Cancer Biology Commons^™

Image Enhancement Of Cancerous Tissue In Mammography Images, Richard Thomas Richardson

CCAC Theses and Dissertations

This research presents a framework for enhancing and analyzing time-sequenced mammographic images for detection of cancerous tissue, specifically designed to assist radiologists and physicians with the detection of breast cancer. By using computer aided diagnosis (CAD) systems as a tool to help in the detection of breast cancer in computed tomography (CT) mammography images, previous CT mammography images will enhance the interpretation of the next series of images. The first stage of this dissertation applies image subtraction to images from the same patient over time. Image types are defined as temporal subtraction, dual-energy subtraction, and Digital Database for Screening Mammography …

Cancer Stem Cells In Recurrent And Drug-Resistant Lung Cancers, Raagini Suresh, Shadan Ali, Aamir Ahmad, Philip Philip, Fazlul Sarkar

Honors College Theses

With a 5-year survival rate of less than 20%, lung cancer is a leading cause of cancer-related deaths worldwide. Considering the treatments currently in place, this statistic is frankly shocking. A possible explanation for the disconnect between sophisticated treatments and the survival rate can be found in the Cancer Stem Cell (CSC) hypothesis. The CSC hypothesis suggests the idea of a subpopulation of tumor cells with the abilities of self-renewal, cancer initiation, and further maintenance of tumors. Lung CSCs have been associated with resistance to radiation and chemotherapeutic treatments. CSCs have also been implicated in recurrent cancers; …

Violacein Induces P44/42 Mitogen-Activated Protein Kinase‑Mediated Solid Tumor Cell Death And Inhibits Tumor Cell Migration, Toral Mehta, Koen Vercruysse, Terrance Johnson, Anthony Okechukwu Ejiofor, Elbert Myles, Quincy Antoine Quick

Biology Faculty Research

Microbial secondary metabolites have emerged as alternative novel drugs for the treatment of human cancers. Violacein, a purple pigment produced by Chromobacterium violaceum, was investigated in the present study for its anti‑tumor properties in tumor cell lines. Clinically applicable concentrations of violacein were demonstrated to inhibit the proliferative capacity of tumor cell lines according to a crystal violet proliferation assay. The underlying mechanism was the promotion of apoptotic cell death, as indicated by poly(ADP ribose) polymerase cleavage and p44/42 mitogen‑activated protein kinase signaling determined by western blot analysis. Collectively, this provided mechanistic evidence that violacein elicits extracellular-signal regulated kinase‑induced apoptosis …

Violacein Induces P44/42 Mitogen-Activated Protein Kinase‑Mediated Solid Tumor Cell Death And Inhibits Tumor Cell Migration, Toral Mehta, Koen P. Vercruysse, Terrance Johnson, Anthony Okechukwu Ejiofor, Elbert Myles, Quincy A. Quick

Chemistry Faculty Research

Microbial secondary metabolites have emerged as alternative novel drugs for the treatment of human cancers. Violacein, a purple pigment produced by Chromobacterium violaceum, was investigated in the present study for its anti‑tumor properties in tumor cell lines. Clinically applicable concentrations of violacein were demonstrated to inhibit the proliferative capacity of tumor cell lines according to a crystal violet proliferation assay. The underlying mechanism was the promotion of apoptotic cell death, as indicated by poly(ADP ribose) polymerase cleavage and p44/42 mitogen‑activated protein kinase signaling determined by western blot analysis. Collectively, this provided mechanistic evidence that violacein elicits extracellular-signal regulated kinase‑induced apoptosis …

Utilizing Systems Level Approaches To Identify Key Mechanisms Of Drug Resistance In Braf Mutated Melanoma, Kim H.T. Paraiso

USF Tampa Graduate Theses and Dissertations

In the last four years, seven new drugs have been FDA approved for the treatment of late stage melanoma, for the field of melanoma, this marks an incredibly exciting. Three of these new therapies, vemurafenib, dabrafenib and trametinib are small molecule kinase inhibitors that target the MAPK pathway and as such have been approved for the treatment of BRAFV600 mutant melanomas. Yet despite recent advances, mechanisms of intrinsic and acquired BRAF inhibitor resistance continue to undermine uniform and long-lasting therapeutic responses. Several studies have shown that the reactivation of MAPK signaling is a critical event leading to BRAF inhibitor resistance. …

Use And Misuse Of Material Transfer Agreements: Lessons In Proportionality From Research, Repositories, And Litigation, Tania M. Bubela, Jenilee Guebert, Amrita Mishra

Office of the Provost

Material transfer agreements exist to facilitate the exchange of materials and associated data between researchers as well as to protect the interests of the researchers and their institutions. But this dual mandate can be a source of frustration for researchers, creating administrative burdens and slowing down collaborations. We argue here that in most cases in pre-competitive research, a simple agreement would suffice; the more complex agreements and mechanisms for their negotiation should be reserved for cases where the risks posed to the institution and the potential commercial value of the research reagents is high.

Targeting Cell Cycle Proteins In Breast Cancer Cells With Sirna By Using Lipid-Substituted Polyethylenimines, Manoj Parmar, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Robert Maranchuk, Judith C. Hugh, Hasan Uludag

Pharmacy Faculty Articles and Research

The cell cycle proteins are key regulators of cell cycle progression whose de-regulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division cycle …

Assign: Context-Specific Genomic Profiling Of Multiple Heterogeneous Biological Pathways, Ying Shen, Mumtahena Rahman, Stephen R. Piccolo, Daniel Gusenleitner, Nader N. El-Chaar, Luis Cheng, Stefano Monti, Andrea H. Bild, W. Evan Johnson

Faculty Publications

Motivation: Although gene-expression signature-based biomarkers are often developed for clinical diagnosis, many promising signatures fail to replicate during validation. One major challenge is that biological samples used to generate and validate the signature are often from heterogeneous biological contexts—controlled or in vitro samples may be used to generate the signature, but patient samples may be used for validation. In addition, systematic technical biases from multiple genome-profiling platforms often mask true biological variation. Addressing such challenges will enable us to better elucidate disease mechanisms and provide improved guidance for personalized therapeutics.

Results: Here, we present a pathway profiling toolkit, Adaptive Signature …

Clinical Significance Of A Point Mutation In Dna Polymerase Beta (Polb) Gene In Gastric Cancer., Xiaohui Tan, Hongyi Wang, Guangbin Luo, Shuyang Ren, Wenmei Li, Jiantao Cui, Harindarpal S. Gill, Sidney W. Fu, Youyong Lu

Medicine Faculty Publications

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal …

Alternative Extraction Method Of Guanidine Metabolites From Marine Sponge, Ptilocaulis Spiculifer, Savannah Barnett, Andrew A. Yeagley, Amorette Barber

Theses & Honors Papers

Marine sponges are known for their use of biologically active allelopathic compounds. With almost every species of sponge having been shown to produce some chemical with medicinal properties, their survival is becoming increasingly important. Current extraction methods used by research teams require a large sample relative to the size of the sponge, which threatens the survival of the organism. 1 Ptilocaulis sp., or the orange tree sponge, is known to produce guanidine metabolites. This derivative has demonstrated biological activity against cell lines of leukemia, uterine, and cervical cancer.2 3 In this study we have developed a method for the chemical …

Ua94/6/15 Student / Alumni Personal Papers Wku Dorris Hutchinson, Wku Archives

WKU Archives Collection Inventories

Correspondence and publications created by and about the Dorris Hutchison during her time at Sloan-Kettering Institute.

Terahertz Imaging Platform To Characterize The Growth Of In-Vitro Breast Tumors, Scarlett-Marie Acklin

Inquiry: The University of Arkansas Undergraduate Research Journal

This study aimed at evaluating the ideal plating method and density for imaging with the terahertz (THz) spectrometer. In this study, different methods were used to grow in-vitro tumors using the 4T1 cell line. Here, attempts to grow breast tumors in-vitro were conducted. Results were produced in two environments, flat-bottomed plates and round-bottomed multiwell plates. The second method allowed for faster clumping and increased cell aggregation, producing tumors up to 7mm. Terahertz spectroscopy produced images that correlated well to photomicrographs taken of the in-vitro tumors. This methodology shows great promise for providing a reliable, parameter-controlled source of in-vitro breast tumors …

The Significance Of Crispr/Cas9-Directed Cul3 Knockout On Human Colorectal Cancer Cells, Zoe A. Lautz

Departmental Honors Projects

Cancer, the second leading cause of death in the US, is caused by mutations in select genes that alter cellular function leading to uncontrolled proliferation. Understanding the specific genes that drive cancer can lead to the generation of novel cancer therapies. To identify novel genes that drive cancer in the colon (CRC), lungs, and ovaries in mice, Starr et al. employed a transposon-based insertional mutagenesis system. One of the genes identified, APC, is mutated in 70-80% of human CRCs. CUL3, suspected to be a general driver gene, was discovered in the lung cancer screen. CUL3 was analyzed for its role …

May Circulating Micrornas Be Gastric Cancer Diagnostic Biomarkers?, Xiaoling Wu, Xiaohui (Jane) Tan, Sidney W. Fu

Medicine Faculty Publications

Gastric cancer (GC) is the third leading cause of cancer-related deaths. More than 80% of the diagnosis was made at the advanced stages of the disease, highlighting the urgent demand for novel biomarkers that can be used for early detection. Recently, a number of studies suggest that circulating microRNAs (miRNAs) could be potential biomarkers for GC diagnosis. Cancer-related circulating miRNAs, as well as tissue miRNAs, provide a hopeful prospect of detecting GC at early stages, and the prospective participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic tests for GC. As miRNAs in blood are …

Expression And Regulatory Effects On Cancer Cell Behavior Of Nell1 And Nell2 In Human Renal Cell Carcinoma, Ritsuko Nakamura, Takeru Oyama, Ryosuke Tajiri, Atsushi Mizokami, Mikiko Namiki, Masaru Nakamoto, Akishi Ooi

Biology Faculty Publications

Neural epidermal growth factor-like like (NELL) 1 and 2 constitute a family of multimeric and multimodular extracellular glycoproteins. Although the osteogenic effects of NELL1 and functions of NELL2 in neural development have been reported, their expression and functions in cancer are largely unknown. In this study, we examined expression of NELL1 and NELL2 in renal cell carcinoma (RCC) using clinical specimens and cell lines. We show that, whereas NELL1 and NELL2 proteins are strongly expressed in renal tubules in non-cancerous areas of RCC specimens, their expression is significantly downregulated in cancerous areas. Silencing of NELL1 and NELL2 mRNA expression was …

Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …

Mechanisms Of Nanosecond Pulsed Electric Field (Nspef)-Induced Cell Death In Cells And Tumors, Stephen J. Beebe

Bioelectrics Publications

The evolution of pulse power technology from high power physics to biology and medicine places nanosecond pulsed electric fields (nsPEFs) in positions for in vitro and in vivo applications as non-ligand agonists that not only bypass plasma membrane receptors for induction of intracellular signaling pathways, but also bypass intracellular oncogenic impasses to induce cell death by regulated mechanisms. Based on work reviewed here, a likely scenario for cell and tumor demise includes nsPEF-induced permeabilization of the plasma membrane, Ca2+ influx, dissipation of the mitochondrial membrane potential, which is likely due to events beyond permeabilization of the inner mitochondrial membrane, cytochrome …

Investigation Of Gain-Of-Function Induced By Mutant P53, Catherine Vaughan

Theses and Dissertations

p53 is mutated in 50% of all human cancers, and up to 70% of lung cancer. Mutant p53 is usually expressed at elevated levels in cancer cells and has been correlated with a poor prognosis. Cancer cells that express mutant p53 show an increase in oncogenic phenotypes including an increase in growth rate, resistance to chemotherapeutic drugs, and an increase in motility and tumorigenicity to name a few. We have identified several genes involved in cell growth and survival that are upregulated by expression of common p53 mutants: NFκB2, Axl, and epidermal growth factor receptor (EGFR). The aim of this …

Pharmacologic Induction Of The Melanocotin 1 Receptor (Mc1r) Pathway Provides Protection Against Sunburn And Enhances Expression Of Antioxidant Enzymes In The Skin, Alexandra Amaro-Ortiz

Theses and Dissertations--Toxicology and Cancer Biology

The inability to tan properly after sun exposure strongly correlates with increased incidence of skin cancer. The melanocortin 1 receptor (MC1R) is a transmembrane Gs-coupled cell surface receptor found on epidermal melanocytes that transmits pro-survival and pro-differentiation signals mediated by the second messenger cAMP. Humans carrying loss-of-function polymorphisms in MC1R signaling exhibit higher incidences of skin cancers including melanoma.

This study focused on the physiologic effects of topical application of forskolin, an adenylate cyclase activator, in extension (Mc1r^e/e) K14-SCF animals, which model the fair-skinned UV-sensitive human. Twice daily application of the drug promoted accelerated pigmentation, increased skin darkening …

Inhalable Nanocomposites And Anticancer Agents For Cancer Therapy, Nathanael A. Stocke

Theses and Dissertations--Chemical and Materials Engineering

Cancer is designated as the leading cause of mortality worldwide and lung cancer is responsible for nearly 30% of all cancer related deaths. Over the last few decades mortality rates have only marginally increased and rates of recurrence remain high. These factors, among others, suggest the need for more innovative treatment modalities in lung cancer therapy. Targeted pulmonary delivery is well established for treating pulmonary diseases such as asthma and provides a promising platform for lung cancer therapy. Increasing local deposition of anticancer agents (ACAs) and reducing systemic exposure of these toxic moieties could lead to better therapeutic outcomes and …