bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A113: Immunomodulatory properties of bromodomain inhibitors in pancreatic cancer cells
Authors: Leal Ana S. , Williams Charlotte R. , Sporn Michael B. , Liby Karen T. 
Published: October 2015

Abstract
Bromodomain and extra terminal domain (BET) proteins function as epigenetic signaling factors that “read” chromatin modifications, controlling numerous genes involved in cell cycle, cell growth, inflammation and cancer. The BET inhibitors, JQ1 and I-BET-762, occupy selective pockets of bromodomains in BET proteins resulting in a release of the chromatin and consequent suppression of the transduction of targeted genes.
Cell lines developed from a pancreatic carcinoma (Panc 1343) and ascites (PanAsc 2159) of LSL-KrasG12d/+;LSL-Trp53R172H/+;Pdx-1-Cre (KPC mouse model) were treated with several concentrations of JQ1 and I-BET-762. JQ1 and I-BET-762 have growth inhibitory properties, with IC50 (48 hr treatment) of 24.5 nM and 94.5 nM, and 1.8 μM and 1.2 μM in PanAsc 2159 and Panc 1343 cells, respectively.
Several cytokines and chemokines, produced by tumor cells, stromal cells or inflammatory infiltrating cells, play important roles in promoting (GM-CSF, IL-6 and CCL2) or suppressing (CCL27, CCL4, IL17A or IL27) tumor progression. RT profiler PCR of PanAsc 2159 cells treated with 300 nM of JQ1 for 24 hr revealed the ability of this compound to upregulate CCL24, IL17a and IL-27 and downregulate CCL7, CXCL1, CCL2, IL16 and IL6. JQ1 and I-BET-762 reduced the protein and RNA levels of CCL2, IL6 and GM-CSF in Panc 1343 and PanAsc 2159 cells, and also in RAW macrophage-like cells stimulated with LPS. JQ1 and I-BET-762 also reduced the protein levels of secreted TNF-α in RAW cells stimulated with LPS.
JQ1 and I-BET-762 appear to have immunomodulatory effects in pancreatic cancer cell lines derived from KPC mice, altering the levels of several chemokines and cytokines. These compounds also have a growth inhibitory effect in these cell lines. Exploring the effects of these compounds in KPC mice is ongoing.
We thank James Bradner for the generous gift of JQ1.
Citation Format: Ana S. Leal, Charlotte R. Williams, Michael B. Sporn, Karen T. Liby. Immunomodulatory properties of bromodomain inhibitors in pancreatic cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A113.
Abstract B76: Targeting Mcl-1 for radiosensitization of pancreatic cancers
Authors: Zhang Qiang , Wei Dongping , Schreiber Jason , Kausar Tasneem , Lawrence Theodore , Sun Yi , Nikolovska-Coleska Zaneta , Morgan Meredith A. 
Published: October 2015

Abstract
In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer and, thus, improve survival in patients with locally advanced pancreatic cancer, we conducted an siRNA library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1), an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to gemcitabine-radiation. Thus, we investigated Mcl-1 inhibition by genetic (siRNA) and pharmacological (small molecule) approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA radiosensitized BxPC-3, Panc-1, and MiaPaCa-2 cells with radiation enhancement ratios (RER) of 1.5±0.06, 1.4±0.03, and 1.3±0.01, respectively, and caused Caspase-3 activation and PARP cleavage. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI-77 (Abulwerdi F et al., Mol Cancer Ther, 2014), to inhibit the anti-apoptotic functions of Mcl-1 and radiosensitize in pancreatic cancer cells. Consistent with inhibition of Mcl-1 anti-apoptotic function, UMI-77 (1-5uM) caused dissociation of Mcl-1 from the pro-apoptotic protein Bak. Under these same conditions, UMI-77 produced significant radiosensitization in BxPC-3 and Panc-1 cells (RER: 1.5±0.1 and 1.3±0.04, respectively; P&lt;0.05) with minimal radiosensitization of MiaPaCa-2 cells (1.2±0.07). Since Mcl-1 expression levels are highest in BxPC-3 and Panc-1 cells and lowest in MiaPaCa-2 cells, these results suggest that elevated Mcl-1 protein levels may be a biomarker for radiosensitization by Mcl-1 inhibition. In addition, radiosensitization by UMI-77 was associated with Caspase-3 activation, PARP cleavage, and increased sub-G1 DNA content. In contrast, ABT-737, a well-established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 in radiation survival. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the efficacy of small molecules which displace Mcl-1 from Bak/Bax as radiosensitizers in pancreatic cancer. Furthermore, these results support continued investigation of UMI-77 and its analogues in animal models and in combination with gemcitabine-radiation as a strategy for radiation and chemoradiation sensitization of pancreatic cancers.
Citation Format: Qiang Zhang, Dongping Wei, Jason Schreiber, Tasneem Kausar, Theodore Lawrence, Yi Sun, Zaneta Nikolovska-Coleska, Meredith A. Morgan. Targeting Mcl-1 for radiosensitization of pancreatic cancers. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B76.
Abstract IA22: Innate immune cell PI3K gamma as a target for suppression of pancreatic ductal adenocarcinoma
Authors: Kaneda Megan , Hardamon Chanae , Schmid Michael C. , Bouvet Michael , Novelli Franco , Hirsch Emilio , Lowy Andrew , Varner Judith A. 
Published: October 2015

Abstract
Ductal adenocarcinoma of the pancreas (PDAC) is a devastating disease that will afflict greater than 40,000 Americans. Less than 5% of these new pancreatic cancer patients will survive 5 years following diagnosis. PDAC is rarely detected in the early stages, with more than 80% of patients presenting with locally unresectable or metastatic disease at the time of diagnosis. As this form of cancer is also resistant to current cytotoxic therapies and ionizing radiation, novel therapeutic and diagnostic approaches are desperately needed to improve patient outcome. A characteristic feature of PDAC is the presence of an abundant, inflammatory infiltrate. In response to tumor-derived chemoattractants, we found that myeloid cells invade tumors where they promote immunosuppression, resulting in tumor growth and metastasis. We discovered that myeloid cell PI3-kinase gamma (PI3Kgamma) controls tumor immunosuppression, as PI3Kgamma signaling inhibits pro-inflammatory gene expression responses in macrophages, monocytes and granulocytes and promotes anti-inflammatory responses. Suppression of PI3Kgamma in mutant mice and in mice treated with pharmacologic inhibitors of PI3Kgamma promotes CD8+ T cell anti-tumor immune responses, leading to a 50% reduction in tumor growth and metastasis in orthotopic mouse models of pancreatic carcinoma and significant extension of survival in GEM models of PDAC (PDX1-cre; LSL-KrasG12D/+; LSL-Trp53 R172H/+). Furthermore, PI3Kgamma inhibition blocks macrophage stimulation of collagen deposition by fibroblasts in PDAC. We are exploring the combination of PI3kinase gamma inhibition with tumor cell and T cell targeted therapeutics could significantly reduce tumor growth and metastasis of PDAC. These approaches could improve patient outcomes by reducing tumor progression and preserving organ function by inhibiting desmoplasia.
Citation Format: Megan Kaneda, Chanae Hardamon, Michael C. Schmid, Michael Bouvet, Franco Novelli, Emilio Hirsch, Andrew Lowy, Judith A. Varner. Innate immune cell PI3K gamma as a target for suppression of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr IA22.
Abstract A15: Development of a multilevel human papillomavirus (HPV) vaccine intervention
Authors: Katz Mira Lynn , Reiter Paul L. , Ruffin Mack T. , Paskett Electra D. 
Published: October 2015

Abstract
Purpose: New strategies to improve human papillomavirus (HPV) vaccine uptake among minority and underserved adolescents are needed. The purpose of this study is to describe the development of a multi-level HPV vaccine intervention to increase adolescent HPV vaccination rates.
Methods: A community-engaged process was used over a one year period. Caregivers (n=18) and providers (n=27) from a Federally Qualified Health Center participated in: 1) focus groups to better understand knowledge and acceptability of the HPV vaccine, and to generate ideas for the intervention content and format; 2) writing sessions to develop the content and intervention components; and 3) review sessions to obtain initial feedback and make revisions prior to pilot testing the intervention.
Results: Intervention components developed were based on the Protection Motivation Theory and the PACE (Present the issue, Ask questions, Check understanding, and Express concerns) communication system. The intervention components developed (English and Spanish) focus on three levels: 1) Caregivers: a) an interactive computer program tailored for the adolescent's gender, age, race/ethnicity, b) a brochure with information about additional resources, and c) a HPV vaccine comic book to assist caregivers with explaining the HPV vaccine to younger adolescents; 2) Providers: a) an automated PowerPoint presentations including current HPV vaccine initiation and completion rates, suggestions to address common barriers, and video clips demonstrating the teach-back methodology, b) current HPV vaccine scientific literature, and c) “Ask me about the HPV vaccine!” pins; and 3) Health Centers: a) posters, and b) refrigerator magnets that serve as reminders for the second and third dose of the HPV vaccine.
Conclusions: Community members provided valuable input into the development of a multi-level HPV vaccine intervention. The input will make the intervention relatable and more acceptable to the priority population. Using this community-engaged approach is more complex, increases costs, and involves additional time and effort from community members and academic researchers. The value of the partnership is critical and the additional time and energy expended is important to successfully address cancer disparities among minority and underserved populations.
Citation Format: Mira Lynn Katz, Paul L. Reiter, Mack T. Ruffin, IV, Electra D. Paskett. Development of a multilevel human papillomavirus (HPV) vaccine intervention. [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 A15.
Abstract A20: What's in the cancer biology part of Community Health Worker Curricula: A systematic review
Authors: Offer Nicole , Jeffries Kierstyn , Wilson Danyell S. 
Published: October 2015

Abstract
Background: Disparities in cancer treatment and outcomes mirror socio-economical, racial, ethnic, and educational backgrounds. An important approach for closing health disparities is increasing scientific and health cancer literacy in the community. This can be achieved by Community Health Workers (CHWs). CHWs are thus at the frontline of our efforts to close these health care gap. However, the current status of a standardized cancer-biology training module for CHWs is unknown.
Hypothesis: If we can identify the material covered in the cancer-biology portion of published CHW training curricula, then a standardized cancer-biology module can be developed based on evidence of best practices and recommendations.
Methods: A comprehensive search of the published literature on training of CHWs using Pubmed and following the guidelines established by the Cochrane Collaboration systematic review process was performed. Methods for completing this systematic review included identification of a topic; selection of articles based on specialized criteria; design and implementation of a data extraction form; and systematic data synthesis and appraisal from the selected articles to diminish bias.
Results: Using this methodology, 49 articles were selected from an initial Pubmed search that yielded 228 literature entries using “Cancer Education Curriculum Community Health Workers” as search criteria. Using this strategy, we will produce a systematic and comprehensive review of the science behind cancer training portion of published CHW curriculum in the U.S. This approach will aid in improving CHW training.
Citation Format: Nicole Offer, Kierstyn Jeffries, Danyell S. Wilson. What's in the cancer biology part of Community Health Worker Curricula: A systematic review. [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 A20.
Abstract A23: Addressing men's health disparities in the District of Columbia
Authors: Dodson Everett 
Published: October 2015

Abstract
The Georgetown University Lombardi Comprehensive Cancer Center Office of Minority Health and Health Disparities Research is a community based center located in Ward 8 of the District of Columbia, which has some of the highest incidence and death from cancer in the city. Programs addressing men's health are very limited in these communities. Our location is easily accessible to the residents in Wards 6, 7, and 8 which are designated by the Department of Health and Human Services as medically underserved. Our mission is to facilitate, stimulate, and to promote synergy in addressing the biological and environmental basis of cancer health disparities via research, training, communication and education. Current programs include breast cancer prevention studies for African American and Hispanic Women, HPV Education, Environmental Justice, exercise studies to relieve the effects of cancer treatments for men and women. The Health Disparities Initiative also conducts community based boot camps, and regular focus groups to engage community support for our programs, and to give the residents the opportunity to let us know what their community needs are. The nearby Capitol Breast Care Center provides women with mammograms and cervical exams and needed follow-up regardless of a woman's ability to pay.
As a Community Health Educator I am a liaison between the residents of these communities and the Health Disparitiess Initiative. I actively participate in community activities that help promote healthy lifestyles and the reduction of chronic diseases. I am actively involved in the recruitment of residents from the community to form our Community Advisory Board and Environmental Justice Advisory Board. And I have accepted the invitation to sit on community boards and committees.
Citation Format: Everett Dodson. Addressing men's health disparities in the District of Columbia. [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 A23.
Abstract A58: Comorbid conditions among African American breast cancer survivors
Authors: Davis Claudia M. , Myers Hector F. 
Published: October 2015

Abstract
Background: There is compelling evidence that ethnicity is a significant independent risk factor for breast cancer disparity among some racial groups in various geographical locations. In California, African American women carry a disproportionate burden of this disease with a higher mortality rate, when compared to other women. Although the etiology of the burden may be due to multiple factors such as an aggressive phenotype, treatment modalities, etc.., there is growing evidence that the existence and possible interplay of co-morbid conditions may have a negative effect on cancer survivorship outcomes. The aim of our study was to investigate the co-morbid conditions among a cohort of African American breast cancer survivors.
Methods: Via recruitment flyers, support groups, and word-of-mouth, we recruited and screened 169 women from breast cancer support groups and community-dwellers in Southern and Northern California. One hundred and sixty women were eligible and n =155 participated. The inclusion criteria were women who self-identified as African/Black American, age 25 years or older, diagnosed with breast cancer and at least 1 year post-active treatment. As part of a larger study, the breast cancer survivors completed a self-report demographic data questionnaire including, height and weight, cigarette smoking, alcohol intake, breast cancer stage, treatment and the presence of co-morbid conditions.
Results: Our study revealed that over 79% of the survivors reported 1 or more co-morbid conditions inclusive of heart disease, diabetes, high cholesterol, hypothyroidism, and hyperthyroidism. Hypertension was the most prominent (24.5 %) co-morbid condition and 20.6% reported that they did not have any co-morbid conditions.
Conclusion: Our findings suggest the importance of assessing for co-morbid conditions among African American breast cancer survivors as we might have a better understanding of risk and facilitate the need for a collaborative care approach and intervention to manage these co-morbid conditions and thus improve survivorship outcomes.
Citation Format: Claudia M. Davis, Hector F. Myers. Comorbid conditions among African American breast cancer survivors. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr A58.
Abstract A70: Mast cells in prostate cancer race disparities: Are the minutemen of the microenvironment the key?
Authors: Hempel Heidi A. , Kulac Ibrahim , Cuka Nathan S. , Cornish Toby C. , Marzo Angelo M. De , Sfanos Karen S. 
Published: October 2015

Abstract
The goal of the current study is to establish the mechanism by which mast cells may serve as a prognostic factor in and possibly explain the racial disparity associated with prostate cancer. There is increasing evidence for a strong association between chronic inflammation and prostate cancer, and the role of mast cells in prostate cancer are of particular interest as they have been suggested to influence cancer progression and immune modulation. It is well established that prostate cancer presents with significant racial disparities, with African American (AA) men being 65% more likely to be diagnosed with prostate cancer than Caucasian American (CA) men and more than two times as likely to die as a result of prostate cancer. In addition, studies have shown AA men to be significantly more likely to present with inflammation in prostate biopsy samples negative for prostate cancer, while microarray data has suggested that inflammatory pathways are highly represented in the differentially expressed mRNA in the tumors of AA vs CA men. Complicating these results, it is probable that inflammatory cells play varied and multiple roles in different regions and grades within the same cancer. With this in mind, we are currently using immunohistochemistry (IHC) and in-situ hybridization techniques to directly visualize and localize mast cells in the prostate microenvironment. These studies are aided by novel digital image analysis using a software framework integrating whole slide imaging, virtual microscopy, and ImageJ based analysis algorithms. Our preliminary results in a 10 case tissue microarray (TMA) are consistent with other reports in the literature indicating that there are higher mast cell densities in better differentiated cancers; however, we are examining this further in a larger full slide cohort in relation to Gleason grade and stage. We are currently utilizing this image analysis technology on a TMA cohort designed to explore differences in mast cell density in AA vs CA men. Furthermore, we aim to examine differences in mast cell subtypes between benign and malignant regions of the prostate and between AA and CA men. Our goal is to establish the mechanism by which mast cells may serve as a prognostic factor in prostate cancer and may help to explain prostate cancer racial disparities.
Citation Format: Heidi A. Hempel, Ibrahim Kulac, Nathan S. Cuka, Toby C. Cornish, Angelo M. De Marzo, Karen S. Sfanos. Mast cells in prostate cancer race disparities: Are the minutemen of the microenvironment the key? [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 A70.