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Shingo Hatakeyama, Tohru Yoneyama, Yuki Tobisawa, Chikara Ohyama
The application of prostate-specific antigen (PSA) in prostate cancer (PC) screening, diagnosis, and prognosis has improved the clinical management of PC patients. However, the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of patients with indolent disease. The United States Preventive Services Task Force incited much debate over PSA-based screening in 2012 by recommending against this approach. However, the PSA assay remains the first-line tool for the early detection of PC...
October 11, 2016: International Journal of Clinical Oncology
Mark E Ebel, Geoffrey S Kansas
Selectins are carbohydrate-binding adhesion molecules that control leukocyte traffic. Induction of selectin ligands on T cells is controlled primarily by cytokines, including TGF-β1, and requires p38α MAPK, but transcriptional mechanisms that underlie cytokine-driven selectin ligand expression are poorly understood. In this study, we show, using mice with conditional deletions of the TGF-β1-responsive transcription factors Smad2, Smad3, or Smad4, that induction of selectin ligands on CD4 cells in response to TGF-β1 requires Smad4 plus either Smad2 or Smad3...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Maibritt Mardahl, Micha F Schröter, Dirk Engelbert, Matthias Pink, Markus Sperandio, Alf Hamann, Uta Syrbe
P-selectin ligands (P-ligs) support the recruitment of lymphocytes into inflamed tissues. Binding to P-selectin is mediated by oligosaccharide groups synthesized by means of several glycosyltransferases including core 2 ß1,6-N-acetylglucosaminyltransferase-I (C2GlcNAcT-I), encoded by the gene Gcnt1. Using Gcnt1(-/-) Th1 cells, we show that C2GlcNAcT-I is crucial for inflammatory T cell homing in vivo. To understand the molecular regulation of Gcnt1 in CD4(+) T helper cells, we performed ChIP-on-chip experiments across the Gcnt1 locus assessing the chromatin structure in P-lig-expressing versus non-expressing CD4(+) T cells...
September 2016: Molecular Immunology
Jennifer Munkley, Daniel Vodak, Karen E Livermore, Katherine James, Brian T Wilson, Bridget Knight, Paul Mccullagh, John Mcgrath, Malcolm Crundwell, Lorna W Harries, Hing Y Leung, Craig N Robson, Ian G Mills, Prabhakar Rajan, David J Elliott
Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer...
June 2016: EBioMedicine
Brandon-Luke L Seagle, Kevin H Eng, Judy Y Yeh, Monica Dandapani, Emily Schiller, Robert Samuelson, Kunle Odunsi, Shohreh Shahabi
Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n =  398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data...
2016: Scientific Reports
Jennifer Munkley, Sebastian Oltean, Daniel Vodák, Brian T Wilson, Karen E Livermore, Yan Zhou, Eleanor Star, Vasileios I Floros, Bjarne Johannessen, Bridget Knight, Paul McCullagh, John McGrath, Malcolm Crundwell, Rolf I Skotheim, Craig N Robson, Hing Y Leung, Lorna W Harries, Prabhakar Rajan, Ian G Mills, David J Elliott
Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure...
October 27, 2015: Oncotarget
Yuta Kojima, Tohru Yoneyama, Shingo Hatakeyama, Jotaro Mikami, Tendo Sato, Kazuyuki Mori, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama, Minoru Fukuda, Yuki Tobisawa
To identify appropriate candidates for aggressive treatment such as radical prostatectomy or radiation therapy of localized prostate cancer (PCa), novel predictive biomarkers of PCa aggressiveness are essential. Core2 β-1,6-N-acetylglucosaminyltransferase-1 (GCNT1) is a key enzyme that forms core 2-branched O-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression to the clinicopathological status of PCa...
2015: PloS One
Reeja Maria Cherian, Chunsheng Jin, Jining Liu, Niclas G Karlsson, Jan Holgersson
Sialylated glycans serve as key elements of receptors for many viruses, bacteria, and bacterial toxins. The microbial recognition and their binding specificity can be affected by the linkage of the terminal sugar residue, types of underlying sugar chains, and the nature of the entire glycoconjugate. Owing to the pathobiological significance of sialylated glycans, we have engineered Chinese hamster ovary (CHO) cells to secrete mucin-type immunoglobulin-fused proteins carrying terminal α2,3- or α2,6-linked sialic acid on defined O-glycan core saccharide chains...
2015: Biomolecules
Mark E Ebel, Olufolakemi Awe, Mark H Kaplan, Geoffrey S Kansas
Selectins are glycan-binding adhesion molecules that mediate the initial steps of leukocyte recognition of endothelium. Cytokines control numerous aspects of CD4 Th cell differentiation, but how cytokines control the induction of ligands for E- and P-selectin on Th cell subsets remains poorly understood. Among 20 cytokines that affect Th cell differentiation, we identified six that induce expression of selectin ligands on murine CD4 T cells above the low levels associated with TCR engagement: IL-12, IL-18, IL-27, IL-9, IL-25, and TGF-β1...
June 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Armen Petrosyan, Melissa S Holzapfel, David E Muirhead, Pi-Wan Cheng
UNLABELLED: Prostate cancer progression is associated with upregulation of sialyl-T antigen produced by β-galactoside α-2,3-sialyltransferase-1 (ST3Gal1) but not with core 2-associated polylactosamine despite expression of core 2 N-acetylglucosaminyltransferase-L (C2GnT-L/GCNT1). This property allows androgen-refractory prostate cancer cells to evade galectin-1 (LGALS1)-induced apoptosis, but the mechanism is not known. We have recently reported that Golgi targeting of glycosyltransferases is mediated by golgins: giantin (GOLGB1) for C2GnT-M (GCNT3) and GM130 (GOLGA2)-GRASP65 (GORASP1) or GM130-giantin for core 1 synthase...
December 2014: Molecular Cancer Research: MCR
Zuxiong Chen, Zulfiqar G Gulzar, Catherine A St Hill, Bruce Walcheck, James D Brooks
BACKGROUND: Protein glycosylation is a common posttranslational modification and glycan structural changes have been observed in several malignancies including prostate cancer. We hypothesized that altered glycosylation could be related to differences in gene expression levels of glycoprotein synthetic enzymes between normal and malignant prostate tissues. METHODS: We interrogated prostate cancer gene expression data for reproducible changes in expression of glycoprotein synthetic enzymes...
July 2014: Prostate
Motohiro Nonaka, Michiko N Fukuda, Chao Gao, Zhen Li, Hongtao Zhang, Mark I Greene, Donna M Peehl, Ten Feizi, Minoru Fukuda
This study reports the determination of the carbohydrate epitope of monoclonal antibody F77 previously raised against human prostate cancer PC-3 cells (Zhang, G., Zhang, H., Wang, Q., Lal, P., Carroll, A. M., de la Llera-Moya, M., Xu, X., and Greene, M. I. (2010) Proc. Natl. Acad. Sci. U. S. A. 107, 732-737). We performed a series of co-transfections using mammalian expression vectors encoding specific glycosyltransferases. We thereby identified branching enzymes and FUT1 (required for Fucα1→2Gal linkage) as being essential for F77 antigen formation...
June 6, 2014: Journal of Biological Chemistry
Jeffrey C Nolz, John T Harty
Memory and naive CD8+ T cells exhibit distinct trafficking patterns. Specifically, memory but not naive CD8+ T cells are recruited to inflamed tissues in an antigen-independent manner. However, the molecular mechanisms that regulate memory CD8+ T cell trafficking are largely unknown. Here, using murine models of infection and T cell transfer, we found that memory but not naive CD8+ T cells dynamically regulate expression of core 2 O-glycans, which interact with P- and E-selectins to modulate trafficking to inflamed tissues...
March 2014: Journal of Clinical Investigation
Yang Ze-Min, Chen Wei-Wen, Wang Ying-Fang
OBJECTIVE: To analyze the metabolic states of the lipids, protein, carbohydrate, and nucleic acid for chronic superficial gastritis patients of splenasthenic syndrome (SS), and to explore the pathogenesis mechanism of SS based on substance and energy metabolisms. METHODS: During June 2004 to March 2005, recruited were four chronic superficial gastritis patients of SS who visited at the First Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Traditional Chinese Medicine...
February 2013: Chinese Journal of Integrated Traditional and Western Medicine
Jiyoung Kim, René Villadsen, Therese Sørlie, Louise Fogh, Signe Z Grønlund, Agla J Fridriksdottir, Irene Kuhn, Fritz Rank, Vera Timmermans Wielenga, Hiroko Solvang, Paul A W Edwards, Anne-Lise Børresen-Dale, Lone Rønnov-Jessen, Mina J Bissell, Ole William Petersen
The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors...
April 17, 2012: Proceedings of the National Academy of Sciences of the United States of America
A Pilz, K Woodward, S Povey, C Abbott
We have set out to produce a comprehensive comparative map between human chromosome 9 (HSA9) and the laboratory mouse. The mouse homologues of 50 loci that were known to map to HSA9 were mapped by interspecific backcross linkage analysis. Ten loci from the short arm of HSA9 were mapped, and 40 from HSA9q, with 24 markers coming from the HSA9q33-q34 region--a part of the chromosome known to be very gene rich. Fifteen new assignments have been made--Ak3, Ctsl, Cntfr, C8g, D2H9S46E, Eng, Gcnt1, Irebp, Pappa, Ptgds, Snf212, Tal2, Tmod, Vav2, and Vldlr, the human homologues of which all map to HSA9...
January 1, 1995: Genomics
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