PubMed · 4381927
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J T McCarthy, P Sachs, C T Nelson, O Canizarez. 1967. Dermal vasculitis with retinal involvement.. https://doi.org/10.1001/archderm.96.1.109
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BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) regulates cellular responses to hypoxia and is rapidly degraded under normoxia through von Hippel-Lindau (VHL) mediated ubiquitination. Although HIF-1alpha stabilization appears to be the molecular basis for VHL-associated cancers, stabilizing mutations in HIF-1alpha have not been reported. METHODS: A series of 15 metastatic androgen independent prostate cancers were examined for mutations in the oxygen-dependent domain (ODD) of HIF-1alpha by PCR amplification and DNA sequencing. RESULTS: A somatic proline to serine mutation in codon 582 (P582S) was identified in one sample. Transfection studies with a HIF-1alpha regulated reporter gene showed increased transcriptional activity that correlated with higher mutant HIF-1alpha protein expression. Increased expression of the P582S mutant induced by iron chelation, which blocks proline hydroxylation of wild-type HIF-1alpha, was markedly attenuated. The mutant also showed increased stability under normoxic versus hypoxic conditions. CONCLUSION: The P582S HIF-1alpha is a stable variant and HIF-1alpha mutation is a mechanism for enhancing HIF-1alpha activity in human cancer. The recent identification of the identical P582S HIF-1alpha as a polymorphism suggests that this variant may increase tumor susceptibility or cause more aggressive biological behavior.
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Atrophic-erosive lichen planus with oral and genital involvement is a rare condition and is often difficult to diagnose. Patients seldom report genital symptoms to the dentist and dentists do not generally investigate about genital lesions. Delays in diagnosis may cause complications and affect the quality of life. We report the clinical and histopathological features of two new cases of oro-vaginal-vulvar lichen planus and review current treatment options for this condition. Genital lichen planus should be suspected in case of atrophic-erosive oral lichen planus. A thorough multidisciplinary medical management and active early treatment are necessary to improve symptoms and prevent genital sequelae. This might also be a relevant prevention strategy for the risk of squamous cell carcinoma, although data to fully support this statement still need investigation.