The crystal structure of an engineered monomer of the lambda Cro repressor shows unexpected expansion of the hydrophobic core of the protein and disorder of the five C-terminal residues [Albright et al. (1996) Biochemistry 35, 735-742]. This structural information has guided the construction of a second generation of monomeric Cro proteins by combinatorial mutagenesis of selected core and C-terminal residues. Clones were identified in a library of randomized cro genes by a genetic screen for protein accumulation in Escherichia coli. Sequencing of candidate genes followed by purification and analysis of their product proteins has identified alternative arrangements of hydrophobic core residues which result in substantial increases in thermal stability. In contrast, residue replacements at the C-terminus have minor effects on stability but may increase protein expression levels.

OBJECTIVES To evaluate the overall survival (OS) and disease‐specific survival (DSS) in men receiving primary androgen‐deprivation therapy (PADT) or salvage medical ADT (SADT) for prostate cancer. PATIENTS AND METHODS After Institutional Review Board approval, we retrospectively reviewed patients receiving ADT for prostate cancer between July 1987 and June 2007. Variables included age at diagnosis and ADT induction, race, PSA level before ADT, ADT schedule (continuous/intermittent), clinical/pathological stage, hormone‐refractory prostate cancer (HRCP) status, PADT or SADT, and deaths. RESULTS In all, 548 men were analysed. The mean age at diagnosis and ADT induction were 70.1 and 72.3 years, respectively, and 321 (58.6%) were African‐American. The median PSA level before ADT was 16.3 ng/mL. ADT was administered continuously in 497 (90.7%) patients; 342 (62.4%) received PADT while 206 (37.6%) received SADT. At mean (range) follow‐up of 81.8 (2.1–445) months, 98 (17.9%) deaths occurred; 31 (31.6%) were cancer‐specific. The OS and DSS in the PADT and SADT groups were not significantly different (P = 0.36 and P = 0.81, respectively). Mortality rates/distributions were similar between groups (P = 0.68). Multivariate predictors of OS and DSS included age at diagnosis (P = 0.03) and ADT induction (P = 0.009), tumour stage (P < 0.001), and PSA level at ADT induction (P = 0.01). Progression to HRPC worsened OS and DSS (both P < 0.001). CONCLUSION PADT and SADT prolong survival in men with prostate cancer. HRPC portends a poor DSS. Age at diagnosis and ADT induction, PSA level before ADT, and disease stage predict both OS and DSS in this population. However, most men died from causes unrelated to prostate cancer, thus questioning the true value of ADT in prolonging patient survival.

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