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11-amino-5-N-methyl-7-fluorine- quindoline derivatives: The Potential Anti-angiogenic Agents Targeting G-quadruplex Structure in Vascular Endothelial Cell Growth Factor Nature Precedings
Tian-miao Ou; Yu-jing Lu; Xiao-dong Wang; Zeng-yun An; Yan-ping Li; Zhi-shu Huang; Lian-quan Gu.
Vascular endothelial growth factor (VEGF), a pluripotent cytokine and angiogenic growth factor, plays crucial roles in embryonic development and tumour progression, and is over-expressed in many types of cancer and generally associated with tumour progression and survival rate. The polypurine/polypyrimide sequence located upstream (-89 to -43) of the promoter region of the human VEGF gene that can form specific G-quadruplex structures and raise the possibility for transcriptional control of the VEGF gene by G-quadruplex ligands. In the present study, we investigated the interaction between the 5-N-methyl-7-fluorine-quindoline derivatives (11-amino-5-N-methyl-7-fluorine- quindoline derivatives) and the G-rich sequence in VEGF's promoter and the...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2008 URL: http://precedings.nature.com/documents/1946/version/1
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11[beta]-hydroxysteroid dehydrogenase-type 2 evolved from an ancestral 17[beta]-hydroxysteroid dehydrogenase-type 2 Nature Precedings
Michael E. Baker.
11[beta]-hydroxysteroid dehydrogenase type-2 (11[beta]-HSD2) regulates the local concentration of cortisol that can activate the glucocorticoid receptor and mineralocorticoid receptor, as well as the concentration of 11-keto-testosterone, the active androgen in fish. Similarly, 17[beta]-HSD2 regulates the levels of testosterone and estradiol that activate the androgen receptor and estrogen receptor, respectively. Interestingly, although human 11[beta]-HSD2 and 17[beta]-HSD2 act at different positions on different steroids, these enzymes are paralogs. Despite the physiological importance of 11[beta]-HSD2 and 17[beta]-HSD2, details of their origins and divergence from a common ancestor are not known. An opportunity to understand their evolution is...
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology; Pharmacology; Bioinformatics; Evolutionary Biology.
Ano: 2010 URL: http://precedings.nature.com/documents/4649/version/1
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14-3-3ζ is Amplified, Overexpressed and Possesses Oncogenic Activities in Head and Neck Squamous Cell Carcinoma Nature Precedings
Mauting Lin; Carl D. Morrison; Susie Jones; Nehad Mohamed; Jason Bacher; Christoph Plass.
Gene amplification, a common mechanism for oncogene activation in cancers, has been used in the discovery of novel oncogenes. DNA amplification is frequently observed in head and neck squamous cell carcinomas (HNSCCs) where numerous amplification events and potential oncogenes have already been reported. Recently, we applied restriction landmark genome scanning (RLGS) to study gene amplifications in HNSCC and located novel amplified and uncharacterized regions in primary tumor samples. DNA amplification on 8q22.3, the location of 14-3-3[zeta] (YWHAZ, KCIP-1) is found in 30-40% HNSCC cases. Data obtained from fluorescent in-situ hybridization (FISH) and immunohistochemistry on HNSCC tissue microarrays confirmed frequent low-level 14-3-3[zeta] copy number...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2008 URL: http://precedings.nature.com/documents/1953/version/1
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3D model of amphioxus steroid receptor complexed with estradiol Nature Precedings
Michael E. Baker; David J. Chang.
The origins of signaling by vertebrate steroids are not fully understood. An important advance was the report that an estrogen-binding steroid receptor [SR] is present in amphioxus, a basal chordate with a similar body plan as vertebrates. To investigate the evolution of estrogen binding to steroid receptors, we constructed a 3D model of amphioxus SR complexed with estradiol. This 3D model indicates that although the SR is activated by estradiol, some interactions between estradiol and human ER[alpha] are not conserved in the SR, which can explain the low affinity of estradiol for the SR. These differences between the SR and ER[alpha] in the steroid-binding domain are sufficient to suggest that another steroid is the physiological regulator of the SR....
Tipo: Manuscript Palavras-chave: Cancer; Developmental Biology; Bioinformatics; Evolutionary Biology.
Ano: 2009 URL: http://precedings.nature.com/documents/3316/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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A Critical Evaluation of Clinical Trials in Cancer and Pharmacogenomics Nature Precedings
I. C. Baianu.
A critical overview of recent clinical trials in cancer is presented focused on signaling pathways blockers or inhibitors with a view to developing successful clinical trials employing personalized cancer therapies. Rational, pharmacogenomic strategies in cancer trials should be adopted that include specific molecular targeting based on adequate data for, and detailed modeling of, cancer cell genomes, modifications of cancer signaling pathways and epigenetic mechanisms. Novel translational oncogenomics research is rapidly expanding through the application of highly sensitive and specific advanced technology, research findings and computational tools and complex models to both pharmaceutical and clinical problems. Multiple sample analyses from several...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry; Developmental Biology; Genetics & Genomics; Immunology; Molecular Cell Biology; Pharmacology; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7052/version/1
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A Linguistic Approach to Aligning Representations of Human Anatomy and Radiology Nature Precedings
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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A network-based signaling mechanism of cancer development and progression Nature Precedings
Edwin Wang.
We conducted a comprehensive analysis of a manually curated human signaling network containing 1634 nodes and 5089 signaling regulatory relations by integrating cancer-associated genetically and epigenetically altered genes. We find that cancer mutating genes are enriched in positive signaling regulatory loops, whereas the cancer-associated methylating genes are enriched in negative signaling regulatory loops. We further characterized an overall picture of the cancer-signaling architectural and functional organization. From the network, we extracted an oncogene-signaling map, which contains 326 nodes, 892 links and the interconnections of mutated and methylated genes. The map can be decomposed into 12 topological regions or oncogene-signaling blocks,...
Tipo: Presentation Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2008 URL: http://precedings.nature.com/documents/2238/version/1
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A new mathematical model for radiation cell killing mechanism: Target cumulating model Nature Precedings
Zhao Liang; Wu Shixiu; Xie Congyin; Zhang Li.
There are numerous mathematical or statistical models have been given out for radiation cell killing mechanism. Unfortunately, none of the model could explain the mechanism perfectly. The more advanced model for it is still necessary to be researched. Following common assumption, a new theoretical model named "target cumulating" model is induced from the molecular and particle physics level. The result of theoretical calculation gives the equation of cell survival rate corresponding to delivered dose and other sensitivity parameters. In addition to fit the cell survival curve well, the new model showed advantages with comparing to previous models. Also, the new model predicts or explains some phenomenon that had been observed in...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2009 URL: http://precedings.nature.com/documents/2880/version/1
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A new potential radiosensitizer: ammonium persulfate modified WCNTs Nature Precedings
Jian-She Yang; Bo-Zhang Yu; Wen-Xin Li.
Radiotherapy plays a very important role in cancer treatment. Radiosensitizers have been widely used to enhance the radiosensitivity of cancer cells at given radiations. Here we fabricate multi-walled carbon nanotubes with ammonium persulfate, and get very short samples with 30-50 nanometer length. Cell viability assay show that f-WCNTs induce cell death significantly. We hypothesize that free radicals originated from hydroxyl and carbonyl groups on the surface of f-WCNTs lead cell damage.
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Chemistry.
Ano: 2007 URL: http://precedings.nature.com/documents/1421/version/1
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A novel regulator of the p53-mediated mitochondrial apoptotic pathway Nature Precedings
Bo Young Ahn; Diane Trinh; Laura Zajchowski; Sung-Woo Kim.
The p53 tumor suppressor protein induces apoptosis in response to genotoxic and environmental stress. Recent studies have revealed the existence of a transcription-independent mitochondrial p53 apoptosis pathway, however the mechanism regulating p53 translocation to mitochondria and subsequent initiation of apoptosis was not known. Here, we show that Tid1, also known as mtHsp40 or Dnaja3, interacts with p53 and directs its translocation to mitochondria in cells exposed to hypoxia. Overexpression of Tid1 in tumor cells promoted mitochondrial localization of both wildtype and mutant forms of p53 and was able to restore the pro-apoptotic activity of mutant p53 proteins that were otherwise unable to induce apoptosis. Tid1's mitochondrial signal...
Tipo: Manuscript Palavras-chave: Cancer; Molecular Cell Biology.
Ano: 2008 URL: http://precedings.nature.com/documents/1892/version/1
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A novel therapeutic strategy for pancreatic neoplasia using a novel RNAi platform targeting PDX-1 Nature Precedings
Shi-He Liu; Donald Rao; John Nemunaitis; Neil Senzer; David Dawson; Marie-Claude Gingras; Zhaohui Wang; Richard Gibbs; Michael Norman; Nancy Templeton; Francesco DeMayo; Kelly Stehling; William Fisher; Charles Brunicardi.
Bi-functional shRNA (bi-shRNA), a novel RNA interference (RNAi) effector platform targeting PDX-1 utilizing a systemic DOTAP-Cholesterol delivery vehicle, was studied in three mouse models of progressive pancreatic neoplasia. Species-specific bi-functional PDX-1 shRNA (bi-shRNAPDX-1) lipoplexes inhibited insulin expression and secretion while also substantially inhibiting proliferation of mouse and human cell lines via disruption of cell cycle proteins in vitro. Three cycles of either bi-shRNA<sup>mousePDX-1</sup> or shRNA<sup>mousePDX-1</sup> lipoplexes administered intravenously prevented death from hyperinsulinemia and hypoglycemia in a lethal insulinoma mouse model. Three cycles of...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics.
Ano: 2011 URL: http://precedings.nature.com/documents/6047/version/1
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A population-based study of glutathione-S-transferase M1, T1 and P1 genotypes Nature Precedings
Monika Sivoňová; Iveta Waczulíková; Dušan Dobrota; Tatiana Matáková; Jozef Hatok; Peter Račay; Ján Kliment.
A retrospective study on healthy, unrelated subjects was conducted in order to estimate population glutathione-S-transferases (GST) genotype frequencies in Slovak population of men and compare our results with already published data (GSEC project)^1^. A further aim of the study was to evaluate frequencies of the _GST_ polymorphisms also in patients with prostate cancer in order to compare the evaluated proportions with those found in the control subjects. Analysis for the _GST_ gene polymorphisms was performed by PCR and PCR-RFLP. We found that the proportions are not significantly different from those estimated in a European multicentre study or from the results published by another group in Slovakia. We found significantly increased age-standardized...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics.
Ano: 2008 URL: http://precedings.nature.com/documents/2559/version/1
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A potential diagnostic biomarker: Proteasome LMP2/b1i-differential expression in human uterus neoplasm Nature Precedings
Takuma Hayashi; Akiko Horiuchi; Hiroyuki Aburatani; Nobuo Yaegashi; Susumu Tonegawa; Ikuo Konishi.
Uterine leiomyosarcoma (ULMS) develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine ULMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker which distinguishes malignant ULMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine ULMS, to establish a treatment method. Proteasome low-molecular mass polypeptide 2(LMP2)/b1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We...
Tipo: Manuscript Palavras-chave: Cancer.
Ano: 2012 URL: http://precedings.nature.com/documents/7082/version/1
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A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies. Nature Precedings
Carl Gregory; Narae Lee; Angela Smolarz; Scott Olson; Odile David; Jacob Reiser; Robert Kutner; Najat Daw; Darwin Prockop; Edwin Horwitz.
Canonical Wnt signaling is an osteo-inductive signal that promotes bone repair through acceleration of osteogenic differentiation by progenitors. Dkk-1 is a secreted inhibitor of canonical Wnt signaling and thus inhibits osteogenesis. To examine a potential osteo-inhibitory role of Dkk-1 in osteosarcoma (OS), we measured serum Dkk-1 in pediatric patients with OS (median age, 13.4 years) and found it to be significantly elevated. We also found that Dkk-1 was maximally expressed by the OS cells at the tumor periphery and _in vitro_ Dkk-1 and RANKL are co-expressed by rapidly proliferating OS cells. Both Dkk-1 and conditioned media from OS cells reduces osteogenesis by human mesenchymal cells and by immuno-depletion of Dkk-1, or by adding a GSK3[beta]...
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer.
Ano: 2007 URL: http://precedings.nature.com/documents/130/version/1
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A prelude report on molecular docking of HER2 protein towards comprehending anti-cancer properties of saponins from Solanum tuberosum Nature Precedings
Puneet K. Singh; Pratyoosh Shukla.
Saponins are extensively known for many biological activities e.g. antimicrobial, anti-palatability, anti-cancer and hemolytic. As cancer cells have a more cholesterol-like compound in their membrane structure the saponins bind cholesterol due to their natural affinity to bind cancer cell membrane. This prevents them from entering the body through the intestinal tract, where they have the ability to attach themselves to vital organs and grow. This study reports the effective use of lower dose saponins like immunotoxin so that they can inhibit the proliferation of cancerous pancreatic cells. The investigation of pancreatic cancer metabolic pathway it was found that proteins 3H3B produced by genes HER-2 are involved in the enhancement of this type of cancer....
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/7147/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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A Roadmap of Cancer Systems Biology Nature Precedings
Edwin Wang.
What is cancer systems biology? Why should we conduct systems biology research in cancer? What is the relationships between systems biology and personalized medicine? How do we conduct cancer systems biology research? This paper illustrates strategies, procedures and computational techniques for the study of cancer systems biology by focusing on network reconstruction, network analysis and modeling. Finally, certain challenges and hurdles in cancer systems biology will also be discussed.
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4322/version/2
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A Roadmap of Cancer Systems Biology Nature Precedings
Edwin Wang.
What is cancer systems biology? Why should we conduct systems biology research in cancer? What is the relationships between systems biology and personalized medicine? How do we conduct cancer systems biology research? This paper illustrates strategies, procedures and computational techniques for the study of cancer systems biology by focusing on network reconstruction, network analysis and modeling. Finally, certain challenges and hurdles in cancer systems biology will also be discussed.
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2010 URL: http://precedings.nature.com/documents/4322/version/1
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A subset of co-expressed genes in Slug-based cancer mesenchymal transition signature remains coexpressed in normal samples in a tissue-specific manner Nature Precedings
Weiyi Cheng; Dimitris Anastassiou.
A recently identified gene expression signature of EMT markers containing the transcription factor Slug was found present in samples from many publicly available cancer gene expression datasets of multiple cancer types except leukemia. We also found many of these genes co-expressed in human cancer xenografted cells, but not in mouse stroma cells, suggesting that the signature is largely produced by cancer cells undergoing some type of EMT. Here we report that a partial signature consisting of a subset of the co-expressed genes of the full signature, including at least Slug (SNAI2), collagens COL1A1, COL1A2, COL3A1, COL6A3 and genes DCN and LUM, is also present in leukemia, in which case it is also strongly associated with the chemokine CXCL12 (aka SDF1)....
Tipo: Manuscript Palavras-chave: Biotechnology; Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2012 URL: http://precedings.nature.com/documents/6813/version/1
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