Citations

B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51–6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.

The biological changes that occur in the brains of Alzheimer's disease (AD) patients are thought to begin long before the onset of clinical symptoms. Although current therapeutic agents have been approved only for patients with mild to moderate AD, Alzheimer‐type pathology in patients with mild to moderate AD is already quite advanced. One impetus for the development of the concept of mild cognitive impairment (MCI) was the attempt to recognize AD early in its clinical expression and to determine whether it is possible through therapeutic interventions to improve the memory impairment at this stage or delay further progression to dementia. To this end, several clinical trials have been conducted in patients with MCI. On September 8 and 9, 2004 a meeting of the Alzheimer's Association Research Roundtable was held at which experts in the field of MCI convened to review the collective experience from these trials and to consider potential approaches that might improve MCI clinical trials in the future. This article summarizes the presentations and discussions of that meeting.