Biology Commons^™

Baculoviral Vector Loaded Mesenchymal Stem Cells As Efficient Gene Therapy Tools For Cancer Treatment, Sedef Hande Aktaş, Hakan Akbulut, Ayşe Eser Elçi̇n, Mahmut Parmaksiz, Arzu Keski̇n Aktan, Arzu Çöleri̇ Ci̇han, Yaşar Murat Elçi̇n, Fi̇kri̇ İçli̇

Turkish Journal of Biology

Insufficient targeting of the therapeutic genes to tumor cells is one of the major reasons for failure in cancer gene therapy. Mesenchymal stem cells (MSCs) seem to be a good candidate as a carrier for gene therapy because of its selective tumor tissue-homing properties. In the current study, we constructed baculoviral vectors (BVs) carrying cytosine deaminase (CD) (BV-CD) or green fluorescence protein (GFP) genes (BV-GFP) and tested the transduction efficiency of the vectors in tumor and mesenchymal stem cells. We also tested the in vivo efficacy of the BV-CD vector in a colon cancer model. Our results showed that the …

Imaging Anti-Proliferative Compounds With Flt-Pet, Christopher Mchugh

Wayne State University Dissertations

Imaging is critical in the detection and management of malignancies, and positron emission tomography (PET) is an imaging approach that provides information regarding cancer physiology through the tracking of molecular pathways and receptors. 3’-fluoro-3’-deoxythymidine (FLT) is a PET tracer designed to image cellular proliferation, which is a hallmark of cancer. FLT has been used to study the response of cancer to a variety of treatments such as chemotherapy, targeted agents, and radiation.

Here we explored FLT retention as a biomarker to monitor the anti-proliferative effect of the synthetic glucocorticoid (GC) dexamethasone (Dex) on non-small cell lung cancer (NSCLC). The basis …

Comparative Proteomic Analysis Of Extracellular Vesicles From Prostate Cancer-Derived Cell Lines, Gloria Polanco

Open Access Theses & Dissertations

Prostate cancer (PCa) is the leading non-cutaneous malignancy and the second deadliest among American men. PCa mortality rates among African American men are much higher than any other ethnic group, and the same is true for men of African ancestry world-wide. There is also a lack of reliable diagnostic markers and effective treatment options. Extracellular vesicles (EVs) have been observed to play an important role in cancer processes such as promotion of tumor growth and metastasis. They are also a promising source of diagnostic markers. This study addresses these problems by studying the proteome of EVs derived from PCa cells …

The Role Of Integrin Alpha 6 On Tumor Metastasis, Shauntell N. Luke Ms.

Honors College Theses

Cancer research is a large topic in science, because over 14 million people are diagnosed worldwide, and of those, 8 million will die annually. Traditional therapies are the mainstays of treatment strategies, but a cure less invasive or with less side effects have not yet been identified. In order to develop a better cure, we need to understand the tumor and molecules present in its tissues. Integrins, cell surface proteins that aid in cell communication, have been found in the tumor tissues of several types of cancers, including prostate, lung and bone. Integrin alpha-6 (ITGA6), in particular, has been found …

Evaluating Human Cell Survival And Dna Damage After Exposure To Various Amounts Of Chlorine Dioxide And Exploring Its Use As A Potential Cancer Chemotherapy Agent, Niuska Mariana Alvarez Fuenmayor

SURF - Summer Undergraduate Research Fellowship Projects

Chlorine Dioxide (ClO₂) is a synthetic, green-yellowish gas with a chlorine-like, irritating odor that is used for the treatment of drinking water and food preservation. The aim of this study was to evaluate the genotoxic potential of the chlorine dioxide in mammalian cells and to determine what dose of ClO₂ is tolerable by normal cells and cells with aberrant DNA repair genes. Human and mouse embryonic cells were treated with various ClO₂ dilutions ranging from 2.5 mM to 25 mM. The cell viability and metabolic activity was determined via MTT, a colorimetric assay. Human HEK293 cells …

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 …

Treatment Strategies That Enhance The Efficacy And Selectivity Of Mitochondria-Targeted Anticancer Agents, Josephine S. Modica-Napolitano, Volkmar Weissig

Biology Faculty Publications

Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including …

Inferring Pathway Dysregulation In Cancers From Multiple Types Of Omic Data, Shelley M. Macneil, William E. Johnson, Dean Y. Li, Stephen R. Piccolo, Andrea H. Bild

Faculty Publications

Although in some cases individual genomic aberrations may drive disease development in isolation, a complex interplay among multiple aberrations is common. Accordingly, we developed Gene Set Omic Analysis (GSOA), a bioinformatics tool that can evaluate multiple types and combinations of omic data at the pathway level. GSOA uses machine learning to identify dysregulated pathways and improves upon other methods because of its ability to decipher complex, multigene patterns. We compare GSOA to alternative methods and demonstrate its ability to identify pathways known to play a role in various cancer phenotypes. Software implementing the GSOA method is freely available from https://bitbucket.org/srp33/gsoa …

Environmental Stimuli And Intragenerational Epigenetics, Nicholas J. Napier

Student Scholarship

Epigenetics is the study of any change in gene expression that is not mediated by DNA sequence. The effects of environmental stimuli on epigenetic changes have been studied extensively in recent years. Multiple reviews have provided comprehensive summations of the effects of environmental stimuli on transgenerational epigenetic changes, but few reviews have focused upon environment-induced intragenerational epigenetic changes. This review will summarize current knowledge of the intragenerational epigenetic changes that are induced by two groups of well-studied environmental stimuli: nutritional deficiencies and carcinogens. This survey of intragenerational epigenetic changes will focus upon the mechanisms behind them, the disorders associated with …

Activating The Msh2/Msh6 Apoptotic Pathway In Cancer Cells Using Non-Reserpine Compounds, Jacob M. Mauceri

Honors College Theses

DNA mismatch repair (MMR) is a system that is highly conserved in both prokaryotes and eukaryotes. The heterodimeric protein MutSα and a suite of associated proteins are essential in the recognition and repair of DNA afflicted with mispaired bases and short insertion/deletion loops, but are also implicated in funneling damaged cells towards apoptosis via a key conformational change in a subunit of the MutSα complex. This conformation can be bound specifically by the small molecule reserpine. Molecular dynamics modeling and virtual screening were used to identify additional small molecule novel ligands with the predicted ability to selectively bind this “death” …

Fluorescent Cell Imaging Studies Of Antitumor Natural Macrocycle Ipomoeassin F, Margaret Grace Oliver

Biological Sciences Undergraduate Honors Theses

Ipomoeassin F is one member of a family of macromolecules isolated from the leaves of the morning glory flower, ipomoea squamosa, which has been used as a homeopathic cancer remedy for centuries (Zhu, Huang, Zheng, Zhu, & Yang, 2013). It has been proven to be highly cytotoxic to many cancer cell lines, but nothing is yet known of its mode of action in the cell (Cao, et al., 2007). To begin progress towards understanding the mode of action of ipomeoassin F, this study aimed to perform fluorescence imaging studies for the ultimate purpose of determining its cellular localization in MDA-MB-231 …

Killer Cell Activation By A Novel Multifunctional Protein: An Immuno/Gene Therapy For Cancer, Ashlee Tietje

All Dissertations

One of the characteristics of advanced tumors is the evasion of the immune system. There are multiple methods that tumor cells employ to achieve this including reducing the expression of activating ligands on the cell surface and a shift in the tumor microenvironment toward pro-tumor cytokines. The purpose of this research is to develop a novel bifunctional fusion protein that will target these two deficiencies in the tumor microenvironment and activate killer cells that are already present. The proposed protein combines the extracellular domain of a ligand for the killer cell activating receptor NKG2D and Interleukin-12 (IL-12). It is hypothesized …

Single-Walled Carbon Nanotube And Graphene: Nano-Delivery Of Gambogic Acid Increases Its Cytotoxicty In Various Cancer Cells, Lamya A. M Saeed

Theses and Dissertations

Nanomedicine is a new branch of medicine that has been developed due to the critical need to treat challenging diseases, especially cancer since it remains a significant cause of morbidity and mortality worldwide and the second most common cause of death after heart disease in the USA. One of the most important health care applications of nanomedicine concerns the development of drug delivery systems. Graphene (Gn), an atom-thick carbon monolayer of sp2- bonded carbon atoms arranged in a two dimensional (2D) honeycomb crystal lattice, and single-walled carbon nanotubes (SWCNTs) (1D, tubular) are among the most promising nanomaterials with the capability …

Oncostatin M Binds To Extracellular Matrix In A Bioactive Conformation: Implications For Inflammation And Metastasis, Randall E. Ryan, Bryan Martin, Liliana Mellor, Reed B. Jacob, Ken Tawara, Owen M. Mcdougal, Julia Thom Oxford, Cheryl L. Jorcyk

Biology Faculty Publications and Presentations

Oncostatin M (OSM) is an interleukin-6-like inflammatory cytokine reported to play a role in a number of pathological processes including cancer. Full-length OSM is expressed as a 26 kDa protein that can be proteolytically processed into 24 kDa and 22 kDa forms via removal of C-terminal peptides. In this study, we examined both the ability of OSM to bind to the extracellular matrix (ECM) and the activity of immobilized OSM on human breast carcinoma cells. OSM was observed to bind to ECM proteins collagen types I and XI, laminin, and fibronectin in a pH-dependent fashion, suggesting a role for electrostatic …

Changes In Gene Expression In Sirt3 Knockout Liver Cells, Randa Tao, Jamie Leclerc, Kübra Yildiz, Seong-Hoon Park, Barbara Jung, David Gius, Özkan Özden

Turkish Journal of Biology

The sirtuin (SIRT) gene family is reported to regulate critical intracellular processes from aging to cellular metabolism and repair. SIRT3 knockout (SIRT3-/-) mice develop receptor positive mammary tumors starting at 13 months and SIRT3 expression is decreased in human breast cancer samples as well as several other diseases. It is established that carcinogenesis results from the accumulation of multiple aberrant genetic events including the activation of oncogenes and inactivation of tumor-suppressor genes. To determine the potential early genomic events that may play a role in the tumor-permissive phenotype observed in SIRT3-/- cells, we compared gene expression profile in SIRT3-/- and …

Rna Aptamers For Molecular Chaperones Hsp27 And Hsp90, Sathishkumar Kumar Munusamy

Legacy Theses & Dissertations (2009 - 2024)

Hsp90 and Hsp27 are members of the heat shock protein family of chaperones that perform multiple roles in cellular maintenance through protein folding and inhibition of apoptosis. They are abundantly expressed in cells and are over-expressed during conditions of stress. Hsp90 requires ATP for its chaperone function while Hsp27 self-associates into higher order oligomers enclosing its substrate. Their ability to interact with other proteins or with themselves lies at the heart of their mechanisms. The specific consequences of each of their interactions on global cellular health have not yet been fully discovered. The sheer diversity of proteins that interact with …

Inhibitory Effects Of Salicylic Acid On A549 Human Lung Adenocarcinoma Cell Viability, Djanan Vejselova, Hati̇ce Mehtap Kutlu

Turkish Journal of Biology

Antiinflammatory drugs, such as salicylic acid and its metabolite acetylsalicylic acid, have been singled out as apoptosis-inducing agents with antitumoral activity. In addition, they reduce the risk of some cancers via an unclear mechanism. In this study, we have investigated the apoptotic, cytotoxic, and growth-inhibiting effects of salicylic acid on A549, the human lung adenocarcinoma, alveolar epithelial cells. Cytotoxicity was tested using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) colorimetric assay. We observed the ultrastructural and morphological changes in A549 cells by using transmission electron microscopy (TEM) and confocal microscopy. Cell viability was decreased by the optimal concentration (IC50) of 6.0 mM salicylic …

S. Cerevisiae $\Beta$-Glucan Reduced Viability Of Mouse Hepatoma Cells In Vitro, Artur Javmen, Ausra Nemeikaite-Ceniene, Saulius Grigiskis, Irena Jonauskiene, Mark Rudenkov, Darius Kacianauskas, Mykolas Mauricas

Turkish Journal of Biology

$\beta$-Glucan is a natural polymer, which is widely studied due to its multiple immunomodulatory properties. In addition, recent findings indicate potent antitumor properties of $\beta$-glucan. Saccharomyces cerevisiae, baker's yeast, is one of the commonly used sources of $\beta$-1,3-glucan. The aim of this work was to investigate S. cerevisiae $\beta$-glucan immunomodulatory activity against cancer cells.In our experiments, BALB/c mice were fed with insoluble whole $\beta$-glucan particles, and then their blood was collected for experiments. MH-22a hepatoma cells were treated with the blood of mice fed with $\beta$-glucan, and tumor cell viability was investigated after the treatment.The obtained results demonstrated that leukocytes …

Human Cytomegalovirus Interleukin-10 Promotes Proliferation And Migration Of Mcf-7 Breast Cancer Cells, Robin K. Bishop, Cendy A. Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Breast cancer is the most common malignancy affecting women worldwide. While a small fraction of breast cancers have a hereditary component, environmental and behavioral factors also impact the development of cancer. Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that is widespread in the general population and has been linked to several forms of cancer. While HCMV DNA has been found in some breast cancer tissue specimens, we wanted to investigate whether a secreted viral cytokine might have an effect on cancerous or even pre-cancerous cells. HCMV encodes an ortholog of the human cellular cytokine interleukin-10 (IL-10). The …

Epigenetic Regulation Of Nuclear Hormone Receptor Dax-1, Michael B. Heskett

Master's Theses

DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of …

Discovery And Elucidation Of The Fgfr3-Tacc3 Recurrent Fusion In Glioblastoma, Brittany C. Parker Kerrigan

Dissertations and Theses (Open Access)

Fusion genes occur due to chromosomal instability where two previously separate genes rearrange and fuse together, forming a hybrid gene. The first fusions were reported in leukemias; however, with the advent of more powerful sequencing technologies, fusions have recently been reported in several solid tumors. Using next-generation deep sequencing approaches, we discovered a fusion gene connecting the fibroblast growth factor receptor 3 (FGFR3) gene to the transforming coiled-coil containing protein 3 (TACC3) gene in glioblastoma multiforme. The fusion occurred in 8.3% of patient samples, but not in low grade or normal samples. FGFR3-TACC3 produced an in-frame …

New Frontiers For The Nfil3 Bzip Transcription Factor In Cancer, Metabolism And Beyond, Megan Keniry, Robert K. Dearth, Michael W. Persans, Ramon Parsons

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

The bZIP transcription factor NFIL3 (Nuclear factor Interleukin 3 regulated, also known as E4 binding protein 4, E4BP4) regulates diverse biological processes from circadian rhythm to cellular viability. Recently, a host of novel roles have been identified for NFIL3 in immunological signal transduction, cancer, aging and metabolism. Elucidating the signaling pathways that are impacted by NFIL3 and the regulatory mechanisms that it targets, inhibits or activates will be critical for developing a clearer picture of its physiological roles in disease and normal processes. This review will discuss the recent advances and emerging issues regarding NFIL3-mediated transcriptional regulation of CEBPb and …

Genomic Classification Of The Ras Network Identifies A Personalized Treatment Strategy For Lung Cancer, Nader N. El-Chaar, Stephen R. Piccolo, Kenneth M. Boucher, Adam L. Cohen, Jeffrey T. Chang, Philip J. Moos, Andrea H. Bild

Faculty Publications

Better approaches are needed to evaluate a single patient's drug response at the genomic level. Targeted therapy for signaling pathways in cancer has met limited success in part due to the exceedingly interwoven nature of the pathways. In particular, the highly complex RAS network has been challenging to target. Effectively targeting the pathway requires development of techniques that measure global network activity to account for pathway complexity. For this purpose, we used a gene-expression-based biomarker for RAS network activity in non-small cell lung cancer (NSCLC) cells, and screened for drugs whose efficacy was significantly highly correlated to RAS network activity. …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Identification Of Microrna Biomarkers In Her2-Positive Breast Cancer, Hossam Tashkandi

Theses and Dissertations

Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 30% of breast cancer patients with poor prognosis. In addition, microRNAs are small non-coding RNA that have been linked to many cancers. Here we investigate which miRNAs are differentially regulated by HER2 overexpression. Using quantitative reverse-transcription prolymerase chain reaction (QRT-PCR) and matching it with the clinical data acquired from Dvinge, we find five candidate miRNAs. When comparing the miRNAs’ effect on patient survival, only three miRNAs stand as good predictors of patient survival outcome. These miRNAs are miR-146a-5p, miR-181d, and miR-195-5p. When miR-146a-5p is up-regulated, which is the case …

Gain-Of-Function Mouse Models To Investigate Biological Roles Of Prmt6, Alessandra Di Lorenzo

Dissertations and Theses (Open Access)

Gain-of-function Mouse Models to Investigate Biological Roles of PRMT6

Alessandra Di Lorenzo, Ph.D. Candidate

Mentor: Dr. Mark T. Bedford

Protein Arginine Methyltransferase 6 (PRMT6) is the histone tail writer that methylates the H3R2 (arginine 2 of histone H3) residue, which counteracts the activating H3K4me3 mark. PRMT6 has been shown to behave both as transcriptional co-repressor (i.e. trhrombospondin-1, p21, p53), and co-activator (nuclear receptors). The co-repressor function of PRMT6 is likely the result of H3K4me3 antagonism, while the mechanism by which PRMT6 exerts its co-activator function has yet to be elucidated. PRMT6 is over-expressed in several types of tumors including small …

Lipid Dependence In Ras-Driven Tumors, Darin Salloum

Dissertations, Theses, and Capstone Projects

Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network. …

Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena

Dissertations, Theses, and Capstone Projects

Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from …

Aging And Cancer: Molecular Facts And Awareness For Turkey, Gülgün Gündüz, Kayahan Fişkin

Turkish Journal of Biology

Two important subjects concerning extension of the human life-span are biological aging processes and their relationship to diseases, and especially to the formation of cancer. It is clear that an aging population poses some challenges for developing countries. We set out to show the demographic structure of Turkey and to discuss the feasibility of decreasing the prevalence of cancer. We overviewed the literature on the relationship between biological aging and cancer formation, the environmental causes of cancer, and age-related characteristics of cancer in the elderly. In addition, some statistical data on the changing demography of Turkey were reviewed. It is …

Autophagy And Cancer, Hacer Ezgi̇ Karakaş, Devri̇m Gözüaçik

Turkish Journal of Biology

Autophagy is an evolutionary conserved intracellular degradation and stress response mechanism that is mainly responsible for the breakdown and recycling of cytoplasmic materials, including long-lived proteins, protein aggregates, and damaged organelles. In this way, autophagy provides the cell with building blocks and allows the maintenance of homeostasis under stress conditions such as growth factor deficiency, nutrient deprivation, hypoxia, and toxins. Consequently, abnormalities of autophagy contribute to a number of pathologies ranging from neurodegenerative diseases to cancer. Autophagy was reported to have a dual role in cancer. Depending on cancer stage, autophagy seems to act as tumor suppressor or as a …