Digital Commons Network^™

Large Scale Matrix Degradation By Stromal Cells Independent Of Invadopodia, Hong Cao, Robbin Eppinga, Eugene W. Krueger, Jing Chen, Mark A. Mcniven

Faculty Work Comprehensive List

Invadopodia are actin-rich structures at the base of many neoplastic cells that sequester matrix metalloproteases that act to degrade the surrounding stroma to facilitate the invasive process. Conventional invadopodia are dependent upon Src kinase and the large GTPase dynamin 2 (Dyn 2). Whether invadopodia are the only mechanism by which cells degrade matrix is unclear. We have observed that cells of mesenchymal origin degrade matrix in an unique way different from tumor cells. The HYPOTHESIS of this study is that fibroblasts, and other cells of mesenchymal origin, degrade matrix by a mechanism distinct from that of epithelial-based tumor cells. The …

Nullomer Derived Anticancer Peptides (Nullops): Differential Lethal Effects On Normal And Cancer Cells In Vitro, Abdelkrim Alileche, Jayita Goswami, William Bourland, Mike Davis, Greg Hampikian

Biology Faculty Publications and Presentations

We demonstrate the first use of the nullomer (absent sequences) approach to drug discovery and development. Nullomers are the shortest absent sequences determined in a species, or group of species. By identifying the shortest absent peptide sequences from the NCBI databases, we screened several potential anti-cancer peptides. In order to improve cell penetration and solubility we added short poly arginine tails (5Rs), and initially solubilized the peptides in1M trehalose. The results for one of the absent sequences 9R (RRRRRNWMWC), and its scrambled version 9S1R (RRRRRWCMNW) are reported here. We refer to these peptides derived from nullomers as PolyArgNulloPs. A control …

A Study On The Function Of 14-3-3sigma In Regulating Cancer Energy Metabolism, Liem M. Phan, Liem M. Phan

Dissertations & Theses (Open Access)

Metabolic reprogramming has been shown to be a major cancer hallmark providing tumor cells with significant advantages for survival, proliferation, growth, metastasis and resistance against anti-cancer therapies. Glycolysis, glutaminolysis and mitochondrial biogenesis are among the most essential cancer metabolic alterations because these pathways provide cancer cells with not only energy but also crucial metabolites to support large-scale biosynthesis, rapid proliferation and tumorigenesis. In this study, we find that 14-3-3σ suppresses all these three metabolic processes by promoting the degradation of their main driver, c-Myc. In fact, 14-3-3s significantly enhances c-Myc poly-ubiquitination and subsequent degradation, reduces c-Myc transcriptional activity, and down-regulates …

Characterization Of A Tumour Suppressor Function Of Ranbpm, Elnaz Atabakhsh

Electronic Thesis and Dissertation Repository

Ran-binding protein M (RanBPM) is an evolutionarily conserved nucleocytosolic protein that has been proposed to regulate various cellular processes, including protein stability, gene expression, receptor-mediated signalling pathways, cell adhesion, development, and apoptosis. Despite the multitude of functions attributed to RanBPM however, little is known regarding the precise mechanisms by which RanBPM executes these cellular roles. In this work, we seek to address this matter by describing functions for RanBPM in the regulation of apoptotic and pro-survival signalling pathways, and in cellular transformation.

We first identify RanBPM as a pro-apoptotic protein that regulates the activation of the intrinsic apoptotic signalling pathway …

Biochemical Pathways In Cancer, Eun-Kyoung Yim Breuer, Mandi M. Murph, Rolf J. Craven

Pharmacology and Nutritional Sciences Faculty Publications

No abstract.

Polysaccharopeptide Enhances The Anticancer Activity Of Doxorubicin And Etoposide On Human Breast Cancer Cells Zr-75-30, Jennifer Man-Fan Wan, Wai Hung Sit, Jimmy Chun Yu Louie

Jimmy Chun Yu Louie

In search of natural bioactive microbial compounds with adjuvant properties, we have previously showed that the polysaccharopeptide (PSP), isolated from Chinese medicinal mushroom Coriolus versicolor, was able to enhance the cytotoxicity of certain S-phase targeted-drugs on human leukemic HL-60 cells via some cell-cycle and apoptotic-dependent pathways. The present study aimed to investigate whether the synergism of mechanisms of PSP with certain chemotherapeutic drugs also applies to human breast cancer. PSP treatment enhanced the cytotoxicity of doxorubicin (Doxo), etoposide (VP-16) but not cytarabine (Ara-C). Bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometry analysis estimated a longer DNA synthesis time (Ts) for the PSP treated …

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Gabriela Ion

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods: Female SV 129 mice were divided into two groups and placed on …

Maternal Consumption Of Canola Oil Suppressed Mammary Gland Tumorigenesis In C3(1) Tag Mice Offspring, Gabriela Ion, Juliana A. Akinsete, W. Elaine Hardman

Elaine Hardman Ph.D.

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring. Methods: Female SV 129 mice were divided into two groups and placed on …

Epigenetic Modification As An Enabling Mechanism For Leukemic Transformation, Vincent Sollars

Vincent E Sollars

Cancer is now thought of as a fundamentally genetic disease, in that changes in the genome result in aberrant gene expression of oncogenes and tumor suppressor genes to promote oncogenesis. However, with our increasing knowledge of gene regulation, it is becoming obvious that changes in nucleotide sequence are not the sole mechanism for eliciting changes in transcription. An additional layer of regulation of gene expression, called epigenetics, is now being realized as increasingly important in oncogenesis. Epigenetics is defined as non-sequence based changes in chromatin that elicit changes in gene expression that are propagated through mitosis and/or meiosis. The alleles …

Diversity In Secreted Pla2-Iia Activity Among Inbred Mouse Strains That Are Resistant Or Susceptible To Apcmin/+ Tumorigenesis, Marina Markova, Revati Koratkar, Karen Silverman, Vincent Sollars, Melina Macphee-Pellini, Rhonda Walters, Juan Palazzo, Arthur Buchberg, Linda Siracusa, Steven Farber

Vincent E Sollars

The secreted phospholipase A₂ type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in Apc^Min/+ mice. To determine if intestinal secreted phospholipase A₂ (sPLA₂) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPLA₂ activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA₂ enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA …

The Epigenomic Viewpoint On Cellular Differentiation Of Myeloid Progenitor Cells As It Pertains To Leukemogenesis, Vincent E. Sollars

Vincent E Sollars

The new millennium has brought with it a surge of research in the field of epigenetics. This has included advances in our understanding of stem cell characteristics and mechanisms of commitment to cell lineages prior to differentiation. The nature of stem cells is similar to that of malignant cells in that they have unlimited self-renewal and protection from apoptosis, leading researchers to suspect that stem cells are the target of oncogenesis. This review will explore the idea of how epigenetic control of gene expression may contribute to mechanisms controlling differentiation of myeloid progenitor cells and its importance to our understanding …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Richard M. Niles

Background Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas. Results HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

Combinatorial Analysis Of Tumorigenic Micrornas Driving Prostate Cancer, William Budd

Theses and Dissertations

Prostate cancer is the leading non-cutaneous malignancy affecting men in the United States. One in every six men will be affected by prostate cancer. Due to the high incidence of prostate cancer, there is a need to develop biomarkers capable of identifying tumors from benign prostatic lesions. miRNAs are small molecules that regulate protein translation and impact cellular integrity when dysregulated. It is widely thought that miRNAs have the potential to serve as biomarkers. This study utilizes a unique combinatorial analysis of miRNA dysregulation to identify key miRNAs involved in prostate tumor initiation, progression and metastasis. Numerous dysregulated miRNAs potentially …

Platelets And Anti-Angiogenic Resistance In Ovarian Carcinoma, Justin N. Bottsford-Miller

Dissertations & Theses (Open Access)

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified.

Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of …

Examining Cancer And Cardiovascular Risk Behaviours In People Attending Residential Substance Abuse Treatment, Peter Kelly, A Baker, Frances Kay-Lambkin, Frank Deane, Billie Bonevski

Peter Kelly

No abstract provided.

Plant Lectin Can Target Receptors Containing Sialic Acid, Exemplified By Podoplanin, To Inhibit Transformed Cell Growth And Migration, Jhon Ochoa-Alvarez, Harini Krishnan, Yongquan Shen, Nimish Acharya, Min Han, Dean Mcnulty, Hitoki Hasegawa

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors …

Star Rna-Binding Protein Quaking Suppresses Cancer Via Stabilization Of Specific Mirna, Natalie Farny, An-Jou Chen, Ji-Hye Paik, Hailei Zhang, Sachet Shukla, Richard Mortensen, Jian Hu, Haoqiang Ying, Baoli Hu, Jessica Hurt, Caroline Dong, Yonghong Xiao, Y. Wang, Pamela Silver, Lynda Chin, Shobha Vasudevan, Ronald Depinho

Natalie G. Farny

Multidimensional cancer genome analysis and validation has defined Quaking (QKI), a member of the signal transduction and activation of RNA (STAR) family of RNA-binding proteins, as a novel glioblastoma multiforme (GBM) tumor suppressor. Here, we establish that p53 directly regulates QKI gene expression, and QKI protein associates with and leads to the stabilization of miR-20a; miR-20a, in turn, regulates TGFβR2 and the TGFβ signaling network. This pathway circuitry is substantiated by in silico epistasis analysis of its components in the human GBM TCGA (The Cancer Genome Atlas Project) collection and by their gain- and loss-of-function interactions in in vitro and …

Depression And Quality Of Life In Cancer Survivors: Is There A Relationship With Physical Activity?, Nancy Humpel, Donald Iverson

Don C. Iverson

Background Evidence is growing on the benefit of physical activity to improve well-being following a cancer diagnosis. This study examined changes in physical activity from pre to post diagnosis and explored this relationship with quality of life and depression. Methods Participants were recruited by posters and by letter of invitation. The questionnaire was completed by 59 prostate and 32 breast cancer survivors. Results Physical activity decreased by 72 minutes per week from pre to post diagnosis, although 20.9% reported having increased activity post diagnosis. Over 30% were considered depressed. Breast cancer participants who increased physical activity post diagnosis reported higher …

Review And Critique Of The Quality Of Exercise Recommendations For Cancer Patients And Survivors, Nancy Humpel, Donald Iverson

Don C. Iverson

The benefit of exercise for cancer patients is starting to become recognized. The purposes of this paper were to review the literature to examine whether research findings are being converted into guidelines for patients and survivors and to examine the quality of evidence on which they were based. A computer search of major health databases was conducted for peer-reviewed literature and books on exercise and cancer, and an Internet search was conducted for cancer websites reporting any exercise guidelines/recommendations for cancer patients. Seven peer-reviewed articles, eight books and eight cancer websites were identified that suggested exercise guidelines for cancer patients …

School-Based Cancer Education Programs: An Opportunity To Affect The National Cancer Problem, Donald Iverson, J Scheer

Don C. Iverson

No abstract provided.

The Danger Of Applying Uniform Clincal Policies Across Populations: The Case Of Breast Cancer In American Indians, Paul Nutting, Ned Calonge, Donald Iverson, Larry Green

Don C. Iverson

OBJECTIVES. This study examined the implications of annual screening mammography for cost and mortality in American Indian populations with differing baseline breast cancer rates. METHODS. A decision tree compared annual screening mammography and screening clinical breast examination with referral for diagnostic mammography when appropriate. The decision tree was constructed to examine the effect of different base-line cancer rates, stage at diagnosis, and stage-specific survival. Outcomes included 5-year relative survival, deaths prevented at 5 years, cost per death prevented, and total costs. RESULTS. The findings suggest that the total cost of breast cancer is 3.6 times higher with the screening mammography …

Workgroup Iv: Public Education. Uicc International Workshop On Facilitating Screening For Colorectal Cancer, Oslo, Norway 2002, R Hiatt, J Wardle, S Vernon, J Austoker, L Bistanti, S Fox, R Gnauck, Donald Iverson

Don C. Iverson

The Workgroup on public education was brought together to formulate an international perspective on public education for the important public health challenge of increasing colorectal cancer screening. The focus of the group did not include professional education, which is an important channel for public education, since another Workgroup covered that topic. The results of the Workgroup represent an expression of expert opinion and did not include a comprehensive review of the literature. However, the recommendations for further research may stimulate a more in-depth examination of the literature in some areas and generate ideas for investigation.

Involving Providers And Patients In Cancer Control And Prevention Efforts. Barriers To Overcome, Donald Iverson

Don C. Iverson

Although progress has been made in providing cancer prevention and control services to the population, there remain sizeable segments of the population that are either uninvolved or underinvolved with national and state efforts. One method of reaching most of the population, including those segments currently not involved or underinvolved, is through primary care clinicians. Effective, albeit imperfect, strategies to increase the involvement of primary care clinicians in cancer prevention and control are available, and there is emerging evidence that these strategies are making a difference. Unfortunately, the progress made to date is at risk of being lost because of economic …

Feasibility Studies Of Low-Fat Diet To Prevent Or Retard Breast Cancer, P Greenwald, C Clifford, R Butrum, Donald Iverson

Don C. Iverson

No abstract provided.

Sleep Quality, Fatigue And Physical Activity Following A Cancer Diagnosis, Nancy Humpel, Donald Iverson

Don C. Iverson

Research on physical activity for cancer survivors suggests a relationship with improved quality of life. The aim of this study was to explore if there was also a relationship of physical activity with sleep difficulties and fatigue, common effects of cancer and its treatments. Recruitment was by posters and flyers in medical waiting rooms and by letter of invitation. Thirty-two breast and 59 prostate cancer survivors completed the questionnaire. Poor sleep quality was reported by 57.8%. A greater proportion of breast cancer (36.7%) than prostate cancer survivors (15.5%) reported poor sleep latency, and sleep disturbance (48.4% vs. 17.2%). The mean …

Australian Women's Awareness Of Breast Cancer Symptoms And Responses To Potential Symptoms, Sandra Jones, Parri Gregory, Caroline Nehill, Lance Barrie, Karen Luxford, A. Nelson, Helen Zorbas, Donald Iverson

Don C. Iverson

Poor awareness of breast cancer symptoms has been associated with patient delay in seeking help; thus reduced survival, more aggressive treatment, and fewer treatment choices. The aim of this study was to develop a representative picture of Australian women’s knowledge of symptoms, experienced potential symptoms, and behavioral responses. A general population sample of approximately 3,000 women aged 30–69 completed a telephone survey; results were compared to previous surveys conducted in 1996 and 2003. The most commonly cited potential symptom of breast cancer was a lump in the breast, identified by 86% of respondents (an increase from 75% in 2003). Other …

Prostate Cancer Screening In The Midst Of Controversy: Canadian Men's Knowledge, Beliefs, Utilization, And Future Intentions, Shawna Mercer, Vivek Goel, Isra Levy, F Ashbury, Donald Iverson, Neill Iscoe

Don C. Iverson

Despite controversy about prostate cancer screening, administrative data show that the use of prostate specific antigen (PSA) testing in Canada has increased. This study sought to determine awareness and knowledge of prostate cancer and screening, use to date, and future intentions to have a digital rectal examination (DRE) and PSA test among Canadian men aged 40 and over. Data were collected through a Canada-wide cross-sectional random digit dial telephone survey of 629 men. Awareness of DRE and PSA, use to date, and future intended use varied with age and education. Although only 9% of respondents had had PSA testing for …

Defining Research Priorities For Pancreatic Cancer In Australia: Results Of A Consensus Development Process, Monica Robotin, Sandra Jones, Andrew Biankin, Louise Waters, Donald Iverson, Helen Gooden, Bruce Barraclough, Andrew Penman

Don C. Iverson

Introduction: Pancreatic cancer (PC) is the sixth leading cause of cancer death in Australia and the fourth in the United States, yet research in PC is lagging behind that in other cancers associated with a high disease burden. In the absence of agreed processes to reliably identify research areas which can deliver significant advances in PC research, the Cancer Council NSW established a strategic partnership with the NSW Pancreatic Cancer Network to define critical research issues and opportunities that could accelerate progress in this field in Australia. Materials and methods: The process consisted of five distinct stages: a literature review …

Australian Women's Perceptions Of Breast Cancer Risk Factors And The Risk Of Developing Breast Cancer, Sandra C. Jones, Christopher A. Magee, Lance R. Barrie, Donald C. Iverson, Parri Gregory, Emma L. Hanks, Anne E. Nelson, Caroline L. Nehill, Helen M. Zorbas

Don C. Iverson

Background Numerous studies have shown that the majority of women overestimate both their own risk and the populations’ risk of developing breast cancer. A number of factors have been found to correlate with perceived risk. Methods This paper reports on a telephone survey of a nationally representative sample of approximately 3,000 Australian women aged 30 to 69 years, conducted in 2007, and compares the findings with those of a similar survey conducted in 2003. Results There was a clear tendency for respondents to overestimate the proportion of women who will develop breast cancer during their lifetime. Approximately half the respondents …

Rok And Rac Mediation Of Prl-1 Function In The Wings Of Drosophila Melanogaster, Rosemary Dinkins

Honors Program Theses

By the time a cancer metastasizes it has reached its most deadly stage. It therefore is essential that the underpinning mechanisms promoting metastasis are understood. Phosphatases of regenerating liver (PRL) have been repeatedly connected to cancer metastasis when overexpressed. However, little is yet known about the normal PRL function and biological pathways let alone the PRL pathway promoting metastasis. The current study explores the relationship between PRL-1 and two other genes, ROK and Rac,that have also been implicated in cell migration and metastasis. Increased PRL-1 function in conjunction with increased or decreased Rac function was forced to the dorsal half …