Studies on Hsp90 have mainly focused on its involvement in the activation of several families of protein kinases and of steroid hormone receptors. Little is known regarding the role of Hsp90 in the folding of nascent proteins. We previously reported that Hsp90 plays an active role in the posttranslational assembly of the C-terminal globular head of the reovirus attachment protein 1. We show here that Hsp90 becomes phosphorylated in this process. However, only the unphosphorylated form of Hsp90 is complexed with 1, suggesting that Hsp90 phosphorylation is coupled to the release of the chaperone from the target protein. Geldanamycin, which blocks 1 maturation by preventing the release of Hsp90 from 1, also inhibits Hsp90 phosphorylation. Taken together, these results demonstrate that Hsp90 phosphorylation is linked to its chaperoning function.

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Despite improvements in treatment of localized prostate cancer, local recurrence remains a significant problem. A total of 46 patients with proven local cancer recurrence following external beam radiotherapy entered a prospective clinical trial using ultrasound-guided cryosurgery to ablate the residual prostate gland. Persistent complications included one urethra-rectal fistula, incontinence (2), retention (3), and treatment induced erectile dysfunction (7). Using the PSA definitions for biochemical failure as PSA X0.3 ng/ml, the Kaplan-Meier plots showed the incidence of patients to be free of biochemical recurrence at 51 and 44% at 1 and 2 y, respectively. For a PSA X1.0, the values at 1 and 2 y were 72 and 58%.

Nephron sparing surgery appears safe for patients with unilateral Wilms tumor associated with predisposing syndrome(s), allowing for the preservation of renal function and good oncologic outcomes for the available followup time. If more studies confirm our observation, current recommendations for the surgical treatment of Wilms tumor may need to reemphasize the value of attempting nephron sparing surgery in this patient population.