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266 results on '"Siedhoff, Matthew T."'

7. A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes

Author

Mortlock, Sally, Corona, Rosario I, Kho, Pik Fang, Pharoah, Paul, Seo, Ji-Heui, Freedman, Matthew L, Gayther, Simon A, Siedhoff, Matthew T, Rogers, Peter AW, Leuchter, Ronald, Walsh, Christine S, Cass, Ilana, Karlan, Beth Y, Rimel, BJ, Consortium, International Endometriosis Genetics Consortium Ovarian Cancer Association, Montgomery, Grant W, Lawrenson, Kate, and Kar, Siddhartha P

Subjects
Endometriosis, Genetics, Cancer, Rare Diseases, Human Genome, Ovarian Cancer, 2.1 Biological and endogenous factors, Aetiology, Carcinoma, Ovarian Epithelial, Female, Genome-Wide Association Study, Humans, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Ovarian Cancer Association Consortium, International Endometriosis Genetics Consortium, Mendelian randomization, endometriosis, epithelial ovarian cancer, genetic association, genetic correlation, genetic risk, histotype, meta-analysis
Abstract

Endometriosis is associated with increased risk of epithelial ovarian cancers (EOCs). Using data from large endometriosis and EOC genome-wide association meta-analyses, we estimate the genetic correlation and evaluate the causal relationship between genetic liability to endometriosis and EOC histotypes, and identify shared susceptibility loci. We estimate a significant genetic correlation (rg) between endometriosis and clear cell (rg = 0.71), endometrioid (rg = 0.48), and high-grade serous (rg = 0.19) ovarian cancer, associations supported by Mendelian randomization analyses. Bivariate meta-analysis identified 28 loci associated with both endometriosis and EOC, including 19 with evidence for a shared underlying association signal. Differences in the shared risk suggest different underlying pathways may contribute to the relationship between endometriosis and the different histotypes. Functional annotation using transcriptomic and epigenomic profiles of relevant tissues/cells highlights several target genes. This comprehensive analysis reveals profound genetic overlap between endometriosis and EOC histotypes with valuable genomic targets for understanding the biological mechanisms linking the diseases.

Published
2022

9. Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube

Author

Dinh, Huy Q, Lin, Xianzhi, Abbasi, Forough, Nameki, Robbin, Haro, Marcela, Olingy, Claire E, Chang, Heidi, Hernandez, Lourdes, Gayther, Simon A, Wright, Kelly N, Aspuria, Paul-Joseph, Karlan, Beth Y, Corona, Rosario I, Li, Andrew, Rimel, BJ, Siedhoff, Matthew T, Medeiros, Fabiola, and Lawrenson, Kate

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Rare Diseases, Cancer, Ovarian Cancer, Aetiology, 2.1 Biological and endogenous factors, Adult, Cell Differentiation, Cell Line, Tumor, Core Binding Factor Alpha 3 Subunit, Endometriosis, Epithelial Cells, Epithelial-Mesenchymal Transition, Fallopian Tubes, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Leiomyoma, Middle Aged, PAX8 Transcription Factor, SOXF Transcription Factors, Signal Transduction, Single-Cell Analysis, Transcriptome, PAX8, RUNX3, SOX17, ciliated epithelial cells, fallopian tube, microenvironment, ovarian cancer, scRNA-seq, secretory epithelial cells, transcription factor, Medical Physiology, Biological sciences
Abstract

The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling of around 53,000 individual cells from 12 primary fallopian specimens to map their major cell types. We identify 10 epithelial subpopulations with diverse transcriptional programs. Based on transcriptional signatures, we reconstruct a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3high intermediate. Computational deconvolution of advanced HGSCs identifies the "early secretory" population as a likely precursor state for the majority of HGSCs. Its signature comprises both epithelial and mesenchymal features and is enriched in mesenchymal-type HGSCs (p = 6.7 × 10-27), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.

Published
2021

11. Essentials in Minimally Invasive Gynecology Manual Skills Construct Validation Trial

Author

Munro, Malcolm G, Advincula, Arnold P, Banks, Erika H, Auguste, Tamika C, Chahine, E Britton, Chen, Chi Chiung Grace, Curlin, Howard L, Jorgensen, Elisa M, Kim, Jin Hee, King, Cara R, Lucas, Joelle, Milad, Magdy P, Mourad, Jamal, Siedhoff, Matthew T, Solnik, M Jonathon, Destephano, Christopher C, and Thayn, Kim

Subjects
Reproductive Medicine, Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Canada, Clinical Competence, Cohort Studies, Female, Genital Diseases, Female, Gynecology, Humans, Internship and Residency, Laparoscopy, Minimally Invasive Surgical Procedures, Prospective Studies, Simulation Training, United States, Essentials in Minimally Invasive Gynecology (EMIG) Steering Committee, Paediatrics and Reproductive Medicine, Obstetrics & Reproductive Medicine, Reproductive medicine
Abstract

ObjectiveTo establish validity evidence for the Essentials in Minimally Invasive Gynecology laparoscopic and hysteroscopic simulation systems.MethodsA prospective cohort study was IRB approved and conducted at 15 sites in the United States and Canada. The four participant cohorts based on training status were: 1) novice (postgraduate year [PGY]-1) residents, 2) mid-level (PGY-3) residents, 3) proficient (American Board of Obstetrics and Gynecology [ABOG]-certified specialists without subspecialty training); and 4) expert (ABOG-certified obstetrician-gynecologists who had completed a 2-year fellowship in minimally invasive gynecologic surgery). Qualified participants were oriented to both systems, followed by testing with five laparoscopic exercises (L-1, sleeve-peg transfer; L-2, pattern cut; L-3, extracorporeal tie; L-4, intracorporeal tie; L-5, running suture) and two hysteroscopic exercises (H-1, targeting; H-2, polyp removal). Measured outcomes included accuracy and exercise times, including incompletion rates.ResultsOf 227 participants, 77 were novice, 70 were mid-level, 33 were proficient, and 47 were experts. Exercise times, in seconds (±SD), for novice compared with mid-level participants for the seven exercises were as follows, and all were significant (P

Published
2020

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