Cancer Biology Commons^™

Oxaliplatin And Oxaliplatin Derivatives: Synthesis, Characterization, And Reactivity With Biologically Relevant Ligands, Amy Poynter

Mahurin Honors College Capstone Experience/Thesis Projects

Oxaliplatin is a third generation anticancer drug that has proven to be successful in fighting ovarian and testicular cancer. We are interested in determining how oxaliplatin and oxaliplatin derivatives interact with proteins, as well as how that interaction is affected by the size and shape of these platinum compounds. We have synthesized oxaliplatin as it is used in cancer treatment, as well as similar platinum compounds with the same diaminocyclohexane ligand as oxaliplatin but with additional bulk added to the nitrogen atoms. We are reacting oxaliplatin with key amino acids, including methionine, and will be comparing the kinetics of this …

Effect Of Combining Bcl-2 Inhibition And Radiation On Apoptotic Cell Death In Human Breast Cancer Cell Lines As Determined By Clonogenic Assay And Western Blots, Amari Sasha Howard

Renée Crown University Honors Thesis Projects - All

Cancer is a group of diseases characterized by abnormal control of cell growth and cell survival. Current treatment for cancer employs a combination of modalities including surgery, radiation, chemotherapeutic drugs, and immunotherapy. Our lab focuses on personalized medicine and treatments that can specifically target molecular features of a tumor as presented by the particular patient being treated. Cancers often exhibit an over-expression or under-expression of certain proteins that play a large role in regulating the process of apoptosis, which is programmed cell death. This study focuses on proposing drug treatment for cancer that is personalized in that it targets a …

Microrna Regulation Of Prostate Cancer Stem/Progenitor Cells And Prostate Cancer Development, Can Liu

Dissertations and Theses (Open Access)

Most human tumors contain a population of cells with stem cell properties, called cancer stem cells (CSCs), which are believed to be responsible for tumor establishment, metastasis, and resistance to clinical therapy. It’s crucial to understand the regulatory mechanisms unique to CSCs, so that we may design CSC-specific therapeutics. Recent discoveries of microRNA (miRNA) have provided a new avenue in understanding the regulatory mechanisms of cancer. However, how miRNAs may regulate CSCs is still poorly understood. Here, we present miRNA expression profiling in six populations of prostate cancer (PCa) stem/progenitor cells that possess distinct tumorigenic properties. Six miRNAs were identified …

14-3-3 Zeta Overexpression Serves As A Novel Molecular Switch Turning Tgf-Beta From Tumor Suppressor To Tumor Promoter, Jia Xu

Dissertations and Theses (Open Access)

TGF-β plays an important role in differentiation and tissue morphogenesis as well as cancer progression. However, the role of TGF-β in cancer is complicate. TGF-β has primarily been recognized as tumor suppressor, because it can directly inhibit cell proliferation of normal and premalignant epithelial cell. However, in the last stage of tumor progression, TGF-β functions as tumor promoter to enhance tumor cells metastatic dissemination and expands metastatic colonies. Currently, the mechanism of how TGF-β switches its role from tumor suppressor to promoter still remains elusive. Here we identify that overexpression of 14-3-3ζ inhibits TGF-β’s cell cytostatic program through destabilizing p53 …

Elucidating The Igfbp2 Signaling Pathway In Glioma Development And Progression, Kristen M. Holmes

Dissertations and Theses (Open Access)

Diffuse gliomas are highly lethal central nervous system malignancies which, unfortunately, are the most common primary brain tumor and also the least responsive to the very few therapeutic modalities currently available to treat them. IGFBP2 is a newly recognized oncogene that is operative in multiple cancer types, including glioma, and shows promise for a targeted therapeutic approach. Elevated IGFBP2 expression is present in high-grade glioma and correlates with poor survival. We have previously demonstrated that IGFBP2 induces glioma development and progression in a spontaneous glioma mouse model, which highlighted its significance and potential for future therapy. However, we did not …

Syntaxin 6- And Microtubule- Mediated Intracellular Trafficking Contributes To Golgi And Nuclear Translocation Of Egfr, Yi Du

Dissertations and Theses (Open Access)

Receptor-mediated endocytosis is well known for its degradation and recycling trafficking. Recent evidence shows that these cell surface receptors translocate from cell surface to different cellular compartments, including the Golgi, mitochondria, endoplasmic reticulum (ER), and the nucleus to regulate physiological and pathological functions. Although some trafficking mechanisms have been resolved, the mechanism of intracellular trafficking from cell surface to the Golgi is not yet completed understood. Here we report a mechanism of Golgi translocation of EGFR in which EGF-induced EGFR travels to the Golgi via microtubule (MT)-dependent movement by interacting with dynein and fuses with the Golgi through syntaxin 6 …

Chronic Stress Promotes Tumor Growth Through Increased Bdnf Production And Neo-Innervation, Julie K. Allen

Dissertations and Theses (Open Access)

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor growth.

Results: First, I examined whether sympathetic nerves are present in human ovarian cancer samples as well as orthotopic ovarian cancer models. Immunohistochemical (IHC) staining for neurofilament revealed that catecholaminergic neurons are present within tumor tissue. In order to determine …

Lmw-E Mediates Mammary Tumorigenesis By Deregulating Acinar Morphogenesis & Generating Cancer Stem Cells, Mylinh T. Duong

Dissertations and Theses (Open Access)

Cyclin E is the regulatory subunit of the cyclin E/CDK2 complex that

mediates the G1-S phase transition. N-terminal cleavage of cyclin E by elastase in

breast cancer generates two low molecular weight (LMW) isoforms that exhibit both

enhanced kinase activity and resistance to p21 and p27 inhibition compared to fulllength cyclin E. Clinically, approximately 27% of breast cancer patients overexpress

LMW-E and associate with poor survival. Therefore, we hypothesize that LMW-E

disrupts normal mammary acinar morphogenesis and serves as the initial route into

breast tumor development. We first demonstrate that LMW-E overexpression in

non-tumorigenic hMECs is sufficient to induce tumor …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations and Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Role Of Human Cytomegalovirus In Breast Cancer, Cendy Valle Oseguera, Juliet V. Spencer

Creative Activity and Research Day - CARD

Cancer results from unregulated cell growth that invades neighboring tissues. While there are many known risk factors for cancer, one area that remains largely unexplored is the impact of infectious disease. Human cytomegalovirus (HCMV) is highly prevalent in the population and has also been found in several types of tumors. We are investigating the possibility that a viral protein released from infected cells, cmvIL-10, promotes tumor metastasis by enhancing the invasive potential of breast cancer cells. These results will clarify the role of HCMV in breast cancer progression and could have broad implications for the diagnosis and treatment of cancer.

Analysis Of Her-2 Positive Breast Cancer Cell Lines, Natzidielly Lerma^, Paloma Valenzuela, Karla Parra, Eduardo Ramirez, Courtney L. Becerril, Irving Miramontes, Cynthia M. Rodriguez, Elizabeth Gamez, Giulio Francia*

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Defeating Cytoplasmic Sequestration Of P53 In Human Breast Cancer Cells; Is Mortalin Involved?, Sarah Yunes

Honors Theses and Capstones

Cytoplasmic sequestration of p53, possibly caused by p53 interacting with mortalin, can prevent p53 from functioning in DNA repair and apoptosis, causing aberrant growth. This project treated SKBR3 breast cancer cells with MKT-077, a dye that is a competitive binder to mortalin to see if it would result in the release of p53 from the cytoplasm and restoration of p53 function. Treatment resulted in partial translocation of a protein suspected to be p53 to the nucleus and apoptosis initiated at the mitochondria.

Inhibition Of Fatty Acid Synthase Attenuates Cd44-Associated Signaling And Reduces Metastasis In Colorectal Cancer, Yekaterina Y. Zaytseva, Piotr G. Rychahou, Pat Gulhati, Victoria Allison Elliott, William Conan Mustain, Kathleen O'Connor, Andrew J. Morris, Manjula Sunkara, Heidi L. Weiss, Eun Young Lee, B. Mark Evers

Markey Cancer Center Faculty Publications

Fatty acid synthase (FASN) and ATP-citrate lyase, key enzymes of de novo lipogenesis, are significantly upregulated and activated in many cancers and portend poor prognosis. Even though the role of lipogenesis in providing proliferative and survival advantages to cancer cells has been described, the impact of aberrant activation of lipogenic enzymes on cancer progression remains unknown. In this study, we found that elevated expression of FASN is associated with advanced stages of colorectal cancer (CRC) and liver metastasis, suggesting that it may play a role in progression of CRC to metastatic disease. Targeted inhibition of lipogenic enzymes abolished expression of …

Chip Sequencing Of Cyclin D1 Reveals A Transcriptional Role In Chromosomal Instability In Mice., Mathew C Casimiro, Marco Crosariol, Emanuele Loro, Adam Ertel, Zuoren Yu, William Dampier, Elizabeth A Saria, Alex Papanikolaou, Timothy J Stanek, Zhiping Li, Chenguang Wang, Paolo Fortina, Sankar Addya, Aydin Tozeren, Erik S Knudsen, Andrew Arnold, Richard G Pestell

Kimmel Cancer Center Faculty Papers

Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1-/- mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN …

Targeting The Cancer Cell Cycle By Cold Atmospheric Plasma, Olga Volotskova, Teresa S. Hawley, Mary Ann Stepp, Michael Keidar

Anatomy and Regenerative Biology Faculty Publications

Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating …

Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry

Pharmacy Faculty Articles and Research

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …

Genetics And Cancer, Sachin Puri

A with Honors Projects

Genes' effect in body and relationship with cancer. Role in cell cycle and angiogenesis.

Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses

Pharmacy Faculty Articles and Research

"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date was based on the …

Cytoplasmic Sequestration Of The Tumor Suppressor P53 By A Heat Shock Protein 70 Family Member, Mortalin, In Human Colorectal Adenocarcinoma Cell Lines, Erin E. Gestl, S. Anne Boettger

Biology Faculty Publications

No abstract provided.

Cancer And You, Diah-Aldeen Judeh

A with Honors Projects

This project discusses ways a person can identify cancer and what to do if cancer is present.