bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract LB-154: Methylation profiling of ovarian cancer shows prognostic heterogeneity of histological subtypes and high-grade serous
Authors: Bodelon Clara 
Published: July 2017

Abstract
Background. Ovarian cancer is a heterogeneous disease that is divisible into multiple subtypes with variable pathogenesis, etiology and biological behavior. We analyzed DNA methylation profiling data to identify biologic subgroups of ovarian cancer and study their relationship with histologic subtypes and prognosis.
Methods. A total of 176 paraffin embedded ovarian epithelial tumor tissues, including the four major epithelial ovarian tumor subtypes (serous, endometrioid, mucinous and clear cell) and tumors of low malignant potential (LMP) were selected from two different sources: The Polish Ovarian Cancer study, an incident population-based case-control study conducted from 2001-2004, and the Surveillance, Epidemiology, and End Results Residual Tissue Repository (SEER RTR), which included ovarian tumors blocks collected between 1994 and 2004 from the Iowa and Hawaii SEER registries. The distributions of tumor histologic subtypes and grades from the studies were similar. All analyses were restricted to Caucasian women. Methylation profiling was conducted using the Illumina 450K methylation array. Analyses were restricted to the 22 autosomal chromosomes and non-SNP probes. Fourteen samples that did not pass quality control were excluded from the analysis.
Results. Among 162 samples, 32 were from the Polish study and 130 were from the SEER RTR. Unsupervised hierarchical clustering of the 5,000 most variable CpG sites showed 4 major clusters: Cluster 1 with 79% invasive serous and 14% endometrioid carcinomas, including the majority of high grade carcinomas; cluster 2 with 77% either endometrioid or clear cell carcinomas; cluster 3 with 71% serous LMP; and cluster 4 with 73% mucinous carcinomas. We observed significant survival differences across these clusters (long-rank test P= 4.27×10-6), similar to differences observed for histologic subtypes. Within high grade (HG) serous carcinomas, clustering showed three subgroups with prognostic significance (long-rank test P= 0.008).
Conclusions. Our results suggest that methylation-based subtypes provide a classification of ovarian tumors that are in agreement with morphologic subtypes and probable mechanisms of origin. Unsupervised clustering analysis of HG serous carcinomas showed subtypes within HG serous with significance survival difference. Ongoing analyses are comparing performance of the methylation subgroups with gene expression subgroups of ovarian cancer.
Citation Format: Clara Bodelon. Methylation profiling of ovarian cancer shows prognostic heterogeneity of histological subtypes and high-grade serous [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-154. doi:10.1158/1538-7445.AM2017-LB-154
Abstract LB-163: Biological differences underlying racial disparity in breast cancer
Authors: Shendre Aditi , Liu Yunlong , Storniolo Anna Maria , Schneider Bryan P. , Han Jiali , He Chunyan 
Published: July 2017

Abstract
Compared to European American (EA) women, African American (AA) women have higher rates of estrogen receptor negative (ER-) breast cancer, more specifically triple-negative (TN) subtype, and show poorer prognosis and survival. Increasing evidence suggests biological differences may contribute to the observed racial disparity. Studies evaluating racial differences in gene expression in breast tumor tissue have reported inconsistent results. Study of normal breast tissue in healthy women may provide new insight into biological mechanisms for cancer development prospectively before tumor occurrence. However, racial influence on gene expression in normal breast tissue has not been extensively studied. In this study, we evaluated racial differences in gene expression in normal breast tissue obtained from 23 healthy women as well as tumor tissue obtained from 108 breast cancer patients. We analyzed RNA-sequencing data and performed differential expression analysis between AA and EA women. We found that differentially expressed genes in normal breast tissue between AA and EA women were enriched in biological pathways related to amino acid metabolism, immune response and signaling, lipid and protein biosynthesis, and cell proliferation and survival. Many of these biological differences persist in tumor tissue between EA and AA women in a subtype-specific manner. For example, in ER- breast cancer, racial differences in gene expression were enriched in amino acid metabolism, cell proliferation and survival pathways, with particular enrichment in immune response and signaling and lipid metabolism pathways in TN breast cancer. For ER+ breast cancer, we did not find any major biological pathway enrichment. In addition, we identified several microRNAs differentially expressed in normal breast tissue between EA and AA women. They may be involved in racial differences in breast carcinogenesis but their potential downstream effects are yet to be determined. Future studies are needed to validate our findings and understand racial-specific biological mechanisms in breast cancer development.
Citation Format: Aditi Shendre, Yunlong Liu, Anna Maria Storniolo, Bryan P. Schneider, Jiali Han, Chunyan He. Biological differences underlying racial disparity in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-163. doi:10.1158/1538-7445.AM2017-LB-163
Abstract LB-166: Risk of anal cancer in women with human papillomavirus-related gynecological neoplasm: Puerto Rico 1987-2013
Authors: Acevedo-Fontanez Adrianna Isabel , Suarez Erick , Torres-Cintron Carlos R. , Ortiz Ana Patricia 
Published: July 2017

Abstract
Objective: This study aimed to: 1) describe age-adjusted incidences for invasive cervical, vulvar, vaginal, and anal cancer cases reported from 1987 to 2013 in Puerto Rico (PR); 2) to estimate the Standardized Incidence Ratio (SIR) of secondary anal cancer among women with HPV-related gynecological neoplasms (cervical, vulvar or vaginal) during 1987-2013; and 3) to estimate the magnitude of these associations, adjusting for age.
Methods: We identified 9,489 women who had been diagnosed with a primary cervical, vaginal or vulvar tumor during 1987-2013 in PR. To describe the trends of cervical, vulvar, vaginal, and anal cancer, the age-standardized incidences were estimated using the direct method (2000 US Std Pop). SIRs (observed/expected) were computed using the indirect standardization method; expected cases were calculated using age-specific rates of anal cancer in women from the general population of PR. The ratio of SIRs was estimated using the Poisson regression model to estimate the magnitude of the association between secondary anal cancer and HPV-related gynecological neoplasms.
Results: A significant increase in the incidence trend for anal cancer was observed from 1987 to 2013 (APC=1.1; p-value&lt;0.05), whereas from 2004 to 2013, a significant increase was observed for cervical cancer incidence (APC=3.3; p-value&lt;0.05). Women with HPV-related gynecological cancers had three times the risk of developing anal cancer in comparison with women with non-HPV-related gynecological cancers (RR: 3.27; 95%CI: 1.37, 7.79).
Conclusion: Anal cancer is increasing among women in PR. Women with gynecological HPV-related tumors are at increased risk of anal cancer as compared to women from the general population and to those with various other primary tumors. Further investigation on the public health implications of this association is needed, as well as appropriate screening guidelines for anal cancer in these populations.
Citation Format: Adrianna Isabel Acevedo-Fontanez, Erick Suarez, Carlos R. Torres-Cintron, Ana Patricia Ortiz. Risk of anal cancer in women with human papillomavirus-related gynecological neoplasm: Puerto Rico 1987-2013 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-166. doi:10.1158/1538-7445.AM2017-LB-166
Abstract LB-169: Targeted tumor prevention in Li-Fraumeni syndrome
Authors: Soragni Alice , Phan Nhan , Eisenberg David 
Published: July 2017

Abstract
Li-Fraumeni syndrome (LFS) is a rare, dominant cancer predisposition disorder. The majority of LFS cases are brought about by germline p53 mutations. Individuals affected develop a spectrum of cancers occurring since childhood or early adulthood (Mai et al, 2012). Tumors associated with LFS include but are not limited to sarcomas, lymphomas and leukemias, breast cancers, brain tumors, etc (Olivier et al, 2010; Mai et al, 2012). p53 is a tumor suppressor gene that regulates many cellular processes and prevents cancer formation, growth and dissemination. When inactivated by mutation, it not only loses its tumor suppressive function, but also acquires oncogenic properties. Mutations of p53 promote destabilization of its three-dimensional structure, which can cause p53 to partially unfold, aggregate and accumulate in cells (Xu et al, 2011). We developed a peptide, ReACp53, to arrest p53 clumping and accumulation, chaperone p53 to a functional state and promote its degradation, hence arresting tumor proliferation (Soragni et al, 2016). ReACp53 can also target p63 and p73 (Zheng et al, 2016). It has shown good tolerability and a favorable safety profile in vivo. In LFS patients and LFS animal models, p53 is undetectable in normal tissues. However, the protein starts to accumulate in tumors and pre-cancerous lesions (Lang et al, 2004; Soragni et al, unpublished data). As p53 accumulation is correlated with aggregation (Xu et al, 2011; Soragni et al, 2016), we postulated that, by periodically administering ReACp53, we could target this initial event early on, and prevent p53 accumulation and/or push the p53 aggregates-ridden cells into apoptosis (Soragni et al, 2016). Here, we tested ReACp53 as a tumor preventive agent, by administering it twice a week from weaning to LFS mice carrying the aggregation-prone R172H mutation (R175H in humans). ReACp53 delayed cancer onset resulting in a significant increase in overall survival (OS). The homozygous cohort (n=16/group) showed a 50% increase in median survival in ReACp53-treated mice (median OS 15.79 vs 23.93 weeks for vehicle vs ReACp53, p=0.005; HR=2.6). Heterozygous mice (n=8/group) showed a 36% increase in OS with a median of 58.86 vs 80.50 weeks for vehicle vs ReACp53 (p=0.03, HR=2.6). No long-term side effect was observed upon ReACp53 administration. The tumor spectrum reported differed between the two groups. Activation of a functional p53 response in mouse cells and LFS patient cells treated with ReACp53 is undergoing. Overall, our study supports ReACp53 therapy as a potential approach to tumor prevention in LFS.
Citation Format: Alice Soragni, Nhan Phan, David Eisenberg. Targeted tumor prevention in Li-Fraumeni syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-169. doi:10.1158/1538-7445.AM2017-LB-169
Abstract LB-174: Patient navigation in Appalachia: results from a survey of current practices
Authors: Dignan Mark B. , Dwyer Sharon , White Carol , Rohan Elizabeth A. , White Dana , Castro Georgina , Wilson Reda , Boyd Mary , Stockton Eric 
Published: July 2017

Abstract
Purpose: The Appalachian region of the US includes 420 counties in 13 states that begin with New York, follow the Appalachian Mountains and extend to Mississippi. The region has a heterogeneous population that shares distinct cultural characteristics, high rates of unemployment, low income, and high rates of chronic disease, including cancer. Patient navigators (PN) provide one-on-one guidance and assistance through the health care continuum from prevention to end-of-life and address barriers and enhance access to healthcare through the use of individual navigators who are sensitive to the needs, interests and values of the community. Although there are numerous PN training programs available, there are no known programs that are designed for the Appalachian population. As a first step in developing such a program, we designed and conducted a survey of PN training needs in Appalachia.
Methods: With guidance from formative research involving a variety of stakeholders, we identified key individuals, professional groups, health care systems, and public health agencies serving the Appalachian region. We developed a 26-item survey to collect information on current patient navigation programs, sources of current training, and training needs. After pretesting, the survey was distributed online. Data were collected from June, 2015 through May, 2016.
Results: A total of 152 responses were received. The responses were from community based organizations (29.3%), academic medical centers (15.5%), hospitals (35.8%), and community cancer centers (19.5%). PN was currently provided by individuals from a variety of professional backgrounds, chiefly nursing (32.8%) and social work (8.4%), and 15.3% were community navigators. Only 63.8% of respondents reported having received formal PN training. About half (47.3%) indicated that they were interested in attending PN training and suggested specific content and format.
Conclusions: Survey respondents identified a need for PN training that focuses on Appalachia. These results supported the development of an Appalachia Patient Navigation Training Program, currently underway.
Note: This abstract was not presented at the meeting.
Citation Format: Mark B. Dignan, Sharon Dwyer, Carol White, Elizabeth A. Rohan, Dana White, Georgina Castro, Reda Wilson, Mary Boyd, Eric Stockton. Patient navigation in Appalachia: results from a survey of current practices [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-174. doi:10.1158/1538-7445.AM2017-LB-174
Abstract LB-175: Gender and racial disparities in incidence trends of tobacco-related cancers from 2010 to 2013
Authors: Wilson Danyell S. , Parish Alice , Guo Yi 
Published: July 2017

Abstract
Over one in three cancer-related deaths are associated with tobacco use. Although the overall incidence trend of tobacco-related cancers (TRCs) has been decreasing in the past a few decades, evidence suggests that not all TRCs have decreasing incidence and there exists gender and racial disparities in the TRC trends. Prior studies of TRC incidence have used the Surveillance, Epidemiology, and End Results Program (SEER) database. However, the SEER database includes limited information regarding the United States southeastern region and has been shown not to be representative of the US. In this study, we analyzed TRC incidence trends from 2010 to 2013 using the Florida cancer registry data, collected from a large ethno-racially diverse state. We computed annual age-adjusted incidence rates and annual percentage change (APC) to characterized the incidence trends of the following cancers: oral cavity, cervical, respiratory (lung, bronchitis, and larynx), urinary (bladder, kidney, and renal pelvis), digestive (esophagus, stomach, and pancreas), non-Hodgkin’s lymphoma, and pharyngeal. All incidence trends were also evaluated stratifying by gender (men and women) and race (Non-Hispanic (NH) Whites, NH Blacks, and Hispanics). Overall, all TRCs had a significant decrease in age-adjusted incidence rates for the study period, except for non-Hodgkin’s lymphoma and pharyngeal cancer for which the incidence remained unchanged. Oral cavity cancer had the biggest decline in age-adjusted incidence rates (APC= −2.5; 95% CI= −3.4, −1.6), while cancers of the digestive system had the smallest decline in incidence rates (APC= −0.6; 95% CI= −1.0, −0.2). When broken down by gender, males have a greater decrease in incidence rates than women for urinary and respiratory cancers. In addition, while pharyngeal cancer incidence rate stayed unchanged overall, there was a significant increase in the rate among male (APC= 1.0; 95% CI= 0.3, 1.7), but not female. When broken down by race and ethnic groups, NH Blacks and Hispanics had greater decline in cancer incidence for cervical cancer, oral cavity cancer, and respiratory cancer. For pharyngeal cancer, there was a significant decrease in incidence among NH Blacks (APC= −3.7; 95% CI= −5.5, −1.9), while the incidence significantly increased among NH Whites (APC= 1.6; 95% CI= 0.7, 2.5). In summary, there was an overall decreasing trend of TRC incidence. However, increasing incidence of pharyngeal cancer was observed for male and NH Whites.
Citation Format: Danyell S. Wilson, Alice Parish, Yi Guo. Gender and racial disparities in incidence trends of tobacco-related cancers from 2010 to 2013 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-175. doi:10.1158/1538-7445.AM2017-LB-175
Abstract LB-182: Differential modulation of the PD-1 pathway impacts the anti-tumor activity of CAR T cells
Authors: Lin Regina J. , Gautron Anne-Sophie , Poirot Laurent , Wong Oi Kwan , Sasu Barbra , Boldajipour Bijan 
Published: July 2017

Abstract
Adoptive T cell therapy using ex vivo expanded tumor-infiltrating lymphocytes (TILs) or T cells engineered with chimeric antigen receptors (CAR T) has shown tremendous success in many hematological diseases, however treatments of solid tumors have been less successful so far. It is presumed that adoptive cell therapy is limited by the presence of immune-suppressive mechanisms within the solid tumor microenvironment. To enhance T cell activity against solid tumors, we seek to overcome these immune barriers and one approach is to do this by blocking checkpoints such as the PD-1 receptor. Using CAR T cells targeting the glioblastoma (GBM) tumor-specific antigen EGFRvIII, we investigated 3 approaches of inhibiting PD-1: (i) shRNA-mediated knockdown, (ii) TALEN®-mediated knockout, and (iii) antibody-mediated blockade. In contrast to the PD-1 antibody that augmented CAR T cell activity in vivo, the PD-1 shRNA impaired the anti-tumor activity of CAR T cells in vitro and in vivo. Detrimental effects of the PD-1 shRNA were associated with impaired survival of CAR T cells in vitro and in vivo. Interestingly, TALEN®-mediated PD-1 knockout generated CAR T cells with superior cytotoxic potency and prolonged functional persistence in vitro. Further characterization of PD-1 TALEN® CAR T cells, and how they compare in activity against the CAR T/anti-PD-1 combination in both subcutaneous and intracranial GBM models, is underway. These studies will not only elucidate the role of PD-1 in CAR T cell biology, but also inform CAR T cell combination therapy approaches for solid tumor indications.
Citation Format: Regina J. Lin, Anne-Sophie Gautron, Laurent Poirot, Oi Kwan Wong, Barbra Sasu, Bijan Boldajipour. Differential modulation of the PD-1 pathway impacts the anti-tumor activity of CAR T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-182. doi:10.1158/1538-7445.AM2017-LB-182
Abstract LB-185: A PSMA-directed natural killer cell approach for prostate cancer immunotherapy
Authors: Brand Lucas J. , Zaslavsky Alexander B. , Palapattu Ganesh S. , Knudsen Karen E. 
Published: July 2017

Abstract
Prostate Cancer (PCa) is the third leading cause of cancer mortality in men in the United States. Locally advanced or metastatic PCa is clinically managed with androgen deprivation therapy (ADT), androgen receptor antagonists, and/or taxane chemotherapy. While initially effective, patients eventually develop resistance, leading to onset of a lethal castration-resistant disease state for which no curative interventions currently exist. Cell-based immunotherapy—which is centered on infusion of modified, tumor-directed immune cells intended to drive a more potent anti-tumor response—could potentially provide a new approach to treating advanced PCa. In this study, we describe the modification of an allogeneic, immortalized human natural killer cell line, NK-92, with a chimeric antigen receptor (CAR) directed against prostate-specific membrane antigen (PSMA), a cell-surface antigen expressed by most prostate tumors. We observed that both unmodified and CAR-bearing NK-92 cells display potent cytolytic activity against the majority of PCa cell lines tested in vitro. Expression of PSMA on PCa cell lines affected the activity of CAR-modified, but not unmodified, NK-92. Combination of NK-92 immunotherapy with ADT and taxanes is also discussed, as well as ongoing in vivo preclinical modeling. Overall, CAR-modified NK-92 cells show promise as a novel immunotherapeutic agent for the treatment of PCa.
Citation Format: Lucas J. Brand, Alexander B. Zaslavsky, Ganesh S. Palapattu, Karen E. Knudsen. A PSMA-directed natural killer cell approach for prostate cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-185. doi:10.1158/1538-7445.AM2017-LB-185