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Ancylostoma Ceylanicum Infective Third-Stage Larvae Are Activated By Co-Culture With Ht-29-Mtx Intestinal Epithelial Cells, Caitlin Feather, John M. Hawdon, John March

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human hookworm larvae arrest development until they enter an appropriate host. This makes it difficult to access the larvae for studying larval development or host-parasite interactions. While there are in vivo and in vitro animal models of human hookworm infection, there is currently no human, in vitro model. While animal models have provided much insight into hookworm biology, there are limitations to how closely this can replicate human infection. Therefore, we have developed a human, in vitro model of the initial phase of hookworm infection using intestinal epithelial cell culture.

Results

Co-culture of the human hookworm Ancylostoma ceylanicum with …

Boiling Histotripsy Lesion Characterization On A Clinical Magnetic Resonance Imaging-Guided High Intensity Focused Ultrasound System., Avinash Eranki, Navid Farr, Ari Partanen, Karun Sharma, Hong Chen, Christopher T Rossi, Satya V V N Kothapalli, Matthew Oetgen, Aerang Kim, Ayele H Negussie, David Woods, Bradford J Wood, Peter C W Kim, Pavel S. Yarmolenko

Pediatrics Faculty Publications

PURPOSE: High intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that can thermally ablate tumors. Boiling histotripsy (BH) is a HIFU approach that can emulsify tissue in a few milliseconds. Lesion volume and temperature effects for different BH sonication parameters are currently not well characterized. In this work, lesion volume, temperature distribution, and area of lethal thermal dose were characterized for varying BH sonication parameters in tissue-mimicking phantoms (TMP) and demonstrated in ex vivo tissues.

METHODS: The following BH sonication parameters were varied using a clinical MR-HIFU system (Sonalleve V2, Philips, Vantaa, Finland): acoustic power, number of cycles/pulse, total …

The Current Consensus On The Clinical Management Of Intracranial Ependymoma And Its Distinct Molecular Variants., Kristian W Pajtler, Stephen C Mack, Vijay Ramaswamy, Christian A Smith, Hendrik Witt, Amy Smith, Eugene Hwang, +Several Additional Authors

Pediatrics Faculty Publications

Multiple independent genomic profiling efforts have recently identified clinically and molecularly distinct subgroups of ependymoma arising from all three anatomic compartments of the central nervous system (supratentorial brain, posterior fossa, and spinal cord). These advances motivated a consensus meeting to discuss: (1) the utility of current histologic grading criteria, (2) the integration of molecular-based stratification schemes in future clinical trials for patients with ependymoma and (3) current therapy in the context of molecular subgroups. Discussion at the meeting generated a series of consensus statements and recommendations from the attendees, which comment on the prognostic evaluation and treatment decisions of patients …

Composite Iron Oxide–Prussian Blue Nanoparticles For Magnetically Guided T1-Weighted Magnetic Resonance Imaging And Photothermal Therapy Of Tumors, Shraddha Kale, Rachel Burga, Elizabeth E. Sweeney, Zungho Zun, Raymond Sze, Anthony Tuesca, J Anand Subramony, Rohan Fernandes

Radiology Faculty Publications

Theranostic nanoparticles offer the potential for mixing and matching disparate diagnostic and therapeutic functionalities within a single nanoparticle for the personalized treatment of diseases. In this article, we present composite iron oxide-gadolinium-containing Prussian blue nanoparticles (Fe3O4@GdPB) as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI) and photothermal therapy (PTT) of tumors. These particles combine the well-described properties and safety profiles of the constituent Fe3O4 nanoparticles and gadolinium-containing Prussian blue nanoparticles. The Fe3O4@GdPB nanoparticles function both as effective MRI contrast agents and PTT agents as determined by characterizing studies performed in vitro and retain their properties in the presence …

H-Ipse Is A Pathogen-Secreted Host Nucleus Infiltrating Protein (Infiltrin) 3 Expressed Exclusively By The Schistosoma Haematobium Egg Stage, Luke Pennington, Abdulaziz Alouffi, Evaristus Mbanefo, Debalina Ray, David Heery, Theodore Jardetzky, Michael Hsieh, Franco Falcone

Urology Faculty Publications

Urogenital schistosomiasis, caused by the parasitic trematode Schistosoma haematobium, affects over 112 million people worldwide. As with S. mansoniinfections, the pathology in urogenital schistosomiasis is mainly related to the egg stage, which induces granulomatous inflammation of affected tissues. Schistosoma eggs and their secretions have been studied extensively for the related S. mansoniorganism which is more amenable to laboratory studies. Indeed, we have shown that IPSE/alpha-1 (M-IPSE herein), a major protein secreted from S .mansoni eggs, can infiltrate host cells. Although M-IPSE function is unknown, its ability to translocate to their nucleus and bind DNA suggests a possible …

Neurovascular Unit Dysfunction And Blood-Brain Barrier Hyperpermeability Contribute To Schizophrenia Neurobiology: A Theoretical Integration Of Clinical And Experimental Evidence, S. Najjar, S. Pahlajani, V. De Sanctis, J. N.H. Stern, A. Najjar, D. Chong

Journal Articles

No abstract provided.

Repurposing Mebendazole As A Replacement For Vincristine For The Treatment Of Brain Tumors, M. De Witt, A. Gamble, D. Hanson, D. Markowitz, C. Powell, S. Al Dimassi, M. Atlas, J. Boockvar, R. Ruggieri, M. Symons

Journal Articles

No abstract provided.

A Role For B Cells In Organic Dust Induced Lung Inflammation, Jill A. Poole, Ted R. Mikuls, Michael J. Duryee, Kristi J. Warren, Todd A. Wyatt, Amy J. Nelson, Debra J. Romberger, William W. West, Geoffrey M. Thiele

Journal Articles: Internal Medicine

BACKGROUND: Agriculture organic dust exposures induce lung disease with lymphoid aggregates comprised of both T and B cells. The precise role of B cells in mediating lung inflammation is unknown, yet might be relevant given the emerging role of B cells in obstructive pulmonary disease and associated autoimmunity.

METHODS: Using an established animal model, C57BL/6 wild-type (WT) and B-cell receptor (BCR) knock-out (KO) mice were repetitively treated with intranasal inhalation of swine confinement organic dust extract (ODE) daily for 3 weeks and lavage fluid, lung tissues, and serum were collected.

RESULTS: ODE-induced neutrophil influx in lavage fluid was not reduced …

Human Liver Sinusoid On A Chip For Hepatitis B Virus Replication Study, Young Bok (Abraham) Kang, Siddhartha Rawat, Nicholas Duchemin, Michael Bouchard, Moses Noh

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

We have developed a miniature human liver (liver-sinusoid-on-a-chip) model using a dual microchannel separated by a porous membrane. Primary human hepatocytes and immortalized bovine aortic endothelial cells were co-cultured on opposite sides of a microporous membrane in a dual microchannel with continuous perfusion. Primary human hepatocytes in this system retained their polygonal morphology for up to 26 days, while hepatocytes cultured in the absence of bovine aortic endothelial cells lost their morphology within a week. In order to demonstrate the utility of our human-liver-sinusoid-on-a-chip, human hepatocytes in this system were directly infected by Hepatitis B Virus (HBV). Expression of the …

A Preliminary Longitudinal Study Of White Matter Alteration In Cocaine Use Disorder Subjects, Liangsuo Ma, Joel L. Steinberg, Qin Wang, Joy M. Schmitz, Edward L. Boone, Ponnada A. Narayana, F. Gerard Moeller

Radiology Publications

Background

Previous diffusion tensor imaging (DTI) studies have consistently shown that subjects with cocaine use disorder (CocUD) had altered white matter microstructure in the corpus callosum. It is believed that these alterations are due to preexisting factors, chronic cocaine use, or both. However, there is no published longitudinal DTI study on human cocaine users yet which could shed light on the relationship between cocaine use and DTI findings.

Methods

This study used a longitudinal design and DTI to test if the white matter microstructure shows quicker alteration in CocUD subjects than controls. DTI data were acquired from eleven CocUD subjects …

Nfatc3 And Vip In Idiopathic Pulmonary Fibrosis And Chronic Obstructive Pulmonary Disease, A. M. Szema, E. Forsyth, B. Ying, S. A. Hamidi, J. J. Chen, S. Hwang, J. C. Li, D. S. Dwyer, J. M. Ramiro-Diaz, L. V. Gonzalez Bosc, +1 Additional Author

Journal Articles

No abstract provided.

Malignant Peripheral Nerve Sheath Tumors State Of The Science: Leveraging Clinical And Biological Insights Into Effective Therapies., Aerang Kim, Douglas R Stewart, Karlyne M Reilly, David Viskochil, Markku M Miettinen, Brigitte C Widemann

Pediatrics Faculty Publications

Malignant peripheral nerve sheath tumor (MPNST) is the leading cause of mortality in patients with neurofibromatosis type 1. In 2002, an MPNST consensus statement reviewed the current knowledge and provided guidance for the diagnosis and management of MPNST. Although the improvement in clinical outcome has not changed, substantial progress has been made in understanding the natural history and biology of MPNST through imaging and genomic advances since 2002. Genetically engineered mouse models that develop MPNST spontaneously have greatly facilitated preclinical evaluation of novel drugs for translation into clinical trials led by consortia efforts. Continued work in identifying alterations that contribute …

Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, Adam Patrick Fischer

Theses, Dissertations and Capstones

Dioxygenase enzymes such as the HIF hydroxylases (PHD1-3, FIH) and the Ten-eleven translocation (TET1-3) enzymes regulate the activity of the hypoxia inducible factor-1_a (HIF1_a) transcription factor and the DNA methylation status of cells, respectively. Aberrant accumulation and activation of HIF-1_a can allow malignant cells to acquire attributes that promote progression, chemotherapy resistance, and survival, while aberrant hypermethylation of gene promoters can silence the expression of tumor suppressor genes essential to preventing tumorigenesis. Inadequate levels of intracellular ascorbic acid (AA), a necessary cofactor for optimal dioxygenase enzyme function, could potentiate these tumorigenic conditions. In fact, plasma levels …

Neuroprotection Through Flavonoid: Enhancement Of The Glyoxalase Pathway., Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural …

Reduced Microrna-503 Expression Augments Lung Fibroblast Vegf Production In Chronic Obstructive Pulmonary Disease, Jun Ikari, Amy J. Nelson, Jannah Obaid, Alvaro Giron-Martinez, Kumiko Ikari, Fumihiko Makino, Shunichiro Iwasawa, Yoko Gunji, Maha Farid, Xingqi Wang, Hesham Basma, Dawn Demeo, Carol Feghali-Bostwick, Olaf Holz, Klaus Rabe, Xiangde Liu, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Alterations in microRNA (miRNA) expression may contribute to COPD pathogenesis. In COPD, lung fibroblast repair functions are altered in multiple ways, including extracellular mediator release. Our prior study revealed miR-503 expression is decreased in COPD lung fibroblasts, although the exact role played by miR-503 is undetermined. The current study examined a role of miR-503 in cytokine, growth factor and fibronectin production by lung fibroblasts from patients with and without COPD. Primary adult lung fibroblasts were isolated from patients with or without COPD. MiR-503 expression and interleukin (IL)-6, -8, PGE2, HGF, KGF, VEGF and fibronectin release were examined with or without …

Anti-Cancer Effects Of Tocotrienols In Nsclc, Lichchavi Raj Raj

Wayne State University Dissertations

Lung cancer is one of the leading causes of death among cancers, with non-small cell lung cancer (NSCLC) accounting for 80-85% of all lung cancers and a five-year survival rate of 5 % at stage IIIB. Delta-tocotrienol (δT) including other tocotrienol isomers has been shown to exhibit anti-tumor activity via inhibition of different signaling pathways in tumors including NSCLC. Previously we reported that δT reduced cell invasion via inhibition of the Notch-1 and NF-κb pathway.

Matrix metallopeptidase 9 (MMP9) dependent cell migration and invasion are key processes in cancer metastasis. Hence, its suppression is a promising strategy for cancer therapeutics. …

Sustained Nitric Oxide-Releasing Nanoparticles Interfere With Methicillin-Resistant Staphylococcus Aureus Adhesion And Biofilm Formation In A Rat Central Venous Catheter Model., Mircea Radu Mihu, Vitor Cabral, Rodney Pattabhi, Moses T Tar, Kelvin P Davies, Adam J Friedman, Luis R Martinez, Joshua D Nosanchuk

Dermatology Faculty Publications

Staphylococcus aureus is frequently isolated in the setting of infections of indwelling medical devices, which are mediated by the microbe's ability to form biofilms on a variety of surfaces. Biofilm-embedded bacteria are more resistant to antimicrobial agents than their planktonic counterparts and often cause chronic infections and sepsis, particularly in patients with prolonged hospitalizations. In this study, we demonstrate that sustained nitric oxide-releasing nanoparticles (NO-np) interfere with S. aureus adhesion and prevent biofilm formation on a rat central venous catheter (CVC) model of infection. Confocal and scanning electron microscopy showed that NO-np-treated staphylococcal biofilms displayed considerably reduced thicknesses and bacterial …

Ptpro Represses Erbb2-Driven Breast Oncogenesis By Dephosphorylation And Endosomal Internalization Of Erbb2., H Dong, L Ma, J Gan, W Lin, Rakesh Kumar, +9 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

The plasma membrane-associated tyrosine phosphatase PTPRO is frequently transcriptionally repressed in cancers and signifies poor prognosis of breast cancer patients. In this study, deletion of Ptpro inMMTV-Erbb2 transgenic mice dramatically shortened the mammary tumor latency and accelerated tumor growth due to loss of Ptpro within the breast cancer cells but not in surrounding tissue as confirmed by hetero-transplantation studies. Both in vitro and in vivo data demonstrated that the phosphatase activity was required for the inactivation of ERBB2 and its downstream signaling. PTPRO regulated the phosphorylation status of ERBB2 at Y1248. Co-immunoprecipitation and proximity ligation assay (Duolink) indicated that …

Anti-Müllerian Hormone And Its Relationships With Subclinical Cardiovascular Disease And Renal Disease In A Longitudinal Cohort Study Of Women With Type 1 Diabetes, Catherine Kim, Yuanyuan Pan, Barbara Braffett, Valerie Arends, Michael Steffes, Hunter Wessells, Aruna V. Sarma

GW Biostatistics Center

Background

Reproductive age may be a risk factor for vascular disease. Anti-Müllerian hormone (AMH) is produced by viable ovarian follicles and reflects reproductive age. We examined whether AMH concentrations were associated with markers of subclinical cardiovascular disease (CVD) and kidney disease among women with type 1 diabetes.

Methods

We performed a cross-sectional analysis of the Epidemiology of Diabetes Interventions and Complications Study. Participants included women with type 1 diabetes and ≥1 AMH measurement (n = 390). In multivariable regression models which adjusted for repeated measures, we examined the associations between AMH with CVD risk factors, estimated glomerular filtration rate, …

Selective Autonomic Stimulation Of The Av Node Fat Pad To Control Rapid Post-Operative Atrial Arrhythmias., Marco A Mercader, Dingchao He, Aditya C Sharma, Mark C Marchitto, Gregory Trachiotis, Gene A Bornzin, Richard A. Jonas, Jeffrey P Moak

Medicine Faculty Publications

Junctional ectopic tachycardia (JET) and atrial fibrillation (AF) occur in patients recovering from open-heart surgery (OHS). Pharmacologic treatment is used for the control of post-operative atrial arrhythmias (POAA), but is associated with side effects. There is a need for a reversible, modulated solution to rate control. We propose a non-pharmacologic technique that can modulate AV nodal conduction in a selective fashion. Ten mongrel dogs underwent OHS. Stimulation of the anterior right (AR) and inferior right (IR) fat pad (FP) was done using a 7-pole electrode. The IR was more effective in slowing the ventricular rate (VR) to AF (52 +/- …

Press-Pulse: A Novel Therapeutic Strategy For The Metabolic Management Of Cancer, Thomas Seyfried, George Yu, Joseph Maroon, Dominic D'Agostino

Urology Faculty Publications

Background

A shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of “Press-Pulse” disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred.

Methods

This general concept can be applied to the management of cancer by creating chronic metabolic stresses on tumor cell energy metabolism (press disturbance) …

Interrelationship Between Climatic, Ecologic, Social, And Cultural Determinants Affecting Dengue Emergence And Transmission In Puerto Rico And Their Implications For Zika Response., Angela Matysiak, Amira Roess

Global Health Faculty Publications

Objective

The global resurgence of dengue has been attributed to rapid population growth, urban expansion, increased air travel, globalization, and climate change. Dengue is now endemic in Puerto Rico. Puerto Rico is at risk for Zika, another emerging arbovirus. The interrelationship between climatic, ecological, social, and cultural factors that affect dengue and other arboviruses' transmission is understudied.

Design

The objective of this systematic review is to examine the interrelationship between climatic, ecological, social, and cultural factors on dengue transmission in Puerto Rico and to draw lessons for Zika response.

Results

A comprehensive search of peer-reviewed journal articles was performed, producing …

Foxc1 Is Associated With Estrogen Receptor Alpha And Affects Sensitivity Of Tamoxifen Treatment In Breast Cancer., Jinhua Wang, Yali Xu, Li Li, Lin Wang, Ru Yao, Qiang Sun, Guanhua Du

Articles, Abstracts, and Reports

FOXC1 is a member of Forkhead box transcription factors that participates in embryonic development and tumorigenesis. Our previous study demonstrated that FOXC1 was highly expressed in triple-negative breast cancer. However, it remains unclear what is the relation between FOXC1 and ERα and if FOXC1 regulates expression of ERα. To explore relation between FOXC1 and ERα and discover regulation of ERα expression by FOXC1 in breast cancer, we analyzed data assembled in the Oncomine and TCGA, and found that there was significantly higher FOXC1 expression in estrogen receptor-negative breast cancer than that in estrogen receptor-positive breast cancer. Overexpression of FOXC1 reduced …

Sting Expression And Response To Treatment With Sting Ligands In Premalignant And Malignant Disease., Jason R Baird, Zipei Feng, Hong D Xiao, David Friedman, Ben Cottam, Bernard A Fox, Gwen Kramer, Rom S Leidner, Richard Bryan Bell, Kristina H Young, Marka R Crittenden, Michael J Gough

Articles, Abstracts, and Reports

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of …

The Effects Of Bone Marrow Adipocytes On Metabolic Regulation In Metastatic Prostate Cancer, Jonathan Diedrich

Wayne State University Dissertations

Bone is a preferential site of metastasis from prostate cancer (PCa). Although there have been many advances in therapeutic options for patients suffering from metastatic PCa, this disease remains incurable with an estimated five-year survival of 33%. To design effective therapeutic interventions for metastatic PCa, it is essential that we elucidate the molecular mechanisms responsible for tumor cell adaptation to and the ability to thrive within the bone metastatic niche. Age and obesity, conditions that increase adipocyte numbers in bone marrow, are risk factors for skeletal metastases from PCa; therefore, our laboratory is focused on the interactions between marrow adipocytes …

The Distinct Metabolic Phenotype Of Lung Squamous Cell Carcinoma Defines Selective Vulnerability To Glycolytic Inhibition, Justin Goodwin, Michael L. Neugent, Shin Yup Lee, Joshua H. Choe, Hyunsung Choi, Dana M. R. Jenkins, Robin J. Ruthenborg, Maddox W. Robinson, Ji Yun Jeong, Masaki Wake, Hajime Abe, Norihiko Takeda, Hiroko Endo, Masahiro Inoue, Zhenyu Xuan, Hyuntae Yoo, Min Chen, Jung-Mo Ahn, John D. Minna, Kristi L. Helke, Pankaj K. Singh, David B. Shackelford, Jung-Whan Kim

Journal Articles: Eppley Institute

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, …

Transcutaneous Auricular Vagus Nerve Stimulation (Tavns): Development, Safety, Parametric Optimization, And Neurophysiological Effects, Bashar W. Badran

MUSC Theses and Dissertations

Cervically implanted vagus nerve stimulation (VNS) is a FDA-approved treatment for epilepsy and major depressive disorder (MDD). Additionally, VNS is a reemerging area of interest, showing promise in numerous animal studies with significant translatable applications. The cost, surgical risk, and human translation difficulty makes noninvasive VNS a highly-desired alternative. We have developed a transcutaneous auricular vagus nerve stimulation (taVNS) system that electrically stimulates the auricular branch of the vagus nerve (ABVN). We aimed to answer the following questions in this body of work: 1) whether taVNS is safe and feasible 2) if taVNS stimulates the vagus system similarly to implanted …

An Rnai Screen To Identify Components Of A Polyamine Transport System, Adam J. Foley

Honors Undergraduate Theses

Polyamines, specifically putrescine, spermidine, and spermine, are small cationic molecules found in all organisms. Cells can biosynthetically make these molecules, or alternatively, they can be transported from the extracellular environment. Malignant cells have been shown to require relatively high amounts of polyamines. There is a chemotherapeutic agent, DFMO, used to block the biosynthesis of polyamines. Many malignant cells can circumvent DFMO therapy by activating their transport system. A potential solution is to simultaneously block biosynthesis and transport of polyamines. However, little is known about the polyamine transport system in higher eukaryotes.

This thesis aims to add to the basic biological …

Differential Phenotypes Of Memory Cd4 And Cd8 T Cells In The Spleen And Peripheral Tissues Following Immunostimulatory Therapy., Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka R Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy

Articles, Abstracts, and Reports

BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis. In this study we expand upon our previous work by evaluating CD4 and CD8-T cell phenotype and distribution in peripheral organs which are more representative …

Astrocytes Promote Progression Of Breast Cancer Metastases To The Brain Via A Kiss1-Mediated Autophagy., Natalya Kaverina, Anton V Borovjagin, Zaira Kadagidze, Anatoly Baryshnikov, Maria Baryshnikova, Dmitry Malin, Dhimankrishhna Ghosh, Nameeta Shah, Danny R Welch, Patrik Gabikian, Apollon Karseladze, Charles Cobbs, Ilya V Ulasov

Articles, Abstracts, and Reports

Formation of metastases, also known as cancer dissemination, is an important stage of breast cancer (BrCa) development. KISS1 expression is associated with inhibition of metastases development. Recently we have demonstrated that BrCa metastases to the brain exhibit low levels of KISS1 expression at both mRNA and protein levels. By using multicolor immunofluorescence and coculture techniques here we show that normal adult astrocytes in the brain are capable of promoting metastatic transformation of circulating breast cancer cells localized to the brain through secretion of chemokine CXCL12. The latter was found in this study to downregulate KISS1 expression at the post-transcriptional level …