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https://www.readbyqxmd.com/read/29022480/evaluation-of-serum-autoantibodies-against-tumor-associated-antigens-as-biomarkers-in-lung-cancer
#1
Pei Li, Jian-Xiang Shi, Meng-Tao Xing, Li-Ping Dai, Ji-Tian Li, Jian-Ying Zhang
We evaluated autoantibodies against nine tumor-associated antigens, including p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA as serological markers in lung cancer. Enzyme-linked immunosorbent assay (ELISA) was used to detect autoantibodies in sera from 50 lung cancer patients and 42 normal controls. Then, four tumor-associated antigens of higher values were selected and validated in sera from validation group. Western blot and serum absorption test were used to confirm positive findings from ELISA...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28903407/mir-331-3p-and-aurora-kinase-inhibitor-ii-co-treatment-suppresses-prostate-cancer-tumorigenesis-and-progression
#2
Michael R Epis, Keith M Giles, Dianne J Beveridge, Kirsty L Richardson, Patrick A Candy, Lisa M Stuart, Jacqueline Bentel, Ronald J Cohen, Peter J Leedman
RNA-based therapeutics could represent a new avenue of cancer treatment. miRNA 331-3p (miR-331-3p) is implicated in prostate cancer (PCa) as a putative tumor suppressor, but its functional activity and synergy with other anti-tumor agents is largely unknown. We found miR-331-3p expression in PCa tumors was significantly decreased compared to non-malignant matched tissue. Analysis of publicly available PCa gene expression data sets showed miR-331-3p expression negatively correlated with Gleason Score, tumor stage, lymph node involvement and PSA value, and was significantly down regulated in tumor tissue relative to normal prostate tissue...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28821441/in-situ-detection-of-the-activation-of-rac1-and-rala-small-gtpases-in-mouse-adipocytes-by-immunofluorescent-microscopy-following-in-vivo-and-ex-vivo-insulin-stimulation
#3
Nobuyuki Takenaka, Yuma Nihata, Sho Ueda, Takaya Satoh
Rac1 has been implicated in insulin-dependent glucose uptake by mechanisms involving plasma membrane translocation of the glucose transporter GLUT4 in skeletal muscle. Although the uptake of glucose is also stimulated by insulin in adipose tissue, the role for Rac1 in adipocyte insulin signaling remains controversial. As a step to reveal the role for Rac1 in adipocytes, we aimed to establish immunofluorescent microscopy to detect the intracellular distribution of activated Rac1. The epitope-tagged Rac1-binding domain of a Rac1-specific target was utilized as a probe that specifically recognizes the activated form of Rac1...
November 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28745416/a-role-for-host-cell-exocytosis-in-inlb-mediated-internalisation-of-listeria-monocytogenes
#4
Hoan Van Ngo, Manmeet Bhalla, Da-Yuan Chen, Keith Ireton
The bacterial surface protein InlB mediates internalisation of Listeria monocytogenes into human cells through interaction with the host receptor tyrosine kinase, Met. InlB-mediated entry requires localised polymerisation of the host actin cytoskeleton. Apart from actin polymerisation, roles for other host processes in Listeria entry are unknown. Here, we demonstrate that exocytosis in the human cell promotes InlB-dependent internalisation. Using a probe consisting of VAMP3 with an exofacial green fluorescent protein tag, focal exocytosis was detected during InlB-mediated entry...
November 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28722830/ralfuranones-contribute-to-mushroom-type-biofilm-formation-by-ralstonia-solanacearum-strain-oe1-1
#5
Yuka Mori, Yuki Hosoi, Shiho Ishikawa, Kazusa Hayashi, Yu Asai, Hideyuki Ohnishi, Mika Shimatani, Kanako Inoue, Kenichi Ikeda, Hitoshi Nakayashiki, Yasuyo Nishimura, Kouhei Ohnishi, Akinori Kiba, Kenji Kai, Yasufumi Hikichi
After invasion into intercellular spaces of tomato plants, the soil-borne plant pathogenic Ralstonia solanacearum strain OE1-1 forms mushroom-shaped biofilms (mushroom-type biofilms, mBFs) on tomato cells, leading to its virulence. The strain OE1-1 produces aryl-furanone secondary metabolites, ralfuranones (A, B, J, K and L), dependent on the quorum sensing (QS) system with methyl 3-hydroxymyristate (3-OH MAME) synthesized by PhcB as a QS signal. Ralfuranones are associated with the feedback loop of the QS system...
July 19, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28666255/mir-331-3p-and-aurora-kinase-inhibitor-ii-co-treatment-suppresses-prostate-cancer-tumorigenesis-and-progression
#6
Michael R Epis, Keith M Giles, Dianne J Beveridge, Kirsty L Richardson, Patrick A Candy, Lisa M Stuart, Jacqueline Bentel, Ronald J Cohen, Peter J Leedman
RNA-based therapeutics could represent a new avenue of cancer treatment. miRNA 331-3p (miR-331-3p) is implicated in prostate cancer (PCa) as a putative tumor suppressor, but its functional activity and synergy with other anti-tumor agents is largely unknown. We found miR-331-3p expression in PCa tumors was significantly decreased compared to non-malignant matched tissue. Analysis of publicly available PCa gene expression data sets showed miR-331-3p expression negatively correlated with Gleason Score, tumor stage, lymph node involvement and PSA value, and was significantly down regulated in tumor tissue relative to normal prostate tissue...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618923/serum-autoantibodies-against-a-panel-of-15-tumor-associated-antigens-in-the-detection-of-ovarian-cancer
#7
Hao Sun, Jian-Xiang Shi, Hong-Fei Zhang, Meng-Tao Xing, Pei Li, Li-Ping Dai, Cheng-Lin Luo, Xiao Wang, Peng Wang, Hua Ye, Liu-Xia Li, Jian-Ying Zhang
In this study, enzyme-linked immunosorbent assay has been used to examine the frequencies of serum autoantibodies against two candidate tumor-associated antigens intensively selected from the Human Protein Atlas database, in combination with 13 tumor-associated antigens available from our lab in sera from 44 OC patients and 50 normal healthy controls. Conventional evaluation (mean + 3SD as the cutoff value to determine a positive reactivity), receiver operating characteristic curve analyses, and classification tree analysis were further used to evaluate the diagnostic performance of autoantibodies against these tumor-associated antigens (anti-tumor-associated antigens) in ovarian cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28545253/encapsulation-of-the-antioxidant-r-%C3%AE-lipoic-acid-in-permethylated-%C3%AE-and-%C3%AE-cyclodextrins-thermal-and-x-ray-structural-characterization-of-the-1-1-inclusion-complexes
#8
Mino R Caira, Susan A Bourne, Buntubonke Mzondo
The naturally occurring compound α-lipoic acid (ALA) is implicated in manifold critical biological roles and its potent antioxidant properties and potential for treatment of various diseases have led to its widespread use as a dietary supplement. However, shortcomings of poor aqueous solubility and low thermal stability have hampered its development as a medicinal agent, prompting the use of cyclodextrins (CDs) to address these problems. The paucity of published structural data on the nature of the interactions between ALA and CDs motivated the present study, which describes the synthesis and X-ray structural elucidation of crystalline inclusion complexes between the biologically relevant R-(+)-α-lipoic acid (RALA) and the host molecules permethylated α-CD (TMA) and permethylated β-CD (TMB)...
May 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28498728/a-family-affair-a-ral-exocyst-centered-network-links-ras-rac-rho-signaling-to-control-cell-migration
#9
Giulia Zago, Marco Biondini, Jacques Camonis, Maria Carla Parrini
Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation...
May 12, 2017: Small GTPases
https://www.readbyqxmd.com/read/28459538/substrate-recognition-of-martx-ras-rap1-specific-endopeptidase
#10
Marco Biancucci, Amy E Rabideau, Zeyu Lu, Alex R Loftis, Bradley L Pentelute, Karla J F Satchell
Ras/Rap1-specific endopeptidase (RRSP) is a cytotoxic effector domain of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin of highly virulent strains of Vibrio vulnificus. RRSP blocks RAS-MAPK kinase signaling by cleaving Ras and Rap1 within the switch I region between Y32 and D33. Although the RRSP processing site is highly conserved among small GTPases, only Ras and Rap1 have been identified as proteolytic substrates. Here we report that residues Y32 and D33 at the scissile bond play an important role in RRSP substrate recognition, while the nucleotide state of Ras has an only minimal effect...
May 30, 2017: Biochemistry
https://www.readbyqxmd.com/read/28436620/arginine-rich-peptide-based-mrna-nanocomplexes-efficiently-instigate-cytotoxic-t-cell-immunity-dependent-on-the-amphipathic-organization-of-the-peptide
#11
Vimal K Udhayakumar, Ans De Beuckelaer, Joanne McCaffrey, Cian M McCrudden, Jonathan L Kirschman, Daryll Vanover, Lien Van Hoecke, Kenny Roose, Kim Deswarte, Bruno G De Geest, Stefan Lienenklaus, Philip J Santangelo, Johan Grooten, Helen O McCarthy, Stefaan De Koker
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast are rare in the context of mRNA vaccination. This paper describes the potential of a cell-penetrating peptide containing the amphipathic RALA motif to deliver antigen-encoding mRNA to the immune system. RALA condenses mRNA into nanocomplexes that display acidic pH-dependent membrane disruptive properties. RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow expression of mRNA inside the dendritic cell cytosol...
April 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28415752/correlation-between-facial-morphology-and-gene-polymorphisms-in-the-uygur-youth-population
#12
Huiyu He, Xue Mi, Jiayu Zhang, Qin Zhang, Yuan Yao, Xu Zhang, Feng Xiao, Chunping Zhao, Shutao Zheng
Human facial morphology varies considerably among individuals and can be influenced by gene polymorphisms. We explored the effects of single nucleotide polymorphisms (SNPs) on facial features in the Uygur youth population of the Kashi area in Xinjiang, China. Saliva samples were collected from 578 volunteers, and 10 SNPs previously associated with variations in facial physiognomy were genotyped. In parallel, 3D images of the subjects' faces were obtained using grating facial scanning technology. After delimitation of 15 salient landmarks, the correlation between SNPs and the distances between facial landmark pairs was assessed...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28363788/mesenchymal-stem-cell-fate-following-non-viral-gene-transfection-strongly-depends-on-the-choice-of-delivery-vector
#13
T Gonzalez-Fernandez, B N Sathy, C Hobbs, G M Cunniffe, H O McCarthy, N J Dunne, V Nicolosi, F J O'Brien, D J Kelly
Controlling the phenotype of mesenchymal stem cells (MSCs) through the delivery of regulatory genes is a promising strategy in tissue engineering (TE). Essential to effective gene delivery is the choice of gene carrier. Non-viral delivery vectors have been extensively used in TE, however their intrinsic effects on MSC differentiation remain poorly understood. The objective of this study was to investigate the influence of three different classes of non-viral gene delivery vectors: (1) cationic polymers (polyethylenimine, PEI), (2) inorganic nanoparticles (nanohydroxyapatite, nHA) and (3) amphipathic peptides (RALA peptide) on modulating stem cell fate after reporter and therapeutic gene delivery...
March 29, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28325821/phosphorylation-of-the-exocyst-protein-exo84-by-tbk1-promotes-insulin-stimulated-glut4-trafficking
#14
Maeran Uhm, Merlijn Bazuine, Peng Zhao, Shian-Huey Chiang, Tingting Xiong, Sheelarani Karunanithi, Louise Chang, Alan R Saltiel
Insulin stimulates glucose uptake through the translocation of the glucose transporter GLUT4 to the plasma membrane. The exocyst complex tethers GLUT4-containing vesicles to the plasma membrane, a process that requires the binding of the G protein (heterotrimeric guanine nucleotide-binding protein) RalA to the exocyst complex. We report that upon activation of RalA, the protein kinase TBK1 phosphorylated the exocyst subunit Exo84. Knockdown of TBK1 blocked insulin-stimulated glucose uptake and GLUT4 translocation; knockout of TBK1 in adipocytes blocked insulin-stimulated glucose uptake; and ectopic overexpression of a kinase-inactive mutant of TBK1 reduced insulin-stimulated glucose uptake in 3T3-L1 adipocytes...
March 21, 2017: Science Signaling
https://www.readbyqxmd.com/read/28325291/systemic-rala-inos-nanoparticles-a-potent-gene-therapy-for-metastatic-breast-cancer-coupled-as-a-biomarker-of-treatment
#15
Cian M McCrudden, John W McBride, Joanne McCaffrey, Ahlam A Ali, Nicholas J Dunne, Vicky L Kett, Jonathan A Coulter, Tracy Robson, Helen O McCarthy
This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28283553/genome-wide-association-study-of-sepsis-in-extremely-premature-infants
#16
Lakshmi Srinivasan, Grier Page, Haresh Kirpalani, Jeffrey C Murray, Abhik Das, Rosemary D Higgins, Waldemar A Carlo, Edward F Bell, Ronald N Goldberg, Kurt Schibler, Beena G Sood, David K Stevenson, Barbara J Stoll, Krisa P Van Meurs, Karen J Johnson, Joshua Levy, Scott A McDonald, Kristin M Zaterka-Baxter, Kathleen A Kennedy, Pablo J Sánchez, Shahnaz Duara, Michele C Walsh, Seetha Shankaran, James L Wynn, C Michael Cotten
OBJECTIVE: To identify genetic variants associated with sepsis (early-onset and late-onset) using a genome-wide association (GWA) analysis in a cohort of extremely premature infants. STUDY DESIGN: Previously generated GWA data from the Neonatal Research Network's anonymised genomic database biorepository of extremely premature infants were used for this study. Sepsis was defined as culture-positive early-onset or late-onset sepsis or culture-proven meningitis. Genomic and whole-genome-amplified DNA was genotyped for 1...
September 2017: Archives of Disease in Childhood. Fetal and Neonatal Edition
https://www.readbyqxmd.com/read/28116815/involvement-of-ralfuranones-in-the-quorum-sensing-signaling-pathway-and-virulence-of-ralstonia-solanacearum-strain-oe1-1
#17
Yuka Mori, Shiho Ishikawa, Hideyuki Ohnishi, Mika Shimatani, Yukino Morikawa, Kazusa Hayashi, Kouhei Ohnishi, Akinori Kiba, Kenji Kai, Yasufumi Hikichi
The soil-borne plant pathogenic Ralstonia solanacearum strain OE1-1 produces and secretes methyl 3-hydroxymyristate (3-OH MAME) as a quorum sensing (QS) signal, which contributes to its virulence. A global virulence regulator, PhcA, functioning through the QS system positively regulates the expression of ralA, which encodes furanone synthase, to produce aryl-furanone secondary metabolites, ralfuranones. A ralfuranone-deficient mutant (ΔralA) is weakly virulent when directly inoculated into tomato xylem vessels...
January 23, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28042326/exosomes-derived-from-mir-140-5p-overexpressing-human-synovial-mesenchymal-stem-cells-enhance-cartilage-tissue-regeneration-and-prevent-osteoarthritis-of-the-knee-in-a-rat-model
#18
Shi-Cong Tao, Ting Yuan, Yue-Lei Zhang, Wen-Jing Yin, Shang-Chun Guo, Chang-Qing Zhang
OBJECTIVES: Osteoarthritis (OA) is the most common joint disease throughout the world. Exosomes derived from miR-140-5p-overexpressing synovial mesenchymal stem cells (SMSC-140s) may be effective in treating OA. We hypothesized that exosomes derived from SMSC-140 (SMSC-140-Exos) would enhance the proliferation and migration abilities of articular chondrocytes (ACs) without harming extracellular matrix (ECM) secretion. METHODS: SMSCs were transfected with or without miR-140-5p...
2017: Theranostics
https://www.readbyqxmd.com/read/27979747/dna-vaccination-for-cervical-cancer-a-novel-technology-platform-of-rala-mediated-gene-delivery-via-polymeric-microneedles
#19
Ahlam A Ali, Cian M McCrudden, Joanne McCaffrey, John W McBride, Grace Cole, Nicholas J Dunne, Tracy Robson, Adrien Kissenpfennig, Ryan F Donnelly, Helen O McCarthy
HPV subtypes (16, 18) are associated with the development of cervical cancer, with oncoproteins E6 and E7 responsible for pathogenesis. The goal of this study was to evaluate our 'smart system' technology platform for DNA vaccination against cervical cancer. The vaccination platform brings together two main components; a peptide RALA which condenses DNA into cationic nanoparticles (NPs), and a polymeric polyvinylpyrrolidone (PVP) microneedle (MN) patch for cutaneous delivery of the loaded NPs. RALA condensed E6/E7 DNA into NPs not exceeding 100nm in diameter, and afforded the DNA protection from degradation in PVP...
April 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/27846370/dissolving-microneedles-for-dna-vaccination-improving-functionality-via-polymer-characterization-and-rala-complexation
#20
Grace Cole, Joanne McCaffrey, Ahlam A Ali, John W McBride, Cian M McCrudden, Eva M Vincente-Perez, Ryan F Donnelly, Helen O McCarthy
DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays...
January 2, 2017: Human Vaccines & Immunotherapeutics
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