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https://www.readbyqxmd.com/read/28646122/nintedanib-a-triple-tyrosine-kinase-inhibitor-attenuates-renal-fibrosis-in-chronic-kidney-disease
#1
Feng Liu, Li Wang, Hualin Qi, Jun Wang, Wei Jiang, Yi Wang, Liuqing Xu, Na Liu, Shougang Zhuang
<span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">Nintedanib (BIBF1120) is a triple kinase inhibitor</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> of </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">platelet derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">, </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">vascular endothelial growth factor receptor (VEGFR)</span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;"> and Src family kinase, </span><span style="margin: 0px; color: black; line-height: 200%; font-family: 'Times New Roman',serif; font-size: 12pt;">that has recently been approved by FDA to treat idiopathic pulmonary fibrosis...
June 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28644480/a-polymer-nanoparticle-with-engineered-affinity-for-a-vascular-endothelial-growth-factor-vegf165
#2
Hiroyuki Koide, Keiichi Yoshimatsu, Yu Hoshino, Shih-Hui Lee, Ai Okajima, Saki Ariizumi, Yudai Narita, Yusuke Yonamine, Adam C Weisman, Yuri Nishimura, Naoto Oku, Yoshiko Miura, Kenneth J Shea
Protein affinity reagents are widely used in basic research, diagnostics and separations and for clinical applications, the most common of which are antibodies. However, they often suffer from high cost, and difficulties in their development, production and storage. Here we show that a synthetic polymer nanoparticle (NP) can be engineered to have many of the functions of a protein affinity reagent. Polymer NPs with nM affinity to a key vascular endothelial growth factor (VEGF165) inhibit binding of the signalling protein to its receptor VEGFR-2, preventing receptor phosphorylation and downstream VEGF165-dependent endothelial cell migration and invasion into the extracellular matrix...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28640223/non-targeted-metabolomics-analysis-of-the-effects-of-tyrosine-kinase-inhibitors-sunitinib-and-erlotinib-on-heart-muscle-liver-and-serum-metabolism-in-vivo
#3
Brian C Jensen, Traci L Parry, Wei Huang, Amro Ilaiwy, James R Bain, Michael J Muehlbauer, Sara K O'Neal, Cam Patterson, Gary L Johnson, Monte S Willis
Background: More than 90 tyrosine kinases have been implicated in the pathogenesis of malignant transformation and tumor angiogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as effective therapies in treating cancer by exploiting this kinase dependency. The TKI erlotinib targets the epidermal growth factor receptor (EGFR), whereas sunitinib targets primarily vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR).TKIs that impact the function of non-malignant cells and have on- and off-target toxicities, including cardiotoxicities...
June 22, 2017: Metabolites
https://www.readbyqxmd.com/read/28639369/a-network-analysis-to-compare-biomarker-profiles-in-patients-with-and-without-diabetes-mellitus-in-acute-heart-failure
#4
Abhinav Sharma, Biniyam G Demissei, Jasper Tromp, Hans L Hillege, John G Cleland, Christopher M O'Connor, Marco Metra, Piotr Ponikowski, John R Teerlink, Beth A Davison, Michael M Givertz, Daniel M Bloomfield, Howard Dittrich, Dirk J van Veldhuisen, Gad Cotter, Justin A Ezekowitz, Mohsin A F Khan, Adriaan A Voors
AIMS: It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways. METHODS AND RESULTS: We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers...
June 21, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28634201/phosphoproteomic-profiling-reveals-alk-and-met-as-novel-actionable-targets-across-synovial-sarcoma-subtypes
#5
Emmy D G Fleuren, Myrella Vlenterie, Winette van der Graaf, Melissa H S Hillebrandt-Roeffen, James Blackburn, Xiuquan Ma, Howard Chan, Mandy C Magias, Anke van Erp, Laurens van Houdt, Sabri Cebeci, Amy van de Ven, Uta E Flucke, Erin E Heyer, David M Thomas, Christopher J Lord, Kieren D Marini, Vijesh Vaghjiani, Tim Mercer, Jason E Cain, Jianmin Wu, Yvonne M H Versleijen-Jonkers, Roger J Daly
Despite intensive multi-modal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical success, urging an unbiased and comprehensive analysis of oncogenic signaling networks to reveal therapeutic targets and personalized treatment strategies. Here we applied mass spectrometry-based phosphoproteomic profiling to the largest and most heterogeneous set of sarcoma cell lines characterized to date and identified novel tyrosine phosphorylation patterns, enhanced tyrosine kinases in specific subtypes, and potential driver kinases...
June 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28629427/targeting-vegfr-3-2-signaling-pathways-with-ad0157-a-potential-strategy-against-tumor-associated-lymphangiogenesis-and-lymphatic-metastases
#6
Melissa García-Caballero, Jenny Paupert, Silvia Blacher, Maureen Van de Velde, Ana Rodríguez Quesada, Miguel Angel Medina, Agnès Noël
BACKGROUND: Lymphatic metastasis is one of the leading causes of death in patients with different types of cancer and is the main prognostic factor for the disease survival. The formation of new lymphatic vessels (lymphangiogenesis) in primary tumors facilitates tumor cell dissemination to regional lymph nodes and correlates with distant metastases. Lymphangiogenesis has thus emerged as a suitable therapeutic target to block metastases, but no anti-lymphangiogenic compounds have been approved for clinical use to date...
June 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28622685/increased-pdgfr-beta-and-vegfr-2-protein-levels-are-associated-with-resistance-to-platinum-based-chemotherapy-and-adverse-outcome-of-ovarian-cancer-patients
#7
Stefanie Avril, Yasemin Dincer, Katharina Malinowsky, Claudia Wolff, Sibylle Gündisch, Alexander Hapfelmeier, Melanie Boxberg, Holger Bronger, Karl-Friedrich Becker, Barbara Schmalfeldt
Despite frequent initial response rates of epithelial ovarian cancer to platinum-based chemotherapy the majority of patients develop drug resistance. Our aim was to evaluate differential expression of signaling-pathway proteins in platinum-sensitive versus platinum-resistant primary epithelial ovarian cancer specimens to identify predictive biomarkers for treatment response.192 patients were studied comprising of independent training (n = 89) and validation (n = 103) cohorts. Full-length proteins were extracted from paraffin-embedded samples including multiple regions per tumor to account for intratumoral heterogeneity...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621580/vegfr-2-inhibitors-and-the-therapeutic-applications-thereof-a-patent-review-2012-2016
#8
Fan-Wei Peng, Da-Ke Liu, Qing-Wen Zhang, Yun-Gen Xu, Lei Shi
Angiogenesis is an important component of certain normal physiological processes, but aberrant angiogenesis contributes to some pathological disorders and in particular to tumor growth. Activation of vascular endothelial growth factor receptor-2 (VEGFR-2) by vascular endothelial growth factor (VEGF) is a critical step in the signal transduction pathway that initiates tumor angiogenesis. Inhibition of angiogenesis via blocking VEGF/VEGFR-2 signaling pathway has emerged as a potential approach to anticancer therapy...
June 16, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28621531/parallels-and-distinctions-in-fgfr-vegfr-and-egfr-mechanisms-of-transmembrane-signaling
#9
Sarvenaz Sarabipour
Receptor tyrosine kinase (RTK) signal transduction is essential in human skeletal, nervous, and vascular development, in homeostasis, and in disease. RTKs are activated by dimerization in the plasma membrane. The mechanisms of receptor dimerization and activation are multifaceted and complex, and unraveling them remains challenging. Most studies of RTKs have been devoted to crystallographic analysis of their isolated extracellular domain and biochemical analysis of the catalytic domain. However, the past few years have seen direct biophysical studies of (intact) RTK dimerization in native membranes lead to significant progress in our fundamental understanding of the mechanisms of their signal transduction across the plasma membrane...
June 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28617188/molecular-mechanisms-underlying-the-inhibitory-effects-of-qingzaojiufei-decoction-on-tumor-growth-in-lewis-lung-carcinoma
#10
Bin Xie, Xiong Xie, Bin Rao, Shengzhang Liu, Hongning Liu
OBJECTIVE: Qingzaojiufei decoction (QD) is an empirical herbal formula from traditional Chinese medicine that is used for the treatment of lung-related diseases. However, the effect of QD on the growth of lung tumor cells has not been investigated. The aim of this study was to examine the antitumor activity of QD in Lewis lung carcinomas (LLC) in vivo and in vitro, and to elucidate the underlying mechanisms. METHODS: The LLC cells were used to assess the antitumor activity of QD by Cell Counting Kit-8 assay in vitro...
February 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28608561/angiogenic-and-restorative-ability-of-human-mesenchymal-stem-cells-were-reduced-following-treatment-with-serum-from-diabetes-mellitus-type-2-patients
#11
Jafar Rezaie, Malek Soleimani Mehranjani, Reza Rahbarghazi, Mohammad Ali Shariatzadeh
This experiment investigated the impact of serum from patients with type 2 diabetes mellitus on the angiogenic behavior of human mesenchymal stem cells in vitro. Changes in the level of Ang-1, Ang-2, cell migration and trans-differentiation into pericytes and endothelial lineage were monitored after 7 days. The interaction of mesenchymal stem cells with endothelial cells were evaluated using surface plasmon resonance technique. Paracrine restorative effect of diabetic stem cells was tested on pancreatic β cells...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28600187/vascular-endothelial-growth-factor-influences-migration-and-focal-adhesions-but-not-proliferation-or-viability-of-human-neural-stem-progenitor-cells-derived-from-olfactory-epithelium
#12
Gerardo Bernabé Ramírez-Rodríguez, Gerardo Rodrigo Perera-Murcia, Leonardo Ortiz-López, Nelly Maritza Vega-Rivera, Harish Babu, Maria García-Anaya, Jorge Julio González-Olvera
In humans, new neurons are continuously added in the olfactory epithelium even in the adulthood. The resident neural stem/progenitor cells (hNS/PCs-OE) in the olfactory epithelium are influenced by several growth factors and neurotrophins. Among these modulators the vascular endothelial growth factor (VEGF) has attracted attention due its implicated in cell proliferation, survival and migration of other type of neural/stem progenitor cells. Interestingly, VEGFr2 receptor expression in olfactory epithelium has been described in amphibians but not in humans...
June 7, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28599887/phase-i-trial-of-cediranib-in-combination-with-cisplatin-and-pemetrexed-in-chemo-naive-patients-with-unresectable-malignant-pleural-mesothelioma-swog-s0905
#13
Anne S Tsao, James Moon, Ignacio I Wistuba, Nicholas J Vogelzang, Gregory P Kalemkerian, Mary W Redman, David R Gandara, Karen Kelly
BACKGROUND: In malignant pleural mesothelioma (MPM), targeting angiogenesis, with cediranib, a vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor (PDGFR) inhibitor, may have therapeutic potential. METHODS: S0905 phase I combined cediranib (2 dose cohorts 30 mg and 20 mg daily) with cisplatin-pemetrexed for 6 cycles followed by maintenance cediranib in unresectable chemo-naïve MPM patients of any histologic subtype. The primary endpoint established the MTD in combination with cisplatin-pemetrexed in a dose de-escalation schema...
June 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28598999/lymphatic-endothelial-progenitors-originate-from-plastic-myeloid-cells-activated-by-toll-like-receptor-4
#14
Lisa D Volk-Draper, Kelly L Hall, Andrew C Wilber, Sophia Ran
BACKGROUND: Myeloid-derived lymphatic endothelial cells (M-LECP) are induced by inflammation and play an important role in adult lymphangiogenesis. However, the mechanisms driving M-LECP differentiation are currently unclear. We previously showed that activation of Toll-like receptor-4 (TLR4) induces myeloid-lymphatic transition (MLT) of immortalized mouse myeloid cells. Here the goals were to assess the potential of different TLR4 ligands to induce pro-lymphatic reprogramming in human and mouse primary myeloid cells and to identify transcriptional changes regulating this process...
2017: PloS One
https://www.readbyqxmd.com/read/28591197/efficacy-of-targeted-drugs-in-germ-cell-cancer-cell-lines-with-differential-cisplatin-sensitivity
#15
Judith Schaffrath, Hans-Joachim Schmoll, Wieland Voigt, Lutz P Müller, Carsten Müller-Tidow, Thomas Mueller
METHODS: The in vitro activity of kinase inhibitors targeting mTOR (RAD001), EGFR, HER2/neu, VEGFR (AEE788) and IGF-1R (AEW541) alone or in combination with cisplatin was tested in the cisplatin sensitive TGCT cell lines H12.1 and GCT72 as well as in the resistant cell lines H12.1RA, H12.1D, 1411HP and 1777NRpmet using the sulforhodamin-B-(SRB)-cytotoxicity-assay. To evaluate the activity of the kinase inhibitors, western blot analysis of the targeted receptors and their phosphorylated state was performed before and after exposure to each substance...
2017: PloS One
https://www.readbyqxmd.com/read/28590926/transcriptional-factor-oct4-promotes-esophageal-cancer-metastasis-by-inducing-epithelial-mesenchymal-transition-through-vegf-c-vegfr-3-signaling-pathway
#16
Chunguang Li, Maoling Zhu, Xiaoli Lou, Chunying Liu, Hezhong Chen, Xuejing Lin, Weidan Ji, Zhigang Li, Changqing Su
The octamer-binding transcription factor 4 (OCT4) can promote cancer proliferation and metastasis. Esophageal carcinoma (ECC) harbors different quantities of OCT4-positive cancer cells. These cells are highly malignant and prone to metastasis; however, the mechanism remains unknown. In this study, we found that OCT4 enhances vascular endothelial growth factor C (VEGF-C) promoter activity to promote VEGF-C expression and activates VEGF receptor 3 (VEGFR-3) in ECC cells, thereby inducing cancer cell epithelial-mesenchymal transition (EMT)...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576411/postnatal-hyperoxia-or-dehp-exposure-leads-to-growth-restriction-and-delayed-lung-development-in-newborn-rats
#17
Zhong-Jie Liang, Qiu-Ping Wu, Bei-Tao Chen, Zhen-Lang Lin, Jing Lin, Shang-Qin Chen
BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in many medical devices. We previously showed that maternal DEHP exposure led to restricted growth and delayed lung maturation in newborn rats. As oxygen toxicity continues to be a major risk factor for bronchopulmonary dysplasia, the aim of this study was to examine the effect of hyperoxia, DEHP or DEHP combined with hyperoxia on the growth and lung maturation of newborn rats. METHODS: Newborn rats received DEHP injection, hyperoxia exposure or DEHP injection combined with hyperoxia exposure for one week or two weeks...
May 10, 2017: Pediatrics and Neonatology
https://www.readbyqxmd.com/read/28575934/dna-interaction-antioxidant-and-in-vitro-cytotoxic-activities-of-some-mononuclear-metal-ii-complexes-of-a-bishydrazone-ligand
#18
Chellaian Justin Dhanaraj, Jijo Johnson
A tridentate ONO donor bishydrazone ligand, 3-(((3-oxoindolin-2-ylidene)hydrazono) methyl)quinoxalin-2(1H)-one (L) was synthesized. Using the ligand, mononuclear metal complexes of the type [M(L)(OAc)] (M=Co(II), Ni(II), Cu(II) and Zn(II), OAc=-OCOCH3) were synthesized. The newly synthesized compounds were thoroughly characterized by various analytical and spectral techniques. Tetrahedral geometry was proposed for Co(II), Ni(II) and Zn(II) complexes, while square planar geometry has been assigned to the Cu(II) complex...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28572048/the-role-of-endothelial-cells-in-the-vasculopathy-of-systemic-sclerosis-a-systematic-review
#19
REVIEW
Y Mostmans, M Cutolo, C Giddelo, S Decuman, K Melsens, H Declercq, E Vandecasteele, F De Keyser, O Distler, J Gutermuth, V Smith
INTRODUCTION: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by fibroproliferative vasculopathy, immunological abnormalities and progressive fibrosis of multiple organs including the skin. In this study, all English speaking articles concerning the role of endothelial cells (ECs) in SSc vasculopathy and representing biomarkers are systematically reviewed and categorized according to endothelial cell (EC) (dys)function in SSc. METHODS: A sensitive search on behalf of the EULAR study group on microcirculation in Rheumatic Diseases was developed in Pubmed, The Cochrane Library and Web of Science to identify articles on SSc vasculopathy and the role of ECs using the following Mesh terms: (systemic sclerosis OR scleroderma) AND pathogenesis AND (endothelial cells OR marker)...
May 29, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28570669/extraocular-motoneurons-of-the-adult-rat-show-higher-levels-of-vascular-endothelial-growth-factor-and-its-receptor-flk-1-than-other-cranial-motoneurons
#20
Silvia Silva-Hucha, Rosendo G Hernández, Beatriz Benítez-Temiño, Ángel M Pastor, Rosa R de la Cruz, Sara Morcuende
Recent studies show a relationship between the deficit of vascular endothelial growth factor (VEGF) and motoneuronal degeneration, such as that occurring in amyotrophic lateral sclerosis (ALS). VEGF delivery protects motoneurons from cell death and delayed neurodegeneration in animal models of ALS. Strikingly, extraocular motoneurons show lesser vulnerability to neurodegeneration in ALS compared to other cranial or spinal motoneurons. Therefore, the present study investigates possible differences in VEGF and its main receptor VEGFR-2 or Flk-1 between extraocular and non-extraocular brainstem motoneurons...
2017: PloS One
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