Review
Genetics & Heredity
Elena Di Nisio, Giuseppe Lupo, Valerio Licursi, Rodolfo Negri
Summary: This review article explores the role of histone lysine methylation changes in regulating the response to radiation-induced genotoxic damage in mammalian cells. It also discusses the effects of histone methyltransferases (HMTs) and histone demethylases (HDMs) on radio-sensitivity of different cell lines, and provides a bioinformatic analysis of mRNA levels of known HMTs and HDMs under different irradiation conditions.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Pavol Kosik, Milan Skorvaga, Igor Belyaev
Summary: Although the causes for the increasing prevalence of leukemia are uncertain, ionizing radiation (IR) has been associated with the development of leukemia through epidemiological studies. IR is known to induce chromosomal translocations, including preleukemic fusion genes (PFGs), which are considered the first step in the development of leukemia. However, it is suggested that secondary mutations and specific cell populations of hematopoetic stem cells with higher leukemogenic potential are also necessary for leukemia to occur. This review focuses on the connection between IR, PFGs, and cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Ken Akamatsu, Naoya Shikazono, Takeshi Saito
Summary: This study characterized clustered DNA damage sites through fluorescence anisotropy measurements, revealing an increase in the apparent base separation values between lesions in a cluster with higher linear energy transfer of radiation. This method has the potential to discover qualitative and quantitative differences in clustered DNA damage produced by various ionizing radiation and other damaging agents.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2021)
Review
Cell Biology
Jessica Honorato Ribeiro, Nazlican Altinisik, Nicholas Rajan, Mieke Verslegers, Sarah Baatout, Jay Gopalakrishnan, Roel Quintens
Summary: DNA-damaging agents and endogenous DNA damage continuously threaten genome integrity. The DNA damage response (DDR) mechanisms play a crucial role in repairing lesions and preventing mutations, especially in brain development. Defects in DNA repair pathways can lead to neurological disorders such as microcephaly. Genetic mutations, exposure to ionizing radiation, and intrauterine infections can cause microcephaly by impairing DNA repair pathways. This review discusses the importance of DDR in normal brain development and the mechanisms and exposures that can result in microcephaly.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Oncology
Sams M. A. Sadat, Melinda Wuest, Igor M. Paiva, Sirazum Munira, Nasim Sarrami, Forughalsadat Sanaee, Xiaoyan Yang, Marco Paladino, Ziyad Binkhathlan, Feridoun Karimi-Busheri, Gary R. Martin, Frank R. Jirik, David Murray, Armin M. Gamper, Dennis G. Hall, Michael Weinfeld, Afsaneh Lavasanifar
Summary: Inhibition of the DNA repair enzyme PNKP using A83B4C63 has shown potential as a radio-sensitizer for solid tumors, with preferential delivery to tumors through nanoparticles to reduce side effects on normal tissue. Results demonstrated increased DNA damage persistence in cells treated with A83B4C63 and radiation, with higher tumor growth delay observed in mice treated with nanoparticle-delivered A83B4C63 compared to other treatments.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Jae Hee Lee, Byeongwook Jeon, Mijeong Park, Jimin Ha, Soo Jung Kim, Mi Kwon Son, Seungho Wang, Joo Han Lee, Youn Kyoung Jeong
Summary: The study showed that BR101801, a DNA-PK inhibitor, can effectively enhance genomic instability induced by ionizing radiation and increase sensitivity in human solid cancer cells through multiple pathways. It affects factors in both the non-homologous end-joining repair pathway and homologous recombination.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemical Research Methods
Victor Kompanets, Svetlana Shelygina, Eteri Tolordava, Sergey Kudryashov, Irina Saraeva, Aleksey Rupasov, Olga Baitsaeva, Roman Khmelnitskii, Andrey Ionin, Yulia Yushina, Sergey Chekalin, Michael Kovalev
Summary: Research has demonstrated the enhanced biocidal efficiency of selective excitation using focused mid-IR femtosecond laser radiation on bacteria compared to uniform excitation. The bacterial inactivation by 6-mu m ultrashort laser pulses is attributed to the dissociative denaturation of lipids and proteins in the cell membranes and intra-cell nucleic acids.
BIOMEDICAL OPTICS EXPRESS
(2021)
Article
Cell Biology
Akram Hamidi, Alexandra Wolf, Rositsa Dueva, Melanie Kaufmann, Kirsten Goepelt, George Iliakis, Eric Metzen
Summary: This study established an in vitro model of murine hepatocyte derived cells and analyzed the role of HIF-1 alpha in apoptosis induction, DNA damage repair, and sensitivity to ionizing radiation. The results showed that HIF-1 alpha deficiency increased radiation sensitivity and affected DNA repair.
Article
Biochemistry & Molecular Biology
Yan Zhang, Qibin Fu, Tuchen Huang, Yang Liu, Gengming Chen, Shaopeng Lin
Summary: Radiotherapy is a crucial treatment for cancer patients, but its effects on cellular mechanics and DNA damage are still not well understood. In this study, the researchers investigated the impact of ionizing radiation on cell mechanics by measuring the compressibility of suspended cells using a microfluidic device. It was found that cell compressibility significantly increased after irradiation, and this was dependent on cell type and radiation dose. The study also revealed that the DNA damage response induced by radiation altered cell mechanics, and the primary cause of changes in cell compressibility was chromatin decondensation caused by radiation-induced DNA damage response.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Oncology
Yen-Yun Wang, Amos C. Hung, Steven Lo, Ya-Ching Hsieh, Shyng-Shiou F. Yuan
Summary: MRE11 plays a crucial role in DNA damage response and its expression in cancer cells is linked to radioresistance, making it a potential marker for radiosensitization strategies. Elevated MRE11 in tumor tissues has been associated with poor survival in radiotherapy patients, although recent findings of ionizing radiation-induced truncation of MRE11 may explain some conflicting observations. Advancements in understanding the biological modulation of MRE11 expression and the potential application of inhibitors for enhancing radiosensitivity are discussed, highlighting the importance of distinguishing between nuclease and non-nuclease activities of MRE11 in cancer cells treated with ionizing radiation.
Article
Plant Sciences
Sera Jung, Kwang Min Koo, Jaihyunk Ryu, Inwoo Baek, Soon-Jae Kwon, Jin-Baek Kim, Joon-Woo Ahn
Summary: The study revealed that CrPRPS plays a crucial role in the response to DNA damage in the green alga Chlamydomonas reinhardtii, with overexpression leading to increased cell growth and survival rates. Additionally, overexpression of CrPRPS enhances the expression of genes associated with DNA damage response.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Oncology
Torin P. Thielhelm, Stefania Goncalves, Scott M. Welford, Eric A. Mellon, Erin R. Cohen, Aida Nourbakhsh, Cristina Fernandez-Valle, Fred Telischi, Michael E. Ivan, Christine T. Dinh
Summary: Vestibular schwannomas (VS) are tumors that originate from Schwann cells of the vestibulocochlear nerve, causing hearing loss and dizziness. Though radiation therapy is common, some tumors are radioresistant, necessitating additional treatment. Understanding VS radiobiology is crucial for improving treatment outcomes.
Review
Cell Biology
Ying Jie Zhou, Yun Tang, Si Jian Liu, Peng Hui Zeng, Li Qu, Qian Cheng Jing, Wen Jun Yin
Summary: The article summarizes the mechanisms and potential treatments of radiation-induced liver disease, highlighting the importance of further research on this disease.
Article
Plant Sciences
Xiaomeng Zhang, Xiaoying Chen, Lei Wang, An Wang, Changhao He, Zhongyu Shi, Shujing Zhang, Qian Fu, Wenhui Xu, Sumin Hu
Summary: This study confirmed the protective effects of YQJD decoction on ionizing radiation-induced spermatogenic cell injury. The findings may provide a new strategy for the application of Chinese herbs in radioprotection.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Diana Rubio-Contreras, Fernando Gomez-Herreros
Summary: This study reveals that double strand breaks (DSBs) induced by DNA topoisomerase I (TOP1) can lead to genome rearrangements, which are repaired by tyrosyl-DNA phosphodiesterase 1 (TDP1), thereby protecting gene transcription and genome stability.
NATURE COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Qing Li, Zhi-Wei Zhou, Jia Lu, Hao Luo, Shu-Nan Wang, Yu Peng, Meng-Sheng Deng, Guan-Bin Song, Jian-Min Wang, Xi Wei, Dong Wang, Kenneth D. Westover, Cheng-Xiong Xu
Summary: This study found that the rs17718883 polymorphism in the PD-L1 gene affects the PD-1/PD-L1 interaction, leading to ineffectiveness of PD-1/PD-L1 blockade therapy in certain gastric cancer patients. The study suggests that rs17718883 could be used as a screening biomarker to exclude patients who are not suitable for PD-1/PD-L1 blockade therapy.
Editorial Material
Biochemistry & Molecular Biology
Kenneth D. Westover
Summary: The functions of Ras members are largely determined by the structural dynamics of the nucleotide-binding switch regions. In this study, Lin et al. focus on the dynamic equilibrium of RhoA to gain insights into the working mechanism of the Ras GTPase family.
Article
Biochemistry & Molecular Biology
Jung Mi Park, Seung Wook Yang, Wei Zhuang, Asim K. Bera, Yan Liu, Deepak Gurbani, Sergei J. von Hoyningen-Huene, Sadie Miki Sakurada, Haiyun Gan, Shondra M. Pruett-Miller, Kenneth D. Westover, Malia B. Potts
Summary: Nutrient-responsive protein kinase SRMS inhibits autophagy and promotes growth in vertebrates, and is amplified in human cancers. Inhibition of SRMS kinase activates autophagy, inhibits cancer growth, and can be achieved using the FDA-approved tyrosine kinase inhibitor ibrutinib.
Article
Chemistry, Organic
Sudershan R. Gondi, Althaf Shaik, Kenneth D. Westover
Summary: A new method for synthesizing substituted quinazolin-dione-N-3-alkyl derivatives from isatin was reported, which is low-cost and scalable, suitable for the synthesis of various derivatives with medicinal uses.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Lianbo Li, Cynthia Meyer, Zhi-Wei Zhou, Ammar Elmezayen, Kenneth Westover
Summary: Allosteric mechanisms are common in nature but rare in human-designed perturbagens. The development of KRAS(G12C) inhibitors suggests that covalent chemistry could expand the use of allosteric inhibitors. This study explores the feasibility of extending this approach to other proteins in the RAS and kinase family, which play important roles in cellular processes, especially in cancer therapy.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Nora-Guadalupe P. Ramirez, Jeon Lee, Yue Zheng, Lianbo Li, Bryce Dennis, Didi Chen, Ashwini Challa, Vicente Planelles, Kenneth D. Westover, Neal M. Alto, Ivan D'Orso
Summary: This study revealed an undescribed modulator, ADAP1, that influences the fate of HIV-1 provirus. The experimental results showed that ADAP1 can enhance T cell signaling and facilitate the escape of latent HIV-1 by activating the ERK-AP-1 axis.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Eric J. Hsu, Jameson T. Mendel, Kristin A. Ward, Mariam El-Ashmawy, Minjae Lee, Hak Choy, Kenneth D. Westover, Dat T. Vo, Robert D. Timmerman, David J. Sher, Puneeth Iyengar
Summary: This study analyzed the treatment outcomes of 90 patients with T1-2 non-small cell lung cancer who received five-fraction stereotactic ablative radiotherapy (SABR). The results identified the clinical parameters predictive of treatment failures with these regimens, providing guidance for treatment selection.
ADVANCES IN RADIATION ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Zhengnian Li, Ryosuke Ishida, Yan Liu, Jinhua Wang, Yina Li, Yang Gao, Jie Jiang, Jianwei Che, Jason M. Sheltzer, Matthew B. Robers, Tinghu Zhang, Kenneth D. Westover, Behnam Nabet, Nathanael S. Gray
Summary: This study describes a medicinal chemistry campaign to identify a CDK11 inhibitor. Through structure-guided medicinal chemistry modifications, a CDK11 probe ZNL-05-044 with improved selectivity was identified, which can arrest cell cycle and impact CDK11-dependent gene splicing in cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kari Kopra, Salla Valtonen, Randa Mahran, Jonas N. Kapp, Nazia Hassan, William Gillette, Bryce Dennis, Lianbo Li, Kenneth D. Westover, Andreas Plueckthun, Harri Harma
Summary: Thermal unfolding methods are commonly used to predict protein's thermal stability and to screen potential drugs. Differential scanning calorimetry is considered the gold standard, but other methods like differential scanning fluorimetry are also used. These methods have relatively low sensitivity. By comparing three thermal stability probes, researchers found that the Protein-Probe is more sensitive and can work at lower concentrations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Wenchao Lu, Yao Liu, Yang Gao, Qixiang Geng, Deepak Gurbani, Lianbo Li, Scott B. Ficarro, Cynthia J. Meyer, Dhiraj Sinha, Inchul You, Jason Tse, Zhixiang He, Wenzhi Ji, Jianwei Che, Audrey Y. Kim, Tengteng Yu, Kenneth Wen, Kenneth C. Anderson, Jarrod A. Marto, Kenneth D. Westover, Tinghu Zhang, Nathanael S. Gray
Summary: In this study, the researchers discovered a specific inhibitor, YL5084, which demonstrates selectivity for JNK2 over JNK1. YL5084 forms a covalent bond with Cys116 of JNK2 and exhibits higher K-inact/K-I than JNK1. However, YL5084 also shows JNK2-independent antiproliferative effects in multiple myeloma cells, suggesting the presence of additional targets in this context. Although not fully optimized, YL5084 represents a useful chemical starting point for developing JNK2-selective chemical probes in the future.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Cynthia Meyer, Melissa McCoy, Lianbo Li, Bruce Posner, Kenneth D. Westover
Summary: Measurements of kinase activity are crucial for drug development and understanding drug resistance mechanisms. A label-free, high-throughput mass spectrometry-based assay is described for studying individual kinase enzymology and drug discovery. This approach is adaptable to various kinase substrates and offers increased sensitivity. It has the potential for research on understudied kinases and kinase drug discovery.
CELL REPORTS PHYSICAL SCIENCE
(2023)
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
J. Visak, B. Cai, M. Lin, A. Pompos, A. Godley, P. Iyengar, C. Park, K. Westover
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
J. Wu, J. Lin, A. Pompos, D. Sher, K. Westover, R. Timmerman, S. Jiang, Y. Yan
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
Y. Gonzalez, B. Meng, D. Parsons, B. Hrycushko, T. Zhuang, B. Cai, Y. Zhang, K. Westover, P. Iyengar, A. Godley, S. Jiang, M. Lin
Article
Oncology
Jiehui Deng, Aatish Thennavan, Igor Dolgalev, Ting Chen, Jie Li, Antonio Marzio, John T. Poirier, David H. Peng, Mirna Bulatovic, Subhadip Mukhopadhyay, Heather Silver, Eleni Papadopoulos, Val Pyon, Cassandra Thakurdin, Han Han, Fei Li, Shuai Li, Hailin Ding, Hai Hu, Yuanwang Pan, Vajira Weerasekara, Baishan Jiang, Eric S. Wang, Ian Ahearn, Mark Philips, Thales Papagiannakopoulos, Aristotelis Tsirigos, Eli Rothenberg, Justin Gainor, Gordon J. Freeman, Charles M. Rudin, Nathanael S. Gray, Peter S. Hammerman, Michele Pagano, John V. Heymach, Charles M. Perou, Nabeel Bardeesy, Kwok-Kin Wong
Summary: The study found that LKB1-deficient lung tumors are sensitive to autophagy inhibition, which can restore impaired antigen presentation and antitumor immune responses, enhancing the effectiveness of PD-1 immunotherapy. Additionally, LKB1 deficiency inhibits antigen processing and presentation, but this can be reversed by targeting the autophagy pathway to restore immunoproteasome activity and antigen presentation.