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Luhua H Zhang, June Ho Shin, Mikel D Haggadone, John B Sunwoo
A tissue-resident population of natural killer cells (NK cells) in the liver has recently been described to have the unique capacity to confer immunological memory in the form of hapten-specific contact hypersensitivity independent of T and B cells. Factors regulating the development and maintenance of these liver-resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut...
September 26, 2016: Journal of Experimental Medicine
Katarzyna Badowska-Rosłonek, Agnieszka Ciesielska, Marta Switalska, Małgorzata Piskozub, Wanda Peczyńska-Czoch, Joanna Wietrzyk, Łukasz Kaczmarek
Novel 5H-indolo[2,3-b]quinoline O-aminoglycosides were synthesized in order to check the hypothesis that the construction of hybrids composed of the active 5H-indolo[2,3-b]quinoline chromophore and daunosaminyl or acosaminyl moiety may result in the cytotoxic activity of the obtained derivatives that is much higher than the one of the parent DIMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline) and 6H-indoloquinoline analogs. Actually, 5H-indolo[2,3-b]indoloquinoline O-aminoglycosides showed the anti-proliferative activity in vitro against human lung adenocarcinoma A549, breast cancer MCF-7, melanoma Hs294T, promyelocytic leukemia HL-60, uterine sarcoma MES-SA and colon cancer LoVo cell lines, which was 10 times higher than that of the 6H-analogs and comparable to the one of the referential DIMIQ...
May 2016: Acta Poloniae Pharmaceutica
Jessica Filtjens, Jiri Keirsse, Els Van Ammel, Sylvie Taveirne, Aline Van Acker, Tessa Kerre, Tom Taghon, Bart Vandekerckhove, Jean Plum, Jo A Van Ginderachter, Georges Leclercq
Natural killer (NK) lymphocytes are part of the innate immune system and are important in immune protection against tumourigenesis. NK cells display a broad repertoire of activating and inhibitory cell surface receptors that regulate NK cell activity. The Ly49 family of NK receptors is composed of several members that recognize major histocompatibility complex class I (MHC-I) or MHC-I-related molecules. Ly49E is a unique inhibitory member, being triggered by the non-MHC-I-related protein urokinase plasminogen activator (uPA) in contrast to the known MHC-I-triggering of the other inhibitory Ly49 receptors...
2016: Scientific Reports
Xuejun Li, Tianhong Liu, Lijun Song, Heng Zhang, Liqun Li, Xin Gao
As one of critical gluten proteins, high-molecular-weight glutenin subunits (HMW-GS) mainly affect the rheological behaviour of wheat dough. The influence of HMW-GS variations at the Glu-A1 and Glu-D1 loci on both secondary and micro structures of gluten and rheological properties of wheat dough was investigated in this study. Results showed that the Amide I bands of the three near-isogenic lines (NILs) shifted slightly, but the secondary structures differed significantly. The micro structure of gluten in NIL 4 (Ax null) showed bigger apertures and less connection, compared to that in Xinong 1330 (Ax1)...
December 15, 2016: Food Chemistry
Jee Won Hwang, Hyewon Cho, Jae Yeon Lee, Youngsic Jeon, Su-Nam Kim, Sang Jin Lee, Gyu-Un Bae, Sungpil Yoon, Raok Jeon, Yong Kee Kim
Multidrug resistance (MDR) caused by P-glycoprotein (P-gp) overexpression impedes successful cancer chemotherapy. In this study, we investigated the anticancer effects of SPA3015, a synthetic ajoene analog, in P-gp-overexpressing MDR cancer cells (KBV20C and MES-SA/DX5). Treatment with SPA3015 caused a dramatic decrease in the cell viabilities of both KBV20C and MES-SA/DX5 cells. This decrease was accompanied by apoptotic cell death without affecting the expression level or drug efflux function of P-gp. SPA3015 selectively suppressed NF-κB reporter gene activity, which led to decreased expression of NF-κB target genes such as CIAP1, CIAP2, XIAP, and Bcl-XL...
October 2016: Food and Chemical Toxicology
Kara L Vine, Lisa Belfiore, Luke Jones, Julie M Locke, Samantha Wade, Elahe Minaei, Marie Ranson
The search for novel anticancer therapeutics with the ability to overcome multi-drug resistance (MDR) mechanisms is of high priority. A class of molecules that show potential in overcoming MDR are the N-alkylated isatins. In particular 5,7-dibromo-N-alkylisatins are potent microtubule destabilizing agents that act to depolymerize microtubules, induce apoptosis and inhibit primary tumor growth in vivo. In this study we evaluated the ability of four dibrominated N-alkylisatin derivatives and the parent compound, 5,7-dibromoisatin, to circumvent MDR...
January 2016: Heliyon
Meijuan Zheng, Rui Sun, Haiming Wei, Zhigang Tian
Although recent clinical studies demonstrate that NK cell function is impaired in hepatitis B virus (HBV)-persistent patients, whether or how NK cells play a role in anti-HBV adaptive immunity remains to be explored. Using a mouse model mimicking acute HBV infection by hydrodynamic injection of an HBV plasmid, we observed that although serum hepatitis B surface Ag and hepatitis B envelope Ag were eliminated within 3 to 4 wk, HBV might persist for >8 wk in CD8(-/-) mice and that adoptive transfer of anti-HBV CD8(+) T cells restored the ability to clear HBV in HBV-carrier Rag1(-/-) mice...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Gaurav Malviya, Tapan Nayak, Christian Gerdes, Rudi A J O Dierckx, Alberto Signore, Erik F J de Vries
A noninvasive in vivo imaging method for NK cell trafficking is essential to gain further understanding of the pathogenesis of NK cell mediated immune response to the novel cancer treatment strategies, and to discover the homing sites and physiological distribution of NK cells. Although human NK cells can be labeled for in vivo imaging, little is known about the murine NK cell labeling and its application in animal models. This study describes the isolation and ex vivo radiolabeling of murine NK cells for the evaluation of cell trafficking in an orthotopic model of human lung cancer in mice...
April 4, 2016: Molecular Pharmaceutics
Charng Choon Wong, Siang Hui Lim, Sreenivasa Rao Sagineedu, Nordin Haji Lajis, Johnson Stanslas
SRJ09 (3,19-(2-bromobenzylidene)andrographolide), a semisynthetic andrographolide (AGP) derivative, was shown to induce G1 cell cycle arrest and eventually apoptosis in breast and colon cancer cell lines. The present investigation was carried out to elucidate the mechanisms cell cycle arrest and apoptosis and evaluate the in vivo antitumor activity of SRJ09. The in vitro growth inhibitory properties of compounds were assessed in colon (HCT-116) and breast (MCF-7) cancer cell lines. Immunoblotting was utilized to quantitate the protein levels in cells...
May 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Annie-Carole Tosello-Trampont, Peter Krueger, Sowmya Narayanan, Susan G Landes, Norbert Leitinger, Young S Hahn
UNLABELLED: Nonalcoholic steatohepatitis (NASH) affects 3%-5% of the U.S. population, having severe clinical complications to the development of fibrosis and end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. A critical cause of NASH is chronic systemic inflammation promoted by innate immune cells, such as liver macrophages (Mϕ) and natural killer (NK) cells. However, little is known about how the crosstalk between Mϕ and NK cells contributes to regulate NASH progression to fibrosis...
March 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jun Lee, You Jin Lee, Jinhee Kim, Ok-Sun Bang
In the search for novel herbal-based anticancer agents, we isolated a new angular-type pyranocoumarin, (+)-cis-(3'S,4'S)-3'-angeloyl-4'-tigloylkhellactone (1) along with 12 pyranocoumarins (2-13), two furanocoumarins (14, 15), and a polyacetylene (16) were isolated from the roots of Peucedanum praeruptorum using chromatographic separation methods. The structures of the compounds were determined using spectroscopic analysis with nuclear magnetic resonance (NMR) and high-resolution-electrospray ionization-mass spectrometry (HR-ESI-MS)...
2015: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Tamara Krneta, Amy Gillgrass, Marianne Chew, Ali A Ashkar
Natural killer (NK) cells are innate immune cells with the ability to identify and eliminate transformed cells. However, within tumors, many studies have described NK cells as non-functional. The developmental stage of tumor-associated NK cells and how this may relate to functionality has not been explored. We examined the developmental state of NK cells from polyoma middle T antigen (pyMT) transgenic mouse (MMTV-pMT) breast tumors. In pyMT tumors, NK cells were immature as evidenced by their decreased expression of DX5 and their CD27(low)CD11b(low) phenotype...
September 2016: Cellular & Molecular Immunology
Mi Kyoung Kim, Kwang-su Park, Hyunah Choo, Youhoon Chong
BACKGROUND: We previously demonstrated that the bioactivity of quercetin could be improved through conjugation with a hydrolysable pivaloxymethyl (POM) group. PURPOSE: Present study aimed to evaluate MDR (multidrug resistance)-modulatory activity of the quercetin-POM conjugates. STUDY DESIGN/METHODS: MDR-modulatory activity was determined by measuring cytotoxicity of various anticancer agents to MDR MES-SA/Dx5 cell lines upon combination with the quercetin-POM conjugates...
July 15, 2015: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Giuseppe La Regina, Ruoli Bai, Antonio Coluccia, Valeria Famiglini, Sveva Pelliccia, Sara Passacantilli, Carmela Mazzoccoli, Vitalba Ruggieri, Annalisa Verrico, Andrea Miele, Ludovica Monti, Marianna Nalli, Romina Alfonsi, Lucia Di Marcotullio, Alberto Gulino, Biancamaria Ricci, Alessandra Soriani, Angela Santoni, Michele Caraglia, Stefania Porto, Eleonora Da Pozzo, Claudia Martini, Andrea Brancale, Luciana Marinelli, Ettore Novellino, Stefania Vultaggio, Mario Varasi, Ciro Mercurio, Chiara Bigogno, Giulio Dondio, Ernest Hamel, Patrizia Lavia, Romano Silvestri
We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression...
August 13, 2015: Journal of Medicinal Chemistry
A Angelini, G Ciofani, P Conti
Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains one of the major obstacles to effective cancer chemotherapy. Several chemosensitizers have been used in vivo and in vitro to reverse MDR but have exhibited several unwanted side effects. Antipsychotics are often administered to treat psychiatric disorders such as delirium, anxiety and sleep disorders in cancer patients during chemotherapy. The present in vitro study, examined the effects of two common antipsychotic compounds, haloperidol and risperidone, and a natural compound such as theobromine on reversing MDR Pgp-mediated, to evaluate their potential use as chemosensitizing agents...
April 2015: Journal of Biological Regulators and Homeostatic Agents
Q Li, A Sato, O Shimozato, M Shingyoji, Y Tada, K Tatsumi, H Shimada, K Hiroshima, M Tagawa
DNA-mediated immunization of a tumour antigen is a possible immunotherapy for cancer, and interleukin (IL)-27 has diverse functions in adaptive immunity. In this study, we examined whether IL-27 DNA administration enhanced antitumour effects in mice vaccinated with DNA encoding a putative tumour antigen, β-galactosidase (β-gal). An intramuscular injection of cardiotoxin before DNA administration facilitated the exogenous gene expression. In mice received β-gal and IL-27 DNA, growth of β-gal-positive P815 tumours was retarded and survival of the mice was prolonged...
October 2015: Scandinavian Journal of Immunology
Che-Chung Yeh, Yanying Fan, Long Jiang, Yi-Lin Yang, Biao He, Liang You, Michael Mann
BACKGROUND: The estrogen-like soy isoflavone genistein can suppress the growth of a number of different types of cancer cells, but its effect on uterine sarcoma is unknown. MATERIALS AND METHODS: The impact of genistein on the proliferation of three uterine sarcoma cell lines, MES-SA, MES-SA-Dx5 and SK-UT-1, was evaluated. TOPflash luciferase reporter assay and western blotting were used to assess the influence of genistein on cellular signaling; DNA fragmentation was assessed as a measure of genistein-induced apoptosis...
June 2015: Anticancer Research
Vassiliki Giannouli, Ioannis K Kostakis, Nicole Pouli, Panagiotis Marakos, Pinelopi Samara, Ourania Tsitsilonis
A number of new substituted fused naphthyridinones has been prepared and their antiproliferative activity was evaluated against a panel of seven human tumor cell lines, including the variant MES-SA/Dx5, reported to be 100-fold resistant to doxorubicin. Certain derivatives exhibited interesting cytotoxic properties, possessing IC50 values in a low μM range.
July 1, 2015: Bioorganic & Medicinal Chemistry Letters
Nelson Garcia, Wei Zhang, Yongrui Wu, Joachim Messing
We took a rather unique approach to investigate the conservation of gene expression of prolamin storage protein genes across two different subfamilies of the Poaceae. We took advantage of oat plants carrying single maize chromosomes in different cultivars, called oat-maize addition (OMA) lines, which permitted us to determine whether regulation of gene expression was conserved between the two species. We found that γ-zeins are expressed in OMA7.06, which carries maize chromosome 7 even in the absence of the trans-acting maize prolamin-box-binding factor (PBF), which regulates their expression...
May 2015: Genome Biology and Evolution
T-H Hung, Y-H Li, C-P Tseng, Y-W Lan, S-C Hsu, Y-H Chen, T-T Huang, H-C Lai, C-M Chen, K-B Choo, K-Y Chong
Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells...
May 2015: Cancer Gene Therapy
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