The impact of Black founding fathers on the specialty of gynecologic oncology.

INTRODUCTION: The formative period of the specialty of gynecologic oncology was from 1968 to 1972 and became a board-certified specialty in 1973. During this formation there were no Black physicians participating in this process. We chronicle and document the incorporation of the first three board-certified Black physicians in the specialty of gynecologic oncology here for historical purposes. METHODS: We highlight the hostile climate experienced by Black physicians before and during the formation of gynecologic oncology, review the acceptance and training of the first three Black physicians in the specialty and recognize their significant contributions to the field. RESULTS: The biographies and the narrative of these men describe their impact and contribution to medicine. We chronicle the historic presence of the first board-certified Black gynecologic oncologists and pelvic surgeons in the United States. CONCLUSION: These three men represent the Black Founding Fathers of gynecologic oncology. Their perseverance in the face of adversity and commitment to excellence have left an indelible impact on the institutions that they developed, the individuals that they trained, and the patients that they served.

Addressing Barriers and Facilitators to African Americans' and Hispanics' Participation in Clinical and Genomic Research Through a Bioethical Sensitive Video.

Research advances on effective methods to prevent, diagnose, and treat cancer continue to emerge through clinical and genomic research. Most clinical trial and genomic research participants identify as White which limits the generalizability of research findings to non-White populations. With the development and access to technology, digital delivery of salient and tailored health education may provide innovative pathways to increase representation of African Americans (AA) and Hispanics in research. This project focused on the creation of a bioethical sensitive education video aimed at increasing participation in clinical trials and genomic research by bringing together experts from the community, healthcare, biomedical research, and public health. The goal was to utilize existing educational resources to create a tailored message to address AA/Hispanics' beliefs, values, and bioethical concerns related to participation in clinical and genomic research. Models of behavior change and communication theories were leveraged to frame key components of the message, which then informed the framework for the animated video. Development of the video consisted of six iterative phases: 1) writing sessions; 2) storyboarding; 3) animating; 4) screening/revisions; 5) acceptability testing; 6) finalization. The final animated video is approximately 5 min in length and covers several topics including the goal of clinical research, disparities in research participation, bioethical concerns, and genomic research regulations. Increasing AA and Hispanic participation in clinical and genomic research is imperative to achieving health equity. Tailored messages via short videos may assist in addressing the barriers and facilitators towards research participation and increase intentions to enroll in trials.

Georgia Primary Care Providers' Knowledge of Hereditary Breast and Ovarian Cancer Syndrome.

Hereditary breast and ovarian cancer syndrome (HBOC) is an inherited condition associated with mutations in the BRCA1 or BRCA2 (BRCA) genes. Identification of individuals with HBOC requires that primary care providers understand the genetic principles required to appropriately collect family history and refer individuals for genetic evaluation. A survey was developed and administered to primary care providers in Georgia to assess their existing knowledge of HBOC and direct targeted educational efforts.We found that Georgia providers demonstrate some knowledge of basic genetic principles but were unable to consistently identify individuals at risk for HBOC. Knowledge deficits included lack of understanding of inheritance patterns and failure to recognize the significance of ovarian cancer history. Strategies for improving identification of patients with HBOC include increasing provider knowledge and integrating HBOC risk assessment tools into practice. Identification of individuals at risk is the critical first step in the process of reducing incidence of breast and ovarian cancer associated with BRCA mutations.

Accuracy of urinary human papillomavirus testing for the presence of cervical human papillomaviruses and higher grades of cervical intraepithelial neoplasia.

BACKGROUND: Although urine-based testing for human papillomavirus (HPV) is being explored as a practical approach for cervical cancer screening, whether the results differ by age, race, or indicators of excess body weight or in populations exposed to HPV vaccines has not been documented by previous studies. The purpose of this study was to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and high-grade cervical intraepithelial lesions (grade 2 and 3 cervical intraepithelial neoplasia [CIN]) by the aforementioned population characteristics. METHODS: The study population consisted of 502 women diagnosed with different grades of CIN. HPV testing was performed with paired urine and cervical cell DNA with the Roche Diagnostics Linear Array test. Agreement coefficient 1 and probabilities were calculated to determine the accuracy of urinary HPV testing for the presence of cervical HPVs and CIN lesions. RESULTS: Substantial to almost perfect agreement (0.66-0.83) was observed in the detection of any HPV genotype in urine specimens versus cervical specimens, regardless of the population characteristics. Although the positive predictive value for the detection of CIN lesions was relatively low, the negative predictive value for CIN-3 was high (≥90%) among women positive for any of the urinary or cervical high-risk human papillomavirus (HR-HPV) genotypes or HPV genotypes not included in currently available HPV vaccines. CONCLUSIONS: The results demonstrate that urinary HPV testing provides highly satisfactory results for excluding the possibility of any cervical HPV infections, including HPV types not included in vaccines and CIN lesions associated with any HR-HPV, regardless of a woman's age, race, or excess body weight. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2836-2844. © 2016 American Cancer Society.

Implementing a screening tool for identifying patients at risk for hereditary breast and ovarian cancer: a statewide initiative.

BACKGROUND: The Georgia Breast Cancer Genomic Health Consortium is a partnership created with funding from the Centers for Disease Control and Prevention (CDC) to the Georgia Department of Public Health to reduce cancer disparities among high-risk minority women. The project addresses young women at increased risk for hereditary breast and ovarian cancer (HBOC) syndrome through outreach efforts. METHODS: The consortium provides education and collects surveillance data using the breast cancer genetics referral screening tool (B-RST) available at www.BreastCancerGeneScreen.org . The HBOC educational protocol was presented to 73 staff in 6 public health centers. Staff used the tool during the collection of medical history. Further family history assessments and testing for mutations in the BRCA1/2 genes were facilitated if appropriate. RESULTS: Data was collected from November 2012 through December 2013, including 2,159 screened women. The majority of patients identified as black/African American and were 18-49 years old. Also, 6.0 % (n = 130) had positive screens, and 60.9 % (n = 67) of the 110 patients who agreed to be contacted provided a detailed family history. A total of 47 patients (42.7 %) met National Comprehensive Cancer Network guidelines when family history was clarified. Fourteen (12.7 %) underwent genetic testing; 1 patient was positive for a BRCA2 mutation, and 1 patient was found to carry a variant of uncertain significance. CONCLUSIONS: The introduction of genomics practice within public health departments has provided access to comprehensive cancer care for uninsured individuals. The successful implementation of the B-RST into public health centers demonstrates the opportunity for integration of HBOC screening into primary care practices.

Prohibitin (PHB) inhibits apoptosis in rat granulosa cells (GCs) through the extracellular signal-regulated kinase 1/2 (ERK1/2) and the Bcl family of proteins.

Mammalian ovarian follicular development is tightly regulated by crosstalk between cell death and survival signals, which include both endocrine and intra-ovarian regulators. Whether the follicle ultimately ovulates or undergoes atresia is dependent on the expression and actions of factors promoting follicular cell proliferation, differentiation or apoptosis. Prohibitin (PHB) is a highly conserved, ubiquitous protein that is abundantly expressed in granulosa cells (GCs) and associated with GC differentiation and apoptosis. The current study was designed to characterize the regulation of anti-apoptotic and pro-apoptotic factors in undifferentiated rat GCs (gonadotropin independent phase) governed by PHB. Microarray technology was initially employed to identify potential apoptosis-related genes, whose expression levels within GCs were altered by either staurosporine (STS) alone or STS in presence of ectopically over-expressed PHB. Next, immunoblot studies were performed to examine the expression patterns of selective Bcl-2 family members identified by the microarray analysis, which are commonly regulated in the intrinsic-apoptotic pathway. These studies were designed to measure protein levels of Bcl2 family in relation to expression of the acidic isoform (phosphorylated) PHB and the components of MEK-Erk1/2 pathway. These studies indicated that over-expression of PHB in undifferentiated GCs inhibit apoptosis which concomitantly results in an increased level of the anti-apoptotic proteins Bcl2 and Bclxl, reduced release of cytochrome c from mitochondria and inhibition of caspase-3 activity. In contrast, silencing of PHB expression resulted in change of mitochondrial morphology from the regular reticular network to a fragmented form, which enhanced sensitization of these GCs to the induction of apoptosis. Collectively, these studies have provided new insights on the PHB-mediated anti-apoptotic mechanism, which occurs in undifferentiated GCs through a PHB → Mek-Erk1/2 → Bcl/Bcl-xL pathway and may have important clinical implications.

The rising relative and absolute incidence of uterine cancer in specific populations.

OBJECTIVE: To assess the contemporary incidence of cancers using American Samoa as a learning set for insights into similar populations. METHODS: A retrospective observational analysis of de-identified data held in public-access databases (2004-2014) and data on uterine cancer from a hospital, both in American Samoa (2015-2016). RESULTS: There were 341 new cases of cancer in 2004-2014 (111 per 100 000 women/year), including breast (20.2%), uterine (19.4%), and cervical (5.0%); and 287 in 2011-2015 (103 per 100 000 women/year), including uterine (24.0%), breast (18.5%), and cervical (5.2%). Uterine cancer increased from 21.4 to 60.3 per 100 000 women/year, becoming the most common cancer in American Samoa. In 2011-2015, the incidence-rate ratio of uterine cancer to other cancers in American Samoa was 1.3-, 3.8-, 4.6-, 7.7-, and 23-fold higher than breast, colon, cervical, ovarian, and lung cancer, respectively. Among the most recent cases (n=33), median age was 55 years (10 [30.3%] <50 years), median BMI was 38.2; and 11 (33.3%) cases had grade 3 histology. CONCLUSION: The pattern of cancers in American Samoa differs from that in the US mainland. The findings reflect significant changes in cancer incidence. Cancer control programs should evaluate the potential of uterine screening in accordance with their community's needs and characteristics.

Infertility knowledge and treatment beliefs among African American women in an urban community.

BACKGROUND: To assess infertility knowledge and treatment beliefs among African American women in an urban community in Atlanta, Georgia. METHODS: This was a cross sectional study at a safety net hospital. A convenience sample of a total of 158 women receiving outpatient obstetrical or gynecologic care from March-April 2017 were recruited. Infertility knowledge and treatment beliefs were assessed using a previously applied and field-tested survey from the International Fertility Decision Making Study. RESULTS: The mean infertility knowledge score was 38.15% for total subjects. Those with a higher level of education (p < 0.0001) and those with paid employment (p = 0.01) had a significantly higher level of infertility knowledge. Those who had a history of infertility therapy were significantly more likely to agree with negative treatment beliefs (p = 0.01). There was no significant difference in infertility knowledge or treatment beliefs based on age, sexuality, parity or being pregnant at the time of survey completion. CONCLUSIONS: African American women in our urban clinic setting seem to have a limited level of knowledge pertaining to infertility. Further research is needed to understand how differences in knowledge and beliefs translate into infertility care decision-making and future childbearing.

Utilizing Community-based Participatory Research Principles in a Safety-Net Hospital to Develop a Research Partnership.

Research at safety-net hospitals may require additional planning to ensure the ethical conduct of research with vulnerable populations. This report discusses application of the principles of community-based participatory research and bioethics to establish a research partnership with a safety-net hospital in the southern U.S.

Prohibitin silencing reverses stabilization of mitochondrial integrity and chemoresistance in ovarian cancer cells by increasing their sensitivity to apoptosis.

Current approaches to the treatment of ovarian cancer are limited because of the development of resistance to chemotherapy. Prohibitin (Phb1) is a possible candidate protein that contributes to development of drug resistance, which could be targeted in neoplastic cells. Phb1 is a highly conserved protein that is associated with a block in the G0/G1 phase of the cell cycle and also with cell survival. Our study was designed to determine the role of Phb1 in regulating cellular growth and apoptosis in ovarian cancer cells. Our results showed that Phb1 content is differentially overexpressed in papillary serous ovarian carcinoma and endometrioid ovarian adenocarcinoma when compared to normal ovarian epithelium and was inversely related to Ki67 expression. Immunofluorescence microscopy and Western analyses revealed that Phb1 is primarily associated with the mitochondria in ovarian cancer cells. Over-expression of Phb1 by adenoviral Phb1 infection resulted in an increase in the percentage of ovarian cancer cells accumulating at G0/G1 phase of the cell cycle. Treatment of ovarian cancer cells with staurosporine (STS) induced apoptosis in a time-dependent manner. Phb1 over-expression induced cellular resistance to STS via the intrinsic apoptotic pathway. In contrast, silencing of Phb1 expression by adenoviral small interfering RNA (siRNA) sensitized ovarian cancer cells to STS-induce apoptosis. Taken together, these results suggest that Phb1 induces block at G0/G1 phase of the cell cycle and promotes survival of cancer cells. Furthermore, silencing of the Phb1 gene expression may prove to be a valuable therapeutic approach for chemoresistant ovarian cancer by increasing sensitivity of cancer cells to apoptosis.

Apoptosis of rat granulosa cells after staurosporine and serum withdrawal is suppressed by adenovirus-directed overexpression of prohibitin.

Prohibitin (Phb1) is a highly conserved mitochondrial protein that is associated with granulosa cell differentiation, atresia, and luteolysis. Although prohibitin has been implicated in the suppression of apoptosis in mammalian cells, its specific role in programmed cell death in granulosa cells is unknown. In the present study, we examined the role of prohibitin in mediating staurosporine (STS) and serum withdrawal induced apoptosis in undifferentiated rat granulosa cells. Treatment of granulosa cells isolated from immature rat ovaries with STS and/or serum withdrawal induced a rapid decrease in the transmembrane potential of mitochondria, resulting in increased prohibitin content and induced apoptosis in a time- and dose-dependent manner. Infection of granulosa cells with a Phb1 adenoviral construct resulted in overexpression of prohibitin that markedly attenuated the ability of STS and serum withdrawal to induce apoptosis via the intrinsic apoptotic pathway. To determine the site of action of Phb1, granulosa cells were transfected with a prohibitin-eGFP fusion construct, and the fusion protein expression patterns were analyzed by fluorescence microscopy and Western blot analysis of cell fractionated samples. These studies indicated that the prohibitin-eGFP fusion protein moved from the cytoplasm into the mitochondria. However, no prohibitin-eGFP fusion protein was observed in the nucleus in response to the STS-induced apoptotic stimulus. This result was corroborated by Western blot analysis with green fluorescent protein-specific antibody. Furthermore, the prohibitin-eGFP fusion protein also inhibited programmed cell death. These results provide evidence that prohibitin could serve an antiapoptotic role in undifferentiated granulosa cells.

Physician and provider education for improving health and eliminating disparities.

The Sixth Annual Primary Care and Prevention Conference and the Eleventh Annual HeLa Women's Health Conference was held on September 11-13, 2006 in Atlanta, Georgia. The reports in this supplement of Ethnicity & Disease provide a sample of the presentations made during the primary care and women's health sessions.

A higher degree of expression of DNA methyl transferase 1 in cervical cancer is associated with poor survival outcome.

BACKGROUND: Even though novel therapies based on aberrant DNA methylation could be of particular importance for the treatment of cervical cancer (CC) because the oncoproteins E6/E7 of high-risk human papillomaviruses, the causative agents for developing CC, have the capacity to bind and upregulate DNA methyltransferases (DNMTs), to our knowledge, no previous studies have evaluated the expression of this enzyme in CC in relation to survival outcomes. The purpose of the study was to evaluate the expression of DNMT1 in CC and its association with survival outcomes. METHODS: The study population consisted of 76 women treated for primary CC and followed up by the University of Alabama at Birmingham (UAB) cancer registry. The expression of DNMT1 was examined using immunohistochemistry, and the degree of expression of DNMT1 was expressed as a percentage of cells positive for DNMT1 and its intensity. Cox proportional hazards model was used to assess the relationship between the degree of expression of DNMT1 and overall survival after adjusting for relevant covariates. RESULTS: The expression of DNMT1 was significantly higher in CC cells compared to that in the normal cervical epithelium. A higher percentage of cells positive for DNMT1 and a higher intensity score for DNMT1 were significantly associated with poor survival outcome (hazard ratio [HR] =4.3, P=0.03 and HR =4.9, P=0.02, respectively). CONCLUSION: Our findings suggested that the degree of expression of DNMT1 could be considered as a target in the epigenetic treatment of CC. Replication of our results in other study populations with CC could create the opportunity of using DNMT inhibitors to treat CC.

Racial and ethnic disparities in cancers of the uterine corpus.

Survival after diagnosis of cancer of the uterine corpus is significantly worse in black women as compared with white women. The etiology of the racial and ethnic disparities that exist in endometrial cancer incidence and outcome is multifactorial and complex. Potential explanations include cancer biology, differences in access to care, sociodemographic characteristics, response to treatment and comorbid factors. In this article, a review was performed to assess the magnitude and reasons for the observed disparity in endometrial cancer mortality. Strategies and recommendations to reduce or eliminate differences in endometrial cancer outcome are explored. These include advocacy for more research to clarify the underlying causes of cancer disparities at all levels, including the molecular basis of disparate outcomes, improving access to quality healthcare services, establishing culturally competent models of healthcare delivery, and developing novel cost-effective screening and early prevention methods.

Body mass index as a prognostic factor in endometrioid adenocarcinoma of the endometrium.

OBJECTIVE: To determine if body mass index (BMI) influences tumor expression of HER-2/neu, estrogen and progesterone receptors (ER/PR), and survival in women with endometrial adenocarcinoma. METHODS: Patients diagnosed between January 1992 and December 2001 with endometrioid adenocarcinoma of the uterus were identified. Clinical and pathologic data were retrospectively collected. HER-2/neu, estrogen and progesterone receptor expression were determined by immunohistochemistry. Differences in these variables and other prognostic factors were analyzed and correlated with effect on survival. RESULTS: One-hundred-sixty-five patients were included in this analysis. Lower BMI was associated with high stage (p=0.04) and HER-2/neu expression (p=0.04). Black race, high grade, high stage and lack of ER/PR expression were all associated with decreased survival. Despite having better prognostic factors, women with a BMI >25 had a lower survival than women with a BMI <25 (p=0.36). When five-year survival rates were calculated for BMI category and stratified by prognostic factors, for almost every high risk factor, survival was lower in overweight patients. CONCLUSION: In patients with endometrioid adenocarcinoma, low BMI is associated with high stage and tumor expression of HER-2/neu. Despite better prognostic factors, overweight women experience poorer survival.

An examination of racial differences in 5-year survival of cervical cancer among African American and white American women in the southeastern US from 1985 to 2010.

Disparities in Cervical Cancer (CC) mortality outcomes between African American (AA) and White women have been studied for decades. However, conclusions about the effect of race on CC survival differ across studies. This study assessed differences in CC survival between AA and White women diagnosed between 1985 and 2010 and treated at two major hospitals in the southeastern US. The study sample included 925 AA and 1192 White women diagnosed with cervical adenocarcinoma, adenosquamous cell carcinoma, or squamous cell carcinoma. Propensity score adjustment and matching were employed to compare 5-year survival between the two racial groups. Crude comparisons suggested relevant racial differences in survival. However, the racial differences became of small magnitude after propensity-score adjustment and in matched analyses. Nonlinear models identified age at diagnosis, cancer stage, mode of treatment, and histological subtype as the most salient characteristics predicting 5-year survival of CC, yet these characteristics were also associated with race. Crude racial differences in survival might be partly explained by underlying differences in the characteristics of racial groups, such as age at diagnosis, histological subtype, cancer stage, and the mode of treatment. The study results highlight the need to improve access to early screening and treatment opportunities for AA women to improve posttreatment survival from CC.

Endometrial carcinoma with ectopic human chorionic gonadotropin expression.

•Aggressive course and treatment resistance characterize ectopic human chorionic gonadotropin.•Recurrence of endometrial cancer with ectopic hCG was treated with brachytherapy and EMACO.•The serum hCG level can serve as a marker in tumors with ectopic hCG expression.

Molecular Mechanism of ß-Catenin Signaling Pathway Inactivation in ETV1-Positive Prostate Cancers.

In the United States of America, prostate cancer is the second most common age-related cancer among men. African-American men have the highest incidence of, and mortality rate from this disease in the United States. According to the American Cancer Society, 29% of all cancer cases and 9% of all cancer deaths are a result of prostate cancer. Individuals who are at highest risk include African-American men, men over 60 years of age, and those with a family history of the disease. African-Americans also have twice the risk of developing prostate cancer as compared to Caucasians. Erythroblastosis virus E26 transformation-specific (ETS) factors play an important role in human cancers. ETS Variant 1 (ETV1), an ETS factor, is notable for its association in prostate cancers, where truncated ETV1 (dETV1) or its full length counterpart is overexpressed in approximately 10% of the prostate cancer patients. Prostate cancer tumorigenesis may be initiated by deregulation of the Wnt/ß-catenin pathway. Mutations that stabilize ß-catenin were shown to contribute to the loss of cell-growth control in tumorigenesis. We hypothesized that ETV1's interaction with components of the Wnt/ß-catenin pathway may alter ß-catenin's interaction with downstream tumor-suppressor genes, which are critical in regulating apoptosis and cell-growth properties of prostate cells. Our results demonstrate for the first time that ETV1 alters ß-catenin activity by activating kinases that regulate Wnt/ß-catenin activity through post-translational modification in prostate cancer cells. We further demonstrate that therapeutic agents such as PD98059, that reverse effect of ETV1 on Wnt/ß-catenin signaling pathway, can be used to target ETV1-positive prostate cancer cells. These therapeutic agents could have a profound impact on prevention and treatment of prostate cancer which may help to reduce health disparity seen in minority patients. Understanding the role of ETV1 in Wnt/ß-catenin pathway will also allow us to develop better diagnostic tools, which can be used as a biomarker for ETV1-positive prostate cancers.

The effect of cell phone type on drivers subjective workload during concurrent driving and conversing.

The effect of three types of cell phones (hand held, hands free with an external speaker and personal hands free) on total subjective workload (including its constituent components; mental demand, physical demand, temporal demand, performance, effort and frustration) and intelligibility was measured using the NASA-task load index (TLX) and the modified rhyme test (MRT), respectively in 13 experienced drivers (nine male, four female, age range 28-65 years), whilst driving on a rural highway. The drivers rated all components of workload for each type of cell phone to be significantly higher than for a control condition in which no cell phone was used. The mean (standard deviation) total workload was lowest for the personal hands free cell phone (7.1(3.65)) and highest for the hands free speaker phone (10.8 (3.63)) (P<0.001). The mean (standard deviation) intelligibility score was highest for the personal hands free cell phone (74.1 (7.9)) and lowest for the hands free speaker phone (55.0 (10.4)) (P<0.001). Frustration was significantly correlated with total workload (0.60, P<0.001) and intelligibility was significantly correlated with frustration (-0.35, P<0.05). Physical demand was not a high contributor to total workload. It is concluded that a personal hands free cell phone would interfere least with the cognitive demands of driving.

Maintaining the reproductive potential of cancer patients during cancer treatment.

Cancer therapies are known to alter the reproductive potential in cancer patients. Due to improved survival rates in cancer patients of reproductive age, considerations of the long-term effects of cancer therapy have become more significant. Oncofertility is a new discipline in medicine that deals with maintaining the reproductive potential of cancer patients while they are receiving gonadotoxic cancer treatment. The purpose of this review is to explore how cancer treatment impairs reproductive functioning and present the current options for preservation of fertility in women. All patients with reproductive potential should be made aware of the possible treatment-related infertility and be offered appropriate fertility preservation options before cancer treatment is instituted. The hope is that, in the future, mechanism(s) can be developed to preserve immature germ cells in the ovary, so that they can be used for fertilization in vivo or in vitro.