Cancer Biology Commons^™

Importance Of Specific Nk Cell Subsets For Antitumor Immunity In Hpv+ Cancers, Madison O'Hara

Dissertations & Theses (Open Access)

High-risk type human papillomaviruses (HPV) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing worldwide. Survival rates for patients with locally advanced disease are poor and variable after standard of care (SOC) treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential for improving clinical outcome. The natural killer (NK) cells are a critical component for antitumor innate effector immunity. Among the multitude of activation and inhibitory receptors on immune cells, HLA-DR is recognized as an important activation marker …

Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha

Dissertations & Theses (Open Access)

Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …

Hpv Mediated Antagonism Of The Il-18 Proinflammatory Pathway In Head And Neck Cancer, Wyatt W. Anderson

Electronic Thesis and Dissertation Repository

In this thesis, I examined the effect of human papillomavirus (HPV) on the proinflammatory IL-18 cytokine pathway in head and neck cancers. I investigated the expression and methylation of genes associated with this pathway using The Cancer Genome Atlas (TCGA) data. In HPV+ cancers, IL18, CASP1, and AIM2 were downregulated, while IL18BP was upregulated compared to HPV- cancers and adjacent non-cancerous tissues, and IL18’s promoter was significantly more methylated. I compared HPV+ and HPV- head and neck cancer cell lines for expression of RNA and protein levels of IL-18 and IL-18BP by qPCR, western blot, and ELISA. IL-18 …

Novel Roles Of Tobacco-Associated Genes Underlying Disparate Survival In Appalachian Head And Neck Squamous Cell Carcinoma, Brenen William Papenberg

Graduate Theses, Dissertations, and Problem Reports

Head and neck squamous cell carcinoma (HNSCC) is an aggressive neoplasm primarily caused by tobacco consumption or human papillomavirus (HPV) infection. Incidence and mortality rates for HNSCC vary geographically. Appalachian residents consume tobacco products to a greater extent than national averages, a risk factor known to promote HPV-negative HNSCC through increased genomic instability. Male Appalachian patients display significantly worse relative survival than Appalachian females or non-Appalachian residents of either sex. Secondary analysis of available cancer registry outcome data from 2007-2013 indicates that white males with stage IV oral cavity/pharyngeal (OC/P) HNSCC are responsible for the decreased male survival observed within …

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of …

Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko

Theses and Dissertations

According to the American Cancer Society, it has been estimated that in 2019 alone, there will be approximately 53,000 new cases of oropharyngeal cancers. Oropharyngeal cancers are the largest subset of head and neck squamous cell carcinomas (HNSCCs), which are the sixth most common cancer across worldwide populations. They, along with other HNSCCs, fall under a category of cancers known as Human papillomavirus (HPV)-associated cancers, and it has been found that upwards of 70% of these cancers can be attributed to high-risk HPV infections.

Specifically, the high-risk HPV gene, E7, plays a key role in relieving cell cycle repression by …

Molecular Mechanisms Of Dna Replication Initiation In Hpvs With Genetic Variations Leading To Cellular Carcinogenesis, Gulden Yilmaz

Graduate School of Biomedical Sciences Theses and Dissertations

Human papillomaviruses are a vast family of double-stranded DNA viruses containing non-carcinogenic and carcinogenic types, whose crucial differences remain unknown, except for the difference in the frequency of DNA replication. The human papillomavirus (HPV) E2 protein regulates the initiation of viral DNA replication and transcription. Its recognition and binding to four 12 bp palindromic sequences in the viral origin is essential for its function. Little is known about the DNA binding mechanism of the E2 protein found in HPV types that have low risk for oncogenicity (low-risk) as well as the roles of various elements of the individual binding sites. …