bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B052: Leveraging the metabolic stress of polyamine biosynthesis in prostate cancer towards a novel therapeutic approach
Authors: Affronti Hayley C. , Pellerite Anthony J. , Rowsam Aryn , Rosario Spencer R. , Casero Robert A. , Nikiforov Mikhail A. , Phillips James , Smiraglia Dominic J. 
Published: February 2019

Abstract
Prostatic epithelial cells secrete high levels of acetylated polyamines into the prostatic lumen. This distinctive characteristic places added strain on connected pathways, forcing increased metabolite production from both one-carbon metabolism and the methionine cycle to maintain nucleotide and S-adenosylmethionine (SAM) pools, respectively. More importantly, this stress is increased in prostate cancer (CaP) due to increased polyamine biosynthesis, DNA synthesis, and proliferation. The metabolic flux is driven by the activity of spermidine/spermine N1-acetyltransferase (SSAT), which acetylates the polyamines leading to their secretion into the lumen, which drives demand for biosynthesis of polyamines. To overcome this stress, the methionine salvage pathway (MSP) recycles the one-carbon unit lost to polyamine biosynthesis back to the methionine cycle, allowing for replenishment of SAM pools. The rate-limiting enzyme involved in this process is methylthioadenosine phosphorylase (MTAP). We have found that CaP relies on the MSP to relieve the strain caused by high polyamine biosynthesis and that both genetic and pharmacologic inhibition of MTAP blocks CaP xenograft growth. We hypothesized that this dependence can be enhanced by increasing the activity of SSAT. Recent results from our lab have shown that pharmacologic inhibition of MTAP alongside SSAT upregulation is synergistic in multiple androgen-sensitive and castration-recurrent CaP cell lines. We are currently exploring the effects of our combination treatment in castration-recurrent xenografts in vivo as well as in human CaP treatment-naïve tumors from radical prostatectomies grown as ex vivo explants. Preliminary results reveal that our treatments are effective at slowing growth in a subset of xenografts in vivo as well as impacting our target enzymes, polyamine levels, and increasing apoptosis in our ex vivo system. We expect that simultaneous targeting of multiple, converging pathways that are exceptionally important for prostate will lead to significant delay or prevention of disease recurrence.
Citation Format: Hayley C. Affronti, Anthony J. Pellerite, Aryn Rowsam, Spencer R. Rosario, Robert A. Casero, Mikhail A. Nikiforov, James Phillips, Dominic J. Smiraglia. Leveraging the metabolic stress of polyamine biosynthesis in prostate cancer towards a novel therapeutic approach [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 B052.
Abstract B090: Personalized research: Establishment and characterization of prostate cancer patient-derived organoids and cells
Authors: Cheaito Katia Anis , Hadadeh Ola , Bahmad Hisham , El-Sabban Marwan , El-Hajj Albert , Mukherji Deborah , Abou-Kheir Wassim 
Published: February 2019

Abstract
Several attempts have been made to understand the exact mechanisms underlying the pathogenesis of prostate cancer (PC); however, the currently available cancer models fail to recapitulate the heterogeneity of this tumor, its metastasis, and progression to castration-resistant states. Moreover, many drug candidates that succeed in preclinical models fail to deliver a good outcome in clinical trials, resulting in ineffective patient treatment and misused resources. In this aspect, the development of three-dimensional (3D) organoid culture systems has rendered it feasible to recap the convolution of organogenesis in vitro, promoting the generation of novel and more representative cancer models. Thus, the aim of this study is to generate patient-specific 3D organoids and cell lines, then characterize these models to identify potential prognostic biomarkers and treatments for PC while correlating the outcome with the collected clinical parameters. In our study, we are employing the R-spondin-1-based organoids technology to generate PC organoids and primary cell lines derived from fresh normal and tumor tissues of patients undergoing radical prostatectomy. Consequently, molecular characterization of the different patient-derived PC organoids and cell lines will be performed, followed by using this model to assess different classical and in-clinical trials drugs. We succeeded in establishing 21 normal and 18 tumor patient-derived organoids, out of a total of 23 patients, and then propagated the established organoids for up to 6 generations. Interestingly, 2D cells were derived from these organoids using the same culture media and were continuously passaged for up to 20 passages so far (more than 3 months). Our newly patient-derived organoids and cells show a typical epithelial phenotype and express CK8 and CK14 (prostate epithelial markers). To the best of our knowledge, this is the first study to address the establishment of primary PC cell lines from organoids, which will likely lead to a comprehensive understanding of mechanisms exploited in PC. Moreover, molecular characterization of this model when combined with pharmacologic profiles can aid in predicting a patient’s drug response; thus, our study represents an attempt to inaugurate what can possibly lead to personalized treatment of PC.
Citation Format: Katia Anis Cheaito, Ola Hadadeh, Hisham Bahmad, Marwan El-Sabban, Albert El-Hajj, Deborah Mukherji, Wassim Abou-Kheir. Personalized research: Establishment and characterization of prostate cancer patient-derived organoids and 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 B090.
Abstract IA19: Phenotype plasticity—a novel mechanism of targeted therapy resistance
Authors: Cyrta Joanna , Wilkes David , Chae Sung Suk , Benelli Matteo , Bareja Rohan , Prandi Davide , Cavaliere Paola Maria Giovanna , Beltran Himisha , Sboner Andrea , Demichelis Francesca , Rubin Mark A. 
Published: February 2019

Abstract
Prostate cancer (PCa) is the most commonly diagnosed cancer and the third highest cause of cancer-related death in men in Europe, where it is responsible for over 90,000 deaths a year. The mainstay of treatment for metastatic PCa is androgen-deprivation therapy (ADT). Although initially effective, the treatment ultimately fails and progression to castration-resistant prostate cancer (CRPC) occurs. Given that CRPC is still driven by hormonal signaling through aberrant activation of the androgen receptor (AR), improved, more potent AR-targeting therapies have been developed for CRPC patients. However, resistance to these therapies ultimately occurs as well. One form of resistance identified by my group results in a phenotypic switch leading to androgen receptor indifference and progression to neuroendocrine prostate cancer (NEPC), which shows a distinct histomorphology and expresses neural-like markers. Unlike more commonly recognized mechanisms of ADT resistance due to AR mutations or amplification, NEPC no longer responds to AR-targeting therapy and has a mean survival of 7 months. There is mounting evidence supporting the role of epigenetic events as a mechanism for transdifferentiation of PCa to an androgen signaling-indifferent state under specific genomic conditions, involving but not limited to TP53, RB1, and PTEN loss. However, the epigenetic regulators at work and the specific changes in the epigenetic landscape are unknown. The SWI/SNF complex is a major epigenetic player, both in regulating normal cell differentiation and in cancer biology. This presentation will focus on novel data supporting the role of alterations in this complex that could contribute to PCa phenotype plasticity.
Citation Format: Joanna Cyrta, David Wilkes, Sung Suk Chae, Matteo Benelli, Rohan Bareja, Davide Prandi, Paola Maria Giovanna Cavaliere, Himisha Beltran, Andrea Sboner, Francesca Demichelis, Mark A. Rubin. Phenotype plasticity—a novel mechanism of targeted therapy resistance [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 IA19.
Abstract A09: Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review
Authors: Smith Brandi Patrice , Madak-Erdogan Zeynep 
Published: February 2019

Abstract
Certain residential characteristics in urban neighborhoods have shown to have negative impacts on health, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer risk, incidence, stage at diagnosis/late stage diagnosis, survival, and mortality in African Americans. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies that included populations of African American women, setting in “urban” areas, and a measure of a neighborhood or residential factor were reviewed. Three parameters related to neighborhood/residential factors were extracted, including neighborhood socioeconomic status (SES), residential segregation, and residential pollution. Eighteen studies were identified for systematic review. 10 studies showed significantly higher odds of late-stage diagnosis, higher mortality, and lower survival in African American women living in lower socioeconomic neighborhoods. One study showed slightly higher odds of upward neighborhood change and probability of distant metastasis at diagnosis of African American woman compared to White women (OR=1.24). Similarly, 5 studies showed significantly high associations between residential segregation and late-stage diagnosis, as well as high associations of residential segregation and higher mortality in African American women. Two studies assessed residential pollution on breast cancer risk. The first study showed a weak rate of breast cancer risk in African American women between differentiating levels of trihalomethane in public water (RR=1.2). The second assessed the association of magnetic field exposure and breast cancer risk and found that the odds of getting breast cancer were not significant in African American women (OR=1.02). This review provides a qualitative synthesis of major neighborhood and residential factors on breast outcomes in African American women. By enacting health policies and utilizing tools such as health informatics, steps can be taken to drive the breast cancer disparity down in this population.
Citation Format: Brandi Patrice Smith, Zeynep Madak-Erdogan. Urban neighborhood and residential factors associated with breast cancer in African American women: A systematic review [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 A09.
Abstract A22: Improving the community's understanding of research through lay ambassadors
Authors: Gonzalez Evelyn T. , Washington Armenta , Esnaola Nestor F. 
Published: February 2019

Abstract
Clinical trials are pathways to the discovery of effective new methods of prevention, treatment and rehabilitation for many diseases, including cancer. In addition, the collection of biospecimens is a critical element in emerging genetic and biologic studies. However, evidence has shown that despite the increasing advances in newly developed novel and targeted biologic therapies and the compelling scientific and social justice arguments for participation by all populations, ethnic and racial minorities continue to be under-represented. One key reason noted is the lack of awareness minority populations have regarding research options. Through our Community Ambassador Training program, we established a connection with African American audiences by educating trusted community stakeholders and representatives about the importance of research participation and how the research process works. Working through community partners and building on prior research efforts, Community Health Educators (CHE) funded by NCI's Center to Reduce Cancer Health Disparities recruited 21 African American lay educators (cancer and noncancer survivors) to participate in the study. Results from the training include changes in knowledge, attitudes, and intent to participate in research; dissemination reach; lessons learned; and next steps in our efforts to enhance and expand the program to address this gap in research participation.
Citation Format: Evelyn T. Gonzalez, Armenta Washington, Nestor F. Esnaola. Improving the community's understanding of research through lay ambassadors [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 A22.
Abstract A32: Trends in cause of death among Puerto Rican and United States multiple myeloma patients
Authors: Castañeda-Avila Maira A. , Ortiz-Ortiz Karen J. , Torres-Cintrón Carlos R. , Epstein Mara M. 
Published: February 2019

Abstract
Background/objective: Multiple myeloma (MM) is an incurable, yet treatable, cancer of plasma cells. Due to recent improvements in treatment, people diagnosed with MM have been living longer, and other comorbid conditions may be of increasing importance. This study examines temporal trends in specific causes of death among MM patients in Puerto Rico (PR) and the United States (U.S.).
Methods: We analyzed primary cause of death among all incident MM cancer cases recorded in the Puerto Rico Central Cancer Registry (PRCCR) (n=3,018) and the US Surveillance, Epidemiology, and End Results Program (SEER) (n=67,733) between 1987-2013, overall and by follow-up time, age, and sex. We calculated the cumulative incidence of death due to seven selected causes and analyzed age-adjusted mortality trends by MM and other causes using joinpoint regression.
Results: MM accounted for 71.7% and 71.3% of all reported deaths in PR and the U.S., respectively, among people diagnosed with MM. In PR, the proportion of patients who died from MM decreased with increasing follow-up time since diagnosis (72.3% of deaths with ≤2 years vs 65.6% with &gt;5 years of follow-up) and the proportion of patients who died from circulatory (4.6% vs 9.0%) and respiratory system (3.7% vs 5.0%) diseases increased slightly. A similar trend of decreasing MM deaths with follow-up time was observed in the U.S. (73.2% of deaths with ≤2 years vs 66.5% with &gt;5 years of follow-up). Joinpoint regression showed a decreasing trend in MM mortality in the U.S. and PR.
Conclusion: In both PR and the U.S., people diagnosed with MM are still more likely to die from MM than from another cause. However, a decrease in MM mortality is evident, particularly in more recent years, but this decrease is lower in Puerto Rico.
Citation Format: Maira A. Castañeda-Avila, Karen J. Ortiz-Ortiz, Carlos R. Torres-Cintrón, Mara M. Epstein. Trends in cause of death among Puerto Rican and United States multiple myeloma 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 A32.
Abstract A35: An integrative model of cancer disparities based on the calcium molecular theory of carcinogenesis
Authors: KADIO Bernard , Yaya Sanni Hashimi , Basak Ajoy , Gomes James , Djè Koffi , Mesenge Christian 
Published: February 2019

Abstract
One key question that comes to mind regarding cancer patterns is what factors account for the differentiated distribution of different cancer types in a given population? In other words, why is prostate cancer, for example, more prevalent among African Americans than in Caucasian Americans? Or why do native Eastern Asians record the highest incidence of gastric cancer worldwide? Beyond the commonly accepted genetic polymorphism to cancer vulnerability, this study is an in-depth exploration of the factors underpinning cancer distribution. Using a population health approach, an ecologic analysis was conducted, based on the current knowledge on the most prevalent cancer types. The calcium molecular theory of carcinogenesis, as published in our earlier work and presented at the Paris 2016 World Cancer Congress, served as basis for the analysis. As a result, cancer distribution appears to be shaped by a complex interaction between some key socioecologic determinants. Most importantly, we established that these determinants have a differentiated impact on intracellular calcium concentrations and trafficking. Thus, specific populations will be selectively vulnerable to a certain cancer type through a distinctive effect of their socioecologic characteristics on internal calcium. We conclude that calcium ion, already known as a cellular messenger, is also an environmental messenger. That molecule mediates the effects of external factors and their cellular responses, and this interaction accounts for cancer type distribution in the population at large. The work is published in two complementary papers: the first relates to cancer determinants while the second will discuss their impact on calcium metabolism.
Note: This abstract was not presented at the conference.
Citation Format: Bernard KADIO, Sanni Hashimi Yaya, Ajoy Basak, James Gomes, Koffi Djè, Christian Mesenge. An integrative model of cancer disparities based on the calcium molecular theory of carcinogenesis [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 A35.
Abstract A56: Racial disparities in colon cancer survival--United States, 2001-2009
Authors: White Arica , Joseph Djenaba , Rim Sun Hee , Johnson Christopher J. , Coleman Michel , Allemani Claudia 
Published: February 2019

Abstract
Background: In the first CONCORD study, five-year survival for colon cancers diagnosed during 1990-1994 in the U.S. was among the highest in the world (60%), but there were large racial disparities in most participating states. The CONCORD-2 study updated these findings to determine survival trends up to 2009 by race and stage.
Methods: We analyzed data from 37 state population-based cancer registries, covering approximately 80% of the U.S. population, for patients diagnosed with colon cancer during 2001-2009 and followed through 2009. Survival up to five years was adjusted for background mortality (net survival) using state- and race-specific life tables, and age-standardized using the International Cancer Survival Standard weights. Survival is presented by race (all, black, white), stage, state, and calendar period (2001–03 and 2004–09) to account for changes in methods used to collect stage.
Results: Five-year net survival was 63.7% for those diagnosed during 2001-2003 and 64.6% for 2004-2009. More black than white patients were diagnosed at distant stage, both in 2001-2003 (21.5% vs. 17.2%, respectively) and in 2004-2009 (23.3% vs 18.8%). Survival varied widely between states and there was a slight increase in many states. Survival improved for both blacks and whites, but blacks had lower survival than whites diagnosed during 2001-2003 (54.7% vs. 64.5%) and 2004-2009 (56.6% vs. 65.4%).
Conclusion: Five-year net survival from colon cancer remained stable over time. Survival remained lower in blacks than in whites but the gap narrowed. These finding suggest a need for more targeted efforts to improve screening and to ensure timely, appropriate treatment.
Citation Format: Arica White, Djenaba Joseph, Sun Hee Rim, Christopher J. Johnson, Michel Coleman, Claudia Allemani. Racial disparities in colon cancer survival--United States, 2001-2009 [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 A56.
Abstract A65: Evaluating an under-studied kinase as a potential druggable target for breast cancer
Authors: Kharabsheh Hamzah , Zhou Xiyou , Scott John 
Published: February 2019

Abstract
Breast cancer is the most frequently diagnosed cancer among women, accounting for 23% of all cancer cases. Triple-negative breast cancer (TNBC) is a very aggressive type of breast cancer that occurs in African-American women at three-fold higher frequency compared to Hispanic and Caucasian women. TNBC has a lower 5-year survival rate compared to other subtypes of breast cancer and no targeted therapeutics. In order to identify novel targets for TNBC, replicate kinome-wide RNAi screens were performed with HCC1806, a basal-like TNBC cell line, using a 4-day cell viability assay. Among the RNAi hits, we identified the COASY gene, encoding Coenzyme A synthase (CoAsy), as an under-studied kinase. Thus, we sought to confirm this RNAi hit and evaluate CoAsy for its potential as a novel druggable target for TNBC. CoAsy is a bifunctional enzyme that carries out the last two steps in the coenzyme A (CoA) biosynthetic pathway, including the phosphorylation of dephospho-CoA to generate CoA. Our hypothesis is that TNBC cells require a higher level of CoA synthase activity for cell proliferation compared to normal cells and thus inhibiting CoA synthase represents a novel therapeutic strategy for TNBC. Using four different individual RNAi targeting COASY, we used transient RNAi transfection of a panel of breast cancer cell lines and a non-transformed breast cell line to determine the effect of CoAsy knock down on cell viability and proliferation. Knockdown of CoAsy protein by RNAi was demonstrated by Western blot. Transient COASY RNAi transfection inhibited the cell viability/proliferation assay for several TNBC cell lines, but not for a normal breast cell line. Thus, these data suggest that knockdown of CoAsy may preferentially inhibit cell proliferation of breast cancer cell lines. In addition, Western blot was performed to determine and compare the expression of CoAsy in a panel of breast cancer cell lines and nontransformed cell lines. Ongoing studies are investigating the dependence of cell line viability and proliferation on the expression level of CoAsy by creating stable inducible shRNA cell lines.
Citation Format: Hamzah Kharabsheh, Xiyou Zhou, John Scott. Evaluating an under-studied kinase as a potential druggable target for breast 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 A65.