Cancer Biology Commons^™

Chmp1 Is Implicated In The Development Of Pancreatic Tumor Via The Retinoic Acid Signaling Pathway, Juliana Adedayo Akinsete

Theses, Dissertations and Capstones

In the present study, we investigated the involvement of Chmp1 (Chromatin ModifyingProtein 1/Charged Multivesicular body Protein 1) in the development of mousepancreatic acinar tumor cell line. CRL 2151 cell line was transfected with Chmp1/CS2vector to compare growth, morphology and expression of Chmp1, p53 and pp53 (ser37) with control-transfected cells. CRL 2151 cells were treated with all-trans retinoicacid (ATRA) to compare growth, morphology and expression of Chmp1 and p53 withcontrol-treated cells. Strabismus was used as control. Results showed inhibition ofgrowth but no morphological change in transfected cells. Western blot analysis showedthat Chmp1 transfection upregulated the expression of p53, pp53 and Stbm …

Organometallic Ruthenium Complexes Of Novel Thiosemicarbazones, Floyd A. Beckford, Amon T. Holt

Journal of the Arkansas Academy of Science

We present the preliminary results of a study of two novel thiosemicarbazones (TSCs) and theirruthenium complexes. The TSCs were prepared by refluxing thiosemicarbazide with 9-anthraldehyde or benzanthrone in ethanol for 3 hours. The metal complex of each ligand (complex I =[(r|6 -C6H6 )Ru(9-ant-TSC )(C1)]C1 and complex II= [(r|6 -C6H6 )Ru(benz-TSC)(Cl)]Cl) was prepared by refluxing the appropriate TSC with [(r|6 -C6H6 )RuCl 2 ] r The compounds were characterized using infrared, ultraviolet-visible, and NMRspectroscopy. Two different methods, the disk diffusion test and luminometry, were used to test the compounds against a variety of different bacterial strains for antibacterial activity. The most …

Potential Of Vibrational Spectroscopy In The Diagnosis Of Human Tumours., Eoghan O'Faolain

Doctoral

Just fewer than 20,000 people are annually diagnosed with some form of cancer in Ireland and one in three people are likely to contract some form of cancer by age 74. With the number of cases increasing at an annual rate of 2%, the early detection and treatment of cancer is becoming increasingly important. Both IR and Raman spectroscopy offer the potential for real time, quantitative detection of cancer and even precancer. This study investigates the potential of Raman and Fourier transform infrared, both benchtop and synchrotron spectroscopies for the detection of cervical cancer. The tissue was classified and its …

Growth Factor–Induced Shedding Of Syndecan-1 Confers Glypican-1 Dependence On Mitogenic Responses Of Cancer Cells, Kan Ding, Martha Lopez-Burks, José A. Sánchez-Duran, Murray Korc, Arthur D. Lander

Dartmouth Scholarship

The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican …

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 …

The Effect Of Rooibos Tea (Aspalathus Linearis) On The Survival And Transformation Of C3h-Bt1 Mouse Fibroblasts, Krista M. Beach, Paul J. Smith

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

Gene Therapy And Targeted Toxins For Glioma, James Curtin, Gwendalyn King, Marianela Candolfi, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted …

Combining Cytotoxic And Immune-Mediated Gene Therapy To Treat Brain Tumors, James Curtin, Gwendalyn King, Marianela Candolfi, Remy Greeno, Kurt Kroeger, Pedro Lowenstein, Maria Castro

Articles

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all …

Isolation Of Cancer Stem Cells From Adult Glioblastoma Multiforme, Xianpeng Yuan, James Curtin, Yizhi Xiong, Gentao Liu, Sebastian Waschsmann-Hogiu, Daniel Farkas, Keith Black, John Yu

Articles

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor and is comprised of a heterogeneous population of cells. It is unclear which cells within the tumor mass are responsible for tumor initiation and maintenance. In this study, we report that brain tumor stem cells can be identified from adult GBMs. These tumor stem cells form neurospheres, possess the capacity for self-renewal, express genes associated with neural stem cells (NSCs), generate daughter cells of different phenotypes from one mother cell, and differentiate into the phenotypically diverse populations of cells similar to those present in the initial GBM. Having a …

Jnk Regulates Hipk3 Expression And Promotes Resistance To Fas-Mediated Apoptosis In Du 145 Prostate Carcinoma Cells, James Curtin, Thomas Cotter

Articles

Elevated endogenous JNK activity and resistance to Fas receptor-mediated apoptosis have recently been implicated in progression of prostate cancer and can promote resistance to apoptosis in response to chemotherapeutic drugs. In addition, JNK has been demonstrated to promote transformation of epithelial cells by increasing both proliferation and survival. Although numerous studies have reported a role for JNK in promoting Fas receptor-mediated apoptosis, there is a paucity in the literature studying the antiapoptotic function of JNK during Fas receptor-mediated apoptosis. Consequently, we have used the recently described specific JNK inhibitor SP600125 and RNA interference to inhibit endogenous JNK activity in the …

The Effects Of Cucurbitacin E And Genistein In Mcf-7 Breast Cancer Cells, Angela Carlson

The Journal of Undergraduate Research

No abstract provided.

Determination Of The Optimal Form Of A Dna Vaccine To Induce An Effective Immune Response Against A Murine B-Cell Lymphoma, Deepti Aurora

All-Inclusive List of Electronic Theses and Dissertations

Tumor vaccines are a promising alternative to chemotherapy for the treatment of cancer. To be effective and safe, a cancer vaccine should specifically target antigens expressed only on tumor cells. The B-cell tumor-derived Ig receptor may be considered a model tumor antigen for cancer vaccine development. Specifically the immunoglobulin idiotype (ld) encoded by the variable region genes (VH and VL) provides a target antigen. Promising results have been obtained in clinical studies of ld vaccination using ld proteins. However, ld protein is laborious and time-consuming to produce. Gene-based vaccines, on the other hand, are inexpensive and offer ease of manipulation …

The Role Of Monocytes In Pristane-Induced Plasmacytoma Escape, Tina L. Sumpter

All-Inclusive List of Electronic Theses and Dissertations

Multiples myelomas are untreatable neoplasias in humans, arising from terminally differentiated B cells (plasma cells). The murine pristane-induced plasmacytoma model offers a system for studying the cellular interactions involved in sustaining the growth of plasma cell tumors. In accord with this model, syngenic plasma cell tumors transplanted into the peritoneal cavity of a genetically susceptible mouse are normally cleared by the mouse's immune system. If the mouse is pretreated with pristane (2,6,10,14- tetramethylpentadecane) intraperitoneally, prior to the transplantation of the plasma cell tumor, the tumor thrives, culminating in the death of the mouse. Intraperitoneal administration of pristane results in an …

Live And Let Die: Regulatory Mechanisms In Fas-Mediated Apoptosis, James Curtin, Thomas Cotter

Articles

Activation of Fas receptor by Fas ligand causes caspase 8 activation and apoptosis in cells and is an important mechanism by which normal tissue homeostasis and function are maintained. Activation of caspase 8 is preceded by the formation of a death-inducing signalling complex (DISC), and a number of redundant mechanisms regulate DISC formation in vivo. Fas receptor is widely expressed in tissues, and dysfunction of the regulatory mechanisms in Fas receptor signalling has been reported in several diseases including autoimmune disease and cancer. This review aims to identify and discuss the various mechanisms employed by cells to alter their sensitivity …

Defects In Death-Inducing Signalling Complex Formation Prevent Jnk Activation And Fas-Mediated Apoptosis In Du 145 Prostate Carcinoma Cells, James Curtin, Thomas Cotter

Articles

Androgen-independent prostate carcinomas are resistant to chemotherapy and cell lines derived from androgen-independent prostate carcinomas such as DU 145 cells are highly resistant to Fas-mediated apoptosis. The incubation of DU 145 cells with anti-Fas IgM agonistic antibody of Fas receptor fails to activate JNK, a stress kinase involved in regulating apoptosis. We have previously shown that JNK activation is sufficient and necessary to promote Fas-mediated apoptosis in DU 145 cells. We investigate the mechanisms by which JNK activation and apoptosis are abrogated. HSP27 is overexpressed in DU 145 cells and has previously been reported to sequester DAXX and prevent JNK …

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 …

Historical Development Of The Linear Nonthreshold Dose-Response Model As Applied To Radiation, Ronald L. Kathren

The University of New Hampshire Law Review

[Excerpt] "Despite the nearly universal adoption of the linear nonthreshold dose response model (LNT) as the primary basis for radiation protection standards for the past half century, the LNT remains highly controversial and a contentious topic of discussion among health physicists, radiation biologists, and other radiological scientists. Indeed, it has been pointed out that the LNT has assumed the status of a paradigm, synonymous with an ideal, standard, or paragon or perhaps to some, a sacred cow. Reduced to its very basics, the LNT postulates that every increment of ionizing radiation dose, however small, carries with it a commensurate increase …

Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter

Articles

Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic …

Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky

Dartmouth Scholarship

All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …

Diverse Roles For The Eph Family Of Receptor Tyrosine Kinases In Carcinogenesis, Masaru Nakamoto, Andrew Bergeman

Biology Faculty Publications

The Eph family of receptor tyrosine kinases and their cell-presented ligands, the ephrins, are frequently overexpressed in a wide variety of cancers, including breast, small-cell lung and gastrointestinal cancers, melanomas, and neuroblastomas. In particular, one Eph family member, EphA2, is overexpressed in many cancers, including 40% of breast cancers. EphA2 can also transform breast epithelial cells in vitro to display properties commonly associated with the development of metastasis. Remarkably, the oncogenic properties of EphA2 contravene traditional dogma with regard to the oncogenic properties of a growth factor and its receptor tyrosine kinase: while stimulation of EphA2 by its ligand (ephrin-A1) …

Preparation Of Novel Hydroxyethyl Amine Isosteres As Potential Cathepsin D Inhibitors, Rose M. Mcconnell, Walter E. Godwin, Amy Stefan, Crystal Newton, Nikki Herring, Crissy Goss

Journal of the Arkansas Academy of Science

Cathepsin D is a lysosomal aspartic protease found in all mammalian cells and is considered to be one of the main catabolic proteinases. Cathepsin D has been suggested to play a role in the metastatic potential of several types of cancer. A high activated cathepsin D level in breast tumor tissue has been associated with an increased incidence of relapse and metastasis. High levels of active cathepsin D have also been found in colon cancer, prostate cancer, uterine cancer, and ovarian cancer. Hydroxyethyl isosteres with cyclic tertiary amine have proven to be clinically useful as inhibitors of aspartyl proteases similar …

A Novel Strategy Utilizing Co-Expression Of Murine Il-12 And Antisense Tgf-Pl Against H238 Tumor Formation, Craig A. Seheult

Loma Linda University Electronic Theses, Dissertations & Projects

Cytokines have a profound effect on immune modulation, thus playing a significant role in cancer gene therapy. A variety of human carcinomas secrete transforming growth factor-beta (TGF-β), a cytokine with potent immunosuppressive properties. Suppressing TGF-β could be a key to successfully combating malignancies, such as gliomas, mammary, and colon cancers, that over-express TGF-β. Conversely, interleukin-12 (IL-12) is a potent immunostimulatory cytokine capable of regulating T and NK cell-mediated cytotoxic responses (Trinchieri, 1994) during an anti-tumor response. Activation of the immune system with such immunostimulatory cytokines renders it inert to the suppressive effects of TGF-β. To better understand these processes our …

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Quantification Of Benzo[A]Pyrene-Guanine Adducts In In Vitro And In Vivo Tissue Samples By Lc Tandem Mass Spectrometry, Po-Chang Chiang

Dissertations

No abstract provided.

The Effects Of R-Flurbiprofen In Reducing Tumors In A Multiple Intestinal Neoplasia Mouse Model, David Douglas Quiggle

Theses Digitization Project

The design of the proposed study was to administer R-FB to 72-day old Min/+ mice for up to 42 days. In order to capture the process of tumor reduction, animals were necropsied at various time points. At each time point animals were evaluated for tumor loads and presence of apoptotic cells along the small intestine. Studies have shown that when R-flurbiprofen (R-FB) is administered in the Min/+ mouse model it can cause the prevention and regression on intestinal tumors.

Antioxidation Activity Of Dhea And Its Mechanisms, Sun Yang, Han Rui

Pharmacy Faculty Articles and Research

Objective: The aim of this study was to determine the anti-oxidative activity of a new chemopreventive agent--dehydroepiandrosterone (DHEA), and the mechanisms of action by which DHEA protect the thymocytes and DNA from oxidative damage. Methods: Agarose gel electrophoresis, flow cytometry, single cel! gel electrophoresis, chemiluminescence assay, triazolyl blue tetrazolumbromide (MTT) colorimetry, and three dimensional collagen gel assay were used. Results: In agarose gel electrophoresis, 10 nmol/L DHEA blocked the typical DNA degradation (DNA Ladder) induced by H₂O₂. DHEA 2. 5 nmol/L and 10 nmol/L both significantly decreased the percentage of characteristic apoptotic DNA …

Interactions Of Igf-Ii And Cathepsin D In Mcf-7 Breast Cancer Cells, Jesika S. Faridi

Loma Linda University Electronic Theses, Dissertations & Projects

A primary role of the IGF-II/M6P receptor is to target lysosomal enzymes from the golgi to the lysosomes. This receptor has distinct binding sites for IGF-II and M6P, however, reciprocal interactions between these ligands have been observed (Kiess et al. 1989, 1990). Since IGF-II modulates the routing of cathepsin D in MCF-7 cells by blocking the intracellular binding of cathepsin D to the IGF-II/M6P receptor (De León et al. 1996), we hypothesized that expressing a mutant form of IGF-II that does not bind the IGF-II/M6P receptor will not interfere with lysosomal enzyme trafficking.

In our present study, we report the …

A Historical Perspective On Cancer, Rafael D, Sorkin

Physics - All Scholarship

It is proposed that cancer results from the breakdown of universal control mechanisms which developed in mutual association as part of the historical process that brought individual cells together into multi-cellular communities. By systematically comparing the genomes of uni-celled with multi-celled organisms, one might be able to identify the most promising sites for intervention aimed at restoring the damaged control mechanisms and thereby arresting the cancer.

Molecular Staging Of Colorectal Cancer: K-Ras Mutation Analysis Of Lymph Nodes Upstages Dukes’ B2 Patients, Jennifer S. Thebo

Dissertations

The successful treatment of colorectal cancer depends upon the ability of staging systems to identify patients who are at risk for recurrence. The currently used systems fail in a significant number of patients. Multiple attempts have been made to improve upon these systems in order to provide better treatment for at-risk patients.

A variety of oncogenes and tumor suppressor genes have been implicated in colorectal cancer. Mutations in one of these, K-ras, occur in 40-60% of colorectal carcinomas. However, the relationship between specific mutations and clinical outcome is unclear.

The purpose of this study was to determine whether or not …

Alterations In Calcium Homeostasis And The Insulin-Like Growth Factor Signaling Pathway Induced By Carcinogenic Polycyclic And Halogenated Aromatic Hydrocarbons In Human Mammary Epithelial Cells, Stacey L. Tannheimer

Pharmaceutical Sciences ETDs

Breast cancer is a major health concern for women, with only a small percent of the risk factors currently identified. It has been estimated that environmental factors may contribute to up to 80% of breast cancer cases. Many environmental carcinogens, such as polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs), are proven mammary carcinogens in animal models. Therefore, these studies were conducted to elucidate potential roles of PAHs and HAHs in alterations in known signaling pathways in human mammary epithelial cells (HMEC). Carcinogenic PAHs have previously been shown to produce sustained alterations in the calcium (Ca2') homeostasis of lymphocytes Therefore, …