Article
Biotechnology & Applied Microbiology
Heon Seok Kim, Susan M. Grimes, Tianqi Chen, Anuja Sathe, Billy T. Lau, Gue-Ho Hwang, Sangsu Bae, Hanlee P. Ji
Summary: This study developed a high-throughput, multiplexed single-cell technology called TISCC-seq to engineer mutations in cells using CRISPR base editors and determine their genotype and transcriptional phenotype. Through engineering and evaluating TP53 mutations, the study classified these mutations based on their single-cell gene expression.
NATURE BIOTECHNOLOGY
(2023)
Article
Genetics & Heredity
Muhammad Sarfaraz Iqbal, Iram Mehboob, Saba Khaliq, Nimra Sardar, Shahid Sherzada, Qurban Ali
Summary: This study found a significant association between MDM2 SNP309 polymorphism and increased risk of thyroid cancer in the Pakistani population.
CYTOLOGY AND GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Chen-Yi Liao, Shun-Fa Yang, Ting-Jian Wu, Han Chang, Chi-Ying F. Huang, Yu-Fan Liu, Chi-Hsiang Wang, Jhong-Chio Liou, Shih-Lan Hsu, Huei Lee, Gwo-Tarng Sheu, Jinghua Tsai Chang
Summary: This study reveals that lung cancer risk is associated with PERP genotypes, with individuals carrying PERP-428CC having the highest risk. PERP-428C can modulate the expression of antioxidant enzymes via regulating p53 protein stability, thus affecting redox status and increasing the risk of lung cancer.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Pathology
Samir Abdullazade, Hans-Michael Behrens, Sandra Krueger, Jochen Haag, Christoph Roecken
Summary: The study validated gene amplification, protein expression, and tumor biological function of MDM2 in gastric cancer, and found a significant correlation between MDM2 amplification and protein expression. However, MDM2 amplification and expression were not associated with patient survival.
Article
Chemistry, Medicinal
Shuai Wang, Fen-Er Chen
Summary: Inhibition of the MDM2-p53 protein-protein interaction using small-molecule inhibitors is a promising strategy for cancer therapy. Many highly potent and selective small-molecule MDM2 inhibitors have been discovered and are currently undergoing different clinical trials. This review provides an overview of the function of MDM2 and the identification, optimization, preclinical, and clinical studies of clinical-stage MDM2 inhibitors. It also discusses challenges, potential toxicity, and future perspectives, which will guide the design of new small-molecule MDM2 inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Yuan Yin, Zhiyuan Jiang, Jiamei Fu, Yang Li, Chao Fang, Xiaonan Yin, Ye Chen, Na Chen, Junshu Li, Yanhong Ji, Xiaolan Su, Meng Qiu, Wei Huang, Bo Zhang, Hongxin Deng, Lei Dai
Summary: The study reveals the expression and function of SLC5 family members in colorectal cancer, showing that downregulation of SLC5A7 correlates with CRC staging and prognosis response. Overexpression of SLC5A7 inhibits CRC growth by promoting p53 protein expression, suggesting a potential therapeutic target for CRC.
Article
Medicine, Research & Experimental
Jialiang Zheng, Fenglin Miao, Zhao Wang, Yuan Ma, Zhenhang Lin, Yaqin Chen, Xu Kong, Yue Wang, Aobo Zhuang, Ting Wu, Wengang Li
Summary: This study conducted a comprehensive analysis of the role of MDM2 in human cancer and found that MDM2 is a reliable prognostic biomarker closely related to cancer immunity, providing a potential immunotherapeutic target for breast cancer, bladder cancer, and ovarian cancer.
Article
Biochemistry & Molecular Biology
Chrisanta Harakandi, Lauraine Nininahazwe, Haiwei Xu, Bingrui Liu, Chenghua He, Yi-Chao Zheng, Hang Zhang
Summary: The USP7-MDM2-p53 network plays a crucial role in regulating p53 and cancer development, with inhibiting USP7 and MDM2 proteins reactivating the p53 signaling pathway leading to cell cycle arrest and apoptosis.
BIOORGANIC CHEMISTRY
(2021)
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
Mu Yun, Li Yingzi, Gao Jie, Liu Guanxin, Zeng Zimei, Cao Zhen, Li Zhi, Nie Yingjie, Sun Lunquan, Chen Tao, Deng Yuezhen, Zhou Chengzhi
Summary: This study found that the upregulation of PPDPF in NSCLC correlated with poor overall survival. PPDPF promoted the growth, colony formation, and invasion of lung cancer cells. Mechanistically, it interacted with BABAM2, blocking its ubiquitination and stabilizing BABAM2, leading to radioresistance in lung cancer cells.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Nayeong Koo, Arun K. Sharma, Satya Narayan
Summary: p53 is a tumor suppressor that regulates cell function through various mechanisms. Researchers aim to reactivate p53 and induce cancer cell death by developing drugs that target the p53-MDM2 interaction, and have identified potential antagonists.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Neha Merchant, Sai Samyuktha Bandaru, Afroz Alam, L. V. K. S. Bhaskar
Summary: This study conducted a meta-analysis to examine the link between MDM2 SNP and HCC. The results showed that MDM2 SNP309 T > G polymorphism elevated the vulnerability of HCC in Asian and Caucasian populations but not among the African population.
Article
Biotechnology & Applied Microbiology
Reham Helwa, Liv B. Gansmo, Merete Bjornslett, Mari Kylleso Halle, Henrica M. J. Werner, Pal Romundstad, Kristian Hveem, Lars Vatten, Anne Dorum, Per E. Lonning, Stian Knappskog
Summary: The study found that the MDM2 SNP55T allele may be associated with a reduced risk of endometrial cancer when combined with the SNP309TT genotype, but not in the context of SNP309G. Additionally, the SNP55T allele was also associated with a reduced risk of endometrial cancer in individuals under 50 years old, regardless of the genotype in neighboring SNPs. No association was observed between SNP55 status and ovarian cancer risk.
Article
Cell Biology
Xiaohua Huang, Bin Wang, Runji Chen, Shuping Zhong, Fenfei Gao, Yanmei Zhang, Yongdong Niu, Congzhu Li, Ganggang Shi
Summary: The study aimed to assess the mechanism of FXR in cervical cancer and found that FXR reduces cell viability, induces apoptosis, and promotes cell cycle arrest. FXR inhibits cervical cancer by upregulating SHP, MDM2, and p53.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Peng Wang, Huajian Zhu, Jianmin Liu, Shaowen Xie, Shengtao Xu, Yu Chen, Jing Xu, Yuqing Zhao, Zheying Zhu, Jinyi Xu
Summary: Protopanoxadiol, an active ingredient derived from Panax ginseng, has shown anti-tumor activity. A new series of AD-1 derivatives were designed and synthesized using PROTAC technology, aiming to improve the limited efficacy of AD-1. One representative compound, A05, exhibited potent anti-proliferative activity against A549 cells and was able to disrupt the interactions between p53 and MDM2, leading to apoptotic death. In vivo assays further demonstrated that compound A05 had anti-proliferative and anti-metastatic activities in a zebrafish tumor xenograft model. These findings suggest that AD-1 based PROTACs targeting MDM2 degradation have promising effects for lung cancer treatment.
BIOORGANIC CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Reham Helwa, Liv B. Gansmo, Merete Bjornslett, Mari Kylleso Halle, Henrica M. J. Werner, Pal Romundstad, Kristian Hveem, Lars Vatten, Anne Dorum, Per E. Lonning, Stian Knappskog
Summary: The study found that the MDM2 SNP55T allele may be associated with a reduced risk of endometrial cancer when combined with the SNP309TT genotype, but not in the context of SNP309G. Additionally, the SNP55T allele was also associated with a reduced risk of endometrial cancer in individuals under 50 years old, regardless of the genotype in neighboring SNPs. No association was observed between SNP55 status and ovarian cancer risk.
Article
Genetics & Heredity
B. Liv Gansmo, A. Benedicte Lie, Marthe T. Maehlen, Lars Vatten, Pal Romundstad, Kristian Hveem, Per E. Lonning, Stian Knappskog
Summary: The study found a potential association between the MDM2 del1518 variant and the risk of rheumatoid arthritis, as well as indications that combinational genotypes and haplotypes in the MDM2 locus may be related to rheumatoid arthritis.
Article
Clinical Neurology
Petter C. Borchgrevink, Mari Glette, Astrid Woodhouse, Stephen Butler, Tormod Landmark, Pal Romundstad, Ola Dale, Tore C. Stiles, Kaare H. Bonaa, Dagfinn Thorsvik, Sabina Thunte, Stein Kaasa
Summary: The purpose of this study was to provide a comprehensive overview, distribution, and ranking of chronic pain conditions in the general population. The findings showed that a higher proportion of participants had chronic pain based on clinical examination compared to self-report in a survey. Among those with examination-verified chronic pain, the majority had chronic primary pain, musculoskeletal pain, and multiple chronic pain conditions. The study also revealed that two-thirds of chronic pain conditions could not be explained by underlying diseases. The most prevalent chronic pain conditions were nonspecific low back pain and neck pain. There was no significant difference in psychopathology between participants with chronic primary pain and chronic secondary pain. Therefore, this study highlights the importance of addressing chronic pain as a public health issue and focusing on prevention and rehabilitation.
Article
Endocrinology & Metabolism
Bjorn-Erik Bertelsen, Kristin Viste, Thomas Helland, Magnus Hagland, Havard Soiland, Jurgen Geisler, Tone Hoel Lende, Per Eystein Lonning, Jorn Sagen, Gunnar Mellgren, Bjorg Almas
Summary: This study developed a liquid chromatography-tandem mass spectrometry (MS/MS) method for simultaneous measurement of serum levels of third-generation aromatase inhibitors (AIs) and ultra-low levels of estrogens. The method is highly valuable for studying drug efficacy and compliance.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Clinical Neurology
Ilari Rautalin, Jaakko Kaprio, Tor Ingebrigtsen, Pekka Jousilahti, Maja-Lisa Lochen, Pal Richard Romundstad, Veikko Salomaa, Anne Vik, Tom Wilsgaard, Ellisiv B. Mathiesen, Marie Sandvei, Miikka Korja
Summary: The study suggests that a lower body mass index (BMI) is associated with an increased risk of subarachnoid hemorrhage (SAH), while a higher BMI is not significantly associated with SAH risk. However, the increased risk of low BMI is only present in smokers and hypertensive men, but not in nonsmokers or men with normal blood pressure. Therefore, smoking and hypertension may have a modifying effect on the previously reported inverse association between BMI and SAH risk.
Article
Multidisciplinary Sciences
Liv B. Gansmo, Nigar Sofiyeva, Merete Bjornslett, Pal Romundstad, Kristian Hveem, Lars Vatten, Anne Dorum, Per E. Lonning, Stian Knappskog
Summary: The germline deletion of APOBEC3A/B is associated with a reduced risk of ovarian cancer, particularly in non-serous and serous cases. Validation from an independent dataset shows similar trends, with a significant risk reduction observed in clear cell cancers.
SCIENTIFIC REPORTS
(2021)
Article
Cardiac & Cardiovascular Systems
Abigail Fraser, Amanda R. Markovitz, Eirin B. Haug, Julie Horn, Pal Richard Romundstad, Havard Dalen, Janet Rich-Edwards, Bjorn Olav Asvold
Summary: Women with a history of obstetric complications have an increased risk of cardiovascular disease, but there is currently no recommendation to specifically target them for CVD screening. However, pregnancy complications can identify women who would benefit from primordial and primary prevention efforts in later life.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Paulina Majewska, Marie Softeland Sandvei, Sasha Gulati, Tomm B. Mueller, Karen Walseth Hara, Pal Richard Romundstad, Ole Solheim
Summary: This study aimed to assess the return to work after the treatment of unruptured intracranial aneurysms (UIAs). A nationwide registry-based study was conducted in Norway from 2008 to 2018, including adult patients of working age with a record of sickness leave on the day of treatment. The results showed that patients who underwent endovascular treatment returned to work earlier compared to those treated with surgical clipping.
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
(2023)
Article
Oncology
Nigar Sofiyeva, Camilla Krakstad, Mari K. Halle, Tracy A. O'Mara, Pal Romundstad, Kristian Hveem, Lars Vatten, Per E. Lonning, Liv B. Gansmo, Stian Knappskog
Summary: The APOBEC3A/B deletion variant is associated with a decreased risk of endometrial cancer in Norwegian women.
Article
Oncology
Cecilie Fredvik Torkildsen, Liv Cecilie Vestrheim Thomsen, Ragnar Kvie Sande, Camilla Krakstad, Ingunn Stefansson, Eva Karin Lamark, Stian Knappskog, Line Bjorge
Summary: In this study, phenotypic markers were combined with targeted DNA sequencing to discover novel biomarkers for guiding surgical management in high-grade serous ovarian carcinoma (HGSOC) patients. The study highlights the potential of a preoperative risk stratification model combining phenotypic traits and single-gene mutational status in predicting surgical outcomes.
Article
Cardiac & Cardiovascular Systems
Marie Klevjer, Humaira Rasheed, Pal R. Romundstad, Erik Madssen, Ben M. Brumpton, Anja Bye
Summary: This study used Mendelian randomization to explore the causal association between resting heart rate (RHR) and atrial fibrillation (AF), and found an inverse causal relationship between them, especially when RHR was below 90 beats per minute. The results challenge the current observational knowledge on RHR and AF.
