FGFR3 and Tp53 mutations in T1G3 transitional bladder carcinomas: independent distribution and lack of association with prognosis.

FGFR3 and Tp53 mutations have been proposed as defining two alternative pathways in the pathogenesis of transitional bladder cancer. FGFR3 mutations are associated with low-grade tumors and a favorable prognosis. Tp53 alterations are associated with advanced tumors and, possibly, with a poor prognosis. We focus here on the subgroup of T1G3 superficial tumors because they are a major clinical challenge. Patients (n = 119) were identified from a prospective study of 1,356 cases. Mutations in FGFR3 (exons 7, 10, and 15) and Tp53 (exons 4-9) were analyzed using PCR and direct sequencing. All cases were followed for recurrence and death. Survival was analyzed using Kaplan-Meier curves and multivariable Cox regression. FGFR3 mutations were detected in 20 (16.8%) tumors; 100 mutations in Tp53 were found in tumors from 78 (65.5%) cases. Multiple alterations in Tp53 were present in 19 tumors (16%). Inactivating mutations were present in 58% of tumors. The combined mutation distribution (FGFR3/Tp53) was: wt/wt (34.5%), mut/wt (7.6%), wt/mut (48.7%), and mut/mut (9.2%), indicating that the presence of either mutation did not depend on the other (P value = 0.767). FGFR3 and Tp53 mutations were not associated with clinicopathologic characteristics of patients and did not predict, alone or in combination, recurrence or survival. Taking the risk of the wt/wt group as reference, the mutation-associated risks of cancer-specific mortality were: mut/wt 1.42 (0.15-13.75), wt/mut 0.67 (0.19-2.31), mut/mut 1.62 (0.27-9.59). These molecular features support the notion that T1G3 tumors are at the crossroads of the two main molecular pathways proposed for bladder cancer development and progression.     

Challenges and rewards of research in marine natural products chemistry in Brazil

Brazil is blessed with a great biodiversity, which constitutes one of the most important sources of biologically active compounds, even if it has been largely underexplored. As is the case of the Amazon and Atlantic rainforests, the Brazilian marine fauna remains practically unexplored in the search for new biologically active natural products. Considering that marine organisms have been shown to be one of the most promising sources of new bioactive compounds for the treatment of different human diseases, the 8000 km of the Brazilian coastline represents a great potential for finding new pharmacologically active secondary metabolites. This review presents the status of marine natural products chemistry in Brazil, including results reported by different research groups with emphasis on the isolation, structure elucidation, and evaluation of biological activities of natural products isolated from sponges, ascidians, octocorals, and Opistobranch mollusks. A brief overview of the first Brazilian program on the isolation of marine bacteria and fungi, directed toward the production of biologically active compounds, is also discussed. The current multidisciplinary collaborative program under development at the Universidade de S?o Paulo proposes to establish a new paradigm toward the management of the Brazilian marine biodiversity, integrating research on the species diversity, ecology, taxonomy, and biogeography of marine invertebrates and microorganisms. This program also includes a broad screening program of Brazilian marine bioresources, to search for active compounds that may be of interest for the development of new drug leads.     

Informant consensus factor and antibacterial activity of the medicinal plants used by the people of San Rafael Coxcatlán, Puebla, México

Using ethnobotanical techniques, the medicinal flora used by the inhabitants of San Rafael Coxcatlán, Puebla was determined. During the field work, two types of interviews were applied (free listing and semi-structured) to 60 informants, who supplied consistent information concerning the use of 46 species of medicinal plants. Further analysis showed 13 categories of different medicinal use. An informant consensus factor was calculated and 16 species were selected due to their utilization in the treatment of diseases of possible bacterial origin. Of these 16 plants, sequential extractions were made with hexane, ethyl acetate and methanol. The obtained extracts were used to assess their antibacterial activity against 14 bacterial strains; 75% of the plants presented antibacterial activity. The medicinal species Jatropha neopauciflora Pax (Euphorbiaceae) and Juliania adstringens (Schldl.) Schldl. (Julianiaceae) were those that showed the biggest activity. Moreover, these species also had the highest informant consensus factor values.     

Hepatocyte and nuclear areas in alcoholic liver cirrhosis: their relationship with the size of the nodules and the degree of fibrosis

The aim of the study in alcoholic cirrhotic patients was to determine if a relationship exists between the areas of hepatocytes and their nuclei and the area of the nodules to which these cells belong as well as the thickness of the fibrous tracts which delimit these nodules. It was found that hepatocyte and nuclear areas were enlarged the smaller the nodules and the thicker the surrounding fibrous tracts. Considering that oxygen supply in liver cirrhosis decreases with increasing fibrosis, our results permit the hypothesis that a low oxygen supply causes an increase not only in liver cell size but also in nuclear size, which is an index of nuclear activity.