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Allam H.,University of Arkansas for Medical Sciences | Aoki K.,University of Georgia | Benigno B.B.,Ovarian Cancer Institute | McDonald J.F.,Georgia Institute of Technology | And 4 more authors.
Journal of Proteome Research | Year: 2015

Biomarkers capable of detecting and targeting epithelial ovarian cancer cells for diagnostics and therapeutics would be extremely valuable. Ovarian cancer is the deadliest reproductive malignancy among women in the U.S., killing over 14â€000 women each year. Both the lack of presenting symptoms and high mortality rates illustrate the need for earlier diagnosis and improved treatment of this disease. The glycosyltransferase enzyme GnT-III encoded by the Mgat3 gene is responsible for the addition of GlcNAc (N-acetylglucosamine) to form bisecting N-linked glycan structures. GnT-III mRNA expression is amplified in ovarian cancer tissues compared with normal ovarian tissue. We use a lectin capture strategy coupled to nano-ESI-RPLC-MS/MS to isolate and identify the membrane glycoproteins and unique glycan structures associated with GnT-III amplification in human ovarian cancer tissues. Our data illustrate that the majority of membrane glycoproteins with bisecting glycosylation are common to both serous and endometrioid histological subtypes of ovarian cancer, and several have been reported to participate in signaling pathways such as Notch, Wnt, and TGFβ. © 2014 American Chemical Society.

Abbott K.L.,University of Georgia | Lim J.-M.,University of Georgia | Wells L.,University of Georgia | Benigno B.B.,Ovarian Cancer Institute | And 3 more authors.
Proteomics | Year: 2010

Epithelial ovarian cancer is diagnosed less than 25% of the time when the cancer is confined to the ovary, leading to 5-year survival rates of less than 30%. Therefore, there is an urgent need for early diagnostics for ovarian cancer. Our study using glycotranscriptome comparative analysis of endometrioid ovarian cancer tissue and normal ovarian tissue led to the identification of distinct differences in the transcripts of a restricted set of glycosyltransferases involved in N-linked glycosylation. Utilizing lectins that bind to glycan structures predicted to show changes, we observed differences in lectin-bound glycoproteins consistent with some of the transcript differences. In this study, we have extended our observations by the use of selected lectins to perform a targeted glycoproteomic analysis of ovarian cancer and normal ovarian tissues. Our results have identified several glycoproteins that display tumor-specific glycosylation changes. We have verified these glycosylation changes on glycoproteins from tissue using immunoprecipitation followed by lectin blot detection. The glycoproteins that were verified were then analyzed further using existing microarray data obtained from benign ovarian adenomas, borderline ovarian adenocarcinomas, and malignant ovarian adenocarcinomas. The verified glycoproteins found to be expressed above control levels in the microarray data sets were then screened for tumor-specific glycan modifications in serum from ovarian cancer patients. Results obtained from two of these glycoprotein markers, periostin and thrombospondin, have confirmed that tumor-specific glycan changes can be used to distinguish ovarian cancer patient serum from normal serum. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.

Mittal V.K.,Georgia Institute of Technology | McDonald J.F.,Georgia Institute of Technology | McDonald J.F.,Ovarian Cancer Institute
Nucleic Acids Research | Year: 2012

The rapid expansion in the quantity and quality of RNA-Seq data requires the development of sophisticated high-performance bioinformatics tools capable of rapidly transforming this data into meaningful information that is easily interpretable by biologists. Currently available analysis tools are often not easily installed by the general biologist and most of them lack inherent parallel processing capabilities widely recognized as an essential feature of next-generation bioinformatics tools. We present here a user-friendly and fully automated RNA-Seq analysis pipeline (R-SAP) with built-in multi-threading capability to analyze and quantitate high-throughput RNA-Seq datasets. R-SAP follows a hierarchical decision making procedure to accurately characterize various classes of transcripts and achieves a near linear decrease in data processing time as a result of increased multi-threading. In addition, RNA expression level estimates obtained using R-SAP display high concordance with levels measured by microarrays. © 2012 The Author(s).

Zhou M.,Georgia Institute of Technology | McDonald J.F.,Georgia Institute of Technology | McDonald J.F.,Ovarian Cancer Institute | Fernandez F.M.,Georgia Institute of Technology
Journal of the American Society for Mass Spectrometry | Year: 2010

Metabolomic fingerprinting of bodily fluids can reveal the underlying causes of metabolic disorders associated with many diseases, and has thus been recognized as a potential tool for disease diagnosis and prognosis following therapy. Here we report a rapid approach in which direct analysis in real time (DART) coupled with time-of-flight (TOF) mass spectrometry (MS) and hybrid quadrupole TOF (Q-TOF) MS is used as a means for metabolomic fingerprinting of human serum. In this approach, serum samples are first treated to precipitate proteins, and the volatility of the remaining metabolites increased by derivatization, followed by DART MS analysis. Maximum DART MS performance was obtained by optimizing instrumental parameters such as ionizing gas temperature and flow rate for the analysis of identical aliquots of a healthy human serum samples. These variables were observed to have a significant effect on the overall mass range of the metabolites detected as well as the signal-to-noise ratios in DART mass spectra. Each DART run requires only 1.2 min, during which more than 1500 different spectral features are observed in a time-dependent fashion. A repeatability of 4.1% to 4.5% was obtained for the total ion signal using a manual sampling arm. With the appealing features of high-throughput, lack of memory effects, and simplicity, DART MS has shown potential to become an invaluable tool for metabolomic fingerprinting. © 2010 American Society for Mass Spectrometry.

Benigno B.B.,Ovarian Cancer Institute
International Journal of Gynecological Cancer | Year: 2013

Background: Gestational trophoblastic disease usually follows a molar pregnancy but can occur also after an abortion or a term pregnancy. In only 10% of cases will treatment be required; and usually, single-agent chemotherapy will suffice. In high-risk disease, the multiagent regimen EMA-CO is usually used; and if that fails, most oncologists will use the EMA-EP regimen. If this does not produce a remission, there is no unanimity of opinion as to how to proceed. Numerous salvage regimens are in current use, and some centers do not consider high-dose chemotherapy. Case: A young woman presented 4 months after a normal spontaneous delivery with an elevated human chorionic gonadotropin level and multiple pulmonary metastases. She failed both the EMA-CO and EMA-EP regimens as well as additional standard chemotherapy. She was then treated with 4 separate courses of high-dose chemotherapy with autologous stem cell support, which produced a complete remission. Conclusion: Even patients with high-risk gestational trophoblastic disease are usually cured with standard chemotherapy. Patients who fail such treatment should be considered for high-dose chemotherapy. Copyright © 2013 by IGCS and ESGO.

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