Review
Biology
Julian M. Rozenberg, Svetlana Zvereva, Aleksandra Dalina, Igor Blatov, Ilya Zubarev, Daniil Luppov, Alexander Bessmertnyi, Alexander Romanishin, Lamak Alsoulaiman, Vadim Kumeiko, Alexander Kagansky, Gerry Melino, Carlo Ganini, Nikolai A. Barlev
Summary: During oncogenesis, cells undergo unrestricted proliferation, altering tissue homeostasis and possibly due to dysregulation of p53 family proteins p63 and p73. While p63 and p73 can compensate for loss of p53 in some cases, their overlap with p53 functions is strongest in regulating p53-dependent gene expression. Surprisingly, p73 is rarely lost or mutated in cancers, with its inactive isoforms often overexpressed and promoting cancer growth by repressing cell death mediated by p73.
Article
Multidisciplinary Sciences
Kyra Nicole Laubach, Wensheng Yan, Xiangmudong Kong, Wenqiang Sun, Mingyi Chen, Jin Zhang, Xinbin Chen
Summary: p73 alpha 1 plays a critical role in tumor suppression and the inflammatory response via regulation of Notch1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Rinka Nakajima, Reika Deguchi, Hideyuki Komori, Lin Zhao, Yaxuan Zhou, Mashiro Shirasawa, Arlene Angelina, Yasuko Goto, Fumiya Tohjo, Kengo Nakahashi, Kimi Nakata, Ritsuko Iwanaga, Andrew P. Bradford, Keigo Araki, Tomoko Warita, Kiyoshi Ohtani
Summary: The TFDP1 gene codes for the heterodimeric partner DP1 of the transcription factor E2F, which plays important roles in cell proliferation. Over-expression of E2F1 and inactivation of the tumor suppressor pRB induce TFDP1 gene expression, suggesting that TFDP1 is a target of E2F. Serum stimulation also induces TFDP1 expression, but with different kinetics compared to other E2F target genes. The TFDP1 promoter contains E2F1-responsive elements, and mutation of GC-rich elements reduces E2F1 responsiveness. Knockdown of DP1 expression enhances ARF gene expression, indicating that TFDP1 activation by deregulated E2F may function as a feedback mechanism to suppress deregulated E2F activity and maintain normal cell growth.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Chinami Matsumoto, Hitomi Sekine, Nana Zhang, Sachiko Mogami, Naoki Fujitsuka, Hiroshi Takeda
Summary: Chemotherapy-induced sarcopenia is a negative prognostic factor that affects postoperative complications and quality of life in cancer patients. Cisplatin, a commonly used chemotherapy drug, causes skeletal muscle loss by affecting mitochondrial function and activating muscle-specific ubiquitin ligases Atrogin-1 and muscle RING finger 1 (MuRF1). Although p53 has been implicated in muscle atrophy, it is unclear if it plays a role in cisplatin-induced atrophy. This study investigated the effect of a p53-specific inhibitor, pifithrin-alpha (PFT-a), on cisplatin-induced muscle atrophy in C2C12 myotubes. The results showed that cisplatin increased p53 levels and upregulated the expression of p53 target genes in C2C12 myotubes. PFT-a reduced reactive oxygen species production, mitochondrial dysfunction, and the increase in the Bax/Bcl-2 ratio induced by cisplatin. However, PFT-a did not ameliorate the decrease in muscle protein synthesis. Overall, this study suggests that cisplatin-induced muscle degradation is p53-dependent, but p53 has minimal involvement in the reduction of muscle protein synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Alanna B. Chan, Gian Carlo G. Parico, Jennifer L. Fribourgh, Lara H. Ibrahim, Michael J. Bollong, Carrie L. Partch, Katja A. Lamia
Summary: Disruption of circadian rhythms can increase the risk of various cancers. Mutations in the CRY2 gene found in human cancers have been shown to accelerate cell growth in mouse fibroblasts expressing high levels of c-MYC. These mutations also have divergent effects on circadian rhythms and interaction with SCFFBXL3.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Keisuke Omori, Shohei Otani, Yuki Date, Tomoya Ueno, Tomoko Ito, Masahiro Umeda, Kosei Ito
Summary: Osteosarcoma is a disease in humans characterized by TP53 mutations. In mice, loss of p53 triggers OS development, and osteoprogenitor-specific p53-deleted mice are widely used to study the process of osteosarcomagenesis. However, the molecular mechanisms underlying the initiation or progression of OS following or parallel to p53 inactivation remain largely unknown. This study reveals a novel tumor suppressive mechanism mediated by C/ebp alpha in p53-deficient osteosarcomagenesis, highlighting the importance of the Runx-Myc oncogenic axis as a therapeutic target for OS.
Article
Nanoscience & Nanotechnology
Cong Wu, Zhiming Shen, Yi Lu, Fei Sun, Hongcan Shi
Summary: This study demonstrates that Fe3O4 nanoparticles can induce ferroptosis in macrophages and elucidates the molecular mechanisms involved in this process. It provides important theoretical insights into the impact of nanoparticles on macrophages and their associated biotoxicity.
ACS APPLIED MATERIALS & INTERFACES
(2022)
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.
Article
Cell Biology
Christian Osterburg, Marco Ferniani, Dario Antonini, Ann-Sophie Frombach, Ludovica D'Auria, Susanne Osterburg, Rebecca Lotz, Frank Loehr, Sebastian Kehrloesser, Huiqing Zhou, Caterina Missero, Volker Doetsch
Summary: This study investigated the impact of known mutations in the p63 DNA binding domain (DBD) associated with developmental syndromes. Four different mechanisms of DNA binding impairment were identified, including direct DNA contact, zinc finger region, H2 region, and dimer interface mutations. Unlike p53 cancer mutations, no p63 mutation induces global unfolding and aggregation of the domain. Dimer interface mutations, which affect DNA binding affinity, retain partial DNA binding capacity and correlate with milder patient phenotypes.
CELL DEATH & DISEASE
(2023)
Article
Engineering, Biomedical
Zaofeng Yang, Marianne M. M. Lee, Michael K. Chan
Summary: The study demonstrates that Pos3Aa crystals can serve as an efficient vehicle for delivering proteins into cells, reversing the inactivation of potential cancer therapeutics and making them more sensitive to chemotherapy drugs.
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
Chemistry, Multidisciplinary
Mingyuan Wang, Qiong Huang, Min Liu, Tianjiao Zhao, Xiangping Song, Qiaohui Chen, Yongqi Yang, Yayun Nan, Zerun Liu, Yuntao Zhang, Wei Wu, Kelong Ai
Summary: Increased incidence of inflammatory bowel disease (IBD) has negatively impacted patients' quality of life. The authors developed a novel oral nanomedicine (OPEN) that inhibits excessive intestinal epithelial cell apoptosis, providing a new strategy for comprehensive IBD therapy.
ADVANCED MATERIALS
(2023)
Article
Medicine, Research & Experimental
Katherine E. Redd Bowman, Lisa Ahne, Liam O'Brien, Erica R. Vander Mause, Phong Lu, Bryce Wallis, Kimberley J. Evason, Carol S. Lim
Summary: Due to the limited curative treatments and high death rate of hepatocellular carcinoma (HCC), there is a need for new therapies. This study explores the potential of re-engineering p53 through fusion with the pro-apoptotic BH3 protein Bad, leading to the development of p53-Bad* as a novel HCC therapeutic. The results demonstrate that p53-Bad* can effectively target mitochondria in liver cancer cell lines, exhibit superior apoptotic activity compared to wild-type p53, and reduce tumor burden in a zebrafish HCC model.
MOLECULAR PHARMACEUTICS
(2023)
Review
Chemistry, Multidisciplinary
Jerson L. Silva, Debora Foguel, Vitor F. Ferreira, Tuane C. R. G. Vieira, Mayra A. Marques, Giulia D. S. Ferretti, Tiago F. Outeiro, Yraima Cordeiro, Guilherme A. P. de Oliveira
Summary: Biomolecular condensates, arising from liquid-liquid phase separation, have dual roles in health and disease. This review focuses on their role in cancer, particularly in relation to the p53 tumor suppressor. Mutations in the TP53 gene, present in over half of malignant tumors, have significant implications for future cancer treatment strategies. Targeting the phase transitions of mutant p53 offers a promising direction for innovative cancer diagnostics and therapeutics.
Article
Multidisciplinary Sciences
Stephanie Hasapis, Isibel Caraballo, Timothy J. Sears, Kennedy D. Brock, John B. Cart, Everett J. Moding, Chang-Lung Lee
Summary: The transcription factor p53 plays a crucial role in controlling the toxicity and malignant transformation of hematopoietic cells induced by genotoxic stress. The gene Phlda3 is robustly induced by radiation and its role in response to radiation in hematopoietic cells is unknown.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Mark V. Mishra, Eli D. Scher, Jocelyn Andrel, Andrew C. Margules, Sarah E. Hegarty, Edouard J. Trabulsi, Terry Hyslop, Robert B. Den, Costas D. Lallas, Leonard G. Gomella, Adam P. Dicker, Timothy N. Showalter
AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS
(2015)
Article
Oncology
Kevin L. Moore, Rachel Schmidt, Vitali Moiseenko, Lindsey A. Olsen, Jun Tan, Ying Xiao, James Galvin, Stephanie Pugh, Michael J. Seider, Adam P. Dicker, Walter Bosch, Jeff Michalski, Sasa Mutic
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2015)
Article
Oncology
Robert B. Den, Kasra Yousefi, Edouard J. Trabulsi, Firas Abdollah, Voleak Choeurng, Felix Y. Feng, Adam P. Dicker, Costas D. Lallas, Leonard G. Gomella, Elai Davicioni, R. Jeffrey Karnes
JOURNAL OF CLINICAL ONCOLOGY
(2015)
Article
Oncology
Jeffrey S. Weber, Laura A. Levit, Peter C. Adamson, Suanna Bruinooge, Howard A. Burris, Michael A. Carducci, Adam P. Dicker, Mithat Goenen, Stephen M. Keefe, Michael A. Postow, Michael A. Thompson, David M. Waterhouse, Susan L. Weiner, Lynn M. Schuchter
JOURNAL OF CLINICAL ONCOLOGY
(2015)
Article
Oncology
Mario Crittenden, Holbrook Kohrt, Ronald Levy, Jennifer Jones, Kevin Camphausen, Adam Dicker, Sandra Demaria, Silvia Formenti
SEMINARS IN RADIATION ONCOLOGY
(2015)
Article
Oncology
Kosj Yamoah, Curtiland Deville, Neha Vapiwala, Elaine Spangler, Charnita M. Zeigler-Johnson, Bruce Malkowicz, David I. Lee, Michael Kattan, Adam P. Dicker, Timothy R. Rebbeck
UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
(2015)
Review
Engineering, Biomedical
Nicholas George Zaorsky, Mark D. Hurwitz, Adam P. Dicker, Timothy N. Showalter, Robert B. Den
EXPERT REVIEW OF MEDICAL DEVICES
(2015)
Article
Multidisciplinary Sciences
Sarah E. Hegarty, Terry Hyslop, Adam P. Dicker, Timothy N. Showalter
Article
Multidisciplinary Sciences
Jennifer Mason Lobo, Adam P. Dicker, Christine Buerki, Elai Daviconi, R. Jeffrey Karnes, Robert B. Jenkins, Nirav Patel, Robert B. Den, Timothy N. Showalter
Article
Health Care Sciences & Services
Christine Tran, Adam Dicker, Benjamin Leiby, Eric Gressen, Noelle Williams, Heather Jim
JOURNAL OF MEDICAL INTERNET RESEARCH
(2020)
Article
Oncology
Heather S. L. Jim, Sarah L. Eisel, Aasha Hoogland, Sandra Shaw, Jennifer C. King, Adam P. Dicker
Summary: Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, but few studies have evaluated patient-reported outcomes (PROs) outside clinical trials. This study assessed PROs in lung cancer registry participants treated with ICIs, revealing worse quality of life and higher rates of adverse events than previously reported.
Review
Oncology
Rahul Banerjee, Nina Shah, Adam P. Dicker
Summary: CAR-T therapy is a paradigm-shifting immunotherapy in oncology, but unique toxicities limit its wider implementation. Digital innovations may improve toxicity monitoring, management, and supportive care. Applying digital tools to CAR-T therapy implementation could enhance its safety and accessibility.
JCO CLINICAL CANCER INFORMATICS
(2021)
Article
Oncology
Nathan R. Handley, Kuang-Yi Wen, Sameh Gomaa, Kelly Brassil, Ayako Shimada, Benjamin Leiby, Lindsey Jackson, Michael McMorris, Anne Calvaresi, Adam P. Dicker
Summary: Digital health coaching for men with prostate cancer is feasible, supporting further evaluation in larger randomized controlled trials.
JCO ONCOLOGY PRACTICE
(2022)
Article
Oncology
Christina I. Tsien, Stephanie L. Pugh, Adam P. Dicker, Jeffrey J. Raizer, Martha M. Matuszak, Enrico C. Lallana, Jiayi Huang, Ozer Algan, Nimisha Deb, Lorraine Portelance, John L. Villano, John T. Hamm, Kevin S. Oh, Arif N. Ali, Michelle M. Kim, Scott M. Lindhorst, Minesh P. Mehta
Summary: This study evaluated whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS) compared to BEV alone in recurrent glioblastoma (GBM). The results showed that the combination of re-RT and BEV significantly improved PFS, but had no difference in OS.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Joanne B. Weidhaas, Chen Hu, Ritsuko Komaki, Gregory A. Masters, George R. Blumenschein, Joe Y. Chang, Bo Lu, Adam P. Dicker, Jeffrey A. Bogart, Yolanda I. Garces, Samir Narayan, Clifford G. Robinson, Vivek S. Kavadi, Joel S. Greenberger, Christopher D. Koprowski, James Welsh, Elizabeth M. Gore, Robert M. Macrae, Rebecca Paulus, Jeffrey D. Bradley
Summary: Although overall survival advantage was not observed in KRAS-variant patients, there is a potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy.
CANCER RESEARCH COMMUNICATIONS
(2023)