Faculty Bibliography

TGF-beta and its signaling pathways are important mediators in the suppression of cancers of the gastrointestinal tract. TGF-beta is released from cells in a latent complex consisting of TGF-beta, the TGF-beta propeptide [latency associated protein (LAP)], and a latent TGF-beta binding protein (LTBP). We previously generated mice in which the LTBP-binding cysteine residues in LAP TGF-beta1 were mutated to serine precluding covalent interactions with LTBP. These Tgfb1(C33S/C33S) mice develop multiorgan inflammation and tumors consistent with reduced TGF-beta1 activity. To test whether further reduction in active TGF-beta levels would yield additional tumors and a phenotype more similar to Tgfb1(-/-) mice, we generated mice that express TGF-beta1(C33S) and are deficient in either integrin beta8 or TSP-1, known activators of latent TGF-beta1. In addition, we generated mice that have one mutant allele and one null allele at the Tgfb1 locus, reasoning that these mice should synthesize half the total amount of TGF-beta1 as Tgfb1(C33S/C33S) mice, and the amount of active TGF-beta1 would be correspondingly decreased compared with Tgfb1(C33S/C33S) mice. These compound-mutant mice displayed more severe inflammation and higher tumor numbers than the parental Tgfb1(C33S/C33S) animals. The level of active TGF-beta1 in compound mutant mice seemed to be decreased compared with Tgfb1(C33S/C33S) mice as determined from analyses of surrogate markers of active TGF-beta, such as P-Smad2, C-Myc, KI-67, and markers of cell-cycle traverse. We conclude that these mutant mice provide a useful system for modulating TGF-beta levels in a manner that determines tumor number and inflammation within the gastrointestinal tract. Cancer Res; 73(1); 459-68. (c)2012 AACR.

PURPOSE: To establish the utility of apparent diffusion coefficient (ADC) entropy in discrimination of benign and malignant adnexal lesions, using histopathology as the reference standard, via comparison of the diagnostic performance of ADC entropy with mean ADC and with visual assessments of adnexal lesions on conventional and diffusion-weighted sequences. MATERIALS AND METHODS: In all, 37 adult female patients with an ovarian mass that was resected between June 2006 and January 2011 were included. Volume-of-interest was drawn to incorporate all lesion voxels on every slice that included the mass on the ADC map, from which whole-lesion mean ADC and ADC entropy were calculated. Two independent radiologists also rated each lesion as benign or malignant based on visual assessment of all sequences. The Mann-Whitney test and logistic regression for correlated data were used to compare performance of mean ADC, ADC entropy, and the visual assessments. RESULTS: No statistically significant difference was observed in mean ADC between benign and malignant adnexal lesions (P = 0.768). ADC entropy was significantly higher in malignant than in benign lesions (P = 0.009). Accuracy was significantly greater for ADC entropy than for mean ADC (0.018). ADC entropy and visual assessment by the less-experienced reader showed similar accuracy (P >/= 0.204). The more experienced reader's accuracy was significantly greater than that of all other assessments (P