bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A22: Patient-derived organoids recapitulate response heterogeneity in head and neck cancer
Authors: King Vincent-Chong Vui , Tracy Erin C. , Baumann Heinz , Hershberger Pamela A , Seshadri Mukund 
Published: September 2020

Abstract
Patient-derived organoids (PDOs) are considered to be a cost-effective, high-throughput preclinical platform for studying cancer biology and evaluating novel therapeutics. While PDOs have been established and characterized for breast, prostate, colon, and pancreatic cancers, PDO models of head and neck squamous cell carcinomas (HNSCC) are limited. To address this paucity, in the present study, we established a panel of PDO models of HNSCC. Five HNSCC samples (3 larynx, 1 tongue, 1 parotid) were procured from donor patients following informed consent and processed to establish organoids. Histologic (H&E) and immunohistochemical evaluation (p16, cytokeratin) was performed along with assessment of PDO response to the alkylating agent, cisplatin, and two tyrosine kinase inhibitors, erlotinib and afatinib. Histologic analyses of established organoids revealed nested cells of squamous cell carcinoma with high N/C ratio similar to donor surgical tumor tissue. Immunohistochemistry revealed strong pan cytokeratin and absence of p16 staining in all samples. Paired PDO and PDX models also successfully retained the squamous histology. Dose-response curves revealed substantial variation in therapeutic profiles of the three agents across the organoid panel. While the IC50 of cisplatin was comparable across the larynx organoids, 2 larynx organoids were sensitive to the two TKIs while one was resistant, exhibiting ~5-fold higher IC50 values. The tongue organoid was relatively sensitive to all agents while the parotid SCC organoid was sensitive to EGFR TKIs but relatively resistant to cisplatin. Collectively, these results demonstrate the ability of organoid models to recapitulate the histologic architecture and response heterogeneity of human HNSCC. Investigation into the molecular profiles of our PDO panel is under way in our laboratory and will enable further development of organoids as a robust platform for evaluation of precision therapeutics against HNSCC.
Citation Format: Vincent-Chong Vui King, Erin C. Tracy, Heinz Baumann, Pamela A Hershberger, Mukund Seshadri. Patient-derived organoids recapitulate response heterogeneity 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 A22.
Abstract A29: Association of support group attendance with quality-of-life metrics in head and neck cancer patients
Authors: Itamura Kyohei , Lam David , Cameron Brian , Chambers Tamara , Kokot Niels , Maceri Dennis , Sinha Uttam , Swanson Mark , Villegas Brenda 
Published: September 2020

Abstract
Quality of life has emerged as an increasingly prominent metric of interest for those with head and neck cancer during the course of their recovery. Although many factors have been shown to affect quality of life, the effect of support group attendance has been limited and mixed in the head and neck cancer literature. There is still controversy with regard to the efficacy of support groups. This study aims to add to the literature by reporting the association of support group attendance on quality-of-life measures in head and neck cancer patients. Our findings will help with recommendations for implementing support groups into head and neck cancer care. This is a cross-sectional, survey-based study employing the University of Washington head and neck cancer quality-of-life questionnaire. This survey has been previously validated in the literature as an objective quality of life measurement tool for head and neck cancer patients. All study participants are head and neck cancer patients who have received treatment. Study participants were separated into two separate groups: 1) patients who have never attended support group in the past; 2) patients who have utilized support group. Survey scores are compared between the two groups via unpaired Mann-Whitney U test. Patients who attended support group (N=32) compared to those who have not (N=52) showed significantly greater quality-of-life median scores on appearance (support group median score = 75 vs. no support group median score = 50, U=513, p=0.02), activity (75 vs. 50, U=463, p=0.004), recreation (75 vs. 50, U=404, p&lt;0.001), mood (75 vs. 50, U=310, p&lt;0.001), anxiety (100 vs. 30, U=164, p&lt;0.001), and overall sense of quality of life (80 vs. 60, U=365, p&lt;0.001). There were no statistically significant differences between the two groups for scores in pain, swallowing, chewing, speech, shoulder mobility, taste, or recent changes in subjective sense of quality of life. Our data suggest that support group attendance is associated with a higher quality of life specifically related to mental health and social well-being. There was no observable benefit in physical functional recovery with support group attendance. There appear to be psychosocial benefits from incorporating support groups into head and neck cancer rehabilitation.
Citation Format: Kyohei Itamura, David Lam, Brian Cameron, Tamara Chambers, Niels Kokot, Dennis Maceri, Uttam Sinha, Mark Swanson, Brenda Villegas. Association of support group attendance with quality-of-life metrics in head and neck cancer patients [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 A29.
Abstract A31: Deregulation of NOTCH 1/NR4A2 signaling axis in head and neck cancer pathogenesis
Authors: Chaudhary Sanjib , Pothuraju Ramesh , Sayed Zafar , Jones Dwight T. , Batra Surinder K. , Macha Muzafar A. 
Published: September 2020

Abstract
Background: Notch1 and its intracellular cytoplasmic domain (NICD) are dysregulated in many solid tumors, including head and neck squamous cell carcinoma (HNSCC), and associated with disease initiation and progression. NICD-mediated upregulation of nuclear receptor related 1 (NURR1/NR4A2) is linked to differentiation/development, homeostasis, and cellular metabolism. However, the role and molecular mechanism(s) of Notch1/NICD- NR4A2 axis in HNSCC pathogenesis are still unknown and need to be investigated.
Methods: The clinicopathologic importance of Notch1 and NR4A2 was investigated using HNSCC patient samples and publicly available databases. NR4A2 was stably knocked out (KO) and Notch1 signaling was blocked using small-molecule inhibitor (PF3084014) in HNSCC cell lines and analyzed for tumorigenic and metastatic potential. We also examined the whole-genome NR4A2 target genes using ChIP sequencing.
Results: Both Notch1 and NR4A2 were highly overexpressed in HNSCC patients. Inhibition of Notch1 signaling or NR4A2 KO significantly decreased the clonogenicity and migratory potential of HNSCC cells. Our ChIP analysis revealed that NR4A2 regulates genes involved in metabolism, hypoxia, cell cycle progression, integrin and Wnt signaling. Interestingly, we observed that NR4A2 regulates stem cell markers including Sox2, Nanog, and CD44 and their expression was drastically reduced upon Notch 1 inhibition.
Conclusion: Targeting Notch1-NR4A2 signaling axis may be crucial for inhibition of cancer stem cell-mediated HNSCC pathogenesis.
Citation Format: Sanjib Chaudhary, Ramesh Pothuraju, Zafar Sayed, Dwight T. Jones, Surinder K. Batra, Muzafar A. Macha. Deregulation of NOTCH 1/NR4A2 signaling axis in head and neck cancer pathogenesis [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 A31.
Abstract A34: Effect of microvesicles on metalloproteinases secretion by myoepithelial cells
Authors: Rena Gabriel Bernardo , Teixeira Lucas Novaes , Araújo Vera Cavalcanti , Demasi Ana Paula Dias , Martinez Elizabeth Ferreira 
Published: September 2020

Abstract
In tumorigenesis, not only genetic and epigenetic alterations but also stromal cells and soluble factors in the tumor microenvironment can affect the progression of different neoplasms. In salivary gland tumors derived from the intercalated duct, the myoepithelial (Myo) component modulates the neoplastic phenotype positively. Indeed, in carcinoma ex-pleomorphic adenoma (CXPA) where the malignant component is represented only by epithelial cells, the Myo cells present a role in the progression of this neoplasia. Nevertheless, great interest has been taken in the mechanisms of cellular communication mediated by microvesicles (MV). These structures are secreted by different cells and may induce epigenetic modifications. In malignant neoplasia, MV may affect different stages of carcinogenesis, which comprise the modulation of the extracellular matrix components, including metalloproteinases (MMPs). MMPs 2 and 9 exert an essential role in the epithelial-mesenchymal transition, consequently increasing the potential of migration and invasion of plethora tumors, including CXPA. The present in vitro study aimed to characterize MV derived from malignant neoplastic epithelial cell cultures (CAL27 cells) and their effect on the expression of MMPs in benign Myo cell cultures. Malignant epithelial cells (CAL 27 cell line) were cultured until they reached confluence. Then, the culture medium was collected and the MV were extracted. The Myo cultures, derived from pleomorphic adenomas explants, were exposed to MV from CAL 27 for 24 h. After this period, the secretion of MMPs 2, 9 and their inhibitors, TIMP-1 and TIMP-2, was assayed by means of ELISA. The Myo cultures not exposed to MV were used as control. The results indicated that Myo exposed to MV exhibited a significant increase of MMP-2 and MMP-9 expression (p&lt;0.05) and a reduction in TIMP-2 expression (p&lt;0.05). TIMP-1 expression in Myo cultures was not affected by MV (p&gt;0.05). In conclusion, the data suggest that MV can modulate MMP and their inhibitors’ expression in Myo cell, which may promote extracellular matrix degradation and CXPA invasion.
Citation Format: Gabriel Bernardo Rena, Lucas Novaes Teixeira, Vera Cavalcanti Araújo, Ana Paula Dias Demasi, Elizabeth Ferreira Martinez. Effect of microvesicles on metalloproteinases secretion by myoepithelial cells [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 A34.
Abstract A35: Diagnostic performance and timing of post-treatment 18F-FDG PET/CT for head and neck cancer surveillance: A meta-analysis of reported studies
Authors: Wong Erin T. , Dmytriw Adam A. , Yu Eugene , Waldron John , Fazelzad Rouhi , de Almeida John , Veit-Haibach Patrick , O’Sullivan Brian , Xu Wei , Huang Shao Hui 
Published: September 2020

Abstract
Purpose: The aims of this meta-analysis are to evaluate the diagnostic performance and to explore the optimal timing of post-treatment 18F-FDG PET/CT for HNSCC.
Methods: January 2010 to August 2016 was the range for study selection. Subgroup analyses were performed for local/regional failure stratified by treatment-to-scan time interval of ≤3 vs. &gt;3 months.
Results: Twenty-four studies (2,256 patients) were included. Compared to ≤3 months, 18F-FDG PET/CT performed &gt;3 months showed significantly improved sensitivity (87% vs. 60%, p=0.020) and specificity (93% vs. 84%, p&lt;0.001) for identifying local failure and marginally improved sensitivity for regional failure (79% vs. 56%, p=0.100). The specificity for regional failure was equally high for &gt;3 months vs. ≤3 months (95% vs. 97%, p=0.35).
Conclusions: This meta-analysis showed high NPV but modest PPV for post-treatment 18F-FDG PET/CT for local and regional failure. Sensitivity is improved if performed &gt;3 months for local failure and marginally improved for regional failure.
Citation Format: Erin T. Wong, Adam A. Dmytriw, Eugene Yu, John Waldron, Rouhi Fazelzad, John de Almeida, Patrick Veit-Haibach, Brian O’Sullivan, Wei Xu, Shao Hui Huang. Diagnostic performance and timing of post-treatment 18F-FDG PET/CT for head and neck cancer surveillance: A meta-analysis of reported studies [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 A35.
Abstract B13: Utilizing metabolic reprogramming to regulate fibroblast phenotype and reduce radiation fibrosis
Authors: Zhao Xiao , Psarianos Pamela , Goldstein David , Gilbert Ralph , Witterick Ian , Ailles Laurie , Haibe-Kains Benjamin , Liu Fei-Fei 
Published: September 2020

Abstract
Introduction: Radiation fibrosis affects up to half of all patients undergoing radiotherapy for head and neck cancer treatment. It is characterized by excess extracellular matrix deposition, leading to tissue dysfunction, distortion, hardening, and pain. There are currently no effective treatments for radiation fibrosis. A fundamental challenge has been to understand and modulate the function of fibroblasts, a key mediator in extracellular matrix production and degradation. Recent evidence has demonstrated that metabolic regulation plays an important role in altering cell behavior in cancer biology and immunology. However, little is known about how metabolic changes affect fibroblast phenotype.
Hypothesis: We propose that metabolic reprogramming may be an effective strategy to modulate fibroblast function and reduce radiation fibrosis.
Results: An interplay between fatty acid oxidation and glycolysis was found to be a convergence point directly governing fibroblast behavior. It was demonstrated that manipulating the balance between FAO and glycolysis in fibroblasts induced either an extracellular matrix anabolic or catabolic phenotype. Specifically, anabolic fibroblasts relied on a fatty acid oxidation to glycolysis shift to produce extracellular matrix components. Reversal of this metabolic shift generated a catabolic fibroblast, which downregulated extracellular matrix synthesis and upregulated extracellular matrix lysosomal degradation. We further uncovered that CD36, a multifunctional fatty acid transporter, was a crucial link connecting fibroblast metabolism with extracellular matrix regulation, as its depletion completely inhibited collagen-1 internalization and degradation. Finally, through metabolic reprogramming using fibroblasts expressing high levels of CD36, but not CD36 knockout fibroblasts, metabolic balance could be restored, and in turn extracellular matrix accumulation was reduced in murine radiation fibrosis.
Conclusions: We have uncovered that a fibroblast’s phenotype can be differentiated and regulated based on its metabolic signature. These findings have significant implications for drug development and for future cellular therapies to reduce radiation fibrosis.
Citation Format: Xiao Zhao, Pamela Psarianos, David Goldstein, Ralph Gilbert, Ian Witterick, Laurie Ailles, Benjamin Haibe-Kains, Fei-Fei Liu. Utilizing metabolic reprogramming to regulate fibroblast phenotype and reduce radiation fibrosis [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 B13.
Abstract B17: Functional characterization of HPV-human fusion transcripts in oropharyngeal cancer
Authors: Pinatti Lisa M. , Walline Heather M. , Carey Thomas E. 
Published: September 2020

Abstract
Human papillomavirus (HPV) genomic integration is frequently seen in oropharyngeal squamous cell carcinoma (OPSCC). Integration into cellular genes can cause the generation of HPV-host fusion transcripts, which have been associated with worse survival in OPSCC patients, but their functional consequences are unknown, as HPV alone is capable of transformation. The forced expression of fusion transcripts versus HPV transcripts in spontaneously immortalized human oral keratinocytes (NOKSI) could demonstrate their effects on cell behavior. Our research focuses on characterizing HPV integration sites and fusion transcripts in cell lines and tumors, followed by in vitro analysis of fusion transcript function. By Detection of Integrated Papillomavirus Sequences (DIPS-PCR) and RT-PCR, we have identified integration events and fusion transcripts in a subset of samples in both intergenic and genic regions of the genome. We began our analysis with two fusion transcripts, one reading from HPV16 E6*-E7-E1 into the tumor suppressor gene TP63 from UM-SCC-47 and the other reading from HPV16 E6*-E4 into the solute carrier gene SLC47A2 from UM-SCC-104. The full fusion transcripts and associated controls were cloned into lentiviral vectors, and stable keratinocyte populations expressing these transcripts were selected. These cultures were subjected to proliferation, migration, and invasion assays. Subsequent in-depth molecular characterization and in vivo studies will help clarify their effects on cancer formation and metastasis. These studies will advance our understanding of how fusion transcripts lead to worse patient survival and help develop new therapies for these patients.
Citation Format: Lisa M. Pinatti, Heather M. Walline, Thomas E. Carey. Functional characterization of HPV-human fusion transcripts in oropharyngeal 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 B17.
Abstract B35: Characterization of exosomes extracted from primary tumor samples of HPV+/- oropharyngeal cancer
Authors: Wu Vivian F. , Dai Xiang Guo , Chopp Michael 
Published: September 2020

Abstract
Objective: To determine if distinctions in exosomal cargo contribute to differences in EMT between HPV-related and HPV-unrelated oropharyngeal disease and can provide a signature for prediction of tumor aggressiveness and metastatic potential.
Subjects and Methods: Specimen from patients with HPV+/- OPSCC were collected according to an IRB-approved protocol including primary tumor, lymph node metastasis, distant metastasis, and serum when available. Exosomes isolated from HPV+ and HPV- tumors were analyzed with miARma-seq and proteomics. These same exosomes were cocultured with well-characterized HPV+ and HPV- cell lines as well as fibroblasts and normal keratinocytes. Tumor aggressiveness, EMT, and potential for metastasis were measured utilizing wound healing scratch assays and transwell invasion assay techniques based on the Boyden Chamber migration assay. Confirmation of epithelial to mesenchymal transition was evaluated by Western blot and qPCR using a panel of well-established EMT markers (e-cadherin, n-cadherin, vimentin, snail, slug, twist, ZEB1/2).
Results: Tumors from HPV+ patients demonstrate exosomal content enriched in EMT markers compared to HPV-negative patient cultures. Exosomes extracted from primary tumor and lymph node metastasis of the same patient demonstrate differential expression of markers of EMT. Exosomes extracted from lymph node and cocultured with fibroblasts demonstrate increased invasion and migration.
Conclusions: Exosomes can be extracted from primary patient tumor cultures of both primary tumor and lymph node metastasis. These exosomes demonstrate differential expression of markers of EMT. Exosomal contents can be exploited for biomarker discovery to aide in prognostication.
Citation Format: Vivian F. Wu, Xiang Guo Dai, Michael Chopp. Characterization of exosomes extracted from primary tumor samples of HPV+/- oropharyngeal 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 B35.
Abstract B40: Trends in lymph node yield for neck dissection and oral cavity carcinoma survival
Authors: Patel Punam , Kedarisetty Suraj , Lango Miriam 
Published: September 2020

Abstract
Objectives: Lymph node yields (LNYs) following neck dissection have been associated with differences in oral cavity cancer survival. The objective of this study was to evaluate temporal trends in LNYs in neck dissections for oral cavity carcinoma.
Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER 18) database. Inclusion criteria included diagnosis of malignant oral cavity cancer (tongue and floor of mouth) squamous cell carcinomas diagnosed from January 1, 2006-December 31, 2016. Patients with AJCC 6th Edition Stages 1-4a who underwent surgery were included. All-cause age-adjusted mortality for tongue and floor of mouth cancers during this period was assessed using SEER*Stat.
Results: The median LNY among 8,580 patients in the sample was 25 LNs (Interquartile range 14-39). LNY statistically increased over time from 22 LNs in 2004 to 27 in 2014 (p &lt; 0.0001). In contrast, there was no change in the median number of positive LNs during the same period (median 2 positive LNs in 2004 and 2014). There was no significant difference in lymph node yield based on sex, region, insurance status, or relative location to a metropolitan center. After adjusting for patient age, sex, race, marital status, regional income, and percent current smokers in the county of residence, tumor subsite and TNM stage, LNY less than 18 was independently associated with a 44% greater risk of death from any cause, compared with greater LNYs (HR 1.44, 95% CI 1.29-1.60, p=.0001). During this period, all-cause age-adjusted mortality declined from 469.7 per 100,000 (468.2-471.2) to 429.0/100,000 (428.2-430.8).
Conclusion: LNY following neck dissection for oral tongue and floor of mouth cancers increased significantly over a decade, during which survival also improved. The cause of improved LNY is not known but may nevertheless be contributing to declining mortality in patients with oral tongue and floor of mouth cancers.
Citation Format: Punam Patel, Suraj Kedarisetty, Miriam Lango. Trends in lymph node yield for neck dissection and oral cavity carcinoma survival [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 B40.