CD24 Expression is an Independent Prognostic Marker in Cholangiocarcinoma

CD24 has been described as an adverse prognostic marker in several malignancies. This study evaluates CD24 expression in cholangiocarcinoma and correlates the findings with clinicopathologic data and patient survival. Between 1996 and 2002, 22 consecutive patients with cholangiocarcinoma were treated at our institution. Demographic data, SEER stage, pathologic data, treatment, expression of CD24, mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%) expression. A negative association was noted between the expression of CD24 and p-MAPK. Median survival for patients with low expression of CD24 was 36 months and high expression was 8 months. Median survival for patients who received chemotherapy with low CD24 expression was 163 months, and for seven patients with high CD24 expression, it was 17 months (p = 0.04). With the addition of radiation therapy, median survival for patients with low expression of CD24 was 52 months and high expression was 17 months (p = 0.08). On multivariate analysis, the use of chemotherapy (p = 0.0014, hazard ratio 0.069) and the CD24 overexpression (p = 0.02, hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in cholangiocarcinoma, and overexpression is predictive of poor survival and possibly of lack of response to chemotherapy and radiation therapy. These findings may improve selection of patients for the appropriate treatment modality and the development of CD24-targeted therapy

TCDD alters pituitary-adrenal function II: Evidence for decreased bioactivity of ACTH

The present study assessed the ability of primary cultures of rat anterior pituitary cells to secrete bioactive ACTH in the presence of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). The bioactivity of the secreted pituitary cell ACTH was determined by its ability to stimulate secretion of corticosterone from primary cultures of rat adrenal cells. ACTH from basal or CRH stimulated pituitary cells treated with TCDD was found to be less capable of stimulating corticosterone secretion from primary rat adrenal cell cultures than equimolar concentrations of ACTH purchased from a commercial supplier. Corticosterone secretion from adrenal cell cultures treated with ACTH from basal or CRH stimulated pituitary cell cultures exposed to TCDD was decreased by 60 and 70%, respectively. The decreased ability to stimulate corticosterone secretion can be overcome when extracts of ACTH from pituitary cell cultures treated with TCDD are supplemented with commercial ACTH. These findings indicate that TCDD may alter the bioactivity of secreted ACTH from the anterior pituitary gland.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30482/1/0000110.pd

TCDD alters pituitary-adrenal function I: Adrenal responsiveness to exogenous ACTH

Plasma ACTH concentrations in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-treated rats (50 [mu]g/kg; single, oral dose) were 2.1-, 2.1-, 2.9-, 1.7-, 1.5-, 2.0- and 3.0-fold greater than control values, respectively, at days 1, 3, 5, 7, 10, and 14. At days 1 and 5 plasma corticosterone concentrations were increased 5.1- and 8.0-fold, respectively; whereas, at days 10 and 14 they were depressed to values of 50% and 39% of controls, respectively. Adrenal glands were exised from rats treated with TCDD and corticosterone production was assessed. Basal corticosterone concentrations produced by treated adrenals were depressed to 81%, 72%, and 71% of control values at days 5, 7, and 14, respectively. Corticosterone secretion by ACTH stimulated adrenals was equivalent to controls. These findings suggest that TCDD exposure decreases the bioactivity of the ACTH secreted by the anterior pituitary.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30481/1/0000109.pd