vhl gene
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2022 ◽  
Vol 2022 ◽  
pp. 1-8
Author(s):  
Yunxiang Gong ◽  
Degang Wang ◽  
Wengang Wang

Objective. In this paper, we study the role of the VHL gene in regulating the proliferation and apoptosis of renal cell carcinoma, as well as the safety and transfection efficiency of ultrasound microbubble gene transfection technology. Method. We use kidney cancer cell lines as an in vitro research object and apply ultrasound microbubble gene transfection technology to transfect the VHL gene into kidney cancer cell line (786-0). The proliferation and apoptosis of cells were measured to clarify the inhibitory effect of the VHL gene in renal cell carcinoma. After that, pEGFP-VHL was transfected using ultrasonic microbubble and liposome gene transfection techniques, respectively, and the transfection efficiency was measured by immunofluorescence. Results. Compared with untreated and 786-0 cells that are transfected with empty vector, the expression level of VHL gene mRNA in 786-0 cells that are transfected with pcDNA3.1-VHL was significantly increased, and the cell growth inhibition rate was significantly higher. The rate of apoptosis increased significantly. Transfection efficiency of the pEGFP-VHL gene after transfection of 786-0 cells for 48 h: control group 0, liposome group ( 35.55 ± 2.77 ) %, ultrasound microbubble group ( 18.27 ± 2.83 ) %, and two transfection methods on cells. There is no significant difference in the impact of vitality. Conclusion. VHL gene expression can significantly inhibit the proliferation ability of renal cancer cell line 786-0 and promote its apoptosis. VHL gene is a potential target for gene therapy of kidney cancer.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dali Tong ◽  
Yao Zhang ◽  
Jun Jiang ◽  
Gang Bi

Abstract Background Classical von Hippel Lindau (VHL) disease/syndrome includes CNS hemangioblastoma, renal or pancreatic cysts, pheochromocytoma, renal carcinoma and exodermic cystadenoma. The syndrome is caused by mutation of VHL tumor suppressor gene. The most prevalent mutations are present in VHL syndrome. To date, > 500 mutations of gene related to the progression of VHL syndrome have been reported. VHL gene mutation presented in single lung or pancreatic tumor has been reported occasionally, but there is no report of both. Methods In this paper, we used CT scan, pathological and genetic examination methods to diagnose a rare atypical VHL syndrome. Results We reported a rare case of atypical VHL syndrome with authenticated VHL mutation at p.Arg167Gln, that was associated with not only bilateral pheochromocytoma but also lung carcinoid and neuroendocrine tumor of pancreas. Based on literature reviews, the patient was recommended to be further subjected to octreotide-based radionuclide therapy. Conclusions Combined with gene detection and clinical diagnosis, we found the inherent relationship between VHL genotype and phenotype, and constructed the standard diagnosis and treatment process of disease with rare VHL mutation from the perspective of gene therapy.


Author(s):  
Ufuk Unal ◽  
Gulsah Cecener ◽  
Havva Tezcan Unlu ◽  
Berna Aytac Vuruskan ◽  
Ecem Efendi Erdem ◽  
...  

2021 ◽  
Author(s):  
Junhui Hu ◽  
Ping Tan ◽  
Moe Ishihara ◽  
Nicholas Bayley ◽  
Shiruyeh Schokrpur ◽  
...  

Abstract To study the impact of intratumoral VHL heterogeneity observed in patient ccRCC primary tumors, we engineered VHL gene deletion in three RCC models, including a new primary tumor cell line derived from an aggressive metastatic ccRCC. The VHL gene-deleted (VHL-KO) cells underwent epithelial-to-mesenchymal transition (EMT) and showed diminished proliferation and tumorigenicity compared to the parental, VHL-expressing (VHL+) cells. Renal tumors with either VHL+ or VHL-KO cells alone exhibit minimal metastatic potential. Interestingly, tumors with both cells displayed rampant lung metastasis, highlighting a novel cooperative metastatic mechanism. The poorly proliferative VHL-KO cells stimulated the proliferation, EMT and motility of neighboring VHL+ cells. We found that periostin (POSTN), a protein product overexpressed and secreted by VHL- cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating vascular escape of tumor cells. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. Our work suggests a new strategy to halt progression in ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.


2021 ◽  
Vol 11 ◽  
Author(s):  
Bo Yang ◽  
Zhenyu Li ◽  
Yubo Wang ◽  
Chaoling Zhang ◽  
Zhen Zhang ◽  
...  

BackgroundHemangioblastoma is a benign tumor of the central nervous system and may appear as a component of von Hippel-Lindau (VHL) disease. At present, approximately 40 cases of optic nerve HGBs have been reported in the literature. VHL disease is a rare autosomal-dominant inherited cancer syndrome with different phenotypes caused by variants in the VHL gene. Herein, the authors describe a case of a pediatric patient with VHL disease and with optic nerve HGB, a rare phenotypic expression. The purpose of this study was to explore the genotype-phenotype, clinical features, treatment and follow-up of VHL-associated hemangioblastomas in pediatric patients.Case DescriptionA 12-year-old boy presented with vision loss, headache and dizziness at our hospital. Magnetic resonance imaging (MRI) revealed a large (19.8 mm*18.5 mm*23.5 mm) irregular mass located in the suprasellar region. The mass was successfully removed after craniotomy and microsurgical treatment. The pathological diagnosis was left optic nerve HGB. Genetic analyses showed p.Pro86Leu (c. 257C>T) heterozygous missense mutations in the VHL gene.ConclusionThis is the first reported pediatric case of VHL-associated optic nerve HGB. The genotype-phenotype correlation of VHL disease may provide new evidences for predicting tumor penetrance and survival. Gross tumor resection combined with stereotactic radiosurgery might be the most beneficial treatment.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1002-A1002
Author(s):  
Gustavo Piech Ricardo ◽  
Nilza Scalissi ◽  
Cristina Bellotti Formiga Bueno ◽  
Renata Da Cunha Scalco ◽  
Jose Viana Lima

Abstract Background: We report the case of a patient with VHL Syndrome with an adrenal lesion compatible with non-functioning pheochromocytoma and it’s diagnostic management. Case Report: JMN, female, 32 years old, referred for screening for VHL syndrome, after diagnosis in a sister, who has clear cell renal carcinoma (ccRCC), cerebellar hemangioblastoma and genetic analysis, by next generation sequencing (NGS), which identified the allelic variant germline pathogenic c. 256C> T in heterozygosis in exon 1 of the VHL gene. The patient is asymptomatic and her physical examination is normal. Optic fundus examination with lesion suggestive of right hemangioblastoma. Family history: mother who died at 59 with a diagnosis of ccRCC, without genetic investigation. Maternal aunt diagnosed with VHL and involvement of the cerebellum, kidney and pancreas. Two brothers with genetic and clinical diagnosis of VHL syndrome, presenting pheochromocytoma and renal carcinoma. Laboratory tests: plasma metanephrine: 0.3 nmol/L (RV <0.5nmol/L), plasma normetanephrine: 0.5 nmol/L (RV <0.9nmol/L), chromogranin A 61 ng/mL (RV <93 ng/ml). Genetic evaluation by NGS identified the pathogenic variant c. 256C> T in heterozygosity in exon 1 of the VHL gene. Topographic examinations: magnetic resonance imaging (MRI) of adrenals with nodule in the left adrenal gland, hypersignal in T2, measuring 2.9 x 2.3 cm, suggestive of pheochromocytoma and whole body scintigraphy with metaiodobenzylguanidine (MIBG) positive in the left adrenal gland. She underwent resection of the tumor in the left adrenal, without complications. Anatomopathology compatible with pheochromocytoma with immunohistochemistry for ki67 <3%. Currently, the patient is clinically stable and with periodic follow-up, as well as family members, performing screening for diseases associated with VHL. Conclusion: VHL syndrome is one of the possible causes of non-functioning pheochromocytomas and paragangliomas, and adrenal lesions with negative metanephrine levels do not exclude them; thus highlighting the importance of exams such as CT or MRI and functional topographic studies (whole body scintigraphy with MIBG and / or PETCT with Galio68DOTA) for their diagnosis.


2021 ◽  
Author(s):  
Cathy D. Vocke ◽  
Christopher J. Ricketts ◽  
Laura S. Schmidt ◽  
Mark W. Ball ◽  
Lindsay A. Middelton ◽  
...  

2021 ◽  
Vol 67 (1) ◽  
pp. 117-122
Author(s):  
Lyidmila Spirina ◽  
Svetlana Chizhevskaya ◽  
Irina Kondakova ◽  
Evgeny Choynzonov ◽  
Irina Kovaleva

Introduction. The oncosuppressor protein VHL plays a decisive or at least important role in the mechanisms of tumor progression. The development of malignant neoplasms of the thyroid gland is associated with the activation of transcriptional and growth factors. However, the role of the VHL gene in the mechanisms of the development of thyroid cancer has hardly been studied. The study aimed to study the clinical and morphological features, expression of transcription, growth factors, and components of the AKT / m-TOR signaling pathway in patients with papillary thyroid cancer depending on the level of expression of the VHL gene. Material and methods. The study included 46 patients with tumor pathology of the thyroid gland: 20 patients with benign thyroid tumors and 26 patients with papillary thyroid cancer T1-4N0-2M0. The expression of parameters was determined by PCR in real-time. Mutation BRAF-V600E was determined in allele-specific PCR in real-time. Results and their discussion. The mRNA level of the VHL gene remained virtually unchanged in the tissue of papillary cancer and benign thyroid tumors. It depended on the prevalence of the disease, the defeat of regional lymph nodes, and the BRAF-V600E status. In the presence of the BRAF-V600E mutation, VHL expression increased 615 times in patients with a mutation compared with patients without this somatic mutation. It was revealed that the expression of NF-κB p65, NF-κB p50, HIF-1, HIF-2, growth factors VEGF and CAIX in patients in the group with a VHL level> 1.0 RU increased compared with patients with a VHL level <1.0 RU. A decrease in PDK, c-RAF, mTOR, 70s 6 kinase, PTEN mRNA levels were also recorded in patients with increased levels of VHL expression compared with patients with VHL expression <1.0 RU. Conclusion. That the association of the VHL expression with tumor progression in papillary thyroid cancer and the mutant protein bRAF presence was found. Also, associations between the VHL expression and the level of mRNA of transcription and growth factors are noted.


Life Sciences ◽  
2021 ◽  
Vol 266 ◽  
pp. 118873
Author(s):  
Min Yang ◽  
Mingming Zhu ◽  
Kang Song ◽  
Tanna Wuren ◽  
Jun Yan ◽  
...  

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