Cells Commons^™

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

A Perfusion Decellularization Heart Model - An Interesting Tool For Cell-Matrix Interaction Studies, Mihai Meșină, Ion Mîndrilă, Cristian Mesina, Cosmin Vasile Obleagă, Octavian Istrătoaie

Journal of Mind and Medical Sciences

Objective. In this paper, we present a technique for whole human, pig, or rat heart decellularization in order to obtain a tool for cell-matrix interaction studies and to obtain the extracellular matrix scaffold with applications to the study of cardiac connective tissue architecture for tissue bioengineering.

Material and methods. In order to achieve tissue decellularization we present two separate protocols, the first for large animal hearts (e.g., pig hearts) and human hearts, the second for smaller hearts (e.g., rat hearts). We have performed the cardiac decellularization technique on 20 pig hearts, 5 human hearts, and 20 rat hearts.

Results. The …

An Ensemble Of Flexible Conformations Underlies Mechanotransduction By The Cadherin–Catenin Adhesion Complex, Martin Bush, Bashir M. Alhanshali, Shuo Qian, Christopher B. Stanley, William T. Heller, Tsutomu Matsui, Thomas M. Weiss, Iain D. Nicholl, Thomas Walz, David J. E. Callaway, Zimei Bu

Publications and Research

The cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the …

Abnormal Response Of Costal Chondrocytes To Acidosis In Patients With Chest Wall Deformity, A. Asmar, Iurii Semenov, R. Kelly Jr., Michael Stacey

Bioelectrics Publications

Costal cartilage is much understudied compared to the load bearing cartilages. Abnormally grown costal cartilages are associated with the inherited chest wall deformities pectus excavatum and pectus carinatum resulting in sunken or pigeon chest respectively. A lack of understanding of the ultrastructural and molecular biology properties of costal cartilage is a major confounder in predicting causes and outcomes of these disorders. Due to the avascular nature of cartilage, chondrocytes metabolize glycolytically, producing an acidic environment. During physical activity hydrogen ions move within cartilage driven by compressive forces, thus at any one time, chondrocytes experience transient changes in pH. A variety …

Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19

Student Publications & Research

Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients’ progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can …

Melatonin-Micronutrients Osteopenia Treatment Study (Mots): A Translational Study Assessing The Effects Of Melatonin, Strontium Citrate, Vitamin D3 And Vitamin K2 On Bone Density, Bone Turnover Markers And Health-Related Quality Of Life In Postmenopausal Osteopenic Women Following A One-Year Double-Blind Randomized Placebo-Controlled Trial And On Osteoblast-Osteoclast Co-Cultures, Sifat Maria

Electronic Theses and Dissertations

Objective: The purpose of this study was to assess if a novel combination of melatonin and three other natural bone-aiding micronutrients: strontium citrate, vitamins D₃ and K₂ (MSDK) could improve bone health by modulating the activity of osteoblasts and osteoclasts in favor of balanced bone remodeling and by improving the overall health-related quality of life in postmenopausal osteopenic women.

Methods: The Melatonin-micronutrients Osteopenia Treatment Study (MOTS) is a translational research study that used both clinical and in vitro approaches to assess the efficacy of MSDK on bone health in women and to identify potential mechanisms for its effects. …

Comparison Of Varying Tissue Freezing Methods On Murine Colonic Tissue, James Hughes

Biomedical Engineering Undergraduate Honors Theses

Histology often requires a tissue specimen to be embedded so that it may be sectioned, stained, and mounted on a microscope slide for viewing. One common method of tissue embedding for rapid histology is freezing, since freezing allows tissue to be stored without the need for fixing. Frozen tissue is often embedded in a medium such as Optimal Cutting Temperature (OCT) compound so that it can be sectioned using a cryostat. However, factors such as ice-crystal formation during the freezing process can cause damage to the tissue. As such, the protocol used to freeze the tissue can affect the quality …

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka

Internal Medicine Faculty Publications

Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 mutation with age-matched controls …

Generation Of A Patient-Derived Brain Metastasis Breast Cancer Cell Line Via Novel Orthotopic Injection Placement And Serial Mouse Transplantation To Develop Pdx Mouse Model, Amber L. Lacrosse, Denise M. Coley, Paul J. Mintz, Santhi D. Konduri, Richard A. Rovin, Amin B. Kassam

Journal of Patient-Centered Research and Reviews

Background: The incidence of brain metastasis appears to be increasing, potentially due to advanced technology that aids early diagnosis. Patient-derived xenografts (PDX) have high translational value, as these models retain key functional characteristics of the patient tumor. PDX models are useful to understand the molecular basis of tumorigenesis and to identify new treatment targets. However, generating a first-line PDX model is challenging as engraftment failure is high. Serial transplanting tumor tissue via mouse-to-mouse propagation increases engraftment rates and decreases PDX development time. Herein we report methods to generate a PDX cell line from patient-derived tumor tissue that includes the cerebral …

Understanding The Chondrogenic Potential Of Articular Chondrocytes, Krishna Sarma

Theses & Dissertations

Articular cartilage is a smooth, visco-elastic, aneural, avascular tissue made of water, an exquisitely organized framework of proteoglycans, glycosaminoglycans, and collagen fibrils and articular chondrocytes. It’s beautiful organization and composition provide it with the flexibility and strength to cover, protect and lubricate the ends of long bones in a diarthrodial joint. Cartilage homeostasis relies on articular chondrocytes to translate the mechanical forces of daily activity into efficient remodeling of the extracellular matrix. Age, joint injury, or other insulting factors can progressively incapacitate articular chondrocytes, resulting in cartilage lesions that devolve to degenerative joint disease. Therefore, the central idea explored in …

Germ-Line Gene Editing And Congressional Reaction In Context: Learning From Almost 50 Years Of Congressional Reactions To Biomedical Breakthroughs, Russell A. Spivak, J.D., I. Glenn Cohen, J.D., Eli Y. Adashi, M.D., M.S.

Journal of Law and Health

On December 18, 2015, President Obama signed into law a policy rider forestalling the therapeutic modification of the human germ line. The rider, motivated by the science’s potential unethical ends, is only the most recent instance in which the legislature cut short the ongoing national conversation on the acceptability of a developing science. This essay offers historical perspective on what bills were proposed and passed surrounding four other then-developing scientific breakthroughs—Recombinant DNA, in vitro fertilization, Cloning, Stem Cells—to better analyze how Congress is, and should, regulate this exciting and promising science.

In Vitro Investigation Of The Effect Of Exogenous Ubiquitin On Processes Associated With Atherosclerosis, Chase W. Mussard

Undergraduate Honors Theses

Atherosclerosis, characterized by the build-up of cholesterol, immune cells and cellular debris within arterial walls, is accelerated following myocardial infarction by poorly understood mechanisms. Ubiquitin, a small, well-studied intracellular protein involved in protein turnover via the proteasome pathway, has recently been shown to exert extracellular effects on cardiac myocytes, in vitro, and in mice undergoing myocardial remodeling. This study investigates the potential role of extracellular ubiquitin in atherosclerosis by determining its effects on two critical atherosclerotic processes: the migration of vascular smooth muscles cells and the uptake of modified LDL by monocyte/macrophages in foam cell formation. In the presence …

Design, Synthesis, And Evaluation Of Chitosan Conjugated Ggrgdsk Peptides As A Cancer Cell-Targeting Molecular Transporter, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat A. Nagieb, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, ¹H NMR, ¹³C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer …

Analysis Of Ca²⁺ Mobilization Of Nanosecond Pulses In Cells, Iurii Semenov

Bioelectrics Publications

Exposure to nanosecond electric pulses (nsEPs) evokes transient rise of cytosolic free Ca²⁺ concentration ([Ca²⁺]i) in the cells. We quantified the external Ca²⁺ uptake, intracellular Ca²⁺ release and uncover interplay of these processes for CHO-K1 cells upon exposure to single 60 ns pulse in the range of amplitudes from 0 to 30 kV/cm. NsEPs are distinguished by the ability to electroporate intracellular membranes. We studied how duration of nsEPs is related to efficiency of intracellular membranes electroporation comparing ability of single 300-, 60- and 10 ns pulses to recruit Ca²⁺ from endoplasmic reticulum (ER) in respect to the uptake of …

In Vitro Modeling Of The Interaction Between Human Epithelial Cells And Lymphocytes Upon Influenza Infection, Natalia A. Ilyushina, Pete F. Wright

Dartmouth Scholarship

Influenza viruses are a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. Data from murine studies, along with limited human data, suggest that CD8(+) cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural influenza proteins are the main mediators of influenza virus clearance. Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross-strain immunity. However, the mechanisms of cellular immunity against influenza viruses are poorly defined in humans, where the CTL response has been hard to measure and interpret. We developed …

Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar

Theses and Dissertations (ETD)

The transcription factor GATA2 is highly expressed in hematopoietic stem cells (HSCs) and is downregulated during differentiation. Overexpression of GATA2 is frequently observed in acute myeloid leukemia. In previous studies, enforced expression of GATA2 using a MSCV GATA2 retroviral vector blocked differentiation of HSC and progenitors without inducing leukemia. We hypothesized that a lower dose of GATA2 can relieve the HSC block and eventually transform myeloid progenitors into leukemia stem cells. To test this hypothesis we generated a MSCV GATA2-ERT vector in which nuclear concentration of GATA2 can be regulated by Tamoxifen (TAM). The GATA2-ERT protein was confirmed to leak …

Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook

PCOM Biomedical Studies Student Scholarship

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …

Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner

Faculty Publications

Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 …

The Roles Of Primary Cilia In Polycystic Kidney Disease, Samred H. Kathem, Ashraf M. Mohieldin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited genetic disorder that results in progressive renal cyst formation with ultimate loss of renal function and other systemic disorders. These systemic disorders include abnormalities in cardiovascular, portal, pancreatic and gastrointestinal systems. ADPKD is considered to be among the ciliopathy diseases due to the association with abnormal primary cilia function. In order to understand the full course of primary cilia and its association with ADPKD, the structure, functions and role of primary cilia have been meticulously investigated. As a result, the focus on primary cilia has emerged to support the vital roles …

The Expression Of Ecotropic Virus Integration Site-1 In Seven Cancer Cell Lines, Wendy Bindeman '12

Student Publications & Research

The ecotropic virus integration site-1 (EVI1) gene is a transcriptional repressor implicated in the control of cell proliferation and frequently over-expressed in cancerous cells. I investigated the expression of this gene across seven cancer cell lines of varying morphologies. The tested lines included leukemia lines Kasumi-3, U937, MOLT-4, and CEM, breast cancer line MCF7, colorectal cancer line HT-29, and glioblastoma line M059K. Kasumi-3 and HT-29 are documented to have high EVI1 expression. Protein concentrations were normalized with respect to actin using SDS-PAGE and Western blotting. Western blots for EVI1 showed expression of an unidentified protein with a molecular weight of …

How To Write An Article: Preparing A Publishable Manuscript!, Vinod B. Shidham, Martha B. Pitman, Richard M. Demay

Department of Pathology

Most of the scientific work presented as abstracts (platforms and posters) at various conferences have the potential to be published as articles in peer-reviewed journals. This DIY (Do It Yourself) article on how to achieve that goal is an extension of the symposium presented at the 36th European Congress of Cytology, Istanbul, Turkey (presentation available on net at http://alturl.com/q6bfp). The criteria for manuscript authorship should be based on the ICMJE (International Committee of Medical Journal Editors) Uniform Requirements for Manuscripts. The next step is to choose the appropriate journal to submit the manuscript and review the 'Instructions to …

Follicle-Stimulating Hormone Promotes Rank Expression On Human Monocytes, Joseph G. Cannon, Barbara Kraj, Gloria Sloan

School of Medical Diagnostics & Translational Sciences Publications

Elevated serum concentrations of follicle-stimulating hormone (FSH) are associated with diminished bone density in women, beginning years before menopause and the decline in estradiol. We hypothesized that FSH promotes development of myeloid cells toward the bone-resorbing osteoclast phenotype. This was tested by isolating peripheral blood mononuclear cells from nine healthy adults, incubating them in the presence of FSH at three different concentrations spanning the physiological range, and then measuring the expression of receptor activator for NF-κB (RANK, a surface marker for osteoclasts) on CD14+ cells by flow cytometry. In the absence of FSH, 3.3±0.5% of the cells expressed high levels …

Interesting Case Presentation: Placental Site Trophoblastic Tumor, Nicole Qualtieri, Ms, Pa (Ascp), Andrea Gadue, Mhs, Pa (Ascp)

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Case Study:

A 26 year-old female (G3P1) had a D&E in March, 2010 for a blighted ovum. The diagnosis on the uterine contents at an outside institution was placental site trophoblastic tumor. No follow up care was obtained. Four months later (July, 2010), the patient presented to her OB-GYN stating that she had missed a period and had a positive home pregnancy test. An ultrasound examination failed to identify a fetus, and the patient was referred to TJUH.

At Jefferson an MRI showed a poorly defined uterine mass that extended into the myometrium. The slides from the original D&E were …

Chemosensitization Of Cancer Cells By Sirna Using Targeted Nanogel Delivery, Erin B. Dickerson, William H. Blackburn, Michael H. Smith, Laura B. Kapa, L. Andrew Lyon, John F. Mcdonald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods: We report here …

Fibrocystin/Polyductin, Found In The Same Protein Complex With Polycystin-2, Regulates Calcium Responses In Kidney Epithelia, Shizuan Wang, Jingjing Zhang, Surya M. Nauli, Xiaogang Li, Patrick G. Starremans, Ying Luo, Kristina A. Roberts, Jing Zhou

Pharmacy Faculty Articles and Research

Recent evidence suggests that fibrocystin/polyductin (FPC), polycystin-1 (PC1), and polycystin-2 (PC2) are all localized at the plasma membrane and the primary cilium, where PC1 and PC2 contribute to fluid How sensation and may function in the same mechanotransduction pathways. To further define the exact subcellular localization of FPC, the protein product encoded by the PKHD1 gene responsible for autosomal recessive polycystic kidney disease (PKD) in humans, and whether FPC has direct and/or indirect cross talk with PC2, which, in turn, is pivotal for the pathogenesis of autosomal dominant PKD, we performed double immunostaining and coimmunoprecipitation as well as a microfluorimetry …

The Expression And Function Of Ppar And Hif-1 In Human Melanoma, Caroline Mills

Theses, Dissertations and Capstones

The first part of my dissertation focuses on the expression and function of PPARs in human melanoma. I found that the A375 cells were significantly growth inhibited in response to _PGJ2 and troglitazone treatment. HEMn-LP showed significant growth inhibition in response to troglitazone. I found that PPARγ and PPARδ mRNA is present in both the SK-Mel 28 and A375 cells. The relative level of PPARα mRNA expression is highest in SK-Mel 28 cells, ~3 fold higher relative to both the normal human melanocytes and A375 cells. PPARγ protein was ~50% higher in both SK-Mel 28 and A375 cells relative to …