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- Kimberly K. Leslie (20)
- Donghai Dai (7)
- Baoli Yang (2)
- Dartmouth Scholarship (2)
- Department of Cancer Biology Faculty Papers (2)
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- Ginny L. Ryan (2)
- Jennifer R Niebyl (2)
- Cardeza Foundation for Hematologic Research (1)
- College of Arts and Sciences Publications and Scholarship (1)
- David P Bender (1)
- Department of Biochemistry and Molecular Biology Faculty Papers (1)
- Department of Emergency Medicine Faculty Papers (1)
- Department of Medicine Faculty Papers (1)
- Department of Neurology Faculty Papers (1)
- Department of Pathology, Anatomy, and Cell Biology Faculty Papers (1)
- Department of Pharmacology and Experimental Therapeutics Faculty Papers (1)
- Journal Articles: Obstetrics & Gynecology (1)
- Journal Articles: Ophthalmology (1)
- Markey Cancer Center Faculty Publications (1)
- Saha Cardiovascular Research Center Faculty Publications (1)
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Articles 1 - 30 of 50
Full-Text Articles in Medicine and Health Sciences
Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak
Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak
Saha Cardiovascular Research Center Faculty Publications
Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …
Divergent Antibody Subclass And Specificity Profiles But Not Protective Hla-B Alleles Are Associated With Variable Antibody Effector Function Among Hiv-1 Controllers, Jennifer I. Lai, Anna F. Licht, Anne-Sophie Dugast, Todd Suscovich, Ickwon Choi, Chris Bailey-Kellogg, Galit Alter, Margaret E. Ackerman
Divergent Antibody Subclass And Specificity Profiles But Not Protective Hla-B Alleles Are Associated With Variable Antibody Effector Function Among Hiv-1 Controllers, Jennifer I. Lai, Anna F. Licht, Anne-Sophie Dugast, Todd Suscovich, Ickwon Choi, Chris Bailey-Kellogg, Galit Alter, Margaret E. Ackerman
Dartmouth Scholarship
Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector …
Racial Differences In Human Platelet Par4 Reactivity Reflect Expression Of Pctp And Mir-376c., Leonard Edelstein, Lukas M Simon, Raúl Teruel Montoya, Michael Holinstat, Edward S Chen, Angela Bergeron, Xianguo Kong, Srikanth Nagalla, Narla Mohandas, David E Cohen, Jing-Fei Dong, Chad Shaw, Paul Bray
Racial Differences In Human Platelet Par4 Reactivity Reflect Expression Of Pctp And Mir-376c., Leonard Edelstein, Lukas M Simon, Raúl Teruel Montoya, Michael Holinstat, Edward S Chen, Angela Bergeron, Xianguo Kong, Srikanth Nagalla, Narla Mohandas, David E Cohen, Jing-Fei Dong, Chad Shaw, Paul Bray
Cardeza Foundation for Hematologic Research
Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and …
Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd
Targeting Cell Cycle And Hormone Receptor Pathways In Cancer., C E S Comstock, M A Augello, J F Goodwin, R De Leeuw, M J Schiewer, W F Ostrander, R A Burkhart, A K Mcclendon, Peter Mccue, Edouard J. Trabulsi, Costas D. Lallas, Leonard G Gomella, Md, M M Centenera, Jonathan Brody, Md, L M Butler, W D Tilley, K E Knudsen, Phd
Department of Cancer Biology Faculty Papers
The cyclin/cyclin-dependent kinase (CDK)/retinoblastoma (RB)-axis is a critical modulator of cell cycle entry and is aberrant in many human cancers. New nodes of therapeutic intervention are needed that can delay or combat the onset of malignancies. The antitumor properties and mechanistic functions of PD-0332991 (PD; a potent and selective CDK4/6 inhibitor) were investigated using human prostate cancer (PCa) models and primary tumors. PD significantly impaired the capacity of PCa cells to proliferate by promoting a robust G1-arrest. Accordingly, key regulators of the G1-S cell cycle transition were modulated including G1 cyclins D, E and A. Subsequent investigation demonstrated the ability …
Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman
Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …
Hrs Promotes Ubiquitination And Mediates Endosomal Trafficking Of Smoothened In Drosophila Hedgehog Signaling, Jun-Kai Fan, Kai Jiang, Yajuan Liu, Jianhang Jia
Hrs Promotes Ubiquitination And Mediates Endosomal Trafficking Of Smoothened In Drosophila Hedgehog Signaling, Jun-Kai Fan, Kai Jiang, Yajuan Liu, Jianhang Jia
Markey Cancer Center Faculty Publications
In Hedgehog (Hh) signaling, the seven-transmembrane protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation, ubiquitination, and cell surface accumulation. However, it is not clear how Smo cell surface accumulation and intracellular trafficking are regulated. Here, we demonstrate that inactivation of Hrs by deletion or RNAi accumulates Smo in the late endosome that is marked by late endosome markers. Inactivation of Hrs enhances the wing defects caused by dominant-negative Smo. We show that Hrs promotes Smo ubiquitination, deleting the ubiquitin-interacting-motif (UIM) in Hrs abolishes the ability of Hrs to regulate Smo ubiquitination. However, the UIM domain …
The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis
The G-Protein-Coupled Estrogen Receptor Agonist G-1 Suppresses Proliferation Of Ovarian Cancer Cells By Blocking Tubulin Polymerization., Cheng Wang, Xiangmin Lv, Chunbo He, G Hua, M-Y Tsai, John S. Davis
Journal Articles: Obstetrics & Gynecology
The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of …
Cardiac Fibroblast-Dependent Extracellular Matrix Accumulation Is Associated With Diastolic Stiffness In Type 2 Diabetes., Kirk R. Hutchinson, C. Kevin Lord, T. Aaron West, James A. Stewart
Cardiac Fibroblast-Dependent Extracellular Matrix Accumulation Is Associated With Diastolic Stiffness In Type 2 Diabetes., Kirk R. Hutchinson, C. Kevin Lord, T. Aaron West, James A. Stewart
College of Arts and Sciences Publications and Scholarship
Cardiovascular complications are a leading cause of death in patients with type 2 diabetes mellitus (T2DM). Diastolic dysfunction is one of the earliest manifestations of diabetes-induced changes in left ventricular (LV) function, and results from a reduced rate of relaxation and increased stiffness. The mechanisms responsible for increased stiffness are not completely understood. Chronic hyperglycemia, advanced glycation endproducts (AGEs), and increased levels of proinflammatory and profibrotic cytokines are molecular pathways known to be involved in regulating extracellular matrix (ECM) synthesis and accumulation resulting in increased LV diastolic stiffness. Experiments were conducted using a genetically-induced mouse model of T2DM generated by …
Fetal Hemorrhage And Platelet Dysfunction In Slp-76-Deficient Mice., J. Clements, J. Lee, B. Gross, Baoli Yang, J. Olson, A. Sandra, S. Watson, S. Lentz, G. Koretzky
Fetal Hemorrhage And Platelet Dysfunction In Slp-76-Deficient Mice., J. Clements, J. Lee, B. Gross, Baoli Yang, J. Olson, A. Sandra, S. Watson, S. Lentz, G. Koretzky
Baoli Yang
The adapter protein SLP-76 is expressed in T lymphocytes and hematopoietic cells of the myeloid lineage, and is known to be a substrate of the protein tyrosine kinases that are activated after ligation of the T-cell antigen receptor. Transient overexpression of SLP-76 in a T-cell line potentiates transcriptional activation after T-cell receptor ligation, while loss of SLP-76 expression abrogates several T-cell receptor-dependent signaling pathways. Mutant mice that lack SLP-76 manifest a severe block at an early stage of thymocyte development, implicating SLP-76 in signaling events that promote thymocyte maturation. While it is clear that SLP-76 plays a key role in …
Requirement For The Leukocyte-Specific Adapter Protein Slp-76 For Normal T Cell Development., J. Clements, Baoli Yang, S. Ross-Barta, S. Eliason, R. Hrstka, R. Williamson, G. Koretzky
Requirement For The Leukocyte-Specific Adapter Protein Slp-76 For Normal T Cell Development., J. Clements, Baoli Yang, S. Ross-Barta, S. Eliason, R. Hrstka, R. Williamson, G. Koretzky
Baoli Yang
The leukocyte-specific adapter molecule SLP-76 (Src homology 2 domain-containing leukocyte protein of 76 kilodaltons) is rapidly phosphorylated on tyrosine residues after receptor ligation in several hematopoietically derived cell types. Mice made deficient for SLP-76 expression contained no peripheral T cells as a result of an early block in thymopoiesis. Macrophage and natural killer cell compartments were intact in SLP-76-deficient mice, despite SLP-76 expression in these lineages in wild-type mice. Thus, the SLP-76 adapter protein is required for normal thymocyte development and plays a crucial role in translating signals mediated by pre-T cell receptors into distal biochemical events.
Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue
Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue
Dartmouth Scholarship
The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …
Intrinsic Differences In The Response Of The Human Lutropin Receptor Versus The Human Follitropin Receptor To Activating Mutations, Meilin Zhang, Ya-Xiong Tao, Ginny Ryan, Xiuyan Feng, Francesca Fanelli, Deborah Segaloff
Intrinsic Differences In The Response Of The Human Lutropin Receptor Versus The Human Follitropin Receptor To Activating Mutations, Meilin Zhang, Ya-Xiong Tao, Ginny Ryan, Xiuyan Feng, Francesca Fanelli, Deborah Segaloff
Ginny L. Ryan
In contrast to the human lutropin receptor (hLHR), very few naturally occurring activating mutations of the structurally related human follitropin receptor (hFSHR) have been identified. The present study was undertaken to determine if one aspect underlying this discrepancy might be a general resistance of the hFSHR to mutation-induced constitutive activity. Five different mutations were introduced into both the hLHR and hFSHR (four based on activating mutations of the hLHR gene, one based on an activating mutation of the hFSHR gene). Our results demonstrate that hFSHR constitutively activating mutants (CAMs) were not as active as hLHR CAMs containing the comparable mutation. …
Evaluating The Roles Of Follicle-Stimulating Hormone Receptor Polymorphisms In Gonadal Hyperstimulation Associated With Severe Juvenile Primary Hypothyroidism, Ginny Ryan, X. Feng, C. D'Alva, M. Zhang, Bradley Van Voorhis, E. Pinto, A. Kubias, S. Antonini, A. Latronico, D. Segaloff
Evaluating The Roles Of Follicle-Stimulating Hormone Receptor Polymorphisms In Gonadal Hyperstimulation Associated With Severe Juvenile Primary Hypothyroidism, Ginny Ryan, X. Feng, C. D'Alva, M. Zhang, Bradley Van Voorhis, E. Pinto, A. Kubias, S. Antonini, A. Latronico, D. Segaloff
Ginny L. Ryan
CONTEXT: Rare activating mutations of the human (h)FSHR have been reported in some women with spontaneous ovarian hyperstimulation in pregnancy, where follicular growth is inappropriately stimulated by elevated concentrations of human chorionic gonadotropin acting through the hFSHR. It is not known whether ovarian hyperstimulation in peripubertal girls with untreated primary hypothyroidism is caused by hFSHR mutations and/or influenced by hFSHR allelic variants, rendering the hFSHR more sensitive to circulating TSH. OBJECTIVE: The aim of the study was to determine whether mutations of the hFSHR and/or hFSHR allelic variants are associated with greater sensitivity of the hFSHR to TSH. DESIGN: The …
Biological Properties Of A Recombinant Human Immunoglobulin Epsilon-Chain Fragment, T. Ishizaka, B. Helm, J. Hakimi, Jennifer Niebyl, K. Ishizaka, H. Gould
Biological Properties Of A Recombinant Human Immunoglobulin Epsilon-Chain Fragment, T. Ishizaka, B. Helm, J. Hakimi, Jennifer Niebyl, K. Ishizaka, H. Gould
Jennifer R Niebyl
A recombinant human immunoglobulin epsilon-chain gene expression product (rFc epsilon) was compared with a human E myeloma protein in the affinity for epsilon-chain Fc fragment receptors (Fc epsilon R) on cultured human basophils. The association-dissociation kinetics of the rFc epsilon-Fc epsilon R interaction are indistinguishable from that of E myeloma protein, indicating that rFc epsilon and IgE have identical affinity for the receptors. The recombinant gene product sensitizes cultured basophils for anti-IgE-induced histamine release. A dose-response curve of histamine release indicates that the gene product is equally efficient in transducing the signal for degranulation as the natural IgE. Both the …
Morphologic And Immunologic Characterization Of Human Basophils Developed In Cultures Of Cord Blood Mononuclear Cells, T. Ishizaka, A. Dvorak, D. Conrad, Jennifer Niebyl, J. Marquette, K. Ishizaka
Morphologic And Immunologic Characterization Of Human Basophils Developed In Cultures Of Cord Blood Mononuclear Cells, T. Ishizaka, A. Dvorak, D. Conrad, Jennifer Niebyl, J. Marquette, K. Ishizaka
Jennifer R Niebyl
Selective growth of human basophilic granulocytes was obtained in suspension cultures of mononuclear cells from umbilical cord blood. Approximately 50 to 80% of nonadherent cells recovered from 2- to 3-wk-old cultures contained metachromatic granules, and these cells were identified as human basophilic granulocytes by electron microscopy. Histamine content of cultured human basophils was comparable to that in peripheral blood basophils. Cultured basophils bear 2.7 to 3.7 X 10(5) IgE receptors per cell that bind both human IgE and rodent IgE with comparable affinity. Average equilibrium constants of the receptors for human IgE and mouse IgE were 2.56 +/- 0.88 X …
Immunomodulatory And Transcriptional Effects Of Progesterone Through Progesterone A And B Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells, S. Davies, Donghai Dai, D. Wolf, Kimberly Leslie
Immunomodulatory And Transcriptional Effects Of Progesterone Through Progesterone A And B Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells, S. Davies, Donghai Dai, D. Wolf, Kimberly Leslie
Donghai Dai
OBJECTIVE: Derivatives of progesterone, progestins, are used to treat endometrial cancer; however, the pathways activated by the hormone have not been fully investigated. Progesterone acts through two receptor isoforms, progesterone receptors A and B (PRA and PRB), transcription factors that control the expression of downstream genes leading to endometrial differentiation. The purpose of this study was to perform an expression analysis to identify the mechanisms underlying progesterone's growth suppressive and immunomodulatory effects in endometrial cancer. METHODS: To study the molecular effects of progesterone, PRs were introduced into Hec50co cells. Expression array analyses followed by confirmatory semiquantitive reverse-transcriptase polymerase chain reaction …
Progesterone Receptor Isoform Identification And Subcellular Localization In Endometrial Cancer, Kimberly Leslie, M. Stein, N. Kumar, Donghai Dai, J. Stephens, A. Wandinger-Ness, D. Glueck
Progesterone Receptor Isoform Identification And Subcellular Localization In Endometrial Cancer, Kimberly Leslie, M. Stein, N. Kumar, Donghai Dai, J. Stephens, A. Wandinger-Ness, D. Glueck
Donghai Dai
OBJECTIVE: These studies were undertaken to characterize the subcellular localization of the two major isoforms of progesterone receptors (PR), PRA and PRB, in endometrial cancer. METHODS: Immunohistochemistry, immunoprecipitation, and confocal microscopy were performed using Hec50co and KLE endometrial cancer cell models expressing PRA or PRB as a consequence of transduction. The location of PRB compared to PRA was determined, and antibodies were tested for specificity with respect to PR isoform recognition. Immunohistochemical analyses of PR expression and subcellular compartmentalization were also performed on 20 formalin-fixed endometrial cancer tumors. RESULTS: Morphological and biochemical evaluations demonstrated that PRA is localized to the …
Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie
Progesterone Inhibits Human Endometrial Cancer Cell Growth And Invasiveness: Down-Regulation Of Cellular Adhesion Molecules Through Progesterone B Receptors, Donghai Dai, D. Wolf, E. Litman, M. White, Kimberly Leslie
Donghai Dai
Progesterone is a critical steroid hormone that controls cell proliferation and differentiation in the female reproductive tract. Progesterone acts through two nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB, respectively), each with unique cellular effects. Loss of PRB has recently been linked to the development of poorly differentiated endometrial tumors, a lethal form of cancer. To study the molecular effects of progesterone, progesterone receptors were introduced into Hec50co endometrial cancer cells by adenoviral vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent kinase inhibitors p21 and p27, thereby significantly reducing the percentage of proliferating cells. Cancer …
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Identification Of A Novel Mechanism Of Nf-Kappab Inactivation By Progesterone Through Progesterone Receptors In Hec50co Poorly Differentiated Endometrial Cancer Cells: Induction Of A20 And Abin-2, S. Davies, Donghai Dai, I. Feldman, G. Pickett, Kimberly Leslie
Donghai Dai
OBJECTIVE: Nuclear factor kappa B (NFkappaB) is a strong anti-apoptotic factor, which is constitutively active in human endometrial cancer cells. Progesterone is the principal growth inhibitory hormone in the endometrial epithelium and promotes apoptosis. To identify the pathways through which progesterone controls NFkappaB function, we explored its genomic and non-genomic effects in endometrial cancer cells. METHODS: PR-negative Hec50co endometrial cancer cells were engineered to express high levels of the A or B isoform of PR (PRA or PRB) by adenoviral infection. Cells were treated with progesterone or vehicle alone, and RNA was isolated. Affymetrix microarrays were performed and transcriptional control …
A Therapeutic Model For Advanced Endometrial Cancer: Systemic Progestin In Combination With Local Adenoviral-Mediated Progesterone Receptor Expression, Donghai Dai, L. Albitar, T. Nguyen, L. Laidler, M. Singh, Kimberly Leslie
A Therapeutic Model For Advanced Endometrial Cancer: Systemic Progestin In Combination With Local Adenoviral-Mediated Progesterone Receptor Expression, Donghai Dai, L. Albitar, T. Nguyen, L. Laidler, M. Singh, Kimberly Leslie
Donghai Dai
Cancer of the uterine endometrium is a frequent gynecologic malignant disease for which few therapeutic options are available for advanced disease. Progesterone is the normal female hormone that limits growth and proliferation of endometrial cancers; however, progesterone receptors are frequently down-regulated, leading to treatment failures. The current studies explored the effectiveness of adenoviral-mediated progesterone receptor gene transduction in combination with progestin therapy in mouse xenograft models. Pretreatment of cells with progesterone receptor-encoding adenovirus and progestin inhibited the development of s.c. tumors in athymic mice. In the i.p. xenograft model, replacement of both isoforms of progesterone receptor, PRA and PRB, in …
Transfection Of C6 Glioma Cells With Glia Maturation Factor Upregulates Brain-Derived Neurotrophic Factor And Nerve Growth Factor: Trophic Effects And Protection Against Ethanol Toxicity In Cerebellar Granule Cells, N. Pantazis, A. Zaheer, Donghai Dai, S. Zaheer, S. Green, R. Lim
Transfection Of C6 Glioma Cells With Glia Maturation Factor Upregulates Brain-Derived Neurotrophic Factor And Nerve Growth Factor: Trophic Effects And Protection Against Ethanol Toxicity In Cerebellar Granule Cells, N. Pantazis, A. Zaheer, Donghai Dai, S. Zaheer, S. Green, R. Lim
Donghai Dai
Glial cells play active roles in neuronal survival, as well as neuroprotection against toxic insult. Recent studies suggest that the brain protein glia maturation factor (GMF) is involved in intracellular signaling in glia. This study investigated whether or not GMF plays a role in the survival-promoting and neuroprotective functions of glia. C6 glioma cells were transfected in vitro with GMF utilizing an adenovirus vector. The transfected cells overexpressed GMF intracellularly, but did not secrete the protein. The conditioned medium (CM) was obtained from the GMF-transfected cells (CM-GMF) and tested on primary neuronal cultures, consisting of cerebellar granule cells (CGC). The …
Preclinical Development Of A Neutral, Estrogen Receptor-Targeted, Tridentate 99mtc(I)-Estradiol-Pyridin-2-Yl Hydrazine Derivative For Imaging Of Breast And Endometrial Cancers, T. Nayak, H. Hathaway, C. Ramesh, J. Arterburn, Donghai Dai, L. Sklar, J. Norenberg, E. Prossnitz
Preclinical Development Of A Neutral, Estrogen Receptor-Targeted, Tridentate 99mtc(I)-Estradiol-Pyridin-2-Yl Hydrazine Derivative For Imaging Of Breast And Endometrial Cancers, T. Nayak, H. Hathaway, C. Ramesh, J. Arterburn, Donghai Dai, L. Sklar, J. Norenberg, E. Prossnitz
Donghai Dai
Breast and endometrial cancers are the most common invasive malignancies in women, with more than 217,000 new diagnoses per year in the United States. These cancers are often classified into 2 subtypes based on the expression of the classical estrogen receptor. In this study, we describe a new structural class of neutral tridentate 99mTc(I)-estradiol-pyridin-2-yl hydrazine derivatives for potential use in breast and endometrial cancer imaging. METHODS: The 99mTc(I)-estradiol-pyridin-2-yl hydrazine derivative was synthesized via the Sonogashira cross-coupling reaction and radiolabeled via the tricarbonyl approach. Radiochemical purity was assessed by high-performance liquid chromatography. Cell-binding studies were performed with human breast adenocarcinoma MCF-7 …
Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie
Hormones And Receptors In Endometrial Cancer, David Bender, Thomas Buekers, Kimberly Leslie
David P Bender
The uterine endometrium is exquisitely sensitive to hormones, in particular estrogen and progesterone and to a lesser extent androgens and glucocorticoids. These hormones tightly regulate the complex functioning of the female reproductive tract and are intimately involved in controlling the growth, development, and remodeling of reproductive tissues as well as the cyclic changes that occur during the menstrual cycle. Steroids function by binding to nuclear receptor proteins that act as transcription factors to modulate the expression of genes, though many non-genomic effects for steroids have also been described. An imbalance of the hormones leads to cancer. In particular, endometrial carcinogenesis …
The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum
The Tweak Receptor Fn14 Is A Therapeutic Target In Melanoma: Immunotoxins Targeting Fn14 Receptor For Malignant Melanoma Treatment., Hong Zhou, Suhendan Ekmekcioglu, John W Marks, Khalid A Mohamedali, Kaushal Asrani, Keeley K Phillips, Sharron A N Brown, Emily Cheng, Michele B Weiss, Walter N Hittelman, Nhan L Tran, Hideo Yagita, Jeffrey A Winkles, Michael G Rosenblum
Department of Cancer Biology Faculty Papers
Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 …
Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang
Lymphotoxin-Α Is A Novel Adiponectin Expression Suppressor Following Myocardial Ischemia/Reperfusion., Wayne Bond Lau, Yanqing Zhang, Jianli Zhao, Baojiang Liu, Xiaoliang Wang, Yuexing Yuan, Theodore A. Christopher, Bernard Lopez, Erhe Gao, Walter J. Koch, Xin L. Ma, Yajing Wang
Department of Emergency Medicine Faculty Papers
Recent clinical observations demonstrate adiponectin (APN), an adipocytokine with potent cardioprotective actions, is significantly reduced following myocardial ischemia/reperfusion (MI/R). However, mechanisms responsible for MI/R-induced hypoadiponectinemia remain incompletely understood. Adult male mice were subjected to 30-min MI followed by varying reperfusion periods. Adipocyte APN mRNA and protein expression and plasma APN and TNFα concentrations were determined. APN expression/production began to decline 3 h after reperfusion (reaching nadir 12 h after reperfusion), returning to control levels 7 days after reperfusion. Plasma TNFα levels began to increase 1 h after reperfusion, peaking at 3 h and returning to control levels 24 h after …
The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner
The Adipose Tissue Production Of Adiponectin Is Increased In End-Stage Renal Disease., Maria P Martinez Cantarin, Scott A Waldman, Cataldo Doria, Adam M Frank, Warren R Maley, Carlo B Ramirez, Scott W Keith, Bonita Falkner
Department of Medicine Faculty Papers
Adiponectin has antidiabetic properties, and patients with obesity, diabetes, and insulin resistance have low plasma adiponectin levels. However, although kidney disease is associated with insulin resistance, adiponectin is elevated in end-stage renal disease. Here we determine whether adipose tissue production of adiponectin is increased in renal disease in a case-control study of 36 patients with end-stage renal disease and 23 kidney donors. Blood and tissue samples were obtained at kidney transplantation and donation. The mean plasma adiponectin level was significantly increased to 15.6 mg/ml in cases compared with 8.4 mg/ml in controls. Plasma levels of the inflammatory adipokines tumor necrosis …
Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange
Differential Expression Of The A And B Isoforms Of Progesterone Receptor In Human Endometrial Cancer Cells. Only Progesterone Receptor B Is Induced By Estrogen And Associated With Strong Transcriptional Activation., Kimberly Leslie, N. Kumar, J. Richer, G. Owen, G. Takimoto, K. Horwitz, C. Lange
Kimberly K. Leslie
No abstract provided.
Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar
Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar
Kimberly K. Leslie
Cancer and its link to reproductive hormones is an area of intense concern for our patients and has been the subject of much speculation. But if estrogen causes breast cancer, for example, most women would eventually develop the disease. We know this is not the case! Actually, estrogen and progesterone have been linked to a decrease as well as an increase in cancer, depending upon the type of tumor under investigation. The purpose of this manuscript is to review the data supporting those relationships.
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Selective Down-Regulation Of Progesterone Receptor Isoform B In Poorly Differentiated Human Endometrial Cancer Cells: Implications For Unopposed Estrogen Action., N. Kumar, J. Richer, G. Owen, E. Litman, K. Horwitz, Kimberly Leslie
Kimberly K. Leslie
The uterine endometrium responds to unopposed estrogen stimulation with rapid cell proliferation. Progesterone protects the endometrium against the hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2 terminus and may function differently from hPRA. Thus, the relative expression of hPRA:hPRB is likely to be important for the action of progesterone. We hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial cancer …
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Estrogen Receptors Are Present In Human Granulosa Cells., B. Hurst, M. Zilberstein, J. Chou, B. Litman, J. Stephens, Kimberly Leslie
Kimberly K. Leslie
Recent studies failed to detect estrogen receptors in primate follicles. This study was initiated to determine whether estrogen receptor (ER) messenger ribonucleic acid (mRNA) is present in human granulosa cells and, further, if functional ER proteins are present. To evaluate the presence of ER, RNA from human granulosa cells obtained at the time of oocyte retrieval for assisted reproduction was extracted, and complementary DNA synthesis was performed by the reverse transcriptase-polymerase chain reaction. Oligonucleotide primers were used to amplify basepairs 570-852 in the B- and C- domains of the ER mRNA. Southern blotting was performed and confirmed that the amplified …