Article
Biochemistry & Molecular Biology
Susu Zhang, Jing Wang, Qi Liu, W. Hayes McDonald, Monica L. Bomber, Hillary M. Layden, Jacob Ellis, Scott C. Borinstein, Scott W. Hiebert, Kristy R. Stengel
Summary: Transcriptional control is a dynamic process that is challenging to study using traditional genetic methods. In this study, we used a chemical-genetic approach to quickly degrade the transcriptional activator PAX3-FOXO1 and investigated its mechanism of action. Our findings revealed that PAX3-FOXO1 is involved in regulating gene expression and maintaining chromatin accessibility and enhancer architecture.
Article
Genetics & Heredity
Line J. Manceau, Julien E. Richard Albert, Pier-Luigi J. Lollini, Maxim V. C. E. Greenberg, Pascale J. Gilardi-Hebenstreit, Vanessa E. Ribes
Summary: The chimeric proteins PAX3-FOXO1 and PAX7-FOXO1, derived from chromosomal translocations, exhibit distinct genomic occupancy and transcriptional activity, leading to different pathological manifestations in alveolar rhabdomyosarcoma.
Article
Oncology
Christine M. Heske, Yueh-Yun Chi, Rajkumar Venkatramani, Minjie Li, Michael A. Arnold, Roshni Dasgupta, Susan M. Hiniker, Douglas S. Hawkins, Leo Mascarenhas
Summary: In patients with localized, FOXO1 fusion-positive RMS, clinical factors such as age at diagnosis and tumor size can impact survival outcomes, with older age and larger tumors being adverse prognostic factors for EFS. Patients with both older age and large tumor size experience significantly inferior outcomes.
Article
Biochemistry & Molecular Biology
Qiande Hu, Liang Zhu, Yuan Li, Jianjun Zhou, Jun Xu
Summary: The study revealed that PAX3-FOXO1 inhibits ACTA1 expression at transcription and protein levels through the RhoA-MKL1-SRF signaling pathway, which may contribute to the tumorigenesis and development of ARMS. Overexpression of ACTA1 in RH30 cells was shown to inhibit cell proliferation and migration in vitro and impair tumor growth in vivo compared to the control groups.
CELL AND BIOSCIENCE
(2021)
Article
Biology
Carla Regina, Ebrahem Hamed, Geoffroy Andrieux, Sina Angenendt, Michaela Schneider, Manching Ku, Marie Follo, Marco Wachtel, Eugene Ke, Ken Kikuchi, Anton G. Henssen, Beat W. Schafer, Melanie Boerries, Amy J. Wagers, Charles Keller, Simone Hettmer
Summary: The study shows that heterogeneous expression of PAX3:FOXO1 at the single cell level in rhabdomyosarcoma cells may provide a critical advantage during tumor progression.
LIFE SCIENCE ALLIANCE
(2021)
Article
Multidisciplinary Sciences
Takuyo Kanayama, Mitsuru Miyachi, Yohei Sugimoto, Shigeki Yagyu, Ken Kikuchi, Kunihiko Tsuchiya, Tomoko Iehara, Hajime Hosoi
Summary: The study found that PAX3-FOXO1 is associated with B7-H3 in alveolar rhabdomyosarcoma, with PAX3-FOXO1 positively regulating B7-H3 expression. Both are involved in multiple pathways related to aggressiveness in ARMS, such as cell migration and myogenic differentiation.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Soeren S. Huettner, Henriette Henze, Dana Elster, Philipp Koch, Ursula Anderer, Bjoern von Eyss, Julia von Maltzahn
Summary: The expression levels of the transcriptional repressor TRPS1 are specifically enhanced in the embryonal subtype of rhabdomyosarcoma, resulting in impaired myogenic differentiation and tumor growth. Reduction of TRPS1 levels may be a therapeutic approach to drive embryonal rhabdomyosarcoma cells into myogenic differentiation.
Article
Cell Biology
Cooper D. Rutland, Jodi Gedallovich, Aihui Wang, Sabrina Zdravkovic, Sushama Varma, Jason L. Hornick, Gregory W. Charville
Summary: This study aimed to explore the diagnostic utility of FOXO1 immunohistochemistry for rhabdomyosarcoma classification. The findings suggest that FOXO1 immunohistochemistry is a highly sensitive and relatively specific surrogate marker of the PAX3/7::FOXO1 fusion oncoprotein in rhabdomyosarcoma.
Article
Cell Biology
Shivendra Singh, Ahmed Abu-Zaid, Hongjian Jin, Jie Fang, Qiong Wu, Tingting Wang, Helin Feng, Waise Quarni, Ying Shao, Lily Maxham, Alireza Abdolvahabi, Mi-Kyung Yun, Sivaraja Vaithiyalingam, Haiyan Tan, John Bowling, Victoria Honnell, Brandon Young, Yian Guo, Richa Bajpai, Shondra M. Pruett-Miller, Gerard C. Grosveld, Mark Hatley, Beisi Xu, Yiping Fan, Gang Wu, Eleanor Y. Chen, Taosheng Chen, Peter W. Lewis, Zoran Rankovic, Yimei Li, Andrew J. Murphy, John Easton, Junmin Peng, Xiang Chen, Ruoning Wang, Stephen W. White, Andrew M. Davidoff, Jun Yang
Summary: This study identifies KDM4B as a therapeutic vulnerability for PAX3-FOXO1(+) RMS. Inhibition of KDM4B delays tumor growth and suppresses the expression of core oncogenic transcription factors, causing epigenetic alterations of PAX3-FOXO1-governed superenhancers.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Matteo Cassandri, Silvia Pomella, Alessandra Rossetti, Francesco Petragnano, Luisa Milazzo, Francesca Vulcano, Simona Camero, Silvia Codenotti, Francesca Cicchetti, Roberto Maggio, Claudio Festuccia, Giovanni Luca Gravina, Alessandro Fanzani, Francesca Megiorni, Marialuigia Catanoso, Cinzia Marchese, Vincenzo Tombolini, Franco Locatelli, Rossella Rota, Francesco Marampon
Summary: The study evaluated the effects of MS-275 in combination with radiation therapy on RMS cells, showing that MS-275 could enhance radio-sensitivity and affect cell growth and DNA repair mechanisms through multiple pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Daniela Di Carlo, Cyrus Chargari, Jean-Yves Scoazec, Sophie Cotteret, Arthur Felix, Salma Moalla, Stephane Temam, Veronique Minard-Colin
Summary: Alveolar rhabdomyosarcoma (ARMS) is commonly associated with PAX3/PAX7-FOXO1 fusion gene, but some tumors without this fusion may have new molecular alterations. A rare case of PAX3-NCOA1 ARMS in a two-year-old girl with tongue and nodal extension was treated with a combination of therapies to preserve oral function and minimize long-term effects. International collaboration is necessary to evaluate the prognostic value of this variant fusion in ARMS.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Biochemistry & Molecular Biology
Tilman L. B. Hoelting, Florencia Cidre-Aranaz, Dana Matzek, Bastian Popper, Severin J. Jacobi, Cornelius M. Funk, Florian H. Geyer, Jing Li, Ignazio Piseddu, Bruno L. Cadilha, Stephan Ledderose, Jennifer Zwilling, Shunya Ohmura, David Anz, Annette Kuenkele, Frederick Klauschen, Thomas G. P. Gruenewald, Maximilian M. L. Knott
Summary: This study demonstrates the potential of utilizing chimeric fusion transcription factors for targeted gene therapy in cancer. By capitalizing on the DNA-binding preferences of these factors, the researchers were able to design a highly potent expression cassette that can express therapeutic genes in pediatric sarcomas. They also identified a specific cell surface antigen, GPR64, for targeted transduction strategies. The results showed that the designed expression cassette can specifically transduce cancer cells and promote the expression of therapeutic genes, resulting in strong anti-tumor effects. The study suggests that this approach could be applicable to other types of cancer addicted to oncogenic transcription factors.
Article
Oncology
Thomas Raze, Eve Lapouble, Brigitte Lacour, Sandra Guissou, Anne-Sophie Defachelles, Nathalie Gaspar, Olivier Delattre, Gaelle Pierron, Emmanuel Desandes
Summary: This study aimed to evaluate the impact of PAX-FOXO1 gene alterations on clinical outcomes in childhood and adolescence patients with ARMS. The study found that patients with PAX3-FOXO1 positive expression were older, had higher metastasis rates, and lower 5-year survival rates. Compared to patients with PAX7-FOXO1 positive and PAX-FOXO1 negative tumors, patients with PAX3-FOXO1 positive tumors had a higher risk of death.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Pathology
Anders Meyer, Natalie Klubickova, Elaheh Mosaieby, Petr Grossmann, Antonina Kalmykova, Olena Koshyk, Michael Michal
Summary: We present a case of a 67-year-old male patient with a sinonasal tumor that displayed classic biphenotypic sinonasal sarcoma (BSNS) and high-grade rhabdomyosarcoma. Immunohistochemistry showed different expression patterns in these two components. Molecular analysis confirmed the presence of the PAX3::MAML3 gene fusion. Despite aggressive treatment, the tumor progression led to the patient's death. This case, along with previous reports, contributes to the understanding of this rare phenomenon and its clinical implications.
Article
Medical Laboratory Technology
Rong Fan, David M. Parham, Larry L. Wang
Summary: This article summarizes the recent advances in molecular genetic alterations in rhabdomyosarcoma and introduces the differences in genotype and phenotype correlation as well as new subtypes. The current classification has been significantly influenced by genotype and phenotype correlation, recognizing that rhabdomyosarcoma is a group of histologically similar but biologically diverse entities.
ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
(2022)
Article
Oncology
Meghan E. McGrady, Donna Lemaster Bredenberg, Lara Danziger-Isakov, Julie Rios, Olivia Frias, Michelle Y. West, Paula Fisher, Ralph Salloum, Joseph G. Pressey, Robin E. Norris
Summary: There is a critical need to engage adolescents and young adults with cancer in conversations regarding safer sexual activity during treatment. This study describes how one pediatric institution assessed and addressed provider barriers to these discussions, and developed an educational handout detailing recommendations for safer sex practices for AYAs with cancer. The adoption, acceptability, appropriateness, and feasibility of the handout are discussed, along with barriers that other institutions may face when developing similar interventions.
JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY
(2021)
Article
Materials Science, Multidisciplinary
Geovani C. Resende, Guilherme A. S. Ribeiro, Orlando J. Silveira, Jessica S. Lemos, Juliana C. Brant, Daniel Rhodes, Luis Balicas, Mauricio Terrones, Mario S. C. Mazzoni, Cristiano Fantini, Bruno R. Carvalho, Marcos A. Pimenta
Summary: In this study, angle-dependent polarized Raman spectroscopy was used to investigate a single-layer triclinic ReSe2, revealing the physical origin of the complex nature of the Raman tensor elements through a new coordinate system. This understanding contributes to the development of new optoelectronic devices based on low-symmetry 2D materials by exploring electron-phonon coupling anisotropy.
Article
Radiology, Nuclear Medicine & Medical Imaging
Samjhana Thapaliya, Leah A. Gilligan, Samuel L. Brady, Christopher G. Anton, Eric J. Crotty, Michael P. Nasser, James Geller, Joseph G. Pressey, Bin Zhang, Jonathan R. Dillman, Andrew T. Trout
Summary: Reduced-dose CT demonstrates over 90% of lung nodules in children and young adults with cancer, with moderate sensitivity and high specificity in nodule detection. The study suggests that CT performed at a 0.3-mSv mean effective dose has acceptable diagnostic performance and potential to reduce patient dose or expand CT utilization in this population.
AMERICAN JOURNAL OF ROENTGENOLOGY
(2021)
Article
Oncology
Alina Sadaf, Sara Szabo, Katelyn Ferguson, Joel Sorger, Janos Sumegi, Julia A. Bridge, Joseph G. Pressey
Summary: A novel ARHGAP23-FER fusion was identified in a metastatic spindle-cell soft-tissue neoplasm, which exhibited a rapid and sustained metabolic response to the tyrosine kinase inhibitor lorlatinib.
Article
Oncology
Nawal Merjaneh, Jennifer Young, Avani Mangoli, Mallery Olsen, Bhuvana Setty, Adam Lane, Rajaram Nagarajan, Joseph G. Pressey, Brian Turpin
Summary: The study found that romiplostim may be beneficial in treating chemotherapy-induced thrombocytopenia in patients with Ewing sarcoma, with efficacy associated with higher drug doses. Radiation therapy had some impact on the occurrence of CIT, but other risk factors were not identified. Concurrent use of romiplostim with chemotherapy was found to be safe and feasible.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Medicine, General & Internal
Eman Al Atrash, Mohammad Fahed Abdullah, Joseph Pressey, Shyam Mohan
Summary: This case emphasizes the importance of proper examination of the stomach, as even in children with a normal appearance, serious medical conditions may be present.
Article
Oncology
Margot A. Lazow, Ralph Salloum, Joseph G. Pressey
Summary: This study found that adolescent and young adult patients with central nervous system tumors or sarcomas have a high burden of baseline comorbidities, which increase with age. These comorbidities contribute to treatment-related toxicity and mortality, highlighting the need for tailored therapeutic and supportive care based on individual comorbidities.
JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY
(2023)
Article
Oncology
Jo Cooke-Barber, Joseph G. Brungardt, Michael Sorger, Joseph G. Pressey, Brian Turpin, Rajaram Nagarajan, Sara Szabo, Joel Sorger, Neil Johnson, Roshni Dasgupta
Summary: This study aimed to evaluate the efficacy of image-guided percutaneous biopsy for pediatric patients with soft tissue and bony masses, and the role of intraoperative image guidance and diagnostic accuracy. The results showed that image-guided percutaneous biopsy is a safe and effective method for obtaining accurate tissue samples in children with soft tissue or bone tumors.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Upendra Kumar Soni, Yuhua Wang, Ram Naresh Pandey, Ryan Roberts, Joseph G. Pressey, Rashmi S. Hegde
Summary: This study analyzed the activation of receptor tyrosine kinase (RTK) pathway in Ewing sarcoma tumors and found that the tumors could be divided into two groups, one insensitive to IGF1R inhibition and the other sensitive to IGF1R or WEE1-targeted inhibitors. Primary and metastatic tumors also exhibited differences in IGF1R localization, replication stress levels, and inhibitor sensitivity. Combined inhibition of IGF1R and WEE1 led to tumor regression. These findings highlight the importance of using biopsy-derived predictive biomarkers at multiple stages of Ewing sarcoma disease management.
CLINICAL CANCER RESEARCH
(2023)
Review
Obstetrics & Gynecology
Brooke E. Sanders, Rebecca Wolsky, Elizabeth S. Doughty, Kristen L. Wells, Debashis Ghosh, Lisa Ku, Joseph G. Pressey, Benjamin B. Bitler, Lindsay W. Brubaker
Summary: This article reports a case of small cell carcinoma of the ovary hypercalcemic type (SCCOHT) with both SMARCA4 and BRCA2 germline mutations. The clinical presentation, histopathology, and treatment process are described, along with spatial transcriptomics analysis of the original tumor.
GYNECOLOGIC ONCOLOGY REPORTS
(2022)
Editorial Material
Oncology
Jo Cooke-Barber, Joseph G. Brungardt, Michael Sorger, Joseph G. Pressey, Brian Turpin, Rajaram Nagarajan, Sara Szabo, Joel Sorger, Neil Johnson, Roshni Dasgupta
ANNALS OF SURGICAL ONCOLOGY
(2023)
Editorial Material
Oncology
Jo Cooke-Barber, Joseph G. Brungardt, Michael Sorger, Joseph G. Pressey, Brian Turpin, Rajaram Nagarajan, Sara Szabo, Joel Sorger, Neil Johnson, Roshni Dasgupta
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Michael E. Johnston, Zishaan A. Farooqui, Rajaram Nagarajan, Joseph G. Pressey, Brian Turpin, Roshni Dasgupta
Summary: This study aimed to investigate the efficacy of ICG as an adjunct to SLNB in the pediatric and young adult population. The results showed that ICG was safer and more effective than blue dye, with a sensitivity of 87% and a PPV of 83% for detection of Tc-99m-hot lymph nodes, and a sensitivity of 84% and a PPV of 91% for detection of pathologically confirmed lymph nodes.
Meeting Abstract
Oncology
M. Macy, T. Cash, N. Pinto, J. G. Pressey, L. Szalontay, W. L. Furman, A. Bukowinski, J. H. Foster, G. K. Friedman, J. HaDuong, E. Fox, B. J. Weigel, J. Grevel, F. Huang, C. Phelps, B. H. Childs, J. Chung, S. Chaturvedi, A. Schulz, S. G. DuBois
EUROPEAN JOURNAL OF CANCER
(2022)
Meeting Abstract
Oncology
Viswatej Avutu, Emily K. Slotkin, J. Andrew Andrew Livingston, Sant P. Chawla, Joseph Gerald Pressey, Preeya Nandkumar, Cheng Zheng, Soamnauth Misir, Philippe Pultar, Dimitris Voliotis, Katherine Anne Thornton, Noah Federman
JOURNAL OF CLINICAL ONCOLOGY
(2022)