No description available.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The role of viruses in most common cancers is undoubtedly important, yet highly underestimated. Human Papilloma Virus (HPV) has been implicated with 99.7% of cervical cancers and its oncogenic mechanism has been clearly identified. The association of cervical cancer with 90% of triple negative breast cancer (TNBC) cases in African countries creates an intriguing possibility of HPV being a candidate oncovirus for breast cancer. In fact, numerous recent tissue studies conducted throughout the world detected HPV DNA in breast cancer tissues of patients with cervical cancer, while high‐risk HPV types (16, 18, 33) were present in invasive ductal carcinomas. 5,6 Prevalence of HPV varied from 4% in Mexican to 86% in American women. The virus was noted to be present in tumor tissue only, with the exception of one study, which identified lower concentration of HPV in normal tissue. 7 Although substantial evidence exists supporting involvement of HPV in breast cancer, no clinical studies have been conducted to elucidate this relationship. The goal of our retrospective chart review was to examine the association of breast cancer and HPV‐related cervical dysplasia in a cohort of women in urban setting. 15% (39/260) had abnormal Pap‐smear, while 8% (16/198) were HPVpositive. No statistically significant difference of Pap‐smear abnormality or of HPV positivity were detected among the groups in all categories. However, we noticed that non‐luminal breast cancers, double negative and triple negative (DN and TN), have higher rate of HPV positivity: 13.3% non‐luminal vs. 6.3% of luminal breast cancers, 12.5% DN breast cancers and 11.5% of TN vs. 6.4% of luminal A and 6.3% of luminal B. This creates an intriguing possibility that HPV might be associated with more than 50% increase of incidence rates of non‐luminal breast cancers, suggesting a need for larger scale studies to confirm this association.

Human Papilloma Virus (HPV) is a conserved DNA virus, which infects mucosal and cutaneous epithelia. Although over 200 types of HPV have been identified which can infect humans, only around 15 high-risk (HR) types have been shown to be responsible for the development of cancer. HPV-16 is the most abundant HR-HPV type being responsible for almost 70% of cervical cancers. HPV-16 consists of 8 genes, the early genes (E1, E2, E4, E5 and the potential oncogenes E6 and E7) responsible for the infection, amplification and proliferation and the late genes (L1 and L2) responsible for the packaging and assembly of the virus. Autophagy, a physiological mechanism of intracellular digestion and recycling of unwanted cellular materials such as aggregated proteins and organelles has been shown to act as a first line defence against invading pathogens. An essential condition for this process is the formation of double membrane structures called the autophagosomes, which can engulf the pathogen or pathogenic proteins and digest them by fusing with endocytic vesicles (lysosomes). Beclin 1 and LC3 are vital proteins involved in the complicated process of the autophagosome formation while SQSTM1/p62 has a key role in the identification and transit of cargo into the forming autophagosomes. This novel work focuses on investigating the role of autophagy in HR-HPV related tumour development and progression in cervical epithelial cells both in vitro and ex vivo.

No description available.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The human microbiome is the collection of microorganisms in the body that exist in a mutualistic relationship with the host. Recent studies indicate that perturbations in the microbiome may be implicated in a number of diseases, including cancer. More specifically, changes in the gut and vaginal microbiomes may be associated with a variety of gynecologic cancers, including cervical cancer, uterine cancer, and ovarian cancer. Current research and gaps in knowledge regarding the association between the gut and vaginal microbiomes and the development, progression, and treatment of gynecologic cancers are reviewed here. In addition, the potential use of probiotics to manage symptoms of these gynecologic cancers is discussed. A better understanding of how the microbiome composition is altered at these sites and its interaction with the host may aid in prevention, optimization of current therapies, development of new therapeutic agents and/or dosing regimens, and possibly limit the side effects associated with cancer treatment.

Master of Science / Division of Biology / Nicholas A. Wallace / Cancer is not a single story, but rather numerous often interwoven tales, each with its own characters and progression. In the case of human papillomavirus (HPV) induced cervical cancer (CaCx), the narrative is about the relationship between virus and host, with the consequences of evolution’s shortsightedness driving the plot. Along with the increased proliferative state characteristic of cancer, cells experience frequent, inaccurate replication and replication stresses (ex. DNA damage and nucleotide starvation). To prevent replication fork stall and collapse generated by these stresses, the cell employs translesion synthesis (TLS). Notably, most of the genes in this pathway are upregulated in CaCx; however, the key protein polymerase eta is not. We have observed that upregulation in this pathway is complicated. It occurs at numerous levels, increasing both mRNA and protein abundance. This research further dissects how TLS upregulation occurs. Data shows that in CaCx-derived cell lines, the stability of some TLS proteins is increased, while the stability of other TLS proteins is unchanged. The increased proliferation, typical of these cell lines, cannot account for the enhanced stability. Despite increased TLS protein stability, these cells fail to adequately activate TLS increasing the risk of DNA damage. Genomic instability is a driving factor in HPV genome integration that prevents viral propagation and leads to cell transformation. It also raises mutagenesis rates, likely creating a selective pressure for tolerating failed TLS. The elevated mutation rate known to be associated with failed TLS could also provide a mechanism for acquired resistance to the drugs commonly used to treat CaCx. Changes in protein abundance are routinely used as biomarkers that can lead to the improved outcomes associated with early cancer detection. Elevated TLS protein could be leveraged to ensure cervical cancers are detected during Stage 1, when the 5-year survival rate is 80-90%, rather than at Stage IV, when the rate dips to around 15%.

Alkaline glutaraldehyde (GTA) has been used as a high level chemical disinfectant and sterilant for many years and is known to kill a broad spectrum of organisms ranging from vegetative eukaryotes to bacterial endospores. Although the mechanism of sporicidal action has been studied on numerous occasions, GTA's exact mechanism(s) of action are still debated. In addition to the uncertainty of GTA's mechanism(s) of action, GTA has also shown significant variability in the time required to kill endospores and naked viruses. A better knowledge of the lethal mechanism(s) of GTA is needed to understand this discrepancy in kill times for GTA against spores of different species. Similar trends have been observed in GTA's activity against non-enveloped viruses. Based on previous work, one proposed major mechanism of GTA's sporicidal activity is related to the number of available primary amines located on the surface of microbes. In this study, we have compared the efficacy of GTA on spores from 5 Bacillus species. We have also developed a method for staining these spores with amine reactive dyes to create fluorescent profiles correlating to the abundance of free amino groups on each spore type. We also describe a method for staining non-enveloped viruses to identify exposed primary amino groups on capsid proteins that may act as targets for GTA, using amine reactive Gold nanoparticles. We found that GTA 6-Log10 reduction times for various spore types varied at both the batch and species level. Spore coat thickness and fluorescence were useful tools in predicting the susceptibility of spores to GTA. Amine reactive gold particles (AuNPs) also proved useful in identifying virus susceptibility to GTA. Ultimately, more reliable disinfection testing methods are needed, and caution should be used when trying to extrapolate data generated from surrogate organisms to other species.

No description available.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / To systematically review all studies examining HPV vaccination acceptability among immigrant and ethnic minority parents and eligible individuals for cervical cancer prevention in the Unites states. MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Cochrane database searches were conducted searching for English language, US‐based studies to examine immigrant and ethnic minority population’s acceptability of HPV vaccination. Thirteen of more than 3,098 potentially relevant articles were included in the final analysis. Results. Latinos were statistically more likely to accept vaccination for both their daughters and sons. Foreign‐born adult Latinas were more accepting of the vaccine than U.S.‐born Latinas after controlling for other variables. Overall African American and Asian American parents were less likely to accept HPV vaccination for their daughters than Hispanic and White parents. Of the African American parents who intended to vaccinate their children the majority were significantly non‐Baptist and had higher levels of education. The majority of Haitian immigrants intended to vaccinate daughters and the rest agreed that they would most likely have their daughters vaccinated if their daughters’ physicians recommended it. More research is needed, particularly in the context of health care provider HPV vaccination recommendation to immigrant and ethnic‐minority populations. Acceptance figures so far suggest that the vaccine is generally well received among Hispanic/Latin and Haitian immigrants, but details of ethnic variations among these groups and a qualitative understanding of lower rates of acceptability among African American and Asian American communities are still being awaited. Despite advances in cervical cancer screening rates in the US, cervical cancer remains disproportionately high among low‐income immigrant and minority women, making this subgroup particularly vulnerable to disparities in screening and its detection. The purpose of this study is to examine the qualitative aspects of institutional and community level interventions of Cervical Intraepithelial Neoplasia (CIN) within the immigrant and refugee populations and the use of HPV vaccination as a prevention method. Combinations of the following keywords/phrases will be used: CIN‐ Cervical Intraepithelial Neoplasia, Cervical diseases, Cervical dysplasia, Refugees, Pap smear, Cervical Cancer Screening, HPV‐ Human Papillomavirus, HPV vaccination, Ethnic minorities, Immigrants. Independent reviews of each article will be conducted to assess the study quality and confirm the accuracy, completeness, and consistency of the abstracted data.

Human papilloma virus (HPV) is the most common viral infection of the reproductive tract and a well-established cause of cervical, anal, and oropharyngeal cancers in both women and men worldwide. Despite data that supports HPV vaccine as an effective measure to prevent such cancers, vaccine uptake has not been optimal in many countries. In the United States (US) for example, rates have stagnated over the past few years and only one-third of adolescents are fully immunized, in contrast to other adolescent vaccines such as Tdap and meningococcal that have double the rates of uptake. Current approaches to HPV vaccine education and delivery have not been successful at improving immunization rates. In this article we propose the implementation of a child rights, social justice, and health equity-based approach to HPV vaccine policy. This approach would promote youth’s participation in medical decision-making and advance policies that allow for independent consent to HPV vaccination. We postulate that by empowering youth to be involved in issues pertaining to their health and well-being, they will be more likely to explore and discuss information about HPV with others, and be able to make informed decisions related to HPV vaccine.