Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells.

Chromosome instability is a commonly observed feature in ovarian carcinoma. Mitotic checkpoint controls are thought to be essential for accurate chromosomal segregation, and MAD2 is a key component of this checkpoint. In this study, we investigated the competence of the mitotic checkpoint and its relationship to the expression of MAD2 protein in seven ovarian cancer cell lines. We found that a significant number (43%, three of seven cell lines) of the tested ovarian cancer cells failed to arrest in the G(2)-M phase of the cell cycle in response to microtubule disruption. This loss of mitotic checkpoint control was associated with reduced expression of the MAD2 protein. To additionally understand the significance of the MAD2 to mitotic checkpoint control, we established an inducible expression system in which MAD2 was induced by the addition of ponasterone A. Notably, the induced expression of MAD2 in two checkpoint-defective ovarian cancer cell lines led to the restoration of mitotic checkpoint response to spindle-disrupting agents. Taken together, our findings suggest that the steady-state amount of MAD2 inside cells may represent a molecular switch for mitotic checkpoint control. This provides a novel insight into the molecular basis of CIN in ovarian carcinoma and has implications for effective use of checkpoint-targeting drugs.

980-nm laser therapy versus varicose vein surgery in racially diverse Penang, Malaysia.

BACKGROUND: Chronic venous disorders are conditions of increasing prevalence in the developing world, and venous ulceration is the terminal sequel. Currently there are only limited data on all aspects of this from Southeast Asia. The aim of the present study was to assess differences in the demography and outcome between varicose vein surgery (VVS) and the relatively new endovenous laser therapy (EVT) in patients from Penang, Malaysia. METHODS: A retrospective study was performed. Patients who presented to the outpatient clinic of the surgical department with saphenofemoral junction and/or saphenopopliteal junction incompetence associated with reflux of the great saphenous vein or small saphenous vein, respectively, underwent either surgery (1999-2004) or laser therapy (2004-2006). A single surgeon at a single institution performed all procedures. RESULTS: A total of 350 limbs were treated from 292 patients. Demographics, symptoms, outcomes and complications that arose in both groups were compared. There were significant improvements in pains, swelling, cramps and heaviness postoperatively (P < 0.001) in both groups. Deep venous thrombosis was present as a complication in the VVS group at 3.0%, but was absent altogether in the EVT group. CONCLUSIONS: Although both are highly effective procedures, laser therapy has become popular as an elective procedure with its minimally invasive nature, cosmesis, rapid recovery and other advantages. Surgery remains an important and very cost-effective procedure, especially in a developing society such as Penang.