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(a) Gating example of flow cytometric analysis for CXCR4+CD45+CD11b+ myeloid cells, neutrophils (CD45+CD11b+Ly6G+F480-.), and macrophages (CD45+CD11b+Ly6G-F480+). (b-d) Flow cytometric analysis of ILCs (CD45+Cd3-Cd90.2+), NK cells (CD45+CD3-NK1.1+) and B cells (CD45+CD3-b220+) in esophagus of different time point mice (n=4-7). (e) Flow cytometric analysis shows an increase trend of CXCR4+CD45+CD11b+ myeloid cell populations in spleen (n=3, age=12 months).

A trend appears that more CXCR4+proliferating cells are present in high-grade dysplasia mice.

Purpose: Barrett's esophagus represents an early stage in carcinogenesis leading to esophageal adenocarcinoma. Considerable evidence supports a major role for chronic inflammation and diverse chemokine pathways in the development of Barrett's esophagus and esophageal adenocarcinoma.Experimental Design: Here we utilized an IL1β transgenic mouse model of Barrett's esophagus and esophageal adenocarcinoma and human patient imaging to analyze the importance of CXCR4-expressing cells during esophageal carcinogenesis.Results: IL1β overexpression induces chronic esophageal inflammation and recapitulates the progression to Barrett's esophagus and esophageal adenocarcinoma. CXCR4 expression is increased in both epithelial and immune cells during disease progression in pL2-IL1β mice and also elevated in esophageal adenocarcinoma patient biopsy samples. Specific recruitment of CXCR4-positive (CXCR4+) immune cells correlated with dysplasia progression, suggesting that this immune population may be a key contributor to esophageal carcinogenesis. Similarly, with progression to dysplasia, there were increased numbers of CXCR4+ columnar epithelial cells at the squamocolumnar junction (SCJ). These findings were supported by stronger CXCR4-related signal intensity in ex vivo fluorescence imaging and autoradiography with advanced dysplasia. Pilot CXCR4-directed PET/CT imaging studies in patients with esophageal cancer demonstrate the potential utility of CXCR4 imaging for the diagnosis and staging of esophageal cancer.Conclusion: In conclusion, the recruitment of CXCR4+ immune cells and expansion of CXCR4+ epithelial cells in esophageal dysplasia and cancer highlight the potential of CXCR4 as a biomarker and molecular target for diagnostic imaging of the tumor microenvironment in esophageal adenocarcinoma. Clin Cancer Res; 24(5); 1048–61. ©2017 AACR.

CXCR4 immunohistochemistry of a patient with EAC that has been imaged by [68Ga]CXCR4-PET/CT showing moderate infiltration with immune cells (open arrow) expressing CXCR4. Only very few epithelial tumor cells were detectable within this biopsy and they did not express CXCR4 (solid arrow)

Lisa Ingermann widmet sich in ihrem Beitrag der Frage, wie historisches Erzählen in Gestalt grafischer Literatur für die bewusste Wahrnehmung von Fiktionalität fruchtbar gemacht werden kann. Die Aspekte auf der übergeordneten Blocktextebene und auf Bild- und Sprechblasenebene, deren Thematisierung für diese bewusste Wahrnehmung erforderlich ist, werden aufgeschlüsselt und darauf untersucht, inwiefern u.a. durch comicspezifische Erzähltechniken Fiktionalisierungen sichtbar werden. Die Wechselbeziehung zwischen beiden Ebenen findet dabei besondere Berücksichtigung. Die abschließende didaktische Reflexion zeigt zusammenfassend Wege auf, wie die Lektüre im Literaturunterricht behandelt werden kann.

Chronic inflammation induces Barrett’s Esophagus (BE) which can advance to esophageal adenocarcinoma. Elevated levels of interleukin (IL)-1b, IL-6 and IL-8 together with activated nuclear factor-kappaB (NF-κB), have been identified as important mediators of tumorigenesis. The inflammatory milieu apart from cancer cells and infiltrating immune cells contains myofibroblasts (MFs) that express aSMA and Vimentin. As we observed that increased NF-κB activation and inflammation correlates with increased MF recruitment and an accelerated phenotype we here analyze the role of NF-κB in MF during esophageal carcinogenesis in our L2-IL-1B mouse model. To analyze the effect of NF-κB signaling in MFs, we crossed L2-IL-1B mice to tamoxifen inducible Vim-Cre (Vim-CreTm) mice and floxed RelA (p65fl/fl) mice to specifically eliminate NF-κB signaling in MF (IL-1b.Vim-CreTm.p65fl/fl). The interaction of epithelial cells and stromal cells was further analyzed in mouse BE organoids and patient-derived human organoids. Histological scoring of IL-1b.Vim-CreTm.p65fl/fl mice showed a significantly attenuated phenotype compared with L2-IL-1B mice, with mild inflammation, decreased metaplasia and no dysplasia. This correlated with decreased proliferation and increased differentiation in cardia tissue of IL-1b.Vim-CreTm.p65fl/fl compared with L2-IL-1B mice. Distinct changes of cytokines and chemokines within the local microenvironment in IL-1b.Vim-CreTm.p65fl/fl mice reflected the histopathological abrogated phenotype. Co-cultured NF-κB inhibitor treated MF with mouse BE organoids demonstrated NF-κB-dependent growth and migration. MFs are essential to form an inflammatory and procarcinogenic microenvironment and NF-κB signaling in stromal cells emerges as an important driver of esophageal carcinogenesis. Our data suggest anti-inflammatory approaches as preventive strategies during surveillance of BE patients.

High fat diet leads to accelerated tumor formation and a markedly changed gut microbiome in a mouse model of Barrett esophagus and esophageal adenocarcinoma. In a germfree environment the phenotype is weakened, linking tumor formation to diet possibly by functional differences of the microbiome and associated inflammatory components. Anti-inflammatory treatment with Aspirin and Sulindac mitigates tumor formation and leads to a changed profile of immune cells, suggesting chemoprevention as a feasible measure for patients. Eine fettreiche Diät führt im Mausmodell für Barrett-Ösophagus und ösophageales Adenokarzinom zu verstärkter Tumorbildung und einem deutlich veränderten Darmmikrobiom. In keimfreier Umgebung ist der Phänotyp allerdings abgeschwächt, sodass die Ernährung die Tumorentstehung möglicherweise durch funktionelle Veränderungen des Mikrobiomes und damit verbundene inflammatorische Komponenten beeinflusst. Eine antiinflammatorische Behandlung mit Aspirin und Sulindac mildert diese Tumorbildung und verändert das Immunzellprofil im Sinne einer Chemoprävention als praktikable Maßnahme für Patienten.

Stormwater has immense impacts on urban flooding and water quality, leaving the marginalized and the impoverished disproportionately impacted by and vulnerable to stormwater hazards. However, the environmental health concerns of socially and economically marginalized individuals are largely underestimated. Through regression analysis of data from three longitudinal surveys, this article examines if and how an individual's race, gender, and education level help predict one's concern about and willingness to participate in stormwater management. We found that people of color, women, and less-educated respondents had a greater willingness to participate in stormwater management than White, male, and more-educated respondents, and their concern about local stormwater hazards drove their willingness to participate. Our analysis suggests that physical exposure and high vulnerability to stormwater hazards may shape an individual's concern about and willingness to participate in stormwater management., Comment: Accepted Manuscript 43 pages, 2 figures, 3 tables

Barrett’s esophagus (BE) is the main known precursor condition of esophageal adenocarcinoma (EAC). BE is defined by the presence of metaplasia above the normal squamous columnar junction and has mainly been attributed to gastroesophageal reflux disease and chronic reflux esophagitis. Thus, the rising incidence of EAC in the Western world is probably mediated by chronic esophageal inflammation, secondary to gastroesophageal reflux disease in combination with environmental risk factors such as a Western diet and obesity. However, (at present) risk prediction tools and endoscopic surveillance have shown limited effectiveness. Chemoprevention as an adjunctive approach remains an attractive option to reduce the incidence of neoplastic disease. Here, we investigate the feasibility of chemopreventive approaches in BE and EAC via inhibition of inflammatory signaling in a transgenic mouse model of BE and EAC (L2-IL1B mice), with accelerated tumor formation on a high-fat diet (HFD). L2-IL1B mice were treated with the IL-1 receptor antagonist Anakinra and the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin or Sulindac. Interleukin-1b antagonism reduced tumor progression in L2-IL1B mice with or without a HFD, whereas both NSAIDs were effective chemoprevention agents in the accelerated HFD-fed L2-IL1B mouse model. Sulindac treatment also resulted in a marked change in the immune profile of L2-IL1B mice. In summary, anti-inflammatory treatment of HFD-treated L2-IL1B mice acted protectively on disease progression. These results from a mouse model of BE support results from clinical trials that suggest that anti-inflammatory medication may be effective in the chemoprevention of EAC.