Article
Cell Biology
Yuxiong Lu, Qing Yang, Yubin Su, Yin Ji, Guobang Li, Xianzhi Yang, Liyan Xu, Zhaoliang Lu, Jiajun Dong, Yi Wu, Jin-Xin Bei, Chaoyun Pan, Xiaoqiong Gu, Bo Li
Summary: MYCN amplification in pediatric neuroblastoma cells increases sensitivity to GPX4-targeting ferroptosis inducers by upregulating TFRC expression, leading to enhanced iron metabolism and lipid peroxidation, suggesting potential therapeutic strategies for treating MYCN-amplified NB.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Marialena Pouliou, Marianna A. Koutsi, Lydia Champezou, Angeliki-Ioanna Giannopoulou, Giannis Vatsellas, Christina Piperi, Marios Agelopoulos
Summary: This study assesses the upregulation of metabolism-related transcription factors (TFs) in neuroblastoma cells due to the amplification of MYCN. The results reveal the regulatory mechanism of MYCN in the metabolic processes of neuroblastoma.
Article
Multidisciplinary Sciences
Trang T. T. Nguyen, Enyuan Shang, Chang Shu, Sungsoo Kim, Angeliki Mela, Nelson Humala, Aayushi Mahajan, Hee Won Yang, Hasan Orhan Akman, Catarina M. Quinzii, Guoan Zhang, Mike-Andrew Westhoff, Georg Karpel-Massler, Jeffrey N. Bruce, Peter Canoll, Markus D. Siegelin
Summary: The inhibition of AURKA can lead to metabolic reprogramming in glioblastoma cells, enhancing mitochondrial activity, and inhibiting oxidative metabolism can sensitize the cells. Combining AURKA inhibitors with FAO inhibitors extends overall survival in GBM models.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Keiichiro Matoba, Yusuke Takeda, Yosuke Nagai, Kensuke Sekiguchi, Rikako Ukichi, Hiroshi Takahashi, Daisuke Aizawa, Masahiro Ikegami, Toshiaki Tachibana, Daiji Kawanami, Yasushi Kanazawa, Tamotsu Yokota, Kazunori Utsunomiya, Rimei Nishimura
Summary: ROCK2 is activated in diabetic models and patients, but its deletion in podocytes provides protection against kidney injury by rescuing PPAR alpha signaling and fatty acid metabolism. Loss of podocytes is a common feature in diabetic renal injury, and ROCK2 plays a critical role in this process. The findings suggest that ROCK2 could be a potential target for the treatment of diabetic podocytopathy.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Ling Tao, Mahmoud A. Mohammad, Giorgio Milazzo, Myrthala Moreno-Smith, Tajhal D. Patel, Barry Zorman, Andrew Badachhape, Blanca E. Hernandez, Amber B. Wolf, Zihua Zeng, Jennifer H. Foster, Sara Aloisi, Pavel Sumazin, Youli Zu, John Hicks, Ketan B. Ghaghada, Nagireddy Putluri, Giovanni Perini, Cristian Coarfa, Eveline Barbieri
Summary: This study reveals that MYCN amplification in neuroblastoma promotes fatty acid uptake and synthesis, and inhibition of a fatty acid transporter can have anti-tumor effects. These findings provide a promising approach for improving current treatment regimens.
NATURE COMMUNICATIONS
(2022)
Review
Medicine, Research & Experimental
Tobias Achu Muluh, Xing-sheng Shu, Ying Ying
Summary: Cancer metabolism is the unique utilization of nutrients and energy by cancer cells to support their growth and proliferation. This metabolic profile is characterized by an increased reliance on glucose and glutamine as energy sources and changes in key metabolic intermediates. The study of cancer metabolism aims to understand these metabolic changes and identify potential therapeutic targets for cancer treatment.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Oncology
Marike W. van Gisbergen, Emma Zwilling, Ludwig J. Dubois
Summary: Malignant cells tend to rewire their metabolic pathways to meet the anabolic demands of proliferation, and differences in metabolic patterns between normal tissue and malignant cells can be utilized to improve the therapeutic ratio. Modulation of cellular metabolism is an emerging field proposing various strategies to optimize treatment outcomes for primary tumors and metastatic lesions.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Aleksandar Krstic, Anja Konietzny, Melinda Halasz, Peter Cain, Udo Oppermann, Walter Kolch, David J. Duffy
Summary: Neuroblastoma, although rare, is responsible for the highest proportion of childhood cancer deaths, with a lack of recurrent somatic mutations suggesting a role for epigenetic alterations. MYCN has been associated with epigenetic machinery, but the mechanisms of these interactions in neuroblastoma are poorly understood. Targeting epigenetic proteins in neuroblastoma cells, especially high-risk MYCN-amplified tumors, shows promising results in reducing cell viability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Jacopo Lidonnici, Massimo M. Santoro, Roxana E. Oberkersch
Summary: Angiogenesis plays an important role in tumor growth and metastasis, and understanding the metabolic characteristics and interactions of tumor endothelial cells (TECs) with tumor cells is crucial. The metabolic differences between normal and tumor vasculature provide a basis for developing targeted therapies with higher specificity and fewer side effects, improving patient outcomes.
Article
Multidisciplinary Sciences
William W. Feng, Scott Bang, Eric M. Takacs, Cora Day, Katherine J. Crawford, Ruba Al-Sheyab, Dara B. Almufarrej, Wendy Wells, Serguei Ilchenko, Takhar Kasumov, Ning Kon, Colleen M. Novak, Wei Gu, Manabu Kurokawa
Summary: This study reveals the crucial role of ubiquitin E3 ligase Huwe1 in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The liver-specific deletion of Huwe1 in mice leads to extensive lipid metabolic reprogramming, resulting in reduced hepatic steatosis and improved glucose tolerance. These findings highlight the critical involvement of Huwe1 in age- and diet-induced NAFLD.
Article
Multidisciplinary Sciences
Wentao Chen, Kurt Yun Mou, Paige Solomon, Rahul Aggarwal, Kevin K. Leung, James A. Wells
Summary: The study demonstrates that MYC overexpression leads to significant remodeling of the cell surface proteome, causing dramatic changes in surface proteins in different cell types, including both up-regulation and down-regulation. These changes impact the sensitivity of cells to toxic nucleoside analogs and increase the expression of proteins driving cell turnover and immune cell attacking signals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Mao-Jie Wang, Huan-Jie Huang, Yong-Yue Xu, Harmjan Vos, Can Gulersonmez, Edwin Stigter, Johan Gerritsen, Marc Pages Gallego, Robert van Es, Li Li, Hao Deng, Lin Han, Run-Yue Huang, Chuan-Jian Lu, Boudewijn M. T. Burgering
Summary: In addition to genetic alterations, the cellular environment plays a crucial role in disease onset and progression. The expression of hsa-microRNA-31-5p (miR-31) in keratinocytes of psoriatic skin is induced by limited glucose availability, leading to increased survival under glucose-deficient conditions and altered metabolism of glutamine. MiR-31 secretion also influences immune response and can induce Th17 cell differentiation, contributing to the development of psoriasis. Inhibitors targeting miR-31-induced metabolic rewiring and immune cell crosstalk show promise in alleviating psoriasis pathology in animal models.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta Yanamandra, Adilene Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O'Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal, Kathleen M. Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J. Ajami, Matthew Wong, Cullen Taniguchi, Joseph F. Petrosino, K. Jagannadha Sastry, Pablo C. Okhuysen, Sara A. Martinez, Lin Tan, Iqbal Mahmud, Philip L. Lorenzi, Jennifer A. Wargo, Ann H. Klopp
Summary: The tumor microbiota, specifically lactate-producing lactic acid bacteria, can affect tumor metabolism and lactate signaling pathways, leading to therapeutic resistance in various cancers. These findings suggest that lactate-producing lactic acid bacteria could be potential therapeutic targets across different types of cancer.
Article
Medicine, Research & Experimental
Chakravarthy Garlapati, Shriya Joshi, Ravi Chakra Turaga, Manjari Mishra, Michelle D. Reid, Shobhna Kapoor, Liana Artinian, Vincent Rehder, Ritu Aneja
Summary: Etn alters GLUT1 trafficking leading to metabolic stress in PCa, upregulates phosphatidylethanolamine (PE) to modulate membrane fluidity and affect mitochondrial structure and function, induces autophagy in PCa cells, thereby promoting apoptosis.
Article
Gastroenterology & Hepatology
Tuo Hu, Surendra K. Shukla, Enza Vernucci, Chunbo He, Dezhen Wang, Ryan J. King, Kanupriya Jha, Kasturi Siddhanta, Nicholas J. Mullen, Kuldeep S. Attri, Divya Murthy, Nina Chaika, Ravi Thakur, Scott E. Mulder, Camila G. Pacheco, Xiao Fu, Robin R. High, Fang Yu, Audrey Lazenby, Clemens Steegborn, Ping Lan, Kamiya Mehla, Dante Rotili, Sarika Chaudhary, Sergio Valente, Marco Tafani, Antonello Mai, Johan Auwerx, Eric Verdin, David Tuveson, Pankaj K. Singh
Summary: SIRT5 functions as a key tumor suppressor in PDAC, inhibiting tumor cell proliferation and correlating with a favorable prognosis. Loss of SIRT5 promotes PDAC development and malignant transformation.
Article
Immunology
Ulrich Baumann, Johannes H. Schulte, Jonathan P. Gross, Rita Beier, Marius Ludwig, Volker Wahn, Jorg Hofmann, Britta Maecker-Kolhoff, Martin Sauer, Petra Kaiser-Labusch, Negin Karimian, Ulrike Blume-Peytavi, Franziska Ghoreschi, Hagen Ott, Ludmila Perelygina, Christian Klemann, Oliver Blankenstein, Horst von Bernuth, Renate Krueger
Summary: We report two patients with DNA repair disorders who developed destructive skin granulomas after receiving live-attenuated rubella vaccinations. Both patients exhibited reduced naive T cells. Hematopoietic stem cell transplantation resulted in rapid resolution of skin lesions. However, one patient with severe complications died 6 months after HSCT. Newborn screening may be beneficial in preventing patients with moderate T-cell deficiencies from receiving rubella vaccine that may lead to granulomas.
FRONTIERS IN IMMUNOLOGY
(2022)
Letter
Hematology
Michael Launspach, Dennis Temel, Emily Ohlendorf, Felix Zirngibl, Bianca Materne, Lena Oevermann, Hedwig E. Deubzer, Anton G. Henssen, Annette Kunkele, Patrick Hundsdorfer, Horst von Bernuth, Axel Pruss, Angelika Eggert, Arend von Stackelberg, Peter Lang, Johannes H. Schulte
Article
Immunology
Sara Marie Ivasko, Kathleen Anders, Laura Grunewald, Michael Launspach, Anika Klaus, Silke Schwiebert, Peter Ruf, Horst Lindhofer, Holger N. N. Lode, Lena Andersch, Johannes H. H. Schulte, Angelika Eggert, Patrick Hundsdoerfer, Annette Kuenkele, Felix Zirngibl
Summary: Despite advances in treatment, relapse is still a concern for a significant number of high-risk neuroblastoma patients. Bispecific trifunctional antibodies (trAbs) have shown promising potential as a new immunotherapy for neuroblastoma. The SUREK trAb has been demonstrated to effectively kill neuroblastoma cells and enhance adaptive immune responses through binding to antigen-presenting cells. Combining trAb therapy with anti-PD-1 checkpoint blockade may further improve treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pediatrics
Marius Ludwig, Alireza Basti, Muege Yalcin, Johannes H. Schulte, Angela Relogio
Summary: This study aims to characterize the circadian clock in pediatric patients with acute leukemia, for the first time. By collecting saliva, blood, and bone marrow samples, the researchers will analyze the expression of core-clock genes. The findings of this study may contribute to adjusting chemotherapy timing and reducing systemic toxicities.
Article
Oncology
Carolina Rosswog, Jana Fassunke, Angela Ernst, Birgid Schoemig-Markiefka, Sabine Merkelbach-Bruse, Christoph Bartenhagen, Maria Cartolano, Sandra Ackermann, Jessica Theissen, Mirjam Blattner-Johnson, Barbara Jones, Kathrin Schramm, Janine Altmueller, Peter Nuernberg, Monika Ortmann, Frank Berthold, Martin Peifer, Reinhard Buettner, Frank Westermann, Johannes H. Schulte, Thorsten Simon, Barbara Hero, Matthias Fischer
Summary: Genomic alterations of the ALK gene occur recurrently in neuroblastoma, with ALK mutations occurring in 10.5% of cases at diagnosis and increasing by 70% at relapse. However, the frequency of ALK amplifications does not change over the course of the disease. Regular monitoring of the genomic ALK status and evaluation of ALK-targeted treatment in intermediate-risk patients is recommended.
BRITISH JOURNAL OF CANCER
(2023)
Article
Hematology
Amadeus T. Heinz, Friso G. J. Calkoen, Alexander Derbich, Lea Miltner, Christian Seitz, Michaela Doering, Christiane Braun, Daniel Atar, Michael Schumm, Florian Heubach, Anne- Marie Arendt, Ansgar Schulz, Friedhelm R. Schuster, Roland Meisel, Brigitte Strahm, Juergen Finke, Beatrice Heineking, Susanne Stetter, Gerda Silling, Daniel Stachel, Bernd Gruhn, Klaus-Michael Debatin, Juergen Foell, Johannes H. Schulte, Wilhelm Woessmann, Christine Mauz-Koerholz, Johanna Tischer, Tobias Feuchtinger, Rupert Handgretinger, Peter Lang
Summary: Therapy-resistant viral reactivations after hematopoietic stem cell transplantation can be effectively reduced by adoptive cellular therapy with virus-specific T cells. In this study, the in-house production of virus-specific T cells in a closed system was successful and showed favorable safety profile and efficacy in 26 patients.
Article
Oncology
Tim Flaadt, Ruth L. Ladenstein, Martin Ebinger, Holger N. Lode, Helga Bjoerk Arnardottir, Ulrike Poetschger, Wolfgang Schwinger, Roland Meisel, Friedhelm R. Schuster, Michaela Doering, Peter F. Ambros, Manon Queudeville, Joerg Fuchs, Steven W. Warmann, Juergen Schaefer, Christian Seitz, Patrick Schlegel, Ines B. Brecht, Ursula Holzer, Tobias Feuchtinger, Thorsten Simon, Johannes H. Schulte, Angelika Eggert, Heiko-Manuel Teltschik, Toni Illhardt, Rupert Handgretinger, Peter Lang
Summary: This study investigates the use of haploidentical stem cell transplantation and the anti-GD2 antibody dinutuximab beta (DB) in treating patients with relapsed high-risk neuroblastoma (rHR-NB). The results show that DB therapy is feasible and improves the chances of cure in rHR-NB patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maximilian Kuner, Jan Lisec, Tatjana Mauch, Joerg Konetzki, Hajo Haase, Matthias Koch
Summary: Ergot alkaloids are mycotoxins found in grass-derived products, and they have been recently regulated in the EU. A new sum parameter method (SPM) targeting all ergot alkaloids simultaneously was developed using lysergic acid hydrazide. The SPM showed comparable results to the established HPLC-MS/MS-based method (ESM) in evaluating food safety, while another method (LFGB) showed deviating results. The SPM is a promising alternative for screening ergot alkaloids in food.
Article
Multidisciplinary Sciences
Bieke Decaesteker, Amber Louwagie, Siebe Loontiens, Fanny De Vloed, Sarah-Lee Bekaert, Juliette Roels, Suzanne Vanhauwaert, Sara De Brouwer, Ellen Sanders, Alla Berezovskaya, Geertrui Denecker, Eva D'haene, Stephane Van Haver, Wouter Van Loocke, Jo Van Dorpe, David Creytens, Nadine Van Roy, Tim Pieters, Christophe Van Neste, Matthias Fischer, Pieter Van Vlierberghe, Stephen S. Roberts, Johannes Schulte, Sara Ek, Rogier Versteeg, Jan Koster, Johan van Nes, Mark Zimmerman, Katleen De Preter, Frank Speleman
Summary: SOX11 is identified as a potential epigenetic master regulator upstream of the core regulatory circuitry in adrenergic high-risk neuroblastoma.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Julia Scheiermann, Annette Kuenkele, Arend von Stackelberg, Angelika Eggert, Peter Lang, Felix Zirngibl, Luise Martin, Johannes Hubertus Schulte, Horst von Bernuth
Summary: Chronic granulomatous disease is a congenital immunodeficiency disorder caused by a disruption in the function of the NADPH oxidase complex. It leads to impaired respiratory burst and inadequate killing of bacteria and fungi. Allogeneic HSCT is the only available curative therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Esther M. M. Smeets, Daphne N. Dorst, Gerben M. Franssen, Merijn S. van Essen, Cathelijne Frielink, Martijn W. J. Stommel, Marija Trajkovic-Arsic, Phyllis F. Cheung, Jens T. Siveke, Ian Wilson, Alessandro Mascioni, Erik H. J. G. Aarntzen, Sanne A. M. van Lith
Summary: Fibroblast activation protein (FAP)-targeted photodynamic therapy shows promise in diagnosing and treating various tumors. By conjugating a FAP-binding minibody with the chelator DTPA and the photosensitizer IRDye700DX, FAP-expressing cells can be selectively recognized and killed. In vivo experiments in mice confirm the tumor-targeting ability of DTPA-700DX-MB and demonstrate its efficacy in inducing apoptosis through light exposure, suggesting the potential of FAP-targeted photodynamic therapy.
Article
Oncology
Jessica C. Hassel, Carola Berking, Andrea Forschner, Christoffer Gebhardt, Lucie Heinzerling, Friedegund Meier, Sebastian Ochsenreither, Jens Siveke, Axel Hauschild, Dirk Schadendorf
Summary: Tebentafusp is the first approved treatment option for HLA-A*02:01 metastatic uveal melanoma and has a new adverse event profile. Recommendations for its treatment, including AE management, were discussed by a national expert group. Patients in good clinical condition and with a low tumor burden are good candidates for Tebentafusp treatment.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Oncology
Dirk Tomsitz, Theresa Ruf, Markus Heppt, Ramon Staeger, Egle Ramelyte, Reinhard Dummer, Marlene Garzarolli, Friedegund Meier, Eileen Meier, Heike Richly, Tanja Gromke, Jens T. Siveke, Cindy Franklin, Kai-Christian Klespe, Cornelia Mauch, Teresa Kilian, Marlene Seegraeber, Bastian Schilling, Lars E. French, Carola Berking, Lucie Heinzerling
Summary: A retrospective, multicenter study was conducted to analyze the outcomes and safety of tebentafusp therapy in 78 patients with metastatic uveal melanoma (mUM). The study showed that patients treated with tebentafusp had a median progression-free survival (PFS) of 3 months and a median overall survival (OS) of 22 months. There was a higher rate of patients with elevated LDH in this cohort compared to a published Phase 3 study. Patients treated with tebentafusp following immune checkpoint inhibitor (ICI) therapy had a trend for a longer OS.
Article
Engineering, Environmental
Christian Vogel, Philipp Roesch, Philipp Wittwer, Christian Piechotta, Jan Lisec, Thomas Sommerfeld, Stephanie Kluge, Hannes Herzel, Thomas Huthwelker, Camelia Borca, Franz-Georg Simon
Summary: Solid wastewater-based fertilizers were screened for PFAS using the EOF sum parameter method. The results showed a wide range of EOF values in these fertilizers, and only a small part of the values could be explained by the usual screened PFAS. The study also found the presence of other fluorinated compounds in these fertilizers, which can degrade to short-chain PFAS in wastewater treatment plants, contributing to the pollution of organic fluorine in the environment.
ENVIRONMENTAL SCIENCE-ADVANCES
(2023)
Article
Chemistry, Analytical
Dariya Tukhmetova, Jan Lisec, Jochen Vogl, Bjoern Meermann
Summary: This paper introduces a data processing application called IsoCor, which can automatically calculate isotope ratios from transient signals and simplify the selection of the most suitable method. The feasibility and reliability of the application are proven through the analysis of isotopes of three elements.
JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY
(2022)