The roles of the tumor suppressor parafibromin in cancer

Zheng, Haixue; Xue, Hang; Zhang, Congyu

doi:10.3389/fcell.2022.1006400

Cited by 4 publications

(5 citation statements)

References 46 publications

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“…Previous research has demonstrated that irisin can promote osteoblast proliferation and differentiation by increasing the phosphorylation of the p38/ERK MAPK signaling pathway [ 49 ]. Additionally, Signal Transducer and Activator of Transcription 1 (STAT1) is a member of the STAT protein family and can activate signaling pathways involved in various physiological and pathological responses [ 50 ]. Multiple studies have indicated that STAT1 can induce cellular apoptosis and hinder fracture repair [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius

Zhang,

Pei,

et al. 2024

Aging

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Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

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Section: Discussionmentioning

confidence: 99%

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius

Zhang,

Pei,

et al. 2024

Aging

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“…Parafibromin protein is a tumor suppressor that is encoded by CDC73. Pathogenic variants in this gene are associated with hyperparathyroid jaw tumor syndrome, parathyroid cancer, and other head and neck, gastric, lung, colorectal, and ovarian malignancies [ 10 ]. Patients with parafibromin-deficient tumors should undergo genetic screening for CDC73 pathogenic variants.…”

Section: Discussionmentioning

confidence: 99%

“…However, in this patient, no germline pathogenic variant was present for CDC73. Parafibromin proteins are known to be involved in the transcription in the nucleus and cell growth in the cytoplasm, while CYP24A1 proteins are involved in vitamin D metabolism in the mitochondria [ 3 , 10 ]. There is currently no evidence suggesting a link between parafibromin and CYP24A1 proteins.…”

Section: Discussionmentioning

confidence: 99%

Severe Hypercalcemia Due to Primary Hyperparathyroidism and Heterozygous Pathogenic Variant of CYP24A1

et al. 2023

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Pathogenic variants of CYP24A1 are associated with hypercalcemia due to disruptions in the ability of 24-hydroxylase to break down 1,25-dihydroxyvitamin D (1,25-DHVD). A case involving a heterozygous pathogenic variant of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been previously reported. A 23-year-old woman presented with fatigue and was found to be hypercalcemic at 13.8 mg/dL [reference range, 8.4-10.2 pg/mL]. Her parathyroid hormone (PTH) was 62 pg/mL [reference range, 19-88 pg/mL] and 1,25-DHVD was elevated to 242.7 pg/mL [reference range, 18-72 pg/mL]. Other laboratory workup was unrevealing. She had a bone scan, whole body CT scan, and thyroid ultrasound that were normal. Her 25-hydroxy-vitamin D to 24,25-dihydroxy-vitamin D ratio was elevated at 25.18 (normal, < 25). Because of concern for primary hyperparathyroidism, she was referred to an endocrine surgeon and underwent a parathyroidectomy with the removal of a 3.5-gram adenoma. Pathology showed a parafibromin-deficient parathyroid neoplasm. Genetic testing demonstrated a heterozygous pathogenic variant in CYP24A1. Three weeks after surgery, PTH was 14 pg/mL (1.48 pmol/L), calcium and 1,25-DHVD normalized. In summary, we report a case where a patient with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism exacerbated by an underlying heterozygous pathogenic variant in CYP24A1.

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“…The CDC73 gene, located on chromosome 1q31.2, parafibromin is the translated product of the CDC73 gene. This protein contributes to inhibition of cell proliferation and regulation of cell growth [ 7 ]. Inactivating the CDC73 tumor suppressor gene (previously HRPT2) increases the susceptibility of heterozygous carriers to a range of conditions, including hyperparathyroidism-jaw (HPT-JT) syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma (PC).…”

Section: Discussionmentioning

confidence: 99%

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

Diao,

Zhang,

Zhao

et al. 2023

BMC Endocr Disord

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Background Primary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor. Case presentation The proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland. Conclusion We report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

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The roles of the tumor suppressor parafibromin in cancer

Cited by 4 publications

References 46 publications

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius

3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius

Severe Hypercalcemia Due to Primary Hyperparathyroidism and Heterozygous Pathogenic Variant of CYP24A1

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

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