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https://www.readbyqxmd.com/read/28938623/mifepristone-inhibits-ovarian-cancer-metastasis-by-intervening-in-sdf-1-cxcr4-chemokine-axis
#1
Ning Zheng, Jiahang Chen, Weiqun Liu, Jian Liu, Tao Li, Hongning Chen, Jichuang Wang, Lee Jia
SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations < IC50 inhibited expression of CXCR4 on cell surface of ovarian cancer SKOV-3 and IGROV-1, and reduced expression of the intracellular CXCR4 protein and its related mRNA activated by SDF-1...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#2
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938090/small-molecule-targets-in-immuno-oncology
#3
REVIEW
Dashyant Dhanak, James P Edwards, Ancho Nguyen, Peter J Tummino
Advances in understanding the role and molecular mechanisms underlying immune surveillance and control of (pre)malignancies is revolutionizing clinical practice in the treatment of cancer. Presently, multiple biologic drugs targeting the immune checkpoint proteins PD(L)1 or CTLA4 have been approved and/or are in advanced stages of clinical development for many cancers. In addition, combination therapy with these agents and other immunomodulators is being intensively explored with the aim of improving primary response rates or prolonging overall survival...
September 21, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28937634/the-physiological-and-pathological-implications-of-the-formation-of-hydrogels-with-a-specific-focus-on-amyloid-polypeptides
#4
REVIEW
Létitia Jean, Alex C Foley, David J T Vaux
Hydrogels are water-swollen and viscoelastic three-dimensional cross-linked polymeric network originating from monomer polymerisation. Hydrogel-forming polypeptides are widely found in nature and, at a cellular and organismal level, they provide a wide range of functions for the organism making them. Amyloid structures, arising from polypeptide aggregation, can be damaging or beneficial to different types of organisms. Although the best-known amyloids are those associated with human pathologies, this underlying structure is commonly used by higher eukaryotes to maintain normal cellular activities, and also by microbial communities to promote their survival and growth...
September 22, 2017: Biomolecules
https://www.readbyqxmd.com/read/28936426/comparison-of-diabetic-and-non-diabetic-human-leukocytic-responses-to-different-capsule-types-of-klebsiella-pneumoniae-responsible-for-causing-pyogenic-liver-abscess
#5
I Russel Lee, Ethel Sng, Kok-Onn Lee, James S Molton, Monica Chan, Shirin Kalimuddin, Ezlyn Izharuddin, David C Lye, Sophia Archuleta, Yunn-Hwen Gan
The major risk factor for Klebsiella liver abscess (KLA) is type 2 diabetes mellitus (DM), but the immunological mechanisms involved in the increased susceptibility are poorly defined. We investigated the responses of neutrophils and peripheral blood mononuclear cells (PBMCs) to hypervirulent Klebsiella pneumoniae (hvKP), the causative agent of KLA. DNA and myeloperoxidase levels were elevated in the plasma of KLA patients compared to uninfected individuals indicating neutrophil activation, but diabetic status had no effect on these neutrophil extracellular trap (NET) biomarkers in both subject groups...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28936224/role-of-crrlk1l-cell-wall-sensors-hercules1-and-2-theseus1-and-feronia-in-growth-adaptation-triggered-by-heavy-metals-and-trace-elements
#6
Julia Richter, Marie Ploderer, Gaëlle Mongelard, Laurent Gutierrez, Marie-Theres Hauser
Cell walls are not only a protective barrier surrounding protoplasts but serve as signaling platform between the extracellular environment and the intracellular physiology. Ions of heavy metals and trace elements, summarized to metal ions, bind to cell wall components, trigger their modification and provoke growth responses. To examine if metal ions trigger cell wall sensing receptor like kinases (RLKs) of the Catharanthus roseus RLK1-like (CrRLK1L) family we employed a molecular genetic approach. Quantitative transcription analyses show that HERCULES1 (HERK1), THESEUS1 (THE1), and FERONIA (FER) were differently regulated by cadmium (Cd), nickel (Ni), and lead (Pb)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28935606/calcimycin-mediates-mycobacterial-killing-by-inducing-intracellular-calcium-regulated-autophagy-in-a-p2rx7-dependent-manner
#7
Shradha Mawatwal, Assirbad Behura, Abhirupa Ghosh, Saqib Kidwai, Abtar Mishra, Amar Deep, Sakshi Agarwal, Sudipto Saha, Ramandeep Singh, Rohan Dhiman
Phenotypic screening led to the identification of calcimycin as a potent inhibitor of Mycobacterium bovis BCG (M. bovis BCG) growth in vitro and in THP-1 cells. In the present study, we aim to decipher the mechanism of antimycobacterial activity of calcimycin. We noticed that treatment with calcimycin led to up-regulation of different autophagy markers like Beclin-1, autophagy-related gene (Atg) 7, Atg 3 and enhanced microtubule-associated protein 1A/1B-light chain 3-I (LC3-I) to LC3-II conversion in macrophages...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28933687/tagging-of-the-vaccinia-virus-protein-f13-with-mcherry-causes-aberrant-virion-morphogenesis
#8
David C J Carpentier, Michael S Hollinshead, Helen A Ewles, Stacey-Ann Lee, Geoffrey L Smith
Vaccinia virus produces two distinct infectious virions; the single-enveloped intracellular mature virus (IMV), which remains in the cell until cell lysis, and the double-enveloped extracellular enveloped virus (EEV), which mediates virus spread. The latter is derived from a triple-enveloped intracellular enveloped virus (IEV) precursor, which is transported to the cell periphery by the kinesin-1 motor complex. This transport involves the viral protein A36 as well as F12 and E2. A36 is an integral membrane protein associated with the outer virus envelope and is the only known direct link between virion and kinesin-1 complex...
September 20, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28933603/autophagy-enables-retromer-dependent-plasma-membrane-translocation-of-slc2a1-glut-to-enhance-glucose-uptake
#9
Srirupa Roy, Jayanta Debnath
Macroautophagy/autophagy is traditionally viewed as an intracellular catabolic pathway that recycles core metabolites during starvation or stress. Recently, we found that autophagy also functions in the control of glucose uptake from the extracellular environment by facilitating cell surface expression of the glucose transporter SLC2A1/GLUT1. In response to increased glycolytic demand or acute glucose starvation, autophagosome induction titrates the RabGAP protein TBC1D5 away from its inhibitory interaction with the retromer complex and into MAP1LC3(+) compartments...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933590/rubcn-rubicon-and-egfr-regulate-lysosomal-degradative-processes-in-the-retinal-pigment-epithelium-rpe-of-the-eye
#10
Luis Muniz-Feliciano, Teresa A Doggett, Zhenqing Zhou, Thomas A Ferguson
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, phagocytosis is performed by cell types such as macrophages and the retinal pigment epithelial (RPE) cells of the eye where it is supported by the noncanonical autophagy process termed LC3-associated phagocytosis (LAP). Autophagy and LAP are distinct pathways that use many of the same mediators and must compete for cellular resources, suggesting that cells may regulate both processes under homeostatic and stress conditions...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28932814/the-gut-commensal-microbiome-of-drosophila-melanogaster-is-modified-by-the-endosymbiont-wolbachia
#11
Rama K Simhadri, Eva M Fast, Rong Guo, Michaela J Schultz, Natalie Vaisman, Luis Ortiz, Joanna Bybee, Barton E Slatko, Horacio M Frydman
Endosymbiotic Wolbachia bacteria and the gut microbiome have independently been shown to affect several aspects of insect biology, including reproduction, development, life span, stem cell activity, and resistance to human pathogens, in insect vectors. This work shows that Wolbachia bacteria, which reside mainly in the fly germline, affect the microbial species present in the fly gut in a lab-reared strain. Drosophila melanogaster hosts two main genera of commensal bacteria-Acetobacter and Lactobacillus. Wolbachia-infected flies have significantly reduced titers of Acetobacter...
September 2017: MSphere
https://www.readbyqxmd.com/read/28932081/-epigallocatechin-3-gallate-enhances-poly-i-c-induced-interferon-%C3%AE-1-production-and-inhibits-hepatitis-c-virus-replication-in-hepatocytes
#12
Yi-Zhong Wang, Jie-Liang Li, Xu Wang, Ting Zhang, Wen-Zhe Ho
AIM: To investigate the effect of (-)-epigallocatechin-3-gallate (EGCG) on polyinosinic-polycytidylic acid (poly I:C)-triggered intracellular innate immunity against hepatitis C virus (HCV) in hepatocytes. METHODS: A cell culture model of HCV infection was generated by infecting a hepatoma cell line, Huh7, with HCV JFH-1 strain (JFH-1-Huh7). Poly I:C with a high molecular weight and EGCG were used to stimulate the JFH-1-Huh7 cells. Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of intracellular mRNAs and of intracellular and extracellular HCV RNA...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28931870/inactivation-of-hmgcl-promotes-proliferation-and-metastasis-of-nasopharyngeal-carcinoma-by-suppressing-oxidative-stress
#13
Wenqi Luo, Liting Qin, Bo Li, Zhipeng Liao, Jiezhen Liang, Xiling Xiao, Xue Xiao, Yingxi Mo, Guangwu Huang, Zhe Zhang, Xiaoying Zhou, Ping Li
Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular β-hydroxybutyrate (β-HB) production, thereby reducing reactive oxygen species (ROS) generation...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931752/l-dopa-sensitizes-vasomotor-tone-by-modulating-the-vascular-alpha1-adrenergic-receptor
#14
Daiki Masukawa, Motokazu Koga, Anna Sezaki, Yuka Nakao, Yuji Kamikubo, Tatsuo Hashimoto, Yuki Okuyama-Oki, Aderemi Caleb Aladeokin, Fumio Nakamura, Utako Yokoyama, Hiromichi Wakui, Hiroshi Ichinose, Takashi Sakurai, Satoshi Umemura, Koichi Tamura, Yoshihiro Ishikawa, Yoshio Goshima
Blood pressure is regulated by extrinsic factors including noradrenaline, the sympathetic neurotransmitter that controls cardiovascular functions through adrenergic receptors. However, the fine-tuning system of noradrenaline signaling is relatively unknown. We here show that l-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of catecholamines, sensitizes the vascular adrenergic receptor alpha1 (ADRA1) through activation of L-DOPA receptor GPR143. In WT mice, intravenous infusion of the ADRA1 agonist phenylephrine induced a transient elevation of blood pressure...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28931592/ubiquitin-ligase-spsb4-diminishes-cell-repulsive-responses-mediated-by-ephb2
#15
Fumihiko Okumura, Akiko Joo-Okumura, Keisuke Obara, Alexander Petersen, Akihiko Nishikimi, Yoshinori Fukui, Kunio Nakatsukasa, Takumi Kamura
Eph receptor tyrosine kinases and their ephrin ligands are overexpressed in various human cancers, including colorectal malignancies, suggesting important roles in many aspects of cancer development and progression as well as in cellular repulsive responses. The ectodomain of EphB2 receptor is cleaved by metalloproteinases (MMPs) MMP-2/MMP-9 and released into the extracellular space after stimulation by its ligand. The remaining membrane-associated fragment is further cleaved by the presenilin-dependent γ-secretase and releases an intracellular peptide that has tyrosine kinase activity...
September 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28931396/il-4-induced-caveolin-1-containing-lipid-rafts-aggregation-contributes-to-muc5ac-synthesis-in-bronchial-epithelial-cells
#16
Yu Xia, Peng-Cheng Cai, Fan Yu, Liang Xiong, Xin-Liang He, Shan-Shan Rao, Feng Chen, Xiang-Ping Yang, Wan-Li Ma, Hong Ye
BACKGROUND: Mucus overproduction is an important feature of asthma. Interleukin (IL)-4 is required for allergen-induced airway inflammation and mucus production. MUC5AC gene expression is regulated by transcript factors NF-κB. The intracellular Ca(2+) ([Ca(2+)]i) signal is required for activation of NF-κB. The transient receptor potential canonical 1 (TRPC1) channel has been shown to contribute for agonist-stimulated Ca(2+) influx in some types of cells. However, the relationships among IL-4, TRPC1 and mucus overproduction in bronchial epithelial cells (BECs) in asthma are poorly understood...
September 20, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28929467/erratum-to-hfe-mrna-expression-is-responsive-to-intracellular-and-extracellular-iron-loading-short-communication
#17
Kosha J Mehta, Sebastien Farnaud, Vinood B Patel
The original article shows an error the co-author name: Sebastien Farnaud. The original article was corrected.
September 19, 2017: Molecular Biology Reports
https://www.readbyqxmd.com/read/28928905/fucoxanthin-a-marine-carotenoid-attenuates-%C3%AE-amyloid-oligomer-induced-neurotoxicity-possibly-via-regulating-the-pi3k-akt-and-the-erk-pathways-in-sh-sy5y-cells
#18
Jiajia Lin, Jie Yu, Jiaying Zhao, Ke Zhang, Jiachen Zheng, Jialing Wang, Chunhui Huang, Jingrong Zhang, Xiaojun Yan, William H Gerwick, Qinwen Wang, Wei Cui, Shan He
Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by neurofibrillary tangles, synaptic impairments, and loss of neurons. Oligomers of β-amyloid (Aβ) are widely accepted as the main neurotoxins to induce oxidative stress and neuronal loss in AD. In this study, we discovered that fucoxanthin, a marine carotenoid with antioxidative stress properties, concentration dependently prevented Aβ oligomer-induced increase of neuronal apoptosis and intracellular reactive oxygen species in SH-SY5Y cells...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28928268/mild-acidosis-delays-neutrophil-apoptosis-via-multiple-signaling-pathways-and-acts-in-concert-with-inflammatory-mediators
#19
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
September 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28928244/selective-inhibitory-effects-of-zinc-on-cell-proliferation-in-esophageal-squamous-cell-carcinoma-through-orai1
#20
Sangyong Choi, Chaochu Cui, Yanhong Luo, Sun-Hee Kim, Jae-Kyun Ko, Xiaofang Huo, Jianjie Ma, Li-Wu Fu, Rhonda F Souza, Irina Korichneva, Zui Pan
Zinc, an essential micronutrient, has a cancer preventive role. Zinc deficiency has been shown to contribute to the progression of esophageal cancer. Orai1, a store-operated Ca(2+) entry (SOCE) channel, was previously reported to be highly expressed in tumor tissues removed from patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis, and elevation of its expression contributes to both hyperactive intracellular Ca(2+) oscillations and fast cell proliferation in human ESCC cells. However, the molecular basis of cancer preventive functions of zinc and its association with Orai1-mediated cell proliferation remains unknown...
September 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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