Interleukin-6 signaling can activate androgen receptor in a ligand-independent manner and may play an important functional role in hormone-refractory prostate cancer (HRCaP) progression and patient survival. Plasma and serum IL-6 levels have been associated with prostate cancer progression in several small studies. In order to evaluate its prognostic significance in metastatic HRCaP patients, we measured IL-6 in plasma collected at baseline from patients in a large cooperative group study [Cancer and Leukemia Group B 9480 (CALGB 9480)].Methods: 191 patients entered on CALGB 9480 had pretreatment plasma collected and centrally stored. Using a human IL-6 immunoassay, quantitative levels of IL-6 were measured in duplicate on 300 ML samples. The proportional hazard model was used to assess the prognostic significance of IL-6 in predicting overall survival.Results: Median IL-6 level for the cohort of 191 patients was 4.80 pg/mL. Survival time among patients with IL-6 levels less than or equal to the median was 19 months (95% CI, 17-22) compared with 11 (95% CI, 8-14) months for patients above the median (P = 0.0004). In multivariate analysis, adjusting on performance status, lactate dehydrogenase, and prostate-specific antigen level, the hazard ratio was 1.38 (95% CI, 1.01-1.89; P = 0.043) using the median level as a cut point. Furthermore, a cut point of 13.31 pg/mL revealed robust prognostic significance with a hazard ratio of 2.02 (95% CI, 1.36-2.98; P = 0.0005).Conclusions: Plasma IL-6 level has prognostic significance in patients with metastatic HRCaP from CALGB 9480. These findings support using IL-6 levels in prognostic models and support the rationale for IL-6-targeted therapy in patients with HRCaP.

OBJECTIVE. The objective of this study was to quantitatively assess cartilage degeneration via T2 mapping to compare patients with and those without meniscal tears. SUBJECTS AND METHODS. Thirty-seven patients (18 men, mean age ± SD, 65.7 ± 7.8 years; 19 women, mean age, 63.8 ± 12.0 years) with clinical symptoms of osteoarthritis were studied on 3-T MRI using a 2D multiecho spin-echo sequence for T2 mapping. Meniscal signal and morphology were qualitatively graded and correlated to the T2 values of cartilage. Analysis of covariance, Bonferroni multiple comparison correction, and Spearman’s correlation coefficients were used for statistical analysis. RESULTS. Patients with meniscal tears (median ± interquartile range, 50.1 ± 6.1 milliseconds) had significantly (p = 0.021) higher T2 values of cartilage than those without meniscal tears (45.7 ± 4.8 milliseconds). T2 values of cartilage were significantly higher in the medial compartment than in the lateral compartment in patients with medial meniscal tears (p = 0.018). CONCLUSION. T2 measurements are increased in patients with meniscal tears; this finding adds support to the theory of an association of osteoarthritis with damage to both the menisci and hyaline cartilage.

Objective To assess the relationship between T2 values of femorotibial cartilage and knee alignment in patients with clinical symptoms of medial osteoarthritis (OA). Methods Twenty-four patients (mean age ± standard deviation, 62.5±9.9 years) with clinical symptoms of medial knee OA, 12 with varus and 12 with valgus alignment of the femorotibial joint, were investigated on 3T MR using a 2D multi-echo spin echo (MESE) sequence for T2 mapping. Analysis of covariance, Spearman correlation coefficients, exact Mann-Whitney tests, and Fisher's exact tests were used for statistical analysis. Results Overall the T2 values of cartilage in the medial compartment (median ± interquartile-range, 49.44±6.58) were significantly higher (P=0.0043) than those in the lateral compartment (47.15±6.87). Patients with varus alignment (50.83±6.30 ms) had significantly higher T2 values of cartilage (P<0.0001) than patients with valgus alignment (46.20±6.00 ms). No statistically significant association between the T2 values of cartilage (in either location) and the Kellgren Lawrence score was found in the varus or in the valgus group. Conclusion T2 measurements were increased in medial knee OA patients with varus alignment, adding support to the theory of an association of OA and joint alignment.

Objectives: Amplified in breast cancer-1 (AIB1) is a steroid receptor coactivator that enhances estrogendependent transcriptional activation by the estrogen receptor. It is unknown whether AIB1 also interacts with the androgen receptor. Because the development and progression of prostate cancer is likely to be partially mediated by steroid hormones, we investigated whether a polymorphic CAG/CAA repeat encoding glutamine in the AIB1 gene is related to prostate cancer risk in a nested study of 581 patients and 786 age-matched control subjects in the Physicians' Health Study. Materials and Methods: DNA was extracted from peripheral whole blood, and the region encompassing the repeat was amplified using fluorescent-labeled primers. The fragments were run on polyacrylamide gels and sized by computer software. We estimated the relative risk (RR) of prostate cancer for AIB1 gluta-mine repeat length from logistic regression models controlling for the matching variables. Results: Three glutamine repeat lengths were prevalent: 29 (47.8% among control subjects), 28 (38.5% among control subjects), and 26 (12.6% among control subjects). Compared to 29 repeats, the RR of prostate cancer was 0.92 (95% confidence interval [CI] 0.72-1.17) for 26 repeats and 1.01 (95% CI 0.86-1.19) for 28 repeats. Compared to 28/29, the RR of prostate cancer was not significantly altered for any of the other common genotypes. No clear associations were present for AIB1 glutamine repeat length genotype by stage at the diagnosis/histologic grade of the tumor. Conclusion: This study does not support an important role in prostate cancer incidence or aggressiveness of AIB1 glutamine repeat length in the range observed in this predominately white cohort.