Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer

Because only 16% of patients with metastatic cervical cancer are alive 5 years after diagnosis, the Gynecologic Oncology Group (GOG) has carefully designed and conducted many phase II studies to identify promising drugs. Cisplatin has emerged as the most active single agent with overall response rates of 19%. Recent phase III trials have documented response rates of 27% and 39% when cisplatin has been combined with either paclitaxel or topotecan, respectively. The comparison of cisplatin to cisplatin plus topotecan in GOG-179 has yielded the first study to show a statistically significant impact on the overall response rate, median progression-free survival, and median survival, with all outcome measures favoring the two-drug regimen. Despite these encouraging results, however, most of the responses are partial and of short duration. The need for novel combinations and the implementation of active biologic agents is implicit. The accumulated data in this disease setting, as evidenced by the experience of the GOG, are presented in this review

Monitoraggio ambientale e biologico nell'esposizione a benzene.

Abstarct accettato e incluso nella tavola rotonda "Valutazione del rischi dell'esposizione professionale ed ambientale a benzene: studio dei meccanismi di attivazione e tossicit\ue0 e degli indicatori di esposizione, effetto e suscettibilit\ue0

Social aspects of dental caries in the context of mother-child pairs

The relationship between mother and child in the context of oral health has traditionally been exposed by the scientific literature in microbiology, which lacks a broad and necessary discussion of health and illness seen as processes, both biological and social. OBJECTIVE: Investigate the family social determinants associated with the caries history of children and the need for dental treatment (NDT) among their mothers was the objective of this study. MATERIAL AND METHODS: This research employed a cross-sectional study of mother-child pairs living in southern Brazil. Data collection occurred in public institutions of early childhood education. The instruments included a structured questionnaire administered to mothers and clinical oral examinations of the mothers and children. The social variables considered were marital status, maternal education, number of children, income, employment status, and frequency of visits to a dental professional. The measured outcomes were the maternal NDT and child caries history. Data were analyzed by the chi-square test (χ2) and by discriminant analysis. RESULTS: The final sample consisted of 272 mother-child pairs and it was found that the greatest need for treatment was among mothers with low educational level and low family income who rarely or never visited a dentist. Tooth decay was less frequent in only child, and most frequent in children of mothers with low educational attainment, and in children in lower income households who rarely or never visited the dentist. The social determinants of caries in children and of the maternal NDT were similar. It follows that the maternal NDT and caries history among children were strongly associated with maternal education (p<0.0001), household income (p<0.0001), and frequency of visits to a dental professional (0.0018). Caries history among children was also associated with number of children in the household (p<0.0001). CONCLUSIONS: The results suggest that the caries experience in children depended less on the family social variables than on the maternal NDT

Dental caries in children participating in a Dentistry for infants Program

Universidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, Pediatric Dentistry of School of Dentistry of AraraquaraUniversidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, School of Dentistry of AraraquaraUniversidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, School of Dentistry of São José dos CamposUniversidade Estadual de Londrina – UELUniversidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, Pediatric Dentistry of School of Dentistry of AraraquaraUniversidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, School of Dentistry of AraraquaraUniversidade Estadual Paulista “Júlio de Mesquita Filho” – UNESP, School of Dentistry of São José dos Campo

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber's hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber's hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategie