bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B039: Multinucleation precedes the emergence of drug resistance in prostate cancer
Authors: Torga Gonzalo , Lin Ke-Chih , Austin Robert H. , Pienta Kenneth J. 
Published: February 2019

Abstract
Metastatic prostate cancer remains a lethal disease. Taxane chemotherapy used to be restricted to the hormone-resistant metastatic setting in which most patients with castration-resistant prostate cancer (CRPC) develop therapeutic resistance to chemotherapy, achieving limited therapeutic benefit. Recently, two trials demonstrated adjuvant chemohormonal therapy to increase survival in men with high-risk metastatic hormone-sensitive prostate cancer.
Although chemotherapy has been extensively used for decades, how it affects tumor heterogeneity at the molecular level is poorly understood. Experiments with drug gradients in our engineered microfluidic device have shown that docetaxel therapy leads to multinucleation with a stiff distribution pattern of heterogeneous cell populations across the concentration gradient. Furthermore, in these experiments, multinucleation always preceded the development of drug resistance. To confirm these findings, we conducted experiments in conventional cell culture using different chemotherapeutic agents in several prostate cancer cell lines and confirmed multinucleation was a common feature among them. Interestingly, multinucleation occurred to some extent, independently of the mechanism of action of the drug tested.
Aneuploidy, an inherent consequence of multinucleation, has been described as a common characteristic of tumors and proposed to drive tumor progression by increasing the potential for cellular transformation. However, whether this is a cause or a consequence of cancer remains unclear. Aneuploidy can be caused by very diverse molecular mechanisms such as mitotic slippage, endo-replication, or cell fusion. In cancer biology, it has been associated with epithelial-mesenchymal transition as well as with gain of stem-like potential. Recent data in prostate cancer demonstrated the association of multinucleation with chemotherapy, androgen-deprivation therapy, and radiotherapy. Although the data supporting the association of multinucleation with drug resistance are extensive, the effects of these therapies on tumor heterogeneity remain unknown. A better understanding of the resistance mechanisms might reveal new targets for cancer therapy.
In this work, we focus on the characterization of the subset of cells within the tumor population that leads to the multinucleated phenotype, particularly the subpopulation with the potential to reverse polyploidy and repopulate tumor heterogeneity after therapy.
Citation Format: Gonzalo Torga, Ke-Chih Lin, Robert H. Austin, Kenneth J. Pienta. Multinucleation precedes the emergence of drug resistance 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 B039.
Abstract B045: Gene expression pathways associated with vigorous physical activity in prostate cancer
Authors: Pernar Claire H. , Parmigiani Giovanni , Giovannucci Edward L. , Rimm Eric B. , Finn Stephen , Fiorentino Michelangelo , Ebot Ericka M. , Mucci Lorelei A. 
Published: February 2019

Abstract
Background: Epidemiologic studies have consistently shown that men engaged in high levels of physical activity have lower risks of advanced and fatal prostate cancer. The mechanisms underlying this association are not well understood but may include changes in hormonal and anti-inflammatory pathways. Our objective was to investigate the link between prediagnostic physical activity and gene expression alterations in prostate tumor and adjacent normal tissue.
Methods: We performed whole-gene expression profiling on tumor (N=248) and adjacent normal tissue (N=117) among a subset of men diagnosed with indolent and lethal prostate cancer between 1986 and 2005 in the prospective Health Professionals Follow-up Study. Men were followed prospectively for prostate cancer outcomes through 2011. Physical activity was ascertained by self-report of the average number of hours per week spent engaged in various forms of recreational physical activity at baseline and every two years thereafter. We examined cumulative average physical activity of vigorous intensity in units of metabolic equivalent of task (MET)-hours/week updated from baseline to the time prostate cancer diagnosis. Gene set enrichment analysis was performed among KEGG and hallmark gene sets to identify pathways with differential expression by vigorous activity.
Results: We identified 33 KEGG and four Hallmark gene sets enriched in the adjacent normal tissue comparing men in the highest compared to the lowest quintile of vigorous activity (false-discovery rate &lt; 0.25). Among the significant gene sets identified were cancer-related pathways as well as vascular smooth muscle contraction, angiogenesis, and insulin-signaling pathways. No gene sets were significantly enriched in the tumor tissue.
Conclusions: These findings suggest that physical activity may influence prostate cancer development through epigenetic alterations in the prostate tissue. Future studies are needed to confirm these findings and further investigate potential mechanisms linking physical activity to risk of lethal prostate cancer.
Citation Format: Claire H. Pernar, Giovanni Parmigiani, Edward L. Giovannucci, Eric B. Rimm, Stephen Finn, Michelangelo Fiorentino, Ericka M. Ebot, Lorelei A. Mucci. Gene expression pathways associated with vigorous physical activity 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 B045.
Abstract B065: Genomic analysis of localized prostate cancer identifies AZIN1 as driver of metastatic progression
Authors: Broeck Thomas Van den , Moris Lisa , Gevaert Thomas , Smeets Elien , Prekovic Stefan , Helsen Christine , Poppel Hendrik van , Everaerts Wouter , Buerki Christine , Davicioni Elai , Joniau Steven , Claessens Frank 
Published: February 2019

Abstract
High-risk PCa (HRPCa) remains very heterogeneous with an unacceptable variation in patient outcome after radical prostatectomy, with cancer-specific mortality rates ranging from 4.6% to 20.3% at 10 years’ follow-up. Clearly, we need a better understanding of the tumor biology to enhance the subclassification, enable the identification of lethal PCa, and eventually allow a more precise decision-making regarding treatment.
We created a matched case-control study of two clinically identical HRPCa patient groups, both treated with radical prostatectomy but where one developed metastatic recurrence (n=19) and the other did not (n=25), despite very-long-term follow-up. The integrated analysis of copy number aberrations and transcriptome analysis highlighted a focal amplification of 8q22.3 in the metastatic group, associated with a higher expression of antizyme inhibitor 1 (AZIN1) in our cohort. This association of high AZIN1 levels with the metastatic HRPCa phenotype suggests a role for AZIN1 as possible predictor and/or target for metastatic HRPCa. AZIN1 is one of the regulators of the polyamine synthesis, which play a central role in many cellular processes. Our in vitro analyses confirmed that modulation of AZIN1 expression determines both growth and migratory potential of prostate cancer cells. Future experiments are planned to confirm these data in the in vivo setting. RNA sequencing after knockdown of AZIN1 in PCa cells revealed several transcriptional programs that are activated/deactivated upon AZIN1 knockdown. This showed among others a significant upregulation of genes involved in extracellular matrix composition, including genes encoding for subunits of the collagen IV, which is an integral part of the basement membrane. Ongoing experiments focus on identifying the mechanism by which AZIN1 regulates collagen IV expression.
Citation Format: Thomas Van den Broeck, Lisa Moris, Thomas Gevaert, Elien Smeets, Stefan Prekovic, Christine Helsen, Hendrik van Poppel, Wouter Everaerts, Christine Buerki, Elai Davicioni, Steven Joniau, Frank Claessens. Genomic analysis of localized prostate cancer identifies AZIN1 as driver of metastatic progression [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 B065.
Abstract IA17: PARP inhibitor resistance in prostate cancer
Authors: D’Andrea Alan D. 
Published: February 2019

Abstract
Large-scale genomic studies have demonstrated that approximately 15% of metastatic castration-resistant prostate cancer (mCRPC) harbors genetic and epigenetic alterations in homologous recombination repair (HRR) pathway genes. The most commonly altered HRR genes are BRCA2, BRCA1, and ATM, followed by other Fanconi anemia genes including FANCN/PALB2 and FANCA. Loss of HRR causes genomic instability, hyperdependence on alternative DNA repair mechanisms, and enhanced sensitivity to platinum analogues and PARP inhibitors (PARPi). The synthetic lethal interaction with PARPi is being exploited therapeutically in diverse clinical contexts and most notably in BRCA2-deficient mCRPC where the PARPi olaparib has demonstrated improvements in progression-free survival. PARPi resistance has already emerged as a vexing clinical problem for the treatment of BRCA1/2-deficient tumors. The most prevalent mechanism of PARPi resistance is secondary events that cancel the original HRR alteration and restore HRR proficiency. These somatic reversions of mutant BRCA2 alleles can be monitored by sequencing of ctDNA. However, PARPi resistance may also develop without restoration of HRR proficiency via disruption of multiple proteins, such as PTIP or CHD4, that leads to replication fork (RF) stabilization. Importantly, this latter mechanism—namely, the restoration of RF stability—appears to be a highly prevalent mechanism of PARP inhibitor resistance in vitro and in vivo, particularly in tumor cells with an underlying BRCA2 deficiency. Due to their underlying deficiency in BRCA2 and inability to generate RAD51 nucleofilaments, these tumor cells are unable to restore HRR mechanisms. Instead, these cells acquire may PARPi resistance by limiting the nucleolytic degradation of their stalled replication forks. We have recently made the surprising observation that BRCA2-deficient ovarian and breast cancer cells can become resistant to PARPi by downregulating the expression of the polycomb repressive complex PRC2, a methyltransferase complex containing EZH2, SUZ12, EED, and RbAp48. Importantly, downregulation of PRC2 results in the reduced recruitment of the nuclease MUS81 to the RF, thereby providing a novel mechanism of RF protection and PARPi resistance. Whether or not the downregulation of the PRC2/MUS81 pathway is also a mechanism of PARPi resistance in mCRPC remains to be determined. A molecular understanding of PARPi resistance mechanisms may allow the generation of a new class of drugs, or a repurposing of existing drugs, which may reverse this resistance and extend the use of PARPi to more tumor types.
Citation Format: Alan D. D’Andrea. PARP inhibitor resistance 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 IA17.
Abstract IA22: Targeting tumor-infiltrating myeloid cells for prostate cancer therapy
Authors: Alimonti Andrea 
Published: February 2019

Abstract
Prostate cancer cells are surrounded by a complex tumor microenvironment that controls prostate cancer progression and treatment resistance. We are interested in understanding the liaison between tumor-infiltrating myeloid cells and prostate cancer cells to identify new molecular mechanisms that regulate cancer progression and the emergence of castration-resistant prostate cancer (CRPC). We have previously demonstrated that myeloid-derived suppressor cells (MDSCs) trigger senescence evasion and immunosuppression in primary prostate cancers, eventually promoting tumor progression. These studies have provided the rationale to develop in the clinic novel immune therapies targeting MDSCs for the therapy of metastatic prostate cancer patients. I will present recent results on additional tumor-promoting functions played by MDSCs and tumor-associated macrophages (TAMs) in prostate cancer, and I will discuss new therapeutic strategies that combine the use of immunotherapy with androgen deprivation therapy for the treatment of CRPC
Citation Format: Andrea Alimonti. Targeting tumor-infiltrating myeloid cells for prostate cancer therapy [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 IA22.
Abstract A18: An enhanced shared decision-making model to address willingness and ability to undergo lung cancer screening and follow-Up treatment
Authors: Erkmen Cherie P. , Mitchell Mark , Randhawa Simran , Sferra Shelby , Kim Rachel , DiSesa Verdi , Kaiser Larry R. , Ma Grace X. 
Published: February 2019

Abstract
Background: Failure to address willingness and ability to undergo lung cancer treatment before lung cancer screening could cause patients unnecessary anxiety, cost, and care. We employed an enhanced shared decision-making (SDM) model to address willingness and ability to undergo lung cancer screening of low-dose CT (LDCT) scanning. We hypothesized that enhanced SDM was feasible and did not discourage patients from undergoing lung cancer screening.
Methods: We performed a prospective study of patients referred for lung cancer screening. We measured adherence to the LCS protocol, including consent to discuss lung cancer treatment if cancer is found and direct questions to patients about willingness and ability to undergo lung cancer treatment. We measured race, gender, adherence to the consent process, and questions regarding willingness and ability to undergo lung cancer treatment and subsequent uptake of LDCT.
Results: All 190 patients have a documented SDM visit addressing the risks and benefits of lung cancer screening and consented to discuss lung cancer treatment if lung cancer is diagnosed. One hundred and seventy-nine (179) of 190 (94%) answered yes to being willing and able to undergo lung cancer treatment. One hundred and eighty-seven (187) patients underwent LDCT (98.4%).
Conclusions: Discussion about willingness and ability to undergo lung cancer treatment should be an essential component of an SDM discussion prior to LDCT. This study demonstrated that an enhanced SDM experience is feasible in a clinical setting. Furthermore, patients proceeded with LDCT following the enhanced SDM process.
Citation Format: Cherie P. Erkmen, Mark Mitchell, Simran Randhawa, Shelby Sferra, Rachel Kim, Verdi DiSesa, Larry R. Kaiser, Grace X. Ma. An enhanced shared decision-making model to address willingness and ability to undergo lung cancer screening and follow-Up treatment [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 A18.
Abstract A43: [Advocate Abstract:] Dot4life multiple myeloma for Caribbean patients
Authors: Brignoni Marisel 
Published: February 2019

Abstract
The population of Puerto Rico decreased from 3,808,610 on April 1, 2000 to 3,725,789 on April 1, 2010. Population estimates for 2011 indicate that the population continues to decrease. The population structure of Puerto Rico got older. The population 65 years of age and older increased from 11.2% in 2000 to 15.2% in 2011. The poverty level in all people in Puerto Rico for 2011.
In 2011, 7.6% of the noninstitutionalized civilian population in Puerto Rico had no health insurance coverage. Puerto Rico has 250 new cases of multiple myeloma every year. The Veterans Hospital has 15 new cases every year for the same cause. Between 2008-2012 we had 1053 new cases of multiple myeloma. Puerto Rico does not have any specialists for multiple myeloma, although it receives a support from one of the hospitals in Florida that came 1 or 2 times a month to see these patients. Giving the patient education, the correct therapy, helping them with financial programs; we will have the engagement for any clinical trials that exist for this cause.
Note: This abstract was not presented at the conference.
Citation Format: Marisel Brignoni. [Advocate Abstract:] Dot4life multiple myeloma for Caribbean patients [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 A43.
Abstract A47: Correlation between non-skin cancer survival, race/ethnicity, and socioeconomic status in the United States
Authors: Song Jingwei , Tian Ligeng , Aliyu Muktar 
Published: February 2019

Abstract
Background: The elimination of disparities in the burden of cancer is one of the overarching themes of the American Cancer Society 2015 challenge goals. However, not much progress has occurred in this area in the U.S, especially among certain populations. This is an area in which progress has yet to be made, even in 2017.
Methods: In 2014, the CDC BFRSS (Behavioral Risk Factor Surveillance System) conducted cancer survivorship telephone surveys in seven states (Alaska, Iowa, Mississippi, Missouri, Nebraska, Ohio, and Wisconsin). We performed logistic regression to determine the cancer survivorship disparities and socioeconomic status of non-skin cancer patients based on race and ethnicity.
Results: A total of 64,202 people participated in the survey. A total of 3,539 persons (age 18 to 79 years) self-reported being diagnosed with at least one non-skin cancer. The prevalence of non-skin cancer was 3.7%, 7.2%, 7.5%, and 10.5% among Hispanics, other non-Hispanics, black non-Hispanics, and white non-Hispanics, respectively. Compared to the other races, White non-Hispanic race was independently associated with being diagnosed with depression (OR=1.72), unable to work (OR=1.85), daily smoking habits (OR=2.07), and having more than one different type of cancer (OR=2.43 for two types of cancers and OR=2.56 for three or more different cancers).
Conclusions: Non-skin cancer is correlated with socioeconomic status and varies by race/ethnicity. These factors include less education, low income, less family support, and lack of a stable job. However, compared to white non-Hispanics, other races reported essentially the same quality of life.
Citation Format: Jingwei Song, Ligeng Tian, Muktar Aliyu. Correlation between non-skin cancer survival, race/ethnicity, and socioeconomic status in the United States [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 A47.
Abstract B07: Asian American women's perspectives toward donating healthy breast tissue: Implications for recruitment methods and messaging
Authors: Ridley-Merriweather Katherine E. 
Published: February 2019

Abstract
As long as they remain in their homelands, Asian women have a lower risk than Caucasians, African Americans, and Latinas of developing breast cancer (BC). Yet once Asians move to the U.S. their risk rates measurably increase. The Susan G. Komen® Tissue Bank at the IU Simon Cancer Center (KTB) is the only biobank of its kind in the world that collects healthy breast tissue from women of all racial groups to use as controls in BC research. The KTB represents a critical tool in efforts to treat and prevent BC; however, Asian American (AA) women display marked reticence towards donating breast tissue to the KTB. Therefore, the purpose of this study is to use the basic components of Grounded Practical Theory to explore potential messaging that may result in AAs' more positive outlook on breast tissue donation.
This study recruited seventeen (N=17) AA women to share their perspectives on donating breast tissue for research purposes. Participants took part in an interactive focus group exploring potential messaging for successfully recruiting AA women to the KTB study. Findings revealed that: a) participants retained a culturally embedded discomfort with donating, and a general distrust that their donation would be handled ethically and appropriately; b) the women possessed an extraordinary need for knowledge about all facets of the donation process; c) participants perceived that they lack a personal connection to BC, making it difficult for them to generate any truly altruistic tendencies to perform the desired behavior, or to understand a need to do so; and d) they possess a strong desire to learn why it seems important to the KTB to collect their tissue, and especially about the increased BC rates and risk for Asians who move to or are born in the U.S. The findings from this study have important implications for others who work in applied clinical settings and are interested in addressing racial disparities in medical research through more effective and targeted recruitment messaging.
Citation Format: Katherine E. Ridley-Merriweather. Asian American women's perspectives toward donating healthy breast tissue: Implications for recruitment methods and messaging [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 B07.