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https://www.readbyqxmd.com/read/28221700/multikinase-inhibitors-sorafenib-and-sunitinib-as-radiosensitizers-in-head-and-neck-cancer-cell-lines
#1
Annette Affolter, Gerson Samosny, Anne-Sophie Heimes, Johanna Schneider, Wilko Weichert, Albrecht Stenzinger, Katharina Sommer, Alexandra Jensen, Arnulf Mayer, Walburgis Brenner, Wolf J Mann, Jürgen Brieger
BACKGROUND: Radioresistance is a common feature of head and neck squamous cell carcinoma (HNSCC). We previously showed that the irradiation- activated vascular endothelial growth factor (VEGF)-extracellular signal-regulated kinase (ERK)-axis is fundamental for the survival of resistant tumors. In this study, we examined if treatment with potent multikinase (MK) inhibitors, sorafenib and sunitinib, could radiosensitize tumor cells. METHODS: Cultured HNSCC cell lines were treated with inhibitors and subsequently irradiated...
February 21, 2017: Head & Neck
https://www.readbyqxmd.com/read/28214522/prelimbic-cortex-extracellular-signal-regulated-kinase-1-2-activation-is-required-for-memory-retrieval-of-long-term-inhibitory-avoidance
#2
Fei Luo, Jian Zheng, Xuan Sun, Wei-Ke Deng, Fang Liu, Bao-Ming Li
Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABAA-receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-hour inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30 min prior to test...
February 15, 2017: Brain Research
https://www.readbyqxmd.com/read/28213961/chrysin-induces-death-of-prostate-cancer-cells-by-inducing-ros-and-er-stress
#3
Soomin Ryu, Whasun Lim, Fuller W Bazer, Gwonhwa Song
Chrysin is a natural flavone found in numerous plant extracts, honey and propolis that has multiple biological activities including anti-cancer effects. Understanding of biological mechanisms mediated in response to chrysin in cancerous cells may provide novel insight into chemotherapeutic approaches with reduced side effects in cancers. In the present study, we investigated functional roles of chrysin in progression of prostate cancer cells using DU145 and PC-3 cell lines. The results showed that chrysin induced apoptosis of cells evidenced by DNA fragmentation and increasing the population of both DU145 and PC-3 cells in the sub-G1 phase of the cell cycle...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28212323/low-intensity-extracorporeal-shock-wave-therapy-enhances-brain-derived-neurotrophic-factor-expression-through-perk-atf4-signaling-pathway
#4
Bohan Wang, Hongxiu Ning, Amanda B Reed-Maldonado, Jun Zhou, Yajun Ruan, Tie Zhou, Hsun Shuan Wang, Byung Seok Oh, Lia Banie, Guiting Lin, Tom F Lue
Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28211011/teoa-a-triterpenoid-from-actinidia-eriantha-induces-autophagy-in-sw620-cells-via-endoplasmic-reticulum-stress-and-ros-dependent-mitophagy
#5
Dandan Zhang, Cuixia Gao, Ruyi Li, Lin Zhang, Jingkui Tian
2α,3α,24-Thrihydroxyurs-12-en-28-oicacid (TEOA), a pentacyclic triterpenoid, isolated from the roots of Actinidia eriantha, exhibits significant cytotoxicity against SW620, BGC-823, HepG-2, A549 and PC-3 cancer cells. In this study, we investigated the underlying molecular mechanism of the anticancer activity of TEOA in SW620 cells. We demonstrated that TEOA induced apoptosis through cleavage of caspase-9 and PARP in SW620 cells. In addition, evidence of TEOA-mediated autophagy included the induction of autophagolysosomes and activation of autophagic markers LC-3B and p62...
February 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28209981/fibulin-6-regulates-pro-fibrotic-tgf-%C3%AE-responses-in-neonatal-mouse-ventricular-cardiac-fibroblasts
#6
Arpita Chowdhury, Lisa Hasselbach, Frank Echtermeyer, Nidhi Jyotsana, Gregor Theilmeier, Christine Herzog
Fibulin-6, an essential component of extracellular matrix determines the architecture of cellular junctions in tissues undergoing strain. Increased expression and deposition of fibulin-6 facilitates fibroblast migration in response to TGF-β, following myocardial infarction in mouse heart. The underlying mechanism still remains elusive. In conjunction with our previous study, we have now demonstrated that in fibulin-6 knockdown (KD) fibroblasts, not only TGF-β dependent migration, but also stress fiber formation, cellular networking and subsequently fibroblast wound contraction is almost abrogated...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28208700/role-of-protein-quality-control-failure-in-alcoholic-hepatitis-pathogenesis
#7
REVIEW
Samuel W French, Maryam Masouminia, Sara Samadzadeh, Brittany C Tillman, Alejandro Mendoza, Barbara A French
: The mechanisms of protein quality control in hepatocytes in cases of alcoholic hepatitis (AH) including ufmylation, FAT10ylation, metacaspase 1 (Mca1), ERAD (endoplasmic reticulum-associated degradation), JUNQ (juxta nuclear quality control), IPOD (insoluble protein deposit) autophagocytosis, and ER stress are reviewed. The Mallory-Denk body (MDB) formation develops in the hepatocytes in alcoholic hepatitis as a consequence of the failure of these protein quality control mechanisms to remove misfolded and damaged proteins and to prevent MDB aggresome formation within the cytoplasm of hepatocytes...
February 8, 2017: Biomolecules
https://www.readbyqxmd.com/read/28202509/sodium-channel-subunit-scnn1b-suppresses-gastric-cancer-growth-and-metastasis-via-grp78-degradation
#8
Jun Yu, Qian Yun, Chi Chun Wong, Jiaying Xu, Huarong Chen, Yanquan Zhang, Wei Kang, Hua Wang, Li Zhang, Weilin Li, Eagle Sh Chu, Minnie Yy Go, Philip Wy Chiu, Enders Kw Ng, Francis Kl Chan, Joseph Jy Sung, Jianmin Si
There remains a paucity of functional biomarkers in gastric cancer. Here we report the identification of the sodium channel subunit SCNN1B as a candidate biomarker in gastric cancer (GC). SCNN1B mRNA expression was silenced commonly by promoter hypermethylation in GC cell lines and primary tumor tissues. Tissue microarray analysis revealed that high expression of SCNN1B was an independent prognostic factor for longer survival in GC patients, especially those with late-stage disease. Functional studies demonstrated that SCNN1B overexpression was sufficient to suppress multiple features of cancer cell pathophysiology in vitro and in vivo...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197636/mir-21-and-klf4-jointly-augment-epithelial%C3%A2-mesenchymal-transition-via-the-akt-erk1-2-pathway
#9
Chen-Hai Liu, Qiang Huang, Zhi-Yuan Jin, Cheng-Lin Zhu, Zhen Liu, Chao Wang
miR-21 induces epithelial-mesenchymal transition (EMT) of human cholangiocarcinoma (CCA) cells. However, the mechanism by which this occurs remains unclear. In the present study, high throughput platform was employed to detect the genes that are differential expressed in QBC939 cells transfected with a hsa-miR-21 antagomir or control vectors. The EMT-related Krüppel-like factor 4 (KLF4) gene was downregulated after miR-21 was knocked down. Overexpression of miR-21 upregulated KLF4, Akt, ERK and mesenchymal cell markers (N-cadherin and vimentin), downregulated the expression of epithelial cell marker E-cadherin and reduced cell migration and invasion...
February 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197379/caspase-2-and-oxidative-stress-underlie-the-immunogenic-potential-of-high-hydrostatic-pressure-induced-cancer-cell-death
#10
Irena Moserova, Iva Truxova, Abhishek D Garg, Jakub Tomala, Patrizia Agostinis, Pierre Francois Cartron, Sarka Vosahlikova, Marek Kovar, Radek Spisek, Jitka Fucikova
High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling immunogenic chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4(+) and CD8(+) T cell-dependent protective immunity in vivo. Moreover, we show that cell death induction by HHP relies on the overproduction of reactive oxygen species (ROS), causing rapid establishment of the integrated stress response, eIF2α phosphorylation by PERK, and sequential caspase-2, -8 and -3 activation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196429/medical-and-psychosocial-factors-and-unfavourable-low-density-lipoprotein-cholesterol-control-in-coronary-patients
#11
John Munkhaugen, Elise Sverre, Jan E Otterstad, Kari Peersen, Erik Gjertsen, Joep Perk, Lars Gullestad, Torbjørn Moum, Toril Dammen, Einar Husebye
Objective Understanding the determinants of low-density lipoprotein cholesterol (LDL-C) control constitutes the basis of modelling interventions for optimal lipid control and prognosis. We aim to identify medical and psychosocial (study) factors associated with unfavourable LDL-C control in coronary patients. Methods A cross-sectional explorative study used logistic and linear regression analysis to investigate the association between study factors and LDL-C in 1095 patients, hospitalized with myocardial infarction and/or a coronary revascularization procedure...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28192116/prrt2-inhibits-the-proliferation-of-glioma-cells-by-modulating-unfolded-protein-response-pathway
#12
Guanghui Bi, Jingfeng Yan, Shuzhen Sun
Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28188223/hypoxic-proliferation-requires-egfr-mediated-erk-activation-in-human-pulmonary-microvascular-endothelial-cells
#13
Hilary A White, Yi Jin, Louis G Chicoine, Bernadette Chen, Yusen Liu, Leif D Nelin
We have previously shown that hypoxic proliferation of human pulmonary microvascular endothelial cells (hPMVEC) depends on epidermal growth factor receptor (EGFR) activation. To determine down-stream signaling leading to proliferation, we tested the hypothesis that hypoxia-induced proliferation in hPMVEC would require EGFR-mediated activation of extracellular signal-regulated kinase (ERK) leading to arginase II induction. To test this hypothesis, hPMVEC were incubated in either normoxia (21% O2, 5% CO2) or hypoxia (1% O2, 5% CO2) and western blotting was performed for EGFR, arginase II, phosphorylated-ERK (pERK), and total ERK (ERK)...
February 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28185700/use-of-spatially-distributed-time-integrated-sediment-sampling-networks-and-distributed-fine-sediment-modelling-to-inform-catchment-management
#14
M T Perks, J Warburton, L J Bracken, S M Reaney, S B Emery, S Hirst
Under the EU Water Framework Directive, suspended sediment is omitted from environmental quality standards and compliance targets. This omission is partly explained by difficulties in assessing the complex dose-response of ecological communities. But equally, it is hindered by a lack of spatially distributed estimates of suspended sediment variability across catchments. In this paper, we demonstrate the inability of traditional, discrete sampling campaigns for assessing exposure to fine sediment. Sampling frequencies based on Environmental Quality Standard protocols, whilst reflecting typical manual sampling constraints, are unable to determine the magnitude of sediment exposure with an acceptable level of precision...
February 6, 2017: Journal of Environmental Management
https://www.readbyqxmd.com/read/28178654/hepatitis-b-virus-surface-proteins-accelerate-cholestatic-injury-and-tumor-progression-in-abcb4-knockout-mice
#15
Daniel Zahner, Hannah Glimm, Tomomitsu Matono, Yuri Churin, Diran Herebian, Ertan Mayatepek, Kernt Köhler, Stefan Gattenlöhner, Anne Stinn, Annette Tschuschner, Martin Roderfeld, Elke Roeb
: Understanding of the pathophysiology of cholestasis associated carcinogenesis could challenge the development of new personalized therapeutic approaches and thus improve prognosis. Simultaneous damage might aggravate hepatic injury, induce chronic liver disease and even promote carcinogenesis. We aimed to study the effect of Hepatitis B virus surface protein (HBsAg) on cholestatic liver disease and associated carcinogenesis in a mouse model combining both impairments. Hybrids of Abcb4-/- and HBsAg transgenic mice were bred on fibrosis susceptible background BALB/c...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178380/pre-ischemia-melatonin-treatment-alleviated-acute-neuronal-injury-after-ischemic-stroke-by-inhibiting-er-stress-dependent-autophagy-via-perk-and-ire1-signalings
#16
Dayun Feng, Bao Wang, Lei Wang, Neeta Abraham, Kai Tao, Lu Huang, Wei Shi, Yushu Dong, Yan Qu
Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre-ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR) related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion (MCAO) mouse model. Pre-ischemia melatonin treatment was able to attenuate IR-induced ER stress and autophagy...
February 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28174720/netrin-1-protects-hepatocytes-against-cell-death-through-sustained-translation-during-the-unfolded-protein-response
#17
Thomas Lahlali, Marie-Laure Plissonnier, Cristina Romero-López, Maud Michelet, Benjamin Ducarouge, Alfredo Berzal-Herranz, Fabien Zoulim, Patrick Mehlen, Romain Parent
BACKGROUND & AIMS: Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation. Netrin-1 blocks apoptosis induced by the prototypical dependence receptors deleted in colorectal carcinoma and uncoordinated phenotype-5. Although the unfolded protein response (UPR) triggers apoptosis on exposure to stress, it first attempts to restore endoplasmic reticulum homeostasis to foster cell survival. Importantly, UPR is implicated in chronic liver conditions including hepatic oncogenesis...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28174265/sgk3-sustains-er%C3%AE-signaling-and-drives-acquired-aromatase-inhibitor-resistance-through-maintaining-endoplasmic-reticulum-homeostasis
#18
Yuanzhong Wang, Dujin Zhou, Sheryl Phung, Charles Warden, Rumana Rashid, Nymph Chan, Shiuan Chen
Many estrogen receptor alpha (ERα)-positive breast cancers initially respond to aromatase inhibitors (AIs), but eventually acquire resistance. Here, we report that serum- and glucocorticoid-inducible kinase 3 (SGK3), a kinase transcriptionally regulated by ERα in breast cancer, sustains ERα signaling and drives acquired AI resistance. SGK3 is up-regulated and essential for endoplasmic reticulum (EnR) homeostasis through preserving sarcoplasmic/EnR calcium ATPase 2b (SERCA2b) function in AI-resistant cells...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28168809/hopscotch-technique-a-novel-method-for-percutaneous-closure-of-paravalvular-leaks
#19
Carlos E Ruiz, Li Chi-Hion, Jelnin Vladimir, Perk Gila, Weiss Dillon, Kronzon Itzhak, Kliger Chad
OBJECTIVES: To describe the feasibility and safety of the Hopscotch Technique, a novel method to close paravalvular leaks. BACKGROUND: Successful closure of paravalvular leaks requires the complete seal of irregular defects, frequently interrupted by remaining sutures or tissue that converts a large defect into a complex series of contiguous smaller defects. Successful treatment with devices placed in a single space is impossible with constrained appearance and significant residual leak; therefore, new techniques to deploy smaller devices in the correct location are needed...
February 7, 2017: Catheterization and Cardiovascular Interventions
https://www.readbyqxmd.com/read/28162804/impairment-of-endoplasmic-reticulum-is-involved-in-%C3%AE-cell-dysfunction-induced-by-microcystin-lr
#20
Yanyan Zhao, Qing Cao, Yaojia He, Qingju Xue, Liqiang Xie, Yunjun Yan
Microcystins (MCs) widely distributed in freshwaters have posed a significant risk to human health. Previous studies have demonstrated that exposure to MC-LR impairs pancreatic islet function, however, the underlying mechanisms still remain unclear. In the present study, we explored the role of endoplasmic reticulum (ER) impairment in β-cell dysfunction caused by MC-LR. The result showed that MC-LR modified ER morphology evidenced by increased ER amount and size at low doses (15, 30 or 60 μM) and vacuolar and dilated ER ultrastructure at high doses (100 or 200 μM)...
February 2, 2017: Environmental Pollution
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