Time dependent changes in tumor growth of NDEA-treated c-Myc transgenic mice.

<p>(A) The organ and tumor volume was assessed by CT and by histopathology. Depicted is the percentage tumor volume at different stages measured either by histopathology (light gray) or by contrast enhanced CT imaging (dark gray). The mean diameter of lesions (B) and the total number of lesions (C) are shown. *p<0.05. **p<0.01.</p

Mean tumor volume for NDEA treated c-Myc transgenic mice separated by gender.

<p>Data were obtained by CT and histopathology and are defined as mean percentage tumor volume and standard error of the mean for NDEA treated animals. Data are broken down by gender. At the age of 5.5 months the tumor incidence was 100% for male and female animals. No gender specific difference in tumor volume was observed except for histopathology findings at the age of 7 months;</p><p>*P<0.05.</p

Histopathology of the liver of c-Myc treated transgenic animals.

<p>(A) Diffuse liver cell dysplasia of physiological saline ( = vehicle) treated transgenic mice at (A1) 50- and (A2) 200-fold magnification. (B) Large cell dysplasia of various degrees in BHT treated animals at (B1) 50- and (B2) 200-fold magnification. (C) Hepatocellular carcinoma of a transgenic mouse treated with the genotoxic carcinogen NDEA at (C1) 50 and (C2) 200-fold magnification.</p

Contrast-enhanced CT, ¹⁸F-FDG-PET and fused images of c-Myc transgenic mice treated with NDEA at the age of 5.5 and 7 months.

<p>(A) CT image demonstrates a single tumor lesion (A1) in a 5.5 months old mouse without increased ¹⁸F-FDG uptake (A2). The fused CT and PET image is depicted in A3. (B) At the age of 7 months expansive tumor growth (B1) as well as an increased tracer uptake in hepatocellular carcinoma (B2) is observed. The fused CT and PET image is depicted in B3. G = gallbladder, K = kidney, L = liver, S = spine, St = stomach, T = tumor.</p

Study groups and imaging protocol.

<p>Histopathology was carried out for all groups and for all time points (4, 5.5, 7, 8.5 months).</p><p>*<b>No CT/PET imaging was done,</b></p><p>**<b>CT/PET was acquired at the age of 8.5 months only. m, months; w, weeks.</b></p

Fused μPET/μCT images of the liver of c-Myc transgenic mice treated with physiological saline, BHT or NDEA.

<p>Depicted are the liver morphology as determined by CT (A1, B1,C1), the glucose metabolism (A2, B2, C2) and fused PET and CT scans (A3, B3, C3) of transgenic animals treated with either physiological saline (A), with BHT (B) or with NDEA (C) at the age of 8.5 months. Note, after treatment with NDEA expansive tumor growth with large increase of liver weight and compression and displacement of adjacent organs was observed. Here, the lesions showed an increased 18F-FDG uptake. In contrast, in corresponding control animals treated with physiological saline no liver lesions were observed. After treatment with BHT small hypodens lesions are noticed, but PET did not show an increased 18F-FDG uptake. K = kidney, L = liver, S = spine, Sp = spleen, St = stomach, T = tumor.</p

CT and histopathology of the lung of NDEA treated c-Myc transgenic mice.

<p>(A) Normal lung parenchyma of a vehicle treated control animal as shown by CT (A1) and by histopathology (A2). CT of NDEA treated animals at the age of 8.5 months. Depicted are lung nodules of different size (red arrows). Histopathology evidenced those lung nodules as metastasis of a poorly differentiated HCC (B2) and as well adenocarcinoma of the lung (C2).</p

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

<div><p>Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.</p></div

Placement of TLD on anaesthetized mouse.

<p>A: Cranial view showing TLD positions 1–7 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044427#pone-0044427-t002" target="_blank">table 2</a>). B: Lateral view showing TLD positions 8 and 9 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044427#pone-0044427-t002" target="_blank">Table 2</a>).</p

TLD positions 1–9 and corresponding dose mean values and standard deviation 75 minutes after intraperitoneal administration of 10 MBq ¹⁸F-FDG.

<p>TLD positions 1–9 and corresponding dose mean values and standard deviation 75 minutes after intraperitoneal administration of 10 MBq ¹⁸F-FDG.</p