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https://www.readbyqxmd.com/read/29413287/parp-inhibition-combined-with-thoracic-irradiation-exacerbates-esophageal-and-skin-toxicity-in-c57bl6-mice
#1
Luiza Madia Lourenco, Yanyan Jiang, Neele Drobnitzky, Marcus Green, Fiona Cahill, Agata Patel, Yasmin Shanneik, John Moore, Anderson J Ryan
PURPOSE: Poly (ADP-ribose) polymerase (PARP) inhibitors have been shown to enhance the radiosensitivity of cancer cells in vitro in a replication-dependent manner. Their in vivo radiosensitizing effects have also been demonstrated in preclinical tumor models. However, whether PARP inhibition can enhance the response to radiation therapy in normal tissues has been largely neglected. We hypothesized that PARP inhibition might also potentiate the response of replicating normal tissues to radiation therapy...
March 1, 2018: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29387241/mitochondrial-pathway-mediated-apoptosis-is-associated-with-erlotinib-induced-cytotoxicity-in-hepatic-cells
#2
Xueqin Chen, Shaoyu Yang, Yuelong Pan, Xin Li, Shenglin Ma
For advanced non-small-cell lung cancer (NSCLC) with mutations to the epidermal growth factor receptor (EGFR), EGFR tyrosine kinase inhibitors, including erlotinib are indicated for the first-line treatment. Liver injury is one of the multiple adverse effects of erlotinib and may affect its safety. The present study investigated the mechanism of erlotinib-induced hepatotoxicity in vitro and provided experimental evidence for the screening of potential hepatoprotectors. Erlotinib induced dose-dependent cytotoxicity in human L-02 hepatic cells 72 h after treatment...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29370087/a-novel-bromophenol-derivative-bos-102-induces-cell-cycle-arrest-and-apoptosis-in-human-a549-lung-cancer-cells-via-ros-mediated-pi3k-akt-and-the-mapk-signaling-pathway
#3
Chuan-Long Guo, Li-Jun Wang, Yue Zhao, Hua Liu, Xiang-Qian Li, Bo Jiang, Jiao Luo, Shu-Ju Guo, Ning Wu, Da-Yong Shi
Bromophenol is a type of natural marine product. It has excellent biological activities, especially anticancer activities. In our study of searching for potent anticancer drugs, a novel bromophenol derivative containing indolin-2-one moiety, 3-(4-(3-([1,4'-bipiperidin]-1'-yl)propoxy)-3-bromo-5-methoxybenzylidene)-N-(4-bromophenyl)-2-oxoindoline-5-sulfonamide (BOS-102) was synthesized, which showed excellent anticancer activities on human lung cancer cell lines. A study of the mechanisms indicated that BOS-102 could significantly block cell proliferation in human A549 lung cancer cells and effectively induce G0/G1 cell cycle arrest via targeting cyclin D1 and cyclin-dependent kinase 4 (CDK4)...
January 25, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29337987/identification-of-a-noncanonical-function-for-ribose-5-phosphate-isomerase-a-promotes-colorectal-cancer-formation-by-stabilizing-and-activating-%C3%AE-catenin-via-a-novel-c-terminal-domain
#4
Yu-Ting Chou, Jeng-Kai Jiang, Muh-Hwa Yang, Jeng-Wei Lu, Hua-Kuo Lin, Horng-Dar Wang, Chiou-Hwa Yuh
Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients' CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC...
January 16, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29306194/downregulation-of-parp1-transcription-by-cdk4-6-inhibitors-sensitizes-human-lung-cancer-cells-to-anticancer-drug-induced-death-by-impairing-ogg1-dependent-base-excision-repair
#5
Dominika Tempka, Paulina Tokarz, Kinga Chmielewska, Magdalena Kluska, Julita Pietrzak, Żaneta Rygielska, László Virág, Agnieszka Robaszkiewicz
Hallmarks of cancer cells include uncontrolled growth and rapid proliferation; thus, cyclin-dependent kinases are a therapeutic target for cancer treatment. Treating non-small lung cancer cells with sublethal concentrations of the CDK4/6 inhibitors, ribociclib (LEE011) and palbociclib (PD0332991), which are approved by the FDA for anticancer therapies, caused cell cycle arrest in the G1 phase and suppression of poly(ADP-ribose) polymerase 1 (PARP1) transcription by inducing recruitment of the RB1-E2F1-HDAC1-EZH2 repressive complex to the PARP1 promoter...
December 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/29304903/locked-nucleic-acid-technology-for-highly-sensitive-detection-of-somatic-mutations-in-cancer
#6
Takayuki Ishige, Sakae Itoga, Kazuyuki Matsushita
The molecular diagnosis of the cancer mutational status is essential for modern clinical laboratory medicine. Mutations in EGFR, KRAS, BRAF, and PIK3CA genes are widely analyzed in solid tumors such as lung cancer, colorectal cancer, breast cancer, and melanoma. The allele-specific polymerase chain reaction, high-resolution melting, and Sanger sequencing are used for detecting and identifying gene mutations in many clinical laboratories. The locked nucleic acid (LNA) is a class of nucleic acid analogs that contain a methylene bridge connecting the 2' oxygen and 4' carbon in the ribose moiety...
2018: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/29275301/cycloartobiloxanthone-induces-human-lung-cancer-cell-apoptosis-via-mitochondria-dependent-apoptotic-pathway
#7
Nattanan Losuwannarak, Boonchoo Sritularak, Pithi Chanvorachote
BACKGROUND: Lung cancer is one of most malignant types of cancer and new anticancer agents are still required. Cycloartobiloxanthone, a flavonoid isolated from stem bark of Artocarpus gomezianus, has potential for being developed for anticancer therapy. MATERIALS AND METHODS: Cytotoxicity of cycloartobiloxanthone was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay against four human lung cancer cell lines (H23, H460, H292 and A549) and their half-maximal inhibitory concentrations (IC50) were assessed...
January 2018: In Vivo
https://www.readbyqxmd.com/read/29250520/design-synthesis-and-evaluation-of-ribose-modified-anilinopyrimidine-derivatives-as-egfr-tyrosine-kinase-inhibitors
#8
Xiuqin Hu, Disha Wang, Yi Tong, Linjiang Tong, Xia Wang, Lili Zhu, Hua Xie, Shiliang Li, You Yang, Yufang Xu
The synthesis of a series of ribose-modified anilinopyrimidine derivatives was efficiently achieved by utilizing DBU or tBuOLi-promoted coupling of ribosyl alcohols with 2,4,5-trichloropyrimidine as key step. Preliminary biological evaluation of this type of compounds as new EGFR tyrosine kinase inhibitors for combating EGFR L858R/T790M mutant associated with drug resistance in the treatment of non-small cell lung cancer revealed that 3-N-acryloyl-5-O-anilinopyrimidine ribose derivative 1a possessed potent and specific inhibitory activity against EGFR L858R/T790M over WT EGFR...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29248440/jtc801-induces-ph-dependent-death-specifically-in-cancer-cells-and-slows-growth-of-tumors-in-mice
#9
Xinxin Song, Shan Zhu, Yangchun Xie, Jiao Liu, Lingyi Sun, Dexing Zeng, Pengcheng Wang, Xiaochao Ma, Guido Kroemer, David L Bartlett, Timothy R Billiar, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. METHODS: We screened a library of 254 compounds that interact with G protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1)...
December 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#10
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ectoenzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
February 9, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29212196/juglanin-inhibits-lung-cancer-by-regulation-of-apoptosis-ros-and-autophagy-induction
#11
Liang Chen, Ya-Qiong Xiong, Jing Xu, Ji-Peng Wang, Zi-Li Meng, Yong-Qing Hong
Juglanin (Jug) is obtained from the crude extract of Polygonum aviculare, exerting suppressive activity against cancer cell progression in vitro and in vivo. Juglanin administration causes apoptosis and reactive oxygen species (ROS) in different types of cells through regulating various signaling pathways. In our study, the effects of juglanin on non-small cell lung cancer were investigated. A significant role of juglanin in suppressing lung cancer growth was observed. Juglanin promoted apoptosis in lung cancer cells through increasing Caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, which is regulated by TNF-related apoptosis-inducing ligand/Death receptors (TRAIL/DRs) relied on p53 activation...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207064/quinalizarin-exerts-an-anti-tumour-effect-on-lung-cancer-a549-cells-by-modulating-the-akt-mapk-stat3-and-p53-signalling-pathways
#12
Ling-Qi Meng, Chang Liu, Ying-Hua Luo, Xian-Ji Piao, Yue Wang, Yi Zhang, Jia-Ru Wang, Hao Wang, Wan-Ting Xu, Yang Liu, Yi-Qin Wu, Hu-Nan Sun, Ying-Hao Han, Mei-Hua Jin, Gui-Nan Shen, Yan-Qing Zang, Jing Li, Nan-Zhu Fang, Yu-Dong Cui, Cheng-Hao Jin
Quinalizarin may be a potential chemical agent for cancer therapy, as it exerts anti‑tumour effects against a variety of different types of cancer. However, the underlying regulatory mechanism and signalling pathways of quinalizarin in lung cancer cells remains unknown. The present study sought to investigate the effects of quinalizarin on proliferation, apoptosis and reactive oxygen species (ROS) generation in lung cancer. MTT assays were used to evaluate the effects of quinalizarin on the viability of lung cancer A549, NCI‑H460 and NCI‑H23 cells...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29186071/volasertib-enhances-sensitivity-to-trail-in-renal-carcinoma-caki-cells-through-downregulation-of-c-flip-expression
#13
Mi-Yeon Jeon, Kyoung-Jin Min, Seon Min Woo, Seung Un Seo, Shin Kim, Jong-Wook Park, Taeg Kyu Kwon
Polo-like kinase 1 (PLK1) plays major roles in cell cycle control and DNA damage response. Therefore, PLK1 has been investigated as a target for cancer therapy. Volasertib is the second-in class dihydropteridinone derivate that is a specific PLK1 inhibitor. In this study, we examined that combining PLK1 inhibitor with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) would have an additive and synergistic effect on induction of apoptosis in cancer cells. We found that volasertib alone and TRAIL alone had no effect on apoptosis, but the combined treatment of volasertib and TRAIL markedly induced apoptosis in Caki (renal carcinoma), A498 (renal carcinoma) and A549 (lung carcinoma) cells, but not in normal cells (human skin fibroblast cells and mesangial cells)...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29152062/rapamycin-sensitizes-cancer-cells-to-growth-inhibition-by-the-parp-inhibitor-olaparib
#14
Atsushi Osoegawa, Joell J Gills, Shigeru Kawabata, Phillip A Dennis
Poly (ADP-ribose) polymerase inhibitors (PARPi) have been developed and tested in a context of combining it with double-stranded (ds) DNA repair defects or inhibitors, as PARP inhibitor impairs single-stranded (ss) DNA break repair, resulting in the activation of the dsDNA break repair machinery. Rapamycin has been widely prescribed for more than a decade and recent studies have revealed that it may inhibit dsDNA break repair. The combination of the PARP inhibitor olaparib and rapamycin synergistically inhibited cell proliferation in non-small cell lung cancer (NSCLC) cells, and even in triple negative breast cancer (TNBC) cells with BRCA1 mutations...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138795/hesperidin-induces-apoptosis-and-g0-g1-arrest-in-human-non-small-cell-lung-cancer-a549-cells
#15
Rongmu Xia, Xin Sheng, Xianlin Xu, Chunbo Yu, Hongling Lu
Lung cancer has high incidence and mortality rates worldwide. In the present study, the mechanisms by which hesperidin decreases the viability and induces the apoptosis of human non-small cell lung cancer (NSCLC) A549 cells were investigated. Initially, MTT and flow cytometric assays were performed to evaluate the effects of hesperidin on the viability and apoptosis of A549 cells and human normal lung epithelial BEAS-2B cells. The results revealed that hesperidin has no negative effects on the human normal lung epithelial BEAS-2B cells and the viability of cells treated with various concentrations of hesperidin was inhibited in a time- and dose-dependent manner compared with the control groups...
November 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29108234/metapristone-ru486-metabolite-suppresses-nsclc-by-targeting-egfr-mediated-pi3k-akt-pathway
#16
Jingwei Shao, Guirong Zheng, Hongning Chen, Jian Liu, Aixiao Xu, Fan Chen, Tao Li, Yusheng Lu, Jianguo Xu, Ning Zheng, Lee Jia
Therapies targeting epidermal growth factor receptor (EGFR) can effectively treat with non-small cell lung cancer (NSCLC), but NSCLC's drug resistance makes it intractable. Herein, we showed that RU486 metabolite metapristone inhibited the proliferation of various NSCLC cell lines with either wild (A549, H1299, H520) or mutated EGFR (H1975, HCC827). The suppression was resulted from inhibition by metapristone of EGFR signaling pathways through down-regulating the EGFR, PTEN, as well as AKT and ERK proteins...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28988534/biochemical-variations-in-cytolytic-activity-of-ortho-and-paramyxoviruses-in-human-lung-tumor-cell-culture
#17
O P Zhirnov
Human lung cancer cells (Calu-3 line) were studied for the development of apoptosis, necrosis, and autophagy in response to infection with ortho- and paramyxoviruses. Biochemical pathways underlying various mechanisms of cell death differed for different viruses. When infected with murine Sendai paramyxovirus, Calu-3 cells demonstrated typical necrotic features such as cell swelling (but not shrinkage), lack of chromatin DNA laddering, of caspase 3 and 8 activation, and of apoptotic cleavage of poly(ADP-ribose) polymerase (PARP) protein; an activation of antiapoptotic protein kinase Akt was also revealed...
September 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28983599/baicalin-potentiates-trail%C3%A2-induced-apoptosis-through-p38-mapk-activation-and-intracellular-reactive-oxygen-species-production
#18
Lei Zhang, Xia Wang, Ruixue Wang, Xuelian Zheng, Na Li, Huannan Li, Xiaoren Cao, Bin Zhou, Yong Lin, Lan Yang
The combination of tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) with other agents has been recognized as a promising strategy to overcome TRAIL resistance in cancer cells. Baicalin (5, 6‑dihydroxy‑7‑o‑glucuronide flavone) is a flavonoid from the root of the medicinal herb Scutellaria baicalensis Georgi, which has been reported to exert antioxidant, anti‑inflammatory, antiviral and anticancer activities in vitro. However, the effect of baicalin on TRAIL‑induced cytotoxicity has not been previously reported...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28982084/mir-484-promotes-non-small-cell-lung-cancer-nsclc-progression-through-inhibiting-apaf-1-associated-with-the-suppression-of-apoptosis
#19
Tao Li, Zong-Li Ding, Yu-Long Zheng, Wei Wang
Increasing studies have indicated that the dysregulated microRNAs (miRNAs) are associated with tumorigenesis, development and even the poor prognosis of a variety of tumors, including the non-small-cell lung cancer (NSCLC). Here in our study, we found that miRNA-484 was expressed highly in NSCLC clinical tumor samples in comparison to the matched adjacent tissues. In addition, high and low expression of miRNA-484 was observed in NSCLC cell lines and lung normal cells, respectively. Furthermore, the capability of migration and proliferation changed accompanied with the altered expression of miR-484 in NSCLC...
October 2, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28978184/poly-adp-ribose-polymerase-inhibitors-as-radiosensitizers-a-systematic-review-of-pre-clinical-and-clinical-human-studies
#20
REVIEW
Paul Lesueur, François Chevalier, Jean-Baptiste Austry, Waisse Waissi, Hélène Burckel, Georges Noël, Jean-Louis Habrand, Yannick Saintigny, Florence Joly
BACKGROUND: Poly-(ADP-Ribose)-Polymerase (PARP) inhibitors are becoming important actors of anti-neoplasic agents landscape, with recent but narrow FDA's approvals for ovarian BRCA mutated cancers and prostatic cancer. Nevertheless, PARP inhibitors are also promising drugs for combined treatments particularly with radiotherapy. More than seven PARP inhibitors have been currently developed. Central Role of PARP in DNA repair, makes consider PARP inhibitor as potential radiosensitizers, especially for tumors with DNA repair defects, such as BRCA mutation, because of synthetic lethality...
September 15, 2017: Oncotarget
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