Life Sciences Commons^™

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …

Treatment Of Canine Transmissible Venereal Tumor Using L-Asparaginase, Prednisone, And Surgery In A Clinical Chemotherapy-Resistant Case, Daniella Matos Da Silva, Mhayara Samile De Oliveira Reusing, Aline Iara Franciosi, Carlos Edvardo Penner Belo, Kamilá Alcala Gonçalves, Renato Silva De Sousa, Simone Domit Guérios

Turkish Journal of Veterinary & Animal Sciences

A 4-year-old intact female dog was presented with a vaginal transmissible venereal tumor (TVT) that had clinically developed multidrug resistance to vincristine, vinblastine, and doxorubicin. Complete remission was obtained with combined-modality therapy with surgery, L-asparaginase, and prednisone.

Rna Interference Targeting Glucose-Regulated-Protein 78 Induces Hepg2 Cell Apoptosis, Brittany Blackman

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a complex genetic disease that is driven by genetic mutations resulting in chronic, inappropriate cell proliferation. Many current cancer therapies lack specificity towards tumor tissues, ultimately leading to adverse side effects and limited clinical efficacy. Recently, selective cancer cell therapy has examined a well-characterized cell surface marker that is preferentially expressed on tumor cells. The over-expression of an endoplasmic reticulum chaperone protein, 78-kDa glucose-regulated-protein (GRP78), has been observed on the surface of cancer cells, but not on normal tissues. By selectively targeting GRP78 with short-interfering RNA (siRNA), potent GRP78 silencing is anticipated by the RNA interference (RNAi) pathway. …

The Glucose Signaling Network In Yeast, Jeong-Ho Kim, Adhiraj Roy, David Jouandot Ii, Kyu Hong Cho

Faculty Publications

Background

Most cells possess a sophisticated mechanism for sensing glucose and responding to it appropriately. Glucose sensing and signaling in the budding yeast Saccharomyces cerevisiae represent an important paradigm for understanding how extracellular signals lead to changes in the gene expression program in eukaryotes.

Scope of review

This review focuses on the yeast glucose sensing and signaling pathways that operate in a highly regulated and cooperative manner to bring about glucose-induction of HXT gene expression.

Major conclusions

The yeast cells possess a family of glucose transporters (HXTs), with different kinetic properties. They employ three major glucose signaling pathways—Rgt2/Snf3, …

Cellular Uptake Mechanism Of Paclitaxel Nanocrystals, Iris K. Archer, Zhaohui Wang, Tonglei Li

The Summer Undergraduate Research Fellowship (SURF) Symposium

Therapeutic options for metastasized human cancer in current practice remain limited and, sadly, there is no cure for metastatic cancer. The typical approach, chemotherapy, has both low efficacy due to poor drug solubility, and cytotoxic side effects to healthy tissue when delivered indiscriminately. To address both of these issues, we are pursuing the use of nanocrystal formulations of current chemotherapeutic agents as delivery platforms. Herein, we have studied cellular uptake mechanisms in cancer cells of nanocrystals of a chemotherapeutic agent, paclitaxel. Our goal in this study is to determine whether the nanocrystals can be taken up via endocytosis, especially when …

Critical Parameters Influencing Chemical-Induced Apoptosis In Human Lymphoid Cell Lines, Matthew Ben Cook, Dr. Kim L. O'Neill

Journal of Undergraduate Research

In 2005, the International Agency for Research on Cancer (IARC) reported that an estimated 10.9 million new cases of cancer were diagnosed in the year 2002 (for a total of 24.6 million persons currently living with cancer) and that 6.7 million deaths were attributable to cancer[1]. Around 300,000 new cases of leukemia, with 222,000 new deaths, were also reported. In many cases, the occurrence of cancer in an individual can be attributed to lifestyle choices, such as smoking, diet, exercise, work environment, etc. However, there are also genetic contributors to cancer.

Induced Modulation Of Membrane Polyunsaturated Fatty Acids Possibilities For Chemotherapeutic Intervention In Cancer, Christopher Trimble, Dr. Byron Murray

Journal of Undergraduate Research

Polyunsaturated fatty acids have several integral functions in the human body. In addition to playing essential structural, metabolic, and cell-signaling roles, fatty acids may be involved in the onset of cancer. The fatty acid profile of a cell, which is defined as the relative ratios of individual fatty acids as compared to the entire cellular fatty acid content, is known to play a direct role in controlling gene expression and the protection of cells from oxidative damage caused by bodily inflammatory responses. It is known that cancer cells have modulated membrane fatty acid profiles, differing gene expression, and increased inflammatory …

Protein Kinase Ck2 Phosphorylates And Activates P21-Activated Kinase 1, Yong Jae Shin, Yong-Bae Kim, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Activation of the p21-activated kinase 1 (PAK1) is achieved through a conformational change that converts an inactive PAK1 dimer to an active monomer. In this paper, we show that this change is necessary but not sufficient to activate PAK1 and that it is, rather, required for CK2-dependent PAK1S223 phosphorylation that converts a monomeric PAK1 into a catalytically active form. This phosphorylation appears to be essential for autophosphorylation at specific residues and overall activity of PAK1. A phosphomimetic mutation (S223E) bypasses the requirement for GTPases in PAK1 activation, whereas the constitutive activity of the PAK1 mutant (PAK1H83,86L), postulated to mimic GTPase-induced …

The Effect Of Isoflavone And Selenium Diets On Body Composition (Biochemical Responses To Phytoestrogen And Selenium Diets In Noble Rats Relating To Reduced Prostate Cancer Risk), Jessica Tolman, Dr. Merrill J. Christensen

Journal of Undergraduate Research

The intent of the following research was to fulfill the thesis requirements for the BYU Honors Program, the following report is complied from excerpts from my Honors Thesis. The results were presented at the 8th International Symposium on Selenium in Biology and Medicine. At the beginning of this project I focused my interests on the effect of isoflavone and selenium on body composition. I later used these findings and the effect of isoflavone and selenium on hormone serum levels to determine the effect of isoflavone and selenium on prostate cancer risk.

Curcumin-Free Turmeric Exhibits Anti-Inflammatory And Anticancer Activities: Identification Of Novel Components Of Turmeric (Abstract), Bharat Aggarwal, Wei Yuan, Shiyou Li, Subash C. Gupta

NCPC Publications and Patents

Abstract attached

Hypothesis Driven Single Nucleotide Polymorphism Search (Hydn-Snp-S), Rebecca J. Swett, Angela Elias, Jeffrey A. Miller, Gregory E. Dyson, G. AndréS Cisneros

Chemistry Faculty Research Publications

The advent of complete-genome genotyping across phenotype cohorts has provided a rich source of information for bioinformaticians. However the search for SNPs from this data is generally performed on a study-by-study case without any specific hypothesis of the location for SNPs that are predictive for the phenotype. We have designed a method whereby very large SNP lists (several gigabytes in size), combining several genotyping studies at once, can be sorted and traced back to their ultimate consequence in protein structure. Given a working hypothesis, researchers are able to easily search whole genome genotyping data for SNPs that link genetic locations …

Effect Of Selenium On The Expression Of The Androgen Receptor And Nuclear Factor Kappa-B In Human Prostate Cancer Cells, Daniel Tandberg, Dr. Merrill J. Christensen

Journal of Undergraduate Research

Selenium has been established as a promising chemopreventive element for prostate cancer. Several different mechanisms have been studied to delineate selenium’s anti-cancer effect, but the exact target and mechanism has yet to be clearly defined. Previous studies have established an inhibitory relationship between the nuclear factor kappa B (NF-κB) and selenium, as well as the Androgen Receptor (AR) and selenium in human LNCap cells. Both NF-κB and AR are constituently active during prostate cancer development, and their deactivation by selenium might be one of the mechanisms by which selenium acts as a chemopreventative agent. The purpose of our research is …

The Creation Of Α2nc1 Transgenic Drosophila Melanogaster, Jordan Olberding

Mahurin Honors College Capstone Experience/Thesis Projects

The α2 isoform of collagen IV’s noncollagenous 1 domain (α2NC1 or canstatin) has shown promise as an anti-cancer molecule, possessing both angiostatic and pro-apoptotic properties. This work aims to further the knowledge of α2NC1 by conducting a truly in vivo study in which the Gal4-induced endogenous overexpression of α2NC1 in Drosophila melanogaster will be used to assess the effects of α2NC1 upon normal development as well as tumorigenesis. To this end, transgenic fly lines capable of overexpressing α2NC1 were created. Initial overexpression studies indicated no developmental phenotype was caused by abundance of α2NC1. However, future overexpression studies in which α2NC1 …

Cancer’S Red Light To The Immune System?, Amanda Enz, Dr. Kim O'Neill

Journal of Undergraduate Research

The field of cancer research is extensive, and there are many avenues being explored into how cancer works inside the body and what we can do to prevent and cure this disease. I chose to look at the way the body’s immune system interacts with different types of cancer cells. I specifically looked at a cell in the human immune system known as a macrophage. The macrophage’s job is to attack foreign invaders by engulfing, or eating them. My question focused on how exactly cancer is sometimes able to evade these macrophages, which allows it to proliferate throughout the body. …

Cancer And The Immune System: A Study Of Cytokine Communication With Macrophages, Charles Daniel Knechtel, Dr. Kim O'Neill

Journal of Undergraduate Research

Macrophages are a part of the early immune system that interacts with abnormal and foreign cells in your body. They are a non-specific defense system that engulfs foreign cells or stimulates other immune system cells to respond. We know they can play a role in fighting cancer, or promoting it, but we don’t fully understand how. According to Frontiers in Bioscience May 2008, “At late stages tumor-associated macrophages are known to produce molecules directly promoting tumor growth, invasion and metastasis….however, if properly activated, macrophages may control initial tumor development”(Nardin, A., Astado, J. 2008). Cytokines are small signaling molecules that play …

Development Of Tools To Assess The Effects Of Lunasin On Normal Development And Tumor Progression In Drosophila Melanogaster, Gillian E. Jones

Masters Theses & Specialist Projects

Soy contains many bioactive molecules known to elicit anti-cancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells while having no cytotoxic effect on non-tumorigenic or established cancer cell lines. In this study we attempt to understand the developmental effects of Lunasin overexpression in vivo and create reagents that will help us understand Lunasin’s anti tumorigenic effects in an intact organism. cDNA encoding lunasin and EGFP-lunasin were cloned into pUAST and microinjected into Drosophila embryos. Tissue-specific overexpression of EGFP-Lun in the resulting transgenic lines was accomplished by crossing transgenics to various GAL4 driver lines. …

The Importance Of Epigenetic Phenomena In Regulating Activity Of The Genetic Material, Sin Chan

Senior Honors Projects

Genetics has taught us that genes are represented as discrete sequences within a larger DNA molecule found embedded within the chromosomes of a living cell. Collectively these chromosomes and their associated genes carry all of the instructions for life. Until recently, the prevailing thought has been that genes are destiny in the life of an individual since the genes carry the information that determines the general traits and characteristics associated with that individual. The relatively recent understanding of mechanisms that underlie epigenetic phenomena has led to a rethinking of this concept. Epigenetics describes cellular mechanisms that explain how two individuals …

Targeted Delivery Of Ribonucleotide Reductase Sirna In Cancer Cells Via Gold Nanoplexes, John Caleb Grenn

Honors Theses

Cancer treatment has much room for improvement, as therapies today cannot differentiate well between what cells are part of a tumor and which are healthy. Our research involves targeting cancer cells by their overexpressed folic acid receptors, and delivering small interfering RNAs (siRNAs) to silence genes crucial to cell survival by the RNA interference gene knockdown pathway. By using Gaussia luciferase siRNA (siGLuc) as a model for cell delivery, we have been able to test our ability to deliver siRNA via a gold nanoparticle delivery system, also developed in our lab. We also synthesized ribonucleotide reductase siRNA (siRRM2), which will …

Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced disease. Although rare and less than 2% of all breast cancer, IBC is responsible for up to 10% of all breast cancer deaths. Despite the name, very little is known about the role of inflammation or immune mediators in IBC. Therefore, we analyzed blood samples from IBC patients and non-IBC patients, as well as healthy donor controls to establish an IBC-specific profile of peripheral blood leukocyte phenotype and function of T cells and dendritic cells and serum inflammatory cytokines.

Emerging evidence suggests that host factors in the microenviromement …

The Micronutrient Profile Of The Typical American Diet Enhances Colorectal Carcinogenesis, Stephany Del Carmen Perez Monsanto

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

The typical Western dietary pattern is characterized by the consumption of energy-dense, nutrient-poor foods and has been linked to increased risk of colorectal cancer (CRC). Our research group previously developed the total Western diet (TWD) that emulates typical human dietary intakes of macro- (carbohydrates, proteins, and fats) and micronutrients (vitamins and minerals) on an energy density basis for rodents. In the present study, we sought to determine the impact of TWD on biomarkers of metabolic syndrome and obesity in comparison to a commercial 45% fat diet used for models of diet-induced obesity (DIO diet) and the standard basal AIN93G diet, …

The Characterization Of Aunp-Pei Conjugates For Sirna Delivery To Cancer Cells, Albert J. Nosser

Honors Theses

Cancer is one of the leading causes of death for people in the United States. Despite the numerous cancer treatments available, many of these chemotherapy treatments cause negative side effects such as hair and weight loss. With this in mind, in the past 15 years, researchers have discovered a mechanism known as RNA interference, which can be used to control certain genes and their activity. This mechanism is based on the function of siRNA molecules, which can be inserted into cells.(12) These siRNA molecules can be manipulated to target and eliminate specific cancer cells. However, these siRNA molecules are normally …

Clinical And Molecular Models Of Glioblastoma Multiforme Survival, R. Piccolo Stephen, J. Frey Lewis

Faculty Publications

Glioblastoma multiforme (GBM), a highly aggressive form of brain cancer, results in a median survival of 12–15 months. For decades, researchers have explored the effects of clinical and molecular factors on this disease and have identified several candidate prognostic markers. In this study, we evaluated the use of multivariate classification models for differentiating between subsets of patients who survive a relatively long or short time. Data for this study came from The Cancer Genome Atlas (TCGA), a public repository containing clinical, treatment, histological and biomolecular variables for hundreds of patients. We applied variable-selection and classification algorithms in a cross-validated design …

Changes In Membrane Physical Properties During Chemotherapy, Dr. John Bell

Journal of Undergraduate Research

Many chemotherapeutic agents treat cancer by inducing programmed cell death (apoptosis) in the tumor. One of the consequences of apoptosis is changes in the physical properties of the cell membrane. Some of these changes are important for other phagocytic cells to recognize and remove the dying cells thereby preventing an inflammatory response. However, other physical changes convert the membrane from its normal state of resistance to hydrolytic attack by enzymes present in the blood to a state of susceptibility. If this susceptibility precedes removal of the apoptotic cells by phagocytes, a harmful inflammatory response could potentially occur. Whether cells become …

Metabolic Rescue Of “Glucose Addicted” Cancer Cells In Vitro, Paolo Vignali

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Transformations in the glycolytic metabolism of neoplasms modulate their robust cellular division. This characteristic leads to an “addiction” to glucose for continued proliferation and viability. This study investigated whether glucose metabolites could rescue cellular viability in glucose-starvation conditions, a model of the inter-tumoral nutrient-deficient environment. Findings illustrated potential cellular viability rescue with pyruvate addition in glucose-deprived conditions, yet the same potential was not observed with lactic acid, a metabolite that exists at characteristically high concentrations within the intertumoral microenvironment. These results could implicate a predominance of certain metabolic pathways in nutrient-starved cells. Molecular transport capacities across plasma membranes are tied …

Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary Anne Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott

Department of Biochemistry: Faculty Publications

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.

Defining The Mechanism Of Enhanced Cellular Invasion Induced By Mechanical Stimulation, Snehal Sunil Ozarkar

Wayne State University Theses

Metastasis is a multistep process driven by various biochemical and mechanical factors, which eventually leads to formation of secondary tumors. The tumor mass is surrounded by basement membrane (BM) and stroma made of various extracellular matrix (ECM) proteins. During metastasis tumor cells disseminate from the primary tumor, breach the BM, invade the stroma, travel through blood and lymph and colonize tissues distant from the primary tumor. Formation of secondary tumors by metastasis is a leading cause of death in cancer patients. Even though plenty of research has been focused on biochemical factors affecting metastasis, information on role of mechanical factors …

Effect Of Folate Deficiency And Aging On Mtor Signaling Network In The Liver Of Dna Polymerase B Haploinsufficient Mice, Amanda Lynn Arrabi

Wayne State University Theses

EFFECT OF FOLATE DEFICIENCY AND AGING ON mTOR SIGNALING NETWORK IN THE LIVER OF DNA POLYMERASE B HAPLOINSUFFICIENT MICE

by

AMANDA ARRABI

August 2013

Advisor: Dr. Ahmad R. Heydari

Major: Nutrition and Food Science

Degree: Masters of Science

The interaction between the dietary nutrients and the human genome causes some alterations in the molecular pathways that could significantly impact the development of cancer. The main approach to such concerns is to closely observe how the diet modifies the gene expressions that control several cellular processes in the human body. Folate deficiency (FD) has established an important role in modulating the …

The Effect Of Thymidylate Synthase Inhibitors On Bone Marrow Derived Cells In The Intestinal Tumor Microenvironment, Grishma Acharya

Theses and Dissertations

Tumors have come to be known as independently functioning complex organs consisting of cancer cells coexisting with a heterogeneous mixture of host-derived non-neoplastic cells that form the tumor stroma. Tumor survival, progression, and metastasis depend on multiple close interactions between the cancer cells and the tumor stromal cells. These tumor stromal cells are mainly bone marrow derived cells (BMDCs) that are recruited to the primary tumor and sites of metastasis by a variety of signals secreted by the cancer cells. Because of the close interaction between the tumor and the tumor stroma, we propose that tumor stromal cells play an …

Computational Approaches For Structure Based Drug Design And Protein Structure-Function Prediction, Sai Lakshmana Kumar Vankayala

USF Tampa Graduate Theses and Dissertations

This dissertation thesis consists of a series of chapters that are interwoven by solving interesting biological problems, employing various computational methodologies. These techniques provide meaningful physical insights to promote the scientific fields of interest. Focus of chapter 1 concerns, the importance of computational tools like docking studies in advancing structure based drug design processes. This chapter also addresses the prime concerns like scoring functions, sampling algorithms and flexible docking studies that hamper the docking successes. Information about the different kinds of flexible dockings in terms of accuracy, time limitations and success studies are presented. Later the importance of Induced fit …

Cancer Immunotherapy Treatments, Shifra Sadowsky

The Science Journal of the Lander College of Arts and Sciences

Cancer is the second leading cause of death in American, with over half a million deaths from cancer reported in 2009. Cancer chemotherapy treatments were developed in the nineteen hundreds and remain the backbone of current treatments; however, they have some limitations. New immunotherapy cancer treatments, where biologic agents are given to patients to influence the body’s natural immune response, are being researched. Among these immunotherapy treatments are co-inhibition blockade of T cells, and combination blockade treatments together with chemotherapy treatment. This review will discuss T cell activation and the role of T cell coinhibitors such as CTLA-4 and PD-1 …