ABSTRACT: To determine how dynamic contrast-enhanced (DCE) MRI at 3T correlates with rectal carcinoma angiogenesis.
Three-dimensional (3D) DCE MRI was performed in 38 patients (23 males, 15 females, mean age 60 years) with histologically-confirmed rectal carcinoma at 3T. Time-intensity curves (TICs) were used to measure peak enhancement ratio (ER(peak)), time to peak enhancement (T(peak)), first enhancement time (T(first-enhance)), and uptake rate for rectal tumor, normal rectal wall, and gluteal muscle. After tumor resection, microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression were determined using immunohistochemistry (IHC) stains on available specimens (N = 24) to correlate with DCE MRI.
Rectal carcinoma showed higher ER(peak) (3.0 +/- 0.9 vs. 1.9 +/- 0.9, P < 0.001), higher uptake rate (2.8 +/- 1.5/minute vs. 1.2 +/- 0.9/minute, P < 0.001), earlier T(peak) (88 +/- 56 seconds vs. 124 +/- 72 seconds, P = 0.027), and earlier T(first-enhance) (34 +/- 6 seconds vs. 40 +/- 7 seconds, P = 0.008) than normal rectal wall. Adenocarcinoma had shorter T(peak) compared to signet cell carcinoma (77 +/- 48 seconds vs. 160 +/- 62 seconds, P = 0.004). T(peak) was negatively correlated with MVD (r = -0.516, P = 0.01) and the mean T(peak) was significantly earlier for the VEGF-positive group compared to the VEGF-negative group (57 +/- 17 seconds vs. 107 +/- 64 seconds, P = 0.021).
DCE MRI parameters help predict rectal tumor angiogenesis measured by MVD and VEGF expression and discriminate malignant from normal tissue.
Journal of Magnetic Resonance Imaging 06/2008; 27(6):1309-16. · 2.70 Impact Factor
ABSTRACT: The purpose of this study was to assess the accuracy of 3-T MRI in the preoperative diagnosis, staging, and planning of surgical management of rectal carcinoma.
Thirty-eight patients (23 men, 15 women) with clinically suspected rectal carcinoma underwent 3-T MRI. Coronal, axial, and sagittal T2-weighted sequences with and without fat suppression; axial T1-weighted spin-echo sequences; axial T1-weighted gradient-echo sequences with and without fat suppression; oblique 2D MR hydrography; and 3D fat-suppressed dynamic contrast-enhanced MRI were performed. Image quality with these sequences was evaluated by three radiologists experienced in body MRI. The significance of difference in results with the sequences was tested. The manner in which MRI staging and feasibility of sphincter-sparing surgery agreed with operative and pathologic findings was evaluated with kappa statistics.
Rectal carcinoma was identified on MRI and confirmed histologically in all 38 patients. MRI findings were correctly predictive of T category in 35 cases (accuracy, 92.1%). In 31 (96.9%) of 32 resectable cases,sphincter-sparing surgical approaches were accurately chosen on the basis of MRI findings. Among the 11 sequences, 3D fat-suppressed dynamic contrast-enhanced MRI best delineated tumor margins. Coronal and axial T2-weighted images also well depicted tumor margins with minimal artifact. T2-weighted images were superior to unenhanced T1-weighted images.
MRI of rectal cancer at 3 T is accurate for prediction of T category and the feasibility of sphincter-sparing surgery. The best images were obtained with coronal, sagittal, and axial T2-weighted sequences and 3D fat-suppressed dynamic contrast-enhanced MRI.
American Journal of Roentgenology 06/2008; 190(5):1271-8. · 2.78 Impact Factor
ABSTRACT: Serine/threonine kinase Akt (also called protein kinase B, PKB) is a downstream effector of phosphoinositide 3-kinase (PI3K) and functions as the focal point for many signal transduction pathways such as glucose metabolism, transcription, cell survival, angiogenesis, and cell motility. Akt is emerging as a central player in tumorigenesis including human ovarian, pancreatic, prostate, breast, and gastric cancers. However, the function and mechanism by which Akt regulate gene transcription in nucleus remains largely unclear. Here we identify histone methyltransferase SETDB1 as a novel nuclear interacting partner of Akt. By yeast two-hybrid screening, we obtained the Akt1-SETDB1 interaction and confirmed the binding both in vitro and in vivo. Both Akt1 and SETDB1 are co-localized in the nucleus in mammalian cells. SETDB1 is not a phosphorylation substrate of Akt kinase. Akt and SETDB1 could coordinate to regulate the activity of certain transcription factors such as forkhead family member. Due to the fact that SETDB1 acts as a specific histone H3, lysine 9-methyltransferase in vivo, we provide the first link between Akt kinase and histone methyltransferase (HMTase). This interaction represents a novel mechanism by which Akt regulates nuclear events including gene transcription.
Molecular and Cellular Biochemistry 12/2007; 305(1-2):35-44. · 2.06 Impact Factor