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https://www.readbyqxmd.com/read/28527274/caracter%C3%A3-sticas-de-la-estructura-molecular-de-las-prote%C3%A3-nas-e-del-virus-del-zika-y-e1-del-virus-de-la-rub%C3%A3-ola-y-posibles-implicaciones-en-el-neurotropismo-y-en-las-alteraciones-del-sistema-nervioso
#1
Luis Alberto Gómez, Gladis Montoya, Hernán Mauricio Rivera, Juan Carlos Hernández
Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV).Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV...
April 1, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28526812/soluble-axl-is-an-accurate-biomarker-of-cirrhosis-and-hepatocellular-carcinoma-development-results-from-a-large-scale-multicenter-analysis
#2
Mirko Dengler, Katharina Staufer, Heidemarie Huber, Rudolf Stauber, Heike Bantel, Karl Heinz Weiss, Patrick Starlinger, Hannelore Pock, Petra Klöters-Plachky, Daniel N Gotthardt, Peter Rauch, Carolin Lackner, Judith Stift, Christine Brostjan, Thomas Gruenberger, Takashi Kumada, Hidenori Toyoda, Toshifumi Tada, Thomas S Weiss, Michael Trauner, Wolfgang Mikulits
Patients with chronic liver disease (CLD) and cirrhosis are at high risk for hepatocellular carcinoma (HCC). Current diagnostic tools for HCC detection include imaging techniques and serum biomarkers such as α-fetoprotein (AFP). Yet, these methods are limited in sensitivity and specificity to accurately detect early HCC. Here we focused on the potential of soluble Axl (sAxl) as a biomarker in CLD patients by analyzing serum samples of 1067 patients and healthy controls from centers in Europe and Asia. We show that serum concentrations of sAxl were significantly increased at early (82...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526769/tam-receptor-tyrosine-kinases-in-cancer-drug-resistance
#3
REVIEW
Mikaella Vouri, Sassan Hafizi
Receptor tyrosine kinases (RTK) are major regulators of key biological processes, including cell growth, survival, and differentiation, and were established early on as proto-oncogenes, with aberrant expression linked to tumor progression in many cancers. Therefore, RTKs have emerged as major targets for selective therapy with small-molecule inhibitors. However, despite improvements in survival rates, it is now apparent that the targeting of RTKs with selective inhibitors is only transiently effective, as the majority of patients eventually become resistant to therapy...
May 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28516360/gilteritinib-a-flt3-axl-inhibitor-shows-antileukemic-activity-in-mouse-models-of-flt3-mutated-acute-myeloid-leukemia
#4
Masamichi Mori, Naoki Kaneko, Yoko Ueno, Masaki Yamada, Ruriko Tanaka, Rika Saito, Itsuro Shimada, Kenichi Mori, Sadao Kuromitsu
Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the activation of FLT3 and has been implicated in the pathogenesis of AML. The studies reported here evaluated the ability of a novel FLT3/AXL inhibitor, gilteritinib, to block mutated FLT3 in cellular and animal models of AML...
May 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28513168/influence-of-rotator-design-on-the-speed-of-self-assembled-four-component-nanorotors-coordinative-versus-dispersive-interactions
#5
Pronay Kumar Biswas, Suchismita Saha, Yerramsetti Nanaji, Anup Rana, Michael Schmittel
Four-component nanorotors are prepared by the self-assembly of stator [Cu4(4)](4+) with its four copper(I)-loaded phenanthroline stations and various rotators carrying one, two, or three pyridine terminals. The fourth component, 1,4-diazabicyclo[2.2.2]octane, serves as a connecting axle between rotator and stator. Capitalizing on the heteroleptic pyridyl and phenanthroline metal complexes concept, the rotator's pyridine terminals are connected to the copper(I)-loaded phenanthroline stations (Npy → [Cu(phen)](+)) in the STOP state and disconnected in the transition state of rotation...
May 17, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28502167/transient-porosity-in-densely-packed-crystalline-carbazole-p-diethynylphenylene-carbazole-rotors-co2-and-acetone-sorption-properties
#6
Andres Aguilar-Granda, Salvador Perez-Estrada, Elí Sánchez-González, J Raziel Álvarez, Joelis Rodriguez-Hernandez, Mario Rodriguez, Arian E Roa, Simón Hernandez-Ortega, Ilich A Ibarra, Braulio Rodríguez-Molina
We report for the first time the high sorption properties of a molecular rotor with no permanent voids or channels in its crystal structure. Such crystalline phase originates either from THF, DCM or by the irreversible desolvation of entrapped benzene molecules. From these, the benzene in its solvate form acts as rotation stopper, as supported by dynamic characterization using solid-state 2H NMR experiments. In the solvent free form, the diffusion of small quantities of iodine vapors caused a significant change in the intramolecular rotation, increasing the known activation energy to rotation from 8...
May 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28500237/resistance-to-ret-inhibition-in-ret-rearranged-nsclc-is-mediated-by-reactivation-of-ras-mapk-signaling
#7
Sarah K Nelson-Taylor, Anh T Le, Minjae Yoo, Laura Schubert, Katie M Mishall, Andrea Doak, Marileila Varella-Garcia, Aik-Choon Tan, Robert C Doebele
Oncogenic rearrangements in RET are present in 1-2% of lung adenocarcinoma (LAD) patients. Ponatinib is a multi-kinase inhibitor with low-nanomolar potency against the RET kinase domain. Here, we demonstrate that ponatinib exhibits potent anti-proliferative activity in RET fusion positive LC-2/ad LAD cells and inhibits phosphorylation of the RET fusion protein and signaling through ERK1/2 and AKT. Using distinct dose-escalation strategies, two ponatinib-resistant LC-2/ad cell lines, PR1 and PR2, were derived...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28492542/lncrna-hotair-regulates-hif-1%C3%AE-axl-signaling-through-inhibition-of-mir-217-in-renal-cell-carcinoma
#8
Quan Hong, Ou Li, Wei Zheng, Wen-Zhen Xiao, Lu Zhang, Di Wu, Guang-Yan Cai, John Cijiang He, Xiang-Mei Chen
Long non-coding RNA HOTAIR was regarded as an oncogene in multiple cancers. Previous studies have shown that HOTAIR is involved in the proliferation and tumorigenesis of renal carcinoma cells, while microRNA (miR)-217 functions as a tumor suppressor in renal cell carcinoma (Rcc). However, the underlying molecular mechanism of HOTAIR in Rcc, especially in association with miR-217, has not been studied. In this study, we first demonstrated that HOTAIR expression was upregulated, which was correlated with tumor progression, and miR-217 downregulated in Rcc tissues and cells...
May 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28486806/molecular-snuggle-and-stretch-of-a-tetraammonium-chain-in-the-construction-of-a-hetero-4-pseudorotaxane-with-cyclopentanoq-6-and-classical-q-7
#9
Wen-Jing Wu, Feng Wu, Anthony I Day
A hetero-pseudo[4]rotaxane was designed to perform a molecular machine function of contraction and expansion utilising the binding features of CyP6Q[6] and classical Q[7]. First, the effect on guest binding of equatorial substitution on Q[6]'s was examined by comparing Me4Q[6] and CyP6Q[6] against classical Q[6] using 8 guest molecules varying in shape, size, neutrality or cations. Second, the binding data provided optimal structural features for the design of a tetraammonium ion chain to effect the synthesis of the hetero-[4]pseudorotaxane...
May 10, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28485160/mir-34a-suppresses-hnscc-growth-through-modulating-cell-cycle-arrest-and-senescence
#10
Y Wang, J Chen, X Chen, F Jiang, Y Sun, Y Pan, W Zhang, J Zhang
MiR-34a acts as a tumor suppressor in various malignancies. In HNSCC, the role of miR-34a in proliferation has not been fully elaborated and the target genes are still bind. Here, we addressed that forced miR-34a expression induced cell cycle arrest and senescence. Hypoxia/HIF1α was found to negatively correlate to the expression of miR-34a in HNSCC tissues and partially reverse miR-34a-imposed cell senescence through suppressing miR-34a expression. In order to screen the possible target genes of miR-34a in HNSCC, the differential genes mediated by miR-34a were screened by mRNA microarray...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28481878/the-ap-1-transcription-factor-fosl1-causes-melanocyte-reprogramming-and-transformation
#11
K Maurus, A Hufnagel, F Geiger, S Graf, C Berking, A Heinemann, A Paschen, S Kneitz, C Stigloher, E Geissinger, C Otto, A Bosserhoff, M Schartl, S Meierjohann
The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28476872/integrative-analysis-identifies-a-novel-axl-pi3-kinase-pd-l1-signaling-axis-associated-with-radiation-resistance-in-head-and-neck-cancer
#12
Heath D Skinner, Uma Giri, Liang P Yang, Manish Kumar, Ying Liu, Michael D Story, Curtis R Pickering, Lauren A Byers, Michelle D Williams, Jing Wang, Li Shen, Suk Y Yoo, You Hong Fan, David P Molkentine, Beth M Beadle, Raymond E Meyn, Jeffrey N Myers, John V Heymach
Purpose: The primary cause of death due to head and neck squamous cell carcinoma (HNSCC) is local treatment failure. The goal of this study was to examine this phenomenon using an unbiased approach.Experimental Design: We utilized human papilloma virus (HPV)-negative cell lines rendered radiation-resistant (RR) via repeated exposure to radiation, a panel of HPV-negative HNSCC cell lines and three cohorts of HPV-negative HNSCC tumors (n = 68, 97, and 114) from patients treated with radiotherapy and subjected to genomic, transcriptomic, and proteomic analysis...
May 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28476049/corneal-k-values-as-a-diagnostic-screening-tool-for-marfan-syndrome
#13
Jan Luebke, Daniel Boehringer, Philipp Eberwein, Thomas Reinhard
PURPOSE: Marfan syndrome (MFS) is diagnosed based on Ghent nosology, including major and minor criteria such as increased axial length (AXL) and flattened corneal curvature (higher K-values) or myopia of more than -3 diopters (D) in its latest revision. Because corneal flattening may, in part, be caused by AXL increase, it may be helpful to consider K-values separately. We present statistical evaluation of using corneal K-values for identifying MFS. METHODS: A retrospective study of K-values of 74 right eyes of 74 patients with MFS, who were compared with an age- and AXL-matched group of 74 right eyes of 74 patients without MFS...
June 2017: Cornea
https://www.readbyqxmd.com/read/28471662/pyridyl-acyl-hydrazone-rotaxanes-and-molecular-shuttles
#14
David A Leigh, Vanesa Marcos, Tugrul Nalbantoglu, Iñigo J Vitorica-Yrezabal, F Tuba Yasar, Xiaokang Zhu
We report on rotaxanes featuring a pyridyl-acyl hydrazone moiety on the axle as a photo/thermal-switchable macrocycle binding site. The pyridyl-acyl E-hydrazone acts as a hydrogen bonding template that directs the assembly of a benzylic amide macrocycle around the axle to form [2]rotaxanes in up to 85% yield; the corresponding Z-hydrazone thread affords no rotaxane under similar conditions. However, the E-rotaxane can be smoothly converted into the Z-rotaxane in 98% yield under UV irradiation. The X-ray crystal structures of the E- and Z-rotaxanes show different intercomponent hydrogen bonding patterns...
May 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28468579/lncrna-malat1-mediated-axl-promotes-cell-invasion-and-migration-in-human-neuroblastoma
#15
Shaojie Bi, Chunyan Wang, Yixin Li, Wei Zhang, Juan Zhang, Zhaopeng Lv, Junxia Wang
Overexpression of Axl has been noted to correlate with several human cancers. However, the regulatory mechanisms and effects of Axl in human neuroblastoma development remain unclear. Here, we explore the expression of Axl in neurobalstoma and related upstream regulatory mechanisms of invasion and migration. We found that Axl was overexpressed in metastatic neuroblastoma tissues and positively associated with long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1. Meanwhile, our data suggested that metastasis-associated lung adenocarcinoma transcript 1 upregulated Axl expression in neuroblastoma cells, resulting in cell invasion and migration...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28464908/a-phase-i-study-of-lapatinib-in-combination-with-foretinib-a-c-met-axl-and-vascular-endothelial-growth-factor-receptor-inhibitor-in-human-epidermal-growth-factor-receptor-2-her-2-positive-metastatic-breast-cancer
#16
Stephen K Chia, Susan L Ellard, Mihaela Mates, Stephen Welch, Catalin Mihalcioiu, Wilson H Miller, Karen Gelmon, Caroline Lohrisch, Vikaash Kumar, Sara Taylor, Linda Hagerman, Rachel Goodwin, Tao Wang, Shingo Sakashita, Ming S Tsao, Elizabeth Eisenhauer, Penelope Bradbury
BACKGROUND: The mechanisms of resistance to anti-human epidermal growth factor receptor 2 (HER 2) therapies are unclear but may include the tyrosine-protein kinase Met (c-Met), vascular endothelial growth factor (VEGF) and AXL pathways. Foretinib is an inhibitor of c-Met, VEGF receptor 2 (VEGFR-2), platelet-derived growth factor receptor beta (PDGFRB), AXL, Fms-like tyrosine kinase 3 (FLT3), angiopoiten receptor (TIE-2), RET and RON kinases. This phase Ib study sought to establish the associated toxicities, pharmacokinetics (PK) and recommended phase II doses (RP2D) of foretinib and lapatinib in a cohort of HER-2-positive patients with metastatic breast cancer (MBC)...
May 2, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28460436/rab10-overexpression-promotes-tumor-growth-and-indicates-poor-prognosis-of-hepatocellular-carcinoma
#17
Wei Wang, Wei-Dong Jia, Bing Hu, Yue-Yin Pan
Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here we report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28455956/targeting-axl-overcomes-resistance-to-docetaxel-therapy-in-advanced-prostate-cancer
#18
Jian-Zhong Lin, Zeng-Jun Wang, Wei De, Ming Zheng, Wei-Zhang Xu, Hong-Fei Wu, Alex Armstrong, Jia-Geng Zhu
Resistance to docetaxel is a major clinical problem in advanced prostate cancer. The overexpression of AXL receptor tyrosine kinase (AXL) has been correlated with chemotherapeutic drug resistance. However, the role of AXL expression in docetaxel resistance in prostate cancer is yet unclear. In this study, we demonstrate that AXL is overexpressed and activated independent of Gas6 in docetaxel-resistant prostate cancer cells (PC3-DR and DU145-DR). Moreover, we show that forced overexpression of AXL in PC3 and DU145 cells is sufficient to induce resistance to docetaxel in these cell lines...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454330/high-bim-mrna-levels-are-associated-with-longer-survival-in-advanced-gastric-cancer
#19
Nandie Wu, Ying Huang, Zhengyun Zou, Ana Gimenez-Capitan, Lixia Yu, Wenjing Hu, Lijing Zhu, Xia Sun, Jose Javier Sanchez, Wenxian Guan, Baorui Liu, Rafael Rosell, Jia Wei
Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28451196/ion-pair-recognition-by-a-neutral-2-rotaxane-based-on-a-bis-calix-4-pyrrole-cyclic-component
#20
J Ramón Romero, Gemma Aragay, Pablo Ballester
In this work, we report our investigations on the synthesis of a [2]rotaxane based on a bis(calix[4]pyrrole) cyclic component and a 3,5-bis-amidepyridyl-N-oxide derivative axle. We isolated the [2]rotaxane in a significant 50% yield through an optimized "in situ" capping strategy using the copper(i)-catalyzed azide-alkyne cycloaddition reaction. The synthetic precursor of the [2]rotaxane, featuring [2]pseudorotaxane topology, could be quantitatively assembled in solution in the presence of one equivalent of tetrabutylammonium chloride or cyanate salts producing a four-particle aggregate...
January 1, 2017: Chemical Science
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