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https://www.readbyqxmd.com/read/27922189/optimal-arac-cytotoxicity-to-aml-cells-requires-erk5-activity
#1
Ruifang Zheng, George P Studzinski
Cytarabine (AraC) has been the primary treatment agent for Acute Myeloid Leukemia (AML) in the past 30 years, but the precise mechanism of its action is not completely known. Here we assessed the role of ERK5 in AraC-induced cell death in AML cell lines HL60 and U937 using ERK5 inhibitors BIX02189 and XMD8-92. We report that inhibition of MEK5/ERK5 activity reduces AraC-induced cell death, DNA damage, the upregulated DNA damage biomarkers, and produced G2 phase cell cycle arrest. In addition, the pro-survival protein P-Bcl2 Ser70 was found to be associated with decreased AraC-induced cell death following XMD8-92 treatment, suggesting a regulatory role of ERK5 on Bcl2 phosphorylation...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922187/tomentosin-induces-telomere-shortening-and-caspase-dependant-apoptosis-in-cervical-cancer-cells
#2
Nawel Merghoub, Hassan El Btaouri, Laila Benbacer, Saïd Gmouh, Chantal Trentesaux, Bertrand Brassart, Mohammed Attaleb, Claudie Madoulet, Thomas Wenner, Saaid Amzazi, Hamid Morjani, Mohamed El Mzibri
Tomentosin, a natural sesquiterpene lactone purified from of Inula viscosa L., was investigated for its anti-proliferative, telomere shortening and apoptotic effects on human cervical cancer HeLa and SiHa cell lines. Tomentosin was found to inhibit the growth of SiHa and HeLa cell lines in dose and time-dependent manner (IC50 values of 7.10 ± 0.78µM and 5.87 ± 0.36µM, respectively after 96h of treatment). As evidenced by TTAGGG telomere length assay, tomentosin target specifically the telomeric overhang lengthening...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922186/characterization-of-the-pro-inflammatory-cytokine-il-1%C3%AE-on-butyrate-oxidation-in-colorectal-cancer-cells
#3
Megan Johnstone, Natalie Bennett, Cynthia Standifer, Alexis Smith, Anna Han, Ahmed Bettaieb, Jay Whelan, Dallas R Donohoe
Cancer, in part, is driven, by alterations in cellular metabolism that promote cell survival and cell proliferation. Identifying factors that influence this shift in cellular metabolism in cancer cells is important. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that has been reported to be elevated in colorectal cancer patients. While much is known towards the effect of dietary nutrients on regulating inflammation and the inflammatory response, which includes cytokines such as IL-1β, far less is understood how cytokines impact nutrient fate to alter cancer cell metabolism...
December 6, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27922138/mitomycin-c-treated-human-induced-pluripotent-stem-cells-as-a-safe-delivery-system-of-gold-nanorods-for-targeted-photothermal-therapy-of-gastric-cancer
#4
Meng Yang, Yanlei Liu, Wenxiu Hou, Xiao Zhi, Chunlei Zhang, Xinquan Jiang, Fei Pan, Yuming Yang, Jian Ni, Daxiang Cui
Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer...
December 6, 2016: Nanoscale
https://www.readbyqxmd.com/read/27922113/non-small-cell-lung-cancer-quantitative-phenotypic-analysis-of-ct-images-as-a-potential-marker-of-prognosis
#5
Jiangdian Song, Zaiyi Liu, Wenzhao Zhong, Yanqi Huang, Zelan Ma, Di Dong, Changhong Liang, Jie Tian
This was a retrospective study to investigate the predictive and prognostic ability of quantitative computed tomography phenotypic features in patients with non-small cell lung cancer (NSCLC). 661 patients with pathological confirmed as NSCLC were enrolled between 2007 and 2014. 592 phenotypic descriptors was automatically extracted on the pre-therapy CT images. Firstly, support vector machine (SVM) was used to evaluate the predictive value of each feature for pathology and TNM clinical stage. Secondly, Cox proportional hazards model was used to evaluate the prognostic value of these imaging signatures selected by SVM which subjected to a primary cohort of 138 patients, and an external independent validation of 61 patients...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922079/proteomic-profiling-reveals-that-collismycin-a-is-an-iron-chelator
#6
Makoto Kawatani, Makoto Muroi, Akira Wada, Gyo Inoue, Yushi Futamura, Harumi Aono, Kenshirou Shimizu, Takeshi Shimizu, Yasuhiro Igarashi, Naoko Takahashi-Ando, Hiroyuki Osada
Collismycin A (CMA), a microbial product, has anti-proliferative activity against cancer cells, but the mechanism of its action remains unknown. Here, we report the identification of the molecular target of CMA by ChemProteoBase, a proteome-based approach for drug target identification. ChemProteoBase profiling showed that CMA is closely clustered with di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone, an iron chelator. CMA bound to both Fe(II) and Fe(III) ions and formed a 2:1 chelator-iron complex with a redox-inactive center...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922078/malat1-and-hotair-long-non-coding-rnas-play-opposite-role-in-estrogen-mediated-transcriptional-regulation-in-prostate-cancer-cells
#7
Aurora Aiello, Lorenza Bacci, Agnese Re, Cristian Ripoli, Francesco Pierconti, Francesco Pinto, Riccardo Masetti, Claudio Grassi, Carlo Gaetano, Pier Francesco Bassi, Alfredo Pontecorvi, Simona Nanni, Antonella Farsetti
In the complex network of nuclear hormone receptors, the long non-coding RNAs (lncRNAs) are emerging as critical determinants of hormone action. Here we investigated the involvement of selected cancer-associated lncRNAs in Estrogen Receptor (ER) signaling. Prior studies by Chromatin Immunoprecipitation (ChIP) Sequencing showed that in prostate cancer cells ERs form a complex with the endothelial nitric oxide synthase (eNOS) and that in turn these complexes associate with chromatin in an estrogen-dependent fashion...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922077/mast-cell-phenotype-tnf%C3%AE-expression-and-degranulation-status-in-non-small-cell-lung-cancer
#8
A Shikotra, C M Ohri, R H Green, D A Waller, P Bradding
Mast cell infiltration of tumour islets represents a survival advantage in non-small cell lung cancer (NSCLC). The phenotype and activation status of these mast cells is unknown. We investigated the mast cell phenotype in terms of protease content (tryptase-only [MCT], tryptase + chymase [MCTC]) and tumour necrosis factor-alpha (TNFα) expression, and extent of degranulation, in NSCLC tumour stroma and islets. Surgically resected tumours from 24 patients with extended survival (ES; mean survival 86.5 months) were compared with 25 patients with poor survival (PS; mean survival 8...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922075/cancer-associated-fibroblasts-treated-with-cisplatin-facilitates-chemoresistance-of-lung-adenocarcinoma-through-il-11-il-11r-stat3-signaling-pathway
#9
Leilei Tao, Guichun Huang, Rui Wang, Yan Pan, Zhenyue He, Xiaoyuan Chu, Haizhu Song, Longbang Chen
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cells in vivo and in vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922057/antiproliferative-activities-of-amaryllidaceae-alkaloids-from-lycoris-radiata-targeting-dna-topoisomerase-i
#10
Gui-Lin Chen, Yong-Qiang Tian, Jian-Lin Wu, Na Li, Ming-Quan Guo
Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50 at 7...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922049/identification-of-kiaa1199-as-a-biomarker-for-pancreatic-intraepithelial-neoplasia
#11
Han Na Suh, Sohee Jun, Ah-Young Oh, Mrinal Srivastava, Sunhye Lee, Cullen M Taniguchi, Songlin Zhang, Won Sup Lee, Junjie Chen, Bum-Joon Park, Jae-Il Park
Pancreatic cancer is one of the most aggressive cancers and has an extremely poor prognosis. Despite recent progress in both basic and clinical research, most pancreatic cancers are detected at an incurable stage owing to the absence of disease-specific symptoms. Thus, developing novel approaches for detecting pancreatic cancer at an early stage is imperative. Our in silico and immunohistochemical analyses showed that KIAA1199 is specifically expressed in human pancreatic cancer cells and pancreatic intraepithelial neoplasia, the early lesion of pancreatic cancer, in a genetically engineered mouse model and in human patient samples...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922047/new-arylated-benzo-h-quinolines-induce-anti-cancer-activity-by-oxidative-stress-mediated-dna-damage
#12
Dharmendra K Yadav, Reeta Rai, Naresh Kumar, Surjeet Singh, Sanjeev Misra, Praveen Sharma, Priyanka Shaw, Horacio Pérez-Sánchez, Ricardo L Mancera, Eun Ha Choi, Mi-Hyun Kim, Ramendra Pratap
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27922010/mek-inhibitors-block-growth-of-lung-tumours-with-mutations-in-ataxia-telangiectasia-mutated
#13
Michal Smida, Ferran Fece de la Cruz, Claudia Kerzendorfer, Iris Z Uras, Barbara Mair, Abdelghani Mazouzi, Tereza Suchankova, Tomasz Konopka, Amanda M Katz, Keren Paz, Katalin Nagy-Bojarszky, Markus K Muellner, Zsuzsanna Bago-Horvath, Eric B Haura, Joanna I Loizou, Sebastian M B Nijman
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#14
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921518/increased-radio-toxicity-in-two-cancerous-cell-lines-irradiated-by-low-and-high-energy-photons-in-the-presence-of-thio-glucose-bound-gold-nanoparticles
#15
Shokouhozaman Soleymanifard, Atefeh Rostami, Seyed Amir Aledavood, Maryam Moghadam Matin, Ameneh Sazgarnia
PURPOSE: Gold nanoparticles modified by thio-glucose have been believed to increase the toxicity of radiotherapy in human malignant cells. We report the effect of thio-glucose-bound gold nanoparticles (Glu-G nanoparticles), 16 nm in size, on two human lung (QU-DB) and breast (MCF7) cancer cell lines combined with kilo and megavoltage X-rays. MATERIALS AND METHODS: The shape and surface characteristics, the size distribution and light absorption spectrum of the prepared nanoparticles were measured by transmission electron microscopy, dynamic light scattering, and Ultraviolet-Visible spectrophotometry, respectively...
December 6, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27921393/the-role-of-the-microvascular-network-structure-on-diffusion-and-consumption-of-anti-cancer-drugs
#16
P Mascheroni, R Penta
We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells...
December 6, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27921386/cytotoxicity-of-a-series-of-norcantharidin-inspired-tetrahydroepoxyisoindole-carboxamides
#17
Christopher Peter Gordon, Lawson K Spare, Pasquale Falsetta, Jayne Gilbert, David G Harman, Mark A Baker, Feng Li, Adam McCluskey, Jack K Clegg, Jennette A Sakoff, Janice R Aldrich-Wright
A series of 28 norcantharidin (NorC) inspired analogues were accessed via a robust two-step Ugi intramolecular Diels-Alder (IMDA) sequence. Four analogues displayed equipotent whole cell cytotoxicity to NorC and cisplatin against a number of cancer cell lines and a normal breast cell line (MCF10A). Notably (3S,3aS,6R)-2-benzyl-7-methyl-N-(naphthalen-2-yl)-1-oxo-1,2,3,6-tetrahydro-3a,6-epoxyisoindole-3-carboxamide (trans-27) displayed superior whole cell activity against breast (MCF-7, GI50 = 2.9 µM) and colon (HT29, GI50 = 6...
December 6, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27921375/visceral-adiposity-and-cancer-survival-a-review-of-imaging-studies
#18
REVIEW
J Xiao, V C Mazurak, T A Olobatuyi, B J Caan, C M Prado
Although obesity is a well-known risk factor for cancer, the association between obesity and cancer survival remains controversial. This is partially due to the inability of conventional obesity measures to directly assess adiposity or adipose tissue distribution. As a metabolic organ, visceral adipose tissue (VAT) secrets a variety of cytokines and cytokine-like factors, potentially affecting cancer survival. The objective of this review was to investigate the influence of imaging-assessed VAT on cancer survival...
December 6, 2016: European Journal of Cancer Care
https://www.readbyqxmd.com/read/27921283/choices-have-consequences-the-nexus-between-dna-repair-pathways-and-genomic-instability-in-cancer
#19
REVIEW
Sonali Bhattacharjee, Saikat Nandi
BACKGROUND: The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored...
December 2016: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/27921280/ph-responsive-triblock-copolymeric-micelles-decorated-with-a-cell-penetrating-peptide-provide-efficient-doxorubicin-delivery
#20
Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K Iyer
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-L-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10(-7) M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7...
December 2016: Nanoscale Research Letters
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