Review
Chemistry, Analytical
Vinayak Juvekar, Hyo Won Lee, Dong Joon Lee, Hwan Myung Kim
Summary: Two-photon microscopy is an important tool for deep-tissue imaging, providing high-resolution fluorescence images beyond millimeter depths. Recent research has focused on developing innovative strategies and probes for quantitative analysis using two-photon fluorescence.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Arne Maes, Camille Pestiaux, Alice Marino, Tim Balcaen, Lisa Leyssens, Sarah Vangrunderbeeck, Grzegorz Pyka, Wim M. De Borggraeve, Luc Bertrand, Christophe Beauloye, Sandrine Horman, Martine Wevers, Greet Kerckhofs
Summary: The authors present a cryogenic contrast-enhanced MicroCT method that improves the visualization of tissue microstructure by freezing stained samples at optimal freezing rates. They successfully applied this method to analyze individual muscle fibers and locate fibrotic regions in murine hearts. This method has significant applications in tissue histology and food preservation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Denise Wolrab, Robert Jirasko, Eva Cifkova, Marcus Horing, Ding Mei, Michaela Chocholouskova, Ondrej Peterka, Jakub Idkowiak, Tereza Hrnciarova, Ladislav Kuchar, Robert Ahrends, Radana Brumarova, David Friedecky, Gabriel Vivo-Truyols, Pavel Skrha, Jan Skrha, Radek Kucera, Bohuslav Melichar, Gerhard Liebisch, Ralph Burkhardt, Markus R. Wenk, Amaury Cazenave-Gassiot, Petr Karasek, Ivo Novotny, Kristina Greplova, Roman Hrstka, Michal Holcapek
Summary: Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients. The study found significant differences in blood lipids between pancreatic cancer patients and healthy controls.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Hiroyuki Koike, Kentaro Iwasawa, Rie Ouchi, Mari Maezawa, Masaki Kimura, Asuka Kodaka, Shozo Nishii, Wendy L. Thompson, Takanori Takebe
Summary: This study introduces a method for continuous patterning of hepatic, biliary and pancreatic structures from human pluripotent stem cells (PSCs) in 3D culture. By fusing anterior and posterior gut spheroids together in one well, the self-patterning of multi-organ (HBP) domains occurs within the boundary region of the two spheroids. Long-term culture of these structures leads to the differentiation of segregated organs with developmentally relevant features.
Article
Chemistry, Analytical
Chi Shu, Hanshu Yan, Wei Zheng, Kan Lin, Anne James, Sathiyamoorthy Selvarajan, Chwee Ming Lim, Zhiwei Huang
Summary: This study developed a deep learning-guided fiberoptic Raman diagnostic platform, with the optimized RS-CNN model showing good diagnostic accuracy and sensitivity in real-time NPC diagnosis, outperforming traditional linear discriminate analysis methods. By investigating saliency maps of the RS-CNN models, the diagnostic capability related to biomolecular variations was validated.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemical Research Methods
Jun Bai, Renbo Tan, Zheng An, Ying Xu
Summary: A novel computational model is proposed for quantitatively estimating the level of oxidative stress in tissues and cells based on their transcriptomic data. The model utilizes marker genes and polynomial functions to capture the oxidizing power, antioxidation capacity, and oxidative stress level, with parameters estimated through an optimization problem. The model is shown to be highly reliable and provides insights based on its application to various databases.
BRIEFINGS IN BIOINFORMATICS
(2022)
Review
Cardiac & Cardiovascular Systems
Kaleb M. Naegeli, Mehmet H. Kural, Yuling Li, Juan Wang, Emmanuelle A. Hugentobler, Laura E. Niklason
Summary: Cardiovascular defects, injuries, and degenerative diseases often require surgical intervention and the use of implantable replacement materials. However, traditional grafts have limitations. Researchers are exploring avenues such as bioengineering to address these limitations.
CIRCULATION RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Lei G. Wang, Antonio R. Montano, Jason R. Combs, Nathan P. McMahon, Allison Solanki, Michelle M. Gomes, Kai Tao, William H. Bisson, Dani A. Szafran, Kimberley S. Samkoe, Kenneth M. Tichauer, Summer L. Gibbs
Summary: Non-destructive diffusion of fluorescent molecules across cell membranes is crucial for quantitative imaging in live cells and tissues. We have developed biologically compatible and cell-membrane-permeable fluorophores called OregonFluor (ORFluor), which allow for quantitative visualization of their intracellular distribution and protein target-specific binding using ratiometric imaging methodology. This provides a chemical toolkit for quantifying drug target availability in live cells and tissues.
Article
Engineering, Biomedical
Kejie Chen, Yi Zheng, Xufeng Xue, Yue Liu, Agnes M. Resto Irizarry, Huaijing Tang, Jianping Fu
Summary: Human embryonic stem cells have the ability to self-organize and form patterned tissues, and they can be manipulated in vitro to generate embryonic-like structures. A 3D suspension culture system has been developed to efficiently produce postimplantation, pre-gastrulation embryonic-like tissues, with the size of the initial cell seeding density impacting the development trajectory and resulting tissue types.
Article
Multidisciplinary Sciences
Ranjay Krishna, Donsuk Lee, Li Fei-Fei, Michael S. Bernstein
Summary: This article introduces a method of formalizing socially situated learning as a reinforcement learning problem, where artificial intelligence agents seek out new information through social interactions. Through interactions with 236,000 social media users, the agent's performance improved significantly.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Medicine, Research & Experimental
Peng Wang, Esra Karakose, Carmen Argmann, Huan Wang, Metodi Balev, Rachel Brody, Hembly G. Rivas, Xinyue Liu, Olivia Wood, Hongtao Liu, Lauryn Choleva, Dan Hasson, Emily Bernstein, Joao A. Paulo, Donald K. Scott, Luca Lambertini, James A. DeCaprio, Andrew F. Stewart
Summary: Resistance to regeneration of insulin-producing pancreatic β cells is a challenge in diabetes. Small molecule inhibitors of DYRK1A kinase have been found to induce proliferation of adult human β cells, but their mechanism of action is not fully understood. Through analysis of transcriptomic databases, researchers identified the DREAM complex as a central regulator of quiescence in human β cells. The DREAM complex consists of transcriptionally repressive proteins that assemble in response to DYRK1A kinase activity, inducing and maintaining cellular quiescence.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Optics
Jiao Li, Cong Wang, Tingting Chen, Tong Lu, Shuai Li, Biao Sun, Feng Gao, Vasilis Ntziachristos
Summary: In this study, a deep learning-based approach for quantitative optoacoustic tomography (QOAT) is proposed, which utilizes unsupervised simulation-to-experiment data translation to generate training data without labeled experimental data. This enables deep tissue imaging in the absence of ground truth data.
Article
Chemistry, Analytical
Xiaoling Su, Deying Chen, Liang Li, Lanjuan Li
Summary: The study demonstrates that perfusion can significantly alter the liver metabolome, recommending the use of non-perfused liver for comprehensive liver metabolomics analysis for high coverage.
ANALYTICA CHIMICA ACTA
(2021)
Article
Multidisciplinary Sciences
Dylan Nicholas Tabang, Danqing Wang, Lingjun Li
Summary: Mass spectrometry is a powerful tool for studying post-translational modifications of proteins, but enrichment is often necessary due to the low abundance of these modifications. Current enrichment methods only focus on one type of modification, but this may overlook the crosstalk between different modifications that is essential for biological functions. This study presents a simultaneous enrichment strategy for glycosylation and phosphorylation modifications, and successfully applies it to post-mortem human pancreatic tissue, enabling the analysis of potential crosstalk between these two important modifications.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Review
Endocrinology & Metabolism
Ruping Pan, Yong Chen
Summary: Obesity is characterized by the overaccumulation of white adipose tissue in the body, leading to various metabolic disorders. Targeting human thermogenic adipose tissues shows promise in combating obesity.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Gastroenterology & Hepatology
Stephan B. Dreyer, Rosie Upstill-Goddard, Viola Paulus-Hock, Clara Paris, Eirini-Maria Lampraki, Eloise Dray, Bryan Serrels, Giuseppina Caligiuri, Selma Rebus, Dennis Plenker, Zachary Galluzzo, Holly Brunton, Richard Cunningham, Mathias Tesson, Craig Nourse, Ulla-Maja Bailey, Marc Jones, Kim Moran-Jones, Derek W. Wright, Fraser Duthie, Karin Oien, Lisa Evers, Colin J. McKay, Grant A. McGregor, Aditi Gulati, Rachel Brough, Ilirjana Bajrami, Stephan Pettitt, Michele L. Dziubinski, Juliana Candido, Frances Balkwill, Simon T. Barry, Robert Grutzmann, Lola Rahib, Amber Johns, Marina Pajic, Fieke E. M. Froeling, Phillip Beer, Elizabeth A. Musgrove, Gloria M. Petersen, Alan Ashworth, Margaret C. Frame, Howard C. Crawford, Diane M. Simeone, Chris Lord, Debabrata Mukhopadhyay, Christian Pilarsky, David A. Tuveson, Susanna L. Cooke, Nigel B. Jamieson, Jennifer P. Morton, Owen J. Sansom, Peter J. Bailey, Andrew Biankin, David K. Chang
Summary: DDR deficiency and replication stress are independent of each other, offering opportunities for therapy in DDR-proficient PC and after platinum therapy. Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes, and serve as a valuable model for studying novel therapeutic strategies targeting DDR and replication stress in PC.
Article
Gastroenterology & Hepatology
Johann Gout, Lukas Perkhofer, Mareen Morawe, Frank Arnold, Michaela Ihle, Stephanie Biber, Sebastian Lange, Elodie Roger, Johann M. Kraus, Katja Stifter, Stephan A. Hahn, Andrea Zamperone, Thomas Engleitner, Martin Mueller, Karolin Walter, Eva Rodriguez-Aznar, Bruno Sainz Jr, Patrick C. Hermann, Elisabeth Hessmann, Sebastian Mueller, Ninel Azoitei, Andre Lechel, Stefan Liebau, Martin Wagner, Diane M. Simeone, Hans A. Kestler, Thomas Seufferlein, Lisa Wiesmueller, Roland Rad, Pierre-Olivier Frappart, Alexander Kleger
Summary: The study identified synergistic effects in inhibiting PARP, ATR, and DNA-PKcs that lead to synthetic lethality in ATM-deficient pancreatic ductal adenocarcinoma. Chemical inhibition of ATM sensitized human PDAC cells towards this combinatorial therapy, which was also found to overcome PARP inhibitor resistance. These findings suggest potential mutation-specific therapeutic strategies that may be applied through ATM inhibition regardless of genotype.
Article
Gastroenterology & Hepatology
Robert C. Grant, Robert Denroche, Gun Ho Jang, Klaudia M. Nowak, Amy Zhang, Ayelet Borgida, Spring Holter, James T. Topham, Julie Wilson, Anna Dodd, Raymond Jang, Rebecca Prince, Joanna M. Karasinska, David F. Schaeffer, Yifan Wang, George Zogopoulos, Scott Berry, Diane Simeone, Daniel J. Renouf, Faiyaz Notta, Grainne O'Kane, Jennifer Knox, Sandra Fischer, Steven Gallinger
Summary: Patients with MMRD pancreatic cancer exhibit longer overall survival, distinct histopathological and genomic features, and may benefit from targeted therapies based on their unique genomic drivers.
Article
Cell Biology
Vinee Purohit, Lidong Wang, Huibin Yang, Jiufeng Li, Gina M. Ney, Erica R. Gumkowski, Akash J. Vaidya, Annie Wang, Amit Bhardwaj, Ende Zhao, Igor Dolgalev, Andrea Zamperone, Ethan V. Abel, Marina Pasca Di Magliano, Howard C. Crawford, Daniel Diolaiti, Thales Y. Papagiannakopoulos, Costas A. Lyssiotis, Diane M. Simeone
Summary: The overexpression of ATDC in pancreatic cancer promotes tumor growth and metastasis by protecting cancer cells from ROS through stabilizing NRF2. This mechanism enhances chemoresistance and modulates redox balance in cancer cells.
GENES & DEVELOPMENT
(2021)
Editorial Material
Oncology
Rafael Winograd, Diane M. Simeone, Dafna Bar-Sagi
Summary: Immune checkpoint blockade has shown efficacy in multiple cancers, but further improvements are needed to increase response rates and achieve clinical efficacy in cold tumors. Mechanistic studies of tumor-specific immunosuppressive pathways can uncover biological barriers to immunotherapy and offer new therapeutic insights.
BRITISH JOURNAL OF CANCER
(2021)
Article
Cell Biology
Brian M. Larsen, Madhavi Kannan, Lee F. Langer, Benjamin D. Leibowitz, Aicha Bentaieb, Andrea Cancino, Igor Dolgalev, Bridgette E. Drummond, Jonathan R. Dry, Chi-Sing Ho, Gaurav Khullar, Benjamin A. Krantz, Brandon Mapes, Kelly E. McKinnon, Jessica Metti, Jason F. Perera, Tim A. Rand, Veronica Sanchez-Freire, Jenna M. Shaxted, Michelle M. Stein, Michael A. Streit, Yi-Hung Carol Tan, Yilin Zhang, Ende Zhao, Jagadish Venkataraman, Martin C. Stumpe, Jeffrey A. Borgia, Ashiq Masood, Daniel V. T. Catenacci, Jeremy Mathews, Demirkan B. Gursel, Jian-Jun Wei, Theodore H. Welling, Diane M. Simeone, Kevin P. White, Aly A. Khan, Catherine Igartua, Ameen A. Salahudeen
Summary: A robust pan-cancer tumor organoid platform with chemically defined media has been established and neural-network-based high-throughput method has been demonstrated to predict patient-specific heterogeneity in drug responses. These resources are expected to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs.
Letter
Oncology
Sheng Pan, Randall E. Brand, Lisa A. Lai, David W. Dawson, Timothy R. Donahue, Stephen Kim, Natalia I. Khalaf, Mohamed O. Othman, William E. Fisher, Mary P. Bronner, Diane M. Simeone, Teresa A. Brentnall, Ru Chen
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Tamas A. Gonda, James Farrell, Michael Wallace, Lauren Khanna, Eileen Janec, Richard Kwon, Michael Saunders, Uzma D. Siddiqui, Randall Brand, Diane M. Simeone
Summary: The adoption of a standardized EUS reporting template will improve consistency in clinical decision-making for individuals at risk of pancreatic cancer and provide complete and accurate reporting of pancreatic abnormalities. Standardization will also facilitate research and clinical trial design, allowing for comparison of results across different centers.
GASTROINTESTINAL ENDOSCOPY
(2022)
Article
Oncology
Jiaqi Shi, Zhujun Yi, Lin Jin, Lili Zhao, Alexander Raskind, Larisa Yeomans, Zeribe C. Nwosu, Diane M. Simeone, Costas A. Lyssiotis, Kathleen A. Stringer, Richard S. Kwon
Summary: (Iso)-butyrylcarnitine has the potential to accurately distinguish malignant from benign pancreatic cysts, with a diagnostic accuracy of 89%. Additionally, 5-oxoproline can differentiate mucinous from non-mucinous cysts with a diagnostic accuracy of 90%, better than glucose.
Review
Gastroenterology & Hepatology
Laura D. Wood, Marcia Irene Canto, Elizabeth M. Jaffee, Diane M. Simeone
Summary: This review discusses the pathogenesis, early detection methods, and treatment considerations of pancreatic ductal adenocarcinoma (PDAC). Recent advances in understanding PDAC have led to significant improvements in detection and treatment, but coordinated efforts are needed to maximize clinical impact for patients and overall survival.
Review
Radiology, Nuclear Medicine & Medical Imaging
Chenchan Huang, Diane M. Simeone, Lyndon Luk, Elizabeth M. Hecht, Gaurav Khatri, Avinash Kambadakone, Hersh Chandarana, Justin M. Ream, Jessica N. Everett, Alexander Guimaraes, Joy Liau, Anil K. Dasyam, Carla Harmath, Alec J. Megibow
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor survival rates. High-risk individuals are recommended to have regular screening with MRI and/or endoscopic ultrasound. The Pancreatic Cancer Early Detection (PRECEDE) Consortium aims to increase survival of PDAC by facilitating earlier diagnosis through standardized MRI screening and reporting.
AMERICAN JOURNAL OF ROENTGENOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Minh Huynh, G. Aaron Hobbs, Antje Schaefer, Mariaelena Pierobon, Leiah M. Carey, J. Nathaniel Diehl, Jonathan M. DeLiberty, Ryan D. Thurman, Adelaide R. Cooke, Craig M. Goodwin, Joshua H. Cook, Lin Lin, Andrew M. Waters, Naim U. Rashid, Emanuel F. Petricoin, Sharon L. Campbell, Kevin M. Haigis, Diane M. Simeone, Costas A. Lyssiotis, Adrienne D. Cox, Channing J. Der
Summary: Missense mutations at the three hotspots in RAS-Gly(12), Gly(13), and Gln(61) show differential distribution among the three RAS isoforms. KRAS(Q61) mutants exhibit various changes in morphology, growth transformation, effector signaling, and metabolism. Differences in biochemical, structural, and biological properties may explain the frequency variations. Targeting KRAS(Q61) mutant-specific signaling and cellular output may be a potential therapeutic strategy.
Article
Oncology
Jessica N. Everett, Shenin A. Dettwyler, Xiaohong Jing, Cody Stender, Madeleine Schmitter, Ariele Baptiste, Jennifer Chun, Emily A. Kawaler, Lauren G. Khanna, Seth A. Gross, Tamas A. Gonda, Nina Beri, Paul E. Oberstein, Diane M. Simeone
Summary: Integrating genetics into a multidisciplinary setting improves compliance with genetic testing for pancreatic ductal adenocarcinoma (PDAC) patients, reduces logistical barriers, and clarifies cancer risks for relatives.
Article
Oncology
Jiheng Xu, Rui Yang, Jingxia Li, Lidong Wang, Mitchell Cohen, Diane M. Simeone, Max Costa, Xue-Ru Wu
Summary: The stem-cell-like behavior of cancer cells in bladder cancer plays a crucial role and its molecular basis remains incompletely defined. This study demonstrates that SNHG1 induces the formation of stem-cell-like spheres and invasion of bladder cancer cells by upregulating Rho GTPase, Rac1. SNHG1 binds to DNMT3A and represses the transcription of miR-129-2-5p, resulting in increased Rac1 protein levels. High expression of Rac1 is associated with poor prognosis in bladder cancer patients.
Article
Gastroenterology & Hepatology
Sharon Pan, Lisa A. Lai, Diane M. M. Simeone, David W. W. Dawson, Yuanqing Yan, Tatjana Crnogorac-Jurcevic, Ru Chen, Teresa A. Brentnall
Summary: Proteomic and functional analysis of extracellular vesicles (EVs) released from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) identified over 1400 nonredundant proteins involved in vesicle-mediated transport and exocytosis. Protein networks relevant to pancreatic tumorigenesis, such as epithelial-mesenchymal transition, complement, and coagulation components, were significantly enriched in EVs from cancer cells or CAFs, suggesting a potential role of EVs in mediating signals related to tumorigenesis and microenvironment interactions.
