Cancer Biology Commons^™

Paracrine-Rescued Lobulogenesis In Chimeric Outgrowths Comprising Progesterone-Receptor-Null Mammary Epithelium And Redirected Wild-Type Testicular Cells, Robert D. Bruno, Corinne A. Boulanger, Sonia M. Rosenfield, Lisa H. Anderson, John P. Lydon, Gilbert H. Smith

School of Medical Diagnostics & Translational Sciences Publications

We have previously shown that non-mammary and tumorigenic cells can respond to the signals of the mammary niche and alter their cell fate to that of mammary epithelial progenitor cells. Here we tested the hypothesis that paracrine signals from mammary epithelial cells expressing progesterone receptor (PR) are dispensable for redirection of testicular cells, and that re-directed wild-type testicular-derived mammary cells can rescue lobulogenesis of PR-null mammary epithelium by paracrine signaling during pregnancy. We injected PR-null epithelial cells mixed with testicular cells from wild-type adult male mice into cleared fat-pads of recipient mice. The testicular cells were redirected in vivo to …

Cancellation Of Cellular Responses To Nanoelectroporation By Reversing The Stimulus Polarity, Andrei G. Pakhomov, Iurii Semenov, Shu Xiao, Olga N. Pakhomova, Betsy Gregory, Karl H. Schoenbach

Bioelectrics Publications

Nanoelectroporation of biomembranes is an effect of high-voltage, nanosecond-duration electric pulses (nsEP). It occurs both in the plasma membrane and inside the cell, and nanoporated membranes are distinguished by ion-selective and potential-sensitive permeability. Here we report a novel phenomenon of bioeffects cancellation that puts nsEP cardinally apart from the conventional electroporation and electrostimulation by milli- and microsecond pulses. We compared the effects of 60- and 300-ns monopolar, nearly rectangular nsEP on intracellular Ca²⁺mobilization and cell survival with those of bipolar 60 + 60 and 300 + 300 ns pulses. For diverse endpoints, exposure conditions, pulse numbers (1-60), and …

Electrochemotherapy: From The Drawing Board Into Medical Practice, Damijan Miklavčič, Barbara Mali, Bor Kos, Richard Heller, Gregor Serša

Bioelectrics Publications

Electrochemotherapy is a local treatment of cancer employing electric pulses to improve transmembrane transfer of cytotoxic drugs. In this paper we discuss electrochemotherapy from the perspective of biomedical engineering and review the steps needed to move such a treatment from initial prototypes into clinical practice. In the paper also basic theory of electrochemotherapy and preclinical studies in vitro and in vivo are briefly reviewed. Following this we present a short review of recent clinical publications and discuss implementation of electrochemotherapy into standard of care for treatment of skin tumors, and use of electrochemotherapy for other targets such as head and …

A Potential Mechanism For Extracellular Matrix Induction Of Breast Cancer Cell Normality, Robert D. Bruno, Gilbert H. Smith

School of Medical Diagnostics & Translational Sciences Publications

Extracellular matrix proteins from embryonic mesenchyme have a normalizing effect on cancer cells in vitro and slow tumor growth in vivo. This concept is suggestive of a new method for controlling the growth and spread of existing cancer cells in situ and indicates the possibility that extracellular proteins and/or embryonic mesenchymal fibroblasts may represent a fertile subject for study of new anti-cancer treatments.

Nanosecond Pulsed Electric Field (Nspef) Ablation As An Alternative Or Adjunct To Surgery For Treatment Of Cancer, Ru Chen, Xinhua Chen, Stephen J. Beebe

Bioelectrics Publications

Surgery as resection or transplantation remains a fundamental means for cancer treatment and often offers an opportunity for a cure. However, surgery is not always possible because of tumor proximity to blood vessels or ducts or when a patient is not healthy enough to undergo surgery. Application of nanosecond pulsed electric fields (nsPEFs) is a new approach to treat cancer using pulse power technology that was originally designed for military purposes. This novel approach deposits extremely short pulses of high power, low energy electric fields into malignant tissues using electrodes to encompass tumors. Pre-clinical studies show that treatments are effective …

Applications For Pulse Power Using Nanosecond Pulsed Electric Fields (Nspefs) In Cell Biology And Cancer Treatment, Stephen J. Beebe

Bioelectrics Publications

No abstract provided.

Late Developing Mammary Tumors And Hyperplasia Induced By A Low-Oncogenic Variant Of Mouse Mammary Tumor Virus (Mmtv) Express Genes Identical To Those Induced By Canonical Mmtv, Robert D. Bruno

School of Medical Diagnostics & Translational Sciences Publications

Background: The canonical milk-transmitted mouse mammary tumor virus (MMTV) of C3H mice (C3H-MMTV) rapidly induces tumors in 90% of infected animals by 8 months of age. Pro-viral insertions of C3H-MMTV into genomic DNA results in the overexpression of common core insertion site (CIS) genes, including Wnt1/10b, Rspo2, and Fgf3. Conversely, infection by either the endogenous Mtv-1 virus (in C3Hf) or the exogenous nodule-inducing virus (NIV) (in Balb/c NIV) induces premalignant mammary lesions and tumors with reduced incidence and longer latency than C3H-MMTV. Here, we asked whether Mtv-1/NIV affected the expression of core CIS genes.

Findings: We confirmed the presence of …

Embryonic Stem Cells Are Redirected To Non-Tumorigenic Epithelial Cell Fate By Interaction With The Mammary Microenvironment, Corinne A. Boulanger, Robert D. Bruno, David L. Mack, Monica Gonzales, Nadia P. Castro, David S. Salomon, Gilbert H. Smith

School of Medical Diagnostics & Translational Sciences Publications

Experiments were conducted to redirect mouse Embryonic Stem (ES) cells from a tumorigenic phenotype to a normal mammary epithelial phenotype in vivo. Mixing LacZ-labeled ES cells with normal mouse mammary epithelial cells at ratios of 1:5 and 1:50 in phosphate buffered saline and immediately inoculating them into epithelium-divested mammary fat pads of immune-compromised mice accomplished this. Our results indicate that tumorigenesis occurs only when normal mammary ductal growth is not achieved in the inoculated fat pads. When normal mammary gland growth occurs, we find ES cells (LacZ+) progeny interspersed with normal mammary cell progeny in the mammary epithelial structures. We …

Synergistic Effects Of Nanosecond Pulsed Electric Fields Combined With Low Concentration Of Gemcitabine On Human Oral Squamous Cell Carcinoma In Vitro, Jing Wang, Jinsong Guo, Shan Wu, Hongqing Feng, Shujun Sun, Jie Pan, Jue Zhang, Stephen J. Beebe

Bioelectrics Publications

Treatment of cancer often involves uses of multiple therapeutic strategies with different mechanisms of action. In this study we investigated combinations of nanosecond pulsed electric fields (nsPEF) with low concentrations of gemcitabine on human oral cancer cells. Cells (Cal-27) were treated with pulse parameters (20 pulses, 100 ns in duration, intensities of 10, 30 and 60 kV/cm) and then cultured in medium with 0.01 mu g/ml gemcitabine. Proliferation, apoptosis/necrosis, invasion and morphology of those cells were examined using MTT, flow cytometry, clonogenics, transwell migration and TEM assay. Results show that combination treatments of gemcitabine and nsPEFs exhibited significant synergistic activities …

Cutaneous Papilloma And Squamous Cell Carcinoma Therapy Utilizing Nanosecond Pulsed Electric Fields (Nspef), Dong Yin, Wangrong G. Yang, Jack Weissberg, Catherine B. Goff, Weikai Chen, Yoshio Kuwayama, Amanda Leiter, Hongtao Xing, Antonie Meixel, Daria Gaut, Fikret Kirkbir, David Sawcer, P. Thomas Vernier, Jonathan W. Said, Martin A. Gundersen, H. Phillip Koeffler

Bioelectrics Publications

Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five …

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

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% …

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 …

Adjacent Slice Prostate Cancer Prediction To Inform Maldi Imaging Biomarker Analysis, Shao-Hui Chuang, Xiaoyan Sun, Lisa Cazares, Julius Nyalwidhe, Dean Troyer, O. John Semmes, Jiang Li, Frederic D. Mckenzie, Nico Karssemeijer (Ed.), Ronald M. Summers (Ed.)

Electrical & Computer Engineering Faculty Publications

Prostate cancer is the second most common type of cancer among men in US [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from the …

The Role Of Human Endogenous Retroviruses In Renal Cell Carcinoma, Michele D. Tisdale

Biological Sciences Theses & Dissertations

Human endogenous retroviruses make up approximately 8-9% of the human genome. A number of expressed HERVs, those that are actively transcribing, have been associated with various cancers. Suppression mechanisms that control HERV expression often fail or become more permissive in tissues where expression should be restricted. Previous studies have identified HERV expression in breast cancer tissues, whereas normal tissue HERV expression remained suppressed. In addition, studies of DNA hypermethylation have correlated with the ability to contribute to cancer development. Hypermethylation of several tumor suppressor genes occurs frequently in cancers and alterations in promoter regions could contribute to the development of …

Prostate Cancer Biomarker Identification: A Comparative Study, Wenjuan Jiang

Computational Modeling & Simulation Engineering Theses & Dissertations

With the current development of proteomics techniques, the discovery of potential molecular biomarkers for early detection of prostate cancer has been greatly improved. In this thesis, we implemented five classifiers including the support vector machine (SVM), Bayesian Classifier, Decision Tree, Random Forest and the Multilayer perceptron (MLP) to test their effectiveness in prostate cancer biomarker identification using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) tissue imaging data. The classifiers were utilized to discriminate cancer mass spectra from normal ones for the data collected at the Eastern Virginia Medical School (EVMS). There are 94 7 spectra from normal tissues and 27 from …

An Efficient Algorithm For Biomarker Identification, Jiang Li, Rick Mckenzie, Lisa Cazares, Richard Drake, John Semmens

Electrical & Computer Engineering Faculty Publications

No abstract provided.

Maldi Mass Spectrometry Imaging For The Discovery Of Prostate Carcinoma Biomarkers, Lisa Harris Cazares

Theses and Dissertations in Biomedical Sciences

The elucidation of new biological markers of prostate cancer (PCa) should aid in the detection, and prognosis of this disease. Diagnostic decision making by pathologists in prostate cancer is highly dependent on tissue morphology. The ability to localize disease-specific molecular changes in tissue would help improve this critical pathology decision making process. Direct profiling of proteins in tissue sections using MALDI imaging mass spectrometry (MALDI-IMS) has the power to link molecular detail to morphological and pathological changes, enhancing the ability to identify candidates for new specific biomarkers. However, critical questions remain regarding the integration of this technique with clinical decision …

Chromosomal Localization Of The Islet Neogenesis Associated Protein (Ingap) Gene In Syrian Hamster By Tyramide Signal Amplification-Fluorescence In Situ Hybridization (Tsa-Fish), Sallie A. Smith

Biological Sciences Theses & Dissertations

Diabetes mellitus is a group of conditions characterized by hyperglycemia due to an inability to produce or properly utilize insulin. The majority of cases fall into two categories, Type I and Type 2. Type I results from the autoimmune destruction of pancreatic β-cells of the islets. The beta cells are the exclusive source of insulin and the patient becomes entirely dependent on exogenous insulin to survive. Patients with Type 2 are distinguished by insulin resistance, a condition that develops due to the inability of the body to effectively use the insulin being produced. The β-cells gradually lose their ability to …

Expression Of Glutathione-S-Transferase Mu 1 (Gstm1) And Glutathione-S-Transferase Theta 1 (Gstt1) In Patients With Aplastic Anemia And Myelodysplastic Syndromes, Aaron Conrad Spivey

Theses and Dissertations in Biomedical Sciences

Aplastic Anemia is a disorder of the hematopoietic bone marrow stem cells that is frequently associated with drug or chemical exposures. Reduced ability to detoxify drugs or chemicals may result in an increased risk of disease. Glutathione S-transferases are Phase II enzymes, which help detoxify xenobiotics. Many patients who have developed aplastic anemia and myelodysplastic syndrome have the null genotype for GSTMI and/or GSTTI. For patients with GSTMI and GSTTI positive genotypes, non-expression of these enzymes may cause an increased risk in developing aplastic anemia or myelodysplastic syndrome. To test whether genotype positive patients have GSTMI or GSTTI null …

Laminin Potentiates Differentiation Of Pcc4uva Embryonal Carcinoma Into Neurons, T. M. Sweeney, Roy C. Ogle, C. D. Little

School of Medical Diagnostics & Translational Sciences Publications

The embryonal carcinoma PCC4uva differentiates into neurons in response to treatment with retinoic acid and dbcAMP. We used this in vitro model system to study the effects of laminin on early neural differentiation. Laminin substrata markedly potentiate neural differentiation of retinoic acid and dbcAMP-treated cultures. Only laminin induced more rapid neural cell body clustering, neurite growth and neurite fasciculation as compared to type IV collagen, type I collagen, and fibronectin substrata. Exogenous laminin substrata promoted greater cell attachment, cellular spreading and growth to confluence than type IV collagen, type I collagen, fibronectin and glass substrata. Laminin-induced effects were inhibited by …

Hypoxanthine-Induced Differentiation Of Cultured Human Leukemia Cells, Gayle Jennette Singleton

Chemistry & Biochemistry Theses & Dissertations

Human cultured leukemia cells appear to have a decreased amount of inosine in their tRNA. When cells with inosine deficient tRNA are placed in a hypoxanthine fortified media, they incorporate hypoxanthine into their tRNA by the action of the enzyme tRNA-hypoxanthine ribosyl transferase. This generates the nucleoside inosine in the tRNA. The cultured human leukemia cell lines, CCRF-CEM, HL-60, and HGPRT(-) HL- 60, incorporate hypoxanthine into their tRNA, as determined by tRNA isolation, hydrolysis, and HPLC analysis. Hypoxanthine treatment dramatically inhibited cell growth in conjunction with partial induction of differentiation in the CCRF-CEM, HL-60, and HGPRT ( - ) HL-60 …

Laminin Receptors For Neurite Formation, H. K. Kleinman, Roy C. Ogle, F. B. Cannon, C. D. Little, T. M. Sweeney, L. Luckenbill-Edds

School of Medical Diagnostics & Translational Sciences Publications

Laminin, a basement membrane glycoprotein promotes both cell attachment and neurite outgrowth. Separate domains on laminin elicit these responses, suggesting that distinct receptors occur on the surface of cells. NG108-15 neuroblastoma-glioma cells rapidly extend long processes in the presence of laminin. We report here that 125I-labeled laminin specifically binds to these cells and to three membrane proteins of 67, 110, and 180 kDa. These proteins were isolated by affinity chromatography on laminin-Sepharose. The 67-kDa protein reacted with antibody to the previously characterized receptor for cell attachment to laminin. Antibodies to the 110-kDa and 180-kDa bands demonstrated that the 110-kDa protein …

Solid Phase Extraction Of Mammalian Cell Mitochondrial Dna And Its Electrophoretic Separation In Agarose Gels, Theresa Brick-Miller

Biological Sciences Theses & Dissertations

An improved and efficient electrophoretic procedure for the isolation of mitochondrial DNA (mtDNA) is described. The solid phase extraction procedure for the isolation of mtDNA involves embedding as few as 200,000 Ehrlich ascites tumor cells into a block of agarose, digestion of cellular membranes by detergent action and subsequent electrophoretic separation of nucleic acids in agarose gels. Genomic DNA remains in the original block of agarose while the mtDNA migrates in the separation gel to a position equivalent to that obtained for mtDNA isolated by traditional procedures.

The efficacy of a large number of detergents, agarose concentrations, embedding conditions, embedding …

Evaluation Of Peptide Assimilation In Ehrlich Ascites Tumor Cells, John M. Castellano

Biological Sciences Theses & Dissertations

The dipeptides glycyl-L-(³H)-leucine and L-phenylalanyl-L-(³H)-leucine were synthesized in radioactive form and utilized in the analysis of peptide transport and hydrolysis by Ehrlich ascites tumor cells. The tumor cells were cultured in the abdominal cavity of CF-1 albino mice and harvested into sterile isotonic buffer for all experimental analyses.

The results of this study reveal that the tumor cells rapidly accumulate radiolabel when incubated with the above mentioned peptides, but that the peptide is most probably hydrolyzed extracellularly and free L-(³)-leucine transported. This hypothesis is based on the observations of reduction in accumulation of radiolabel …

The Analysis Of S-Adenosylmethionine And S-Adenosylhomocysteine In Normal And Neoplastic Cells, Kathryn Elizabeth Godburn

Chemistry & Biochemistry Theses & Dissertations

Altered patterns of methylation have been shown in both ribosomal and transfer RNA isolated from cancer cells. In contrast to the elevated activity of the methyltransferases responsible for this modification, hypomethylation appears as a general characteristic. The endogenous levels of S-adenosylmethionine and S-adenosylhomocysteine are important in relationship to their role as substrate and product of the transmethylation reaction. The levels of S-adenosylmethionine and S-adenosylhomocysteine were determined using phosphocellulose cation exchange or high pressure liquid chromatography. High voltage paper electrophoresis was used in a modified procedure to directly resolve (³⁵s) labeled S-adenosylmethionine and S-adenosylhomocysteine in small quantities of cell …

The Effects Of 712-Dimethylbenz (A) Anthracene On Ovarian Steroidogenesis And Uterine Growth In The Mouse, Jeffrey Lynn Clark

Biological Sciences Theses & Dissertations

It has been previously demonstrated that 7,12-dimethylbenz(a) anthracene (DMBA) is an initiator of ovarian granulosa cell tumors. It is also known that DMBA leads to destruction of primordial oocytes, and that tumor induction may involve the interaction of pituitary gonadotropins. However, the effects of DMBA on ovarian steroidogenesis and uterine growth in relation to the tumorigenic process have not been investigated. Therefore, the present study was conducted to examine these parameters using adult C57Bl/6N mice treated in proestrus and diestrus II with 0.1 ml corn oil with or without 1.5 mg DMBA and killed 44 hours later. The uteri and …

Detection Of Unique Tumor-Associated Proteins In The Urine Of Patients With Transitional Cell Carcinoma By High Resolution Two-Dimensional Polyacrylamide Gel Electrophoresis, Robert David Lehman

Biological Sciences Theses & Dissertations

A two-dimensional polyacrylamide gel electrophoretic technique was developed for the detection of unique tumor-associated proteins in urine of patients with transitional cell carcinoma (TCC) of the urinary bladder. This technique yielded high resolution of polypeptides in the urine of cancer patients. Urine was chosen as a source of tumor-associated components because the location of the tum or should release already solublized tum or substances in to the urine.

Urinary proteins were concentrated and then analyzed by the two - dimensional electrophoretic technique using isoelectric focusing in the first dimension and sodium dodecylsulfate - polyacrylamide gel electrophoresis in the second dimension. …