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https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#1
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777910/differentially-expressed-novel-alternatively-spliced-transcript-variant-of-tumor-suppressor-stk11-gene-in-mouse
#2
Hassan Mubarak Ishqi, Tarique Sarwar, Mohammed Amir Husain, Sayeed Ur Rehman, Mohammad Tabish
Serine/threonine kinase 11 (STK11) is a protein kinase that is encoded by Stk11 gene located on chromosome 19 and 10 in humans and mouse respectively. It acts as a master kinase of adenine monophosphate-activated protein kinase (AMPK) pathway that coordinates the regulation of cellular energy metabolism and cell division. STK11 exerts effect by activating more than 14 kinases including AMPK and AMPK-related kinases. It is also known to regulate cell polarity and acts as tumor suppressor. Alternative splicing of pre-mRNA is a mechanism which results in multiple transcript variants of a single gene...
May 16, 2018: Gene
https://www.readbyqxmd.com/read/29777904/axed-muc4-muc4-x-aggravates-pancreatic-malignant-phenotype-by-activating-integrin-%C3%AE-1-fak-erk-pathway
#3
Rahat Jahan, Muzafar A Macha, Satyanarayana Rachaghani, Srustidhar Das, Lynette M Smith, Sukhwinder Kaur, Surinder K Batra
Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest and polymorphic exon 2, along with exon 3...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777873/cinnamaldehyde-protects-vsmcs-against-ox-ldl-induced-proliferation-and-migration-through-s-arrest-and-inhibition-of-p38-jnk-mapks-and-nf-%C3%AE%C2%BAb
#4
Weifeng Li, Wenbing Zhi, Jinmeng Zhao, Qing Yao, Fang Liu, Xiaofeng Niu
Cinnamaldehyde (Cin), as a traditional flavor constituent isolated from the bark of Cinnamonum cassia Presl, has been commonly used for - digestive, cardiovascular and immune system diseases. The pathology of vascular smooth muscle cells (VSMCs) accelerated the progression of atherosclerosis. In our study, we found that cinnamaldehyde significantly suppressed ox-LDL-induced VSMCs proliferation, migration and inflammatory cytokine overproduction, as well as foam cell formation in VSMCs and macrophages. Moreover, cinnamaldehyde inhibited the phosphorylation of p38, JNK and p65 NF-κB and increased heme oxygenase-1 (HO-1) activity...
May 16, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29777870/profiling-modifications-for-glioblastoma-proteome-using-ultra-tolerant-database-search-are-the-peptide-mass-shifts-biologically-relevant-or-chemically-induced
#5
Irina A Tarasova, Peter M Chumakov, Sergei A Moshkovskii, Mikhail V Gorshkov
Peptide mass shifts were profiled using ultra-tolerant database search strategy for shotgun proteomics data sets of human glioblastoma cell lines demonstrating strong response to the type I interferon (IFNα-2b) treatment. The main objective of this profiling was revealing the cell response to IFN treatment at the level of protein modifications. To achieve this objective, statistically significant changes in peptide mass shift profiles between IFN treated and untreated glioblastoma samples were analyzed. Detailed analysis of MS/MS spectra allowed further interpretation of the observed mass shifts and differentiation between post-translational and artifact modifications...
May 16, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29777862/revealing-a-raf-functions-through-its-interactome
#6
Xin-Yu Zhang, Hui Guo, Bing Han, Xu-Min Zhang, Ying Huang, Yang Yang, Ying Liu, Xiao-Xi Guo, Qian Hao, Su An, Tian-RuiXu
A-Raf is a member of the Raf kinase family. Unlike B-Raf and C-Raf, the functions of A-Raf remain obscure. To gain more insight into the biological functions of A-Raf, we investigated the A-Raf interactome using proteomics. We found 132 proteins that interact with A-Raf and confirmed the interaction of 12 of these proteins with A-Raf by western blotting. Our data suggested that A-Raf regulates apoptosis, RNA catabolism, GTPase activity, and cell adhesion by interacting with proteins located in different cellular compartments...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777834/erwinia-amylovora-phage-vb_eamm_y3-represents-another-lineage-of-hairy-myoviridae
#7
Colin Buttimer, Yannick Born, Alan Lucid, Martin J Loessner, Lars Fieseler, Aidan Coffey
To date, a small number of jumbo myoviruses have been reported to possess atypical whisker-like structures along the surface of their contractile tails. Erwinia amylovora phage vB_EamM_Y3 is another example. It possesses a genome of 261,365 kbp with 333 predicted ORFs. Using a combination of BLASTP, Interproscan and HHpred, about 21% of its putative proteins could be assigned functions involved in nucleotide metabolism, DNA replication, virion structure and cell wall degradation. The phage was found to have a signal-arrest-release (SAR) endolysin (Y3_301) possessing a soluble lytic transglycosylase domain...
May 16, 2018: Research in Microbiology
https://www.readbyqxmd.com/read/29777831/microcystis-bloom-containing-microcystin-lr-induces-type-2-diabetes-mellitus
#8
Qiong Zhang, Wendi Qin, Liuyan Yang, Jing An, Xuxiang Zhang, Hao Hong, Lizhi Xu, Yaping Wang
Epidemiological data from Lake Taihu showed significantly higher incidences of type 2 diabetes mellitus (T2DM) than in other areas of China. This may be related to the occurrence of a Microcystis bloom in Lake Taihu in the summer and autumn every year. The objective of this study is to investigate whether the contaminated water from the Microcystis bloom and the derivative pollutant microcystin-LR (MC-LR) can explain the higher incidences of T2DM. Healthy male mice were fed with water from different regions of Lake Taihu, and were either acutely or chronically exposed to MC-LR through oral administration or intraperitoneal injection...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29777784/cd146-mediates-an-e-cadherin-to-n-cadherin-switch-during-tgf-%C3%AE-signaling-induced-epithelial-mesenchymal-transition
#9
Yanbin Ma, Haofeng Zhang, Chaoliang Xiong, Zheng Liu, Qingji Xu, Jing Feng, Jun Zhang, Zhaoqing Wang, Xiyun Yan
Cadherin switch is an initiating factor of epithelial-mesenchymal transition (EMT) and is intimately correlated with cancer metastatic potential; however, its underlying mechanisms remain unclear. Here, using a transforming growth factor-β (TGF-β)-induced EMT model, we provide explicit evidence that CD146, with elevated expression and activity in a variety of cancers, is a key factor involved in the cadherin switch. We show that CD146 can be induced by TGF-β signaling. Moreover, CD146 expression is positively correlated with the activation levels of STAT3/Twist and ERK pathways...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777777/mir-128-3p-directly-targets-vegfc-vegfr3-to-modulate-the-proliferation-of-lymphatic-endothelial-cells-through-ca-2-signaling
#10
Jie Zhou, Zhiyou He, Le Guo, Jizhang Zeng, Pengfei Liang, Licheng Ren, Minghua Zhang, Pihong Zhang, Xiaoyuan Huang
Lymphangiogenesis has been regarded as a physiological response to pathologic stimuli. The abnormal proliferation of lymphatic endothelial cell (LECs) and lymphangiogenesis is involved in the development of lymphatic disorders. Reportedly, VEGFC/VEGFR3 plays a key role in lymphangiogenesis; moreover, VEGFC/VEGFR3 exerts their cellular effects through activation of Ca2+ signaling in several cell types. Herein, we demonstrated that VEGFC significantly up-regulated LEC proliferation through VEGFR3; moreover, VEGFC/VEGFR3 induced Ca2+ signaling activation...
May 16, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29777776/distinct-roles-for-the-cell-adhesion-molecule-contactin2-in-the-development-and-function-of-neural-circuits-in-zebrafish
#11
Suman Gurung, Emilia Asante, Devynn Hummel, Ashley Williams, Oren Feldman-Schultz, Mary C Halloran, Vinoth Sittaramane, Anand Chandrasekhar
Contactin2 (Cntn2)/Transient Axonal Glycoprotein 1 (Tag1), a neural cell adhesion molecule, has established roles in neuronal migration and axon fasciculation in chick and mouse. In zebrafish, antisense morpholino-based studies have indicated roles for cntn2 in the migration of facial branchiomotor (FBM) neurons, the guidance of the axons of the nucleus of the medial longitudinal fascicle (nucMLF), and the outgrowth of Rohon-Beard (RB) central axons. To study functions of Cntn2 in later stages of neuronal development, we generated cntn2 mutant zebrafish using CRISPR-Cas9...
May 16, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29777774/mir-125b-5p-is-involved-in-oxygen-and-glucose-deprivation-injury-in-pc-12-cells-via-cbs-h-2-s-pathway
#12
Yaqi Shen, Zhuqing Shen, Lingyan Guo, Qiuyan Zhang, Zhijun Wang, Lei Miao, Minjun Wang, Jian Wu, Wei Guo, Yizhun Zhu
AIMS: Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (H2 S) plays a critical role in hypoxia-induced injury in the central nervous system. Cystathionine β-synthase (CBS) is the main enzyme catalyzing the production of H2 S in brain. The objective of this study was to investigate the effect of miR-125b-5p on protecting against oxygen and glucose deprivation (OGD) injury in PC-12 cells by regulating CBS and H2 S generation...
May 16, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29777734/gga-mir-454-suppresses-infectious-bursal-disease-virus-ibdv-replication-via-directly-targeting-ibdv-genomic-segment-b-and-cellular-suppressors-of-cytokine-signaling-6-socs6
#13
Mengjiao Fu, Bin Wang, Xiang Chen, Zhiyuan He, Yongqiang Wang, Xiaoqi Li, Hong Cao, Shijun J Zheng
MicroRNAs (miRNAs), as post-transcriptional regulators, play important roles in the process of viral infection through inhibiting virus replication or modulating host immune response. However, the role of miRNAs in host response against infectious bursal disease virus (IBDV) infection is still unclear. In this study, we found that gga-miR-454 of the host was decreased in response to IBDV infection and that transfection of DF-1 cells with miR-454 inhibited IBDV replication via directly targeting the specific sequence of IBDV genomic segment B, while blockage of endogenous miR-454 by inhibitors enhanced virus replication...
May 16, 2018: Virus Research
https://www.readbyqxmd.com/read/29777731/tumor-necrosis-factor-receptor-2-is-required-for-ischemic-preconditioning-mediated-neuroprotection-in-the-hippocampus-following-a-subsequent-longer-transient-cerebral-ischemia
#14
Jae-Chul Lee, Chan Woo Park, Myoung Cheol Shin, Jun Hwi Cho, Hyang-Ah Lee, Young-Myeong Kim, Joon Ha Park, Ji Hyeon Ahn, Jeong Hwi Cho, Hyun-Jin Tae, In Koo Hwang, Tae-Kyeong Lee, Moo-Ho Won, Il Jun Kang
Tumor Necrosis Factor-α (TNF-α) is a proinflammatory cytokine implicated in neuronal damage in response to cerebral ischemia. Ischemic preconditioning (IPC) provides neuroprotection against a subsequent severer or longer transient ischemia by ischemic tolerance. Here, we focused on the role of TNF-α in IPC-mediated neuroprotection against neuronal death following a subsequent longer transient cerebral ischemia (TCI). Gerbils used in this study were randomly assigned to eight groups; sham group, TCI operated group, IPC plus (+) sham group, IPC + TCI operated group, sham + etanercept (an inhibitor of TNF-a) group, TCI + etanercept group, IPC + sham + etanercept group, and IPC + TCI + etanercept group...
May 16, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29777725/strain-related-differences-in-mouse-lung-gene-expression-over-a-two-year-period-of-inhalation-exposure-to-styrene-relevance-to-human-risk-assessment
#15
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol E Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Debra B Layko, Patrick D McMullen
Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting from 1-day to 2-years in male mice from these two strains, including a Cyp2f2(-/-) knockout (C57BL/6-KO) and a Cyp2F1/2A13/2B6 transgenic mouse (C57BL/6-TG). With short term exposures (1-day to 1-week), CD-1 and C57BL/6-WT mice had thousands of differentially expressed genes (DEGs), consistent with changes in pathways for cell proliferation, cellular lipid metabolism, DNA-replication and inflammation...
May 16, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29777722/ca-2-signaling-and-spinocerebellar-ataxia
#16
REVIEW
Chihiro Hisatsune, Kozo Hamada, Katsuhiko Mikoshiba
Spinocerebellar ataxia (SCA) is a neural disorder, which is caused by degenerative changes in the cerebellum. SCA is primarily characterized by gait ataxia, and additional clinical features include nystagmus, dysarthria, tremors and cerebellar atrophy. Forty-four hereditary SCAs have been identified to date, along with >35 SCA-associated genes. Despite the great diversity and distinct functionalities of the SCA-related genes, accumulating evidence supports the occurrence of a common pathophysiological event among several hereditary SCAs...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777710/mir-616-3p-promotes-angiogenesis-and-emt-in-gastric-cancer-via-the-pten-akt-mtor-pathway
#17
Zhen-Hua Wu, Chen Lin, Chen-Chen Liu, Wei-Wei Jiang, Ming-Zhu Huang, Xin Liu, Wei-Jian Guo
Dysregulation of microRNAs has been demonstrated to be involved in a variety of biological events related to cancer, including proliferation, metastasis, angiogenesis and immune escape. miR-616-3p is located on the chromosome region 12q13.3, however, its potential role and clinical implications in gastric cancer remain poorly understood. The current study aimed to investigate the potential role of miR-616-3p in gastric cancer. The results showed that miR-616-3p was up-regulated in cancer tissues. Higher expression of miR-616-3p in tumor tissues also predicted poor prognosis...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777705/membrane-proteins-significantly-restrict-exosome-mobility
#18
Mikhail Skliar, Vasiliy S Chernyshev, David M Belnap, German V Sergey, Samer M Al-Hakami, Philip S Bernard, Inge J Stijleman, Rakesh Rachamadugu
Exosomes are membrane nanovesicles implicated in cell-to-cell signaling in which they transfer their molecular cargo from the parent to the recipient cells. This role essentially depends on the exosomes' small size, which is the prerequisite for their rapid migration through the crowded extracellular matrix and into and out of circulation. Here we report much lower exosome mobility than expected from the size of their vesicles, implicate membrane proteins in a substantially impeded rate of migration, and suggest an approach to quantifying the impact...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777703/bacterial-metabolite-s-equol-modulates-glucagon-like-peptide-1-secretion-from-enteroendocrine-l-cell-line-glutag-cells-via-actin-polymerization
#19
Kazuki Harada, Shoko Sada, Hidekazu Sakaguchi, Mai Takizawa, Rika Ishida, Takashi Tsuboi
S-equol is one of gut bacterial metabolites produced from soybean isoflavone daizein. While S-equol is known to promote glucose-induced insulin secretion from pancreatic β cells, whether S-equol affects glucagon-like peptide-1 (GLP-1) secretion from enteroendoceine L cells remains unclear. Here we assessed the effect of S-equol on GLP-1 secretion from mouse enteroendocrine L cell line GLUTag cells. GLUTag cells expressed GPR30 and estrogen receptors, which are putative S-equol receptors. Application of S-equol induced an increase in intracellular Ca2+ levels via GPR30...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#20
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
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