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https://www.readbyqxmd.com/read/28738767/synthesis-and-anticancer-evaluation-of-thiazacridine-derivatives-reveals-new-selective-molecules-to-hematopoietic-neoplastic-cells
#1
Moacyr Jesus Barreto de Melo Rêgo, Wanessa Layssa Batista de Sena, Ricardo Olímpio de Moura, Iris Trindade Tenório Jacob, Thiago Ubiratan Lins E Lins, Michelly Cristiny Pereia, Maria do Carmo Alves de Lima, Marina Rocha Galdino-Pitta, Ivan da Rocha Pitta, Maira Galdino da Rocha Pitta
Cancer has become one of the leading causes of morbidity and mortality worldwide. Limitations associated with existing agents increase the need to develop more effective anticancer drugs to improve the therapeutic arsenal available. Here, we describe the synthesis, characterization, toxicity and selectivity in vitro of three novel thiazacridine derivatives (ATZD): (Z)-5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-4-thioxo-thiazolidin-2-one (LPSF/AC-99), (Z)-5-acridin-9-ylmethylene-3-(4-chloro-benzyl)-4-thioxo-thiazolidin-2-one (LPSF/AC-119) and (Z)-5-acridin-9-ylmethylene-3-(3-chloro-benzyl)-4-thioxo-thiazolidin-2-one (LPSF/AC-129)...
July 24, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28735186/development-of-a-robust-reporter-gene-assay-to-measure-the-bioactivity-of-anti-pd-1-anti-pd-l1-therapeutic-antibodies
#2
Lan Wang, Chuanfei Yu, Yalan Yang, Kai Gao, Junzhi Wang
Being regarded as the 'cancer panacea', the anti-PD-1/anti-PD-L1 monoclonal antibodies (mAbs) have become the R&D focus of biopharmaceutical industries. Several marketed such mAbs have been proved particularly effective in treating various cancers. However, the cell-based bioassay to measure the biological activities of the anti-PD-1/anti-PD-L1 mAbs as the lot release or stability test has been a great challenge to quality control laboratories due to the immunomodulating nature of the mAbs. Here, we describe the development and validation of a reporter gene assay consisting of two-cell systems to measure the bioactivity of the anti-PD-1/anti-PD-L1 mAbs...
May 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28733556/transmembrane-tnf-%C3%AE-promotes-activation-induced-cell-death-by-forward-and-reverse-signaling
#3
Meng Zhang, Jing Wang, Lingwei Jia, Jin Huang, Cheng He, Fuqing Hu, Lifei Yuan, Guihua Wang, Mingxia Yu, Zhuoya Li
Secretory tumor necrosis factor-alpha (sTNF-α) is known to mediate activation- induced cell death (AICD). However, the role of tmTNF-α in AICD is still obscure. Here, we demonstrated that tmTNF-α expression significantly increased accompanied with enhanced apoptosis during AICD in Jurkat and primary human T cells. Knockdown or enhancement of tmTNF-α expression in activated T cells suppressed or promoted AICD, respectively. Treatment of activated T cells with exogenous tmTNF-α significantly augmented AICD, indicating that tmTNF-α as an effector molecule mediates AICD...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28722776/esterified-trehalose-analogs-protect-mammalian-cells-from-heat-shock
#4
Jack T Bragg, Hannah K D'Ambrosio, Timothy J Smith, Caroline A Gorka, Faraz A Khan, Joshua T Rose, Andrew J Rouff, Terence S Fu, Brittany J Bisnett, Michael Boyce, Sudhir Khetan, Margot G Paulick
Trehalose is a disaccharide that is produced by many organisms to better enable them to survive environmental stresses, including heat, cold, desiccation, and reactive oxygen species. Mammalian cells do not naturally biosynthesize trehalose; however, when introduced into mammalian cells, trehalose provides protection from the damages associated with freezing and drying. One of the major difficulties in using trehalose as a cellular protectant for mammalian cells is the delivery of this disaccharide into the intracellular environment; mammalian cell membranes are impermeable to the hydrophilic sugar trehalose...
July 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28715864/in-vitro-and-in-vivo-anticancer-activity-of-2-acetyl-benzylamine-isolated-from-adhatoda-vasica-l-leaves
#5
C Balachandran, Y Arun, B Sangeetha, V Duraipandiyan, S Awale, N Emi, S Ignacimuthu, P T Perumal
One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28715128/sibiriline-a-new-small-chemical-inhibitor-of-receptor-interacting-protein-kinase-1-prevents-immune-dependent-hepatitis
#6
Fabienne Le Cann, Claire Delehouzé, Sabrina Penna-Leverrier, Aveline Filliol, Arnaud Comte, Olivier Delalande, Nathalie Desban, Blandine Baratte, Isabelle Gallais, Claire Piquet-Pellorce, Florence Faurez, Marion Bonnet, Yvette Mettey, Peter Goekjian, Michel Samson, Peter Vandenabeele, Stéphane Bach, Marie-Thérèse Dimanche-Boitrel
Necroptosis is a regulated form of cell death involved in several disease models including in particular liver diseases. Receptor-Interacting Protein Kinases, RIPK1 and RIPK3, are the main serine/threonine kinases driving this cell death pathway. We screened a non-commercial kinase-focused chemical library allowed us to identify Sibiriline as new inhibitor of necroptosis induced by TNF in Fas-Associated protein with Death Domain (FADD)-deficient Jurkat cells. Moreover, Sib inhibits necroptotic cell death induced by various death ligands in human or mouse cells while not protecting from caspase-dependent apoptosis...
July 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28710416/calquo-2-automated-fourier-space-population-level-quantification-of-global-intracellular-calcium-responses
#7
Angela M Lee, Huw Colin-York, Marco Fritzsche
Intracellular calcium acts as a secondary messenger in a wide variety of crucial biological signaling processes. Advances in fluorescence microscopy and calcium sensitive dyes has led to the routine quantification of calcium responses in non-excitable cells. However, the automatization of global intracellular calcium analysis at the single-cell level within a large population simultaneously remains challenging. One software, CalQuo (Calcium Quantification), offers some automatic features in calcium analysis...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701719/dynamic-gene-expression-response-to-altered-gravity-in-human-t-cells
#8
Cora S Thiel, Swantje Hauschild, Andreas Huge, Svantje Tauber, Beatrice A Lauber, Jennifer Polzer, Katrin Paulsen, Hartwin Lier, Frank Engelmann, Burkhard Schmitz, Andreas Schütte, Liliana E Layer, Oliver Ullrich
We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693316/rapid-dissolution-of-zno-nanoparticles-induced-by-biological-buffers-significantly-impacts-cytotoxicity
#9
Josh Eixenberger, Catherine Anders, Rebecca Hermann, Raquel Brown, K M Reddy, Alex Punnoose, Denise Wingett
Zinc oxide nanoparticles (nZnO) are one of the most highly produced nanomaterials and are used in numerous applications including cosmetics and sunscreens despite reports demonstrating their cytotoxicity. Dissolution is viewed as one of the main sources of nanoparticle (NP) toxicity, however dissolution studies can be time-intensive to perform and complicated by issues such as particle separation from solution. Our work attempts to overcome some of these challenges by utilizing new methods using UV/vis and fluorescence spectroscopy to quantitatively assess nZnO dissolution in various biologically relevant solutions...
July 10, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28690878/the-guanine-nucleotide-exchange-factor-caldag-gefi-fine-tunes-functional-properties-of-regulatory-t-cells
#10
Jana Niemz, Stefanie Kliche, Marina C Pils, Eliot Morrison, Annika Manns, Christian Freund, Jill R Crittenden, Ann M Graybiel, Melanie Galla, Lothar Jänsch, Jochen Huehn
Using quantitative phosphopeptide sequencing of unstimulated versus stimulated primary murine Foxp3(+) regulatory and Foxp3(-) conventional T cells (Tregs and Tconv, respectively), we detected a novel and differentially regulated tyrosine phosphorylation site within the C1 domain of the guanine-nucleotide exchange factor CalDAG GEFI. We hypothesized that the Treg-specific and activation-dependent reduced phosphorylation at Y523 allows binding of CalDAG GEFI to diacylglycerol, thereby impacting the formation of a Treg-specific immunological synapse...
June 2017: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/28681874/functional-insights-into-the-cellular-response-triggered-by-a-bile-acid-platinum-compound-conjugated-to-biocompatible-ferric-nanoparticles-using-quantitative-proteomic-approaches
#11
Paula Díez, María González-Muñoz, María González-González, Rosa Ma Dégano, Ricardo Jara-Acevedo, Sara Sánchez-Paradinas, Rafael Piñol, José Luis Murillo, Gustavo Lou, Fernando Palacio, María Jesús Almendral, Ángel Millán, Emilio Rodríguez-Fernández, Julio J Criado, Nieves Ibarrola, Manuel Fuentes
At present, bioferrofluids are employed as powerful multifunctional tools for biomedical applications such as drug delivery, among others. The present study explores the cellular response evoked when bile-acid platinum derivatives are conjugated with bioferrofluids by testing the biological activity in osteosarcoma (MG-63) and T-cell leukemia (Jurkat) cells. The aim of this work is to evaluate the biocompatibility of a bile-acid platinum derivative conjugated with multi-functional polymer coated bioferrofluids by observing the effects on the protein expression profiles and in intracellular pathways of nanoparticle-stimulated cells...
July 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28674297/characterization-of-therapeutic-monoclonal-antibodies-by-using-fc%C3%AE-r-expressing-reporter-cell-lines
#12
Minoru Tada, Akiko Ishii-Watabe
 Fcγ receptors (FcγRs), which bind to the Fc regions of antibodies, play an important role in antibody effector functions. In humans, there are four types of activating FcγRs: FcγRI, FcγRIIa, FcγRIIIa, and FcγRIIIb. These are expressed on various effector cells such as natural killer (NK) cells, neutrophils and macrophages. FcγRIIIa expressed on NK cells is known to play a pivotal role in antibody-dependent cellular cytotoxicity (ADCC) by therapeutic monoclonal antibodies (mAbs). To assess the ADCC activity of mAbs, the killing of target cells is often measured using human peripheral mononuclear blood cells (hPBMCs) or isolated primary NK cells as effector cells...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28671679/2-deoxyadenosine-5-diphosphoribose-is-an-endogenous-trpm2-superagonist
#13
Ralf Fliegert, Andreas Bauche, Adriana-Michelle Wolf Pérez, Joanna M Watt, Monika D Rozewitz, Riekje Winzer, Mareike Janus, Feng Gu, Annette Rosche, Angelika Harneit, Marianne Flato, Christelle Moreau, Tanja Kirchberger, Valerie Wolters, Barry V L Potter, Andreas H Guse
Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca(2+)-permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca(2+) signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca(2+) entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10...
June 26, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28671563/dose-dependent-responses-of-i3c-and-dim-on-t-cell-activation-in-the-human-t-lymphocyte-jurkat-cell-line
#14
Man Liu, Rumana Yasmeen, Naomi K Fukagawa, Liangli Yu, Young S Kim, Thomas T Y Wang
Indole-3-carbinol (I3C) and its dimer diindolylmethane (DIM) are bioactive metabolites of a glucosinolate, glucobrassicin, found in cruciferous vegetables. Both I3C and DIM have been reported to possess pro-apoptotic, anti-proliferative and anti-carcinogenic properties via modulation of immune pathways. However, results from these studies remain inconclusive since they lack thorough evaluation of these bioactives' physiological versus pharmacological effects. In the present study, we investigated I3C and DIM's dose-dependent effects on cytokines production in human T lymphocytes Jurkat cell line (Clone E6-1)...
July 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28666825/triptonide-acts-as-a-novel-potent-anti-lymphoma-agent-with-low-toxicity-mainly-through-inhibition-of-proto-oncogene-lyn-transcription-and-suppression-of-lyn-signal-pathway
#15
Ping Yang, Fulu Dong, Quansheng Zhou
Lyn is a proto-oncogene overexpressed and constitutively activated in lymphoma, and plays an important role in lymphoma initiation and malignant progression. Hence, the oncogenic Lyn has recently been targeted for novel anti-lymphoma drug discovery; however, the effective Lyn-targeted drug for lymphoma treatment with low toxicity is absent in the clinical setting. The goal of this study is to explore powerful and low toxic Lyn-targeted anti-lymphoma agent. Here we show that triptonide, a small molecule purified from the herb Tripterygium wilfordii Hook F, potently inhibits the proliferation of human B-lymphoma Raji and T-lymphoma Jurkat cells with IC50 of 5...
June 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28665310/artinm-mediates-murine-t-cell-activation-and-induces-cell-death-in-jurkat-human-leukemic-t-cells
#16
Thiago Aparecido da Silva, Patrícia Kellen Martins Oliveira-Brito, Thiago Eleutério Gonçalves, Patrícia Edivânia Vendruscolo, Maria Cristina Roque-Barreira
The recognition of cell surface glycans by lectins may be critical for the innate and adaptive immune responses. ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus, activates antigen-presenting cells by recognizing TLR2 N-glycans and induces Th1 immunity. We recently demonstrated that ArtinM stimulated CD4⁺ T cells to produce proinflammatory cytokines. Here, we further studied the effects of ArtinM on adaptive immune cells. We showed that ArtinM activates murine CD4⁺ and CD8⁺ T cells, augmenting their positivity for CD25, CD69, and CD95 and showed higher interleukin (IL)-2 and interferon (IFN)-γ production...
June 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28662964/synthesis-and-biological-activity-of-cyclolinopeptide-a-analogues-modified-with-%C3%AE-4-bis-homo-phenylalanine
#17
Karol Jędrzejczak, Paweł Hrynczyszyn, Małgorzata Szczesio, Jolanta Artym, Tomasz Jastrząbek, Maja Kocięba, Marek Główka, Krzysztof Huben, Iwona Kochanowska, Michał Zimecki, Janusz Zabrocki, Stefan Jankowski, Beata Kolesińska
Cyclolinopeptide A (CLA), an immunosuppressive nonapeptide derived from linen seeds, was modified with S or R-γ(4)-bis(homo-phenylalanine) in positions 3 or 4, or both 3 and 4. These modifications changed the flexibility of new analogues and distribution of intramolecular hydrogen bonds. Analogues 11 c(Pro(1)-Pro(2)-Phe(3)-S-γ(4)-hhPhe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)), 13 c(Pro(1)-Pro(2)-S-γ(4)-hhPhe(3)-R-γ(4)-hhPhe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)) and 15 c(Pro(1)-Pro(2)-R-γ(4)-hhPhe(3)-Phe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)) existed as a mixture of stable cis/trans isomers of Pro-Pro peptide bond...
June 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28662510/the-deubiquitinating-enzyme-usp14-regulates-leukemic-chemotherapy-drugs-induced-cell-apoptosis-by-suppressing-ubiquitination-of-aurora-kinase-b
#18
Chunge Song, Ruojin Ma, Xiaoyu Yang, Sulei Pang
BACKGROUND/AIMS: Aurora kinase B is a mitotic checkpoint kinase that plays a pivotal role in mitosis by ensuring correct chromosome segregation and normal progression through mitosis. Aurora B has been found to be amplified and overexpressed in several types of leukemia. The deubiquitinating enzyme USP14 is one of three proteasome-associated deubiquitinating enzymes and plays critical roles in diverse biological processes including cancer. However, whether USP14 has a role in leukemia cells remains elusive...
June 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28645575/prediction-of-drug-induced-immune-mediated-hepatotoxicity-using-hepatocyte-like-cells-derived-from-human-embryonic-stem-cells
#19
Dong Eon Kim, Mi-Jin Jang, Young Ran Kim, Joo-Young Lee, Eun Byul Cho, Eunha Kim, Yeji Kim, Mi Young Kim, Won-Il Jeong, Seyun Kim, Yong-Mahn Han, Seung-Hyo Lee
Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events...
July 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28644062/4-nerolidylcatechol-apoptosis-by-mitochondrial-mechanisms-with-reduction-in-cyclin-d1-at-g0-g1-stage-of-the-chronic-myelogenous-k562-cell-line
#20
Polyana Lopes Benfica, Renato Ivan de Ávila, Bruna Dos Santos Rodrigues, Alane Pereira Cortez, Aline Carvalho Batista, Marilisa Pedroso Nogueira Gaeti, Eliana Martins Lima, Kênnia Rocha Rezende, Marize Campos Valadares
CONTEXT: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells. OBJECTIVES: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells. MATERIALS AND METHODS: Cytotoxicity of 4-NRC (4.17-534.5 μM) over 24 h of exposure was evaluated by MTT assay. 4-NRC-induced apoptosis in K562 cells was investigated by phosphatidylserine (PS) externalization, cell cycle, sub-G1, mitochondrial evaluation, cytochrome c, cyclin D1 and intracellular reactive oxygen species (ROS) levels, and caspase activity analysis...
December 2017: Pharmaceutical Biology
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