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https://www.readbyqxmd.com/read/28734947/platelet-derived-growth-factor-receptor-alpha-contributes-to-human-hepatic-stellate-cell-proliferation-and-migration
#1
Alexander Kikuchi, Tirthadipa Pradhan-Sundd, Sucha Singh, Shanmugam Nagarajan, Nick Loizos, Satdarshan Monga
Platelet-derived growth factor receptor alpha (PDGFRα), a tyrosine kinase receptor, is up-regulated in hepatic stellate cells (HSCs) during chronic liver injury. HSCs mediate hepatic fibrosis through their activation from a quiescent state partially in response to pro-fibrotic growth factors. HSC activation entails enhanced expression of pro-fibrotic genes, increase in proliferation, and increase in motility, which facilitates migration within the hepatic lobule. We show co-localization of PDGFRα in murine carbon tetrachloride, bile duct ligation (BDL), and 0...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28734845/leveraging-siglec-8-endocytic-mechanisms-to-kill-human-eosinophils-and-malignant-mast-cells
#2
Jeremy A O'Sullivan, Daniela J Carroll, Yun Cao, Adriano N Salicru, Bruce S Bochner
BACKGROUND: Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a cell-surface protein expressed selectively on human eosinophils, mast cells, and basophils, making it an ideal target for the treatment of diseases involving these cell types. However, the effective delivery of therapeutic agents to these cells requires an understanding of the dynamics of Siglec-8 surface expression. OBJECTIVE: To determine whether Siglec-8 is endocytosed in human eosinophils and malignant mast cells, identify mechanisms underlying its endocytosis, and demonstrate whether a toxin can be targeted to Siglec-8-bearing cells to kill these cells...
July 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28734822/icotinib-versus-whole-brain-irradiation-in-patients-with-egfr-mutant-non-small-cell-lung-cancer-and-multiple-brain-metastases-brain-a-multicentre-phase-3-open-label-parallel-randomised-controlled-trial
#3
Jin-Ji Yang, Caicun Zhou, Yisheng Huang, Jifeng Feng, Sun Lu, Yong Song, Cheng Huang, Gang Wu, Li Zhang, Ying Cheng, Chengping Hu, Gongyan Chen, Li Zhang, Xiaoqing Liu, Hong Hong Yan, Fen Lai Tan, Wenzhao Zhong, Yi-Long Wu
BACKGROUND: For patients with non-small-cell lung cancer (NSCLC) and multiple brain metastases, whole-brain irradiation (WBI) is a standard-of-care treatment, but its effects on neurocognition are complex and concerning. We compared the efficacy of an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), icotinib, versus WBI with or without chemotherapy in a phase 3 trial of patients with EGFR-mutant NSCLC and multiple brain metastases. METHODS: We did a multicentre, open-label, parallel randomised controlled trial (BRAIN) at 17 hospitals in China...
July 19, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28734578/phosphatidylserine-is-the-signal-for-tam-receptors-and-their-ligands
#4
REVIEW
Greg Lemke
Nature repeatedly repurposes, in that molecules that serve as metabolites, energy depots, or polymer subunits are at the same time used to deliver signals within and between cells. The preeminent example of this repurposing is ATP, which functions as a building block for nucleic acids, an energy source for enzymatic reactions, a phosphate donor to regulate intracellular signaling, and a neurotransmitter to control the activity of neurons. A series of recent studies now consolidates the view that phosphatidylserine (PtdSer), a common phospholipid constituent of membrane bilayers, is similarly repurposed for use as a signal between cells and that the ligands and receptors of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases (RTKs) are prominent transducers of this signal...
July 19, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28734476/quantifying-the-interaction-between-egfr-dimers-and-grb2-in-live-cells
#5
Nuala Del Piccolo, Kalina Hristova
Adaptor proteins are a class of cytoplasmic proteins that bind to phosphorylated residues in receptor tyrosine kinases and trigger signaling cascades that control critically important cellular processes, such as cell survival, growth, differentiation, and motility. Here, we seek to characterize the interaction between epidermal growth factor receptor (EGFR) and the cytoplasmic adaptor protein growth factor receptor-bound protein 2 (Grb2) in a cellular context. To do so, we explore the utility of a highly biologically relevant model system, mammalian cells under reversible osmotic stress, and a recently introduced Förster resonance energy transfer microscopy method, fully quantified spectral imaging...
July 19, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28733795/early-response-of-c-reactive-protein-as-a-predictor-of-survival-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors
#6
Yosuke Yasuda, Kazutaka Saito, Takeshi Yuasa, Sho Uehara, Naoko Kawamura, Minato Yokoyama, Junichiro Ishioka, Yoh Matsuoka, Shinya Yamamoto, Tetsuo Okuno, Junji Yonese, Kazunori Kihara, Yasuhisa Fujii
BACKGROUND: Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs. METHODS: A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder)...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28733794/fatigue-associated-with-newly-approved-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors-in-cancer-patients-an-up-to-date-meta-analysis
#7
REVIEW
Jing Li, Jian Gu
The fatigue associated with five newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) is poorly understood. We conducted this systematic review to fully investigate the fatigue associated with these VEGFR-TKIs in cancer patients. Relevant studies of randomized controlled trials in cancer patients treated with the five VEGFR-TKIs were retrieved and a systematic evaluation was conducted. EMBASE, MEDLINE, and PubMed were searched for articles published until March 2017...
July 21, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28733706/phage-display-selection-in-vitro-characterization-and-correlative-pet-imaging-of-a-novel-her3-peptide
#8
Benjamin M Larimer, Nicholas Phelan, Eric Wehrenberg-Klee, Umar Mahmood
PURPOSE: HER3 (ERBB3) is a receptor tyrosine kinase that is implicated in treatment resistance across multiple cancers, including those of the breast, lung, and prostate. Overexpression of HER3 following targeted therapy can occur rapidly and heterogeneously both within a single lesion and across sites of metastasis, making protein quantification by biopsy highly challenging. A global, non-invasive methodology such as positron emission tomography (PET) imaging can permit serial quantification of HER3, providing a useful approach to monitor HER3 expression across the entire tumor burden both prior to and following treatment...
July 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28733559/dynamics-of-egfr-mutations-in-plasma-recapitulates-the-clinical-response-to-egfr-tkis-in-nsclc-patients
#9
Liwen Xiong, Shaohua Cui, Jingyan Ding, Yun Sun, Longfu Zhang, Yizhuo Zhao, Aiqin Gu, Tianqing Chu, Huimin Wang, Hua Zhong, Xin Ye, Yi Gu, Xin Zhang, Min Hu, Liyan Jiang
OBJECTIVES: Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. PATIENTS AND METHODS: Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28733457/role-of-bone-morphogenetic-proteins-in-sprouting-angiogenesis-differential-bmp-receptor-dependent-signaling-pathways-balance-stalk-vs-tip-cell-competence
#10
Andreas Benn, Christian Hiepen, Marc Osterland, Christof Schütte, An Zwijsen, Petra Knaus
Before the onset of sprouting angiogenesis, the endothelium is prepatterned for the positioning of tip and stalk cells. Both cell identities are not static, as endothelial cells (ECs) constantly compete for the tip cell position in a dynamic fashion. Here, we show that both bone morphogenetic protein (BMP) 2 and BMP6 are proangiogenic in vitro and ex vivo and that the BMP type I receptors, activin receptor-like kinase (ALK)3 and ALK2, play crucial and distinct roles in this process. BMP2 activates the expression of tip cell-associated genes, such as DLL4 (delta-like ligand 4) and KDR (kinase insert domain receptor), and p38-heat shock protein 27 (HSP27)-dependent cell migration, thereby generating tip cell competence...
July 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28733346/regulation-and-action-of-early-growth-response-1-in-bovine-granulosa-cells
#11
Peng Han, Hilda Guerrero-Netro, Anthony Estienne, Binyun Cao, Christopher Price
Fibroblast growth factors (FGF) modify cell proliferation and differentiation through receptor tyrosine kinases, which stimulate the expression of transcription factors including members of the early growth response (EGR) family. In ovarian granulosa cells, most FGFs activate typical response genes, although the role of EGR proteins has not been described. In the present study, we determined the regulation of EGR mRNA by FGFs and explored the role of EGR1 in the regulation of FGF response genes. Addition of FGF1, FGF2, FGF4 or FGF8b increased EGR1 and EGR3 mRNA levels, whereas FGF18 increased only EGR1 mRNA abundance...
July 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28732351/tropomyosin-isoform-tpm2-1-regulates-collective-and-amoeboid-cell-migration-and-cell-aggregation-in-breast-epithelial-cells
#12
HyeRim Shin, Dayoung Kim, David M Helfman
Metastasis dissemination is the result of various processes including cell migration and cell aggregation. These processes involve alterations in the expression and organization of cytoskeletal and adhesion proteins in tumor cells. Alterations in actin filaments and their binding partners are known to be key players in metastasis. Downregulation of specific tropomyosin (Tpm) isoforms is a common characteristic of transformed cells. In this study, we examined the role of Tpm2.1 in non-transformed MCF10A breast epithelial cells in cell migration and cell aggregation, because this isoform is downregulated in primary and metastatic breast cancer as well as various breast cancer cell lines...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732214/crispr-cas9-technology-based-xenograft-tumors-as-candidate-reference-materials-for-multiple-eml4-alk-rearrangements-testing
#13
Rongxue Peng, Rui Zhang, Guigao Lin, Xin Yang, Ziyang Li, Kuo Zhang, Jiawei Zhang, Jinming Li
The echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (EML4-ALK) rearrangement is an important biomarker that plays a pivotal role in therapeutic decision making for non-small-cell lung cancer (NSCLC) patients. Ensuring accuracy and reproducibility of EML4-ALK testing by fluorescence in situ hybridization, immunohistochemistry, RT-PCR, and next-generation sequencing requires reliable reference materials for monitoring assay sensitivity and specificity...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28732181/irf6-and-spry4-signaling-interact-in-periderm-development
#14
Y A Kousa, R Roushangar, N Patel, A Walter, P Marangoni, R Krumlauf, O D Klein, B C Schutte
Rare mutations in IRF6 and GRHL3 cause Van der Woude syndrome, an autosomal dominant orofacial clefting disorder. Common variants in IRF6 and GRHL3 also contribute risk for isolated orofacial clefting. Similarly, variants within genes that encode receptor tyrosine kinase (RTK) signaling components, including members of the FGF pathway, EPHA3 and SPRY2, also contribute risk for isolated orofacial clefting. In the mouse, loss of Irf6 or perturbation of Fgf signaling leads to abnormal oral epithelial adhesions and cleft palate...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28731495/significance-of-neutrophil-to-lymphocyte-ratio-in-western-advanced-egfr-mutated-non-small-cell-lung-cancer-receiving-a-targeted-therapy
#15
Fausto Meriggi, Claudio Codignola, Giordano D Beretta, Giovanni L Ceresoli, Alberto Caprioli, Mario Scartozzi, Anna P Fraccon, Tiziana Prochilo, Chiara Ogliosi, Alberto Zaniboni
PURPOSE: Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy...
July 14, 2017: Tumori
https://www.readbyqxmd.com/read/28731282/altered-signaling-associated-with-chronic-arsenic-exposure-in-human-skin-keratinocytes
#16
Sartaj Ahmad Mir, Santosh Renuse, Gajanan Sathe, Aafaque Ahmad Khan, Arun H Patil, Vishalakshi Nanjappa, Firdous Ahmad Bhat, T S Keshava Prasad, Ashok K Giri, Aditi Chatterjee, Harsha Gowda
Modulation of signaling pathways upon chronic arsenic exposure remains poorly studied. Here we carried out SILAC-based quantitative phosphoproteomics analysis to dissect the signaling induced upon chronic arsenic exposure in human skin keratinocyte cell line, HaCaT. We identified 4,171 unique phosphosites derived from 2,000 proteins. We observed differential phosphorylation of 406 phosphosites (2-fold) corresponding to 305 proteins. Several pathways involved in cytoskeleton maintenance and organization were found to be significantly enriched (p<0...
July 21, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28731189/identification-of-pivotal-genes-and-pathways-for-spinal-cord-injury-via-bioinformatics-analysis
#17
Zonghao Zhu, Qiang Shen, Liang Zhu, Xiaokang Wei
The present study aimed to identify key genes and pathways associated with spinal cord injury (SCI) and subsequently investigate possible therapeutic targets for the condition. The array data of GSE20907 was downloaded from the Gene Expression Omnibus database and 24 gene chips, including 3‑day, 4‑day, 1‑week, 2‑week and 1‑month post‑SCI together with control propriospinal neurons, were used for the analysis. The raw data was normalized and then the differentially expressed genes (DEGs) in the (A) 2‑week post‑SCI group vs...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#18
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28730963/increased-expression-of-ire1%C3%AE-associates-with-the-resistant-mechanism-of-osimertinib-azd9291-resistant-non-small-cell-lung-cancer-hcc827-osir-cells
#19
Zheng-Hai Tang, Min-Xia Su, Xia Guo, Xiao-Ming Jiang, Lin Jia, Xiuping Chen, Jin-Jian Lu
BACKGROUND: Osimertinib (OSI), also known as AZD9291, is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of non-small cell lung cancer (NSCLC) patients. OBJECTIVE: Establishment of the OSI-resistant HCC827/OSIR cell line and study of its resistant mechanism. METHOD: The anti-proliferative effect was studied through MTT and colony formation assays. The protein expression was detected by Western blot assay...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28730960/protein-kinases-as-tumor-biomarkers-and-therapeutic-targets
#20
Chuntao Quan, Juanjuan Xiao, Lin Liu, Qiuhong Duan, Ping Yuan, Feng Zhu
Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied in clinical settings and have achieved very good treatment efficacy, many cancer patients died of tumor metastasis, drug toxicity or drug resistance due to tumor heterogeneity. Targeted molecular treatments based on the genes, receptors, and kinases expressed by a tumor make individualized treatment possible...
July 20, 2017: Current Pharmaceutical Design
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