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https://www.readbyqxmd.com/read/29651367/-lazarus-response-to-olaparib-in-a-virtually-chemonaive-breast-cancer-patient-carrying-gross-brca2-gene-deletion
#1
Vladimir M Moiseyenko, Vyacheslav A Chubenko, Fedor V Moiseyenko, Lyudmila A Zagorskaya, Yuliya A Zaytseva, Nataliya E Gesha, Evgeny N Zykov, Valeriya I Ni, Elena V Preobrazhenskaya, Anna P Sokolenko, Evgeny N Imyanitov
This report describes an estrogen receptor-positive breast cancer patient, who relapsed at two and a half years after the completion of adjuvant chemotherapy while being on the aromatase inhibition. Based on the clinical evidence for potential sensitivity of the tumor to hormone ablation, everolimus was added to continuing exemestane treatment. Oral chemotherapy was administered at further disease progression, however, it lasted only for 10 days due to rapidly deteriorating condition of the patient. BRCA test was performed just before the failure of endocrine therapy and revealed a gross deletion within BRCA2 gene...
February 4, 2018: Curēus
https://www.readbyqxmd.com/read/29604436/investigational-chemotherapy-and-novel-pharmacokinetic-mechanisms-for-the-treatment-of-breast-cancer-brain-metastases
#2
REVIEW
Neal Shah, Afroz S Mohammad, Pushkar Saralkar, Samuel A Sprowls, Schuyler D Vickers, Devin John, Rachel M Tallman, Brandon Lucke-Wold, Katherine E Jarrell, Mark Pinti, Richard L Nolan, Paul R Lockman
In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms...
March 28, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29584673/effects-of-the-combination-of-gliotoxin-and-adriamycin-on-the-adriamycin-resistant-non-small-cell-lung-cancer-a549-cell-line
#3
Le Van Manh Hung, Yeon Woo Song, Somi Kim Cho
Acquired drug resistance constitutes an enormous hurdle in cancer treatment, and the search for effective compounds against resistant cancer is still advancing. Marine organisms are a promising natural resource for the discovery and development of anticancer agents. In this study, we examined whether gliotoxin (GTX), a secondary metabolite isolated from marine-derived Aspergillus fumigatus , inhibits the growth of adriamycin (ADR)-resistant non-small-cell lung cancer (NSCLC) cell lines A549/ADR. We investigated the effects of GTX on A549/ADR cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the induction of apoptosis in A549/ADR cells treated with GTX via fluorescence-activated cell sorting analysis, Hoechst staining, annexin V/propidium iodide staining, tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, and western blotting...
March 27, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29570891/poly-adp-ribose-polymerase-1-as-a-potential-therapeutic-target-in-merkel-cell-carcinoma
#4
Renata Ferrarotto, Robert Cardnell, Shirley Su, Lixia Diao, A Karina Eterovic, Victor Prieto, William H Morrisson, Jing Wang, Merrill S Kies, Bonnie S Glisson, Lauren Averett Byers, Diana Bell
BACKGROUND: Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma. METHODS: We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples...
March 23, 2018: Head & Neck
https://www.readbyqxmd.com/read/29545967/egfr-tyrosine-kinase-inhibitor-hs-10182-increases-radiation-sensitivity-in-non-small-cell-lung-cancers-with-egfr-t790m-mutation
#5
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
https://www.readbyqxmd.com/read/29541201/mir-145-suppresses-the-proliferation-invasion-and-migration-of-nsclc-cells-by-regulating-the-bax-bcl-2-ratio-and-the-caspase-3-cascade
#6
Yi Pan, Conglin Ye, Qingshan Tian, Songxin Yan, Xiaoping Zeng, Chu Xiao, Lingyun Wang, Hongmei Wang
Although microRNA (miR)-145 has been identified to be a tumor suppressor in various types of tumor, it promotes the progression of non-small cell lung cancer (NSCLC). However, the precise underlying molecular mechanism of its action remains unclear. The present study investigated the effects of miR-145 on the proliferation, invasion, metastasis and apoptosis of the NSCLC A549 cell line and the underlying molecular mechanism of its action. In vitro cell proliferation, invasion, migration and apoptosis assays were employed, and the expression levels of matrix metalloproteinase (MMP)-2, MMP-9, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3and poly(ADP-ribose) polymerase (PARP) were evaluated by western blot analysis...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29524123/bci-induces-apoptosis-via-generation-of-reactive-oxygen-species-and-activation-of-intrinsic-mitochondrial-pathway-in-h1299-lung-cancer-cells
#7
Jong-Woon Shin, Sae-Bom Kwon, Yesol Bak, Sang-Ku Lee, Do-Young Yoon
The compound (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as an inhibitor of dual specific phosphatase 1/6 and mitogen-activated protein kinase. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on the viability of non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460 were evaluated. We confirmed that BCI significantly inhibited the viability of p53(-) NCI-H1299 cells as compared to NCI-H460 and A549 cells, which express wild-type p53...
March 28, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29413287/parp-inhibition-combined-with-thoracic-irradiation-exacerbates-esophageal-and-skin-toxicity-in-c57bl6-mice
#8
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
#9
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
#10
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
#11
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 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
#12
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...
May 2018: Redox Biology
https://www.readbyqxmd.com/read/29304903/locked-nucleic-acid-technology-for-highly-sensitive-detection-of-somatic-mutations-in-cancer
#13
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
#14
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
#15
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 t BuOLi-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
#16
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
#17
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
#18
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
#19
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...
February 2018: 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
#20
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
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