Article
Cell Biology
Fang Cao, Yunpeng Jiang, Lin Chang, Hongzhen Du, De Chang, Chunxiao Pan, Xiaozheng Huang, Donglin Yu, Mi Zhang, Yongna Fan, Xiaocui Bian, Kailong Li
Summary: Pancreatic cancer is characterized by early metastasis and limited response to current therapies. Through a genetic screening platform, YWHAZ has been identified as a key regulator of pancreatic cancer metastasis. Overexpression of YWHAZ promotes cell migration and invasion, and is associated with poor prognosis in pancreatic cancer patients.
CELL DEATH & DISEASE
(2023)
Article
Medicine, Research & Experimental
Yun-Wen Lin, Hsiao-Jung Kao, Wei-Ting Chen, Cheng-Fu Kao, Jer-Yuarn Wu, Yuan-Tsong Chen, Yi-Ching Lee
Summary: This study established a monitoring system for FGFR3 activation and identified a plant extract and two bioactive porphyrins that can suppress FGFR3 signaling. Further research showed that these compounds can reduce excessive FGFR3 activity and improve skeletal abnormalities.
Article
Genetics & Heredity
Lin Zhou, Siqi Zheng, Fernando R. Rosas Bringas, Bjorn Bakker, Judith E. Simon, Petra L. Bakker, Hinke G. Kazemier, Michael Schubert, Maurits Roorda, Marcel A. T. M. van Vugt, Michael Chang, Floris Foijer
Summary: The study revealed that the overexpression of MELK plays a significant role in cancer by affecting tumor growth, chemotherapy resistance, and recurrence. Through high-throughput screening of genes, two potential synthetic lethal interactions with MELK were identified: LAG2 and HDA3. One of these interactions was found to be conserved in mammalian cells, suggesting HDA3 as a novel potential drug target for tumors overexpressing MELK.
G3-GENES GENOMES GENETICS
(2021)
Article
Genetics & Heredity
Lin Zhou, Siqi Zheng, Fernando R. Rosas Bringas, Bjorn Bakker, Judith E. Simon, Petra L. Bakker, Hinke G. Kazemier, Michael Schubert, Maurits Roorda, Marcel A. T. M. van Vugt, Michael Chang, Floris Foijer
Summary: MELK is frequently overexpressed in cancer, and its roles in tumor growth, chemotherapy resistance, and tumor recurrence are still unclear. A high-throughput screen identified LAG2 and HDA3 as genes whose inhibition in combination with MELK overexpression is synthetically lethal in tumor cells, indicating a novel potential drug target for tumors overexpressing MELK.
G3-GENES GENOMES GENETICS
(2021)
Article
Genetics & Heredity
Hans M. Dalton, Raghuvir Viswanatha, Roderick Brathwaite, Jae Sophia Zuno, Alexys R. Berman, Rebekah Rushforth, Stephanie E. Mohr, Norbert Perrimon, Clement Y. Chow
Summary: Scientists have found that inhibiting the mannosyltransferase Dpm1 or its downstream glycosylation pathways can treat DPAGT1-CDG, and they have discovered a relationship between fructose metabolism and ER stress.
Review
Oncology
Chen Wang, Hui Fang, Jiawei Zhang, Ying Gu
Summary: Synthetic lethal screening is a promising method for identifying novel drug targets, particularly for targeting undruggable proteins like c-Myc. Inhibiting important functional nodes related to c-Myc in non-oncogene addicted networks may have catastrophic effects on tumor cells but not on normal cells. This research field has made progress in identifying these functional nodes and holds great potential for potent tumor treatment.
FRONTIERS OF MEDICINE
(2021)
Article
Multidisciplinary Sciences
Akil Hamza, Leanne Amitzi, Lina Ma, Maureen R. M. Driessen, Nigel J. O'Neil, Philip Hieter
Summary: Genetic screens can identify synthetic lethal interactions for potential anticancer therapeutic targets. By using missense mutations to model protein inhibition, this study found different mechanisms underlying synthetic lethal interactions, pointing to the utility of trapping mutations in pursuit of clinically relevant interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Kelly Waldeck, Jessica Van Zuylekom, Carleen Cullinane, Twishi Gulati, Kaylene J. Simpson, Richard W. Tothill, Benjamin Blyth, Rodney J. Hicks
Summary: A genome-wide CRISPR/Cas9 screen identified potential gene targets for sensitivity and resistance to LuTate, offering opportunities for novel combination therapies for NET patients. Regulation of DNA damage repair pathways may enhance the efficacy of LuTate treatment.
Article
Multidisciplinary Sciences
Nafisa Neault, Sean O'Reilly, Aiman Tariq Baig, Julio Plaza-Diaz, Mehrdad Azimi, Faraz Farooq, Stephen D. Baird, Alex MacKenzie
Summary: DM1 is the most common form of adult muscular dystrophy, caused by gene mutations affecting RNA structure and splicing factors. PACT has been identified as a novel modulator of foci integrity, with knockdown leading to increased MBNL1 protein levels, but not sufficient for significant correction of downstream spliceopathies.
Article
Oncology
Jenan Al-Matouq, Latifa Al-Haj, Maher Al-Saif, Khalid S. A. Khabar
Summary: This study investigated the post-transcriptional control of amplified cancer genes and found that ERBB2 overexpression could enhance this effect. Treatment with ERBB1/2 inhibitors reversed the aberrant ARE-mediated process and accelerated ARE-mRNA decay in ERBB2-amplified breast cancer cells. Targeting the ARE-mediated pathway itself may offer alternative therapeutic approaches.
Article
Cell Biology
Mark J. Henderson, Kathleen A. Trychta, Shyh-Ming Yang, Susanne Back, Adam Yasgar, Emily S. Wires, Carina Danchik, Xiaokang Yan, Hideaki Yano, Lei Shi, Kuo-Jen Wu, Amy Q. Wang, Dingyin Tao, Gergely Zahoranszky-Kohalmi, Xin Hu, Xin Xu, David Maloney, Alexey Zakharov, Ganesha Rai, Fumihiko Urano, Mikko Airavaara, Oksana Gavrilova, Ajit Jadhav, Yun Wang, Anton Simeonov, Brandon K. Harvey
Summary: The study identifies several clinically used drugs, including bromocriptine, that can prevent the redistribution of ER proteins under pathological conditions. These drugs exhibit protective effects in cell-based models and in vivo models of stroke and diabetes. Bromocriptine analogs with reduced dopamine receptor activity also show efficacy in stabilizing the ER proteome, suggesting a non-canonical mechanism of action.
Article
Microbiology
Jacob E. Lazarus, Alyson R. Warr, Kathleen A. Westervelt, David C. Hooper, Matthew K. Waldor
Summary: Serratia marcescens has inherent resistance to antibiotics and potential modifiers of antibiotic susceptibility have been discovered in its genome. Further characterization of the unknown gene ydgH revealed its impact on susceptibility to multiple antibiotics in the bacterium.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Mateusz Legut, Zoran Gajic, Maria Guarino, Zharko Daniloski, Jahan A. Rahman, Xinhe Xue, Congyi Lu, Lu Lu, Eleni P. Mimitou, Stephanie Hao, Teresa Davoli, Catherine Diefenbach, Peter Smibert, Neville E. Sanjana
Summary: Engineering autologous T cells has significantly improved cancer treatment. CRISPR-based loss-of-function screens have limitations and safety concerns. In this study, overexpression of specific genes enhanced T cell functions and a new method called OverCITE-seq was developed for analyzing genetically engineered T cells. LTBR, a highly ranked gene, showed increased T cell effector functions and resistance to exhaustion. These findings have potential implications for future T cell therapies.
Article
Biochemistry & Molecular Biology
Punit Saraon, Jamie Snider, Wiebke Schormann, Ankit Rai, Nikolina Radulovich, Maria Sanchez-Osuna, Jasmin Coulombe-Huntington, Caroline Huard, Mohammed Mohammed, Evelyne Lima-Fernandes, Brigitte Theriault, Levon Halabelian, Manuel Chan, Dhananjay Joshi, Luka Drecun, Zhong Yao, Shivanthy Pathmanathan, Victoria Wong, Anna Lyakisheva, Farzaneh Aboualizadeh, Li Niu, Fengling Li, Taira Kiyota, Ratheesh Subramanian, Babu Joseph, Ahmed Aman, Michael Prakesch, Methvin Isaac, Ahmed Mamai, Gennady Poda, Masoud Vedadi, Richard Marcellus, David Uehling, Natasha Leighl, Adrian Sacher, Miroslav Samarzija, Marko Jakopovic, Cheryl Arrowsmith, Mike Tyers, Ming-Sound Tsao, David Andrews, Rima Al-awar, Igor Stagljar
Summary: The small molecule EM166 was identified to inhibit mutant EGFR signalling and growth in NSCLC cells via a novel mechanism. EM166 affects the expression and signalling of certain proteins, alters subcellular localization, and modulates the ER stress response pathway in mutant EGFR lung cancer cells.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Oncology
Bin Lan, Siyuan Zeng, Shuman Zhang, Xiaofan Ren, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Benjamin Frey, Nathalie Britzen-Laurent, Robert Gruetzmann, Nils Cordes, Christian Pilarsky
Summary: Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries. Radiation therapy has not yielded satisfactory results in treating pancreatic cancer, and understanding radioresistance mechanisms and developing new therapeutic targets have become major challenges. In this study, the researchers used CRISPR-Cas9 screening and 3D cell culture to identify DYRK1A as a sensitive target for radiotherapy in pancreatic cancer. Furthermore, they showed that DYRK1A-targeted inhibitors could enhance the efficacy of radiotherapy. These findings support the use of CRISPR-Cas9 screening to identify novel therapeutic targets and develop strategies to improve radiotherapy efficacy in pancreatic cancer.
Article
Oncology
Ali Al-Fatlawi, Negin Malekian, Sebastian Garcia, Andreas Henschel, Ilwook Kim, Andreas Dahl, Beatrix Jahnke, Peter Bailey, Sarah Naomi Bolz, Anna R. Poetsch, Sandra Mahler, Robert Gruetzmann, Christian Pilarsky, Michael Schroeder
Summary: The study identified predictive RNA variants from blood samples of patients with pancreatic diseases, combining them with CA19-9 for deep learning to differentiate pancreatic cancer from chronic pancreatitis with high accuracy. This approach has the potential to greatly improve noninvasive clinical diagnosis and early treatment of pancreatic cancer.
Article
Oncology
Raphaela Schwappacher, Walburga Dieterich, Dejan Reljic, Christian Pilarsky, Debabrata Mukhopadhyay, David K. Chang, Andrew Biankin, Juergen Siebler, Hans J. Herrmann, Markus F. Neurath, Yurdagul Zopf
Summary: Exercise-induced cytokines in serum from advanced-stage pancreatic cancer patients inhibit cancer cell growth and migration, and induce cancer cell death. This study provides new insights into the cancer-protective function of exercise in pancreatic cancer and supports the use of sport therapies for cancer patients.
Article
Oncology
Bin Lan, Siyuan Zeng, Shuman Zhang, Xiaofan Ren, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Benjamin Frey, Nathalie Britzen-Laurent, Robert Gruetzmann, Nils Cordes, Christian Pilarsky
Summary: Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries. Radiation therapy has not yielded satisfactory results in treating pancreatic cancer, and understanding radioresistance mechanisms and developing new therapeutic targets have become major challenges. In this study, the researchers used CRISPR-Cas9 screening and 3D cell culture to identify DYRK1A as a sensitive target for radiotherapy in pancreatic cancer. Furthermore, they showed that DYRK1A-targeted inhibitors could enhance the efficacy of radiotherapy. These findings support the use of CRISPR-Cas9 screening to identify novel therapeutic targets and develop strategies to improve radiotherapy efficacy in pancreatic cancer.
Article
Oncology
Sebastian Krug, Maryam Khosravian, Julia Weissbach, Katharina George, Marko Damm, Jakob Garbe, Jens Walldorf, Philipp A. Reuken, Tania Amin, Alexander Siebenhuener, Jonas Rosendahl, Thomas M. Gress, Patrick Michl, Joerg Schrader, Anja Rinke
Summary: The COVID-19 pandemic has posed significant challenges for the medical care of neuroendocrine tumor (NET) patients. A comprehensive survey was conducted to investigate healthcare structure and patient-specific concerns during the crisis, with a focus on social and emotional distress. The survey revealed that most NET patients were worried about their tumor treatment during the crisis and considered themselves at risk of severe COVID-19 infection. Increased distress in the social and psycho-emotional domains indicated a need for optimization in the medical care of NET patients.
Article
Oncology
Simone Luecke, Christian Fottner, Harald Lahner, Henning Jann, Dominik Zolnowski, Detlef Quietzsch, Patricia Grabowski, Birgit Cremer, Sebastian Maasberg, Ulrich-Frank Pape, Hans-Helge Mueller, Thomas Matthias Gress, Anja Rinke
Summary: This study analyzed real-world data from the German NET Registry, focusing on therapeutic and prognostic aspects. The study found that the median overall survival for NEN G3 patients was 31 months, and stage, performance status, and Ki67 value were significant prognostic factors in multivariate analysis.
Article
Gastroenterology & Hepatology
Petros Stathopoulos, Malte Zumblick, Sabine Waechter, Leif Schiffmann, Thomas M. Gress, Detlef Bartsch, Guido Seitz, Ulrike W. Denzer
Summary: Through retrospective analysis, we confirmed the effectiveness of endoscopic vacuum therapy (EVT) in the treatment of acute esophageal perforation. Prompt initiation of EVT is crucial for preventing abscess formation and promoting defect closure.
ENDOSCOPY INTERNATIONAL OPEN
(2022)
Article
Endocrinology & Metabolism
Elettra Merola, Aurel Perren, Anja Rinke, Alessandro Zerbi, Mairead G. McNamara, Ruza Arsenic, Nicola Fazio, Wouter de Herder, Juan W. Valle, Thomas M. Gress, Bertram Wiedenmann, Andreas Pascher, Marianne E. Pavel
Summary: The study found that in more than half of the cases with relapse after radical surgery for entero-pancreatic neuroendocrine tumors, a higher proliferative index and potentially more aggressive behavior were observed. Therefore, histological reassessment should be considered at disease recurrence to guide tailored therapeutic strategies.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Gastroenterology & Hepatology
Thomas Seufferlein, Julia Mayerle, Stefan Boeck, Thomas Brunner, Thomas J. Ettrich, Lars Grenacher, Thomas Mathias Gress, Thilo Hackert, Volker Heinemann, Angelika Kestler, Marianne Sinn, Andrea Tannapfel, Ulrich Wedding, Waldemar Uhl
ZEITSCHRIFT FUR GASTROENTEROLOGIE
(2022)
Article
Oncology
Hai Yang, Bin Liu, Dongxue Liu, Zhirong Yang, Shuman Zhang, Pengyan Xu, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Christian Pilarsky
Summary: Pancreatic cancer is a highly lethal cancer with limited treatment options. Chemotherapy, especially with gemcitabine, is the primary choice for patients; however, chemoresistance presents a significant challenge to its effectiveness. In this study, we used genome-wide CRISPR/Cas9 screening to identify DCK and CCNL1 as genes contributing to gemcitabine resistance in pancreatic cancer. Furthermore, we explored the mechanism of CCNL1-related resistance and found that the loss of CCNL1 activates the ERK/AKT/STAT3 pathway, leading to resistance to gemcitabine.
Review
Chemistry, Analytical
Yusong Wu, Yuqing Wang, Yanjun Lu, Xiaomei Luo, Yinghong Huang, Ting Xie, Christian Pilarsky, Yuanye Dang, Jianye Zhang
Summary: This review provides an overview of the conventional methods and microfluidic-based technologies for exosome separation, with a focus on the efficiency of exosome isolation by microfluidic devices. Additionally, advances in integrated microfluidics technologies for exosome separation and analysis are introduced.
Article
Oncology
Hang He, Shuman Zhang, Hai Yang, Pengyan Xu, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Deliang Fu, Christian Pilarsky
Summary: This study identified PCSK6 as a critical gene involved in liver metastasis in pancreatic cancer and investigated its biological functions and molecular mechanisms using CRISPR/Cas9 technology. It was found that inactivation of PCSK6 could efficiently suppress liver metastasis, suggesting its potential as a novel therapeutic target for liver metastasis in pancreatic cancer.
Article
Chemistry, Physical
Jonas Dinter, Ralf. P. P. Friedrich, Hai Yang, Christian Pilarsky, Harald Mangge, Marina Poettler, Christina Janko, Christoph Alexiou, Stefan Lyer
Summary: Pancreatic ductal adenocarcinoma is a difficult-to-treat cancer with poor long-term survival rates. In this study, a 3D cell culture model of human pancreatic ductal adenocarcinoma was used to investigate the potential use of superparamagnetic iron oxide nanoparticles (SPIONs) as a drug delivery system for the chemotherapeutic agent mitoxantrone (MTO). The results showed that MTO-loaded SPIONs induced cell death in tumor spheroids, with increased uptake in spheroids with a SMAD4 mutation. This suggests that MTO-loaded SPIONs could be a promising approach for treating pancreatic ductal adenocarcinomas.
Article
Virology
Christian Bauer, Elisabeth Mack, Veronique Hefter, Alexandra Fischer, Kirsten Volland, Chrysanthi Skevaki, Andreas Neubauer, Thomas Gress, Stephan Becker, Christian Keller
Summary: Clearance of nucleocapsid antigen is delayed in severely ill COVID-19 patients, and detecting the antigen after 8 days postdiagnosis is a characteristic of patients requiring intensive care.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Gastroenterology & Hepatology
Malte Zumblick, Petros Stathopoulos, Thomas Mathias Gress, Ulrike Walburga Denzer
Summary: Serious iatrogenic bowel injuries during screening colonoscopy are rare. This report presents a successful case of endoscopic vacuum therapy (EVT) for a rectal perforation during colonoscopy. EVT should be considered for iatrogenic rectal perforation when signs of systemic inflammation are present and primary mechanical wound closure appears critical due to the depth of the defect and the presumed risk of abscess formation.
CASE REPORTS IN GASTROENTEROLOGY
(2022)
Article
Endocrinology & Metabolism
R. Fijalkowski, D. Reher, A. Rinke, T. M. Gress, J. Schrader, R. P. Baum, D. Kaemmerer, D. Hoersch
NEUROENDOCRINOLOGY
(2022)