Felipe Amstalden Trevisan

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies.

OBJECTIVE: Identify prognostic factors associated to late urinary toxicity in patients with prostate cancer submitted to radical conformal radiotherapy (3DCRT). MATERIALS AND METHODS: From July 1997 to January 2002, 285 patients with localized prostate cancer were consecutively treated with 3DCRT and retrospectively analyzed. Thirty seven (13%) patients were submitted to transurethral prostate resection previously to 3DCRT. The median dose delivered to the prostate was 7920 cGy (7020-8460). Patient and treatment characteristics were analyzed and correlated to late urinary toxicity grade 2-3, especially whether certain radiation doses applied to certain bladder volumes, when visualized through computerized tomography (CT) planning, correlated with the observed actuarial incidences of late urinary complications, using bladder volume as a continuous variable. RESULTS: On a median follow-up of 53.6 months (3.6-95.3), the 5-year actuarial free from late urinary toxicity grade 2-3 survival was 91.1%. Seven and fifteen patients presented late urinary toxicity grades 2 and 3, respectively. Prior transurethral resection of prostate and radiation dose over 70 Gy on 30% of initial bladder volume were independent prognostic factors for late urinary toxicity grade 2-3. CONCLUSIONS: This study suggests that restricting radiation doses to 70 Gy or less on 30% of bladder volume, visualized through CT planning, may reduce late urinary complications. It furthermore suggests that patients with prior transurethral resection of prostate may indicate a group of patients with a greater risk for late urinary toxicity grade 2-3 after 3DCRT.

Este estudo propõe-se a avaliar o complexo nasossinusal, a fim de identificar os principais achados e determinar as doenças desta área. A análise precisa da extensão local e disseminação tumoral, dada pela tomografia computadorizada e ressonância magnética, desempenha papel importante no planejamento terapêutico, influenciando também o prognóstico.

We evaluated the potential effects of ATO in different pediatric SHH-MB cell lines (ONS-76: TP53-wild type; DAOY and UW402: TP53-mutated). MB cell lines molecular subgroup was confirmed and TP53 mutations were validated. Cell viability, clonogenicity and apoptosis were evaluated after ATO treatment at different concentrations (1-16 µM) alone or combined with irradiation doses (0.5, 1, 2 and 4 Gy). Rad51 and Ku86 proteins were evaluated by WB. ATO treatment reduced cell viability for all SHH-MB cell lines. Significant decrease of clonogenic capacity and higher apoptosis rates were also observed after ATO exposure, being cell death more pronounced (>70%) for the SHH-MB TP53-mutated. Combined treatment of ATO with irradiation also reduced colonies formation in UW402 tumor cells, which was independent of DNA damage repair proteins Rad51 and Ku86. In silico analyses suggested that a set of genes from cell cycle and p53 pathways are differentially expressed in SHH tumor subtypes, suggesting that cell lines may respond to therapies according to the gene expression profiles. Herein, we showed ATO cytotoxicity in pediatric SHH cell lines, with marked radiosensitizing effect for the MB-SHH TP53-mutated cells. These results highlight the potential of ATO, alone or in combination with radiotherapy, supporting further clinical investigations.