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https://www.readbyqxmd.com/read/28915640/marsdenia-tenacissima-extract-overcomes-axl-and-met-mediated-erlotinib-and-gefitinib-cross-resistance-in-non-small-cell-lung-cancer-cells
#1
Shu-Yan Han, Wei Zhao, Hai-Bo Han, Hong Sun, Dong Xue, Yan-Na Jiao, Xi-Ran He, Shan-Tong Jiang, Ping-Ping Li
Tyrosine kinase inhibitors (TKIs) are an effective treatment strategy for non-small cell lung cancer (NSCLC) patients harboring mutations that result in constitutive activation of the epidermal growth factor receptor (EGFR). However, most patients eventually develop resistance to TKIs. This occurs due to additional EGFR mutations or the activation of bypass signaling pathways. In our previous work, we demonstrated that Marsdenia tenacissima extract (MTE) restored gefitinib sensitivity in resistant NSCLC cells with EGFR T790M or K-ras mutations...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904208/genome-wide-screen-of-gamma-secretase-mediated-intramembrane-cleavage-of-receptor-tyrosine-kinases
#2
Johannes A M Merilahti, Veera K Ojala, Anna M Knittle, Arto T Pulliainen, Klaus Elenius
Receptor tyrosine kinases (RTK) have been demonstrated to signal via regulated intramembrane proteolysis (RIP), in which ectodomain shedding and subsequent intramembrane cleavage by gamma-secretase leads to release of a soluble intracellular receptor fragment with functional activity. For most RTKs, however, it is not known whether they can exploit this new signaling mechanism or not. Here we used a system-wide screen to address the frequency of susceptibility to gamma-secretase cleavage among human RTKs. The screen covering 45 of the 55 human RTKs identified 12 new as well as all 9 previously published gamma-secretase substrates...
September 13, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28904132/inhibition-of-the-receptor-tyrosine-kinase-axl-restores-paclitaxel-chemosensitivity-in-uterine-serous-cancer
#3
Marguerite L Palisoul, Jeanne M Quinn, Emily Schepers, Ian S Hagemann, Lei Guo, Kelsey Reger, Andrea R Hagemann, Carolyn K McCourt, Premal H Thaker, Matthew A Powell, David G Mutch, Katherine C Fuh
Uterine serous cancer (USC) is aggressive, and the majority of recurrent cases are chemoresistant. Because the receptor tyrosine kinase AXL promotes invasion and metastasis of USC and is implicated in chemoresistance in other cancers, we assessed the role of AXL in paclitaxel resistance in USC, determined the mechanism of action, and sought to restore chemosensitivity by inhibiting AXL in vitro and in vivo. We used small hairpin RNAs and BGB324 to knock down and inhibit AXL. We assessed sensitivity of USC cell lines to paclitaxel and measured paclitaxel intracellular accumulation in vitro in the presence or absence of AXL...
September 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28898759/cuprous-oxide-nanoparticles-trigger-er-stress-induced-apoptosis-by-regulating-copper-trafficking-and-overcoming-resistance-to-sunitinib-therapy-in-renal-cancer
#4
Qiwei Yang, Ye Wang, Qing Yang, Yi Gao, Xiaopeng Duan, Qingcheng Fu, Chuanmin Chu, Xiuwu Pan, Xingang Cui, Yinghao Sun
While the current standard first-line treatment for advanced renal cell carcinoma (RCC) is sunitinib, patients inevitably develop resistance to this drug. However, the rapid development of nanotechnology has provided emerging techniques for the treatment of advanced tumours, including RCC. In our previous research, cuprous oxide nanoparticles (CONPs) showed ideal anti-tumour effects and low systemic toxicity. While many inorganic nanomedicines, including CONPs, have similar pharmacological effects, their detailed mechanisms remain unknown...
September 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28887116/residual-angle-closure-one-year-after-laser-peripheral-iridotomy-in-primary-angle-closure-suspects
#5
Mani Baskaran, Elizabeth Yang, Sameer Trikha, Rajesh S Kumar, Hon Tym Wong, Mingguang He, Paul Tk Chew, Paul J Foster, David Friedman, Tin Aung
PURPOSE: To determine the incidence and baseline clinical and anterior segment optical coherence tomography (AS-OCT) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS). DESIGN: Sub-analysis of randomized controlled trial data METHODS: AS-OCT images (Visante, Carl Zeiss Meditec, Dublin, CA) from 181 PACS subjects ≥ 50 years of age, were analyzed using customized software, prior to, and 1 year after LPI...
September 5, 2017: American Journal of Ophthalmology
https://www.readbyqxmd.com/read/28883618/cg200745-an-hdac-inhibitor-induces-anti-tumour-effects-in-cholangiocarcinoma-cell-lines-via-mirnas-targeting-the-hippo-pathway
#6
Dawoon E Jung, Soo Been Park, Kahee Kim, Chanyang Kim, Si Young Song
Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881658/decitabine-vorinostat-combination-treatment-in-acute-myeloid-leukemia-activates-pathways-with-potential-for-novel-triple-therapy
#7
Christine S Young, Kathryn M Clarke, Laura M Kettyle, Alexander Thompson, Ken I Mills
Despite advancements in cancer therapeutics, acute myeloid leukemia patients over 60 years old have a 5-year survival rate of less than 8%. In an attempt to improve this, epigenetic modifying agents have been combined as therapies in clinical studies. In particular combinations with Decitabine and Vorinostat have had varying degrees of efficacy. This study therefore aimed to understand the underlying molecular mechanisms of these agents to identify potential rational epi-sensitized combinations. Combined Decitabine-Vorinostat treatment synergistically decreased cell proliferation, induced apoptosis, enhanced acetylation of histones and further decreased DNMT1 protein with HL-60 cells showing a greater sensitivity to the combined treatment than OCI-AML3...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881571/phospho-axl-is-widely-expressed-in-glioblastoma-and-associated-with-significant-shorter-overall-survival
#8
Julia Onken, Peter Vajkoczy, Robert Torka, Claudia Hempt, Victor Patsouris, Frank L Heppner, Josefine Radke
Receptor tyrosine kinase AXL (RTK-AXL) is regarded as a suitable target in glioblastoma (GBM) therapy. Since AXL kinase inhibitors are about to get approval for clinical use, patients with a potential benefit from therapy targeting AXL need to be identified. We therefore assessed the expression pattern of Phospho-AXL (P-AXL), the biologically active form of AXL, in 90 patients with newly diagnosed GBM, which was found to be detectable in 67 patients (corresponding to 74%). We identified three main P-AXL expression patterns: i) exclusively in the tumor vasculature (13%), ii) in areas of hypercellularity (35%), or iii) both, in the tumor vasculature and in hypercellular areas of the tumor tissue (52%)...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880215/the-effect-of-flexible-pavement-mechanics-on-the-accuracy-of-axle-load-sensors-in-vehicle-weigh-in-motion-systems
#9
Piotr Burnos, Dawid Rys
Weigh-in-Motion systems are tools to prevent road pavements from the adverse phenomena of vehicle overloading. However, the effectiveness of these systems can be significantly increased by improving weighing accuracy, which is now insufficient for direct enforcement of overloaded vehicles. Field tests show that the accuracy of Weigh-in-Motion axle load sensors installed in the flexible (asphalt) pavements depends on pavement temperature and vehicle speeds. Although this is a known phenomenon, it has not been explained yet...
September 7, 2017: Sensors
https://www.readbyqxmd.com/read/28878389/gas6-derived-from-cancer-associated-fibroblasts-promotes-migration-of-axl-expressing-lung-cancer-cells-during-chemotherapy
#10
Ryu Kanzaki, Hisamichi Naito, Kazuyoshi Kise, Kazuhiro Takara, Daisuke Eino, Masato Minami, Yasushi Shintani, Soichiro Funaki, Tomohiro Kawamura, Toru Kimura, Meinoshin Okumura, Nobuyuki Takakura
Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavior of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874532/schwann-cells-use-tam-receptor-mediated-phagocytosis-in-addition-to-autophagy-to-clear-myelin-in-a-mouse-model-of-nerve-injury
#11
Amanda Brosius Lutz, Won-Suk Chung, Steven A Sloan, Glenn A Carson, Lu Zhou, Emilie Lovelett, Sean Posada, J Bradley Zuchero, Ben A Barres
Ineffective myelin debris clearance is a major factor contributing to the poor regenerative ability of the central nervous system. In stark contrast, rapid clearance of myelin debris from the injured peripheral nervous system (PNS) is one of the keys to this system's remarkable regenerative capacity, but the molecular mechanisms driving PNS myelin clearance are incompletely understood. We set out to discover new pathways of PNS myelin clearance to identify novel strategies for activating myelin clearance in the injured central nervous system, where myelin debris is not cleared efficiently...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28854781/molecular-analysis-of-alternative-transcripts-of-equine-axl-receptor-tyrosine-kinase-gene
#12
Jeong-Woong Park, Ki-Duk Song, Nam Young Kim, Jae-Young Choi, Seul A Hong, Jin Hyeog Oh, Si Won Kim, Jeong Hyo Lee, Tae Sub Park, Jin-Kyoo Kim, Jong Geun Kim, Byung-Wook Cho
OBJECTIVE: Since athletic performance is a most importance trait in horses, most research focused on physiological and physical studies of horse athletic abilities. In contrast, the molecular analysis as well as the regulatory pathway studies remain insufficient for evaluation and prediction of horse athletic abilities. In our previous study, we identified AXL receptor tyrosine kinase (AXL) gene which was expressed as alternative spliced isoforms in skeletal muscle during exercise. In the present study, we validated two AXL alternative splicing transcripts (named as AXLa for long form and AXLb for short form) in equine skeletal muscle to gain insight(s) into the role of each alternative transcript during exercise...
October 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28852098/selinexor-kpt-330-has-antitumor-activity-against-anaplastic-thyroid-carcinoma-in-vitro-and-in-vivo-and-enhances-sensitivity-to-doxorubicin
#13
Manoj Garg, Deepika Kanojia, Anand Mayakonda, Trivadi S Ganesan, Bindhya Sadhanandhan, Sidhanth Suresh, Sneha S, Rohit P Nagare, Jonathan W Said, Ngan B Doan, Ling-Wen Ding, Erkan Baloglu, Sharon Shacham, Michael Kauffman, H Phillip Koeffler
Anaplastic thyroid carcinoma (ATC) is one of the most lethal malignancies having no effective treatment. Exportin-1 (XPO1) is the key mediator of nuclear export of many tumor suppressor proteins and is overexpressed in human cancers. In this study, we examined the therapeutic potential of selinexor (XPO1 inhibitor) against human ATC cells both in vitro and in vivo. Here, we showed that XPO1 is robustly expressed in primary ATC samples and human ATC cell lines. Silencing of XPO1 by either shRNA or selinexor significantly reduced cellular growth and induced cell cycle arrest, apoptosis of ATC cells by altering the protein expression of cancer-related genes...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842481/protonation-dependent-stepped-rotation-of-the-f-type-atp-synthase-c-ring-observed-by-single-molecule-measurements
#14
Seiga Yanagisawa, Wayne D Frasch
The two opposed rotary molecular motors of the FOF1 ATP synthase work together to provide the majority of ATP in most biological organisms. Rotation occurs in 120° power strokes separated by dwells when F1 synthesizes or hydrolyzes ATP. FO and F1 complexes connect via a central rotor stalk and a peripheral stator stalk. A major unresolved question is the mechanism in which the interaction between subunit a and rotating subunit c-ring in the FO motor uses the flux of H(+) across the membrane to induce clockwise rotation against the force of counterclockwise rotation driven by the F1-ATPase...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28832662/oxygen-dependent-regulation-of-tumor-growth-and-metastasis-in-human-breast-cancer-xenografts
#15
Kristine Yttersian Sletta, Maria K Tveitarås, Ning Lu, Agnete S T Engelsen, Rolf K Reed, Annette Garmann-Johnsen, Linda Stuhr
BACKGROUND: Tumor hypoxia is relevant for tumor growth, metabolism, resistance to chemotherapy and metastasis. We have previously shown that hyperoxia, using hyperbaric oxygen treatment (HBOT), attenuates tumor growth and shifts the phenotype from mesenchymal to epithelial (MET) in the DMBA-induced mammary tumor model. This study describes the effect of HBOT on tumor growth, angiogenesis, chemotherapy efficacy and metastasis in a triple negative MDA-MB-231 breast cancer model, and evaluates tumor growth using a triple positive BT-474 breast cancer model...
2017: PloS One
https://www.readbyqxmd.com/read/28828649/specific-and-generic-isolation-of-extracellular-vesicles-with-magnetic-beads
#16
Ketil W Pedersen, Bente Kierulf, Axl Neurauter
This chapter covers magnetic bead-based isolation and analysis of the smallest members of extracellular vesicles (EVs), the exosomes (30-150 nm), generally regarded to originate from the multivesicular bodies (MVBs). Also included, are descriptions of how to prepare samples prior to isolations. The magnetic bead-based isolation workflow is dramatically shortened both by omitting the pre-enrichment step and providing an option for a very short capture time. Three direct exosome isolation strategies are described: (1) "Specific and Direct," (2) "Semi Generic and Direct" and (3) "Generic and Direct" as well as exosome release from the magnetic beads...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28810265/viral-retinopathy-in-experimental-models-of-zika-infection
#17
Zhenyang Zhao, Matthew Yang, Sasha R Azar, Lynn Soong, Scott C Weaver, Jiaren Sun, Yan Chen, Shannan L Rossi, Jiyang Cai
Purpose: Emerging evidence has shown that both congenital and adult Zika virus (ZIKV) infection can cause eye diseases. The goals of the current study were to explore mechanisms and pathophysiology of ZIKV-induced eye defects. Methods: Wild-type or A129 interferon type I receptor-deficient mice were infected by either FSS13025 or Mex1-7 strain of ZIKV. Retinal histopathology was measured at different time points after infection. The presence of viral RNA and protein in the retina was determined by in situ hybridization and immunofluorescence staining, respectively...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28804597/size-and-concentration-analyses-of-extracellular-vesicles-by-nanoparticle-tracking-analysis-a-variation-study
#18
Beate Vestad, Alicia Llorente, Axl Neurauter, Santosh Phuyal, Bente Kierulf, Peter Kierulf, Tore Skotland, Kirsten Sandvig, Kari Bente F Haug, Reidun Øvstebø
Current methods for characterisation of extracellular vesicles (EVs) need further standardisation in order to obtain an acceptable level of data comparability. Size and concentration of EVs can be determined by nanoparticle tracking analysis (NTA). However, both the heterogeneity of EVs and the choice of instrument settings may cause an appreciable analytical variation. Intra-assay (within-day, n = 6) and inter-assay (day-to-day, n = 6) variations (coefficient of variation, % CV) of different preparations of EVs and artificial vesicles or beads were determined using two NanoSight NS500 instruments, located at different laboratories...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28800189/supramolecular-host-guest-inclusion-for-distinguishing-cucurbit-7-uril-based-pseudorotaxanes-from-small-molecule-ligands-in-coordination-assembly-with-uranyl-center
#19
Wei-Qun Shi, Lei Mei, Zhen-Ni Xie, Kong-Qiu Hu, Li-Yong Yuan, Zeng-Qiang Gao, Zhi-Fang Chai
Although the capability of supramolecular pseudorotaxane/rotaxane systems as ligands for coordination with actinides has been identified by the on-going emerging of uranyl-organic polyrotaxane compounds, it is, however, still unknown how supramolecular inclusion affects the coordination assembly of the simple 'axle' ligand with uranyl species. Herein, a semi-rigid organic dicarboxylate compound [BzBPCEt]Br2 (L1) is selected as a small-molecule 'axle' ligand and the corresponding cucurbit[7]uril (CB7)-based [2]pseudorotaxane ligand, [BzBPCEt]Br2@CB7 (L1@CB7) has been also synthesized through CB7-based inclusion in this work...
August 11, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28799754/threading-of-an-inherently-directional-calixarene-wheel-with-oriented-ammonium-axles
#20
Pellegrino La Manna, Carmen Talotta, Carmine Gaeta, Annunziata Soriente, Margherita De Rosa, Placido Neri
The threading of monostoppered alkylbenzylammonium axles 7(+) and 8(+) with the calix[6]-wheel 3 can occur by both routes of entering the macrocycle 3 in the cone conformation: passage through the upper rim and the through the lower rim. Thus, under thermodynamic conditions, with both the axles 7(+) and 8(+), the two possible orientations of calix[2]pseudorotaxane, namely, endo-benzyl and endo-alkyl, are formed by a stereoselectivity controlled by the endo-alkyl rule. Interestingly, by (1)H NMR monitoring of the threading process between 8(+) and 3, we revealed two calix[2]pseudorotaxane isomers in which the calix-wheel adopts 1,2,3-alternate and cone conformations, which represent the kinetic and thermodynamic species, respectively...
August 21, 2017: Journal of Organic Chemistry
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