bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B67: Regulation of a novel cell surface protein in macrophage activity in tumor microenvironment
Authors: Ray Rashmi , Rai Vivek 
Published: February 2019

Abstract
Inflammatory cells and their mediators are an essential component of the tumor microenvironment. Tumor associated macrophages (TAMs) represent a predominant population of inflammatory cells present in the solid tumor and tumor microenvironment. TAMs are associated with tumor progression and metastasis and the infiltration of TAMs or the enrichment of TAM-associated genes relates to poor prognosis and disease outcome in most human tumor types. However, the stimulus and triggers for the tumor cells-macrophage interaction remain unclear. Autotaxin, an ectoenzyme generates smallest phospholipid, lyophosphatidic acid (LPA) from lysophosphatidylcholine (LPC). Autotaxin is also known to play important roles in breast cancer, ovarian cancer and many other cancers. LPA is involved in numerous biological processes encompassing cell growth, cell proliferation, cell migration, cancer and metastasis. LPA exerts its functions on different cell types via its different G-protein coupled receptors (GPCRs). More progress has been made in recent years in dissecting the mechanisms of LPA generation and how it directly acts on its target cells. Recently we have shown that LPA converts monocytes into macrophages both in mice and humans. Here, we show that cancer cells in tumor growth are associated with tumor associated macrophages via a signature paracrine link. Our studies identify an unknown signaling link between tumor cells and macrophages. Furthermore, we have functionally characterized these macrophages and the suppression of this paracrine network leads to decrease in tumor growth and its progression. Our preliminary data also shows that blocking of this paracrine link decreases the secretion of proangiogenic factor such as TGF-b, TNF-a, MMP-9, and VEGF. This study suggests that suppression of this paracrine network can act as a new therapeutic approach to control cancer and metastasis. New insights into the role of LPA in regulating immune responses via cancer cells should be explored in the near future.
Citation Format: Rashmi Ray, Vivek Rai. Regulation of a novel cell surface protein in macrophage activity in tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B67.
Abstract B72: Secretory autophagy in tumor-associated fibroblasts alter effector function of natural killer cells against HNSCC
Authors: Enders Jonathan David , New Jacob , Aliani Rana , Thomas Sufi Mary 
Published: February 2019

Abstract
Tumor-associated fibroblasts (TAFs) are the most abundant cell type in the microenvironment of head and neck squamous cell carcinoma (HNSCC). We and others previously reported that secreted factors from TAFs increase the proliferation, migration, and invasion of HNSCC. Further studies revealed that HNSCC-secreted factors induce secretory autophagy in TAFs. However, the contribution of TAF autophagy to immune-evasion in the HNSCC microenvironment is unknown. Natural killer (NK) cells are an essential arm of anti-tumor immunity; thus, our study set out to determine the role of TAF autophagy in suppressing NK cell effector functions against HNSCC. To address this, we treated the NK cell line NK-92MI with conditioned media from primary HNSCC TAFs or normal fibroblasts derived from cancer-free subjects and assessed changes in IFN-γ production and cytotoxicity, measures of NK cell activation. We then assessed the role of TAF autophagy in mediating this effect by repeating the studies using conditioned media from TAFs whose autophagy had either been inhibited by chloroquine treatment or knocked down by siRNA. Finally, we assessed the mechanisms by which autophagy in the TAF affects NK cell function. Our data demonstrate HNSCC tumor cells orchestrate a complex mechanism of NK cell inhibition through the modulation of TAFs in the microenvironment. Treatment with TAF-conditioned media induced IFN-γ mRNA expression in NK-92MI cells. Interestingly, TAF-conditioned media also reduced NK cell-mediated cytotoxicity as compared to conditioned media from normal fibroblasts. Knockdown of key regulators in the secretory autophagy pathway by siRNA abrogated release of TAF-secreted factors, including hepatocyte growth factor (HGF). HGF induced NK-92MI expression of IFN-γ mRNA, which could be abrogated by an inhibitor of the HGF receptor, c-MET. In conclusion, these data describe a previously undefined effect of TAFs on NK cell function in the HNSCC microenvironment.
Citation Format: Jonathan David Enders, Jacob New, Rana Aliani, Sufi Mary Thomas. Secretory autophagy in tumor-associated fibroblasts alter effector function of natural killer cells against HNSCC [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B72.
Abstract IA06: Enhancing combination immunotherapy and adoptive cell therapy of cancer via lymph node-targeted vaccines
Authors: Irvine Darrell J. 
Published: February 2019

Abstract
Lymph node targeting is achieved clinically is sentinel lymph node mapping in cancer patients, where small-molecule dyes are efficiently delivered to lymph nodes by binding to serum albumin. To mimic this process in vaccine delivery, we synthesized amphiphile-vaccines (lipid-polymer conjugates of peptides, proteins, or molecular adjuvants) designed to non-covalently bind vaccine antigens and adjuvants to endogenous albumin. These amphiphile conjugates both protect peptide antigens from premature degradation and greatly increase their delivery to lymph nodes. Such “albumin-hitchhiking” amphiphiles elicited as much as 30-fold amplified cellular immune responses and antitumor immunity against multiple antigens, and further enable mucosal delivery of therapeutic vaccines through albumin-mediated transport across epithelial barriers via the neonatal Fc receptor. When combined with complementary immunotherapy agents, these lymph node-targeted vaccines are capable of eradicating large established tumors in several mouse models, providing a blueprint for curative immunotherapies. We have further demonstrated that amph-vaccines can be used to deliver ligands for chimeric antigen receptor (CAR) T cells to lymph nodes, creating efficient booster vaccines for CAR T cells.
Citation Format: Darrell J. Irvine. Enhancing combination immunotherapy and adoptive cell therapy of cancer via lymph node-targeted vaccines [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA06.
Abstract IA07: Genetic engineering of therapeutic T cells using synthetic nanoparticles
Authors: Moffett Howell F. , Smith Tyrel T. , Stephan Matthias T. 
Published: February 2019

Abstract
Despite the obvious advantages afforded by targeted T-cell cancer therapies (compared with the blunt instruments of chemotherapy, radiotherapy, and surgery), the complexity and costs involved in producing genetically modified lymphocytes remain major obstacles to their implementation as standard of care. Work in our laboratory aims to obviate these problems by integrating materials science, immunology, and gene therapy to make cellular immunotherapy more effective, practical, and widespread. In this talk, I will highlight two examples: In the first segment, I will describe a new strategy to genetically imprint therapeutically desirable phenotypes in cultured T cells, simply by mixing them with a targeted mRNA-carrying nanoreagent. When they are added to a culture of cells, these engineered nanoparticles bind to targeted T cell populations and induce major biologic effects on the basis of transient “hit-and-run” gene therapy without the necessity of resorting to complicated protocols or complex ancillary equipment. Our approach provides significant advantages over those currently used to create cytoreagents (i.e., viral transfection and electroporation), which require specialized equipment and demanding production steps. In the second part of my presentation, I will introduce a new injectable reagent our group developed that that can quickly program tumor-recognizing capabilities into circulating T cells without the need for laboratory manipulations. We demonstrate that, once they are adapted with lymphocyte-targeting ligands, polymeric nanocarriers can selectively deliver leukemia-specific chimeric antigen receptor (CAR) genes into host T cells in situ. These nanoparticles are easy to manufacture and are stable, which simplifies long-term storage and reduces cost. This technology may therefore provide a practical, broadly applicable treatment that can generate antitumor immunity at the time of diagnosis in a variety of settings.
Citation Format: Howell F. Moffett, Tyrel T. Smith, Matthias T. Stephan. Genetic engineering of therapeutic T cells using synthetic nanoparticles [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA07.
Abstract IA12: Integrative genomics and immune contexture approach to immuno-oncology
Authors: Galon Jérôme 
Published: February 2019

Abstract
To date the anatomic extent of tumor (TNM classification) has been by far the most important factor to predict the prognosis of cancer patients. However, this classification provides limited prognostic information and does not predict response to therapy.
We showed that tumors from human colorectal cancer with a high density of infiltrating memory and effector-memory T-cells (Tem) are less likely to disseminate to lymphovascular and perineural structures and to regional lymph nodes. We demonstrated the critical tumor-microenvironment parameters determining the dissemination to distant metastasis. We showed that the combination of immune parameters associating the nature, the density, the functional immune orientation, and the location of immune cells within the tumor was essential to accurately define the impact of the local host-immune reaction on patient prognosis. We defined these parameters as the “immune contexture.” We characterized the immune landscape within human tumors, and showed the importance of adaptive immune cells including cytotoxic T cells, Th1 cells, B cells, and T follicular-helper (Tfh) cells. We described the immunopenotype and antigenome associated with immune escape mechanisms and demonstrated mechanisms associated with preexisting and proliferating intratumoral T cells.
Based on the immune contexture, a standardized, simple, and powerful digital pathology-based immune stratification-system, termed Immunoscore, was delineated having a prognostic power superior to that of the currently used cancer staging system. Tumor invasion parameters were statistically dependent on the host-immune reaction. A worldwide Immunoscore consortium validated the prognostic value of Immunoscore, using a standardized assay. Recent data are supporting the significant role of Immunoscore within lung, liver, and brain metastases. Thus, tumor progression, invasion, and recurrence are dependent on preexisting immunity and on Immunoscore, and the role of the immune contexture in predicting response to immunotherapy will be discussed.
Citation Format: Jérôme Galon. Integrative genomics and immune contexture approach to immuno-oncology [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA12.
Abstract IA14: An atlas of the tumor immune ecosystem
Authors: Pe’er Dana 
Published: February 2019

Abstract
We created a comprehensive atlas of breast tumor-immune ecosystem by collecting a dataset of over 50,000 single immune cell transcriptomes from different types of human breast cancer, normal breast tissue, peripheral blood, and the lymph node using single-cell RNA-seq, and analyzed with novel computational clustering and normalization techniques. Our analyses revealed remarkably increased heterogeneity of intratumoral cells of both lymphoid and myeloid cell lineages, which occupy significantly expanded contiguous phenotypic space in comparison to normal breast tissue. The observed continuum of cell states is associated with their progressive cellular activation and differentiation and argues strongly against the notion of few discrete states of differentiation or activation of individual cell types shaping the tumor microenvironment. The substantial heterogeneity of cell states within major cell types and across patients is also driven by complex coexpression relationships between genes, and by extension their potential suitability as therapeutic cotargets.
Citation Format: Dana Pe’er. An atlas of the tumor immune ecosystem [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA14.
Abstract IA22: Fusobacterium nucleatum and colon cancer
Authors: Garrett Wendy S. 
Published: February 2019

Abstract
Cancer has largely been considered a disease of genetic and environmental factors; however, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping systemic and tumor microenvironment immunity and promoting tumor growth and spread. Herein, we discuss both human data from meta’omics analyses and data from mechanistic studies in cell culture and animal models that support that specific bacteria act as potentiators of colonic tumorigenesis, with a focus on Fusobacterium nucleatum.
Citation Format: Wendy S. Garrett. Fusobacterium nucleatum and colon cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA22.
Abstract PR05: Preventing the recurrence of breast cancer at the metastatic niche using resolution-phase macrophages
Authors: Gilon Odelya , Feuermann Yonatan David , Schif-Zuck Sagie , Weidenfeld Keren , Huth Palle Von , Sabo Edmond , Ariel Amiram , Barkan Dalit 
Published: February 2019

Abstract
Breast cancer that recurs as metastatic disease many years after primary tumor resection and adjuvant therapy appears to arise from tumor cells that disseminated early in the course of the disease but did not develop into clinically apparent lesions. These long-term surviving, quiescent disseminated dormant tumor cells (QDTC) are resistant to conventional therapies that target actively dividing cells. The mechanisms responsible for maintaining the survival and outgrowth of QDTC remain largely unknown. Recently, we found that fibrotic-like microenvironment with extensive deposition of Type I collagen (Col-I) and fibroectin, established at the site of the residing QDTC, promoted the outbreak of QDTC. Therefore, we hypothesized that promoting resolution—the endogenous mechanism that terminates inflammation and fibrotic responses and actively directs tissue return to homeostasis—at the permissive site will “normalize” it and prevent metastatic outbreak. Here we demonstrate that soluble factors secreted by ex vivo generated pro-resolving CD11blow macrophages can inhibit the establishment of a fibrotic niche resulting in the inhibition of the metastatic outgrowth of QDTC. The inhibition of the fibrotic niche was due to inhibition of TGFβ1-induced differentiation of fibroblasts to myofibroblasts and myofibroblasts’ apoptosis. Interestingly, our data also demonstrate that the blockade of fibroblast differentiation to myofibroblasts is not mediated by inhibition of the canonical signaling of TGFβ1. Taken together our results demonstrate a pioneering conceptual approach to “normalize” the microenvironment that supports the outgrowth of QDTC by promoting the tissue resolution axis.
This abstract is also being presented as Poster B36.
Citation Format: Odelya Gilon, Yonatan David Feuermann, Sagie Schif-Zuck, Keren Weidenfeld, Palle Von Huth, Edmond Sabo, Amiram Ariel, Dalit Barkan. Preventing the recurrence of breast cancer at the metastatic niche using resolution-phase macrophages [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr PR05.
ПОШИРЕНІСТЬ УРОЛОГІЧНОЇ ПАТОЛОГІЇ ТА ПРОБЛЕМИ ОРГАНІЗАЦІЇ НАДАННЯ УРОЛОГІЧНОЇ ДОПОМОГИ НАСЕЛЕННЮ (ОГЛЯД НАУКОВОЇ ЛІТЕРАТУРИ)
Authors: Diachuk M. D. 
Published: January 2019

Мета: виявлення сучасного стану розробки проблеми організації медичної допомоги пацієнтам урологічного профілю та перспективи подальших досліджень.
Матеріали і методи. При виконанні дослідження використано бібліографічний метод та метод контент-аналізу.
Результати. Незважаючи на тягар медико-соціальних проблем, пов’язаних із хворобами сечостатевої системи, дослідження з цієї тематики є вкрай нечисленні. Вони присвячені вивченню масштабів поширення патології, провідних чинників впливу, удосконаленню технологій лікування, вирішенню питань боротьби з окремими хворобами сечостатевої системи, насамперед із сечокам’яною хворобою, інфекціями та хронічними хворобами нирок, та організації медичної допомоги окремим категоріям населення, переважно в регіональному контексті.
Залишаються невирішеними питання медико-організаційного характеру. Це вимагає комплексного підходу з урахуванням широкого спектра патології, багатьох чинників впливу, сучасних стратегій розвитку урологічної служби, інтегративних тенденцій, профілактичних концепцій, пацієнторієнтованого підходу тощо.
Висновки. Аналіз наукової літератури виявив недостатню розробку проблеми скорочення урологічної патології, її негативних наслідків, засвідчив необхідність наукового обґрунтування удосконалення системи надання урологічної допомоги населенню за умов реформування охорони здоров’я.
Racial Differences in Sudden Cardiac Death
Authors: Zhao Di , Post Wendy S. , Blasco-Colmenares Elena , Cheng Alan , Zhang Yiyi , Deo Rajat , Pastor-Barriuso Roberto , Michos Erin D. , Sotoodehnia Nona , Guallar Eliseo 
Published: February 2019

Background:
Blacks have a higher incidence of out-of-hospital sudden cardiac death (SCD) in comparison with whites. However, the racial differences in the cumulative risk of SCD and the reasons for these differences have not been assessed in large-scale community-based cohorts. The objective of this study is to compare the lifetime cumulative risk of SCD among blacks and whites, and to evaluate the risk factors that may explain racial differences in SCD risk in the general population.

Methods:
This is a cohort study of 3832 blacks and 11 237 whites participating in the Atherosclerosis Risk in Communities Study (ARIC). Race was self-reported. SCD was defined as a sudden pulseless condition from a cardiac cause in a previously stable individual, and SCD cases were adjudicated by an expert committee. Cumulative incidence was computed using competing risk models. Potential mediators included demographic and socioeconomic factors, cardiovascular risk factors, presence of coronary heart disease, and electrocardiographic parameters as time-varying factors.

Results:
The mean (SD) age was 53.6 (5.8) years for blacks and 54.4 (5.7) years for whites. During 27.4 years of follow-up, 215 blacks and 332 whites experienced SCD. The lifetime cumulative incidence of SCD at age 85 years was 9.6, 6.6, 6.5, and 2.3% for black men, black women, white men, and white women, respectively. The sex-adjusted hazard ratio for SCD comparing blacks with whites was 2.12 (95% CI, 1.79–2.51). The association was attenuated but still statistically significant in fully adjusted models (hazard ratio, 1.38; 95% CI, 1.11–1.71). In mediation analysis, known factors explained 65.3% (95% CI 37.9–92.8%) of the excess risk of SCD in blacks in comparison with whites. The single most important factor explaining this difference was income (50.5%), followed by education (19.1%), hypertension (22.1%), and diabetes mellitus (19.6%). Racial differences were evident in both genders but stronger in women than in men.

Conclusions:
Blacks had a much higher risk for SCD in comparison with whites, particularly among women. Income, education, and traditional risk factors explained ≈65% of the race difference in SCD. The high burden of SCD and the racial–gender disparities observed in our study represent a major public health and clinical problem.
The Practice of Khulʿ in Germany: Pragmatism versus Conservativism
Authors: Jaraba Mahmoud 
Published: February 2019

AbstractIn this article, I examine how Muslim women who ae religiously-married in Germany might initiate no-fault divorce in the absence of a German registered civil marriage. Because there is no Muslim state authority to consult, local imams and Islamic leaders can resort to a community-led practice known as khulʿ (divorce initiated by the woman) to dissolve an Islamic marriage (nikāḥ) that is not recognized by civil authorities. In this article, which is the culmination of three years of fieldwork in Germany, I analyze and interpret the views and practices of two groups of religious actors - conservatives and pragmatists - towards khulʿ in cases of nikāḥ. I find that conservatives only permit a woman to divorce through khulʿ with her husband’s consent, whereas pragmatists use Muslim minority jurisprudence (fiqh al-aqalliyyāt al-Muslima) to argue that the husband’s consent is not essential to legitimize a khulʿ pronouncement.
Arresting Alternatives
Authors: Rauhala Marika 
Published: February 2019

AbstractAncient Greek descriptions of ecstatic and mystic rituals, here broadly labeled as Bacchantic worship, regularly include elements of moral corruption and dissolution of social unity. Suspicions were mostly directed against unofficial cult groups that exploited Dionysiac experiences in secluded settings. As the introduction of copious new cults attests, Greek religion was receptive to external influences. This basic openness, however, was not synonymous with tolerance, and pious respect for all deities did not automatically include their worshippers. This article reconsiders the current view of ancient religious intolerance by regarding these negative stereotypes as expressions of prejudice and by investigating the social dynamics behind them. Prejudices against private Bacchantic groups are regarded as part of the process of buttressing the religious authority of certain elite quarters in situations where they perceive that their position is being threatened by rival claims. It is suggested that both the accentuation and alleviation of prejudice is best understood in relation to the relative stability of the elite and the religious control it exerted.
The (Ancient Greek) Subject Supposed to Believe
Authors: Eidinow Esther 
Published: February 2019

AbstractThis article discusses the challenges facing scholars exploring the nature of belief in ancient Greek religion. While recent scholarship has raised questions about individual religious activities, and work on ritual, the body, and the senses has broadened our methodological palette, the nature and dynamics of generally held “low intensity” beliefs still tend to be described simply as “unquestioned” or “embedded” in society. But examining scholarship on divine personifications suggests that ancient beliefs were — and our perceptions of them are — more complex. This article first explores the example of Tyche (“Chance”), in order to highlight some of the problems that surround the use of the term “belief.” It then turns to the theories of “ideology” of Slavoj Žižek and Robert Pfaller and argues that these can offer provocative insights into the nature and dynamics of ritual and belief in ancient Greek culture.