13 research outputs found

    Deep Underground Science and Engineering Lab: S1 Dark Matter Working Group

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    A study of the current status of WIMP dark matter searches has been made in the context of scientific and technical planning for a Deep Underground Science and Engineering Laboratory (DUSEL) in the U.S. The table of contents follows: 1. Overview 2. WIMP Dark Matter: Cosmology, Astrophysics, and Particle Physics 3. Direct Detection of WIMPs 4. Indirect Detection of WIMPs 5. Dark Matter Candidates and New Physics in the Laboratory 6. Synergies with Other Sub-Fields 7. Direct Detection Experiments: Status and Future Prospects 8. Infrastructure 9. International Context 10. Summary and Outlook 11. AcknowledgmentsComment: Final working group report of 17 Feb 2007 updated to address reviewer comments (Latex, 32 pages

    PIK3CA mutations are frequent in esophageal squamous cell carcinoma associated with chagasic megaesophagus and are associated with a worse patient outcome

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    Chronic diseases such as chagasic megaesophagus (secondary to Chagas' disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood.Background Chronic diseases such as chagasic megaesophagus (secondary to Chagas’ disease) have been suggested as etiological factors for esophageal squamous cell carcinoma; however, the molecular mechanisms involved are poorly understood. Objective We analyzed hotspot PIK3CA gene mutations in a series of esophageal squamous cell carcinomas associated or not with chagasic megaesophagus, as well as, in chagasic megaesophagus biopsies. We also checked for correlations between the presence of PIK3CA mutations with patients’ clinical and pathological features. Methods The study included three different groups of patients: i) 23 patients with chagasic megaesophagus associated with esophageal squamous cell carcinoma (CM/ESCC); ii) 38 patients with esophageal squamous cell carcinoma not associated with chagasic megaesophagus (ESCC); and iii) 28 patients with chagasic megaesophagus without esophageal squamous cell carcinoma (CM). PIK3CA hotspot mutations in exons 9 and 20 were evaluated by PCR followed by direct sequencing technique. Results PIK3CA mutations were identified in 21.7% (5 out of 23) of CM/ESCC cases, in 10.5% (4 out of 38) of ESCC and in only 3.6% (1 case out of 28) of CM cases. In the CM/ESCC group, PIK3CA mutations were significantly associated with lower survival (mean 5 months), when compared to wild-type patients (mean 2.0 years). No other significant associations were observed between PIK3CA mutations and patients’ clinical features or TP53 mutation profile. Conclusion This is the first report on the presence of PIK3CA mutations in esophageal cancer associated with chagasic megaesophagus. The detection of PIK3CA mutations in benign chagasic megaesophagus lesions suggests their putative role in esophageal squamous cell carcinoma development and opens new opportunities for targeted-therapies for these diseases.CAPES and FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo [Grant number 2015/20077–3 to FFM] and Barretos Cancer Hospital internal research funds (PAIP)info:eu-repo/semantics/publishedVersio
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