@article{williams_saggese_toups_frahm_an_li_lebrilla_muddiman_2008, title={Investigations with O-linked protein glycosylations by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry}, volume={43}, ISSN={["1076-5174"]}, url={http://europepmc.org/abstract/med/18324610}, DOI={10.1002/jms.1398}, abstractNote={AbstractPosttranslational modifications such as glycosylation can play a fundamental role in signaling pathways that transform an ordinary cell into a malignant one. The development of a protocol to detect these changes in the preliminary stages of disease can lead to a sensitive and specific diagnostic for the early detection of malignancies such as ovarian cancer in which differential glycan patterns are linked to etiology and progression. Small variations in instrument parameters and sample preparation techniques are known to have significant influence on the outcome of an experiment. For an experiment to be effective and reproducible, these parameters must be optimized for the analyte(s) under study. We present a detailed examination of sample preparation and matrix‐assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI‐FT‐ICR‐MS) analysis of O‐linked glycans globally cleaved from mucin glycoproteins. Experiments with stable isotope‐labeled biomolecules allowed for the establishment of appropriate acquisition times and excitation voltages for MALDI‐FT‐ICR‐MS of oligosaccharides. Quadrupole ion guide optimization studies with mucin glycans identified conditions for the comprehensive analysis of the entire mass range of O‐linked carbohydrates in this glycoprotein. Separately optimized experimental parameters were integrated in a method that allowed for the effective study of O‐linked glycans. Copyright © 2008 John Wiley & Sons, Ltd.}, number={9}, journal={JOURNAL OF MASS SPECTROMETRY}, author={Williams, Taufika Islam and Saggese, Diana A. and Toups, Kristina L. and Frahm, Jennifer L. and An, Hyun Joo and Li, Bensheng and Lebrilla, Carlito B. and Muddiman, David C.}, year={2008}, month={Sep}, pages={1215–1223} } @article{williams_saggese_muddiman_2008, title={Studying O-linked protein glycosylations in human plasma}, volume={7}, ISSN={["1535-3893"]}, url={http://europepmc.org/abstract/med/18422354}, DOI={10.1021/pr800066e}, abstractNote={Recent investigations have implicated aberrant glycosylations in various malignancies, including epithelial ovarian cancer (EOC). The protocol here identifies O-linked carbohydrate patterns in EOC plasma glycoproteins through chemical cleavage and purification of these glycans. Dialyzed plasma is subjected to reductive beta-elimination with alkaline borohydride to release O-linked oligosaccharides from glycoproteins. Enrichment of released glycans, as well as removal of peptide and other contaminants, is followed by carbohydrate pattern analysis with MALDI-FT-ICR-MS.}, number={6}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Williams, Taufika Islam and Saggese, Diana A. and Muddiman, David C.}, year={2008}, month={Jun}, pages={2562–2568} } @article{williams_saggese_wilcox_martin_muddiman_2007, title={Effect of matrix crystal structure on ion abundance of carbohydrates by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry}, volume={21}, ISSN={["0951-4198"]}, url={http://europepmc.org/abstract/med/17279479}, DOI={10.1002/rcm.2904}, abstractNote={AbstractSample preparation techniques for carbohydrate analysis using matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) are explored, with particular emphasis on analyte/matrix co‐crystallization procedures. While carbohydrates are known to prefer 2,5‐dihydroxybenzoic acid (2,5‐DHB) as the matrix of choice, these analytes are quite specific about matrix crystal structure, which in turn is dependent on the rate of drying of analyte/matrix spots on the MALDI target. With N‐acetylglucosamine (GlcNAc) and N‐acetylneuraminic acid (sialic acid or NeuAc) as test monosaccharides, significant increases in ion abundances are demonstrated with 2,5‐DHB/NeuAc spots (>10‐fold improvement) and 2,5‐DHB/GlcNAc spots (∼5‐fold improvement) with active drying. The fine structure of crystals generated in active and passive drying was investigated using powder diffraction. Passively dried samples were shown to consist of an ordered polymorph, crystallizing in the space group P21/a, while the actively dried samples produced a disordered phase crystallizing in the space group Pa. These data provide the wherewithal to engineer a matrix best suited for carbohydrate analyses. Copyright © 2007 John Wiley & Sons, Ltd.}, number={5}, journal={RAPID COMMUNICATIONS IN MASS SPECTROMETRY}, author={Williams, Taufika Islam and Saggese, Diana A. and Wilcox, Robert J. and Martin, James D. and Muddiman, David C.}, year={2007}, pages={807–811} } @misc{williams_toups_saggese_kalli_cliby_muddiman_2007, title={Epithelial ovarian cancer: Disease etiology, treatment, detection, and investigational gene, metabolite, and protein biomarkers}, volume={6}, ISSN={["1535-3907"]}, url={http://europepmc.org/abstract/med/17583933}, DOI={10.1021/pr070041v}, abstractNote={Cancer research in recent years has immensely benefited from the development of novel technologies that enable scientists to perform detailed investigations of genomes, transcriptomes, proteomes, and metabolomes. This has invariably furthered knowledge of tumorigenesis and etiology of cancer. The resulting information can, in the foreseeable future, effect a significant change in the pace of cancer research, thereby producing improvements in patient care. Ovarian cancer in particular has received the interest of the scientific community, being the most frequent cause of death from gynecological cancers, characterized by few early symptoms, diagnosis at an advanced stage, as well as poor prognosis. Ovarian cancer is a malignancy in which normal ovarian cells begin to grow in an uncontrolled, abnormal manner and produce tumors in one or both ovaries. Epithelial cancers, the most common ovarian cancers (>80%), develop from cells lining the ovarian surface. Most ovarian cancer research is primarily focused on the early detection and treatment of epithelial ovarian cancer, the more common ovarian malignancy. This review offers an introduction to ovarian cancer, with particular emphasis on human epithelial ovarian cancer. Current methods of detection and therapy are discussed. A survey of promising new protein, gene, and metabolite biomarkers on the horizon is provided. Future prospects for improved diagnosis are offered.}, number={8}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Williams, Taufika Islam and Toups, Kristina L. and Saggese, Diana A. and Kalli, Kimberly R. and Cliby, William A. and Muddiman, David C.}, year={2007}, month={Aug}, pages={2936–2962} }