The epigenetic landscape of renal cancer

This is an accepted manuscript of an article published by Nature in Nature Reviews: Nephrology on 28/11/2016, available online: https://doi.org/10.1038/nrneph.2016.168 The accepted version of the publication may differ from the final published version.The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling. In this Review, we discuss how altered DNA methylation, microRNA dysregulation and mutations in histone-modifying enzymes disrupt cellular pathways in renal cancers

Association of Herpes Zoster Ophthalmicus With Acquired Immunodeficiency Syndrome and Acute Retinal Necrosis

We conducted a review to investigate the prevalence of human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS), in patients with herpes zoster ophthalmicus, as well as the incidence of acute retinal necrosis after herpes zoster ophthalmicus. All charts of patients seen at our institution between 1987 and 1992 with a primary diagnosis of herpes zoster ophthalmicus were reviewed. Of 112 patients with herpes zoster ophthalmicus, 29 (26%) had HIV or AIDS. All these patients were younger than 50 years at the time of diagnosis. Five of 29 (17%) immunocompromised patients had acute retinal necrosis after herpes zoster ophthalmicus. No acute retinal necrosis was identified in the nonimmunocompromised patients after herpes zoster ophthalmicus. We recommend that all patients younger than 50 years who have herpes zoster ophthalmicus at initial examination be tested for HIV. Additionally, HIV-infected patients should be monitored closely after herpes zoster ophthalmicus for development of acute retinal necrosis. Long-term oral prophylactic as well as initial high-dose intravenous acyclovir may be appropriate in HIV-infected individuals with herpes zoster

Effects of 4-nonylphenol on proliferation of AGS gastric cells

Objectives: Nonylphenol (NP) is present ubiquitously in both aquatic and terrestrial environments. This compound is considered an important endocrine disruptor and its toxic/oestrogenic activity has been investigated in a number of in vitro and in vivo studies. Human exposure to NP may occur by cutaneous absorption, ingestion of contaminated food or water and inhalation. Moreover, while the cytotoxic effects of NP are known and studied, its effects on cell death and related mechanisms are not known. Our group decided to investigate NP effects on a gastric epithelial cell line (AGS), in particular NP effects on AGS cell cycle and apoptosis. Materials and methods: Cell cycle was analysed by flow cytometry, p21 and p27 induction, and apoptosis was analysed by flow cytometry and annexin-V assays, Fas, Fas-L, caspase 8 and caspase 3 activation. Results: We have demonstrated that NP affected cell cycle and apoptosis in a time- and dose-dependent manner, reaching the most notable effect at concentration of 10-7m, for 48h. Flow cytometry revealed that treatment with 10-7m NP led to accumulation of cells at G2/M transition and increased percentage population of apoptotic cells. Results have shown that NP at concentration 10-7m induced marked increase in Fas and Fas-L expression. Moreover, 107m NP induced activation of caspases 8 and 3, but not activation of caspase 9. Conclusions: The results reported suggest that gastric cells can be useful as screening population for appropriate study of developmental toxicity. © 2011 Blackwell Publishing Ltd

Effects of 4-nonylphenol on proliferation of AGS gastric cells

Objectives: Nonylphenol (NP) is present ubiquitously in both aquatic and terrestrial environments. This compound is considered an important endocrine disruptor and its toxic/oestrogenic activity has been investigated in a number of in vitro and in vivo studies. Human exposure to NP may occur by cutaneous absorption, ingestion of contaminated food or water and inhalation. Moreover, while the cytotoxic effects of NP are known and studied, its effects on cell death and related mechanisms are not known. Our group decided to investigate NP effects on a gastric epithelial cell line (AGS), in particular NP effects on AGS cell cycle and apoptosis. Materials and methods: Cell cycle was analysed by flow cytometry, p21 and p27 induction, and apoptosis was analysed by flow cytometry and annexin-V assays, Fas, Fas-L, caspase 8 and caspase 3 activation. Results: We have demonstrated that NP affected cell cycle and apoptosis in a time- and dose-dependent manner, reaching the most notable effect at concentration of 10-7m, for 48h. Flow cytometry revealed that treatment with 10-7m NP led to accumulation of cells at G2/M transition and increased percentage population of apoptotic cells. Results have shown that NP at concentration 10-7m induced marked increase in Fas and Fas-L expression. Moreover, 107m NP induced activation of caspases 8 and 3, but not activation of caspase 9. Conclusions: The results reported suggest that gastric cells can be useful as screening population for appropriate study of developmental toxicity. © 2011 Blackwell Publishing Ltd