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Articles 1 - 14 of 14

Full-Text Articles in Cancer Biology

Prevalence Of A Variant Gastrin Receptor Rna And Correlating Genomic Polymorphism In Human Pancreatic Cancer, Rebekah Jones May 2019

Prevalence Of A Variant Gastrin Receptor Rna And Correlating Genomic Polymorphism In Human Pancreatic Cancer, Rebekah Jones

Honors Projects and Presentations: Undergraduate

Currently, the five-year survival rate of pancreatic cancer is an abysmal 5%. Our lab has focused on the etiology of CCK2i4svR, a hyperactive splice variant of the gastrin receptor (CCK2R), which has been associated with increased pancreatic tumor aggressiveness. To determine if a correlation exists between a single nucleotide polymorphism (SNP) in the receptor, and expression of the variant RNA in patients, we aim to genotype human pancreatic tumor samples and quantify CCK2R and CCK2i4svR mRNA. Initial analysis of RNA samples by Real Time RT‐PCR has demonstrated successful quantification of CCK2R expression in both tumor and normal tissue samples ...


Clarifying The Connection Between Oncgenic Kras And Gastrin/Cck2r Signaling In Pancreatic Tumorigensis, Andrew Larow, John F. Harms Jan 2019

Clarifying The Connection Between Oncgenic Kras And Gastrin/Cck2r Signaling In Pancreatic Tumorigensis, Andrew Larow, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic ductal adenocarcinoma (PDAC) is an extremely deadly cancer: the overall five-year survival rate is 8%. This is mainly due to the difficulty of diagnosing PDAC in its early stage: only 9% of patients are diagnosed with localized cancer. Cancer cells display rapid growth and cell division, due in part to oncogene activation and stimulation of mitogenic pathways. In PDAC, mutant K-ras, an oncogene and intracellular signaling protein, is present in 90% of all cases. Because of this high correlation and the role of mutant K-ras in PDAC, it has been repeatedly targeted for cancer therapy, but with little success ...


Can Pancreatic Cancer Be Controlled By Cellular Immunity?, Kirby Robbins, John Harms, Lawrence Mylin Jan 2017

Can Pancreatic Cancer Be Controlled By Cellular Immunity?, Kirby Robbins, John Harms, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is aggressive and poorly understood with a five-year survival rate of only 9% because most cases are diagnosed at a late stage. Because of ambiguous symptoms, pancreatic cancer is very difficult to detect early, and often when it is finally diagnosed, the cancer has already metastasized or has become too robust to cure. Current treatments are largely ineffective, so there is a great need for a novel approach to targeting this debilitating disease. To determine whether an intracellular peptide target expressed only in pancreatic cancer cells can be utilized to control or eradicate pancreatic cancer tumors by T ...


Developing A Cr281 Peptide Specific T Lymphocyte Immune Response To Target Pancreatic Cancer Cck2i4sv Receptor, Taylor Hook Dec 2016

Developing A Cr281 Peptide Specific T Lymphocyte Immune Response To Target Pancreatic Cancer Cck2i4sv Receptor, Taylor Hook

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is a debilitating disease with a poor survival rate. There are no effective treatments for pancreatic cancer necessitating research to find new targets for treatment. The basis of this research is to determine whether a novel target located inside of pancreatic cancer cells can be utilized to control or eradicate pancreatic tumors by T cell-based immunity. Gastrin and Cholecystokinin (CCK) are hormones that regulate activity of the gastrointestinal tract.Each can signal via CCK-BR, which normally acts as an on/off switch for pancreatic cells to secrete enzymes and bicarbonate. An altered form of the CCK-B receptor, CCK2i4sv ...


Cd4+ T Cell Regulation Of Immune Responses To The Simian Virus 40 Large Tumor Antigen Is Complex And Involves Multiple Layers Of Coordination Dependent On Immune Conditions, Arielle Raugh, Lawrence Mylin Dec 2016

Cd4+ T Cell Regulation Of Immune Responses To The Simian Virus 40 Large Tumor Antigen Is Complex And Involves Multiple Layers Of Coordination Dependent On Immune Conditions, Arielle Raugh, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

Cytotoxic (CD8+) and Helper (CD4+) T lymphocytes play an important role in the immune detection and destruction of tumors. The induction of Cytotoxic T cell responses by multiple CD8 epitopes located within the Simian Virus 40 Large Tumor Antigen (SV40 T ag) oncoprotein has been well characterized, and we have begun to characterize the role(s) of CD4+ Helper T cells in controlling cellular immune responses to the SV40 T ag. The goal of this study was to characterize the cytokines produced by activated SV40T ag-specific Helper T cells in order to identify subset(s) of Helper T cells that ...


Characterizing Monoclonal Antibodies Against The Cholecystokinin 2 Receptor (Cck2r) And A Splice Variant For Use In Pancreatic Cancer Studies, Laura Ritenour May 2016

Characterizing Monoclonal Antibodies Against The Cholecystokinin 2 Receptor (Cck2r) And A Splice Variant For Use In Pancreatic Cancer Studies, Laura Ritenour

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is an extremely aggressive cancer with a five-year survival rate of less than 6%, largely due to the lack of early detection and effective treatment options. A better understanding of the mechanisms leading to malignant transformation is necessary to improve patient outcomes. One known contributor to tumor aggression is the cholecystokinin 2 receptor (CCK2R), a G-protein coupled receptor that binds the gastrointestinal hormones CCK and gastrin. A constitutively-active form of the receptor, the intron 4 splice variant (CCK2i4svR), has also been observed in cancer cells. To facilitate studies of CCK2i4svR, a monoclonal antibody specific to an insertion in ...


A Novel Synthetic Pathway For Aspernigrin A, Brady Marburger, Anne Reeve Apr 2016

A Novel Synthetic Pathway For Aspernigrin A, Brady Marburger, Anne Reeve

Honors Projects and Presentations: Undergraduate

Aspernigrin A (6-benzyl-4-oxo-1,4-dihydropyridine-3-carboxamide)is a natural product isolated from the fungus Aspergillus nigerfound in the Mediterranean sea sponge, Axinelladamicornis. This secondary metabolite has proven to becytotoxic to certain colon cancer cell lines. The synthesis of aspernigrin A is required to obtain enough material to study its bioactivity and potentially optimize it for clinical drug use. The new synthetic pathway being tested utilizes ethyl acetoacetateto create an enaminone capable of being directly converted to the pyridinone required for aspernigrin A. Through reaction in a DMF-Me2SO4adduct, ethyl acetoacetatewas successfully reacted to give the enaminone product, ethyl-2-[(dimethylamino)methylene]-3-oxobutanoate, at an ...


Increasing The Stability And Expression Of Green Fluorescent Protein In Pancreatic Cancer Cells For Metastasis Assays, Holly M. Ross, John F. Harms Jan 2016

Increasing The Stability And Expression Of Green Fluorescent Protein In Pancreatic Cancer Cells For Metastasis Assays, Holly M. Ross, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is the fourth leading cause of cancer death in the United States, with only 11% of patients diagnosed with metastatic disease surviving the first year. Even so, few studies exist to characterize the mechanism of metastasis in this highly aggressive form of cancer. Consequently, it is imperative that techniques, such as tagging cells with green fluorescent protein (GFP), are developed to track cancerous cells over the course of their spread. Unfortunately, the existing GFP vector contains a cytomegalovirus promotor, which is readily silenced by cells and decreases the vector’s usefulness for long-term studies in vivo. It was ...


Transfection Of Primary Kidney Cells With Mutated Sv40 T Ag Dna Containing A Cckcr Intron-Derived Sequence, Kaitlyn Grando, Courtnry Burkett, Lawrence Mylin Jan 2015

Transfection Of Primary Kidney Cells With Mutated Sv40 T Ag Dna Containing A Cckcr Intron-Derived Sequence, Kaitlyn Grando, Courtnry Burkett, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

Cholecystokinin-C receptor (CCKCR) is an alternatively spliced version of cholecystokinin-B receptor (CCKBR) found in pancreatic cells. CCKCR is uniquely expressed by cancer cells, making it an important target for immune therapy. Simian Virus 40 Large Tumor Antigen (SV40 T ag) has proven to be a powerful model in the study of cell-mediated immune responses to tumors. Our goal was to construct cells which express a derivative of SV40 T ag that incorporates the retained intron sequence from CCKCR to use as a tool in the study of cellmediated immunity targeting this unique sequence. Two variations of plasmids containing mutated T ...


Investigating Cellular Immunity Using The Sv40 Large Tumor Antigen, Matthew Lauver, Caitlin Mason, Stephanie Schell, Lawrence Mylin Jan 2015

Investigating Cellular Immunity Using The Sv40 Large Tumor Antigen, Matthew Lauver, Caitlin Mason, Stephanie Schell, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

The Simian Virus 40 Large Tumor antigen (SV40 T ag) is a viral oncoprotein that is capable of inducing tumors and serving as the target for anti-tumor T cell responses. Because of this, the SV40 T ag has been studied extensively as a model to better understand immune control of solid tumors. Our laboratory has recently identified three CD4+ epitopes within the T ag and is conducting studies to characterize their role(s) in regulating cellular immunity to the SV40 T ag. Towards this goal, we have generated a cell line (C2a) that expresses a derivative of the T ag ...


Toward The Synthesis Of Aspernigrin A Precursor 6-Benzyl-4- Hydroxypyran-2-One: Optimization And Cross-Coupling Strategies, Seth A. Sharber, Anne M. Reeve Mar 2014

Toward The Synthesis Of Aspernigrin A Precursor 6-Benzyl-4- Hydroxypyran-2-One: Optimization And Cross-Coupling Strategies, Seth A. Sharber, Anne M. Reeve

Honors Projects and Presentations: Undergraduate

A viable pathway toward the synthesis of the benzyl pyrone 6-benzyl-4-hydroxypyran2-one, a key precursor to the secondary metabolite natural product aspernigrin A, 6- benzyl-4-oxo-1,4-dihydropyridine-3-carboxamide, has been realized and partially optimized. This benzyl pyrone is the hinge point of the retrosynthetic plan that guides many of our schemes, which is predicated on the construction of a benzyl pyridone from the commercially available pyrone 4-hydroxy-6-methyl-2-pyrone. Synthesis of the benzyl pyrone relies on the Stille palladium catalyzed cross-coupling reaction of the bromopyrone 6-(bromomethyl)-4-methoxy-pyran-2-one with tributylphenylstannane, a reaction which is yet to be studied in our lab. The protection, oxidation, and ...


Investigating An Alternate Synthesis Pathway For Aspernigrin A, Wesley S. Robertson Jan 2014

Investigating An Alternate Synthesis Pathway For Aspernigrin A, Wesley S. Robertson

Honors Projects and Presentations: Undergraduate

Aspernigrin A (2) is a secondary metabolite obtained from the fungus Aspergillus niger found on the Mediterranean sea sponge Axinella damicornus. This compound has been seen to exhibit inhibitory properties on the growth of the human colon cancer cell line SW1116, as well as xanthine oxidase, making it a potential drug candidate. Several synthetic schemes have been proposed for the synthesis of aspernigrin A involving the bromination of a methyl group to activate the position for a cross-coupling reaction to join a phenyl group to the more substituted ring of aspernigrin A. One such scheme involves the bromination of 6-methyl-1 ...


Expression Of The Human Gastrin Receptors Cckbr And Cckcr In Panco2 Murine Pancreatic Cancer Cells, Shannon V. Sell, Glenn R. Jones, Gail L. Matters, John F. Harms Jan 2013

Expression Of The Human Gastrin Receptors Cckbr And Cckcr In Panco2 Murine Pancreatic Cancer Cells, Shannon V. Sell, Glenn R. Jones, Gail L. Matters, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is the fourth leading cause of cancer mortality. The gastrointestinal hormone, gastrin, stimulates human pancreatic cancer growth via its receptor, CCKBR, and a splice-variant of CCKBR (termed CCKCR) detected only in cancer cells. This cancer-associated variant retains the fourth intron and exhibits increased cell signaling. Recently, a single nucleotide polymorphism (SNP; C>A) in the fourth intron was identified. Presence of SNP(A) was correlated with CCKCR protein expression in pancreatic cancer specimens and decreased patient survival. We hypothesize expression of human CCKCR in murine pancreatic cancer cells will increase tumor growth and metastasis relative to expression of ...


Construction Of A Novel System To Analyze Recognition Of Mhc Class Ii-Restricted Epitopes By Cd4+ T Cell Hybridoma Clones In Vitro, Samuel Bray, Lawrence Mylin Jan 2013

Construction Of A Novel System To Analyze Recognition Of Mhc Class Ii-Restricted Epitopes By Cd4+ T Cell Hybridoma Clones In Vitro, Samuel Bray, Lawrence Mylin

Honors Projects and Presentations: Undergraduate

The Simian Virus 40 large tumor antigen (SV40 Tag) is an excellent model system for studies in cancer immunology because it is strongly immunogenic, but capable of causing tumors when expressed as a transgene in vivo when protected by immune tolerance. The CD8+ T cell response to Tag in the C57BL/6 murine system is directed against four well-characterized epitopes. However, the CD4+ T cell response in this system remains uncharacterized. Recent work using Tag-specific CD4+ hybridoma clones and immune splenocytes to screen a 175 member, overlapping 15-mer peptide library corresponding to the 708 amino acid Tag protein sequence have ...