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3. The death of laparoscopy

Author

Ferrari, Davide, Violante, Tommaso, Novelli, Marco, Starlinger, Patrick P., Smoot, Rory L., Reisenauer, Janani S., and Larson, David W.

Published
2024
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11. Metabolome-wide association identifies altered metabolites and metabolic pathways in the serum of patients with cholangiocarcinoma

Author

Jackson, Linsey E., Tomlinson, Jennifer L., Alva-Ruiz, Roberto, Gregory, Lindsey A., Byeon, Seul Kee, Abdelrahman, Amro M., Mun, Dong-Gi, Grant, Caroline W., Fogarty, Zachary C., Wang, Chen, Roberts, Lewis R., Graham, Rondell P., Borad, Mitesh J., Ilyas, Sumera I., Gores, Gregory J., Pandey, Akhilesh, Athreya, Arjun P., and Smoot, Rory L.

Published
2024
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18. An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure

Author

Santol, Jonas, Kim, Sarang, Gregory, Lindsey A., Baumgartner, Ruth, Murtha-Lemekhova, Anastasia, Birgin, Emrullah, Gloor, Severin, Braunwarth, Eva, Ammann, Markus, Starlinger, Johannes, Pereyra, David, Ammon, Daphni, Ninkovic, Marijana, Kern, Anna E., Rumpf, Benedikt, Ortmayr, Gregor, Herrmann, Yannic, Dong, Yawen, Huber, Felix X., Weninger, Jeremias, Thiels, Cornelius A., Warner, Susanne G., Smoot, Rory L., Truty, Mark J., Kendrick, Michael L., Nagorney, David N., Cleary, Sean P., Beldi, Guido, Rahbari, Nuh N., Hoffmann, Katrin, Gilg, Stefan, Assinger, Alice, Gruenberger, Thomas, Hackl, Hubert, and Starlinger, Patrick

Published
2023
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29. YAP‐TEAD inhibition is associated with upregulation of an androgen receptor mediated transcription program providing therapeutic escape.

Author

Alva‐Ruiz, Roberto, Watkins, Ryan D., Tomlinson, Jennifer L., Yonkus, Jennifer A., Abdelrahman, Amro M., Conboy, Caitlin B., Jessen, Erik, Werneburg, Nathan W., Kuipers, Hendrien, Sample, Jack W., Gores, Gregory J., Ilyas, Sumera I., Truty, Mark J., and Smoot, Rory L.

Subjects
FIBROBLAST growth factor receptors, HIPPO signaling pathway, YAP signaling proteins, LIVER cancer, RNA sequencing
Abstract

Cholangiocarcinoma (CCA) is a highly aggressive form of liver cancer and is an increasing cause of cancer‐related death worldwide. Despite its increasing incidence globally and alarming mortality, treatment options for CCA have largely remained unchanged, stressing the importance of developing new effective therapies. YAP activation is common in CCA, and its major transcriptional signaling partners are the TEAD proteins. CA3 is a small‐molecule YAP‐TEAD disrupter discovered utilizing a TEAD reporter assay. Utilizing CCA, gastric cancer cell lines, and patient‐derived xenograft models (PDX), we demonstrate that CA3 is effective in inducing cell death and delaying tumor growth in both FGFR2 fusion and wild‐type models. CA3 was associated with on‐target decreases in YAP‐TEAD target gene expression, TEAD reporter activity, and overall TEAD levels. Hippo pathway signaling was not altered as there was no change in YAP phosphorylation status in the cells exposed to CA3. RNA sequencing of gastric cancer and CCA models demonstrated upregulation of an androgen receptor–mediated transcriptional program following exposure to CA3 in five unique models tested. Consistent with this upstream regulator analysis, CA3 exposure in CCA cells was associated with increased AR protein levels, and combinatorial therapy with CA3 and androgen receptor blockade was associated with increased cancer cell death. CA3 behaves functionally as a YAP‐TEAD disrupter in the models tested and demonstrated therapeutic efficacy. Exposure to CA3 was associated with compensatory androgen receptor signaling and dual inhibition improved the therapeutic effect. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Pancreatic Cancer is More Frequently Early Stage at Diagnosis in Surgically Resected Intraductal Papillary Mucinous Neoplasms With Preoperative Surveillance

Author

de la Fuente, Jaime, Lui, Jacob, Lennon, Ryan J., Chatterjee, Arjun, Graham, Rondell P., Zhang, Lizhi, Kendrick, Michael L., Truty, Mark J., Cleary, Sean P., Smoot, Rory L., Nagorney, David M., Gleeson, Ferga C., Levy, Michael J., Chandrasekhara, Vinay, Pearson, Randall K., Petersen, Bret T., Vege, Santhi S., Chari, Suresh T., and Majumder, Shounak

Published
2022
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32. LCK inhibition downregulates YAP activity and is therapeutic in patient-derived models of cholangiocarcinoma

Author

Conboy, Caitlin B., Yonkus, Jennifer A., Buckarma, EeeLN H., Mun, Dong-Gi, Werneburg, Nathan W., Watkins, Ryan D., Alva-Ruiz, Roberto, Tomlinson, Jennifer L., Guo, Yi, Wang, Juan, O’Brien, Daniel, McCabe, Chantal E., Jessen, Erik, Graham, Rondell P., Buijsman, Rogier C., Vu, Diep, de Man, Jos, Ilyas, Sumera I., Truty, Mark J., Borad, Mitesh, Pandey, Akhilesh, Gores, Gregory J., and Smoot, Rory L.

Published
2022
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37. Hepatocellular Adenoma

Author

Young, Jason R., Mounajjed, Taofic, Smoot, Rory L., Harnois, Denise M., Musto, Kaitlyn R., Venkatesh, Sudhakar K., Roberts, Lewis R., editor, Yang, Ju Dong, editor, and Venkatesh, Sudhakar K., editor

Published
2020
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43. Diversity of post-translational modifications and cell signaling revealed by single cell and single organelle mass spectrometry.

Author

Mun, Dong-Gi, Bhat, Firdous A., Joshi, Neha, Sandoval, Leticia, Ding, Husheng, Jain, Anu, Peterson, Jane A., Kang, Taewook, Pujari, Ganesh P., Tomlinson, Jennifer L., Budhraja, Rohit, Zenka, Roman M., Kannan, Nagarajan, Kipp, Benjamin R., Dasari, Surendra, Gaspar-Maia, Alexandre, Smoot, Rory L., Kandasamy, Richard K., and Pandey, Akhilesh

Subjects
POST-translational modification, SINGLE cell proteins, MASS spectrometry, CELL communication, PROTEIN-protein interactions, PROTEOMICS, ORGANELLES
Abstract

The rapid evolution of mass spectrometry-based single-cell proteomics now enables the cataloging of several thousand proteins from single cells. We investigated whether we could discover cellular heterogeneity beyond proteome, encompassing post-translational modifications (PTM), protein-protein interaction, and variants. By optimizing the mass spectrometry data interpretation strategy to enable the detection of PTMs and variants, we have generated a high-definition dataset of single-cell and nuclear proteomic-states. The data demonstrate the heterogeneity of cell-states and signaling dependencies at the single-cell level and reveal epigenetic drug-induced changes in single nuclei. This approach enables the exploration of previously uncharted single-cell and organellar proteomes revealing molecular characteristics that are inaccessible through RNA profiling. This study explored single cells and single organelles to reveal unique molecular characteristics such as mutant peptides and modulation of diverse post-translational modifications that are inaccessible through DNA/RNA profiling. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma

Author

Loeuillard, Emilien, Yang, Jingchun, Buckarma, EeeLN, Wang, Juan, Liu, Yuanhang, Conboy, Caitlin, Pavelko, Kevin D., Li, Ying, O'Brien, Daniel, Wang, Chen, Graham, Rondell P., Smoot, Rory L., Dong, Haidong, and Ilyas, Sumera

Subjects
Macrophages -- Analysis, Disease susceptibility -- Development and progression, Immunotherapy -- Analysis, RNA sequencing -- Analysis, Biliary tract cancer -- Development and progression, T cells -- Analysis, Health care industry
Abstract

Immune checkpoint blockade (ICB) has revolutionized cancer therapeutics. Desmoplastic malignancies, such as cholangiocarcinoma (CCA), have an abundant tumor immune microenvironment (TIME). However, to date, ICB monotherapy in such malignancies has been ineffective. Herein, we identify tumor-associated macrophages (TAMs) as the primary source of programmed death-ligand 1 (PD-L1) in human and murine CCA. In a murine model of CCA, recruited [PD-L1.sup.+] TAMs facilitated CCA progression. However, TAM blockade failed to decrease tumor progression due to a compensatory emergence of granulocytic myeloid-derived suppressor cells (G-MDSCs) that mediated immune escape by impairing T cell response. Singlecell RNA sequencing (scRNA-Seq) of murine tumor G-MDSCs highlighted a unique ApoE G-MDSC subset enriched with TAM blockade; further analysis of a human scRNA-Seq data set demonstrated the presence of a similar G-MDSC subset in human CCA. Finally, dual inhibition of TAMs and G-MDSCs potentiated ICB. In summary, our findings highlight the therapeutic potential of coupling ICB with immunotherapies targeting immunosuppressive myeloid cells in CCA., Introduction Cholangiocarcinoma (CCA) is the most common biliary malignancy and the second most common primary hepatic malignancy (1). CCAs are highly lethal neoplasms with limited therapeutic options and a dismal [...]

Published
2020
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49. Safety, Diagnostic Accuracy, and Effects of Endoscopic Ultrasound Fine-Needle Aspiration on Detection of Extravascular Migratory Metastases

Author

Rustagi, Tarun, Gleeson, Ferga C., Chari, Suresh T., Lehrke, Heidi D., Takahashi, Naoki, Malikowski, Thomas M., Abu Dayyeh, Barham K., Chandrasekhara, Vinay, Iyer, Prasad G., Kendrick, Michael L., Pearson, Randall K., Petersen, Bret T., Rajan, Elizabeth, Smoot, Rory L., Storm, Andrew C., Topazian, Mark D., Truty, Mark J., Vege, Santhi S., Wang, Kenneth K., and Levy, Michael J.

Published
2019
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