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https://www.readbyqxmd.com/read/29052145/cell-death-pathways-a-novel-therapeutic-approach-for-neuroscientists
#1
REVIEW
G Morris, A J Walker, M Berk, M Maes, B K Puri
In the first part, the following mechanisms involved in different forms of cell death are considered, with a view to identifying potential therapeutic targets: tumour necrosis factor receptors (TNFRs) and their engagement by tumour necrosis factor-alpha (TNF-α); poly [ADP-ribose] polymerase (PARP)-1 cleavage; the apoptosis signalling kinase (ASK)-c-Jun N-terminal kinase (JNK) axis; lysosomal permeability; activation of programmed necrotic cell death; oxidative stress, caspase-3 inhibition and parthanatos; activation of inflammasomes by reactive oxygen species and the development of pyroptosis; oxidative stress, calcium dyshomeostasis and iron in the development of lysosomal-mediated necrosis and lysosomal membrane permeability; and oxidative stress, lipid peroxidation, iron dyshomeostasis and ferroptosis...
October 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29051731/parp-1-and-p53-regulate-the-increased-susceptibility-to-oxidative-death-of-lymphocytes-from-mci-and-ad-patients
#2
Felipe Salech, Daniela P Ponce, Carol D SanMartín, Nicole K Rogers, Carlos Chacón, Mauricio Henríquez, Maria I Behrens
Mild cognitive impairment (MCI) is a clinically detectable initial stage of cognitive deterioration with a high conversion rate to dementia. There is increasing evidence that some of the cerebral alterations present in Alzheimer type dementia can be found in peripheral tissues. We have previously shown that lymphocytes from Alzheimer's disease (AD) patients have increased susceptibility to hydrogen peroxide (H2O2)-induced death that depends on dementia severity. We here investigated whether lymphocytes from MCI patients show increased vulnerability to death, and explored the involvement of Poly [ADP-ribose] polymerase (PARP-1) and p53 in the regulation of this process...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29050241/combination-treatment-with-rucaparib-rubraca-and-mdm2-inhibitors-nutlin-3-and-rg7388-has-synergistic-and-dose-reduction-potential-in-ovarian-cancer
#3
Maryam Zanjirband, Nicola Curtin, Richard J Edmondson, John Lunec
Ovarian cancer is the seventh most common cancer worldwide for females and the most lethal of all gynecological malignancies. The treatment of ovarian cancer remains a challenge in spite of advances in debulking surgery and changes in both chemotherapy schedules and routes of administration. Cancer treatment has recently been improving with the introduction of targeted therapies to achieve greater specificity and less cytotoxicity. Both PARP inhibitors and MDM2-p53 binding antagonists are targeted therapeutic agents entered into clinical trials...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049980/the-dual-role-of-poly-adp-ribose-polymerase-1-in-modulating-parthanatos-and-autophagy-under-oxidative-stress-in-rat-cochlear-marginal-cells-of-the-stria-vascularis
#4
Hong-Yan Jiang, Yang Yang, Yuan-Yuan Zhang, Zhen Xie, Xue-Yan Zhao, Yu Sun, Wei-Jia Kong
Oxidative stress is reported to regulate several apoptotic and necrotic cell death pathways in auditory tissues. Poly(ADP-ribose) polymerase-1 (PARP-1) can be activated under oxidative stress, which is the hallmark of parthanatos. Autophagy, which serves either a pro-survival or pro-death function, can also be stimulated by oxidative stress, but the role of autophagy and its relationship with parthanatos underlying this activation in the inner ear remains unknown. In this study, we established an oxidative stress model in vitro by glucose oxidase/glucose (GO/G), which could continuously generate low concentrations of H2O2 to mimic continuous exposure to H2O2 in physiological conditions, for investigation of oxidative stress-induced cell death mechanisms and the regulatory role of PARP-1 in this process...
October 7, 2017: Redox Biology
https://www.readbyqxmd.com/read/29048673/the-ethanol-extracts-of-sporoderm-broken-spores-of-ganoderma-lucidum-inhibit-colorectal-cancer-in-vitro-and-in-vivo
#5
Kang Li, Kun Na, Tingting Sang, Kaikai Wu, Ying Wang, Xingya Wang
The medicinal mushroom Ganoderma lucidum (G. lucidum) has been reported to possess a variety of pharmacological activities including anticancer effects. However, the anti-colorectal cancer effects and the potential molecular mechanisms of the ethanol extracts of sporoderm-broken spores of G. lucidum (BSGLEE), which mainly contains triterpenoids, have not been reported. The aim of the present study was to investigate the anticancer effects and molecular mechanisms exerted by BSGLEE on colorectal cancer in vitro and in vivo...
September 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29048645/establishment-and-characterization-of-human-osteosarcoma-cells-resistant-to-pyropheophorbide-%C3%AE-methyl-ester-mediated-photodynamic-therapy
#6
Yong Tao, Yunsheng Ou, Hang Yin, Yanyang Chen, Shenxi Zhong, Yongjian Gao, Zenghui Zhao, Bin He, Qiu Huang, Qianxing Deng
The present study was performed to establish and characterize new human osteosarcoma cell lines resistant to pyropheophorbide-α methyl ester‑mediated photodynamic therapy (MPPa-PDT). MPPa-PDT-resistant cells are isolated from the human osteosarcoma MG63 and HOS cell lines and two resistant populations were finally acquired, including MG63/PDT and HOS/PDT. Cell Counting Kit-8 (CCK-8) assay was used to determine the MPPa-PDT, cisplatin (CDDP) resistance and proliferation of MG63, MG63/PDT, HOS and HOS/PDT cells...
September 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29048624/liquiritin-induces-apoptosis-and-autophagy-in-cisplatin-ddp-resistant-gastric-cancer-cells-in-vitro-and-xenograft-nude-mice-in-vivo
#7
Feng Wei, Xin Jiang, Hao-Yue Gao, Shuo-Hui Gao
Gastric cancer is reported as one of the leading factors resulting in tumor-related death worldwide. However, the therapies to suppress gastric cancer are still limited and the emergence of drug resistance makes it necessary to develop new and effective anticancer drugs and combinational chemotherapy schemes. Liquiritin (LIQ) is a major constituent of Glycyrrhiza Radix, exhibiting various pharmacological activities, including anticancer. In this study, we investigated the role of LIQ in human gastric cancer cells with cisplatin (DDP) resistance...
September 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29047155/maduramicin-induces-apoptosis-and-necrosis-and-blocks-autophagic-flux-in-myocardial-h9c2-cells
#8
Xin Chen, Long Chen, Shanxiang Jiang, Shile Huang
Maduramicin, a polyether ionophore antibiotic, is widely used as an anticoccidial agent in the poultry industry. It has been reported that maduramicin may cause heart and skeletal muscle cell damage, resulting in heart failure, skeletal muscle degeneration and even death in animals and humans, if improperly used. However, the molecular mechanism behind its capability to cause death of cardiac cells is not known. Here, we show that maduramicin induced apoptosis and necrosis in rat myocardial cells (H9c2). Maduramicin did not apparently upregulate the expression of pro-apoptotic proteins (e...
October 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29045554/veliparib-with-temozolomide-or-carboplatin-paclitaxel-versus-placebo-with-carboplatin-paclitaxel-in-patients-with-brca1-2-locally-recurrent-metastatic-breast-cancer-randomized-phase-ii-study
#9
H S Han, V Diéras, M Robson, M Palácová, P K Marcom, A Jager, I Bondarenko, D Citrin, M Campone, M L Telli, S M Domchek, M Friedlander, B Kaufman, J E Garber, Y Shparyk, E Chmielowska, E H Jakobsen, V Kaklamani, W Gradishar, C K Ratajczak, C Nickner, Q Qin, J Qian, S P Shepherd, S J Isakoff, S Puhalla
Background: Homologous recombination defects in BRCA1/2-mutated tumors result in sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, which interfere with DNA damage repair. Veliparib, a potent PARP inhibitor, enhanced the antitumor activity of platinum agents and temozolomide in early phase clinical trials. This phase II study examined the safety and efficacy of intermittent veliparib with carboplatin/paclitaxel (VCP) or temozolomide (VT) in patients with BRCA1/2-mutated breast cancer...
September 29, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045036/endoplasmic-reticulum-stress-regulates-oxygen-glucose-deprivation-induced-parthanatos-in-human-sh-sy5y-cells-via-improvement-of-intracellular-ros
#10
Hai-Feng Wang, Zong-Qi Wang, Ye Ding, Mei-Hua Piao, Chun-Sheng Feng, Guang-Fan Chi, Yi-Nan Luo, Peng-Fei Ge
AIMS: Endoplasmic reticulum (ER) stress has been demonstrated to regulate neuronal death caused by ischemic insults via activation of apoptosis, but it still remains unclear whether ER stress participates in regulation of parthanatos, a new type of programmed cell death characterized by PARP-1 overactivation and intracellular accumulation of PAR polymer. METHODS: we used oxygen-glucose deprivation (OGD) and human SH-SY5Y cells to simulate neuronal damage caused by ischemia...
October 16, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29042952/protective-effect-of-ulinastatin-on-severe-pulmonary-infection-under-immunosuppression-and-its-molecular-mechanism
#11
Wenshuai Liu, Guozhong Pang, Shengyan Wang, Aiqin Sun
The objective of the present study was to investigate the protective effect of ulinastatin on severe pulmonary infection under immunosuppression, and its molecular mechanism. Mice were treated with methylprednisolone and lipopolysaccharide (LPS) to establish the model of severe pulmonary infection under immunosuppression. Mice were randomly divided into group A (model group; treated with equal volumes of saline), group B (treated with 1×10(5) U/kg ulinastatin), and group C (normal control group). Bronchoalveolar lavage fluid (BALF) was collected, and the concentrations of cytokines in BALF were measured by enzyme-linked immunosorbent assay (ELISA)...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29039524/synergistic-effects-of-baicalein-with-gemcitabine-or-docetaxel-on-the-proliferation-migration-and-apoptosis-of-pancreatic-cancer-cells
#12
Pan Liu, Jiarui Feng, Meng Sun, Wen Yuan, Ruijing Xiao, Jie Xiong, Xiaoxin Huang, Meng Xiong, Wu Chen, Xin Yu, Qian Sun, Xiaojie Zhao, Qiuping Zhang, Liang Shao
Baicalein, a type of flavonoids extracted from Scutellaria baicalensis Georgi, has been reported to be a very promising drug for pancreatic cancer. However, it is unclear whether combination of baicalein with gemcitabine or docetaxel is synergistic to the treatment for pancreatic cancer (PC). We investigated the combinational effects of baicalein with gemcitabine or docetaxel on proliferation, cell cycle, migration and apoptosis of human PC cells. Administration of baicalein alone significantly inhibit the proliferation of PC cells...
October 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039493/actein-induces-apoptosis-in-leukemia-cells-through-suppressing-rhoa-rock1-signaling-pathway
#13
Wen-Di Zhou, Xiang Wang, Xing-Zhen Sun, Jian Hu, Rong-Rong Zhang, Ze Hong
Actein is a tetracyclic triterpenoid compound, extracted from the rhizome of Cimicifuga foetida, exhibiting anticancer activities as previously reported. However, the effects of actein on human leukemia have not been explored before. In this study, the role of actein in regulating apoptosis induction in human leukemia cells was investigated. Actein administration significantly enhanced apoptosis, especially in human leukemia cell line of U937 and the primary human leukemia cells. The promotion was accompanied by caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c (Cyto-c) release...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29039470/effects-of-baicalein-on-proliferation-apoptosis-migration-and-invasion-of-ewing-s-sarcoma-cells
#14
Conglin Ye, Xiaolong Yu, Jin Zeng, Min Dai, Bin Zhang
Ewing's sarcoma (ES) is a rare tumor that is more frequent in pediatric and adolescent age groups. In the past few decades, long-term survival in affected patients has improved due to the success of multimodal therapy. However, long-term survival is inevitably restricted by the late side-effects of chemotherapy. Besides, early metastasis also contributes to the poor prognosis of ES. Recently, traditional Chinese medicines (TCMs) have increasingly attracted interest due to the promising clinical results and fewer side-effects for the treatment of cancers...
October 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29038547/a-novel-fer-fert-targeting-compound-selectively-evokes-metabolic-stress-and-necrotic-death-in-malignant-cells
#15
Yoav Elkis, Moshe Cohen, Etai Yaffe, Shirly Satmary-Tusk, Tal Feldman, Elad Hikri, Abraham Nyska, Ariel Feiglin, Yanay Ofran, Sally Shpungin, Uri Nir
Disruption of the reprogrammed energy management system of malignant cells is a prioritized goal of targeted cancer therapy. Two regulators of this system are the Fer kinase, and its cancer cell specific variant, FerT, both residing in subcellular compartments including the mitochondrial electron transport chain. Here, we show that a newly developed inhibitor of Fer and FerT, E260, selectively evokes metabolic stress in cancer cells by imposing mitochondrial dysfunction and deformation, and onset of energy-consuming autophagy which decreases the cellular ATP level...
October 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29036264/immature-colon-carcinoma-transcript-1-promotes-proliferation-of-gastric-cancer-cells
#16
Zishu Wang, Gongsheng Jin, Qiong Wu, Rui Wang, Yumei Li
Gastric cancer is the fourth most common malignant tumor and has been considered as one of the leading causes of cancer-related death worldwide. The identification of the molecular mechanism during gastric cancer progression is urgently needed, which will help to develop more effective treatment strategies. As a component of the human mitoribosome, immature colon carcinoma transcript-1 (ICT1) might be involved in tumor formation and progression. However, its biological function and the corresponding mechanism in gastric cancer have been poorly characterized...
October 3, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29036189/inhibition-of-cug-binding-protein-1-and-activation-of-caspases-are-critically-involved-in-piperazine-derivative-bk10007s-induced-apoptosis-in-hepatocellular-carcinoma-cells
#17
Ju-Ha Kim, Hee Young Kwon, Dong Hoon Ryu, Min-Ho Nam, Bum Sang Shim, Jin Han Kim, Jae Yeol Lee, Sung-Hoon Kim
Though piperazine derivative BK10007S was known to induce apoptosis in pancreatic cancer xenograft model as a T-type CaV3.1 a1G isoform calcium channel blocker, its underlying antitumor mechanism still remains unclear so far. Thus, in the present study, the antitumor mechanism of BK10007S was elucidated in hepatocellular carcinoma cells (HCCs). Herein, BK10007S showed significant cytotoxicity by 3-[4,5-2-yl]-2,5-diphenyltetra-zolium bromide (MTT) assay and anti-proliferative effects by colony formation assay in HepG2 and SK-Hep1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/29035827/ginsenoside-rg3-enhances-the-anti-proliferative-activity-of-erlotinib-in-pancreatic-cancer-cell-lines-by-downregulation-of-egfr-pi3k-akt-signaling-pathway
#18
Jin Jiang, Zuguo Yuan, Yiqing Sun, Yuan Bu, Wenfeng Li, Zhenghua Fei
Erlotinib has shown activity in the management of pancreatic cancer. However, the benefit of EGFR blockade is limited due to EGFR independent PI3K/Akt signaling pathway. Studies have reported that Ginsenoside Rg3 strongly inhibited PI3K-Akt signaling pathway of many carcinomas. We aimed to investigate the activity of Ginsenoside Rg3 to sensitize erlotinib in treating pancreatic cancer in vitro and in vivo. Human pancreatic cancer cell lines BxPC-3 and AsPC-1 were used. Cell proliferation and colony formation assay, Annexin V/PI apoptosis analysis, Western blot analysis, immunohistochemistry and in vivo study were carried out...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29032182/catalpol-suppresses-osteosarcoma-cell-proliferation-through-blocking-epithelial-mesenchymal-transition-emt-and-inducing-apoptosis
#19
Lei Wang, Gui-Bin Xue
Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell viability. The migration of osteosarcoma cells was also consistently suppressed by catalpol treatment using the wound healing and transwell migration analysis. Catalpol reduced the expressions of Kras, receptor for activated C-kinase 1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner, revealing the blockage of migration...
October 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29031068/platinum-iv-prodrugs-multiply-targeting-genomic-dna-histone-deacetylases-and-parp-1
#20
Zichen Xu, Weiwei Hu, Zhimei Wang, Shaohua Gou
Several Pt(IV) prodrugs containing SAA, a histone deacetylases inhibitor, were designed and prepared for multiply targeting genomic DNA, histone deacetylases and PARP-1. The resulting Pt(IV) prodrug had significantly strong antiproliferative activity against the tested cancer cell lines, especially SAA1, derived from the conjugation of cisplatin and SAA, had potent ability to overcome cisplatin resistance. Under the combined action of DNA platination and inhibition of HDACs and PARP-1 activity, the cytotoxic activity of SAA1 was 174-fold higher than cisplatin against cisplatin-resistant SGC7901/CDDP cancer cells...
October 3, 2017: European Journal of Medicinal Chemistry
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