bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A76: MicroRNA mediated negative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities
Authors: Guo Qi Jin , King Brooke , Blake Bobbie , LaRue Amanda C. , Salley Judith D. , Ford Marvella E. , Evans-Knowell Ashley , Findlay Victoria J.
Published: October 2015

Although rates of breast cancer incidence are lower in African American (AA) women, the mortality rates are significantly higher compared to non-Hispanic white (WNH) women. This shocking statistic illustrates the racial disparities in breast cancer, as AA women have a poorer prognosis compared to WNH women. While this may be due in part to socioeconomic and standard of care issues, increasing evidence suggests that the racial disparity exists independent of these issues and could also be attributed to poorly understood inherent genetic and molecular characteristics within racial specific tumors. Caveolin-1 (Cav1) is a scaffolding protein with a tumor suppressor role. Loss of Cav1 in the tumor stromal compartment has emerged as a novel biomarker for predicting poor clinical outcome in all of the most common subtypes of human breast cancer, including the more lethal triple negative subtype which is significantly more common in AA women. While the loss of stromal Cav1 is becoming well established as a marker of poor outcome in breast cancer, the mechanism of this loss is still unknown. We propose that differences in microRNA mediated stromal Cav1 loss between AA and WNH women is driving the racial disparity in breast cancer. MicroRNAs (miRNAs) are short, endogenous, non-coding RNA that function as negative regulators of gene expression. miR-510 is an oncogenic miRNA that has been shown to be elevated in breast tumors. Cav1 is a predicted target of miR-510 and therefore miR-510 mediated negative regulation may be a novel mechanism of Cav1 loss in the tumor stroma. Our research shows that Cav1 is directly targeted by miR-510 by luciferase reporter assay and that overexpression of miR-510 leads to downregulation of Cav1 protein expression, specifically in the stromal compartment. Tumor epithelium and stroma co-culture assays demonstrate that epithelial derived miR-510 may be transferred to neighboring stromal cells and negatively regulate Cav1 expression in the stromal compartment. This may be racially significant as our supporting studies also show that miR-510 levels are elevated and Cav1 levels are reduced in AA breast cancer patients compared to their white counterparts. Our results suggest that the difference in miR-510 mediated regulation of stromal Cav1 is driving racial disparity in breast cancer.

Citation Format: Qi Jin Guo, Brooke King, Bobbie Blake, Amanda C. LaRue, Judith D. Salley, Marvella E. Ford, Ashley Evans-Knowell, Victoria J. Findlay. MicroRNA mediated negative regulation of caveolin 1 as a biological mechanism driving breast cancer disparities. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A76.
Abstract A80: p53 protects against MG132-induced apoptosis in a cell state-dependent manner
Authors: Legesse-Miller Aster , Cheng Jacky Ho Wa
Published: October 2015

Since the approval of proteasome inhibitor, Bortezomib, for use in multiple myeloma in 2003, pharmacological proteasome inhibitors has been shown to be an important strategy for treating many types of cancer. While proteasome inhibitors induce apoptosis in certain rapidly proliferating cancer cells, some cells enters quiescence and survives. The mechanism by which quiescent cells become resistant to proteasome inhibitors is largely unknown. The tumor suppressor protein p53 plays an essential role in establishing and maintain quiescence in human cells. It also regulates several cell survival mechanisms, including cell cycle arrest, autophagy, and activation of reactive oxygen detoxifying enzymes. Here, we investigated the role of p53 in establishing resistance against proteasome inhibitors in quiescent cells. We found that MG132 (a know proteasome inhibitor) treatment induces the accumulation of p53 and its downstream target p21 more in quiescent cells than in proliferating primary human fibroblasts. shRNA mediated down-regulation of p53 sensitizes both proliferating and quiescent fibroblasts to MG132-mediated apoptosis and cell death, suggesting that p53 plays a protective role in all cell states. Additional experiments demonstrated that proliferating fibroblasts are susceptible to inhibition of cytoplasmic p53 activity, whereas quiescent fibroblasts are sensitive to inhibition of nuclear p53 activity. These findings suggest that p53 induces different protective mechanisms against MG132-mediated cell death, depending of the proliferative state of the cells. Autophagy, an alternative degradation pathway regulated by p53, is also induced in both cell states upon MG132 treatment. Identification of p53-mediated regulatory mechanisms that are activated in quiescent cells in response to proteasome inhibition may help to suggest strategies for improving the effectiveness of proteasome inhibitors in treating cancer.

Citation Format: Aster Legesse-Miller, Jacky Ho Wa Cheng. p53 protects against MG132-induced apoptosis in a cell state-dependent manner. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A80.
Abstract A87: Cardiovascular disease (CVD) and hospitalization costs among lung cancer patients: Examining the effect of race and gender
Authors: Husaini Baqar , Selove Rebecca , Williams Elizabeth , Novotny Meggan , Emerson Janice , Cain Van , Whalen Margaret , Levine Robert
Published: October 2015

Objective: Delineate race and gender variations in cardiovascular disease associated with lung cancer and hospitalization cost of Tennessee lung cancer patients in 2008.

Methods: We examined Tennessee Hospital Discharge Database for2008 for patients (aged 20+) discharged with a primary diagnosis of lung cancer (LC). The LC patient sample (n= 6665) included black males (BM; n=494), white males (WM; n=3286), black females (BF; n=387); and white females (WF; n=2498). For each patient, we extracted data on cardiovascular risk factors and hospitalization costs for the entire year of 2008. Age-adjusted hospitalization rate for lung cancer (LC) per 100K 2000 US population for white and black as well as male & female groups were developed per CDC methodology. To delineate CVD risk factors, multivariate logistic models were used for each group separately to determine CVD risk factors of LC.

Results: Our analyses revealed four major trends: (i) Age-adjusted LC rates were higher for blacks and males compared to white and females; (ii) LC patients had an average of 3 co-morbid conditions which varied from 3 conditions among WM, to 2.86 among BF, 2.75 among BM, and 2.70 among WF; (iii) Regression analyses revealed COPD predicted LC for all four groups. In addition, BM had cardiac arrhythmia and high cholesterol, The same factors were associated with LC among both WM and WF. Among BF, hypertension and COPD predicted higher rates of LC; and (iv) hospitalization cost for the year was highest among BF ($97,085) and lowest among WF ($66,758). Among males, the cost was higher among BM compared to WM ($91,384 vs. 71,716, p<.001). Hospitalization costs were higher among blacks compared to whites ($94,235 vs. 69,237, p<.001), in part, due to longer hospitalization compared to whites.

Conclusion: Lung cancer rates and hospitalization costs are higher for blacks. While males have higher LC rate compared to females, the hospitalization costs are similar among them. COPD, cardiac arrhythmia, and high cholesterol are CVD factors that are associated with lung cancer and need to be aggressive managed through intensive population-based education programs in the minority populations.

Citation Format: Baqar Husaini, Rebecca Selove, Elizabeth Williams, Meggan Novotny, Janice Emerson, Van Cain, Margaret Whalen, Robert Levine. Cardiovascular disease (CVD) and hospitalization costs among lung cancer patients: Examining the effect of race and gender. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A87.
Abstract B02: DNA promoter methylation of HIST1H2BB as a potential early detection biomarker to reduce ovarian cancer disparities in the United States
Authors: Valle Blanca L. , Kuhn Elisabetta , Sidransky David , Guerrero-Preston Rafael
Published: October 2015

Background: Ovarian cancer disproportionately affects African American women in the United States (US) at all stages of the disease, from presentation through treatment, and ultimately leads to increased mortality and decreased survival, compared to non-Hispanic White women. Till recently, epithelial ovarian cancers were thought to arise from the ovarian surface epithelial cells. However, recent studies suggest that the majority of high-grade serous carcinomas (HGSCs) arise from lesions in the fallopian tubes. DNA promoter hypermethylation of certain genes is often an early event in tumorigenesis, and it can be detected in blood and other bodily fluids, making it a feasible biomarker strategy for early detection of tumors.

Purpose of study: Therefore, we sought to determine the methylation profile of HGSCs as compared to fallopian tube epithelium. Using the Infinium HumanMethylation 450 Array, that permits to quantitatively assess over 450,000 methylation sites, within and outside of CpG islands and more than 20,000 genes per sample, at single-nucleotide resolution, we have obtained the genome-wide methylation profile of HGSC and fallopian tubal epithelium. We conducted a pilot study by comparing the global methylation status in 12 HGSC tissue samples to 15 fallopian tube epithelium samples. In addition, we compared the methylation profile among long-term survivors (more than 5 years) and short-term survivors (2-3 years) of HGSCs.

Results: Our results identified the HIST1H2BB promoter as the most differentially methylated region when comparing HGSC with normal fallopian tube samples. Furthermore, we also found that HIST1H2BB is differentially methylated in HGSC patients with long-term survival when compared to patients with short-term survival.

Conclusions: Taken together, these results support the potential use of HIST1H2BB promoter methylation as a diagnostic and prognostic biomarker for ovarian cancer. Our findings could lead to the development of a biomarker for the diagnosis and/or prognosis of ovarian cancer. An early detection biomarker for ovarian cancer could contribute to the reduction and eventual elimination of ovarian cancer health disparities in the US.

Citation Format: Blanca L. Valle, Elisabetta Kuhn, David Sidransky, Rafael Guerrero-Preston. DNA promoter methylation of HIST1H2BB as a potential early detection biomarker to reduce ovarian cancer disparities in the United States. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B02.
Abstract B08: Correlations between weight gain and physical health among African American breast cancer survivors
Authors: Smith Selina A. , Claridy Mechelle D. , Whitehead Mary S. , Sheats Joyce Q. , Baban Bakak , Yoo Wonsuk , Gonzalez-Perez Ruben R. , Alema-Mensah Ernest
Published: October 2015

Purpose: Weight gain after diagnosis is common among women with breast cancer and may affect physical functioning and recurrence; yet few studies have addressed this problem among African American breast cancer survivors. The purpose of our study was to examine associations between weight gain and physical functioning in a population with disparities in overweight/obesity, health-related quality of life (HR-QoL) and breast cancer recurrence.

Procedures: We examined the effects of weight gain in a cohort of 220 African-American women diagnosed with breast cancer. Participants completed a 45-minute assessment tool recording weight and breast cancer history, physical health and general well being. Factorial analysis of variance (ANOVA) was used to assess the association between weight gain (pounds) and HR-QoL. We also determined the moderating effects of demographic variables on post-breast cancer diagnosis weight gain.

Results: More than half of the study sample (n=113) gained 10 pounds or more after breast cancer diagnosis. Predictors for weight gain included: 1) breast cancer recurrence-78% (p=0.0067); 2) annual income- from $25,000 to $49,999 55% (p=0.0167); 3) some college education-51% (0.0205), and 4) unmarried 46% (p=0.0007). Participants reporting poorer overall quality of life (p=0.0109), poorer physical health quality of life (p=0.0002), and poorer physical functioning (p=0.0263) were more likely to report weight gain after breast cancer diagnosis than those who reported a better quality of life.

Conclusions: These results highlight the importance of weight control for African American women after breast cancer diagnosis.

Citation Format: Selina A. Smith, Mechelle D. Claridy, Mary S. Whitehead, Joyce Q. Sheats, Bakak Baban, Wonsuk Yoo, Ruben R. Gonzalez-Perez, Ernest Alema-Mensah. Correlations between weight gain and physical health among African American breast cancer survivors. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B08.
Abstract B15: Motivation for cancer control changes among African Americans
Authors: Jefferson Melanie S. , Briggs Vanessa , Delmoor Ernestine , Rice LaShanta , Johnson Jerry , Hughes-Halbert Chanita
Published: October 2015

Background: Healthy dietary behaviors are critical strategies for cancer control. Despite this, many African Americans do not meet the recommended guidelines for fruit and vegetable intake. To develop effective cancer control interventions for African Americans, it is first necessary to understand within group variation in motivations for making dietary behavior changes and identify socioeconomic, social, and clinical factors that have significant independent associations with these motivations.

Objectives: To characterize motivations for making dietary changes among African Americans and to identify socioeconomic, social, and clinical factors having significant independent associations with these intrinsic and extrinsic motivations among African American adults (n=530).

Results: The mean (SD) level for intrinsic motivation was 26.5 (3.5) whereas the mean (SD) level for extrinsic motivation was 16.1 (4.8). Increasing age (Beta=0.03, p=0.03) and membership in at least one community organization (Beta=1.20, p=0.0003) had significant independent associations in the regression model for intrinsic motivation (n=479, F=5.97, p=0.0001). Lower incomes (Beta=-1.10, p=0.02) and age (Beta=0.06, p=0.006) had significant independent associations with extrinsic motivation. None of the clinical factors were associated significantly with intrinsic and extrinsic motivation.

Conclusions: African Americans may be motivated to make dietary changes for cancer control because of intrinsic motivations. Different variables had significant independent associations with intrinsic and extrinsic motivations to make dietary changes among African Americans. It may be important to use alternative strategies to enhance these motivations as part of cancer control interventions that are developed for these individuals.

Citation Format: Melanie S. Jefferson, Vanessa Briggs, Ernestine Delmoor, LaShanta Rice, Jerry Johnson, Chanita Hughes-Halbert. Motivation for cancer control changes among African Americans. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B15.
Abstract B28: Racial/ethnic differences in the association of obesity with hepatocellular carcinoma risk
Authors: Setiawan Veronica Wendy , Lipworth Loren , Wilkens Lynne R. , Marchand Loic Le , Blot William J. , Henderson Brian E.
Published: October 2015

The increasing trend of obesity is suggested to have contributed to the increasing hepatocellular carcinoma (HCC) incidence rates in the United States. However, no studies have examined whether the association between obesity and HCC differs across racial/ethnic groups. We examined body mass index (BMI) in relation to HCC risk in two large prospective cohort studies: the Multiethnic Cohort (MEC) and the Southern Community Cohort Study (SCCS). Between the two cohorts, a total of 637 incident HCC cases (86 Whites, 165 Blacks, 36 Native Hawaiians, 177 Japanese Americans, and 173 Latinos) were identified. BMI and other known HCC risk factor information were assessed from the baseline questionnaire (MEC: 1993-1996; SCCS: 2002-2009). The association between BMI and HCC incidence was examined using a nested case-control approach with four matched controls per case (MEC: 536 cases/2,131 controls; SCCS: 101 cases/404 controls). Conditional logistic regression, accounting for the matching factors was used to calculate multivariable odds ratios (ORs) and 95% confidence intervals (CI) for incident HCC in relation to BMI (<25, 25-<30, and 30 kg/m2, or per 5 kg/m2) in each racial/ethnic group. Additional covariates such as smoking status, diabetes, and alcohol intake were included in the models. Increasing BMI was associated with an elevated HCC risk in Japanese Americans (OR per 5 kg/m2 increase in BMI=1.69; 95% CI: 1.31, 2.16), Whites (OR=1.34; 95% CI: 0.98, 1.82), Native Hawaiians, (OR=1.23; 95% CI: 0.80, 1.89), and Latinos (OR=1.15; 95% CI: 0.95, 1.40), but not in Blacks in the MEC (OR=0.92; 95% CI: 0.70, 1.22) or in the SCCS (OR =0.93; 95% CI: 0.75, 1.15). The combined OR for Blacks across the two cohorts was 0.93 (95% CI: 0.78, 1.10; P heterogeneity=0.95). The association of BMI with HCC differed significantly across racial/ethnic groups (P heterogeneity=0.003). Our results suggest that the association of obesity, as measured by BMI, with HCC incidence varies across racial/ethnic groups. The null association in Blacks is particularly interesting and warrants further investigation.

Citation Format: Veronica Wendy Setiawan, Loren Lipworth, Lynne R. Wilkens, Loic Le Marchand, William J. Blot, Brian E. Henderson. Racial/ethnic differences in the association of obesity with hepatocellular carcinoma risk. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B28.
Abstract B36: Helicobacter pylori exposure among Hispanic and non-Hispanic white men in San Antonio, Texas: Implications for gastric cancer risk disparities
Authors: Parma Dorothy Long , Munoz Edgar , Ogden Susan M. , Leach Robin J. , Thompson Ian M. , Ramirez Amelie G.
Published: October 2015

Background: Chronic Helicobacter pylori (H. pylori) infection is the most common gastric adenocarcinoma (GCA) risk factor. GCA more commonly affects U.S. Hispanics compared to non-Hispanic whites (NHWs). No study has examined this infection in South Texas Hispanics, a population facing multiple health disparities. This pilot project aimed to determine H. pylori exposure rates in Hispanic and NHW men residing in Bexar County, and examine relationships with ethnicity, residence, socioeconomic status, smoking history and cancer family history.

Methods: Age- and zip-code-matched subjects from a large community-dwelling cohort were randomly selected. Sera from 286 (143 Hispanic, 143 NHW) men were analyzed by enzyme immunoassay for H. pylori antibodies.

Results: Almost 20% of samples were H. pylori-positive; exposure was significantly higher among Hispanics (30.1%) compared to NHWs (9.1%). Unconditional logistic regression analyses of the seropositive-matched subsample showed strong associations between H. pylori seropositivity and Hispanic ethnicity (odds ratio [O.R.]=17.5; p<0.001) and BMI category (O.R.=6.5; p=0.01 overweight and 4.0; p=0.02 obese). Ethnicity remained the strongest predictor of seropositivity after adjusting for all other factors (adjusted O.R.=16.9; p<0.001). Adjusted O.R.s for overweight/obesity were high but non-significant.

Conclusions: H. pylori exposure rates are higher in South Texas Hispanic men and parallel the disproportionately-higher rates of GCA. Obesity is a contributing factor. This is the first study to explore the relationship between H. pylori exposure and Hispanic ethnicity and other GCA risk factors in South Texas. Results have implications for future studies on preventive measures targeted at reducing infectious burden and GCA risk in this vulnerable population.

Citation Format: Dorothy Long Parma, Edgar Munoz, Susan M. Ogden, Robin J. Leach, Ian M. Thompson, Jr., Amelie G. Ramirez. Helicobacter pylori exposure among Hispanic and non-Hispanic white men in San Antonio, Texas: Implications for gastric cancer risk disparities. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B36.
Abstract B59: Epithelial ovarian cancer, comorbidity, and racial disparities
Authors: Fields Nicole Danielle , Whiteside Martin , Terry Paul Daniel
Published: October 2015

The purpose of our study was to determine if co-morbidities influenced survival among ovarian cancer patients and whether associations varied according to race. Ovarian cancer is one of the most deadly cancers among women in the United States, with an overall 5-year survival of 33%[1]. Tennessee ranks 14th highest in the United States for ovarian cancer incidence, with an age-adjusted rate of 11.8 per 100,000 cases. There have been few studies published addressing the relative contribution of comorbidity to the association between ovarian cancer and survival. Therefore, we identified epithelial ovarian cancer cases from the Tennessee Cancer Registry between 2004-2010, and linked these data to inpatient hospital discharge information from 2007 to 2009. Pre-diagnosis comorbid conditions were grouped into 7 broad categories: Heart Disease, Peripheral Vascular Disease, Gastrointestinal (GI) Disorders, Infectious Disease, Kidney Disease, Musculoskeletal Disease, and Non-Malignant Lung Disease. The median age of patients was 76.4 years and the median follow-up time was 103 days. We found that 53.8% of GI Disorder patients had Stage 4 ovarian cancer, with a relatively high median follow-up time of 130 days. 33.3% of Infectious Disease patients had Stage 4 cancer, and had the highest follow-up time of 196 days. In contrast, Kidney Disease patients had the lowest median follow-up time at 60 days, suggesting that this comorbidity was among the most predictive of poor survival. Median survival times of other comorbidities were within these latter two extremes. Race was not a substantial mediating factor in the associating among comorbidities and survival in ovarian cancer patients. Rather, the patient's age, stage at diagnosis, and the type of diagnosis had the greatest impact on survival.

Citation Format: Nicole Danielle Fields, Martin Whiteside, Paul Daniel Terry. Epithelial ovarian cancer, comorbidity, and racial disparities. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B59.
Abstract IA01: Disparities in HPV infection
Authors: D'Souza Gypsyamber
Published: October 2015

Human papillomavirus (HPV) is a common sexually transmitted infection that can cause cervical, anal, vaginal, penile, and oropharyngeal cancers. There is heterogeneity in HPV prevalence across racial and socioeconomic groups as well as by age-cohort. These differences in HPV infection contribute to disparities observed in the rates of HPV-related cancer rates in these groups. This talk reviews what is known about genital, anal, and oral HPV infection, and how infection differs among groups. Reasons for disparities in HPV infection are discussed, including the roles of sexual behavior, sexual network, and co-factors (such as tobacco use). Common questions and answers about HPV infection will be discussed.

Citation Format: Gypsyamber D'Souza. Disparities in HPV infection. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA01.
Abstract IA05: Enhancing HIT platform design and employing novel analytic perspectives to reduce cancer
Authors: Gibbons M. Chris
Published: October 2015

The potential of Information and Communications technologies to help address cancer health disparities is significant. A growing body of evidence focuses on the efficacy of devices and tools. This literature suggests that both clinical and consumer oriented Health IT can positively impact health outcomes. Despite this literature, comparatively less work has been done detailing principles of effective Health IT design, particularly for underserved populations who may have unique physical, cultural and or environmental user characteristics that impact the usability of electronic tools, rendering them less useful, desirable or effective among these populations. If left unaddressed, sub optimal health IT design could contribute to increases in cancer disparities. In addition, little work has also been done focusing on the development of health technology platforms specifically for health coaches, navigators and health workers working with individuals from underserved population groups. Finally advances in Health IT are enabling the collection of vast amounts of data. This data may, in the future, be used to gain novel disparities insights not currently possible. This presentation will discuss evidence based design principles that can enhance the development of electronic health tools to address cancer disparities. The presentation will also provide examples of emerging platforms as well as novel analytic perspectives that could prove important in helping to effectively address and ultimately eliminate Cancer health disparities.

Citation Format: M. Chris Gibbons. Enhancing HIT platform design and employing novel analytic perspectives to reduce cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA05.
Abstract IA13: Connecting science to law: Understanding the policymaking process
Authors: Berman Micah L.
Published: October 2015

Tobacco use remains the leading cause of preventable death in the U.S., killing 480,000 Americans a year. To address the death and disease caused by tobacco use, Congress enacted the Family Smoking Prevention and Tobacco Control Act (FSPTCA) in 2009, granting the U.S. Food and Drug Administration (FDA) broad authority to regulate the manufacture, marketing, and sale of tobacco products.

In order to help build the science base for tobacco regulation, the FDA has invested heavily in “tobacco regulatory science.” In partnership with the National Institutes of Health (NIH), it is investing $273 million over five years in the Tobacco Centers of Regulatory Science (TCORS) initiative. The TCORS program funds 14 centers at academic institutions (including Ohio State) that conduct research relevant to the FDA's regulation of tobacco. This initiative is a unique partnership between a regulatory agency and researchers, developed with the explicit expectation that the research will directly inform the FDA's regulatory actions.

To conduct research that will assist the FDA in fulfilling its regulatory mission, researchers must venture outside of their comfort zone and consider the relevant legal and policy environment. More specifically, scientists engaged in tobacco regulatory science must consider at least four different questions: (1) what FDA regulatory action(s) might my research inform?; (2) what types of evidence would the FDA need to consider in order to take such actions?; and (3) if such a regulation were reviewed in court, what questions would the courts ask about the available evidence? Failure to consider these questions may lead to research that, while scientifically valid, does not advance the FDA's ability to fulfill its regulatory mission. Thus, in order for the TCORS program to succeed, there must be a productive and ongoing dialogue between scientists and attorneys familiar with the regulatory landscape.

This presentation will discuss the need for better coordination between scientists and attorneys, particularly in the context of tobacco regulatory research. It will also discuss how law acts as a social determinant of health that has a significant impact (both positive and negative) on health disparities.

Citation Format: Micah L. Berman. Connecting science to law: Understanding the policymaking process. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA13.
Abstract IA34: Who benefits from patient navigation: Updates from the National Patient Navigation Research Program
Authors: Freund Karen M.
Published: October 2015

Patient navigation programs continue to proliferate across the country, as evidence of their effectiveness in addressing health disparities continues to grow. However, cancer centers are concerned about the sustainability of patient navigation programs, as they are usually not supported through insurance reimbursement of care. Therefore, it is useful to identify where patient navigation is the most effective, which patients benefit the most from navigation, and what aspects of patient navigation programs provide the greatest impact on patient care. This information is critical for programs to develop the most effective programs with limited resources.

e present new analyses from the National Patient Navigation Research Program, to address which patients benefit the most from patient navigation. Our findings indicate that a number of variables that can be collected at the time of referral to a cancer program are predictors of patients in need of navigation and patients who benefit from navigation. These include sociodemographic characteristics, such as education, employment, income and housing status, medical comorbidities, and social and logistic barriers to care. Systems with the greatest delays in care benefit the most from navigation. Navigators are most effective when their roles focus on direct interaction time with patients, their caregivers, and the health care team. Excess efforts by patient navigators to address limitations with electronic medical records detract from their clinical effectiveness.

These findings may help programs develop and refine their patient navigation programs to provide the greatest impact and support to patients.

Citation Format: Karen M. Freund. Who benefits from patient navigation: Updates from the National Patient Navigation Research Program. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA34.
Abstract PR06: Empowering Latina breast cancer patients to make informed decisions about clinical trials: A multicommunication approach
Authors: Chalela Patricia , Muñoz Edgar , Gallion Kipling J. , Karnad Anand , Ramirez Amelie G.
Published: October 2015

Background: Without adequate minority representation in clinical trials, researchers cannot assess differential effects in outcomes or ensure the safety of therapies across a range of biological and genetic characteristics among groups, nor can they ensure generalizability of trial results. In response, this theory-based educational intervention aims to empower Latinas to make informed decisions about breast cancer clinical trials (BCCTs) by enhancing their knowledge, attitudes, skills and self-efficacy required to support discussion of BCCTs as a treatment option with doctors and family members.

Methods: This is a cohort study with random assignment of 112 Latina breast cancer patients eligible to participate in a BCCT at the Cancer Therapy & Research Center at the University of Texas Health Science Center at San Antonio. The intervention includes: participation in a culturally sensitive, individually tailored, computer-based BCCTs video; a bilingual, low-literacy booklet; and assistance from a patient navigator. The control includes usual care clinical trial information materials for eligible patients.

Results: Preliminary analysis showed that participants exposed to the intervention had significant higher awareness of clinical trials, particularly understanding their purpose and requirements, benefits and risks and their potential as an appropriate treatment for a serious disease, than participants in the usual care control group. In addition, patients in the intervention group showed significant changes between baseline and post intervention on stages of change compared to the control group. In the intervention group the percentage of women in preparation increased from 26.4% at baseline to 62.3% at post-intervention and the proportion of those in action rose from 35.8% to 67.9% at post-intervention.

Conclusion: Computer-based videos if specifically tailored to Latinos may be a cost-effective strategy to effectively address awareness, cultural and attitudinal barriers and decision making skills needed to make informed decisions about clinical trial participation.

The study is funded by the Susan G. Komen for the Cure (Award No. SAB08-00005) and the Cancer Therapy & Research Center (Grant No. P30 CA054174).

This abstract was also presented as Poster A5.

Citation Format: Patricia Chalela, Edgar Muñoz, Kipling J. Gallion, Anand Karnad, Amelie G. Ramirez. Empowering Latina breast cancer patients to make informed decisions about clinical trials: A multicommunication approach. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr PR06.
Abstract PR11: Loss of imprinting: Tying prenatal diet to the aggressive biology of triple-negative breast cancer
Authors: Desai Shraddha R. , Dietze Eric C. , Skaar David , Jirtle Randy L. , Seewaldt Victoria L.
Published: October 2015

Background: Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. Loss of normal imprinting results in a functional diploid state and overexpression of the imprinted gene. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancers; however, KCNK9 gene amplification accounts for increased expression in <10% of these breast cancers.

Methods and Results: Using patient samples we showed that KCNK9 has imprinted expression in breast tissue, and identified the differentially methylated region (DMR) controlling its imprint status. We showed that loss of methylation (LOM) at the DMR, coupled with biallelic expression of KCNK9, occurred in 75% of triple-negative breast cancers (TNBC), and that association between LOM and TNBC status was highly significant in African-Americans, but not in Caucasians. Functional studies show that loss of KCNK9 imprinting leads to an increase in mitochondrial membrane potential and apoptosis resistance. Further, expression of a dominant-negative TASK3 in TASK3-overexpressing TNBC cells resulted in decreased mitochondrial membrane potential, decreased glucose uptake and apoptosis-sensitivity; conversely, overexpression of TASK3 in mammary epithelial cells with baseline TASK3 protein expression, increased mitochondrial membrane potential, increased glucose uptake and promoted apoptosis-resistance.

Significance: This is the first identification of the KCNK9 DMR, and demonstration that its LOM is associated with increases in mitochondrial membrane potential, glucose uptake and apoptosis resistance. Thus, patients with TNBC and KCNK9 overexpression may benefit from known low toxicity TASK3 inhibitors for the prevention and treatment of breast cancer.

This abstract was also presented as Poster A79.

Citation Format: Shraddha R. Desai, Eric C. Dietze, David Skaar, Randy L. Jirtle, Victoria L. Seewaldt. Loss of imprinting: Tying prenatal diet to the aggressive biology of triple-negative breast cancer. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr PR11.
Abstract A04: Characterization of VPS34-IN1, a specific inhibitor of Vps34 reveals that the phosphatidylinositol 3-phosphate binding SGK3 protein kinase is regulated by class III PI-3 kinase
Authors: Bago Ruzica , Sommer Eeva , Malik Nazma , Munson Michael J. , Prescott Alan R. , Davies Paul , Natalia Shpiro , Ganley Ian G. , Alessi Dario R.
Published: October 2015

The Vps34 Class III phosphoinositide 3-kinase (PI3K) phosphorylates phosphatidylinositol (PtdIns) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX and FYVE domains. Here we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50 in vitro but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of Class I as well as Class II PI3K. Administration of VPS34-IN1 to cells, induces a rapid dose dependent dispersal of GFP-2xFYVEHrs , a specific PtdIns(3)P binding probe, from endosome membranes. Previous studies revealed that serum and glucocorticoid regulated kinase-3 (SGK3) possesses a PtdIns(3)P binding N-terminal PX domain. SGK3 was first identified as a novel isoform of SGK1 that played a role in enabling the IL-3-dependent survival of hematopoietic cells. We explored whether SGK3, the only protein kinase known to interact specifically with PtdIns(3)P, might be controlled by Vps34. We utilised U2OS Flp/In inducible cell line to find that the mutations disrupting PtdIns(3)P-binding, ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop (PDK1 site) and hydrophobic motif (mTOR site) residues. Also, treatment of cells with VPS34-IN1 induced a rapid ∼50-60% loss of SGK3 phosphorylation and activity. Furthermore, a Class I PI3K inhibitor (GDC-0941) that does not inhibit Vps34, suppressed SGK3 activity by ∼30-40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ∼80-90% similar to treatment with an mTOR inhibitor (AZD8055). This data suggest that SGK3 phosphorylation and hence activity is mainly controlled by the activity of PI3K Class I and Class III and the regulation of SGK3 activity through Vps34 may provide a prosurvival signal and a resistance mechanism during the treatment of cancer cells with PI3K Class I inhibitors.

Citation Format: Ruzica Bago, Eeva Sommer, Nazma Malik, Michael J. Munson, Alan R. Prescott, Paul Davies, Shpiro Natalia, Ian G. Ganley, Dario R. Alessi. Characterization of VPS34-IN1, a specific inhibitor of Vps34 reveals that the phosphatidylinositol 3-phosphate binding SGK3 protein kinase is regulated by class III PI-3 kinase. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A04.
Abstract A12: Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC
Authors: Amato Katherine , Wang Shan , Hastings Andrew , Youngblood Victoria , Santapuram Pranav , Chen Haiying , Cates Justin , Colvin Daniel , Ye Fei , Brantley-Sieders Dana , Cook Rebecca , Tan Li , Gray Nathanael , Chen Jin
Published: October 2015

Genome-wide analyses determined previously that the receptor tyrosine kinase (RTK) EPHA2 is commonly overexpressed in non-small cell lung cancers (NSCLCs). EPHA2 overexpression is associated with poor clinical outcomes; therefore, EPHA2 may represent a promising therapeutic target for patients with NSCLC. In support of this hypothesis, we have shown that targeted disruption of EPHA2 in a murine model of aggressive KRAS-mutant NSCLC impairs tumor growth. Knockdown of EPHA2 in human NSCLC cell lines reduced cell growth and viability, confirming the epithelial cell autonomous requirements for EPHA2 in NSCLCs. Targeting EPHA2 in NSCLCs decreased S6K1-mediated phosphorylation of cell death agonist BAD and induced apoptosis. Furthermore, an ATP-competitive EPHA2 RTK inhibitor, ALW-II-41-27, reduced the number of viable NSCLC cells in a time-dependent and dose-dependent manner in vitro and induced tumor regression in human NSCLC xenografts in vivo. Collectively, these data demonstrate a role for EPHA2 in the maintenance and progression of NSCLCs and provide evidence that ALW-II-41-27 effectively inhibits EPHA2-mediated tumor growth in preclinical models of NSCLC.

Citation Format: Katherine Amato, Shan Wang, Andrew Hastings, Victoria Youngblood, Pranav Santapuram, Haiying Chen, Justin Cates, Daniel Colvin, Fei Ye, Dana Brantley-Sieders, Rebecca Cook, Li Tan, Nathanael Gray, Jin Chen. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A12.
Abstract A20: Insulin receptor signaling in mammary epithelial cells
Authors: Poloz Yekaterina , Sheikh Mariam Z. El , Petschnigg Julia , Groisman Bella , Kotlyar Max , Jurisica Igor , Stagljar Igor , Stambolic Vuk
Published: October 2015

Obesity has recently emerged as a major adverse factor in the prevalence and severity of many types of cancers, including breast cancer (BC). Obesity is often accompanied by hyperinsulinemia and the development of type 2 diabetes. Elevated circulating insulin levels are thought to mediate some of the adverse prognostic effects of obesity in BC (Goodwin et al., 2002). Insulin receptor (IR) is expressed in many human BCs and the activation of the IR/receptor tyrosine kinase signaling pathway is characteristic of most BCs (Mulligan et al., 2007). We hypothesize that ectopic expression of IR in BCs sensitizes BC cells to the action of insulin, leading to signaling events specific to epithelial cells, functionally distinct from the insulin responses in physiological insulin-target tissues. To further understand the role of IR in BC we have implemented the recently developed Mammalian Membrane Two Hybrid (MaMTH) (Petschnigg et al., 2014) screen to identify IR interactors in human mammary epithelial MCF10A cells. The ongoing screen has to date identified 99 IR protein-protein interactions (PPIs), 51 of which are insulin-dependent. Coimmunoprecipitation and shRNA knockdown analyses are being used to validate the PPIs and provide insight into the functional significance of IR associations for growth and proliferation of MCF10A cells. Ultimately, the epithelial cell IR-interactome is meant to provide an insight into the insulin contribution to the activation of RTK signaling in BC, and provide a roadmap for further exploration of IR signaling in cancer.

Citation Format: Yekaterina Poloz, Mariam Z. El Sheikh, Julia Petschnigg, Bella Groisman, Max Kotlyar, Igor Jurisica, Igor Stagljar, Vuk Stambolic. Insulin receptor signaling in mammary epithelial cells. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A20.
Abstract A22: Identification of a novel protein that blocks the Rag-Ragulator interaction and inhibits mTORC1
Authors: Schweitzer Lawrence D. , Sabatini David M.
Published: October 2015

mTORC1 controls key pathways that maintain cell viability, including translation, ribosome biogenesis and autophagy. Amino acids are a crucial input to mTORC1 activation, resulting in the recruitment of the complex to the surface of lysosomal membrane. The kinase activity of mTORC1 is subsequently turned on at the lysosome downstream of growth factor signaling. mTORC1 is brought to the lysosome by the Rag GTPases, which are tethered to the membrane by their lysosomal scaffold and guanine nucleotide exchange factor, Ragulator. We have identified a novel regulator of mTORC1 activity that inhibits mTORC1 through binding to the Ragulator. This binding prevents the interaction between the Ragulator and its only known substrate, the Rag GTPases, both in cells and in vitro. This disruption of the Rag-Ragulator interaction results in impaired mTORC1 activation by amino acids. However, the novel Ragulator-interacting protein is not regulated by amino acids; it behaves as a link that integrates another signal transduction pathway that inhibits mTORC1 regardless of the presence of amino acids.

Citation Format: Lawrence D. Schweitzer, David M. Sabatini. Identification of a novel protein that blocks the Rag-Ragulator interaction and inhibits mTORC1. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A22.