- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- Protease and Inhibitor Mechanisms
- Proteoglycans and glycosaminoglycans research
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- Toxin Mechanisms and Immunotoxins
- Peptidase Inhibition and Analysis
- Fibroblast Growth Factor Research
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- Nanoparticle-Based Drug Delivery
- Signaling Pathways in Disease
- Caveolin-1 and cellular processes
- Neuroscience and Neuropharmacology Research
- Immune Cell Function and Interaction
- TGF-β signaling in diseases
- Immune cells in cancer
- Cancer, Stress, Anesthesia, and Immune Response
- Neuroendocrine Tumor Research Advances
- Bacterial Genetics and Biotechnology
University of Illinois Chicago
2012-2024
Engelhardt Institute of Molecular Biology
1997-2017
Northwestern University
2007-2010
University of Missouri
2010
University of Illinois Urbana-Champaign
2009
University at Buffalo, State University of New York
1997-2007
Molecular Biology Consortium
2006
University of Georgia
1997
University of York
1997
Dendritic spine morphogenesis contributes to brain function, cognition, and behavior, is altered in psychiatric disorders. Kalirin a brain-specific guanine-nucleotide exchange factor (GEF) for Rac-like GTPases key regulator of morphogenesis. Here, we show that KALRN-knockout mice have specific reductions cortical, but not hippocampal, Rac1 signaling density, exhibit reduced cortical glutamatergic transmission. These robust deficits working memory, sociability, prepulse inhibition, paralleled...
Abstract An early event in the metastasis of epithelial ovarian carcinoma is shedding cells from primary tumor into peritoneal cavity followed by diffuse i.p. seeding secondary lesions. Anchorage-independent metastatic are present as both single and multicellular aggregates (MCA), latter which adhere to disaggregate on human mesothelial cell monolayers, subsequently forming invasive foci. Although this unique mechanism presents a distinct set therapeutic challenges, factors that regulate MCA...
Late stage ovarian cancer is characterized by disseminated intraperitoneal metastasis as secondary lesions anchor in the type I and III collagen-rich submesothelial matrix. Ovarian carcinoma cells preferentially adhere to interstitial collagen, collagen-induced integrin clustering up-regulates expression of transmembrane collagenase membrane 1 matrix metalloproteinase (MT1-MMP). Collagenolytic activity important metastasis, potentiating invasion through mesothelial cell layer colonization...
Abstract Epithelial ovarian carcinoma (EOC) is a deadly disease, and little known about the mechanisms underlying its metastatic progression. Using human specimens established cell lines, we determined that G-protein–coupled seven-transmembrane fractalkine receptor (CX3CR1) expressed in primary cells. Ovarian cells robustly migrated toward CX3CL1, specific ligand of CX3CR1, CX3CR1-dependent manner. Silencing CX3CR1 reduced migration ascites fluid by approximately 70%. Importantly, adhesion...
The majority of women diagnosed with epithelial ovarian carcinoma (EOC) succumb due to complications metastatic disease, suggesting that antimetastatic therapies may improve patient survival. EOC metastasis involves intraperitoneal shedding cells from the primary tumor, followed by adhesion and localized penetration submesothelial matrix anchor implants. Accumulation malignant ascites is also common. Thus, a unique microenvironmental niche established, which includes plethora soluble factors...
Cells respond to changes in the physical properties of extracellular matrix with altered behavior and gene expression, highlighting important role microenvironment regulation cell function. In current study, culture epithelial ovarian cancer cells on three-dimensional collagen I gels led a dramatic down-regulation Wnt signaling inhibitor dickkopf-1 concomitant increase nuclear β-catenin enhanced β-catenin/Tcf/Lef transcriptional activity. Increased gel invasion was accompanied by...
Abstract Chemokine receptor-ligand interactions are important to support functioning of both normal and pathologic cells. The expression function chemokine receptors in epithelial ovarian carcinoma (EOC) is largely unknown. Here, we report that the lymphotactin receptor (XCR1) was expressed primary metastatic human specimens cell lines. In contrast, XCR1 not detected ovary or surface Our data indicate XCL1 XCL2 either present malignant ascites by addition (XCL1 XCL2) stimulated migration...
Although metastatic disease is the primary cause of death from epithelial ovarian carcinoma, to authors' knowledge cellular mechanisms that regulate intraperitoneal metastasis are largely unknown. Metastasizing carcinoma cells encounter a collagen-rich microenvironment because submesothelial matrix comprised mainly interstitial collagens Types I and III.Immunohistochemistry using samples was employed detect expression Wilms tumor gene protein 1 (WT1). Three-dimensional (3D) collagen culture,...
The X-ray structure of tyrosine phenol-lyase (TPL) complexed with a substrate analog, 3-(4'-hydroxyphenyl)propionic acid, shows that Arg 381 is located in the binding site, side-chain NH1 4.1 A from 4'-OH analog. has been deduced at 2.5 resolution using crystals belong to P2(1)2(1)2 space group = 135.07 A, b 143.91 and c 59.80 A. To evaluate role TPL catalysis, we prepared mutant proteins replacing arginine alanine (R381A), isoleucine (R381I), valine (R381V). beta-elimination activity R381A...
Epithelial ovarian carcinoma is the deadliest gynecologic malignancy. One reason underlying treatment failure resistance to paclitaxel. Expression of microtubule associated protein tau has recently been proposed as a predictor response paclitaxel in patients. was probed using immunohistochemistry 312 specimens primary, and 40 metastatic, carcinoma. Serous epithelial cell line models were used determine expression by Western blot immunofluorescence staining. Subcellular fractionation employed...
Epithelial ovarian carcinoma is a deadly disease characterized by overt peritoneal metastasis. Individual cells and multicellular aggregates, or spheroids, seed these metastases, both commonly found in ascites. Mechanisms that foster spheroid attachment to the tissues preceding formation of secondary lesions are largely unknown. Cell culture models SKOV-3, OVCAR3, OVCAR4, Caov-3, IGROV-1, A2780 were used. In this report role versican was examined adhesion EOC spheroids mesothelial cell...
Abstract Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancies, due mainly to the prevalence undetected metastatic disease. The process cell invasion during intraperitoneal anchoring lesions requires concerted regulation many processes, including modulation adhesion extracellular matrix and localized invasion. Exploratory cDNA microarray analysis early response genes (altered after 4 hr 3D collagen culture) coupled with confirmatory real‐time...
Disseminating epithelial ovarian cancer cells often become assembled into spheroids prior to their arrival at metastatic sites within the peritoneal cavity. Although carcinoma (EOC) is deadliest gynecologic malignancy, mechanisms regulating formation and potential of are poorly understood. We show that expression a cell surface glycoprotein CD44 an important contributing factor for spheroid adhesion mesothelial cells, its loss impairs mesenteric metastasis. In contrast, resulted in...