Cancer Biology Commons^™

Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry

Pharmacy Faculty Articles and Research

Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …

Chemotherapy: The Physiological Cost Of A Cure, Megan Ellis

A with Honors Projects

This project focuses on the common long term side effects of cancer treatments, apart from cure. In addition to physiological function changes, it focuses on the chemical composition of chemotherapy drugs.

Role Of Prostaglandin E2 In The Regulation Of Pancreatic Stellate Cells Hyper Activity Associated With Pancreatic Cancer, Chantale Charo

Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most lethal type of cancer due to its high metastasis rate and resistance to chemotherapy. Pancreatic fibrosis is a constant pathological feature of chronic pancreatitis and the hyperactive stroma associated with pancreatic cancer. Strong evidence supports an important role of cyclooxygenase-2 (COX-2) and COX-2 generated prostaglandin E2 (PGE2) during pancreatic fibrosis. Pancreatic stellate cells (PSC) are the predominant source of extracellular matrix production (ECM), thus being the key players in both diseases. Given this background, the primary objective is to delineate the role of PGE2 on human pancreatic stellate cells (PSC) hyper activation associated …

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

Biochemistry and Microbiology

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 …

Regulation Of Pim1 Under Hypoxia In Prostate Cancer, Eva Sahakian

Loma Linda University Electronic Theses, Dissertations & Projects

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

Chemosensitization Of Cancer Cells By Sirna Using Targeted Nanogel Delivery, Erin B. Dickerson, William H. Blackburn, Michael H. Smith, Laura B. Kapa, L. Andrew Lyon, John F. Mcdonald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods: We report here …

Cytotoxic And Anti-Human Papillomavirus Activites In Selected Vegetables., Maizatul Azmah Ab. Latiff

Student Works (2010-2019)

An appropriate way to control cancer is chemoprevention as a large number of compounds have been observed to prevent the occurrence of cancer and variety of mechanisms exists for producing such protective effects. Numerous epidemiological studies have shown that diets rich in vegetables are associated with a decreased risk of cancer. Chemoprevention involves the use of natural or laboratory made substances to prevent cancer or reduce risk cancer.The E6 oncoprotein from oncogenic Human papillomaviruses (HPVs) has exhibit functions in tumorigenesis, regulation of transcriptions and apoptosis. E6 product from oncogenic viral type like HPV 16 can bind the tumor suppressor p53 …

Wnt Pathway Reprogramming During Human Embryonal Carcinoma Differentiation And Potential For Therapeutic Targeting, Grace E. Snow, Allison C. Kasper, Alexander M. Busch, Elisabeth Schwarz, Katherine E. Ewings, Thomas Bee, Michael J. Spinella, Ethan Dmitrovsky, Sarah J. Freemantle

Dartmouth Scholarship

Testicular germ cell tumors (TGCTs) are classified as seminonas or non-seminomas of which a major subset is embryonal carcinoma (EC) that can differentiate into diverse tissues. The pluripotent nature of human ECs resembles that of embryonic stem (ES) cells. Many Wnt signalling species are regulated during differentiation of TGCT-derived EC cells. This study comprehensively investigated expression profiles of Wnt signalling components regulated during induced differentiation of EC cells and explored the role of key components in maintaining pluripotency.

Expression Of An Alternate Splice Form Of Bmi-1 In Multiple Myeloma, Adam Austin, Kristine Veys, Debbie Wong, James Tung

Undergraduate Research Opportunities Program (UROP)

The concept of “tumor stem cells” has garnered much attention in the last few years. Tumor stem cells are believed to exist among a heterogeneous group of cells that constitute a tumor. These tumor stem cells often express genes that are important for stem cell function, cell division, and maintenance of pluripotent state in stem cells. Stem cell or stem cell maintenance genes such as SALL 4 and Bmi-1 are often seen in these cancer cells and contribute to self-renewing divisions and cancer cell survival. In particular, high expression of Bmi-1 (B lymphoma mouse Moloney leukemia virus insertion region), a …

Pdest Fg12-Cmv Dsred Vector, Jarod Wolffis, Sheri L. Holmen

Undergraduate Research Opportunities Program (UROP)

Melanoma is the most rapidly increasing malignancy among young people in the United States. If detected early, the disease is easily treated; however, once the disease has metastasized it is largely refractory to conventional therapies and is associated with a high mortality rate. The development of human cancer from a pre-malignant primary tumor to a metastatic lesion that develops at secondary sites is thought to be a multi-step process, requiring many genetic and epigenetic events that provide a growth advantage to cells. It is still unclear which of the many genetic changes in human cancers are required for metastasis. Therefore, …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

Role Of Transient Receptor Potential Canonical-6 (Trpc6) Channel In Metastasis Of Glioblastoma Multiforme, Rajarajeshwari Venkataraman

Electronic Theses and Dissertations

Glioblastoma multiforme (GBM) is one of the extremely fatal brain tumors. The main reason that makes it so lethal is its capability to invade and spread to other parts of CNS producing secondary tumors. Among other factors hypoxia, reduced oxygen availability, is linked to higher metastatic potential of cancers. Hypoxia causes numerous changes in genome and proteome of the cell. These changes help a normal cell to adapt to nutritional deficiency, but the same changes can increase the malignancy and metastasis in tumor cells. Extensive research by a number of curious scientists reveal that various pathways involving numerous proteins cross-talk …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Oral Cancer Screening, Damon Omar Watson

Honors Theses

Cancers of the oral cavity and pharynx have increased throughout the decades. Since oral cancer represents a small percentage of the total cancers in the United States, it is often overlooked. Though this is the case, the results of this cancer can be devastating. To address this issue, an Oral Cancer Screening was organized on August 14, 1996 at the West Michigan Cancer Center in Kalamazoo. This was a joint collaboration between the author, the West Michigan Cancer Center, and the Kalamazoo Valley Dental Society. This event allowed research to take place concerning the data obtained. Confidential results and information …

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 …

Clinical Use Of A Standard Kit-Preparation Of Radiolabeled Monoclonal Antibody 96.5 In The Diagnostic Imaging Of Metastatic Melanoma., Mansoor Saleh, D M. Miller, L Peterson, C D. Russell, M W. Unger

Haematology and Oncology, East Africa

We studied the efficiency of a standard-kit preparation using 1 mg 111In-labeled 96.5 monoclonal antibody in combination with 19 mg of unlabeled antibody in the diagnostic imaging of 27 patients with documented metastatic melanoma. Twenty-three of 26 patients (88%) demonstrated immunoscintigraphic localization of tumor. Of 104 metastatic sites previously documented by conventional studies, 62 (60%) were identified by immunoscintigraphy. A total of 77 sites demonstrated localization of radiolabeled antibody. Fifty-four (70%) corresponded to known sites of disease; eight sites (10%) were "discovered" by immunoscintigraphy and subsequently confirmed by conventional studies; 15 imaged sites (20%) could not be confirmed by conventional …

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 …

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. …