Article in JNCI cancer spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
23 authors.
Jared S RosenblumNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0001-5941-9082
Yasemin ColeNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-9492-5885
Danielle DangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-5004-1033
Pashayar P LookianNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-2436-9254
Hussam AlkaissiNational Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-0861-9348
Mayank PatelSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-3148-3717
Anthony J CappadonaNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-5938-0568
Abhishek JhaSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-1489-2471
Nancy EdwardsSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0001-5689-3328
Danielle R DonahueMouse Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-3371-665X
Jeeva MunasingheMouse Imaging Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-5295-5437
Herui WangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0003-2293-4819
Russell H KnutsenLaboratory of Vascular and Matrix Genetics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0001-6761-6502
Alberto S PappoDivision of Solid Tumor, St Jude Children's Research Hospital, Memphis, TN, United States.ORCID 0000-0002-5338-3979
Ronald M LechanDivision of Endocrinology, Diabetes & Metabolism, Tufts Medical Center, Boston, MA, United States.ORCID 0000-0003-0404-2323
Beth A KozelLaboratory of Vascular and Matrix Genetics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-9757-7118
James G SmirniotopoulosDepartment of Radiology, George Washington University, Washington, DC, United States.ORCID 0000-0001-8422-7525
H Jeffrey KimDepartment of Otolaryngology, Georgetown University School of Medicine, Washington, DC, United States.
Alexander VortmeyerClinical Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.ORCID 0000-0001-5437-5092
Markku MiettinenGeneral Surgical Pathology Section, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-3282-8107
John D HeissSurgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-3890-0165
Zhengping ZhuangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-0009-7370
Karel PacakSection on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.ORCID 0000-0002-3541-3767
Funding
UNC Medical Scientist Training ProgramT32GM152316 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Toni Darville, Mohanish P Deshmukh · 2024 to 2026
$4.3M
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNCI NIH HHSNIGMS NIH HHS T32 GM152316
6 · The paper itself
Abstract
backgroundHead and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.
methodsWe evaluated a cohort of patients with PZS (n = 9) for HNPGL by positron emission tomography, magnetic resonance imaging, and computed tomography and measured carotid body size compared to literature reference values. Resected tumors were evaluated by histologic sectioning and staining. We evaluated the corresponding mouse model at multiple developmental stages (P8 and adult) for lesions of the head and neck by high resolution ex vivo imaging and performed immunohistochemical staining on histologic sections of the identified lesions.
resultshree patients had imaging consistent with HNPGL, one of which warranted resection and was confirmed on histology. Three additional patients had carotid body enlargement (Z-score > 2.0), and 3 had carotid artery malformations. We found that 9 of 10 adult variant mice had carotid body tumors and 6 of 8 had a paraganglioma on the cranio-caval vein, the murine homologue of the superior vena cava; these were also found in 4 of 5 variant mice at post-natal day 8. These tumors and the one resected from a patient were positive for tyrosine hydroxylase, synaptophysin, and chromogranin A. Brown fat in a resected patient tumor carried the EPAS1 pathogenic variant.
conclusionsThese findings (1) suggest HNPGL as a feature of PZS and (2) show that these pathogenic variants are sufficient to cause the development of these tumors, which we believe represents a continuous spectrum of disease starting from hyperplasia.
Indexed as
Basic Helix-Loop-Helix ProteinsHead and Neck NeoplasmsParagangliomaAdultAnimalsCarotid BodyDisease Models, AnimalEndothelial PAS Domain-Containing Protein 1FemaleHumansMagnetic Resonance ImagingMaleMiceMiddle AgedPositron-Emission TomographySyndromeBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.
Head and neck paraganglioma in Pacak-Zhuang syndrome. · full record | OpenQuestion