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Modulation Of Immune Checkpoints By Chemotherapy In Human Colorectal Liver Metastases., Neda Jabbari, Heidi L Kenerson, Christopher Lausted, Xiaowei Yan, Changting Meng, Kevin M Sullivan, Priyanka Baloni, Dani E Bergey, Venu G Pillarisetty, Leroy Hood, Raymond S Yeung, Qiang Tian

Articles, Abstracts, and Reports

Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression …

Primary Sclerosing Cholangitis: Epidemiology, Genetics, Diagnosis, And Current Management., Eric Gochanour, Channa Jayasekera, Kris V Kowdley

Articles, Abstracts, and Reports

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-reading-gochanour a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-3-interview-kowdley an interview with the author.

Tumor Slice Culture As A Biologic Surrogate Of Human Cancer., Heidi L Kenerson, Kevin M Sullivan, Yongwoo D Seo, Kathryn M Stadeli, Cigdem Ussakli, Xiaowei Yan, Christopher G Lausted, Venu G Pillarisetty, James O Park, Kimberly J Riehle, Matthew Yeh, Qiang Tian, Raymond S Yeung

Articles, Abstracts, and Reports

Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and

Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression …

Methylation Signatures In Peripheral Blood Are Associated With Marked Age Acceleration And Disease Progression In Patients With Primary Sclerosing Cholangitis., Michael Trauner, Yevgeniy Gindin, Zhaoshi Jiang, Chuhan Chung, G Mani Subramanian, Robert P Myers, Aliya Gulamhusein, Kris V Kowdley, Cynthia Levy, Zachary Goodman, Michael P Manns, Andrew J Muir, Christopher L Bowlus

Articles, Abstracts, and Reports

Background & Aims: A DNA methylation (DNAm) signature derived from 353 CpG sites (the Horvath clock) has been proposed as an epigenetic measure of chronological and biological age. This epigenetic signature is accelerated in diverse tissue types in various disorders, including non-alcoholic steatohepatitis, and is associated with mortality. Here, we assayed whole blood DNAm to explore age acceleration in patients with primary sclerosing cholangitis (PSC).

Methods: Using the MethylationEPIC BeadChip (850K) array, DNAm signatures in whole blood were analyzed in 36 patients with PSC enrolled in a 96-week trial of simtuzumab (Ishak F0-1, n = 13; F5-6, n = 23). …