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https://www.readbyqxmd.com/read/28644973/il-18-il-15-il-12-synergy-induces-elevated-and-prolonged-ifn-%C3%AE-production-by-ex-vivo-expanded-nk-cells-which-is-not-due-to-enhanced-stat4-activation
#1
Evan Lusty, Sophie M Poznanski, Karen Kwofie, Talveer S Mandur, Dean A Lee, Carl D Richards, Ali A Ashkar
The synergistic effect of IL-18/IL-15/IL-12 stimulation potently activates NK cells, inducing high levels of IFN-γ production. As a result of this potent stimulatory effect, NK cell pre-activation with IL-18/IL-15/IL-12 is being developed as a cancer immunotherapy. Ex vivo expansion of NK cells enables the efficient generation of large numbers of NK cells for wide-scale and repeated therapeutic use, and is thus an important source of NK cells for clinical application. However, the effects of IL-18/IL-15/IL-12 stimulation on ex vivo expanded NK cells have not yet been assessed...
June 20, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28644129/anti-cd47-antibodies-induce-phagocytosis-of-live-malignant-b-cells-by-macrophages-via-the-fc-domain-resulting-in-cell-death-by-phagoptosis
#2
Lucy E Métayer, Anna Vilalta, G A Amos Burke, Guy C Brown
When expressed on the surface of cells, CD47 inhibits phagocytosis of these cells by phagocytes. Most human cancers overexpress CD47, and antibodies to CD47 have shown a remarkable ability to clear a range of cancers in animal models. However, the mechanism by which these antibodies cause cancer cell death is unclear. We find that CD47 is expressed on the surface of three B-cell lines from human malignancies: 697 (pre-B-ALL lymphoblasts), Ramos and DG-75 (both mature B-cells, Burkitt's lymphoma), and anti-CD47 antibodies greatly increase the phagocytosis of all three cell line by macrophages...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643325/surface-expression-of-anti-cd3scfv-stimulates-locoregional-immunotherapy-against-hepatocellular-carcinoma-depending-on-the-e1a-engineered-human-umbilical-cord-mesenchymal-stem-cells
#3
Qing Zhang, Xiang-Fei Yuan, Yang Lu, Zhen-Zhen Li, Shi-Qi Bao, Xiao-Long Zhang, Yuan-Yuan Yang, Dong-Mei Fan, Yi-Zhi Zhang, Chen-Xuan Wu, Hong-Xing Guo, Yan-Jun Zhang, Ye Zhou, Dong-Sheng Xiong
Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction...
June 23, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28642787/mutational-signatures-are-critical-for-proper-estimation-of-purifying-selection-pressures-in-cancer-somatic-mutation-data-when-using-the-dn-ds-metric
#4
Jimmy Van den Eynden, Erik Larsson
Large cancer genome sequencing initiatives have led to the identification of cancer driver genes based on signals of positive selection in somatic mutation data. Additionally, the identification of purifying (negative) selection has the potential to identify essential genes that may be of therapeutic interest. The most widely used way of quantifying selection pressures in protein-coding genes is the dN/dS metric, which compares non-synonymous to synonymous substitution rates. In this study, we examine whether and how this metric is influenced by the mutational processes that have been active during tumor evolution...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28642044/crossregulation-between-the-insertion-of-hexadecylphosphocholine-miltefosine-into-lipid-membranes-and-their-rheology-and-lateral-structure
#5
Yenisleidy de Las Mercedes Zulueta Díaz, María Laura Fanani
Hexadecylphosphocholine (HePC, miltefosine) is an alkylphospholipid used clinically for the topical treatment of cancer and against leishmaniasis. The mechanism of action of HePC, not yet elucidated, involves its insertion into the plasma membrane, affecting lipid homeostasis. It has also been proposed that HePC directly affects lipid raft stability and function in cell membranes. The present work deals with two main questions in the understanding of the action of HePC: the bases for membrane selectivity and as a membrane perturbator agent...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641473/co-targeting-intracellular-ph-and-essential-amino-acid-uptake-cooperates-to-induce-cell-death-of-t-all-ll-cells
#6
Véronique Imbert, Marielle Nebout, Didier Mary, Hitoshi Endou, Michael F Wempe, Claudiu T Supuran, Jean-Yves Winum, Jean-François Peyron
Cancer cells reprogram their metabolism to optimize their growth and proliferation in the host microenvironment. For this purpose, they enhance the uptake of extracellular nutrients and deal with the metabolic waste products through the overexpression of numerous membrane proteins including amino-acid transporters (LAT1) and acid-base regulating enzymes, such as carbonic anhydrases (CAs). Here we describe the anti-tumoral effects of a new class of CAXII inhibitors, the glycosyl coumarins on T-ALL/LL cells. These effects appeared to be mediated through inhibition of mTOR/Akt pathway and c-myc downregulation...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28641308/detection-of-phosphatidylserine-positive-exosomes-for-the-diagnosis-of-early-stage-malignancies
#7
Raghava Sharma, Xianming Huang, Rolf A Brekken, Alan J Schroit
BACKGROUND: There has been increasing interest in the detection of tumour exosomes in blood for cancer diagnostics. Most studies have focussed on miRNA and protein signatures that are surrogate markers for specific tumour types. Because tumour cells and tumour-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker. METHODS: This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumour exosomes in the blood of tumour-bearing mice...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28640312/speciation-in-human-blood-of-metvan-a-vanadium-based-potential-anti-tumor-drug
#8
Daniele Sanna, Valeria Ugone, Giovanni Micera, Péter Buglyó, Linda Bíró, Eugenio Garribba
The first report on the anti-cancer activity of the compound Metvan, [V(IV)O(Me2phen)2(SO4)], where Me2phen is 4,7-dimethyl-1,10-phenanthroline, dates back to 2001. Although it was immediately identified as one of the most promising multitargeted anti-cancer V compounds, no development on the medical experimentation was carried out. One of the possible reasons is the lack of information on its speciation in aqueous solution and its thermodynamic stability, factors which influence the transport in the blood and the final form which reaches the target organs...
June 22, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28639122/targeting-prostate-specific-membrane-antigen-psma-with-f-18-labeled-compounds-the-influence-of-prosthetic-groups-on-tumor-uptake-and-clearance-profile
#9
Vincent Bouvet, Melinda Wuest, Justin J Bailey, Cody Bergman, Nancy Janzen, John F Valliant, Frank Wuest
PURPOSE: Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in the majority of prostate cancers. The favorable positron emission tomography (PET) imaging profile of the PSMA imaging agent 2-(3-(1-carboxy-5-[(6-[(18)F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentane-dioic acid [(18)F]DCFPyL in preclinical prostate cancer models and in prostate cancer patients stimulated the development and validation of other fluorine-containing PSMA inhibitors to further enhance pharmacokinetics and simplify production methods...
June 21, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28638884/anticancer-activity-of-5-7-dimethoxyflavone-against-liver-cancer-cell-line-hepg2-involves-apoptosis-ros-generation-and-cell-cycle-arrest
#10
Hengping Li, Xiaolei Zhang, Weixing Wang
BACKGROUND: Flavonoids are considered potential anticancer agents owing to their properties to interact with a diversity of cellular entities. Among flavonoids, methylated flavones are more efficient anticancer agents due to their higher stability in vivo. The purpose of the present study was, therefore, to evaluate the anticancer effect of methylated natural flavonoid 5, 7-dimethoxyflavone (5, 7-DMF). MATERIALS AND METHODS: MTT assay was used to determine the anticancer activity and IC50 of 5, -DMF)...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28638867/antitumor-effects-of-chrysanthemin-in-pc-3-human-prostate-cancer-cells-are-mediated-via-apoptosis-induction-caspase-signalling-pathway-and-loss-of-mitochondrial-membrane-potential
#11
De-Kang Sun, Lin Wang, Peng Zhang
BACKGROUND: The main objective of the current research work was to investigate the antitumor and apoptotic effects of chrysanthemin in PC-3 human prostate cancer cells. MATERIALS AND METHODS: MTT assay was used to evaluate the effects of chrysanthemin on cell viability whereas flow cytometry along with fluorescence microscopy were used to study apoptotic induction in these cells. Effects on caspase activation were detected through western blot assay. RESULTS: Results showed that chrysanthemin inhibited cancer cell growth in PC-3 cancer cells in a time-dependent as well as concentration-dependent manner...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28638479/should-low-molecular-weight-psma-targeted-ligands-get-bigger-and-use-albumin-ligands-for-psma-targeting
#12
EDITORIAL
Steve S Huang, Warren D W Heston
Prostate Specific Membrane Antigen (PSMA) is strongly expressed in prostate cancer. Recently a number of low-molecular-weight inhibitors have demonstrated excellent PSMA targeting activity for both imaging as well as Lutecium-177 radiotherapy in human trials. The paper by Choy et al raises the question of whether we can further increase the effectiveness of PSMA targeted therapy by adding an albumin-binding entity to low-molecular-weight agents.
2017: Theranostics
https://www.readbyqxmd.com/read/28638478/-177-lu-labeled-phosphoramidate-based-psma-inhibitors-the-effect-of-an-albumin-binder-on-biodistribution-and-therapeutic-efficacy-in-prostate-tumor-bearing-mice
#13
Cindy J Choy, Xiaoxi Ling, Jonathan J Geruntho, Sophia K Beyer, Joseph D Latoche, Beatrice Langton-Webster, Carolyn J Anderson, Clifford E Berkman
Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a (177)Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401)...
2017: Theranostics
https://www.readbyqxmd.com/read/28638287/use-of-sodium-hyaluronate-carboxymethylcellulose-bioresorbable-membrane-in-loop-ileostomy-construction-facilitates-stoma-closure
#14
Danielle M Bertoni, Kerry L Hammond, David E Beck, Terry C Hicks, Charles B Whitlow, H David Vargas, David A Margolin
BACKGROUND: Loop ileostomy is a common adjunct to surgical procedures for low rectal cancers and inflammatory bowel disease. Ileostomy closure through a limited incision can be technically challenging. We hypothesized that placing a sodium hyaluronate/carboxymethylcellulose (SH/CMC) bioresorbable membrane at loop ileostomy creation would decrease stoma closure time without increasing morbidity. METHODS: In a retrospective review at a single institution with 6 board-certified colorectal surgeons, patients with loop ileostomy creation and closure between September 1999 and December 2011 were grouped based on SH/CMC placement at ileostomy creation...
2017: Ochsner Journal
https://www.readbyqxmd.com/read/28638048/maternal-folate-deficiency-causes-inhibition-of-mtor-signaling-down-regulation-of-placental-amino-acid-transporters-and-fetal-growth-restriction-in-mice
#15
Fredrick J Rosario, Peter W Nathanielsz, Theresa L Powell, Thomas Jansson
Maternal folate deficiency is linked to restricted fetal growth, however the underlying mechanisms remain to be established. Here we tested the hypothesis that mTOR functions as a folate sensor in vivo in mice and that maternal folate deficiency inhibits placental mTOR signaling and amino acid transporter activity and causes fetal growth restriction. Folate deficient mice had lower serum folate (-60%). In late pregnancy, fetal weight in the folate deficient group was decreased (-17%, p < 0.05), whereas placental weight, litter size and crown rump length were unaltered...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637799/-68-ga-psma-pet-ct-and-volumetric-morphology-of-pet-positive-lymph-nodes-stratified-by-tumor-differentiation-of-prostate-cancer
#16
Maria Vinsensia, Peter L Choyke, Boris Hadaschik, Tim Holland-Letz, Jan Moltz, Klaus Kopka, Isabel Rauscher, Walter Mier, Markus Schwaiger, Uwe Haberkorn, Tobias Maurer, Clemens Kratochwil, Matthias Eiber, Frederik Giesel
(68)Ga prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computer tomography (CT) is a new method to detect early nodal metastases in patients with biochemical relapse of prostate cancer (PCa). In this retrospective investigation the dimensions, volume, localization and maximum standardized uptake value (SUVmax) of nodes identified by (68)Ga-PSMA were correlated to their Gleason score (GS) at diagnosis. Methods: All PET/CT images were acquired 60±10 min after intravenous injection of (68)Ga-PSMA (mean dose 176 MBq)...
June 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28637688/fus-ddit3-fusion-protein-driven-igf-ir-signaling-is-a-therapeutic-target-in-myxoid-liposarcoma
#17
Marcel Trautmann, Jasmin Menzel, Christian Bertling, Magdalene Cyra, Ilka Isfort, Konrad Steinestel, Sandra Elges, Inga Grünewald, Bianca Altvater, Claudia Rossig, Stefan Fröhling, Susanne Hafner, Thomas Simmet, Pierre Åman, Eva Wardelmann, Sebastian Huss, Wolfgang Hartmann
Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS-DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS‑DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28637250/use-of-spytag-spycatcher-to-construct-bispecific-antibodies-that-target-two-epitopes-of-a-single-antigen
#18
Kyohei Yumura, Hiroki Akiba, Satoru Nagatoishi, Osamu Kusano-Arai, Hiroko Iwanari, Takao Hamakubo, Kouhei Tsumoto
Bispecific antibody targeting of two different antigens is promising, but when fragment-based antibodies are used, homogeneous production is difficult. To overcome this difficulty, we developed a method using the SpyTag/SpyCatcher system in which a covalent bond is formed between the two polypeptides. Using this method, we constructed a bispecific antibody that simultaneously interacted with two different epitopes of ROBO1, a membrane protein associated with cancer progression. A bispecific tetravalent antibody with an additional functional moiety was also constructed by using a dimeric biotin-binding protein...
June 16, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28636979/exosomes-in-diagnosis-and-therapy-of-prostate-cancer
#19
REVIEW
Jun Pan, Meng Ding, Kai Xu, Chunhua Yang, Li-Jun Mao
Exosomes are small vesicular bodies released by a variety of cells. Exosomes contain miRNAs, mRNAs and proteins with the potential to regulate signaling pathways in recipient cells. Exosomes deliver nucleic acids and proteins to mediate the communication between cancer cells and stroma cells. In this review, we summarize recent progress in our understanding of the role of exosomes in prostate cancer. The tumorigenesis, metastasis and drug resistance of prostate cancer are associated with the cargos of exosomes such as miRNAs, lncRNAs and proteins...
June 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636040/tamoxifen-like-metallocifens-target-the-thioredoxin-system-determining-mitochondrial-impairment-leading-to-apoptosis-in-jurkat-cells
#20
Valeria Scalcon, Michèle Salmain, Alessandra Folda, Siden Top, Pascal Pigeon, Hui Zhi Shirley Lee, Gérard Jaouen, Alberto Bindoli, Anne Vessières, Maria Pia Rigobello
Tamoxifen-like metallocifens (TLMs) of the group-8 metals (Fe, Ru, and Os) show strong anti-proliferative activity on cancer cell lines resistant to apoptosis, owing to their unique redox properties. In contrast, the thioredoxin system, which is involved in cellular redox balance, is often overexpressed in cancer cells, especially in tumour types resistant to standard chemotherapies. Therefore, we investigated the effect of these three TLMs on the thioredoxin system and evaluated the input of the metallocene unit in comparison with structurally related organic tamoxifens...
June 21, 2017: Metallomics: Integrated Biometal Science
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