Protein Analysis of the TGFBI
            R124H
            Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

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Multi-omic profiling of lung and liver tumor microenvironments of metastatic pancreatic cancer reveals site-specific immune regulatory pathways

Genome Biology ◽

10.1186/s13059-021-02363-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Won Jin Ho ◽

Rossin Erbe ◽

Ludmila Danilova ◽

Zaw Phyo ◽

Emma Bigelow ◽

...

Keyword(s):

Mouse Model ◽

Primary Tumors ◽

Regulatory Pathways ◽

Tumor Microenvironments ◽

Clinical Responses ◽

Cellular Pathways ◽

Autopsy Specimens ◽

Rapid Autopsy ◽

Insight Into ◽

Systemic Therapies

Abstract Background The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed at the metastatic stage, and standard therapies have limited activity with a dismal 5-year survival rate of only 8%. The liver and lung are the most common sites of PDAC metastasis, and each have been differentially associated with prognoses and responses to systemic therapies. A deeper understanding of the molecular and cellular landscape within the tumor microenvironment (TME) metastasis at these different sites is critical to informing future therapeutic strategies against metastatic PDAC. Results By leveraging combined mass cytometry, immunohistochemistry, and RNA sequencing, we identify key regulatory pathways that distinguish the liver and lung TMEs in a preclinical mouse model of metastatic PDAC. We demonstrate that the lung TME generally exhibits higher levels of immune infiltration, immune activation, and pro-immune signaling pathways, whereas multiple immune-suppressive pathways are emphasized in the liver TME. We then perform further validation of these preclinical findings in paired human lung and liver metastatic samples using immunohistochemistry from PDAC rapid autopsy specimens. Finally, in silico validation with transfer learning between our mouse model and TCGA datasets further demonstrates that many of the site-associated features are detectable even in the context of different primary tumors. Conclusions Determining the distinctive immune-suppressive features in multiple liver and lung TME datasets provides further insight into the tissue specificity of molecular and cellular pathways, suggesting a potential mechanism underlying the discordant clinical responses that are often observed in metastatic diseases.

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Deep Anterior Lamellar Keratoplasty With Melles Technique for Granular Corneal Dystrophy

Cornea ◽

10.1097/ico.0b013e3181861cdd ◽

2009 ◽

Vol 28 (2) ◽

pp. 140-143 ◽

Cited By ~ 18

Author(s):

Ramin Salouti ◽

Hamid Hosseini ◽

Masoomeh Eghtedari ◽

Mohammad R Khalili

Keyword(s):

Corneal Dystrophy ◽

Lamellar Keratoplasty ◽

Deep Anterior Lamellar Keratoplasty ◽

Anterior Lamellar Keratoplasty ◽

Granular Corneal Dystrophy

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Differential diagnosis between granular corneal dystrophy Groenouw type I and paraproteinemic crystalline keratopathy

Acta Ophthalmologica ◽

10.1111/j.1755-3768.1993.tb04635.x ◽

2009 ◽

Vol 71 (4) ◽

pp. 552-555 ◽

Cited By ~ 3

Author(s):

H. U. Møller ◽

N. Ehlers ◽

M. Bojsen-Møller ◽

Alan Ridgway

Keyword(s):

Differential Diagnosis ◽

Corneal Dystrophy ◽

Type I ◽

Crystalline Keratopathy ◽

Granular Corneal Dystrophy

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Experimentally Approaching the ICU: Monitoring Outcome-Based Responses in the Two-Hit Mouse Model of Posttraumatic Sepsis

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/357926 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Susanne Drechsler ◽

Katrin M. Weixelbaumer ◽

Heinz Redl ◽

Martijn van Griensven ◽

Soheyl Bahrami ◽

...

Keyword(s):

Mouse Model ◽

Femur Fracture ◽

Cecal Ligation ◽

Blood Sampling ◽

Cecal Ligation And Puncture ◽

Organ Function ◽

Daily Monitoring ◽

Circulating Cells ◽

Facial Vein ◽

Insight Into

To simulate and monitor the evolution of posttraumatic sepsis in mice, we combined a two-hit model of trauma/hemorrhage (TH) followed by polymicrobial sepsis with repetitive blood sampling. Anesthetized mice underwent femur fracture/sublethal hemorrhage and cecal ligation and puncture (CLP) 48 h later. To monitor outcome-dependent changes in circulating cells/biomarkers, mice were sampled daily (facial vein) for 7 days and retrospectively divided into either dead (DIE) or surviving (SUR) by post-CLP day 7. Prior to CLP, AST was 3-fold higher in DIE, while all other post-TH changes were similar between groups. There was a significant post-CLP intergroup separation. In SUR, RBC and Hb were lower, platelets and neutrophils higher, and lymphocytes mixed compared to DIE. In DIE, all organ function markers except glucose (decrease) were few folds higher compared to SUR. In summary, the combination of daily monitoring with an adequate two-hit model simulates the ICU setting, allows insight into outcome-based responses, and can identify biomarkers indicative of death in the acute posttraumatic sepsis in mice.

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