Article
Biochemistry & Molecular Biology
Tatyana Grigoreva, Aleksandra Sagaidak, Angelina Romanova, Daria Novikova, Aleksander Garabadzhiu, Viacheslav Tribulovich
Summary: The development of chemoresistance in colorectal cancer cells was replicated in vitro by gradually increasing the drug content in the medium, resulting in reduced sensitivity to drugs of different mechanisms of action in resistant cell lines. The cells were found to utilize a universal efflux defense mechanism, which could be partially neutralized by inhibitors of ABC transport proteins, such as P-glycoprotein, confirming its role in chemoresistance.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Engineering, Biomedical
Carlotta Pucci, Attilio Marino, Oezlem Sen, Daniele De Pasquale, Martina Bartolucci, Nerea Iturrioz-Rodrguez, Nicoletta Di Leo, Giuseppe De Vito, Doriana Debellis, Andrea Petretto, Gianni Ciofani
Summary: This study proposes an anticancer approach based on ultrasound-responsive drug-loaded organic piezoelectric nanoparticles. The nanoparticles can be remotely activated with ultrasound-based mechanical stimulations to induce drug release and to locally deliver anticancer electric cues. The combination of chemotherapy treatment with chronic piezoelectric stimulation shows promising results in reducing drug resistance and inhibiting the growth and migration of glioblastoma cells.
ACTA BIOMATERIALIA
(2022)
Article
Mathematical & Computational Biology
Juenu Yang, Fang Yan, Haihong Liu
Summary: This study focuses on the impact of Nutlin drug on the p53 pathway, analyzing how factors such as protein synthesis, drug response time delay, protein degradation rate, and key parameters in the integrated network system influence p53 oscillatory behavior. It examines the stability of the positive equilibrium point and the existence of Hopf bifurcation, providing criteria to determine the direction and stability of the bifurcated periodic solution. The results suggest that time delays and key parameters play a crucial role in the oscillation of p53, offering insights for understanding the biological functions of the p53 pathway and potential implications for cancer treatment.
MATHEMATICAL BIOSCIENCES AND ENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Kester Mo Henningsen, Valentina Manzini, Anna Magerhans, Sabrina Gerber, Matthias Dobbelstein
Summary: MDM2 can remove p53 from promoters by rapidly terminating its interactions with chromatin in a ubiquitin-dependent manner, in addition to its antagonism through covering the transactivation domain and destabilization.
Review
Biochemistry & Molecular Biology
Lucia Haronikova, Ondrej Bonczek, Pavlina Zatloukalova, Filip Kokas-Zavadil, Martina Kucerikova, Philip J. Coates, Robin Fahraeus, Borivoj Vojtesek
Summary: This review discusses the mechanism of action, determinants of sensitivity, and resistance issues of MDM2 inhibitors, emphasizing the need for patient stratification based on these aspects to achieve better clinical responses.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Wei-Lun Chang, Chih-Hsiung Hsieh, I-Ying Kuo, Chien-Hsun Lin, Yu-Lin Huang, Yi-Ching Wang
Summary: A novel therapeutic agent, Nutlin-3, has been proposed to enhance the treatment efficacy of chemoradiation-resistant ESCC by regulating the expression of transcription factor proteins p53 and RB and downregulating the level of DNA methyltransferase. It has the potential for clinical application.
MOLECULAR CARCINOGENESIS
(2022)
Review
Medicine, General & Internal
Giorgio Zauli, Sara AlHilali, Samar Al-Swailem, Paola Secchiero, Rebecca Voltan
Summary: This review summarizes the ocular manifestations and transmission of SARS-CoV-2 infection, and suggests the potential use of small molecule non-genotoxic inhibitors to protect the eyes from infection.
FRONTIERS IN MEDICINE
(2022)
Article
Cell Biology
Rasoul Pourebrahim, Rafael Heinz Montoya, Zoe Alaniz, Lauren Ostermann, Patrick P. Lin, Bin Liu, Edward Ayoub, Jared K. Burks, Michael Andreeff
Summary: Mesenchymal stromal cells (MSCs) play a crucial role in supporting hematopoietic stem cells in the bone marrow (BM) niche. This study demonstrates the essential function of Mdm2 in the emergence, maintenance, and hematopoietic support of BM-MSCs. Additionally, the p53 pathway is shown to be involved in the survival and protection of BM-MSCs in acute myeloid leukemia (AML) against hematopoietic toxicity caused by MDM2is. These findings provide new insights into the mechanism of MDM2is-induced hematopoietic toxicity.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Sharad S. Singhal, Saumya Srivastava, Tamara Mirzapoiazova, David Horne, Sanjay Awasthi, Ravi Salgia
Summary: Metastatic melanoma treatment is hindered by dysregulation of signaling pathways like MAP and RLIP, causing cell apoptosis and regression. CDE plays a crucial role in promoting melanoma cell proliferation.
Article
Oncology
Ken Ito, Hirotaka Ishida, Fumiyoshi Fujishima, Yasuhiro Nakamura, Takuro Konno, Kazue Ise, Shuko Hata, Yohei Ozawa, Yusuke Taniyama, Takashi Kamei, Hironobu Sasano
Summary: This study found that the combination of nutlin-3 and chemotherapeutic agents may be a novel therapeutic strategy for esophageal cancer over-expressing MDM2, potentially leading to anti-tumor effects.
ANTICANCER RESEARCH
(2022)
Review
Oncology
Arianna Romani, Enrico Zauli, Giorgio Zauli, Saleh AlMesfer, Samar Al-Swailem, Rebecca Voltan
Summary: MDM2 is the main inhibitor of p53, and MDM2 inhibitors can disrupt the physical interaction between MDM2 and p53. The short half-life of p53 in normal cells and tissues may have potential harmful effects if its levels increase uncontrollably. While p53 mutations are rare in retinoblastoma, therapeutic strategies aimed at increasing the expression levels of wild-type p53 are attractive. This minireview discusses the potential use of nutlin-3, a prototype small molecule inhibitor that disrupts the MDM2-p53 interaction, for treating retinoblastoma. The review also explores the relative contribution of p53-mediated gene transcription and mitochondrial perturbation to retinoblastoma treatment.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Elzbieta Speina, Marcin Wilczek, Adam Mieczkowski
Summary: In this study, a synthesis method for two benzodiazepine dimers was developed, and the synthesized compounds showed promising cytotoxic activity against lung cancer and carcinoma cell lines while exhibiting selectivity against normal cells. These compounds can be considered as a new group of anticancer agents and convenient structures for further optimization in the search for more active and selective molecules.
Article
Oncology
Christophe Deben, Laurie Freire Boullosa, Andreas Domen, An Wouters, Bart Cuypers, Kris Laukens, Filip Lardon, Patrick Pauwels
Summary: This study investigates the characteristics of acquired nutlin-3 resistant NSCLC cells, revealing mutations in the TP53 gene, upregulation of mutant p53 protein, enrichment of genes related to EMT and immune checkpoints, as well as reduced cisplatin-induced cell death. The findings highlight the importance of studying resistance mechanisms to chemotherapy, immunomodulation, immune checkpoints, EMT, and invasion in nutlin-3 resistant cancer cells.
CANCER DRUG RESISTANCE
(2021)
Article
Chemistry, Multidisciplinary
Wen-fang Li, Leader Alfason, Can Huang, Yu Tang, Li Qiu, Makoto Miyagishi, Shou-rong Wu, Vivi Kasim
Summary: This study reveals that p52-ZER6 may be a potential biomarker for determining patients appropriate for MDM2-p53 binding inhibition-based antitumor therapy, and demonstrates the potential of combinatorial therapy using MDM2-p53 binding inhibitors and p52-ZER6 inhibition.
ACTA PHARMACOLOGICA SINICA
(2023)
Correction
Oncology
Tongsen Zheng, Jiabei Wang, Xuan Song, Xianzhi Meng, Shangha Pan, Hongchi Jiang, Lianxin Liu
Summary: There was a misplaced image in Fig.4a in the original article.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Oncology
Mirco Friedrich, Markus Hahn, Julius Michel, Roman Sankowski, Michael Kilian, Niklas Kehl, Manina Guenter, Theresa Bunse, Stefan Pusch, Andreas von Deimling, Wolfgang Wick, Stella E. Autenrieth, Marco Prinz, Michael Platten, Lukas Bunse
Summary: The study reveals that glioma-associated dendritic cells are abundant in human IDHwt and mutant tumors, interacting with other immune cells in the tumor microenvironment. IDH mutations in gliomas result in specifically educated, dysfunctional dendritic cells through paracrine reprogramming of infiltrating monocytes, laying the foundation for combinatorial immunotherapy concepts against IDH mutant gliomas.
Review
Oncology
Julie J. Miller, L. Nicolas Gonzalez Castro, Samuel McBrayer, Michael Weller, Timothy Cloughesy, Jana Portnow, Ovidiu Andronesi, Jill S. Barnholtz-Sloan, Brigitta G. Baumert, Mitchell S. Berger, Wenya Linda Bi, Ranjit Bindra, Daniel P. Cahill, Susan M. Chang, Joseph F. Costello, Craig Horbinski, Raymond Y. Huang, Robert B. Jenkins, Keith L. Ligon, Ingo K. Mellinghoff, L. Burt Nabors, Michael Platten, David A. Reardon, Diana D. Shi, David Schiff, Wolfgang Wick, Hai Yan, Andreas von Deimling, Martin van den Bent, William G. Kaelin, Patrick Y. Wen
Summary: This article discusses the diagnosis and management of IDH-mutant gliomas, as well as new treatment methods and future research directions.
Article
Oncology
Florian Selt, Romain Sigaud, Gintvile Valinciute, Philipp Sievers, Julia Zaman, Clara Alco, Simone Schmid, Heike Peterziel, Jessica W. Tsai, Romain Guiho, Juan Pedro Martinez-Barbera, Stefan Pusch, Jing Deng, Yifan Zhai, Cornelis M. van Tilburg, Martin U. Schuhman, Ahmed E. L. Damaty, Pratiti Bandopadhayay, Christel Herold-Mende, Andreas von Deimling, Stefan M. Pfister, Joan Montero, David Capper, Ina Oehme, Felix Sahm, David T. W. Jones, Olaf Witt, Till Milde
Summary: Our study demonstrates that BCL-XL is critical for the survival of senescent PA tumor cells and provides evidence for the use of clinically available BCL-XL-dependent senolytic agents.
Article
Clinical Neurology
Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Federico Roncaroli, Shivaram Avula, Martin G. McCabe, James T. Hayden, Pieter Wesseling, Ingrid Ora, Monica Nister, Mariette E. G. Kranendonk, Bastiaan B. J. Tops, Michal Zapotocky, Josef Zamecnik, Alexandre Vasiljevic, Tanguy Fenouil, David Meyronet, Katja von Hoff, Ulrich Schuller, Hugues Loiseau, Dominique Figarella-Branger, Christof M. Kramm, Dominik Sturm, David Scheie, Tuomas Rauramaa, Jouni Pesola, Johannes Gojo, Christine Haberler, Sebastian Brandner, Tom Jacques, Alexandra Sexton Oates, Richard Saffery, Ewa Koscielniak, Suzanne J. Baker, Stephen Yip, Matija Snuderl, Nasir Ud Din, David Samuel, Kathrin Schramm, Mirjam Blattner-Johnson, Florian Selt, Jonas Ecker, Till Milde, Andreas von Deimling, Andrey Korshunov, Arie Perry, Stefan M. Pfister, Felix Sahm, David A. Solomon, David T. W. Jones
Summary: Pediatric central nervous system (CNS) tumors are the leading cause of cancer-related death in children aged 0-14 years. A newly identified CNS tumor type characterized by PLAGL1/2 amplification and a lack of recurrent genetic alterations has been described. These tumors are composed of primitive embryonal-like cells and are associated with intermediate survival, but the cell of origin and optimal treatment strategies are yet to be determined.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Thomas Hielscher, Martin Sill, Philipp Sievers, Damian Stichel, Sebastian Brandner, David T. W. Jones, Andreas von Deimling, Felix Sahm, Sybren L. N. Maas
Summary: Risk prediction for meningioma tumors has traditionally relied on morphological features, but incorporating molecular features improves accuracy. This study confirms the practicality of using a newer brain tumor classifier and suggests that additional testing for certain mutations may not be necessary when calculating risk scores for individual patients.
Article
Oncology
Jonas Ecker, Florian Selt, Dominik Sturm, Martin Sill, Andrey Korshunov, Steffen Hirsch, David Capper, Nicola Dikow, Christian Sutter, Carina Mueller, Romain Sigaud, Angelika Eggert, Thorsten Simon, Tim Niehues, Andreas von Deimling, Kristian W. Pajtler, Cornelis M. van Tilburg, David T. W. Jones, Felix Sahm, Stefan M. Pfister, Olaf Witt, Till Milde
Summary: The PTT 2.0 program aims to improve diagnostic accuracy and detect actionable alterations in relapsed pediatric oncology patients, even with limited tumor material. The study utilized molecular analyses such as DNA methylation array, targeted gene panel sequencing, RNA sequencing, and immunohistochemistry to provide relevant and robust information for diagnosis and treatment decisions.
EUROPEAN JOURNAL OF CANCER
(2023)
Letter
Virology
Lauren J. Hayes, Hannah Uri, Denisa Bojkova, Jindrich Cinatl, Mark N. Wass, Martin Michaelis
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Oncology
P. Dao Trong, M. Gluszak, D. Reuss, A. von Deimling, A. Wick, L. Koenig, J. Debus, C. Herold-Mende, A. Unterberg, C. Jungk
Summary: This study analyzed elderly patients with lower-grade glioma and found that surgical resection and adjuvant treatment can achieve favorable outcomes, with comparable progression-free survival to younger patients.
JOURNAL OF NEURO-ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Sahin Cangaz, Oliver Lohrberg, Thomas Abendroth, Christian Heubner, Florian Schmidt, Holger Althues, Susanne Doerfler, Alexander Michaelis, Stefan Kaskel
Summary: The study finds that using moderately thick copper current collectors can effectively reduce the mechanical failure caused by volumetric expansion of silicon anode materials, thereby increasing the energy density of lithium-ion batteries.
ADVANCED MATERIALS INTERFACES
(2023)
Article
Neurosciences
Konstantin Okonechnikov, Aniello Federico, Daniel Schrimpf, Philipp Sievers, Felix Sahm, Jan Koster, David T. W. Jones, Andreas von Deimling, Stefan M. Pfister, Marcel Kool, Andrey Korshunov
Summary: Currently, medulloblastoma can be treated successfully using risk-stratified approaches, but relapses remain a challenge. RNA sequencing was used to analyze the transcriptome profiles of primary-relapse MB pairs, revealing molecular features and potential predictive markers for survival.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Johanna Maier, David Werner, Vinzenz Geske, Thomas Behnisch, Mathias Ahlhelm, Tassilo Moritz, Alexander Michaelis, Maik Gude
Summary: Freeze foams are cellular, ceramic structures with hierarchical pore structures that can cover a wide range of applications by tailoring their morphology and strength. The correlation between pore-forming influencing factors and resulting mechanical properties was quantified in order to manufacture foams that align with component requirements, which is an important step towards the widespread application of these promising materials. Foams with independently adjustable porosities were produced and systematically investigated, revealing different material failure characteristics.
Article
Biochemical Research Methods
Erik K. R. Hanko, Tariq A. Joosab Noor Mahomed, Ruth A. Stoney, Rainer Breitling
Summary: TFBMiner is a tool that identifies putative metabolite-responsive transcription factor-based biosensors (TFBs) through data mining and analysis. It utilizes a heuristic rule-based gene organization model to identify gene clusters involved in the catabolism of user-defined molecules and their associated transcriptional regulators, providing wet-lab scientists with a ranked list of candidates. The pipeline was validated by identifying known sensors and discovering a biosensor for S-mandelic acid.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Electrochemistry
Nils Buettner, Foelke Purr, Clara Sangros Gimenez, Maria Richter, Laura Nousch, Sabrina Zellmer, Alexander Michaelis
Summary: Battery models are mathematical systems that simulate real battery cells accurately. This work presents an electrochemical and thermal model of sodium-nickel-chloride/iron-chloride battery cells. The model allows for predicting internal cell processes and has a low computational effort, making it a useful tool for battery development.
Article
Materials Science, Ceramics
Eric Schwarzer-Fischer, Uwe Scheithauer, Alexander Michaelis
Summary: Aluminum nitride (AlN) is a high-performance material used in heat sinks for various electronic applications. This study successfully developed a 3D printing process for AlN based on a commercial powder, achieving excellent thermal conductivities and densities comparable to conventionally manufactured components. The results demonstrate the potential of this technology for producing complex-shaped components with high performance.
CERAMICS-SWITZERLAND
(2023)