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
Oncology
Irene Veneziani, Paola Infante, Elisa Ferretti, Ombretta Melaiu, Cecilia Battistelli, Valeria Lucarini, Mirco Compagnone, Carmine Nicoletti, Aurora Castellano, Stefania Petrini, Marzia Ognibene, Annalisa Pezzolo, Lucia Di Marcotullio, Roberto Bei, Lorenzo Moretta, Vito Pistoia, Doriana Fruci, Vincenzo Barnaba, Franco Locatelli, Loredana Cifaldi
Summary: The study demonstrated that Nutlin-3a could enhance NK cell-mediated killing of neuroblastoma cells by restoring p53 function and increasing ligand expression for NK-ARs. Adoptive transfer of human NK cells into neuroblastoma-bearing mice resulted in tumor shrinkage and improved overall survival. Nutlin-3a also boosted NK cell-mediated cytotoxicity against neuroblastoma spheroids by increasing ligand expression in primary neuroblastoma cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Physics, Multidisciplinary
Han Zhou, Yi-Zhao Geng, Shi-Wei Yan
Summary: P53 is a tumor suppressor protein that regulates various cellular processes. It is negatively regulated by MDM2, which inhibits its activity. Inhibitors like Nutlin-3a can disrupt the interaction between p53 and MDM2, leading to the activation of p53 pathway and inhibition of tumor growth.
ACTA PHYSICA SINICA
(2023)
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
Oncology
Dasom Kim, Dongwha Min, Joohee Kim, Min Jung Kim, Yerim Seo, Byung Hwa Jung, Seung-Hae Kwon, Hyunju Ro, Seoee Lee, Jason K. Sa, Ji-Yun Lee
Summary: In this study, nutlin-3a, an MDM2 antagonist, was found to inhibit the KRAS-PI3K/Akt-mTOR pathway and disrupt the fusion of autophagosomes and macropinosomes with lysosomes. This led to a non-apoptotic and catastrophic macropinocytosis-like cell death, which was dependent on GFPT2 of the hexosamine biosynthetic pathway in KRAS mutant/p53 wild type NSCLC cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
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)
Review
Pharmacology & Pharmacy
Jincheng Yang, Lirui Jia, Zhonggui He, Yongjun Wang
Summary: DNA topoisomerase I plays a vital role in DNA replication and RNA transcription. Camptothecin and its derivatives are known to inhibit topoisomerase I and have shown clinical benefits in cancer treatment. However, the compound 7-ethyl-10-hydroxycamptothecin (SN-38), which has potent cytotoxicity, has some undesirable properties that hinder effective delivery to tumor sites. This article reviews strategies to address these issues, including basic nanodrug delivery systems like nanoparticles, liposomes, and micelles, as well as functionalized nanodrug delivery systems, prodrugs, active targeted nanodrug delivery systems, and systems designed to overcome drug resistance. The challenges of formulation development and clinical translation of SN-38 drug delivery systems are discussed.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Toxicology
Hong-Gyu An, Sangyun Shin, Boyoung Lee, Yeonju Kwon, Tae-Uk Kwon, Yeo-Jung Kwon, Young-Jin Chun
Summary: The study compares the cytotoxic effects of TMS and Nutlin-3a individually and in combination in HeLa cells. It demonstrates that the combination treatment exerts a synergistic effect on cancer cell death by increasing pro-apoptotic factors and promoting translocation of apoptosis-inducing factors. This suggests that the combination of TMS and Nutlin-3a could be a novel therapeutic strategy for cervical cancer.
TOXICOLOGICAL 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
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
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
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
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
Immunology
Chiara Focaccetti, Monica Benvenuto, Chiara Pighi, Alessandra Vitelli, Federico Napolitano, Nicola Cotugno, Doriana Fruci, Paolo Palma, Paolo Rossi, Roberto Bei, Loredana Cifaldi
Summary: Adoptive transfer of engineered NK cells has become an important clinical approach for cancer treatment. This study aimed to improve the clinical efficacy and safety of NK cell-based immunotherapy through the development of new strategies. Human NK cells expressing DNAM-1 or DNAM-1-based chimeric receptors were generated, and their functionality was evaluated. The results showed that DNAM-1-CD3 zeta-engineered NK cells exhibited the strongest response, and the combination with Nutlin-3a could enhance the therapeutic effect for solid tumors carrying dysfunctional p53.
FRONTIERS IN IMMUNOLOGY
(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
Xinlei Li, Scott D. Smid, Jun Lin, Zhihong Gong, Si Chen, Fangning You, Yan Zhang, Zhilong Hao, Hongzheng Lin, Xiaomin Yu, Xinyi Jin
Article
Pharmacology & Pharmacy
Carly Eggers, Masaya Fujitani, Ryuji Kato, Scott Smid
BIOCHEMICAL PHARMACOLOGY
(2019)
Article
Multidisciplinary Sciences
Carla Claser, Samantha Yee Teng Nguee, Akhila Balachander, Shanshan Wu Howland, Etienne Becht, Bavani Gunasegaran, Siddesh V. Hartimath, Audrey W. Q. Lee, Jacqueline Theng Theng Ho, Chee Bing Ong, Evan W. Newell, Julian Goggi, Lai Guan Ng, Laurent Renia
NATURE COMMUNICATIONS
(2019)
Correction
Multidisciplinary Sciences
Carla Claser, Samantha Yee Teng Nguee, Akhila Balachander, Shanshan Wu Howland, Etienne Becht, Bavani Gunasegaran, Siddesh V. Hartimath, Audrey W. Q. Lee, Jacqueline Theng Theng Ho, Chee Bing Ong, Evan W. Newell, Julian Goggi, Lai Guan Ng, Laurent Renia
NATURE COMMUNICATIONS
(2019)
Review
Neurosciences
Graziella dos Reis Rosa Franco, Scott Smid, Claudio Viegas Jr
Summary: Research into Cannabis and its constituent phytocannabinoids has shown potential applications in the treatment of neurodegenerative diseases, while novel cannabis phytochemicals could be promising alternatives for disease treatment.
CURRENT NEUROPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Amelia Jerram, Thomas V. Guy, Lucinda Beutler, Bavani Gunasegaran, Ronald Sluyter, Barbara Fazekas de St Groth, Helen M. McGuire
Summary: The study found that storing blood samples at room temperature before PBMC preparation had a more positive impact on cell yield compared to refrigeration. Room temperature storage led to co-purification of low density neutrophils with PBMCs, but did not affect the proportions of multiple cell subsets significantly.
BIOSCIENCE REPORTS
(2021)
Review
Food Science & Technology
S. Shrestha, W. Zhang, S. D. Smid
Summary: Phlorotannins are polyphenolic compounds mainly found in brown seaweed, with a range of bioactivities including neuroprotective, antidiabetic, anticancer properties. Current research is mainly based on biochemical and cell-based assays, highlighting the need for further preclinical and clinical studies to investigate their bioavailability, efficacy and safety.
Article
Immunology
Yang Cheng, Bavani Gunasegaran, Harsimran D. Singh, Charles-Antoine Dutertre, Chiew Yee Loh, Jia Qi Lim, Jeremy Chase Crawford, Hong Kai Lee, Xiaomeng Zhang, Bernett Lee, Etienne Becht, Wan Jun Lim, Joe Yeong, Chung Yip Chan, Alexander Chung, Brian K. P. Goh, Pierce K. H. Chow, Jerry K. Y. Chan, Florent Ginhoux, David Tai, Jinmiao Chen, Seng Gee Lim, Weiwei Zhai, Su Pin Choo, Evan W. Newell
Summary: The study revealed that hepatocellular carcinoma patients have multiple antigen-specific T cells, with HBV-specific CD8(+) Trm cells potentially playing a crucial role in tumor control. These non-terminally exhausted cells exhibit characteristics of active involvement and effective antitumor response.
Article
Plant Sciences
John Staton Laws III, Scott D. Smid
Summary: This review evaluated the neuroprotective potential of Cannabis sativa's active constituents for potential therapeutic use in dementia and Alzheimer's disease, emphasizing the significance of cannabis components as a novel treatment approach.
Article
Biochemistry & Molecular Biology
Dylan T. Marsh, Scott D. Smid
Summary: This study investigated the intestinal epithelial barrier-protective and antioxidant capacity of the novel flavonoid 2-D08 in chemotherapy-induced gastrointestinal mucositis (GIM). The results showed that 2-D08 effectively inhibited the increase in epithelial permeability induced by SN-38 and cytokines, while transilitin and myricetin had lesser barrier protective roles, unrelated to their antioxidant capacity.
Review
Chemistry, Multidisciplinary
Dylan T. Marsh, Scott D. Smid
Summary: This review discusses the relationship between the phytochemical diversity of cannabis and its neuroprotective properties, as well as the potential effects of selected phytocannabinoids and other cannabis phytochemicals on inflammation, oxidative stress, and neurodegenerative diseases.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Blagojce Jovcevski, Sukanya Das, Scott Smid, Tara Louise Pukala
ACS CHEMICAL NEUROSCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Srijan Shrestha, Wei Zhang, Alexander J. Begbie, Tara L. Pukala, Scott D. Smid
Article
Toxicology
Kathryn Page, Walter Westerink, Kristie Sullivan, Thomas McDonald, Clive Roper
Summary: This study developed a new method to assess the skin irritation of antimicrobial cleaning products. The method utilized a more human-like model and demonstrated its effectiveness through comparison with in vivo rabbit skin irritation data.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Arupam Patra, Thirukumaran Kandasamy, Siddhartha Sankar Ghosh, Gurvinder Kaur Saini
Summary: This study successfully produced recombinant anisoplin and demonstrated its significant anti-cancer effect and ability to induce apoptosis in breast cancer cells. The activation of related signaling pathways may be the key to cell death.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Thomas Haller, Alexander Jesacher, Alberto Hidalgo, Christina Schmidt
Summary: This study used live cell imaging to observe the accumulation of amiodarone in primary rat alveolar type II cells, and found that it specifically accumulates in lamellar bodies. The uptake is rapid, while storage is persistent. The main mechanisms for intracellular bioaccumulation of amiodarone are proposed to be passive diffusion, ion-trapping, and lipophilic interactions.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Filiz Bakar-Ates, Erva Ozkan
Summary: This study investigated the ferroptotic effect of CuB in breast cancer cells and evaluated its combination with erastin, a ferroptosis inducer. The results showed that the combination treatment significantly activated the ferroptotic pathways and altered the expression of iron-related proteins in breast cancer cells.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Rachel Z. Bennie, Ian C. Shaw
Summary: Estrogen mimics are synthetic and naturally occurring compounds that can interact with estrogen receptors in animals. In vitro transactivation reporter gene assay and in silico molecular modelling can be used to predict the mimicry of these compounds, reducing reliance on animal studies.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Sevda Isik, Semra Cicek
Summary: This study found that high doses of riboflavin can cause cytotoxicity in rainbow trout gonad cells and affect the transcriptional expressions of antioxidant enzymes and growth and reproductive genes, potentially leading to DNA damage and cell death.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Ying Wang, Jie Wu, Mengqi Wan, Dou Yang, Fasheng Liu, Kehao Li, Manxin Hu, Yuanyuan Tang, Huiqiang Lu, Shouhua Zhang, Yuanzhen Xiong
Summary: m-Cresol is commonly used as an intermediate for pesticides and other industrial applications. This study investigated the hepatotoxicity of m-cresol using zebrafish larvae and explored its molecular mechanisms. The results suggest that m-cresol may induce liver damage in zebrafish larvae through oxidative stress and cell apoptosis pathways.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Vincent J. Manna, Shannon Dwyer, Vanessa Pizutelli, Salvatore J. Caradonna
Summary: The widespread use of electronic cigarettes and the emergence of a new illness have raised concerns about the effects of e-cigarette vapor on respiratory tissues. Researchers have developed a simple device to mimic the response of human airway tissue after long-term exposure to e-cigarette vapor, and have identified differences in the effects of different vapor compositions on airway tissue.
TOXICOLOGY IN VITRO
(2024)