CT Urography for Evaluation of the Ureter.

Over the past decade, computed tomographic (CT) urography has emerged as the primary imaging modality for evaluating the urinary tract in various clinical settings, including the initial workup of hematuria. With the widespread implementation of CT urography, it is critical for radiologists to understand normal ureteral anatomy and the varied appearance of pathologic ureteral conditions at CT urography. Pathologic findings at CT urography include congenital abnormalities, filling defects, dilatation, narrowing, and deviations in course. These abnormalities are reviewed, along with the indications for CT urography, current imaging protocols with specific techniques for optimal evaluation of the ureter, and dose reduction strategies.

Transforming growth factor-ß2 promotes Snail-mediated endothelial-mesenchymal transition through convergence of Smad-dependent and Smad-independent signalling.

EndMT (endothelial-mesenchymal transition) is a critical process of cardiac development and disease progression. However, little is know about the signalling mechanisms that cause endothelial cells to transform into mesenchymal cells. In the present paper we show that TGF-ß2 (transforming growth factor-ß2) stimulates EndMT through the Smad, MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase], PI3K (phosphinositide 3-kinase) and p38 MAPK signalling pathways. Inhibitors of these pathways prevent TGF-ß2-induced EndMT. Furthermore, we show that all of these pathways are essential for increasing expression of the cell-adhesion-suppressing transcription factor Snail. Inhibition of Snail with siRNA (small interfering RNA) prevents TGF-ß2-induced EndMT. However, overexpression of Snail is not sufficient to cause EndMT. Chemical inhibition of GSK-3ß (glycogen synthase kinase-3ß) allows EndMT to be induced by Snail overexpression. Expression of a mutant Snail protein that is resistant to GSK-3ß-dependent inactivation also promotes EndMT. These results provide the foundation for understanding the roles of specific signalling pathways in mediating EndMT.

Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition.

Fibroblasts are key mediators of fibrosis in the kidney and other organs, but their origin during fibrosis is still not completely clear. Activated fibroblasts likely arise from resident quiescent fibroblasts via epithelial-to-mesenchymal transition and from the bone marrow. Here, we demonstrate that endothelial cells also contribute to the emergence of fibroblasts during kidney fibrosis via the process of endothelial-to-mesenchymal transition (EndMT). We examined the contribution of EndMT to renal fibrosis in three mouse models of chronic kidney disease: (1) Unilateral ureteral obstructive nephropathy, (2) streptozotocin-induced diabetic nephropathy, and (3) a model of Alport renal disease. Approximately 30 to 50% of fibroblasts coexpressed the endothelial marker CD31 and markers of fibroblasts and myofibroblasts such as fibroblast specific protein-1 and alpha-smooth muscle actin. Endothelial lineage tracing using Tie2-Cre;R26R-stop-EYFP transgenic mice further confirmed the presence of EndMT-derived fibroblasts. Collectively, our results demonstrate that EndMT contributes to the accumulation of activated fibroblasts and myofibroblasts in kidney fibrosis and suggest that targeting EndMT might have therapeutic potential.

Basement membrane derived fibulin-1 and fibulin-5 function as angiogenesis inhibitors and suppress tumor growth.

The fibulins are a family of secreted glycoproteins that are characterized by repeated epidermal-growth-factor-like domains and a unique C-terminus structure. Fibulins modulate cell morphology, growth, adhesion, and motility. Our initial basement membrane degradome screen using Cathepsin D, a tumor microenvironment-associated protease, contained fragments of fibulin-1 and full length fibulin-5. In this report, we evaluate the antiangiogenic activity of fibulin-1 and fibulin-5. Tumor studies demonstrate that both fibulin-1 and fibulin-5 suppress HT1080 tumor growth. CD31 labeling and TUNEL assay further reveal that fibulin-1 suppression of HT1080 tumor growth is associated with diminished angiogenesis and also enhanced apoptosis of endothelial cells and tumor cells. In contrast, fibulin-5 inhibits tumor angiogenesis with a minimal anti-apoptotic affect. Cathepsin D digestion of fibulin-1 produces a fragment with nearly the same molecular weight as fibulin-5, and this fragment (named Neostatin) inhibits endothelial cell proliferation. Additionally, degradation of basement membrane by cathepsin D liberates both fibulin-1 fragments and fibulin-5, which function to inhibit angiogenesis.

Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts.

Activated fibroblasts are associated with many different tumors. Myofibroblasts, activated fibroblasts, and perivascular mesenchymal cells such as pericytes play a role in cancer progression. Many studies suggest that myofibroblasts facilitate tumor growth and cancer progression. The source for myofibroblasts and other activated fibroblasts within the tumors is still debated. Although de novo activation of quiescent fibroblasts into alpha-smooth muscle actin (alpha SMA)-positive myofibroblasts is one likely source, epithelial to mesenchymal transition and bone marrow recruitment are also evolving as possible mechanisms for the emergence of a heterogeneous population of carcinoma-associated fibroblasts. Here, we show that transforming growth factor-beta1 could induce proliferating endothelial cells to undergo a phenotypic conversion into fibroblast-like cells. Such endothelial to mesenchymal transition (EndMT) is associated with the emergence of mesenchymal marker fibroblast-specific protein-1 (FSP1) and down-regulation of CD31/PECAM. Additionally, we show EndMT in tumors using the B16F10 melanoma model and the Rip-Tag2 spontaneous pancreatic carcinoma model. Crossing Tie2-Cre mice with R26Rosa-lox-Stop-lox-LacZ mice allows for irreversible tagging of endothelial cells. We provide unequivocal evidence for EndMT at the invasive front of the tumors in these transgenic mice. Collectively, our results show that EndMT is a unique mechanism for the accumulation of carcinoma-associated fibroblasts and suggest that antiangiogenic treatment of tumors may have a direct effect in decreasing activated fibroblasts that likely facilitate cancer progression.

Torque-actuated valves for microfluidics.

This paper describes torque-actuated valves for controlling the flow of fluids in microfluidic channels. The valves consist of small machine screws (> or =500 microm) embedded in a layer of polyurethane cast above microfluidic channels fabricated in poly(dimethylsiloxane) (PDMS). The polyurethane is cured photochemically with the screws in place; on curing, it bonds to the surrounding layer of PDMS and forms a stiff layer that retains an impression of the threads of the screws. The valves were separated from the ceiling of microfluidic channels by a layer of PDMS and were integrated into channels using a simple procedure compatible with soft lithography and rapid prototyping. Turning the screws actuated the valves by collapsing the PDMS layer between the valve and channel, controlling the flow of fluids in the underlying channels. These valves have the useful characteristic that they do not require power to retain their setting (on/off). They also allow settings between "on" and "off" and can be integrated into portable, disposable microfluidic devices for carrying out sandwich immunoassays.

18F-FDG PET in evaluation of adrenal lesions in patients with lung cancer.

UNLABELLED: The purpose of this study was to assess the role of PET with (18)F-FDG in differentiating benign from metastatic adrenal masses detected on CT or MRI scans of patients with lung cancer. METHODS: This retrospective study analyzed (18)F-FDG PET scans of patients with lung cancer who were found to have an adrenal mass on CT or MRI scans. One hundred thirteen adrenal masses (75 unilateral and 19 bilateral; size range, 0.8-4.7 cm) were evaluated in 94 patients. PET findings were interpreted as positive if the (18)F-FDG uptake of the adrenal mass was greater than or equal to that of the liver. PET findings were interpreted as negative if the (18)F-FDG uptake of the adrenal mass was less than that of the liver. All studies were reviewed independently by 3 nuclear medicine physicians, and the results were then correlated with clinical follow-up or biopsy results when available. RESULTS: PET findings were positive in 71 adrenal masses. Sixty-seven of these were eventually considered to be metastatic adrenal disease. In the remaining 4, no changes in lesion size were noted on follow-up examinations. PET findings were negative in 42 adrenal masses, of which 37 eventually proved to be benign. Among the 5 adrenal masses that were false-negative, one was a large necrotic metastasis; 1 was a 2.4-cm lesion with central hemorrhaging, and the remaining 3 were lesions of less than 11 mm. The sensitivity, specificity, and accuracy for detecting metastatic disease were 93%, 90%, and 92%, respectively. CONCLUSION: (18)F-FDG PET is an accurate, noninvasive technique for differentiating benign from metastatic adrenal lesions detected on CT or MRI in patients with lung cancer. In addition, PET has the advantage of assessing the primary cancer sites and detecting other metastases.

18F-FDG PET for evaluation of the treatment response in patients with gastrointestinal tract lymphomas.

UNLABELLED: (18)F-FDG PET is highly sensitive and specific for evaluation of the treatment response of nodal and extranodal diseases in patients with malignant lymphomas. However, no data are available in the literature with regard to (18)F-FDG PET for evaluation of the treatment response in patients with lymphomas with gastrointestinal tract (GIT) involvement. This study was undertaken to investigate the usefulness of (18)F-FDG PET in monitoring the response to the treatment of lymphomas in this setting. METHODS: We retrospectively analyzed 19 patients with different types of lymphomas (10 diffuse large B-cell lymphomas, 4 follicular lymphomas, 3 mantle cell lymphomas, and 2 Hodgkin's disease) involving GIT. Among 19 patients, 4 had gastric involvement, 13 had small bowel involvement, and 2 had small bowel plus colon involvement by lymphomas. All patients underwent (18)F-FDG PET before and after the completion of therapy. The results of (18)F-FDG PET were compared with the results of CT and clinical outcome; the presence of relapse was determined on the basis of positive biopsy results or clinical follow-up data. RESULTS: Of the 19 posttreatment PET scans, 13 showed no pathologic (18)F-FDG uptake, whereas 6 showed persistent (18)F-FDG uptake. Among the 13 patients who had negative PET scans, only 1 patient (7.7%) relapsed, whereas all 6 patients (100%) who had persistent abnormal (18)F-FDG uptake on posttherapy PET scans relapsed. Posttreatment CT scans were negative for 10 patients but showed persistent disease in the remaining 9 patients. Among the 10 patients who had negative CT scans, 9 remained in remission and 1 (10%) relapsed. Of the 9 patients who showed persistent disease, 6 (67%) relapsed and 3 (33%) remained in remission after the mean follow-up of 20 mo. The sensitivity, specificity, positive and negative predictive values, and accuracy of posttherapy (18)F-FDG PET were 86%, 100%, 100%, 92%, and 95%, respectively. The corresponding values for CT were 67%, 75%, 75%, 90%, and 79%, respectively. Patients with positive (18)F-FDG PET results had statistically significantly lower disease-free survival (DFS) (0%) than did those with positive CT results (33%) (P = 0.04). There was no statistically significant difference in DFS between patients with negative (18)F-FDG PET results and patients with negative CT results. CONCLUSION: A positive (18)F-FDG PET scan after the completion of chemotherapy in patients with lymphomas with GIT involvement is a strong predictor of relapse. (18)F-FDG PET has higher diagnostic accuracy than CT in the detection of residual disease after therapy. Despite the mild physiologic (18)F-FDG uptake in the GIT, (18)F-FDG PET has potential value in monitoring the response to treatment in patients with GIT lymphomas, particularly when pretreatment PET results are positive.