Statin-AE: a novel angiostatin-endostatin fusion protein with enhanced antiangiogenic and antitumor activity

The combination of angiostatin and endostatin has been shown to have synergistic antiangiogenic and antitumor effects when the genes for these proteins are delivered to tumor cells by retroviral gene transfer. Here we report the construction of a murine angiostatin–endostatin fusion gene (Statin-AE) which shows enhanced antiangiogenic activity on human umbilical vein endothelial cell (HUVEC) tube formation in vitro compared with angiostatin or endostatin alone. Similarly, the fusion gene demonstrates antiangiogenic effects in vivo and antitumor activity in a B16F10 melanoma model when co-delivered by retroviral packaging cell inoculation in mice. The fusion gene demonstrates significantly greater inhibition of tumor growth compared with angiostatin, endostatin or the combination of genes. This revised version was published online in June 2006 with corrections to the Cover Date.     

Methacholine inhalation challenge after rapid saline infusion in healthy subjects

Five healthy subjects were challenged with methacholine on 2 different days, 1 week apart, the second day after acute intravenous 30 ml/kg 0.9% saline infusion. After infusion, we observed a significant reduction in vital capacity (VC), maximal expiratory volume in 1 s (FEV1), provocation dose producing a 35% fall in SGaw (PD35SGaw) and in 25% of maximal expiratory flow (MEF25), and an increase in the slopes of log dose-response curves. Our results suggest an increased bronchial reactivity in acute minimal interstitial lung edema.     

A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol

The Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) 0496 protocol, through the central handling of bone marrow samples at presentation, allowed us to combine cytogenetic and molecular information on a large series of adults with acute lymphoblastic leukemia (ALL) treated homogeneously, enabling us to define as broadly as possible their genetic profile and to determine the impact on outcome of the cytogenetic-molecular signature. Of 414 patients centrally processed, 325 were considered for the categorization into the following cytogenetic-molecular subgroups: normal, t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1;19)/E2A-PBX1, 9p/p15-p16 deletions, 6q deletions, miscellaneous structural abnormalities, and hyperdiploid. The inclusion into each subgroup was based on a hierarchical approach: molecular abnormalities with adverse prognosis had precedence over karyotypic changes with less-defined prognosis and the latter over ploidy. Patients without abnormalities and those with isolated 9p/p15-p16 deletions showed a relatively favorable outcome (median disease-free survival [DFS], > 3 years). The t(9;22)/BCR-ABL, t(4;11)/MLL-AF4, t(1; 19)/E2A-PBX1 defined a group with dismal prognosis (median DFS, 7 months), whereas 6q deletions, miscellaneous aberrations, and hyperdiploidy predicted an intermediate prognosis (median DFS, 19 months). This study highlights the importance of a combined cytogenetic-molecular profiling of adult ALL at presentation as a critical independent determinant of their outcome, providing further evidence of the necessity of a risk-adapted therapeutic algorithm for an optimal management of these patients.     

Homeless teen mothers: social and psychological aspects

Aims

This study proposes to investigate the life contexts and experiences of motherhood among homeless adolescents and their relation with the “uncertainty reduction” theory.

Subjects and Methods

A total of 21 teens, living in eight temporary shelters in the city of São Paulo, were intentionally selected. In-depth, face-to-face semi-structured interviews were subsequently conducted. The study was performed by means of qualitative methodology.

Results

Six themes emerged in the content analysis with the agreement of judges: “circulation” or domestic instability; incapacity to rely on one’s own parents and relatives; the street as a solution; fear of theft of the child; need for support; motherhood as hope and search for identity.

Conclusion

Motherhood acquires the function of giving meaning to existence and opens a window of opportunity for reorganizing their lives around more stable bonds. The results suggest that the reduction in uncertainty could partly explain the relevant role of motherhood in these teens.