Review
Cell Biology
Julian M. Rozenberg, Olga S. Rogovaya, Gerry Melino, Nickolai A. Barlev, Alexander Kagansky
Summary: p63 and p73 cooperate in genome stability surveillance, with specific interactors contributing to transcriptional repression and spindle assembly checkpoint for p73, and mRNA processing and splicing regulation for p63. This analysis reveals the diversification of RNA and DNA specific functions within the p53 family.
Review
Cell Biology
Kyra Laubach, Jin Zhang, Xinbin Chen
Summary: The p53 family of tumor suppressors, including p53, p63, and p73, play critical roles in various biological processes such as cell cycle arrest, apoptosis, differentiation, development, multiciliogenesis, and fertility. This review focuses on the roles of p53, p63, and p73 in lipid and iron metabolism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Genetics & Heredity
Li Lei, Qixiong Lu, Guifang Ma, Tao Li, Jiahong Deng, Weijia Li
Summary: P53 protein, derived from the P53 gene, is a well-known tumor suppressor gene. Its function and mechanisms in anti-neoplasms have been studied for many years. While previous research has largely focused on other organs and systems, recent studies have indicated that P53 also plays a significant role in CNS tumors, cerebral stroke, and neurodegenerative diseases. This review aims to summarize the research achievements on the relationship between P53 and CNS diseases, providing new insights for future studies.
FRONTIERS IN GENETICS
(2023)
Review
Biochemistry & Molecular Biology
Ignacija Vlasic, Andela Horvat, Ana Tadijan, Neda Slade
Summary: Metastatic melanoma, a highly aggressive tumor, is often characterized by mutations in the MAPK pathway, particularly in the protein kinase BRAF. However, resistance to BRAF inhibitors is a major obstacle in melanoma treatment, with the reactivation of MAPK or PI3K/AKT pathways and the involvement of the p53 pathway contributing to acquired resistance. In melanoma, the canonical tumor suppressor p53 is frequently inactivated through various mechanisms. The TP53 gene and its family members TP63 and TP73 encode multiple protein isoforms with diverse functions in tumorigenesis. Some p53 isoforms are expressed in melanoma cells and have been shown to play specific roles in proliferation, survival, metastasis, invasion, migration, and treatment response. Particularly, p53 isoforms involved in acquired resistance to MAPK inhibitors present potential therapeutic targets to overcome resistance in melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Kiyohiro Ando, Akira Nakagawara
Summary: The RUNX family plays a crucial role in neural crest cell differentiation and may also be involved in neuroblastoma tumorigenesis. Its function in tumor development can vary depending on the specific context, including the response to chemotherapy. In primary neuroblastomas, RUNX3 acts as a tumor suppressor, while RUNX1 regulates cell proliferation in a dual manner influenced by genetic and epigenetic factors, including MYCN. This review focuses on the mechanism through which the RUNX family regulates neurotrophin receptors (Trk family) associated with neuroblastoma aggressiveness, as well as their potential involvement in functional alterations of the p53 family members in neuroblastoma tumorigenesis. Understanding the contribution of the RUNX family to neuroblastoma tumorigenesis is crucial for future molecular-based therapies.
Article
Oncology
Yuanzheng Yang, Zhanglong Peng, Elsa R. Flores, Eugenie S. Kleinerman
Summary: Outcomes for patients with osteosarcoma have remained stagnant for more than 3 decades, and the search for novel therapeutic agents is crucial. This study shows that Pramlintide, an FDA-approved drug for type 2 diabetes, may have potential efficacy against osteosarcoma by interfering with tumor glycolysis and leading to decreased cell growth and increased cell death. Injection of Pramlintide into osteosarcoma tumor nodules resulted in significantly smaller tumors, indicating its potential as a novel therapeutic approach for relapsed osteosarcoma patients.
Article
Biochemistry & Molecular Biology
Emine Guven-Maiorov, Nozomi Sakakibara, Roshini M. Ponnamperuma, Kun Dong, Hector Matar, Kathryn E. King, Wendy C. Weinberg
Summary: Members of the p53 family, including p53, p63, and p73, share high homology but can be activated differently and have distinct roles in different tissues. By predicting interaction partners and modeling their 3D structures, we gain insights into the functions and mechanisms of these family members.
MOLECULAR CARCINOGENESIS
(2022)
Review
Biochemistry & Molecular Biology
Bi-He Cai, Yun-Chien Hsu, Fang-Yu Yeh, Yu-Rou Lin, Rui-Yu Lu, Si-Jie Yu, Jei-Fu Shaw, Ming-Han Wu, Yi-Zhen Tsai, Ying-Chen Lin, Zhi-Yu Bai, Yu-Chen Shih, Yi-Chiang Hsu, Ruo-Yu Liao, Wei-Hsin Kuo, Chao-Tien Hsu, Ching-Feng Lien, Chia-Chi Chen
Summary: p53 family members p53, p63, and p73 have tumor suppressor function, but p53 has a high mutation rate in cancers causing loss of its function. This review discusses drug therapies for nonsense and missense mutations in p53, and proposes p63 and p73 activators as potential anti-cancer drugs to replace mutant p53. Strategies to improve the response of these activators, particularly for p53 gain-of-function mutants, are also discussed.
Review
Cell Biology
Zhiyuan Ning, Ying Liu, Daji Guo, Wei-Jye Lin, Yamei Tang
Summary: This article reviews the basic knowledge of NK cell biology and recent advances in their roles in the healthy CNS and pathological conditions. The authors highlight the interactions between NK cells and diverse cell types in the CNS, as well as the potential value of NK cells as novel therapeutic targets for CNS diseases.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Rami Abou Zeinab, H. Helena Wu, Yasser Abuetabh, Sarah Leng, Consolato Sergi, David D. Eisenstat, Roger P. Leng
Summary: Pirh2, a member of the RING-H2 family, has been identified as a key regulator of AIP4, inhibiting p73 function by downregulating AIP4 expression and ubiquitinating it. Despite AIP4's role in promoting p73 ubiquitination and degradation, Pirh2's interaction can disrupt the AIP4-p73 negative regulatory pathway and maintain p73 cell cycle arrest function.
Article
Multidisciplinary Sciences
Jacob Haagsma, Bart Kolendowski, Adrian Buensuceso, Yudith Ramos Valdes, Gabriel E. DiMattia, Trevor G. Shepherd
Summary: Ovarian high-grade serous carcinoma (HGSC) is a lethal malignancy with early detection and late-stage treatment challenges. This study developed an in vitro model of HGSC based on a TP53 mutation in mouse oviductal epithelial cells. The results showed that cells expressing missense mutant p53(R175H) had increased spheroid survival and anchorage-independent growth, and highlighted the potential anti-apoptosis gain-of-function mechanism of p53(R175H).
SCIENTIFIC REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Sandeep Kaur, Manabu Kurokawa
Summary: Apoptosis is a crucial process in maintaining cellular balance and development in the ovarian reserve. While a large number of oocytes are generated in the fetal ovary, most of them undergo apoptosis before birth. During puberty, primordial follicles develop into mature follicles, but only one dominant follicle is selected for ovulation, while smaller ones undergo apoptosis. The molecular mechanism of oocyte death is still not fully understood, despite extensive studies. This review discusses the roles of apoptosis regulators and the transcription factor p63 in oocyte death and survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Priyanka Joshi, Akansha Bisht, Sushil Joshi, Deepak Semwal, Neelesh Kumar Nema, Jaya Dwivedi, Swapnil Sharma
Summary: Curcumin, a compound isolated from turmeric, has strong antioxidant and anti-inflammatory potential, making it a promising therapeutic candidate for various disorders. Studies have shown that curcumin can ameliorate neurodegenerative diseases by improving mitochondrial dysfunction, inflammation, oxidative stress, and apoptosis-mediated neural cell degeneration, through the modulation of various molecular pathways.
PHYTOTHERAPY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Guanglin Niu, Isabel Hellmuth, Tatiana Flisikowska, Hubert Pausch, Beate Rieblinger, Alexander Carrapeiro, Benjamin Schade, Brigitte Boehm, Eva Kappe, Konrad Fischer, Bernhard Klinger, Katja Steiger, Reiner Burgkart, Jean-Christophe Bourdon, Dieter Saur, Alexander Kind, Angelika Schnieke, Krzysztof Flisikowski
Summary: The mutation in TP53 gene in pig models leads to the development of tumors like osteosarcoma, pointing out similarities with human TP53. Specific TP53 isoforms determine the tumor spectrum in pigs, with circTP53 playing a critical role in malignant transformation.
Article
Pathology
Giovanni Micheloni, Marta Carnovali, Giorgia Millefanti, Manuel Rizzetto, Vittoria Moretti, Giuseppe Montalbano, Francesco Acquati, Cristina Giaroni, Roberto Valli, Lucy Costantino, Fulvio Ferrara, Giuseppe Banfi, Massimo Mariotti, Giovanni Porta
Summary: The study shows that a soy-dependent diet negatively affects intestinal morphology and immune function in adult zebrafish, leading to acute inflammation and potentially initiating chronic inflammation. Adult zebrafish may serve as a promising model to explore the mechanisms of food-dependent intestinal inflammation.
INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY
(2022)
Review
Oncology
Chengsen Chai, H. Helena Wu, Yasser Abuetabh, Consolato Sergi, Roger Leng
Summary: This review focuses on the role and regulation of PTEN in triple-negative breast cancer (TNBC). PTEN inactivation is associated with aggressive tumor phenotype and plays a crucial role in negatively regulating cell proliferation and migration. The review provides a summary of genomic alterations of PTEN, discusses the transcriptional regulation and posttranslational modifications of PTEN, and explores the prospects of PTEN protein in TNBC.
Article
Cell Biology
Benfan Wang, H. Helena Wu, Yasser Abuetabh, Sarah Leng, Sandra T. Davidge, Elsa R. Flores, David D. Eisenstat, Roger Leng
Summary: The study reveals that p63 isoforms physically interact with and stabilize Ago2, thereby regulating its dual functions in tumor progression. MiR-144 activates p63 by directly targeting p63's E3 ligase Itch, enhancing its tumor suppressor function and inhibiting cell invasion.
CELL DEATH & DISEASE
(2022)
Article
Surgery
Joseph de Nanassy, David Mack, Marcos Bettolli, Consolato M. Sergi
Summary: We report a case of a pediatric patient with Crohn disease who presented with a non-Meckel diverticulum in the colonic wall of the cecum. This is the first report of such a diverticulum in a child with Crohn disease and we examine the underlying mechanics. The diverticulum formed at the site of maximum stricture and weakest point in the bowel wall due to the inflammatory bowel disease. The time interval between diagnosis of ileocecal stricture and surgery was important for the development of this diverticulum. Continued follow-up in adulthood is necessary due to the increased risk of intestinal diverticular disease and neoplasms in patients with Crohn disease.
JOURNAL OF SURGICAL CASE REPORTS
(2022)
Article
Religion
Consolato M. Sergi, Tomy Mullur
Summary: Despite advancements in technology and medical care, the reasons for perinatal loss can still remain a mystery. It is important for medical professionals to prioritize culturally sensitive discussions, but religious and spiritual beliefs often get overlooked. This article highlights the significance of spiritual and theological responses in helping parents cope with stillbirth and emphasizes the critical role of chaplains in supporting both families and physicians.
JOURNAL OF PASTORAL CARE & COUNSELING
(2022)
Letter
Medicine, General & Internal
Consolato M. Sergi
ARCHIVES OF MEDICAL SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Jong Hoon Lee, Badar Kanwar, Asif Khattak, Jenny Balentine, Ngoc Huy Nguyen, Richard E. Kast, Chul Joong Lee, Jean Bourbeau, Eric L. Altschuler, Consolato M. Sergi, Tuan Ngoc Minh Nguyen, Sangsuk Oh, Mun-Gi Sohn, Michael Coleman
Summary: SARS-CoV-2 induces immune-mediated type 1 interferon production, which leads to exacerbated interferonopathies. Aspirin inhibits cGAS-mediated signaling to regulate immune response. Additionally, aspirin and dapsone inhibit the activation of IFN-1 and NF-kappa B by targeting cGAS. Timely alleviation of the pathologic course is necessary for immune cell reactions and viral clearance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Irene Donato, Kiran K. Velpula, Andrew J. Tsung, Jack A. Tuszynski, Consolato M. Sergi
Summary: This study proposes a mathematical and computational approach to diagnose neuroblastoma by calculating image entropy, fractal dimension, and lacunarity. The method is able to automatically predict tumor malignancy and may challenge the current classification of neuroblastoma.
Article
Medicine, Research & Experimental
H. Helena Wu, Sarah Leng, Yasser Abuetabh, Consolato Sergi, David D. Eisenstat, Roger Leng
Summary: The tumor suppressor p53 is crucial in cancer pathogenesis and maintaining normal cell growth by regulating p53 expression. UBE4B is an E3/E4 ubiquitin ligase involved in a negative-feedback loop with p53, playing a role in its degradation. Therefore, targeting the p53-UBE4B interaction is a promising strategy for anticancer therapy. In this study, we found that the UBE4B U box does not bind to p53 but is essential for its degradation. Certain mutants of UBE4B lose their ability to degrade p53, and a SWIB/Hdm2 motif of UBE4B is vital for p53 binding. Furthermore, a novel UBE4B peptide activates p53 functions by blocking the p53-UBE4B interaction, suggesting a new approach for p53 activation therapy in cancer.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Review
Medicine, General & Internal
Josef Hager, Consolato M. Sergi
Summary: Factors such as population migration, tourism, dog translocations, and poor hygiene practices contribute to the spread of echinococcosis. Prompt diagnosis of cystic echinococcosis (CE) should be considered when a cyst-like mass is found in the liver or lung of individuals with a history of exposure to sheepdogs in endemic areas. Routine imaging techniques and serologic investigations are used for detection and confirmation. Treatment options for pediatric echinococcosis include drug therapy and surgical interventions.
Editorial Material
Medicine, General & Internal
Consolato M. Sergi
Summary: Road accidents involving dangerous chemical compounds pose a hazard to public health worldwide. This commentary briefly reviews a recent event in East Palestine, Ohio and discusses one of the chemicals involved, which has a predisposition to initiate a carcinogenic process. The author, as a consultant for the International Agency for Research on Cancer, has reviewed numerous chemical compounds.
Review
Medicine, General & Internal
Consolato M. Sergi, Deborah Spencer, Taher Al-Jishi
Summary: This article summarizes the most frequent findings discussed at multidisciplinary team (MDT) meetings, including pathological findings of stillbirth and the importance of the placenta.
JOURNAL OF LABORATORY PHYSICIANS
(2023)
Letter
Obstetrics & Gynecology
Consolato M. Sergi, Tomy Mullur
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
(2023)
Article
Toxicology
A. Khan, J. Feulefack, C. M. Sergi
Summary: This study conducted a systematic review and meta-analysis to establish the potential link between parental pesticide exposure and the occurrence of Wilms' tumor in children. The findings suggest that there is a correlation between exposure to organophosphate compounds and an increased risk of pediatric cancer, emphasizing the need for stronger action by public health agencies.
HUMAN & EXPERIMENTAL TOXICOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yasser Abuetabh, H. Helena Wu, Chengsen Chai, Habib Al Yousef, Sujata Persad, Consolato M. Sergi, Roger Leng
Summary: This article discusses the role of tumor suppressor protein p53 in response to DNA damage, as well as the proteins and pathways that interact with it. A deeper understanding of this network could reveal new targets for cancer therapy.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
