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Total 146 results found since Jan 2013.

Abstract 1428: Targeting RRM2 by siRNA inhibits cellular invasion and represents a rational approach for inhibition of metastasis of head and neck and lung cancers
Background: Ribonucleotide reductase subunit M2 (RRM2) has been frequently observed to be aberrantly overexpressed in various tumors. RRM2 is a key enzyme, and essential regulator of balanced deoxyribonucleotides (dNTPs). It is critical for DNA replication and repair, and hence cell survival. In addition to DNA synthesis, it has been reported to modulate cellular invasiveness. However, the mechanisms through which RRM2 affects the invasive phenotype have not been elucidated.Methods: We evaluated the expression of RRM2 protein in metastatic (n = 40) and non-metastatic (n = 40) head and neck squamous cell carcinoma (HNSCC) t...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Rahman, M. A., Amin, A. R. M. R., Zhang, J., Nannapaneni, S., Saba, N. F., Chen, Z. G., Shin, D. M. Tags: Tumor Biology Source Type: research

Abstract 768: A kinome-wide siRNA screen identifies modifiers of sensitivity to the EGFR T790M-targeted tyrosine kinase inhibitor (TKI), AZD9291, in EGFR mutant lung adenocarcinoma
In conclusion, through a kinome wide siRNA screen, we identified that gene products in the MAP kinase signaling pathway modify sensitivity to AZD9291. Such sensitivity may be associated with ERK re-phosphorylation within 96h of drug treatment. Collectively, these data suggest rational drug combinations that could be used to forestall resistance to AZD9291. Additional hits from the screen are currently under investigation.This study is supported by AstraZeneca Oncology Innovative Medicines, National Institutes of Health (NIH) NCI grants R01-CA121210, P01-CA129243, U54-CA143798, and the Uehara Memorial Foundation.Citation Fo...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Ichihara, E., Bauer, J. A., Lu, P., Ye, F., Cross, D., Pao, W., Lovly, C. M. Tags: Experimental and Molecular Therapeutics Source Type: research

07 The approach to generate oncolytic adenovirus by sirna mediated e1b silencing
Conclusion In addition to knockout of the E1B coding cassette, siRNA mediated E1B also serves as an approach to prepare oncolytic adenovirus. Acknowledgements Supported by grants from UICC (ICRETT Fellowship), Guangdong Commission of Health and Family Plan (Grant No. 2014A276).
Source: Journal of Investigative Medicine - November 24, 2017 Category: Research Authors: Zhang, X., Matskova, L., Zheng, B., Ernberg, I., He, Z., Huang, Z. Tags: Abstracts Source Type: research

Abstract C81: Identification of novel synergistic targets for rational drug combinations with PI3 kinase inhibitors using siRNA synthetic lethality screening against GBM
In this study, we performed a synthetic lethality screen to identify genes or pathways whose inactivation, in combination with the PI3K inhibitors PX-866 and NVPBEZ-235, might result in a lethal phenotype in glioblastoma multiforme (GBM) cells. We screened GBM cells (U87, U251, and T98G) with a large-scale, short hairpin RNA library (GeneNet), which contains 43 800 small interfering RNA sequences targeting 8500 well-characterized human genes. To decrease off-target effects, we selected overlapping genes among the 3 cell lines that synergized with PX- 866 to induce cell death. To facilitate the identification of potential t...
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kim, Y.-W. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 16, 2019 Category: Microbiology Source Type: research

Modeling Modulation of the Tick Regulome in Response to Anaplasma phagocytophilum for the Identification of New Control Targets
Conclusion Our modeling of the modulation of the tick regulome in response to A. phagocytophilum infection provided new insights into the mechanisms that target specific functions in different tick tissues. These results supported the use of network analysis for the study of regulome response to infection. Although general mechanisms affected by A. phagocytophilum infection may be conserved even between tick and human cells (de la Fuente et al., 2016b), the effect of vector-pathogen co-evolution on pathogen isolates adaptation to grow in tick cells (Alberdi et al., 2015) may result in differences between isolates in the m...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

Resveratrol Promotes Diabetic Wound Healing via SIRT1-FOXO1-c-Myc Signaling Pathway-Mediated Angiogenesis
Conclusion: Our findings indicate that the positive role of RES in diabetic wound healing via its SIRT1-dependent endothelial protection and pro-angiogenic effects involves the inhibition of FOXO1 and the de-repression of c-Myc expression. Introduction Diabetes mellitus is a metabolic disease with an increasing incidence worldwide (Zimmet et al., 2014). The disease often leads to the development of serious complications such as microangiopathy, mainly including retinopathy, nephropathy, neuropathy, and diabetic non-healing skin ulcers (Zheng et al., 2018). Diabetic non-healing skin ulcers such as foot ulcers are ca...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Silencing of NILCO by Small Interfering RNA Effects MDR1 in Colon Cancer Cells
In conclusion, knockdown of NILCO genes is effective in regulating MDR1 expression, which is a hallmark in chemoresistance. The present study was supported by Eskisehir Osmangazi University Scientific Research Projects (BAP) Coordination Unit (grant no. 202011D11).PMID:35557372 | DOI:10.1096/fasebj.2022.36.S1.L7435
Source: Cancer Control - May 13, 2022 Category: Cancer & Oncology Authors: Nilufer Erkasap Aysel Gultekin Rumeysa Ozyurt Mete Ozkurt Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Auranofin, an Anti-rheumatic Gold Drug, Aggravates the Radiation-Induced Acute Intestinal Injury in Mice
Conclusion In this study, we found that a non-toxic dose of auranofin significantly aggravated the severity of the radiation-induced intestinal injury. This suggests that auranofin treatment can be an independent factor that influences the risk of intestinal complications after pelvic or abdominal radiotherapy. Ethics Statement All the protocols used in this study were approved by the Institutional Animal Care and Use Committee of the Korean Institute of Radiological and Medical Sciences (IACUC permit number: KIRAMS217-0007). Author Contributions H-JL, JS, and Y-BL designed the experiments. EL and JK conducted the exp...
Source: Frontiers in Pharmacology - April 23, 2019 Category: Drugs & Pharmacology Source Type: research

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
In this study, we sought to investigate whether SH0165 (serovar 5, high-virulent strain) and HN0001 (serovar 6, non-virulent strain) infection induces autophagy and the specific role of autophagy in bacterial invasion and inflammation during H. parasuis infection. Moreover, we explored the mechanism underlying autophagy regulated inflammation through inflammatory signaling cascades during H. parasuis infection. This observation could provide useful information for further understanding the role of autophagy in H. parasuis infection and improve our knowledge of new strategies against this pathogen. Materials and Methods B...
Source: Frontiers in cellular and infection microbiology - April 15, 2019 Category: Microbiology Source Type: research

Oligomeric S100A4 Is Associated With Monocyte Innate Immune Memory and Bypass of Tolerance to Subsequent Stimulation With Lipopolysaccharides
Conclusion: Bypass of tolerance by DAMPs might be a phenomenon as important as TI, since it could explain how chronic inflammation can be maintained in spite of an environment with multiple TLR2/TLR4-ligands. In RA monocytes, a PRDM8-dependent TI mechanism could be responsible for sustained chemokine/cytokines levels. Introduction Monocytes and macrophages play a central role in the pathophysiology of inflammation. For instance, in rheumatoid arthritis (RA), activated monocytes massively infiltrate synovial tissues and produce tumor necrosis factor-α (TNFα) (1–3). Accordingly, therapies aime...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research