Modulation of vinblastine sensitivity by dipyridamole in multidrug resistant fibrosarcoma cells lacking mdr1 expression.

We examined the ability of dipyridamole (DPM) to act synergistically with vinblastine (VBL) in HT1080 fibrosarcoma cells and a drug-resistant variant, HT1080/DR4, which lacks mdr1 expression, in order to determine whether DPM requires P-glycoprotein to modulate drug sensitivity. Median effect analysis of clonogenic assay was used to produce the combination index (CI50, values less than 1 indicate synergy). DPM was mildly synergistic with VBL producing a CI50 of 0.83 +/- 0.13 for HT1080 cells and 0.80 +/- 0.16 for HT1080/DR4 cells. HT1080 and HT1080/DR4 cells accumulated 6.7 +/- 0.7 and 5.6 +/- 0.9 pmol 3H-VBL mg cells-1 at steady state (Css) and 20 microM DPM elevated the Css by 1.8 and 2.9-fold, respectively. In comparison, the CI50 was 1.1 +/- 0.2 in parental KB-3-1 cells and 0.1 +/- 0.1 in mdr1-expressing KB-GRC1 cells. The KB-3-1 and KB-GRC1 cells had a Css of 3.8 +/- 0.8 and 0.7 +/- 0.2 pmol 3H-VBL mg cells-1, respectively, and DPM elevated the Css by 9.2-fold in KB-GRC1 cells. These studies demonstrate that DPM can produce synergy independently of mdr1 expression but that much greater levels of synergy are achievable in mdr1-expressing tumour cells

Enhancing the effectiveness of interdisciplinary mental health treatment teams

Mental health administrators often lack guidelines for promoting and evaluating the effectiveness of interdisciplinary clinical treatment teams. This article describes the use of a model of group effectiveness that elucidates several aspects of team effectiveness. Also discussed are how administrators can support such teams by reviewing their initial set-up, how the organization influences the team's productivity and longevity, and how team members can better understand one another's personal and professional frames of reference to improve mutual collaboration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44090/1/10488_2005_Article_BF02106536.pd