keyword
MENU ▼
Read by QxMD icon Read
search

Synthetic lethality

keyword
https://www.readbyqxmd.com/read/29777901/interrogation-of-ethnomedicinal-plants-for-synthetic-lethality-effects-in-combination-with-deficiency-in-the-dna-repair-endonuclease-rad1-using-a-yeast-cell-based-assay
#1
Hsu Mon Aung, Chananya Huangteerakul, Wittaya Panvongsa, Amornrat N Jensen, Arthit Chairoungdua, Suchada Sukrong, Laran T Jensen
ETHNOPHARMACOLOGICAL RELEVANCE: Plant materials used in this study were selected based on the ethnobotanical literature. Plants have either been utilized by Thai practitioners as alternative treatments for cancer or identified to exhibit anti-cancer properties. AIM OF THE STUDY: To screen ethnomedicinal plants using a yeast cell-based assay for synthetic lethal interactions with cells deleted for RAD1, the yeast homologue of human ERCC4 (XPF) MATERIALS AND METHODS: Ethanolic extracts from thirty-two species of medicinal plants utilized in Thai traditional medicine were screened for synthetic lethal/sick interactions using a yeast cell-based assay...
May 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29777036/pol%C3%AE-a-y-family-translesion-synthesis-polymerase-promotes-cellular-tolerance-of-myc-induced-replication-stress
#2
Kiminori Kurashima, Takayuki Sekimoto, Tsukasa Oda, Tsuyoshi Kawabata, Fumio Hanaoka, Takayuki Yamashita
Growth of precancerous and cancer cells relies on their tolerance of oncogene-induced replication stress (RS). Translesion synthesis (TLS) plays an essential role in cellular tolerance of various types of RS and bypasses replication barriers by employing specialized polymerases. However, limited information is available about the role of TLS polymerases in oncogene-induced RS. Here, we report that Polη, a Y-family TLS polymerase, promotes cellular tolerance of Myc-induced RS. Polη was recruited to Myc-induced RS sites, and Polη depletion enhanced the Myc-induced slowing and stalling of replication forks and the subsequent generation of double-strand breaks (DSBs)...
May 18, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29774145/evaluation-of-attenuative-effect-of-tert-butylhydroquinone-against-diazinon-induced-oxidative-stress-on-hematological-indices-in-male-wistar-rats
#3
Saman Sargazi, Hamidreza Galavi, Sadegh Zarei
Diazinon is an organophosphate toxicant that has been identified to induce oxidative stress within biological systems through altering biochemical and hematological indices, by generating free radicals while deteriorating the cellular antioxidant defense system. The present study was designed to evaluate the effectiveness of tert-butylhydroquinone (TBHQ), a synthetic food additive, in serving as an antioxidant against sub-lethal diazinon-induced oxidative stress in male Wistar rats. Animals were randomly divided into 4 groups: Control (treated with corn oil as a vehicle), diazinon (10 mg/kg/day), TBHQ (0...
June 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29771981/antimicrobial-activity-of-bovine-nk-lysin-derived-peptides-on-mycoplasma-bovis
#4
Rohana P Dassanayake, Shollie M Falkenberg, Karen B Register, Daniel Samorodnitsky, Eric M Nicholson, Timothy A Reinhardt
Antimicrobial peptides (AMPs) are a diverse group of molecules which play an important role in the innate immune response. Bovine NK-lysins, a type of AMP, have been predominantly found in the granules of cytotoxic T-lymphocytes and NK-cells. Bovine NK-lysin-derived peptides demonstrate antimicrobial activity against various bacterial pathogens, including several involved in bovine respiratory disease complex (BRDC) in cattle; however, such studies are yet to be performed with one important contributor to the BRDC, Mycoplasma bovis...
2018: PloS One
https://www.readbyqxmd.com/read/29768208/the-cst-complex-mediates-end-protection-at-double-strand-breaks-and-promotes-parp-inhibitor-sensitivity-in-brca1-deficient-cells
#5
Marco Barazas, Stefano Annunziato, Stephen J Pettitt, Inge de Krijger, Hind Ghezraoui, Stefan J Roobol, Catrin Lutz, Jessica Frankum, Fei Fei Song, Rachel Brough, Bastiaan Evers, Ewa Gogola, Jinhyuk Bhin, Marieke van de Ven, Dik C van Gent, Jacqueline J L Jacobs, Ross Chapman, Christopher J Lord, Jos Jonkers, Sven Rottenberg
Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration of BRCA1-independent homologous recombination through loss of factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection of DNA double-strand breaks (DSBs). To identify additional factors involved in this process, we performed CRISPR/SpCas9-based loss-of-function screens and selected for factors that confer PARP inhibitor (PARPi) resistance in BRCA1-deficient cells...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29764852/combined-hdac-and-bromodomain-protein-inhibition-reprograms-tumor-cell-metabolism-and-elicits-synthetic-lethality-in-glioblastoma
#6
Yiru Zhang, Chiaki Tsuge Ishida, Wataru Ishida, Sheng-Fu L Lo, Junfei Zhao, Chang Shu, Elena Bianchetti, Giulio Kleiner, Maria Sanchez-Quintero, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Peter Canoll, Markus D Siegelin
PURPOSE: Glioblastoma remain a challenge in oncology in part due to tumor heterogeneity. EXPERIMENTAL DESIGN: Patient-derived xenograft and stem-like glioblastoma cells were used as the primary model systems. RESULTS: Based on a transcriptome and subsequent gene set enrichment analysis (GSEA), we show by using clinically validated compounds that combined histone deacetylase (HDAC) inhibition and Bromodomain protein (BRD) inhibition results in pronounced synergistic reduction in cellular viability in patient-derived xenograft and stem-like glioblastoma cells...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29760044/nk-cells-mediate-synergistic-antitumor-effects-of-combined-inhibition-of-hdac6-and-bet-in-a-sclc-preclinical-model
#7
Yan Liu, Yuyang Li, Shengwu Liu, Dennis O Adeegbe, Camilla L Christensen, Max M Quinn, Ruben Dries, Shiwei Han, Kevin Buczkowski, Xiaoen Wang, Ting Chen, Peng Gao, Hua Zhang, Fei Li, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic regulations play a major role in SCLC disease evolution. Here we performed a synthetic lethal screen using the BET inhibitor JQ1 and an shRNA library targeting 550 epigenetic genes in treatment-refractory SCLC xenograft models and identified HDAC6 as a synthetic lethal target in combination with JQ1...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29757282/optimizing-the-use-of-a-liquid-handling-robot-to-conduct-a-high-throughput-forward-chemical-genetics-screen-of-arabidopsis-thaliana
#8
B K Amos, Victoria G Pook, Seth Debolt
Chemical genetics is increasingly being employed to decode traits in plants that may be recalcitrant to traditional genetics due to gene redundancy or lethality. However, the probability of a synthetic small molecule being bioactive is low; therefore, thousands of molecules must be tested in order to find those of interest. Liquid handling robotics systems are designed to handle large numbers of samples, increasing the speed with which a chemical library can be screened in addition to minimizing/standardizing error...
April 30, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29753961/the-role-of-parp-inhibition-in-triple-negative-breast-cancer-unraveling-the-wide-spectrum-of-synthetic-lethality
#9
REVIEW
Marios Papadimitriou, Giannis Mountzios, Christos A Papadimitriou
Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancers and is characterized by a lack of immunohistochemical expression of estrogen receptors (ER), progesterone receptors (PR) and HER2. TNBC is associated with poor long-term outcomes compared with other breast cancer subtypes. Many of these tumors are also basal-like cancers which are characterized by an aggressive biological behavior with a distant recurrence peak observed early at 3 years following diagnosis. Furthermore, metastatic TNBC bears a dismal prognosis with an average survival of 12 months...
May 2, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29751332/rhamnolipid-influences-biosorption-and-biodegradation-of-phenanthrene-by-phenanthrene-degrading-strain-pseudomonas-sp-ph6
#10
Zhao Ma, Juan Liu, Richard P Dick, Hui Li, Di Shen, Yanzheng Gao, Michael Gatheru Waigi, Wanting Ling
Given the sub-lethal risks of synthetic surfactants, rhamnolipid is a promising class of biosurfactants with the potential to promote the bioavailability of polycyclic aromatic hydrocarbons (PAHs), to provide a favorable substitute for synthetic surfactants. However, few previous studies have integrated the behavior and mechanism behind rhamnolipid-influenced PAH biosorption and biodegradation. This is, to our knowledge, the first report of a bacterial envelope regulated link between phenanthrene (PHE) biosorption and biodegradation by rhamnolipid-induced PHE-degrading strain Pseudomonas sp...
May 8, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29750868/brca-status-does-not-predict-synergism-of-a-carboplatin-and-olaparib-combination-in-high-grade-serous-ovarian-cancer-cell-lines
#11
Yen Ting Shen, James C Evans, Gaetano Zafarana, Christine Allen, Micheline Piquette-Miller
Over 50% of epithelial ovarian cancers express the BRCAness profile that leads to a dysfunctional homologous recombination repair system. The combination of a dysfunctional homologous recombination repair system and a poly (ADP-ribose) polymerase (PARP) inhibitor results in a synthetic lethal phenotype. The PARP inhibitor olaparib, approved as a monotherapy for patients with a germline BRCA mutation, has shown promising results in preclinical studies when combined with DNA damaging agents such as carboplatin...
May 11, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29743557/inhibition-of-bcl-2-bcl-xl-and-c-met-causes-synthetic-lethality-in-model-systems-of-glioblastoma
#12
Yiru Zhang, Chiaki Tsuge Ishida, Chang Shu, Giulio Kleiner, Maria J Sanchez-Quintero, Elena Bianchetti, Catarina M Quinzii, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin
Recent data suggest that glioblastomas (GBM) activate the c-MET signaling pathway and display increased levels in anti-apoptotic Bcl-2 family members. Therefore, targeting these two deregulated pathways for therapy might yield synergistic treatment responses. We applied extracellular flux analysis to assess tumor metabolism. We found that combined treatment with ABT263 and Crizotinib synergistically reduces the proliferation of glioblastoma cells, which was dependent on dual inhibition of Bcl-2 and Bcl-xL. The combination treatment led to enhanced apoptosis with loss of mitochondrial membrane potential and activation of caspases...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29743404/-epigenetic-aberrations-in-adult-t-cell-leukemia-lymphoma-and-development-of-a-novel-ezh1-2-inhibitor
#13
Makoto Yamagishi
Histone H3 lysine 27 tri-methylation (H3K27me3) -dependent transcription regulation is a fundamental process of gene control. Although EZH2 mutation is observed in certain lymphoma types, many other cancers show global H3K27me3 accumulation irrespective of mutation. However, the underlying mechanisms of gene silencing and therapeutic efficacies of epigenetic drugs remain unclear. In this study, we showed that globally-accumulated H3K27me3 is induced by both cis-bound EZH1 and EZH2 in mature lymphocyte-derived malignancies...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29721631/multiple-chemo-genetic-interactions-between-a-toxic-metabolite-and-the-ubiquitin-pathway-in-yeast
#14
Delphine Albrecht, Hans C Hürlimann, Johanna Ceschin, Christelle Saint-Marc, Benoît Pinson, Bertrand Daignan-Fornier
AICAR is the precursor of ZMP, a metabolite with antiproliferative properties in yeast and human. We aim at understanding how AICAR (and its active form ZMP) affects essential cellular processes. In this work, we found that ZMP accumulation is synthetic lethal with a hypomorphic allele of the ubiquitin-activating enzyme Uba1. A search for gene-dosage suppressors revealed that ubiquitin overexpression was sufficient to restore growth of the uba1 mutant upon AICAR treatment, suggesting that the ubiquitin pool is critical for cells to cope with AICAR...
May 2, 2018: Current Genetics
https://www.readbyqxmd.com/read/29720560/targeting-the-mevalonate-pathway-suppresses-vhl-deficient-cc-rcc-through-a-hif-dependent-mechanism
#15
Jordan M Thompson, Alejandro Alvarez, Monika K Singha, Matthew W Pavesic, Quy H Nguyen, Luke J Nelson, David A Fruman, Olga V Razorenova
Clear Cell Renal Cell Carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advance stages. The objective of this study was to investigate HMG-CoA Reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins...
May 2, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29717261/antagonizing-cd105-enhances-radiation-sensitivity-in-prostate-cancer
#16
Anisha Madhav, Allen Andres, Frank Duong, Rajeev Mishra, Subhash Haldar, Zhenqiu Liu, Bryan Angara, Roberta Gottlieb, Zachary S Zumsteg, Neil A Bhowmick
Radiation therapy is the primary intervention for nearly half of the patients with localized advanced prostate cancer and standard of care for recurrent disease following surgery. The development of radiation-resistant disease is an obstacle for nearly 30-50% of patients undergoing radiotherapy. A better understanding of mechanisms that lead to radiation resistance could aid in the development of sensitizing agents to improve outcome. Here we identified a radiation-resistance pathway mediated by CD105, downstream of BMP and TGF-β signaling...
May 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29705685/translational-genomics-in-pancreatic-ductal-adenocarcinoma-a-review-with-re-analysis-of-tcga-dataset
#17
REVIEW
Jeffery Ho, Xianchun Li, Lin Zhang, Yonghao Liang, Wei Hu, Johnny C W Yau, Hung Chan, Tony Gin, Matthew T V Chan, Gary Tse, William K K Wu
Malignancy of the pancreas is a leading cause of cancer-related mortality, with the highest case-fatality of all cancers. Nevertheless, the lack of sensitive biomarkers and presence of biological heterogeneity precludes its early detection and effective treatment. The recent introduction of next-generation sequencing allows characterization of multiple driver mutations at genome- and exome-wide levels. Sequencing of DNA and RNA from circulating tumour cells has also opened an exciting era of non-invasive procedures for tumour detection and prognostication...
April 25, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29688721/nano-encapsulation-of-novel-inhibitors-of-pnkp-for-selective-sensitization-to-ionizing-radiation-and-irinotecan-and-induction-of-synthetic-lethality
#18
Zahra Shire, Mohammad Reza Vakili, Timothy D R Morgan, Dennis G Hall, Afsaneh Lavasanifar, Michael Weinfeld
There is increasing interest in developing and applying DNA repair inhibitors in cancer treatment to augment the efficacy of radiation and conventional genotoxic chemotherapy. However, targeting the inhibitor is required to avoid reducing the repair capacity of normal tissue. The aim of this study was to develop nano-delivery systems for the encapsulation of novel imidopiperidine-based inhibitors of the DNA 3'-phosphatase activity of polynucleotide kinase/phosphatase (PNKP), a DNA repair enzyme that plays a critical role in rejoining DNA single- and double-strand breaks...
April 24, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29688214/-extracranial-aneurysms-of-carotid-arteries-in-the-practice-of-a-vascular-surgeon
#19
R N Lar'kov, S S Zagarov, M V Vishniakova, R V Shilov
The present study was aimed at retrospectively analysing the results of examination and open surgical treatment of patients diagnosed with extracranial aneurysms of carotid arteries. PATIENTS AND METHODS: We analysed the results of examination and outcomes of surgical treatment in a total of 11 patients (6 men and 5 women) presenting with an aneurysm of the extracranial portion of the carotid artery and undergoing treatment at the Department of Vascular and CAD Surgery of the Moscow Regional Research Clinical Institute from 2005 to 2016...
2018: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29686061/prevention-of-hepatocellular-carcinoma-by-targeting-mycn-positive-liver-cancer-stem-cells-with-acyclic-retinoid
#20
Xian-Yang Qin, Harukazu Suzuki, Masao Honda, Hikari Okada, Shuichi Kaneko, Ikuyo Inoue, Etsuko Ebisui, Kosuke Hashimoto, Piero Carninci, Keita Kanki, Hideki Tatsukawa, Naoto Ishibashi, Takahiro Masaki, Tomokazu Matsuura, Hiroyuki Kagechika, Kan Toriguchi, Etsuro Hatano, Yohei Shirakami, Goshi Shiota, Masahito Shimizu, Hisataka Moriwaki, Soichi Kojima
Hepatocellular carcinoma (HCC) is a highly lethal cancer that has a high rate of recurrence, in part because of cancer stem cell (CSC)-dependent field cancerization. Acyclic retinoid (ACR) is a synthetic vitamin A-like compound capable of preventing the recurrence of HCC. Here, we performed a genome-wide transcriptome screen and showed that ACR selectively suppressed the expression of MYCN, a member of the MYC family of basic helix-loop-helix-zipper transcription factors, in HCC cell cultures, animal models, and liver biopsies obtained from HCC patients...
April 23, 2018: Proceedings of the National Academy of Sciences of the United States of America
keyword
keyword
16878
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"