Constitutive and stimulated production of VEGF by human megakaryoblastic cell lines: effect on proliferation and signaling pathway.

Release of vascular endothelial growth factor (VEGF) and other candidate angiogenic factors such as basic fibroblast growth factor and transforming growth factor beta, may play a role in sustaining neoplastic cell proliferation and tumor growth. We evaluated VEGF expression and synthesis in the two erythromegakaryocytic cell lines B1647, HEL and one megakaryocytic cell line MO7 expressing erythroid markers. In this study RT-PCR was performed to evaluate VEGF expression and that of its receptor KDR; VEGF production was assayed by Elisa test and western blot analysis; sensitivity to VEGF was tested by thymidine incorporation. VEGF and its receptor KDR were expressed in B1647 and HEL, both as mRNAs and as proteins, while only KDR transcript was found in MO7 cells. Only B1647 and HEL cells showed a strong spontaneous proliferating activity. In fact, measurable amounts of VEGF were present in the unstimulated cell medium, thus suggesting an autocrine production of VEGF by B1647 and HEL cells, but not by MO7, which was inhibited in mRNA-silencing conditions. This production could not be further boosted by other growth factors, whereas it was inhibited by TGF-beta1. Finally, analysis of Shc signal transduction proteins following stimulation with VEGF indicated that only p46 was tyrosine phosphorylated. These data indicate that leukemic cells may be capable of autocrine production of VEGF which, in turn, maintains cell proliferation, possibly mediated by Shc p46 phosphorylation.

VEGF inhibition and cytotoxic effect of aplidin in leukemia cell lines and cells from acute myeloid leukemia.

BACKGROUND: Aplidine (APL) is a marine depsipeptide isolated from the Mediterranean tunicate Aplidium albicans that is under clinical phase II development. In contrast to the lack of bone marrow toxicity reported in phase I/II studies, it has been shown to induce cytotoxicity at very low concentration against lymphoblastic leukemia blast, as well as having an impact in the vascular endothelial growth factor (VEGF)/VEGF receptor 1 loop. PATIENTS AND METHODS: To confirm these findings we investigated APL-related VEGF inhibition and its cytotoxic effect on myeloid leukemic cells lines (K-562, HEL and HL60) and fresh leukemia blasts derived from 30 patients with acute myeloid leukemia (AML). The conventional active 4-demetoxi-daunorubicin (idarubicin; IDA) was included as a positive control. RESULTS: APL was found to be significantly (P<0.001) more active than IDA in obtaining 50% growth-inhibition in K-562, HEL and HL60 cell lines. Results obtained with AML blast cells were super imposible. ID(50) ranged from 0.024 to 0.610 microM for IDA (0.200+/-0.176) and from 0.001 to 0.108 microM for APL (0.020+/-0.031). Annexin V tests and cell cycle analysis performed on cell lines confirmed the stronger citotoxic capability of APL as apoptotic inducer and as a G(1) blocker. The inhibitory effects of APL on VEGF release and secretion have been confirmed by ELISA tests performed on HEL: the VEGF concentration in cell surnatant was reduced from 169 to 36 pg/ml after 24 h of exposure to a pharmacological concentration of APL. CONCLUSIONS: APL harbors a strong in vitro antileukemic activity at a concentration achievable in patients at non-myelotoxic doses. Our data also support the notion of an impact on VEGF secretion. Clinical studies with this new marine-derived compound in relapsed/resistant leukemia are underway.

Utilization of the Brief Symptom inventory to discriminate between violent and nonviolent male relationship partners.

This study reports on the use of the Brief Symptom Inventory, a shortened version of the Symptom Check List-90-Revised, to measure psychopathological symptoms that predict male domestic violence. A sample of 152 men and their partners reported on the severity of violent behavior present in their relationship. Discriminant analysis indicated variation in men's violent status as a function of psychopathological symptoms. Violent men evidenced higher scores on 7 of the 9 subscales of the Brief Symptom Inventory, namely, Depression, Anxiety, Hostility, Phobia, Paranoid Ideation, Interpersonal Sensitivity, and Psychoticism.

Multiple views on family data: the sample case of adolescent, maternal, and paternal perspectives on family differentiation levels.

The major objective of this article is to demonstrate a data analysis technique--confirmatory factor analysis with structural equation modeling--that can be used when the researcher has multiple perspectives on the same variables. The present data set was constructed from two samples that contained information collected on adolescents', mothers', and fathers' perspectives on family differentiation levels as measured by the Differentiation in the Family System Scale (DIFS; Anderson & Sabatelli, 1992). Results of the combined sample confirmatory factor analysis procedures indicated that the family members' perspectives converged and could be used as a single latent variable. The methodological implications of these findings are discussed.

Perceived social support from family and friends in a clinical sample of adolescents.

This study reports on the use of the Perceived Social Support from Family and Perceived Social Support from Friends scales (Procidano & Heller, 1983) in a sample of adolescents at the initiation of outpatient treatment. Reliability and validity evidence is presented that generally replicates earlier studies utilizing these instruments. Multiple regression results are also reported, indicating that different combinations of perceived support from family and friends significantly predict psychosocial maturity levels in this clinical adolescent sample.

Guiding transitional events for children and adolescents through a modern day rite of passage.

The following paper is directed towards highlighting contemporary society's need to maintain rituals of initiation. It focuses on the process of rites of passage. The rite of passage historically has been an important cultural and individual developmental milestone, and is by and large absent in contemporary culture. A three-stage community intervention is described as one example of guiding transitional events for children and adolescents through a modern day rite of passage. Attention is directed towards the process component of such a community intervention, and suggests that an unrealistic amount of focus has been directed towards the content of curriculum and program materials rather than towards the process of a community intervention.

A test of the Olson Circumplex Model: examining its curvilinear assumption and the presence of extreme types.

The debate over the usefulness of different family models continues. Recent attention has been paid to comparisons between the Olson Circumplex Model and the Beavers Systems Model. The present study seeks to contribute evidence that bears directly upon one of the most fundamental points of controversy surrounding the Olson model--the linear versus curvilinear nature of the cohesion and adaptability dimensions. A further contribution is an examination of the actual occurrence of the Circumplex Model's extreme types in a clinical population.