Cancer Biology Commons^™

Effects Of A Particular Heptapeptide On The Ifn-Α-Sensitive Cml Cells, Fulan Yang, Fangzhi Chen, Xinxing Wan, Xi Zhou, Meijuan Zhou, Hanchun Chen, Junjiang Fu, Dianzheng Zhang

PCOM Scholarly Papers

Abstract: Using the phage display biopanning technique, we have previously identified a heptapeptide KLWVIPQ which specifically bind to the surface of the IFN-α sensitive but not the IFN-α-resistant CML cells. The effects of this heptapeptide to the IFN-α-sensitive CML cells were investigated in the present study. IFN-α-sensitive KT-1/A3 and IFN-α-resistant KT-1/A3R CML cells were transfected by pEGFP KLWVIPQ expression vector and/or induced by IFN-α. WST-1 cell proliferation assay, flow cytometry and western blotting were performed to determine the effects of this heptapeptide and/or IFN-α on CML cells. The viability of the KT-1/A3 cells w as inhibited and apoptosis was induced …

Investigating The Role Of Cholesterol Metabolism And Synthesis In Metastasis And Radiation Response In Aggressive Subtypes Of Breast Cancer, Adam Wolfe

Dissertations & Theses (Open Access)

Aggressive breast cancers, triple-negative breast cancer (TNBC) and inflammatory breast cancer (IBC), metastasize at a high rate and are notoriously resistant to standard treatments. Research has shown diets high in cholesterol increase the incidence of aggressive breast cancers and pre-clinical research has shown cholesterol can fuel the growth of breast cancer in vivo. Studies at MD Anderson have shown that IBC patients taking cholesterol lowering drugs, statins, have improved survival outcomes, and also statins can improve the response to radiation in vitro. Furthermore, statins have been shown to target the cells with stem like-properties called cancer stem cells (CSCs) which …

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Zijian Xie

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Joseph I Shapiro MD

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

The Role Of The Pleckstrin Homology Domain-Containing Protein Ckip-1 In Activation Of P21-Activated Kinase 1 (Pak1), Yong-Bae Kim, Yong Jae Shin, Adhiraj Roy, Jeong-Ho Kim

Biochemistry and Molecular Medicine Faculty Publications

Upon growth factor stimulation, PAK1 is recruited to the plasma membrane and activated by a mechanism that requires its phosphorylation at S223 by the protein kinase CK2. However, the upstream signaling molecules that regulate this phosphorylation event are not clearly defined. Here, we demonstrate a major role of the CK2α-interacting protein CKIP-1 in activation of PAK1. CK2α, CKIP-1 and PAK1 are translocated to membrane ruffles in response to the epidermal growth factor (EGF), where CKIP-1 mediates the interaction between CK2α, and PAK1 in a PI3K-dependent manner. Consistently, we observe that PAK1 mediates phosphorylation and modulation of the activity of p41-Arc, …

Targeting Neddylation Induces Dna Damage And Checkpoint Activation And Sensitizes Chronic Lymphocytic Leukemia B Cells To Alkylating Agents, C Paiva, J C. Godbersen, A Berger, J R. Brown, A V. Danilov

Dartmouth Scholarship

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 …

Selenoprotein P Influences Colitis-Induced Tumorigenesis By Mediating Stemness And Oxidative Damage., C. W. Barrett, V. K. Reddy, S. P. Short, A. K. Motley, M. K. Lintel, A. M. Bradley, T. Freeman, J. Vallance, W. Ning, B. Parang, Shenika Poindexter Toliver

Faculty and Staff Publications

Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1). Target tissues also produce SEPP1, which is thought to possess an endogenous antioxidant function. Here, we have shown that mice with Sepp1 haploinsufficiency or mutations that disrupt either the selenium transport or the enzymatic domain of SEPP1 exhibit increased colitis-associated carcinogenesis as the result of increased genomic instability and …

Targeting Il13ralpha2 Activates Stat6-Tp63 Pathway To Suppress Breast Cancer Lung Metastasis, Panagiotis Papageorgis, Sait Ozturk, Arthur W. Lambert, Christiana M. Neophytou, Alexandros Tzatsos, Chen K. Wong, Sam Thiagalingam, Andreas I. Constantinou

Anatomy and Regenerative Biology Faculty Publications

Introduction

Basal-like breast cancer (BLBC) is an aggressive subtype often characterized by distant metastasis, poor patient prognosis, and limited treatment options. Therefore, the discovery of alternative targets to restrain its metastatic potential is urgently needed. In this study, we aimed to identify novel genes that drive metastasis of BLBC and to elucidate the underlying mechanisms of action.

Methods

An unbiased approach using gene expression profiling of a BLBC progression model and in silicoleveraging of pre-existing tumor transcriptomes were used to uncover metastasis-promoting genes. Lentiviral-mediated knockdown of interleukin-13 receptor alpha 2 (IL13Ralpha2) coupled with whole-body in vivo bioluminescence imaging was …

Numerical Simulation Of Terahertz Wave Interaction With Breast Cancer Tumor Tissue Sections, Abayomi Omotola Omolewu

Graduate Theses and Dissertations

This thesis presents numerical simulation of terahertz (THz) wave interaction with breast cancer tumor tissue sections. The obtained results are expressed in THz images of heterogeneous material that mimics the excised breast cancer tissue sections. The finite-element software package ANSYS High Frequency Structural Simulator (HFSS) was used in this work. HFSS is a full wave frequency domain three-dimensional (3D) electromagnetic simulation package. In this work, four breast cancer tissue models based on pathology images were simulated and images of the models were obtained at 1 THz. An incident Gaussian beam was raster scanned over tissue model configurations and the reflected …

Effect Of Sirna Pre-Exposure On Subsequent Response To Sirna Therapy, Hamidreza Montazeri Aliabadi, Parvin Mahdipoor, Cezary Kucharski, Nicole Chan, Hasan Uludag

Pharmacy Faculty Articles and Research

PURPOSE. An alternative cancer therapy based on RNA interference (RNAi) has shown considerable promise but the possibility of resistance development is not known. This study explored the possibility of therapeutic resistance against siRNA nanoparticles in human cancer cells. METHODS. Two approaches to siRNA treatment were undertaken using lipid-modified polyethylenimines, a single high concentration (shock) and repeated increasing concentrations (gradual). The targets were Mcl-1, RPS6KA5 and KSP in MDA-MB-435 cells. RESULTS. There was no evidence of resistance development in shock-treated cells, while the decrease in mRNA levels of targeted proteins was not as robust in naïve cells in gradual treatment. However, …

The Lung Microenvironment Influences The Metastatic Behaviour Of Breast Cancer Cells In An Innovative 3d Ex Vivo Pulmonary Metastasis Model, Matt M. Piaseczny

Electronic Thesis and Dissertation Repository

Lung metastasis remains a leading cause of death in breast cancer patients. This study established an innovative 3D ex vivo pulmonary metastasis assay (PuMA) to test the hypothesis that the lung microenvironment promotes metastatic behaviour of whole population and stem-like ALDH^hiCD44⁺ breast cancer cells. Following in vivo delivery of breast cancer cells to mice, lungs were excised, maintained in culture and imaged to observe breast cancer growth over time. We observed metastatic progression of breast cancer cells in the PuMA, most notably of ALDH^hiCD44⁺ cells which progressed rapidly from single cells to multicellular colonies …

Role Of Metabolic Shifts In Protection From Mutation Damage: Characterizing Mitochondrial Membrane Potential In C. Elegans Gas-1 Mutants, Lauren S. Muñoz-Tremblay

PSU McNair Scholars Online Journal

Many terminal human diseases are caused by mutations affecting mitochondrial functioning. Mitochondria are essential organelles responsible for producing cellular energy, adenosine triphosphate (ATP) via oxidative phosphorylation (OXPHOS) at mitochondrial electron transport chains (ETC). Proper ETC functioning relies on maintenance of the electrochemical gradient essential for energy production, known as mitochondrial membrane potential (ΔψM). The inner mitochondrial membrane is the site of the ETC and is most closely in contact with the enzymatic processes occurring within the mitochondrial matrix. Mutations affecting protein components of the ETC are especially troublesome for organelle health. ETC mutants commonly express altered ΔψM, as well as …

Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke

Electronic Thesis and Dissertation Repository

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H₂S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H₂S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H₂S-specific probes, it was found that H₂S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H₂S-producing enzymes could reduce the proliferation, metabolism …

Klf4-Sqstm1/P62-Associated Prosurvival Autophagy Contributes To Carfilzomib Resistance In Multiple Myeloma Models., Irene Riz, Teresa S. Hawley, Robert G. Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. Because of a high rate of immunoglobulin synthesis, the endoplasmic reticulum of MM cells is subjected to elevated basal levels of stress. Consequently, proteasome inhibitors, which exacerbate this stress by inhibiting ubiquitin-proteasome-mediated protein degradation, are an important new class of chemotherapeutic agents being used to combat this disease. However, MM cells still develop resistance to proteasome inhibitors such as carfilzomib. Toward this end, we have established carfilzomib-resistant derivatives of MM cell lines. We found that resistance to carfilzomib was associated with elevated levels of prosurvival autophagy, and Kruppel-like factor 4 …

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio

Arthur M. Mercurio

The role of ERbeta in prostate cancer is unclear, although loss of ERbeta is associated with aggressive disease. Given that mice deficient in ERbeta do not develop prostate cancer, we hypothesized that ERbeta loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERbeta is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERbeta is important for tumor formation. ERbeta transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. …

A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio

Arthur M. Mercurio

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.

Light Microscopy Reflection Focusing Cells And Coverglass, George Mcnamara

George McNamara

Light Microscopy Reflection Focusing Cells and Coverglass 20150520Wed

Many light microscopes have the capability of using camera based brightfield, phase contrast, or fluorescence to find the most contrasty specimen focus. When I worked for UIC (1992-1997) we offered this with a combination of Ludl MAC2000 controller, Z-drive, video card thingy, and video camera (most customers at the time used analog video cameras).

Many automated light microscopes now have clever -- and pricey -- autofocus systems based on an NIR LED structured illumination reflecting light off the bottom of the coverglass.

I encourage a simpler approach - my hardware details are …

Analyzation Of Metabolic Reprogramming In Drug-Resistant Mcf-7 Cells, Derick Han, Ho Leung, Andrew Vo

Student Scholar Symposium Abstracts and Posters

The Warburg effect states that cancer cells mainly receive their energy from anaerobic glycolysis. Thus, mitochondria play a different role in the metabolism of cancer cells as opposed to normal, healthy cells. In chemotherapy, there is always a chance of the cancer regressing. Making drug-resistant cancer cells to analyze their metabolism may change how cancer is treated. This study aimed to create drug-resistant MCF-7 cell lines with doxorubicin in order to determine the metabolic changes that have occurred in the process of becoming resistant to drug treatments.

Exploring Egr-1 As A Master Regulator Of Prostate Field Cancerization, Kristin Gabriel, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

Field cancerization denotes the presence of molecular aberrations (genetic, epigenetic, biochemical) in structurally intact cells residing in histologically normal tissues adjacent to tumors. Markers of field cancerization in prostate tissues have the potential to improve the clinical management of this malignancy through their potential to act as indicators of early disease and to serve as molecular targets for early intervention. However, for this, a detailed understanding of the functional pathways underlying field cancerization is necessary. We have recently identified four protein markers of prostate field cancerization, i.e. the key transcription factor early growth response 1 (EGR-1), the lipogenic enzyme fatty …

Prostate Field Cancerization – Thinking Outside The Tumor, Dor Shoshan

Student Scholar Symposium Abstracts and Posters

Analysis of tumor adjacent tissue is assumed to reveal a temporal record of molecular pathways that define oncogenesis. The present study determines expression of the key transcription factor and potential marker of field cancerization early growth response 1 (EGR-1) in human prostate tissues derived from prostatectomies and biopsies. Expression was detected using immunofluorescence and quantified using ImageJ software. Accordingly, EGR-1 expression was similar in cancerous and in histologically normal adjacent tissues from prostatectomy and biopsy specimens. EGR-1 could be exploited as pre-surgical disease indicator in false negative biopsies, identify areas of repeat biopsy, and add molecular information to surgical margins.

Clinical Applications Of A Combination Chemotherapy Using 8-Chloro Camp And 8-Chloro Adenosine, Erik Munoz, Andrea Saich, Andrew Cox, Yu-An Peter Chang

Student Scholar Symposium Abstracts and Posters

Dr. Cho-Chung from the NIH first thought to use halogenated cAMP derivatives as competitive inhibitors of cAMP to slow down cancer cell mitosis. While the iodine and bromine substituted versions showed very little therapeutic actions, 8-Chloro cAMP has been shown to have strong anti-cancer effects. This has been shown in the phase II clinical trials this drug has undergone. However, these trials have had issues with solubility and toxicity. The drug is similar to vitamin C and is excreted quickly. Scientists tried to overcome this by using a peristaltic pump to give patients a continuous dosage, but this proved too …

Effect Of Curcumin Analog Ca27 On Androgen Receptor Translocation In Prostate Cancer Cells, Lijah Vann Gardner

Student Scholar Symposium Abstracts and Posters

The androgen receptor (AR) plays an essential role in promoting the development and progression of metastatic prostate cancer and represents an important molecular target for therapeutic intervention. We have recently described a series of synthetic analogs of the natural product diferuloylmethane (curcumin), some of which induce the down-regulation of AR expression in prostate cancer cells by an as yet largely unknown mechanism of action. While such analogs may in the long term be lead structures for the development of therapeutic drugs, we hypothesize here that they represent ideal molecular probes to identify the mechanism(s) of action for AR down-regulation. We …

Effect Of Cmvil-10 On Exosome Production By Human Breast Cancer Cells, Susanna N. Basappa

Undergraduate Honors Theses

Human cytomegalovirus (HCMV) is a ubiquitous virus that infects 70-90% of the general population, primarily the immunocompromised, but has been implicated in several forms of cancer, including breast cancer. Breast cancer is the second leading cause of cancer related deaths in women in North America, usually from metastasis. Exosomes are 30-100nm vesicles produced by most cells which carry protein and RNA to cells in their microenvironment. The aim of this study is to investigate the impact of HCMV-infection of a secreted viral cytokine, cmvIL-10, on exosome production by highly metastatic breast cancer cells.

MDA-MB-231 cells were cultured in vitro, …

Investigation Of Zyflamend On Ampk Signaling And Potential Interactions Of Its Components, Yi Zhao

Doctoral Dissertations

The reductionist approach contributes greatly to our understanding of anticancer properties of phytonutrients, but in vitro studies demand concentrations that are 100-1000 times higher than achievable in humans, producing results with little physiologic relevance, resulting in disappointing outcomes in clinical trials. However, maintaining these bioactives in the presence of other compounds originally derived from the food/extract of origin may synergistically lower the bioactive dose so translatability becomes feasible. The first objective of this study was to determine if bioefficacy of phytonutrients can be enhanced when used in combination at doses that are ineffective when used in isolation. In this project, …

Radium-223 For The Treatment Of Castration-Resistant Prostate Cancer, Joelle El-Amm, Jeanny B. Aragon-Ching

Medicine Faculty Publications

The vast majority of patients with metastatic castration-resistant prostate cancer (mCRPC) develop bone metastases. Bone metastases are a source of significant morbidity and affect quality of life in these patients. Several bone-targeting agents are approved for the treatment of bone metastases in prostate cancer, including bisphosphonates, denosumab, and radiopharmaceuticals. Radium-223 is a novel first-in-class alpha-emitting radiopharmaceutical that has been approved for treatment of patients with mCRPC with bone metastases. Radium-223 delivers cytotoxic radiation to the sites of bone metastases and offers the advantage of minimal myelosuppression. The landmark Phase III ALSYMPCA trial demonstrated that, in addition to providing bone-related palliation, …

Impact Of Differentiation Status Of Kidney Progenitors In Wilms Tumor Development, Le Huang

Dissertations & Theses (Open Access)

Wilms tumor is one of the most common solid tumors in children. It is an embryonic cancer of the kidney and is thought to arise from undifferentiated renal mesenchyme. However, the differentiation status of cells in the mesenchyme that can give rise to Wilms tumors is unknown. Gene expression analysis of a large panel of Wilms tumor patients has identified different subsets of Wilms tumors that are distinct in their clinical outcomes and gene expression signatures. These subsets express specific genes that correspond to different stages of differentiation during renal development, suggesting that Wilms tumors may arise from transformed cells …

Cancer Associated Fibroblast Derived Angiogenic Factor Mfap5 In Ovarian Cancer Progression, Sze Lee Cecilia Leung

Dissertations & Theses (Open Access)

Advanced stage ovarian cancer is the most lethal gynecologic malignancy. No major improvement on patient survival has been achieved in the past decade. Therefore, identification of predictive or prognostic markers and further understanding of the molecular mechanisms in ovarian cancer progression are of paramount importance.

While cancer cells have always been the targets for the identification of prognostic and predictive markers, the potential for developing new diagnosis and treatments based on the tumor supporting stromal microenvironment is relatively unexplored. Using transcriptome profiling analysis on microdissected stromal and epithelial components of normal and malignant ovarian tissues, we identified a gene signature …

Understanding The Role Of Sumoylation In Regulating Lkb1 Function, Joan W. Ritho

Dissertations & Theses (Open Access)

Energy homeostasis in a cell is critical for its survival during metabolic stress. Liver kinase B1 (LKB1), one of the key regulators of cellular energy balance, was initially discovered as a tumor suppressor mutated in patients with Peutz-Jeghers syndrome. Germline mutations in LKB1 predispose patients to develop several benign and malignant tumors including gastrointestinal and lung cancers. In 2003, several groups demonstrated that LKB1is a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), directly associating it with the regulation of energy balance in cells. During energy stress, LKB1 phosphorylates AMPK at threonine 172 (T172) resulting in AMPK …

Deciphering The Functional Collaboration Of Mid And Bric-A-Brac 2 As Potential Regulators Of Cellular Proliferation Within Adult Drosophila Ovaries, Petra Visic

Master's Theses

Stem cell niches are highly organized and specialized microenvironments located within specific tissues of both vertebrate and invertebrate organisms [1]. In Drosophila melanogaster, three distinct stem cell niches have been identified within the ovary including the germline stem cell (GSC), follicle stem cell (FSC), and escort stem cell (ESC) niche. Recently, Fregoso-Lomas et al. [2] reported that Gurken/Epidermal Growth Factor Receptor (EGFR) signaling is modulated within posterior ovarian follicle cells by Midline (Mid). The mid gene encodes a T-box transcription factor protein that specifies cell fates in the developing heart [3][4], central nervous system [5][6], epidermis [7], and eye …