therapeutics for the treatment of cardiovascular diseases. This ultimately prompts to explore structural geometries of these inhibitors to obtain insights on next generation CyPA inhibitors through rational drug designing. Herein, 2D similarity search for the seven CyPA inhibitors was performed using Ligand.Info database. Small subsets of 2800 molecules from one million compounds were predicted to have activity against cardiovascular drug target CyPA. The binding strength of 2800 ligands with CyPA was assessed through molecular docking analysis using Schrödinger software 2011. The CyPA co-crystal structure and ligand...
Tipo: Presentation Palavras-chave: Cancer; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6529/version/1
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Antibodies targeting Cancer stem cells, A novel pattern in Immunotherapy Nature Precedings
Sarfaraz Alam.
Antibody targeting of cancer is showing clinical and commercial success after deep research and development over the last 3 decades. They have the great potential to deliver long-term cures but a shift in thinking towards a cancer stem cell (CSC) model for tumour development is certain to have an impact on how antibodies are selected and developed, the targets they bind to and the drugs used in combination with them. CSCs have been identified from many human tumours and share many of the characteristics of normal stem cells such as the ability to renew and metabolically or physically protect themselves from xenobiotic and DNA damage. Targeting CSCs could be a strategy to improve the outcome of cancer therapy. Monoclonal antibodies are clinically and...
Tipo: Presentation Palavras-chave: Cancer; Immunology; Molecular Cell Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/5428/version/1
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High-order chromatin architecture determines the landscape of chromosomal alterations in cancer Nature Precedings
Geoffrey Fudenberg; Gad Getz; Matthew Meyerson; Leonid Mirny.
The rapid growth of cancer genome structural information provides an opportunity for a better understanding of the mutational mechanisms of genomic alterations in cancer and the forces of selection that act upon them. Here we test the evidence for two major forces, spatial chromosome structure and purifying (or negative) selection, that shape the landscape of somatic copy-number alterations (SCNAs) in cancer. Using a maximum likelihood framework we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule (FG) model. This analysis provides evidence that the distribution of chromosomal alterations in cancer is spatially related to...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2011 URL: http://precedings.nature.com/documents/6356/version/1
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Synchronized Mammalian Cells in Culture: A Comparison of Normal and KB Cancer Cell Growth Nature Precedings
I. C. Baianu.
Experimentation and tests with cells in culture and cell synchronization or synchrony are important in order to be able to make both reliable and high-sensitivity measurements. This is also very important for mechanistic studies of cell division control, oncogenesis and tumor growth. A comparison is made in this article between the initially synchronized cell growth of rabbit and KB cells in synchronized cultures.
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry; Developmental Biology; Genetics & Genomics; Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7128/version/1
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The Hepatocellular Hypoxia Criteria:2’Nitroimidazole Effect on Hepatocyte Carbohydrate Metabolizing Enzymes Nature Precedings
Rakesh Sharma.
Aim: to understand the 2’-nitroimidazole induced hypoxia and liver cell interaction, we proposed a “Hapatocellular Hypoxia Criteria”. Hypothesis: The nitroimidazole induced metabolic energy loss and oxygen depletion (hypoxia) in liver cell mitochondria causes the phagocytosis. Based on it, ten control subjects with 2’-nitroimidazole therapy were studied for their carbohydrate metabolizing enzymes in serum and hepatocellular enzymes in liver biopsy tissues. Materials and Methods: Proven ten control subjects were studied for hypoxia by enzyme assays. The 2’nitroimidazole treated paired ten subjects were studied for hypoxia using enzyme assays and hepatocellular cytomorphology by electron microscopy....
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Pharmacology.
Ano: 2008 URL: http://precedings.nature.com/documents/2738/version/1
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