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https://www.readbyqxmd.com/read/28088579/the-microrna-449-family-inhibits-tgf-%C3%AE-mediated-liver-cancer-cell-migration-by-targeting-sox4
#1
Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
BACKGROUND & AIMS: Modulation of microRNA expression is considered for treatment of hepatocellular carcinoma (HCC). Therefore, we characterized the epigenetically regulated microRNA-449 family (miR-449a, miR-449b, miR-449c) with regards to its functional effects and target genes in HCC. METHODS: After transfection of miR-449a, miR-449b, and/or miR-449c, tumor-relevant functional effects were analyzed using in vitro assays and a xenograft mouse model. Binding specificities, target genes, and regulated pathways of each microRNA were identified by microarray analyses...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28087780/oncogenes-without-a-neighboring-tumor-suppressor-gene-are-more-prone-to-amplification
#2
William K K Wu, Xiangchun Li, Xiansong Wang, Rudin Z W Dai, Alfred S L Cheng, Maggie H T Wang, Thomas Kwong, Tai C Chow, Jun Yu, Matthew T V Chan, Sunny H Wong
Focal copy number gains or losses are important genomic hallmarks of cancer. The genomic distribution of oncogenes and tumor-suppressor genes (TSG) in relation to focal copy number aberrations is unclear. Our analysis revealed that the mean distance of TSGs from oncogenes was significantly shorter than that of non-cancer genes, suggesting that oncogenes and TSGs tend to be in close physical proximity in the human genome. Such relationship was conserved in mouse and drosophila. Pan-cancer analysis using data from The Cancer Genome Atlas indicated that oncogenes without a nearby TSG are more prone to amplification...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087667/prmt5-selective-inhibitors-suppress-inflammatory-t-cell-responses-and-experimental-autoimmune-encephalomyelitis
#3
Lindsay M Webb, Stephanie A Amici, Kyle A Jablonski, Himanshu Savardekar, Amanda R Panfil, Linsen Li, Wei Zhou, Kevin Peine, Vrajesh Karkhanis, Eric M Bachelder, Kristy M Ainslie, Patrick L Green, Chenglong Li, Robert A Baiocchi, Mireia Guerau-de-Arellano
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cell-mediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28086830/sigma-2-receptor-agonist-derivatives-of-1-cyclohexyl-4-3-5-methoxy-1-2-3-4-tetrahydronaphthalen-1-yl-propyl-piperazine-pb28-induce-cell-death-via-mitochondrial-superoxide-production-and-caspase-activation-in-pancreatic-cancer
#4
Maria Laura Pati, John R Hornick, Mauro Niso, Francesco Berardi, Dirk Spitzer, Carmen Abate, William Hawkins
BACKGROUND: Despite considerable efforts by scientific research, pancreatic cancer is the fourth leading cause of cancer related mortalities. Sigma-2 receptors, which are overexpressed in several tumors, represent promising targets for triggering selective pancreatic cancer cells death. METHODS: We selected five differently structured high-affinity sigma-2 ligands (PB28, PB183, PB221, F281 and PB282) to study how they affect the viability of diverse pancreatic cancer cells (human cell lines BxPC3, AsPC1, Mia PaCa-2, and Panc1 and mouse Panc-02, KCKO and KP-02) and how this is reflected in vivo in a tumor model...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28086829/genomic-pathways-modulated-by-twist-in-breast-cancer
#5
Farhad Vesuna, Yehudit Bergman, Venu Raman
BACKGROUND: The basic helix-loop-helix transcription factor TWIST1 (Twist) is involved in embryonic cell lineage determination and mesodermal differentiation. There is evidence to indicate that Twist expression plays a role in breast tumor formation and metastasis, but the role of Twist in dysregulating pathways that drive the metastatic cascade is unclear. Moreover, many of the genes and pathways dysregulated by Twist in cell lines and mouse models have not been validated against data obtained from larger, independant datasets of breast cancer patients...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28081464/tumor-angiogenesis-of-sclc-inhibited-by-decreased-expression-of-fmod-via-downregulating-angiogenic-factors-of-endothelial-cells
#6
Zhi Ao, Shilong Yu, Pin Qian, Wenhong Gao, Ruiling Guo, Xiaoxiao Dong, Jianping Xu, Ruijie Zhang, Chaowen Jiang, Fuyun Ji, Guisheng Qian
Fibromodulin (FMOD), an ECM small leucine-rich proteoglycan (SLRP), was reported to promote angiogenesis not only during wound healing, but also in optical and cutaneous angiogenesis-dependent diseases. However, whether it plays important roles in tumor angiogenesis remains unclear. To explore the role of FMOD in tumor angiogenesis of human small cell lung cancer (SCLC), initially the study analyzed the relationship of FMOD expression in cancer tissues of SCLC with clinical characteristics. The analysis revealed that the positive FMOD expression was significantly associated with extensive stage of SCLC and higher vascular density...
January 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#7
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28077158/ccl2-driven-inflammation-increases-mammary-gland-stromal-density-and-cancer-susceptibility-in-a-transgenic-mouse-model
#8
Xuan Sun, Danielle J Glynn, Leigh J Hodson, Cecilia Huo, Kara Britt, Erik W Thompson, Lucy Woolford, Andreas Evdokiou, Jeffrey W Pollard, Sarah A Robertson, Wendy V Ingman
BACKGROUND: Macrophages play diverse roles in mammary gland development and breast cancer. CC-chemokine ligand 2 (CCL2) is an inflammatory cytokine that recruits macrophages to sites of injury. Although CCL2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. METHODS: Transgenic mice were generated wherein CCL2 is driven by the mammary epithelial cell-specific mouse mammary tumour virus 206 (MMTV) promoter...
January 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28077049/evaluation-on-biological-compatibility-of-carboxymethyl-chitosan-as-biomaterials-for-antitumor-drug-delivery
#9
Zhiwen Jiang, Baoqin Han, Wanshun Liu, Yanfei Peng
Carboxymethyl-chitosan, a water-soluble derivative of chitosan, has emerged as a promising candidate for biomedical applications due to its excellent water solubility, biodegradation, biocompatibility, hydrating, antimicrobial, and nontoxicity. In this paper, the antitumor proliferation and metastasis was studied in vitro and in vivo to evaluate biocompatibility of carboxymethyl-chitosan as biomaterials for antitumor drug delivery. The results showed that carboxymethyl-chitosan could significantly reduce the clone formation and tumor migration of human cancer cells including kidney cancer cell line OS-RC-2, gastric cancer cell line SGC-7901, colon cancer cell line HT-29, and nonsmall cell lung cancer cell line NCI-H1650 in vitro...
January 1, 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/28074226/synergistic-effects-of-host-b7-h4-deficiency-and-gemcitabine-treatment-on-tumor-regression-and-anti-tumor-t-cell-immunity-in-a-mouse-model
#10
Joanne Leung, Philippe St-Onge, John Stagg, Woong-Kyung Suh
B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control...
January 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28074003/dna-polymerase-beta-germline-variant-confers-cellular-response-to-cisplatin-therapy
#11
Antonia A Nemec, Laura Abriola, Jane S Merkel, Elisa deStanchina, Michelle DeVeaux, Daniel Zelterman, Peter M Glazer, Joann B Sweasy
: Resistance to cancer chemotherapies leads to deadly consequences, yet current research focuses only on the roles of somatically acquired mutations in this resistance. The mutational status of the germline is also likely to play a role in the way cells respond to chemotherapy. The carrier status for the POLB rs3136797 germline mutation encoding P242R DNA polymerase beta (Pol β) is associated with poor prognosis for lung cancer, specifically in response to treatment with cisplatin. Here, it is revealed that the P242R mutation is sufficient to promote resistance to cisplatin in human cells and in mouse xenografts...
January 10, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28073412/-clinical-effect-of-ultrasound-guided-injection-of-biodegradable-poly-lactic-co-glycolic-acid-fe3o4-in-situ-implant-for-magnetic-thermal-ablation-in-treatment-of-nude-mice-with-human-liver-cancer-smmc-7721-cells
#12
B Liang, G Q Zuo, Y Y Zheng, S He, D Y Zuo
Objective: To prepare the Fe3O4-loaded biodegradable liquid-solid phase inversion poly(lactic-co-glycolic acid) (PLGA) in situ implant for ultrasound-guided injection into nude mouse tumor model, and to investigate its clinical effect in thermomagnetic treatment of nude mice with human liver cancer SMMC-7721 cells in an alternating magnetic field. Methods: An in situ implant containing 10% Fe3O4 was prepared, and 50 μl Fe3O4-PLGA-NMP gel was injected into the subcutaneous tissue of Kunming mice. The degradation of this material was observed for 2 consecutive months, and the changes in body weight were recorded...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28073348/wild-carrot-pentane-based-fractions-suppress-proliferation-of-human-hacat-keratinocytes-and-protect-against-chemically-induced-skin-cancer
#13
Wassim N Shebaby, Mohamad A Mroueh, Petra Boukamp, Robin I Taleb Ri, Kikki Bodman-Smith, Mirvat El-Sibai, Costantine F Daher
BACKGROUND: Previous studies in our laboratory showed that the Lebanese Daucus carota ssp. carota (wild carrot) oil extract possesses in vitro and in vivo anticancer activities. The present study aims to examine the cytotoxic effect of Daucus carota oil fractions on human epidermal keratinocytes and evaluate the chemopreventive activity of the pentane diethyl ether fraction on DMBA/TPA induced skin carcinogenesis in mice. METHODS: Wild carrot oil extract was chromatographed to yield four fractions (F1, 100% pentane; F2, 50:50 pentane:diethyl ether; F3, 100% diethyl ether; F4 93:7 chloroform:methanol)...
January 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28072391/braf-v600e-cooperates-with-cdx2-inactivation-to-promote-serrated-colorectal-tumorigenesis
#14
Naoya Sakamoto, Ying Feng, Carmine Stolfi, Yuki Kurosu, Maranne Green, Jeffry Lin, Megan Green, Kazuhiro Sentani, Wataru Yasui, Martin McMahon, Karin M Hardiman, Jason R Spence, Nobukatsu Horita, Joel K Greenson, Rork Kuick, Kathy R Cho, Eric R Fearon
While 20-30% of colorectal cancers (CRCs) may arise from precursors with serrated glands, only 8-10% of CRCs manifest serrated morphology at diagnosis. Markers for distinguishing CRCs arising from 'serrated' versus 'conventional adenoma' precursors are lacking. We studied 36 human serrated CRCs and found CDX2 loss or BRAF mutations in ~60% of cases and often together (p= .04). CDX2(Null)/BRAF(V600E) expression in adult mouse intestinal epithelium led to serrated morphology tumors (including carcinomas) and BRAF(V600E) potently interacted with CDX2 silencing to alter gene expression...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28069875/15%C3%A2-methoxypuupehenol-induces-antitumor-effects-in-vitro-and-in-vivo-against-human-glioblastoma-and-breast-cancer-models
#15
Tyvette Hilliard, Gabriella Miklossy, Christopher Chock, Peibin Yue, Philip Williams, James Turkson
Studies with 15∝-methoxypuupehenol (15∝-MP), obtained from the extracts of Hyrtios sp., identified putative targets that are associated with its antitumor effects against human glioblastoma (GBM) and breast cancer. In the human GBM (U251MG) or breast cancer (MDA-MB-231) cells, treatment with 15∝-MP repressed pY705Stat3 (Signal Transducer and Activator of Transcription 3), pErk1/2 (extracellular signal-regulated kinase), pS147CyclinB1, pY507Alk (Anaplastic lymphoma kinase), and pY478ezrin levels, and induced pS10merlin, without inhibiting pJAK2 (Janus kinase) or pAkt induction...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28069602/oncogenic-zeb2-activation-drives-sensitivity-towards-kdm1a-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#16
Steven Goossens, Sofie Peirs, Wouter Van Loocke, Jueqiong Wang, Mina Takawy, Filip Matthijssens, Stefan E Sonderegger, Katharina Haigh, Thao Nguyen, Niels Vandamme, Magdaline Costa, Catherine Carmichael, Filip Van Nieuwerburgh, Dieter Deforce, Oded Kleifeld, David J Curtis, Geert Berx, Pieter Van Vlierberghe, Jody J Haigh
Elevated expression of the Zinc finger E-box binding homeobox transcription factor-2 (ZEB2) is correlated with poor prognosis and patient outcome in a variety of human cancer subtypes. Using a conditional gain-of-function mouse model, we recently demonstrated that ZEB2 is an oncogenic driver of immature T-cell acute lymphoblastic leukemia (T-ALL), a heterogenic subgroup of human leukemia characterized by a high incidence of remission failure or hematological relapse after conventional chemotherapy. Here, we identified the Lysine-specific demethylase KDM1A as a novel interaction partner of ZEB2 and demonstrated that mouse and human T-ALLs with increased ZEB2 levels critically depend on KDM1A activity for survival...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28069038/motility-of-glioblastoma-cells-is-driven-by-netrin-1-induced-gain-of-stemness
#17
Irene Ylivinkka, Harri Sihto, Olli Tynninen, Yizhou Hu, Aki Laakso, Riku Kivisaari, Pirjo Laakkonen, Jorma Keski-Oja, Marko Hyytiäinen
BACKGROUND: Glioblastoma is an untreatable brain cancer. The tumors contain a population of stem-like cells which are highly invasive and resistant to therapies. These cells are the main reason for the lethality of glioblastoma. Extracellular guidance molecule netrin-1 promotes the invasiveness and survival of various cancer cell types. We have previously found that netrin-1 activates Notch signaling, and Notch signaling associates with cell stemness. Therefore, we have here investigated the effects of netrin-1 on glioblastoma pathogenesis and glioblastoma cell stemness...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28067089/metabolomic-applications-in-radiation-biodosimetry-exploring-radiation-effects-through-small-molecules
#18
Evan L Pannkuk, Albert J Fornace, Evagelia C Laiakis
PURPOSE: Exposure of the general population to ionizing radiation has increased in the past decades, primarily due to long distance travel and medical procedures. On the other hand, accidental exposures, nuclear accidents, and elevated threats of terrorism with the potential detonation of a radiological dispersal device or improvised nuclear device in a major city, all have led to increased needs for rapid biodosimetry and assessment of exposure to different radiation qualities and scenarios...
January 9, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28063905/trichloroethylene-induced-formic-aciduria-in-the-male-c57-bl-6-mouse
#19
Edward A Lock, Paul Keane, Philip H Rowe, John R Foster, Daniel Antoine, Christopher M Morris
1, 1, 2-Trichloroethylene (TCE) is of environmental concern, due to evaporation while handling, chemical processing and leakage from chemical waste sites, leading to its contamination of ground water and air. For several decades there has been issues about possible long term health effects of TCE but recently the International Agency for Research on Cancer (IARC) and the US Environmental Protection Agency classified TCE as a human carcinogen. Links having been established between occupational exposures and kidney cancer and possible links to non-Hodgkin lymphoma and liver cancer, but there is more still more to learn...
January 4, 2017: Toxicology
https://www.readbyqxmd.com/read/28062807/junctional-adhesion-molecule-a-expression-in-the-murine-epididymal-tract-and-accessory-organs-and-acquisition-by-maturing-sperm
#20
Kathie Z Wu, Kun Li, Deni S Galileo, Patricia A Martin-DeLeon
STUDY QUESTION: Is junctional adhesion molecule A (JAM-A), a sperm protein essential for normal motility, expressed in the murine post-testicular pathway and involved in sperm maturation? SUMMARY ANSWER: JAM-A is present in the prostate and seminal vesicles and in all three regions of the epididymis where it is secreted in epididymosomes in the luminal fluid and can be delivered to sperm in vitro. WHAT IS KNOWN ALREADY: JAM-A shares with the plasma membrane Ca(2+)ATPase 4 (PMCA4, the major Ca(2+) efflux pump in murine sperm) a common interacting partner, CASK (Ca(2+)/CaM-dependent serine kinase)...
January 6, 2017: Molecular Human Reproduction
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