Review
Biochemistry & Molecular Biology
Moo-Kon Song, Byeong-Bae Park, Ji-Eun Uhm
Summary: Acute myeloid leukemia (AML) is a heterogeneous hematopoietic neoplasm characterized by genetic abnormalities that have significant prognostic implications. Understanding the molecular abnormalities of the disease may lead to the development of novel targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
John F. F. Marcelletti, Branimir I. I. Sikic
Summary: The purpose of this study was to evaluate the safety, tolerability, potential efficacy, and pharmacodynamics of Zos in combination with GO in elderly patients with RR AML. The results showed that the combination of Zos and GO achieved a significant ORR in elderly patients with RR AML, and the P-gp+ subgroup had a better OS.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Weirong Lai, Shengyan Zhao, Qinhuai Lai, Wei Zhou, Mengdan Wu, Xiaohua Jiang, Xin Wang, Yujia Peng, Xian Wei, Liang Ouyang, Lantu Gou, Hao Chen, Yuxi Wang, Jinliang Yang
Summary: A novel series of hybrid molecules combining PBD and anthracenecarboxyimide pharmacophores were synthesized and tested for in vitro cytotoxicity, with the most potent compound 37b3 exhibiting subnanomolar cytotoxicity. By conjugating 37b3 with trastuzumab, the ADC T-PBA showed promising killing effects on Her2-positive cancer cells in vitro and inhibited tumor growth in xenograft mouse models.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Engineering, Environmental
Qian-Yuan Wu, Xue-Si Lu, Ming-Bao Feng, Wen-Long Wang, Ye Du, Lu-Lin Yang, Hong-Ying Hu
Summary: Ferrate(VI) (Fe(VI)) effectively reduces the cytotoxicity and genotoxicity of secondary effluents by oxidizing and coagulating organic matter and heavy metals, alleviating oxidative stress in cells. The Fe(VI) treatment showed better performance in removing organic matter, cytotoxicity, and genotoxicity compared to ferric chloride, highlighting its potential in advanced wastewater treatment processes.
Article
Medicine, Research & Experimental
Sonia Jaramillo, Johannes Krisam, Lucian Le Cornet, Markus Kratzmann, Lukas Baumann, Tim Sauer, Martina Crysandt, Andreas Rank, Dirk Behringer, Lino Teichmann, Martin Goerner, Ralf-Ulrich Trappe, Christoph Roellig, Stefan Krause, Maher Hanoun, Olaf Hopfer, Gerhard Held, Sebastian Buske, Lars Fransecky, Sabine Kayser, Christoph Schliemann, Kerstin Schaefer-Eckart, Yousef Al-Fareh, Joerg Schubert, Thomas Geer, Martin Kaufmann, Arne Brecht, Dirk Niemann, Meinhard Kieser, Martin Bornhaeuser, Uwe Platzbecker, Hubert Serve, Claudia D. Baldus, Carsten Mueller-Tidow, Richard F. Schlenk
Summary: This randomized phase III trial aims to investigate the efficacy of adding gemtuzumab ozogamicin (GO) and glasdegib to the traditional treatment for older patients with acute myeloid leukemia (AML). A total of 252 evaluable patients will be needed to address the endpoints of measurable residual disease (MRD) and event-free survival (EFS) with a 2 by 2 factorial design. Ethical approval has been obtained and trial results will be disseminated through peer-reviewed journals and scientific conferences.
Article
Biotechnology & Applied Microbiology
Yan Luo, Yanpeng Xu, Xue Li, Xiaoqi Shi, Pei Huang, Yan Chen, Zhixu He
Summary: In this study, a prognostic risk model of AML was developed and validated using seven immune genes. The model accurately predicts the 5-year survival rate and reflects the changes in the immune microenvironment of AML patients.
BIOMED RESEARCH INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Cherine Sifri, Lisa Hoeg, Daniel Durocher, Dheva Setiaputra
Summary: 53BP1 is a chromatin-binding protein that recruits downstream effectors RIF1, shieldin, and CST to promote DNA double-strand break repair. The structural details of protein-protein interactions within the 53BP1-RIF1-shieldin-CST pathway, essential for DNA repair, are largely unknown. In this study, we used AlphaFold2-Multimer (AF2) to predict and provide structural models for seven previously characterized interactions in this pathway. Our analysis also revealed a novel binding interface between RIF1 and SHLD3. Experimental validation demonstrated that the RIF1-SHLD3 binding is crucial for shieldin recruitment, antibody class switch recombination, and PARP inhibitor sensitivity, highlighting the essential role of this interaction in the 53BP1-RIF1-shieldin-CST pathway activity.
Article
Oncology
Upasana Sunil Arvindam, Paulien M. M. van Hauten, Dawn Schirm, Nicolaas Schaap, Willemijn Hobo, Bruce R. Blazar, Daniel A. Vallera, Harry Dolstra, Martin Felices, Jeffrey S. Miller
Summary: The development of a CLEC12A TriKE molecule targeting AML blasts and LSCs, which activates NK cells and drives NK cell priming while sparing healthy cells, highlights the potential clinical efficacy for the treatment of AML.
Review
Oncology
Sonia Jaramillo, Richard F. Schlenk
Summary: Recent developments in AML treatment, including the approval of new agents and the use of MRD measurement, have changed the approach to consolidation and maintenance therapy, guiding the duration and type of treatment as well as the optimal timing for allo-HCT.
CURRENT ONCOLOGY REPORTS
(2021)
Article
Oncology
Thorsten Derlin, Natalia Bogdanova, Fiona Ohlendorf, Dhanya Ramachandran, Rudolf A. Werner, Tobias L. Ross, Hans Christiansen, Frank M. Bengel, Christoph Henkenberens
Summary: Assessment of gamma-H2AX and 53BP1 foci formation in peripheral blood lymphocytes of patients receiving radioligand therapy may hold promise for predicting early treatment response and subclinical hematotoxicity.
Article
Biology
Masahiro Nishida, Takeshi Terabayashi, Shigeru Matsuoka, Tomoko Okuma, Sawako Adachi, Tadashi Tomo, Masanori Kawano, Kazuhiro Tanaka, Hiroshi Tsumura, Hirofumi Anai, Toshimasa Ishizaki, Yoshihiro Nishida, Katsuhiro Hanada
Summary: This study characterized the effect of a non-camptothecin inhibitor, Genz-644282 (Genz), on TOP1 inhibition. The results showed that Genz exhibited potent activity against camptothecin-resistant cells through double-strand break induced cytotoxicity. The study also revealed the mechanism of action of Genz and the crucial amino acid residues involved in its binding with TOP1.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Naomi Inoue, Takeshi Terabayashi, Yuri Takiguchi-Kawashima, Daisuke Fujinami, Shigeru Matsuoka, Masanori Kawano, Kazuhiro Tanaka, Hiroshi Tsumura, Toshimasa Ishizaki, Hisashi Narahara, Daisuke Kohda, Yoshihiro Nishida, Katsuhiro Hanada
Summary: The benzylisoquinoline alkaloids berberine and coptisine induce mild DNA double-stranded breaks (DSBs) dependent on the function of topoisomerase I (Topo I) and MUS81-EME1 endonuclease. These alkaloids inhibit Topo I's catalytic activity, contrary to camptothecin (CPT), and can effectively act against CPT-resistant mutants, suggesting they may be used in combination to increase efficiency in eliminating cancer cells.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Daisuke Tomizawa, Shin-ichi Tsujimoto, Shiro Tanaka, Jun Matsubayashi, Takahiro Aoki, Shotaro Iwamoto, Daisuke Hasegawa, Kozo Nagai, Kentaro Nakashima, Koji Kawaguchi, Takao Deguchi, Nobutaka Kiyokawa, Kentaro Ohki, Hidefumi Hiramatsu, Norio Shiba, Kiminori Terui, Akiko Moriya Saito, Motohiro Kato, Takashi Taga, Tsugumichi Koshinaga, Souichi Adachi
Summary: This study aims to establish an appropriate treatment for children with de novo acute myeloid leukemia, based on recurrent leukemic cytogenetic abnormalities and flow-cytometric minimal residual disease. It also aims to validate the safety and efficacy of gemtuzumab ozogamicin combined with post-induction chemotherapy for non-low-risk patients.
JAPANESE JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Sarah M. Akram, Ali Z. Al-Saffar, Noora A. Hadi, Sally M. Akram
Summary: In this study, Au NPs-PEG-Lectin was prepared as a drug targeting system for leukemia treatment, showing significant cytotoxic activity against HL-60 and K562 cells.
Article
Biology
Teruaki Konishi, Tamon Kusumoto, Yota Hiroyama, Alisa Kobayashi, Taisei Mamiya, Satoshi Kodaira
Summary: This study investigated whether radiation cancer therapy with ultra-high dose rate (UHDR) exposure could effectively reduce DNA damage. The results showed that UHDR proton beam irradiation significantly reduced the induction rate of single strand breaks (SSBs) and formamidopyrimidine-DNA glycosylase (Fpg) enzyme sensitive sites (ESS), but had no significant effect on double strand breaks (DSBs) and non-DSB cluster damages.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)