A5008638322- Endometrial and Cervical Cancer Treatments
- Ovarian cancer diagnosis and treatment
- Genetic Associations and Epidemiology
- Kruppel-like factors research
- Asthma and respiratory diseases
- Genomic variations and chromosomal abnormalities
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Dermatology and Skin Diseases
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- IL-33, ST2, and ILC Pathways
- Eosinophilic Esophagitis
- Brain Metastases and Treatment
- Genetic factors in colorectal cancer
- Congenital heart defects research
- Helicobacter pylori-related gastroenterology studies
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- HIV Research and Treatment
- Microtubule and mitosis dynamics
- Immune Cell Function and Interaction
- CAR-T cell therapy research
Dana-Farber Cancer Institute
2019-2025
University of Colorado Denver
2018-2025
University of Colorado Anschutz Medical Campus
2018-2020
University of California, San Diego
2016
University College London
2005
Abstract Epithelial-to-mesenchymal transition (EMT) is associated with tumor initiation, metastasis, and drug resistance. However, the mechanisms underlying these associations are largely unknown. We studied several types to identify source of EMT gene expression signals a potential mechanism resistance immuno-oncology treatment. Across types, EMT-related was strongly stroma-related genes. Based on RNA sequencing multiple patient-derived xenograft models, enriched in stroma versus...
While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)-present in some but not all cells-remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering at loci recurrently mutated clonal blood disorders. Likely early-developmental were more common (0.91%) than controls (0.51%, p = 2.68e-4), with recurrent deletions exons 1-5
Mcm2–7 (MCM) proteins are part of the origin licensing machinery that regulates initiation DNA replication. Geminin is a repressor and prevents reinitiation replication during S–G2–M phase by blocking reloading at origins. Here, we have analysed these factors (RLFs) to determine whether pathway becomes deregulated mammary carcinogenesis, assessed their potential value as prognostic markers. Protein expression profiles were generated for Ki67, Mcm2, geminin, HER-2, ER PR in series reduction...
Abstract In the United States, Endometrial carcinoma (EC) is most frequently occurring gynecologic cancer. Many ECs harbor mutations in cell cycle regulatory genes including TP53 and RB1, amongst others. RB p53 both regulate G1/S transition while also regulates G2/M mitotic progression, all of which rely on targetable kinases. It likely that many defects some aspect regulation, but there has been no profiling p53- or RB- linked functional capacity corresponding therapeutic vulnerabilities EC...
<p>Supplementary Figure S22</p>
<p>Aurora kinase B inhibitor sensitive endometrial carcinoma cells reveal more rapidly decreasing percentages of mitotic than resistant in the setting Aurora inhibition. <b>A,</b> A cartoon demonstrating experimental setup is shown. <b>B,</b> HEC1B and ARK1 were treated with vehicle (DMSO) or a dose curve CDK1 (CDK1i) Ro-3306 for 16 hours. The then underwent bromodeoxyuridine (BrdU)/propidium iodide (PI) cell cycle flow cytometry profiling. Shown here are bar...
<p>Supplementary Figure S13</p>
<p>Supplementary Figure S1</p>
<p>Supplementary Figure S12</p>
<p>Supplementary Figure S10</p>
<p>Endometrial carcinomas with transcriptionally evident mitotic spindle organization or progression regulatory defects are sensitive to Aurora Kinase B inhibition. <b>A,</b> Cartoon illustrating the different kinases governing G2/M transition and what part of mitosis inhibitors these target (Aurora kinase A (AURKA), (AURKB), Polo-like 1 (PLK1)). <b>B</b> <b>C,</b> Protein lysates were prepared from untreated cell lines (<b>B</b>)...
<p>Supplementary Figure S19</p>
<p>Supplementary Figure S6</p>
<p>RB and some form of p53 are expressed in the majority endometrial carcinoma cells regardless genomic status but have varying regulatory or functional ability. <b>A</b> <b>B,</b> Protein lysates were prepared from untreated cell lines (left each panel) organoid (right analyzed by western blot. In <b>A</b>, membranes for type probed RB, stripped re-probed tubulin as a loading control. B, p53, then <b>C</b> <b>D,</b> Organoids...
<p>Immunohistochemical, genomic, functional/regulatory, and related therapeutic sensitivity status of p53 RB in endometrial carcinoma models</p>
<p>Endometrial carcinoma cell sensitivity to G1/S targeted therapies correlates with RB regulatory status. <b>A</b> and <b>B,</b> Protein lysates were prepared from untreated lines (left in each panel) organoid (right analyzed by western blot. In <b>A</b>, membranes for type probed CDK4, stripped re-probed CDK6, tubulin as a loading control. <b>B</b>, Cyclin E1, then An arrow indicates the main E1 isoform, below that, low molecular weight...
<p>RB intact regulation and mitotic progression deficient endometrial carcinoma cells demonstrate different responses to cell cycle targeting therapies <i>in vivo</i>. <b>A,</b> Cartoon demonstrating vivo</i> study experimental setup. For each study, after treatment initiation, mice were euthanized once they developed signs of morbidity; then ascites volume was obtained, gross photos taken, residual tumor harvested for all animals possible....
<p>Supplementary Figure S3</p>
<p>Supplementary Figure S20</p>
<p>This file contains Supplementary Materials and Methods along with accompanying References.</p>
<p>Aurora kinase B inhibitor sensitive endometrial carcinoma cells show more rapidly decreasing percentages of mitotic than resistant models in the setting nocodazole-induced microtubule instability. <b>A,</b> A cartoon demonstrating experimental setup is shown. <b>B,</b> HEC1B, ARK1, and AN3CA were treated for 24 hours with vehicle (DMSO) or a dose curve nocodazole (Noc) then underwent bromodeoxyuridine (BrdU)/propidium iodide (PI) flow cytometry cell cycle...
<div>Abstract<p>In the United States, Endometrial carcinoma (EC) is most frequently occurring gynecologic cancer. Many ECs harbor mutations in cell cycle regulatory genes including <i>TP53</i> and <i>RB1</i>, amongst others. RB p53 both regulate G1/S transition while also regulates G2/M mitotic progression, all of which rely on targetable kinases. It likely that many defects some aspect regulation, but there has been no profiling p53- or RB- linked...