bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract D048: Social support, quality of life and mental health factors affecting Filipino cancer survivors
Authors: Valdez-Dadia Annalyn
Published: September 2020

Background: Cancer survivorship rates are increasing and the growing number of cancer survivors will present new challenges to the health care system with regards to follow-up care and long-term health care needs. More specifically, cancer survivors are dealing with the physical and mental health consequences of cancer long after treatments are completed, and many of the physical symptoms and side effects that evolved from such treatments have had long-lasting physical and psychological effects. Studies aimed at understanding how social support and quality of life impacts survivorship is limited and there is a paucity in research investigating factors that affect the health-related quality of life and the long-term health care needs of Filipino cancer survivors. Significance: Physical symptoms of cancer survivors can be detected and treated by health care providers, but any psychological distress experienced by these individuals are not easily identified or assessed. Depression and anxiety are common among individuals diagnosed with cancer and many survivors often report experiencing emotional distress and feelings of abandonment after intensive support during the treatment phase. Objective: This study aims to explore the cultural perceptions of mental health, identify the types of social support that impacts the psychological well-being of Filipino cancer survivors post-treatment, and explore the health-related quality of life and prevalence of psychological distress among Filipino cancer survivors. Methods: Individual, semi-structured interviews were conducted with 10 Filipino cancer survivors residing in Southern California. Thematic analysis was performed to explore and identify cultural perceptions of social support, quality of life and mental health. Results: This exploratory study found that post-treatment needs of Filipino cancer survivors vary by cancer type and treatment received. Although social support (physical and functional) is available, lack of emotional support increases psychological distress and may affect their overall quality of life. Physical health problems are easily identified and readily addressed, but the mental well-being of survivors is often overlooked and rarely discussed. Discussion/Conclusion: Further investigation of post-treatment experiences of Filipino cancer survivors is needed in order to identify the services and resources that would be most beneficial in addressing the emotional support and psychological distress needs during survivorship.

Citation Format: Annalyn Valdez-Dadia. Social support, quality of life and mental health factors affecting Filipino cancer survivors [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D048.
Abstract D051: Targeting ubiquitin receptor ADRM1 for the treatment of quadruple-negative breast cancer
Authors: Karanam Balasubramanyam , Anchoori Ravi , Roden Richard , Yates Clayton
Published: September 2020

Quadruple Negative Breast cancer (QNBC) is a subtype of Triple Negative Breast Cancer (TNBC) with loss of Androgen receptor (AR). We determined the expression of AR and its relationship to breast cancer subtypes, using Gene Expression Omnibus (GEO) profiles that contained racial and clinical outcomes data totaling 1061 patients. Expression of the AR protein level was confirmed in an additional multi-institutional cohort of 197 breast cancer patients, for a total of 1258 patient evaluated. Relative to White women, African American women had higher percentage (81%) of AR-negative tumors, and, for both races, AR-negative tumors correlated with the basal subtype, a shorter time to progression, and worse overall survival (OS) compared to White women. Currently available treatments are unable to eradicate metastatic breast cancer (TNBC and QNBC), and median survival for these patients is only 2–4 years. Improving the survival rates for metastatic disease has been the subject of intense investigation, and new agents and strategies are actively being evaluated. Targeting the UPS (Ubiquitin-proteasome system) with small molecules can an effective can cancer therapy. We have developed an orally-available proteasome inhibitor bis-benzylidine piperidone (RA190), that binds to the ubiquitin receptor RPN13/ADRM1 on the 19S regulatory particle of the proteasome and directly kills cancer cells by triggering proteotoxic stress. The objective of this study is to investigate the expression of ADRM1 in QNBC patients and target ADRM1 with RA190 for the treatment of QNBC., We used forest plot analysis of TCGA patient samples to determine the expression of Ubiquitin receptor ADRM1, and invitro assays to find the sensitivity of RA190 against AR-positive and AR-Negative breast cancer cells. Our results indicate that ADRM1 is significantly elevated and in QNBC breast tumors of African American patients. Our cell culture data show that, AR-positive and AR-Negative breast cancer cells have differential sensitivity in IC50 values to inhibitor RA190. Our findings will advance our knowledge of vulnerable pathways in QNBC/TNBCs optimal control and reveal if this mechanism is more likely to occur in African American patients.

Citation Format: Balasubramanyam Karanam, Ravi Anchoori, Richard Roden, Clayton Yates. Targeting ubiquitin receptor ADRM1 for the treatment of quadruple-negative breast cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D051.
Abstract D062: Mechanistic insights into phase 1b/2 study of chitosan for pharmacologic manipulation of AGE (advanced glycation endproducts) levels in prostate cancer patients
Authors: Brown Shanora G , Sutton Brandon , Biotidara Taiwo , Turner Dave , Wilson Robert , Lilly Michael
Published: September 2020

Lifestyle choices have long been known to have a major role in the development or prevention of cancer. Diet, chronic stress, smoking, poverty, physical activity, and socioeconomic variables are recognized as significant factors in prevention of cancer. Increasingly, these behaviors are studied as variables that affect cancer survivorship and response to treatment as well. One general mechanism through which diet could affect cancer growth is through promoting or inhibiting the accumulation of advanced glycation endproducts. Advanced glycation endproducts (AGEs) are reactive metabolites produced as by-products of sugar metabolism and oxidative stress. Furthermore, among PCa patients, AGE accumulation is higher in blacks with African ancestry (AAs) than in European Americans (EAs). As AGEs appear to promote cancer survival and growth, interventions to limit their accumulation may be viewed as potential cancer therapeutic agents. Chitosan, a polysaccharide obtained from shellfish or mushrooms that is thought to be poorly absorbed, directly binds AGE-modified proteins in aqueous solutions. No studies to date have demonstrated that chitosan can reduce either serum or tissue levels of AGEs in humans with AGE-related diseases. The investigators are conducting a Phase 1, assay-guided trial of chitosan in patients with prostate cancer on ADT and propose that chitosan will act as an absorbent of pre-formed AGEs, preventing their absorption from the gut and thus reducing their levels in the body. This intervention produced an 80% reduction in the plasma level of carboxymethyl lysine (CML) AGE adducts and more remarkably there was also a reduction in tissue AGE levels as determined by skin autofluorescence. These data support the idea that chitosan could be an active AGE-reducing agent that is clinically tolerable. Plasma and stool bio-fluid specimens have been collected from the four patients enrolled in the clinical trial and will be assayed. As these mechanistic studies are ongoing, the result will document any systemic effects from the chitosan intervention on inflammation, bowel permeability and microbiome diversity.

Citation Format: Shanora G Brown, Brandon Sutton, Taiwo Biotidara, Dave Turner, Robert Wilson, Michael Lilly. Mechanistic insights into phase 1b/2 study of chitosan for pharmacologic manipulation of AGE (advanced glycation endproducts) levels in prostate cancer patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D062.
Abstract D095: Plasma levels of polychlorinated biphenyls (PCBs) and breast cancer mortality: The Carolina Breast Cancer Study
Authors: Parada Humberto , Sun Xuezheng , Tse Chiu-Kit , Engel Lawrence S. , Olshan Andrew F. , Troester Melissa A.
Published: September 2020

Background: Polychlorinated biphenyls (PCBs) are a group of 209 synthetic organic chemicals, several of which are known carcinogens or endocrine disruptors. PCBs are hypothesized to influence the risk of developing breast cancer; however, whether PCBs influence the risk of mortality following breast cancer is poorly understood. We examined plasma levels of 17 PCB congeners in association with mortality among women who participated in the population-based Carolina Breast Cancer Study (CBCS). Methods: Participants included 456 white and 292 black women who were diagnosed with primary invasive breast cancer from 1993-1996, and who had PCB and lipid measurements from blood samples obtained on average 4.1 months after diagnosis. Using the National Death Index, we identified 392 deaths including 210 from breast cancer, over a median follow-up of 20.6 years. We used Cox regression to estimate covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and breast cancer-specific 5-year mortality, and 20-year mortality conditional on 5-year survival in relation to tertiles and continuous ln-transformed lipid-adjusted PCB levels. We also examined effect measure modification by race. Results: The highest (vs. lowest) tertile of PCB118 was associated with a 5-year breast cancer-specific mortality HR of 1.86 (95% CI=1.07-3.23). One-ln unit increases in PCB74, PCB99, PCB118, and total PCBs were associated with 5-year breast cancer-specific mortality HRs ranging from 1.33 (95% CI=1.02-1.74) for PCB74 to 1.40 (95% CI=1.02-1.92) for PCB118. By race, a one-ln unit increase in PCB74 was associated with a HR of 1.47 (95% CI=1.01-2.14) among black women and with a HR of 1.19 (95% CI=0.79-1.77) among white women (P-Interaction=0.05). Continuous PCB levels were associated with 20-year conditional all-cause mortality HRs ranging from 1.20 (95% CI=1.03-1.41) for a one-ln unit increase in PCB182+PCB187 to 1.37 (95% CI=1.12-1.68) for a one-ln unit increase in PCB118. PCBs were not associated with 5-year all-cause mortality or with 20-year conditional breast cancer-specific mortality. Conclusion: PCBs may increase the risk of short-term breast cancer-specific mortality as well as long-term all-cause mortality among women with breast cancer.

Citation Format: Humberto Parada, Xuezheng Sun, Chiu-Kit Tse, Lawrence S. Engel, Andrew F. Olshan, Melissa A. Troester. Plasma levels of polychlorinated biphenyls (PCBs) and breast cancer mortality: The Carolina Breast Cancer Study [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D095.
Abstract D120: Similarities and differences between genomic profiles of prostate cancers from African American and European American men with implications for precision cancer medicine
Authors: Koga Yusuke , Song Hanbing , Chalmers Zachary , Newberg Justin , Frampton Garrett , Campbell Joshua , Huang Franklin
Published: September 2020

Background: African American (AA) men have the highest mortality rate from prostate cancer compared to men from other races. Differences in the spectrum of somatic genomic alterations in tumors between AA men differs from non-AA men has not been well characterized as relatively few AA men have been included in prostate cancer genomic studies. To address this, we examined 5 publicly-available and commercial genomic datasets containing AA men with prostate cancer to identify novel alterations associated with race. Methods: In a meta-analysis of 4 public datasets, we investigated the mutational frequencies of 14 genes across 252 AA men and 635 non-AA men with primary prostate cancer. We also examined genomic alterations from the tumors of 436 AA men and 3018 EA men with primary or metastatic prostate cancer using the Foundation One assay. Results: We identified mutations in ZFHX3 and focal deletions in ETV3 more frequently in tumors from AA patients. The mutational frequency of TP53 was strongly associated with increasing Gleason grade. Using the commercial assay, we identified alterations in PTEN and TMPRSS2-ERG as less frequent in AA patients compared to non-AA patients in both primary and metastatic tumors. MYC amplifications were more frequent in AA patients with metastatic prostate cancer. Furthermore, we found that genomic alterations in KMT2D and CCND1 were more frequent in primary prostate tumors from AA patients, resulting in differential cell cycle genes and KMT alterations. MYC amplifications were more frequent in AA patients with metastatic prostate cancer. Genomic alterations in DNA repair genes were found at similar frequencies between EA and AA patients. Conclusion: While these results indicate that differences in mutational profiles may exist between racial groups in prostate cancers, additional sequencing studies that profile AA and EA men from the same clinical setting and that are matched for clinical covariates may be needed to confirm these findings. Overall, these results have implications for applying precision cancer medicine in AA prostate cancer patients.

Citation Format: Yusuke Koga, Hanbing Song, Zachary Chalmers, Justin Newberg, Garrett Frampton, Joshua Campbell, Franklin Huang. Similarities and differences between genomic profiles of prostate cancers from African American and European American men with implications for precision cancer medicine [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D120.
Abstract IA07: Cancer survivorship among sexual minority people: Health, interventions, and next steps
Authors: Tree Jennifer M. Jabson
Published: September 2020

In the United States, approximately 1 million cancer survivors are sexual minority (cancer survivors who identify as gay, lesbian, bisexual) cancer survivors. The experience of cancer survivorship is not the same for all cancer survivors, and sexual minority cancer survivors experience barriers to health and positive outcomes as compared to heterosexual cancer survivors. Inequity in mortality risk, psychological distress, insurance denial, alcohol, tobacco, and substance use, poor self-rated health, and elevated stress and discrimination contribute to the risk for and prevalence of poorer outcomes after cancer treatment during the survivorship period for sexual minority cancer survivors. In an effort to improve health and reduce risk for poor outcomes after cancer, a few behavioral interventions have been introduced and tested for this unique group of cancer survivors. In this portion of the plenary I will discuss what is known about the existing behavioral interventions designed for sexual minority cancer survivors and their preliminary outcomes. The presentation of these interventions will be organized according to primary, secondary, and tertiary levels of prevention.

Citation Format: Jennifer M. Jabson Tree. Cancer survivorship among sexual minority people: Health, interventions, and next steps [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA07.
Abstract IA11: Cancer disparities and survivorship challenges facing young Latina women (<50 years) on the U.S.-Mexico border
Authors: Palacios Rebecca
Published: September 2020

Disparities in the incidence of specific cancers are prevalent among young Latinas (i.e., < 50 years). Although research focusing exclusively on Latina cancer survivors is limited, mixed-sample research suggests that Latina cancer survivors experience greater distress relative to non-Latina white (NLW) survivors, predisposing them toward poorer cancer outcomes. Young Latina survivors who are parenting school-age children may be at even higher risk of poor cancer survivorship, given research demonstrating that young NLW women experience worse physical and psychological well-being and greater illness intrusiveness compared to older NLW women (i.e., >50 years). This presentation describes the cancer disparities and survivorship challenges encountered by young Latina women living along the Paso del Norte U.S.-Mexico border region.

Methodology: Cancer registries were used to identify cancer disparities in the U.S.-Mexico border counties. Elicitation and focus group interviews conducted with diagnosed child-rearing Latina mothers explored their challenges in coping with cancer while parenting school-age children. Findings from the qualitative research informed the cultural adaptation of an evidence-based program, Enhancing Connections, to help Latina cancer survivors and their children cope with cancer. A subsequent study examined the feasibility and short-term efficacy of the culturally adapted Conexiones program.

Results: Based on research conducted exclusively with Latina women along the U.S.-Mexico border, this presentation will demonstrate (1) how cancer disparities worsen as the focus shifts from the national level to the U.S.-Mexico border region, (2) the challenges in cancer survivorship along the Paso del Norte U.S.-Mexico border region, and (3) research efforts designed to improve the quality of survivorship among young Hispanic mothers diagnosed with cancer.

Citation Format: Rebecca Palacios. Cancer disparities and survivorship challenges facing young Latina women (<50 years) on the U.S.-Mexico border [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA11.
Abstract IA23: Housing discrimination and cancer disparities research: How are key decisions made?
Authors: Beyer Kirsten M. M.
Published: September 2020

Housing discrimination, including residential racial segregation, is of growing interest as an upstream influence on cancer disparities. However, there are a number of measures available at various spatial scales, and decisions must be made along the way when choosing how to include these constructs in empirical research. In this presentation, we will discuss how these decisions are made, including: (1) how do you choose a measure of housing discrimination? (2) how do you choose a spatial scale (e.g., metropolitan area, tract, ZIP code)? (3) how do you select a study design? (4) where do you get the data? (5) how might these choices be informed by a conceptual model? and (6) how do you interpret findings? We will draw upon the Breast Cancer, Race and Place study, based in Milwaukee, Wisconsin, to illustrate these decisions and share recent findings from this ongoing project.

Citation Format: Kirsten M. M. Beyer. Housing discrimination and cancer disparities research: How are key decisions made? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr IA23.
Abstract A07: Improved prognosis of HPV-positive oropharyngeal cancers is associated with a suppression of TGF-β-mediated immune evasion
Authors: Bolyos Anthony , Bose Pinaki
Published: September 2020

Among head and neck squamous carcinoma (HNSC), human papilloma virus (HPV)-driven tumors are known to enjoy more favorable prognostic outcomes compared to non-HPV-driven disease. This is especially true of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), which is associated with significantly improved outcomes compared to HPV-positive non-OPSCC and HPV-negative HNSC. Previous reports have suggested that increased immune infiltration and expression of the estrogen receptor α (ERα) may play a role in conferring improved prognosis to HPV-positive OPSCC. However, the underlying signaling pathways specifically driven by HPV in the oropharynx have remained elusive. Here we analyzed HPV-positive OPSCC and non-OPSCC tumors from The Cancer Genome Atlas (TCGA) and found that HPV-positive OPSCC is associated with significantly improved overall and disease-specific survival and progression-free interval compared to HPV-positive non-OPSCC. Among HPV-positive HNSC, we observed a distinct separation of OPSCC from non-OPSCC tumors based on unsupervised clustering of gene expression, microRNA, and methylation profiling data. Separation based on anatomic site was not observed among HPV-negative HNSC, suggesting that common biology drives the carcinogenesis of HPV-negative HNSC across subsites. In line with a recent report that ERα mRNA expression is elevated HPV-positive OPSCC, we found significantly higher ERα mRNA levels in HPV-positive OPSCC compared to HPV-positive non-OPSCC, where ERα mRNA expression mirrored that in HPV-negative HNSC. We also found that HPV induces downregulation of TGF-β signaling and extracellular matrix (ECM)-associated genes while upregulating a T-cell and dendritic cell-associated immune response signature in an OPSCC-specific manner. Our analyses suggest that HPV induces downregulation of TGF-β signaling and ECM components in OPSCC to improve immune access to these tumors, facilitating tumor clearance and improved patient survival. These findings are in line with our recent report establishing TGF-β-mediated immunosuppression through ECM deregulation and its negative effect on patient prognosis.

Citation Format: Anthony Bolyos, Pinaki Bose. Improved prognosis of HPV-positive oropharyngeal cancers is associated with a suppression of TGF-β-mediated immune evasion [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A07.
Abstract A11: STAT1 mediates resistance to experimental oral cancer that is associated with enhanced antitumor T-cell responses
Authors: Ryan Nathan , Anderson Kelvin , Volpedo Greta , Hamza Omar , Varikuti Sanjay , Satoskar Abhay , Oghumu Steve
Published: September 2020

Cancers of the oral cavity and pharynx remain among the 10 most prevalent cancers in the United States. Signal Transducer and Activation of Transcription 1 (STAT1) is a transcription factor primarily involved in mediating responses to IFNs, as well as interleukin (IL) 21, 27, and 35. STAT1 has been shown to promote or suppress tumors in different cancer types, but its role in oral cavity cancers has not been examined. We examined the role of STAT1 in oral cancer using orthotopic models in wild-type (WT) and STAT1-deficient BALB/c mice. Metastatic (LY2) or nonmetastatic (B4B8) HNSCC cell lines were injected into the oral cavity and tumor development was monitored over a period of three or six weeks, respectively. At terminal sacrifice, tumors, spleens, draining lymph nodes, and bone marrow tissues were analyzed for tumor growth, metastasis, and immunologic responses. Tumors from STAT1-deficient mice injected with B4B8 cells were twice as large as tumors from WT mice. Interestingly, LY2-injected STAT1-deficient mice possessed tumors that were five times as large as tumors from LY2-injected WT mice. The increased tumor burdens in metastatic tumors were associated with a decrease in CD4+ and CD8+ T-cell infiltration into the draining lymph nodes of tumor-bearing STAT1-deficient mice compared to WT mice. Further, lymph node and splenic CD4+ and CD8+ T cells in tumor-bearing STAT1-deficient mice produced significantly lower TNF-alpha compared to WT mice. Finally, tumor-bearing STAT1-deficient mice displayed a significant accumulation of CD11b+ Ly6G+ myeloid cells in the spleens and bone marrow compared to WT counterparts in both metastatic and nonmetastatic HNSCC models. Our results demonstrate that STAT1 mediates resistance to oral tumor development that is associated with enhanced T-cell migration, TNF-alpha mediated antitumor T-cell responses, and diminished accumulation of tumor-promoting CD11b+ Ly6G+ myeloid cells.

Citation Format: Nathan Ryan, Kelvin Anderson, Greta Volpedo, Omar Hamza, Sanjay Varikuti, Abhay Satoskar, Steve Oghumu. STAT1 mediates resistance to experimental oral cancer that is associated with enhanced antitumor T-cell responses [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A11.
Abstract A25: Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma
Authors: Guo Theresa , Zambo Kristina D. A. , Zamuner Fernando T. , Ou Tingting , Hopkins Christopher , Kelley Dylan Z. , Wulf Hildegard A. , Danilova Ludmila V. , Considine Michael , Sidransky David , Favorov Alexander V. , Florea Liliana , Fertig Elana J. , Gaykalova Daria A.
Published: September 2020

Human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a unique disease entity within head and neck cancer with rising incidence. Previous work has shown that alternative splicing events (ASEs) are prevalent in HPV+ OPSCC, but further validation is needed to understand the regulation of this process and its role in these tumors. In this study, eleven ASEs (GIT2, CTNNB1, MKNK2, MRPL33, SIPA1L3, SNHG6, SYCP2, TPRG1, ZHX2, ZNF331, and ELOVL1) were selected for validation from 109 previously published candidate ASEs to elucidate the post-transcriptional mechanisms of oncogenesis in HPV+ disease. In vitro qRT-PCR confirmed differential expression of 9 of 11 ASE candidates, and in silico analysis within the TCGA cohort confirmed 8 of 11 candidates. Six ASEs (MRPL33, SIPA1L3, SNHG6, TPRG1, ZHX2, and ELOVL1) showed significant differential expression across both methods. Further evaluation of chromatin structure revealed that ASEs strongly correlated with the cancer-specific distribution of acetylated lysine 27 of histone 3 (H3K27ac). Subsequent epigenetic treatment of HPV+ HNSCC cell lines (UM-SCC-047 and UPCI-SCC-090) with JQ1 not only induced downregulation of cancer-specific ASE isoforms but also growth inhibition in both cell lines. The UPCI-SCC-090 cell line, with greater ASE expression, also showed more significant growth inhibition after JQ1 treatment. This study confirms several novel cancer-specific ASEs in HPV+OPSCC and provides evidence for the role of chromatin structure in regulation of alternative splicing in HPV+OPSCC. Our findings highlight the role of epigenetic changes in the oncogenesis of HPV+OPSCC, which represents a unique, unexplored target for biomarkers, neoantigens, and therapeutics.

Citation Format: Theresa Guo, Kristina D. A. Zambo, Fernando T. Zamuner, Tingting Ou, Christopher Hopkins, Dylan Z. Kelley, Hildegard A. Wulf, Ludmila V. Danilova, Michael Considine, David Sidransky, Alexander V. Favorov, Liliana Florea, Elana J. Fertig, Daria A. Gaykalova. Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A25.
Abstract A33: Fungal beta-glucans, EphA2, and oral cancer: Preliminary observations
Authors: Maskal Sara , Ghosh Santosh , Zender Chad , Thuener Jason , Weinberg Aaron
Published: September 2020

Introduction: Although Candida spp. are associated with invasive candidiasis in immunocompromised hosts, rates of asymptomatic colonization with the fungus are high. Candida has been associated with a variety of cancers and is thought to play a role in carcinogenesis. Beta glucans are polysaccharide components of the fungal cell wall that are more highly expressed in the more invasive, hyphal form of Candida. Recent data suggests that EPHA2, a tyrosine kinase receptor on oral epithelial cells, acts as a pattern recognition receptor for beta-glucans. We tested the hypothesis that beta-glucans promote proliferation and/or migration of squamous cell carcinoma cells through interactions with EPHA2.

Methods: W18 cells, with wild-type EPHA2 expression, were derived from murine squamous cell carcinoma cells induced by classical DMBA/TPA protocol. SCC-728 is a squamous cell carcinoma cell line from an EphA2 KO mouse. The SCC-728 cell line was also used to generate an EPHA2-reconstituted cell line. HIGK cells are an immortalized oral epithelial cell line. Cells were cultured in 6 well plates to confluence in DMEM at 37° Celsius. Plates were scratched using a 200-microliter pipette tip and treated. Microscopic images from 0 and 24 hours were compared and analyzed visually by ImageJ. Beta-glucan from Saccharomyces was tested at 12.5 micrograms/milliliter. EGF (20 nanograms/milliliter) was the positive control for cell proliferation. Mitomycin C (10micrograms/milliliter) was the negative control for proliferation. Other glucans tested include zymosan (12.5 micrograms/milliliter) and pullulans (12.5 micrograms/milliliter). Results In the presence of beta-glucan, wild-type SCC cells (p<0.05) and EPHA2-reconstitued cells showed significant closure compared to control. EPHA2-KO cells did not show significant closure compared to controls on exposure to beta-glucans. All cell lines showed significant closure on treatment with EGF. Treatment with mitomycin C, alone or in combination with EGF or beta-glucan, prevented significant closure in all cell lines. Significant closure was seen with zymosan- and pullulans-treated cells.

Conclusion: SCC cells showed increased proliferation in the presence of beta-1,6-glucan and beta-1,3-glucan from Saccharomyces. SCC cells showed migration or proliferation in the presence of alpha-1,4- and alpha-1,6-glucan, but less significant than beta-1,6-glucan and beta-1,3-glucan. Beta-glucan can induce EphA2-dependent cell membrane retraction similar to its native ligands.

Citation Format: Sara Maskal, Santosh Ghosh, Chad Zender, Jason Thuener, Aaron Weinberg. Fungal beta-glucans, EphA2, and oral cancer: Preliminary observations [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A33.
Abstract A42: Total laryngopharyngoesophagectomy with gastric transposition for hypopharyngeal cancer: A tertiary care center experience
Authors: Rao Prerit , Devaraja K. , Pujary Kailesh , Nayak Dipak Ranjan , Balakrishnan R.
Published: September 2020

Introduction: With the emergence of organ preservation protocol in head and neck cancer, management of hypopharyngeal carcinoma is generally by nonsurgical approach; however, a significant number of hypopharyngeal cancer patients present in advanced stage and exhibit poor prognosis. For such cases, thorough aggressive surgical excision of laryngopharyngoesophageal complex with appropriate reconstruction might be a viable option.

Objective: To evaluate quality-of-life measures and survival outcomes in hypopharyngeal carcinoma cases undergoing above-mentioned procedure at a tertiary health care center.

Methodology: A retrospective study on patients with hypopharyngeal carcinoma undergoing above-mentioned procedure was done in our tertiary care institute between September 2016 to October 2018.

Results: A total of 12 patients were operated during the study period; however, 3 patients were excluded due to inadequate data. In our study, mean age of presentation was 51.3 years and majority were men (n=8). Most of the patients at the time of presentation were stage IVA or more. Postcricoid was most common subsite, followed by pyriform fossa. 4 out of 12 were operated after failed chemoradiation. Perioperative morbidity primarily in terms of complications and duration of hospital stay and quality-of-life measures consisting mainly of swallowing score were analyzed, which suggested that this procedure is tolerable and produces a reliable outcome.

Conclusion: Total laryngopharyngoesophagectomy with gastric transposition is a feasible and efficacious treatment option with reasonable quality of life in carcinoma hypopharynx patients, especially after failed chemoradiation.

Citation Format: Prerit Rao, K. Devaraja, Kailesh Pujary, Dipak Ranjan Nayak, R. Balakrishnan. Total laryngopharyngoesophagectomy with gastric transposition for hypopharyngeal cancer: A tertiary care center experience [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A42.
Abstract B14: Variations in the proteasome activity are associated with human papilloma virus (HPV) gene expression and patient survival in HPV+ oropharyngeal tumors
Authors: Gleber-Netto Frederico O. , Gao Meng , Shen Li , Wang Jing , Myers Jeffrey N. , Johnson Faye M. , Pickering Curtis R.
Published: September 2020

Variations in the molecular function of human papillomavirus (HPV) have been associated with outcome in HPV-positive oropharyngeal squamous cell carcinomas (HPV+OPSCC). HPV-mediated carcinogenesis is initiated by the E6 and E7 proteins, which promotes the inhibition of the p53 and pRb proteins by targeting them for degradation by the proteasome system. Considering that the proteasome system is an important mediator of HPV molecular activity, we hypothesize that its activity may be an important modifier of HPV+OPSCC phenotypes. To test this hypothesis, we analyzed the in silico expression of proteasome genes among HPV+ oropharyngeal squamous cell carcinoma cases from The Cancer Genome Atlas (TCGA) and explored the proteasome activity of HPV+ squamous cell carcinoma cell lines in vitro. Higher expression of proteasome genes was significantly associated with worse 5-year overall survival (p=0.0003), lower expression levels of E1^E4 gene (p = 0.032), and more HPV integration (p = 0.028). In vitro analysis indicated that proteasome activity was distinct between E1^E4 negative and E1^E4 positive HPV+ cell lines. Interestingly, E1^E4 negative cell lines, which exhibited higher levels of some proteasome genes, were more sensitive to proteasome inhibition than E1^E4 positive cells. These results indicate that proteasome activity may vary significantly among HPV+ OPSCC cases and may represent an important modulator of tumor phenotypes. Expression of proteasome genes and also proteasome activity was highly correlated with expression of HPV genes and may function as a potential predictive biomarker. Finally, proteasome targeting may represent a potential therapeutic alternative for a subgroup of HPV+ OPSCC patients.

Citation Format: Frederico O. Gleber-Netto, Meng Gao, Li Shen, Jing Wang, Jeffrey N. Myers, Faye M. Johnson, Curtis R. Pickering. Variations in the proteasome activity are associated with human papilloma virus (HPV) gene expression and patient survival in HPV+ oropharyngeal tumors [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B14.
Abstract B25: Anticancer effects of disulfiram in head and neck squamous cell carcinoma via autophagic cell death
Authors: Park Young Min , Kim Da Hee , Kang Min Seok , Koh Yoon Woo , Choi Eun Chang , Kim Se-Heon
Published: September 2020

Objective: Disulfiram (DSF), which is used to treat alcohol dependence, has been reported to have anticancer effects in various malignant tumors. However, the anticancer effects and mechanism of DSF in head and neck squamous cell carcinoma (HNSCC) have not yet been studied. In this study, we investigated the anticancer effects and mechanism of DSF in HNSCC.

Materials and Methods: Head and neck squamous carcinoma cell lines (FaDu and Hep2) were used to analyze the anticancer effects of DSF. The anticancer effects of DSF were confirmed in vivo using a FaDu xenograft tumor model.

Results: The anticancer effects of DSF in HNSCC were found to be copper (Cu) dependent. Specifically, DSF/Cu markedly inhibited HNSCC at a concentration of 1 μM, and their combined inhibitory effect was dose-dependent. After DSF/Cu administration, production of reactive oxygen species (ROS) was remarkable starting at 0.5 μM, suggesting that the inhibitory effects of DSF/Cu on HNSCC are mediated through the formation of ROS. In the HNSCC cell lines, levels of phospho-JNK, phospho-cJun and phospho-p38 were increased after DSF/Cu treatment while levels of phospho-Akt were decreased. These results suggested that the inhibitory effects of DSF/Cu on HNSCC cells involve ROS formation and downregulation of Akt-signaling. Through these molecular mechanisms, DSF ultimately induces the inhibitory effects on HNSCC cell lines mainly through autophagic cell death, not apoptotic cell death. Lastly, we investigated the clinical relevance of DSF/Cu using a HNSCC xenograft animal model, which showed that tumor growth was remarkably decreased by DSF (50 mg/kg injection).

Conclusion: Treating patients with both HNSCC and alcohol dependence with DSF may contribute to improved patient survival. The anticancer effects of DSF on HNSCC may suggest new therapeutic potential for this medication in HNSCC patients.

Citation Format: Young Min Park, Da Hee Kim, Min Seok Kang, Yoon Woo Koh, Eun Chang Choi, Se-Heon Kim. Anticancer effects of disulfiram in head and neck squamous cell carcinoma via autophagic cell death [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B25.
Abstract IA17: Cellular interactions and regulatory mechanisms in head and neck cancer
Authors: Vignali Dario A.A.
Published: September 2020

Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environment carcinogens or malignant transformation by human papilloma virus (HPV). Two studies will be discussed. First, we have performed transcriptional profiling of single cells from peripheral and intratumoral immune populations in HPV- and HPV+ HNSCC and healthy donors. We found a spectrum of transcriptional relationships from very similar to highly divergent between the tumor microenvironments (TME) in HPV- and HPV+ HNSCC. Our comprehensive survey of the TME in in HPV- and HPV+ HNSCC highlights the diversity of immune states and complexity of crosstalk between immune populations, and is a benchmark for analysis of the TME in human cancer. Second, many cancer patients do not develop a durable response to current standard of care immunotherapies despite substantial advances in targeting immune inhibitory receptors. A potentially important and unappreciated compounding issue, which may serve as a dominant resistance mechanism, is the inherent systemic immune dysfunction that is often associated with advanced cancer. Although this has been described for decades, primary mechanisms and drivers remain unknown. Lack of response to inhibitory receptor blockade therapy and increased disease burden has been associated with circulating, peripheral CD8+ T-cell exhaustion, which is defined by poor T-cell function linked to increased inhibitory receptor expression (PD1 or LAG3). Our recent studies have assessed if LAG3 and PD1 impact systemic T-cell function.

Citation Format: Dario A.A. Vignali. Cellular interactions and regulatory mechanisms in head and neck cancer [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr IA17.
Abstract A06: Synthetic peptides derived from the cell adhesion molecule Nectin-4 inhibit the formation of ovarian cancer 3D spheroids
Authors: Boylan Kristin L.M. , Manion Rory D. , Shah Heena , Skubitz Amy P.N.
Published: September 2020

A unique aspect of ovarian cancer progression is the collection of ascites fluid in the abdominal cavity, which contains free-floating tumor cells in the form of single cells and also multicellular aggregates or spheroids. Spheroids are more resistant to standard chemotherapy due in part to their slow proliferation rate and also to the protection afforded by the tight cell aggregation. Agents that prevent spheroid formation have the potential to improve chemotherapeutic response. Our previous work on the function of the cell surface adhesion molecule Nectin-4 in ovarian cancer demonstrates that it plays a key role in the formation of ovarian cancer spheroids. We also showed that synthetic peptides derived from the amino acid sequences of Nectin-4 and its binding partner Nectin-1 could inhibit cell adhesion in an in vitro assay. The purpose of this study was to further examine the role of Nectin-4 in the formation of ovarian cancer spheroids using live-cell digital microscopy to monitor spheroid formation over time. Synthetic peptides derived from the amino acid sequences of Nectin-4 and Nectin-1 were tested for their ability to alter the spheroid formation of two ovarian cancer cell lines. Several peptides disrupted ovarian cancer spheroid formation, warranting further investigation. For the peptide with the strongest inhibitory effect on spheroid formation, we tested scrambled versions of the peptide, which did not affect the formation of spheroids. This peptide also inhibited spheroid formation in a concentration-dependent manner and was not cytotoxic. These results suggest that Nectin-derived peptides could augment the effect of chemotherapy, as they would maintain the cancer cells as single cells or small aggregates that are more sensitive to chemotherapy.

Citation Format: Kristin L.M. Boylan, Rory D. Manion, Heena Shah, Amy P.N. Skubitz. Synthetic peptides derived from the cell adhesion molecule Nectin-4 inhibit the formation of ovarian cancer 3D spheroids [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A06.
Abstract A11: Copy-number analysis of understudied black women ovarian cancers
Authors: Delaney Joe R.
Published: September 2020

Cancer disparities research has a sample number problem, especially in serous ovarian cancer (SOC). Driver genes for SOC are mutated in <10% of patients, with the sole exception of p53. Even with hundreds of patients, this limits the ability to perform gene-oriented statistics between racial groups, even in the relatively diverse population in the United States. Yet research is needed; the CONCORD-2 study and researchers at the Hollings Cancer Center have consistently found worse prognosis for black patients with SOC, despite correcting for socioeconomic factors. Biologic tumor-intrinsic factors may explain some aspects of the worse prognosis. The Cancer Genome Atlas (TCGA) well mapped the US population for Caucasians and African Americans (77% white, 12% black), but with only 12% of samples within the second most prevalent racial group, driver genes are missed. For example, while BRCA1 mutation was found in tumors from white patients, it was not found in tumors from black patients. However, research need not be limited to amino-acid level mutations and indels; copy-number alterations (CNAs) likely drive the biology of SOC, with the average number of genes affected per TCGA tumor around 16,000. Pathway-level analyses of these widely disrupted genes can find significant differences between racial/ethnic groups. Here, we present evidence that significant differences are present in somatic CNA data for the pathways: xenobiotic metabolism, cAMP kinase signaling, and adaptive immune response. An expansion of research into somatic CNAs is warranted in underrepresented minority groups to better understand how treatment options and prognostic markers may differ.

Citation Format: Joe R. Delaney. Copy-number analysis of understudied black women ovarian cancers [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A11.