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https://www.readbyqxmd.com/read/28548675/inducible-bcl-2-gene-rna-interference-mediated-by-aptamer-integrated-hdv-ribozyme-switch
#1
Yuanyuan Zhang, Jine Wang, Hui Cheng, Na Sun, Min Liu, Zhengyan Wu, Renjun Pei
The regulation of RNA interference (RNAi) could be a powerful method for the study of temporal and dose dependent effects of gene expression. In this study, we designed the hepatitis delta virus (HDV) ribozyme with an embedded theophylline aptamer as the sensor domain and the pri-miRNA of endogenous gene Bcl-2 as the effector domain to engineer an RNAi-regulatory device in MCF-7 cells. The system allowed us to control gene expression by adding theophylline into the culture media in a dose dependent fashion...
May 26, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28545088/transcriptional-activation-of-hif-1-by-a-ros-erk-axis-underlies-the-resistance-to-photodynamic-therapy
#2
María Julia Lamberti, María Florencia Pansa, Renzo Emanuel Vera, Martín Ernesto Fernández-Zapico, Natalia Belén Rumie Vittar, Viviana Alicia Rivarola
Photodynamic therapy (PDT), a promising treatment option for cancer, involves the activation of a photosensitizer (PS) by local irradiation with visible light. Excitation of the PS leads to a series of photochemical reactions and consequently the local generation of harmful reactive oxygen species (ROS) causing limited or none systemic defects. However, the development of resistance to this promising therapy has slowed down its translation into the clinical practice. Thus, there is an increase need in understanding of the molecular mechanism underlying resistance to PDT...
2017: PloS One
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#3
James M Larner, Sukumar Sarkar, David L Brautigan
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer (CRPC). Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28535374/discovery-of-stromal-regulatory-networks-that-suppress-ras-sensitized-epithelial-cell-proliferation
#4
Huayang Liu, James A Dowdle, Safiya Khurshid, Nicholas J Sullivan, Nicholas Bertos, Komal Rambani, Markus Mair, Piotr Daniel, Esther Wheeler, Xing Tang, Kyle Toth, Michael Lause, Markus E Harrigan, Karl Eiring, Connor Sullivan, Matthew J Sullivan, Serena W Chang, Siddhant Srivastava, Joseph S Conway, Raleigh Kladney, Joseph McElroy, Sooin Bae, Yuanzhi Lu, Ali Tofigh, Sadiq M I Saleh, Soledad A Fernandez, Jeffrey D Parvin, Vincenzo Coppola, Erin R Macrae, Sarmila Majumder, Charles L Shapiro, Lisa D Yee, Bhuvaneswari Ramaswamy, Michael Hallett, Michael C Ostrowski, Morag Park, Helen M Chamberlin, Gustavo Leone
Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28535015/the-circadian-clock-gene-per2-plays-an-important-role-in-tumor-suppression-through-regulating-tumor-associated-genes-in-human-oral-squamous-cell-carcinoma
#5
Xiaoli Su, Dan Chen, Kai Yang, Qin Zhao, Dan Zhao, Xiaoqiang Lv, Yiran Ao
Low expression of the clock gene PER2 is closely related to carcinogenesis and the development of cancer; however, the mechanism of the low expression of PER2 that led to cell malignant transformation remains unclear. This study used RNA interference (RNAi) technology to silence PER2 in SCC15 human oral squamous cell carcinoma (OSCC) cells. Then it was found that the ability of cancer cell proliferation, migration, and invasion were markedly increased (P<0.05), and the ability of cancer cell apoptosis and the number of cells in G1/G0 phase were markedly reduced (P<0...
May 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28533810/tc003132-is-essential-for-the-follicle-stem-cell-lineage-in-telotrophic-tribolium-oogenesis
#6
Matthias Teuscher, Nadi Ströhlein, Markus Birkenbach, Dorothea Schultheis, Michael Schoppmeier
BACKGROUND: Stem cells are undifferentiated cells with a potential for self-renewal, which are essential to support normal development and homeostasis. To gain insight into the molecular mechanisms underlying adult stem cell biology and organ evolution, we use the telotrophic ovary of the beetle Tribolium. To this end, we participated in a large-scale RNAi screen in the red flour beetle Tribolium, which identified functions in embryonic and postembryonic development for more than half of the Tribolium genes...
2017: Frontiers in Zoology
https://www.readbyqxmd.com/read/28533089/synergistic-anti-tumor-effects-of-bevacizumab-and-tumor-targeted-polymerized-vegf-sirna-nanoparticles
#7
Myung Goo Kim, Sung Duk Jo, Ji Young Yhee, Beom Suk Lee, So Jin Lee, Sung Gurl Park, Sun-Woong Kang, Sun Hwa Kim, Ji Hoon Jeong
A variety of VEGF inhibitors have been reported to treat cancers by suppressing tumor angiogenesis. Bevacizumab, a monoclonal VEGF antibody, was the first FDA approved anti-angiogenic agent for cancer treatments. However, bevacizumab shows modest therapeutic efficiency and often cause resistant problem in significant populations of cancer patients. To solve these problem, we investigated the therapeutic efficacy of siRNA drugs targeting VEGF and combination of the RNAi drug with bevacizumab for cancer treatments...
May 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28532996/histone-methyltransferase-g9a-promotes-liver-cancer-development-by-epigenetic-silencing-of-tumor-suppressor-gene-rarres3
#8
Lai Wei, David Kung-Chun Chiu, Felice Ho-Ching Tsang, Dicky Cheuk-Ting Law, Carol Lai-Hung Cheng, Sandy Leung-Kuen Au, Joyce Man-Fong Lee, Carmen Chak-Lui Wong, Irene Oi-Lin Ng, Chun-Ming Wong
BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a major leading cause of cancer mortality worldwide. Epigenetic deregulation is a common trait of human HCC. G9s is an important epigenetics regulator. However, its roles in liver carcinogenesis remain to be investigated. METHODS: Gene expressions were determined by RNA-Seq and qRT-PCR. G9a knockdown and knockout cell lines were established by lentiviral-based shRNA and CRISPR/Cas9 gene editing system. Tumor promoting functions of G9a was studied by both in HCC cell lines and nude mice model...
May 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28523942/combinatorial-therapeutic-approaches-with-rnai-and-anticancer-drugs-using-nanodrug-delivery-systems
#9
Anish Babu, Anupama Munshi, Rajagopal Ramesh
RNA interference (RNAi) is emerging as a powerful approach in cancer treatment. siRNA is an important RNAi tool that can be designed to specifically silence the expression of genes involved in drug resistance and chemotherapeutic inactivity. Combining siRNA and other therapeutic agents can overcome the multidrug resistance (MDR) phenomenon by simultaneously silencing genes and enhancing chemotherapeutic activity. Moreover, the therapeutic efficiency of anticancer drugs can be significantly improved by additive or synergistic effects induced by siRNA and combined therapies...
May 19, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28523286/synthetic-lethality-screens-using-rnai-in-combination-with-crispr-based-knockout-in-drosophila-cells
#10
Benjamin E Housden, Hilary E Nicholson, Norbert Perrimon
A synthetic lethal interaction is a type of genetic interaction where the disruption of either of two genes individually has little effect but their combined disruption is lethal. Knowledge of synthetic lethal interactions can allow for elucidation of network structure and identification of candidate drug targets for human diseases such as cancer. In Drosophila, combinatorial gene disruption has been achieved previously by combining multiple RNAi reagents. Here we describe a protocol for high-throughput combinatorial gene disruption by combining CRISPR and RNAi...
February 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28521675/chemotherapy-with-si-rna-and-anti-cancer-drugs
#11
Kamaljeet Kaur, Goutam Rath, Saket Chandra, Ranjit Singh, Amit K Goyal
To treat cancer, chemotherapy is a key therapeutic approach which is associated with several limitations. This chemotherapeutical agents exhibit multi drug resistance coupled with undesirable side effects. This multidrug resistance is exhibited by tumor cell due to actuation of drug out flow mechanism, programmed cell death and protection mechanisms etc. One of the therapeutic approaches to cure cancer is RNA interference (RNAi). Small interfering RNA (si-RNA) is considered as a major therapeutic tool used to control expression of a particular gene...
May 18, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/28520795/birc6-mediates-imatinib-resistance-independently-of-mcl-1
#12
Denis O Okumu, Michael P East, Merlin Levine, Laura E Herring, Raymond Zhang, Thomas S K Gilbert, David W Litchfield, Yanping Zhang, Lee M Graves
Baculoviral IAP repeat containing 6 (BIRC6) is a member of the inhibitors of apoptosis proteins (IAPs), a family of functionally and structurally related proteins that inhibit apoptosis. BIRC6 has been implicated in drug resistance in several different human cancers, however mechanisms regulating BIRC6 have not been extensively explored. Our phosphoproteomic analysis of an imatinib-resistant chronic myelogenous leukemia (CML) cell line (MYL-R) identified increased amounts of a BIRC6 peptide phosphorylated at S480, S482, and S486 compared to imatinib-sensitive CML cells (MYL)...
2017: PloS One
https://www.readbyqxmd.com/read/28515148/nemo-a-transcriptional-target-of-estrogen-and-progesterone-is-linked-to-tumor-suppressor-pml-in-breast-cancer
#13
Kelli E Valdez, Hanan S Elsarraj, Yan Hong, Sandra L Grimm, Lawrence R Ricci, Fang Fan, Ossama Tawfik, Lisa May, Therese Cusick, Marc Inciardi, Mark Redick, Jason Gatewood, Onalisa Winblad, Susan G Hilsenbeck, Dean P Edwards, Christy Hagan, Andrew K Godwin, Carol J Fabian, Fariba Behbod
The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in breast cancer remains controversial. Here we report a beneficial mechanism of E+P treatment in breast cancer cells driven by transcriptional upregulation of the NFκB modulator NEMO, which in turn promotes expression of the tumor suppressor protein PML. E+P treatment of patient-derived epithelial cells derived from ductal carcinoma in situ (DCIS) increased secretion of the pro-inflammatory cytokine IL-6. Mechanistic investigations indicated that IL-6 upregulation occurred as a result of transcriptional upregulation of NEMO, the gene for which harbored estrogen receptor (ER) binding sites within its promoter...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28512247/targetable-t-type-calcium-channels-drive-glioblastoma
#14
Ying Zhang, Nichola Cruickshanks, Fang Yuan, Baomin Wang, Mary Pahuski, Julia Wulfkuhle, Isela Gallagher, Alexander F Koeppel, Sarah Hatef, Christopher Papanicolas, Jeongwu Lee, Eli E Bar, David Schiff, Stephen Turner, Emanuel F Petricoin, Lloyd S Gray, Roger Abounader
Glioblastoma stem-like cells (GSC) promote tumor initiation, progression and therapeutic resistance. Here we show how GSC can be targeted by the FDA approved drug mibefradil which inhibits the T-type calcium channel Cav3.2. This calcium channel was highly expressed in human GBM specimens and enriched in GSC. Analyses of the TCGA and REMBRANDT databases confirmed upregulation of Cav3.2 in a subset of tumors and showed that overexpression associated with worse prognosis. Mibefradil treatment or RNAi-mediated attenuation of Cav3...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511875/visible-light-switched-cytosol-release-of-sirna-by-amphiphilic-fullerene-derivative-to-enhance-rnai-efficacy-in-vitro-and-in-vivo
#15
Jing Wang, Lifei Xie, Tao Wang, Fengxin Wu, Jie Meng, Jian Liu, Haiyan Xu
Cationic macromolecules are attractive for use as small interfering RNA (siRNA) carriers due to their performance in non-immunological reactions, customization during synthesis, and low costs compared to viral carriers. However, their low transfection efficiency substantially hinders their application in both clinical practices and academic research, which is mostly attributable to the low capacity of siRNA/cationic macromolecule complexes to escape lysosomes. To address this challenge, we designed an amphiphilic fullerene derivative (C60-Dex-NH2) for efficient and controllable siRNA delivery...
May 13, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28502307/-knock-down-of-dab2-interacting-protein-dab2ip-promotes-proliferation-and-inhibits-apoptosis-of-bladder-cancer-cells
#16
Kai Zhang, Weiyi Wang, Kaijie Wu, Chen Ding, Jianning Zhu, Yiqing DU, Zhenfeng Guan, Xinyang Wang, Jinhai Fan
Objective To study the expression of DAB2 interacting protein (DAB2IP) in human bladder cancer tissues and analyze its relationship with pathological grade and clinical stage, and observe its role in drug resistance of bladder cancer cells. Methods The expression of DAB2IP in primary and recurrent bladder cancers was detected by immunohistochemical staining. RNA interference (RNAi) technique was used to down-regulate the expression of DAB2IP in 5637 and 253J bladder cancer cells. MTT assay and clone formation assay were performed to test the sensitivity of cancer cells to pirarubicin...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28490518/chk1-inhibition-in-small-cell-lung-cancer-produces-single-agent-activity-in-biomarker-defined-disease-subsets-and-combination-activity-with-cisplatin-or-olaparib
#17
Triparna Sen, Pan Tong, C Allison Stewart, Sandra Cristea, Aly Valliani, David S Shames, Abena Redwood, Youhong Fan, Lerong Li, Bonnie S Glisson, John Minna, Julien Sage, Don L Gibbons, Helen Piwnica-Worms, John Heymach, Jing Wang, Lauren Averett Byers
Effective targeted therapies for small cell lung cancer (SCLC), the most aggressive form of lung cancer, remain urgently needed. Here we report evidence of preclinical efficacy evoked by targeting the overexpressed cell cycle checkpoint kinase CHK1 in SCLC. Our studies employed RNAi-mediated attenuation or pharmacological blockade with the novel second-generation CHK1 inhibitor prexasertib (LY2606368), currently in clinical trials. In SCLC models in vitro and in vivo, LY2606368 exhibited strong single-agent efficacy, augmented the effects of cisplatin or the PARP inhibitor olaparib, and improved the response of platinum-resistant models...
May 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/28482505/sirna-nanoparticle-conjugate-in-gene-silencing-a-future-cure-to-deadly-diseases
#18
REVIEW
Rituparna Acharya, Suman Saha, Sayantan Ray, Sugata Hazra, Manoj K Mitra, Jui Chakraborty
Alzheimers, cancer, acquired immune deficiency syndrome (AIDS) are considered to be some of the most deadly diseases of the 21st century on account of their severity and rapid increase in the number of affected population and with scarce cases of recovery, they still remain a troubling paradox. Specifically, with millions of cancer patients worldwide and lack of proper cure for the same, understanding the deadly disease at the molecular level and planning a therapeutic strategy in the same line is the need of the hour...
July 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28469794/silencing-of-cxcr4-and-cxcr7-expression-by-rna-interference-suppresses-human-endometrial-carcinoma-growth-in-vivo
#19
Yu Huang, Yuanying Ye, Ping Long, Shuping Zhao, Lei Zhang, Yanni A
In this paper, the effect of silencing the expression of CXCR4 and CXCR7 by RNAi on the growth of endometrial carcinoma (EC), in vivo, was evaluated. To establish endometrial carcinoma model, thirty nude mice were subcutaneously inoculated with 1 × 10(7) Ishikawa cells. All tumor-bearing mice were randomly assigned to five groups (six mice in each group) when the tumor xenografts reached 5-7 mm in diameter, and treated with CXCR4-siRNA (5 nmol), CXCR7-siRNA (5 nmol), CXCR4-siRNA (5 nmol) plus CXCR7-siRNA (5 nmol), negative-siRNA (5 nmol) and normal saline, respectively...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468827/hmg-coa-synthase-1-is-a-synthetic-lethal-partner-of-braf-v600e-in-human-cancers
#20
Liang Zhao, Jun Fan, Siyuan Xia, Yaozhu Pan, Shuangping Liu, Guoqing Qian, Zhiyu Qian, Hee-Bum Kang, Jack L Arbiser, Brian P Pollack, Ragini Kudchadkar, David H Lawson, Michael Rossi, Omar Abdel-Wahab, Taha Merghoub, Hanna J Khoury, Fadlo R Khuri, Lawrence H Boise, Sagar Lonial, Fangping Chen, Jing Chen, Ruiting Lin
Contributions of metabolic changes to cancer development and maintenance have received increasing attention in recent years. Although many human cancers share similar metabolic alterations, it remains unclear whether oncogene-specific metabolic alterations are required for tumor development. Using RNAi-based screen targeting the majority of the known metabolic proteins, we recently found that oncogenic BRAF(V600E) upregulates HMG-CoA lyase (HMGCL), which converts HMG-CoA to acetyl-CoA and a ketone body, acetoacetate, that selectively enhances BRAFV600E-dependent MEK1 activation in human cancer...
May 3, 2017: Journal of Biological Chemistry
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