keyword
MENU ▼
Read by QxMD icon Read
search

PARP

keyword
https://www.readbyqxmd.com/read/29150161/improved-pharmacodynamic-pd-assessment-of-low-dose-parp-inhibitor-pd-activity-for-radiotherapy-and-chemotherapy-combination-trials
#1
Rosemarie de Haan, Dick Pluim, Baukelien van Triest, Michel van den Heuvel, Heike Peulen, Damien van Berlo, Jay George, Marcel Verheij, Jan H M Schellens, Conchita Vens
BACKGROUND: PARP inhibitors are currently evaluated in combination with radiotherapy and/or chemotherapy. As sensitizers, PARP inhibitors are active at very low concentrations therefore requiring highly sensitive pharmacodynamic (PD) assays. Current clinical PD-assays partly fail to provide such sensitivities. The aim of our study was to enable sensitive PD evaluation of PARP inhibitors for clinical sensitizer development. MATERIAL AND METHODS: PBMCs of healthy individuals and of olaparib and radiotherapy treated lung cancer patients were collected for ELISA-based PD-assays...
November 14, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/29149203/alc1-chd1l-a-chromatin-remodeling-enzyme-is-required-for-efficient-base-excision-repair
#2
Masataka Tsuda, Kosai Cho, Masato Ooka, Naoto Shimizu, Reiko Watanabe, Akira Yasui, Yuka Nakazawa, Tomoo Ogi, Hiroshi Harada, Keli Agama, Jun Nakamura, Ryuta Asada, Haruna Fujiike, Tetsushi Sakuma, Takashi Yamamoto, Junko Murai, Masahiro Hiraoka, Kaoru Koike, Yves Pommier, Shunichi Takeda, Kouji Hirota
ALC1/CHD1L is a member of the SNF2 superfamily of ATPases carrying a macrodomain that binds poly(ADP-ribose). Poly(ADP-ribose) polymerase (PARP) 1 and 2 synthesize poly(ADP-ribose) at DNA-strand cleavage sites, promoting base excision repair (BER). Although depletion of ALC1 causes increased sensitivity to various DNA-damaging agents (H2O2, UV, and phleomycin), the role played by ALC1 in BER has not yet been established. To explore this role, as well as the role of ALC1's ATPase activity in BER, we disrupted the ALC1 gene and inserted the ATPase-dead (E165Q) mutation into the ALC1 gene in chicken DT40 cells, which do not express PARP2...
2017: PloS One
https://www.readbyqxmd.com/read/29145487/defining-external-factors-that-determine-neuronal-survival-apoptosis-and-necrosis-during-excitotoxic-injury-using-a-high-content-screening-imaging-platform
#3
Ujval Anilkumar, Petronela Weisova, Jasmin Schmid, Tytus Bernas, Heinrich J Huber, Heiko Düssmann, Niamh M C Connolly, Jochen H M Prehn
Cell death induced by excessive glutamate receptor overactivation, excitotoxicity, has been implicated in several acute and chronic neurological disorders. While numerous studies have demonstrated the contribution of biochemically and genetically activated cell death pathways in excitotoxic injury, the factors mediating passive, excitotoxic necrosis are less thoroughly investigated. To address this question, we developed a high content screening (HCS) based assay to collect high volumes of quantitative cellular imaging data and elucidated the effects of intrinsic and external factors on excitotoxic necrosis and apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/29143372/a-critical-role-of-trpm2-channel-in-a%C3%AE-42-induced-microglial-activation-and-generation-of-tumor-necrosis-factor-%C3%AE
#4
Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin-Hua Jiang
Amyloid β (Aβ)-induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin-related 2 (TRPM2) channel in Aβ-induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor-α (TNF-α), a key cytokine implicated in AD...
November 16, 2017: Glia
https://www.readbyqxmd.com/read/29143351/apoptotic-and-antiproliferative-properties-of-3%C3%AE-hydroxy-%C3%AE-5-steroidal-congeners-from-a-partially-purified-column-fraction-of-dendronephthya-gigantea-against-hl-60-and-mcf-7-cancer-cells
#5
I P Shanura Fernando, K K Asanka Sanjeewa, Hyun-Soo Kim, Lei Wang, Won Woo Lee, You-Jin Jeon
Organisms belonging to the genus Dendronephthya are among a group of marine invertebrates that produce a variety of terpenoids with biofunctional properties. Many of these terpenoids have been proven effective as anticancer drugs. Here, we report the antiproliferative effect of 3β-hydroxy-Δ5-steroidal congeners against the proliferation of HL-60 human leukemia cells and MCF-7 human breast cancer cells. The sterol-rich fraction (DGEHF2-1) inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 13...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29138847/srpk1%C3%A2-sirna-suppresses-k562-cell-growth-and-induces-apoptosis-via-the-parp%C3%A2-caspase3-pathway
#6
Hailian Wang, Wei Ge, Wen Jiang, Dong Li, Xiuli Ju
Serine-arginine protein kinase 1 (SRPK1) has been used as an important signal mediator, and is associated with cancer development. However, studies have yet to determine whether SRPK1 suppresses leukemia cell growth and induces apoptosis. Studies have also yet to reveal the underlying mechanisms. In the present study, the effects of downregulating SRPK1 gene expression on chronic myeloid leukemia cell lines (K562 cells) were investigated through RNA interference (RNAi) and the proliferation inhibition and apoptosis induction of SRPK1 in K562 cells were analyzed...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138572/current-status-of-poly-adp-ribose-polymerase-inhibitors-and-future-directions
#7
REVIEW
Akihiro Ohmoto, Shinichi Yachida
Inhibitors of poly(ADP-ribose) polymerases (PARPs), which play a key role in DNA damage/repair pathways, have been developed as antitumor agents based on the concept of synthetic lethality. Synthetic lethality is the idea that cell death would be efficiently induced by simultaneous loss of function of plural key molecules, for example, by exposing tumor cells with inactivating gene mutation of BRCA-mediated DNA repair to chemically induced inhibition of PARPs. Indeed, three PARP inhibitors, olaparib, rucaparib and niraparib have already been approved in the US or Europe, mainly for the treatment of BRCA-mutant ovarian cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29138344/targeting-the-mycn-parp-dna-damage-response-pathway-inneuroendocrine-prostate-cancer
#8
Wei Zhang, Bo Liu, Wenhui Wu, Likun Li, Bradley M Broom, Spyridon M Basourakos, Dimitrios Korentzelos, Yang Luan, Jianxiang Wang, Guang Yang, Sanghee Park, Abul K Azad, Xuhong Cao, Jeri Kim, Paul Corn, Christopher Logothetis, Ana M Aparicio, Arul M Chinnayan, Nora M Navone, Patricia Troncoso, Timothy C Thompson
PURPOSE: We investigated MYCN-regulated molecular pathways in castration-resistant prostate cancer (CRPC) classified by morphological criteria as adenocarcinoma or neuroendocrine to extend the molecular phenotype, establish driver pathways, and identify novel approaches to combination therapy for NEPC. RESULTS: Using comparative bioinformatics analyses of CRPC-Adeno and CRPC-Neuro RNA sequence data from public datasets and a panel of 28 PDX models we identified a MYCN-PARP-DNA damage response (DDR) pathway that is enriched in CRPC with neuroendocrine differentiation (NED) and CRPC-Neuro...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29137114/natural-cyclopeptide-ra-xii-a-new-autophagy-inhibitor-suppresses-protective-autophagy-for-enhancing-apoptosis-through-ampk-mtor-p70s6k-pathways-in-hepg2-cells
#9
Lihua Song, Zhe Wang, Yurong Wang, Di Guo, Jianhong Yang, Lijuan Chen, Ninghua Tan
Liver cancer is a progressive, irreversible and aggressive malignant disease, which has no effective chemotherapeutic drugs. RA-XII, a natural cyclopeptide isolated from the traditional Chinese medicine Rubia yunnanensis, exerts anti-cancer and anti-inflammatory activities. This work aimed to investigate the effects of RA-XII on a hepatic tumor and its underlying mechanisms in human hepatoma HepG2 cells. The results showed that RA-XII effectively inhibited the proliferation of HepG2 cells. Consistently, RA-XII significantly induced apoptosis in HepG2 cells by decreasing the expression of caspase 3, 8, 9, and promoting the Cleavage of PARP...
November 11, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29136949/minocycline-improves-cardiac-function-after-myocardial-infarction-in-rats-by-inhibiting-activation-of-parp-1
#10
Hua Zhao, Jianjun Zhang, Gang Hong
To investigate whether Minocycline can protect myocardial cells after myocardial infarction and improve myocardial remodeling through inhibiting PARP-1 activity, thus improving cardiac function. 50 male Wistar rats aged 4 months were used to establish the myocardial infarction model. The experimental rats underwent the echocardiography at 3d, 14d and 28d after operation. After 28days, the rats were executed and the myocardial tissues in the infarct-related zone were treated with immumohistochemical staining and molecular biology detection...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136560/cytoprotective-effects-of-glycyrrhetinic-acid-liposome-against-cyclophosphamide-induced-cystitis-through-inhibiting-inflammatory-stress
#11
Bo Ge, Daping Yang, Xinmou Wu, Jing Zhu, Wu Wei, Bin Yang
This study was designed to investigate the pharmacological efficacy of glycyrrhetinic acid liposome (GAL) against female mice with nonbacterial cystitis induced by cyclophosphamide (CPS). Mice in different groups were subjected to tests for lactate dehydrogenase (LD), cytokine contents (IL-6, TNF-α) in serum, and histological changes in bladder tissue and to immunoassays. As a result, cyclophosphamide-induced cystitis in mice showed an increased LD level in serum, and the contents of cytokines (IL-6, TNF-α) were elevated...
November 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29134494/expression-of-telomere-associated-proteins-is-interdependent-to-stabilize-native-telomere-structure-and-telomere-dysfunction-by-g-quadruplex-ligand-causes-terra-upregulation
#12
Ratan Sadhukhan, Priyanka Chowdhury, Sourav Ghosh, Utpal Ghosh
Telomere DNA can form specialized nucleoprotein structure with telomere-associated proteins to hide free DNA ends or G-quadruplex structures under certain conditions especially in presence of G-quadruplex ligand. Telomere DNA is transcribed to form non-coding telomere repeat-containing RNA (TERRA) whose biogenesis and function is poorly understood. Our aim was to find the role of telomere-associated proteins and telomere structures in TERRA transcription. We silenced four [two shelterin (TRF1, TRF2) and two non-shelterin (PARP-1, SLX4)] telomere-associated genes using siRNA and verified depletion in protein level...
November 13, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29133592/parp1-trapping-and-dna-replication-stress-enhance-radiosensitization-with-combined-wee1-and-parp-inhibitors
#13
Leslie A Parsels, David Karnak, Joshua Parsels, Qiang Zhang, Jonathan Vélez-Padilla, Zachery Reichert, Daniel R Wahl, Jonathan Maybaum, Mark J O'Connor, Theodore S Lawrence, Meredith A Morgan
KRAS mutations in non-small cell lung cancer (NSCLC) cause increased levels of DNA damage and replication stress, suggesting that inhibition of the DNA damage response (DDR) is a promising strategy for radiosensitization of NSCLC. This study investigates the ability of a WEE1 inhibitor (AZD1775) and a PARP inhibitor (olaparib) to radiosensitize KRAS mutant NSCLC cells and tumors. In addition to inhibiting the DDR, these small-molecule inhibitors of WEE1 and PARP induce DNA replication stress via nucleotide exhaustion and PARP trapping, respectively...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133135/characterization-detection-and-treatment-approaches-for-homologous-recombination-deficiency-in-cancer
#14
REVIEW
Grainne M O'Kane, Ashton A Connor, Steven Gallinger
Investigations of carcinogenesis have evolved from the identification of clonal driver mutations in candidate genes to the integration of large volumes of genomic and transcriptomic data revealing recurrently altered pathways and signatures of mutational processes. Inactivation of BRCA1, BRCA2, or PALB2 impairs efficient double-strand break repair (DSBR), giving rise to a spectrum of homologous recombination deficiency (HRD) cancer phenotypes. Harnessing HRD therapeutically has been promising in a number of tumors; these approaches include leveraging synthetic lethality by targeting alternative repair pathways via PARP inhibition, inducing HRD to modulate potential tumor vulnerabilities, and preventing mechanisms of drug resistance...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29133049/design-and-synthesis-of-novel-c14-urea-tetrandrine-derivatives-with-potent-anti-cancer-activity
#15
Junjie Lan, Lan Huang, Huayong Lou, Chao Chen, Tangjingjun Liu, Shengcao Hu, Yao Yao, Junrong Song, Jun Luo, Yazhou Liu, Bin Xia, Lei Xia, Xueyi Zeng, Yaacov Ben-David, Weidong Pan
Tetrandrine is a dibenzyltetrahydroisoquinoline alkaloid, isolated from traditional Chinese medicinal plant Stephania tetrandra, with anti-tumor activity. Our previous study identified several derivatives of tetrandrine showing better activities than parental compound against human hepatocellular carcinoma cells. To increase diversity and cytotoxic activities of the original compound, a series of novel 14-urea-tetrandrine derivatives were synthesized through structural modification of tetrandrine. These derivaties demonstrated a moderate to strong anti-proliferative activities against human cell lines HEL and K562 (Leukemia), prostate (PC3), breast (MDA-MB-231) and melanoma (WM9)...
November 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29133035/design-and-synthesis-of-novel-thiobarbituric-acid-derivatives-targeting-both-wild-type-and-braf-mutated-melanoma-cells
#16
Srinivasa Rao Ramisetti, Manoj K Pandey, Sang Y Lee, Deepkamal Karelia, Satya Narayan, Shantu Amin, Arun K Sharma
A series of novel thio- and seleno-barbituric acid derivatives were synthesized by varying the substituents at N1 and N3 (ethyl, methyl, allyl, and phenyl), and C5 tethered with dienyl and trienyl moieties attached to substituents such as phenyl, 2-furanyl, 2-thiophenyl, 1-naphthyl, and 3-pyridyl. The cytotoxic potential of these derivatives was evaluated by using MTT assay against melanoma cell lines expressing either wild-type (CHL-1) or mutant (UACC 903) BRAF gene. Among all, 2b and 8b were identified as the most potent compounds...
November 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29132924/impact-of-capsaicin-an-active-component-of-chili-pepper-on-pathogenic-chlamydial-growth-chlamydia-trachomatis-and-chlamydia-pneumoniae-in-immortal-human-epithelial-hela-cells
#17
Kazuya Yamakawa, Junji Matsuo, Torahiko Okubo, Shinji Nakamura, Hiroyuki Yamaguchi
Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. Capsaicin, a component of chili pepper, which can stimulate actin remodeling via capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) and anti-inflammatory effects via PPARγ (peroxisome proliferator-activated receptor-γ) and LXRα (liver X receptor α), is a potential candidate to control chlamydial growth in host cells. We examined whether capsaicin could inhibit C. trachomatis growth in immortal human epithelial HeLa cells...
November 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29132683/-impairment-of-dna-damage-response-and-cancer
#18
REVIEW
Chloé Rancoule, Alexis Vallard, Jean-Baptiste Guy, Sophie Espenel, Sylvie Sauvaigo, Claire Rodriguez-Lafrasse, Nicolas Magné
Maintaining the genetic integrity is a key process in cell viability and is enabled by a wide network of repair pathways. When this system is defective, it generates genomic instability and results in an accumulation of chromosomal aberrations and mutations that may be responsible for various clinical phenotypes, including susceptibility to develop cancer. Indeed, these defects can promote not only the initiation of cancer, but also allow the tumor cells to rapidly acquire mutations during their evolution. Several genes are involved in these damage repair systems and particular polymorphisms are predictive of the onset of cancer, the best described of them being BRCA...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29132681/-dna-repair-as-a-therapeutic-target
#19
REVIEW
Lauriane Eberst, Medhi Brahmi, Philippe A Cassier
The transmission of an intact and stable genetic code at each cell division relies on different DNA repair systems. Germline mutations of some of these genes cause cancer predisposition, whereas somatic mutations are frequently found in various cancer types, generating genomic instability. As a consequence, cancer cell becomes more susceptible to additional DNA damage. Pharmacological inhibition of DNA repair pathways exploits this frailty: it triggers more damages than cancer cell can tolerate, finally leading to apoptosis...
November 10, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29131243/photodynamic-therapy-with-5-aminolevulinic-acid-suppresses-ifn-%C3%AE-induced-k17-expression-in-hacat-cells-via-mapk-pathway
#20
X-L Wang, Q Sun
OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder that greatly affects the patient's quality of life. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has recently been applied for inflammatory dermatoses including psoriasis. However, the therapeutic effect of ALA-PDT is yet to be validated, and the underlying mechanisms remain unclear. MATERIALS AND METHODS: In this study, a psoriatic model was established by treating HaCaT cells with 250 U/ml IFN-γ for 48 h...
October 2017: European Review for Medical and Pharmacological Sciences
keyword
keyword
13735
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"