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- All Subjects: Cancer
- Creators: Lake, Douglas
- Creators: Brian, Jennifer
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Resource Type: Text
Description
Programmed cell death ligand-1 (PD-L1) is an overexpressed protein on many tumor cell types. PD-L1 is involved in normal immune regulation, playing an important role in self-tolerance and controlling autoimmunity. However, ligation of PD-L1 to PD-1 on activated T cells leads to tumor-mediated T cell suppression. Inhibiting the PD-1/PD-L1 pathway has emerged as an effective target for anti-tumor immunotherapies. Monoclonal antibodies (mAbs) targeting tumor-associated antigens such as PD-L1 have proven to be effective checkpoint blockades, improving therapeutic outcomes for cancer patients and receiving FDA approval as first line therapies for some cancers. A single chain variable fragment (scFv) is composed of the variable heavy and light chain regions of a mAb, connected by a flexible linker. We hypothesized that scFv proteins based on the published anti-PD-L1 monoclonal antibody sequences of atezolizumab and avelumab would bind to cell surface PD-L1. Four single chain variable fragments (scFvs) were constructed based on the sequences of these mAbs. PCR was used to assemble, construct, and amplify DNA fragments encoding the scFvs which were subsequently ligated into a eukaryotic expression vector. Mammalian cells were transfected with the scFv and scFv-IgG plasmids. The scFvs were tested for binding to PD-L1 on tumor cell lysates by western blot and to whole tumor cells by staining and flow cytometry analysis. DNA sequence analysis demonstrated that the scFv constructs were successfully amplified and cloned into the expression vectors and recombinant scFvs were produced. The binding capabilities of the scFvs constucts to PD-L1 protein were confirmed by western blot and flow cytometry analysis. This lead to the idea of constructing a CAR T cell engineered to target PD-L1, providing a possible adoptive T cell immunotherapy.
ContributorsPfeffer, Kirsten M. (Author) / Lake, Douglas (Thesis director) / Ho, Thai (Committee member) / Hastings, Karen (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Through a standpoint feminist perspective (Harding 2009) I conducted a situational analysis (Clarke, 2015) that examined academic literature and cancer support discussion boards (DBs) to identify how Western biomedicine, specifically oncology, can integrate complementary and alternative medicine (CAM) to improve cancer treatment in children. The aims of this project were: 1) to identify the CAM treatments that are being used to alleviate the side effects from oncological treatments and/or treat pediatric cancers; 2) to compare the subjective experience of CAM to Western biomedicine of cancer patients who leave comments on Group Loop, Cancer Compass and Cancer Forums, which are online support groups (N=20). I used grounded theory and situational mapping to analyze discussion threads. The participants identified using the following CAM treatments: herbs, imagery, prayer, stinging nettle, meditation, mind-body therapies and supplements. The participants turned to CAM treatments when their cancer was late-stage or terminal, often as an integrative and not exclusively to treat their cancer. CAM was more "effective" than biomedical oncology treatment at improving their overall quality of life and functionality. We found that youth on discussion boards did not discuss CAM treatments like the adult participants, but all participants visited these sites for support and verification of their cancer treatments. My main integration recommendation is to combine mind-body CAM therapies with biomedical treatment. This project fills the gap in literature that ignores the ideas of vulnerable populations by providing the experiences of adult and pediatric cancer patients, and that of their families. It is applicable to areas of the social studies of medicine, patient care, and families suffering from cancer. KEYWORDS: Cancer; Complementary and Alternative Medicine; Situational Analysis; Standpoint Feminism
ContributorsEsposito, Sydney Maria (Author) / Martinez, AirÃÂn (Thesis director) / Hruschka, Daniel (Committee member) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Exosomes have been known to secrete an increased amount of miRNA and noncoding genes that are abnormally expressed in various cancer subtypes. Thus, they may be an early marker for pediatric cancer types that are more difficult to diagnosis without invasive techniques, and may also help identify progression of the disease. In the project, six types of pediatric cancer cell lines, along with their extracted exosomes, were analyzed and tested for different monoclonal antibodies through western blot analysis. The genes EWS-FLI1 and FGFR4 were also identified in some cancer cell lines through Reverse-Transcriptase Polymerase Chain Reaction analysis (RT-PCR). The results were indicative of similar protein markers being found in both the originating cells and their corresponding exosomes.
ContributorsKaur Bhinder, Harsimran (Author) / Lake, Douglas (Thesis director) / Azorsa, David (Committee member) / Barrett, The Honors College (Contributor)
Created2017-12
Description
The rate of cancer incidence is a morbid figure. Twenty years ago, 1 in 2 men and 1 in 3 women were predicted to be afflicted by cancer throughout their lifetime (Cancer Facts & Figures- 1998). In 2017, the rate remains the same ("Cancer Statistic Center"). Every year, more people are affected by cancer, which is a physiologically, psychologically, emotionally and socially devastating disease. And yet the language and metaphors we use to describe cancer focus our attention on the "fight" of the heroic individual against the brutal disease or on finding a cure. Despite this narrow rhetoric, there are many meaningful, supportive, and palliative measures designed to substantively and holistically care for cancer patients, beyond their medical treatment. Many of these interventions help the patient feel supported (and less alone in this "battle") by building robust communities. In this thesis, I argue the summer camps for children affected by cancer are meaningful interventions that offer palliative care throughout their treatment by creating support networks with peers going through similar medical procedures. Drawing on anecdotal evidence from three cancer camps and a detailed literature review of a subset of palliative interventions designed to promote well-being, this thesis proposes a new model for a summer camp that focuses on emotional processing emotional expression, positive psychology in order to improve palliative care for cancer patients.
ContributorsPearce, Spencer Taylor (Author) / Miller, April (Thesis director) / Brian, Jennifer (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Cancer is one of the leading causes of death in the world and represents a tremendous burden on patients, families and societies. S. Typhimurium strains are specifically attracted to compounds produced by cancer cells and could overcome the traditional therapeutic barrier. However, a major problem with using live attenuated Salmonella as anti-cancer agents is their toxicity at the dose required for therapeutic efficacy, but reducing the dose results in diminished efficacy. In this project, we explored novel means to reduce the toxicity of the recombinant attenuated Salmonella by genetically engineering those virulence factors to facilitate maximal colonization of tumor tissues and reduced fitness in normal tissues. We have constructed two sets of Salmonella strains. In the first set, each targeted gene was knocked out by deletion of the gene. In the second set, the predicted promoter region of each gene was replaced with a rhamnose-regulated promoter, which will cease the synthesis of these genes in vivo, a rhamnose-free environment.
ContributorsBenson, Lee Samuel (Author) / Kong, Wei (Thesis director) / Martin, Thomas (Committee member) / Lake, Douglas (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor) / Center for Infectious Diseases and Vaccinology (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
The long-term survival of patients with glioblastoma multiforme is compromised by the tumor's proclivity for local invasion into the surrounding normal brain. These invasive cells escape surgery and display resistance to chemotherapeutic- and radiation-induced apoptosis. We have previously shown that tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell invasion and survival via binding to the fibroblast growth factor-inducible 14 (Fn14) receptor and subsequent activation of the Rac1/NF-kappaB pathway. In addition, we have reported previously that Fn14 is expressed at high levels in migrating glioma cells in vitro and invading glioma cells in vivo. Here we demonstrate that TWEAK can act as a chemotactic factor for glioma cells, a potential process to drive cell invasion into the surrounding brain tissue. Specifically, we detected a chemotactic migration of glioma cells to the concentration gradient of TWEAK. Since Src family kinases (SFK) have been implicated in chemotaxis, we next determined whether TWEAK:Fn14 engagement activated these cytoplasmic tyrosine kinases. Our data shows that TWEAK stimulation of glioma cells results in a rapid phosphorylation of the SFK member Lyn as determined by multiplex Luminex assay and verified by immunoprecipitation. Immunodepletion of Lyn by siRNA oligonucleotides suppressed the chemoattractive effect of TWEAK on glioma cells. We hypothesize that TWEAK secretion by cells present in the glioma microenvironment induce invasion of glioma cells into the brain parenchyma. Understanding the function and signaling of the TWEAK-Fn14 ligand-receptor system may lead to development of novel therapies to therapeutically target invasive glioma cells.
ContributorsJameson, Nathan Meade (Author) / Anderson, Karen (Thesis director) / Lake, Douglas (Committee member) / Tran, Nhan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
Description
Treating a minor diagnosed with cancer is a difficult situation. However, cases in which doctors and the patient's family disagree about the proper course of treatment present complex scenarios when it comes to patient care. The forced treatment of Cassandra Callender came as a result of challenging interactions between the patient, the medical establishment, and the state. While the Connecticut Supreme Court mainly considered Cassandra's maturity and her mother's actions when deciding this case, there were more factors contributing to Cassandra's quality of care than her ability to make decisions. An evaluation of these factors demonstrates important implications for ensuring a minor receives the best care. Cassandra wished to pursue a means of treatment that would have fewer serious side effects than chemotherapy, but her assessment of her prognosis was markedly different than that of her doctors. While it is clear that Cassandra did not fully grasp the likelihood of death without chemotherapy treatment, her perspective should not have been fully ignored. The forced treatment inflicted serious (though short term) harm. To understand the full context of this case, this paper considers relevant legal doctrine, decision-making capabilities of minors, the problems and perils of chemotherapy, the role of the media, and the doctor-patient relationship. Developing a perspective based on these facets of Cassandra's case is important in determining how to facilitate the best interaction between doctor and patient and to make sure that future cases aid the patient and his or her family to make the best decision given the situation. Even when there is no consensus about what is best for a patient, more consideration must be given to the patient's perspective, beyond attempting to solely extend life.
ContributorsStoffer, Sidney Rae (Author) / Brian, Jennifer (Thesis director) / Cook-Deegan, Robert (Committee member) / School of Criminology and Criminal Justice (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
The purpose of this project is to analyze the current state of cancer nanomedicine and its challenges. Cancer is the second most deadly illness in the United States after heart disease. Nanomedicine, the use of materials between 1 and 100 nm to for the purpose of addressing healthcare-related problems, is particularly suited for treating it since nanoparticles have properties such as high surface area-to-volume ratios and favorable drug release profiles that make them more suitable for tasks such as consistent drug delivery to tumor tissue. The questions posed are: What are the current nanomedical treatments for cancer? What are the technical, social, and legal challenges related to nanomedical treatments and how can they be overcome? To answer the questions mentioned above, information from several scientific papers on nanomedical treatments for cancer as well as from social science journals was synthesized. Based on the findings, nanomedicine has a wide range of applications for cancer drug delivery, detection, and immunotherapy. The main technical challenge related to nanomedical treatments is navigating through biological barriers such as the mononuclear phagocyte system, the kidney, the blood-brain barrier, and the tumor microenvironment. Current approaches to meeting this challenge include altering the size, shape, and charge of nanoparticles for easier passage. The main social and legal challenge related to nanomedical treatments is the difficulty of regulating them due to factors such as the near impossibility of detecting nanowaste. Current approaches to meeting this challenge include the use of techniques such as scanning tunneling microscopy and atomic force microscopy to help distinguish nanowaste from the surroundings. More research will have to be done in these and other areas to enhance a major cancer-fighting tool.
ContributorsAbraham, Alfred Francy (Author) / Brian, Jennifer (Thesis director) / Liu, Yan (Committee member) / Materials Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05