bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A03: Novel polyisoprenylated small molecules as potential new therapies for triple negative breast cancer
Authors: Salako Olufisayo O. , Nkembo Augustine T. , Ntantie Elizabeth , Lamango Nazarius S. 
Published: December 2017

Abstract
Breast cancer patients whose tumors do not overexpress estrogen, progesterone or HER2 receptors do not benefit from the effective therapies targeting these receptors. Knowing what drives the tumors in the latter group of patients, known as triple negative breast cancer (TNBC), is important for developing more effective and less toxic therapies directed at these drivers. We have developed a novel class of compounds, the polyisoprenylated cysteinyl amide inhibitors (PCAIs) that target the aberrant growth signaling by EGFR and/or constitutively active mutant K-Ras in a significant proportion of TNBC and other aggressive cancers such as of the pancreas, colon and lungs. The PCAIs induced apoptotic cell death with EC50 values ranging from 2.2 to 2.7 µM. The PCAIs induced apoptosis in MDA-MB-231 spheroids as well as inhibited the spheroid formation at 1 and 2 µM, respectively. The PCAIs, at 1 µM, inhibited over 80% colony formation in MDA-MB-231 cells. At 1 and 2 µM, MDA-MB-231 Transwell cell invasion was inhibited by 80 and 94%, respectively. The PCAIs blocked tube formation in cultured HUVEC cells at 0.2 to 0.5 µM and vessel formation in chick embryos at 0.12 µg/egg. The PCAIs can thus be used as targeted therapies to inhibit tumor growth, cell migration and angiogenesis in TNBC and other cancers with excessive growth factors receptor and mutant K-Ras signaling.
Citation Format: Olufisayo O. Salako, Augustine T. Nkembo, Elizabeth Ntantie, Nazarius S. Lamango. Novel polyisoprenylated small molecules as potential new therapies for triple negative breast cancer [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A03.
Abstract 21: Grading dysphagia as a toxicity of head and neck cancer: Differences in severity classification based on MBS DIGEST and clinical CTCAE grades
Authors: Goepfert Ryan P. , Lewin Jan S. , Barrow Martha P. , Warneke Carla L. , Fuller Clifton D. , Lai Stephen Y. , Weber Randal S. , Hutcheson Katherine A. 
Published: December 2017

Abstract
Background: Clinician-reported toxicity grading through Common Terminology Criteria for Adverse Events (CTCAE) stages dysphagia based on symptoms, diet, and tube dependence. The new Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) tool offers a similarly scaled 5-point ordinal summary grade of pharyngeal swallowing as determined through results of a modified barium swallow (MBS) study. This study aims to inform clinicians on the similarities and differences between dysphagia severity according to clinical CTCAE and MBS-derived DIGEST grading.
Methods: A cross-sectional sample of 95 MBS studies was randomly selected from a prospectively-acquired MBS database among patients treated with organ preservation strategies for head and neck cancer. MBS DIGEST and clinical CTCAE dysphagia grades were compared.
Results: DIGEST and CTCAE dysphagia grades had “fair” agreement per weighted k of 0.358 (95% CI .231-.485). Using a threshold of DIGEST ≥3 as reference, CTCAE had an overall sensitivity of 0.50, specificity of 0.84, and area under the curve (AUC) of 0.67 to identify severe MBS-detected dysphagia. At less than 6 months, sensitivity was 0.72, specificity was 0.76, and AUC was 0.75 while at greater than 6 months, sensitivity was 0.22, specificity was 0.90, and AUC was 0.56 for CTCAE to detect dysphagia as determined by DIGEST.
Conclusions: Classification of pharyngeal dysphagia on MBS using DIGEST augments our understanding of dysphagia severity according to the clinically derived CTCAE while maintaining the simplicity of an ordinal scale. DIGEST likely complements CTCAE toxicity grading through improved specificity for physiologic dysphagia in the acute-phase and improved sensitivity for dysphagia in the late-phase.
Citation Format: Ryan P. Goepfert, Jan S. Lewin, Martha P. Barrow, Carla L. Warneke, Clifton D. Fuller, Stephen Y. Lai, Randal S. Weber, Katherine A. Hutcheson. Grading dysphagia as a toxicity of head and neck cancer: Differences in severity classification based on MBS DIGEST and clinical CTCAE grades [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 21.
Abstract 54: Genome-wide CRISPR screen identifies potential therapeutic combination of EGFR and FGFR inhibitors in oral cancer
Authors: Ludwig Megan , Birkeland Andrew , Nimmagadda Sai , Foltin Sue , Kulkarni Aditi , Jiang Hui , Carey Thomas , Brenner J. Chad 
Published: December 2017

Abstract
Oral squamous cell carcinoma (OSCC) is a disease with poor survival with few novel treatment options in development. While EGFR is commonly over-expressed, targeting EGFR has had limited success possibly because of compensatory pathways rescuing cell survival. Inhibiting compensatory pathways in combination with EGFR signaling may result in greater efficacy. To identify compensatory pathways, we used a Genome-wide CRISPR-Cas9 Knock-Out (GeCKO) library to identify genetic knockouts that sensitized OSCC cell lines to EGFR inhibition. This CRISPR library established a pool of knockouts targeting over 18,000 genes, and upon selection of the GeCKO pool we identified gene knockouts in the FGFR pathway increased sensitivity to the EGFR inhibitor gefitinib. We further profiled this combination with viability assays and found that 6/14 (43%) cell lines responded to the combination of EGFR and FGFR inhibition, suggesting that the FGFR pathway could be a common compensatory mechanism to loss of EGFR signaling. In complement, we again used CRISPR-Cas9 to generate a syngeneic EGFR knockout (KO) OSCC cell line. The parent OSCC cell line is responsive to the EGFR and FGFR dual inhibition, and the EGFR KO derivative retains sensitivity to FGFR-targeted monotherapies. We expect that this EGFR KO cell line will be a useful tool in further evaluating the compensatory mechanism of the FGFR pathway. In total, we describe the use of genome-wide CRISPR-Cas9 library to discover the synergistic combination of EGFR and FGFR inhibition, with follow-up indicating that the FGFR pathway could be a common compensatory mechanism to EGFR inhibition. Targeting compensatory mechanisms in combination with EGFR-targeted therapy could be clinically beneficial, including the combination of EGFR and FGFR inhibition.
Citation Format: Megan Ludwig, Andrew Birkeland, Sai Nimmagadda, Sue Foltin, Aditi Kulkarni, Hui Jiang, Thomas Carey, J. Chad Brenner. Genome-wide CRISPR screen identifies potential therapeutic combination of EGFR and FGFR inhibitors in oral 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; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 54.
Abstract 59: Novel mechanisms-guided treatments for betel nuts-related head and neck squamous cell carcinoma in Taiwan
Authors: Chen Jo-Pai , Chang Jui-Ying , Hong Ruey-Long 
Published: December 2017

Abstract
Background: Betel nuts-related HNSCCs in Taiwan will cause (1) strong inflammation, invasion, and angiogenesis; (2) poor response to chemotherapy, radiation, and epidermal growth factor receptor inhibitors.
Methods: HNSCC cell lines (SCC4, SCC9, SCC15, SCC25, FaDu, KB, Cal27, SAS, and TW2.6, betel nuts-related) were used to evaluate (1) the in vitro drug sensitivity; (2) synergistic effects of different treatment combinations with MTT assay, colony formation, flow cytometry, and Western blotting; (3) invasion capacity by wound healing. TW2.6 had already been proved to possess defective p53, p16 loss, and increased Bcl2.
Results: TW2.6 was resistant to chemotherapies, radiation, and EGFR inhibition, but sensitive to PI3K/mTOR dual inhibition (BEZ235), CDK4/6 inhibitor (palbociclib), Bcl2 inhibitor (ABT-199), WEE1 inhibitor(AZD1775), FGFR inhibitor(BGJ398), ALK/IGF-1R inhibitor (ceritinib), and eribulin. Polo-like kinase inhibitor (volasertib) with radiation, resulting in G2/M arrest in flow-cytometry and increased cyclin B levels in Western blotting, caused TW2.6 apoptosis. Nintedanib and regorafenib (VEGFR/PDGFR/FGFR inhibitor) and foretinib (VEGFR/c-MET/Axl inhibitor) would suppress HUVEC, block invasion capacity of TW2.6, inhibit TW2.6 growth, and resensitize TW2.6 to docetaxel, afatinib, and volasertib. Western blotting showed (1) mesenchymal markers (Slug, Snail, Axl, Twist, Vimentin, Claudin-1), PI3K/Akt/mTOR signaling (p-Akt and p70S6K), and BMI-1 dropped after nintedanib, regorafenib, and foretinib; (2) PDL1 drop after foretinib use. BYL719, ABT-199, and ceritinib also sensitize TW2,6 to docetaxel. Astragalus polysaccharides, minimally cytotoxic on TW2.6, could inhibit tumor migration, suppress epithelial-mesenchymal transformation and PI3K/AKT/mTOR pathway, and induce PDL1 drop. APS re-sensitizes TW2.6 to afatinib and volasertib. Olaparib (PARP inhibitor) also had poor effect on TW2.6, but volasertib, AZD1775, and foretinib could reverse olaparib resistance.
Conclusions: TW2.6 might reflect treatment refractoriness of betel nuts-related HNSCC in Taiwan. Several novel mechanisms-guided treatment combinations should be tried in the future.
Citation Format: Jo-Pai Chen, Jui-Ying Chang, Ruey-Long Hong. Novel mechanisms-guided treatments for betel nuts-related head and neck squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 59.
Abstract 60: Characterization of papillary thyroid carcinoma primary cell culture derived cancer stem-like cells
Authors: Simental Alfred , Lee Steve , Filho Pedro A. De Andrade , Peterson Nathaniel R. , Mirshahidi Saied , Duerksen-Hughes Penelope , Yuan Xiangpeng 
Published: December 2017

Abstract
Papillary thyroid carcinoma is the most frequent type of thyroid cancer. Although most PTC patients can be treated successfully and have an excellent prognosis, 10-20% of patients with stage I/II disease experience recurrence, developing invasive tumors and/or distant metastases. For these patients, a greater understanding of the mechanisms that govern PTC tumor initiation and progression would aid in developing effective therapeutic strategies to target the disease. It is becoming evident that thyroid tumors may follow the cancer stem cell model (CSC), where a population of cancer stem cells is responsible for tumor initiation and progression. Currently, the CSC biology of PTC is still poorly understood. In this study, we isolated sphere-growing cells from PTC specimen-derived primary cells using serum-free culture. In vivo transplantation analysis revealed that the sphere cells were capable of generating xenograft tumors that recapitulated the original tumor phenotypes. Analyzing the sphere cells for aldehyde dehydrogenase (ALDH) expression, a marker commonly used in CSC study, revealed that around half of the sphere cells did not express ALDH. When the sphere cells were sorted into ALDH- and ALDH+ subpopulations, both subpopulations demonstrated capabilities of re-initiating subspheres in vitro and generating serial xenograft tumors in vivo with the ALDH+ cells exhibiting a slightly higher efficiency of sphere-formation and cancer-initiation. Of major importance, the sphere cell population without sorting demonstrated the higher levels of cancer-initiating cell frequency, and quicker xenograft tumor progression than the subpopulations of ALDH- and ALDH+ cells. Furthermore, histologic investigation of xenograft tumors generated by the sphere population and the sphere-sorted subpopulations, respectively, revealed similar morphological features that recapitulated the characteristics of original human PTC from which the sphere cells were isolated. Our data established a vital role of ALDH- cancer stem-like cells and revealed a potential synergistic activity between ALDH- and ALDH+ cells in the tumor initiation and progression of PTC. Further exploring the biological property of ALDH- cancer stem-like cells may lead to development of novel therapeutic solutions to treating aggressive PTC.
Citation Format: Alfred Simental, Steve Lee, Pedro A. De Andrade Filho, Nathaniel R. Peterson, Saied Mirshahidi, Penelope Duerksen-Hughes, Xiangpeng Yuan. Characterization of papillary thyroid carcinoma primary cell culture derived cancer stem-like 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; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 60.
Abstract IA15: Molecular navigation for cancer diagnosis and surgery: Imaging tumors and nerves
Authors: Nguyen Quyen T. 
Published: December 2017

Abstract
Although treatment algorithms vary, surgery is the primary treatment modality for most solid cancers. The fundamental goal of a curative oncologic surgery is complete cancer removal but equally important from the patient's point of view is function preservation and pain control. Currently, there is an increasing trend to adopt minimally invasive technologies such as endoscopic and robotic surgery in order to decrease patient morbidity. However, the ability for surgeons to distinguish between normal and diseased tissue by texture or consistency is significantly reduced with these techniques (due to lack of ability to physically touch the tissue) and is limited to visual inspection alone. Using white light reflectance which is the current standard mode of illumination in operating rooms, the visual difference between normal and cancerous tissue can be imperceptible. The inability of surgeons to visually distinguish between tumor and normal tissue leads to residual cancer cells left behind at the edges of resection, i.e. positive surgical margins and can be as high as 20-40% in breast cancer lumpectomy, 21% for radical prostatectomy, and 13% for HNSCC.
Molecular imaging with fluorescence provides enhanced visual definition between diseased and normal tissue and have been shown to decrease PSM in both animal models and patients. Molecular imaging with fluorescence can also provide enhanced visualization of important structures such as nerves to improve preservation and minimize inadvertent injury. Our laboratory has extensive experience in development of both nerve and tumor injectable markers for surgical visualization. In presentation we will discuss the development of nerve and tumor markers combinations to improve intraoperative visualization---aka color-coded surgery.
Citation Format: Quyen T. Nguyen. Molecular navigation for cancer diagnosis and surgery: Imaging tumors and nerves [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA15.
Abstract IA24: Biomarkers and checkpoint inhibition in HNSCC
Authors: Cohen Ezra E. W. 
Published: December 2017

Abstract
There has been tremendous progress made in development of checkpoint inhibitors in HNSCC with antibodies directed against the PD1/PDL1 axis leading the way. Recent data reveal that these agents are active in patients with refractory disease and improve survival compared with standard of care even in unselected patient populations. Nonetheless, the need for biomarkers to predict which patients benefit most from PD1/PDL1 blockade remains acute while interrogating tissue samples to define mechanisms of resistance is just beginning. To date, it appears that PDL1 expression has some utility to predict activity of PD1/PDL1 blockade. Moreover, gene expression signatures corresponding to an interferon-gamma antitumor response or quantifying mutational burden seem to provide survival predictability. Furthermore, immune signatures of gene expression have been correlated with survival in patients with locally advanced disease. These aspects of checkpoint blockade will be discussed in detail with a view towards where the field is moving in the near term and what to anticipate in the extended future.
Citation Format: Ezra E. W. Cohen. Biomarkers and checkpoint inhibition in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA24.
Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer
Authors: Ohlmann Carsten-Henning , Gross-Langenhoff Marco 
Published: December 2017

<b><i>Introduction:</i></b> We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard®, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany. <b><i>Materials and Methods:</i></b> Data was pooled from 2 prospective, open-label, non-interventional studies in which 1,906 patients were treated for 12 months with either the 3-month (<i>n</i> = 633) or 6-month (<i>n</i> = 1,273) LA formulation. <b><i>Results:</i></b> Median prostate-specific antigen levels in the pooled patient population declined from 12.0 ng/mL at baseline to 0.5 ng/mL after 12 months. Prostate-specific antigen reduction was achieved in treatment-naïve and pre-treated patients. Adverse events were documented in 8.8% of patients. <b><i>Conclusions:</i></b> These pooled data from routine clinical practice in Germany indicate that LA 3- and 6-month depot injections can effectively reduce prostate-specific antigen levels in a broad patient population with advanced prostate cancer.
Genesis as a Hidden Source of Manichaeism
Authors: Moiseeva Evgenia 
Published: December 2017

There exists an entrenched notion, supported by both Christian and Manichaean texts, that Manicheans rejected the Old Testament as a product of Satan. However, scholars have noted the presence of loans from the Old Testament in Manichaean works. The Manichaean priest, Felix, in his dispute with St Augustine, documented in Augustine’s Contra Felicem Manicheum, cites Genesis 1:1-2 to demonstrate its agreement with Mani’s teachings. This and other examples show that the Manichaean attitude towards the Old Testament was more complicated than that of simple rejection. In this report, I review textual evidence from multiple Manichaean sources indicating that Jewish texts in general, and Genesis in particular, should be counted among the sources of Manichaeism. Furthermore, I address the question how this evidence could be reconciled with the long-standing view of the Manichaean rejection of the Old Testament.
Predicting Airport Screening Officers’ Visual Search Competency With a Rapid Assessment
Authors: Mitroff Stephen R. , Ericson Justin M. , Sharpe Benjamin 
Published: December 2017

Objective The study’s objective was to assess a new personnel selection and assessment tool for aviation security screeners. A mobile app was modified to create a tool, and the question was whether it could predict professional screeners’ on-job performance. Background A variety of professions (airport security, radiology, the military, etc.) rely on visual search performance—being able to detect targets. Given the importance of such professions, it is necessary to maximize performance, and one means to do so is to select individuals who excel at visual search. A critical question is whether it is possible to predict search competency within a professional search environment. Method Professional searchers from the USA Transportation Security Administration (TSA) completed a rapid assessment on a tablet-based X-ray simulator (XRAY Screener, derived from the mobile technology app Airport Scanner; Kedlin Company). The assessment contained 72 trials that were simulated X-ray images of bags. Participants searched for prohibited items and tapped on them with their finger. Results Performance on the assessment significantly related to on-job performance measures for the TSA officers such that those who were better XRAY Screener performers were both more accurate and faster at the actual airport checkpoint. Conclusion XRAY Screener successfully predicted on-job performance for professional aviation security officers. While questions remain about the underlying cognitive mechanisms, this quick assessment was found to significantly predict on-job success for a task that relies on visual search performance. Application It may be possible to quickly assess an individual’s visual search competency, which could help organizations select new hires and assess their current workforce.
Tympanoplasty following Blast Injury
Authors: Keller Matthew , Sload Ryan , Wilson Justin , Greene Howard , Han Peggy , Wise Sean 
Published: December 2017

ObjectivesTo assess outcomes following tympanoplasty for blast‐induced tympanic membrane perforations in a military population.Study DesignCase series with chart review.SettingTertiary care medical centers.Subjects and MethodsMilitary personnel (N = 254) undergoing tympanoplasty for blast‐related tympanic membrane perforations sustained between April 2005 and July 2014 were identified from the Expeditionary Medical Encounter Database. Descriptive statistics were obtained regarding demographics, primary and revision surgery success rates, hearing status pre‐ and postsurgery, and frequency of ossicular reconstruction. Rates of successful perforation closure were assessed against perforation size and character (central vs marginal) and time to surgery. Rates and types of complications were additionally explored.ResultsThere were a total of 352 operations among 254 subjects, with an 82.1% rate of successful closure following primary surgery. For successful primary tympanoplasty, the mean improvement in pure tone average was 11.7 ± 12.1 dB. Ossiculoplasty was performed in 9.1% (32 of 352) of cases. There was no significant relationship between successful perforation closure and perforation size, perforation character, or time between injury and surgery. Cholesteatoma complicated 4.3% (15 of 352) of cases. A significant relationship was identified between risk of cholesteatoma development and increasing perforation size and marginal perforations.ConclusionTympanoplasty success rates for blast‐induced tympanic membrane perforations are lower than for other common injury mechanisms. Due to appreciable rates of postoperative cholesteatoma development, close clinical surveillance is recommended.