bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B012: Histone demethylase JMJD1A promotes the generation of androgen receptor variant 7 (AR-V7) in prostate cancer cells
Authors: Fan Lingling , Zhang Fengbo , Fazli Ladan , Gleave Martin , Dong Xuesen , Qi Jianfei 
Published: February 2019

Abstract
Generation of androgen receptor (AR) splicing variant, AR-V7, has been shown to contribute to the resistance of prostate cancer to androgen deprivation therapy and development of castration-resistant prostate cancer (CRPC). We and others have reported that histone demethylase JMJD1A promotes the transcriptional activity of AR by functioning as an AR coactivator. Here, we identified a new role for JMJD1A in the generation of AR-V7 in prostate cancer cells through interaction with HNRFPF. Knockdown of JMJD1A or HNRNPF reduced the mRNA and protein level of AR-V7 but had little effect on the full-length AR (AR-FL). Mechanistically, we found that JMJD1A and HNRNPF cooperatively bound to a polyG motif adjacent to the 5′ splicing site of Exon3b of AR gene, where they promoted the assembly of splicesome. Re-expression of AR-V7 in the JMJD1A-knockdown cells partly rescued the growth defect of prostate cancer cells in vitro and in the mouse xenograft model. The staining of AR-V7 paralleled that of JMJD1A or HNRNFP in a human prostate cancer tissue microarray. Together, our data reveal that JMJD1A enhances the castration-resistant growth of prostate cancer cells through coactivation of AR-FL and generation of AR-V7.
Citation Format: Lingling Fan, Fengbo Zhang, Ladan Fazli, Martin Gleave, Xuesen Dong, Jianfei Qi. Histone demethylase JMJD1A promotes the generation of androgen receptor variant 7 (AR-V7) in prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B012.
Abstract B013: Combined molecular targeting Src and mTOR pathways to impair prostate cancer cell survival
Authors: Dai Yao , Siemann Dietmar W. 
Published: February 2019

Abstract
Overexpression of oncoproteins Src and mTOR has been shown to be highly associated with prostate cancer progression and poor clinical outcomes; therefore, small-molecule Src or mTOR inhibitors are being extensively evaluated in clinical trials for advanced prostate cancer. However, clinical data suggest that single treatment with any of these inhibitors only yields limited effects in patients. One possibility is that redundant signaling pathways in tumor cells exist that allow tumor cell uninterrupted upon blockade of purely one pathway. We hypothesize that Src and mTOR are two compensatory pathways that may cooperate to promote prostate cancer survival. Here we studied treatment effects of combining inhibitors targeting Src (saracatinib) and mTOR (rapamycin) on functional behaviors associated with tumor growth in prostate cancer cells with high level expression of both kinases. Combination of both inhibitors was found to inhibit cell proliferation and clonogenic survival more strongly than either single agent, as assessed by MTT and colony formation assay, respectively. Western blot analysis demonstrated that co-targeting Src and mTOR kinases leads to not only inhibition on phosphorylation of these oncoproteins but also greater blockade of multiple downstream pathways such as focal adhesion kinase (FAK), Akt, ERK, S6K, and 4E-BP1. These data indicate that combined application of small-molecule inhibitors targeting two different key pathways may cause significant impairment of phenotypes associated with prostate cancer growth and survival, suggesting that this combinative intervention modality may serve as a potential anticancer strategy that could be further tested in advanced prostate cancer models in vivo.
Citation Format: Yao Dai, Dietmar W. Siemann. Combined molecular targeting Src and mTOR pathways to impair prostate cancer cell survival [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B013.
Abstract B026: Axl may support dormancy of disseminated tumor cells by inducing cell clustering and decreasing proliferation of metastatic prostate cancer cells
Authors: Axelrod Haley D. , Valkenburg Kenneth C. , Hicks Jessica L. , DeMarzo Angelo M. , Pienta Kenneth J. 
Published: February 2019

Abstract
While the majority of prostate cancer (PCa) patients are cured by radical prostatectomy and/or radiation, 10-15% of these men eventually develop recurrent disease in the form of lethal metastases. The most common site for PCa metastasis is the bone marrow. The time from primary tumor removal to recurrence can range from 1-2 years to decades, and constitutes a period of minimal residual disease in which cancer cells remain in the body but are clinically undetectable. It is thought that these disseminated tumor cells (DTCs) are able to maintain a state of cellular dormancy in the bone marrow in which they are not proliferating or dying, and may be the seeds for lethal metastases. By understanding the mechanism(s) that regulate dormancy, we may be able to prevent metastasis altogether. Our group has previously found that the secreted bone marrow factor Gas6 and the expression of its receptor Axl are associated with dormant DTCs in xenograft mouse models. Thus, we hypothesize that Gas6 signaling through Axl mediates dormancy. In this study, we sought to functionally support this hypothesis both in vitro and in human PCa tissue. Overexpression of Axl in the C42B PCa cell line decreased proliferation in vitro, and this was independent of Gas6 when Axl was highly overexpressed. Axl overexpression also led to aggregation of C42B cells, suggestive of a possible role in circulating tumor cell (CTC) clustering to survive the circulation and inhabit the bone marrow. Furthermore, immunohistochemical staining of a PCa tissue microarray showed almost no Axl positivity in cancer cells, regardless of Gleason score and other clinical outcomes. Negative staining was also observed in sections from liver, lymph node, and tibial metastases. Consistent with this, Axl expression correlates with decreased incidence of biochemical recurrence and increased overall survival in the GRID and TCGA databases, respectively. These results indicate an antiproliferative role for Axl in PCa, and suggest its temporal expression during the natural history of PCa. Ongoing work includes assessing the expression of Axl on patient CTCs and DTCs, and using xenograft mouse models of metastasis to analyze the effects of Axl overexpression and knockout in PCa cell lines.
Citation Format: Haley D. Axelrod, Kenneth C. Valkenburg, Jessica L. Hicks, Angelo M. DeMarzo, Kenneth J. Pienta. Axl may support dormancy of disseminated tumor cells by inducing cell clustering and decreasing proliferation of metastatic prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B026.
Abstract B069: Drug response variability between luminal and basal prostate cancer tumors
Authors: Den Robert , Lehrer Jonathan , Takhar Mandeep , Alshalalfa Mohammed , Erho Nicholas , Davicioni Elai , Feng Felix 
Published: February 2019

Abstract
Introduction: Prostate cancer (PCa) is a genomically heterogeneous disease that has been subtyped into molecularly distinct subtypes. Over the past several years, multiple drugs have demonstrated improvements in overall survival in men with advanced prostate cancer, prompting further investigations of these drugs. However, characterizing drug response in the localized disease setting and in the context of PCa molecular subtypes needs further investigation. Here in a large prospective cohort of men with adverse pathology we explore the heterogeneity of patient drug response between basal, luminal, and neuroendocrine prostate cancer subtypes.
Methods: Whole-transcriptome RNA expression profiles of 9,640 radical prostatectomy (RP) samples from prospective use of the Decipher test were obtained from the GRID registry database. Patients were subtyped into basal, luminal A, luminal B, and neuroendocrine subtypes using the PAM50 and small cell gene expression signatures. Drug response scores (DRS) predicting patient sensitivity for 89 oncology drugs were determined using in vitro drug sensitivity and microarray data from the NCI-60 panel. Pearson’s chi squared test was used to determine significant differences in drug sensitivity among PCa subtypes.
Results: Applying the subtype signatures to the cohort, we classified 43% of samples as basal, 26% as luminal A, 30% as luminal B, and 2% as neuroendocrine. DRS was highly variable across the subtypes. Basal tumors showed a distinct drug response profile where basal tumors were more sensitive to kinase inhibitors (e.g., cabozantanib, dasatnib, erlotinib), mTOR inhibitors (e.g., everolimus, temsirolumus), DNA repair inhibitors (e.g., olaparib, mitoxantrone), and alkylating (e.g., cisplatin, carboplatin) chemotherapy. Luminal A and B were more sensitive to steroid inhibition (e.g., abiraterone, tamoxifen) and anti-microtuble (e.g., docetaxel, paclitaxel, vinorelbine) chemotherapy, whereas neuroendocrine had highest DRS for antiproliferative agents (e.g., mitomycin, cytabarine, carmustine, topotecan), Significant differences in average DRS scores in subtypes were observed for all 89 drugs (p&lt;0.001).
Conclusion: Prostate cancer subtypes in the localized disease setting have distinct drug response profiles, suggesting that subtyping and DRS scores may be useful for selecting candidates for systemic therapy trials.
Citation Format: Robert Den, Jonathan Lehrer, Mandeep Takhar, Mohammed Alshalalfa, Nicholas Erho, Elai Davicioni, Felix Feng. Drug response variability between luminal and basal prostate cancer tumors [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B069.
Abstract IA15: Targeting oligometastatic disease in prostate cancer
Authors: Pienta Kenneth J. 
Published: February 2019

Abstract
Clinical reports of limited and treatable cancer metastases, a disease state that exists in a transitional zone between localized and widespread systemic disease, have been noted on occasion historically and termed oligometastasis (OM). The ramification of a diagnosis of oligometastasis is a change in treatment paradigm, i.e., if the primary cancer site (if still present) is controlled or resected, and the metastatic sites are ablated (surgically or with radiation), a prolonged disease-free interval, and perhaps even cure, may be possible. Contemporary imaging diagnostics are identifying more and more OM patients. For example, in prostate cancer the use of PSMA-Pyl PET imaging is leading to the diagnosis of many OM patients who have no disease on conventional clinical imaging. It is unclear if these are truly isolated sites of disease (curable) or simply a reflection of more widespread microscopic disease (incurable or at best a bridging therapy). This is especially true in the biochemical recurrence (bcr) space after primary treatment. We will present our experience with identifying and treating prostate cancer OM disease.
Citation Format: Kenneth J. Pienta. Targeting oligometastatic disease in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA15.
Abstract A42: Association between neighborhood deprivation and lung cancer risk in the Southern Community Cohort Study
Authors: Sanderson Maureen , Aldrich Melinda C. , Levine Robert S. , Kilbourne Barbara , Cai Qiuyin , Blot William J. 
Published: February 2019

Abstract
Purpose: Counties with the highest rates of lung cancer mortality in the United States from the 1980s have been located in the South. This finding is related to high regional smoking prevalence, but we hypothesized that area-level socioeconomic deprivation may also contribute. We used data from the Southern Community Cohort Study to examine this exposure in a multilevel nested case-control study of incident lung cancer.
Methods: Men and women with incident lung cancer were identified through linkage with state cancer registries and the National Death Index (1,334 cases). Approximately four controls were matched to each case on sex, race, age at diagnosis, and year of recruitment (5,315 controls). Individual-level smoking and socioeconomic status were obtained through baseline surveys, while block group-level neighborhood deprivation was obtained from U.S. Census data.
Results: After adjustment for smoking and other confounders, but prior to adjustment for individual-level measures of socioeconomic status, there was an increased risk of lung cancer for persons living in neighborhoods with the greatest quartile of deprivation relative to those in neighborhoods with the least (odds ratio (OR) 1.28, 95% confidence interval (CI) 1.00-1.63). Additional adjustment for individual-level measures of socioeconomic status weakened this effect (OR 1.21, 95% CI 0.94-1.55). There was no evidence of effect modification by race or sex.
Conclusions: Area-level measures of socioeconomic status were associated with lung cancer risk in this population after control for smoking.
Citation Format: Maureen Sanderson, Melinda C. Aldrich, Robert S. Levine, Barbara Kilbourne, Qiuyin Cai, William J. Blot. Association between neighborhood deprivation and lung cancer risk in the Southern Community Cohort Study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A42.
Abstract A59: Racial comparisons of the gut microbiota of generally healthy black and white women for insights into colorectal cancer disparities
Authors: Carson Tiffany L. , Wang Fuchenchu , Cui Xiangqin , Jackson Bradford E. , Pol Liam Van Der , Lefkowitz Elliot J. , Morrow Casey , Baskin Monica 
Published: February 2019

Abstract
Racial health disparities persist among black and white women for colorectal cancer (CRC). Since the gut microbiota has been linked to CRC, understanding racial differences in the gut microbiota may yield new insight into unexplained disparities in CRC incidence. Generally healthy non-Hispanic black or white females who were at least 19 years old provided survey data, anthropometrics, and stool samples. Fecal DNA was collected and isolated from a wipe. PCR was used to amplify the V4 region of the 16SrRNA gene and 250 bases were sequenced using the MiSeq platform. Microbiome data were analyzed using the QIIME package. OTU data were log transformed and normalized. Linear models in R Package “limma” were used to test statistical significance differences. Fecal samples were analyzed for 80 females (47 black, 33 white). Mean age and BMI were 39.9 years and 30.1 kg/m2, respectively. Blacks had a higher average BMI than whites (33.3 vs. 27.5 kg/m2; p&lt;0.01) and larger waist circumference (98.3 vs. 86.6 cm; p&lt;0.01). Unadjusted comparisons revealed no racial differences in alpha diversity. Racial differences were observed in beta diversity and abundance of top-10 OTUs. Blacks had higher abundances than whites of Faecalibacterium (p=0.03) and Bacteroides (p=0.04). The association between race and Bacteroides (logFC=1.72; 0=0.02) persisted in fully adjusted models. Black race was associated with a higher abundance of Bacteroides, which has been linked to CRC. Other racial differences in the gut microbiota were also observed. Efforts to cultivate an “ideal” gut microbiota may help reduce CRC risk and health disparities.
Citation Format: Tiffany L. Carson, Fuchenchu Wang, Xiangqin Cui, Bradford E. Jackson, Liam Van Der Pol, Elliot J. Lefkowitz, Casey Morrow, Monica Baskin. Racial comparisons of the gut microbiota of generally healthy black and white women for insights into colorectal cancer disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A59.
Abstract A69: Racial disparity in breast cancer hospital treatment costs: Examining the effect of depression
Authors: Husaini Baqar , Miller Oscar , Jones Jessica , Levine Robert 
Published: February 2019

Abstract
Objective: The effect of depression on hospital costs for breast cancer (BC) patients by race remains unknown. This presentation examines two issues by race: (i) hospitalized prevalence of BC and depression among discharged patients, and (ii) racial variation regarding the effect of depression on hospital costs of BC patients.
Methods: For BC, available 2008 Tennessee Hospital Discharge Data System (HDDS) was examined. The BC sample (n=2,522) was mostly white (86%) with an average age of 63 years. We computed age-adjusted BC rates per CDC methodology, and determined racial disparity. We compared the hospital costs for BC patients with depression (BC+D) vs. without depression (BCND).
Results: Age-adjusted BC rates (per 100K) were higher among white than black patients (43.3 vs. 9.2, p&lt;.001). Further, 25% of BC patients were depressed (depression was higher among white than black patients [26% vs. 14%, p&lt;.01]). Hospital costs for BC were 30% higher compared to non-BC patients. Further, the cost for depressed patients (BC+D) was 56% higher compared to nondepressed (BCND) patients ($64,439 vs. $41,344). Importantly, the higher costs for depressed patients (BC+D) were similarly higher among both black and white female patients compared to their nondepressed (BCND) peers.
Conclusion: BC prevalence rate is higher among white females compared to black females. Depression increases hospital costs for both white and black patients. Since depression increased cost for both racial groups of patients, considerable cost savings might be attained by screening and treating depression among BC patients before their hospitalization.
Citation Format: Baqar Husaini, Oscar Miller, Jessica Jones, Robert Levine. Racial disparity in breast cancer hospital treatment costs: Examining the effect of depression [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A69.
Abstract A70: [Advocate Abstract:] We have breast too! A male breast cancer awareness program
Authors: Dornan Wayne 
Published: February 2019

Abstract
This poster will highlight a proposed male breast cancer educational program that will be carried out throughout Tennessee.
Citation Format: Wayne Dornan. [Advocate Abstract:] We have breast too! A male breast cancer awareness program [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A70.
Abstract A74: [Advocate Abstract:] The brown faces of colorectal cancer
Authors: Henley Candace 
Published: February 2019

Abstract
The poster will explore the various stories of misdiagnosis, patients fighting to get a colonoscopy under the age of 50, patients and stories of survival through as it relates to minorities and the various challenges it took to find out they had colorectal cancer.
Citation Format: Candace Henley. [Advocate Abstract:] The brown faces of colorectal cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A74.
Abstract B19: Screen to Save (S2S) implementation across National Outreach Network (NON) region 2
Authors: Fleming Khaliah F. , Lopez Jomar D. 
Published: February 2019

Abstract
Background: S2S aims to increase colorectal cancer (CRC) screening rates among community members aged 50-75 years from racially and ethnically diverse communities. The National Cancer Institute's (NCI) National Outreach Network (NON) and Partnerships to Advance Cancer Health Equity (PACHE) community health educators (CHEs) are implementing a culturally sensitive, evidence-based nationwide CRC outreach and screening initiative. This poster reports on S2S activities within NON Region 2 among multilingual and multicultural populations.
Methods: NCI tasked sites with conducting phase 1 or phase 1 and 2 of S2S. Phase 1 consists of CRC prevention, early detection, and screening education via NCI CRC resources and materials. Phase 2 consists of providing the education and fecal immunochemical test (FIT) kits to those who qualify. Both phases consist of pre- and post-knowledge assessments coupled with demographic information of attendees. A 3-month follow-up survey is administered post the S2S session to determine participants' CRC-screening- related actions. Effective strategies for initiative recruitment include electronic and in-person flyer dissemination, social media postings, and community partner engagement. Colorectal cancer models, a miniature portable toilet, and an NCI-developed S2S PowerPoint presentation have been utilized across the region as educational tools.
Results: Four NON and PACHE CHEs in the region are implementing the S2S initiative with the aid of community partnerships. To date, more than 81 individuals have received CRC education through a total of 5 S2S sessions. A total of 66 FIT kits have been disseminated and 16 returned.
Conclusion: Lessons learned from this ongoing initiative include the importance of having a multilevel educational approach and collaborations at local, state, and national levels for CRC education and screening. Leveraging partnerships for CRC education and screening is an effective strategy to improve CRC awareness and promote FIT uptake.
Citation Format: Khaliah F. Fleming, Jomar D. Lopez. Screen to Save (S2S) implementation across National Outreach Network (NON) region 2 [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B19.