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https://www.readbyqxmd.com/read/29793168/olive-oil-polyphenols-reduce-oxysterols-induced-redox-imbalance-and-pro-inflammatory-response-in-intestinal-cells
#1
Gessica Serra, Alessandra Incani, Gabriele Serreli, Laura Porru, M Paola Melis, Carlo I G Tuberoso, Daniela Rossin, Fiorella Biasi, Monica Deiana
Dietary habits may strongly influence intestinal homeostasis. Oxysterols, the oxidized products of cholesterol present in cholesterol-containing foodstuffs, have been shown to exert pro-oxidant and pro-inflammatory effects, altering intestinal epithelial layer and thus contributing to the pathogenesis of human inflammatory bowel diseases and colon cancer. Extra virgin olive oil polyphenols possess antioxidant and anti-inflammatory properties, and concentrate in the intestinal lumen, where may help in preventing intestinal diseases...
May 16, 2018: Redox Biology
https://www.readbyqxmd.com/read/29793091/effects-of-surface-modification-of-as-2-o-3-loaded-plga-nanoparticles-on-its-anti-liver-cancer-ability-an-in-vitro-and-in-vivo-study
#2
Xiaoli Song, Juan You, Hongxia Shao, Caifeng Yan
As2 O3 -loaded nanoparticles (NPs) based on poly (lactic-co-glycolic acid) (PLGA) were prepared by double emulsion-solvent evaporation method. Then Lactose acid (LA) and/or PEG were modified onto the NPs by chemical covalent coupling through -NH2 and -COOH. The FTIR results showed that LA and PEG could be successfully modified onto the surface of the NPs. All the As2 O3 -loaded PLGA NPs (As2 O3 @PLGA NPs) presented suitable physical stability, favorable size, and spherical shape. The in vitro release rate of As2 O3 from the NPs depended on the surface of the NPs...
May 21, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29793087/skin-allografting-activates-anti-tumor-immunity-and-suppresses-growth-of-colon-cancer-in-mice
#3
Xiang Li, Xu Lan, Grace Wang, Yi Liu, Ke Zhao, Shan-Zheng Lu, Xiao-Xi Xu, Gang-Gang Shi, Kui Ye, Bao-Ren Zhang, Yi-Ming Zhao, Hong-Qiu Han, Cai-Gan Du, Thomas E Ichim, Hao Wang
INTRODUCTION: The tumor cells could escape from the immune elimination through the immunoediting mechanisms including the generation of immunosuppressive or immunoregulative cells. By contrast, allograft transplantation could activate the immune system and induce a strong allogenic response. The aim of this study was to investigate the efficacy of allogenic skin transplantation in the inhibition of tumor growth through the activation of allogenic immune response. METHODS: Full-thickness skin transplantation was performed from C57BL/6 (H-2b ) donors to BALB/c (H-2d ) recipients that were receiving subcutaneous injection of isogenic CT26 colon cancer cells (2 × 106 cells) at the same time...
May 21, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29792947/trail-attenuates-sulforaphane-mediated-nrf2-and-sustains-ros-generation-leading-to-apoptosis-of-trail-resistant-human-bladder-cancer-cells
#4
Cheng-Yun Jin, Ilandarage Menu Neelaka Molagoda, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Sang-Hyuck Kang, Cheol Park, Gi-Young Kim, Yung Hyun Choi
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can preferentially initiate apoptosis in malignant cells with minimal toxicity to normal cells. Unfortunately, many human cancer cells are refractory to TRAIL-induced apoptosis through many unknown mechanisms. Here, we report that TRAIL resistance can be reversed in human bladder cancer cell lines by treatment with sulforaphane (SFN), a well-known chemopreventive isothiocyanate in various cruciferous vegetables. Combined treatment with SFN and TRAIL (SFN/TRAIL) significantly induced apoptosis concomitant with activation of caspases, loss of mitochondrial membrane potential (MMP), Bid truncation, and induction of death receptor 5...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792945/cross-linking-by-epichlorohydrin-and-diepoxybutane-correlates-with-cytotoxicity-and-leads-to-apoptosis-in-human-leukemia-hl-60-cells
#5
Phuong M Le, Vanesa L Silvestri, Samuel C Redstone, Jordanne B Dunn, Julie T Millard
The bifunctional alkylating agents epichlorohydrin (ECH) and diepoxybutane (DEB) have been linked to increased cancer risks in industrial workers. These compounds react with DNA and proteins, leading to genotoxic effects. We used the comet assay to monitor formation of cross-links in HL-60 cells treated with ECH, DEB, and the structurally related anti-cancer drug mechlorethamine (HN2). We report a time- and dose-dependent cytotoxicity that correlated with cross-linking activity, following the order HN2 > DEB > ECH...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792893/tox-expression-decreases-with-progression-of-colorectal-cancers-and-is-associated-with-cd4-t-cell-density-and-fusobacterium-nucleatum-infection
#6
Ting Chen, Qing Li, Xiaoyan Zhang, Ran Long, Yaxin Wu, Jiao Wu, Xiangsheng Fu
Fusobacterium nucleatum (F. nucleatum) in the tumor microenvironment plays an important role in the development of colorectal cancer (CRC). The underlying mechanism of action, however, remains to be elucidated. We evaluated the relation of F. nucleatum amount to thymocyte selection-associated high-mobility group box (TOX) protein expression and CD4+ T cell density in 138 human colorectal tissues. TOX expression and CD4+ T cell density in F. nucleatum negative tissues were significantly higher compared to those in F...
May 21, 2018: Human Pathology
https://www.readbyqxmd.com/read/29792670/biomarker-based-metabolic-labeling-for-redirected-and-enhanced-immune-response
#7
Shanshan Li, Bingchen Yu, Jiajia Wang, Yueqin Zheng, Huajie Zhang, Margaret J Walker, Zhengnan Yuan, He Zhu, Jun Zhang, Peng George Wang, Binghe Wang
Installation of an antibody-recruiting moiety on the surface of disease-relevant cells can lead to the selective destruction of targets by the immune system. Such an approach can be an alternative strategy to traditional chemotherapeutics in cancer therapy and possibly other diseases. Herein we describe the development of a new strategy to selectively label targets with an antibody-recruiting moiety through its covalent and stable installation, complementing existing methods of employing reversible binding...
May 24, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29792310/bet-inhibition-overcomes-receptor-tyrosine-kinase-mediated-cetuximab-resistance-in-hnscc
#8
Brandon Leonard, Toni M Brand, Rachel A O'Keefe, Eliot Lee, Yan Zang, Jacquelyn D Kemmer, Hua Li, Jennifer R Grandis, Neil E Bhola
Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK) including HER3, MET, and AXL. In an effort to overcome cetuximab resistance and circumvent toxicities associated with the administration of multiple RTK inhibitors, we sought to identify a common molecular target that regulates expression of multiple RTK...
May 23, 2018: Cancer Research
https://www.readbyqxmd.com/read/29792298/nanobody-antigen-conjugates-elicit-hpv-specific-anti-tumor-immune-responses
#9
Andrew W Woodham, Ross W Cheloha, Jingjing Ling, Mohammad Rashidian, Stephen C Kolifrath, Maia Mesyngier, Joao N Duarte, Justin M Bader, Joseph G Skeate, Diane M Da Silva, W Martin Kast, Hidde L Ploegh
High-risk human papillomavirus-associated cancers express viral oncoproteins (e.g., E6 and E7) that induce and maintain the malignant phenotype. The viral origin of these proteins makes them attractive targets for development of a therapeutic vaccine. Camelid-derived single-domain antibody fragments (nanobodies or VHHs) that recognize cell surface proteins on antigen-presenting cells (APCs) can serve as targeted delivery vehicles for antigens attached to them. Such VHHs were shown to induce CD4+ and CD8+ T-cell responses against model antigens conjugated to them via sortase, but antitumor responses had not yet been investigated...
May 23, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29792199/nanoparticle-delivery-of-grape-seed-derived-proanthocyanidins-to-airway-epithelial-cells-dampens-oxidative-stress-and-inflammation
#10
S Castellani, A Trapani, A Spagnoletta, L di Toma, T Magrone, S Di Gioia, D Mandracchia, G Trapani, E Jirillo, M Conese
BACKGROUND: Chronic respiratory diseases, whose one of the hallmarks is oxidative stress, are still incurable and need novel therapeutic tools and pharmaceutical agents. The phenolic compounds contained in grape are endowed with well-recognized anti-oxidant, anti-inflammatory, anti-cancer, and anti-aging activities. Considering that natural anti-oxidants, such as proanthocyanidins, have poor water solubility and oral bioavailability, we have developed a drug delivery system based on solid lipid nanoparticles (SLN), apt to encapsulate grape seed extract (GSE), containing proanthocyanidins...
May 23, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29792147/crystal-structure-of-mistletoe-lectin-i-ml-i-from-viscum-album-in-complex-with-4-n-furfurylcytosine-at-2-85-%C3%A3-resolution
#11
Malik Shoaib Ahmad, Saima Rasheed, Sven Falke, Binish Khaliq, Markus Perbandt, M Iqbal Choudhary, Wojciech T Markiewicz, Jan Barciszewski, Christian Betzel
BACKGROUND: Viscum album (the European mistletoe) is a semi-parasitic plant, which is of high medical interest. It is widely found in Europe, Asia and North America. It contains at least three distinct lectins (i.e. ML-I, II, and III), varying in molecular mass and specificity. Among them ML-I is in focus of medical research for various activities, including anti-cancer activities. To understand the molecular basis for such medical applications a few studies have already addressed the structural and functional analysis of ML-I in complex with ligands...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29792136/zinc-dependent-histone-deacetylase-inhibitors-in-cancer-therapeutics-recent-update
#12
Panagiotis I Georgianos, Maria Divani, Theodoros Eleftheriadis, Peter R Mertens, Vassilios Liakopoulos
BACKGROUND: Despite optimal management of diabetic kidney disease (DKD) with intensive glycemic control and administration of agents blocking the renin-angiotensin-aldosterone-system, the residual risk for nephropathy progression to end-stage-renal-disease (ESRD) remains high. Sodium-glucose co-transporter type 2 (SGLT-2)-inhibitors represent a newly-introduced anti-diabetic drug class with pleiotropic actions extending above their glucose-lowering efficacy. Herein, we provide an overview of preclinical and clinical-trial evidence supporting a protective effect of SGLT-2 inhibitors on DKD...
May 23, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29792038/downregulation-of-cancer-stemness-by-novel-diterpenoid-ovatodiolide-inhibits-hepatic-cancer-stem-cell-like-traits-by-repressing-wnt-formula-see-text-catenin-signaling
#13
Mingche Liu, Oluwaseun Adebayo Bamodu, Kuang-Tai Kuo, Wei-Hwa Lee, Yen-Kuang Lin, Alexander T H Wu, Hsiao M, Yew-Min Tzeng, Chi-Tai Yeh, Jo-Ting Tsai
The hierarchical tumor propagation or cancer stem cells (CSCs) model of carcinogenesis postulates that like physiologic adult stem cell (ASC), the CSCs positioned at the apex of any tumor population form the crux of tumor evolution with a constitutive regenerative capacity and differentiation potential. The propagation and recurrence of the characteristically heterogeneous and therapy-resistant hepatocellular carcinoma (HCC), adds to accumulating evidence to support this CSCs model. Based on the multi-etiologic basis of HCC formation which among others, focuses on the disruption of the canonical Wnt signaling pathway, this study evaluated the role of cembrane-type phytochemical, Ovatodiolide, in the modulation of the Wnt/[Formula: see text]-catenin pathway, and its subsequent effect on liver CSCs' activities...
May 24, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29791792/normalizing-tumor-microenvironment-based-on-photosynthetic-abiotic-biotic-nanoparticles
#14
Diwei Zheng, Bin Li, Lu Xu, Qiu-Ling Zhang, Jin-Xuan Fan, Chu-Xin Li, Xian-Zheng Zhang
Tumor hypoxia has attained the status of a core hallmark of cancer that globally affected the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a Photosynthetic Leaf-inspired Abiotic/biotic Nano-Thylakoid (PLANT) system was designed by fusing thylakoid membrane with synthetic nanoparticles for efficient O2 generation in vivo. Under 660 nm laser irradiation, PLANT system exhibited intracellular O2 generation and the anaerobic respiration of multicellular tumor spheroid was suppressed by PLANT as well...
May 23, 2018: ACS Nano
https://www.readbyqxmd.com/read/29791768/vaccine-immunotherapy-with-arnax-induces-tumor-specific-memory-t-cells-and-durable-anti-tumor-immunity-in-mouse-models
#15
Yohei Takeda, Sumito Yoshida, Ken Takashima, Noriko Ishii-Mugikura, Hiroaki Shime, Tsukasa Seya, Misako Matsumoto
Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with TLR3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In this study, four different OVA-expressing tumor cell lines were implanted into syngeneic mice and subjected to antitumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a Toll-like receptor 3-specific agonist that does not activate the MAVS pathway, and thus does not induce systemic inflammation...
May 23, 2018: Cancer Science
https://www.readbyqxmd.com/read/29791254/a-genome-wide-mirna-screen-identifies-regulators-of-tetraploid-cell-proliferation
#16
Marc A Vittoria, Elizabeth M Shenk, Kevin P O'Rourke, Amanda F Bolgioni, Sanghee Lim, Victoria Kacprzak, Ryan J Quinton, Neil J Ganem
Tetraploid cells, which are most commonly generated by errors in cell division, are genomically unstable and have been shown to promote tumorigenesis. Recent genomic studies have estimated that ∼40% of all solid tumors have undergone a genome-doubling event during their evolution, suggesting a significant role for tetraploidy in driving the development of human cancers. To safeguard against the deleterious effects of tetraploidy, non transformed cells that fail mitosis and become tetraploid activate both the Hippo and p53 tumor suppressor pathways to restrain further proliferation...
May 23, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29791241/neutrophil-mediated-delivery-of-pixantrone-loaded-liposomes-decorated-with-poly-sialic-acid-octadecylamine-conjugate-for-lung-cancer-treatment
#17
Xiang Luo, Ling Hu, Huangliang Zheng, Mingqi Liu, Xinrong Liu, Cong Li, Qiujun Qiu, Zitong Zhao, Xiaobo Cheng, Chaoyang Lai, Yuqing Su, Yihui Deng, Yanzhi Song
Poly(sialic acid) (PSA) is a natural hydrophilic biodegradable and non-immunogenic biopolymer, receptors for its monomer are expressed on peripheral blood neutrophils (PBNs), which plays important roles in the progression and invasion of tumors. A poly(sialic acid)-octadecylamine conjugate (PSA-ODA) was synthesized and then anchor it on the surface of liposomal pixantrone (Pix-PSL), to achieve an improved anticancer effect. The liposomes were prepared using a remote loading method via a pH gradient, and then assessed for particle size, zeta potential encapsulation efficiency, in vitro release, and in vitro cytotoxicity...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29791145/slow-starter-enzymes-role-of-active-site-architecture-in-the-catalytic-control-in-the-biosynthesis-of-taxadiene-by-taxadiene-synthase
#18
Tamar Ansbacher, Yehoshua Freud, Dan Thomas Major
Taxadiene synthase (TXS) catalyzes the formation of the natural product Taxa-4(5),11(12)-diene (henceforth Taxadiene). Taxadiene is the precursor in the formation of Taxol, which is an important natural anti-cancer agent. In the current study, we present a detailed mechanistic view of the biosynthesis of Taxadiene by TXS, using a hybrid quantum mechanics-molecular mechanics potential in conjunction with free energy simulation methods. The obtained free energy landscape displays initial endergonic steps followed by a step-wise downhill profile, which is an emerging free energy fingerprint for type I terpene synthases...
May 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/29791021/immtac-anti-pd-1-combination-to-enhance-killing-of-cancer-cells-by-reversing-treg-mediated-immunosuppression
#19
Huanling Zhang, Yanyan Li, Xiaoping Liu, Zhaoduan Liang, Mengyong Yan, Qiang Liu, Anan Chen, Yifeng Bao, Chengzhi Zhou, Shiyue Li, Cassian Yee, Yi Li
Recently, bi-functional molecules that can redirect immune effectors to tumor cells have emerged as potentially robust mediators of tumor regression in clinical trials. Two modalities, in particular, bi-specific antibodies for T cell redirection and activation (BiTe) and immune-mobilizing monoclonal T-cell receptors against cancer (ImmTAC) are being evaluated in efficacy studies as 'off-the-shelf' reagents. Optimal therapy will require an understanding and means to address regulatory mechanisms of limiting efficacy...
May 23, 2018: Immunology
https://www.readbyqxmd.com/read/29790920/elucidating-the-role-of-the-maternal-embryonic-leucine-zipper-kinase-melk-in-adrenocortical-carcinoma
#20
Katja Kiseljak-Vassiliades, Yu Zhang, Adwitiya Kar, Raud Razzaghi, Mei Xu, Katherine Gowan, Christopher D Raeburn, Maria Albuja-Cruz, Kenneth L Jones, Hilary Somerset, Lauren Fishbein, Stephen Leong, Margaret E Wierman
Adrenocortical carcinoma (ACC) is an aggressive cancer with a five-year survival less than 35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified Maternal Embryonic Leucine Zipper Kinase (MELK) as 4.1-fold overexpressed in ACC compared to normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells...
May 21, 2018: Endocrinology
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