Jennifer Young Pierce

Transcriptional Suppression, DNA Methylation, and Histone Deacetylation of the Regulator of G-Protein Signaling 10 (RGS10) Gene in Ovarian Cancer Cells

RGS10 regulates ovarian cancer cell growth and survival, and RGS10 expression is suppressed in cell models of ovarian cancer chemoresistance. However, the mechanisms governing RGS10 expression in ovarian cancer are poorly understood. Here we report RGS10 suppression in primary ovarian cancer and CAOV-3 ovarian cancer cells compared to immortalized ovarian surface epithelial (IOSE) cells, and in A2780-AD chemoresistant cells compared to parental A2780 cells. RGS10-1 and RGS10-2 transcripts are expressed in ovarian cancer cells, but only RGS10-1 is suppressed in A2780-AD and CAOV-3 cells, and the RGS10-1 promoter is uniquely enriched in CpG dinucleotides. Pharmacological inhibition of DNA methyl-transferases (DNMTs) increased RGS10 expression, suggesting potential regulation by DNA methylation. Bisulfite sequencing analysis identified a region of the RGS10-1 promoter with significantly enhanced DNA methylation in chemoresistant A2780-AD cells relative to parental A2780 cells. DNA methylation in CAOV-3 and IOSE cells was similar to A2780 cells. More marked differences were observed in histone acetylation of the RGS10-1 promoter. Acetylated histone H3 associated with the RGS10-1 promoter was significantly lower in A2780-AD cells compared to parental cells, with a corresponding increase in histone deacetylase (HDAC) enzyme association. Similarly, acetylated histone levels at the RGS10-1 promoter were markedly lower in CAOV-3 cells compared to IOSE cells, and HDAC1 binding was doubled in CAOV-3 cells. Finally, we show that pharmacological inhibition of DNMT or HDAC enzymes in chemoresistant A2780-AD cells increases RGS10 expression and enhances cisplatin toxicity. These data suggest that histone de-acetylation and DNA methylation correlate with RGS10 suppression and chemoresistance in ovarian cancer. Markers for loss of RGS10 expression may identify cancer cells with unique response to therapeutics.

An Association Between Trichomonas vaginalis and High-Risk Human Papillomavirus in Rural Tanzanian Women Undergoing Cervical Cancer Screening

OBJECTIVE The goal of this study was to determine the prevalence of vaginitis and its association with high-risk human papillomavirus (HR HPV) in women undergoing cervical cancer screening in rural Tanzania. METHODS For the purpose of cervical cancer screening, cytology and HR HPV polymerase chain reaction data were collected from 324 women aged between 30 and 60 years. Microscopy and gram stains were used to detect yeast and bacterial vaginosis. Cervical nucleic acid amplification test specimens were collected for the detection of Trichomonas vaginalis (TV), Chlamydia trachomatis, and Neisseria gonorrhoeae. RESULTS The majority of women were married (320 of 324) and reported having a single sexual partner (270 of 324); the median age of participants was 41 years. HR HPV was detected in 42 participants. Forty-seven percent of women had vaginitis. Bacterial vaginosis was the most common infection (32.4%), followed by TV (10.4%), and yeast (6.8%). In multivariable logistic regression analysis, TV was associated with an increased risk of HR HPV (odds ratio, 4.2 [95% CI, 1.7-10.3]). Patients with TV were 6.5 times more likely to have HPV type 16 than patients negative for TV (50% vs 13.3%) (odds ratio, 6.5 [95% CI, 1.1-37]). CONCLUSIONS Among rural Tanzanian women who presented for cervical cancer screening, Trichomonas vaginitis was significantly associated with HR HPV infection (specifically type 16).

Suppression of GNAI2 message in ovarian cancer

BackgroundUnderstanding the integration of hormone signaling and how it impacts oncogenesis is critical for improved cancer treatments. Here we elucidate GNAI2 message alterations in ovarian cancer (OvCa). GNAI2 is a heterotrimeric G protein which couples cell surface hormone receptors to intracellular enzymes, and is best characterized for its direct role in regulating cAMP response element-binding protein (CREB) function by decreasing intracellular cAMP through inhibiting adenylyl cyclase.MethodsWe probed the Origene human OvCa array for the presence of polymorphisms and gene expression alterations of GNAI2 using directing sequencing and qPCR. These data were supported by database mining of the [NCBI NIH GSE:6008, GSE:14764, GSE:29450, GDS:4066, GDS:3297, GSE:32474, and GSE:2003] datasets.ResultsNo significant polymorphisms were found, including an absence of the gip 2 oncogene. However, 85.9% of (506 of 589) OvCa patients had decreased GNAI2 message. Further characterization demonstrated that the GNAI2 message was on average decreased 54% and maximally decreased by 2.8 fold in clear cell carcinoma. GNAI2 message decreased in early stage cancer while message was increased compared to normal in advanced cancers. The changes in GNAI2 also correlated to deregulation of CREB, Fos, Myc, cyclins, Arf, the transition from estrogen dependence to independence, and metastatic potential.ConclusionThese data strongly implicate GNAI2 as a critical regulator of oncogenesis and an upstream driver of cancer progression in OvCa.

Protecting the Next Generation Elaborating the Health Belief Model to Increase HPV Vaccination Among College-Age Women

This study guides social marketing campaigns to increase human papillomavirus (HPV) vaccination among young women by elaborating the health belief model (HBM). A self-administered, anonymous, web-based questionnaire was e-mailed to all entering female college students at a large, public university in the mid-Atlantic region of the United States. Findings elaborate the HBM constructs of perceived threat, benefits, barriers, and cues to action. Almost all participants had heard about the HPV vaccine and the majority of first-year students had received at least one shot in the vaccination series. Results expand understandings of perceived threat in relation to the HPV vaccine by explicating misinformation and knowledge gaps. Participants indicated that parents and physicians were their most trusted sources of vaccine information. Television and Internet cues to action were negatively associated with HPV vaccination among these women. Structural equation modeling results affirmed the HBM’s fit (comparative fit index = 0.935, normative fit index = 0.921, and root mean square error of approximation = 0.077). This finding suggests the importance of multimodal sources of information, expanding the dichotomous internal and external cues to action. Perceptions of vaccine safety remained a significant barrier to the uptake of HPV vaccination among participants. Racial disparities between White and non-White students could have a considerable impact on the established inequality in HPV vaccination rates in the United States. Results inform future social marketing campaign messages and strategies based on the HBM.

Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care.

Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11–12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11–12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child’s vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation (RR 0.72, 95% CI 0.61–0.85 and RR 0.85, 95% CI 0.72–1.01, respectively). In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort.

Morbidity and mortality of vulvar and vaginal cancers: Impact of 2-, 4-, and 9-valent HPV vaccines

ABSTRACT Vaginal and vulvar cancers do not account for a large proportion of gynecologic malignancies but their impact is significant. Both vaginal and vulvar lesions have precursors and display levels of dysplasia before progression to invasive disease. Human Papillomavirus (HPV) is a known causative agent of such dysplasia and can be detected now more readily than ever with adequate recognition techniques and provider awareness. Although HPV vaccination is still lagging compared to other recommended childhood vaccinations, the impact on lower genital tract neoplasia is promising. The bivalent and quadrivalent vaccines have been shown to be efficacious and the newest nonavalent vaccine should add even more of impact on coverage of cancer-causing HPV types. Although it is still early to show true clinical and population-based disease reduction due to low disease incidence and relatively short time of vaccine availability, the potential is noteworthy.

Why do we continue to overtreat stage Ia carcinoma of the cervix

The current recommended treatment for stage Ia2 cervical cancer is a radical or modified radical hysterectomy. Although in the United States the incidence of cervical cancer is low and declining, almost 50% of the >4000 new cases will present in early stages. An estimated 2200 women each year will undergo radical hysterectomy and many will have both early- and late-onset complications. The purpose of this review is to examine if there is still a role for radical hysterectomy in the proper treatment of stage Ia2 cervical cancer given most recent data. Sufficient histological evidence suggests that although parametrial involvement and lymph node metastases can increase the risk for recurrence, they are relatively uncommon at early stages. Worldwide data that challenge radical hysterectomy as standard of care have shown that conservative management of stage Ia2 cervical cancer results in similar survival and recurrence rates. It is the recommendation based on all reviewed data that radical hysterectomy should no longer be considered standard of care in all cases of stage Ia2 cervical cancer.

Increasing HPV vaccination through policy for public health benefit.

ABSTRACT Vaccines against specific types of human papillomavirus (HPV) linked to cancer and other diseases have been met with mixed acceptance globally and in the United States. Policy-level interventions have been shown to be effective in increasing public health benefit. Government policies and mandates may result in improved HPV vaccination coverage and reduced disease burden, and alternative policies that improve unhindered access to HPV vaccination may allow success as well. The purpose of this commentary is to summarize policy efforts to maximize the public health benefit of HPV vaccination. We examine selected examples of HPV vaccination policy in global contexts and in the United States.

Lymphovascular space invasion in uterine corpus cancer: What is its prognostic significance in the absence of lymph node metastases?

OBJECTIVE Lymphovascular space invasion (LVSI) is a poor prognostic indicator in uterine cancer, primarily due to its association with lymph node metastases. We sought to determine if LVSI provides any prognostic information for uterine cancer subjects in the absence of nodal disease. METHODS A retrospective review was performed using a database of women treated for uterine cancer at MUSC from 2005 to 2012. Subjects with negative nodes after complete staging were identified. Multiple regression modeling was used to adjust for demographic and histopathologic covariates. The C-index was calculated for models of survival that included LVSI and those that did not. Competing risks analysis was conducted to examine factors associated with time to recurrence. RESULTS Two hundred and five subjects were completely staged and had negative nodes, 24 with LVSI and 181 without. Factors significantly associated with survival included age, race, stage, grade, histology, and LVSI. Regression models for recurrence-free survival (RFS) and overall survival (OS) had similar C-indices regardless of whether LVSI was included. Competing risks analysis confirmed no significant difference in time to recurrence for subjects with LVSI compared to those without, after adjusting for other prognostic factors (P=0.53). CONCLUSIONS LVSI is associated with shorter recurrence-free and overall survival in uterine cancer subjects with negative lymph nodes. However, after adjusting for other prognostic factors, LVSI status does not provide additional prognostic information. This finding suggests that recurrence-free and overall survival for uterine cancer patients with negative lymph nodes can be estimated without factoring in LVSI.

It’s My Time: applying the health belief model to prevent cervical cancer among college-age women

Cervical cancer (CxCa) incidence and mortality remain unacceptably high in South Carolina, USA, presenting an ideal opportunity for intervention. To address this need, Cervical Cancer-Free South Carolina developed an academic-community partnership with researchers and students at a public university to design, implement, and evaluate a theory-based CxCa communication campaign, It’s My Time. The paper aims to discuss this issue.,The goal of this campaign was to decrease CxCa by increasing human papillomavirus (HPV) vaccination and appropriate screening. This paper describes the development, implementation, and evaluation of a successful theory-based CxCa prevention communication campaign for college women based on formative audience research and targeted messages delivered to audience segments through new and traditional communication channels. The health belief model (HBM) served as a theoretical framework for the campaign throughout development, implementation, and evaluation.,This campaign demonstrated the effectiveness of the HBM to address CxCa prevention, including HPV vaccine acceptability. The campaign aimed to increase perceptions of susceptibility, which were low, by emphasizing that HPV is a sexually transmitted infection. A community-based grassroots approach to addressing disparities in CxCa prevention increased benefits and decreased barriers. Social media emerged as a particularly appropriate platform to disseminate cues to action. In total, 60 percent of participants who responded to an anonymous web-based survey evaluation indicated that they received the HPV vaccine as a result of campaign messages.,This paper offers practical suggestions to campaign planners about building academic-community partnerships to develop theory-based communication campaigns that include conducting formative research, segmenting target audiences, engaging with young people, and incorporating social media.