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https://www.readbyqxmd.com/read/28098854/lsd1-sustains-estrogen-driven-endometrial-carcinoma-cell-proliferation-through-the-pi3k-akt-pathway-via-di-demethylating-h3k9-of-cyclin%C3%A2-d1
#1
Chunqin Chen, Yanan Wang, Shiyu Wang, Yuan Liu, Jiawen Zhang, Yuyao Xu, Zhenbo Zhang, Wei Bao, Sufang Wu
A recent study reported that histone lysine specific demethylase 1 (LSD1, KDM1A) is overexpressed in endometrioid endometrial carcinoma (EEC) and associated with tumor progression as well as poor prognosis. However, the physiological function and mechanism of LSD1 in endometrial cancer (EC) remains largely unknown. In this study, we demonstrate that β-estradiol (E2) treatment increased LSD1 expression via the GPR30/PI3K/AKT pathway in endometrial cancer cells. Both siGPR30 and the PI3K inhibitor LY294002 block this effect...
January 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28094937/click-qms-identifies-piwil3-as-a-mechanistic-target-of-rna-interference-activator-enoxacin-in-cancer-cells
#2
Nathan Abell, Marvin Mercado, Tatiana Cañeque, Raphaël Rodriguez, Blerta Xhemalce
Enoxacin is a small molecule that stimulates RNA interference (RNAi) and acts as a growth inhibitor selectively in cancer but not in untransformed cells. Here, we used alkenox, a clickable enoxacin surrogate, coupled with quantitative Mass Spectrometry, to identify PIWIL3 as a mechanistic target of enoxacin. PIWIL3 is an Argonaut protein of the PIWI subfamily that is mainly expressed in the germline and that mediates RNAi through piRNAs. Our results suggest that cancer cells re-express PIWIL3 to repress RNAi through miRNAs and thus open a new opportunity for cancer specific targeting...
January 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28092499/nanoparticles-for-sirna-based-gene-silencing-in-tumor-therapy
#3
Anish Babu, Ranganayaki Muralidharan, Narsireddy Amreddy, Meghna Mehta, Anupama Munshi, Rajagopal Ramesh
Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems...
December 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28089848/sparc-preserves-follicular-epithelium-integrity-in-insect-ovaries
#4
Paula Irles, Saray Ramos, Maria-Dolors Piulachs
The importance of juvenile hormone regulating insect oogenesis suggests looking for genes whose expression is regulated by this hormone. SPARC is a calcium-binding glycoprotein that forms part of the extracellular membranes, which in vertebrates participates in bones mineralization or regulating cell proliferation in some cancer types. This large number of functions described for SPARC in different species might be related to the significant differences in its structure observed when comparing different species-groups...
January 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28087713/functional-genomics-reveals-that-tumors-with-activating-phosphoinositide-3-kinase-mutations-are-dependent-on-accelerated-protein-turnover
#5
Teresa Davoli, Kristen E Mengwasser, Jingjing Duan, Ting Chen, Camilla Christensen, Eric C Wooten, Anthony N Anselmo, Mamie Z Li, Kwok-Kin Wong, Kristopher T Kahle, Stephen J Elledge
Activating mutations in the phosphoinositide 3-kinase (PI3K) signaling pathway are frequently identified in cancer. To identify pathways that support PI3K oncogenesis, we performed a genome-wide RNAi screen in isogenic cell lines harboring wild-type or mutant PIK3CA to search for PI3K synthetic-lethal (SL) genes. A combined analysis of these results with a meta-analysis of two other large-scale RNAi screening data sets in PI3K mutant cancer cell lines converged on ribosomal protein translation and proteasomal protein degradation as critical nononcogene dependencies for PI3K-driven tumors...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28075475/mir-134-suppresses-the-migration-and-invasion-of-non%C3%A2-small-cell-lung-cancer-by-targeting-itgb1
#6
Qin Qin, Furong Wei, Jianbo Zhang, Baosheng Li
Most cancer-related deaths are caused by the development of metastatic disease. Thus, investigation of the underlying mechanisms of metastasis is urgent to design more effective targeted drugs and to treat metastatic disease more effectively. MicroRNAs (miRNAs) have emerged as potential targets for cancer treatment. In the present study, we aimed to identify the roles of miR-134 in non-small cell lung cancer (NSCLC) cell migration and invasion. We demonstrated that overexpression of miR-134 inhibited migration and invasion of A549 and H1299 cells...
February 2017: Oncology Reports
https://www.readbyqxmd.com/read/28070831/the-prolyl-oligopeptidase-inhibitor-suam-14746-attenuates-the-proliferation-of-human-breast-cancer-cell-lines-in-vitro
#7
Satoshi Tanaka, Kanayo Suzuki, Minoru Sakaguchi
BACKGROUND: Prolyl oligopeptidase (POP, EC 3.4.1.26) is a serine peptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We previously reported that POP inhibition suppressed the growth of NB-1 human neuroblastomas cells and KATO III human gastric cancer cells. POP activity is commonly elevated in many cancers, which includes breast cancer. However, the effect of POP inhibition as a candidate breast cancer therapy is unknown. METHODS: The effects of POP inhibition and knockdown on the proliferation of cultured human estrogen receptor-positive (ER+) MCF7 and T47D, and ER-negative (ER-) MDA-MB-231 breast cancer cell lines and the MCF12A non-tumorigenic epithelial cell line were tested by analyzing their influence on cell proliferation (WST-1 assay), cell viability (trypan blue exclusion assay), and cell cycle arrest (cell cycle analysis, cell cycle regulator proteins expression)...
January 9, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28063496/measuring-phospholipase-d-enzymatic-activity-through-biochemical-and-imaging-methods
#8
F Philip, E E Ha, M A Seeliger, M A Frohman
The phospholipase D (PLD) enzymatic superfamily regulates a wide range of cell biological and physiological pathways, including platelet activation, immune responses, cancer, and spermatogenesis. The three main enzymatic actions of the superfamily entail (i) hydrolyzing membrane phospholipids (phosphatidylcholine (PC) and cardiolipin) to generate choline and the second messenger signaling lipid phosphatidic acid (PA), (ii) using ethanol to transphosphatidylate PC to generate the long-lived metabolite phosphatidylethanol, and (iii) hydrolyzing RNA transcripts to generate piRNAs, the third form of endogenous RNAi...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28061540/metallothionein-2a-an-interactive-protein-linking-phosphorylated-fadd-to-nf-%C3%AE%C2%BAb-pathway-leads-to-colorectal-cancer-formation
#9
Faiz M M T Marikar, Guanghui Jin, Wang Sheng, Dingyuan Ma, Zichun Hua
BACKGROUND: The rapid increase in the incidence rate of colorectal cancer has led to the search and identification of biomarkers that can predict risk for and future behavior of this malignancy and management. To study the biological role of the phosphorylated Fas associated death domain (pFADD) gene in colorectal cancer, we performed a GAL4-based yeast two-hybrid screening of a human heart cDNA library. METHODS: A series of two yeast hybrid method was used to identification of protein-protein interaction...
December 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28059079/trim14-is-a-putative-tumor-suppressor-and-regulator-of-innate-immune-response-in-non-small-cell-lung-cancer
#10
Josephine Hai, Chang-Qi Zhu, Tao Wang, Shawna L Organ, Frances A Shepherd, Ming-Sound Tsao
Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states. We investigated the functional and prognostic role of TRIM14 in NSCLC using in vitro and in vivo perturbation model systems. Firstly, a pooled RNAi screen identified TRIM14 to effect cell proliferation/survival in NSCLC cells...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28058629/rnai-mediated-knockdown-of-mcm7-gene-on-cml-cells-and-its-therapeutic-potential-for-leukemia
#11
Liang Tian, Juan Liu, Guo-Hua Xia, Bao-An Chen
MCM7 is one of the subunits of MCM2-7 complex, which is essential to DNA replication licensing and the control of cell cycle progression. It has been demonstrated that MCM7 participates in mRNA transcription and DNA damage regulation as well. MCM7 gene is found to be over-expressed in multiple cancers, but there are few reports about its effect in leukemia. Recent studies have proven that MCM7 expression has a relationship with diagnosis and prognosis, which has led to their potential clinical application as a marker for cancer screening...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28057848/a-pipeline-for-drug-target-identification-and-validation
#12
Eusebio Manchado, Chun-Hao Huang, Nilgun Tasdemir, Darjus F Tschaharganeh, John E Wilkinson, Scott W Lowe
Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant survival and proliferation of tumor cells has yielded remarkable success in some malignancies such as BRAF-mutant melanoma and BCR-ABL expressing chronic myeloid leukemia. However, the direct inhibition of several well-established oncoproteins in some of these cancers is not possible or produces only transient benefits...
January 5, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28050890/nanoengineered-strategies-for-sirna-delivery-from-target-assessment-to-cancer-therapeutic-efficacy
#13
REVIEW
Dinesh Kumar Mishra, Neelam Balekar, Pradyumna Kumar Mishra
The promise of RNA interference (RNAi) technology in cancer therapeutics aims to deliver small interfering RNA (siRNA) for silencing of gene expression in cell type-specific pathway. However, the challenge for the delivery of stable siRNA is hindered by an immune-hostile tumor microenvironment and physiological barriers of the circulatory system. Therefore, the development and validation of safe, stable, and efficient nanoengineered delivery systems are highly essential for effective delivery of siRNA into cancer cells...
January 3, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/28045069/local-alignment-vectors-reveal-cancer-cell-induced-ecm-fiber-remodeling-dynamics
#14
Byoungkoo Lee, Jessica Konen, Scott Wilkinson, Adam I Marcus, Yi Jiang
Invasive cancer cells interact with the surrounding extracellular matrix (ECM), remodeling ECM fiber network structure by condensing, degrading, and aligning these fibers. We developed a novel local alignment vector analysis method to quantitatively measure collagen fiber alignment as a vector field using Circular Statistics. This method was applied to human non-small cell lung carcinoma (NSCLC) cell lines, embedded as spheroids in a collagen gel. Collagen remodeling was monitored using second harmonic generation imaging under normal conditions and when the LKB1-MARK1 pathway was disrupted through RNAi-based approaches...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043128/formulation-and-evaluation-of-anisamide-targeted-amphiphilic-cyclodextrin-nanoparticles-to-promote-therapeutic-gene-silencing-in-a-3d-prostate-cancer-bone-metastases-model
#15
James C Evans, Meenakshi Malhotra, Kathleen A Fitzgerald, Jianfeng Guo, Michael F Cronin, Caroline M Curtin, Fergal J O'Brien, Raphael Darcy, Caitriona M O'Driscoll
In recent years, RNA interference (RNAi) has emerged as a potential therapeutic offering the opportunity to treat a wide range of diseases, including prostate cancer. Modified cyclodextrins have emerged as effective gene delivery vectors in a range of disease models. The main objective of the current study was to formulate anisamide-targeted cyclodextrin nanoparticles to interact with the sigma receptor (overexpressed on the surface of prostate cancer cells). The inclusion of octaarginine in the nanoparticle optimized uptake and endosomal release of siRNA in two different prostate cancer cell lines (PC3 and DU145 cells)...
January 3, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28042832/r-flurbiprofen-traps-prostaglandins-within-cells-by-inhibition-of-multidrug-resistance-associated-protein-4
#16
Ivonne Wobst, Lisa Ebert, Kerstin Birod, Marthe-Susanna Wegner, Marika Hoffmann, Dominique Thomas, Carlo Angioni, Michael J Parnham, Dieter Steinhilber, Irmgard Tegeder, Gerd Geisslinger, Sabine Grösch
R-flurbiprofen is the non-COX-inhibiting enantiomer of flurbiprofen and is not converted to S-flurbiprofen in human cells. Nevertheless, it reduces extracellular prostaglandin E₂ (PGE₂) in cancer or immune cell cultures and human extracellular fluid. Here, we show that R-flurbiprofen acts through a dual mechanism: (i) it inhibits the translocation of cPLA2α to the plasma membrane and thereby curtails the availability of arachidonic acid and (ii) R-flurbiprofen traps PGE₂ inside of the cells by inhibiting multidrug resistance-associated protein 4 (MRP4, ABCC4), which acts as an outward transporter for prostaglandins...
December 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28042312/antitumor-therapeutic-application-of-self-assembled-rnai-aunp-nanoconstructs-combination-of-vegf-rnai-and-photothermal-ablation
#17
Sejin Son, Namho Kim, Dong Gil You, Hong Yeol Yoon, Ji Young Yhee, Kwangmeyung Kim, Ick Chan Kwon, Sun Hwa Kim
Nucleic acid-directed self-assembly provides an attractive method to fabricate prerequisite nanoscale structures for a wide range of technological applications due to the remarkable programmability of DNA/RNA molecules. In this study, exquisite RNAi-AuNP nanoconstructs with various geometries were developed by utilizing anti-VEGF siRNA molecules as RNAi-based therapeutics in addition to their role as building blocks for programmed self-assembly. In particular, the anti-VEGF siRNA-functionalized AuNP nanoconstructs can take additional advantage of gold-nanoclusters for photothermal cancer therapeutic agent...
2017: Theranostics
https://www.readbyqxmd.com/read/28039357/key-survival-factor-mcl-1-correlates-with-sensitivity-to-combined-bcl-2-bcl-xl-blockade
#18
Michelle Williams, Linus Lee, Donna J Hicks, Meghan M Joly, David Elion, Bushra Rahman, Courtney McKernan, Violeta Sanchez, Justin M Balko, Thomas Stricker, Monica Valeria Estrada, Rebecca S Cook
: An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use anti-apoptotic Bcl-2 proteins to bind to and neutralize apoptotic activators, such as Bim. Investigation of anti-apoptotic Bcl-2 family members in clinical breast cancer datasets, revealed greater expression and more frequent gene amplification of MCL1 as compared to BCL2 or BCL2L1 (Bcl-xL) across three major molecular breast cancer subtypes, Luminal (A and B), HER2-enriched, and Basal-like...
December 30, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28035350/silencing-lpaat%C3%AE-inhibits-tumor-growth-of-cisplatin-resistant-human-osteosarcoma-in-vivo-and-in-vitro
#19
Lei Song, Ping Duan, Yibo Gan, Pei Li, Chen Zhao, Jianzhong Xu, Zehua Zhang, Qiang Zhou
Cisplatin-resistance has become a major impediment in the medical treatment of cancers such as osteosarcoma, the most common primary malignancy of bone. Since lysophosphatidic acid acyltransferase β (LPAATβ) was reported to be critically involved in osteosarcoma, our study investigated the role of LPAATβ in human osteosarcoma with cisplatin-resistance. Expression of LPAATβ or other relevant proteins were analyzed in 40 osteosarcoma patients by immunohistochemistry analysis (IHC), and in cisplatin‑resistant sublines by real-time PCR and western blotting...
February 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28031411/a-systematic-analysis-of-negative-growth-control-implicates-the-dream-complex-in-cancer-cell-dormancy
#20
James MacDonald, Yudith Ramos-Valdes, Piru Perampalam, Larisa Litovchick, Gabriel E DiMattia, Frederick A Dick
: Epithelial ovarian cancer (EOC) generates multicellular aggregates called spheroids that detach from the primary tumor and disseminate through ascites. Spheroids possess a number of characteristics of tumor dormancy including withdrawal from the cell cycle and resistance to chemotherapeutics. This report systematically analyzes the effects of RNAi depletion of 21 genes that are known to contribute to negative regulation of the cell cycle in 10 ovarian cancer cell lines. Interestingly, spheroid cell viability was compromised by loss of some Cyclin Dependent Kinase Inhibitors such as p57Kip2, as well as Dyrk1A, Lin52, and E2F5 in most cell lines tested...
December 28, 2016: Molecular Cancer Research: MCR
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