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https://www.readbyqxmd.com/read/28343338/expression-of-typical-osteoclast-markers-by-pbmcs-after-peg-induced-fusion-as-a-model-for-studying-osteoclast-differentiation
#1
Luz M Castillo, Carlos A Guerrero, Orlando Acosta
Bone is a metabolically active organ subjected to continuous remodeling process that involves resorption by osteoclast and subsequent formation by osteoblasts. Osteoclast involvement in this physiological event is regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). Fusion of mono-nuclear pre-osteoclasts is a critical event for osteoclast differentiation and for bone resorption. Here we show that PBMCs can be successfully fused with polyethylenglicol (PEG) in order to generated viable osteoclast-like cells that exhibit tartrate-resistant acid phosphatase (TRAP) and bone resorptive activities...
March 25, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#2
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
March 23, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28342318/distinct-patterns-of-stromal-and-tumor-expression-of-ror1-and-ror2-in-histological-subtypes-of-epithelial-ovarian-cancer
#3
C E Henry, C Emmanuel, N Lambie, C Loo, B Kan, C J Kennedy, A de Fazio, N F Hacker, C E Ford
OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics...
March 22, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28339780/adverse-kidney-effects-of-epidermal-growth-factor-receptor-inhibitors
#4
Hassan Izzedine, Mark A Perazella
The epidermal growth factor receptor (EGFR) is implicated in various malignancies. The past decade has seen the development and widespread use of EGFR inhibitors for the successful treatment of such cancers. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Class-related renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies. Tubular injury is common and mainly due to monoclonal antibodies while glomerulopathy is rare and related to various anti-EGFR agents...
February 23, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339693/neuronal-signaling-repertoire-in-the-mammalian-sperm-functionality
#5
Alfredo Ramírez-Reveco, Franz Villarroel-Espíndola, Joan E Rodríguez-Gil, Ilona I Concha
The common embryonic origin has been a recurrent explanation to understand the presence of "neural receptors" in sperm. However, this designation has conditioned a bias marked by the classical neurotransmission model, dismissing the possibility that neurotransmitters can play specific roles in the sperm function by themselves. For instance, the launching of acrosome reaction, a fundamental sperm function, includes several steps that recall the process of presynaptic secretion. Unlike of postsynaptic neuron, whose activation is mediated by molecular interaction between neurotransmitter and postsynaptic receptors, the oocyte activation is not mediated by receptors, but by cytosolic translocation of sperm phospholipase (PLCζ)...
February 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339163/next-generation-sequencing-of-urine-specimens-a-novel-platform-for-genomic-analysis-in-patients-with-non-muscle-invasive-urothelial-carcinoma-treated-with-bacille-calmette-gu%C3%A3-rin
#6
Sasinya N Scott, Irina Ostrovnaya, Caroline M Lin, Nancy Bouvier, Bernard H Bochner, Gopakumar Iyer, David Solit, Michael F Berger, Oscar Lin
BACKGROUND: Biopsies from patients with high-risk (HR) non-muscle-invasive urothelial carcinoma (NMIUC), especially flat urothelial carcinoma in situ, frequently contain scant diagnostic material or denuded mucosa only, and this precludes further extensive genomic analysis. This study evaluated the use of next-generation sequencing (NGS) analysis of urine cytology material from patients with HR NMIUC in an attempt to identify genetic alterations that might correlate with clinical features and responses to bacille Calmette-Guérin (BCG) treatment...
March 24, 2017: Cancer
https://www.readbyqxmd.com/read/28339142/selective-effects-of-oral-anti-angiogenic-tyrosine-kinase-inhibitors-on-an-animal-model-of-hereditary-hemorrhagic-telangiectasia
#7
Yong Hwan Kim, Mi-Jung Kim, Se-Woon Choe, Dennis Sprecher, Young Jae Lee, S Paul Oh
BACKGROUND: Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult onset arteriovenous malformations (AVMs). OBJECTIVES: The goal of this study is to evaluate potential therapeutic effects of oral delivery of four anti-angiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult onset AVMs in a murine model of HHT...
March 24, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28339027/su6668-modulates-prostate-cancer-progression-by-downregulating-mtdh-akt-signaling-pathway
#8
Benjiang Qian, Yi Yao, Changming Liu, Jiabing Zhang, Huihong Chen, Huizhang Li
Prostate cancer is the second leading cause of cancer deaths among men in Western counties and has increased in incidence also in China in recent years. Although diagnosis modalities for primary prostate cancer have markedly improved, there are still no effective therapies for metastatic prostate cancer. SU6668 is an inhibitor of the tyrosine kinase activity of three angiogenic receptors VEGFR2, PDGFRβ and FGFR1. There is strong experimental evidence that SU6668 can induce growth inhibition of various primary tumors...
March 22, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338646/type-iv-secretion-and-signal-transduction-of-helicobacter-pylori-caga-through-interactions-with-host-cell-receptors
#9
REVIEW
Steffen Backert, Nicole Tegtmeyer
Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA...
March 24, 2017: Toxins
https://www.readbyqxmd.com/read/28338617/egfr-family-members-regulation-of-autophagy-is-at-a-crossroads-of-cell-survival-and-death-in-cancer
#10
REVIEW
Elizabeth Henson, Yongqiang Chen, Spencer Gibson
The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients...
March 24, 2017: Cancers
https://www.readbyqxmd.com/read/28338397/clove-and-its-active-compound-attenuate-free-fatty-acid-mediated-insulin-resistance-in-skeletal-muscle-cells-and-in-mice
#11
Safina Ghaffar, Shabbir Khan Afridi, Meha Fatima Aftab, Munazza Murtaza, Rahman M Hafizur, Sara Sara, Sabira Begum, Rizwana Sanaullah Waraich
Several reports indicate anti-hyperglycemic effects of Syzygium aromaticum. In the present study, we report for the first time that clove extract (SAM) and its compound nigricin (NGC) decreases free fatty acid-mediated insulin resistance in mouse myoblasts. In addition, NGC was able to diminish insulin resistance in a diabetic mouse model. We observed that SAM and its compound NGC exhibited significant antioxidant activity in murine skeletal muscle cells. They also modulated stress signaling by reducing p38 MAP kinase phosphorylation...
March 24, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28338017/a-role-of-the-sam-domain-in-epha2-receptor-activation
#12
Xiaojun Shi, Vera Hapiak, Ji Zheng, Jeannine Muller-Greven, Deanna Bowman, Ryan Lingerak, Matthias Buck, Bing-Cheng Wang, Adam W Smith
Among the 20 subfamilies of protein receptor tyrosine kinases (RTKs), Eph receptors are unique in possessing a sterile alpha motif (SAM domain) at their C-terminal ends. However, the functions of SAM domains in Eph receptors remain elusive. Here we report on a combined cell biology and quantitative fluorescence study to investigate the role of the SAM domain in EphA2 function. We observed elevated tyrosine autophosphorylation levels upon deletion of the EphA2 SAM domain (EphA2ΔS) in DU145 and PC3 prostate cancer cells and a skin tumor cell line derived from EphA1/A2 knockout mice...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337370/role-of-epidermal-growth-factor-receptor-in-lung-cancer-and-targeted-therapies
#13
REVIEW
Tie-Cheng Liu, Xin Jin, Yan Wang, Ke Wang
Lung cancer is the foremost cause of cancer-related deaths world-wide. Both, the major forms of lung cancer, Non-small cell lung cancer (NSCLC) and Small cell lung cancers (SCLC), have responded effectively to chemo-, radiation and adjuvant-therapies. Tumor removal through surgery also appeared as a good therapeutic strategy. However, these therapies demonstrated unfavourable side-effects, and hence novel drugs targeting lung cancer emerged essential. Activation of epidermal growth factor receptor (EGFR)-tyrosine kinases is a key reason for lung cancer progression...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337120/antidyskinetic-effects-of-mek-inhibitor-are-associated-with-multiple-neurochemical-alterations-in-the-striatum-of-hemiparkinsonian-rats
#14
Guiqin Chen, Shuke Nie, Chao Han, Kai Ma, Yan Xu, Zhentao Zhang, Stella M Papa, Xuebing Cao
L-DOPA-induced dyskinesia (LID) represents one of the major problems of the long-term therapy of patients with Parkinson's disease (PD). Although, the pathophysiologic mechanisms underlying LID are not completely understood, activation of the extracellular signal regulated kinase (ERK) is recognized to play a key role. ERK is phosphorylated by mitogen-activated protein kinase kinase (MEK), and thus MEK inhibitor can prevent ERK activation. Here the effect of the MEK inhibitor PD98059 on LID and the associated molecular changes were examined...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28336955/progress-of-antibody-based-inhibitors-of-the-hgf-cmet-axis-in-cancer-therapy
#15
REVIEW
Ki-Hyun Kim, Hyori Kim
Dysregulated receptor tyrosine kinase signaling in human cancer cells leads to tumor progression, invasion and metastasis. The receptor tyrosine kinase cMET is frequently overexpressed in cancer tissue, and activation of cMET signaling is related to drug resistance and the processes of carcinogenesis, invasion and metastasis. For that reason, cMET and its ligand, hepatocyte growth factor (HGF), are considered prime targets for the development of anticancer drugs. At least eight anti-cMET and four anti-HGF antibodies have been tested or are being tested in clinical trials...
March 24, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28336813/the-innate-immune-response-in-fetal-lung-mesenchymal-cells-targets-vegfr2-expression-and-activity
#16
Rachel M Medal, Amanda M Im, Yasutoshi Yamamoto, Omar Lakhdari, Timothy S Blackwell, Hal M Hoffman, Debashis Sahoo, Lawrence S Prince
In preterm infants, soluble inflammatory mediators target lung mesenchymal cells, disrupting airway and alveolar morphogenesis. However, how mesenchymal cells respond directly to microbial stimuli remains poorly characterized. Our objective was to measure the genome-wide innate immune response in fetal lung mesenchymal cells exposed to the bacterial endotoxin lipopolysaccharide (LPS). Using Affymetrix MoGene 1.0st arrays, we showed that LPS induced expression of unique innate immune transcripts heavily weighted toward CC and CXC family chemokines...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336715/monitoring-cell-surface-n-glycoproteome-dynamics-by-quantitative-proteomics-reveals-mechanistic-insights-into-macrophage-differentiation
#17
Mathias Kalxdorf, Stephan Gade, H Christian Eberl, Marcus Bantscheff
The plasma membrane proteome plays a crucial role in inter- and intracellular signaling, cell survival and cell identity. As such it is a prominent target for pharmacological intervention. The relatively low abundance of this subproteome in conjunction with challenging extractability and solubility still hampers their comprehensive analysis. Here, we combined a chemical glycoprotein tagging strategy with mass spectrometry to enable comprehensive analysis of the cell surface glycoprotome. To benchmark this workflow and provide guidance for cell line selection for functional experiments, we generated an inventory of the N-linked cell surface glycoproteome of 15 standard laboratory human cell lines and three primary lymphocytic cell types...
March 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28336561/mice-lacking-the-inhibitory-collagen-receptor-lair-1-exhibit-a-mild-thrombocytosis-and-hyperactive-platelets
#18
Christopher W Smith, Steven G Thomas, Zaher Raslan, Pushpa Patel, Maxwell Byrne, Marie Lordkipanidzé, Danai Bem, Linde Meyaard, Yotis A Senis, Steve P Watson, Alexandra Mazharian
OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif-containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored...
March 23, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28335387/dectin-1-mediated-pathway-contributes-to-fusarium-proliferatum-induced-cxcl-8-release-from-human-respiratory-epithelial-cells
#19
Chang-Ching Yeh, Huann-Cheng Horng, Hong Chou, Hsiao-Yun Tai, Horng-Der Shen, Shie-Liang Hsieh, Peng-Hui Wang
Fusarium species are causative agents of human respiratory disorders and are distributed widely in our environment. Little is known of their interaction with human respiratory epithelial cells, which may contribute to allergic airway responses. In this study, we report on the release of C-X-C motif chemokine ligand 8 (CXCL-8) from human bronchial epithelial BEAS-2B cells upon stimulation with Fusarium proliferatum extracts. F. proliferatum-induced cytokine release from BEAS-2B cells was determined by cytokine array and CXCL-8 enzyme-linked immunosorbent assay (ELISA) kits...
March 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28334974/efficacy-and-safety-of-sequential-use-of-everolimus-in-japanese-patients-with-advanced-renal-cell-carcinoma-after-failure-of-first-line-treatment-with-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitor-a-multicenter-phase-ii-clinical-trial
#20
Masafumi Oyama, Takayuki Sugiyama, Masahiro Nozawa, Kiyohide Fujimoto, Takeshi Kishida, Go Kimura, Noriaki Tokuda, Shiro Hinotsu, Kojiro Shimozuma, Hideyuki Akaza, Seiichiro Ozono
Objective: Many studies have shown the efficacy of everolimus after pretreatment with vascular endothelial growth factor receptor-tyrosine kinase inhibitors. We investigated the efficacy and safety of everolimus as a second-line treatment after the failure of vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy in Japanese patients with advanced renal cell carcinoma. Methods: This was an open-label, multicenter, phase II trial conducted in Japan through the central registration system...
March 1, 2017: Japanese Journal of Clinical Oncology
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