bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A10: Facebook advertisement effects on conversions and enrollment to a SMS/text smoking cessation service for young adult Latinos
Authors: Chalela Patricia , McAlister Alfred L. , Gallion Kipling J. , Muñoz Edgar , Despres Cliff , Akopian David , Perez Arely , Garcia Robert , Ramirez Amelie G.
Published: May 2016

Evidence shows that variations in the degree and type of a message's emotional arousal, particularly disgust, can influence message impact on smokers' interest in quitting and likelihood of seeking help. Negative emotional appeals are widely used to attract attention of Latino audiences, but positive appeals, especially those designed to increase smokers' confidence in their ability to quit, are also recommended as a way to attract them to enroll in cessation services.

Methods: We employed positive and negative variations in Facebook advertising appeals to study their effects on “conversions” and subsequent enrollment in a tobacco cessation service (a bilingual text messaging and mobile media service specifically targeting Latino young adults in South Texas). Differences in advertisement characteristics on conversion rate and enrollment were examined using exact Chi-squared tests for proportions and 95% confidence intervals for their corresponding odds ratios.

Results: The negative advertisement received a higher conversion rate than the positive ad, with 1,441/130,000 (1.11%) vs. 1,249/130,000 (1.96%) clicking the ad to visit our service's home page (OR= 1.16, 95% CI 1.07, 1.25). But subsequent texted enrollments in the cessation service were received by 76/1,249 (5.76%) of those exposed to the positive message and 55/1,441 (3.82%) of those exposed to the negative message (OR= 1.54, CI1.06, 2.25). The former were 54% more likely than the latter to become enrolled.

Conclusion: Negative-appealing advertising attracted more clicks to further information, but positive appeals were more likely to lead to subsequent enrollment. Negative advertising can gain attention and spark minor actions toward behavior change, but positive advertising appealing to the consumer's self-confidence is more likely to lead to an actual first step toward behavior change.

Citation Format: Patricia Chalela, Alfred L. McAlister, Kipling J. Gallion, Edgar Muñoz, Cliff Despres, David Akopian, Arely Perez, Robert Garcia, Amelie G. Ramirez. Facebook advertisement effects on conversions and enrollment to a SMS/text smoking cessation service for young adult Latinos. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A10.
Abstract A39: Profiles, motivations, and networks of prostate cancer advocates in southern black communities
Authors: Gilbert Lauren Rose
Published: May 2016

Black men have the highest number of new cases and mortality rates for prostate cancer: 1.6 and 2.4, respectively when compared to whites (NCI, 2015). Also, black men are more likely to have an advanced stage and grade of prostate cancer at initial presentation. Prostate cancer disparities are a complex problem that needs to be assuaged with complex and multifaceted strategies. Advocates can be one of the many tools used to alleviate the prostate cancer health disparities that are observed today in black communities. While there is no shortage of research being done on black men and prostate cancer, there is a very little research on the work of advocates for prostate cancer awareness in black communities. Advocates are already engaging on different levels with black communities to increase prostate cancer awareness.

This research seeks to further illuminate the advocates' efforts and voices, exploring their strategies and approaches. Through the use of qualitative methods, data collection yielded a total of 24 in-depth interviews and 14 ethnographic observations. These expanded methods capture a more nuanced and complex understanding of prostate cancer advocacy. Major findings include (1) the description of the advocates, including their demographics and self-definitions, (2) the interrelated internal and external sources of motivation for their advocacy efforts; and (3) an examination of the complex networks of advocacy that incorporate social networks, organizations, and research and political entities. These insights can help to create and support more effective interventions that are specifically developed for men in black communities.

Citation Format: Lauren Rose Gilbert. Profiles, motivations, and networks of prostate cancer advocates in southern black communities. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A39.
Abstract B03: PVT1 exon 9 is a potential non-invasive biomarker that regulates apoptosis and the cell cycle in aggressive prostate cancer in black males
Authors: Ilboudo Adeodat , Das Dibash , Ogunwobi Olorunseun O.
Published: May 2016

Prostate cancer (PCA) is the most common non-skin cancer and the second leading cause of cancer-related death for men in the U.S. Black males have a higher incidence of PCA, compared to White males. In fact, Black race is a confirmed, non-modifiable risk factor for PCA with a 2.5 fold greater risk of lethal PCA compared to Caucasian males. Discovery of effective early detection strategies are necessary to address the profound health disparity. The chromosomal region 8q24 is associated with aggressive PCA in Black men and variants of this region have been identified to interact with the PVT1 non-protein coding gene in PCA. PVT1 is located at 8q24 and is transcribed into a long non-protein coding RNA that has been implicated in PCA. Using a panel of eight prostate epithelial cell lines modeling a variety of clinical characteristics of PCA, we investigated the expression of 12 exons of PVT1 in PCA. We discovered that exon 9 of PVT1 is consistently significantly upregulated (by about 2-folds) in aggressive PCA cell lines derived from Black males (MDA PCa 2b and E006AA-hT) in comparison to indolent PCA cells from a Black male E006AA, and both indolent and aggressive PCA cell lines derived from White males. Cell-free PVT1 exon 9 was detectable in cell culture medium, and found to be detectable at significantly higher levels from the aggressive E006AA-hT cell line in comparison to the indolent E006AA cell line from which it was derived. PVT1 exon 9 was efficiently silenced by a custom-designed siRNA. We observed that silencing of PVT1 exon 9 expression resulted in apoptosis and cell cycle arrest at G1 phase in the MDA PCa 2b cell line derived from a Black male. Consequently, PVT1 exon 9 may regulate apoptosis and the cell cycle in aggressive PCA in Black males. Our ability to detect cell-free PVT1 exon 9 indicates that PVT1 exon 9 may have potential future role in non-invasive early detection of aggressive PCA in Black males.

Citation Format: Adeodat Ilboudo, Dibash Das, Olorunseun O. Ogunwobi. PVT1 exon 9 is a potential non-invasive biomarker that regulates apoptosis and the cell cycle in aggressive prostate cancer in black males. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B03.
Abstract B35: Molecular characterization of colorectal tumors from Puerto Rican Hispanic patients
Authors: Díaz-Algorri Yaritza , Pérez-Mayoral Julyann , González-Pons Maria , Rodríguez Natalia , Suárez Belisa , Colón Giancarlo , Sevilla Javier , Jorge Daphne L. , Llor Xavier , Xicola Rosa , Tous Luis , Reyes José S. , Torres Marla , Goel Ajay , Rodriguez Segundo , Cruz-Correa Marcia
Published: May 2016

Background and Objectives: Accumulating evidence supports that colorectal cancer (CRC) is comprised of different genetic diseases affecting the same organ. The molecular classification of CRC is evolving as we gain a comprehensive knowledge about the mechanisms and processes resulting in colorectal carcinogenesis. Tumors display distinct characteristics depending on the molecular subtype, which may affect response to treatment, prognosis, and survival. CRC is the leading cause of cancer deaths among Puerto Rican Hispanics (PRH). The aim of this study was to characterize colorectal tumors at a molecular level in a cohort of PRH in order to determine the prevalence of molecular markers.

Methods: The molecular markers evaluated were microsatellite instability (MSI), CpG island methylation phenotype (CIMP), and mutations in KRAS and BRAF oncogenes. In addition, HPV infection status was assessed, as it has been associated with CRC. Sociodemographic and clinicopathological characteristics were evaluated according to MSI, CIMP, KRAS/BRAF mutation and HPV-status using Pearson's Chi-Square and Mann-Whitney U-test.

Results: A total of 201 CRC tumors were included in our study. Of the evaluated tumors 2.6% (n=3) showed MSI and 1.8% of the studied tumors had CIMP high phenotype (n=2). The incidence of KRAS and BRAF mutations for our study was 30.6% (n= 38) and 9.2% (n=11), respectively. Furthermore, KRAS positive individuals were more likely to have private or Medicare insurance (p=0.017). In addition, BRAF mutation-positive tumor were more likely to be poorly differentiated when compared to BRAF mutation-negative tumors (p=0.009). HPV infection was not associated with any molecular characteristics examined.

Conclusions: We present for the first time the molecular characterization of CRC tumors in PRH. The observation of a different molecular signature for the CRC tumors (low MSI, CIMP Zero and mainly wild-type for KRAS and BRAF) suggests that CRC in this population might be driven by additional genetic, epigenetic and environmental factors than other racial/ethnic groups.

Citation Format: Yaritza Díaz-Algorri, Julyann Pérez-Mayoral, Maria González-Pons, Natalia Rodríguez, Belisa Suárez, Giancarlo Colón, Javier Sevilla, Daphne L. Jorge, Xavier Llor, Rosa Xicola, Luis Tous, José S. Reyes, Marla Torres, Ajay Goel, Segundo Rodriguez, Marcia Cruz-Correa. Molecular characterization of colorectal tumors from Puerto Rican Hispanic patients. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B35.
Abstract C06: Examining reasons for breast cancer disparities in African American women in Duval County, FL
Authors: Osian Sarah , Albertie Monica , Monticalvo David , Ames Steven , Samiian Laila , Colon-Otero Gerardo
Published: May 2016

Background/Purpose: Cancer registry data suggests that Duval County (greater Jacksonville, FL) has the highest breast cancer mortality rate for African American (AA) women in the southeastern US. Recent research revealed that race, residence, and insurance were associated with significantly poorer breast cancer outcomes in this area. Therefore we conducted a series of focus groups with AA breast cancer survivors from the urban core of Jacksonville, FL to directly address the disparities observed in our quantitative data.

Methods: A series of focus groups were conducted to obtain qualitative data topics that included: breast cancer beliefs; delays to diagnosis and treatment; disparities; and health behaviors.

Results: A total of 56 AA breast cancer survivors living in the urban core, with either Medicaid or who were uninsured, participated in the focus groups. Mean age was 62 years, with an average of 3.4 years since diagnosis. Only 21% of women were employed. Participants reported their mean time to see a doctor initially for their breast cancer was 39 days, and mean time to first treatment was 178 days. Participants responded that fear, financial limitations, and personal beliefs played the biggest roles in delays to diagnosis and treatment. Participants responded that poor health behaviors, genetics, lack of education, and personal beliefs accounted for both causing breast cancer, and the disparities observed in breast cancer mortality, and felt that environmental factors from living in the urban core also contribute.

Conclusions: Our findings highlight several areas for potential intervention to reduce disparities in breast cancer.

Citation Format: Sarah Osian, Monica Albertie, David Monticalvo, Steven Ames, Laila Samiian, Gerardo Colon-Otero. Examining reasons for breast cancer disparities in African American women in Duval County, FL. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C06.
Abstract C26: Epigenetics and pancreatic cancer: The role of nutrigenomics in cancer health disparities
Authors: Lyn-Cook Beverly , Word Beverly , Joseph Stancy , Hammons Goorge
Published: May 2016

In vivo, in vitro and epidemiological studies have shown that an individual's diet may contribute to their susceptibility to develop cancer. Pancreatic cancer remains a very complex and challenging disease that is increasing in African Americans. This cancer carries one of the worst prognosis of any major malignancy, mainly due to its lack of early detection and lack of effective therapeutic agents. Although improvements in imaging technology has aided in diagnosis and identification of patients with the disease, these new technologies have not greatly improved the mortality rate of pancreatic cancer. Evidence has shown that epigenetic mechanisms play an important role early in this cancer and furthermore, epigenetic modifications can be altered by external or internal environmental factors, such as components found in diets, and have the potential to also be reversed. We and others have shown that dietary agents found in cruciferous vegetables, such as indole-3-carbinol, have tremendous anti-cancer effects and can modulate key signals in pancreatic cancer through various mechanisms, such as inactivation of STAT3, reactivation of p16, the ability to up-regulate critical drug transporters such as hENT, to increase drug efficacy and recently modulate Wnt signaling pathways. All of these targets are potentially significant in developing chemopreventive strategies for reducing cancer health disparities among higher risk populations. Results will be shown where indole-3-carbinol has demonstrated effects on all of these targets in pancreatic cancer. Educational strategies are needed to increase knowledge of the importance of proper diet to vulnerable populations.

Citation Format: Beverly Lyn-Cook, Beverly Word, Stancy Joseph, Goorge Hammons. Epigenetics and pancreatic cancer: The role of nutrigenomics in cancer health disparities. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C26.
Abstract C50: Sensitivity of triple-negative breast cancer cell lines to cytotoxic and targeted agents as a function of molecular subtype
Authors: Colley Heather , Saxena Roopali , Ogden Angela , Cantuaria Guilherme , Reid Michelle D. , Li Xiaoxian (Bill) , Krishnamurthy Uma , Rida Padmashree CG , Aneja Ritu
Published: May 2016

Triple-negative breast cancer is a heterogeneous disease with no approved targeted therapies. The disease course is very aggressive, characterized by relapse within 3 years of treatment and metastases to the viscera, including the brain. The prognosis in the setting of distant metastases is grim, as median survival is less than one year. Recently, insight into the molecular complexity of TNBC was provided by gene expression analysis, which identified six unique subtypes with distinct gene ontologies that differ with respect to drug sensitivity. These subtypes, each enriched in unique molecular components and pathways, suggest target-based strategies for treatment. A multiplicity of targeted drugs has entered clinical trials for the potential treatment of TNBC, but no uncontested victor has emerged that can appreciably extend overall survival. For instance, one of the most promising experimental drugs is iniparib, which significantly improved outcomes in a Phase II clinical trial of metastatic TNBC when combined with carboplatin/gemcitabine; however, overall survival was still unacceptably short at ~1 year. Therefore, there remains a dire need to identify novel therapeutic modalities for TNBC. A promising research strategy towards this goal is to determine the differential sensitivities of the TNBC molecular subtypes to combinations of cytotoxic and targeted drugs. We are determining the responses of a panel of TNBC cell lines representing different molecular subtypes, including the basal-like 1 (HCC1143 and MDA-MB-468), basal-like 2 (HCC1806 and HCC70), immunomodulatory (HCC1187), mesenchymal stem-like (MDA-MB-436, MDA-MB-231, and MDA-MB-157), and luminal androgen receptor (MFM-223) subtypes, to variable doses of carboplatin, capecitabine, cyclophosphamide, docetaxel, and everolimus, used alone and in combination. These drugs were chosen because they target molecular regulators of prominent signaling pathways specific to certain TNBC molecular subtypes, so we expect to find that sensitivity to these drugs is a function of subtype. The results of this study will enable characterization of TNBC subtypes in finer detail and provide a preclinical framework for the development of subtype-dependent regimens for TNBC treatment.

Citation Format: Heather Colley, Roopali Saxena, Angela Ogden, Guilherme Cantuaria, Michelle D. Reid, Xiaoxian (Bill) Li, Uma Krishnamurthy, Padmashree CG Rida, Ritu Aneja. Sensitivity of triple-negative breast cancer cell lines to cytotoxic and targeted agents as a function of molecular subtype. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C50.
Abstract C52: Targeting the obesity/leptin link to TNBC: A breast cancer disparity problem
Authors: Dill Courtney D. , Harbuzariu Adriana , Harmon Tia L. , Lipsey Crystal C. , Loye Ayobami , Gonzalez-Perez Ruben Rene
Published: May 2016

Triple Negative Breast Cancer (TNBC) is an aggressive cancer associated with poor prognosis and is difficult to treat. Standard therapy for TNBC includes a combination of chemotherapeutic drugs: doxorubicin (DOX), paclitaxel (TAX), and cyclophosphamide (CTX). Current epidemiological data show that obesity increases TNBC incidence, which is more relevant for African American women. Recent findings suggest that leptin (an adipokine increased in obesity) is involved in TNBC acquired drug resistance via induction of breast cancer stem cells (BCSCs). Understanding the role of obesity in TNBC is vital to the development of new and effective therapies. Chemotherapeutic drugs exhibit shortcomings that may be due to increased drug resistance, survival, proliferation, and angiogenic signal redundancy induced by leptin. Our lab has developed and tested a novel, specific inhibitor of leptin signaling, LPrA2. A pegylated derivative of LPrA2 (PEG-LPrA2) has previously shown to enhance, 68 fold, LPrA2's bioavailability in mouse breast cancer models. The objective of this study was to determine the adjuvant effects of PEG-LPrA2 on TNBC in vitro. We hypothesized that PEG-LPrA2 can serve as an adjuvant for standard TNBC chemotherapeutics. This adjuvant would allow for the reduction of chemoresistance and TNBC recurrence. It could also reduce chemotherapeutic dose and undesirable side effects associated with standard therapy for the disease. Two human TNBC cell lines were cultured: MDA-MB-231 (highly metastatic) and MDA-MB-468 (minimally invasive). Cellometer imaging technologies were used to determine S-phase progression in cells treated with PEG-LPrA2 and leptin. Flow cytometry technologies were used to determine the effects of leptin on BCSC surface markers. Additionally, in vitro toxicity of PEG-LPrA2 was tested in non-malignant mammary cells (MCF-10A) via MTT assay. Our data shows that leptin (1.2 nM, equivalent to serum levels of overweight individuals) induced S-phase progression and increased BCSC markers and the formation of TNBC tumorspheres. Remarkably, PEG-LPrA2 (1.2 nM) abrogated leptin induction of S-phase, BCSC markers, and tumorspheres. It also showed no toxicity in non-malignant cells. These results suggest leptin-signaling inhibition could be used as an adjuvant strategy for chemotherapy of TNBC. These results are most relevant for obese African American women suffering from TNBC.

Citation Format: Courtney D. Dill, Adriana Harbuzariu, Tia L. Harmon, Crystal C. Lipsey, Ayobami Loye, Ruben Rene Gonzalez-Perez. Targeting the obesity/leptin link to TNBC: A breast cancer disparity problem. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C52.
Abstract C73: A relationship between mast cells and the racial disparity of prostate cancer
Authors: Hempel Heidi A. , Kulac Ibrahim , Cuka Nathan S. , Cornish Toby C. , Marzo Angelo M. De , Sfanos Karen S.
Published: May 2016

Prostate cancer afflicts African American men to a greater degree than European American men, with a 60% greater incidence and 2-3 times greater mortality. In addition, studies have shown that the incidence rate of distant metastasis is 4 times greater in African American men than in European American men, consistent with the notion that prostate cancer is more aggressive in African Americans. Of interest, African American men are also significantly more likely to present with inflammation in benign prostate biopsies, and studies have shown higher expression of a number of inflammatory markers in prostate cancer tissue from African Americans compared to European Americans. One immune cell type of particular interest in the context of prostate cancer are mast cells, which have the potential to play a number of roles in cancer, and have also been shown to increase in number in prostate cancer versus benign regions of the prostate. In the present study, immunohistochemistry (IHC) was used to directly visualize and localize mast cells in the prostate microenvironment of African American and European American men in a tissue microarray (TMA) containing tumor and benign tissues from 75 African American and 75 European American prostate cancer patients matched on tumor grade and stage. Automated counting of mast cell numbers as well as the calculation of mast cell-to-epithelial ratio (MC/Ep) and mast cell numbers per total tissue area (density) was aided by novel digital image analysis using a software framework integrating whole slide imaging, virtual microscopy, and ImageJ based analysis algorithms. Key results to date include the finding that mast cell density in prostate tumor tissues of African American men is significantly lower than that of Caucasian Americans (p < 0.0001). This same trend was observed for total mast cell numbers and MC/Ep (p=0.001). These results suggest the intriguing possibility that a decrease in tumor-infiltrating mast cells may contribute to the racial disparity observed in association with prostate cancer and additional studies are underway to determine the biological function of mast cells in the prostate tumor microenvironment.

Citation Format: Heidi A. Hempel, Ibrahim Kulac, Nathan S. Cuka, Toby C. Cornish, Angelo M. De Marzo, Karen S. Sfanos. A relationship between mast cells and the racial disparity of prostate cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C73.
Abstract C78: NILCO: A marker for obesity-related endometrial cancer in African American women
Authors: Daley-Brown Danielle , Oprea-Ilies Gabriela , Lee Regina , Vann Kiara T. , Lanier Viola , Quarshie Alexander , Lillard James , Pattillo Roland , Gonzalez-Perez Ruben Rene
Published: May 2016

Obesity is a pandemic in Western countries and has a significant impact on endometrial cancer (EmCa) incidence and prognosis. Although EmCa is more common in Caucasian women, higher mortality is found in African Americans who also show higher incidence of obesity. The reasons for this cancer health disparity are not completely understood. Obesity is characterized by high levels of leptin. Leptin signaling may play a key role in the progression of the more aggressive form of EmCa, Type II, which is independent from hormonal cues. We have shown that leptin induces a signaling crosstalk in breast cancer with oncogenic and angiogenic factors (NILCO: Notch, IL-1 and Leptin Crosstalk Outcome). Hence, we hypothesize that NILCO could play an important role in Type II Emca developed by obese African American women. However, no data on NILCO signaling in EmCa is currently available. Real-Time PCR, Immunohistochemistry and Western Blot analyses were used to determine whether NILCO components are differentially expressed in EmCa biopsies (Type I vs Type II EnCa) obtained from obese African American women. All tissue samples had a paired control sample from adjacent non-tumor endometrial tissue determined by pathologists. The tissue samples (n=29) were obtained from Grady Memorial Hospital, Atlanta, GA. Patient's written informed consent was obtained for all samples collected as well as IRB approval from Morehouse School of Medicine, Atlanta, GA. In addition, commercially available EmCa tissue arrays from Chinese patients were co-examined for the expression of NILCO. Biopsy features included age, grading, and TNM staging. However, no body weight or body mass index information was available. Each array contained 150 cores, including 75 cases in duplicate. Overall, NILCO molecules were expressed higher in Type II EmCa regardless of obesity status. Notably, Type II EmCa from obese African American women showed the highest expression of NILCO. Present data suggest for the first time that NILCO could be instrumental for the development of EmCa; more specifically for obesity-related Type II EmCa, and may play a role as potential biomarkers for the disease.

Citation Format: Danielle Daley-Brown, Gabriela Oprea-Ilies, Regina Lee, Kiara T. Vann, Viola Lanier, Alexander Quarshie, James Lillard, Roland Pattillo, Ruben Rene Gonzalez-Perez. NILCO: A marker for obesity-related endometrial cancer in African American women. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C78.
Abstract IA11: Understanding and overcoming cancer disparities in the U.S. and abroad
Authors: Lowy Douglas R.
Published: May 2016

In the United States, although differences in cancer-associated mortality rates between various minority groups have decreased somewhat, substantial disparities remain for several cancer types. Groups with these disparities are, therefore, high-risk populations whose risk factors need to be understood and overcome when feasible. Several factors – including biology, lifestyle, and health care access/utilization – contribute to these differences. For a given cancer type, research can, in principle, determine the relative importance of each factor, the mechanisms, and the potential for short-term and long-term intervention to mitigate them. The National Cancer Institute is committed to supporting research with the potential to make substantial advances in this important field.

In low- and middle-income countries (LMICs), cancer incidence and mortality rates are projected to increase for the foreseeable future. Many factors contribute to these increases. They include success against acute infectious diseases, increased life expectancy, increased tobacco consumption, limited resources, and inadequate infrastructure. There are many opportunities for research to advance understanding and mitigation of cancer in LMICs. Here, I highlight how technological advances and ongoing research – with HPV vaccination and cervical cancer screening – can lead to the cost-effective ability in LMICs to drastically reduce the incidence and mortality from cervical cancer, which remains the third most common cancer of women worldwide and is the most common female cancer in many LMICs.

Citation Format: Douglas R. Lowy. Understanding and overcoming cancer disparities in the U.S. and abroad. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA11.
Abstract IA25: Immunotherapy: Is it within everyone's reach?
Authors: Salazar Lupe G.
Published: May 2016

Cancer immunotherapy is an exciting and active area of cancer research; and several new immunotherapies have been approved for treatment of melanoma and lung cancer. Moreover, in melanoma, treatment with these immunotherapeutic agents has shown to nearly double the survival rate of patients with metastatic disease. Additionally, in on-going clinical trials, immunotherapy is also showing promise in regards to both safety and effectiveness in other types of cancer including breast and ovarian. However, access to these new immunotherapies is not the same for all cancer patients. Within medically underserved populations there are various factors that prohibit cancer patients from receiving these new and promising therapies. This presentation will review current cancer immunotherapeutic agents, their effectiveness and cost, as well as the challenges around ensuring that all patients who would benefit from these agents have access to them.

Citation Format: Lupe G. Salazar. Immunotherapy: Is it within everyone's reach? [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr IA25.
Abstract A16: Loss of Hugl1 induces an EGF-dependent cellular transdifferentiation
Authors: Greenwood Erin , Ebertz David , Fabiano Anthony , Schroeder Joyce A.
Published: May 2016

Maintenance of cell polarity and tissue architecture are essential in preventing neoplasia. Three different protein complexes control cellular polarity, including the Par3/aPKC/Par6 complex, the Crumbs/Pals/Patj complex and the Scribble/Dlg/Lgl complex. Of these, only the loss of Lgl promotes massive tissue growth and cellular migration in Drosophila as well as altered cellular polarity. Humans have two well-conserved homologs, Hugl1 and Hugl2. Expression of Hugl1 is downregulated, lost, or mutated in many cancers, including colorectal, endometrial, hepatocellular carcinoma, malignant melanomas, and breast cancer. We have previously examined the role of Hugl1 and Hugl2 in breast epithelial cells and found that Hugl1 loss results in a failure of growth control, gain of mesenchymal phenotypes, and a loss of both apicobasal and planar polarity. We have now determined that these phenotypes represent a fundamental change in cellular differentiation and that loss of Hugl1 results in cellular transdifferentiation. Loss of Hugl1 expression in breast epithelial cells results in the induction of a mixed-phenotype population (composed of CD44high/CD49flow and CD44low/CD49fhigh), whose growth and migration are driven by the Epidermal Growth Factor Receptor (EGFR). These populations exhibit increased anchorage-independent growth and form soft agar colonies in an EGF-dependent manner, and these behaviors are selectively enhanced in the CD44high/CD49flow population. Hugl1 loss results in the mislocalization of EGFR, resulting in TAZ and SLUG nuclear translocation. Together, these data indicate that when Hugl1 is lost in normal epithelial cells, polarity loss is accompanied by a transdifferentiation and increased anchorage-independent growth and migration.

Citation Format: Erin Greenwood, David Ebertz, Anthony Fabiano, Joyce A. Schroeder. Loss of Hugl1 induces an EGF-dependent cellular transdifferentiation. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A16.
Abstract A41: Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression
Authors: Hassan Ahmed Osama , Ibrahim Sherif A. , El-Ghonaimy Eslam A. , Hassan Hebatallah , El-Mamlouk Tahani , El-Shinawi Mohamed , Mohamed Mona M.
Published: May 2016

Hormonal-receptor positive (HRP) breast cancer patients with positive metastatic axillary lymph nodes (LNs) are characterized by poor prognosis and increase the mortality rate. The mechanisms by which cancer cells invade lymph node have not been fully explored yet. Studies showed that the expression of interleukin-6 (IL-6) cytokine and the proteolytic enzyme cathepsin B (CTSB) are associated with breast cancer poor prognosis. In the present study, we tested the effect of different concentration of IL-6 on invasiveness capacity of HRP breast cancer cell lines MCF-7 cells using in vitro invasion chamber assay. Moreover, we investigated the impact of IL-6 on expression and activity of CTSB. Our findings indicates that IL-6 fosters invasion potential of MCF-7 cells in a dose-dependent manner. Furthermore, MCF-7 cells displayed increased CTSB expression and activity with acquisition of fibroblastic morphology upon IL-6 induction. To validate our results in vivo we assessed the level of expression of IL-6 and CTSB in the carcinoma tissues of positive and negative axillary metastatic lymph-nodes in HRP breast cancer patients., Western blot and immunohistochemistry showed that the expression of IL-6 and CTSB were higher in carcinoma tissues with positive lymph node compared to carcinoma tissues of patients with negative lymph node. Collectively, our findings suggest that IL-6 and CTSB may play a role in lymph node in HRP breast cancer patients. Targeting IL-6-CTSB axis may emerge as a therapeutic approach for hormonal-receptor positive with positive lymph node breast cancer patients.

Note: This abstract was not presented at the conference.

Citation Format: Ahmed Osama Hassan, Sherif A. Ibrahim, Eslam A. El-Ghonaimy, Hebatallah Hassan, Tahani El-Mamlouk, Mohamed El-Shinawi, Mona M. Mohamed. Hormonal-receptor positive breast cancer: IL-6 augments invasion and lymph node metastasis via stimulating cathepsin B expression. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A41.
Abstract A45: Breast tumor metabolism
Authors: Possemato Richard
Published: May 2016

Proliferative cells have an increased need for macromolecular precursors required to sustain proliferation. Therefore, alteration of metabolic pathway flux and metabolite consumption is a hallmark of the transformed state. We have begun to investigate the specific metabolic pathway rewiring that occurs in the transformation of human breast cells, and the different metabolic phenotypes exhibited in breast cancers of specific molecular subtypes. These efforts have focused on the contribution of proper amino acid management in supporting breast tumor metabolism. For example, we have observed that ER-negative breast cancers exhibit activation of the serine biosynthetic pathway, controlled primarily by the expression of the enzyme PHGDH. ER-negative breast cancer cell lines with high PHGDH expression depend on its continued expression to maintain viability, and PHGDH expression permits cells to survive in the absence of extracellular serine. We have also identified the enzyme SHMT2, responsible for catabolizing serine for use in cellular methylation reactions, as an important determinant for cellular survival in low oxygen conditions. Finally, we have uncovered a key enzyme required to catabolize cysteine for the biosynthesis of iron-sulfur clusters, as being required for breast cancer cells to proliferate in high-oxygen environments, or under conditions of oxidative damage. We will discuss our development of mouse models to both investigate the contribution of these metabolic pathways to breast tumorigenesis and develop strategies to impact breast cancer growth and development.

This work is supported by a Susan G. Komen Career Catalyst grant.

Citation Format: Richard Possemato. Breast tumor metabolism. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A45.
Abstract A48: Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer
Authors: Ni Thomas K. , Kuperwasser Charlotte
Published: May 2016

There is increasing appreciation that alterations to epigenetic mechanisms contribute directly to breast cancer development. In cancer cells, one such mechanism, called alternative polyadenylation (APA), has been observed to cause a general shortening of mRNA through the usage and premature cleavage of upstream poly(A) signals (PAS). However, while it is hypothesized that APA may be linked to cancer pathogenesis, specific examples of causality between APA and cancer development have remained elusive. We report the identification of a truncated tumor suppressor, MAGI3, at both the mRNA and protein levels from the MDA-MB-231 breast cancer cell line. Using 3' rapid amplification of cDNA ends (RACE), we have determined that the truncated transcript arises due to premature cleavage and APA at a cryptic intronic PAS. We have previously demonstrated genetically and biochemically that MAGI3 functions as a mammary tumor suppressor by antagonizing the oncoprotein and Hippo pathway effector, YAP, via a physical sequestration mechanism. Importantly, here we find that the truncated gene product encoded by this aberrant MAGI3 transcript acts as a dominant-negative protein, preventing MAGI3-YAP physical association and thereby causing YAP nuclear activation and malignant transformation of cells. Since “epi-mutations” such as these play an important role in breast cancer development, yet cannot be detected by microarray or genome sequencing methodologies, we are currently undertaking analysis of large-scale, breast cancer RNA-Seq data to identify tumors that express the truncated driver mRNA and to determine the frequency of APA products in breast cancer. Knowledge of the clinically relevant proteins produced by APA that are unique to cancer cells may lead to new therapeutic opportunities for breast cancer.

Citation Format: Thomas K. Ni, Charlotte Kuperwasser. Role of premature mRNA cleavage and alternative polyadenylation in driving breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A48.
Abstract A52: The microRNA control of 17β-hydroxysteroid dehydrogenase type 1 and 2 in breast cancer
Authors: Hilborn Erik , Stal Olle , Jansson Agneta
Published: May 2016

Introduction: Breast cancer is primarily a steroid hormone dependent disease, and up to 80% of all breast cancers express the estrogen receptors. Regulation of steroid hormone activity in the breast tissue is mediated by the aromatase enzyme and by the 17β-hydroxysteroid dehydrogenase (17β-HSD) enzyme family. 17β-HSD1s primary role is in catalyzing the NADH dependent reduction of esterone to estradiol. 17β-HSD2 acts in opposition to 17β-HSD1 and mediates a NAD(H) dependent conversion of estradiol to esterone. The combination of these two enzymes has been shown to be a good indicator of tamoxifen treatment benefit, as tumors with a high 17βHSD1/17βHSD2 ratio have less benefit from tamoxifen treatment. Furthermore, patients with high 17βHSD1 mRNA expression were shown to have shorter overall disease free survival and increased risk of relapse. Despite this, next to nothing is known about the control of the expression 17βHSD1 and 17βHSD2 by microRNA in breast cancer.

Aim: To identify key microRNA responsible for the regulation of 17βHSD1 and 17βHSD2 in breast cancer.

Materials and methods: We screened for the effect of microRNA mimics by in vitro transient transfection of breast cancer epithelial cell-lines T47D, MCF-7 and ZR75-1 as well as the epithelial cell-line MCF10A.

Results: The endogenous expression of 17β-HSD type 1 in MCF-7 is low while ZR75-1 and MCF10A express moderate levels and T47D expresses high levels. Here we show that microRNA-210, 4508, 1304-3p, 6832-5p, 892a and 3674 down regulate 17β-HSD type 1 mRNA levels to 20-60% of control levels in MCF-7 and T47D. The same miRs had either a reduced effect, or no effect in ZR75-1 and MCF10A. Furthermore, we show that miR-17, 873-5p, 744-5p and 4794 result in a 2-5 fold increase in the expression of 17β-HSD type 1 ZR75-1, T47D and MCF7. This effect was reduced to 0.5 fold in MCF10A. The endogenous expression of 17β-HSD type 2 is low in MCF7, moderate in ZR75-1 and T47D and very high in MCF10A. We show that miRs 2045p, 211-5p, 5006-3p, 4251, 4745-5p, 302d-5p, 498, 1305 and 205-3p down regulates 17β-HSD type 2 expression to 10-60% of endogenous levels in ZR75-1 and MCF7, and to 30-70% of endogenous levels in MCF10A.

Conclusion: These findings are the first which start to map out the microRNA regulation of 17β-HSD type 1 and 2 in breast cancer, and this may be one important mechanism by which their expression levels are regulated in the pathogenesis of breast cancer.

Citation Format: Erik Hilborn, Olle Stal, Agneta Jansson. The microRNA control of 17β-hydroxysteroid dehydrogenase type 1 and 2 in breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A52.
Abstract A53: An analysis of breast cancer incidence in young women: A single site study
Authors: Makharadze Tamta
Published: May 2016

Background: Breast Cancer cases in women are on the rise. It is estimated to raise breast cancer cases in young women. There are no screening guidelines for women younger than 45 years old. Breast cancer in this age group is associated with higher morbidity and mortality compared to older women, thus the impact of the disease is significant.

Methods: A retrospective chart review was conducted for women diagnosed and treated for breast cancer at clinic from 2012 to 2014. Patients were stratified by age, under 45 y.o and over 45 y.o., Subjects with different grade and disease subtypes(triple negative; ER/PR+/HER1-, ER/PR+/HER3+) were selected in those groups. Descriptive analysis was performed.

Results: 130 patients were reviewed from 2012 to 2014. The analysis demonstrated that of all reviewed samples, breast cancer was detected in 23% of patients younger than 45 y.o. Data analysis also showed that ER/PR-, HER2 1+ (triple negative) samples were detected in 26% of women under 45 y.o., which is 18% more than in women over 45 y. o. (26% vs. 7.6%). ER/PR+/HER2 1+ 13% vs. 20% (difference 7%), ER/PR+/HER3+ 39% vs. 2.5%, G3 - 47% vs. 37.5; G2 - 43% vs. 60% respectively.

Conclusions: This retrospective study indicates that breast cancer diagnosed in women younger than 45 y.o. is associated with an aggressive clinical and molecular subtype. Delay in diagnosis has been a concern among this age group given the lack of screening guidelines. In our country Georgia screening starts from 40 years. More awareness, screening programs and trainings to both practitioners and young women should be implemented.

Note: This abstract was not presented at the conference.

Citation Format: Tamta Makharadze. An analysis of breast cancer incidence in young women: A single site study. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A53.
Abstract A57: Evaluation of the pathologic predictors of treatment response to neoadjuvant chemotherapy for invasive lobular breast cancer
Authors: Tsai Michaela L. , Finkelstein Marsha J. , Lillemoe Tamera J. , Susnik Barbara , Grimm Erin , Kang Sung-Hae , Kelly Caitlin , Swenson Karen K.
Published: May 2016

Introduction: Neoadjuvant chemotherapy (NAC) is becoming the standard of care for locally advanced breast cancer as a tool to objectively measure treatment response prior to surgery, and to downstage tumors to permit breast conserving surgery. Invasive lobular carcinoma (ILC) comprises approximately 10% of all invasive breast cancers, but is less likely than invasive ductal carcinoma to respond to NAC. The purpose of this study was to explore pathological and molecular predictors of response to NAC in patients with ILC.

Study Methods: Retrospective pathology review was conducted of all consecutive cases of non-metastatic ILC patients who had received NAC and subsequent surgery for ILC (n=32) within the Allina Health system. Pre-treatment tumor size, grade, stage, HER2 status, hormone receptor status, sub-type, Ki-67 index, and post-treatment Residual Cancer Burden (RCB) were determined by breast pathologists. Mann-Whitney U and Chi-square tests with exact methods were used to test for between group difference of responders (RCB 0-1) versus non-responders (RCB 2-3) to NAC on continuous and dichotomous variables. Multivariate logistic regression was conducted to determine significant predictors of response to NAC.

Findings: On univariate analysis, pleomorphic subtype (p=.004), Ki-67 (p=0.013), and HER2 status (p=.054) were significant predictors of response to NAC. On multivariate analysis, HER2 and Ki-67 provided the most efficient model for predicting response to NAC. This model correctly classified 81.3% of patients, 81.8% of RCB 0/1 and 80% of RCB 2/3. Pleomorphic subtype was highly correlated to KI-67.

Conclusions: Despite a limited sample size, this study shows that pathologic predictors (pleomorphic subtype, Ki-67, and HER2 status) are significant predictors of response to NAC, and may be useful in determining which ILC patients will benefit from NAC. This is an important finding because NAC for non-responders may delay the initiation of surgery and hormonal treatments for ILC.

Citation Format: Michaela L. Tsai, Marsha J. Finkelstein, Tamera J. Lillemoe, Barbara Susnik, Erin Grimm, Sung-Hae Kang, Caitlin Kelly, Karen K. Swenson. Evaluation of the pathologic predictors of treatment response to neoadjuvant chemotherapy for invasive lobular breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A57.