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https://www.readbyqxmd.com/read/28888937/low-density-lipoprotein-receptor-class-a-domain-containing-4-ldlrad4-promotes-tumorigenesis-of-hepatic-cancer-cells
#1
Zhenxing Liu, Xin Huo, Shuang Zhao, Jingjing Yang, Wenxia Shi, Lei Jing, Wei Li, Yuyin Li, Long Ma, Yingtang Gao, Aipo Diao
LDLRAD4 was previously identified and shown to be connected with psychiatric disorders. The structure of LDLRAD4 protein is similar to that of TMEPAI protein, which is overexpressed in many tumors. However, it is still unknown whether LDLRAD4 is involved in tumorigenesis. In this study, the potential role of LDLRAD4 in tumorigenesis was investigated. LDLRAD4 is elevated in hepatic cancer cells and tumor tissues, and expression of LDLRAD4 promotes hepatic cancer cell HepG2 and SMMC-7721 proliferation and migration...
September 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28884480/blood-monocytes-sample-melana-mart1-antigen-for-long-lasting-cross-presentation-to-cd8-t-cells-after-differentiation-into-dendritic-cells
#2
Florence Faure, Mabel Jouve, Isabelle Lebhar-Peguillet, Charlotte Sadaka, Fernando Sepulveda, Olivier Lantz, Stefano Berre, Raphael Gaudin, Silvia Sánchez-Ramón, Sebastian Amigorena
Human blood monocytes are very potent to take up antigens. Like macrophages in tissue, they efficiently degrade exogenous protein and are less efficient than dendritic cells at cross-presenting antigens to CD8(+) T cells. Although it is generally accepted that dendritic cells take up tissue antigens and then migrate to lymph nodes to prime T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented so far. In the present work, we show that monocytes loaded in vitro with MelanA long peptides retain the capacity to stimulate antigen-specific CD8(+) T cell clones after 5 days of differentiation into monocytes-derived dendritic cells (MoDC)...
September 7, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28883791/proteasome-inhibitor-ysy01a-abrogates-constitutive-stat3-signaling-via-down-regulation-of-gp130-and-jak2-in-human-a549-lung-cancer-cells
#3
Wei Huang, Xia Yuan, Ting Sun, Shujie Fan, Jun Wang, Quan Zhou, Wei Guo, Fuxiang Ran, Zemei Ge, Huayu Yang, Runtao Li, Jingrong Cui
Proteasome inhibition interfering with many cell signaling pathways has been extensively explored as a therapeutic strategy for cancers. Proteasome inhibitor YSY01A is a novel agent that has shown remarkable anti-tumor effects; however, its mechanisms of action are not fully understood. Here we report that YSY01A is capable of suppressing cancer cell survival by induction of apoptosis. Paradoxically, we find that YSY01A abrogates constitutive activation of STAT3 via proteasome-independent degradation of gp130 and JAK2, but not transcriptional regulation, in human A549 non-small cell lung cancer cells...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28852060/fmnl2-and-3-regulate-golgi-architecture-and-anterograde-transport-downstream-of-cdc42
#4
Frieda Kage, Anika Steffen, Adolf Ellinger, Carmen Ranftler, Christian Gehre, Cord Brakebusch, Margit Pavelka, Theresia Stradal, Klemens Rottner
The Rho-family small GTPase Cdc42 localizes at plasma membrane and Golgi complex and aside from protrusion and migration operates in vesicle trafficking, endo- and exocytosis as well as establishment and/or maintenance of cell polarity. The formin family members FMNL2 and -3 are actin assembly factors established to regulate cell edge protrusion during migration and invasion. Here we report these formins to additionally accumulate and function at the Golgi apparatus. As opposed to lamellipodia, Golgi targeting of these proteins required both their N-terminal myristoylation and the interaction with Cdc42...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28842335/concurrently-suppressing-multidrug-resistance-and-metastasis-of-breast-cancer-by-co-delivery-of-paclitaxel-and-honokiol-with-ph-sensitive-polymeric-micelles
#5
Ziqi Wang, Xinru Li, Dishi Wang, Yang Zou, Xiaoyou Qu, Chuyu He, Yunqiang Deng, Yao Jin, Yuanhang Zhou, Yanxia Zhou, Yan Liu
To concurrently suppress multidrug resistance (MDR) and metastasis of breast cancer cells, paclitaxel (PTX) and honokiol (HNK) were coencapsulated into pH-sensitive polymeric micelles based on poly(2-ethyl-2-oxazoline)-poly(D, L-lactide) (PEOz-PLA). The physicochemical properties of dual drug-loaded PEOz-PLA micelles were characterized in size, drug loading and in vitro release. The efficiency of MDR reversal for the micelles was testified by synergetic enhancement of cytotoxicity and uptake by MCF-7/ADR cells...
August 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28789934/targeting-calpains-a-novel-immunomodulatory-approach-for-microbial-infections
#6
REVIEW
Vijay Kumar, Ahmad Ali
Calpains are a family of Ca(2+) dependent cytosolic non-lysosomal proteases with well conserved cysteine-rich domains for enzymatic activity. Due to their functional dependency on Ca(2+) concentrations, they are involved in various cellular processes that are regulated by intracellular ca(2+) concentration (i.e. embryo development, cell development and migration, maintenance of cellular architecture and structure etc.). Calpains are widely studied proteases in mammalian (i.e. mouse and human) physiology and pathophysiology due to their ubiquitous presence...
August 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28754879/addition-of-2-ethylamino-acetonitrile-group-to-nitroxoline-results-in-significantly-improved-anti-tumor-activity-in-vitro-and-in-vivo
#7
Ana MitroviÄ, Izidor SosiÄ, Špela Kos, Urša Lampreht Tratar, Barbara Breznik, Simona Kranjc, Bojana MirkoviÄ, Stanislav Gobec, Tamara Lah, Maja Ä emaÅ Ar, Gregor Serša, Janko Kos
Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751541/downregulation-of-cavin-1-expression-via-increasing-caveolin-1-degradation-prompts-the-proliferation-and-migration-of-vascular-smooth-muscle-cells-in-balloon-injury-induced-neointimal-hyperplasia
#8
Li-Jun Zhou, Xue-Ying Chen, Shui-Ping Liu, Lin-Lin Zhang, Ya-Nan Xu, Pan-Wei Mu, Deng-Feng Geng, Zhi Tan
BACKGROUND: Percutaneous coronary intervention has been widely used in the treatment of ischemic heart disease, but vascular restenosis is a main limitation of percutaneous coronary intervention. Our previous work reported that caveolin-1 had a key functional role in intimal hyperplasia, whereas whether Cavin-1 (another important caveolae-related protein) was involved is still unknown. Therefore, we will investigate the effect of Cavin-1 on neointimal formation. METHODS AND RESULTS: Balloon injury markedly reduced Cavin-1 protein and enhanced ubiquitin protein expression accompanied with neointimal hyperplasia in injured carotid arteries, whereas Cavin-1 mRNA had no change...
July 27, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28745237/anethole-inhibits-the-proliferation-of-human-prostate-cancer-cells-via-induction-of-cell-cycle-arrest-and-apoptosis
#9
Ayman Ibrahim Elkady
BACKGROUND: Prostate cancer-associated mortality is increasing at an alarming rate, which highlights the inevitability for unearthing novel agent for the management of this disease. Anethole, a major constituent of Foeniculum vulgare (fennel) essential oil, is widely used in folk medicine; it possesses anti-oxidant, anti-inflammatory, anti-proliferative and tumoricidal potentialities. OBJECTIVE: The current research was conducted to assess the impact of anethole on prostate cancer cell line, PC-3, and to delineate the molecular mechanism of action...
July 25, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28735522/characterization-of-the-role-of-rilp-in-cell-migration
#10
Azzurra Margiotta, Cinzia Progida, Oddmund Bakke, Cecilia Bucci
Rab-interacting lysosomal protein (RILP) is a regulator of late stages of endocytosis. Recent work proved that depletion of RILP promotes migration of breast cancer cells in wound healing assay, whereas its overexpression influences re-arrangements of actin cytoskeleton. Here, we further characterized the role of RILP in cell migration by analyzing several aspects of this process. We showed that RILP is fundamental also for migration of lung cancer cells regulating cell velocity. RILP silencing did not affect Golgi apparatus nor microtubules reorientation during migration...
May 31, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28733362/loss-of-cln5-causes-altered-neurogenesis-in-a-childhood-neurodegenerative-disorder
#11
E Savchenko, Y Singh, H Konttinen, K Lejavova, L Mediavilla Santos, A Grubman, V Kärkkäinen, V Keksa-Goldsteine, N Naumenko, P Tavi, A R White, T M Malm, J Koistinaho, K M Kanninen
Neural stem/progenitor cells (NPCs) generate new neurons in the brain throughout the lifetime in an intricate process called neurogenesis. Neurogenic alterations are a common feature of several adult-onset neurodegenerative diseases. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited neurodegenerative diseases that mainly affect children. Pathological features of the NCLs include accumulation of lysosomal storage material, neuroinflammation, and neuronal degeneration, yet the exact cause of this group of diseases remains poorly understood...
July 21, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28717168/dynamics-and-function-of-cxcr4-in-formation-of-the-granule-cell-layer-during-hippocampal-development
#12
Yuka Mimura-Yamamoto, Hiroshi Shinohara, Taichi Kashiwagi, Toru Sato, Seiji Shioda, Tatsunori Seki
In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708385/chloroquine-modified-hydroxyethyl-starch-as-a-polymeric-drug-for-cancer-therapy
#13
Richard Sleightholm, Bin Yang, Fei Yu, Ying Xie, David Oupický
Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. Atomic force microscopy was used to demonstrate a pH-dependent assembly of CQ-HES into well-defined nanoparticles...
July 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28687334/a-cysteine-protease-cathepsin-z-from-disk-abalone-haliotis-discus-discus-genomic-characterization-and-transcriptional-profiling-during-bacterial-infections
#14
G I Godahewa, N C N Perera, Sukkyoung Lee, Myoung-Jin Kim, Jehee Lee
Cathepsin Z (CTSZ) is lysosomal cysteine protease of the papain superfamily. It participates in the host immune defense via phagocytosis, signal transduction, cell-cell communication, proliferation, and migration of immune cells such as monocytes, macrophages, and dendritic cells. Hence, CTSZ is also acknowledged as an acute-phase protein in host immunity. In this study, we sought to identify the CTSZ homolog from disk abalone (AbCTSZ) and characterize it at the molecular, genomic, and transcriptional levels...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28644509/comparative-transcriptomic-analysis-of-two-important-life-stages-of-angiostrongylus-cantonensis-fifth-stage-larvae-and-female-adults
#15
Liang Yu, Binbin Cao, Ying Long, Meks Tukayo, Chonglv Feng, Wenzhen Fang, Damin Luo
The mechanisms involved in the fast growth of Angiostrongylus cantonensis from fifth-stage larvae (L5) to female adults and how L5 breaks through the blood-brain barrier in a permissive host remain unclear. In this work, we compared the transcriptomes of these two life stages to identify the main factors involved in the rapid growth and transition to adulthood. RNA samples from the two stages were sequenced and assembled de novo. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of 1,346 differentially expressed genes between L5 and female adults was then undertaken...
April 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#16
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28610928/kinetic-and-biophysical-characterization-of-a-lysosomal-%C3%AE-l-fucosidase-from-the-fresh-water-mussel-lamellidens-corrianus
#17
A Venugopal, C Sudheer Kumar, Nadimpalli Siva Kumar, Musti J Swamy
Kinetic and biophysical studies have been carried out on a lysosomal α-l-fucosidase purified from the fresh water mussel, Lamellidens corrianus. The enzyme migrates as a single band in SDS-PAGE as well as native PAGE corresponding to a Mr of 56kDa. Mass spectrometric analysis yielded a molecular mass of 56175.1Da for the enzyme, and peptide mass fingerprinting studies showed that it shares sequence homology with other fucosidases. Zymogram analysis showed that the α-l-fucosidase hydrolyzed 4-methyl umbelliferyl α-l-fucopyranoside...
November 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28599312/cullin-3spop-ubiquitin-e3-ligase-promotes-the-poly-ubiquitination-and-degradation-of-hdac6
#18
Yuyong Tan, Yanpeng Ci, Xiangpeng Dai, Fei Wu, Jianping Guo, Deliang Liu, Brian J North, Jirong Huo, Jinfang Zhang
The histone deacetylase 6 (HDAC6) plays critical roles in human tumorigenesis and metastasis. As such, HDAC6-selective inhibitors have entered clinical trials for cancer therapy. However, the upstream regulator(s), especially ubiquitin E3 ligase(s), responsible for controlling the protein stability of HDAC6 remains largely undefined. Here, we report that Cullin 3SPOP earmarks HDAC6 for poly-ubiquitination and degradation. We found that the proteasome inhibitor MG132, or the Cullin-based E3 ligases inhibitor MLN4924, but not the autophagosome-lysosome inhibitor bafilomycin A1, stabilized endogenous HDAC6 protein in multiple cancer cell lines...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28548682/arthrotomy-based-pre-clinical-models-of-particle-induced-osteolysis-a-systematic-review
#19
REVIEW
Meghan M Moran, Brittany M Wilson, Ryan D Ross, Amarjit S Virdi, D Rick Sumner
We completed a systematic literature review of in vivo animal models that use arthrotomy-based methods to study particle-induced peri-implant osteolysis. The purpose of the review was to characterize the models developed to date, to determine the questions addressed, to assess scientific rigor and transparency and to identify gaps in knowledge. We probed three literature databases (Medline, Embase and Scopus) and found 77 manuscripts that fit the search parameters. In the most recent 10 years, researchers mainly used rat and mouse models, whereas in the previous 20 years large animal, canine and rabbit models were more common...
May 26, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28534963/n-acetylglucosaminyltransferase-iva-promotes-invasion-of-choriocarcinoma
#20
Kimihiro Nishino, Eiko Yamamoto, Kaoru Niimi, Yoko Sekiya, Yoriko Yamashita, Fumitaka Kikkawa
Gestational trophoblastic neoplasia (GTN) results from the malignant transformation of placental trophoblasts which secrete human chorionic gonadotropin (hCG) as do normal placenta or hydatidiform mole. N-acetylglucosaminyltransferase IV (GnT-IV) is a glycosyltransferase which catalyses the formation of β1,4GlcNAc branches on the mannose core of N-glycans. Previous studies reported that β1,4GlcNAc branches on hCG were detected in GTN but not in normal pregnancy or hydatidiform mole. The aim of the present study was to understand the role of GnT-IVa in choriocarcinoma and find the target proteins for GnT-IVa glycosylation which contribute to the malignancy of choriocarcinoma...
May 23, 2017: Oncology Reports
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