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Total 146 results found since Jan 2013.

Abstract 4405: Tumor-targeted nanotherapeutics
Directing anticancer agents specifically to tumors and/or cancer cells by targeting specific extracellular receptors fulfills the following three most important tasks: (1) preventing or at least substantially limiting adverse side effects on healthy tissues, (2) enhancing drug internalization by cancer cells, and (3) overcoming (at least in part) resistance mechanisms that are based on the active efflux of exogenous drugs from cancer cells.We developed several tumor-targeted nanoscale-based formulations: various nanocarriers (liposomes, lipid nanoparticles, dendrimers, polymers, quantum dots, mesoporous silica and supermag...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Garbuzenko, O. B., Kuzmov, A., Sapiezynski, J. E., Taratula, O., Shah, V., Zhang, M., Savla, R., John, S., Rodriguez-Rodriguez, L., Minko, T. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 5504: Penfluridol suppresses triple negative breast cancer metastasis to brain by inhibiting {alpha}6{beta}4 integrins
Breast cancer is the second leading cause of cancer related deaths in the United States. Breast tumor metastasis to brain is primary cause of deaths. Brain metastasis of triple negative breast cancer cells (TNBC) is highly resistant to current therapies and is a cause of reduced survival rates in patients. In the current study, we evaluated the anti-cancer effects of penfluridol, a first generation antipsychotic drug against three different highly aggressive TNBC cell line. The IC50 of penfluridol was around 6 μM in 4T1, MDA-MB-231 and HCC-1806, breast cancer cells respectively. Our result showed that the expression of in...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ranjan, A., Gupta, P., Srivastava, S. Tags: Experimental and Molecular Therapeutics Source Type: research

miR-92a Corrects CD34+ Cell Dysfunction in Diabetes by Modulating Core Circadian Genes Involved in Progenitor Differentiation
In this study, we examine expression of the clock genes Clock, Bmal, Per1, Per2, Cry1, and Cry2 in CD34+ cells of diabetic and nondiabetic origin and determine the small encoding RNA (miRNA) profile of these cells. The degree of diabetic retinopathy (DR) was assessed. As CD34+ cells acquired mature endothelial markers, they exhibit robust oscillations of clock genes. siRNA treatment of CD34+ cells revealed Per2 as the only clock gene necessary to maintain the undifferentiated state of CD34+ cells. Twenty-five miRNAs targeting clock genes were identified. Three of the miRNAs (miR-18b, miR-16, and miR-34c) were found only in...
Source: Diabetes - November 24, 2015 Category: Endocrinology Authors: Bhatwadekar, A. D.; Yan, Y.; Stepps, V.; Hazra, S.; Korah, M.; Bartelmez, S.; Chaqour, B.; Grant, M. B. Tags: Complications Source Type: research

Cyclin E1 plays a key role in balancing between totipotency and differentiation in human embryonic cells
STUDY HYPOTHESIS We aimed to investigate if Cyclin E1 (CCNE1) plays a role in human embryogenesis, in particular during the early developmental stages characterized by a short cell cycle. STUDY FINDING CCNE1 is expressed in plenipotent human embryonic cells and plays a critical role during hESC derivation via the naïve state and, potentially, normal embryo development. WHAT IS KNOWN ALREADY A short cell cycle due to a truncated G1 phase has been associated with the high developmental capacity of embryonic cells. CCNE1 is a critical G1/S transition regulator. CCNE1 overexpression can cause shortening of the cell c...
Source: Molecular Human Reproduction - November 30, 2015 Category: Molecular Biology Authors: Krivega, M. V., Geens, M., Heindryckx, B., Santos-Ribeiro, S., Tournaye, H., Van de Velde, H. Tags: Articles Source Type: research

Abstract A65: A novel regulatory mechanism involving Ras-mediated activation of the zinc-finger transcription factor, SAF-1/MAZ induces EGFR/HER1 expression in breast cancer cells
Tumor microenvironment (TME) plays a critical role in tumor growth, invasion and metastasis. In TME, epidermal growth factor receptor (EGFR) family members, including HER1, HER2, HER3 and HER4, are involved in determining aggressive growth of breast cancer due to their ability to transduce the growth promoting functions of growth factors. This activity is potentiated by the over-expression of these receptor molecules in cancer cells. To reduce the activity of EGFR molecules, various inhibitors have been developed. EGFR/HER1 tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, show antitumor activity but these drugs ...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Ray, A., Havis, B., Ray, B. Tags: EGFR / Her2: Poster Presentations - Proffered Abstracts Source Type: research

Abstract PR06: Analysis of enhancer transcription reveals novel gene regulatory networks in breast cancer
Enhancer transcription is a defining feature of active enhancers. We and others have shown that enhancers that produce transcripts (so called “eRNAs”) are more likely to (1) be associated with active chromatin marks, such as H3K4me1 and K3K27ac, (2) loop to target gene promoters, and (3) be associated with target gene activation. Thus, enhancer transcription is a good predictor of active enhancers. In this regard, we have shown that enhancer transcription can be used in the absence of any other genomic information to predict enhancers. We have used Global Run-On coupled deep sequencing (GRO-seq) in 14 different breast ...
Source: Cancer Research - January 14, 2016 Category: Cancer & Oncology Authors: Franco, H. L., Nagari, A., Xi, Y., Li, W., Richardson, D., Tanaka, K., Li, J., The CPRIT LONESTAR Consortium, Barton, M. C., Shi, X., Keyomarsi, K., Bedford, M. T., , Dent, S. Y. R., Kraus, W. L. Tags: Enhancers Source Type: research

Abstract A12: Establishment of myeloid lineage cell line that resembles myeloid-derived suppressive cells
Myeloid-derived suppressive cells (MDSCs) are inflammatory cells that play critical roles in promoting cancer growth and metastasis. In order to facilitate characterization of biochemical and cellular mechanisms of MDSCs, it is urgent to establish an "MDSC-like" cell line for pharmacological and immunotherapeutic applications. Lysosomal acid lipase (LAL) is a critical lipid enzyme in the metabolic signaling pathway that hydrolyzes cholesteryl esters (CE) and triglycerides (TG) in lysosomes. In mice, lack of LAL in genetically ablated knockout mice (lal-/-) shows systemic expansion of MDSCs, which directly stimulate cancer ...
Source: Molecular Cancer Research - January 15, 2016 Category: Cancer & Oncology Authors: Yan, C., Ding, X., Wu, L., Du, H. Tags: Cancer Metabolic Pathways: Poster Presentations - Proffered Abstracts Source Type: research

Id: 85: cross-talk between estrogen receptors and insulin-like growth factor type-1 receptor modulates human prostate stem/progenitor cell amplification
We previously demonstrated that estrogen regulates human prostate stem/progenitor cell amplification by directly targeting estrogen receptors (ERs); ERα stimulates whereas ERβ suppresses stem cell self-renewal. In addition to ERα and ERβ, we find that human prostate stem/progenitor cells express robust level of IGF-1R. Since ER actions can be modified by IGF-1R through ligand-independent ER phosphorylation, we herein sought to characterize potential cross-talk between estrogen and IGF-1 signaling pathways in regulating human prostate stem/progenitor cell amplification. Human prostate stem/progenitor c...
Source: Journal of Investigative Medicine - March 21, 2016 Category: Research Authors: Rinaldi, J., Hu, W., Majundar, S., Hu, D., Prins, G., Justulin, L., Felisbino, S. Tags: Endocrinology/Metabolism Source Type: research

Hu Antigen R Is a Positive Regulator of ALS-Associated RNA Binding Proteins TDP-43 and FUS (P5.008)
Conclusions: 1. ALS-associated RNA abnormalities may stem from disruption of a network of RBPs. 2. HuR positively regulates TDP-43 and FUS through posttranscriptional mechanism. 3. Loss of HuR-mediated RNA processing in astrocytes may participate in ALS pathogenesis. Study supported by: Study supported by NIH/NINDS Grant NS057664, NS064133Disclosure: Dr. Lu has nothing to disclose. Dr. Zheng has nothing to disclose. Dr. Si has nothing to disclose. Dr. King has nothing to disclose.
Source: Neurology - April 3, 2016 Category: Neurology Authors: Lu, L., Zheng, L., Si, Y., King, P. Tags: Neuromuscular and Clinical Neurophysiology Poster Discussion Session Source Type: research

The Role of Staufen1 in Aberrant RNA Metabolism in SCA2 (P6.396)
Conclusions: Our results unravel a novel function for Staufen1 in aberrant RNA processing events and indicate its role in SCA2 pathogenesis. Our results further support a role for aberrant RNA metabolism in neurodegeneration thereby revealing its potential as a therapeutic target. Study Supported by: This work was supported by Grants RO1NS33123 and RC4NS073009 from the National Institutes of Neurological Disorders and Stroke to SMP.Disclosure: Dr. Paul has nothing to disclose. Dr. Dansithong has nothing to disclose. Dr. Figueroa has nothing to disclose. Dr. Scoles has nothing to disclose. Dr. Pulst has received personal co...
Source: Neurology - April 3, 2016 Category: Neurology Authors: Paul, S., Dansithong, W., Figueroa, K., Scoles, D., Pulst, S. Tags: Movement Disorders: Spinocerebellar Ataxias Source Type: research

17 {beta}-Estradiol promotes vascular endothelial growth factor expression via the Wnt/{beta}-catenin pathway during the pathogenesis of endometriosis
STUDY HYPOTHESIS Do estrogen and Wnt/β-catenin signaling promote vascular endothelial growth factor (VEGF) expression in endometriosis and how? STUDY FINDING 17β-Estradiol (E2)-drives β-catenin triggered up-regulation of VEGF in effector human primary endometrial stromal cells (ESCs) and thus enhances their ability to establish a new blood supply to the human exfoliated endometrium. WHAT IS KNOWN ALREADY Implantation and survival of exfoliated endometrium is crucially dependent on neovascularization and Wnt/β-catenin signaling plays an important role in stimulating angiogenesis. STUDY DESIGN, SAMPLES...
Source: Molecular Human Reproduction - July 11, 2016 Category: Molecular Biology Authors: Zhang, L., Xiong, W., Xiong, Y., Liu, H., Liu, Y. Tags: Original Research Source Type: research

Oncostatin M and Adipose Tissue Homeostasis Molecular Bases of Disease
Oncostatin M (OSM) is a multifunctional gp130 cytokine. Although OSM is produced in adipose tissue, it is not produced by adipocytes. OSM expression is significantly induced in adipose tissue from obese mice and humans. The OSM-specific receptor, OSM receptor β (OSMR), is expressed in adipocytes, but its function remains largely unknown. To better understand the effects of OSM in adipose tissue, we knocked down Osmr expression in adipocytes in vitro using siRNA. In vivo, we generated a mouse line lacking Osmr in adiponectin-expressing cells (OSMRFKO mice). The effects of OSM on gene expression were also assessed in vitro ...
Source: Journal of Biological Chemistry - August 11, 2016 Category: Chemistry Authors: Elks, C. M., Zhao, P., Grant, R. W., Hang, H., Bailey, J. L., Burk, D. H., McNulty, M. A., Mynatt, R. L., Stephens, J. M. Tags: Signal Transduction Source Type: research

ID2 mediates the transforming growth factor-{beta}1-induced Warburg-like effect seen in the peritoneum of women with endometriosis
STUDY QUESTION Is inhibitor of DNA-binding protein 2 (ID2) a mediator of the transforming growth factor (TGF)-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis? SUMMARY ANSWER The TGF-β1-induced changes in the metabolic phenotype of peritoneal mesothelial cells from women with endometriosis are mediated through the ID2 pathway. WHAT IS KNOWN ALREADY TGF-β1 induces the metabolic conversion of glucose to lactate via aerobic glycolysis (the ‘Warburg effect’) in the peritoneum of women with endometriosis, through increased expression of the transcription factor hypox...
Source: Molecular Human Reproduction - September 6, 2016 Category: Molecular Biology Authors: Young, V. J., Ahmad, S. F., Brown, J. K., Duncan, W. C., Horne, A. W. Tags: Original article Source Type: research

Abstract P5-08-24: How do real-world treatment patterns compare to guideline recommendations for first-line metastatic breast cancer patients in US community clinics?
Epidemiological studies have indicated that alcohol consumption is an established risk factor for breast cancer. The association of alcohol consumption and breast cancer is more pronounced in ER+ cases than in ER- cases. However, this molecular mechanism remains to be determined. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular tRNAs and 5S rRNA production, increasing translational capacity to promote cell transformation and tumor formation. Our results reveal that alcohol increases Pol III gene transcription in both normal and cancer breast cell lines. The induction of Pol III genes by alcohol ...
Source: Cancer Research - February 13, 2017 Category: Cancer & Oncology Authors: L Chu, B Yoo, G Carrigan, C Lai, M Beattie, C Reyes Tags: Poster Session Abstracts Source Type: research

Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase.
Abstract Poly(ADP-ribosylation) of proteins following DNA damage is well studied and the use of poly(ADP-ribose) polymerase (PARP) inhibitors as therapeutic agents is an exciting prospect for the treatment of many cancers. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleave glycosidic bonds, rapidly reversing the action of PARP enzymes. Like addition of poly(ADP-ribose) (PAR) by PARP, removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for continued replication at perturbed forks. Here we use siRNA to show a synthetic lethal relation...
Source: DNA Repair - February 16, 2017 Category: Genetics & Stem Cells Authors: Gravells P, Grant E, Smith KM, James DI, Bryant HE Tags: DNA Repair (Amst) Source Type: research