Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer.

Clinical trials are evaluating the effect of neoadjuvant chemotherapy on men with high-risk prostate cancer. Little is known about the clinical significance of postchemotherapy tumor histopathologic features. We assessed the prognostic and predictive value of histologic features (intraductal carcinoma, vacuolated cell morphologic features, inconspicuous glands, cribriform architecture, and inconspicuous cancer cells) observed in 50 high-risk prostate cancers treated with preprostatectomy docetaxel and mitoxantrone.

Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer.

Background: : A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence.

Methods: : Fifty-seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m(2) and escalating mitoxantrone to 4 mg/m(2) before prostatectomy.

CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity.

Background: Metastatic prostate cancer is either inherently resistant to chemotherapy or rapidly acquires this phenotype after chemotherapy exposure. In this study, we identified a docetaxel-induced resistance mechanism centered on CCL2.

Methods: We compared the gene expression profiles in individual human prostate cancer specimens before and after exposure to chemotherapy collected from previously untreated patients who participated in a clinical trial of preoperative chemotherapy.

The iroquois homeobox gene 5 is regulated by 1,25-dihydroxyvitamin D3 in human prostate cancer and regulates apoptosis and the cell cycle in LNCaP prostate cancer cells.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the most active metabolite of vitamin D3, has significant antitumor activity in a broad range of preclinical models of cancer. In this study, we show that the Iroquois homeobox gene 5 (Irx5) is down-regulated by 1,25(OH)2D3 in human prostate cancer samples from patients randomly assigned to receive weekly high-dose 1,25(OH)2D3 or placebo before radical prostatectomy. Down-regulation of Irx5 by 1,25(OH)2D3 was also shown in the human androgen-sensitive prostate cancer cell line LNCaP and in estrogen-sensitive MCF-7 breast cancer cells.

Evaluation of the glutamate decarboxylase genes Gad1 and Gad2 as candidate genes for acute ethanol withdrawal severity in mice.

Previous studies in crosses between the C57BL/6J (B6) and the DBA/2J (D2) mice have implicated a role of the genes encoding for the 67- and 65-kDa isoforms of the glutamate decarboxylase (Gad1 and Gad2) in the manifestation and severity of multiple ethanol-related traits such as acute ethanol withdrawal severity [Buck, K.J., Metten, P.