Background:The standard approach to generalized peritonitis due to perforated diverticulitis involves open surgery and diversion of faecal content. This study assessed the feasibility of laparoscopic peritoneal lavage.Methods: A prospective multi-institutional study of 100 patients was undertaken. All consenting patients with perforated diverticulitis causing generalized peritonitis underwent attempted laparoscopic peritoneal lavage. The degree of peritonitis, according to the Hinchey grading system, was recorded. Primary endpoints were operative success and resolution of symptoms.

Purpose : Associations between p160 coactivator proteins and the development of resistance to endocrine treatment have been described. We hypothesized that nuclear receptor coregulatory proteins may interact with nonsteroid receptors. We investigated the mitogen-activated protein kinase -activated transcription factors, Ets, as possible interaction proteins for the coactivators SRC-1 and AIB1 and the corepressor NCoR in human breast cancer.Experimental Design: Expression and coexpression of Ets and the coregulatory proteins was investigated using immunohistochemistry and immunofluorescence in a cohort of breast tumor patients (N = 134). Protein expression, protein-DNA interactions and protein-protein interactions were assessed using Western blot, electromobility shift, and coimmunoprecipitation analysis, respectively.Results: Ets-1 and Ets-2 associated with reduced disease-free survival (P < 0.0292, P < 0.0001, respectively), whereas NCoR was a positive prognostic indicator (P < 0.0297). Up-regulation of Ets-1 protein expression in cell cultures derived from patient tumors in the presence of growth factors associated with tumor grade (P < 0.0013; n = 28). In primary breast tumor cell cultures and in the SKBR3 breast cell line, growth factors induced interaction between Ets and their DNA response element, induced recruitment of coactivators to the transcription factor-DNA complex, and up-regulated protein expression of HER2. Ets-1 and Ets-2 interacted with the coregulators under basal conditions, and growth factors up-regulated Ets-2 interaction with SRC-1 and AIB1. Coexpression of Ets-2 and SRC-1 significantly associated with the rate of recurrence and HER expression, compared with patients who expressed Ets-2 but not SRC-1 (P < 0.0001 and P < 0.0001, respectively).Conclusions: These data describe associations and interactions between nonsteroid transcription factors and coregulatory proteins in human breast cancer.

Background: In human breast cancer, the growth factor receptor HER2 is associated with disease progression and resistance to endocrine treatment. Growth factor induced mitogen activated protein kinase activity can phosphorylate not only the oestrogen receptor, but also its coactivator proteins AIB1 and SRC-1. Aim: To determine whether insensitivity to endocrine treatment in HER2 positive patients is associated with enhanced expression of coactivator proteins, expression of the HER2 transcriptional regulator, PEA3, and coregulatory proteins, AIB1 and SRC-1, was assessed in a cohort of patients with breast cancer of known HER2 status. Methods: PEA3, AIB1, and SRC-1 protein expression in 70 primary breast tumours of known HER2 status (HER2 positive, n = 35) and six reduction mammoplasties was assessed using immunohistochemistry. Colocalisation of PEA3 with AIB1 and SRC-1 was determined using immunofluorescence. Expression of PEA3, AIB1, and SRC-1 was correlated with clinicopathological parameters. Results: In primary breast tumours expression of PEA3, AIB1, and SRC-1 was associated with HER2 status (p = 0.0486, p = 0.0444, and p = 0.0012, respectively). In the HER2 positive population, PEA3 expression was associated with SRC-1 (p = 0.0354), and both PEA3 and SRC-1 were significantly associated with recurrence on univariate analysis (p = 0.0345; p,0.0001). On multivariate analysis, SRC-1 was significantly associated with disease recurrence in HER2 positive patients (p = 0.0066). Conclusion: Patients with high expression of HER2 in combination with SRC-1 have a greater probability of recurrence on endocrine treatment compared with those who are HER2 positive but SRC-1 negative. SRC-1 may be an important predictive indicator and therapeutic target in breast cancer.

The oestrogen receptor (ER) interacts with coactivator proteins to modulate genes central to breast tumour progression. Oestrogen receptor is encoded for by two genes, ER-a and ER-b. Although ER-a has been well characterized, the role of ER-b as a prognostic indicator remains unresolved. To determine isoform-specific expression of ER and coexpression with activator proteins, we examined the expression and localisation of ER-a, ER-b and the coactivator protein steroid receptor coactivator 1 (SRC-1) by immunohistochemistry and immunofluorescence in a cohort of human breast cancer patients (n ¼ 150). Relative levels of SRC-1 in primary breast cultures derived from patient tumours in the presence of b-oestradiol and tamoxifen was assessed using Western blotting (n ¼ 14). Oestrogen receptor-b protein expression was associated with disease-free survival (DFS) and inversely associated with the expression of HER2 (P ¼ 0.0008 and Po0.0001, respectively), whereas SRC-1 was negatively associated with DFS and positively correlated with HER2 (Po0.0001 and Po0.0001, respectively). Steroid receptor coactivator 1 protein expression was regulated in response to b-oestradiol or tamoxifen in 57% of the primary tumour cell cultures. Protein expression of ER-b and SRC-1 was inversely associated (P ¼ 0.0001). The association of ER-b protein expression with increased DFS and its inverse relationship with SRC-1 suggests a role for these proteins in predicting outcome in breast cancer.