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https://www.readbyqxmd.com/read/28723928/erbb-activation-signatures-as-potential-biomarkers-for-anti-erbb3-treatment-in-hnscc
#1
Diego Alvarado, Gwenda F Ligon, Jay S Lillquist, Scott B Seibel, Gerald Wallweber, Veronique M Neumeister, David L Rimm, Gerald McMahon, Theresa M LaVallee
Head and neck squamous cell carcinoma (HNSCC) accounts for 3-5% of all tumor types and remains an unmet medical need with only two targeted therapies approved to date. ErbB3 (HER3), the kinase-impaired member of the EGFR/ErbB family, has been implicated as a disease driver in a number of solid tumors, including a subset of HNSCC. Here we show that the molecular components required for ErbB3 activation, including its ligand neuregulin-1 (NRG1), are highly prevalent in HNSCC and that HER2, but not EGFR, is the major activating ErbB3 kinase partner...
2017: PloS One
https://www.readbyqxmd.com/read/28722660/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#2
Wei Cheng, Po-Chun Huang, Hsiao-Mei Chao, Yung-Ming Jeng, Hey-Chi Hsu, Hung-Wei Pan, Wuh-Liang Hwu, Yu-May Lee
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722351/%C3%AE-mangostin-suppresses-human-hepatocellular-carcinoma-cell-invasion-through-inhibition-of-mmp-2-and-mmp-9-expression-and-activating-the-erk-and-jnk-pathways
#3
Chien-Feng Huang, Ying-Hock Teng, Fung-Jou Lu, Wen-Hung Hsu, Chia-Liang Lin, Chia-Chen Hung, Jai-Nien Tung, Yi-Hsien Hsieh, Chung-Jung Liu
β-mangostin is a dietary xanthone that has been reported to have the anticancer properties in some human cancer cell types. However, the antimetastatic effect and molecular mechanism of β-mangostin action in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we found that β-mangostin did not induce cytotoxicity in human HCC cells (SK-Hep-1, Huh-7 and HA22T/VGH cells). β-mangostin could inhibit migration and invasion of human HCC cells. Meanwhile, β-mangostin significantly decreased the protein activities and expression of matrix metalloproteinase (MMP)-2 and MMP-9 via increasing the activation of MEK1/2, ERK1/2, MEK4 and JNK1/2 signaling pathways...
July 19, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28721018/salidroside-pretreatment-attenuates-apoptosis-and-autophagy-during-hepatic-ischemia-reperfusion-injury-by-inhibiting-the-mitogen-activated-protein-kinase-pathway-in-mice
#4
Jiao Feng, Qinghui Zhang, Wenhui Mo, Liwei Wu, Sainan Li, Jingjing Li, Tong Liu, Shizan Xu, Xiaoming Fan, Chuanyong Guo
Ischemia-reperfusion injury (IRI) contributes to liver damage in many clinical situations, such as liver resection and liver transplantation. In the present study, we investigated the effects of the antioxidant, anti-inflammatory, and anticancer agent salidroside (Sal) on hepatic IRI in mice. The mice were randomly divided into six groups: normal control, Sham, Sal (20 mg/kg), IRI, IRI + Sal (10 mg/kg), and IRI + Sal (20 mg/kg). We measured liver enzymes, proinflammatory cytokines, TNF-α and interleukin-6, and apoptosis- and autophagy-related marker proteins at 2, 8, and 24 hours after reperfusion...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28720574/fructose-1-6-bisphosphatase-inhibits-erk-activation-and-bypasses-gemcitabine-resistance-in-pancreatic-cancer-by-blocking-iqgap1-mapk-interaction
#5
Xin Jin, Yunqian Pan, Liguo Wang, Tao Ma, Lizhi Zhang, Amy H Tang, Daniel D Billadeau, Heshui Wu, Haojie Huang
Dysregulation of the mitogen-activated protein kinase (MAPK) pathway correlates with progression of pancreatic ductal adenocarcinoma (PDAC) progression. IQ motif containing GTPase activating protein 1 (IQGAP1) is a MAPK scaffold that directly regulates the activation of RAF, MEK, and extracellular signaling-regulated kinases (ERK). Fructose-1,6-bisphosphatase (FBP1), a key enzyme in gluconeogenesis, is transcriptionally downregulated in various cancers, including PDAC. Here we demonstrate that FBP1 acts as a negative modulator of the IQGAP1-MAPK signaling axis in PDAC cells...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28720517/transient-receptor-potential-trpm3-channels-pharmacology-signaling-and-biological-functions
#6
REVIEW
Gerald Thiel, Sandra Rubil, Andrea Lesch, Lisbeth A Guethlein, Oliver G Rössler
The transient receptor potential melastatin-3 (TRPM3) channel belongs to the family of transient receptor potential (TRP) cation channels that are expressed in a variety of tissues and cell types, including dorsal root ganglia, cardiomyocytes and pancreatic beta-cells. Although its natural ligands are currently unknown, TRPM3 channels can be activated by the neurosteroid pregnenolone sulfate, the synthetic ligand CIM0216, and by noxious heat. TRPM3 channels are regulated by phosphoinositides, and perhaps by calmodulin...
July 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28719635/differential-protein-expression-profile-in-the-hypothalamic-gt1-7-cell-line-after-exposure-to-anabolic-androgenic-steroids
#7
Freddyson J Martínez-Rivera, Juliana Pérez-Laspiur, María E Santiago-Gascot, Abner G Alemán-Reyes, Emanuel García-Santiago, Yolanda Rodríguez-Pérez, Cristhian Calo-Guadalupe, Inelia Otero-Pagán, Roxsana N Ayala-Pagán, Magdiel Martínez, Yisel M Cantres-Rosario, Loyda M Meléndez, Jennifer L Barreto-Estrada
The abuse of anabolic androgenic steroids (AAS) has been considered a major public health problem during decades. Supraphysiological doses of AAS may lead to a variety of neuroendocrine problems. Precisely, the hypothalamic-pituitary-gonadal (HPG) axis is one of the body systems that is mainly influenced by steroidal hormones. Fluctuations of the hormonal milieu result in alterations of reproductive function, which are made through changes in hypothalamic neurons expressing gonadotropin-releasing hormone (GnRH)...
2017: PloS One
https://www.readbyqxmd.com/read/28719152/a-first-in-human-phase-i-multicenter-open-label-dose-escalation-study-of-the-oral-raf-vegfr-2-inhibitor-raf265-in-locally-advanced-or-metastatic-melanoma-independent-from-braf-mutation-status
#8
Benjamin Izar, William Sharfman, F Stephen Hodi, Donald Lawrence, Keith T Flaherty, Ravi Amaravadi, Kevin B Kim, Igor Puzanov, Jeffrey Sosman, Reinhard Dummer, Simone M Goldinger, Lyhping Lam, Shefali Kakar, Zhongwen Tang, Oliver Krieter, David F McDermott, Michael B Atkins
To establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety profile, and anti-tumor efficacy of RAF265. We conducted a multicenter, open-label, phase-I, dose-escalation trial of RAF265, an orally available RAF kinase/VEGFR-2 inhibitor, in patients with advanced or metastatic melanoma. Pharmacokinetic (PK) analysis, pharmacodynamics (PD) and tumor response assessment were conducted. We evaluated metabolic tumor response by 18[F]-fluorodeoxyglucose-positron-emission tomography (FDG-PET), tissue biomarkers using immunohistochemistry (IHC), and modulators of angiogenesis...
July 18, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28718842/secreted-protein-acidic-and-rich-in-cysteine-sparc-enhances-cell-proliferation-migration-and-epithelial-mesenchymal-transition-and-sparc-expression-is-associated-with-tumor-grade-in-head-and-neck-cancer
#9
Chih-Hau Chang, Meng-Chi Yen, Ssu-Hui Liao, Yu-Ling Hsu, Chung-Sheng Lai, Kao-Ping Chang, Ya-Ling Hsu
Secreted protein acidic and rich in cysteine (SPARC) is a secreted protein which is involved in various biological processes. SPARC expression is associated with tumor metastasis and poor prognosis in several types of cancer. However, the SPARC-induced signaling pathway was not fully understood in head and neck cancer. In this study, our results showed that SPARC treatment promoted cell proliferation and migration in head and neck cancer cell lines FaDu and Detroit 562. In addition, SPARC induced expression of epithelial mesenchymal transition (EMT) regulators, including Slug, Snail, and Twist in Detroit 562...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718669/fruit-peel-polyphenolic-extract-induced-apoptosis-in-human-breast-cancer-cells-is-associated-with-ros-production-and-modulation-of-p38mapk-erk1-2-and-the-akt-signaling-pathway
#10
Martin Kello, Lucia Kulikova, Janka Vaskova, Alexandra Nagyova, Jan Mojzis
Polyphenols represent a large group of natural substances with different biological properties. Currently, polyphenols are well studied due to their free radicals' scavenging and antioxidant activities. However, some studies indicate that polyphenols also exhibit pro-oxidant properties. In this study, the possible involvement of the pro-oxidant activities of fruit polyphenols was investigated in relation to apoptosis induction. To determine the type of cell death induced by fruit polyphenols (Flavine; F7), we assessed a series of assays, including measurements of caspase-7 activation, membrane mitochondrial potential changes, reactive oxygen (ROS) and nitrogen species production, lipid peroxidation, antioxidant enzymes activities, and PARP cleavage...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28718440/selective-targeting-of-rsk-isoforms-in-cancer
#11
REVIEW
Kimberly A Casalvieri, Christopher J Matheson, Donald S Backos, Philip Reigan
The p90 ribosomal S6 kinase family (RSK1-4) is a group of highly conserved Ser/Thr kinases that act as downstream effectors of the Ras/Raf/MEK/ERK signaling pathway. The RSKs phosphorylate a range of substrates involved in transcription, translation, cell cycle regulation, and cell survival. Although the RSKs have a high degree of sequence homology, their functional differences in cancer are of great interest. Current RSK inhibitors target more than one RSK isoform, and this may limit their efficacy as anticancer agents...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718429/activated-erk-an-emerging-player-in-mirna-downregulation
#12
Yiping Qu, Bingyin Shi, Peng Hou
To date, the mechanisms underlying global downregulation of miRNAs in cancer remain largely unclear. Recent findings indicate that activated ERK can cause widespread miRNA repression through suppressing the major steps of miRNA biogenesis. Here we discuss how ERK signaling globally downregulates miRNAs and how this contributes to tumorigenesis.
March 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718196/retracted-cannabinoid-cb-2-receptors-modulate-erk-1-2-kinase-signalling-and-no-release-in-microglial-cells-stimulated-with-bacterial-lipopolysaccharide-by-s-merighi-s-gessi-k-varani-c-simioni-d-fazzi-p-mirandola-and-p-a-borea-british-journal-of-pharmacology
#13
(no author information available yet)
The above article, published by the British Journal of Pharmacology in March 2012 (http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01673.x/full), has been retracted by agreement between the authors, the Journal Editor in Chief and John Wiley & Sons Ltd. The authors wish to state that in preparation of the original manuscript errors occurred resulting in duplication. This issue relates specifically to Figures 2A and 2B, lanes 3-5 of the pJNK1/2 in Figure 3B and lanes 1-3 of the pJNK1/2 blot from Figure 3C...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28717410/fish-scale-collagen-peptides-protect-against-cocl2-tnf-%C3%AE-induced-cytotoxicity-and-inflammation-via-inhibition-of-ros-mapk-and-nf-%C3%AE%C2%BAb-pathways-in-hacat-cells
#14
Fazli Subhan, Hae Yeong Kang, Yeseon Lim, Muhammad Ikram, Sun-Yong Baek, Songwan Jin, Young Hun Jeong, Jong Young Kwak, Sik Yoon
Skin diseases associated with inflammation or oxidative stress represent the most common problem in dermatology. The present study demonstrates that fish scale collagen peptides (FSCP) protect against CoCl2-induced cytotoxicity and TNF-α-induced inflammatory responses in human HaCaT keratinocyte cells. Our study is the first to report that FSCP increase cell viability and ameliorate oxidative injury in HaCaT cells through mechanisms mediated by the downregulation of key proinflammatory cytokines, namely, TNF-α, IL-1β, IL-8, and iNOS...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28716954/synaptically-driven-phosphorylation-of-ribosomal-protein-s6-is-differentially-regulated-at-active-synapses-versus-dendrites-and-cell-bodies-by-mapk-and-pi3k-mtor-signaling-pathways
#15
Patricia Salgado Pirbhoy, Shannon Farris, Oswald Steward
High-frequency stimulation of the medial perforant path triggers robust phosphorylation of ribosomal protein S6 (rpS6) in activated dendritic domains and granule cell bodies. Here we dissect the signaling pathways responsible for synaptically driven rpS6 phosphorylation in the dentate gyrus using pharmacological agents to inhibit PI3-kinase/mTOR and MAPK/ERK-dependent kinases. Using phospho-specific antibodies for rpS6 at different sites (ser235/236 versus ser240/244), we show that delivery of the PI3-kinase inhibitor, wortmannin, decreased rpS6 phosphorylation throughout the somatodendritic compartment (granule cell layer, inner molecular layer, outer molecular layer), especially in granule cell bodies while sparing phosphorylation at activated synapses (middle molecular layer)...
August 2017: Learning & Memory
https://www.readbyqxmd.com/read/28716813/inhibition-of-heparanase-in-pediatric-brain-tumor-cells-attenuates-their-proliferation-invasive-capacity-and-in-vivo-tumor-growth
#16
Argyris Spyrou, Soumi Kundu, Lulu Haseeb, Di Yu, Tommie Olofsson, Keith Dredge, Edward Hammond, Uri Barash, Israel Vlodavsky, Karin Forsberg-Nilsson
Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor and current treatment causes long-term complications. Malignant brain tumors infiltrate the healthy brain tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of the extracellular matrix (ECM), modulate the activities of a variety of proteins. The major enzyme that degrades HS, heparanase (HPSE), is an important regulator of the ECM...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28716524/the-e3-ligase-hectd3-promotes-esophageal-squamous-cell-carcinoma-escc-growth-and-cell-survival-through-targeting-and-inhibiting-caspase-9-activation
#17
Yi Li, Xiaowei Wu, Lin Li, Yongshuo Liu, Chengshan Xu, Dan Su, Zhihua Liu
Apoptosis resistance is an acquired hallmark of cancer cells and many factors can contribute to the tumor cell apoptosis resistance. In this study, we demonstrated that HECTD3, overexpressed in human esophageal squamous cell carcinoma (ESCC), confers cells resistance to cisplatin-induced apoptosis and promotes cancer cell survival. HECTD3 can bind and ubiquitinate caspase-9, which leads to inhibiting caspase-9 oligomerization and association with Apaf-1, and results in suppressing caspase-9 activation and inhibiting apoptosis...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28716092/the-role-of-microglial-p2x7-modulation-of-cell-death-and-cytokine-release
#18
Yingbo He, Natalie Taylor, Lawrence Fourgeaud, Anindya Bhattacharya
BACKGROUND: ATP-gated P2X7 is a non-selective cation channel, which participates in a wide range of cellular functions as well as pathophysiological processes including neuropathic pain, immune response, and neuroinflammation. Despite its abundant expression in microglia, the role of P2X7 in neuroinflammation still remains unclear. METHODS: Primary microglia were isolated from cortices of P0-2 C57BL/6 wild-type or P2X7 knockout (P2X7(-/-)) mouse pups. Lipopolysaccharide, lipopolysaccharide plus IFNγ, or IL4 plus IL13 were used to polarize microglia to pro-inflammatory or anti-inflammatory states...
July 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28716058/srf-modulates-seizure-occurrence-activity-induced-gene-transcription-and-hippocampal-circuit-reorganization-in-the-mouse-pilocarpine-epilepsy-model
#19
Pascal Lösing, Cristina Elena Niturad, Merle Harrer, Christopher Meyer Zu Reckendorf, Theresa Schatz, Daniela Sinske, Holger Lerche, Snezana Maljevic, Bernd Knöll
A hallmark of temporal lobe epilepsy (TLE) is hippocampal neuronal demise and aberrant mossy fiber sprouting. In addition, unrestrained neuronal activity in TLE patients induces gene expression including immediate early genes (IEGs) such as Fos and Egr1.We employed the mouse pilocarpine model to analyze the transcription factor (TF) serum response factor (SRF) in epileptogenesis, seizure induced histopathology and IEG induction. SRF is a neuronal activity regulated TF stimulating IEG expression as well as nerve fiber growth and guidance...
July 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#20
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
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