bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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&lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
Cancer disparities research has a sample number problem, especially in serous ovarian cancer (SOC). Driver genes for SOC are mutated in &lt;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.