bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B062: Proteomic characterization of the secretome from prostate cancer and bone progenitor cell coculture
Authors: Anselmino Nicolás , Páez Alejandra , Vickers Sofía Lage , Cotignola Javier , Valacco Pía , Gueron Geraldine , Vázquez Elba
Published: February 2019

Prostate cancer (PCa) is one of the most frequent sites of primary tumor development in human beings. PCa tumor cells tend to disseminate to and form metastatic lesions in the bone. Given the evident prevalence and clinical significance of bone metastases, unraveling the mechanisms exploited by cancer to form these destructive lesions is of critical interest. This is partly due to the fact that the metastatic cascade encompasses many rate-limiting steps demanding tumor cells to employ new mechanisms at each stage.

Our work aimed at evaluating which soluble factors could mediate the chemical crosstalk between PCa cells and bone progenitor cells. For this purpose, we used coculture transwell systems of PC3 (human PCa cells) with the preosteoclastic Raw264.7 or preosteoblastic MC3T3 cell lines (murine cells), where cells shared the culture media (CMs) without physical contact for 24h.

We employed mass spectrometry—nanoLC-MS/MS(Orbitrap) —for the secretome analysis of the CMs. The obtained spectra were analyzed with the Proteome Discover Software and compared with both human and murine protein databases. Results highlight a differential secretome profile released to the CM when tumor cells are grown in coculture compared to controls. These results could potentially explain the altered mRNA expression levels assessed by RTqPCR in PCa cells growing in coculture, displaying significant upregulation for HO-1 ANXA2, ANXA2R, OPG, and PTHrP (p<0.05). Of note, coculture secretomes showcase highly bone-associated proteins released by tumoral cells such as periostin, cartilage oligomeric matrix protein, OPN, BMP and ILGF-II, IL-7, FGF, Mx-1—involved in prostate carcinogenesis—compared to controls, evidencing a misregulated microenvironment.

These results may offer a better understanding of the molecular affinity between PCa cells and the bone microenvironment, allowing the improvement of PCa patient prognosis

Citation Format: Nicolás Anselmino, Alejandra Páez, Sofía Lage Vickers, Javier Cotignola, Pía Valacco, Geraldine Gueron, Elba Vázquez. Proteomic characterization of the secretome from prostate cancer and bone progenitor cell coculture [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 B062.
Abstract B071: Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer
Authors: Josefsson Andreas , Larsson Karin , Åhs Daniel , Brisby Helena , Damber Jan-Erik , Welén Karin
Published: February 2019

Background: Circulating tumor cells (CTC) are promising biomarkers in advanced prostate cancer. Since they are seeded from metastases, they may also serve as liquid biopsies for skeletal metastases that are difficult to sample. The aim of the present study was to evaluate to which extent CTCs reflect the phenotype of skeletal metastases, and thereby their potential to serve as a clinical tool in individualizing treatment of metastatic prostate cancer.

Materials and Method: CTC and tissue from skeletal metastases were sampled from 22 patients (8 GnRH-naïve and 14 castration-resistant) during surgery for spinal cord compression symptoms. CTCs were sampled prior to removal of metastatic tissue, and isolated with AdnaTest ProstateCancerSelect/Detect (Qiagen). Resulting cDNA was preamplified in a multiplex reaction and analyzed for expression of 37 genes related to prostate cancer progression and metastasis with qPCR. RNA was extracted from the metastatic tissue with RNeasy Plus Universal Mini kit (Qiagen), and gene expression was assessed in the same way as for CTCs. EPCAM expression level was used as internal control to enable normalization to epithelial content (CTCs or tumor tissue) of the samples. Correlation of detected signals between matched CTC and tissue was calculated with Pearson correlations.

Results: 12 of the 37 genes displayed expression patterns that were correlating in paired CTC and metastatic samples. Using this subset of genes, the metastases could be grouped similarly to when all 37 genes were included in hierarchical clustering analyses. Using a smaller subset of genes and patients, defined by gene detection frequency in CTC samples, hierarchical clustering of gene expression in CTCs could group the patients similar to when expression data from the metastases were used. In addition, a subset of genes discriminating GnRH-naïve from castration-resistant metastases could be analyzed in CTCs, where it, to a large extent, could identify the same groups of patients.

Conclusion: This study shows that gene expression patterns in CTCs can reflect those of metastases. However, careful selection of the genes to include is important. In addition, insufficient detection sensitivity in CTC analyses limits the range of the genes to be analyzed with current methodology. Taken together, the results imply that CTC phenotyping is a promising tool for individualized therapy in metastatic prostate cancer.

Citation Format: Andreas Josefsson, Karin Larsson, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén. Circulating tumor cells as liquid biopsies of skeletal metastases from 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 B071.
Abstract B073: Stat5a/b blockade sensitizes prostate cancer to radiation through inhibition of Rad51 and DNA repair
Authors: Maranto Cristina , Udhane Vindhya , Dagvadorj Ayush , Hoang David T. , Gu Lei , Alexeev Vitali , Malas Kareem , Cardenas Karmel , Koptyra Mateusz , Brody Jonathan R. , Rodeck Ulrich , Bergom Carmen , Iczkowski Ken A. , Jacobsohn Ken , See William , Schmitt Sara M. , Nevalainen Marja T.
Published: February 2019

Purpose: The standard treatment for organ-confined prostate cancer (PC) is surgery or radiation, and locally advanced PC is typically treated with radiotherapy alone or in combination with androgen-deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in PC, and if Stat5 inhibition may provide a novel strategy to sensitize PC to radiation therapy.

Experimental Design: Stat5a/b regulation of DNA repair in PC was evaluated by comet assay and clonogenic survival assay, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end-joining (NHEJ) DNA repair. For HR DNA repair, Stat5a/b regulation of Rad51 and the mechanisms underlying the regulation were investigated in PC cells, xenograft tumors, and patient-derived PCs ex vivo in 3D explant cultures. Stat5a/b induction of Rad51 and HR DNA repair and responsiveness to radiation were evaluated in vivo in mice bearing PC xenograft tumors.

Results: Stat5a/b is critical for Rad51 expression in PC via Jak2-dependent mechanisms by inducing Rad51 mRNA levels. Consistent with this, genetic knockdown of Stat5a/b suppressed HR DNA repair while not affecting NHEJ DNA repair. Pharmacologic Stat5a/b inhibition potently sensitized PC cell lines and PC tumors to radiation, while not affecting radiation sensitivity of the neighboring tissues.

Conclusion: This work introduces a novel concept of a pivotal role of Jak2-Stat5a/b signaling for Rad51 expression and HR DNA repair in PC. Inhibition of Jak2-Stat5a/b signaling sensitizes PC to radiation and, therefore, may provide an adjuvant therapy for radiation to reduce radiation-induced damage to the neighboring tissues.

Citation Format: Cristina Maranto, Vindhya Udhane, Ayush Dagvadorj, David T. Hoang, Lei Gu, Vitali Alexeev, Kareem Malas, Karmel Cardenas, Mateusz Koptyra, Jonathan R. Brody, Ulrich Rodeck, Carmen Bergom, Ken A. Iczkowski, Ken Jacobsohn, William See, Sara M. Schmitt, Marja T. Nevalainen. Stat5a/b blockade sensitizes prostate cancer to radiation through inhibition of Rad51 and 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 B073.
Abstract B075: The role of TET1 and hydroxymethylation in high-risk prostate cancer
Authors: Smeets Elien , Spans Lien , Prekovic Stefan , Broeck Thomas Van den , Moris Lisa , Gevaert Thomas , Helsen Christine , Joniau Steven , Claessens Frank
Published: February 2019

The Ten-eleven translocation (TET) proteins are dioxygenases that catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) as part of the DNA demethylation pathway. Gene silencing through cytosine methylation contributes to cancer formation, but how hydroxymethylation affects gene expression is largely unknown. In this work, TET1 and genomic hydroxymethylation were investigated in a high-risk prostate cancer cohort for which exome sequencing data are available (1).

Immunohistochemical analysis of tumor versus nontumor prostate biopsies from high-risk prostate cancer showed a strong reduction of genome-wide 5hmC and milder but still significant reduction of 5mC levels in prostate cancer tissue compared to control tissue. Copy number analysis of high-risk prostate cancer showed a loss of the TET1 genomic region in 6 out of 39 samples of our cohort. As expected, the mRNA levels of TET1 were decreased in these tumor samples. Recently, an alternative promoter of TET1 was discovered. This promoter generates a novel isoform lacking the CXXC-domain, which is called TET1ALT (2). We therefore performed functional analyses of the two TET1 promoters in prostate cancer cells. Interestingly, the promoter controlling expression of the endogenous full-length TET1 is less active in prostate cancer cell line PC-3, while the alternative promoter generating TET1ALT is more active in these cells. This is shown by luciferase constructs driven by the two promoter regions.

In conclusion, our findings indicate that there is a drop in (hydroxy)methylation levels in high-risk prostate cancer that correlates with decreased TET1 expression levels and in some cases by a copy number loss of TET1. We are currently working on a more detailed analysis of TET1 promoter usage and control. This will unravel the regulation of hydroxymethylation in prostate cancer, which is crucial for the understanding of prostate cancer development and progression.

References:

1. Spans L, Van den Broeck T, Smeets E, et al. Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1. Oncotarget 2016;7(17):24326-38.

2. Good CR, Madzo J, Patel B, et al. A novel isoform of TET1 that lacks a CXXC domain is overexpressed in cancer. Nucleic Acids Res 2017;45(14):8269-81.

Citation Format: Elien Smeets, Lien Spans, Stefan Prekovic, Thomas Van den Broeck, Lisa Moris, Thomas Gevaert, Christine Helsen, Steven Joniau, Frank Claessens. The role of TET1 and hydroxymethylation in high-risk 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 B075.
Abstract B077: 3D reconstruction and machine learning-based analysis of prostate cancer from histologic images
Authors: Ruusuvuori Pekka , Valkonen Mira , Kartasalo Kimmo , Visakorpi Tapio , Nykter Matti , Latonen Leena
Published: February 2019

Prostate cancer is multifocal in nature, and histologic grading is the key clinical prognostic factor. Imaging-based tools are required for decreasing the subjectivity of histologic grading, providing quantitative information of the tissue and the pathologic changes in it, and to allow quantitative associations of histologic alterations with other types of information collected from the tissues, such as genomic data.

To enable imaging-based diagnosis, methods for quantifying both the naturally occurring heterogeneity of normal tissue and morphologic changes due to pathology need to be developed. On the other hand, accurate distinction of early pathologic changes from natural variation could provide novel information about development of tumors. Furthermore, the 3-dimensional evolution and growth patterns of tumors should be considered as, traditionally, histologic scoring mostly relies on individual tissue sections extracted from their spatial context.

To build nonsubjective histologic analysis tools, and to model the multifocality of prostate cancer within the organ, we use analysis of histologic images to quantitatively describe prostate cancer. We present an approach for 1) imaging the whole organ into digital pathology slides, 2) reconstruction of the 3D structure of the organ based on the histologic images, and 3) both feature-based and deep learning-based quantitative analysis of the digital images. Our approach enables characterization of tissue morphology with numerical descriptors, enabling subsequent analysis, such as determining the likelihood of pathologic changes. Our current efforts show how heterogeneity in prostate tissue due to spatial location or cancer can be quantified with image-derived features. In addition, we use mouse prostate as a model to visualize and reconstruct a whole organ from high-resolution whole-slide images, and combine tissue type classification in the 3D reconstruction. Further development of these methods and their application for human samples will improve our understanding of human prostate pathologies and cancer evolution within the 3D environment of the organ.

Citation Format: Pekka Ruusuvuori, Mira Valkonen, Kimmo Kartasalo, Tapio Visakorpi, Matti Nykter, Leena Latonen. 3D reconstruction and machine learning-based analysis of prostate cancer from histologic images [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 B077.
Abstract B078: Expression of activated STAT3 in the epithelial cells of hormone-naïve prostate cancer
Authors: Krzyzanowska Agnieszka , Don-Doncow Nicholas , Marginean Felicia-Elena , Watson William , Hellsten Rebecka , Bjartell Anders
Published: February 2019

Introduction: The Signal Transducer and Activator of Transcription 3 (STAT3) pathway is thought to be phosphorylated (pSTAT3) and constitutively activated in prostate cancer (PCa). Previous results from our laboratory showed high pSTAT3 levels in PCa metastases. In the present study we investigated the expression of pSTAT3 in tissue microarrays of two cohorts of localized hormone-naïve PCa patients and correlated it with disease outcome.

Methods: The expression of pSTAT3 in the nuclei of epithelial cells of prostatic glands was examined in two TMAs of paraffin-embedded prostatic tissue. The TMAs consisted of tissue originated from hormone-naïve radical prostatectomy patients from two different sites: Malmö (n=300) and Dublin (n=99).

Results: In the Malmö cohort, the average expression levels of pSTAT3 in the epithelial cells of benign glands were significantly higher than in the cancerous glands. Patients with low pSTAT3 levels in the epithelial cells of the cancerous glands showed reduced times to biochemical recurrence, compared to those with higher levels; however, adding the pSTAT3 expression data to Gleason score or pathologic T stage did not improve their prognostic values. The results for the Dublin cohort showed similar trends.

Conclusions: Low pSTAT3 expression in epithelial cells of cancerous prostatic glands in hormone-naïve PCa was associated with faster disease progression; however, pSTAT3 is unlikely to be a good biomarker in the early stages of PCa.

Citation Format: Agnieszka Krzyzanowska, Nicholas Don-Doncow, Felicia-Elena Marginean, William Watson, Rebecka Hellsten, Anders Bjartell. Expression of activated STAT3 in the epithelial cells of hormone-naïve 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 B078.
Abstract B093: Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test
Authors: Donovan Michael Joseph , Fernandez Gerardo , Scott Richard , Zeineh Jack , Koll Giovanni , Khan Faisal , Gladoun Nataliya , Charytonowicz Elizabeth , Tewari Ash , Cordon-Cardo Carlos
Published: February 2019

Background: Postoperative risk assessment remains an important variable in the treatment of prostate cancer. We aimed to develop and validate a tissue-based on-slide prognostic risk model test to identify which patients would benefit most from early intervention.

Methods: Prospectively designed retrospective study utilizing 892 patients, post radical prostatectomy, followed for a median of 8 years. We constructed a matched 50:50 training and test cohort to identify compound features using protein multiplex immunofluorescence combined with novel morphometry generated by advanced image analysis and machine learning tools. The primary endpoint was the development of a postoperative clinical failure (CF) including PSA rise post-adjuvant treatment, or metastasis or prostate cancer specific mortality. Time to event C-index and Kaplan-Meier were used to assess accuracy.

Results: The Precise postop model in training (n=306) selected 4 compound imaging features and one clinical variable to predict CF with a performance C-index of 0.82, [95%CI: 0.76-0.86], HR:6.7, [95%CI: 3.59-12.45], p <0.00001. Of importance, the derived androgen receptor/Ki67/morphometric imaging features successfully replaced the subjective clinical Gleason grading in the final model. In validation, increasing Precise postop scores predicted shortened time to disease progression (n=284) with a C-index 0.77 [95%CI: 0.72-0.81], HR=5.4, [95%CI: 2.74-10.52], p <0.00001.

Conclusion: Patients with high Precise postop scores had a higher likelihood of having disease progression within 8 years with a reduced durable response to androgen-deprivation therapy. The Precise postop algorithm-based model guided by machine learning replaces subjective Gleason grading with novel image features that combine morphometry with biologic attributes that more accurately reflect disease potential.

Citation Format: Michael Joseph Donovan, Gerardo Fernandez, Richard Scott, Jack Zeineh, Giovanni Koll, Faisal Khan, Nataliya Gladoun, Elizabeth Charytonowicz, Ash Tewari, Carlos Cordon-Cardo. Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test [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 B093.
Abstract IA05: Emerging therapeutic strategies for androgen indifferent prostate cancer
Authors: Beltran Himisha
Published: February 2019

The development of castration resistance in prostate cancer most commonly involves reactivation of androgen receptor (AR) signaling; this knowledge has informed the clinical development of potent AR-targeted agents now commonly used in the clinic. However, a subset of prostate cancers may evolve under therapeutic pressure of the AR towards non-AR driven, or “androgen indifferent,” disease. This has been associated with aggressive clinical features with repeat biopsies enriched with TP53 and RB1 genomic loss, overexpression of MYCN, epigenetic changes, and activation of alternative lineage programs such as neuronal and neuroendocrine pathways. One extreme manifestation is complete transformation to a small cell/neuroendocrine carcinoma with loss of AR expression. Although castration-resistant neuroendocrine prostate cancer evolves clonally from prostate adenocarcinoma likely through a trans-differentiation process, it acquires molecular alterations seen in other poorly differentiated neuroendocrine cancers. This talk will focus on emerging biomarker-driven therapeutic strategies for androgen-indifferent disease, including updates on targeting the N-myc/Aurora kinase A complex, the potential role for epigenetic therapies, and new data to inform ADC and immunotherapy development for this subset.

Citation Format: Himisha Beltran. Emerging therapeutic strategies for androgen indifferent 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 IA05.
Abstract IA09: Early, highly specific risk stratification for lethal prostate cancer using a prespecified statistical model based on four kallikrein markers in blood
Authors: Lilja Hans
Published: February 2019

Prostate-specific antigen (PSA) and human kallikrein-related peptidase 2 (hK2) are 237-aa single chain glycoproteins with uniquely different serine proteinase activity and products of two highly homologous primate-lineage specific, androgen receptor-regulated genes (KLK3 and KLK2) with abundant prostate-restricted expression. In blood from healthy middle-aged men not subject to PSA testing, million-fold lower levels of multiple noncatalytic forms of PSA and hK2 are very strongly associated with 20+ year- risk of metastasis or death from prostate cancer (PC), whereas prospective randomized trials in Europe show that early detection by systematic PSA testing reduces PC-specific deaths but remains controversial due to harm from overdiagnosis and overtreatment. Population-based findings of longer lead time at Gleason Grade Group ≥2 (GGG2) versus GGG1 at PC diagnosis provide evidence of grade progression over time. However, our estimates of a ≤6% risk of ≥GGG2-PC by a predefined statistical model based on four kallikrein markers in blood in middle-aged men with modestly elevated PSA is strongly associated with 15-20-year risk of PC death or metastasis below population average. By contrast, a smaller subset of these middle-aged men with modestly elevated PSA and a ≥6% four kallikrein risk-score have 15-20-year risk of PC death or metastasis that is multiple folds higher than the population average. Although evidence exists that mutations in germline DNA are associated with PC-death or metastasis, it is currently unclear how we could integrate these findings in programs aimed at early specific detection of lethal PC.

Citation Format: Hans Lilja. Early, highly specific risk stratification for lethal prostate cancer using a prespecified statistical model based on four kallikrein markers in blood [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 IA09.
Abstract IA11: Germline genetic testing in prostate cancer
Authors: Pritchard Colin C.
Published: February 2019

Recent studies have revealed a higher than expected frequency of germline autosomal dominant cancer predisposition gene mutations in men with high-risk and advanced prostate cancer. These mutations have important implications for risk-stratification and precision therapy, as well as for cancer risks in family members. This has led to relatively rapid adoption of germline panel genetic testing in clinical practice, and facilitated identification of cancer-free men who are mutation carriers at elevated risk for prostate cancer. This talk will cover the spectrum of germline cancer predisposition genes associated with prostate cancer, issues surrounding clinical genetic panel testing, and emerging data on how germline genetic information may be used to inform screening and risk.

Citation Format: Colin C. Pritchard. Germline genetic testing 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 IA11.
Abstract IA20: Lineage plasticity in antiandrogen resistance
Authors: Abida Wassim
Published: February 2019

Resistance to the novel androgen receptor (AR)-directed therapies enzalutamide and abiraterone acetate can evolve with an aggressive clinical phenotype and atypical histology, including neuroendocrine features. Genomic studies have also revealed enrichment in TP53 and RB1 alterations in advanced metastatic CRPC when compared with primary disease. In recent work, the Sawyers and Goodrich groups have independently shown that concurrent loss of TP53 and RB1 confers resistance to antiandrogen and lineage plasticity through upregulation of the transcription factor SOX2. These studies implicate key tumor suppressors in lineage switching in resistant prostate cancer, and suggest that antiandrogen resistance may be targeted by epigenetic agents in advanced disease.

Citation Format: Wassim Abida. Lineage plasticity in antiandrogen 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 IA20.
Abstract IA24: Making immunotherapy work in prostate cancer
Authors: Gulley James L.
Published: February 2019

Immunotherapeutic approaches can only be successful when the immune system recognizes the tumor and generates a response that causes immune effector cells to seek out and destroy the tumor. Recent clinical advances in immunotherapy have capitalized on tumors that the immune system has developed an immune response to, but is prevented from killing by specific immune checkpoints that protect normal tissue from autoimmune attack. Tumor cells use these checkpoints to escape immune attack. However, many tumors, including the vast majority of prostate tumors, do not have an underlying immune response. A variety of modalities, some more efficient than others, can lead to immune recognition, but cannot be fully effective when used as monotherapies. Optimal clinical benefit will be achieved with rational combination therapies that generate a robust immune response and allow those generated effector cells to remain functional within the tumor microenvironment.

Citation Format: James L. Gulley. Making immunotherapy work 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 IA24.
Abstract A05: Genetic factors associated with racial disparities of liver cancer
Authors: Cui Zihan , Wang Zhe , Zhao Tingting , Sang Qingxiang Amy , Zhang Jinfeng
Published: February 2019

Liver cancer (hepatocellular carcinoma [HCC]) is a leading cause of cancer-related morbidity and mortality worldwide. Racial disparities in HCC have been well-known among several racial and ethnic groups in the U.S. The incidence rates (per 100,000/year) for non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanics (HISP), and Asian/Pacific Islanders (API) are 7.0, 15.7, 11.8, and 18.6, respectively. The 5-year survival rates (%) for the four population groups are 18.2, 15.1, 19.2, and 24.4, respectively. NHWs have the lowest incidence rates, while APIs have the highest 5-year survival rate among the four racial and ethnic groups. Previous studies have indicated that socioeconomic status, in general, is associated with HCC health disparity; however, they alone cannot fully explain the disparity between different racial and ethnic groups. Few studies have investigated the biologic factors that may be associated with the health disparity in HCC. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we have performed a comprehensive analysis of differentially expressed genes and pathways between Caucasian and Asian American liver cancer patients and identified hundreds of differentially expressed genes. We also identified a handful of genes that are differentially mutated between Caucasian American and Asian American HCC patients using the somatic mutation data from TCGA. We will discuss in details the differentially expressed genes and pathways, and their implications for the HCC health disparity. As far as we know, our study represents the largest-scale study on the biologic factors for HCC health disparity between Caucasian and Asian American liver cancer patients.

Note: This abstract was not presented at the conference.

Citation Format: Zihan Cui, Zhe Wang, Tingting Zhao, Qingxiang Amy Sang, Jinfeng Zhang. Genetic factors associated with racial disparities of liver 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 A05.
Abstract A15: Challenges and successes in delivering a cancer survivorship support program among rural Latinas
Authors: Ceballos Rachel M.
Published: February 2019

Introduction: Rates of cancer survivorship are increasing for most cancers. However, Latina cancer survivors tend to experience lower quality of life and higher levels of distress following cancer compared to non-Latina Whites (NLW). While social support resources can alleviate the negative psychosocial impact of cancer sequelae, there are often limited resource availability and uptake among Latina cancer survivors.

Objective: This presentation will include descriptions of the qualitative and quantitative study design, recruitment strategies, cultural adaptations of the intervention, challenges, and successes in data collection and intervention delivery.

Methods: This study included a qualitative needs assessment of Latina survivors of breast and gynecologic cancers living in a rural region of Washington State, development of a 10-week Spanish-language survivor-support program, and a randomized control trial (RCT) whose effectiveness was evaluated with psychosocial and biologic outcomes. Intervention delivery and qualitative and quantitative data collection were conducted by promotores (lay health workers).

Conclusion: Challenges and successes of conducting the qualitative assessment, delivering the intervention, and data collection will be discussed. Future studies can build on the methodologic insight gained from this project.

Citation Format: Rachel M. Ceballos. Challenges and successes in delivering a cancer survivorship support program among rural Latinas [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 A15.
Abstract A17: [Advocate Abstract:] Culturally sensitive outreach for clinical trials and research studies is key to addressing biologic contributors to health disparities
Authors: Holloway Jamie
Published: February 2019

Background: I will present a quick look at outcome disparities and some specific cases where there is a clear biologic basis for outcome disparities in cancer. It would also be relevant to look at some statistics of the racial makeup of participants in clinical trials.

Data: I will incorporate the survey results from a high school student (who will be listed as a coauthor) that will address attitudes toward clinical trial participation, stratified by race. I will also present some of the strategies that a team I am leading at Howard University hopes to employ as they use social media and local outreach to increase enrollment of African American patients in the MBC project.

Citation Format: Jamie Holloway. [Advocate Abstract:] Culturally sensitive outreach for clinical trials and research studies is key to addressing biologic contributors to health disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A17.
Abstract A51: Disparities in cervical cancer patients by race and histology
Authors: Huang Ying , Tarney Christopher , Tian Chunqiao , Bateman Nicholas , Conrads Thomas , Hamilton Chad , Maxwell George , Darcy Kathleen
Published: February 2019

Introduction: The incidence and mortality of cervical cancer in the United States has decreased over the last four decades given screening and vaccination programs. Nevertheless, this statement cannot be generalized among all races. We investigated cancer-related mortality (CRM) and non-cancer related mortality (NCM) for cervical cancer patients among racial groups.

Methods: Women diagnosed with cervical cancer from 1990-2014 were identified from the Surveillance, Epidemiology and End Results database. Racial disparities in survival for non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic (HSP), and Asian/Pacific Islander (API) patients were compared using a competing risk model that accounted for both CRM and NCM. Analyses were particularly performed by histologic subtype for squamous cell carcinoma (SCC) vs. adenocarcinoma and adenosquamous carcinoma (AC/ASC).

Results: 62,887 cervical patients were analyzed: 34,520 (54.8%) NHW, 8,650 (13.8%) NHB, 13,937 (22.2%) HSP, and 5,780 (9.2%) API. From 1990 to 2014, the proportion of SCC has decreased, while the proportion of AC/ASC has increased among all racial groups with the exception of NHB patients who saw a smaller increase in AC/ASC (P<.0001). NHB patients were more likely to be diagnosed at advanced stages, and upon adjusting for known prognostic factors, NHB patients had the worst CRM and NCM among all racial groups (P<.0001). HSP patients had better CRM for both SCC and AC/ASC (P<.0001), whereas API patients had worse CRM for AC/ASC (P<.0001) when compared to NHW patients.

Conclusions: Both CRM and NCM significantly vary among racial groups, with the worst survival being seen in NHB patients.

Citation Format: Ying Huang, Christopher Tarney, Chunqiao Tian, Nicholas Bateman, Thomas Conrads, Chad Hamilton, George Maxwell, Kathleen Darcy. Disparities in cervical cancer patients by race and histology [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 A51.
Abstract A58: Racial disparities in head and neck cancers in an urban hospital
Authors: Zeigler-Johnson Charnita , Keith Scott , Guiles Frances , Cognetti David , Bar-Ad Voichita , Axelrod Rita
Published: February 2019

Introduction: Although head and neck cancer incidence rates are higher for white residents in Philadelphia, PA, related mortality rates are highest for black residents. It is not clear how clinical factors and risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with advanced head and neck cancers in a diverse sample of patients from a Philadelphia hospital.

Methods: Cancer registry data from Thomas Jefferson University (957 beds, Philadelphia, PA) were used to obtain clinical records from 922 head and neck cancer patients diagnosed from 2011-2015. One patient of other race was removed from these analyses. We examined advanced cancer among the primary racial groups represented in our hospital population. Chi-square tests were used to examine differences in categorical variables. The Kruskal-Wallis test was used to compare continuous variables. Logistic and Cox regression models were designed to examine independent associations with advanced disease and time to mortality. Covariates included age, race, tumor stage, HPV status, smoking status, gender, and treatment type.

Results: Our sample included 921 patients (788 white, 96 black, 37 Asian). Our descriptive analysis showed that among the three groups, blacks were more likely to be female (p=0.033). Positive HPV status was most prevalent for white patients (p=0.004). Oral and nasopharyngeal cancers were most common among Asians, and oropharyngeal cancers were most common among whites. In univariate analysis, black patients were most likely to die from their cancer. Multivariable analyses showed that current smoking (compared to never smoking) was associated with T3/T4 stage at diagnosis (OR=6.85, 95% CI=1.11-42.2). Time to death was significantly shorter for older individuals (HR=1.02 95% CI=1.01-1.05), current smokers (HR=2.24, 95% CI=1.25-4.00) and patients receiving radiation only (HR=7.70, 95% CI=1.38-42.95). Positive HPV status was protective (HR=0.29, 95% CI=0.19-0.44). No significant race effects were observed in these models.

Conclusions: The results of this study suggest that race is not independently associated with head and neck cancer or associated mortality. These results also suggest that some risk factors for head and neck cancer and related outcomes may be modified by educational and behavioral interventions.

Citation Format: Charnita Zeigler-Johnson, Scott Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita Axelrod. Racial disparities in head and neck cancers in an urban hospital [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 A58.
Abstract A67: The effects of SAHA and EGCG on metastatic potential in triple-negative breast cancer
Authors: Lewis Kayla Ashlyn , Tollefsbol Trygve O.
Published: February 2019

Approximately 12% of breast cancers are triple negative, and are nearly two times more common in black women that white women. These cancers have a poorer short-term prognosis than other types due to the lack of targeted therapies. The purpose of this study was to use suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor used to treat cutaneous T cell lymphoma (CTCL), and epigallocatechin-3-gallate (EGCG), a DNA methyltransferase (DNMT) inhibitor found in green tea, to decrease metastatic potential in triple-negative breast cancer (TNBC) cells. SAHA and EGCG were administered singly and in combination to determine if the combination was more efficacious than either compound alone in their effects on cell viability and foci, or colony, formation. RNA and protein analysis was performed to evaluate epithelial versus mesenchymal markers, while scratch tests provided phenotypic evidence of changes in migration capability. We found that the combination of SAHA and EGCG at optimal concentrations of 3 μM SAHA and 5 μM reduced breast cancer cellular viability in an additive manner while this combination had no significant effect on control breast cells. This is a very low dose of EGCG compared to most anticancer studies. The colonies formed by the breast cancer cells decreased in size and number. Interestingly, EGCG administered singly increased colony formation. The combination of SAHA and EGCG also reactivated estrogen receptor alpha (ERα), and decreased the expression of miR-221/222, which are microRNAs involved in migration and invasion. The scratch tests supported these findings, with the breast cancer cells exhibiting a decreased ability to migrate. These findings demonstrate the abilities of combined SAHA and EGCG to decrease metastatic potential through epigenetic mechanisms in TNBC.

Citation Format: Kayla Ashlyn Lewis, Trygve O. Tollefsbol. The effects of SAHA and EGCG on metastatic potential in triple-negative 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 A67.
Abstract A72: [Advocate Abstract:] Community initiatives for all women's health
Authors: Lucio Araceli
Published: February 2019

My poster will describe four community programs I have established at The Resurrection Project. The first focuses on breast cancer education workshops to address the lack of knowledge, cultural misconceptions, fear, and shame in my community and other underserved communities. The second focuses on breast cancer navigation to address the lack of insurance and cost issues in my community and in other underserved communities. The third focuses on breast cancer survivorship and empowerment to address the need for peer role models in my community and for other underserved communities. The fourth focuses on policy advocacy to address the need for resources for other underserved women.

Citation Format: Araceli Lucio. [Advocate Abstract:] Community initiatives for all women's health [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 A72.
Abstract A75: [Advocate Abstract:] Colorectal cancer and health disparities with African American population
Authors: Nalls Erika
Published: February 2019

This poster will focus on some of the specific challenges around colorectal cancer within African American communities. It will look at current statistics, barriers to better outcomes in the areas of screening, prevention and survivorship. It will also look at issue (controlled for income and education) and still lack of more positive outcomes.

All information provided will be evidence based. I have used information from Colon Cancer Alliance for a work event that I organized and will most likely use some of this again, along with other evidence-based research. It will also raise questions.

Citation Format: Erika Nalls. [Advocate Abstract:] Colorectal cancer and health disparities with African American population [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 A75.
Abstract B39: A pilot study of neuropsychological functions, APOE, and amyloid imaging in patients with gliomas
Authors: Correa Denise , Kryza-Lacombe Maria , Zhou Xiaosun , Baser Raymond , Beattie Brad , Beiene Zodina , Orlow Irene , Humm John , DeAngelis Lisa , Weber Wolfgang , Osborne Joseph
Published: February 2019

Patients with brain tumors treated with radiotherapy (RT) often develop cognitive dysfunction, and recent studies suggest that the apolipoprotein (APOE) ε-4 allele may influence cognitive outcome. The ε-4 allele promotes beta (β) amyloid deposition in the cortex, and preliminary evidence suggests that RT may be associated with β-amyloid deposition. In this pilot study, we assessed neuropsychological functions and β-amyloid retention using 18F-florbetaben PET in a subset of brain tumor patients who participated in our study of APOE polymorphisms and cognitive functions. Twenty glioma patients treated with conformal RT ± chemotherapy participated in the study: 6 were APOE ε-4 carriers and 14 were non-ε-4 carriers. Patients completed a neuropsychological reevaluation and brain MRI and 18F-florbetaben PET scans. The results of Wilcoxon rank sums test comparisons between prior and current assessments showed a significant decline in selective attention (Brief Test of Attention, p=0.018), and a near-significant decline in verbal learning (Hopkins Verbal Learning Test-Learning, p=0.07). Comparisons between assessments by APOE status showed a significant decline in attention and working memory (WAIS-III digits forward, p=0.028 and digits backward, p=0.032) among APOE ε-4 carriers. Comparisons of PET regional standard uptake value ratios (SUVRs) showed near-significant differences for the medial temporal cortex (p=0.069) and the putamen (p=0.069), with non-ε-4 carriers having higher SUVRs. The findings suggest that glioma patients may experience progressive worsening in attention and executive functions several years after treatment with RT ± chemotherapy, and that the APOE ε-4 allele may moderate cognitive decline.

Note: This abstract was not presented at the conference.

Citation Format: Denise Correa, Maria Kryza-Lacombe, Xiaosun Zhou, Raymond Baser, Brad Beattie, Zodina Beiene, Irene Orlow, John Humm, Lisa DeAngelis, Wolfgang Weber, Joseph Osborne. A pilot study of neuropsychological functions, APOE, and amyloid imaging in patients with gliomas [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 B39.
Abstract B57: Distinct genomic alterations in prostate cancer of African American men
Authors: Dobi Albert , Petrovics Gyorgy , Li Hua , Young Denise , Chen Yongmei , Kagan Jacob , Srivastava Sudhir , Ebner Reinhard , Rosner Inger L. , Cullen Jennifer , Freedman Matthew L. , Sesterhenn Isabell A. , Szallasi Zoltan , Srivastava Shiv
Published: February 2019

This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR01) of the Conference Proceedings.

Note: This abstract was not presented at the conference.

Citation Format: Albert Dobi, Gyorgy Petrovics, Hua Li, Denise Young, Yongmei Chen, Jacob Kagan, Sudhir Srivastava, Reinhard Ebner, Inger L. Rosner, Jennifer Cullen, Matthew L. Freedman, Isabell A. Sesterhenn, Zoltan Szallasi, Shiv Srivastava. Distinct genomic alterations in prostate cancer of African American men [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 B57.