bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract C098: Correlates of cervical cancer screening among Pacific Islander women on Guam and Hawaii
Authors: Badowski Grazyna , Dulana Louis , Somera Lilnabeth P , Cassel Kevin , Lee Hye-ryeon
Published: September 2020

Background There are significant disparities in cervical cancer incidence and mortality rates among Pacific Islander women. Native Hawaiian females have the highest incidence rates for cervical cancer in HI, and Chamorro and Micronesian have the highest incidence rates on Guam. The objective of this study was to examine the rates and the correlates of Pap smear test among Pacific Islander women. Methods This study conducted a cross-sectional survey using respondent driven sampling (RDS) of 802 women aged 21-65, including 235 Native Hawaiians, 190 Chuukese, 119 Marshallese, 157 Chamorro and 62 Filipino from Guam and Hawaii. Self-reported screening rates were compared across ethnic groups and migrant status using chi-square and Fisher’s exact tests. Binary logistic regression was used to identify significant predictors of cervical cancer screening. Results Only 64% of our sample had received a screening for cervical cancer within the past 3 years. Filipino women had the highest screening rates (71%) followed by Chamorro (69%), Marshallese (68%), Native Hawaiian (64%) and Chuukese (58%). There was no significant difference in screening rates between women aged 21-39 and 40-65. Recent migrants were less likely to have been screen within the past 3 years when compared to US born respondents (OR=0.37; 95% CI: 0.16, 0.84) even after adjusting for education and having health care. Those women agreeing with the statement that health systems treat people unfairly based on their ethnic background were less likely to be screen (OR=0.52; 95% CI: 0.31, 0.81) when compared with those who did not agree. Conclusion The rates for cervical cancer screening tests for Pacific Island women remain far below the goals set forth in Healthy People 2010. Culturally competent, community-based care for women is needed to increase Pap smear screening among minority groups

Citation Format: Grazyna Badowski, Louis Dulana, Lilnabeth P Somera, Kevin Cassel, Hye-ryeon Lee. Correlates of cervical cancer screening among Pacific Islander women on Guam and Hawaii [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 C098.
Abstract C119: Cancer screening disparities among rural sexual minority individuals: Implication for prevention and policy
Authors: Lee Min Jee , Jenkins Wiley , Boakye Eric Adjei
Published: September 2020

Introduction: Although a few studies have examined screening uptake among sexual minority, almost none have examined it in the specific context of rural populations. Therefore, the objective was to assess how cancer screening utilization might vary by residence (rural versus urban) and sexual orientation. Methods: Publicly available population-level data from the 2014 and 2016 Behavioral Risk Factor Surveillance System (BRFSS) were utilized. Study outcomes included recommended recent breast, cervical, and colorectal cancer (CRC) screening receipt. Independent variables of interest were residence (rural/urban) and sexual orientation (heterosexual/gay/bisexual). Weighted proportions and multivariable logistic regressions were used to assess the association between the independent variables and the outcomes. Analyses were conducted in 2018. Results: Rates for all three screenings were lowest in rural areas and among sexual minority populations (cervical cancer among lesbians, rural at 64.8%; breast cancer among lesbians, rural at 66.8%; and CRC among bisexual, rural men at 52.4%). For CRC screening, both rural gay and heterosexual rural males were less likely to receive screening (aOR=0.45; 95%=0.24-0.73 and aOR=0.79; 95%=0.72-0.87, respectively) while only rural heterosexual females were less likely (aOR=0.87; 95%=0.80-0.94). For cervical cancer screening, heterosexuals were less likely to be screened (aOR=0.83; 95%=0.72-0.94), and there were no differences for breast cancer. Conclusions: We found that rural sexual minorities may experience disparities in cancer screening utilization associated with the compounding barriers of rural residence and sexual orientation. Further work is needed to identify factors influencing these disparities and how they might be addressed.

Citation Format: Min Jee Lee, Wiley Jenkins, Eric Adjei Boakye. Cancer screening disparities among rural sexual minority individuals: Implication for prevention and policy [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 C119.
Abstract D055: Molecular mechanisms of cisplatin-induced toxicity to acute promyelocytic leukemia cells
Authors: Tchounwou Paul , Kumar Sanjay , Brown Andrea
Published: September 2020

Purpose: Acute promyelocytic leukemia (APL), is a blood cancer that accounts for about 10% of all acute myloid leukemia cases. Each year in the United States, APL affects about 1,500 patients of all age groups and causes approximately 1.2% of cancer deaths. Research has also pointed out the Hispanic populations have a higher incidence of APL compared to other racial groups. Cisplatin) is a widely used anti-tumor drug for the treatment of a broad range of human malignancies with successful therapeutic outcomes for head and neck, ovarian, and testicular cancers. It has been found to inhibit cell cycle progression and to induce oxidative stress and apoptosis in APL cells. However, its molecular mechanisms of cytotoxic action are poorly understood. We hypothesized that cisplatin induces cytotoxicity through DNA adduct formation, oxidative stress, transcriptional factors (p53 and AP-1), cell cycle regulation, stress signaling and apoptosis in APL cells. Methods: We used the APL cell line as a model, and applied a variety of molecular tools (cytotoxicity and oxidative stress assays, western blot analysis, flow cytometry, and confocal microscopy) to elucidate cytototoxic mode of action of cisplatin. Results: We found that cisplatin inhibited cell proliferation by a cytotoxicity characterized by DNA-adduct formation, oxidative stress, cell cycle arrest, stress signaling and apoptosis in APL cells. Cisplatin also activated p53 and phosphorylated activator protein (AP-1) component, c-Jun at serine (63, 73) residue simultaneously leading to cell cycle arrest through stimulation of p21 and down regulation of cyclins and cyclin dependent kinases (cdks) in APL cell lines. It strongly activated the intrinsic pathway of apoptosis through alteration of the mitochondrial membrane potential, release of cytochrome C, and up-regulation of caspase 3 activity by modulating p38MAPK pathway in APL cells. Conclusion: Overall the findings from this study provide novel targets of cisplatin mode of action that may be very useful in designing of new APL drugs.

Citation Format: Paul Tchounwou, Sanjay Kumar, Andrea Brown. Molecular mechanisms of cisplatin-induced toxicity to acute promyelocytic leukemia cells [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 D055.
Abstract D112: Development of an organoid assay for studying racial disparity in pancreatic acinar ductal metaplasia
Authors: Bray Julie , Ait-Oudhia Sihem , Campbell-Thompson Martha , Schmittgen Thomas D
Published: September 2020

Blacks have a higher rate of incidence and mortality of pancreatic cancer compared to whites. In an effort to identify a biological basis for this disparity, we propose examining the early events in the development of pancreatic cancer. The process by which pancreatic acini transdifferentiate into ductal epithelial cells (i.e. acinar ductal metaplasia or ADM) is one of the earliest events in the development of pancreatic ductal adenocarcinoma. We adapted the classic in vitro ADM assay, by which primary mouse pancreatic acini undergo ADM once plated onto the extracellular matrix matrigel, to an assay to culture and transdifferentiate human pancreatic organoids. Human pancreatic acini was received from black (n=5), white (n=3) and Hispanic (n=6) donors from pancreatic islet transplantation centers. The gender distribution was 8 males and 6 females. The acinar cells were cultured on matrigel and allowed to undergo ADM over a 5 to 6 day period. The number of ductal epithelial cells were microscopically counted and the rate of transdifferentiation was determined. Using this technique, we successfully cultured and transdifferentiated 14 of 14 human pancreatic acinar cells. Preliminary data from our study suggests that females undergo ADM at a greater rate than males. Data on race was inconclusive due to the low number of samples. In summary, we have developed an assay to culture and study pancreatic ADM using human specimens. Future studies using increased sample size will investigate if racial disparity exists for pancreatic ADM.

Citation Format: Julie Bray, Sihem Ait-Oudhia, Martha Campbell-Thompson, Thomas D Schmittgen. Development of an organoid assay for studying racial disparity in pancreatic acinar ductal metaplasia [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 D112.
Abstract IA01: It doesn't have to be this way: What is public health doing to address health equity in cancer?
Authors: Richardson Lisa C.
Published: September 2020

Public health is the science of protecting and improving the health of people and their communities. Overall, public health is concerned with protecting the health of entire populations. These populations can be as small as a local neighborhood or as big as an entire country. The Centers for Disease Control and Prevention’s (CDC’s) main mission is to collect and analyze data to show where differences in outcomes occur and to design and implement programs to alleviate these differences. Dr. Richardson will present on the role of CDC’s cancer control programs in identifying these differences and what they are doing address them. CDC works in collaboration with other governmental organizations and community leaders to lessen the cancer burden for everyone.

Citation Format: Lisa C. Richardson. It doesn't have to be this way: What is public health doing to address health equity in 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 IA01.
Abstract IA09: Border health overview: Challenges and opportunities
Authors: Elizondo Amy
Published: September 2020

The rural areas of the United States-Mexico border are impacted by challenges that are uniquely different for health care providers and patients compared to those seen in urban areas. Rural populations, on average, have relatively more elderly, unemployment and underemployment, and poor, uninsured, and underinsured residents. They are more vulnerable to economic downturns because of their economic specialization than their urban counterparts. The US-Mexico border is one of the busiest in the world, spanning 2,000 miles between California to Texas, with roughly 30% of the estimated 30 million residing in rural areas of the border. In June of 2008, the National Rural Health Association (NRHA) convened the first meeting towards implementing an NRHA Border Health Initiative, a partnership for addressing the access needs of rural communities in this vast region of the country. Since the start of the initiative, partnerships between the NRHA and federal, state, and community-based organizations have been established to help address border specific issues through advocacy, communications, education, and research. This presentation will highlight the challenges and opportunities along rural areas of the US-Mexico border and discuss some of the outcomes of the NRHA’s initiative that have developed over the last 11 years. Attendees can expect to 1) have a better understanding of specific health, population, and systemic issues occurring in this part of the country; 2) become familiar with some of the partners making an impact in this area; and 3) learn about recommendations for establishing progress.

Citation Format: Amy Elizondo. Border health overview: Challenges and opportunities [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 IA09.
Abstract A28: DEAD-box RNA helicase DP103 enhances YAP sumoylation for YAP-TEAD dependence and statin sensitivity in triple-negative breast cancer
Authors: Lai Xianning , Wang Tingting , Tan Tuan Zea , Casey Patrick J , Hong Wanjin , Sudol Marius , Tergaonkar Vinay , Lee Soo Chin , Kumar Alan Prem
Published: September 2020

Simvastatin (SMV), a lipophilic statin used for lowering cholesterol, inhibits 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the key enzyme of the mevalonate pathway. Studies have shown that cancer cells express deregulated level of HMGCR and statins exert antitumoral activities. We first assessed correlation between mevalonate pathway genes and DP103 (DDX20, Gemin-3) in 1,325 breast cancer patients and observed a positive correlation between DP103 and the mevalonate pathway genes. Having this data, we then proceeded to explore the effect of statins on DP103 expression. We used various in vitro cell lines and in vivo statin clinical trial patients’ specimens, mouse xenograft, mouse intravenous tail injection, and Drosophila (wild-type vs. Gemin-3 knockdown vs. Gemin-3 overexpression flies) models. We show exposure to statin decreases the expression of DP103. Through a series of add-back experiments, we show that the decrease in DP103 expression by statins is via the mevalonate pathway and downstream of RhoA. In clinical specimens, we observed breast cancer patients with high baseline DP103 positively correlate with high baseline YAP-TEAD expression. Having known that SUMOylation of YAP maintains its activity and that DP103 is a critical enhancer of the SUMOlyation machinery, we showed through a series of experiments that a physical interaction between DP103 and YAP is crucial for maintaining SUMOylation of YAP, thereby decreasing its ubiquitination and degradation. Interestingly, we also identified for the first time that DP103 is a direct target of YAP-TEAD complex and that maintenance of DP103 expression is needed as a positive feedback, forming an Achilles heel for sustained YAP-TEAD activity.

Citation Format: Xianning Lai, Tingting Wang, Tuan Zea Tan, Patrick J Casey, Wanjin Hong, Marius Sudol, Vinay Tergaonkar, Soo Chin Lee, Alan Prem Kumar. DEAD-box RNA helicase DP103 enhances YAP sumoylation for YAP-TEAD dependence and statin sensitivity in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr A28.
Abstract IA12: Targeting autopalmitoylation of TEAD transcription factors
Authors: Wu Xu
Published: September 2020

TEAD transcription factors bind to the transcription co-activators YAP/TAZ and control the transcriptional output of the Hippo pathway. Deregulation of Hippo-YAP signaling is implicated in diverse human cancers; however, it remains difficult to directly target TEAD-YAP complex with small molecules. We previously reported that TEADs possess intrinsic “enzyme-like” activities and undergo autopalmitoylation. Palmitate binds into a deep hydrophobic pocket and is essential for TEAD protein stability and transcriptional activation. Here we report MGH-CP1 as a small-molecule inhibitor of TEAD autopalmitoylation. We determined the crystal structure of inhibitor-bound TEAD2 and showed that MGH-CP1 binds to the conserved lipid-binding pocket in TEAD2 and displaces palmitate binding. In cells, MGH-CP1 maintains TEAD stability and TEAD-Vgll4 repressor complex and allosterically inhibits TEAD-YAP association and YAP-induced transcriptional activation. Through a large-scale profiling of cancer cell line growth inhibition, followed by intersecting with the Cancer Dependence Map analysis, we demonstrate that the sensitivity to MGH-CP1 treatment correlates significantly with YAP-dependency in a broad range of human cancer cells. Furthermore, we show that MGH-CP1 blocks YAP-dependent liver overgrowth induced by liver-specific Lats1/2 deletion in mice and inhibits xenograft tumor growth of human uveal melanoma cells in vivo. Together, our work suggests pharmacologic inhibition of TEAD palmitoylation as a promising therapeutic strategy for diseases associated with deregulated Hippo signaling, and opens a door to target “autopalmitoylation” of proteins.

Citation Format: Xu Wu. Targeting autopalmitoylation of TEAD transcription factors [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr IA12.
Abstract A09: Activation of the CD45 receptor on leukocytes by the C24D peptide results in immune-mediated head and neck squamous cell carcinoma apoptosis
Authors: Mizrachi Aviram , Hikri Elad , Ritter Amit , Dick-Lipovetsky Julia , Simchi Sivan , Popovtzer Aron , Yerushalmi Rinat , Bachar Gideon , Raiter Anat
Published: September 2020

Objectives: CD45 is a highly conserved receptor-linked protein tyrosine phosphatase that is expressed on all leucocytes. C24D, a novel 24-amino acid dimer peptide, previously shown to activate immune-modulated breast cancer cell killing, binds to CD45, triggering leukocyte activation against cancer cells. The aim of this study was to evaluate the efficacy of C24D in activating leukocytes against head and neck squamous cell carcinoma (HNSCC).

Methods: We performed a series of in vitro studies using 3 HNSCC cell lines (Cal33, FaDu, and A431). HNSCC cells were cocultured with peripheral blood mononuclear cells (PBMC) from healthy donors and subsequently treated with either C24D peptide or a scrambled control version. C24D activity was evaluated by tumor cell density and apoptosis analysis. Leukocyte activation by the peptide was evaluated by interferon gamma (IFN-γ) secretion.

Results: Cocultures of HNSCC cells and PBMCs treated with C24D resulted in a substantial decrease in tumor cell density and increased apoptosis. IFN-γ levels were significantly elevated in the C24D treated PBMCs cocultured with HNSCC, suggesting leukocyte activation.

Conclusions: C24D peptide activates leukocytes via CD45, causing immune cell-mediated killing of HNSCC cell lines.

Citation Format: Aviram Mizrachi, Elad Hikri, Amit Ritter, Julia Dick-Lipovetsky, Sivan Simchi, Aron Popovtzer, Rinat Yerushalmi, Gideon Bachar, Anat Raiter. Activation of the CD45 receptor on leukocytes by the C24D peptide results in immune-mediated head and neck squamous cell carcinoma apoptosis [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 A09.
Abstract A23: Transoral robotic surgery for primary oncologic resection: Outcomes from a rural academic medical center
Authors: Eisen Eric , Rees Christiaan , Magro Isabelle , LeClair Karissa , Paydarfar Joseph
Published: September 2020

Objective: to report the outcomes of oncologic transoral robotic surgery (TORS) performed by a single surgeon.

Study Design: Retrospective chart review.

Methods: All patients who underwent a TORS primary oncologic resection between the years of 2010-2018 were reviewed. Data regarding demographics, comorbidities, prior treatment, tumor characteristics, surgery, complications, adjuvant therapy, and survival were obtained.

Results: Sixty-four patients were included in the chart review with a median age of 60.8 years. Fifty patients were male and 17 were female. Average overall robotic operating time was 137.9 minutes. Forty-one cases were presented using the Da Vinci Si while 23 cases were performed using the Da Vinci Xi. There was no significant difference between these two groups with regards to operative time, complication rate, or survival. Average robotic operative times for tonsil and tongue base primaries were 151.3 and 112.1 minutes, respectively. The difference was approaching statistical significance (p=0.053). Forty-two patients underwent ligation of external carotid artery (ECA) branches whereas 23 patients did not. One major oropharyngeal bleeding complication occurred in a patient who did not receive ECA branch ligation, which resulted in death. No major bleeding complication occurred in the ligation cohort. There was no significant difference in the overall rate of complications between low ACE 27 and high ACE 27 individuals (p = 0.22). However, the number of reported complications is significantly greater in the high ACE 27 group relative to the low ACE 27 group (0.74 vs. 1.82, p = 0.016). There was no significant difference in survival between HPV+ and HPV- tumors.

Conclusion: Transoral robotic surgery represents a safe and effective means for resection of malignancies of the oropharynx. Although statistical significance cannot be demonstrated, ECA branch ligation should be considered prior to TORS given the severity of potential complications.

Citation Format: Eric Eisen, Christiaan Rees, Isabelle Magro, Karissa LeClair, Joseph Paydarfar. Transoral robotic surgery for primary oncologic resection: Outcomes from a rural academic medical center [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 A23.
Abstract B06: Repositioning the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal carcinoma
Authors: Huq Sakibul , Casaos Joshua , Peters Michael , Xia Yuanxuan , Ding Andy , Morales Manuel , Gorelick Noah , Serra Riccardo , Zhao Tianna , Ishida Wataru , Perdomo-Pantoja Alexander , Cecia Arba , Ji Chenchen , Suk Ian , Sidransky David , Brait Mariana , Brem Henry , Skuli Nicolas , Tyler Betty
Published: September 2020

Purpose: Nasopharyngeal carcinoma (NPC) is a squamous cell carcinoma that is often diagnosed at an advanced stage, leading to poor disease-free and overall survival. Accumulating literature suggests that elevated protein expression of enhancer of zeste homolog 2 (EZH2), eukaryotic initiation factor 4E (eIF4E), and inosine-5’-monophosphate dehydrogenase (IMPDH)—proteins implicated in myriad cancers—correlates with poor prognosis in NPC. These three proteins are modulated by the Food and Drug Administration-approved antiviral drug ribavirin, which has recently been repositioned by our laboratory and others as a promising anticancer agent. Based on this intersection of molecular signature and drug targets, we investigated the potential of ribavirin as a therapeutic agent for NPC.

Experimental Design: We assessed antineoplastic efficacy of ribavirin on six human NPC cell lines in vitro using cellular growth assays, flow cytometry, and scratch wound assays. Mechanistic pathways involved were investigated using genomic expression datasets, Western blots, and enzymatic activity assays. The effects of combining ribavirin with radiation were assessed using clonogenic assays and flow cytometry. Finally, we evaluated the effects of ribavirin on tumor growth in vivo using two human cell line-derived xenograft models.

Results: Ribavirin significantly decreased NPC cellular proliferation and migratory capacity in addition to promoting cell cycle arrest and cell death. Modulation of the EZH2, Snail, eIF4E, and IMPDH pathways was observed in response to ribavirin treatment. Ribavirin significantly enhanced the cytotoxic effects of radiation therapy in NPC. Most importantly, ribavirin significantly reduced flank tumor growth in two NPC xenograft models.

Conclusions: Our work suggests that ribavirin has potent anticancer effects in NPC and could represent a safe and promising addition to current NPC treatment regimens.

Citation Format: Sakibul Huq, Joshua Casaos, Michael Peters, Yuanxuan Xia, Andy Ding, Manuel Morales, Noah Gorelick, Riccardo Serra, Tianna Zhao, Wataru Ishida, Alexander Perdomo-Pantoja, Arba Cecia, Chenchen Ji, Ian Suk, David Sidransky, Mariana Brait, Henry Brem, Nicolas Skuli, Betty Tyler. Repositioning the FDA-approved antiviral drug ribavirin as targeted therapy for nasopharyngeal 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 B06.
Abstract B28: HPV-related oropharyngeal cancer: Knowledge and beliefs among staff at community-based HIV/AIDS service organizations (ASOs)
Authors: Tomar Aditi , Balcezak Hannah Catherine , Wigfall Lisa Tisdale
Published: September 2020

This study explores knowledge and beliefs about HPV-related oropharyngeal cancer among ASO staff (n=51) from five ASOs located in South Carolina (N=3/5 ASOs; N=30/51 staff) and Texas (N=2/5 ASOs; N=21/51 staff). ASO staff completed a 118-item, self-administered needs assessment survey. Data were analyzed using Stata/SE 15.1. ASO staff (n=51) were 78% non-Hispanic Black [mean age (years): 44.2 ± 12.8 SD]; range 21.6-68.2. More than half (59%) were females and predominantly heterosexual (61%). Most (67%) had at least an undergraduate degree, and 65% had more than five years of experience working with HIV-positive clients. Only 18% had ever looked for information about oropharyngeal cancer. Almost half (48%) were not sure about the role of HPV in causing oropharyngeal cancer, and fewer (31%) thought that the HPV vaccine is pretty/very successful in preventing oropharyngeal cancer. Over half (53%) did not think that a woman can do much to reduce her chances of getting HPV, and 60% believed the same for men. Very few (16%) thought of smoking as a risk factor for HPV-related health problems such as genital warts and cancer. A large proportion (73%) thought that quitting smoking can have a huge impact in lowering its harmful effects. People living with HIV (PLWH) are disproportionately affected by HPV-related oropharyngeal cancer. ASO staff play an instrumental role in educating their clients about HIV/AIDS-related health topics, and therefore fostering their knowledge and beliefs about HPV-related oropharyngeal cancer could help improve outcomes for PLWH.

Citation Format: Aditi Tomar, Hannah Catherine Balcezak, Lisa Tisdale Wigfall. HPV-related oropharyngeal cancer: Knowledge and beliefs among staff at community-based HIV/AIDS service organizations (ASOs) [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 B28.
Abstract B30: Locoregional control in laryngeal and hypopharyngeal cancer patients treated with radiotherapy using direct gross tumor volume to planning target volume expansion
Authors: Burr Adam R. , Harari Paul M. , Witek Matthew E.
Published: September 2020

Purposes/Objectives(s): To evaluate clinical outcomes and patterns of failure using a direct gross tumor volume to planning target volume expansion in patients treated for laryngeal or hypopharyngeal squamous cell carcinomas.

Methods and Materials: We performed a retrospective review of patients with laryngeal or hypopharyngeal squamous cell carcinomas treated between 2002-2017 with primary radiotherapy with or without concurrent systemic therapy. Patient and disease characteristics associated with disease control and clinical outcomes were analyzed by Cox proportional hazards regression and Kaplan-Meier analyses. Deformable image registration between imaging at the time of failure and the treatment planning scan was used to determine patterns of failure.

Results: Seventy-nine patients with laryngeal or hypopharyngeal squamous cell carcinoma were identified with a median follow-up of 54 months among surviving patients. Overall survival at 5 years was 62.9% (95% CI: 51.1%-74.7%). Five-year primary tumor control was 71.6% (95% CI: 61.4%-81.8%) and regional control was 78.8% (95% CI: 68.4%-89.2%). A total of 28 patients experienced a locoregional recurrence, of whom 18 had treatment plans available. Of these, 89% (n=16) experienced failures that were 95% contained within the high-dose treatment volume. One patient failed in an intermediate-dose volume and 1 exhibited a marginal failure in the high-dose volume. There were no factors associated with overall survival or locoregional control on multivariate analysis.

Conclusion: Management of patients with laryngeal or hypopharyngeal squamous cell carcinoma using definitive radiotherapy and a high-dose planning target volume created without a gross tumor volume to clinical tumor volume expansion resulted in high locoregional control, with the vast majority of failures occurring within the high-dose field. These data support prospective evaluation of this technique.

Citation Format: Adam R. Burr, Paul M. Harari, Matthew E. Witek. Locoregional control in laryngeal and hypopharyngeal cancer patients treated with radiotherapy using direct gross tumor volume to planning target volume expansion [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 B30.
Abstract IA05: Intratumor genetic heterogeneity as a predictive biomarker in head and neck squamous cell carcinoma
Authors: Mroz Edmund A. , Rocco James W.
Published: September 2020

The presence of heritable genetic differences among cancer cells within a tumor, called intratumor genetic heterogeneity, has long been suspected of playing a role in the poor responses of some tumors to traditional therapies. Research over the past decade has now documented the existence of genetic heterogeneity within tumors of individual patients and acknowledged its potential clinical significance. The research methods for identifying intratumor genetic heterogeneity were not readily adaptable to widespread clinical application until the development of a quantitative measure (MATH—mutant allele tumor heterogeneity) based on whole-exome sequencing of individual tumor samples. MATH values could be readily derived from biopsy or surgical specimens prior to the decision to utilize adjuvant radiation or chemotherapy. MATH analysis has now been used in HNSCC genomic data sets, along with clinical outcome data, to document a relation of high intratumor genetic heterogeneity to shorter overall survival (OS) in a large, multi-institutional study. Recent analysis examining the impact of high and low heterogeneity as measured by MATH suggests that the relation of intratumor heterogeneity to OS likely depends on the specific type of adjuvant therapy used. Our results demonstrate that patients with high intratumor heterogeneity (high MATH scores) would benefit from adjuvant radiation even when NCCN clinical treatment guidelines suggest that it could be omitted. In contrast, patients with low MATH tumors should likely adhere to these guidelines. Our results also support that patients with high MATH tumors will likely not benefit from the addition of adjuvant chemotherapy to radiotherapy, and thus could be spared the additional morbidity of complications from combination therapy. Current HNSCC NCCN treatment guidelines are based on either clinical or pathologic tumor stage and in the postoperative setting the presence or absence of high-risk pathologic features such as positive or close margins and tumor extra nodal extension. Intratumor genetic heterogeneity as measured by MATH analysis has the potential to further inform stage- and pathology-based treatment decisions and consequently should be evaluated in controlled prospective trials that compare adjuvant radiation against chemoradiation following surgery for HNSCC.

Citation Format: Edmund A. Mroz, James W. Rocco. Intratumor genetic heterogeneity as a predictive biomarker in head and neck 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 IA05.
Abstract A36: Developing a novel treatment for advanced ovarian cancer by targeting the c-Met pathway
Authors: Chaparala Anusha , Swetzig Wendy M. , Strohl Anna E. , Wei Jian-Jun , Matei Daniela , Shahabi Shohreh
Published: September 2020

Approximately one-third of epithelial ovarian tumors exhibit higher levels of c-Met, a receptor tyrosine kinase, activated by Hepatocyte Growth Factor (HGF). c-Met plays an important role in the growth and metastasis of tumor cells. Increased c-Met expression is associated with decreased survival and resistance to chemotherapy in various tumors. More recently, our team identified c-Met overexpression as a mechanism of resistance to neoadjuvant chemotherapy (NACT) in ovarian cancer (OC). The c-Met pathway has been explored as a therapeutic target in various solid tumors, and antibodies targeting c-Met have been proposed as novel anticancer agents. This project aims to investigate the effectiveness of a c-Met monoclonal antibody-drug conjugate (c-Met ADC) in OC models. Here we show that the anti-c-Met antibody alone effectively diminishes c-Met signaling (phosphorylation of c-Met and downstream Akt) but does not inhibit OC cell proliferation. In contrast, the c-Met ADC significantly decreases viability and induces apoptosis in c-Met-expressing OC cells. To validate c-Met expression as a predictor of resistance to NACT in OC, we analyzed c-Met expression in matched pre- and post-treatment samples collected from OC patients undergoing treatment with NACT and in a tissue microarray containing 20 ovarian tumors post-NACT. Detectable c-Met was recorded in ~50% of post-NACT specimens. We evaluated the in vitro antitumor activity of c-Met-ADC on the primary cells isolated from patients, before and after NACT, to assess tumor cell sensitivity to c-Met ADC. The results from these studies support the development of c-Met-ADC as a novel treatment for OC.

Citation Format: Anusha Chaparala, Wendy M. Swetzig, Anna E. Strohl, Jian-Jun Wei, Daniela Matei, Shohreh Shahabi. Developing a novel treatment for advanced ovarian cancer by targeting the c-Met pathway [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 A36.
Abstract A43: Centrosome amplification favors survival and impairs ovarian cancer progression
Authors: Morretton Jean-Philippe , Herbette Aurelie , Cosson Camille , Mboup Bassirou , Latouche Aurelien , Gestraud Pierre , Popova Tatiana , Stern Marc-Henri , Nemati Fariba , Decaudin Didier , Bataillon Guillaume , Becette Veronique , Meseure Didier , Nicolas Andre , Mariani Odette , Bonneau Claire , Barbazan Jorge , Vincent-Salomon Anne , Mechta-Grigoriou Fatima , Roman-Roman Sergio , Rouzier Roman , Sastre-Garau Xavier , Goundiam Oumou , Basto Renata
Published: September 2020

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The most common subtype of EOC is high-grade serous (HGSOC), which responds at least initially to chemotherapy but has a worse overall prognosis. Genomic, transcriptomic, and proteogenomic profiling of HGSOC suggested a whole spectrum of molecular diversity, including homologous recombination pathway deficiencies (HRD). The centrosome is the main microtubule (MT)-organizing center of animal cells. It facilitates the accuracy of chromosome segregation during mitosis and influences cell polarity and migration. The presence of more than two centrosomes in a cell, centrosome amplification, has long been associated with tumorigenesis. However, little is known about the real status of centrosome numbers in human cancers and whether numerical alterations are solely associated with poor prognosis. We screened 100 samples of primary EOCs including 88 HGSOC, using immunofluorescence and state-of-the-art microscopy, to determine the centrosome-nucleus index (CNI). We integrated these data with genomic alterations, HRD status, and patient outcome. We found that EOCs are highly heterogeneous, with infrequent but strong centrosome amplifications leading to higher CNI than in healthy tissues. Strikingly, while a correlation between CNI and genomic alterations, such as aneuploidy or chromosome rearrangements, could not be established, we found that high CNI correlates with increased patient survival and sensitivity to chemotherapy, independently of HRD status. Using ovarian cancer cellular models to manipulate centrosome numbers and patient-derived xenografts (PDXs), we found that higher CNIs can positively impact the response to chemotherapy and inhibit peritoneal cell dissemination.

Citation Format: Jean-Philippe Morretton, Aurelie Herbette, Camille Cosson, Bassirou Mboup, Aurelien Latouche, Pierre Gestraud, Tatiana Popova, Marc-Henri Stern, Fariba Nemati, Didier Decaudin, Guillaume Bataillon, Veronique Becette, Didier Meseure, Andre Nicolas, Odette Mariani, Claire Bonneau, Jorge Barbazan, Anne Vincent-Salomon, Fatima Mechta-Grigoriou, Sergio Roman-Roman, Roman Rouzier, Xavier Sastre-Garau, Oumou Goundiam, Renata Basto. Centrosome amplification favors survival and impairs ovarian cancer progression [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 A43.
Abstract A45: Quinacrine induces necrosis of ovarian high-grade serous carcinoma cells by breaking the mitochondria ROS balance
Authors: Huang Ching-I , Chu Tang-Yuan , Huang Hsuan-Shun
Published: September 2020

Ovarian high-grade serous ovarian carcinoma (HGSC) was found to be initiated and promoted by repeated exposure of fimbrial epithelium to ovulatory ROS with resultant intolerable stress of oxidative damages and DNA repair load. Consequential cell apoptosis is overcome on the one hand by quenching excessive ROS by hemoglobin contributed by retrograde menstruation and on the other by upregulation of antioxidant machinery. A dangerous balance is achieved between the oxidative stress and antioxidation and between DNA damage stress and repair. Breaking of this balance on the stress side such as by DNA chelating agent such as cisplatin or inhibitors targeting on DNA repair enzyme such as PARP leads to therapeutic cell killing. In this report, we show ROS enhancing drug such as quinacrine effectively kill HGSC cells and its tubal precursor cells with p53 and Rb defect. Quinacrine is a traditional antimalarial drug with wide antitumor effect in either a single agent or combined with chemotherapy drugs. We show here that quinacrine has a cytotoxic effect in two HGSC cell lines (KURAMOCHI, OVSAHO) and in an HPV E6/E7-immortalized human fimbrial epithelial cells, which are readily fully transformed by ovulatory follicular fluid. Cytotoxicity was observed dose-dependently at concentrations ranging from 2.5μM to 25μM. Flow cytometry analysis indicated a cell necrosis (PI +, annexin V-) 48hr post-treatment. We further found a significant induction of the mitochondrial ROS upon quinacrine treatment, and ROS inhibitor N-acetyl-l-cysteine considerably reversed this cytotoxic effect. The study proves the concept of breaking the balance of mitochondria-ROS is a feasible strategy for the development of a new drug for ovarian HGSC.

Note: This abstract was not presented at the conference.

Citation Format: Ching-I Huang, Tang-Yuan Chu, Hsuan-Shun Huang. Quinacrine induces necrosis of ovarian high-grade serous carcinoma cells by breaking the mitochondria ROS balance [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 A45.
Abstract A57: Identification of novel targets for ovarian cancer treatment
Authors: Noriega Ricardo , Reyes Jeyshka , Quiñones Blanca , Serrano Joseline , Vivas Pablo , Pérez Josué
Published: September 2020

Ovarian cancer remains one of the most lethal diseases for the female reproductive system with 22,530 new cases and more than 13,980 deaths predicted for 2019 in the United States alone, according to the American Cancer Society. Currently, there is no effective therapy for ovarian cancer patients, in particular for those who become resistant to chemotherapy (cisplatin). We need to identify novel targets for ovarian cancer therapy. We performed RNA deep-sequencing studies in cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Several RNA (messengers and long noncoding) were differentially abundant in cisplatin-resistant versus cisplatin-sensitive cells. Many of these RNAs have not been previously studied in ovarian cancer. Therefore, we performed rigorous bioinformatic studies that included data filtering and survival rates (using Kaplan-Meier plot analysis) and IPA (Ingenuity Pathway Analysis) to select key candidate genes that can be used as potential targets for ovarian cancer therapy. Additional data filtering was used to select a list of candidate genes whose expression correlates with the overall survival and progression-free survival of ovarian cancer patients. Future experiments will investigate the biologic consequence of targeting each of these candidate genes in ovarian cancer cells and ovarian cancer mouse models.

Citation Format: Ricardo Noriega, Jeyshka Reyes, Blanca Quiñones, Joseline Serrano, Pablo Vivas, Josué Pérez. Identification of novel targets for ovarian cancer treatment [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 A57.
Abstract A58: HR-ESI-MS identification of novel triterpenoid antitumor substances in securidaca 1, using activity-guided SRB assay
Authors: Obasi Titus Chukwuemeka , Oprean Radu
Published: September 2020

Background: Securidaca 1 is a triterpenoid saponin fraction obtained from African medicinal plant S. longipedunculata, whose action activated apoptosis via inhibition of PI3K-AKT downstream. Preliminary studies show an IC50 of 7.03 (μg/mL), with RT-qPCR gene expression revealing a fold-change reduction of MCL-1 and BCL2L1 antiapoptotic proteins, as well as the inhibition of AKT-3, VEGFA, and CDH-1. Therefore, considering the role of PI3K-AKT pathway in tumoral resistance of ovarian cancer and epithelial-mesenchymal transition during development, our major aim was to isolate and identify the components of securidaca 1 responsible for the activity.

Experimental Procedure: Freeze-dried sample of securidaca 1 was fractionated by FLASH chromatography (RP-C18) and the resultant fractions screened by SRB cytotoxicity assay (96-well format) using HeLa cell line. The most promising subfraction was further purified by semipreparative HPLC (reversed-phase). Isolated substances were identified by HR-ESI-MS and IC50s determined and compared with 5-fluorouracil (5-FU) reference standard.

Results: The HR-ESI-MS spectrum under negative ion mode revealed the parent molecular ion peaks of the semipreparative fractions (FR15-6 and FR15-7), whose IC50s were confirmed at 3.84 and 4.83 μg/mL, respectively, on HeLa cell line, more sensitive than 5-FU. MS/MS fragmentation spectra (negative ion mode) show putative fragments of molecular ions 455 and 425 (m/z), respectively, typically indicating oleanine triterpenoid aglycone. Post-TLC derivatization tested positive to Liebermann Burckhard and Carr Price reactions, and sugars.

Conclusion: FR15-6 and FR15-7 are potential candidates for anticancer development whose actions may be responsible for antitumor activities previously seen in securidaca 1. Work is ongoing to evaluate their capacities in blocking tumor development via antiapoptotic effectors of PI3K-AKT downstream pathway.

Note: This abstract was not presented at the conference.

Citation Format: Titus Chukwuemeka Obasi, Radu Oprean. HR-ESI-MS identification of novel triterpenoid antitumor substances in securidaca 1, using activity-guided SRB assay [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 A58.