bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A81: Investigation of possible cell state dependent differential protein homeostasis mechanism(s)
Authors: Fon Gordon-Victor , Keller Chandler R. , Perlman David H. , Legesse-Miller Aster
Published: October 2015

Proteasome inhibition has been shown to be an important strategy for treating many types of cancer. Although proteasome inhibitors are effective at eradicating rapidly proliferating cancer cells, a subset of cancer cells enter quiescence and survive, contributing to tumor recurrence. Using primary human fibroblasts as a model system we have shown that quiescent cells have decreased reactive oxygen species levels and protein aggregates, and undergo apoptosis less frequently than proliferating cells in response to proteasome inhibition. However, the precise mechanism by which quiescent cells become resistant to proteasome inhibition remains largely unknown. Using a GFP-tagged proteasome reporter, we investigated mechanisms protecting quiescent cells from proteasome inhibition-induced apoptosis. We found that, in proliferating cells, proteasome inhibition by MG132 led to high levels of a GFP-tagged proteasome reporter with a visible ubiquitination pattern. In contrast, MG132 treatment of quiescent cells resulted in reduced levels of the ubiquitinated form of this reporter as observed by Western blot analysis. Interestingly, preliminary immunoprecipitation followed by mass-spectrometry analysis revealed none canonical ubiquitin modification on lysine 27 of the reporter in quiescent cells. These findings suggested that quiescent cells may have one or more alternative pathways preventing specific proteasome substrates accumulation in response to proteasome inhibition. Moreover, our data has shown that, upon proteasome inhibition, a GFP-tagged proteasome reporter was secreted into the condition medium. Secretion of cytoplasmic proteins in response to proteasome inhibition is one possible mechanism for reducing protein aggregation and cytotoxicity. Identification of 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 cancer treatment.

Citation Format: Gordon-Victor Fon, Chandler R. Keller, David H. Perlman, Aster Legesse-Miller. Investigation of possible cell state dependent differential protein homeostasis mechanism(s). [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 A81.
Abstract A88: Medicaid expansion and access to care among breast cancer survivors
Authors: Tarazi Wafa W.
Published: October 2015

Background: Breast cancer survival is improving due to early detection of the disease and advances in treatment. In the United States, there are more than 3 million breast cancer survivors and approximately 240 thousand women diagnosed with the disease every year. To receive effective treatment, breast cancer survivors need to follow a treatment plan prescribed by their physicians. However, access to healthcare services remains a barrier to completing needed treatment. Medicaid expansion under the Affordable Care Act improves access to care among vulnerable populations, but almost half of the states opted out of the expansion.

Research Objective: We shed light on the potential effect of Medicaid expansion on access to care among breast cancer survivors by assessing inability to see a doctor due to cost before Medicaid expansion in non-expansion states versus expansion states.

Study Design: We use a logistic model (accounting for the weighted sample) and control for demographics, insurance status, and general health. We calculate the odd ratios of inability of survivors of breast cancer to see a doctor in the past year due to cost.

Population Studied: We use data from the Behavioral Risk Factor Surveillance (BRFSS) for the years 2009, 2010, and 2012, which are the only years containing data on cancer survivorship. The BRFSS is a nationally representative survey that collects information on self-reported preventive health practices and risk behaviors. The sample used for this study consists of women ages 40 to 64, in all 50 states and Washington D.C., and who were diagnosed with breast cancer (n = 3,223).

Results: Preliminary results suggest that breast cancer survivors in non-expansion states had significantly higher odds of being unable to see a doctor due to cost (OR = 1.63, 95% CI =1.10, 2.42).

Conclusions: Living in a state that expands Medicaid will be an advantage for low-income breast cancer survivors because it will improve their access to healthcare services. Existing disparities in access to care are likely to widen between survivors of breast cancer in non-expansion states and expansion states as a result of lack of affordable insurance coverage for low-income cancer survivors in non-expansion states.

Citation Format: Wafa W. Tarazi. Medicaid expansion and access to care among 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 A88.
Abstract A93: Treatment and survival after head and neck cancer diagnosis by race in Louisiana's public hospital system
Authors: Peters Edward S. , Brashear Meghan M. , Ferguson Tekeda F.
Published: October 2015

Incidence and survival rates of head and neck cancer (HNC) vary by demographic characteristics, with significant disparities for men and African Americans. Depending on tumor site and stage, treatments options vary, albeit most often are a combination of surgery, radiotherapy and chemotherapy. The objectives of this study are to examine the effect of race on HNC treatment and survival in Louisiana public hospitals from 2000 to 2010. Cases of HNC were identified using Louisiana Health Care Services Division ICON database, which is composed of diagnostic and billing data for all patients undergoing primary treatment in the facilities. This data was subsequently linked to the Louisiana Tumor Registry (LTR) database. Survival rates by, race, sub-site and stage were calculated. Data were analyzed using SAS Version 9.3. Chi-square statistics were used to calculate difference in proportions while log adjusted mixed models were implemented to evaluate the impact of time to first course treatment between groups. Finally, Cox regression models were performed to estimate hazard ratios. A total of 1,168 HNC cases were diagnosed with from 2000 to 2010. Blacks initiated first course treatment after diagnosis 5.7 days (p=0.002) later than whites, adjusted for site, age and stage. While there was no age difference at the time of diagnosis, blacks were significantly more likely to be diagnosed with a late stage HNC compared to whites (p=0.003). In addition it does not appear that treatment type varied by race. Survival functions by stage and tumor site consistently demonstrated poorer survival among blacks compared to whites. The current study suggests that survival differences between blacks and whites in Louisiana are more likely to be influenced by time to treatment and stage rather than any specific treatment differences.

Citation Format: Edward S. Peters, Meghan M. Brashear, Tekeda F. Ferguson. Treatment and survival after head and neck cancer diagnosis by race in Louisiana's public hospital system. [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 A93.
Abstract B01: PEG3 DNA methylation and cervical intraepithelial neoplasia in African American and European American women
Authors: Vidal Adriana C. , Skaar David , Huang Zhiquing , Valea Fidel , Bentley Rex , Gradison Margaret , Yarnall Kimberly S. H. , Ford Anne , Overcash Francine , Grant Katherine , Murphy Susan K. , Hoyo Cathrine
Published: October 2015

Background: Epigenetic mechanisms are hypothesized to be etiologically involved in progression of cervical intraepithelial neoplasia (CIN) to invasive cervical cancer (ICC), although empirical data are lacking.

Methods: A total of 304 women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV was genotyped by HPV linear array. To ascertain the presence of CIN, the biopsies underwent pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of IGF2/H19 PEG1/MEST, KCNQ1OT1, MEG3, HYMAI, PEG10 and PEG3 imprinted domains, using Sequenom EpiTYPER assays. Logistic regression models were used to estimate odd ratios (ORs) and to evaluate the associations between HPV infection and DMR methylation, respectively.

Results: After accounting for age, HPV infection, parity, hormonal contraceptive use, and cigarette smoking, methylation differences at the PEG3 DMR were associated with a modest but significant higher risk of CIN2/3 (OR=1.08, 95%CI 1.02-1.18, p=0.022) in all women. This association remained significant in European American (OR=1.13, 95%CI 1.03-1.27, p=0.011), but not in African American women (OR=1.03, 95%CI 0.90-1.16, p=0.715). HPV infection was associated with altered PEG3 DMR methylation in both groups of women, an association that was also stronger in European Americans (β= -3.42, p=0.041), than in African Americans (β= -2.55, p=0.132). Though altered methylation at IGF2/H19 and PEG10 DMRs was associated with CIN1, no associations were observed with CIN2/3 lesions. No associations were found for PEG1/MEST, KCNQ1OT1, MEG3, and HYMAI DMRs.

Conclusions: Aberrant DNA methylation at the regulatory region of the PEG3 imprinted gene may increase susceptibility to CIN2/3; an association that may be stronger in European American women and which persisted after accounting for HPV infection. If confirmed in larger studies, these findings support the hypothesis that DNA methylation at PEG3 may represent a susceptibility locus that can be exploited to identify, from among a large number of abnormal colposcopy cases, those likely to progress to CIN or worse.

Citation Format: Adriana C. Vidal, David Skaar, Zhiquing Huang, Fidel Valea, Rex Bentley, Margaret Gradison, Kimberly S. H. Yarnall, Anne Ford, Francine Overcash, Katherine Grant, Susan K. Murphy, Cathrine Hoyo. PEG3 DNA methylation and cervical intraepithelial neoplasia in African American and European American women. [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 B01.
Abstract B09: Acculturation, behavioral factors, and family history of breast cancer among Mexican and Mexican-American women
Authors: Nodora Jesse , Cooper Renee , Martinez Maria Elena , Talavera Gregory , Thompson Patricia , Komenaka Ian , Bondy Melissa , Brewster Abenaa , Daneri-Navarro Adrian , Meza-Montenegro Maria Mercedes , Gutierrez-Millan Luis Enrique
Published: October 2015

Introduction: Incidence rates for breast cancer are higher among Mexican-American (MA) women in the US than women living in Mexico. Studies have shown higher prevalence of breast cancer risk factors in higher vs. lower acculturated Hispanic/Latina women in the US. We compared the prevalence for behavioral risk factors and family history of breast cancer by level of acculturation and country of residence in women of Mexican descent.

Methods: Data were collected from 1,201 recently diagnosed breast cancer patients living in Mexico (n=581) and MAs in the US (n=620). MA participants were categorized into three acculturation groups (Spanish dominant, bilingual and English dominant) according to responses to an 8-item language acculturation scale, while women living in Mexico were used as the reference group. Prevalence of behavioral risk factors and family history of breast cancer were compared among the acculturation groups adjusting for age at diagnosis and education level.

Results: In the final adjusted models, bilingual and English-dominant MAs were significantly more likely to have a body mass index > 30 kg/m2, consume more than one alcoholic beverage a week, and report having a family history of breast cancer when compared to women living in Mexico. All three US acculturation groups were significantly more likely to have low total energy expenditure (<533 kcal/day) than women in Mexico. English-dominant women were significantly less likely to smoke cigarettes than the Mexican comparison group.

Conclusions: Our findings on acculturation and distributions of behavioral risk factors and family history of breast cancer add to the growing body of evidence suggesting acculturation has both positive and negative impacts on health behavior in Hispanic/Latino populations living in the US. Interventions and public health policies may benefit from considering these relationships when targeting health programs and campaigns to Mexican-American and Mexican women.

Citation Format: Jesse Nodora, Renee Cooper, Maria Elena Martinez, Gregory Talavera, Patricia Thompson, Ian Komenaka, Melissa Bondy, Abenaa Brewster, Adrian Daneri-Navarro, Maria Mercedes Meza-Montenegro, Luis Enrique Gutierrez-Millan. Acculturation, behavioral factors, and family history of breast cancer among Mexican and Mexican-American women. [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 B09.
Abstract B22: Significance of ethnic-based disparities in prostate cancer risk and outcomes
Authors: Hayes Vanessa M. , Tindall Elizabeth A. , Bornman Riana
Published: October 2015

Ethnic-based disparities have been significantly associated with prostate cancer incidence, age and pathological/biochemical presentation, and mortality. Risk for these parameters are lowest in Asian men relative to men of European ancestry, while the highest in men of African ancestry, in particular African-Americans. Limited studies have, however, addressed clinical presentation and contributing factors within the context of Africa. We established the Southern African Prostate Cancer Study (SAPCS), a unique resource to investigate clinical presentation and risk factors within non-migrant Africans. Enrolling over 1000 men to date we report skewing towards significantly higher prostate specific antigen (PSA) levels in cases (83.0% present with a PSA≥20mg/L; median PSA=98.8mg/L) relative to men with no detectable PCa (18.5% present with a PSA≥20mg/L; median PSA=9.1mg/L). Compared with African-Americans, non-migrant Africans presented with significantly more aggressive disease defined by Gleason score >7 (17% and 36%, respectively) and PSA≥20mg/L (17.2% and 83.2%, respectively), which is further exasperated in men from rural versus urban localities. To determine if the observed clinical presentation is driven by genetics and/or environmental factors, we investigated the power for the most significant genome-wide association study (GWAS) identified PCa risk alleles (n=46) as well as epidemiological measures to predict PCa status and/or disease outcomes within the SAPCS. While we show no evidence that previously defined PCa risk alleles predict disease status within Africa, we show associations with family history of cancer, diabetes, current sexual activity and erectile dysfunction, balding pattern, frequent aspirin usage and high PSA levels. We propose that the SAPCS provides a unique non-PSA tested resource to enhance our understanding that drives significant disparities in PCa associated with ethnic background.

Citation Format: Vanessa M. Hayes, Elizabeth A. Tindall, Riana Bornman. Significance of ethnic-based disparities in prostate cancer risk and outcomes. [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 B22.
Abstract B34: Breast cancer risk factors and screening practices among Hispanics subgroups in the United States
Authors: Diaz-Santana Mary Vanellys , Reeves Katherine W.
Published: October 2015

Hispanics are the fastest growing minority group in the United States (US). In the US, breast cancer (BC) is the most frequently diagnosed cancer among Hispanic women. Differences observed in BC risk by Hispanic origin may be due to variations in the exposure to known BC risk factors. However the heterogeneity of the prevalence of BC risk factors among Hispanic subgroups has not been characterized. We sought to assess differences in BC screening and the distribution of BC risk factors among US Hispanic women by subgroups using data from the 2012 National Health Interview Survey. We compared modifiable BC risk factors (body mass index, physical activity, alcohol use, and smoking) and BC screening (mammogram use) among Hispanic subgroups (Mexican American, South/Central American, Caribbean American, Other Hispanic) using multinomial logistic regression. After adjusting for several confounders, South/Central American women were less likely (OR=0.76; 95% CI: 0.57-1.02) and women from Other Hispanic origin were more likely (OR=1.49; 95% CI: 0.90-2.46) to be obese compared to Mexican Americans. Also, compared to Mexican Americans, women of Other Hispanic origin were more likely to be former and current smokers (OR=1.38; 95% CI: 0.77-3.56; OR=3.52; 95% CI: 2.03-6.11, respectively). Caribbean American women were 49% (OR=0.51; 95% CI: 0.35-0.74) less likely to meet the national guidelines for physical activity as compared to Mexican American women. Among women aged 40 years and older, Caribbean American women were 40% (OR=1.40; 95% CI: 1.07-1.83) more likely to have had a mammogram in the past 12 months as compared to Mexican Americans. These data demonstrate important breast cancer risk factor differences among Hispanic subgroups. The current findings will be useful for developing interventions targeted to reduce the burden of BC among Hispanic women.

Citation Format: Mary Vanellys Diaz-Santana, Katherine W. Reeves. Breast cancer risk factors and screening practices among Hispanics subgroups 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 B34.
Abstract B41: Hyperlipidemia and prostate cancer in African American men
Authors: Springfield Sparkle , Murphy Adam , Chukwudozie Beverly Ifeanyi , Martin Iman , Ahaghotu Chiledum , Kittles Rick
Published: October 2015

Background: African American men suffer disproportionately from prostate cancer. Evidence suggests that hyperlipidemia may increase prostate cancer risk; however, studies examining the disease processes within African American men are limited. We evaluated hyperlipidemia in African American men with and without prostate cancer (PCa) to investigate new and existing associations of serum lipid levels and prostate cancer risk.

Methods: From 2000 to 2004, 250 African American men, aged 40-97 years were recruited from an urban academic urology clinic. Cases had histologically confirmed prostate cancer. Controls were men without clinical cancer who were seen at the same clinic. Hyperlipidemia was defined as patient having one or more of the following: high triglycerides (>200mg/dL), high LDL (>160mg/dL), and/or high total cholesterol(>240mg/dL) serum levels. Binary logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) between lipid exposures and PCa. The adjusted model included age,family history of prostate cancer, obesity, alcohol use, annual income, and Gleason index.

Results: From the patient population, we obtained 141 incident PCa cases and 109 healthy controls. We observed a significant association between hyperlipidemia (OR= 1.7 [1.0-3.1]; unadjusted) and PCa, as well as hypertriglyceridemia (OR= 2.1[1.0-4.5]; adjusted) and PCa. Hypertriglyceridemia showed significant associations with aggressive disease (Gleason≥7) in both unadjusted (OR = 2.8[1.1–7.4]) and adjusted models (OR = 3.5 [1.1–10.7]). Both income (OR=2.2[1.1-4.0]) and alcohol (OR=0.5[0.3-0.9]) were significantly associated with PCa. Furthermore, we observed significant interaction between hyperlipidemia and obesity (OR=4.7[1.0-21.8]; adjusted). There were no associations found between hypercholesterolemia or elevated LDL serum and PCa.

Conclusions: This study adds to recent evidence that hyperlipidemia has a positive relationship with PCa in African American men.

Citation Format: Sparkle Springfield, Adam Murphy, Beverly Ifeanyi Chukwudozie, Iman Martin, Chiledum Ahaghotu, Rick Kittles. Hyperlipidemia and prostate cancer in African American men. [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 B41.
Abstract B53: Racial variation in the uptake of a 21-tumor gene assay in the Carolina Breast Cancer Study cohort
Authors: Roberts Megan C. , Wheeler Stephanie B. , Reeder-Hayes Katie , Dusetzina Stacie B. , Dinan Michaela , Weinberger Morris
Published: October 2015

Background: In 2004, a 21-gene assay became commercially available with the potential to aid adjuvant chemotherapy treatment decision-making for women with early stage, hormone receptor positive breast cancer. This assay predicts not only risk of recurrence, but also benefit of adjuvant chemotherapy. With its incorporation into clinical practice guidelines in 2007, this assay may reduce overuse of adjuvant chemotherapy for eligible women and improve the quality of care for women with breast cancer. We examine whether racial differences in the use of the 21-gene assay exists among a large, representative sample of women with breast cancer who receive care in diverse health care settings.

Methods: Data come from Phase III of the Carolina Breast Cancer Study (CBCS-III), a unique and rich dataset that includes survey and medical record abstraction data for 3000 women (1500 white, 1500 black) across North Carolina with invasive breast cancer diagnoses between 2008 and 2013. We will build logistic regression models to examine the impact of race on the use of this assay among women ages 20-74 with early-stage, hormone receptor positive, invasive breast cancer. We will control for patient-level tumor, treatment, and demographic characteristics.

Results: We will present preliminary results regarding racial variation in the uptake of this assay. Furthermore, we will compare the characteristics of women who use the assay with the characteristics of those who do not.

Conclusions: As genomic technologies shift cancer treatment towards personalized therapies, it is critical to understand utilization patterns across racial subgroups. This study will examine whether racial differences exist in the use of a 21-gene assay. Ultimately, these data will be important to understand how genomic technologies may influence racial disparities in cancer processes and outcomes.

Citation Format: Megan C. Roberts, Stephanie B. Wheeler, Katie Reeder-Hayes, Stacie B. Dusetzina, Michaela Dinan, Morris Weinberger. Racial variation in the uptake of a 21-tumor gene assay in the Carolina Breast Cancer Study cohort. [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 B53.
Abstract B63: Disparities in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009
Authors: Houston Keisha , Henley S. Jane , Li Jun , White Mary C. , Richards Thomas B.
Published: October 2015

Objective: Surveillance of lung cancer by histology type is important for monitoring population trends that have implication for etiology and prevention, clinical diagnosis, prognosis and choice of targeted therapies. This study provides a comprehensive and recent description of disparities in histologic lung cancer incidence rates and trends for U.S. adults.

Methods: Histologic lung cancer incidence was analyzed from CDC's National Program of Cancer Registries (NPCR) and the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program. Standardized rates and trends were calculated for men and women by age, race/ethnicity, and U.S. Census region. Rate ratios were examined for differences in rates between men and women, and annual percent change was calculated to quantify changes in incidence rates over time.

Results: Adenocarcinoma and squamous cell carcinoma were the two most common histologic subtypes. Adenocarcinoma rates continued to increase in men and women, and squamous cell rates increased in women only. All histologic subtype rates for white women exceeded rates for black women, and histologic rates for black men exceeded those for white men, except for small cell carcinoma where rates were higher among white men. Among both men and women, the rate for Hispanics was nearly half the rate for non-Hispanic (NH) blacks and NH whites. Men had higher incidence rates than women for race and ethnic groups, but the relative size of this difference by sex was higher for NH blacks, NH Asian/Pacific Islanders and Hispanics compared with NH whites. The relative difference in incidence rates between men and women was slightly lower for NH American Indian/Alaska Native (AI/AN) populations than for whites. Differences between men and women living in the West were less pronounced compared to those living in other Census regions.

Conclusion: The variations observed by race and ethnicity, continuing rise in incidence rates of lung adenocarcinoma, and rise of squamous cell cancer rates in women suggest more research is needed to comprehensively understand factors that may be contributing to observed differences in lung cancer histology. Identification of these factors acting in addition to, or in synergy with cigarette smoking, may provide public health agencies with guidance for targeted messages to groups at higher risk.

Citation Format: Keisha Houston, S. Jane Henley, Jun Li, Mary C. White, Thomas B. Richards. Disparities in lung cancer incidence rates and trends by histologic type in the United States, 2004-2009. [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 B63.
Abstract B64: Cancer clinical trials: Real answers, real options, real miracles, right here in West Michigan
Authors: Gavin Patrick W.
Published: October 2015

Mission Statement:

“Cancer survivors sharing clinical trial experiences to increase awareness and knowledge in the search for prevention and cure.”

Vision Statement:

Our goal is to increase the awareness of cancer clinical trials available in West Michigan. The Patient Advisory Committee for Clinical Research was formed to capture the passion that clinical trial participants possess in searching for a cure for a disease that has personally affected them. Fear often accompanies a cancer diagnosis. The vision is to replace fear with the knowledge that is brought through clinical trials. The Patient Advisory Committee for Clinical Research's objective is to make cancer clinical trials information available and increase general public awareness of this treatment option.

Citation Format: Patrick W. Gavin. Cancer clinical trials: Real answers, real options, real miracles, right here in West Michigan. [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 B64.
Abstract B88: Examining differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanic and island Puerto Rican women
Authors: Morales-Campos Daisy Y. , Vanderpool Robin C.
Published: October 2015

Background: Despite having guidelines recommending vaccination against the human papillomavirus (HPV) and widespread coverage for the vaccine, HPV vaccination rates among U.S. Hispanic and island Puerto Rican (PR) girls are low. In 2012, only 16% of PR girls aged 11–18 and 42% of U.S. Hispanic girls aged 13-17 were vaccinated with all three HPV vaccine doses; far fewer than the Healthy People 2020 goal of 80%. Parents are crucial to the success of HPV vaccine uptake efforts. Few studies focusing on parents have examined possible differences in HPV knowledge and vaccine acceptability within ethnic groups. The purpose of the study is to assess potential differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanic and island PR women.

Methods: We utilized data from the Health Information National Trends Survey (HINTS) 2007 and HINTS Puerto Rico 2009. For the current study, we restricted our analyses to female respondents in both surveys for a total sample of 792 women (n = 375; U.S. Hispanic HINTS 2007 and n = 417; Puerto Rican HINTS-PR 2009). Using the Wald chi-square test, we assessed if there were significant differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanics and island PR women.

Results: Island PR women had significantly higher HPV vaccine awareness (66.9% vs. 61.0%; Wald X2 F(1, 97) = 16.03, p < .001) and were more accepting of the HPV vaccine for a real or hypothetical daughter (74.8% vs. 56.1%; Wald X2 F(2, 96) = 7.18, p < .001) compared to U.S. Hispanic women. Both groups were highly knowledgeable that HPV causes cancer (89.2% in both samples) and HPV is a sexually transmitted infection (78.1% [U.S. Hispanics] and 84.7% [PR]). Less than 10% of both groups recognized that HPV can go away on its own without treatment.

Conclusions: Our study found that island PR women were more aware of and accepting of the HPV vaccine when compared to U.S. Hispanic women. Future research should further explore these in-group differences to determine what in the PR socio-cultural context or environment may have led to higher HPV vaccine awareness and acceptability. Findings may also assist in developing culturally appropriate health education programs and media to promote HPV vaccination among both groups.

Citation Format: Daisy Y. Morales-Campos, Robin C. Vanderpool. Examining differences in HPV knowledge, vaccine awareness, and acceptability between U.S. Hispanic and island Puerto Rican women. [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 B88.
Abstract IA12: Collaborators to the Sovereigns: Learning from history to make new chapters in research with American Indians and Alaska Natives
Authors: Haring Rodney C.
Published: October 2015

Purpose/Objective(s): Cancer death rates in the US have declined. However, this trend is not true for American Indians and Alaska Natives (AI/AN) where rates have remained unchanged. Further, AI/ANs have experienced the poorest five-year cancer survival rates of all racial and ethnic groups. The presentation will touch upon the historical traumas and contemporary resiliencies which have had influences on health behaviors, lifestyles, and the investigations of disparities among AI/AN Peoples and communities. The objectives will include 1) the movement of tribes exerting research sovereignty; 2) sharing the state of the science about bio-ethics in the landscapes of Indigenous Peoples; and 3) how cancer centers and academic institutions are becoming effective partners in the research process. Newsworthy exemplars of research in Indian Country will be shared.

Materials/Methods: This multifaceted presentation will share 1) research sovereignty through a tribal protocol and recommendations from the US Health and Human Services, AI/AN Research Advisory Council; 2) experiences gained from work with cancer and bio-ethics projects with an AI/AN urban population; 3) how legal cases such as Havasupai vs. Arizona State University have shaped new chapters in research with AI/AN Nations and lastly, 4) a showcase of challenges and resiliencies of Native Nations and their response to various types of health disparity research.

Summary: The literature discussed provides a foundation for understanding cancer and health disparity research from a historical perspective that should inform future practices. This includes the importance of building relationships, community based participation, tribally driven research agendas, the sharing of sovereign philosophies, and the highlighting of resiliencies.

Conclusions: The development of respectful relationships is important to solidify trust in AI/AN communities where researchers intend to collaborate. This is especially true in sensitive research fields such as genetics, bio-specimen, and cancer and health disparity clinical trials. Community based participatory research should be implemented from the beginning with the community in an effort to jointly build research agendas that are both scientifically novel and beneficial to AI/AN landscapes.

Citation Format: Rodney C. Haring. Collaborators to the Sovereigns: Learning from history to make new chapters in research with American Indians and Alaska Natives. [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 IA12.
Abstract IA19: Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color
Authors: Gonzalo Susana
Published: October 2015

Breast cancer is the leading cause of cancer death in women worldwide. BRCA1-deficient and triple-negative breast cancers (TNBC) are particularly aggressive, strike younger, Hispanic and African American women, and are most difficult to treat. These tumors exhibit DNA repair defects, making them vulnerable to DNA damaging therapies. Currently, the most promising therapeutic agents are poly(ADP-ribose) polymerase inhibitors (PARPi), which render cells already deficient in DNA repair, with an unbearable load of DNA damage. Excitement about PARPi has been fueled by clinical trials showing that these compounds, either as single agents or in combination with chemotherapy, have very encouraging outcomes in BRCA1-related and TNBC and with minimal toxicity. However, a significant fraction of these cancers acquire resistance to PARPi. Understanding the molecular mechanisms that confer PARPi resistance will have a big therapeutic impact.

Elegant studies demonstrated that loss of the DNA repair factor 53BP1 contributes to progression of BRCA1-deficient and TNBC and to their resistance to PARPi. Thus, raising the levels of 53BP1 in these tumors could represent a new therapeutic strategy. Our team identified a new pathway modulating the levels of 53BP1, which could be exploited to stabilize protein levels. We found that BRCA1-deficient cells activate the degradation of 53BP1 by the protease cathepsin-L (CTSL), and that CTSL inhibition by vitamin D stabilizes 53BP1, reduces proliferation, and increases PARPi and radiation sensitivity. Our studies in human breast tumors also suggest that deficiencies in vitamin D/vitamin D receptor (VDR) axis, more prevalent in women of color, could underlie the activation of CTSL-mediated degradation of 53BP1 in BRCA1-deficient and TNBC. Our current studies are testing the ability of vitamin D treatment to reduce the growth of BRCA1-deficient and TNBC cells, as well as their resistance to PARPi, providing a novel modality of treatment for these cancer patients.

Citation Format: Susana Gonzalo. Regulation of 53BP1 in BRCA1-deficient cells: Why vitamin D matters and how disparities in vitamin D levels could promote aggressive TNBC in women of color. [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 IA19.
Abstract IA48: Cultural determinants of disparities in lung cancer care and outcomes
Authors: Wisnivesky Juan
Published: October 2015

The outcome of patients with lung cancer remains poor, particularly among individuals of ethnic and racial minorities. Two well-documented causes for the currently observed disparities in survival are diagnosis at a more advanced stage and lower rates of indicated treatment of minority patients. The underlying reasons for these disparities however, are not clear. A range of potential explanations have been suggested including patient-level (beliefs, preferences, and expectations regarding lung cancer care), physician-level (biases, stereotyping, and uncertainty), patient-provider interaction-level (barriers in cross-cultural relationships) and system-level (health system organization, accessibility) factors. Understanding the influence and relative importance of these factors is an important first step towards designing interventions to improve the outcomes of minority patients with lung cancer.

In this presentation, we will review the underlying reasons for the observed disparities in stage at diagnosis, treatment, and end-of-life care of minority patients, with a particular focus on cultural factors. We will discuss results from a recently completed, four-site study assessing behavioral and cultural barriers to appropriate diagnosis and treatment of minorities with lung cancer. Our focus will be on potentially modifiable barriers that could be the target for future interventions aimed at reducing disparities in care.

Citation Format: Juan Wisnivesky. Cultural determinants of disparities in lung cancer care and outcomes. [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 IA48.
Abstract IA51: Ethnic disparities in chronic liver disease in the U.S
Authors: Poordad Fred
Published: October 2015

Chronic liver disease is the 12th leading cause of death in the US, but ranks 6th among Hispanics. Cirrhosis rates are highest in Hispanics, followed by blacks and whites. In the 45-64 year age groups, chronic liver disease is the 3rd leading cause of death in Hispanics.

Much of this disparity is driven by the frequency of fatty liver disease, which occurs in 45% of Hispanics, 33% of blacks and 24% of whites. Other risk factors for liver disease include viral hepatitis C, alcoholic liver disease, diabetes, and metabolic syndrome. Many of these risk factors are more common in the Mexican American and black populations compared to whites. Largely for this reason, hepatocellular cancer rates are highest in Hispanics, after Asians and Pacific Islanders. These trends are expected to continue.

Citation Format: Fred Poordad. Ethnic disparities in chronic liver disease in the U.S. [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 IA51.
Abstract IA53: Challenges of implementing interventions in “small populations.”
Authors: Srinivasan Shobha , Moser Richard P. , Willis Gordon , Riley William , Alexander Mark
Published: October 2015

The ability to harness the benefits of big data has had a revolutionary impact on science, with its focus on the volume and variety of data sources and application of both traditional and innovative analytic methods appropriate for large, aggregated datasets. We are concerned, however, about the opposite: small data for which the size, dispersion, or accessibility of the population of interest makes it difficult to obtain adequate sample sizes to test specific research questions. Data from these groups, however, are critical if we want to include health-related issues across all populations in cancer research.

An example of the potential negative ramifications of not including underrepresented groups in research or inappropriately aggregating them across groups-- comes from the study of racial and ethnic health disparities and issues of equity in the US. Intervention research often does not include a wide range of racial/ethnic subgroups; so it is not feasible to test whether an intervention created specifically for the majority group is also efficacious for the subgroups. Likewise, the ability to test whether an intervention can be altered for a particular subgroup is also often not possible. Epidemiologic and surveillance research usually involves the inclusion of “minority or underserved populations” in addition to white/non-Hispanic white (NHW) groups. While this has allowed for a better understanding of these smaller populations and provides some progress toward addressing health inequities, there remain pockets of communities that are severely underrepresented within the broader minority and underserved populations.

Citation Format: Shobha Srinivasan, Richard P. Moser, Gordon Willis, William Riley, Mark Alexander. Challenges of implementing interventions in “small populations.” [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 IA53.
Abstract PR13: Disparities in centrosomal profiles: Prediction of metastatic risk in African American and European American breast cancer patients
Authors: Wright Nikita , Pannu Vaishali , Rida Padmashree , Mittal Karuna , Klimov Sergey , Yada Farida N. , Reid Michelle D. , Cantuaria Guilherme , Aneja Ritu
Published: October 2015

Centrosome amplification has long been established as a hallmark of cancer. More than 80% of invasive breast tumors display this cellular trait. Centrosomal aberrations underlie chromosome instability (CIN) thus corroborating the extensive clonal intratumoral heterogeneity existent within breast lesions that fuels tumor evolution. Sub-clonal heterogeneity drives emergence of aggressive clones with a propensity to migrate and invade, resulting in tumor dissemination and metastases. Thus, centrosome amplification is a critical driver of tumor progression and metastases. Although numerous studies have linked centrosomal overload to tumor aggressiveness, no studies have yet quantified this cell-biological feature to establish a well-defined relationship between the severity and extent of centrosome amplification and tumor aggressiveness. Utilizing an innovative and rationally-guided approach, we have derived an algorithm that allows the precise quantitation of the frequency and severity of both structural and numerical aberrations in supernumerary centrosomes present in clinical samples. Our novel method thus uncovers previously unrecognized differences in the centrosomal profiles of grade-matched breast tumors from African-American (AA) (n=71) and European American (EA) (n=104) women. Our data demonstrate that AA breast tumors exhibit higher numeral, structural and total centrosome amplification scores than grade-matched EA tumors. Interestingly, tumors displaying lymph node and distant metastasis exhibited higher structural amplification than grade-matched non-metastatic tumors. Hence, our novel quantification tool offers valuable information that can potentially predict the risk of AA breast tumors rapidly progressing to metastatic disease and uncovers a hitherto unappreciated organelle-specific disparity marker among racially distinct breast tumors.

This abstract was also presented as Poster B6.

Citation Format: Nikita Wright, Vaishali Pannu, Padmashree Rida, Karuna Mittal, Sergey Klimov, Farida N. Yada, Michelle D. Reid, Guilherme Cantuaria, Ritu Aneja. Disparities in centrosomal profiles: Prediction of metastatic risk in African American and European American breast cancer patients. [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 PR13.
Abstract A33: Utilizing insulin the treatment of prostate cancer with BKM120 abrogates the therapeutic effect of PI3K pathway inhibition
Authors: Wang Lily C. , Kim Sunnie S. , Nanus David M. , Cantley Lewis C.
Published: October 2015

Genetic aberrations in PTEN, the negative regulator of phosphoinositide 3-kinase (PI3K) signaling, are common in prostate cancers (PCA) with high Gleason Scores and correlate with adverse outcome. Currently, PI3K inhibitors, as single agents and in combination, have entered Phase I and II clinical trials for metastatic castrate resistant PCA. Alpha-specific and pan-PI3K inhibitors cause hyperglycemia as an on-target side effect by blocking insulin-dependent PI3K signaling in the liver and muscle and patients develop hyperinsulinemia in response to hyperglycemia, and insulin treatment is often needed to manage drug-induced hyperglycemia. Using human and murine prostate cancer cell lines, we examined the effect of adding insulin to BKM120 treatment on PI3K pathway activation.

Using human prostate cancer cell lines LNCaP and PC3 which both express insulin receptor (IR) and IGF-1 receptor (IGF-1R), we found downregulation of the PI3K pathway by BKM120 treatment and upregulation of the PI3K pathway by insulin treatment, as assessed by AKT phosphorylation. In both cell lines, the PI3K pathway is reactivated when insulin is added to BKM120 treatment. Using cells derived from PTEN-/-P53-/- murine PCA which express low levels of IR and IGF-1R, we found minimal activation of the PI3K pathway with insulin, either alone or in combination with BKM120. Conversely, using cells derived from Myc-overexpressing mice which express high levels of IR and IGF-1R, we found robust activation of the PI3K pathway with insulin treatment. More importantly, while BKM120 abolished PI3K activity in the Myc-overexpressing cells, the addition of insulin to BKM120 resulted in the reactivation of the PI3K pathway to the level of PI3K pathway activity without BKM120 treatment. Together these findings suggest that the use of insulin in combination with BKM120 abrogates the therapeutic effect of PI3K inhibition. In addition, they indicate that PCAs that have high levels of IR and/or IGF-1 expression are particularly sensitive to PI3K inhibitors as well as insulin reactivation of the PI3K pathway.

Citation Format: Lily C. Wang, Sunnie S. Kim, David M. Nanus, Lewis C. Cantley. Utilizing insulin the treatment of prostate cancer with BKM120 abrogates the therapeutic effect of PI3K pathway inhibition. [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 A33.