Article
Biochemistry & Molecular Biology
Md Harunur Rashid, Dinesh Babu, Arno G. Siraki
Summary: NQO1 and NQO2 are important antioxidant enzymes that reduce the generation of harmful quinone-like compounds through two-electron reduction, playing a crucial role in oxidative stress. Studies have shown that induction or depletion of NQO1 and NQO2 can affect susceptibility to oxidative stress. These enzymes play critical roles when other detoxification pathways are overwhelmed.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Omar Prado-Carrillo, Abner Arenas-Ramirez, Monserrat Llaguno-Munive, Rafael Jurado, Jazmin Perez-Rojas, Eduardo Cervera-Ceballos, Patricia Garcia-Lopez
Summary: This study established an imatinib-resistant CML cell line and found that overexpression of P-gp plays a significant role in imatinib resistance. Ketoconazole can reverse this resistance by inhibiting P-gp.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Hyacinthe Johnson-Ansah, Benjamin Maneglier, Francoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, Valerie Coiteux, Laurent Sutton, Wajed Abarah, Camille Pouaty, Jean-Michel Pignon, Bachra Choufi, Sorin Visanica, Benedicte Deau, Laure Morisset, Emilie Cayssials, Mathieu Molimard, Stephane Bouchet, Francois-Xavier Mahon, Franck Nicolini, Philippe Aegerter, Jean-Michel Cayuela, Marc Delord, Heriberto Bruzzoni-Giovanelli, Philippe Rousselot
Summary: This study evaluated the value of therapeutic drug monitoring (TDM) in imatinib treatment for patients with chronic myelogenous leukemia. The results showed that TDM strategy significantly increased the plasma concentration of imatinib and improved the treatment outcome for patients.
Article
Pharmacology & Pharmacy
An-Ni Zhong, Yi Yin, Bing-Jie Tang, Lei Chen, Hong-Wei Shen, Zhi-Ping Tan, Wen-Qun Li, Qun He, Bao Sun, Yan Zhu, Jie Xiao, Zhi-Ping Jiang, Ping Xu
Summary: The study revealed that hsa_circ_0058493 was significantly overexpressed in PBMCs of CML patients and associated with poor clinical efficacy of imatinib. Silencing this circRNA significantly inhibited the development of imatinib-resistant CML cells, suggesting its potential as a therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesc Xavier Ruiz, Xavier Pares, Jaume Farres
Summary: Human aldo-keto reductase 1B10 (AKR1B10) is overexpressed in many cancer types and has been identified as an interesting drug target. Differences in inhibitor binding between AKR1B10 and aldose reductase (AR) have been observed, highlighting specific features that a selective AKR1B10 inhibitor should possess.
Article
Oncology
Fang Cheng, Guolin Yuan, Qiang Li, Zheng Cui, Weiming Li
Summary: This study confirmed the long-term efficacy and safety of imatinib for treating Chinese CML patients. Additionally, it demonstrated the feasibility of imatinib dose reduction and treatment-free remission attempts in patients with sustained stable deep molecular response after years of imatinib treatment in real-life settings.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Elzbieta Janda, Concetta Martino, Concetta Riillo, Maddalena Parafati, Antonella Lascala, Vincenzo Mollace, Jean A. Boutin
Summary: The study found that NQO2 may be a key factor in flavonoid-induced autophagy, with some flavonoids releasing pro-autophagic signals while inhibiting NQO2 activity. Additionally, AMP kinase activation plays an important role in flavonoid-induced autophagy.
Article
Multidisciplinary Sciences
George E. Ghanim, Adam J. Fountain, Anne-Marie M. van Roon, Ramya Rangan, Rhiju Das, Kathleen Collins, Thi Hoang Duong Nguyen
Summary: Telomerase is crucial in embryogenesis and cancer, and understanding its structure and function is essential for developing treatments targeting diseases. The high-resolution structure of human telomerase provides insights into its assembly and active site, paving the way for therapeutic interventions.
Article
Hematology
Aram Bidikian, Elias Jabbour, Ghayas C. C. Issa, Nicholas J. J. Short, Koji Sasaki, Hagop Kantarjian
Summary: Achieving major molecular response (MMR) with BCR::ABL1 tyrosine kinase inhibitors (TKIs) is important in the treatment of chronic myeloid leukemia (CML). However, patients who achieve a major cytogenetic response (MCyR) within the first 2 years of TKI therapy can still have good long-term outcomes, even without achieving MMR. The value of MMR is less pronounced among older CML patients, who often face mortality due to comorbidities unrelated to CML.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Chemistry, Analytical
Stefano Tartaggia, Anna Meneghello, Ottavia Bellotto, Ariana Soledad Poetto, Martina Zanchetta, Bianca Posocco, David Bunka, Federico Polo, Giuseppe Toffoli
Summary: This study developed a detection assay for the anticancer drug imatinib using a ssDNA aptamer, demonstrating excellent selectivity and stability for therapeutic drug monitoring (TDM). By utilizing surface plasmon resonance (SPR) analysis, a quantitative assay in the concentration range of 400 to 6000 ng mL(-1) was established, showing high precision and accuracy. The method, validated according to regulatory guidelines, offers a feasible aptasensor for TDM in patients receiving imatinib treatment.
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Environmental
Wenda Shi, Jianbo Guo, Caicai Lu, Zhi Chen, Haibo Li, Yuanyuan Song, Yi Han, Yanan Hou
Summary: The research found that NR and TPPS can significantly enhance the perchlorate bioreduction rate by accelerating electron transfer, promoting cell metabolic activity, and enhancing perchlorate reductase activity.
CHEMICAL ENGINEERING JOURNAL
(2021)
Article
Oncology
Fang Cheng, Fang Zeng, Qiang Li, Zheng Cui, Yilin Chen, Weiming Li, Yu Zhang
Summary: This study explores the optimization of imatinib dose in CML patients based on therapeutic drug monitoring (TDM). The results show that imatinib concentration is closely associated with clinical response and adverse reactions. Dose reduction based on TDM is feasible and safe for patients exhibiting optimal response, improving adverse reactions without affecting molecular relapse-free survival rate.
Article
Chemistry, Physical
Hovan Lee, Cedric Weber, Edward B. Linscott
Summary: We present the first density functional theory and dynamical meanfield theory calculations for iron-bound human serum transferrin. Our results are in good agreement with experimental measurements, showing peaks in the optical conductivity at 250, 300, and 450 nm. Spin multiplet analysis suggests that the ground state is a mixed state with high entropy, emphasizing the significance of strong electronic correlation in the chemistry of this system.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Oncology
Meike Kaehler, Pia Osteresch, Axel Kuenstner, Stella Juliane Vieth, Daniela Esser, Marius Moeller, Hauke Busch, Inga Vater, Malte Spielmann, Ingolf Cascorbi, Inga Nagel
Summary: The resistance of anti-cancer treatment is caused by clonal evolution and clonal selection. In chronic myeloid leukemia (CML), the formation of the BCR::ABL1 kinase is the main cause of the disease. Treatment with tyrosine kinase inhibitors (TKIs) has shown great success, but resistance to TKIs can result in loss of molecular remission in CML patients.
FRONTIERS IN ONCOLOGY
(2023)
Editorial Material
Hematology
Oliver Hantschel
Review
Biochemistry & Molecular Biology
Oliver Hantschel, Matthew Biancalana, Shohei Koide
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Daniel P. Duarte, Allan J. Lamontanara, Giuseppina La Sala, Sukyo Jeong, Yoo-Kyoung Sohn, Alejandro Panjkovich, Sandrine Georgeon, Tim Kukenshoner, Maria J. Marcaida, Florence Pojer, Marco De Vivo, Dmitri Svergun, Hak-Sung Kim, Matteo Dal Peraro, Oliver Hantschel
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Eva Meixner, Ulrich Goldmann, Vitaly Sedlyarov, Stefania Scorzoni, Manuele Rebsamen, Enrico Girardi, Giulio Superti-Furga
MOLECULAR SYSTEMS BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Mattia D. Pizzagalli, Ariel Bensimon, Giulio Superti-Furga
Summary: This review provides an overview of the SLC superfamily of transporter proteins and their roles in regulating metabolism and environmental conditions at the cell surface, with a focus on their involvement in cancer development and progression.
Article
Multidisciplinary Sciences
Gregory La Sala, Camille Michiels, Tim Kuekenshoener, Tania Brandstoetter, Barbara Maurer, Akiko Koide, Kelvin Lau, Florence Pojer, Shohei Koide, Veronika Sexl, Laure Dumoutier, Oliver Hantschel
NATURE COMMUNICATIONS
(2020)
Article
Hematology
Afsar Ali Mian, Isabella Haberbosch, Hazem Khamaisie, Abed Agbarya, Larissa Pietsch, Elizabeh Eshel, Dally Najib, Claudia Chiriches, Oliver Gerhard Ottmann, Oliver Hantschel, Ricardo M. Biondi, Martin Ruthardt, Jamal Mahajna
Summary: The study found that crizotinib can effectively inhibit the growth of Ph+ leukemia cells without affecting Ph- cells. Its efficacy has been validated in different models, demonstrating a unique dual mechanism of action.
ANNALS OF HEMATOLOGY
(2021)
Article
Immunology
Zsofia Agnes Bittner, Xiao Liu, Maria Mateo Tortola, Ana Tapia-Abellan, Sangeetha Shankar, Liudmila Andreeva, Matthew Mangan, Marianne Spalinger, Hubert Kalbacher, Peter Duewell, Marta Lovotti, Karlotta Bosch, Sabine Dickhoefer, Ana Marcu, Franziska Herster, Yamel Cardona Gloria, Tzu-Hsuan Chang, Francesca Bork, Carsten L. Greve, Markus W. Loeffler, Olaf-Oliver Wolz, Nadine A. Schilling, Jasmin B. Kuemmerle-Deschner, Samuel Wagner, Anita Delor, Bodo Grimbacher, Oliver Hantschel, Michael Scharl, Hao Wu, Eicke Latz, Alexander N. R. Weber
Summary: The study reveals that Bruton's tyrosine kinase (BTK) affects multiple levels of NLRP3 regulation by interacting with NLRP3 and phosphorylating conserved tyrosine residues upon inflammasome activation, promoting NLRP3 relocalization, oligomerization, ASC polymerization, and inflammasome assembly. This suggests BTK as a multifunctional positive regulator of NLRP3 regulation and its phosphorylation of NLRP3 as a potential therapeutic target for controlling inflammation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Georgios N. Hatzopoulos, Tim Kuekenshoener, Niccolo Banterle, Tatiana Favez, Isabelle Flueckiger, Virginie Hamel, Santiago Andany, Georg E. Fantner, Oliver Hantschel, Pierre Goenczy
Summary: The study presents the development of monobodies against Chlamydomonas reinhardtii SAS-6 and their effects on ring assembly and stacking, using X-ray crystallography, atomic force microscopy, and cryo-electron microscopy.
NATURE COMMUNICATIONS
(2021)
Article
Clinical Neurology
Mohammed Salman Shazeeb, Robert M. King, Vania Anagnostakou, Zeynep Vardar, Afif Kraitem, Josephine Kolstad, Christopher Raskett, Natacha Le Moan, Jonathan A. Winger, Lauren Kelly, Ana Krtolica, Nils Henninger, Matthew J. Gounis
Summary: This study demonstrated that intravenous delivery of a novel oxygen carrier can delay infarct progression in a large vessel occlusion stroke model, suggesting a promising approach for treating ischemic stroke, especially in patients who cannot undergo definitive reperfusion therapy in a timely manner.
Article
Multidisciplinary Sciences
Evandro Ferrada, Giulio Superti-Furga
Summary: This study provides an integrative classification of solute carriers by combining evolutionary information with proteome-wide structure models. The results reveal approximately 180 independent evolutionary origins of solute carriers and identify 24 structurally distinct transmembrane folds. In addition, a new solute carrier member and details of noncanonical solute carriers are discovered.
Article
Biology
Patrick Essletzbichler, Vitaly Sedlyarov, Fabian Frommelt, Didier Soulat, Leonhard X. Heinz, Adrijana Stefanovic, Benedikt Neumayer, Giulio Superti-Furga
Summary: Phagocytosis is a crucial process for tissue clearance and host defense, but its dysregulation is linked to various diseases. This study used a genome-wide CRISPRko FACS screen to identify 716 genes involved in phagocytosis. By mapping the hits to a protein-protein interaction network, novel phagocytosis regulators were discovered and validated. This comprehensive network provides insights into cargo uptake and transformation, and can aid in the identification of potential drivers for endo-lysosomal diseases.
LIFE SCIENCE ALLIANCE
(2023)
Review
Pharmacology & Pharmacy
Vojtech Dvorak, Giulio Superti-Furga
Summary: Solute carriers (SLCs) are the largest group of membrane transporters in the human genome, and they are central in controlling metabolism compartmentalization, with most of this superfamily being linked to human diseases. Despite being considered attractive therapeutic targets, many SLCs still lack functional and structural annotations.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Nina Schmidt, Frank Abendroth, Olalla Vazquez, Oliver Hantschel
Summary: The d- and l-versions of the Bcr-Abl SH2 domain were successfully synthesized with key optimizations. These versions exhibit folding and activity similar to the recombinant protein. This study has significant implications for developing mirror-image monobody antagonists targeting the central oncoprotein Bcr-Abl.
RSC CHEMICAL BIOLOGY
(2022)
Review
Hematology
Peter Valent, Alberto Orfao, Stefan Kubicek, Philipp Staber, Torsten Haferlach, Michael Deininger, Karoline Kollmann, Thomas Lion, Irene Virgolini, Georg Winter, Oliver Hantschel, Lukas Kenner, Johannes Zuber, Florian Grebien, Richard Moriggl, Gregor Hoermann, Olivier Hermine, Michael Andreeff, Christoph Bock, Tariq Mughal, Stefan N. Constantinescu, Robert Kralovics, Veronika Sexl, Radek Skoda, Giulio Superti-Furga, Ulrich Jaeger
Summary: As our understanding of molecular mechanisms and cellular interactions in malignant blood cell disorders has improved, precision medicine and personalized medicine have become important disciplines supporting clinicians in making accurate diagnoses, predicting outcomes, and selecting optimal interventional therapies for patients. However, there are still many questions surrounding the implementation and affordability of precision medicine tools in healthcare systems, as well as the need to define and relate specific terminologies and strategies in basic and applied science.