50 results on '"George Tseng"'
Search Results
2. Human Milk Supports Robust Intestinal Organoid Growth, Differentiation, and Homeostatic Cytokine Production
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Lauren Smith, Eduardo Gonzalez Santiago, Chino Eke, Weihong Gu, Wenjia Wang, Dhana Llivichuzhca-Loja, Tessa Kehoe, Kerri St Denis, Madison Strine, Sarah Taylor, George Tseng, and Liza Konnikova
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Intestinal Development ,Breast Milk ,Necrotizing Enterocolitis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Background and Aims: Necrotizing enterocolitis is a severe gastrointestinal complication of prematurity. Using small intestinal organoids derived from fetal tissue of a gestational age similar to an extremely preterm infant, this study aims to assess the effect of diet on intestinal epithelial growth and differentiation to elucidate the role nutrition type plays in intestinal development and modifies the risk for necrotizing enterocolitis. Methods: Organoids were cultured for 5 days in growth media and 5 days in differentiation media supplemented 1:40 with 4 different diets: parental milk, donor human milk, standard formula, or extensively hydrolyzed formula. Images were captured daily and organoids were quantified. Organoids were preserved for RNA sequencing and immunofluorescence staining with Ki67, cleaved caspase 3, and chromogranin-A. Media was saved for cytokine/chemokine and growth factor analysis. Results: Human milk supplementation improved growth and differentiation of intestinal organoids generating larger organoids during the growth phase and organoids with longer and wider buds during differentiation compared to formula. Ki67 staining confirmed the proliferative nature of milk-supplemented organoids and chromogranin A staining proved that MM-supplemented organoids induced highest enteroendocrine differentiation. Human milk supplementation also upregulated genes involved in Wnt signaling and fatty acid metabolism pathways and promoted a homeostatic immune landscape, including via increased secretion of tumor necrosis factor-related apoptosis-inducing ligand among other cytokines. Conversely, organoids supplemented with formula had a downregulation of cell-cycle-promoting genes and a more inflammatory immune signature, including a reduced level of leukemia inhibitory factor. Conclusion: Our results demonstrate that parental milk, and to a lesser extent donor human milk, support robust intestinal epithelial proliferation, differentiation, and homeostatic cytokine production, suggesting a critical role for factors enriched in human milk in intestinal epithelial health. more...
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- 2024
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Catalog
3. Diagnosis of T-cell-mediated kidney rejection by biopsy-based proteomic biomarkers and machine learning
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Fei Fang, Peng Liu, Lei Song, Patrick Wagner, David Bartlett, Liane Ma, Xue Li, M. Amin Rahimian, George Tseng, Parmjeet Randhawa, and Kunhong Xiao
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biomarker ,quantitative proteomics ,machine learning ,FFPE ,kidney transplantation ,diagnosis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundBiopsy-based diagnosis is essential for maintaining kidney allograft longevity by ensuring prompt treatment for graft complications. Although histologic assessment remains the gold standard, it carries significant limitations such as subjective interpretation, suboptimal reproducibility, and imprecise quantitation of disease burden. It is hoped that molecular diagnostics could enhance the efficiency, accuracy, and reproducibility of traditional histologic methods.MethodsQuantitative label-free mass spectrometry analysis was performed on a set of formalin-fixed, paraffin-embedded (FFPE) biopsies from kidney transplant patients, including five samples each with diagnosis of T-cell-mediated rejection (TCMR), polyomavirus BK nephropathy (BKPyVN), and stable (STA) kidney function control tissue. Using the differential protein expression result as a classifier, three different machine learning algorithms were tested to build a molecular diagnostic model for TCMR.ResultsThe label-free proteomics method yielded 800-1350 proteins that could be quantified with high confidence per sample by single-shot measurements. Among these candidate proteins, 329 and 467 proteins were defined as differentially expressed proteins (DEPs) for TCMR in comparison with STA and BKPyVN, respectively. Comparing the FFPE quantitative proteomics data set obtained in this study using label-free method with a data set we previously reported using isobaric labeling technology, a classifier pool comprised of features from DEPs commonly quantified in both data sets, was generated for TCMR prediction. Leave-one-out cross-validation result demonstrated that the random forest (RF)-based model achieved the best predictive power. In a follow-up blind test using an independent sample set, the RF-based model yields 80% accuracy for TCMR and 100% for STA. When applying the established RF-based model to two public transcriptome datasets, 78.1%-82.9% sensitivity and 58.7%-64.4% specificity was achieved respectively.ConclusionsThis proof-of-principle study demonstrates the clinical feasibility of proteomics profiling for FFPE biopsies using an accurate, efficient, and cost-effective platform integrated of quantitative label-free mass spectrometry analysis with a machine learning-based diagnostic model. It costs less than 10 dollars per test. more...
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- 2023
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4. Patient treatment and outcome after breast cancer orbital and periorbital metastases: a comprehensive case series including analysis of lobular versus ductal tumor histology
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Martin Blohmer, Li Zhu, Jennifer M. Atkinson, Sushil Beriwal, Joshua L. Rodríguez-López, Margaret Rosenzweig, Adam M. Brufsky, George Tseng, Peter C. Lucas, Adrian V. Lee, Steffi Oesterreich, and Rachel C. Jankowitz more...
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Breast cancer ,Invasive lobular carcinoma ,Metastasis ,Eye ,Ophthalmology ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Breast cancer is the most common malignancy to spread to the orbit and periorbit, and the invasive lobular carcinoma (ILC) histologic subtype of breast cancer has been reported to form these ophthalmic metastases (OM) more frequently than invasive ductal carcinomas (IDC). We herein report our single academic institution experience with breast cancer OM with respect to anatomical presentation, histology (lobular vs. ductal), treatment, and survival. Methods We employed the natural language processing platform, TIES (Text Information Extraction System), to search 2.3 million de-identified patient pathology and radiology records at our institution in order to identify patients with OM secondary to breast cancer. We then compared the resultant cohort, the “OM cohort,” to two other representative metastatic breast cancer patient (MBC) databases from our institution. Histological analysis of selected patients was performed. Results Our TIES search and manual refinement ultimately identified 28 patients who were diagnosed with breast cancer between 1995 and 2016 that subsequently developed OM. Median age at diagnosis was 54 (range 28–77) years of age. ER, PR, and HER2 status from the 28 patients with OM did not differ from other patients with MBC from our institution. The relative proportion of patients with ILC was significantly higher in the OM cohort (32.1%) than in other MBC patients in our institution (11.3%, p = 0.007). Median time to first OM in the OM cohort was 46.7 months, and OM were the second most frequent first metastases after bony metastases. After diagnosis of the first distant metastasis of any kind, median survival of patients with ILC (21.4 months) was significantly shorter than that of patients with IDC (55.3 months, p = 0.03). Nine patients developed bilateral OM. We observed a significant co-occurrence of OM and central nervous system metastases (p = 0.0053). The histological analysis revealed an interesting case in which the primary tumor was of a mixed ILC/IDC subtype, while only ILC was present in the OM. Conclusions OM from breast cancer are illustrative of the difference in metastatic behavior of ILC versus IDC and should be considered when treating patients with ILC, especially in those with complaints of visual acuity changes. more...
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- 2020
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5. Diurnal rhythms in gene expression in the prefrontal cortex in schizophrenia
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Marianne L. Seney, Kelly Cahill, John F. Enwright, Ryan W. Logan, Zhiguang Huo, Wei Zong, George Tseng, and Colleen A. McClung
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Science - Abstract
Sleep disturbance is common in psychiatric disease, and this may contribute to altered circadian rhythm in gene expression. Here the authors show that rhythms in gene expression in the dorsolateral prefrontal cortex in schizophrenia are different to that seen in healthy controls. more...
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- 2019
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6. In utero human intestine harbors unique metabolome, including bacterial metabolites
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Yujia Li, Jessica M. Toothaker, Shira Ben-Simon, Lital Ozeri, Ron Schweitzer, Blake T. McCourt, Collin C. McCourt, Lael Werner, Scott B. Snapper, Dror S. Shouval, Soliman Khatib, Omry Koren, Sameer Agnihorti, George Tseng, and Liza Konnikova more...
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Gastroenterology ,Metabolism ,Medicine - Abstract
Symbiotic microbial colonization through the establishment of the intestinal microbiome is critical to many intestinal functions, including nutrient metabolism, intestinal barrier integrity, and immune regulation. Recent studies suggest that education of intestinal immunity may be ongoing in utero. However, the drivers of this process are unknown. The microbiome and its byproducts are one potential source. Whether a fetal intestinal microbiome exists is controversial, and whether microbially derived metabolites are present in utero is unknown. Here, we aimed to determine whether bacterial DNA and microbially derived metabolites can be detected in second trimester human intestinal samples. Although we were unable to amplify bacterial DNA from fetal intestines, we report a fetal metabolomic intestinal profile with an abundance of bacterially derived and host-derived metabolites commonly produced in response to microbiota. Though we did not directly assess their source and function, we hypothesize that these microbial-associated metabolites either come from the maternal microbiome and are vertically transmitted to the fetus to prime the fetal immune system and prepare the gastrointestinal tract for postnatal microbial encounters or are produced locally by bacteria that were below our detection threshold. more...
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- 2020
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7. Recent Advances in Computer-Assisted Algorithms for Cell Subtype Identification of Cytometry Data
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Peng Liu, Silvia Liu, Yusi Fang, Xiangning Xue, Jian Zou, George Tseng, and Liza Konnikova
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CyTOF ,manual gating ,cell type identification ,clustering ,auto-gating ,visualization ,Biology (General) ,QH301-705.5 - Abstract
The progress in the field of high-dimensional cytometry has greatly increased the number of markers that can be simultaneously analyzed producing datasets with large numbers of parameters. Traditional biaxial manual gating might not be optimal for such datasets. To overcome this, a large number of automated tools have been developed to aid with cellular clustering of multi-dimensional datasets. Here were review two large categories of such tools; unsupervised and supervised clustering tools. After a thorough review of the popularity and use of each of the available unsupervised clustering tools, we focus on the top six tools to discuss their advantages and limitations. Furthermore, we employ a publicly available dataset to directly compare the usability, speed, and relative effectiveness of the available unsupervised and supervised tools. Finally, we discuss the current challenges for existing methods and future direction for the new generation of cell type identification approaches. more...
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- 2020
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8. Gene Expression Signatures Can Aid Diagnosis of Sexually Transmitted Infection-Induced Endometritis in Women
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Xiaojing Zheng, Catherine M. O'Connell, Wujuan Zhong, Taylor B. Poston, Harold C. Wiesenfeld, Sharon L. Hillier, Maria Trent, Charlotte Gaydos, George Tseng, Brandie D. Taylor, and Toni Darville
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biomarker ,mRNA ,Chlamydia ,gonorrhea ,pelvic inflammatory disease ,Microbiology ,QR1-502 - Abstract
Sexually transmitted infection (STI) of the upper reproductive tract can result in inflammation and infertility. A biomarker of STI-induced upper tract inflammation would be significant as many women are asymptomatic and delayed treatment increases risk of sequelae. Blood mRNA from 111 women from three cohorts was profiled using microarray. Unsupervised analysis revealed a transcriptional profile that distinguished 9 cases of STI-induced endometritis from 18 with cervical STI or uninfected controls. Using a hybrid feature selection algorithm we identified 21 genes that yielded maximal classification accuracy within our training dataset. Predictive accuracy was evaluated using an independent testing dataset of 5 cases and 10 controls. Sensitivity was evaluated in a separate test set of 12 women with asymptomatic STI-induced endometritis in whom cervical burden was determined by PCR; and specificity in an additional test set of 15 uninfected women with pelvic pain due to unknown cause. Disease module preservation was assessed in 42 women with a clinical diagnosis of pelvic inflammatory disease (PID). We also tested the ability of the biomarker to discriminate STI-induced endometritis from other diseases. The biomarker was 86.7% (13/15) accurate in correctly distinguishing cases from controls in the testing dataset. Sensitivity was 83.3% (5/6) in women with high cervical Chlamydia trachomatis burden and asymptomatic endometritis, but 0% (0/6) in women with low burden. Specificity in patients with non-STI-induced pelvic pain was 86.7% (13/15). Disease modules were preserved in all 8 biomarker predicted cases. The 21-gene biomarker was highly discriminatory for systemic infections, lupus, and appendicitis, but wrongly predicted tuberculosis as STI-induced endometritis in 52.4%. A 21-gene biomarker can identify asymptomatic women with STI-induced endometritis that places them at risk for chronic disease development and discriminate STI-induced endometritis from non-STI pelvic pain and other diseases. more...
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- 2018
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9. High fidelity copy number analysis of formalin-fixed and paraffin-embedded tissues using Affymetrix Cytoscan HD chip.
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Yan P Yu, Amantha Michalopoulos, Ying Ding, George Tseng, and Jian-Hua Luo
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Medicine ,Science - Abstract
Detection of human genome copy number variation (CNV) is one of the most important analyses in diagnosing human malignancies. Genome CNV detection in formalin-fixed and paraffin-embedded (FFPE) tissues remains challenging due to suboptimal DNA quality and failure to use appropriate baseline controls for such tissues. Here, we report a modified method in analyzing CNV in FFPE tissues using microarray with Affymetrix Cytoscan HD chips. Gel purification was applied to select DNA with good quality and data of fresh frozen and FFPE tissues from healthy individuals were included as baseline controls in our data analysis. Our analysis showed a 91% overlap between CNV detection by microarray with FFPE tissues and chromosomal abnormality detection by karyotyping with fresh tissues on 8 cases of lymphoma samples. The CNV overlap between matched frozen and FFPE tissues reached 93.8%. When the analyses were restricted to regions containing genes, 87.1% concordance between FFPE and fresh frozen tissues was found. The analysis was further validated by Fluorescence In Situ Hybridization on these samples using probes specific for BRAF and CITED2. The results suggested that the modified method using Affymetrix Cytoscan HD chip gave rise to a significant improvement over most of the previous methods in terms of accuracy in detecting CNV in FFPE tissues. This FFPE microarray methodology may hold promise for broad application of CNV analysis on clinical samples. more...
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- 2014
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10. Distinct genes related to drug response identified in ER positive and ER negative breast cancer cell lines.
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Kui Shen, Shara D Rice, David A Gingrich, Dakun Wang, Zhibao Mi, Chunqiao Tian, Zhenyu Ding, Stacey L Brower, Paul R Ervin, Michael J Gabrin, George Tseng, and Nan Song
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Medicine ,Science - Abstract
Breast cancer patients have different responses to chemotherapeutic treatments. Genes associated with drug response can provide insight to understand the mechanisms of drug resistance, identify promising therapeutic opportunities, and facilitate personalized treatment. Estrogen receptor (ER) positive and ER negative breast cancer have distinct clinical behavior and molecular properties. However, to date, few studies have rigorously assessed drug response genes in them. In this study, our goal was to systematically identify genes associated with multidrug response in ER positive and ER negative breast cancer cell lines. We tested 27 human breast cell lines for response to seven chemotherapeutic agents (cyclophosphamide, docetaxel, doxorubicin, epirubicin, fluorouracil, gemcitabine, and paclitaxel). We integrated publicly available gene expression profiles of these cell lines with their in vitro drug response patterns, then applied meta-analysis to identify genes related to multidrug response in ER positive and ER negative cells separately. One hundred eighty-eight genes were identified as related to multidrug response in ER positive and 32 genes in ER negative breast cell lines. Of these, only three genes (DBI, TOP2A, and PMVK) were common to both cell types. TOP2A was positively associated with drug response, and DBI was negatively associated with drug response. Interestingly, PMVK was positively associated with drug response in ER positive cells and negatively in ER negative cells. Functional analysis showed that while cell cycle affects drug response in both ER positive and negative cells, most biological processes that are involved in drug response are distinct. A number of signaling pathways that are uniquely enriched in ER positive cells have complex cross talk with ER signaling, while in ER negative cells, enriched pathways are related to metabolic functions. Taken together, our analysis indicates that distinct mechanisms are involved in multidrug response in ER positive and ER negative breast cells. more...
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- 2012
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11. Fusion Gene Detection in Prostate Cancer Samples Enhances the Prediction of Prostate Cancer Clinical Outcomes from Radical Prostatectomy through Machine Learning in a Multi-Institutional Analysis
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Yan-Ping Yu, Silvia Liu, Bao-Guo Ren, Joel Nelson, David Jarrard, James D. Brooks, George Michalopoulos, George Tseng, and Jian-Hua Luo
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Pathology and Forensic Medicine - Published
- 2023
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12. Major depression, physical health and molecular senescence markers abnormalities
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Johanna Seitz-Holland, Benoit H. Mulsant, Charles F. Reynolds III, Daniel M. Blumberger, Jordan F. Karp, Meryl A. Butters, Ana Paula Mendes-Silva, Erica L. Vieira, George Tseng, Eric J. Lenze, and Breno S. Diniz more...
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Previous studies suggested the role of cellular senescence in late-life depression (LLD). However, it is unclear how this finding relates to common features of LLD, such as medical and cognitive problems. We applied factor analyses to an extensive battery of clinical variables in 426 individuals with LLD. Here we tested the relationship between these factors, age and sex, with an index of cellular senescence based on 22 senescence-associated secretory phenotype proteins. We found four factors: ‘depression and anxiety severity’, ‘cognitive functioning’, ‘cardiovascular and cardiometabolic health’ and ‘blood pressure’. A higher senescence-associated secretory phenotype index was associated with poorer ‘cognitive functioning’ and ‘cardiovascular and cardiometabolic health’ but not with ‘depression and anxiety severity’. These findings highlight the role of cellular senescence in poorer physical and cognitive health in LLD. They are consonant with the viewpoint that co-occurring medical burdens and their associated disabilities are part of a phenotype of accelerated ageing in LLD. more...
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- 2023
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13. Data from Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens
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Steffi Oesterreich, Robert P. Edwards, Esther Elishaev, Adrian V. Lee, Karen McLean, Kunle Odunsi, Gina M. Mantia-Smaldone, Paul Haluska, Uma Chandran, Soumya Luthra, Yongseok Park, George Tseng, Alec Christie, Tianzhou Ma, Michelle M. Boisen, Matthew J. Sikora, and Courtney L. Andersen more...
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Purpose: High-grade serous ovarian cancer (HGSOC) is an aggressive disease with few available targeted therapies. Despite high expression of estrogen receptor-alpha (ERα) in approximately 80% of HGSOC and some small but promising clinical trials of endocrine therapy, ERα has been understudied as a target in this disease. We sought to identify hormone-responsive, ERα-dependent HGSOC.Experimental Design: We characterized endocrine response in HGSOC cells across culture conditions [ two-dimensional (2D), three-dimensional (3D), forced suspension] and in patient-derived xenograft (PDX) explants, assessing proliferation and gene expression. Estrogen-regulated transcriptome data were overlapped with public datasets to develop a comprehensive panel of ERα target genes. Expression of this panel and ERα H-score were assessed in HGSOC samples from patients who received endocrine therapy. Time on endocrine therapy was used as a surrogate for clinical response.Results: Proliferation is ERα-regulated in HGSOC cells in vitro and in vivo, and is partly dependent on 3D context. Transcriptomic studies identified genes shared by cell lines and PDX explants as ERα targets. The selective ERα downregulator (SERD) fulvestrant is more effective than tamoxifen in blocking ERα action. ERα H-score is predictive of efficacy of endocrine therapy, and this prediction is further improved by inclusion of target gene expression, particularly IGFBP3.Conclusions: Laboratory models corroborate intertumor heterogeneity of endocrine response in HGSOC but identify features associated with functional ERα and endocrine responsiveness. Assessing ERα function (e.g., IGFBP3 expression) in conjunction with H-score may help select patients who would benefit from endocrine therapy. Preclinical data suggest that SERDs might be more effective than tamoxifen. Clin Cancer Res; 23(14); 3802–12. ©2017 AACR. more...
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- 2023
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14. Suppl Table S1 from Complement Pathway Is Frequently Altered in Endometriosis and Endometriosis-Associated Ovarian Cancer
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Anda M. Vlad, Robert P. Edwards, Suketu Mansuria, Ted Lee, George Tseng, Tianzhou Ma, Gina Mantia-Smaldone, Nicole Donnellan, SungHwan Kim, Lixin Zhang, Raluca A. Budiu, Esther Elishaev, Xin Huang, and Swati Suryawanshi more...
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Suppl Table S1. Differentially expressed genes from different group comparisons
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- 2023
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15. Supplementary Materials and Methods from Complement Pathway Is Frequently Altered in Endometriosis and Endometriosis-Associated Ovarian Cancer
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Anda M. Vlad, Robert P. Edwards, Suketu Mansuria, Ted Lee, George Tseng, Tianzhou Ma, Gina Mantia-Smaldone, Nicole Donnellan, SungHwan Kim, Lixin Zhang, Raluca A. Budiu, Esther Elishaev, Xin Huang, and Swati Suryawanshi more...
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Supplementary Materials and Methods
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- 2023
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16. Data from Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity
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Anda M. Vlad, Pawel Kalinski, Robert P. Edwards, William Gooding, George Tseng, Chaeryon Kang, Esther Elishaev, Alexandra Pusateri, Adria Suarez Mora, Lixin Zhang, Mainpal Rana, Ibrahim Uygun, Mary Strange, Yusi Fang, Haider Mahdi, and Brian Orr more...
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Purpose:Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC.Patients and Methods:Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received intraperitoneal IFNα at 2, 6, and 18 million units (MU), respectively. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and intraperitoneal wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively.Results:The P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 months, respectively. Longitudinal sampling of the peritoneal cavity via intraperitoneal washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 week.Conclusions:The chemokine-modulating intraperitoneal-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial.See related commentary by Aranda et al., p. 1993 more...
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- 2023
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17. Suppl Fig S1 from Complement Pathway Is Frequently Altered in Endometriosis and Endometriosis-Associated Ovarian Cancer
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Anda M. Vlad, Robert P. Edwards, Suketu Mansuria, Ted Lee, George Tseng, Tianzhou Ma, Gina Mantia-Smaldone, Nicole Donnellan, SungHwan Kim, Lixin Zhang, Raluca A. Budiu, Esther Elishaev, Xin Huang, and Swati Suryawanshi more...
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Suppl Fig S1. Venn diagram of DE genes from 3 group comparisons
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- 2023
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18. Supplementary File 3 from Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens
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Steffi Oesterreich, Robert P. Edwards, Esther Elishaev, Adrian V. Lee, Karen McLean, Kunle Odunsi, Gina M. Mantia-Smaldone, Paul Haluska, Uma Chandran, Soumya Luthra, Yongseok Park, George Tseng, Alec Christie, Tianzhou Ma, Michelle M. Boisen, Matthew J. Sikora, and Courtney L. Andersen more...
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Supplementary File 3 contains the available pre- and post-treatment CA-125 data for our patient cohort.
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- 2023
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19. Supplementary File 1 from Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens
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Steffi Oesterreich, Robert P. Edwards, Esther Elishaev, Adrian V. Lee, Karen McLean, Kunle Odunsi, Gina M. Mantia-Smaldone, Paul Haluska, Uma Chandran, Soumya Luthra, Yongseok Park, George Tseng, Alec Christie, Tianzhou Ma, Michelle M. Boisen, Matthew J. Sikora, and Courtney L. Andersen more...
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Supplementary File 1 contains the genes included in the "EndoRx" NanoString code set.
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- 2023
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20. Supplementary Table from Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity
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Anda M. Vlad, Pawel Kalinski, Robert P. Edwards, William Gooding, George Tseng, Chaeryon Kang, Esther Elishaev, Alexandra Pusateri, Adria Suarez Mora, Lixin Zhang, Mainpal Rana, Ibrahim Uygun, Mary Strange, Yusi Fang, Haider Mahdi, and Brian Orr more...
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Supplementary Table from Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity more...
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- 2023
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21. Supplementary Figure from Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity
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Anda M. Vlad, Pawel Kalinski, Robert P. Edwards, William Gooding, George Tseng, Chaeryon Kang, Esther Elishaev, Alexandra Pusateri, Adria Suarez Mora, Lixin Zhang, Mainpal Rana, Ibrahim Uygun, Mary Strange, Yusi Fang, Haider Mahdi, and Brian Orr more...
- Abstract
Supplementary Figure from Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity more...
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- 2023
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22. Supplementary Figures from Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens
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Steffi Oesterreich, Robert P. Edwards, Esther Elishaev, Adrian V. Lee, Karen McLean, Kunle Odunsi, Gina M. Mantia-Smaldone, Paul Haluska, Uma Chandran, Soumya Luthra, Yongseok Park, George Tseng, Alec Christie, Tianzhou Ma, Michelle M. Boisen, Matthew J. Sikora, and Courtney L. Andersen more...
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This document contains the supplementary figures for the manuscript.
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- 2023
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23. Supplementary Table 2 from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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Jian-Hua Luo, George Michalopoulos, Reza Zarnegar, Marie Defrances, Joel Nelson, Kathleen Cieply, George Tseng, Guoying Yu, and Yan P. Yu
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Supplementary Table 2 from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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- 2023
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24. Data from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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Jian-Hua Luo, George Michalopoulos, Reza Zarnegar, Marie Defrances, Joel Nelson, Kathleen Cieply, George Tseng, Guoying Yu, and Yan P. Yu
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Glutathione peroxidase 3 is a selenium-dependent enzyme playing a critical role in detoxifying reactive oxidative species and maintaining the genetic integrity of mammalian cells. In this report, we found that the expression of glutathione peroxidase 3 (GPx3) was widely inactivated in prostate cancers. Complete inactivation of GPx3 correlates with a poor clinical outcome. Deletions (hemizygous and homozygous) of GPx3 gene are frequent in prostate cancer samples, occurring in 39% of the samples studied. The rate of methylation of the GPx3 exon 1 region in prostate cancer samples reaches 90%. Overexpression of GPx3 in prostate cancer cell lines induced the suppression of colony formation and anchorage-independent growth of PC3, LNCaP, and Du145 cells. PC3 cells overexpressing GPx3 reduced invasiveness in Matrigel transmigration analysis by an average of 2.7-fold. Xenografted PC3 cells expressing GPx3 showed reduction in tumor volume by 4.8-fold, elimination of metastasis (0/16 versus 7/16), and reduction of animal death (3/16 versus 16/16). The tumor suppressor activity of GPx3 seems to relate to its ability to suppress the expression of c-met. The present findings suggest that GPx3 is a novel tumor suppressor gene. [Cancer Res 2007;67(17):8043–50] more...
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- 2023
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25. Supplementary Table 1 from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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Jian-Hua Luo, George Michalopoulos, Reza Zarnegar, Marie Defrances, Joel Nelson, Kathleen Cieply, George Tseng, Guoying Yu, and Yan P. Yu
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Supplementary Table 1 from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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- 2023
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26. Supplementary Figure 1 from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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Jian-Hua Luo, George Michalopoulos, Reza Zarnegar, Marie Defrances, Joel Nelson, Kathleen Cieply, George Tseng, Guoying Yu, and Yan P. Yu
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Supplementary Figure 1 from Glutathione Peroxidase 3, Deleted or Methylated in Prostate Cancer, Suppresses Prostate Cancer Growth and Metastasis
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- 2023
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27. 98. Cellular Senescence in Late-Life Depression
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Johanna Seitz-Holland, Benoit H. Mulsant, Charles F. Reynolds, Daniel M. Blumberger, Jordan F. Karp, Meryl A. Butters, Ana Paula Mendes-Silva, Erica L. Vieira, George Tseng, Eric J. Lenze, and Breno S. Diniz more...
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Biological Psychiatry - Published
- 2023
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28. 452. The 12 h Transcriptome in Human Prefrontal Cortex and Striatal Subregions and Abnormalities in Schizophrenia
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Madeline Scott, Kyle Ketchesin, Wei Zong, Mariah Hildebrand, Marianne Seney, Jill Glausier, David Lewis, George Tseng, and Colleen McClung
- Subjects
Biological Psychiatry - Published
- 2023
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29. DiffCircaPipeline: a framework for multifaceted characterization of differential rhythmicity
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Xiangning Xue, Wei Zong, Zhiguang Huo, Kyle D Ketchesin, Madeline R Scott, Kaitlyn A Petersen, Ryan W Logan, Marianne L Seney, Colleen McClung, and George Tseng
- Subjects
Statistics and Probability ,Computational Mathematics ,Computational Theory and Mathematics ,Molecular Biology ,Biochemistry ,Computer Science Applications - Abstract
Summary Circadian oscillations of gene expression regulate daily physiological processes, and their disruption is linked to many diseases. Circadian rhythms can be disrupted in a variety of ways, including differential phase, amplitude and rhythm fitness. Although many differential circadian biomarker detection methods have been proposed, a workflow for systematic detection of multifaceted differential circadian characteristics with accurate false positive control is not currently available. We propose a comprehensive and interactive pipeline to capture the multifaceted characteristics of differentially rhythmic biomarkers. Analysis outputs are accompanied by informative visualization and interactive exploration. The workflow is demonstrated in multiple case studies and is extensible to general omics applications. Availability and implementation R package, Shiny app and source code are available in GitHub (https://github.com/DiffCircaPipeline) and Zenodo (https://doi.org/10.5281/zenodo.7507989) Supplementary information Supplementary data are available at Bioinformatics online. more...
- Published
- 2023
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30. Novel Murine Cell Lines with Defined Mutations Model Different Histological Subtypes of Ovarian Cancer
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Lixin Zhang, Yusi Fang, Ibrahim Uygun, Mary Strange, Syed Zaidi, Julia Knight, Mackenzy Radolec, Esther Elishaev, George Tseng, Sandra Cascio, Robert P. Edwards, Ronald Buckanovich, and Anda Vlad
- Published
- 2023
- Full Text
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31. 446. Comparative Rhythmic Transcriptome Profiling of Human and Mouse Striatal Subregions
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Kaitlyn Petersen, Wei Zong, Kyle Ketchesin, Lauren Depoy, Madeline Scott, Vaishnavi Shankar, Jennifer Burns, Allison Cerwensky, Sam-Moon Kim, Jill Glausier, David Lewis, Marianne Seney, George Tseng, and Colleen McClung more...
- Subjects
Biological Psychiatry - Published
- 2023
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32. Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine
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Emma Mastrobattista, Eric J. Lenze, Charles F. Reynolds, Benoit H. Mulsant, Julie Wetherell, Gregory F. Wu, Daniel M. Blumberger, Jordan F. Karp, Meryl A. Butters, Ana Paula Mendes-Silva, Erica L. Vieira, George Tseng, and Breno S. Diniz more...
- Subjects
Male ,Psychiatry and Mental health ,Depressive Disorder, Major ,Aging ,Growth Differentiation Factor 15 ,Depression ,Humans ,Female ,Comorbidity ,Geriatrics and Gerontology ,Biomarkers ,Aged - Abstract
In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance.This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals.After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression.Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging. more...
- Published
- 2022
33. A sparse negative binomial classifier with covariate adjustment for RNA-seq data
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Tanbin Rahman, Hsin-En Huang, Yujia Li, An-Shun Tai, Wen-Ping Hseih, Colleen A. McClung, and George Tseng
- Subjects
Statistics and Probability ,Modeling and Simulation ,Statistics, Probability and Uncertainty - Published
- 2022
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34. Phase I trial combining chemokine-targeting with loco-regional chemo-immunotherapy for recurrent, platinum-sensitive ovarian cancer shows induction of CXCR3 ligands and markers of type 1 immunity
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Brian Orr, Haider Mahdi, Yusi Fang, Mary Strange, Ibrahim Uygun, Mainpal Rana, Lixin Zhang, Adria Suarez Mora, Alexandra Pusateri, Esther Elishaev, Chaeryon Kang, George Tseng, William Gooding, Robert P. Edwards, Pawel Kalinski, and Anda M. Vlad more...
- Subjects
Ovarian Neoplasms ,Cancer Research ,Receptors, CXCR3 ,Carcinoma, Ovarian Epithelial ,Ligands ,Article ,Toll-Like Receptor 3 ,Oncology ,Cyclooxygenase 2 ,Tumor Microenvironment ,Humans ,Female ,Immunotherapy ,Neoplasm Recurrence, Local ,Chemokines ,Peritoneal Neoplasms - Abstract
Purpose: Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC. Patients and Methods: Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received intraperitoneal IFNα at 2, 6, and 18 million units (MU), respectively. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and intraperitoneal wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively. Results: The P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 months, respectively. Longitudinal sampling of the peritoneal cavity via intraperitoneal washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 week. Conclusions: The chemokine-modulating intraperitoneal-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial. See related commentary by Aranda et al., p. 1993 more...
- Published
- 2022
35. Immune landscape of human placental villi using single-cell analysis
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Jessica M. Toothaker, Oluwabunmi Olaloye, Blake T. McCourt, Collin C. McCourt, Tatiana N. Silva, Rebecca M. Case, Peng Liu, Dean Yimlamai, George Tseng, and Liza Konnikova
- Subjects
B-Lymphocytes ,Macrophages ,Placenta ,T-Lymphocytes ,Human Development ,Antigens, Differentiation, Myelomonocytic ,Receptors, Cell Surface ,HLA-DR Antigens ,Flow Cytometry ,Lymphocyte Activation ,B7-H1 Antigen ,Killer Cells, Natural ,Memory T Cells ,Fetus ,Antigens, CD ,Pregnancy ,Pregnancy Trimester, Second ,Humans ,Leukocyte Common Antigens ,Female ,Receptors, Chemokine ,Chorionic Villi ,Single-Cell Analysis ,Molecular Biology ,Developmental Biology - Abstract
Maintenance of a healthy pregnancy is reliant on a successful balance between the fetal and maternal immune systems. Although the maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Consistent with recent reports in other fetal organs, T cells with memory phenotypes, although rare in abundance, were detected within the PV tissue and vasculature. Moreover, we determined that T cells isolated from PV samples may be more proliferative after T cell receptor stimulation than adult T cells at baseline. Collectively, we identified multiple subtypes of fetal immune cells within the PV and specifically highlight the enhanced proliferative capacity of fetal PV T cells. more...
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- 2022
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36. Mixed invasive ductal lobular carcinoma is clinically and pathologically more similar to invasive lobular than ductal carcinoma
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Azadeh Nasrazadani, Yujia Li, Yusi Fang, Osama Shah, Jennifer M. Atkinson, Joanna S. Lee, Priscilla F. McAuliffe, Rohit Bhargava, George Tseng, Adrian V. Lee, Peter C. Lucas, Steffi Oesterreich, and Norman Wolmark more...
- Subjects
Cancer Research ,Oncology - Abstract
Mixed invasive ductal lobular carcinoma (mDLC) remains a poorly understood subtype of breast cancer composed of coexisting ductal and lobular components.We sought to describe clinicopathologic characteristics and determine whether mDLC is clinically more similar to invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC), using data from patients seen at the University of Pittsburgh Medical Center.We observed a higher concordance in clinicopathologic characteristics between mDLC and ILC, compared to IDC. There is a trend for higher rates of successful breast-conserving surgery after neoadjuvant chemotherapy in patients with mDLC compared to patients with ILC, in which it is known to be lower than in those with IDC. Metastatic patterns of mDLC demonstrate a propensity to develop in sites characteristic of both IDC and ILC. A meta-analysis evaluating mDLC showed shared features with both ILC and IDC with significantly more ER-positive and fewer high grades in mDLC compared to IDC, although mDLCs were significantly smaller and included fewer late-stage tumours compared to ILC.These findings support clinicopathologic characteristics of mDLC driven by individual ductal vs lobular components and given the dominance of lobular pathology, mDLC features are often more similar to ILC than IDC. This study exemplifies the complexity of mixed disease. more...
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- 2022
37. Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer
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Steffi Oesterreich, Azadeh Nasrazadani, Jian Zou, Neil Carleton, Tiffany Onger, Matthew D Wright, Yujia Li, Kathryn Demanelis, Bhuvaneswari Ramaswamy, George Tseng, Adrian V Lee, Nicole Williams, and Megan Kruse more...
- Subjects
Cancer Research ,Carcinoma, Lobular ,Oncology ,Receptors, Estrogen ,Carcinoma, Ductal, Breast ,Humans ,Female ,Breast Neoplasms ,Retrospective Studies - Abstract
Background There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC). Methods The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values. Results Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P Conclusions This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management. more...
- Published
- 2022
38. Association of Molecular Senescence Markers in Late-Life Depression With Clinical Characteristics and Treatment Outcome
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Breno S, Diniz, Benoit H, Mulsant, Charles F, Reynolds, Daniel M, Blumberger, Jordan F, Karp, Meryl A, Butters, Ana Paula, Mendes-Silva, Erica L, Vieira, George, Tseng, and Eric J, Lenze
- Subjects
Ontario ,Depressive Disorder, Major ,Treatment Outcome ,Depression ,Humans ,Female ,General Medicine ,Antidepressive Agents ,Biomarkers ,Aged - Abstract
Many older adults with depression do not experience remission with antidepressant treatment, and markers of cellular senescence in late-life depression (LLD) are associated with greater severity of depression, greater executive dysfunction, and higher medical illness burden. Since these clinical characteristics are associated with remission in LLD, molecular and cellular senescence abnormalities could be a possible biological mechanism underlying poor treatment response in this population.To examine whether the senescence-associated secretory phenotype (SASP) index was associated with the likelihood of remission from a depressive episode in older adults.A nonrandomized, open-label clinical trial was conducted between August 2009 and August 2014 in Pittsburgh, Pennsylvania; St Louis, Missouri; and Toronto, Ontario, Canada, with older adults in a current major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnostic criteria. Data from biomarker analyses were reported according to the clinical trial archived plasma samples run in March 2021. Data were analyzed from June to November 2021.Venlafaxine extended release (dose ranging from 37.5 mg to 300 mg daily) for up to 12 weeks.The association between a composite biomarker-based index (SASP index) and treatment remission in older adults with major depression was measured using clinical data and blood samples.There were 416 participants with a mean (SD) age of 60.02 (7.13) years; 64% (265 participants) were self-reported female, and the mean (SD) Montgomery-Asberg Depression Rating Scale score was 26.6 (5.7). Higher SASP index scores were independently associated with higher rates of nonremission, with an increase of 1 unit in the SASP index score increasing the odds of nonremission by 19% (adjusted odds ratio, 1.19; 95% CI, 1.05-1.35; P = .006). In contrast, no individual SASP factors were associated with remission in LLD.Using clinical data and blood samples from a nonrandomized clinical trial, the results of this study suggest that molecular and cellular senescence, as measured with the SASP index, is associated with worse treatment outcomes in LLD. Combining this index score reflecting interrelated biological processes with other molecular, clinical, and neuroimaging markers may be useful in evaluating antidepressant treatment outcomes. These findings inform a path forward for geroscience-guided interventions targeting senescence to improve remission rates in LLD.ClinicalTrials.gov Identifier: NCT00892047. more...
- Published
- 2022
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39. Integrative Sparse
- Author
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Zhiguang, Huo and George, Tseng
- Subjects
Article - Abstract
Cancer subtypes discovery is the first step to deliver personalized medicine to cancer patients. With the accumulation of massive multi-level omics datasets and established biological knowledge databases, omics data integration with incorporation of rich existing biological knowledge is essential for deciphering a biological mechanism behind the complex diseases. In this manuscript, we propose an integrative sparse K-means (is-K means) approach to discover disease subtypes with the guidance of prior biological knowledge via sparse overlapping group lasso. An algorithm using an alternating direction method of multiplier (ADMM) will be applied for fast optimization. Simulation and three real applications in breast cancer and leukemia will be used to compare is-K means with existing methods and demonstrate its superior clustering accuracy, feature selection, functional annotation of detected molecular features and computing efficiency. more...
- Published
- 2017
40. Integrating Omics Data
- Author
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George Tseng, Debashis Ghosh, Xianghong Jasmine Zhou, George Tseng, Debashis Ghosh, and Xianghong Jasmine Zhou
- Subjects
- Genomics--Statistical methods, Meta-analysis
- Abstract
In most modern biomedical research projects, application of high-throughput genomic, proteomic, and transcriptomic experiments has gradually become an inevitable component. Popular technologies include microarray, next generation sequencing, mass spectrometry and proteomics assays. As the technologies have become mature and the price affordable, omics data are rapidly generated, and the problem of information integration and modeling of multi-lab and/or multi-omics data is becoming a growing one in the bioinformatics field. This book provides comprehensive coverage of these topics and will have a long-lasting impact on this evolving subject. Each chapter, written by a leader in the field, introduces state-of-the-art methods to handle information integration, experimental data, and database problems of omics data. more...
- Published
- 2015
41. Meta-analytic framework for sparse
- Author
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Zhiguang, Huo, Ying, Ding, Silvia, Liu, Steffi, Oesterreich, and George, Tseng
- Subjects
Article - Abstract
Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K-means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups. more...
- Published
- 2016
42. Integrating Omics Data
- Author
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George Tseng, Debashis Ghosh, and Xianghong Jasmine Zhou
- Abstract
In most modern biomedical research projects, application of high-throughput genomic, proteomic, and transcriptomic experiments has gradually become an inevitable component. Popular technologies include microarray, next generation sequencing, mass spectrometry and proteomics assays. As the technologies have become mature and the price affordable, omics data are rapidly generated, and the problem of information integration and modeling of multi-lab and/or multi-omics data is becoming a growing one in the bioinformatics field. This book provides comprehensive coverage of these topics and will have a long-lasting impact on this evolving subject. Each chapter, written by a leader in the field, introduces state-of-the-art methods to handle information integration, experimental data, and database problems of omics data. more...
- Published
- 2015
- Full Text
- View/download PDF
43. Reduction of anterior shoulder dislocation by external rotation
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Tai‐Wai Wong, Kai‐Cho Yeung, George Tseng, and Winston Tan
- Subjects
medicine.medical_specialty ,External rotation ,business.industry ,medicine.medical_treatment ,medicine ,Initial treatment ,Anterior shoulder ,Nerve palsy ,Traction (orthopedics) ,Dislocation ,business ,Anterior shoulder dislocation ,Surgery - Abstract
Objective: To examine the efficacy of external rotation as initial treatment for anterior shoulder dislocation. Design: Prospective uncontrolled study of the efficacy and adverse effects of external rotation when used as the initial technique to reduce anterior shoulder dislocation. Results: Ninety two cases of anterior shoulder dislocation were treated over an 18 month period. External rotation was used successfully to reduce the dislocation in 72 cases (78%). A further nine cases were reduced by external rotation with the aid of traction (total 88%). Six of eight cases complicated by fracture of a humeral tuberosity were reduced by external rotation. Twenty six reductions were achieved without the use of analgesia. Two cases of nerve palsy were seen, both associated with the use of traction. Conclusions: External rotation is a simple and safe method of reduction for anterior dislocations of the shoulder. The technique is recommended as the initial reduction technique for anterior shoulder dislocations. The use of traction should be discouraged. more...
- Published
- 2009
- Full Text
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44. Meta-Analytic Framework for Sparse K-Means to Identify Disease Subtypes in Multiple Transcriptomic Studies
- Author
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Zhiguang Huo, Ying Ding, Silvia Liu, Steffi Oesterreich, George Tseng, Zhiguang Huo, Ying Ding, Silvia Liu, Steffi Oesterreich, and George Tseng
- Abstract
Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step toward this goal. In this article, we extend a sparse K-means method toward a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer datasets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups. Supplementary materials for this article are available online. more...
- Published
- 2016
- Full Text
- View/download PDF
45. Gene deletions and amplifications in human hepatocellular carcinomas: correlation with hepatocyte growth regulation
- Author
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Michael A, Nalesnik, George, Tseng, Ying, Ding, Guo-Sheng, Xiang, Zhong-liang, Zheng, YanPing, Yu, James W, Marsh, George K, Michalopoulos, and Jian-Hua, Luo
- Subjects
Carcinoma, Hepatocellular ,DNA Copy Number Variations ,Liver Neoplasms ,Microfilament Proteins ,Gene Amplification ,Receptor-Like Protein Tyrosine Phosphatases, Class 2 ,Chromosome Mapping ,Regular Article ,DNA Fragmentation ,DNA, Neoplasm ,Liver Regeneration ,Neoplasm Proteins ,Hepatocytes ,Cluster Analysis ,Hepatectomy ,Humans ,Cell Division ,Gene Deletion ,Genes, Neoplasm - Abstract
Tissues from 98 human hepatocellular carcinomas (HCCs) obtained from hepatic resections were subjected to somatic copy number variation (CNV) analysis. Most of these HCCs were discovered in livers resected for orthotopic transplantation, although in a few cases, the tumors themselves were the reason for the hepatectomies. Genomic analysis revealed deletions and amplifications in several genes, and clustering analysis based on CNV revealed five clusters. The LSP1 gene had the most cases with CNV (46 deletions and 5 amplifications). High frequencies of CNV were also seen in PTPRD (21/98), GNB1L (18/98), KIAA1217 (18/98), RP1-1777G6.2 (17/98), ETS1 (11/98), RSU1 (10/98), TBC1D22A (10/98), BAHCC1 (9/98), MAML2 (9/98), RAB1B (9/98), and YIF1A (9/98). The existing literature regarding hepatocytes or other cell types has connected many of these genes to regulation of cytoskeletal architecture, signaling cascades related to growth regulation, and transcription factors directly interacting with nuclear signaling complexes. Correlations with existing literature indicate that genomic lesions associated with HCC at the level of resolution of CNV occur on many genes associated directly or indirectly with signaling pathways operating in liver regeneration and hepatocyte growth regulation. more...
- Published
- 2011
46. PD-L1 blockade and upregulation in an ovarian cancer treatment model (TUM2P.1017)
- Author
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Shannon Grabosch, Lixin Zhang, Feitianzhi Zeng, Jyothi Mony, Tianzhou Ma, George Tseng, Robert Edwards, and Anda Vlad
- Subjects
Immunology ,Immunology and Allergy - Abstract
Objective: We explored mechanisms of PD-L1 upregulation in ovarian cancer cells and tested in vivo the efficacy of intraperitoneal anti-PD-L1 therapy in two different ovarian cancer mouse models. Methods: We have derived several novel murine ovarian cancer cell lines from orthotopic ovarian tumors of triple transgenic mice. 129x SvJ and C57Bl/6 tumor-bearing mice were treated with 200 μg anti-PD-L1 antibody (or rat IgG as control) every two weeks for three doses. Immune gene profiling of splenocytes collected at necropsy was performed using 561 Nanostring probes. Results: Cell cycle analysis of in vitro cultured tumor cells demonstrates that PD-L1 expression increases preferentially on cells in G2/M cells. Exposure to cisplatin modifies PD-L1 levels, although the effect varies according to tumors’ baseline susceptibility. In vivo, we observed murine PD-L1 upregulation on ascites resident tumor cells, an effect reproduced ex vivo upon exposure of tumor cells to ascites fluid. PD-L1 blockade triggers increase in survival in both preclinical models with immune gene signatures pointing to cytotoxic anti-tumor immune response. Conclusion: PD-L1 expression increases in response to inflammatory stimuli from cell-free ascites and shows preference for dividing cells. PD-L1 upregulation varies according to tumor cells’ susceptibility to cisplatin. PD-L1 blockade increases systemic T cell responses and intratumoral T cell accumulation suggesting therapeutic potential in ovarian cancer. more...
- Published
- 2015
- Full Text
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47. SST is hypermethylated in the aged human PFC
- Author
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Brandon McKinney, Hyunjung Oh, Chien-Wei Lin, George Tseng, David Lewis, Etienne Sibille, Brandon McKinney, Hyunjung Oh, Chien-Wei Lin, George Tseng, David Lewis, and Etienne Sibille
- Published
- 2014
- Full Text
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48. New complement roles revealed by immune gene profiling in endometriosis and endometriosis-associated ovarian cancer (TUM7P.957)
- Author
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Anda Vlad, Swati Suryawanshi, Xin Huang, Raluca Budiu, Esther Elishaev, SungHwan Kim, George Tseng, and Robert Edwards
- Subjects
Immunology ,Immunology and Allergy - Abstract
Endometriosis is a largely benign, chronic inflammatory disease that may predispose to some of the ovarian tumors histotypes, collectively called endometriosis-associated ovarian cancers (EAOC). Although it is widely accepted that chronic inflammation drives cancer, the immune deregulation in chronic precursors of ovarian cancer has not been systematically studied. We performed here the first comprehensive gene profile of the tissue immune microenvironment in normal endometrium, benign endometriosis and EAOC (n=133), using Nanostring and the nCounter® GX Human Immunology Kit comprising probes for 511 immune genes. We found that the complement pathway was most prominently upregulated, suggesting its involvement in the transition from chronic endometriosis to atypical (premalignant) endometriosis and to EAOC. Complement protein expression was confirmed via immunohistochemistry, which identified upregulation of complement in epithelial cells. To explore the roles of complement in early EAOC carcinogenesis, we derived several novel ovarian cell lines with conditional mutations that can be turned on and off, using the Cre-loxP system. Using this in vitro model we demonstrate that genetic instability triggers upregulation of complement genes in epithelial cells, but without an advantage on cell death. These findings reveal an early link between epithelium and innate immune environment and further support a paradigm shift on complement roles in supporting cancer growth. more...
- Published
- 2014
- Full Text
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49. UPREGULATION OF PI3K‐AKT PATHWAY FOLLOWING TREATMENT WITH EGFR SPECIFIC shRNA IN REGENERATING RAT LIVERS
- Author
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Paranjpe, Shirish, primary, Bowen, William C., additional, George, Tseng C., additional, Luo, Jian‐Hua, additional, Orr, Ann V., additional, and Michalopoulos, George K., additional
- Published
- 2010
- Full Text
- View/download PDF
50. Clinicopathologic implications of "flat epithelial atypia" in core needle biopsy specimens of the breast.
- Author
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Mamatha Chivukula, Rohit Bhargava, George Tseng, and David J Dabbs
- Subjects
CLINICAL pathology ,NEEDLE biopsy ,EPITHELIAL cells ,HEALTH outcome assessment ,HYPERPLASIA ,BREAST diseases - Abstract
Flat epithelial atypia (FEA) is an emerging entity of uncertain clinical significance, and outcome data are sparse. The aim of this study was to evaluate the clinicopathologic significance of this entity for proper management. All core needle biopsy (CNB) specimens diagnosed as atypical ductal hyperplasia (ADH) from January 2006 to April 2008 were retrieved. H&E-stained slides of 5 levels on each case were reviewed. The differences in upstaging in subsequent excisions in the FEA and ADH group (31/189 [16.4%]) vs the pure FEA group (5/35 [14%]) and pure FEA (5/35 [14%]) vs pure ADH (5/45 [11%]) were not statistically significant. We observed that FEA evolved into ADH at the same site at an average of 3 to 4 levels. Our study concludes that there is an association of FEA with ADH on multiple levels of CNB specimens, and follow-up surgical excision findings for FEA are clinically significant. [ABSTRACT FROM AUTHOR] more...
- Published
- 2009
- Full Text
- View/download PDF
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