Article
Multidisciplinary Sciences
Alyssa M. Klein, Lynn Biderman, David Tong, Bita Alaghebandan, Sakina A. Plumber, Helen S. Mueller, Anne van Vlimmeren, Chen Katz, Carol Prives
Summary: This study suggests that MDM2 and MDMX may play a p53-independent role in maintaining cell-cycle progression by affecting the activity of E2F family members and p73, making them a potential target of interest in cancers lacking wild-type p53.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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.
Article
Medicine, General & Internal
Sahar Javadi, Yue Li, Jie Sheng, Lucy Zhao, Yao Fu, Daifeng Wang, Xinyu Zhao
Summary: Transient Nutlin-3 treatment can prevent neurogenesis and cognitive deficits in mature adult FXS mice, potentially through modulating the adult neurogenic niche.
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
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
Shin-Yi Chung, Yi-Ping Hung, Yi-Ru Pan, Yu-Chan Chang, Chiao-En Wu, Dennis Shin-Shian Hsu, Peter Mu-Hsin Chang, Meng-Lun Lu, Chi-Ying F. Huang, Yeu Su, Michael Hsiao, Chun-Nan Yeh, Ming-Huang Chen
Summary: The study demonstrates a positive correlation between ALDH1A3 and malignant behavior of cholangiocarcinoma, and suggests that ruxolitinib may suppress ALDH1A3 activation through the JAK2/STAT1/3 pathway, leading to reduced cell migration abilities and tumor size in cholangiocarcinoma.
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
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)
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
Oncology
Konstantina Psatha, Laxmikanth Kollipara, Elias Drakos, Elena Deligianni, Konstantinos Brintakis, Eustratios Patsouris, Albert Sickmann, George Z. Rassidakis, Michalis Aivaliotis
Summary: The activation of wild-type p53 protein in human lymphoma is a promising therapeutic strategy. An in vitro integrative comparative multi-omics analysis of different lymphoma types before and after p53 activation can shed light on the molecular mechanisms involved. Our findings provide valuable insights into the role of specific proteins and pathways in lymphoma pathogenesis and the global effect of nutlin-3a, which can guide targeted studies on lymphoma progression and resistance.
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)
Review
Biochemistry & Molecular Biology
Neha Bhatia, Rakesh Khator, Swanand Kulkarni, Yogesh Singh, Pradeep Kumar, Suresh Thareja
Summary: The discovery of MDM2 and MDM2-p53 interaction inhibitors has revolutionized anticancer research due to their involvement in about 50% of cancer cases globally. In addition to inhibiting MDM2, targeting the interaction between MDM2 and p53 has proven to be an effective strategy for anticancer drug development. Both natural and synthetic molecules have shown promising MDM2 inhibitory potential. This review focuses on the pathophysiology of the MDM2-p53 interaction loop, characteristics of the active site, and the efficacy of various inhibitors from recent patents.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Bente A. Somsen, Fenna W. B. Craenmehr, Wei-Hong W. Liu, Auke A. Koops, Marloes A. M. Pennings, Emira J. Visser, Christian Ottmann, Peter J. Cossar, Luc Brunsveld
Summary: Molecular glues represent a novel approach in drug discovery, however, the targeted stabilization of protein complexes is still challenging due to a lack of drug design rules. This study demonstrates the successful development of a peptide-based molecular glue that selectively stabilizes the 14-3-3/ChREBP protein-protein interaction by utilizing the functional mapping of hotspots.
Article
Pharmacology & Pharmacy
Giada Lodi, Valentina Gentili, Fabio Casciano, Arianna Romani, Giorgio Zauli, Paola Secchiero, Enrico Zauli, Carolina Simioni, Silvia Beltrami, Mercedes Fernandez, Roberta Rizzo, Rebecca Voltan
Summary: SARS-CoV viruses downregulate antiviral defenses by manipulating p53, a key molecule for cell homeostasis and immune control. Using MDM2 inhibitors to raise p53 levels can inhibit cell cycle and virus release, as well as reduce the expression of inflammatory cytokines. Therefore, p53 and MDM2 inhibitors may be potential therapies against SARS-CoV-2.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Public, Environmental & Occupational Health
Manida Suksawat, Jutarop Phetcharaburanin, Poramate Klanrit, Nisana Namwat, Narong Khuntikeo, Attapon Titapun, Apiwat Jarearnrat, Vanlakhone Vilayhong, Prakasit Sa-ngiamwibool, Anchalee Techasen, Arporn Wangwiwatsin, Panupong Mahalapbutr, Jia V. Li, Watcharin Loilome
Summary: This study used metabolomics to analyze the metabolic characteristics in tissues and sera of CCA patients, and identified predictive biomarkers for gemcitabine and cisplatin sensitivity. These biomarkers can not only predict chemotherapy response, but also minimize the adverse effects of chemotherapy.
FRONTIERS IN PUBLIC HEALTH
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Meng Zhou, Dan Shan, Chunhui Zhang, Jianhua Nie, Guangyu Wang, Yanqiao Zhang, Yang Zhou, Tongsen Zheng
Summary: This study found that imaging features of hepatobiliary phase in Gd-EOB-DTPA-MRI, such as rim enhancement, capsule enhancement, arterial halo sign and hepatobiliary features, were associated with the occurrence of microvascular invasion (MVI) in small hepatocellular carcinoma (sHCC). The morphology of hepatobiliary phase imaging, especially the spicule sign, showed high accuracy in diagnosing MVI of sHCC. Rim enhancement was a significant predictor of MVI in sHCC diagnosis.
BMC MEDICAL IMAGING
(2021)
Article
Cell Biology
Mingjiao Weng, Yukuan Feng, Yan He, Weiwei Yang, Jing Li, Yuanyuan Zhu, Tianzhen Wang, Chuhan Wang, Xiao Zhang, Yu Qiao, Qi Li, Lingyu Zhao, Shuangshu Gao, Lei Zhang, Yiqi Wu, Ran Zhao, Guangyu Wang, Zhiwei Li, Xiaoming Jin, Tongsen Zheng, Xiaobo Li
Summary: Hypoxia induces the production of LIN28A mRNA but segregates it into P-bodies, inhibiting LIN28A protein expression. Non-coding LIN28A mRNA promotes colon cancer cell metastasis by up-regulating METAP2 expression, independently of LIN28A protein, indicating a distinctive role of hypoxia in manipulating metastasis and proliferation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Jianhua Nie, Dan Shan, Shun Li, Shuyuan Zhang, Xiaolin Zi, Fan Xing, Jiaqi Shi, Caiqi Liu, Tianjiao Wang, Xiaoyuan Sun, Qian Zhang, Meng Zhou, Shengnan Luo, Hongxue Meng, Yanqiao Zhang, Tongsen Zheng
Summary: The study established a prognosis model related to ferroptosis in colon cancer, consisting of five genes, which could predict survival of CC patients to a certain degree. High- and low-risk patients had significant differences in survival probability, and immune status was also found to be distinct between the two groups, with potential implications for further research on the crosstalk between ferroptosis and immune responses.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Jiaqi Shi, Caiqi Liu, Shengnan Luo, Tingyu Cao, Binlin Lin, Meng Zhou, Xiao Zhang, Song Wang, Tongsen Zheng, Xiaobo Li
Summary: The combination therapy of STING agonist diABZI and IDO inhibitor 1-MT shows significant inhibition of tumor growth in CRC, leading to increased recruitment of immune cells and decreased infiltration of suppressor cells. This combination therapy holds promise as a potential option for the treatment of CRC.
CELLULAR IMMUNOLOGY
(2021)
Article
Oncology
Guangyu Wang, Dandan Xu, Zicheng Zhang, Xinhui Li, Jiaqi Shi, Jie Sun, Huan-Zhong Liu, Xiaobo Li, Meng Zhou, Tongsen Zheng
Summary: This study reveals the complex interplay between EMT and immune evasion, as well as their significant impact on tumor behavior and clinical outcomes. Quantitative analysis identified factors associated with the balance between EMT and immune evasion, such as cellular composition, mutation burden, chromosomal stability, and oncogenic gene alterations. The proposed EMT-CYT Index (ECI) scoring model emerged as a superior predictor of prognosis and immunotherapy response across different malignancies.
NPJ PRECISION ONCOLOGY
(2021)
Correction
Oncology
Lisha Li, Dongfeng Song, Ling Qi, Mingxia Jiang, Yiming Wu, Junqing Gan, Kui Cao, Yanjing Li, Yuxian Bai, Tongsen Zheng
Review
Biochemistry & Molecular Biology
Shun Li, Ruisi Na, Xuehan Li, Yanqiao Zhang, Tongsen Zheng
Summary: Although immune checkpoint inhibitors have gained attention in cancer management, only a minority of patients benefit from them, especially those with immunologically cold tumors. IL-17 could be a potential target to increase tumor cell sensitivity to ICIs. This review highlights the role of IL-17 in ICIs resistance and summarizes the clinical evidence for combination therapy.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Article
Gastroenterology & Hepatology
Xiaoyuan Sun, Huijun Chu, Ke Lei, Yandong Ci, Haijun Lu, Jia Wang, Meng Zhou, He Ren, Tongsen Zheng
Summary: In this study, the roles of GPR120 in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) were investigated. It was found that GPR120 was highly expressed in PDAC tissues and its activation led to promotion of proliferation inhibition, apoptosis, EMT, and angiogenesis in PDAC.
Article
Biochemical Research Methods
Jiaqi Shi, Caiqi Liu, Shengnan Luo, Yingying Zhang, Mingwei Li, Meng Zhou, Mingjiao Weng, Xiaobo Li, Tongsen Zheng
Summary: In this article, a protocol for detecting two STING isoforms in human peripheral blood mononuclear cells or mouse splenocytes using Western blot and PCR is presented. The steps for constructing plasmids encoding each isoform and transferring them into mouse and human cell lines are described. Finally, the detection of cell membrane localization of pmSTING using flow cytometry, immunoprecipitation, and immunofluorescence is explained. This protocol is suitable for proteins with well-predicted topological structures. For complete details, please refer to Li et al.1.
Article
Biochemistry & Molecular Biology
Meng Zhou, Ruisi Na, Shihui Lai, Ying Guo, Jiaqi Shi, Jianhua Nie, Shuyuan Zhang, Yuan Wang, Tongsen Zheng
Summary: Biliary tract cancer (BTC) is a highly malignant tumor originating from the bile duct epithelium. Interleukin-6 (IL-6) plays a pivotal role in the development and progression of BTC, serving as a clinical biomarker for diagnosis and prognosis. Preclinical evidence suggests that IL-6 antibodies may enhance the efficacy of immune checkpoint inhibitors (ICIs) by modulating the tumor microenvironment. However, more research is needed to determine the potential of IL-6 antibodies in overcoming resistance to ICIs in BTC.
Meeting Abstract
Oncology
Shanzhi Gu, Yulin Tan, Huan Zhou, Hongtao Hu, Tongsen Zheng, Zhendong Zheng, Xu Zhu, Mu Yuan
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Tongsen Zheng, Xianzhi Meng, JiaBei Wang, Xi Chen, Dalong Yin, Yingjian Liang, Xuan Song, Shangha Pan, Hongchi Jiang, LianXin Liu
JOURNAL OF CELLULAR BIOCHEMISTRY
(2022)
Article
Surgery
Ruifeng Wang, Zhen Quan, Tongsen Zheng, Kai Wang, Yang Liu, Zhaoguo Han, Xiance Wang, Shiling Ma, Lianxin Liu, Wan Yee Lau, Xilin Sun
Summary: This study used multiple imaging methods to assess the pathophysiological mechanisms of the future liver remnant (FLR) and tumors after the first stage of ALPPS. Changes in tumor volume, metabolism, and hemodynamics were observed. Molecular and functional imaging are promising non-invasive methods for investigating the pathophysiological mechanisms of ALPPS.
BRITISH JOURNAL OF SURGERY
(2022)
Article
Medicine, Research & Experimental
Xiaobo Li, Yuanyuan Zhu, Xiao Zhang, Xiang An, Mingjiao Weng, Jiaqi Shi, Song Wang, Caiqi Liu, Shengnan Luo, Tongsen Zheng
Summary: The study reveals the signaling mechanism of STING base cGAMP in activating anti-tumor immune response. It identifies an alternatively spliced STING isoform, pmSTING, which can sense extracellular cGAMP on the plasma membrane and promote interferon production through interaction with TBK1 and IRF3.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Gastroenterology & Hepatology
Caiqi Liu, Yuan Wang, Jiaqi Shi, Chunhui Zhang, Jianhua Nie, Shun Li, Tongsen Zheng
Summary: Helicobacter pylori (HP) is a major pathogenic factor in diseases such as chronic gastritis, peptic ulcer, and gastric cancer. Increasing antibiotic resistance rates have affected the eradication rate of commonly used therapies. Emerging treatment regimens, such as bismuth-containing quadruple therapy and concomitant therapy, have shown acceptable eradication rates and safety, but drug resistance remains a challenge to be addressed.
THERAPEUTIC ADVANCES IN GASTROENTEROLOGY
(2021)