Article
Oncology
Jingkai Sun, Wenfeng Lin, Chaoming Li, Hideo Ueki, Ruizhi Xue, Takuya Sadahira, Hao Hu, Koichiro Wada, Na Li, Chunxiao Liu, Motoo Araki, Abai Xu, Peng Huang
Summary: Posaconazole inhibits tumor progression in embryonal rhabdomyosarcoma by inducing G0/G1 arrest and autophagy through downregulating Hedgehog signaling pathway, showing promising potential as an anti-tumor agent targeting ERMS.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yang Gu, Yanying Wang, Luyun He, Jiahang Zhang, Xiaoxiao Zhu, Nian Liu, Jianyi Wang, Tiankun Lu, Lei He, Yong Tian, Zusen Fan
Summary: This study identified circIPO11 as highly expressed in HCC tumor tissues and liver CSCs, playing a critical role in self-renewal maintenance of liver CSCs and HCC development. Mechanistically, circIPO11 activates the Hedgehog signaling pathway, promoting tumor cell propagation. Targeting circIPO11 and the Hedgehog pathway may provide new potential for HCC treatment.
Article
Endocrinology & Metabolism
Giulia Pontarollo, Bettina Kollar, Amrit Mann, My Phung Khuu, Klytaimnistra Kiouptsi, Franziska Bayer, Ines Brandao, Valeriya V. V. Zinina, Jennifer Hahlbrock, Frano Malinarich, Maximilian Mimmler, Sudhanshu Bhushan, Federico Marini, Wolfram Ruf, Meriem Belheouane, John F. F. Baines, Kristina Endres, Scott M. M. Reba, Verena K. K. Raker, Carsten Deppermann, Christoph Welsch, Markus Bosmann, Natalia Soshnikova, Benoit Chassaing, Mattias Bergentall, Felix Sommer, Fredrik Backhed, Christoph Reinhardt
Summary: The gut microbiota weakens the intestinal barrier by suppressing epithelial neuropilin-1 (NRP1) and Hedgehog (Hh) signaling. Activation of Toll-like receptor-2 (TLR2) by commensal microbiota dampens Hh pathway signaling, resulting in decreased NRP1 protein levels. Conversely, elevated NRP1 levels in germ-free mice are associated with a strengthened gut barrier.
Article
Cell Biology
Simona Camero, Giulia Vitali, Paola Pontecorvi, Simona Ceccarelli, Eleni Anastasiadou, Francesca Cicchetti, Elisabetta Flex, Silvia Pomella, Matteo Cassandri, Rossella Rota, Francesco Marampon, Cinzia Marchese, Amalia Schiavetti, Francesca Megiorni
Summary: The overexpression of DNMT3A and DNMT3B may contribute to radiotherapy failure in RMS, and their inhibition could be a promising radiosensitizing strategy for the treatment of patients with metastatic or recurrent RMS tumors.
Article
Cell Biology
Raquel Maeso-Diaz, George D. Dalton, Sehhoon Oh, Kuo Du, Linda Tang, Tianyi Chen, Rajesh K. Dutta, Jessica H. Hartman, Joel N. Meyer, Anna Mae Diehl
Summary: Aging impairs liver regeneration by reducing the resiliency of hepatocytes. This study reveals that Hedgehog signaling becomes dysregulated in old hepatocytes, leading to decreased resiliency and enhanced vulnerability to damage. The dysregulated Hedgehog signaling accelerates aging, impairing liver regeneration and promoting inflammation and metabolic dysfunction.
Review
Pharmacology & Pharmacy
Delphine Quatannens, Yannick Verhoeven, Peter Van Dam, Filip Lardon, Hans Prenen, Geert Roeyen, Marc Peeters, Evelien L. J. Smits, Jonas Van Audenaerde
Summary: PDAC is a leading cause of cancer related death, with urgent need for effective therapies. Aberrant activation of the Hh signaling pathway in PDAC prompts it as a possible target for treatment, despite ongoing debate on its clinical benefits.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
Gianni Bisogno, Joerg Fuchs, Roshni Dasgupta, Andrea Ferrari, Josephine H. Haduong, Timothy Rogers, David O. Walterhouse, Beatrice Coppadoro, Wei Xue, Christian Vokuhl, Douglas S. Hawkins, Guido Seitz, Johannes H. M. Merks, Monika Sparber-Sauer, Rajkumar Venkatramani
Summary: This study aimed to investigate the prognosis of completely resected embryonal RMS at sites other than paratesticular, uterine, or vaginal primary sites. The results showed that patients with nonalveolar RMS completely resected at diagnosis have excellent survival rates when arising from nonparatesticular, uterine, and vaginal sites, and can be successfully treated with low-intensity chemotherapy.
Article
Biochemistry & Molecular Biology
Yue Wang, Lixin Zheng, Wenjing Shang, Zongcheng Yang, Tongyu Li, Fen Liu, Wei Shao, Lin Lv, Li Chai, Lingxin Qu, Qing Xu, Jie Du, Xiuming Liang, Jiping Zeng, Jihui Jia
Summary: The activation of the Wnt/β-catenin signaling pathway attenuates lipid ROS production in gastric cancer cells and inhibits ferroptosis. The β-catenin/TCF4 transcription complex induces the expression of GPX4, suppressing ferroptotic cell death. TCF4 deficiency promotes cisplatin-induced ferroptosis.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemistry & Molecular Biology
Shekoufeh Almasi, Sahar SarmastiEmami, Stephen Baird, Zhibin Ning, Daniel Figeys, Jocelyn Cote, Kyle N. Cowan, Bernard J. Jasmin
Summary: This study found the differential role of STAU1 in mitochondrial metabolism in cancerous versus non-malignant skeletal muscle cells. Depletion of STAU1 reduced oxidative phosphorylation and inhibited cell proliferation in ERMS cells. Additionally, STAU1 depletion negatively impacted the HIF2 alpha pathway, which further modulated mitochondrial metabolism. Therefore, targeting STAU1 could be a novel approach to inhibit mitochondrial metabolism in ERMS.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sheng Li, Leilei Zhang, Guoan Zhang, Guoqiang Shangguan, Xitan Hou, Wanglin Duan, Yan Xi, Nan Xu, Bowen Zhang, Junli Dong, Yequan Wang, Wen Cui, Su Chen
Summary: Autophagy is a crucial biological process for maintaining cell homeostasis, with levels usually lower under normal conditions but still with important regulatory factors present. A study revealed that the autophagy-related protein ATG5 regulates c-Myc protein degradation through the ubiquitin-proteasome pathway in normal conditions, limiting cell growth and playing a key role in embryonic stem cell differentiation.
Article
Medicine, Research & Experimental
Xu Han, Yang Mei, Rama K. Mishra, Honghao Bi, Atul D. Jain, Gary E. Schiltz, Baobing Zhao, Madina Sukhanova, Pan Wang, Arabela A. Grigorescu, Patricia C. Weber, John J. Piwinski, Miguel A. Prado, Joao A. Paulo, Len Stephens, Karen E. Anderson, Charles S. Abrams, Jing Yang, Peng Ji
Summary: Myeloproliferative neoplasms (MPNs) are characterized by the activated JAK2/STAT pathway. Pleckstrin-2 (Plek2) is a downstream target of the JAK2/STAT5 pathway and is overexpressed in patients with MPNs. Plek2-specific small molecule inhibitors show potent inhibitory effects on cell proliferation.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Naoki Nohira, Sayaka Shinji, Shunichi Nakamura, Yuma Nihashi, Takeshi Shimosato, Tomohide Takaya
Summary: In this study, it was found that embryonal rhabdomyosarcoma (ERMS) cells express nucleolin and their growth can be inhibited by anti-nucleolin aptamers. Further investigation revealed that iSN04 and AS1411, the two anti-nucleolin aptamers, not only suppress the proliferation of ERMS cells, but also promote their differentiation and myogenesis. Additionally, these anti-nucleolin aptamers disrupt the formation of tumor spheres in three-dimensional culture. Therefore, anti-nucleolin aptamers have the potential to be used as nucleic acid drugs for chemotherapy against ERMS.
Article
Medicine, Research & Experimental
Jingchun Wang, Huakan Zhao, Lu Zheng, Yu Zhou, Lei Wu, Yanquan Xu, Xiao Zhang, Guifang Yan, Halei Sheng, Rong Xin, Lu Jiang, Juan Lei, Jiangang Zhang, Yu Chen, Jin Peng, Qian Chen, Shuai Yang, Kun Yu, Dingshan Li, Qichao Xie, Yongsheng Li
Summary: The study reveals that the FGF19/FGFR4 axis promotes the self-renewal of LCSCs by activating the SOCE/NFATc2 pathway, with NFATc2 transcriptionally activating FGF19 expression, providing insights into a potential strategy for improving the therapeutic efficacy of HCC.
Article
Multidisciplinary Sciences
S. S. Hoepner, Ana Raykova, R. Radpour, M. A. Amrein, D. Koller, G. M. Baerlocher, C. Riether, A. F. Ochsenbein
Summary: The study demonstrates that LIGHT and its receptor LT beta R promote quiescence and self-renewal of HSCs, while LT beta R deficiency contributes to survival in a mouse leukemia model.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Hsin Yao Chiu, Amos Hong Pheng Loh, Reshma Taneja
Summary: Embryonal rhabdomyosarcoma (ERMS) is characterized by the elevated expression of mitochondrial calcium uniporter (MCU). Knockdown of MCU impairs mitochondrial calcium uptake and reduces mitochondrial reactive oxygen species (mROS) levels, leading to reduced cellular proliferation and motility, and increased differentiation. RNA sequencing reveals the involvement of MCU in TGF beta signaling, which plays significant roles in oncogenesis and myogenic differentiation. Modulation of mROS production impacts TGF beta signaling. Targeting the MCU complex to restore mitochondrial calcium homeostasis could be a potential therapeutic approach in ERMS.
CELL DEATH & DISEASE
(2022)
Article
Obstetrics & Gynecology
Nicole Ochsenbein-Kolble, Simone Brandt, Peter Bode, Franziska Krahenmann, Margaret Husler, Ueli Mohrlen, Luca Mazzone, Martin Meuli, Roland Zimmermann
FETAL DIAGNOSIS AND THERAPY
(2019)
Article
Microbiology
Ales Chrdle, Tomas Trnka, David Musil, Sandro F. Fucentese, Peter Bode, Peter M. Keller, Yvonne Achermann
JOURNAL OF CLINICAL MICROBIOLOGY
(2019)
Article
Oncology
Johannes Ommer, Joanna L. Selfe, Marco Wachtel, Eleanor M. O'Brien, Dominik Laubscher, Michaela Roemmele, Stephanie Kasper, Olivier Delattre, Didier Surdez, Gemma Petts, Anna Kelsey, Janet Shipley, Beat W. Schafer
Article
Cardiac & Cardiovascular Systems
Guoliang Li, Guy H. Fontaine, Shuanliang Fan, Yang Yan, Peter K. Bode, Firat Duru, Robert Frank, Ardan M. Saguner
CARDIOLOGY JOURNAL
(2019)
Article
Biochemistry & Molecular Biology
Eva Brack, Marco Wachtel, Anja Wolf, Andres Kaech, Urs Ziegler, Beat W. Schafer
CELL DEATH AND DIFFERENTIATION
(2020)
Correction
Oncology
H. Pfeifer, G. Cazzaniga, V. H. J. van der Velden, J. M. Cayuela, B. Schafer, O. Spinelli, S. Akiki, S. Avigad, I. Bendit, K. Borg, H. Cave, L. Elia, S. C. Reshmi, G. Gerrard, S. Hayette, M. Hermanson, A. Juh, T. Jurcek, M. C. Chillon, C. Homburg, G. Martinelli, V. Kairisto, T. Lange, T. Lion, M. C. Mueller, F. Pane, L. Rai, C. Damm-Welk, T. Sacha, S. Schnittger, T. Touloumenidou, H. Valerhaugen, P. Vandenberghe, J. Zuna, H. Serve, E. Herrmann, S. Markovic, J. J. M. van Dongen, O. G. Ottmann
Article
Immunology
Amandine Bovay, Sina Nassiri, Helene Maby-El Hajjami, Paula Marcos Mondejar, Rama S. Akondy, Rafi Ahmed, Benton Lawson, Daniel E. Speiser, Silvia A. Fuertes Marraco
Article
Oncology
Guenther H. S. Richter, Tim Hensel, Oxana Schmidt, Vadim Saratov, Kristina von Heyking, Fiona Becker-Dettling, Carolin Prexler, Hsi-Yu Yen, Katja Steiger, Simone Fulda, Uta Dirksen, Wilko Weichert, Shudong Wang, Stefan Burdach, Beat W. Schaefer
Article
Biology
Joana G. Marques, Berkley E. Gryder, Blaz Pavlovic, Yeonjoo Chung, Quy A. Ngo, Fabian Frommelt, Matthias Gstaiger, Young Song, Katharina Benischke, Dominik Laubscher, Marco Wachtel, Javed Khan, Beat W. Schafer
Article
Multidisciplinary Sciences
Berkley E. Gryder, Marco Wachtel, Kenneth Chang, Osama El Demerdash, Nicholas G. Aboreden, Wardah Mohammed, Winston Ewert, Silvia Pomella, Rossella Rota, Jun S. Wei, Young Song, Benjamin Z. Stanton, Beat Schafer, Christopher R. Vakoc, Javed Khan
Article
Genetics & Heredity
Melanie Generali, Sampoorna Satheesha, Peter K. Bode, Debora Wanner, Beat W. Schaefer, Elisa A. Casanova
Summary: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, and fusion-positive RMS (FPRMS) with PAX3/7-FOXO1 expression has a worse prognosis compared to fusion-negative RMS (FNRMS). This study found no stable cancer stem cell subpopulation in FPRMS, unlike FNRMS. The high frequency of tumor propagating stem-like cells in FPRMS may explain their higher propensity for metastasis and relapse.
Article
Medicine, General & Internal
Jurgen Hetzel, Laetitia A. A. Mauti, Jonas Winkler, Sabine Cardoso Almeida, Philip Jermann, Miklos Pless, Lukas Bubendorf, Peter Karl Bode, Maik Haentschel
Summary: Personalized treatment of metastatic non-squamous NSCLC requires comprehensive molecular characterization of the tumor, including detection of driver mutations and PD-L1 expression. Different sampling techniques may be necessary to obtain sufficient tumor material. This case report highlights the importance of biopsy technique for precise tumor characterization. Only EBUS-TBLNC provided complete characterization, demonstrating PD-L1 expression without actionable genetic alterations.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Oncology
Silvia Pomella, Sara G. Danielli, Rita Alaggio, Willemijn B. Breunis, Ebrahem Hamed, Joanna Selfe, Marco Wachtel, Zoe S. Walters, Beat W. Schaefer, Rossella Rota, Janet M. Shipley, Simone Hettmer
Summary: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children and adolescents, characterized by aberrant muscle differentiation. Abnormalities in the regulatory transcription factors (MRFs) involved in skeletal muscle development contribute to tumorigenesis in RMS. Core regulatory circuitries (CRCs) and hierarchically organized subsets of cells play a role in maintaining the disease-driving fusion oncogene and promoting malignancy in RMS. Understanding the genetic and epigenetic framework of abnormal muscle differentiation in RMS provides insights into its mechanisms and potential therapeutic strategies.
Article
Oncology
Nagjie Alijaj, Sandrine Moutel, Zelia L. Gouveia, Maxim Gray, Maurizio Roveri, Dzhangar Dzhumashev, Florian Weber, Gianmarco Meier, Paola Luciani, Jochen K. Rossler, Beat W. Schafer, Franck Perez, Michele Bernasconi