Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with mr imaging.

PURPOSE: To assess magnetic resonance (MR) measures of vascular permeability of prostate cancer treated with androgen deprivation and to correlate these with morphologic appearances and serum prostate-specific antigen (PSA) levels. MATERIALS AND METHODS: MR examinations in 56 consecutive patients with prostate cancer were performed before and after luteinizing hormone-releasing hormone analog treatment. T2-weighted and contrast medium-enhanced T1-weighted MR images were obtained. Pre- and posttreatment comparisons of morphologic features, glandular volume, and enhancement-related parameters (capillary permeability, leakage space, gadolinium accumulation) were made. RESULTS: Fifty-five tumors were seen before treatment; 42, after treatment. Signal intensity in the peripheral zone and seminal vesicles decreased on T2-weighted images in 42 (75%) and 25 (45%) patients, respectively. Median volume in tumor decreased by 65% (95% CI: 55%, 76%); in central gland, by 30% (95% CI: 25%, 35%). Reductions in tumor permeability (P <.001) and changes in washout patterns were observed (P <.001). Tumor permeability reductions coincided with a decrease in serum PSA levels in 91% of patients. A weak correlation between tumor permeability and volume change was seen (r = 0.55, P =.04). Reductions in peripheral zone (P <.001) and central gland (P =.009) permeability were noted. CONCLUSION: Androgen deprivation decreases tumor volume and vascular permeability and impairs detection of prostate cancers. Use of MR estimates of permeability may be an additional way of assessing prostatic tumor response to antiandrogen treatment.

Dynamic contrast enhanced MRI of prostate cancer: correlation with morphology and tumour stage, histological grade and PSA.

AIM: To quantify MRI enhancement characteristics of normal and abnormal prostatic tissues and to correlate these with tumour stage, histological grade and tumour markers. MATERIALS AND METHODS: Quantitative gradient recalled echo MR images were obtained following bolus injection of gadopentetate dimeglumine in 48 patients with prostate cancer. Turbo spin-echo T2-weighted images at the same anatomical position were reviewed for the presence of tumours (45 regions), normal peripheral zone (33 regions), and normal appearing central gland (30 regions). Time-signal intensity parameters (onset time, mean gradient and maximal amplitude of enhancement and wash-out score) and modelling parameters (permeability surface area product, lesion leakage space and maximum gadolinium concentration) were correlated with tumour stage, histological grade (Gleason score) and serum prostatic specific antigen (PSA) levels. RESULTS: Significant differences were noted between peripheral zone and tumour with respect to signal intensity and modelling parameters (P = 0.0001), except onset time. No differences between central gland and tumour enhancement values were seen. There was weak correlation between MRI tumour stage and tumour vascular permeability (r(2) = 12%; P = 0.02) and maximum tumour gadolinium concentration (r(2) = 14%; P = 0.015). However, no significant correlations were seen with Gleason score or PSA levels. CONCLUSION: Quantification of MR contrast enhancement characteristics allows tissue discrimination in prostate cancer consistent with known variations in microvessel density estimates.

Phosphorylation sequences in h-caldesmon from phorbol ester-stimulated canine aortas.

The high molecular weight form of caldesmon (h-caldesmon) is phosphorylated in vascular smooth muscle. The stoichiometry of caldesmon phosphorylation increases in response to stimulation of the muscle by several contractile agonists; however, the responsible kinase has not been identified. In this study, we have sequenced the phosphopeptides prepared from h-caldesmon phosphorylated in vitro by protein kinase C (PKC) as well as the phosphopeptides prepared from caldesmon phosphorylated in intact canine aortas that were stimulated to contract with PDBu. PKC phosphorylated three sites located in the C terminus: GSS*LKIEE, AEFLNKS*VQK and NLWEKQS*VDK, while h-caldesmon from intact tissue was phosphorylated at two separate sites also in the C terminus: VTS*PTKV and S*PAPK. By comparison to known substrate consensus sequences for various protein kinases these data suggest that h-caldesmon is directly phosphorylated by a proline-directed protein kinase and not by PKC.