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2014

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Articles 1 - 27 of 27

Full-Text Articles in Cell Biology

Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov Nov 2014

Amphiphilic Degradable Polymer/Hydroxyapatite Composites As Smart Bone Tissue Engineering Scaffolds: A Dissertation, Artem B. Kutikov

GSBS Dissertations and Theses

Over 600,000 bone-grafting operations are performed each year in the United States. The majority of the bone used for these surgeries comes from autografts that are limited in quantity or allografts with high failure rates. Current synthetic bone grafting materials have poor mechanical properties, handling characteristics, and bioactivity. The goal of this dissertation was to develop a clinically translatable bone tissue engineering scaffold with improved handling characteristics, bioactivity, and smart delivery modalities. We hypothesized that this could be achieved through the rational selection of Food and Drug Administration (FDA) approved materials that blend favorably with hydroxyapatite (HA), the principle ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Katherine A. Fitzgerald

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo Sep 2014

Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo

Gyongyi Szabo

Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis ...


Temporal Trends In Serum Concentrations Of Polychlorinated Dioxins, Furans, And Pcbs Among Adult Women Living In Chapaevsk, Russia: A Longitudinal Study From 2000 To 2009, Olivier Humblet, Oleg Sergeyev, Larisa Altshul, Susan A. Korrick, Paige L. Williams, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Mary M. Lee, Boris Revich, Andrey Shelepchikov, Denis Feshin, Russ Hauser Sep 2014

Temporal Trends In Serum Concentrations Of Polychlorinated Dioxins, Furans, And Pcbs Among Adult Women Living In Chapaevsk, Russia: A Longitudinal Study From 2000 To 2009, Olivier Humblet, Oleg Sergeyev, Larisa Altshul, Susan A. Korrick, Paige L. Williams, Claude Emond, Linda S. Birnbaum, Jane S. Burns, Mary M. Lee, Boris Revich, Andrey Shelepchikov, Denis Feshin, Russ Hauser

Mary M. Lee

BACKGROUND: The present study assessed the temporal trend in serum concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls (PCBs) among residents of a Russian town where levels of these chemicals are elevated due to prior industrial activity.

METHODS: Two serum samples were collected from eight adult women (in 2000 and 2009), and analyzed with gas chromatography-high-resolution mass spectrometry.

RESULTS: The average total toxic equivalency (TEQ) decreased by 30% (from 36 to 25 pg/g lipid), and the average sum of PCB congeners decreased by 19% (from 291 to 211 ng/g lipid). Total TEQs decreased for seven of the eight women ...


Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock Aug 2014

Evaluation Of The Contribution Of Multiple Damps And Damp Receptors In Cell Death-Induced Sterile Inflammatory Responses, Hiroshi Kataoka, Hajime Kono, Zubin Patel, Kenneth L. Rock

Open Access Articles

When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been ...


Hsa-Mir-30c Promotes The Invasive Phenotype Of Metastatic Breast Cancer Cells By Targeting Nov/Ccn3, Jason R. Dobson, Hanna Taipaleenmaki, Yu-Jie Hu, Deli Hong, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap Aug 2014

Hsa-Mir-30c Promotes The Invasive Phenotype Of Metastatic Breast Cancer Cells By Targeting Nov/Ccn3, Jason R. Dobson, Hanna Taipaleenmaki, Yu-Jie Hu, Deli Hong, Andre J. Van Wijnen, Janet L. Stein, Gary S. Stein, Jane B. Lian, Jitesh Pratap

Open Access Articles

BACKGROUND: For treatment and prevention of metastatic disease, one of the premier challenges is the identification of pathways and proteins to target for clinical intervention. Micro RNAs (miRNAs) are short, non-coding RNAs, which regulate cellular activities by either mRNA degradation or translational inhibition. Our studies focused on the invasive properties of hsa-mir30c based on its high expression in MDA-MB-231 metastatic cells and our bioinformatic analysis of the Cancer Genome Atlas that identified aberrant hsa-mir-30c to be associated with poor survival.

METHODS: Contributions of hsa-mir-30c to breast cancer cell invasion were examined by Matrigel invasion transwell assays following modulation of hsa-mir-30c ...


Th17 Cell-Associated Response To Borrelia Burgdorferi Outer Surface Protein A, Megan Elizabeth Johnson Aug 2014

Th17 Cell-Associated Response To Borrelia Burgdorferi Outer Surface Protein A, Megan Elizabeth Johnson

Theses and Dissertations

Arthritis is a common symptom of Lyme disease, a debilitating condition resulting from infection with Borrelia burgdorferi. A protein found on the surface of B. burgdorferi, outer surface protein A (OspA), is known to elicit an inflammatory immune response involving T helper cells. T helper 17 (Th17) cells are associated with the inflammatory cytokines interleukin-17 (IL-17) and interleukin-23 (IL-23) and have been implicated in the development of Lyme arthritis. The objective of this thesis is to provide further characterization of the immune response to B. burgdorferi OspA. The central hypothesis of this thesis is: Vaccination with OspA will predispose mice ...


Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti Aug 2014

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

UT GSBS Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but ...


Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson Jun 2014

Phosphoinositides: Minor Lipids Make A Major Impact On Photoreceptor Cell Functions, Raju V. S. Rajala, Ammaji Rajala, Andrew J. Morris, Robert E. Anderson

Internal Medicine Faculty Publications

Activation of the phosphoinositide (PI) cycle generates the second messengers that control various aspects of cellular signaling. We have previously shown that two PI cycle enzymes, type II phosphatidylinositol 5-phosphate 4-kinase (PIPK IIα) and phosphoinositide 3-kinase (PI3K), are activated through light stimulation. In our earlier studies, we measured enzyme activities, instead of directly measuring the products, due to lack of sensitive analytical techniques. Cells have very low levels of PIs, compared to other lipids, so special techniques and sensitive analytical instruments are necessary for their identification and quantification. There are also other considerations, such as different responses in different cell ...


High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song May 2014

High Performance Amphiphilic Polymer/Hydroxyapatite Composite Tissue Scaffolds, Artem B. Kutikov, Jie Song

UMass Center for Clinical and Translational Science Research Retreat

There is a critical clinical need for alternatives to autograft and allograft bone for over 500,000 bone grafting operations performed each year in the United States. Current synthetic bone grafts suffer from poor handling characteristics, brittle mechanical properties, and inconsistent bioactivity. By blending a biodegradable amphiphilic polymer with hydroxyapatite (HA), the main mineral component in bone, we developed an improved synthetic bone graft. The polymer/HA composites were fabricated in both 2-D and 3-D forms by electrospinning and 3-D printing. These materials exhibited unique handling characteristics such as high tensile elasticity (>200% failure strain) and self-stiffening properties upon hydration ...


Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li May 2014

Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li

Theses and Dissertations

Bioactive peptides derived from food sources with anti-proliferative properties against cancer have drawn more attention in recent years. A pentapeptide derived from rice bran has shown anti-proliferative propertiesagainst human breast cancer cells. The objective of this study was to investigate the mechanistic action of the pentapeptide-induced apoptosis in breast cancer cell models (MCF-7 and MDA-MB-231). The growth inhibition activity of the pentapeptide was

evaluated by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3- arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assayand trypan blue assay in a dose- and time-dependent manner.

The apoptotic properties of pentapeptide-induced apoptosis on cancerous breast cells were evaluated by ...


Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman Mar 2014

Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman

Graduate Theses and Dissertations

Ovarian carcinoma afflicts over 22,000 women each year with a 5 year survival rate of only 18% for stage IV patients [23]. Current treatment options are limited due to high rates of drug resistance and recurrence. Further, the identity of "precursor lesions" which give rise to various subclasses of epithelial ovarian cancer has been evasive. This is due to discovery of the cancer at already an advanced stage. Interestingly, endometriosis a benign but invasive gynecological disease has been described as a "precursor lesion" in the development of specific subtypes of ovarian cancer. Endometriotic cyst development involves the accumulation of ...


Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois Feb 2014

Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois

All Dissertations, Theses, and Capstone Projects

Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces ...


Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro Jan 2014

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair ...


Pregnancy-Associated Breast Cancers Are Driven By Differences In Adipose Stromal Cells Present During Lactation, Jessica Mccready, Lisa M. Arendt, Eugene Glover, Vandana Iyer, Jerrica L. Briendel, Stephen Lyle, Stephen P. Naber, Daniel G. Jay, Charlotte Kuperwasser Jan 2014

Pregnancy-Associated Breast Cancers Are Driven By Differences In Adipose Stromal Cells Present During Lactation, Jessica Mccready, Lisa M. Arendt, Eugene Glover, Vandana Iyer, Jerrica L. Briendel, Stephen Lyle, Stephen P. Naber, Daniel G. Jay, Charlotte Kuperwasser

Open Access Articles

INTRODUCTION: The prognosis of breast cancer is strongly influenced by the developmental stage of the breast when the tumor is diagnosed. Pregnancy-associated breast cancers (PABCs), cancers diagnosed during pregnancy, lactation, or in the first postpartum year, are typically found at an advanced stage, are more aggressive and have a poorer prognosis. Although the systemic and microenvironmental changes that occur during post-partum involution have been best recognized for their role in the pathogenesis of PABCs, epidemiological data indicate that PABCs diagnosed during lactation have an overall poorer prognosis than those diagnosed during involution. Thus, the physiologic and/or biological events during ...


Roles Of Dendritic Cells In Immunity To Toxoplasma Gondii, Christopher David Dupont Jan 2014

Roles Of Dendritic Cells In Immunity To Toxoplasma Gondii, Christopher David Dupont

Publicly Accessible Penn Dissertations

Toxoplasma gondii is an intracellular protozoan parasite that actively invades host cells. During toxoplasmosis, dendritic cells (DCs) promote CD4+ and CD8+ T cell responses, which are critical for long-term immunity. Despite this critical role of DCs, questions remain regarding how this population is regulated during infection, and the specific types of interactions (phagocytosis or active invasion) between parasites and DCs that are necessary to induce T cell responses.

Previous studies have observed an infection-induced expansion of DC populations during toxoplasmosis, but the factors that regulate this expansion are currently unknown. Mice deficient in the cytokine Flt3L, which promotes the proliferation ...


Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden Jan 2014

Combating Resistance To Epidermal Growth Factor Recpetor Inhibitors In Triple Negative Breast Cancer, Julie Marie Madden

Wayne State University Dissertations

Triple negative breast cancer (TNBC) patients suffer from a highly malignant and aggressive cancer that lacks an effective targeted therapeutic. Although many TNBCs, both in vitro and in vivo, have increased expression of epidermal growth factor receptor (EGFR), EGFR targeted inhibitors, such as gefitinib (GEF), have yet to demonstrate efficacy. Using mass spectrometry to identify pathways that remain activated in the presence of GEF, we found that components of the mTOR signaling pathway remain phosphorylated. While inhibiting mTOR with temsirolimus (TEM) decreased mTOR signaling, EGFR signaling pathways remained activated and the TNBC cell lines continued to proliferate. However, dual treatment ...


Functional Genomic And Proteomic Analysis Of Highly Drug Resistant Chronic Myeloid Leukemia, Derrick Matthew Oaxaca Jan 2014

Functional Genomic And Proteomic Analysis Of Highly Drug Resistant Chronic Myeloid Leukemia, Derrick Matthew Oaxaca

Open Access Theses & Dissertations

Chronic Myeloid Leukemia (CML) has served as a model for how cancer can be selectively targeted with advanced forms of chemotherapies known as kinase inhibitors. Such new therapies have significantly altered the field of oncology and have led to monumental increases in both survival rates and quality of life for cancer patients. However, approximately one-third of CML patients will go on to develop drug resistance against major kinase inhibitors. Along with this, other cancers are showing increased incidences of drug resistance. Understanding how these cancers, such as CML, overcome drug sensitivity is of major importance within the clinic. To predict ...


Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully Jan 2014

Classical And Alternative Nuclear Factor-Kappab In Epithelium: Impacts In Allergic Airway Disease And Avenues For Redox Regulation, Jane Elizabeth Tully

Graduate College Dissertations and Theses

Nuclear Factor kappaB (NF-êB) is a transcription factor whose activation is increased in settings of allergic asthma. At least two parallel NF-êB pathways exist: the classical pathway, which plays a role in inflammation and cell survival, and the alternative pathway, which regulates lymphoid cell development and organogenesis. The classical NF-êB pathway regulates inflammatory responses derived from lung epithelial cells; however, the role of the alternative pathway in lung epithelial cells remains unclear. We demonstrate that both classical and alternative NF-êB are activated in lung epithelial cells in response to multiple pro-inflammatory agonists, and siRNA-mediated knockdown of alternative NF-êB proteins largely ...


Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz Jan 2014

Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz

Publicly Accessible Penn Dissertations

The impact of EBV on human health is substantial, but vaccines that prevent primary EBV infections or treat EBV-associated diseases are not yet available. The Epstein-Barr nuclear antigen 1 (EBNA1) is an important target for vaccination because it is the only protein expressed in all forms of latency and in all EBV-associated malignancies. The overarching goal throughout this dissertation was to determine if EBNA1 is a suitable target for vaccine development. This was addressed in two ways. First, because an improved understanding of EBNA1-specific T cell responses benefits EBV vaccine development, we characterized responses against EBNA1 of the EBV-homologous rhesus ...


Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie Jan 2014

Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie

Publicly Accessible Penn Dissertations

Formation of a functional immune response requires the regulated transfer of information between T cells, and APCs, which leads to a variety of functional outcomes. In many cases this information transfer occurs at a regulated area of cell - cell contact termed the immunological synapse (IS). In T cells responding to APCs there is a robust accumulation of F-actin on the T cell side of the synapse. This F-actin response is characterized by robust polymerization at the periphery of the contact site followed by centripetal flow of the network towards the center of the IS. While it is well known that ...


T Cells Bearing A Chimeric Antigen Receptor Against The Tumor Vasculature Destroy The Tumor Endothelium And Result In Tumor Regression, Stephen Santoro Jan 2014

T Cells Bearing A Chimeric Antigen Receptor Against The Tumor Vasculature Destroy The Tumor Endothelium And Result In Tumor Regression, Stephen Santoro

Publicly Accessible Penn Dissertations

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of pro-tumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here I describe the development of two chimeric antigen receptors (CAR)s against the tumor vasculature, targeting either tumor endothelial marker 1 (TEM1) or prostate-specific membrane antigen (PSMA). CAR T cells incorporating scFv78, an scFv isolated against TEM1, were able to recognize immobilized plate-bound TEM1 protein, but were unable to recognize TEM1 on the surface of endothelial cell targets. In contrast, anti-PSMA CAR ...


Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin Jan 2014

Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin

Publicly Accessible Penn Dissertations

The trafficking of innate-like lymphocytes, such as γδ T cells and B-1 B cells, has garnered comparatively little attention from the immunological community relative to conventional T and B cells. However, recent studies have shown that innate-like cell subsets are critical for immune regulation and host defense. In this study, we use a classic ovine lymph cannulation model to describe the phenotype and function of γδ T cells migrating through the skin. We find that γδ T cells traveling in the skin-draining afferent lymph are IFN-γ- and/or IL-17-producing effector cells that express high levels of the skin- and inflammation-seeking ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...


Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler Jan 2014

Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler

Publicly Accessible Penn Dissertations

Hematopoiesis in human bone marrow generates every second about 105 – 106 anucleated platelets and red blood cells as well as nucleated white blood cells that are capable of infiltrating distant tissues. The thesis begins in the marrow with a description of (1) nuclear membrane ‘lamina’ physicochemical properties that influence marrow-to-circulation trafficking, and proceeds to detail (2) the physicochemical roles of membrane cortex ‘myosin’ in key marrow processes of motility and division as well as platelet biogenesis and disease. The thesis finishes with (3) studies of macrophages in peripheral tissues far from the marrow and aspects of how such ...


A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith Jan 2014

A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.


Paracrine-Rescued Lobulogenesis In Chimeric Outgrowths Comprising Progesterone-Receptor-Null Mammary Epithelium And Redirected Wild-Type Testicular Cells, Robert D. Bruno, Corinne A. Boulanger, Sonia M. Rosenfield, Lisa H. Anderson, John P. Lydon, Gilbert H. Smith Jan 2014

Paracrine-Rescued Lobulogenesis In Chimeric Outgrowths Comprising Progesterone-Receptor-Null Mammary Epithelium And Redirected Wild-Type Testicular Cells, Robert D. Bruno, Corinne A. Boulanger, Sonia M. Rosenfield, Lisa H. Anderson, John P. Lydon, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

We have previously shown that non-mammary and tumorigenic cells can respond to the signals of the mammary niche and alter their cell fate to that of mammary epithelial progenitor cells. Here we tested the hypothesis that paracrine signals from mammary epithelial cells expressing progesterone receptor (PR) are dispensable for redirection of testicular cells, and that re-directed wild-type testicular-derived mammary cells can rescue lobulogenesis of PR-null mammary epithelium by paracrine signaling during pregnancy. We injected PR-null epithelial cells mixed with testicular cells from wild-type adult male mice into cleared fat-pads of recipient mice. The testicular cells were redirected in vivo to ...