bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA29: The Hippo pathway integrates PI3K-Akt signals with mechanical cues to control tissue growth
Authors: Thompson Barry 
Published: September 2020

Abstract
The Hippo signaling pathway restricts cell proliferation in animal tissues by inhibiting YAP (or YAP1) and TAZ (or WWTR1), coactivators of the Scalloped (Sd or TEAD) DNA-binding transcription factor. Drosophila has a 24 single YAP/TAZ homolog named Yorkie (Yki) that can be mechanically regulated during development. Here we show that Yki translocates to the nucleus to drive Sd-mediated cell proliferation in the ovarian follicle cell epithelium in response to mechanical stretching caused by the growth of the germline. Importantly, mechanically induced Yki nuclear translocalization also requires nutritionally induced Insulin/IGF-1 signaling via PI3K, PDK1, and Akt in the follicular epithelium. We find similar results in the developing Drosophila wing, where Yki becomes nuclear in the mechanically stretched cells of the wing pouch during larval feeding, which induces Insulin/IGF-1 signaling, but translocates to the cytoplasm upon cessation of feeding in the third instar stage. Ectopic activation of PI3K or Akt is sufficient to maintain nuclear Yki in the wing disc even after feeding ceases. An Akt phosphorylation site in the Hpo kinase domain is required to attenuate Hpo kinase activity, enabling further inhibition of Hippo signaling by mechanical stimuli to drive Yki activation. Finally, Insulin/IGF-1 signaling also promotes YAP nuclear localization in response to mechanical cues in mammalian skin epithelia. Thus, the Hippo pathway has a physiologic function as an integrator of mechanical and nutritional cues to control cell proliferation and tissue growth in both Drosophila and mammals.
Citation Format: Barry Thompson. The Hippo pathway integrates PI3K-Akt signals with mechanical cues to control tissue growth [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 IA29.
Abstract PR06: Mechanistic insights for TEAD/YAP activation
Authors: Holden Jeffrey K. , Cunningham Christian N. 
Published: September 2020

Abstract
Transcriptional enhanced associate domain (TEAD) transcription factors activate the transcription of cell growth and proliferation genes in the presence of the transcriptional coactivators YAP or TAZ. TEAD proteins consist of two major domains connected by a proline-rich linker: a DNA binding domain and a coactivator binding domain. Although multiple structural models of individual TEAD and YAP domains have been solved, the structures of either the full-length proteins or the heterodimeric complex remain elusive. Characterization of the higher-order architecture of the TEAD:YAP complex is a prerequisite to elucidating the mechanism of Hippo-dependent transcriptional activation and potential therapeutic intervention. To better understand how TEAD and YAP interact, we have successfully been able to express and purify full-length versions of each protein and have used these novel reagents to interrogate their structural interactions using a variety of biophysical and biochemical methodologies in the presence or absence of DNA. Our findings uncover a novel interaction interface between TEAD and YAP that is required to stabilize TEAD in a DNA-binding competent conformation and begin to shed light on the mechanism of TEAD-based transcriptional activation.
This abstract is also being presented as Poster A25.
Citation Format: Jeffrey K. Holden, Christian N. Cunningham. Mechanistic insights for TEAD/YAP activation [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 PR06.
Abstract A21: Increasing use of adjuvant radiation for parathyroid carcinoma is associated with improved survival outcomes: A population-based study
Authors: Cannon Richard B. , Carpenter Patrick S. , Buchmann Luke O. , Hunt Jason P. , Lloyd Shane , Hitchcock Ying , Monroe Marcus M. 
Published: September 2020

Abstract
Objectives: Parathyroid carcinoma is rare and treatment for these cancers varies between institutions. The primary purposes of this study were to use the Surveillance, Epidemiology, and End Results (SEER) database to evaluate current practice patterns in the use of adjuvant radiation for parathyroid cancers and to investigate the efficacy in a population-based setting.
Methods: There were 508 patients treated surgically for parathyroid cancer from 1973 to 2013 identified in the SEER database. Patients with metastatic disease and other prior malignancies were excluded. Three hundred and twenty-one patients (63%) had local disease, while 187 had regional lymph node involvement (37%). Of these patients, 78 (15%) were treated with adjuvant radiation. 5-year disease-specific survival (DSS) and overall survival (OS) were the primary outcomes.
Results: Treatment with adjuvant radiation therapy was significantly associated with improved 5-year DSS (94% versus 89%; p=0.045) and OS (81% versus 74%; p=0.036). Improved DSS and OS were significant after controlling for other known covariates on multivariate analysis (HR 0.59, 95% CI 0.44-0.87, p&lt;0.001; HR 0.65, 95% CI 0.47-0.92, p&lt;0.001). The percent utilization of adjuvant radiation for patients with parathyroid carcinoma has significantly increased through the study time period from 7% (1973 to 1986) to 11% (1987 to 2000) to 18% (2001 to 2013) (p=0.011).
Conclusion: Adjuvant radiation appears to provide a survival benefit for patients with parathyroid carcinoma. Utilization of adjuvant radiation is increasing over time for these patients.
Citation Format: Richard B. Cannon, Patrick S. Carpenter, Luke O. Buchmann, Jason P. Hunt, Shane Lloyd, Ying Hitchcock, Marcus M. Monroe. Increasing use of adjuvant radiation for parathyroid carcinoma is associated with improved survival outcomes: A population-based study [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 A21.
Abstract A27: Differential protein-interactome of MYB-NF1B fusion in adenoid cystic carcinoma
Authors: Humtsoe Joseph O. , Kim Hyun-Su , Soucheray Margaret , Swaney Danielle , Ha Patrick K. 
Published: September 2020

Abstract
Chromosomal translocations occur frequently in adenoid cystic carcinomas (ACC). In salivary gland ACC, the commonly identified rearrangement occurs at chromosome t(6:9), resulting in the fusion of the transcription factor genes, MYB and NF1B. The gene fusion encoding a chimeric MYB-NF1B is a unique genetic feature, regarded as a hallmark in ACC carcinogenesis. Although MYB-NF1B may be involved in the deregulation of MYB expression and its downstream gene targets, the precise role of MYB-NF1B in the development and maintenance of ACC remains to be clearly defined. Here, we engineered an inducible system to express either MYB or MYB-NF1B in ACC-01 cells, which express low levels of endogenous MYB but not MYB-NF1B, to study the molecular and mechanistic role of MYB-NF1B. Immunoprecipitation and mass spectrometry analysis revealed the presence of previously unreported MYB- and MYB-NF1B-interacting partners, including vimentin and nuclear myosin (MYO1C). These interactions were positively validated in several patient-derived xenograft models of ACC. Interestingly, MYB and MYB-NF1B interaction with vimentin and MYO1C appeared to be differentially regulated, and altering vimentin expression reduces MYB levels, while maintaining relatively steady levels of MYB-NF1B. MYO1C is involved in transcriptional regulation, and altered MYB-NF1B binding activity with nuclear myosin may modulate downstream gene targets. While detailed further study is needed, these findings suggest a potential distinct function of MYB-NF1B that may play an important role in ACC pathogenesis.
Citation Format: Joseph O. Humtsoe, Hyun-Su Kim, Margaret Soucheray, Danielle Swaney, Patrick K. Ha. Differential protein-interactome of MYB-NF1B fusion in adenoid cystic 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 A27.
Abstract B02: Efficacy of EPA-enriched supplement compared with standard formula on body weight changes in malnourished head and neck cancer patients undergoing surgery: A randomized study
Authors: Jantharapattana Kitti , Orapipatpong Orachat 
Published: September 2020

Abstract
Background: Eicosapentaenoic acid (EPA) containing nutritional supplement can reverse weight loss and increase lean body mass in a perioperative period of head and neck cancer patients. There is no randomized study to clinically compare an EPA-enriched supplement over a conventional supplement in head and neck cancer patients. Thus the aim of this study was to compare an EPA-enriched supplement with a conventional supplement in malnourished head and neck cancer patients following surgery. The primary outcome of this study was defined as perioperative weight changes, with postoperative complications a secondary outcome.
Methods: The patients were stratified into 4 groups based on the extent of their surgery: primary tumor resection or neck dissection, primary tumor resection and neck dissection, primary tumor resection and flap reconstruction, and primary tumor resection and neck dissection and flap reconstruction. Pretreatment randomization was conducted in each stratified group for the selection of nutritional supplement, whether EPA-enriched or standard formula. The supplements were prescribed 7 days preoperative through 14 days postoperative. Body weight and composition including serum parameters were measured from 7 days preoperative until 4 months postoperative. The hospitalized courses were recorded.
Results: Thirty-one patients in each group consumed EPA-enriched and standard formula supplements. There were no significant body weight or composition changes perioperatively. From 7 days before surgery to 4 months after surgery, mean body weight reduced by 2.95 (SD 4.70) kg and 2.82 (SD 4.78) kg in the EPA-enriched and standard formula groups, respectively. The mean overall patient weight loss was 2.89 kg or 5% throughout the period of study. No significant differences in lean body mass and body composition changes from the beginning to the end of the study were observed between the groups. No significant differences in the hospitalized days and postoperative complications were observed.
Conclusions: Body weight changes in malnourished head and neck cancer patients following surgery were not influenced by EPA additives to perioperative nutritional supplements.
Citation Format: Kitti Jantharapattana, Orachat Orapipatpong. Efficacy of EPA-enriched supplement compared with standard formula on body weight changes in malnourished head and neck cancer patients undergoing surgery: A randomized study [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 B02.
Abstract B09: Inactivating the EGFR-Arf1 axis by HDAC-targeted therapy to suppress invasiveness of head and neck squamous cell carcinoma
Authors: He Leilei , Gao Lixia , Lang Liwei , Shay Chloe , Teng Yong 
Published: September 2020

Abstract
Histone deacetylase (HDAC)-targeted treatment has the great potential to treat head and neck squamous cell carcinoma (HNSCC). However, little has been reported regarding the beneficial role of HDAC inhibition in anti-HNSCC therapy and the underlying molecular mechanisms remain elusive. Here, we demonstrate that ADP-ribosylation factor 1 (Arf1), a small GTPase coordinating vesicle-mediated intracellular trafficking, can be inactivated by HDAC inhibitors TSA and PXD101, through histone acetylation-independent degradation of epidermal growth factor receptor (EGFR) in HNSCC cells. Mechanistically, activated Arf1 (GTP-Arf1) is maintained by binding to phosphorylated EGFR on the cancer cell plasma membrane. Decreased EGFR phosphorylation is associated with reduced EGFR protein levels in the presence of HDAC inhibitors, which inactivates Arf1 and eventually inhibits its dependent invasion in HNSCC cells. This novel finding represents the first example of modulating the EGFR-Arf1 complex in HNSCC by small-molecule agents. Our insights not only explore the critical role of the EGFR-Arf1 complex in driving HNSCC progression, but also shed light onto the molecular events accounting for HDAC-targeted therapy.
Citation Format: Leilei He, Lixia Gao, Liwei Lang, Chloe Shay, Yong Teng. Inactivating the EGFR-Arf1 axis by HDAC-targeted therapy to suppress invasiveness of 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 B09.
Abstract B29: Intraoperative identification of critical vascular landmarks of the lateral oropharynx and tongue base using transoral robotic ultrasound (TORUS)
Authors: Liu Wen P. , Holsinger F. Chris , Vendra Varun 
Published: September 2020

Abstract
Transoral robotic surgery (TORS) is an expanding domain of minimally invasive surgery, which has been employed since 2009 in the United States primarily for the management of upper aerodigestive tract tumors (1). Tongue base reduction is an emergent application of TORS in obstructive sleep apnea (2). The technique uses the da Vinci surgical system (Intuitive Surgical, Sunnyvale, CA, USA) to deliver a camera and instruments on three robotic arms. Identification of large-caliber blood vessels emanating from the external carotid artery is a critical step in TORS for tongue base and lateral oropharynx disease. Specifically, control of the lingual artery and facial artery branches is necessary for safe surgical dissection (3). Previously, the use of ultrasound has been described in TORS for the intraoperative localization of retropharyngeal lymph nodes (4-6). One case series in the literature has described the use of a handheld ultrasound probe in TORS for pharyngeal and base of tongue tumors (7). We describe the use of a novel miniaturized ultrasound probe (Mindray North America, San Jose, CA, USA) capable of being manipulated by the da Vinci arm to allow intraoperative transoral robotic ultrasonography (TORUS). The ergonomics of this system was evaluated in human cadavers, followed by an efficacy trial in a porcine model. Two surgeons, one experienced (FCH) and one novice (VV), performed ultrasound-guided identification of the lingual and buccal arteries. Time to identification was measured. Mean time in seconds for the localization of the buccal artery was 53.0 for the experienced robotic surgeon versus 27.5 for the novice surgeon (p=0.10), and 55.0 versus 268.0, respectively, for the lingual arteries (p=0.003). Herein, we show the feasibility of TORUS to identify the large-caliber blood vessels of the oral cavity and oropharynx during TORS. This platform may allow for safer dissection, without a significant increase in operative time or need to interrupt the robotic setup. Future directions include human clinical trials, measurement of tumor volume, depth of invasion, and identification of additional surgical landmarks.
Citation Format: Wen P. Liu, F. Chris Holsinger, Varun Vendra. Intraoperative identification of critical vascular landmarks of the lateral oropharynx and tongue base using transoral robotic ultrasound (TORUS) [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 B29.
Abstract B32: Impact of cancer-associated fibroblasts on head and neck cancer stem cells
Authors: Neal Molly E. Heft , Owen John Henry J. , Spector Matthew E. , Carey Thomas E. , Prince Mark E.P. , Chinn Steven B. 
Published: September 2020

Abstract
Background: The tumor microenvironment (TME) is made up of epithelial cancer cells and mesenchymal stromal cells including tumor-infiltrating lymphocytes, cancer-associated fibroblasts (CAFs) and endothelial cells. Within the cancer cell population are cancer stem cells (CSC), a subpopulation of cells defined as having the capacity for self-renewal, tumorigenesis, and the ability to recapitulate a heterogeneous tumor. The interaction of the TME with cancer cells remains of interest. The focus of this study is to investigate the effect of patient-derived CAFs on head and neck CSC and tumor activity.
Methods: Patient-derived head and neck cancer cell lines and patient-derived fibroblasts lines have previously been established by our group. Tumor cells were grown alone or in combination with patient-matched fibroblasts in a coculture chamber system, allowing for mixture of media but not cells. Scratch tests were performed and closure rates were compared between the two conditions (tumor cells alone and coculture). Tumor cells were then grown alone or in direct contact with matched fibroblasts for one week. Cancer cells were selected for based on epithelial cell adhesion molecule (EpCAM) status and in vitro tumor growth and stem cells percentages (defined as proportion of CD44-high and ALDH-positive cells) were calculated.
Results: Patient-derived cancer cells cocultured with matched fibroblasts showed a significant increase in closure rates compared with tumor cells alone at three defined time points (p=0.03-0.002). Coculture conditions resulted in greater in vitro tumor growth after one week (6.4-fold vs. 3.7-fold increase) and an increased proportion of CD44-high tumor cells (9% vs. 5%). The effect of coculture on ALDH-positive percentages was variable.
Conclusion: CAFs have previously been shown to potentiate tumorigenesis and metastases. We validated these findings with matched patient derived tumor cells and CAFs. We were then able to demonstrate that CAFs increase the proportion of head and neck CSC, suggesting the mechanism for CAF-associated increased tumor activity may be mediated through CSC. Further studies investigating the relationship between CAFs and CSC are warranted.
Citation Format: Molly E. Heft Neal, John Henry J. Owen, Matthew E. Spector, Thomas E. Carey, Mark E.P. Prince, Steven B. Chinn. Impact of cancer-associated fibroblasts on head and neck cancer stem 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 B32.
Abstract B38: Identification of stage-wise miRNAs signature as potential biomarker in head and neck squamous cell carcinoma
Authors: Kumar Sugandh , Dixit Anshuman 
Published: September 2020

Abstract
The head and neck squamous cell carcinoma (HNSCC) is one of the predominant causes of cancer-related casualties globally. The high mortality rate of HNSCC is due to late diagnosis, and the overall survival rate is less than 50%. The early detection of a primary tumor and prevention of relapse are the major research challenges associated with various cancer including HNSCC. However, currently, not one molecular marker has been widely accepted for routine use in managing patients with HNSCC. Therefore, a study relating the association between clinical stages and different coding/noncoding expression profiles is very much required to identify the potential biomarker for early detection and therapeutics. In the current study, we have analyzed TCGA transcriptomics (i.e., miRNAs, mRNAs) profile to extract meaningful molecular signature in different TNM stages of HNSCC. Further, we used machine learning and other regression approaches to identify the signature miRNAs as a biomarker in various stages of cancer. The analysis revealed uncovered miRNAs with stage-dependent alterations in expression (has-miR-31, miR-143, miR-202, miR-135b, let-7, etc.) specifically expressed in early clinical stages whereas (miR-636, miR-1, miR-99a and miR-3934) specifically expressed in later stages. Kaplan-Meier survival analysis also revealed that some of the identified miRNA used as a potential prognostic biomarker. The top enriched regulatory genes involved in ECM degradation, Nicotine Degradation III, EMT, Integrin signaling and IL-10 in early stages were at later stage pathways, i.e., glucose metabolism. The combination of stage-specific miRNAs could be used for the target of oncogenesis and chemoresistance pathways. Initial stage biomarkers may prove to be essential tools in the timely diagnosis of the disease and improved overall survival outcome. We hope the current study for biomarker identification will open new opportunities for the development of effective diagnostic and therapeutic drug for HNSCC in the future.
Citation Format: Sugandh Kumar, Anshuman Dixit. Identification of stage-wise miRNAs signature as potential 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 B38.