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https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#1
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28209619/lapatinib-resistance-in-breast-cancer-cells-is-accompanied-by-phosphorylation-mediated-reprogramming-of-glycolysis
#2
Benjamin Ruprecht, Esther A Zaal, Jana Zecha, Wei Wu, Celia R Berkers, Bernhard Kuster, Simone Lemeer
HER2/ERBB2-overexpressing breast cancers targeted effectively by the small molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In this study, we employed explorative mass spectrometry to profile proteomic, kinomic, and phosphoproteomic changes in an established model of lapatinib resistance to systematically investigate initial inhibitor response and subsequent reprogramming in resistance. The resulting dataset, which collectively contains quantitative data for >7,800 proteins, >300 protein kinases and >15,000 phosphopeptides, enabled deep insight into signaling recovery and molecular reprogramming upon resistance...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28208648/n-butylidenephthalide-regulated-tumor-stem-cell-genes-ezh2-axl-and-reduced-its-migration-and-invasion-in-glioblastoma
#3
Ssu-Yin Yen, Hong-Meng Chuang, Mao-Hsuan Huang, Shinn-Zong Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207520/characterization-of-ocular-biometrics-and-aqueous-humor-dynamics-in-primary-angle-closure-suspects
#4
Li Guo, Yuan Deng, Li Fang, Chaoqi Liu, Tao Guo
Detailed characterizations of ocular biometrics and parameters of aqueous humor dynamics are lacking in primary angle closure suspect (PACS) patients. This study aims to characterize these parameters and compare them with age-matched healthy volunteers.Elderly healthy volunteers (60.6 ± 7.2 years of age, mean ± SD, n = 28) and PACS patients (64.1 ± 11.6 years, n = 30) completed the study. Parameters investigated were axial length (AXL), anterior chamber depth (ACD), anterior chamber volume (ACV), central cornea thickness (CCT), intraocular pressure (IOP), aqueous flow (Fa), outflow facility (C), episcleral venous pressure (EVP), and uveoscleral outflow (Fu)...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28199818/cabozantinib-versus-sunitinib-as-initial-targeted-therapy-for-patients-with-metastatic-renal-cell-carcinoma-of-poor-or-intermediate-risk-the-alliance-a031203-cabosun-trial
#5
Toni K Choueiri, Susan Halabi, Ben L Sanford, Olwen Hahn, M Dror Michaelson, Meghara K Walsh, Darren R Feldman, Thomas Olencki, Joel Picus, Eric J Small, Shaker Dakhil, Daniel J George, Michael J Morris
Purpose Cabozantinib is an oral potent inhibitor of vascular endothelial growth factor receptor 2, MET, and AXL and is a standard second-line therapy for metastatic renal cell carcinoma (mRCC). This randomized phase II multicenter trial evaluated cabozantinib compared with sunitinib as first-line therapy in patients with mRCC. Patients and Methods Eligible patients had untreated clear cell mRCC and Eastern Cooperative Oncology Group performance status of 0 to 2 and were intermediate or poor risk per International Metastatic Renal Cell Carcinoma Database Consortium criteria...
February 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28188446/treatment-options-for-egfr-t790m-negative-egfr-tyrosine-kinase-inhibitor-resistant-non-small-cell-lung-cancer
#6
Salvatore Corallo, Ettore D'Argento, Antonia Strippoli, Michele Basso, Santa Monterisi, Sabrina Rossi, Alessandra Cassano, Carlo M Barone
The introduction of first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib and afatinib) for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC) has dramatically improved patients' prognosis and quality of life (QoL). Unfortunately, after an initial and sometimes durable benefit from EGFR-TKI therapy, all patients with EGFR-mutant lung cancer eventually become resistant to the treatment and experience disease progression. In approximately 50% of these patients, genomic alterations in the EGFR kinase domain resulting in the mutant T790M are responsible for the resistance and this has led to the development of novel EGFR inhibitors active against mutant-T790M EGFR...
February 10, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28184013/phosphatidylserine-sensing-by-tam-receptors-regulates-akt-dependent-chemoresistance-and-pd-l1-expression
#7
Canan Kasikara, Sushil Kumar, Stanley Kimani, Wen-I Tsou, Ke Geng, Viralkumar Davra, Ganapathy Sriram, Connor Devoe, Khanh-Quynh Nguyen, Anita Antes, Allen Krantz, Grzegorz Rymarczyk, Andrzej Wilczynski, Cyril Empig, Bruce D Freimark, Michael Gray, Kyle Schlunegger, Jeff Hutchins, Sergei V Kotenko, Raymond B Birge
: Tyro3, Axl and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases (RTKs) that bind vitamin K-dependent endogenous ligands, Protein S (ProS) and Growth arrest specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radio-resistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment (TME) that can suppress host anti-tumor immunity...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28174963/p002-inhibition-of-axl-signaling-by-bgb324-reduces-fibrogenesis-in-human-intestinal-cells-and-human-intestinal-organoids
#8
C Steiner, E Rodansky, L A Johnson, S Huang, J Spence, P D Higgins
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28170008/metal-organic-frameworks-utilising-an-interlocked-hexadentate-linker-containing-a-tetra-carboxylate-axle-and-a-bis-pyridine-wheel
#9
Ghazale Gholami, Giorgio Baggi, Kelong Zhu, Stephen J Loeb
A [2]rotaxane linker was synthesized which combines an H-shaped axle containing four 3-carboxyphenyl groups and a macrocyclic wheel with two 4-pyridyl groups. Metal-organic framework materials were prepared with Cu(II) and Zn(II) ions X-ray structures show that the materials contain unique frameworks that are threaded solely due to the interpenetrated nature of the linker.
February 7, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28168152/plugging-a-bipyridinium-axle-into-multichromophoric-calix-6-arene-wheels-bearing-naphthyl-units-at-different-rims
#10
Guido Orlandini, Giulio Ragazzon, Valeria Zanichelli, Lorenzo Degli Esposti, Massimo Baroncini, Serena Silvi, Margherita Venturi, Alberto Credi, Andrea Secchi, Arturo Arduini
Tris-(N-phenylureido)-calix[6]arene derivatives are heteroditopic non-symmetric molecular hosts that can form pseudorotaxane complexes with 4,4'-bipyridinium-type guests. Owing to the unique structural features and recognition properties of the calix[6]arene wheel, these systems are of interest for the design and synthesis of novel molecular devices and machines. We envisaged that the incorporation of photoactive units in the calixarene skeleton could lead to the development of systems the working modes of which can be governed and monitored by means of light-activated processes...
February 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28167751/axl-dependent-infection-of-human-fetal-endothelial-cells-distinguishes-zika-virus-from-other-pathogenic-flaviviruses
#11
Audrey Stéphanie Richard, Byoung-Shik Shim, Young-Chan Kwon, Rong Zhang, Yuka Otsuka, Kimberly Schmitt, Fatma Berri, Michael S Diamond, Hyeryun Choe
Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28160507/strong-and-selective-halide-anion-binding-by-neutral-halogen-bonding-2-rotaxanes-in-wet-organic-solvents
#12
Jason Y C Lim, Thanthapatra Bunchuay, Paul D Beer
The design and construction of neutral interlocked host molecules for anion recognition are rare. Using an active-metal template approach, the preparation of a family of neutral halogen bonding rotaxanes containing two, three and four iodotriazole groups integrated into the macrocycle and axle components is achieved. In spite of the interlocked hosts' neutrality, such rotaxane systems are capable of binding halide anions strongly and selectively in wet organic solvent mixtures. Importantly, halide binding strength and selectivity can be modulated by varying the number and position of the halogen bond-donor iodotriazole groups within the interlocked cavity; the rotaxane containing the largest number of halogen bond donor groups exhibits the highest halide anion binding affinities...
February 4, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28159915/strategies-to-overcome-bypass-mechanisms-mediating-clinical-resistance-to-egfr-tyrosine-kinase-inhibition-in-lung-cancer
#13
REVIEW
Hatim Husain, Michael Scur, Ayesha Murtuza, Nam Bui, Brian Woodward, Razelle Kurzrock
The vast majority of patients with metastatic lung cancers who initially benefit from EGFR-targeted therapies eventually develop resistance. An increasing understanding of the number and complexity of resistance mechanisms highlights the challenge of treating tumors resistant to EGFR inhibitors. Resistance mechanisms include new, second-site mutations within EGFR (e.g., T790M and C797S), upregulation of MET kinase, upregulation of insulin growth factor receptor (IGFR), HER2 amplification, increased expression of AXL, BIM modulation, NF-κB activation, histologic switch to small-cell cancer, epithelial-to-mesenchymal transition, PDL1 expression with subsequent immune tolerance, and release of cytokines such as TGFβ and IL6...
February 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28145633/optical-distinction-between-slow-and-fast-translational-motion-in-degenerate-molecular-shuttles
#14
V Nicholas Vukotic, Kelong Zhu, Giorgio Baggi, Stephen J Loeb
A series of six [2]rotaxane molecular shuttles was designed which contain an axle with a benzo-bis(imidazole) core (in either a neutral or dicationic form) and a single 24-membered, crown ether wheel (24C6, B24C6, or DMB24C6), and the shuttling rates of the ring along the axle were determined. The charged versions showed much slower shuttling rates as a result of the increase in noncovalent interactions between the axle and wheel. The [2]rotaxane with a B24C6 wheel shows a difference in fluorescence between the charged and neutral species, while the [2]rotaxane with a DMB24C6 wheel exhibits a difference in color between the charged and neutral compounds...
February 1, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28145605/the-tam-receptor-tyro3-regulates-myelination-in-the-central-nervous-system
#15
Rainer Akkermann, Andrea Aprico, Ashwyn A Perera, Helena Bujalka, Alistair E Cole, Junhua Xiao, Judith Field, Trevor J Kilpatrick, Michele D Binder
Myelin is an essential component of the mammalian nervous system, facilitating rapid conduction of electrical impulses by axons, as well as providing trophic support to neurons. Within the central nervous system, the oligodendrocyte is the specialized neural cell responsible for producing myelin by a process that is thought to be regulated by both activity dependent and independent mechanisms but in incompletely understood ways. We have previously identified that the protein Gas6, a ligand for a family of tyrosine kinase receptors known as the TAM (Tyro3, Axl, and Mertk) receptors, directly increases oligodendrocyte induced myelination in vitro...
February 1, 2017: Glia
https://www.readbyqxmd.com/read/28133969/enantiodifferentiation-in-the-photoisomerization-of-z-z-1-3-cyclooctadiene-in-the-cavity-of-%C3%AE-cyclodextrin-curcubit-6-uril-wheeled-4-rotaxanes-with-an-encapsulated-photosensitizer
#16
Zhiqiang Yan, Qinfei Huang, Wenting Liang, Xingke Yu, Dayang Zhou, Wanhua Wu, Jason J Chruma, Cheng Yang
A biphenyl photosensitizer axle was implanted into the cavities of native and capped γ-cyclodextrins through rotaxanation using a cucubit[6]uril-templated azide-alkyne 1,3-dipolar cycloaddition, resulting in the construction of highly defined chiral binding/sensitizing sites. The orientation and interaction of the axle and capping moieties at the ground and excited states were interrogated by NMR, UV-vis, circular dichroism, and fluorescence spectroscopic studies. In situ photoisomerization of (Z,Z)-1,3-cyclooctadiene sensitized in the cavity of these [4]rotaxanes afforded (Z,E)-1,3-cyclooctadiene in up to 15...
January 30, 2017: Organic Letters
https://www.readbyqxmd.com/read/28127639/increased-mer-and-axl-receptor-tyrosine-kinase-expression-on-glomeruli-in-lupus-nephritis
#17
Shanshan Li, Qianyu Guo, Huaqun Zhu, Zhanguo Li, Yin Su, Bao Dong
Mer and Axl receptor tyrosine kinases (MerTK and AxlTK) play important roles in the clearance of apoptotic cells and the inhibition of inflammatory responses. Previous studies demonstrated that they might participate in glomerular injury in mice model. This study aimed to elucidate the expression of MerTK and AxlTK on glomeruli and analyze their clinical significance in lupus nephritis (LN) patients. Twenty-nine LN and 10 primary nephrotic syndrome (NS) patients were recruited. The expression of MerTK and AxlTK on glomeruli was measured by immunohistochemistry...
January 26, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28118606/protein-s-drives-oral-squamous-cell-carcinoma-tumorigenicity-through-regulation-of-axl
#18
Ghada Abboud-Jarrous, Shivam Priya, Avi Maimon, Stuart Fischman, Mayan Cohen-Elisha, Rakefet Czerninski, Tal Burstyn-Cohen
The TAM family of proto-oncogenic receptor protein tyrosine kinases, comprising of TYRO3, AXL, and MERTK, is implicated in many human cancers. Their activation leads to cancer cell proliferation, enhanced migration, invasion, and drug resistance; however how TAMs are activated in cancers is less understood. We previously showed that Protein S (PROS1) is a ligand of the TAM receptors. Here we identify PROS1 as a mediator of Oral Squamous Cell Carcinoma (OSCC) in proliferation, cell survival and migration. We demonstrate that excess PROS1 induces OSCC proliferation and migration...
January 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115012/exosomes-derived-from-human-menstrual-blood-derived-stem-cells-alleviate-fulminant-hepatic-failure
#19
Lu Chen, Bingyu Xiang, Xiaojun Wang, Charlie Xiang
BACKGROUND: Human menstrual blood-derived stem cells (MenSCs) are a novel source of MSCs that provide the advantage of being easy to collect and isolate. Exosomes contain some mRNAs and adhesion molecules that can potentially impact cellular and animal physiology. This study aimed to investigate the therapeutic potential of MenSC-derived exosomes (MenSC-Ex) on AML12 cells (in vitro) and D-GalN/LPS-induced FHF mice (in vivo). METHODS: Transmission electron microscopy and Western blot were used to identify MenSC-Ex...
January 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28109086/grade-dependent-expression-of-nima-related-kinase-2-in-glioma-and-its-cellular-upregulatory-activity-on-proliferation-and-invasion
#20
Li Tian, Peng Cheng, Huaiyu Sun, Yulin Wang, Lei Zhang, Zongze Guo
Glioma is one of the most common tumors in central nervous system. The median life expectancy for glioma patients is only 13-15 months. NIMA-related expressed kinase 2 (NEK2) is a kind of serine-threonine kinases and involves in carcinogenesis and progression of cancer, however, the specific roles in the glioma remains unknown. We found the high expression of NEK2 was positively correlated with deteriorated severity of glioma. Therefore, we sought to investigate the effects of NEK2 on U87 and U251 cells. To explore the expression of NEK2 and alteration of signaling pathway factors, qRT-PCR and Western blot analysis were performed...
January 20, 2017: Oncology Research
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