Tumor microenvironmental 15-PGDH depletion promotes fibrotic tumor formation and angiogenesis in pancreatic cancer.

The arachidonic acid cascade is a major inflammatory pathway that produces prostaglandin E2 (PGE2). Although inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is reported to lead to PGE2 accumulation, the role of 15-PGDH expression in the tumor microenvironment remains unclear. We utilized Panc02 murine pancreatic cancer cells for orthotopic transplantation into wild-type and 15-pgdh+/- mice and found that 15-pgdh depletion in the tumor microenvironment leads to enhanced tumorigenesis accompanied by an increase in cancer-associated fibroblasts (CAFs) and the promotion of fibrosis. The fibrotic tumor microenvironment is widely considered to be hypovascular; however, we found that the angiogenesis level is maintained in 15-pgdh+/- mice, and these changes were also observed in a genetically engineered PDAC mouse model. Further confirmation revealed that fibroblast growth factor 1 (FGF1) is secreted by pancreatic cancer cells after PGE2 stimulation, consequently promoting CAF proliferation and vascular endothelial growth factor A (VEGFA) expression in the tumor microenvironment. Finally, in 15-pgdh+/- Acta2-TK mice, depletion of fibroblasts inhibited angiogenesis and cancer cell viability in orthotopically transplanted tumors. These findings highlighted the role of 15-pgdh downregulation in enhancing PGE2 accumulation in the pancreatic tumor microenvironment and in subsequently maintaining the angiogenesis level in fibrotic tumors along with CAF expansion.

Quantitative Evaluation of Soil Structure and Strain in Three Dimensions under Shear Using X-ray Computed Tomography Image Analysis.

The objective of this study is to quantitatively evaluate the soil structure behavior when under shear stress to understand the mechanism of shear zone formation using a micro-focus X-ray computed tomography (CT) scanner to visualize the internal samples without causing disturbance. A new image-analysis method was proposed to systematically evaluate the particle length and direction by fitting the particle as an ellipsoid. Subsequently, a direct shear experiment was conducted on soil materials, and shear band was scanned using a micro-focus X-ray CT scanner. After validating the proposed method, the soil structure was evaluated in the shear zone via image analysis on the CT images. Furthermore, the strain inside the specimen was evaluated using digital image correlation. The results showed that a partial change in the particle direction occurred when the volume expansion inside the shear zone exceeded the peak. In addition, the width of the shear zone was ~7.1 times the median grain size of the sand used; however, the region exhibiting a change in the direction of the particles was narrow and confined to the vicinity of the shear plane.

Sample Preparation for Computed Tomography-based Three-dimensional Visualization of Murine Hind-limb Vessels.

Blood vessels are complex networks with tree-like structures, and vascular networks are essential for maintaining both circulation and maintaining organ function. Clarifying the mechanism of blood vessel formation is therefore extremely useful for elucidating developmental processes and pathological mechanisms. Murine hind-limb vessels are often used as a model for physiological and pathological angiogenesis. Evaluation is mainly performed via a two-dimensional method using tissue sections. However, methods for evaluating three-dimensional (3D) vascular morphology are particularly limited. This paper introduces a method for visualizing murine hind-limbs using computed tomography (CT). Radiation-opaque resin is injected through the descending aorta, and whole vessels are filled with dye. By adjusting the time of dye injection, arterial-specific filling is also possible, and samples can be obtained with any micro-X-ray CT device. This contrast method provides a basic technique for the 3D evaluation of murine blood vessels in the lower extremities. Furthermore, this method can be used to visualize all blood vessels below the diaphragm and evaluate blood vessels in the abdominal organs.

Evaluation of Collateral Source Characteristics With 3-Dimensional Analysis Using Micro-X-Ray Computed Tomography.

BACKGROUND: Collateral arteries provide an alternative blood supply and protect tissues from ischemic damage in patients with peripheral artery disease. However, the mechanism of collateral artery development is difficult to validate. METHODS AND RESULTS: Collateral arteries were visualized using micro-x-ray computed tomography. Developmental characteristics were assessed using confocal microscopy. We conducted a single-center, retrospective, observational study and assessed the dilatation of collateral arteries on ischemic sides. We quantified the vascular volume in both ischemic and nonischemic legs. A prominent increase in vascular volume was observed in the ischemic leg using a murine hind-limb ischemia model. We also performed qualitative assessment and confirmed that the inferior gluteal artery functioned as a major collateral source. Serial analysis of murine hind-limb vessel development revealed that the inferior gluteal artery was a remnant of the ischial artery, which emerged as a representative vessel on the dorsal side during hind-limb organogenesis. We retrospectively analyzed consecutive patients who were admitted for the diagnosis or treatment of peripheral artery disease. The diameter of the inferior gluteal artery on the ischemic side showed significant dilatation compared with that on the nonischemic side. CONCLUSIONS: Our findings indicate that an embryonic remnant artery can become a collateral source under ischemic conditions. Flow enhancement in the inferior gluteal artery might become a novel therapeutic approach for patients with peripheral artery disease.

Transluminal attenuation-gradient coronary CT angiography on a 320-MDCT volume scanner: Effect of scan timing, coronary artery stenosis, and cardiac output using a contrast medium flow phantom.

PURPOSE: Transluminal-attenuation-gradient (TAG) may reflect patient characteristics and physiological parameters. Furthermore, TAG may be affected by factors such as the CT scanner speed, scanning method, scan timing after contrast-medium (CM) injection, and the injection methods. The purpose of our study was to investigate quantitative TAG at different scan timing points after CM injection for coronary CT angiography. MATERIALS AND METHODS: Using a CM flow phantom and two types of connecting tube mimicking 0% and 70% coronary artery stenosis, we performed 320-detector volume scanning. The heart rate was set at 60bpm and cardiac-output (CO) at 2.0 and 4.0 l/min, respectively. The acquisition time repeated at 0.5-s intervals for 40 and 25s at a CO of 2.0- and 4.0 l/min. We measured the CT number on the same slice level, calculated the time-density-curve (TDC) and the TAG at each time point. RESULTS: At COs of 2.0 and 4.0 l/min at 0% stenosis, TAG exhibited smaller variations (-3.02 to +0.55HU/cm at 2.0 l/min, -2.63 to +0.43HU/cm at 4.0 l/min) than at 70% stenosis at each time point along the TDC. Compared with a CO at 2.0 l/min with 70% stenosis, the TAG curve for a CO at 4.0 l/min gradually changed with time (-6.64 to +1.18HU/cm at 2.0 l/min vs. -3.46 to +2.75HU/cm at 4.0 l/min). CONCLUSION: The TAG value was affected by scan timing after CM injection and by CO although the size of the connecting tube with and without stenosis was identical.

Unprotected left main intervention for surgery-ineligible patients with coronary artery disease-Usefulness of micro-CT images for stent.

BACKGROUND: Percutaneous coronary intervention (PCI) for unprotected left main truncus (LMT) lesions is controversial. Inoperable status with advanced age, renal dysfunction, frailty, or patient request may require an unprotected left main PCI. PCI for LMT is not recommended in the typical clinical situation; however, when it is the only feasible option, the performance is not bad. We demonstrated the result of a cobalt-chromium everolimus-eluting stent (CoCr-EES) in the LMT stenting and serial changes via micro-computed tomography (µCT). µCT is an established imaging technique used for high-resolution, non-destructive assessment of vascular samples. The technique has drawn increasing interest for investigations of atherosclerotic arteries in both humans and animal models. There are no reports regarding the linkage between clinical results and µCT images. METHODS AND RESULTS: Between January 2009 and December 2014, we recruited 118 consecutive, unprotected LMT stenting cases in our institution. We examined the clinical outcomes and angiographic results with a CoCr-EES compared with a first-generation drug-eluting stent. The primary endpoint of this registry was the rate of one-year major adverse cardiac events (MACE). The one-year MACE rate was 2.54%; this did not include the CoCr-EES. We established LMT bifurcation models (mini-crush and culotte) using a CoCr-EES and obtained µCT images of the CoCr-EES. The images showed no deformation or strut apposition. CONCLUSION: CoCr-EES performed well in LMT in our institution and according to µCT. µCT images may be useful for anatomical simulation in stent deployment.