Using cDNA database mining strategies and real-time quantitative reverse transcription-PCR, we identified B7-H4 as a novel gene that is overexpressed in ovarian and breast cancer tissues when compared with normal tissues. The gene encodes a protein of 282 amino acids with a signal sequence, an immunoglobulin domain, and a COOH-terminal hydrophobic transmembrane domain. Immunohistochemistry experiments show plasma membrane staining in serous ovarian and breast cancer, confirming the tissue specificity and cell surface localization. We have developed a sensitive dual monoclonal antibody sandwich ELISA to analyze the level of B7-H4 protein in >2,500 serum samples, ascites fluids, and tissue lysates. High levels of B7-H4 protein were detected in ovarian cancer tissue lysates when compared with normal tissues. B7-H4 was present at low levels in all sera but showed an elevated level in serum samples from ovarian cancer patients when compared with healthy controls or women with benign gynecologic diseases. The median B7-H4 concentration in endometrioid and serous histotypes was higher than in mucinous histotypes, consistent with results of immunohistochemical staining. The multivariate logistic regression analysis of B7-H4 and CA125 measured in the same sample set resulted in an area under the curve (AUC) of 0.86 for all stages and 0.86 for stage I/II patients, which was significantly higher than the AUC for either marker alone. In early-stage patients, the sensitivity at 97% specificity increased from 52% for CA125 alone to 65% when used in combination with B7-H4. We conclude that B7-H4 is a promising new biomarker for ovarian carcinoma.

OBJECTIVE -1,5-Anhydroglucitol (1,5AG) is a major circulating polyol arising primarily from ingestion and excreted competitively with glucose. Japanese studies have demonstrated reduced concentrations of 1,5AG in serum in hyperglycemic patients in comparison with euglycemic subjects and a gradual normalization of 1,5AG values for patients responding to antihyperglycemic therapies. In this first U.S. study, we assessed the ability of 1,5AG measurements to monitor glycemic control in a cohort of 77 patients with diabetes (22 with type 1 diabetes, 55 with type 2 diabetes) who presented with suboptimal glycemic control at baseline (defined as HbA 1c Ն7%).RESEARCH DESIGN AND METHODS -Each patient received therapies consisting of combinations of diabetes education, nutritional counseling, and addition or dose adjustment of various insulins or oral antihyperglycemic medications. Therapy was targeted to reduce mean HbA 1c by Ն1.0% over the monitoring period. 1,5AG, HbA 1c , fructosamine, and random glucose measurements were performed at baseline and at 2, 4, and 8 weeks after the initiation of therapy.RESULTS -1,5AG, fructosamine, and glucose values progressed significantly toward euglycemia by week 2 of monitoring (Wilcoxon's signed-rank test, P Ͻ 0.05), with median changes of 93, Ϫ7, and Ϫ13% for 1,5AG, fructosamine, and glucose, respectively. In contrast, HbA 1c values did not respond significantly to therapy until week 4. On an individual patient basis, 89.6% of patients displayed longitudinal changes of 1,5AG from baseline to week 8 in concordance with HbA 1c . 1,5AG was also highly correlated with HbA 1c and fructosamine (Spearman ϭ Ϫ0.6459 and Ϫ0.6751, respectively; both P Ͻ 0.0001).CONCLUSIONS -We conclude that 1,5AG responds sensitively and rapidly to changes in glycemia and monitors glycemic control in accordance with established markers.

PCA3 clinical performance was validated in the largest repeat biopsy study to date. Increased PCA3 scores indicated increased risk of contemporaneous cancers and predicted future biopsy outcomes. Use of PCA3 in combination with serum prostate specific antigen and other risk factors significantly increased diagnostic accuracy.

Elevated Lp-PLA2 levels predict CHD events in apparently healthy older adults, independent of CHD risk factors.

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