bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A074: Aberrant activation of a gastrointestinal transcriptional circuit in prostate cancer mediates castration resistance
Authors: Shukla Shipra , Cyrta Joanna , Murphy Devan , Walczak Edward , Ran Leili , Agrawal Praveen , Xie Yuanyuan , Chen Yuedan , Wang Shangqian , Zhan Yu , Wong Wai Pung E. , Sboner Andrea , Beltran Himisha , Mosquera Juan-Miguel , Sher Jessica , Cao Zhen , Wongvipat John , Koche Richard P. , Gopalan Anuradha , Zheng Deyou , Rubin Mark , Scher Howard I. , Chi Ping , Chen Yu
Published: February 2019

Prostate cancer exhibits a remarkable lineage-specific dependence on androgen signaling. Lineage-directed therapy using androgen deprivation has been the mainstay of prostate cancer treatment for 70 years. Castration resistance involves reactivation of androgen signaling or activation of alternative lineage programs to bypass androgen requirement. Our studies found that an aberrant gastrointestinal lineage transcriptome is expressed in ~5% of primary prostate cancer that is characterized by abbreviated response to androgen deprivation therapy and in ~30% of castration-resistant prostate cancer. This program is governed by a transcriptional circuit consisting of HNF4G and HNF1A. Cistrome and chromatin analyses revealed that HNF4G is a pioneer factor that generates and maintains enhancer landscape at gastrointestinal lineage genes, independent of AR signaling. In HNF4G/1A-negative prostate cancer, exogenous expression of HNF4G at physiologic levels recapitulates the GI transcriptome, chromatin landscape and leads to relative castration resistance.

Citation Format: Shipra Shukla, Joanna Cyrta, Devan Murphy, Edward Walczak, Leili Ran, Praveen Agrawal, Yuanyuan Xie, Yuedan Chen, Shangqian Wang, Yu Zhan, Wai Pung E. Wong, Andrea Sboner, Himisha Beltran, Juan-Miguel Mosquera, Jessica Sher, Zhen Cao, John Wongvipat, Richard P. Koche, Anuradha Gopalan, Deyou Zheng, Mark Rubin, Howard I. Scher, Ping Chi, Yu Chen. Aberrant activation of a gastrointestinal transcriptional circuit in prostate cancer mediates castration 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 A074.
Abstract B009: Amalgamated c-MYC activation and p53 loss drives rapid prostate tumorigenesis and lethal epididymis tumors in Ai-Myc model
Authors: Wang Wei , Meng Yanling , Dong Bingning , Yang Feng
Published: February 2019

c-Myc is one of the most frequently amplified genes in human cancers, including prostate cancer (PCa). It is also frequently overexpressed in PCa as early as prostatic intraepithelial neoplasia (PIN). c-Myc overexpression has been shown to induce pathologic changes of mouse prostate, from mostly normal histology, hyperplasia, mPIN, to invasive prostate tumors. Here we describe an Ai-Myc model designed to ectopically express c-Myc and an enhanced luciferase (Luc2) in any tissue in a Cre-inducible manner. To study PCa, Ai-Myc mice were crossed with PB-Cre4 mice to turn on c-Myc expression in prostate epithelia. Once turned on, the expression of transgenes no longer depends on androgen, which allows studying castration of PCa. These mice developed early onset of mPIN along with enhanced apoptosis; only a small fraction of aged mice developed prostate tumors, indicating that c-Myc alone is not sufficient for effectively driving prostate tumorigenesis. Although mutation or loss of p53 is not common in early PCa, it is strongly correlated to PCa disease stages, metastasis, and castration resistance, and p53 is the most significantly altered gene in metastatic castration-resistant PCa. Therefore, we performed conditional ablation of p53 in the PB-Cre4/Ai-Myc mice to model a significant fraction of advanced PCa and to investigate whether loss of p53 inhibits c-Myc oncogene induced apoptosis for robust prostate tumorigenesis. Indeed, these mice rapidly developed prostate tumors; however, within 3-5 months, all mice also unexpectedly developed lethal epididymis tumors, a rare type of cancer in human. Early castration to fully remove epididymis followed by implantation of testosterone pellets allows these mice to develop advanced prostate tumors with metastasis. In summary, we have developed a novel c-Myc induced PCa model and demonstrated that amalgamated c-Myc activation and p53 loss drives rapid prostate tumorigenesis. Our study also unexpectedly revealed a potent tumorigenesis pathway for cancer of epididymis, a rare and poorly understood type of cancer accounting for at most 0.03% of male cancers.

Citation Format: Wei Wang, Yanling Meng, Bingning Dong, Feng Yang. Amalgamated c-MYC activation and p53 loss drives rapid prostate tumorigenesis and lethal epididymis tumors in Ai-Myc model [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 B009.
Abstract B023: Identification and biochemical validation of piperlongumine as a potent therapeutic against neuroendocrine prostate cancer
Authors: Yadav Kamlesh K. , Shameer Khader , Stockert Jennifer A. , Elaiho Cordelia , Readhead Ben , Yadav Shalini S. , Dudley Joel , Tewari Ashutosh K.
Published: February 2019

Introduction and Objectives: Recent studies have highlighted the existence of a highly lethal and drug-resistant variant of prostate cancer (PCa) termed neuroendocrine prostate cancer (NEPC). We have used a genomics-based drug-repositioning approach to identify piperlongumine, a natural product constituent of the fruit of the long pepper (Piper longum), as a potential therapeutic against NEPC. The efficacy of this drug was tested in the NEPC cell line model NCI-H660 and compared to several other PCa cell lines in a modified WST-1 assay. Preclinical testing in mouse xenograft models of NEPC was also undertaken. Finally, the ability of piperlongumine to inhibit p-STAT3 signaling and promote apoptosis in cell lines and extracted tumors were measured by Western blot analyses.

Methods: PCa cell lines (LNCaP, 22Rv1, Du145, PC3, H660, and RWPE) were grown in complete media (RPM1 10% FBS, Advanced DMEM 5% FBS, or Keratinocyte-SFM) and treated with piperlongumine for 3 or 7 days. IC50 values were generated from WST assay data using Prism6. Nude mice (n=5) were injected with 1.5x106 H660 cells on each flank, and intraperitoneally administered with either 2.5mg/kg piperlongumine (n=3) or DMSO (n=2) daily for 3 weeks after tumors formed 200mm3 in volume. Tumor volume was measured daily with calipers. Western blot analyses were performed on protein lysates extracted from tumors and PCa cells treated with 0-10 μM of drug.

Results: Piperlongumine was highly effective in inhibiting the growth of H660 cells

(IC50 = 0.4 μM) compared to LNCaP, 22Rv1, Du145, PC3, and RWPE cells. On average, the growth rate of untreated tumors was 2.7 times greater than those treated was piperlongumine. Treated H660 cells exhibited significant inhibition of p-STAT3 and increases in cPARP1 levels while other cell lines displayed little to no fluctuation.

Conclusions: Using drug-repositioning approaches we have identified a lead compound that inhibits the growth of the highly drug-resistant NEPC cell line NCI-H660. Remarkably, piperlongumine happens to be a water-soluble plant product with no known side effects.

Citation Format: Kamlesh K. Yadav, Khader Shameer, Jennifer A. Stockert, Cordelia Elaiho, Ben Readhead, Shalini S. Yadav, Joel Dudley, Ashutosh K. Tewari. Identification and biochemical validation of piperlongumine as a potent therapeutic against neuroendocrine 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 B023.
Abstract B030: MEK5 downregulation enhances radiosensitization of human prostate cancer cells by inhibiting DNA repair
Authors: Broustas Constantinos G.
Published: February 2019

Radiotherapy is commonly used to treat a variety of solid human tumors, including localized prostate cancer. However, treatment failure almost always ensues due to tumor intrinsic or acquired radioresistance.

Mitogen-activated protein kinase kinase 5 (MAP2K5 or MEK5), belongs to the family of MAP kinases. It is activated by the upstream kinases MEKK2 and MEKK3 at Ser311/Thr315. MEK5, in turn, phosphorylates and activates extracellular signal-regulated kinase 5 (ERK5 or BMK1) at Thr218/Tyr220. MEK5/ERK5 pathway plays a pivotal role in tumor initiation and progression. MEK5 protein is overexpressed in prostate cancer cells compared with normal prostate epithelial cells, and MEK5 levels are correlated with prostate cancer metastasis. High expression of ERK5 in prostate cancer is also found to correlate with poor disease-specific survival and can serve as an independent prognostic factor.

To determine whether the MEK5/ERK5 pathway is activated in response to ionizing radiation (IR), RNA interference was used to deplete MEK5 from PC3 and DU145 cells. Western blot analysis demonstrated that control cells with normal levels of MEK5 exposed to 3-Gy γ-rays had an increase in phospho-ERK5 levels at 5 and 15 min post-IR, diminishing at later time points. No activated ERK5 was detected in MEK5-depleted cells. Downregulation of MEK5 did not impact on cell cycle checkpoint activation in irradiated cells. In contrast, depletion of MEK5 markedly impaired phosphorylation of DNA-PKcs at Ser2056 in response to IR treatment. Furthermore, MEK5 knockdown did not influence the initial appearance of γH2AX or 53BP1 foci after irradiation, but significantly delayed the resolution of radiation-induced γH2AX and 53BP1 foci, detectable even 48 h post-irradiation, indicating a DNA repair defect. Cell based assay showed that nonhomologous end-joining is compromised in PC3 cells with ablated MEK5 protein expression. Finally, long-term clonogenic survival analyses and short-term cell growth assays indicated that MEK5 knockdown sensitized PC3 and DU145 prostate cancer cell lines to IR. Likewise, the topoisomerase II inhibitor etoposide that causes double-strand breaks also sensitized MEK5-depleted cells.

These data indicate that MEK5 influences the response of prostate cancer cells to radiation and MEK5 downregulation is associated with delayed double-strand break repair kinetics. Inhibition of MEK5 in combination with radiation may provide a strategy to improve survival of prostate cancer patients.

Citation Format: Constantinos G. Broustas. MEK5 downregulation enhances radiosensitization of human prostate cancer cells by inhibiting DNA repair [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 B030.
Abstract B047: Biochemical parameters of prostate cancer patients in Nigeria
Authors: Iweala Emeka , Rotimi Solomon , Kanu Faith , Ogo Chidiebere
Published: February 2019

The screening of biochemical parameters of cancer patients and their development into reliable and specific diagnostic and prognostic biomarkers has been reported in several studies. The biochemical signature of prostate cancer patients in Nigeria may vary from others and can serve as important leads in discovery of new biomarkers for the disease. This will ultimately provide more information on the specific causes and prognosis of the disease as well as improve its diagnosis and management. This study examined some biochemical parameters including alanine transaminase (ALT), alkaline phosphatase (ALP), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TRIG), reduced glutathione (GSH), lipid peroxidation and peroxidase (POD) in the plasma of prostate cancer patients and controls. The data obtained indicate that there were no significant differences in the ALT, LDL, HDL, and POD while ALP and TRIG were significantly increased. Also, there was a significant reduction in GSH. This indicates the possible implication of ALP, TRIG, and GSH in prostate cancer disease in Nigeria and their potential to be further developed into diagnostic and prognostic biomarkers.

Citation Format: Emeka Iweala, Solomon Rotimi, Faith Kanu, Chidiebere Ogo. Biochemical parameters of prostate cancer patients in Nigeria [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 B047.
Abstract B048: Androgen metabolism and incidence of prostate cancer in Nigeria
Authors: Rotimi Solomon , Ogo Chidiebere , Ogunlana Olubanke , Chinedu Shalom , Iweala Emeka
Published: February 2019

The risk of prostate cancer among blacks, especially of Nigerian descent, is higher than other races. This could be attributed to biologic and genetic variability. The role of androgen metabolism in prognosis of prostate cancer has been delineated and reported. One of the enzymes involved in androgen metabolism is CYP3A4, which has not been studied in Nigerian men afflicted with prostate cancer. Racial differences in this functional gene may contribute to variations in incidence of prostate cancer across ethnic divides. Therefore, identifying a diagnostic and prognostic biomarker such as CYP3A4 polymorphism for prostate cancer in black men will improve the treatment and management of the disease. In this study, we investigated the genotypes of CYP3A4 of prostate cancer patients from Nigeria for possible correlation to the high incidence of the disease in Nigerian men. The results obtained showed a preponderance of the GG genotypes, which indicates a possible correlation between this genotype of CYP3A4 and higher risk of prostate cancer among Nigerian men.

Citation Format: Solomon Rotimi, Chidiebere Ogo, Olubanke Ogunlana, Shalom Chinedu, Emeka Iweala. Androgen metabolism and incidence of prostate cancer in Nigeria [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 B048.
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

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

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

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

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

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

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 >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 >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

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

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

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.
Abstract A91: [Advocate Abstract:] Evidence-based, human-powered, patient-centric
Authors: Fuller Juliana
Published: February 2019

The Lymphoma Research Foundation (LRF) is the nation's largest nonprofit organization devoted exclusively to funding innovative lymphoma research and providing people with lymphoma and health care professionals with up-to-date information about this type of cancer. We are dedicated to funding biomedical research focused on the origins, treatment, and identification of a cure for lymphoma; to raising public awareness of the disease; and to providing support and services to people with lymphoma, their families, and caregivers. The Lymphoma Research Foundation has awarded more than $60 million in research grants to date. Guided by its world-leading Scientific Advisory Board (SAB), LRF has awarded over 340 evidence-based research grants since its inception, and with its unique commitment to young investigators, LRF continues to fund more than 40,000 research hours for early-career lymphoma scientists each year. LRF assists members of the lymphoma community by providing comprehensive, disease-specific programs and services, including Clinical Trials Information Services, Disease-Specific Publications and Websites, Focus on Lymphoma Mobile Apps, and In-person Workshops and Educational Forums.

Citation Format: Juliana Fuller. [Advocate Abstract:] Evidence-based, human-powered, patient-centric [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 A91.
Abstract B14: Promising effects of a culturally tailored pilot intervention to increase HPV vaccination uptake among female and male adolescents
Authors: Ma Grace X. , Tan Yin , Zhai Shumenghui , Siu Philip , Lai Sarah , Zhu Lin , Ilboudo Adeodat , Wang Min Qi
Published: February 2019

Background: HPV vaccination is recommended for female and male adolescents in the U.S. to prevent HPV-related cancer, yet the uptake remains suboptimal nationwide. Asian American female adolescents have the lowest HPV vaccine rates. Successful HPV vaccine depends heavily on parents' attitudes, perceptions, and willingness to have their adolescents vaccinated.

Objective: This study was designed to test the feasibility and outcomes of a provider-based culturally tailored intervention among Asian American parents and their eligible adolescents.

Methods: Asian American parents (n=120) who had adolescent girls and boys aged 11 to 18 (n=170) were recruited from a primary-care community health center. The primary outcome was first and second shots of HPV vaccination uptake 6 months following the intervention. Secondary outcomes included third shot of HPV vaccine at 6 months after the intervention for adolescents over the age of 12, increase in knowledge and belief in HPV vaccine, and engagement of adolescents in decision-making at post intervention.

Results: Among 170 adolescents, 68% of them received first and second shots of HPV vaccine (73% for girls vs 63% for boys). Among 81 adolescents over the age of 12, 63% of them received third shot (63% for girls vs 76% for boys). Parents' (n=120) knowledge and belief in HPV vaccine and engagement of adolescents in decision-making have significantly increased from baseline to post intervention (p<0.001).

Conclusion: A culturally tailored pilot intervention in a clinical setting demonstrated promising effects, which can potentially yield significant increase in HPV vaccine uptake among Asian American and other underserved ethnic minority female and male adolescents to prevent cancer.

Citation Format: Grace X. Ma, Yin Tan, Shumenghui Zhai, Philip Siu, Sarah Lai, Lin Zhu, Adeodat Ilboudo, Min Qi Wang. Promising effects of a culturally tailored pilot intervention to increase HPV vaccination uptake among female and male adolescents [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 B14.
Abstract B36: Overexpression of PVT1 exons 4A, 4B, and 9 is characteristic of aggressive prostate cancer in males of African ancestry
Authors: Ilboudo Adeodat , Orunmuyi Akintunde , Bach Cuong , Ogunwobi Olorunseun
Published: February 2019

African ancestry is an established nonmodifiable risk factor for aggressive prostate cancer (PCa). The underlying biologic mechanisms are still unclear. We previously demonstrated that exon 9 of PVT1, a long nonprotein coding gene, may be involved in racial disparity in PCa. Using the most recent full-genome variability panel from the 1000 Genomes project, we recently identified a string of 75 SNPs in a 26-kb region spanning PVT1 exons 4A and 4B as consistently showing the highest level of genetic differentiation between African and non-African populations. However, the expression of PVT1 exons 4A, 4B, and 9 in prostate tissues of males of African ancestry (MoAA) has never been investigated. We aimed to determine the expression of PVT1 exons 4A, 4B, and 9 in histologically confirmed normal prostate (n=22), benign tumor prostate (n=35), and malignant tumor prostate tissue (n=28) samples obtained from males who had undergone prostatectomy or transrectal ultrasound-guided biopsy in Nigeria, a sub-Saharan Black African population. Tissues were collected in compliance with Institutional Review Board-approved protocols and histopathologic analysis was performed. RNA extraction, cDNA synthesis, and quantitative-PCR were performed to analyze mRNA expression of PVT1 exon 4A, PVT1 exon 4B, and PVT1 exon 9. There was a statistically significant difference in the expression of PVT1 exon 4A (F(2,61)=9.031, p=0.000); PVT1 exon 4B (F(2,61)=5.294, p=0.004); and PVT1 exon 9 (F(2,61)=3.700, p=0.029) between groups as determined by one-way ANOVA. Tukey post-hoc test revealed mean expression of PVT1 exon 4A = 3.15±0.49 (95% CI [2.13, 4.17]), PVT1 4B = 2.24±0.360 (CI [1.47, 2.95]), and PVT1 exon 9 = 1.644±0.95 (95% CI [1.265, 2.023]) in prostate tumor tissues. The results show an overexpression of PVT1 exon 4A, PVT1 exon 4B, and PVT1 exon 9 in malignant prostate tissue compared with nonmalignant tissue in MoAA. Also, using RNA ISH, PVT1 exon 9 was detected overexpressed primarily in the epithelium of prostate tumor tissue. In conclusion, the results also suggest that (1) the overexpression of PVT1 exon 4A, PVT1 exon 4B, and PVT1 exon 9 is characteristic of PCa in MoAA and (2) overexpression of PVT1 exon 4B and PVT1 exon 9 is specific for PCa, and that PVT1 exon 4B may distinguish between indolent and aggressive PCa in MoAA.

Citation Format: Adeodat Ilboudo, Akintunde Orunmuyi, Cuong Bach, Olorunseun Ogunwobi. Overexpression of PVT1 exons 4A, 4B, and 9 is characteristic of aggressive prostate cancer in males of African ancestry [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 B36.
Abstract B41: Transcriptome-wide profiling identifies novel differential genes associated with health disparity of prostate cancer
Authors: Ali Hamdy , Lung Pei-Yau , Gad Shaimaa , Sholl Andrew , Ali Hamed I. , Zhang Jinfeng , Elmageed Zakaria Y. Abd
Published: February 2019

Background: The incidence and mortality rates of prostate cancer (PCa) are twice as high in African American (AA) than in Caucasian American (CA) men. The molecular alterations associated with this racial disparity have not been fully elucidated. We aim to compare the expression profile of AA and CA men using microarray available data and paraffin-embedded tissues to identify the underlying molecular mechanisms contributing to the disproportionate of PCa among AA men.

Methods: Microarray data of 619 PCa patients, 412 AA and 207 CA, were retrieved from 11 data sets deposited in Gene Expression Omnibus (GEO) database. False discovery rates (FDR) were used for reporting differentially expressed genes and the differentially regulated pathways of these genes were predicted. To validate the microarray data, qPCR analyses were performed in forty paraffin-embedded samples collected from AA and CA men.

Results: Of 362 differential transcripts of array data, TIMP4, LTC4S, SHH, ADIPOQ, and ALOX12 were downregulated (p<0.001) while KLK2, COX5A, AZGP1, AMD1, and ALDH1A3 were upregulated (p<0.001) in PCa AA compared to CA men. qPCR analyses demonstrated that OAT, NKX3, LTC4S, APPL2, TPD52, ALDH, and AMD1 were significantly upregulated (p<0.05) in AA regarding CA men with PCa. Overexpression of OAT, LTC4S, and TPD52 in AA cell lines was confirmed by Western blot analysis. These genes were involved in regulation of cell apoptosis, lipid metabolism, migration, angiogenesis, and response to reactive oxygen species. These transcripts are involved in focal adhesion, PI3K/Akt, EGFR, beta-catenin, and MAPK signaling pathways.

Conclusions: Gene expression data from PCa specimens and microarray suggest that dysregulation of transcripts in PCa of AA compared to CA men may underlie health disparity of PCa. These data might provide new insights into development of reliable diagnostic and prognostic markers of aggressive PCa.

Citation Format: Hamdy Ali, Pei-Yau Lung, Shaimaa Gad, Andrew Sholl, Hamed I. Ali, Jinfeng Zhang, Zakaria Y. Abd Elmageed. Transcriptome-wide profiling identifies novel differential genes associated with health disparity of prostate 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 B41.