keyword
MENU ▼
Read by QxMD icon Read
search

CRISPR/Cas9 cell death

keyword
https://www.readbyqxmd.com/read/29222162/dual-inhibition-of-pik3c3-and-fgfr-as-a-new-therapeutic-approach-to-treat-bladder-cancer
#1
Chun-Han Chen, C Changou, Tsung-Han Hsieh, Yu-Ching Lee, Cheng-Ying Chu, Kai-Cheng Hsu, Hao-Ching Wang, Yu-Chen Lin, Yan-Ni Lo, Yun-Ru Liu, Jing-Ping Liou, Yun Yen
PURPOSE: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms. EXPERIMENTAL DESIGN: Autophagy flux, morphology and intracellular organelles were evaluated by western blotting, transmission electron microscope and fluorescence microscope. Molecular docking, surface plasmon resonance assay were performed to identify drug-protein interaction...
December 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29221169/targeting-pp2a-activates-ampk-signaling-to-inhibit-colorectal-cancer-cells
#2
Cuiping Dai, Xuning Zhang, Da Xie, Peipei Tang, Chunmei Li, Yi Zuo, Baofei Jiang, Caiping Xue
LB-100 is a novel PP2A inhibitor. Its activity in human colorectal cancer (CRC) cells was tested. The in vitro studies demonstrated that LB-100 inhibited survival and proliferation of both established CRC cells (HCT-116 and HT-29 lines) and primary human colon cancer cells. Further, LB-100 activated apoptosis and induced G1-S cell cycle arrest in CRC cells. LB-100 inhibited PP2A activity and activated AMPK signaling in CRC cells. AMPKα1 dominant negative mutation, shRNA-mediated knockdown or complete knockout (by CRISPR/Cas9 method) largely attenuated LB-100-induced AMPK activation and HCT-116 cytotoxicity...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217433/hypertrophic-cardiomyopathy-linked-mutation-in-troponin-t-causes-myofibrillar-disarray-and-pro-arrhythmic-action-potential-changes-in-human-ipsc-cardiomyocytes
#3
Lili Wang, Kyungsoo Kim, Shan Parikh, Adrian Gabriel Cadar, Kevin R Bersell, Huan He, Jose R Pinto, Dmytro O Kryshtal, Bjorn C Knollmann
BACKGROUND: Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. OBJECTIVES: To study the effects of the TnT-I79N mutation in human cardiomyocytes...
December 4, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29193607/comparative-genomics-reveals-that-loss-of-lunatic-fringe-lfng-promotes-melanoma-metastasis
#4
Martin Del Castillo Velasco-Herrera, Louise van der Weyden, Jeremie Nsengimana, Anneliese O Speak, Marcela K Sjöberg, D Timothy Bishop, Göran Jönsson, Julia Newton-Bishop, David J Adams
Metastasis is the leading cause of death in patients with advanced melanoma, yet the somatic alterations that aid tumour cell dissemination and colonization are poorly understood. Here, we deploy comparative genomics to identify and validate clinically relevant drivers of melanoma metastasis. To do this we identified a set of 976 genes whose expression level was associated with a poor outcome in patients from two large melanoma cohorts. Next, we characterised the genomes and transcriptomes of mouse melanoma cell lines defined as weakly metastatic, and their highly metastatic derivatives...
November 29, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29184850/internalization-of-the-active-subunit-of-the-aggregatibacter-actinomycetemcomitans-cytolethal-distending-toxin-is-dependent-upon-cellugyrin-synaptogyrin-2-a-host-cell-non-neuronal-paralog-of-the-synaptic-vesicle-protein-synaptogyrin-1
#5
Kathleen Boesze-Battaglia, Lisa P Walker, Anuradha Dhingra, Konstantin Kandror, Hsin-Yao Tang, Bruce J Shenker
The Aggregatibacter actinomycetemcomitans cytolethal distending toxin (Cdt) is a heterotrimeric AB2 toxin capable of inducing lymphocytes, and other cell types, to undergo cell cycle arrest and apoptosis. Exposure to Cdt results in binding to the cell surface followed by internalization and translocation of the active subunit, CdtB, to intracellular compartments. These events are dependent upon toxin binding to cholesterol in the context of lipid rich membrane microdomains often referred to as lipid rafts. We now demonstrate that, in addition to binding to the plasma membrane of lymphocytes, another early and critical event initiated by Cdt is the translocation of the host cell protein, cellugyrin (synaptogyrin-2) to the same cholesterol-rich microdomains...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29183726/gsdme-mediates-caspase-3-dependent-pyroptosis-in-gastric-cancer
#6
Yubin Wang, Bo Yin, Dinuo Li, Guijun Wang, Xiangdong Han, Xuejun Sun
Gastric cancer is a malignancy that starts from the cells in the stomach with relatively low overall survival rate. Chemotherapy following resection surgery has been recommended as a curative strategy for gastric cancer. However, the mechanism of the chemotherapy drugs on gastric cancer is not completely understood. Pyroptosis is a form of programmed cell death and plays critical role in immunity. The role of pyroptosis on cancer cells is less known. In this study, we treated SGC-7901 and MKN-45 with 5-FU and found that the cell viability was significantly decreased...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29178829/encore-an-efficient-software-for-crispr-screens-identifies-new-players-in-extrinsic-apoptosis
#7
Dietrich Trümbach, Susanne Pfeiffer, Manuel Poppe, Hagen Scherb, Sebastian Doll, Wolfgang Wurst, Joel A Schick
BACKGROUND: As CRISPR/Cas9 mediated screens with pooled guide libraries in somatic cells become increasingly established, an unmet need for rapid and accurate companion informatics tools has emerged. We have developed a lightweight and efficient software to easily manipulate large raw next generation sequencing datasets derived from such screens into informative relational context with graphical support. The advantages of the software entitled ENCoRE (Easy NGS-to-Gene CRISPR REsults) include a simple graphical workflow, platform independence, local and fast multithreaded processing, data pre-processing and gene mapping with custom library import...
November 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29175330/activation-of-amp-activated-protein-kinase-by-compound-991-protects-osteoblasts-from-dexamethasone
#8
Yong-Yi Xu, Feng-Li Chen, Feng Ji, Hao-Dong Fei, Yue Xie, Shou-Guo Wang
Dexamethasone (Dex) induces direct cytotoxicity to cultured osteoblasts. The benzimidazole derivative compound 991 ("C991") is a novel and highly-efficient AMP-activated protein kinase (AMPK) activator. Here, in both MC3T3-E1 osteoblastic cells and primary murine osteoblasts, treatment with C991 activated AMPK signaling, and significantly attenuated Dex-induced apoptotic and non-apoptotic cell death. AMPKα1 knockdown (by shRNA), complete knockout (by CRISPR/Cas9 method) or dominant negative mutation (T172A) not only blocked C991-mediated AMPK activation, but also abolished its pro-survival effect against Dex in osteoblasts...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29167274/distinct-cellular-mechanisms-underlie-smooth-muscle-turnover-in-vascular-development-and-repair
#9
Urmas Roostalu, Bashar Aldeiri, Alessandra Albertini, Neil E Humphreys, Maj Simonsen-Jackson, Jason K Wong, Giulio Cossu
Rationale: Vascular smooth muscle turnover has important implications for blood vessel repair and for the development of cardiovascular diseases, yet lack of specific transgenic animal models has prevented it's in vivo analysis. Objective: To characterize the dynamics and mechanisms of vascular smooth muscle turnover from the earliest stages of embryonic development to arterial repair in the adult. Methods and Results: We show that CD146 is transiently expressed in vascular smooth muscle development. By using CRISPR-Cas9 genome editing and in vitro smooth muscle differentiation assay we demonstrate that CD146 regulates the balance between proliferation and differentiation...
November 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/29163048/nicotinic-acetylcholine-receptor-subtype-alpha-9-mediates-triple-negative-breast-cancers-based-on-a-spontaneous-pulmonary-metastasis-mouse-model
#10
Li-Chi Huang, Ching-Ling Lin, Jia-Zheng Qiu, Chun-Yu Lin, Kai-Wen Hsu, Ka-Wai Tam, Jung-Yu Lee, Jinn-Moon Yang, Chia-Hwa Lee
Triple-negative breast cancer (TNBC) subtype is associated with poor prognosis and a high risk of recurrence-related death in women. Despite the aggressiveness of TNBCs, targeted TNBC therapy is not yet available in the clinic. To overcome this challenge, we generated highly metastatic TNBC cells (LM) derived from metastasized lung cells via a serial spontaneous pulmonary metastasis animal model to identify targetable molecules for attenuating the progression of TNBC metastasis. Gene analysis of primary tumor (P), first-round (1LM) and second-round (2LM) metastasized lung cells revealed that mesenchymal-related genes were significantly expressed in LM cells, especially in 2LM cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29112685/serum-squamous-cell-carcinoma-antigen-as-an-early-indicator-of-response-during-therapy-of-cervical-cancer
#11
Stephanie Markovina, Songyan Wang, Lauren E Henke, Cliff J Luke, Stephen C Pak, Todd DeWees, John D Pfeifer, Julie K Schwarz, Weijun Liu, Shuai Chen, David Mutch, Xiaowei Wang, Matthew A Powell, Barry A Siegel, Farrokh Dehdashti, Gary A Silverman, Perry W Grigsby
BACKGROUND: Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance. METHODS: Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included...
November 7, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29109113/generation-and-characterization-of-sult4a1-mutant-mouse-models
#12
Patrick L Garcia, Mohammed I Hossain, Shaida A Andrabi, Charles N Falany
Sulfotransferase 4A1 (SULT4A1) belongs to the cytosolic sulfotransferase (SULT) superfamily of enzymes that catalyze sulfonation reactions with a variety of endogenous and exogenous substrates. Of the SULTs, SULT4A1 was shown to have the highest sequence homology between vertebrate species, yet no known function or enzymatic activity have been identified for this orphan SULT. To better understand SULT4A1 function in mammalian brain, two mutant SULT4A1 mouse strains were generated utilizing CRISPR-Cas9 technology...
November 6, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29084003/a-genome-wide-comprehensive-analysis-of-alterations-in-driver-genes-in-non-small-cell-lung-cancer
#13
Jun Yi, Xiang Wei, Xinqiang Li, Lei Wan, Jiashou Dong, Rui Wang
Lung cancer is one of the most common malignancies and the leading cause of cancer-related deaths worldwide. Although many oncogenes and tumor suppressors have been uncovered in the past decades, the pathogenesis and mechanisms of lung tumorigenesis and progression are unclear. The advancement of high-throughput sequencing technique and bioinformatics methods has led to the discovery of some unknown important protein-coding genes or noncoding RNAs in human cancers. In this study, we tried to identify and validate lung cancer driver genes to facilitate the diagnosis and individualized treatment of patients with this disease...
October 27, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29083112/immunity-to-crispr-cas9-and-cas12a-therapeutics
#14
REVIEW
Wei Leong Chew
Genome-editing therapeutics are poised to treat human diseases. As we enter clinical trials with the most promising CRISPR-Cas9 and CRISPR-Cas12a (Cpf1) modalities, the risks associated with administering these foreign biomolecules into human patients become increasingly salient. Preclinical discovery with CRISPR-Cas9 and CRISPR-Cas12a systems and foundational gene therapy studies indicate that the host immune system can mount undesired responses against the administered proteins and nucleic acids, the gene-edited cells, and the host itself...
October 30, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/29042501/plasmodium-falciparum-calcium-dependent-protein-kinase-2-is-critical-for-male-gametocyte-exflagellation-but-not-essential-for-asexual-proliferation
#15
Abhisheka Bansal, Alvaro Molina-Cruz, Joseph Brzostowski, Jianbing Mu, Louis H Miller
Drug development efforts have focused mostly on the asexual blood stages of the malaria parasite Plasmodium falciparum Except for primaquine, which has its own limitations, there are no available drugs that target the transmission of the parasite to mosquitoes. Therefore, there is a need to validate new parasite proteins that can be targeted for blocking transmission. P. falciparum calcium-dependent protein kinases (PfCDPKs) play critical roles at various stages of the parasite life cycle and, importantly, are absent in the human host...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29036432/copb2-is-essential-for-embryogenesis-and-hypomorphic-mutations-cause-human-microcephaly
#16
Andrew DiStasio, Ashley Driver, Kristen Sund, Milene Donlin, Ranjith M Muraleedharan, Shabnam Pooya, Beth Kline-Fath, Kenneth M Kaufman, Cynthia A Prows, Elizabeth Schorry, Biplab DasGupta, Rolf W Stottmann
Primary microcephaly is a congenital brain malformation characterized by a head circumference less than three standard deviations below the mean for age and sex and results in moderate to severe mental deficiencies and decreased lifespan. We recently studied two children with primary microcephaly in an otherwise unaffected family. Exome sequencing identified an autosomal recessive mutation leading to an amino acid substitution in a WD40 domain of the highly conserved Coatomer Protein Complex, Subunit Beta 2 (COPB2)...
September 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29024560/enhanced-stem-cell-differentiation-and-immunopurification-of-genome-engineered-human-retinal-ganglion-cells
#17
Valentin M Sluch, Xitiz Chamling, Melissa M Liu, Cynthia A Berlinicke, Jie Cheng, Katherine L Mitchell, Derek S Welsbie, Donald J Zack
Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols are often lacking. Here, we describe the generation of clustered regularly-interspaced short palindromic repeats(CRISPR)-Cas9 engineered reporter knock-in embryonic stem cell lines in which tdTomato and a unique cell-surface protein, THY1...
November 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28976960/cancer-drug-addiction-is-relayed-by-an-erk2-dependent-phenotype-switch
#18
Xiangjun Kong, Thomas Kuilman, Aida Shahrabi, Julia Boshuizen, Kristel Kemper, Ji-Ying Song, Hans W M Niessen, Elisa A Rozeman, Marnix H Geukes Foppen, Christian U Blank, Daniel S Peeper
Observations from cultured cells, animal models and patients raise the possibility that the dependency of tumours on the therapeutic drugs to which they have acquired resistance represents a vulnerability with potential applications in cancer treatment. However, for this drug addiction trait to become of clinical interest, we must first define the mechanism that underlies it. We performed an unbiased CRISPR-Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for 'addiction genes'...
October 12, 2017: Nature
https://www.readbyqxmd.com/read/28945328/inactivated-sendai-virus-particles-upregulate-cancer-cell-icam-1-expression-with-enhancing-nk-cell-sensitivity-on-cancer-cell
#19
Simin Li, Tomoyuki Nishikawa, Yasufumi Kaneda
We have already reported that the inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) has multiple anti-cancer effects, including induction of cancer-selective cell death and activation of anti-cancer immunity. HVJ-E stimulates dendritic cells (DCs) to produce cytokines and chemokines such as IFN-β, IL-6, CCL5 and CXCL10, which activate both CD8(+) T cells and NK cells and recruit them to the tumor microenvironment. However, the effect of HVJ-E on modulating the sensitivity of cancer cells to immune cell attack has yet to be investigated...
September 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28942966/haploinsufficiency-of-the-chromatin-remodeler-bptf-causes-syndromic-developmental-and-speech-delay-postnatal-microcephaly-and-dysmorphic-features
#20
Paweł Stankiewicz, Tahir N Khan, Przemyslaw Szafranski, Leah Slattery, Haley Streff, Francesco Vetrini, Jonathan A Bernstein, Chester W Brown, Jill A Rosenfeld, Surya Rednam, Sarah Scollon, Katie L Bergstrom, Donald W Parsons, Sharon E Plon, Marta W Vieira, Caio R D C Quaio, Wagner A R Baratela, Johanna C Acosta Guio, Ruth Armstrong, Sarju G Mehta, Patrick Rump, Rolph Pfundt, Raymond Lewandowski, Erica M Fernandes, Deepali N Shinde, Sha Tang, Juliane Hoyer, Christiane Zweier, André Reis, Carlos A Bacino, Rui Xiao, Amy M Breman, Janice L Smith, Nicholas Katsanis, Bret Bostwick, Bernt Popp, Erica E Davis, Yaping Yang
Bromodomain PHD finger transcription factor (BPTF) is the largest subunit of nucleosome remodeling factor (NURF), a member of the ISWI chromatin-remodeling complex. However, the clinical consequences of disruption of this complex remain largely uncharacterized. BPTF is required for anterior-posterior axis formation of the mouse embryo and was shown to promote posterior neuroectodermal fate by enhancing Smad2-activated wnt8 expression in zebrafish. Here, we report eight loss-of-function and two missense variants (eight de novo and two of unknown origin) in BPTF on 17q24...
October 5, 2017: American Journal of Human Genetics
keyword
keyword
92901
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"