• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1977-1980
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• 2015

Objective: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. Materials and Methods: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. Results: Three novel mutations (H125P, 623(^TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding ${\beta}$-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(^TTTGTtG) carriers presented VHL type 2B or type 2C. Conclusions: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(^TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research intoVHLD pathogenesis.

• Journal of Korean Neurosurgical Society
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• v.42 no.6
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• pp.436-440
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• 2007

Objective : Spinal cord hemangioblastoma is an uncommon vascular neoplasm with a benign nature and is associated with von Hippel-Lindau (VHL) disease in 20-30% of patients. Total removal of these tumors without significant neurological deficit remains a great challenge. The purpose of this study was to investigate the efficacy of VHL mutation analysis and to evaluate surgical outcome of patients with spinal cord hemangioblastomas. Methods : This study included nine patients treated for spinal cord hemangioblastomas at our institute between December 1994 and March 2006. There were four male and five female patients. Mean age was 37.8 years. The mean follow-up period was 22.4 months. Magnetic resonance imaging (MRI) of the complete neuraxis was done in all cases and VHL mutation analysis was performed in three cases for a definite diagnosis. Results : Six patients had intramedullary tumor, and the remaining patients had intradural extramedullary lesions. Five patients were associated with VHL disease. The von Hippel-Lindau mutation analysis was done in three patients and two of them showed VHL gene abnormality. Tumors were located in the cervical cord in five cases and in the thoracic cord in four cases. All patients underwent surgical intervention, and total removal was achieved in six cases. All patients showed improvement or, at least, clinically stationary state. Surgical complications did not develop in any cases. Conclusion : Spinal hemangioblastoma in this series has been safely and effectively removed via a posterior approach. Postoperatively, clinical outcome was excellent in the majority of cases. The VHL mutation analysis was useful in patients with family history and in those with multiple hemangioblastomas.

• Genomics & Informatics
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• v.20 no.1
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• pp.6.1-6.15
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• 2022

Litorilituus sediminis is a Gram-negative, aerobic, novel bacterium under the family of Colwelliaceae, has a stunning hypothetical protein containing domain called von Hippel-Lindau that has significant tumor suppressor activity. Therefore, this study was designed to elucidate the structure and function of the biologically important hypothetical protein EMK97_00595 (QBG34344.1) using several bioinformatics tools. The functional annotation exposed that the hypothetical protein is an extracellular secretory soluble signal peptide and contains the von Hippel-Lindau (VHL; VHL beta) domain that has a significant role in tumor suppression. This domain is conserved throughout evolution, as its homologs are available in various types of the organism like mammals, insects, and nematode. The gene product of VHL has a critical regulatory activity in the ubiquitous oxygen-sensing pathway. This domain has a significant role in inhibiting cell proliferation, angiogenesis progression, kidney cancer, breast cancer, and colon cancer. At last, the current study depicts that the annotated hypothetical protein is linked with tumor suppressor activity which might be of great interest to future research in the higher organism.

• Journal of Yeungnam Medical Science
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• v.30 no.2
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• pp.101-104
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• 2013

Von Hippel-Lindau (VHL) disease is an autosomal dominant hereditary disorder caused by a germline mutation of the VHL gene. It is a multi-systemic disorder that is predisposed to benign or malignant tumors of visceral organs such as hemangioblastoma of the central nervous system, renal cell carcinoma, retinal angioma and pheochromocytoma. We report herein a case of VHL disease that initially manifested with aortic valve insufficiency.

• Korean Journal of Veterinary Research
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• v.43 no.1
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• pp.25-29
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• 2003

This study was carried out to investigate a usefulness of the microsatellite DNA markers for parentage verification of Thoroughbred (TB) horses. 9 TB horses samples were genotyped for nine international minimum standard markers (AHT4, 5, ASB2, HMS3, 6, 7, HTG4, 10, and VHL20), and the additional panel of four markers, ASB17, CA425, LEX33, and TKY321. This methods consisted of multiplexing PCR procedures, and it showed reasonable amplification of all PCR products. Genotyping was performed with an ABI 310 genetic analyzer. Foal I was excluded according to principles of Mendelian genetics in AHT4 (H/K), ASB2 (Q/Q), HMS3 (I/P), HTG4 (M/O), HTG1O (K/R), VHL20 (M/P), ASB17 (F/N), LEX33 (M/O), and TKY321 (G/I) markets. Foal II was excluded with markers AHT5 (K/M), ASB2 (M/N), HMS7 (N/N), HTG1O (K/K), VHL20 (I/I), ASB17 (F/F) and TKY321 (G/I). Foal III was excluded with markers AHT4 (O/O), AHT5 (K/K), ASB2 (M/R), HMS6 (M/P), HMS7 (O/O), HTG10 (R/S), VHL20 (L/M), and ASB17 (N/O). These results suggest that the present DNA typing is so useful for parentage verification of TB horses.

• Korean Journal of Head & Neck Oncology
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• v.39 no.2
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• pp.65-69
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• 2023

We report a unique case of hemangioma of the nasal cavity in von Hippel-Lindau (VHL) syndrome. A 26-year-old female with VHL syndrome who had previously undergone surgery for pancreatic and adrenal mass presented with a 4-month history of left-sided nasal obstruction. The patient had an expansile mass lesion in the left nasal cavity and an imaging test demonstrated the mass in the left maxillary sinus extending to the nasal cavity. The tumor was removed with an endoscopic prelacrimal recess approach considering the possibility of not only a benign tumor such as hemangioma but also a malignant tumor of the maxillary sinus and histopathologic examination confirmed cavernous hemangioma. This case is the rarely reported manifestation of the paranasal sinus in VHL disease.

• BMB Reports
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• v.48 no.6
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• pp.301-302
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• 2015

Hypoxia is associated with many pathological conditions as well as the normal physiology of metazoans. We identified a lactate-dependent signaling pathway in hypoxia, mediated by the oxygen- and lactate-regulated protein NDRG family member 3 (NDRG3). Oxygen negatively regulates NDRG3 expression at the protein level via the PHD2/VHL system, whereas lactate, produced in excess under prolonged hypoxia, blocks its proteasomal degradation by binding to NDRG3. We also found that the stabilized NDRG3 protein promotes angiogenesis and cell growth under hypoxia by activating the Raf-ERK pathway. Inhibiting cellular lactate production abolishes NDRG3-mediated hypoxia responses. The NDRG3-Raf-ERK axis therefore provides the genetic basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases in addition to advancing our understanding of the normal physiology of hypoxia responses. [BMB Reports 2015; 48(6): 301-302]

• Journal of Korean Neurosurgical Society
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• v.30 no.8
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• pp.1019-1022
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• 2001

Although brain metastasis of renal cell carcinoma is a major cause of death in Von Hippel-Lindau disease(VHL), it is not easy to distinguish local recurrence of hemangioblastoma from distant metastasis. In addition, hemangioblastoma has several characteristics suitable for recipient of "tumor-to-tumor metastasis". Authors report a case of Von Hippel-Lindau disease that had metastases of renal cell carcinomas.

• Journal of Korean Neurosurgical Society
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• v.57 no.6
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• pp.465-468
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• 2015

Hemangioblastomas in the pituitary stalk are especially rare. Most pituitary stalk hemangioblastomas reported in the literature were associated with von Hippel-Lindau (VHL) disease. Here, we report only the 3rd case of sporadic pituitary stalk hemangioblastoma diagnosed in a 60-year-old woman. Despite the danger of potential complications due to excessive vascularity or proximity to important neural structures, the tumor in our case was successfully removed while preserving pituitary function. In this case, complete surgical excision was shown to be an effective treatment option for symptomatic pituitary stalk hemangioblastoma, and we suggest careful evaluation of any highly enhancing mass with a signal void in the pituitary stalk preoperatively, even if no VHL disease is evident.

• Journal of Korean Neurosurgical Society
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• v.39 no.3
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• pp.234-237
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• 2006

The filum terminale is an exceptional location for isolated hemangioblastoma, and most commonly hemangioblastomas are present In patients with von Hippel-Lindau[VHL] syndrome. We describe here a case of hemangioblastoma of filum terminale not associated with VHL, presenting with the history of progressive back pain, particularly severe in recumbent posture, and recurrent bilateral sciatica. MRI and spinal angiography revealed a well-vasculized mass lesion in filum terminale. The tumor was resected surgically. Histological examination confirmed the hemangioblastoma diagnosis. We recommended that, although rare, hemangiblastoma of the filum terminale be included in the differential diagnosis of a patient with low back pain.