Life Sciences Commons^™

Augmentation Of Ras-Induced Cell Transformation : A New Role For Mir-200a In Malignancy., Lindsey Erin Becker

Electronic Theses and Dissertations

Cancer is a multistep disease that begins with malignant cell transformation and frequently culminates in metastasis and death. MicroRNAs (miRNAs) are small regulatory 21-25-nt RNA molecules and are frequently deregulated in cancer. The majority of miRNAs are estimated to be co-expressed with neighboring miRNAs as clusters. Many miRNA clusters coordinately regulate multiple members of cellular signaling pathways or protein interaction networks. miR-200a is a member of the miR-200 family, which are known to be strong inhibitors of the epithelial to mesenchymal transition. As such, the tumor suppressive role of miR-200a in oncogenesis has been well studied; however, recent studies have …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

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 …

Recent Advances In The Molecular Characterization Of Circulating Tumor Cells, Lori E. Lowes, Alison L. Allan

Anatomy and Cell Biology Publications

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs …

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 …

Bax Over-Expression Coupled With Bcl-2 Suppression Under The Control Of The Cancer-Specific Thymidine Kinase Promoter, Brian H. Ladle, Dr. Kim L. O'Neill

Journal of Undergraduate Research

As researchers continue to discover the molecular origins of cancer, gene therapy targeting cellular processes gone awry shows great promise as the future in cancer treatment. Extensive research is being done to develop more effective techniques targeting different cellular events. One pathway receiving increased attention is apoptosis (the default mechanisms activated intracellularly by extensive damage, causing the cell to kill itself). Often cancer will develop when genetic mutations or other cellular events render the cells unable to die by apoptosis. My research investigates a novel gene therapy that will restore the cancer cell’s ability to die by apoptosis, while limiting …

Investigation Into The Anti-Angiogenic Activities Of Convolvulus Arvensis Extract, Jeremy F. Mcbride, Rachelle R. Olsen, Dr. Kim L. O'Neill

Journal of Undergraduate Research

Angiogenesis, the development and differentiation of new blood vessels from the pre-existing vasculature, is a fundamental physiological process involved in growth, development, and wound healing. Loss of control over the biological molecules which regulate this process can lead to pathologic angiogenesis, or neoangiogenesis, a process associated with such diseases as retinopathies, psoriasis, arthritis, and most importantly, cancer.

Selenium Regulation Of Nf-Κb Binding In Cancerous Human Prostate Epithelial Cells, Wayne K. Nelson, Dr. Merrill Christensen

Journal of Undergraduate Research

According to the National Cancer Institute, prostate cancer is the most frequently diagnosed nonskin cancer in men. In 1997 alone, it is estimated that 209,900 men were diagnosed as having the disease. Prostate cancer is also the second leading cause of cancer related death in the United States and, in 1997, claimed the lives of an estimated 41,800 people (1).

Selenium Alters Nf- B-Regulated Gene Expression In Human Prostate Cancer Cells, Aimee L. Taylor, Dr. Merrill J. Christensen

Journal of Undergraduate Research

The American Cancer Society estimates that prostate cancer will account for 30% of new cancers in men, totaling over 189,000 new cases, with 30,200 deaths in 2002 (1). Because of its high prevalence and long latency time prostate cancer is an ideal candidate for chemoprevention (2). Recent research suggests an inverse relationship between high dietary selenium (Se) intake or status and risk for prostate cancer. However, the mechanisms for Se’s protective effects against prostate cancer have not yet been determined. This project focused sharply on a single mechanism by which Se may alter gene expression and affect risk for prostate …

Analysis Of Microvesicles To Determine Susceptibility To The Enzyme Phospholipase A2, Brent Brimhall, Joseph Callister

Journal of Undergraduate Research

Microvesicles are small membrane-bound spheres released from certain cells undergoing the decay process. Little is known today about their properties and function at the cellular level. It is hypothesized that microvesicles play a role in cancer metastasis through the action of metalloproteinases enclosed within these spheres. Metalloproteinases are enzymes that act to break up the extracellular matrix of cells. This matrix serves as a type of glue that holds groups of cells together. Without this extracellular matrix in place cells are allowed to break free and migrate to other places of the body. In the case of cancerous cells this …

Ethnobotany Of Camptotheca Decaisne: New Discoveries Of Old Medicinal Uses, Shiyou Li, Wanli Zhang

NCPC Publications and Patents

Camptotheca trees had been used as fuelwood and an ornamental species in its native China. There were no reports on medicinal uses of Camptotheca in China and thus it was believed the trees had no medicinal before its antitumor activity discovered in 1957. We conducted national surveys of Camptotheca in China from 1994 to 1999. We found that Camptotheca acuminate is commonly known as happytree (xi shu) because the trees can be used as folk medicine to cure stubborn phlegm as well as other diseases, thus making patients “happy”. There are three local names to refer the uses of C. …

Lost In Translation: Animal Models And Clinical Trials In Cancer Treatment, Isabella W.Y. Mak, Nathan Evaniew, Michelle Ghert

Human Clinical Trials Collection

Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal models can serve as an important source of in vivo information, but alternative translational approaches have emerged that may eventually replace the link between in vitro studies and …

Absence Of Manganese Superoxide Dismutase Delays P53-Induced Tumor Formation., Adam J. Case, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation, as well as MnSOD's potent antioxidant enzymatic activity, MnSOD has been suggested as a tumor suppressor for over 30 years. However, testing this postulate has proven difficult due to the early post-natal lethality of the MnSOD constitutive knock-out mouse. We have previously used a conditional tissue-specific MnSOD knock-out mouse to study the effects of MnSOD loss on the development of various cell types, but long-term cancer development studies have not been performed. We hypothesized the complete loss of …

The Effect Of Lactic Acid On Mast Cell Function, Andrew J. Spence

Theses and Dissertations

This study shows for the first time the effect that L-(+)-lactic acid has on mast cell activation. Lactic acid is a byproduct of anaerobic glycolysis and is associated with inflammatory environments such as wounds, tumors and, asthma. In this study, pre-treatment with lactic acid altered cytokine production by bone marrow-derived mast cells (BMMC). Specifically, lactic acid enhanced cytokine secretion following IgE cross-linking, but decreased IL-33 mediated cytokine production. These effects were altered by genetic background, since C57BL/6 mast cells demonstrated the aforementioned result, but lactic acid had no effect on IgE-mediated cytokine production in 129/SvJ mast cells. The affected cytokines …

Synthesis And Characterization Of Pt(Ii) Complexes For Anticancer Therapy, Mihaela A. Ciulei, Pradip K. Bhowmik

McNair Poster Presentations

The first platinum-based drug was discovered and approved by Food and Drug Administration (FDA) in 1978 is cis-diamminedichloroplatinum (II) (cisplatin or CDDP). Cisplatin is used for about 50% of the chemotherapeutic cancer treatments along with its two analogues carboplatin and oxaliplatin. So far these drugs have been used extensively as treatment for ovarian, bladder, head and neck, and lung cancers. Although cisplatin has been used so often, it has toxic side effects and drug resistance.1-4 Due to these limitations other compounds have been synthesized. Specifically, our lab in conjunction with a biochemistry lab has recently published one article …

Effect Of Folate Deficiency On Mtor Signaling Network On The Liver Of Wild Type Mice, Essra Moussawi

Wayne State University Theses

Through various studies of dietary nutrients on the affects of the physiological and molecular pathways are a key study in understanding the interaction between dietary nutrients and the human genome that may severely impact the development of various cancers. A primary approach is observing the dietary nutrients, that we consume and how it plays a role in the cellular pathway of our bodies through experimental methods. Folate deficiency (FD) has shown, through studies, to play a role anti-cancer progression. Our goal was to observe the autophagy related proteins in the mTOR signaling pathway as it was suggested that mTOR may …

Effect Of Long Term Rapamycin Treatment On Mtor Signalling Network In Colon And Liver Of C57bl/6 Mice, John Sorge

Wayne State University Theses

Many studies have investigated the effects of rapamycin on aging and cancer. However, the effects of long-term rapamycin supplementation on a cancer model have not been performed. This is the first study that investigates the effects of long-term supplementation of rapamycin in a cancer model. ACF analysis of colon tissues in mice showed no significant difference between controls and those supplemented with rapamycin. Factors such as energy balance, cellular environment, PI3K/Akt/mTOR pathway, and more have been assessed in this study. The duration of rapamycin supplementation seems to play an important role in the protection against cancer. Ultimately, this study suggests …

I Wish I Had Known This!: Impact Of Age On Life Choices And Testing Satisfaction For Brca1/2 Mutation Carriers Who Underwent Genetic Testing By Age 25, Sarah Elaine King

Theses and Dissertations

Objective: To examine if BRCA1/2 mutation carriers who received their positive genetic test result by age 25 were satisfied with their decision to undergo genetic testing and with the choices made regarding family planning, surveillance, and surgery. Methods: 72 participants recruited via social media completed a survey hosted by SurveyMonkey.com. Sixty-three met study criteria and were asked 40 quantitative and qualitative questions designed to assess family planning, surveillance, and surgery needs of young BRCA carriers, which included a six question Satisfaction with Decision Scale. Results: Regardless of age, participants were very satisfied with the decision to undergo genetic testing. Recommendations …

Molecular Studies On The Anti-Tumor Effects Of Metal-Based Complexes: Involvement Of The Ubiquitin-Proteasome And Apoptotic Pathways, Sara M. Schmitt

Wayne State University Dissertations

The ubiquitin-proteasome pathway is crucial to normal cellular function, and as such, has been extensively investigated as a potential target for cancer therapeutics. Many compounds have been tested for their proteasome inhibitory ability, including various small peptide aldehydes, and, following the success of cisplatin, several metal-containing complexes. The efficacy of these compounds in preclinical studies ultimately resulted in the development and approval of the first-in-class proteasome inhibitor bortezomib, the use of which, unfortunately, has been hindered by toxicity and resistance. These limitations have led to a massive push toward designing and developing new, less toxic proteasome inhibitors for clinical use. …

The Role Of Af9 And Af9-Mediated Protein Interactions In Hematopoiesis And Leukemogenesis, Alyson Anne Lokken

Dissertations

The AF9 protein is one of the most common chromosomal translocation partners of the MLL gene in MLL leukemia. Wild-type AF9 is a member of the pTEFb transcription elongation complex, and interacts with gene regulatory proteins such as AF4/AF5q31, DOT1L, Pc3/CBX8 and BCoR. These interactions are retained in the oncogenic MLL-AF9 fusion protein, and may be required for leukemic transformation.

Using bone marrow progenitor cells isolated from conditional Af9 knockout mice, we examined in vitro differentiation of hematopoietic progenitor cells to the erythroid, myeloid and megakaryocytic lineages in the presence or absence of Af9. Based on previously published studies, we …

Triumph Or Tragedy: Progress In Cancer, Ayşe Şebnem Erenler, Hi̇kmet Geçki̇l

Turkish Journal of Biology

Cancer is probably the number one research area among all human endeavors, receiving the largest portion of science funding in most countries. This is because cancer remains one of the oldest conundrums among all human maladies. Although we now have a greater understanding of the biological and molecular basis of cancer, its diagnosis and therapy still pose great challenges. In this review, our aim is not to establish a comprehensive understanding of cancer, which is essentially impossible, but to outline, in a more provocative way, why cancer research in the pursuit of a cure did not live up to its …

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 …

It Takes 2 Antioxidants To Tango: The Interaction Between Manganese Superoxide Dismutase And Glutathione Peroxidase-1, Dede N. Ekoue, Alan M. Diamond

Turkish Journal of Biology

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H_{2}O_{2}, and the subsequent conversion of H_{2}O_{2} into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate …

Failure Of Immunological Cells To Eradicate Tumor And Cancer Cells: An Overview, Rohit Sharma, Daizee Talukdar, Parth Malik, Tapan K. Mukherjee

Turkish Journal of Biology

Inflammation can be broadly understood as a successive immune response of an organism's immune system towards nonnative or foreign antigens. This is a protective mechanism of the immune system, mediated by diverse immunological cells, to ensure homeostasis of an individual. Once activated, these immunological cells release a number of cytokines, chemokines, reactive oxygen species, reactive nitrogen species, histamines, prostaglandins, and other materials leading to inflammation. Tumor cells express altered proteins due to mutations of their genes, DNA modifications such as histone modification, DNA methylation, or other mechanisms of altered protein expression. The body's immunological cells actively recognize these altered proteins, …

The Role Of Abc Transporters In Anticancer Drug Transport, Serhan Karvar

Turkish Journal of Biology

The main clinical problem in cancer treatment is the development of multidrug resistance. Tumors can be intrinsically drug-resistant or develop resistance to chemotherapy. Multidrug resistance can develop by diverse mechanisms including decreased rate of drug uptake, increased drug efflux, alterations in drug metabolism, mutation of drug targets, activation of DNA repair mechanisms, and evasion of apoptosis. The use of modern genomic, proteomic, bioinformatic, and systems biology approaches has resulted in a substantial increase in our ability to identify molecular mechanisms that are involved in multidrug resistance in cancer and to find drugs that may block or reverse the development of …

Noncoding Rnas And Cancer, Hesna Begüm Akman Tuncer, Ayşe Eli̇f Erson Bensan

Turkish Journal of Biology

New and diverse groups of noncoding RNAs are beginning to be discovered. These noncoding RNAs are grouped based on their sizes, genomic positions, or distinctive functions ranging from the regulation of chromatin structure and gene expression to genome stability maintenance. Among noncoding RNAs, microRNAs are the best studied and understood small RNAs with direct and indirect roles in normal and in cancer cells. Given the high rate of transcription from noncoding parts of the genome, other noncoding elements are also of great interest. It is also of interest to understand that there may be interesting cases of crosstalk and/or coregulation …

Identification Of New Genes Required For The Maintenance Of Chromosome Integrity In Drosophila Melanogaster, Francesca Ceprani, Franco Spirito, Roberto Piergentili

Turkish Journal of Biology

Although genome-wide RNA interference (RNAi) screens for mitotic genes are not new in the literature, most of them lack the cytological characterization of the cell karyotype as for chromosome integrity. Here, the effects of RNAi on chromosome structure in S2 cultured cells of Drosophila melanogaster were analyzed. The cytological phenotype of 1132 genes selected by coexpression with known mitotic genes was scored. Cytological and statistical analysis of the treated cells allowed the identifying of 81 loci whose inactivation brings a level of chromosome breakage significantly higher than in the control. Many of the genes characterized in the present work had …

How Do Patients With Advanced Cancer Cope With An Uncertain Disease Trajectory? Implications For Grief Counselling, Elizabeth A. Lobb

Health Sciences Papers and Journal Articles

A growing number of cancer patients are living longer with incurable disease. This paper describes strategies that patients use to cope with the uncertain trajectory of their disease. Twenty-seven patients with a prognosis of 12 months were recruited from the oncology and palliative care service at three metropolitan Sydney hospitals. A semi-structured face-to-face interview was conducted, which was audiotaped and transcribed verbatim. The patients coped with the uncertain trajectory of their disease through avoidance, maintaining a normal life, comparing themselves favourably with others in a similar situation and remaining positive. Participants indicated that they did not wish referral for psychological …