p53 mutations in classic and pleomorphic invasive lobular carcinoma of the breast

Contains fulltext : 110338.pdf (publisher's version ) (Open Access)BACKGROUND: p53 is a tumor suppressor that is frequently mutated in human cancers. Although alterations in p53 are common in breast cancer, few studies have specifically investigated TP53 mutations in the breast cancer subtype invasive lobular carcinoma (ILC). Recently reported conditional mouse models have indicated that functional p53 inactivation may play a role in ILC development and progression. Since reports on the detection of TP53 mutations in the relatively favorable classic and more aggressive pleomorphic variants of ILC (PILC) are rare and ambiguous, we performed a comprehensive analysis to determine the mutation status of TP53 in these breast cancer subtypes. METHODS: To increase our understanding of p53-mediated pathways and the roles they may play in the etiology of classic ILC and PILC, we investigated TP53 mutations and p53 accumulation in a cohort of 22 cases of classic and 19 cases of PILC by direct DNA sequencing and immunohistochemistry. RESULTS: We observed 11 potentially pathogenic TP53 mutations, of which three were detected in classic ILC (13.6%) and 8 in PILC (42.1%; p = 0.04). While p53 protein accumulation was not significantly different between classic and pleomorphic ILC, mutations that affected structure and protein function were significantly associated with p53 protein levels. CONCLUSION: TP53 mutations occur more frequently in PILC than classic ILC.1 april 201

Long-Term Sustainability of Using Hemodialyzers to Inexpensively Provide Pathogen-Free Water to Remote Villages Lacking Electricity

The provision of clean water to remote communities is a major goal of both the World Health Organization and the United Nations. We report on the long-term sustainability of filter-sterilizing polluted water in remote villages in Ghana that lack electricity. Contaminated water pumped several times a week via a gasoline pump into a 1000 L elevated tank is filtered through polysulfone hemodialyzers on demand. The 3 nm fiber pore size rejects all bacteria, parasites, and viruses. Villagers flush organic matter from the dialyzers thrice daily to maintain a flow of up to 250 L/h. Having previously reported a 73% reduction in diarrheal episodes, we now address system sustainability. After passing through the hemodialyzer filters, a fecally polluted water source remains consistently free of pathogens even after the system has been in place for >1 year in most villages. Filters are easily replaced when needed. Daily cost for unlimited clean water is less than USD 2.22 per village over five years. Villagers have continued to independently fill the tank and flush the system, because they appreciate the clean water and health benefits. We demonstrate that over 2–6 years this system providing pathogen-free drinking water can be maintained independently by villagers for long-term sustainability. It does not require electricity nor disinfectants to be added to the product water and is ready for far broader application in similarly remote settings