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- All Subjects: Cancer
Description
Cancer remains one of the leading killers throughout the world. Death and disability due to lung cancer in particular accounts for one of the largest global economic burdens a disease presents. The burden on third-world countries is especially large due to the unusually large financial stress that comes from late tumor detection and expensive treatment options. Early detection using inexpensive techniques may relieve much of the burden throughout the world, not just in more developed countries. I examined the immune responses of lung cancer patients using immunosignatures – patterns of reactivity between host serum antibodies and random peptides. Immunosignatures reveal disease-specific patterns that are very reproducible. Immunosignaturing is a chip-based method that has the ability to display the antibody diversity from individual sera sample with low cost. Immunosignaturing is a medical diagnostic test that has many applications in current medical research and in diagnosis. From a previous clinical study, patients diagnosed for lung cancer were tested for their immunosignature vs. healthy non-cancer volunteers. The pattern of reactivity against the random peptides (the ‘immunosignature’) revealed common signals in cancer patients, absent from healthy controls. My study involved the search for common amino acid motifs in the cancer-specific peptides. My search through the hundreds of ‘hits’ revealed certain motifs that were repeated more times than expected by random chance. The amino acids that were the most conserved in each set include tryptophan, aspartic acid, glutamic acid, proline, alanine, serine, and lysine. The most overall conserved amino acid observed between each set was D - aspartic acid. The motifs were short (no more than 5-6 amino acids in a row), but the total number of motifs I identified was large enough to assure significance. I utilized Excel to organize the large peptide sequence libraries, then CLUSTALW to cluster similar-sequence peptides, then GLAM2 to find common themes in groups of peptides. In so doing, I found sequences that were also present in translated cancer expression libraries (RNA) that matched my motifs, suggesting that immunosignatures can find cancer-specific antigens that can be both diagnostic and potentially therapeutic.
ContributorsShiehzadegan, Shima (Author) / Johnston, Stephen (Thesis director) / Stafford, Phillip (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2015-12
Description
Cancer is a disease that has no bias based on race, gender, sexuality, socioeconomic status, or religious beliefs. Millions upon millions of people are affected every day by this disease in many different ways. In order to show support and raise funds for these people to help with treatment costs, housing, and much more American Cancer Society created and event called Relay for Life. Relay for Life is an event that many people may describe as a walk-a-thon fundraiser, but to those who have had a personal experience with cancer they understand that Relay is much more. Relay for Life is more than a fundraiser; it is an event that brings hope, love, and care into a community. Many people across the country show up to a Relay event to hear the success stories of those who are in remission, show support for their family and friends who are still fighting, and simply volunteer in order to further remember those that they lost to cancer.
The impacts that Relay for Life supplies go beyond monetary value and branch into the world of emotional and mental value. The stories that you hear from cancer patients, caregivers, survivors, friends, and family all show the appreciation for this event even in the smallest of communities. Looking at the Relay for Life website you can see the thousands of submissions detailing exactly why that individual participates in this event. You can read stories of sorrow, drive, friendships that have formed, and hope that has sprouted because of Relay for Life. An event such as this that celebrates the fight and works to give the world more birthdays truly empowers its participants to make a difference and make a connection with each other.
In this project, I set out to reveal the importance of Relay for Life that can be seen and heard through everyone who participates across the nation. It is important to take both personal experience and monetary value into account when looking at how Relay has had a positive impact on the lives of those affected by cancer, but when looking at the broad picture it becomes obvious how this event means more than money.
The impacts that Relay for Life supplies go beyond monetary value and branch into the world of emotional and mental value. The stories that you hear from cancer patients, caregivers, survivors, friends, and family all show the appreciation for this event even in the smallest of communities. Looking at the Relay for Life website you can see the thousands of submissions detailing exactly why that individual participates in this event. You can read stories of sorrow, drive, friendships that have formed, and hope that has sprouted because of Relay for Life. An event such as this that celebrates the fight and works to give the world more birthdays truly empowers its participants to make a difference and make a connection with each other.
In this project, I set out to reveal the importance of Relay for Life that can be seen and heard through everyone who participates across the nation. It is important to take both personal experience and monetary value into account when looking at how Relay has had a positive impact on the lives of those affected by cancer, but when looking at the broad picture it becomes obvious how this event means more than money.
ContributorsTrisko, Rebecca Lynn (Author) / Roen, Duane (Thesis director) / Wales, Anna (Committee member) / Division of Teacher Preparation (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
PD-L1 blockade has shown recent success in cancer therapy and cancer vaccine regimens. One approach for anti-PD-L1 antibodies has been their application as adjuvants for cancer vaccines. Given the disadvantages of such antibodies, including long half-life and adverse events related to their use, a novel strategy using synbodies in place of antibodies can be tested. Synbodies offer a variety of advantages, including shorter half-life, smaller size, and cheaper cost. Peptides that could bind PD-L1 were identified via peptide arrays and used to construct synbodies. These synbodies were tested with inhibition ELISA assays, SPR, and pull down assays. Additional flow cytometry analysis was done to determine the binding specificity of the synbodies to PD-L1 and the ability of those synbodies to inhibit the PD-L1/PD-1 interaction. Although analysis of permeabilized cells expressing PD-L1 indicated that the synbodies could successfully bind PD-L1, those results were not replicated in non-permeabilized cells. Further assays suggested that the binding of the synbodies was non-specific. Other tests were done to see if the synbodies could inhibit the PD-1/PD-L1 interaction. This assay did not yield any conclusive results and further experimentation is needed to determine the efficacy of the synbodies in inhibiting this interaction.
ContributorsMujahed, Tala (Author) / Johnston, Stephen (Thesis director) / Blattman, Joseph (Committee member) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Currently, treatment for multiple myeloma (MM), a hematological cancer, is limited to post-symptomatic chemotherapy combined with other pharmaceuticals and steroids. Even so, the immuno-depressing cancer can continue to proliferate, leading to a median survival period of two to five years. B cells in the bone marrow are responsible for generating antigen-specific antibodies, but in MM the B cells express mutated, non-specific monoclonal antibodies. Therefore, it is hypothesized that antibody-based assay and therapy may be feasible for detecting and treating the disease. In this project, 330k peptide microarrays were used to ascertain the binding affinity of sera antibodies for MM patients with random sequence peptides; these results were then contrasted with normal donor assays to determine the "immunosignatures" for MM. From this data, high-binding peptides with target-specificity (high fluorescent intensity for one patient, low in all other patients and normal donors) were selected for two MM patients. These peptides were narrowed down to two lists of five (10 total peptides) to analyze in a synthetic antibody study. The rationale behind this originates from the idea that antibodies present specific binding sites on either of their branches, thus relating high binding peptides from the arrays to potential binding targets of the monoclonal antibodies. Furthermore, these peptides may be synthesized on a synthetic antibody scaffold with the potential to induce targeted delivery of radioactive or chemotherapeutic molecular tags to only myelomic B cells. If successful, this would provide a novel alternative to current treatments that is less invasive, has fewer side effects, more specifically targets the cause of MM, and reliably diagnoses the cancer in the presymptomatic stage.
ContributorsBerry, Jameson (Co-author) / Buelt, Allison (Co-author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Division of Teacher Preparation (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05