Cancer Biology Commons^™

Leptin Protects Dendritic Cells From Chemically-Induced Cell Death, Yadira Arellano^, Jeffrey Charles Sivils, Kristine Marie Garza*

COURI Symposium Abstracts, Spring 2011

Leptin is a pleiotropic adipokine that exerts its physiological effects by binding to its receptor, which is expressed in many immune cells including T cells, macrophages, and dendritic cells. Multidrug resistance-associated protein (MRP) is a transmembrane transporter commonly associated with cancer cells conferring resistance to chemotherapy. The purpose of this study is to determine if leptin supersedes the cytotoxic death signal in dendritic cells. We further hypothesize that the mechanism underlying leptin protection is a result of over expression of MRPs. To address this question, we examined the effect of leptin on monocytes treated with cytotoxic drugs in vitro.  Bone …

Angiostatin Like Peptides In Milk: Potential Development For Dairy Products Capable Of Cancer Prevention, Erin Stefanutti

Master's Theses

For the past 40 years, antiangiogenic approaches have been of major interest in the development of methods to cure and prevent cancer. Angiogenesis, the development of blood vessels from pre-existing vascularization, is essential for cancer growth and spread of metastasis through the delivery of nutrients and oxygen essential to sustain the metabolic activity of these malignant cells. Blocking access to blood will cause cancerous cells to assume a dormant state creating inactive micro-tumors innocuous to the host. Angiostatin, the internal fragment of the fibrinolytic zymogen plasminogen, has shown great potential in reducing cancer size and number of metastatic colonies in …

Expression Of Genes Involved In A Radiation-Induced Bystander Effect, Hayley Furlong

Conference Papers

The radiation induced bystander effect is relevant to carcinogenesis, it may have significant implications for risk estimation for radiation exposure. Currently the mechanisms and cellular events are the subject of intense investigation, because little is known. It is thought that the radiation induced bystander response is due to a bystander factor secreted in the medium post irradiation. However the biological nature of this factor is currently unknown, but it is thought to be a protein of some sort that may be involved in the apoptosis cascade. Materials and Methods: HaCaT epithelial cells were used in this study and exposed to …

Modeling Measurement Error In Tumor Characterization Studies, Cyril Rakovski, Daniel J. Weisenberger, Paul Marjoram, Peter W. Laird, Kimberly D. Siegmund

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Etiologic studies of cancer increasingly use molecular features such as gene expression, DNA methylation and sequence mutation to subclassify the cancer type. In large population-based studies, the tumor tissues available for study are archival specimens that provide variable amounts of amplifiable DNA for molecular analysis. As molecular features measured from small amounts of tumor DNA are inherently noisy, we propose a novel approach to improve statistical efficiency when comparing groups of samples. We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon …

Bcc Skin Cancer Diagnosis Based On Texture Analysis Techniques, Shao-Hui Chuang, Xiaoyan Sun, Wen-Yu Chang, Gwo-Shing Chen, Adam Huang, Jiang Li, Frederic D. Mckenzie

Electrical & Computer Engineering Faculty Publications

In this paper, we present a texture analysis based method for diagnosing the Basal Cell Carcinoma (BCC) skin cancer using optical images taken from the suspicious skin regions. We first extracted the Run Length Matrix and Haralick texture features from the images and used a feature selection algorithm to identify the most effective feature set for the diagnosis. We then utilized a Multi-Layer Perceptron (MLP) classifier to classify the images to BCC or normal cases. Experiments showed that detecting BCC cancer based on optical images is feasible. The best sensitivity and specificity we achieved on our data set were 94% …

Comparative Study Of Long-And Short-Pulsed Electric Fields For Treating Melanoma In An In Vivo Mouse Model, Xinhua Chen, Xinmei Chen, Karl H. Schoenbach, Shusen Zheng, R. James Swanson

Bioelectrics Publications

A mouse melanoma model was set up with green fluorescent protein (GFP) expression in vivo. With the same energy, long- (1 ms) and short- (300 ns) pulsed electric fields were delivered to two melanomas injected into the same mouse. The tumor growth and green fluorescence were followed up to compare the different treatment efficacy of long and short pulses. After two days post treatment, short pulse-treated tumors showed a significantly lower tumor volume compared with long pulse-treated tumors (n=8, p

The Energy Landscape Analysis Of Cancer Mutations In Protein Kinases, Anshuman Dixit, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The growing interest in quantifying the molecular basis of protein kinase activation and allosteric regulation by cancer mutations has fueled computational studies of allosteric signaling in protein kinases. In the present study, we combined computer simulations and the energy landscape analysis of protein kinases to characterize the interplay between oncogenic mutations and locally frustrated sites as important catalysts of allostetric kinase activation. While structurally rigid kinase core constitutes a minimally frustrated hub of the catalytic domain, locally frustrated residue clusters, whose interaction networks are not energetically optimized, are prone to dynamic modulation and could enable allosteric conformational transitions. The results …

Analyzing The Role Of Αvβ8 Integrin In Glioma-Induced Angiogenesis, Jeremy H. Tchaicha

Dissertations and Theses (Open Access)

In this study we aimed to determine the functional roles for αvβ8 integrin in astrocytoma-induced angiogenesis. These studies originate from our analyses of αvβ8 integrin in developmental brain angiogenesis. αv and β8 knockout (KO) mice develop brain-specific vascular phenotypes that resemble vascular pathologies observed in the malignant astrocytoma, glioblastoma multiforme (GBM). Indeed, a murine xenograft model of astrocytoma suggested a role for the integrin in glioma-induced angiogenesis. Primary mouse astroglia were cultured from wild type (WT) and β8 KO neonates and were immortalized (HPV:E6/E7) and transformed (HRas:G12V). WT and β8 KO transformed astroglia were intracranially injected into athymic mice. WT …

Mcam/Muc18 Regulates Melanoma Progression By Modulating The Expression Of Id-1, Maya Zigler

Dissertations and Theses (Open Access)

The acquisition of the metastatic melanoma phenotype is associated with increased expression of the melanoma cell adhesion molecule MCAM/MUC18 (CD146). However, the mechanism by which MUC18 contributes to melanoma metastasis remains unclear. Herein, we stably silenced MUC18 expression utilizing lentivirus-incorporated small hairpin RNA, in two metastatic melanoma cell lines, A375SM and C8161, and conducted cDNA microarray analysis. We identified and validated that the transcriptional regulator, Inhibitor of DNA Binding-1 (Id-1), previously shown to function as an oncogene in several malignancies, was downregulated by 5.6-fold following MUC18 silencing. Additionally, we found that MUC18 regulated Id-1 expression at the transcriptional level via …

Ruthenium Complexes As Dna Photonucleases In Treatment Of Malignant Skin Carcinoma, Devi Kalyan Karumanchi

All Capstone Projects

A variety of Ruthenium complexes possessing terpyridine complexes as ligands in their coordination sphere have been investigated extensively as DNA photo nucleases in vitro. This work has led to the realization that compounds of Ruthenium bind to DNA purines and that the interactions are of an unprecedented bridging variety. Owing to the molar absorptivity of these complexes in the visible region, direct cleavage of duplex DNA by these complexes requires irradiation in the range of 400-500 nm.

Although the observation of DNA photo cleavage in vitro makes these systems good candidates for further investigation, it does not provide any information …

Dispersion Of Cytotoxic Properties Of Multi-Walled Carbon Nanotubes Suspended In Biological Solutions With Tween 80: Their Role In Enhancing Killing Effects Of Nanosecond Pulse Electric Fields On Tumor Cell Lines, Bhargava S. Kalluri

Biological Sciences Theses & Dissertations

The objective of this study was to determine whether multi-walled carbon nanotubes (MWCNTs) suspended in the surfactant Tween 80 give an additive killing effect on tumor cells when exposed to nsPEFs. In this study, MWCNTs were suspended in DMEM and RPMI with or without T80 (surfactant). The size distribution of MWCNTs suspended in these solutions was evaluated with a Delsa™ Nano Zeta potential and sub micro particle Size Analyzer and confirmed with microscopy. The cytotoxicity of MWCNTs dispersed in different concentrations of T80 was evaluated in PANC1 (Human pancreatic cancer cell line) and Jurkat cell lines (Human T-cell lymphoblast cell …

Cd277 Is A Negative Co-Stimulatory Molecule Universally Expressed By Ovarian Cancer Microenvironmental Cells, Juan R. Cubillos-Ruiz, Diana Martinez, Uciane K. Scarlett, Melanie R. Rutkowski, Yolanda C. Nesbeth, Ana L. Camposeco-Jacobs, Jose R. Conejo-Garcia

Dartmouth Scholarship

CD277, a member of the butyrophilin subfamily 3 (BTN3), shares significant sequence similarities and predicted common structural features with inhibitory B7-H4 and other members of the B7 superfamily. Here we report that CD277 is consistently expressed in stromal, as well as tumor cells in the microenvironment of human advanced ovarian carcinoma specimens, both of primary and metastatic origin. MHC-II+ myeloid antigenpresenting leukocytes (dendritic cells and macrophages) express significantly higher levels of surface CD277, compared to other tumor-infiltrating leukocyte subsets, and this expression is significantly up-regulated by multiple common tumor microenvironmental signals, including VEGF and CCL3. Most importantly, engagement of CD277 …

The Role Of Tyrosine Phosphorylation In The Functions Of The Tumor Suppressor Gprc5a, Xiaofeng Lin

Dissertations and Theses (Open Access)

The retinoic acid inducible G protein coupled receptor family C group 5 type A (GPRC5A) is expressed preferentially in normal lung tissue but its expression is suppressed in the majority of human non-small cell lung cancer cell lines and tissues. This differential expression has led to the idea that GPRC5A is a potential tumor suppressor. This notion was supported by the finding that mice with a deletion of the Gprc5a gene develop spontaneous lung tumors. However, there are various tumor cell lines and tissue samples, including lung, that exhibit higher GPRC5A expression than normal tissues and some reports by other …

Loss Of Gprc5a Enhances Survival In Normal And Malignant Lung Epithelial Cells By Eliciting Persistent Stat3 Activation Induced By Autocrine Lif, Yulong Chen

Dissertations and Theses (Open Access)

Signal transduction and activator of transcription 3 (Stat3) is activated by cytokines and growth factors in many cancers. Persistent activation of Stat3 plays important role in cell growth, survival, and transformation through regulating its targeted genes.

Previously, we found that mice with a deletion of the G protein-coupled receptor, family C, group 5, member a (Gprc5a) gene develop lung tumors indicating that Gprc5a is a tumor suppressor. In the present study, we examined he mechanism of Gprc5a-mediated tumor suppression. We found that epithelial cells from Gprc5a knockout mouse lung (Gprc5a^-/- cells) survive better in vitro in medium deprived …

Nherf1 – New Modifier Of Colorectal Cancer Progression, Yuho Hayashi

Dissertations and Theses (Open Access)

Colorectal cancer (CRC) develops from multiple progressive modifications of normal intestinal epithelium into adenocarcinoma. Loss of cell polarity has been implicated as an early event in this process, but the molecular players involved are not well known. NHERF1 (Na+/H+ Exchanger Regulatory Factor 1) is an adaptor protein with apical membrane localization in polarized epithelia. In this study, we tested our hypothesis that NHERF1 plays a role in CRC. We examined surgical CRC resection specimens for changes in NHERF1 expression, and modeled these changes in two- and three-dimensional (2D and 3D) Caco-2 CRC cell systems. NHERF1 had significant alterations from normal …

E2f1 And Tumor Suppression: The Role Of P21, Mirnas, And The Dna Damage Response, Regina L. Weaks

Dissertations and Theses (Open Access)

E2F1 is a multi-faceted protein that has roles in a number of important cellular processes including cell cycle regulation, apoptosis, proliferation, and the DNA damage response (DDR). Moreover, E2F1 has opposing roles in tumor development, acting as either a tumor suppressor or an oncogene depending on the context. In human cancer, E2F1 is often deregulated through aberrations in the Rb-p16INK4a-cyclin D1 pathway. In these studies we examined three mechanisms by which E2F1 might mediate its tumor suppressive properties: p21-induced senescence, miRNAs, and the DNA damage response. We found that E2F1 acts as a tumor suppressor in response to ras activation …

Role And Regulation Of Epha2 In Pancreatic Cancer, Pavel A. Levin

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cancer cause of death in the US. Gemcitabine is the first-line therapy for this disease, but unfortunately it shows only very modest benefit. The focus of the current study was to investigate the role and regulation of EphA2, a receptor tyrosine kinase expressed in PDAC, to further understand this disease and identify new therapeutic targets.

The role of EphA2 was determined in PDAC by siRNA mediated silencing. In combination with gemcitabine, silencing of EphA2 caused a dramatic increase in apoptosis even in highly resistant cells in vitro. Furthermore, EphA2 silencing was found …

Genetic Polymorphisms Of Cyp2e1, Gstp1, Nqo1 And Mpo And The Risk Of Nasopharyngeal Carcinoma In A Han Chinese Population Of Southern China, Xiuchan Guo, Yi Zeng, Hong Deng, Jian Liao, Yuming Zheng, Ji Li, Bailey Kessing, Stephen J. O'Brien

Biology Faculty Articles

Background

Southern China is a major area for endemic nasopharyngeal carcinoma (NPC). Genetic factors as well as environmental factors play a role in development of NPC. To investigate the roles of previously described carcinogen metabolism gene variants for NPC susceptibility in a Han Chinese population, we conducted a case-control study in two independent study population groups afflicted with NPC in Guangdong and Guangxi Provinces of southern China.

Methods

Five single nucleotide polymorphisms (SNPs) of CYP2E1-rs2031920, CYP2E1-rs6413432, GSTP1-rs947894, MPO-rs2333227 and NQO1-rs1800566 were genotyped by PCR-based RFLP, sequencing and TaqMan assay in 358 NPC cases and 629 …

Release Of Hmgb1 In Response To Pro-Apoptotic Glioma Killing Strategies: Efficacy And Neurotoxicity, Marianela Candolfi, Kader Yagiz, David Foulad, Gabrielle Alzadeh, Matthew Tesarfreund, Akm Ghulam Muhammad, Mariana Puntel, Kurt Kroeger, Chunyan Liu, Sharon Lee, James Curtin, Gwendalyn D. King, Jonathan Lerner, Katsuaki Sato, Yohei Mineharu, Weidong Xiong, Pedro R. Lowenstein, Maria Castro

Articles

Purpose In preparation for a Phase I clinical trial utilizing a combined cytotoxic/immunotherapeutic strategy using adenoviruses expressing Flt3L (Ad-Flt3L) and thymidine kinase (Ad-TK) to treat glioblastoma (GBM), we tested the hypothesis that Ad-TK+GCV would be the optimal tumor killing agent in relation to efficacy and safety when compared to other pro-apoptotic approaches. Experimental Design and Results The efficacy and neurotoxicity of Ad-TK+GCV was compared with Ads encoding the pro-apoptotic cytokines (TNF-α, TRAIL, FasL), alone or in combination with Ad-Flt3L. In rats bearing small GBMs (day 4), only Ad-TK+GCV or Ad-FasL improved survival. In rats bearing large GBMs (day 9), the …

Regulation Of Pim1 Under Hypoxia In Prostate Cancer, Eva Sahakian

Loma Linda University Electronic Theses, Dissertations & Projects

A defining characteristic of solid tumors is the capacity to divide and spread under conditions of nutrient deprivation and limited oxygen availability. These microenvironmental stresses arise from structural abnormalities in tumor vessels that lead to aberrant microcirculation. Hypoxia acts as a physiological “selection pressure” in the progression of cancer by activating pathways and enhancing the expression of specific genes in tumor cells which eventually diminish their apoptotic potential. Ultimately, hypoxic microenvironment functions as a “stress factor”, selecting cells with the ability to survive and divide under anoxic conditions. The members of the PIM family of cytoplasmic serine threonine kinases are …