bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 33: CEACAM1 blockade increases NK cell cytotoxicity in head and neck squamous cell carcinoma
Authors: Tam Kenric , Lee Yunqin , Schoppy David , Sunwoo John B. 
Published: December 2017

Abstract
In conjunction with advances made in cytotoxic chemotherapy, radiation, and surgery, immunotherapy has emerged in recent years as a promising fourth modality of treatment for head and neck squamous cell carcinoma (HNSCC). Cetuximab, an anti-EGFR antibody, is now routinely used as an adjunct to radiation therapy and in the recurrent/metastatic setting following treatment failure with concurrent cisplatin and radiation. Understanding the fundamental mechanisms by which HNSCC evades the immune system will aid the development of new therapies and strategies to augment an antitumor immune response.
Carcinoembryonic-antigen-related cell-adhesion molecule 1 (CEACAM1) is a cell surface receptor that is expressed on HNSCC cells, as well as on lymphocytes, such as NK cells. Overexpression of CEACAM1 in HNSCC has been associated with a poor prognosis, higher clinical stage, recurrence, and lymph node metastasis. A phase I trial (NCT02346955) of an anti-CEACAM1 antibody is currently underway for a variety of non-HNSCC malignancies.
We demonstrate that in mice inoculated with TUBO-EGFR, a murine cancer cell line, treatment with an anti-CEACAM1 antibody rescues NK cell effector function from exhaustion resulting in reduced tumor growth and enhanced antibody-dependent cell-mediated cytotoxicity. The addition of Cetuximab has an additive effect and results in additional tumor shrinkage. Thus, these data indicate that CEACAM1 is a novel checkpoint molecule on NK cells.
CEACAM1 is also expressed on tumor cells themselves; its expression in HNSCC is associated with suppression of NK cell cytotoxicity. In vitro co-incubation of NK cells with PCI-13, a human HNSCC cell line, results in IFNγ-mediated upregulation of CEACAM1 on the tumor cells. IFNγ-exposed cells are more resistant to NK cytotoxicity compared to untreated cells, suggesting that immune pressure induces upregulation of NK inhibitors. Importantly, CEACAM1+ NK cells have decreased cytotoxicity against HNSCC tumor cells compared to CEACAM1- NK cells, but the addition of an anti-CEACAM1 antibody restores NK cell effector function. Together, these data indicate that CEACAM1 acts as a checkpoint molecule and that a blocking antibody against CEACAM1 releases its immunosuppressive effects and could serve as a novel immunotherapy for HNSCC.
Citation Format: Kenric Tam, Yunqin Lee, David Schoppy, John B. Sunwoo. CEACAM1 blockade increases NK cell cytotoxicity 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; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 33.
Abstract 34: Wee1 inhibition sensitizes tumor cells with variable antigenicity to T cell mediated lysis
Authors: Moore Ellen , Sun Lillian , Friedman Jay , Waes Carter Van , Allen Clint 
Published: December 2017

Abstract
Antigen-specific elimination of tumor cells by cytotoxic T-lymphocytes (CTL) inherently relies upon the sensitivity of target cells to effector products such as granzyme B, TNFa, TNF-related apoptosis-inducing ligand (TRAIL), and Fas ligand (FasL). Cell cycle progression is critically required for granzyme B and TNF superfamily-induced apoptosis. Thus, we hypothesized that inhibition of Wee1 with AZD1775 would release the G2/M cell cycle checkpoint and enhance sensitivity of oral cavity cancer cells to CTL killing. To explore this hypothesis, we stably transduced murine oral cancer 1 (MOC1) cells with a construct encoding the fluorescent protein mKate2 and SIINFEKL, the H2-Kb-restricted epitope of ovalbumin (MOC1mK2SIIN). Using in-vitro generated SIINFEKL-specific OT-1 CTLs as effectors, we demonstrated in a real-time, impedance-based assay of cytotoxicity that physiologic concentrations of AZD1775 (250 nM) significantly sensitized MOC1mK2SIIN cells to CTL killing at low E:T ratios. The same concentration of AZD1775 had negligible effects on the MOC1mK2SIIN cells alone, and OT-1 CTL cytotoxicity was antigen-specific as OT-1 effectors did not kill parental MOC1 cells with or without AZD1775 treatment. This effect was partially reversed with the perforin inhibitor concanamycin A, implicating involvement of granzyme B. Further, by mixing MOC1mK2SIIN and parental MOC1 cells, we could alter the ratio of antigen clonality present within the target cell population. Inhibition of Wee1 with AZD1775 significantly enhanced OT-1 CTL control of target cell populations where 5, 10, 15, 20, 25, and 50% lack SIINFEKL antigen. Treatment of MOC1mK2SIIN and parental MOC1 cells with recombinant TNFa, TRAIL and FasL with and without AZD1775 confirmed enhanced TNF superfamily-induced tumor cell control following Wee1 inhibition. These data suggest that Wee1 inhibition broadly sensitizes antigen positive and negative cells to CTL effector products and that AZD1775 may induce “bystander killing” of antigen negative cells in target cell populations with mixed antigenicity. Experiments combining AZD1775 with immune-activating therapies in vivo are underway.
Citation Format: Ellen Moore, Lillian Sun, Jay Friedman, Carter Van Waes, Clint Allen. Wee1 inhibition sensitizes tumor cells with variable antigenicity to T cell mediated lysis [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 34.
Abstract 52: Dynamic rewiring of apoptotic signaling networks by combined EGFR/FRGR inhibition enhances killing of head and neck squamous tumor by DNA damage
Authors: Dayma Yogesh , Yaffe Michael B. 
Published: December 2017

Abstract
We have previously shown that a subset of triple-negative breast cancers can be dramatically sensitized to killing by DNA-damaging chemotherapy by time-staggered inhibition of EGFR. This sensitization effect results from dynamic re-wiring of apoptotic signaling pathways to engage a caspase-8-dependent cell death mechanism (Figure 1). Here we explored whether combined EGFR and/or FGFR inhibition could enhance the killing of head and neck squamous cell cancers by DNA damaging treatments through a similar re-wiring mechanism.
The epidermal growth factor receptor (EGFR) and FGFR pathways are two of the most dysregulated molecular pathways in human head-and-neck squamous cell carcinoma (HNSCC). Despite overexpression in approximately 90% of HNSCC tumors, EGFR inhibitors alone have not exerted a major therapeutic impact on tumor response or patient survival. A recent study provides evidence that the insensitivity of the majority of HNSCC to EGFR inhibitors is mediated by dominant activity of alternative receptor tyrosine kinase (RTK) systems such as FGFR signaling (Clinical Cancer Research 2011).
We have found that time-staggered administration of either EGFR inhibitors, or FGFR inhibitors, can dramatically enhance the apoptotic response of HNSCCs to DNA damage from doxorubicin. Importantly, combined inhibition of both the EGFR and FGFR pathways was more effective than inhibition of either pathway alone, at inducing sensitization to cytotoxic chemotherapy through dynamic network re-rewiring. Enhanced cell death by dual EGFR/FGFR inhibition and subsequent genotoxic injury results from greater activation of Caspase-8 than that seen by either EGFR or FGFR inhibitors alone. This enhanced Caspase-8 acitivty, together with Caspase-9 activation, accounts for the majority of apoptotic death. Our data further suggest that Src family kinases are a critical downstream node of EGFR/FGFR activity since treatment of HNSCC cell lines with Src kinase inhibitors resulted in similar sensitization to doxorubicin treatment.
In summary, our data extend the utility of therapeutic dynamic rewiring for the targeting of tumors with redundant receptor signaling pathways as well as their critical downstream nodes.
Citation Format: Yogesh Dayma, Michael B. Yaffe. Dynamic rewiring of apoptotic signaling networks by combined EGFR/FRGR inhibition enhances killing of head and neck squamous tumor by DNA damage [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 52.
Abstract 58: Therapeutically targeting the cell cycle in head and neck cancer
Authors: Diab Ahmed , Chang Xu , Kao Michael , Clurman Bruce , Galloway Denise , Eduardo Mendez 
Published: December 2017

Abstract
Head and neck squamous cell carcinomas (HNSCC) have a complex mutational spectrum with tumor suppressor and cell cycle dysregulation as the most prominent features. Additionally, HPV infection has been shown to be a cause of some HNSCC, particularly oropharyngeal cancer, and it is increasing in the US. Our recent studies have established WEE1 inhibition as a new therapeutic strategy in HNSCC. WEE1 inhibition not only leads to premature mitosis by weakening the G2/M checkpoint but also causes replication stress in S-phase particularly in tumors with deficient TP53. Given that HPV infection causes genetic instability by inactivating tumor suppressor pathways (TP53 and Rb) and impairing proper DNA damage repair (DDR) response, we aim to explore targets that will synergize with WEE1 and decrease reliance on chemotherapy.
To this end, we performed a q-PCR array profiling p53 dependent gene expression in a pair of isogenic HNSCC cell lines for p53 knockdown (vs wildtype control). Using a similar profiling technique in an isogenic pair of immortalized human oral keratinocytes (OKF4 cells) over expressing HPV16 E6/E7 proteins, we profiled the expression of DDR genes in response to DNA damage in wildtype vs. E6E7 expressing keratinocytes. A functional high-throughput siRNA library screen for DDR genes was performed to functionally validate the pathways identified. We looked for DDR genes that specifically sensitized p53 deficient HNSCC cells as well as E6/E7 expressing cells to WEE1 inhibition.
TP53 deficient cells exhibited elevated levels of DDR related genes in response to DNA damage when compared to isogenic wildtype. We identified potential survival DDR pathways for E6E7- mediated transformation, targeting of which represents a novel therapeutic strategy. The DDR siRNA screen with WEE1 inhibition provided a functional validation for our findings. Gene ontology analysis of top 10% of WEE1 sensitizers identified BRCA1 related DNA damage response genes as top sensitizers for WEE1 inhibition in p53 deficient cells. Collectively, these results would help develop a new therapeutic paradigm for HPV-positive HNSCC by providing tailored mechanism-based therapies.
Citation Format: Ahmed Diab, Xu Chang, Michael Kao, Bruce Clurman, Denise Galloway, Mendez Eduardo. Therapeutically targeting the cell cycle 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; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 58.
Abstract 68: Functional interactions of HPV and PARP-1 in head and neck cancer
Authors: Gary Cyril S. , Hajek Michael , Biktasova Asel , Sewell Andrew , Wendell Yarbrough G. , Issaeva Natalia 
Published: December 2017

Abstract
Though the overall incidence of head and neck cancer has been declining over the last several decades, there has been a concomitant and worrisome rise in human-papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV infection is a necessary but not sufficient condition for cancer development. Unlike in cervical cancer, where several co-factors including smoking and co-infection with other agents are well established, how HPV drives malignant transformation in head and neck cancer and which cellular factors are required are not well characterized. Recent evidence from our group has shown that poly (ADP-ribose) polymerase-1 (PARP-1) is overexpressed and overactive in HPV-positive (HPV(+)), but not HPV-negative (HPV(-)), oropharyngeal squamous cell carcinoma (OPSCC). The significance of PARP-1 overexpression and hyperactivation in cancer is only beginning to emerge. High levels of PARP-1 are found in a fraction of hepatocellular and breast cancers and correlate with poor prognosis. Recently, PARP-1 was implicated in prostate cancer progression. This study explores the role of PARP-1 in HPV infection and HNSCC carcinogenesis.
Biochemical methods were used to determine PARP activity in vitro, in head and neck tumors, and during infection with HPV16 pseudovirus (PsV) or overexpression of HPV16 proteins in epithelial cells. The response to PARP inhibition was evaluated with clonogenic survival assays. HPV L1 mRNA in HNSCC was detected using quantitative real-time PCR and HPV L1 protein levels were determined by immunohistochemistry.
Here, we show that the HPV16 major capsid protein L1 directly binds PARP-1 and activates poly(ADP-ribosyl)ation in the absence of DNA damage in vitro and in HPV(-) cells. Using PARP-1 knockout cells, we found that PARP-1 expression and enzymatic activity supports initial HPV infection. Furthermore, HPV(-) cells were sensitized to PARP inhibition both after L1 overexpression and after infection with HPV16 PsV particles.
In conclusion, we report functional interactions between the viral capsid and cellular protein, signifying a vital role played by PARP-1 in HPV infection and carcinogenesis. Importantly, our data provide a mechanistic explanation for pharmacological PARP inhibition as an intriguing therapeutic opportunity for HPV(+) head and neck cancers.
Citation Format: Cyril S. Gary, Michael Hajek, Asel Biktasova, Andrew Sewell, Yarbrough G. Wendell, Natalia Issaeva. Functional interactions of HPV and PARP-1 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; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 68.
Abstract IA27: Current perspectives on the treatment of nasopharyngeal carcinoma (NPC)
Authors: Chan Anthony T. C. 
Published: December 2017

Abstract
70% of NPC patients present with UICC stages III and IV locoregionally advanced (LA) disease. A recently completed population screening study using plasma EBV DNA may change this picture.
For LA NPC, despite a high locoregional control rate after concurrent cisplatin-IMRT, the rate of distant metastases remains around 30%. Recent phase III studies adding induction chemotherapy have reported conflicting results, while studies adding adjuvant chemotherapy in unselected population have been negative. HKNPC 0502 and NRG HN001 are studies attempting to risk-stratify adjuvant therapy using post-RT plasma EBV DNA levels.
With the publication of exome and whole genome sequencing of NPC, precision targeted therapies and immunotherapies are being investigated. Early results using immune checkpoint inhibitors in patients with recurrent and metastatic disease are encouraging.
Citation Format: Anthony T. C. Chan. Current perspectives on the treatment of nasopharyngeal carcinoma (NPC) [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 IA27.
Of Cats and Men
Authors: Soler Nieves Pascual 
Published: December 2017

AbstractThe study analyzes the gender narratives linked to cats in Nestlé Purina Pet Care Company (NPPC) advertising. Out of the ten cat food products lines it markets, each offering from one to nine different formulas, nine are discussed. The focus is on dried food in pouch packages. It is argued that against the traditional association between cats and women, cat food advertising privileges masculine experiences. To support this claim, this article (a) analyzes the relationship between gender and food patterns; (b) probes the background for the perception of companion animals as projections of the human self; (c) examines representations of cats and food on selectNPPClabels; and (d) matches gender narratives with the new demographics ofUScat caregivers.
Religion, Resistance, and Contentious Politics in China (中国的宗教、抵抗与抗争政治)
Authors: Laliberté André 
Published: December 2017

In this essay, I present the concepts of religious resistance and contentious politics, in which religions represent a source of inspiration, before moving to the issue of how these concepts apply to China. I note that there is little literature on this particular subject, which is always politically sensitive. As the Communist Party of China has increasingly recognized the relevance of religion in contemporary society, it has tried to keep it in check and thereby ensure that independent associations with a religious background will not become involved in contentious politics. This article then briefly introduces the four case studies in this special issue on the theme of religion and contentious politics in China: two cases of persecution of Christians and Catholics during the period of Mao, and two articles about Buddhism, which has a more complex relationship with the state.本文首先阐述了宗教抵抗与抗争政治的概念—其中宗教发挥了启发鼓舞的作用而后将之用于分析中国经验。由于政治敏感性，有关此议题的文献很少。因为逐渐意识到宗教在当代社会中的重要性，中国共产党试图管控宗教防止具有宗教背景的独立团体参与抗争政治。本文最后介绍本期中有关中国宗教与抗争政治的四篇个案研究：两篇文章讨论毛泽东时期对基督徒和天主教徒的压迫，另外两篇是关于佛教及其与国家的复杂关系。
Typification of the Linnaean name Corispermum squarrosum, with notes on C. hyssopifolium and nomenclatural implications for Agriophyllum (Chenopodiaceae: Corispermeae)
Authors: MOSYAKIN SERGEI L. , SPENCER MARK A. 
Published: December 2017

The Linnaean name Corispermum squarrosum (Chenopodiaceae, Corispermeae) is lectotypified here by the specimen LINN 12.3. This specimen is identifiable with the plant currently known as C. uralense, a species occurring in southeasternmost regions of Europe and adjacent parts of Siberia and Kazakhstan, and the name C. squarrosum should be now applied to it. Our lectotypification of C. squarrosum restores the original taxonomic application by Linnaeus to an East European species of Corispermum. It is demonstrated that the epithet “squarrosum” was misapplied to several species of Corispermum and one species of Agriophyllum. This long-standing nomenclatural confusion was initiated by Pallas, who, contrary to Linnaeus, considered a species of Agriophyllum as “the only true C. squarrosum”. That concept was then accepted by Moquin-Tandon and Aellen and followed by some other authors. Nomenclatural implications of the lectotypification of C. squarrosum are explained. As a result of our lectotypification, the most widespread species of Agriophyllum (widely known as A. arenarium and “A. squarrosum” sensu Moquin-Tandon), should be called A. pungens. The generic name Agriophyllum was not validly published by Marschall von Bieberstein in 1819 (provisional name), but it was validated by C.A. Meyer in 1831. Relevant updated nomenclatural citations are provided.
Estimating River Bathymetry from Surface Velocity Observations Using Variational Inverse Modeling
Authors: Almeida Thomas G. , Walker David T. , Warnock April M. 
Published: December 2017

AbstractAccurate river bathymetry characterization is important to understanding all aspects of the riparian environment and provides crucial information for ensuring the safe passage of vessels and guiding channel maintenance operations. Verified models based on readily collected physical data facilitate accurate predictions of changes to a riverbed caused by traffic, weather, and other influences. This paper presents a methodology for estimating river bathymetry from surface velocity data by applying variational inverse modeling to the shallow-water equations. The paper describes the mathematical framework for the methodology and the algorithm, and the numerical tools developed to test the methodology. The hydrodynamic modeling uses 2D depth-averaged solvers (under the hydrostatic assumption) and applies a standard empirical correlation that relates depth-averaged velocity to surface velocity. The application of the bathymetry estimation algorithm to water-surface velocity data was tested on a 95-km reach of the Columbia River in Washington State. The root-mean-square error (RMSE) of the estimated bathymetry field relative to the ground truth data is approximately 2 m over the entire reach. The results of the test case indicate that this approach can be used to estimate river bathymetry to a close approximation based on the bank-to-bank surface velocity data on the reach of interest.
Informed But Insecure: Employment Conditions and Social Protection among Paid Domestic Workers in Guayaquil
Authors: Masi de Casanova Erynn , Rodriguez Leila , Roldán Rocío Bueno 
Published: December 2017

Salaried domestic labor in private homes in Latin America is informal, precarious, and exploitative, but for thousands of women who have no other options it is their occupation and the sustenance of their families. The results of a study based on 400 surveys of paid domestic workers in Guayaquil, Ecuador, about social protection and labor rights show that workers possess a high level of knowledge about their labor rights but the majority do not belong to the social security system and many do not enjoy any of the benefits guaranteed them by law. Understanding the situation and experiences of these workers is a precondition for creating strategies to recognize the importance of their work and to guarantee their labor rights. En América Latina, el trabajo remunerado en casas privadas es informal, precario, y explotador; para miles de mujeres que no tienen otras opciones, es su ocupación y el sustento de su familia. Los resultados de un estudio basado en 400 encuestas de la protección social y derechos laborales de las mujeres trabajadoras remuneradas del hogar de Guayaquil, Ecuador, demuestran un alto nivel de conocimiento de los derechos laborales entre las trabajadoras. Sin embargo, la mayoría de las participantes no estaba afiliada al sistema de seguro social, y muchas no gozaban de ninguno de los beneficios garantizados por la ley. Entender la situación y las experiencias de las trabajadoras del hogar es necesario para crear estrategias que reconozcan la importancia de la reproducción social y defiendan los derechos laborales.