Purpose: Loss of vascular barrier function has been observed shortly following vasculartargeting photodynamic therapy. However, the mechanism involved in this event is still not clear, and the therapeutic implications associated with this pathophysiologic change have not been fully explored. Experimental Design: The effect of vascular-targeting photodynamic therapy on vascular barrier function was examined in both s.c. and orthotopic MatLyLu rat prostate tumor models and endothelial cells in vitro, using photosensitizer verteporfin. Vascular permeability to macromolecules (Evans blue-albumin and high molecular weight dextran) was assessed with dye extraction (ex vivo) and intravital microscopy (in vivo) methods. Intravital microscopy was also used to monitor tumor vascular functional changes after vascular-targeting photodynamic therapy. The effects of photosensitization on monolayer endothelial cell morphology and cytoskeleton structures were studied with immunofluorescence staining. Results: Vascular-targeting photodynamic therapy induced vascular barrier dysfunction in the MatLyLu tumors. Thus, tumor uptake of macromolecules was significantly increased following photodynamic therapy treatments. In addition to vascular permeability increase, blood cell adherence to vessel wall was observed shortly after treatment, further suggesting the loss of endothelial integrity. Blood cell adhesion led to the formation of thrombi that can occlude blood vessels, causing vascular shutdown. However, viable tumor cells were often detected at tumor periphery after vascular-targeting photodynamic therapy. Endothelial cell barrier dysfunction following photodynamic therapy treatment was also observed in vitro by culturing monolayer endothelial cells on Transwell inserts. Immunofluorescence study revealed microtubule depolymerization shortly after photosensitization treatment and stress actin fiber formation thereafter. Consequently, endothelial cells were found to retract, and this endothelial morphologic change led to the formation of intercellular gaps. Conclusions: Vascular-targeting photodynamic therapy permeabilizes blood vessels through the formation of endothelial intercellular gaps, which are likely induced via endothelial cell microtubule depolymerization following vascular photosensitization. Loss of endothelial barrier function can ultimately lead to tumor vascular shutdown and has significant implications in drug transport and tumor cell metastasis.
Peripheral artery disease (PAD), secondary to atherosclerotic disease, is currently the leading cause of morbidity and mortality in the western world. While PAD is common, it is estimated that the majority of patients with PAD are undiagnosed and undertreated. The challenge to the treatment of PAD is to accurately diagnose the symptoms and determine treatment for each patient. The varied presentations of peripheral vascular disease have led to numerous classification schemes throughout the literature. Consistent grading of patients leads to both objective criteria for treating patients and a baseline for clinical follow-up. Reproducible classification systems are also important in clinical trials and when comparing medical, surgical, and endovascular treatment paradigms. This article reviews the various classification systems for PAD and advantages to each system.
Chronic treatment of mice with an enterically released formulation of rapamycin (eRapa) extends median and maximum life span, partly by attenuating cancer. The mechanistic basis of this response is not known. To gain a better understanding of these in vivo effects, we used a defined preclinical model of neuroendocrine cancer, Rb1+/− mice. Previous results showed that diet restriction (DR) had minimal or no effect on the lifespan of Rb1+/− mice, suggesting that the beneficial response to DR is dependent on pRb1. Since long-term eRapa treatment may at least partially mimic chronic DR in lifespan extension, we predicted that it would have a minimal effect in Rb1+/− mice. Beginning at 9 weeks of age until death, we fed Rb1+/− mice a diet without or with eRapa at 14 mg/kg food, which results in an approximate dose of 2.24 mg/kg body weight per day, and yielded rapamycin blood levels of about 4 ng/ml. Surprisingly, we found that eRapa dramatically extended life span of both female and male Rb1+/− mice, and slowed the appearance and growth of pituitary and decreased the incidence of thyroid tumors commonly observed in these mice. In this model, eRapa appears to act differently than DR, suggesting diverse mechanisms of action on survival and anti-tumor effects. In particular the beneficial effects of rapamycin did not depend on the dose of Rb1.
Common and rare arterial collateral pathways are reviewed by 3D volume-rendered CT images. Visceral and lower extremity arterial embryology is reviewed.
Purpose-Magnetic resonance imaging (MRI) of the prostate has increasingly become more important in clinical medicine due to the risk of over-detection of low-grade, low-volume prostate cancer as well as due to the poor sampling of transrectal ultrasound-guided prostate biopsy in high-risk patients. We sought to determine the access, imaging protocols, and indications for MRI imaging of the prostate in the United States.
Materials and Methods-A brief survey was sent through mailing lists to members of the Society of Abdominal Radiology and Texas Radiological Society.Results-Thirty-six academic centers responded to the survey, 88.9% of which routinely perform prostate MRI. Nine centers routinely performed imaging at 1.5T with an endorectal coil (25%), 11 performed at 3.0T without an endorectal coil (31%), and 10 performed at 3.0T with an endorectal coil (28%). All institutions used T1-weighted axial and orthogonal T2-weighted sequences. Most groups used diffusion weighted imaging (94.7%) and dynamic contrast enhancement (81.6%). Only 21.1% of groups performing prostate MRI routinely performed magnetic resonance spectroscopy as part of their protocol.Conclusions-Prostate MRI is becoming a commonly performed examination at academic institutions, with most locations performing prostate MRI at minimum standards. There is a need to educate non-academic practices regarding the addition of functional MRI techniques to anatomic techniques, increase the number of institutions that regularly perform prostate MRI, and increase access to direct MRI-guided biopsy in institutions that perform prostate MRI on a regular basis.
Ultrasound-guided breast interventions (core biopsies, needle-wire localizations, and fine-needle cyst aspirations) are common procedures performed by radiologists. Residents must gain competency in these interventions during training. Phantoms and simulations have been advocated for teaching interventions, and various systems are available for standard breast interventions. However, simulations for difficult/high-risk interventions are not readily available. We describe an inexpensive method for simulating difficult ultrasound-guided breast procedures, including masses over breast implants, deep masses along the chest wall, and lymph nodes adjacent to axillary vessels.
Both transjugular and percutaneous liver biopsy techniques are efficacious and safe. Contraindications such as thrombocytopenia, coagulopathy, and ascites are indicators of greater complications but are not necessarily prevented by transjugular biopsy. Percutaneous biopsy more frequently yields a diagnostic specimen than transjugular biopsy.
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