Medical Cell Biology Commons^™

Cutaneous Human Papillomavirus Infection And Development Of Subsequent Squamous Cell Carcinoma Of The Skin, Shalaka S. Hampras, Rhianna A. Reed, Spencer Bezalel, Michael Cameron, Basil Cherpelis, Neil Fenske, Vernon K. Sondak, Jane Messina, Massimo Tommasino, Tarik Gheit, Dana E. Rollison

Pathology and Cell Biology Faculty Publications

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC () enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations …

Role Of Sulfiredoxin Interacting Proteins In Lung Cancer Development, Hedy Chawsheen

Theses and Dissertations--Toxicology and Cancer Biology

Sulfiredoxin (Srx) is an antioxidant enzyme that can be induced by oxidative stress. It promotes oncogenic phenotypes of cell proliferation, colony formation, migration, and metastasis in lung, skin and colon cancers. Srx reduces the overoxidation of 2-cysteine peroxiredoxins in cells, in addition to its role of removing glutathione modification from several proteins. In this study, I explored additional physiological functions of Srx in lung cancer through studying its interacting proteins. Protein disulfide isomerase (PDI) family members, thioredoxin domain containing protein 5 (TXNDC5) and protein disulfide isomerase family A member 6 (PDIA6), were detected to interact with Srx. Therefore, I proposed …

Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell

Theses and Dissertations--Physiology

Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a G_s protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …

Profiling Igg N-Glycans As Potential Biomarker Of Chronological And Biological Ages: A Community-Based Study In A Han Chinese Population, Xinwei Yu, Youix Wang, Jasminka Krištić, Jing Dong, Xi Chu, Siqi Ge, Hao Wang, Honghong Fang, Qing Gao, Di Lui, Zhongya Zhao, Hongli Peng, Maja P. Baković, Lijuan Wu, Manshu Song, Igor Rudan, Harry Campbell, Gordan Lauc, Wei Wang

Research outputs 2014 to 2021

As an important post-translation modifying process, glycosylation significantly affects the structure and function of immunoglobulin G (IgG) molecules and is essential in many steps of the inflammatory cascade. Studies have demonstrated the potential of using glycosylation features of IgG as a component of predictive biomarkers for chronological age in several European populations, whereas no study has been reported in Chinese. Herein, we report various patterns of changes in IgG glycosylation associated with age by analyzing IgG glycosylation in 701 community-based Han Chinese (244 males, 457 females; 23-68 years old). Eleven IgG glycans, including FA2B, A2G1, FA2[6]G1, FA2[3]G1, FA2[6]BG1, FA2[3]BG1, A2G2, …

Human Oocytes And Embryos Viewed By Time-Lapse Videography, And The Development Of An Embryo Deselection Model, Yanhe Liu

Theses: Doctorates and Masters

Despite its wide application today, in vitro fertilization (IVF) treatment continues to have relatively low efficacy, largely due to inaccuracy in selecting the best quality embryo(s) from the cohort for transfer. Novel methodologies for improved selection are being developed, and time-lapse observation of human embryos is gaining increasing popularity due to the more detailed morphokinetic information obtained plus uninterrupted culture conditions. The morphokinetic information enables the use of quantitative timings in developmental milestones of embryos and qualitative measures of abnormal biological events, to assist embryo selection/deselection. This project aimed to identify current limitations in the use of such measures and …

Suppression Of Neutrophil-Mediated Tissue Damage—A Novel Skill Of Mesenchymal Stem Cells, Dongsheng Jiang, Jana Muschhammer, Yu Qi, Andrea Kügler, Juliane C. De Vries, Mona Saffarzadeh, Anca Sindriaru, Seppe V. Beken, Meinhard Wlaschek, Mark A. Kluth, Christoph Ganss, Natasha Y. Frank, Markus H. Frank, Klaus T. Preissner, Karin Scharffetter-Kochanek

Research outputs 2014 to 2021

Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and regeneration. Though of prime interest, their potentially protective role on neutrophil-induced tissue damage, associated with high morbidity and mortality, has not been explored in sufficient detail. Here we report the therapeutic skill of MSCs to suppress unrestrained neutrophil activation and to attenuate severe tissue damage in a murine immune-complex mediated vasculitis model of unbalanced neutrophil activation. MSC-mediated neutrophil suppression was due to intercellular adhesion molecule 1-dependent engulfment of neutrophils by MSCs, decreasing overall neutrophil numbers. Similar to MSCs in their endogenous niche of murine and human vasculitis, therapeutically injected MSCs …

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee

LSU New Orleans Theses and Dissertations

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …

Epacs: Epigenetic Regulators That Affect Cell Survival In Cancer., Catherine Murari

Theses & Dissertations

Cyclic adenosine monophosphate (cAMP) is a second messenger responsive to many external stimuli, playing an important role in cellular gene expression, metabolism, migration, differentiation, hypertrophy, apoptosis and secretion. All of these cellular functions are important in many diseases including cancer. Most of its effects were initially attributed to the classical protein kinase A (PKA) protein, but cellular functions such as proliferation and migration were found to be PKA independent and dependent on the newly discovered exchange proteins directly activated by cAMP (EPACs). EPACs are single polypeptides that primarily function as guanine exchange factors (GEFs) for Rap proteins that allow the …

Progtar: A Database Of Prognostically Inversely Correlated Mirnas And Genes (Pics) In Multiple Cancers, Chirayu Pankaj Goswami

Department of Pathology, Anatomy, and Cell Biology Posters

ABSTRACT

PROGTar is a database of Prognostically Inversely Correlated miRNA-mRNA pairs (PIC’s) in 23 cancer types. Partner miRNA and mRNA in a PIC show inverse correlation of expression and opposite hazards. We analyzed miRNA and mRNA expression data downloaded from The Cancer Genome Atlas (TCGA) in a 3 step approach to identify PICs in different cancer types. In first step we performed correlation analysis between miRNAs and mRNAs for each cancer type. This was followed by performing hazard analysis separately for miRNAs and mRNAs using expression data and survival related clinical variables. In the third step we merged the correlation …

Comprehensive Profiling Of Metaplastic Breast Carcinoma Reveals Frequent Over-Expression Of Pd-L1, Zoran Gatalica, Upasana Joneja, Md, Anatole Ghazalpour, Jeffrey Swensen, Rebecca Feldman, Fred Cai, Sting Chen, Nick Xiao, Sandeep Reddy, Semir Vranić

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background:

Metaplastic breast carcinoma (MBC) is a rare subtype of breast carcinoma less responsive to conventional chemotherapy relative to usual breast carcinomas such as ductal and lobular subtype. In molecular terms, MBC usually clusters with triple negative breast cancers (TNBC), but MBCs portray a worse prognosis in comparison with TNBC. Published studies investigating MBCs for specific biomarkers of therapy response are rare and limited by the methodological approaches.

Methods:

297 samples [MBC (n=75), triple-negative breast cancer of no-special-type (TNBC-NOS, n=106), HER2-positive breast cancers (n=32) and luminal breast cancers (n=84)] were profiled using direct sequencing analysis [Illumina MiSeq Next Generation Sequencing …

The Development Of A Platform For Expression And Purification Of The Mammalian Transmembrane Transporter Abca4, Amaryllis Ortiz

Graduate School of Biomedical Sciences Theses and Dissertations

Purpose- ABCA4 is an ATP Binding Cassette (ABC) protein localized at cone and rod photoreceptor outer segments of the retina. Though mutations in ABCA4 have been found to cause a broad spectrum of disorders, ABCA4's high molecular weight (~210 kDa) and biochemical transmembrane properties have made ABCA4 functional studies unsuccessful. Identifying how ABCA4 functions might have significant clinical impact and open unanticipated avenues for therapeutic interventions. Thus, the objective of this study was to develop a new expression system able to produce the full-length, correctly folded and fully functional ABCA4 protein.

Methods- the ABCA4 gene was amplified from the PCMV6-ABCA4 …

In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor that is highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. The von Hippel-Lindau tumor suppressor gene is frequently mutated in ccRCC resulting in unregulated transcriptional activity of hypoxia-inducible factors (HIF) 1α and 2α. HIF-mediated transcription leads to increased growth factor expression and growth factor receptor (GFR)-mediated signaling. NFκB and STAT3 are phosphorylated in response to GFR activation and modulate gene expression, which promotes cell growth and invasion. Activated NFκB and STAT3 expression is …

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Journal of Patient-Centered Research and Reviews

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs.

Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of …

T(3;8)(Q26;Q24) With Myc Rearrangement In Acute Myeloid Leukemia: A Case Report, Vandi Ly, Md, Renu Bajaj, Phd, Jerald Z. Gong, Md, Zi-Xuan Wang, Phd, Stephen C Peiper, Md, Guldeep Uppal, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rearrangements of 3q26 have been described in 5% of de novo or therapy related acute myeloid leukemia, myelodysplastic syndrome (MDS), and blast phase of chronic myeloid leukemia. The most common translocations involving 3q26 are t(3;12)(q26;p13), t(3;21)(q26;q22), t(3;3)(q21;q26), t(2;3)(p15∼23;q26∼27) and rarely t(3;7)(q26;q21). However, t(3;8)(q26;q24) with or without monosomy 7 is a rare phenomenon and has been reported in only 10 patients so far. Hereby, we describe a 58 year old patient who was diagnosed with refractory anemia with multilineage dysplasia. Cytogenetic studies revealed monosomy 7. He was then lost to follow-up. A year later he was found to have worsening cytopenias …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Intracellular Information Processing Through Encoding And Decoding Of Dynamic Signaling Features., Hirenkumar K Makadia, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cell signaling dynamics and transcriptional regulatory activities are variable within specific cell types responding to an identical stimulus. In addition to studying the network interactions, there is much interest in utilizing single cell scale data to elucidate the non-random aspects of the variability involved in cellular decision making. Previous studies have considered the information transfer between the signaling and transcriptional domains based on an instantaneous relationship between the molecular activities. These studies predict a limited binary on/off encoding mechanism which underestimates the complexity of biological information processing, and hence the utility of single cell resolution data. Here we pursue a …

Gsk-3Β Regulates Tumor Growth And Angiogenesis In Human Glioma Cells., Peng Zhao, Qi Li, Zhumei Shi, Charlie Li, Lin Wang, Xue Liu, Chengfei Jiang, Xu Qian, Yongping You, Ning Liu, Ling-Zhi Liu, Lianshu Ding, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Glioma accounts for the majority of primary malignant brain tumors in adults.

METHODS: Glioma specimens and normal brain tissues were analyzed for the expression levels of GSK-3β and p-GSK-3β (Ser9) by tissue microarray analysis (TMA) and Western blotting. Glioma cells over-expressing GSK-3β were used to analyze biological functions both in vitro and in vivo.

RESULTS: The levels of p-GSK-3β (Ser9), but not total GSK-3β, are significantly up-regulated in glioma tissues compared to normal tissues, and are significantly correlated with the glioma grades. Ectopic expression of GSK-3β decreased the phosphorylation levels of mTOR and p70S6K1; and inhibited β-catenin, HIF-1α and …

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer …

Mir-497 Decreases Cisplatin Resistance In Ovarian Cancer Cells By Targeting Mtor/P70s6k1., Shaohua Xu, Guang-Bo Fu, Zhen Tao, Jun Ouyang, Fanfei Kong, Bing-Hua Jiang, Xiaoping Wan, Ke Chen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The mechanism of cisplatin resistance in ovarian cancer is not clearly understood. In the present investigation, we found that the expression levels of miR-497 were reduced in chemotherapy-resistant ovarian cancer cells and tumor tissues due to hypermethylation of miR-497 promoter. Low miR-497 expression levels were associated with chemo-resistant phonotype of ovarian cancer. By analyzing the expression levels of miR-497, mTOR and p70S6K1 in a clinical gene-expression array dataset, we found that mTOR and p70S6K1, two proteins correlated to chemotherapy-resistance in multiple types of human cancers, were inversely correlated with miR-497 levels in ovarian cancer tissues. By using an orthotopic ovarian …

Eisosomes Provide Membrane Reservoirs For Rapid Expansion Of The Yeast Plasma Membrane, Ruth Kabeche, Louisa Howard, James B. Moseley

Dartmouth Scholarship

Cell surface area rapidly increases during mechanical and hypoosmotic stresses. Such expansion of the plasma membrane requires 'membrane reservoirs' that provide surface area and buffer membrane tension, but the sources of this membrane remain poorly understood. In principle, the flattening of invaginations and buds within the plasma membrane could provide this additional surface area, as recently shown for caveolae in animal cells. Here, we used microfluidics to study the rapid expansion of the yeast plasma membrane in protoplasts, which lack the rigid cell wall. To survive hypoosmotic stress, yeast cell protoplasts required eisosomes, protein-based structures that generate long invaginations at …