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https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#1
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28440492/axl-and-gas6-co-expression-in-lung-adenocarcinoma-as-a-prognostic-classifier
#2
Masahiro Seike, Cheol-Hong Kim, Fenfei Zou, Rintaro Noro, Mika Chiba, Arimi Ishikawa, Shinobu Κunugi, Kaoru Kubota, Akihiko Gemma
AXL, a receptor tyrosine kinase implicated in cell survival, proliferation, and migration, is also associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor therapy. However, its prognostic significance in lung adenocarcinoma (AD) remains unclear. We therefore evaluated the prognostic significance of the expression of AXL and/or its ligand, growth arrest-specific 6 (GAS6), in completely resected lung AD. We evaluated the relationship between AXL, GAS6, and vimentin expression, as determined by immunohistochemistry (IHC) analysis, with overall survival and disease-free survival in 113 patients with stages I-III lung AD...
April 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#3
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II(+) microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28426214/calix-5-arene-through-the-annulus-threading-of-dialkylammonium-guests-weakly-paired-to-the-tfpb-anion
#4
Margherita De Rosa, Carmen Talotta, Carmine Gaeta, Annunziata Soriente, Placido Neri, Sebastiano Pappalardo, Giuseppe Gattuso, Anna Notti, Melchiorre F Parisi, Ilenia Pisagatti
The through-the-annulus threading of calix[5]arene penta-O-ethers by dialkylammonium cations coupled to the loosely coordinating superweak TFPB- anion has been successfully accomplished. 1H NMR titration data show that the preorganization of the calix[5]arene scaffold leads to great thermodynamic stability of the pseudorotaxane complexes as well as to a favorable kinetic of threading. Accordingly, calix[5]arene 1c, bearing tert-butyl groups at the wide rim, was threaded by all the cations under study (with the exception of the dibenzylammonium 2b+) more tightly than the other derivatives under investigation (Kas up to 2...
April 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28426123/cabozantinib-in-hepatocellular-carcinoma-results-of-a-phase-2-placebo-controlled-randomized-discontinuation-study
#5
R K Kelley, C Verslype, A L Cohn, T-S Yang, W-C Su, H Burris, F Braiteh, N Vogelzang, A Spira, P Foster, Y Lee, E Van Cutsem
Background: Cabozantinib, an orally bioavailable inhibitor of tyrosine kinases including MET, AXL, and VEGF receptors, was assessed in patients with hepatocellular carcinoma (HCC) as part of a phase 2 randomized discontinuation trial with nine tumor-type cohorts. Patients and methods: Eligible patients had Child-Pugh A liver function and ≤1 prior systemic anticancer regimen, completed ≥4 weeks before study entry. The cabozantinib starting dose was 100 mg daily...
March 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28423548/axl-acts-as-a-tumor-suppressor-by-regulating-light-expression-in-t-lymphoma
#6
Eun-Hee Lee, Eun-Mi Kim, Kon-Young Ji, A-Reum Park, Ha-Rim Choi, Hwa-Youn Lee, Su-Man Kim, Byung Yeoup Chung, Chul-Hong Park, Hyo Jin Choi, Young-Hyeh Ko, Hyoung-Woo Bai, Hyung-Sik Kang
Axl is an oncogenic receptor tyrosine kinase that plays a role in many cancers. LIGHT (Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells) is a ligand that induces robust anti-tumor immunity by enhancing the recruitment and activation of effector immune cells at tumor sites. We observed that mouse EL4 and human Jurkat T lymphoma cells that stably overexpressed Axl also showed high expression of LIGHT. When Jurkat-Axl cells were treated with Gas6, a ligand for Axl, LIGHT expression was upregulated through activation of the PI3K/AKT signaling pathway and transcriptional induction by Sp1...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423319/tam-receptors-are-not-required-for-zika-virus-infection-in-mice
#7
Andrew K Hastings, Laura J Yockey, Brett W Jagger, Jesse Hwang, Ryuta Uraki, Hallie F Gaitsch, Lindsay A Parnell, Bin Cao, Indira U Mysorekar, Carla V Rothlin, Erol Fikrig, Michael S Diamond, Akiko Iwasaki
Tyro3, Axl, and Mertk (TAM) receptors are candidate entry receptors for infection with the Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we used several routes of viral inoculation and compared viral replication in wild-type versus Axl(-/-), Mertk(-/-), Axl(-/-)Mertk(-/-), and Axl(-/-)Tyro3(-/-) mice in various organs. Pregnant and non-pregnant mice treated with interferon-α-receptor (IFNAR)-blocking (MAR1-5A3) antibody and infected subcutaneously with ZIKV showed no reliance on TAMs for infection...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28422142/g-protein-coupled-kiss1-receptor-is-overexpressed-in-triple-negative-breast-cancer-and-promotes-drug-resistance
#8
Alexandra Blake, Magdalena Dragan, Rommel G Tirona, Daniel B Hardy, Muriel Brackstone, Alan B Tuck, Andy V Babwah, Moshmi Bhattacharya
Triple-negative breast cancer (TNBC) lacks the expression of estrogen receptor α, progesterone receptor and human epidermal growth factor receptor 2 (HER2). TNBC patients lack targeted therapies, as they fail to respond to endocrine and anti-HER2 therapy. Prognosis for this aggressive cancer subtype is poor and survival is limited due to the development of resistance to available chemotherapies and resultant metastases. The mechanisms regulating tumor resistance are poorly understood. Here we demonstrate that the G protein-coupled kisspeptin receptor (KISS1R) promotes drug resistance in TNBC cells...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28412798/-intraocular-lens-power-calculation-for-high-myopic-eyes-with-cataract-comparison-of-three-formulas
#9
X J Zhu, W W He, Y Du, D J Qian, J H Dai, Y Lu
Objective: To compare the accuracy of three different formulas for intraocular lens power calculation in high myopic eyes with cataract and analyze their influencial factors. Methods: One hundred and three high myopic patients of cataract (103 eyes), with average age of 60.2±8.8 years old (39.0-77.0), including 45 male and 54 female and with axial length ≥ 26 mm were enrolled in this retrospective case-series study. All of them underwent routine ocular examination and IOLMastermeasurement preoperatively and then underwent phacoemulsification through temporal clear-corneal incision with implantation of HumanOptic posterior chamber Intraocular lens (IOL)...
April 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28412392/diminished-airway-macrophage-expression-of-the-axl-receptor-tyrosine-kinase-is-associated-with-defective-efferocytosis-in-asthma
#10
Aleksander M Grabiec, Nicholas Denny, John A Doherty, Kaisa E Happonen, Jenny Hankinson, Emma Connolly, Mark E Fife, Toshifumi Fujimori, Naoya Fujino, Anu Goenka, Susan Holden, Gaël Tavernier, Rajesh Shah, Peter C Cook, Andrew S MacDonald, Robert M Niven, Björn Dahlbäck, Stephen J Fowler, Angela Simpson, Tracy Hussell
The apoptotic cell recognition receptor Axl is highly expressed on human airway/alveolar macrophages, its expression is driven by the lung microenvironment and is significantly reduced in asthma, which may explain defects in apoptotic cell clearance.
April 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28409890/four-state-molecular-shuttling-of-2-rotaxanes-featuring-ammonium-aniline-anilinium-and-tetra-ethylene-glycol-stations-in-response-to-acid-base-and-alkali-metal-cation-stimuli
#11
Masaki Kimura, Takuma Mizuno, Masahiro Ueda, Shinobu Miyagawa, Tsuneomi Kawasaki, Yuji Tokunaga
In this study we synthesized [2]rotaxanes possessing three recognition sites-a dialkylammonium, an alkylarylamine, and a tetra(ethylene glycol) station-in their dumbbell-like axle component and dibenzo[24]crown-8 (DB24C8) as their macrocyclic component. These [2]rotaxanes behaved as four-state molecular shuttles: (i) under acidic conditions, the DB24C8 unit encircled both the dialkylammonium and alkylarylammonium stations; (ii) under neutral conditions, the dialkylammonium unit was the predominant station for the DB24C8 component; (iii) under basic conditions, when both ammonium centers were deprotonated, the alkylarylamine unit became a suitable station for the DB24C8 component; and (iv) under basic conditions in the presence of an alkali metal cation, the tetra(ethylene glycol) unit recognized the DB24C8 component through cooperative binding of the alkali metal ion...
April 13, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28408301/impact-of-braf-kinase-inhibitors-on-the-mirnomes-and-transcriptomes-of-melanoma-cells
#12
Ines Kozar, Giulia Cesi, Christiane Margue, Demetra Philippidou, Stephanie Kreis
BACKGROUND: Melanoma is an aggressive skin cancer with increasing incidence worldwide. The development of BRAF kinase inhibitors as targeted treatments for patients with BRAF-mutant tumours contributed profoundly to an improved overall survival of patients with metastatic melanoma. Despite these promising results, the emergence of rapid resistance to targeted therapy remains a serious clinical issue. METHODS: To investigate the impact of BRAF inhibitors on miRNomes and transcriptomes, we used in vitro melanoma models consisting of BRAF inhibitor-sensitive and -resistant cell lines generated in our laboratory...
April 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28407786/bioinformatics-analysis-to-screen-the-key-prognostic-genes-in-ovarian-cancer
#13
Li Li, Shengyun Cai, Shengnan Liu, Hao Feng, Junjie Zhang
BACKGROUND: Ovarian cancer (OC) is a gynecological oncology that has a poor prognosis and high mortality. This study is conducted to identify the key genes implicated in the prognosis of OC by bioinformatic analysis. METHODS: Gene expression data (including 568 primary OC tissues, 17 recurrent OC tissues, and 8 adjacent normal tissues) and the relevant clinical information of OC patients were downloaded from The Cancer Genome Atlas database. After data preprocessing, cluster analysis was conducted using the ConsensusClusterPlus package in R...
April 13, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/28404378/axl-molecular-targeting-counteracts-aggressiveness-but-not-platinum-resistance-of-ovarian-carcinoma-cells
#14
Cristina Corno, Laura Gatti, Noemi Arrighetti, Nives Carenini, Nadia Zaffaroni, Cinzia Lanzi, Paola Perego
Ovarian carcinoma, the most common gynecological cancer, is characterized by high lethality mainly due to late diagnosis and treatment failure. The efficacy of platinum drug-based therapy in the disease is limited by the occurrence of drug resistance, a phenomenon often associated with increased metastatic potential. Because the Tyr-kinase receptor Axl can be deregulated in ovarian carcinoma and plays a pro-metastatic/anti-apoptotic role, the aim of this study was to examine if Axl inhibition modulates drug resistance and aggressive features of ovarian carcinoma cells, using various pairs of cisplatin-sensitive and -resistant cell lines...
April 9, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28401178/targeting-the-axl-signaling-pathway-in-ovarian-cancer
#15
Ruby Yun-Ju Huang, Jane Antony, Tuan Zea Tan, David Shao-Peng Tan
In a recent publication in Science Signaling, we showed that a Mes molecular subtype of epithelial ovarian cancer (EOC) harboring epithelial-mesenchymal transition (EMT) features has a unique signaling network downstream of the GAS6/AXL pathway. Our finding leads to a potential strategy for treating the Mes subtype of EOC by targeting AXL.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28399420/dietary-rose-hip-exerts-antiatherosclerotic-effects-and-increases-nitric-oxide-mediated-dilation-in-apoe-null-mice
#16
Michele Cavalera, Ulrika Axling, Catarina Rippe, Karl Swärd, Cecilia Holm
Atherosclerosis is a disease in which atheromatous plaques develop inside arteries, leading to reduced or obstructed blood flow that in turn may cause stroke and heart attack. Rose hip is the fruit of plants of the genus Rosa, belonging to the Rosaceae family, and it is rich in antioxidants with high amounts of ascorbic acid and phenolic compounds. Several studies have shown that fruits, seeds and roots of these plants exert antidiabetic, antiobesity and cholesterol-lowering effects in rodents as well as humans...
March 21, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28396340/myopic-glaucomatous-eyes-with-or-without-optic-disc-shape-alteration-a-longitudinal-study
#17
Junki Kwon, Kyung Rim Sung, Ji Min Park
AIMS: To compare the clinical courses of patients with myopic primary open angle glaucoma (POAG) with and without optic disc shape alterations. METHODS: In this longitudinal retrospective study, 146 eyes from 146 patients with myopic (axial length(AXL),>24 mm) POAG were classified according to optic disc shape alterations defined by optic disc tilt and/or rotation. Glaucomatous progression was determined by either serial optic disc/retinal nerve fibre layer photographs or visual field (VF) exams...
April 10, 2017: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/28386842/vitamin-k2-inhibits-rat-vascular-smooth-muscle-cell-calcification-by-restoring-the-gas6-axl-akt-anti-apoptotic-pathway
#18
Cuiting Qiu, Haijun Zheng, Huiren Tao, Wenjun Yu, Xiaoyu Jiang, Aiqin Li, Hui Jin, Anlin Lv, Huan Li
Vascular calcification is associated with cardiovascular disease as a complication of hypertension, hyperlipidemia, diabetes mellitus, and chronic kidney disease. Vitamin K2 (VK2) delays vascular calcification by an unclear mechanism. Moreover, apoptosis modulates vascular smooth muscle cell (VSMC) calcification. This paper aimed to study VK2-modified VSMC calcification and survival cell signaling mediated by growth arrest-specific gene 6 (Gas6) and its tyrosine kinase receptor Axl. Primary-cultured VSMCs were dose-dependently treated with VK2 in the presence of calcification medium for 8 days, or pre-treated for 1 h with/without the Axl inhibitor R428 (2 μmol/L) or the caspase inhibitor Z-VAD-fmk (20 μmol/L) followed by treatment with VK2 (10 μmol/L) or rmGas6 (200 nmol/L) in calcification medium for 8 days...
April 6, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28381274/role-of-tumour-associated-macrophages-in-oral-squamous-cells-carcinoma-progression-an-update-on-current-knowledge
#19
REVIEW
Maria Noel Marzano Rodrigues Petruzzi, Karen Cherubini, Fernanda Gonçalves Salum, Maria Antonia Zancanaro de Figueiredo
BACKGROUND: Oral squamous cell carcinoma (OSCC) accounts over 90% of malignant neoplasms of the oral cavity. This pathological entity is associated to a high mortality rate that has remained unchanged over the past decades. Tumour-associated macrophages (TAMs) are believed to have potential involvement in OSCC progression. However, the molecular networks involved in communication between stroma and cancer cells have not yet been fully elucidated. MAIN BODY: The role of M2 polarized cells in oral carcinogenesis is supported by a correlation between TAMs accumulation into OSCC stroma and poor clinical outcome...
April 5, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28377632/integrated-analysis-of-gene-expression-and-copy-number-identified-potential-cancer-driver-genes-with-amplification-dependent-overexpression-in-1-454-solid-tumors
#20
Keiichi Ohshima, Keiichi Hatakeyama, Takeshi Nagashima, Yuko Watanabe, Kaori Kanto, Yuki Doi, Tomomi Ide, Yuji Shimoda, Tomoe Tanabe, Sumiko Ohnami, Shumpei Ohnami, Masakuni Serizawa, Koji Maruyama, Yasuto Akiyama, Kenichi Urakami, Masatoshi Kusuhara, Tohru Mochizuki, Ken Yamaguchi
Identification of driver genes contributes to the understanding of cancer etiology and is imperative for the development of individualized therapies. Gene amplification is a major event in oncogenesis. Driver genes with tumor-specific amplification-dependent overexpression can be therapeutic targets. In this study, we aimed to identify amplification-dependent driver genes in 1,454 solid tumors, across more than 15 cancer types, by integrative analysis of gene expression and copy number. Amplification-dependent overexpression of 64 known driver oncogenes were found in 587 tumors (40%); genes frequently observed were MYC (25%) and MET (18%) in colorectal cancer; SKP2 (21%) in lung squamous cell carcinoma; HIST1H3B (19%) and MYCN (13%) in liver cancer; KIT (57%) in gastrointestinal stromal tumors; and FOXL2 (12%) in squamous cell carcinoma across tissues...
April 4, 2017: Scientific Reports
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