Cancer is among the most common causes of human deaths globally. Because of limitations and adverse effects of conventional cancer treatments, the need for new treatments is imminent. A rapidly expanding field in cancer therapy is cancer immunotherapy, which aims to, in one way or another, aid the patient’s own immune system in its battle against the tumor cells. A type of cancer immunotherapy is oncolytic virotherapy which utilizes viruses that either have a natural inclination to infect and replicate inside tumor cells or have been engineered to specially replicate in tumor cells causing oncolysis. An example of an oncolytic virus is the Lokon Oncolytic Adenovirus (LOAd). This virus specifically replicates inside cancer cells and is based on adenovirus serotype 5 but with a serotype 35 fiber, causing it to infect via the cluster of differentiation 46 receptor, which is ubiquitously expressed on somatic and tumor cells. A notable virus with the LOAd backbone, that is being evaluated in several clinical trials, is LOAd703, which is armed with the immunostimulatory transgenes 4-1BB ligand and a trimerized cluster of differentiation 40 ligands. In this project, I describe the development and evaluation of Ad703+, a cell killing adenovirus carrying the transgenes of LOAd703 as well as a novel cytotoxic transgene that never has been used in oncolytic virotherapy previously. This virus was developed using the AdEasy system, which is a replication-deficient virus platform based on adenovirus serotype 5. This virus enters cells using the human coxsackie and adenovirus receptor, which is homologous to the murine equivalent.  The ability to express the immunostimulatory transgenes and the cell killing ability of Ad703+ was evaluated in two different human cell lines, HEK293 which allows the replication of Ad703+, and the lung cancer model A549. Ad703+ was shown to express the immunostimulatory transgenes in both of the cell lines, but in a replication-dependent manner. Ad703+ was also shown to exhibit cell killing ability in a replication-independent manner on par with other oncolytic viruses.  The ability of Ad703+ to trigger cell death in a replication-independent manner opens up for the possible application in pre-clinical in vivo studies using mice due to its theoretical ability to infect murine cells and simulate viral oncolysis.

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Purpose: The relationship between testicular cancer and working as a firefighter has been a relatively brushed off scope of concentration until recent years and recent developments in hopes of presenting new protocols and better guidelines to screen for testicular cancer in this occupation. The purpose of this study was to perform a scoping review to present the current data concerning testicular cancer and its association to the occupation of firefighters. Methods: PubMed as a data base was used and articles concerning firefighters and testicular cancer were found and screened for eligibility with respect to the kind of study and the data it entailed. Data was reported in this study and discussed. Results: It was found that testicular cancer has the highest or second highest incidence and mortality rate among all the cancers that firefighters suffer from at the P < 0.001 significance. Among the second highest were also skin, pleural, and thyroid cancer. Conclusion: While testicular cancer is highly treatable due to its high survival rate, it has a strong and alarming prominent presence in the firefighter occupation. The results should be interpreted with caution due to the limitations of the studies evaluated, however in all studies, testicular cancer had a far more significant incidence and mortality risk than the other cancers firefighters were evaluated for.

Lung cancer is the leading cause of cancer death in the United States and worldwide. The higher mortality among patients with lung cancer is related to cases being diagnosed in late stage where treatment is limited. Urban and rural health outcomes are potentially influenced by differences in accessibility to health care services. We are unaware of existing research examining geographic differences in or factors related to lung cancer mortality in Florida. Therefore, this study aims to examine lung cancer mortality differences between urban and rural counties in Florida. We examined all 67 counties in Florida to investigate if a rural disparity exists in lung cancer mortality. We collected data from the National Cancer Institute (NCI) State Cancer Profile. We assigned urban and rural designation using the United States Census Bureau definition based on population density. We then used a t-test for unequal variances to compare the mean lung cancer mortality rate for the urban counties versus rural counties using Microsoft Excel. We used ArcGIS Pro software to create three maps: one showing urban and rural county designations, one showing lung cancer mortality, and a third bivariate map of urban and rural designations combined with age-adjusted lung cancer mortality rates together to examine the geographic distributions in Florida. We observed a mean age-adjusted lung cancer mortality of 62.7 per 100,000 for rural counties in Florida and a mean of 44.2 per 100,000 for urban counties which was significantly different using a t-test for unequal variances (p < 0.0001). The counties with the highest lung cancer mortality were grouped geographically in Florida’s Big Bend area. Overall, rural counties had a significantly higher average lung cancer mortality than the urban counties in Florida. Future research should examine factors affecting higher lung cancer mortality in rural counties such as screening locations and access to care.

Various studies show a variety of interventions for radiotherapy-induced skin toxicity. Radiotherapy-induced skin toxicity is the most common side effect for women with breast cancer who undergo radiotherapy sessions. Intervention agents include topical creams, barrier films, oral agents, as well as laser therapy. However, despite the variety of intervention agents available, there is still a lack of accepted guidelines to manage radiotherapy-induced skin toxicity. This thesis aims to conduct a systematic review and meta-analysis of published randomized controlled trials with the primary purpose of exploring the available intervention methods to prevent radiotherapy-induced skin toxicity and evaluate the effects of different interventions for radiotherapy-induced skin toxicity among breast cancer patients. A total of 37 studies were included in the study. The overall results for the study revealed that the available interventions for radiotherapy-induced skin toxicity reside within non-steroid creams, steroid creams, oral supplements, laser therapy, and films. In addition, oral supplements were most effective in preventing radiotherapy-induced skin toxicity. Other groups showed preventive results but were not statistically significant, but other factors were taken into consideration. This systematic review and meta-analysis provide insight to oncologists by helping make better clinical decisions for their patients, having comprehensive evidence readily available to offer the best treatment for radiotherapy-induced skin toxicity and to have a more efficient overall treatment for breast cancer patients. Finally, this systematic review and meta-analysis can guide a path that leads to an accepted treatment for radiotherapy-induced skin toxicity.

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