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BACKGROUND@#Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.@*METHODS@#By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hre-gfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).@*RESULTS@#In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.@*CONCLUSIONS@#The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.
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Objective To evaluate the value of acoustic radiation force impulse(ARFI)imaging in the diagnosis of early non-alcoholic steatohepatitis(NASH).Methods Totally 32 SD rats were randomly divided into high-fat diet group(n=24)and normal-diet group(n=8)by using the random number table. At the end of the 4,8,12,and 16week,six rats from the high-diet group and two rats from the normal-diet group were selected blindly for weighting,blood biochemical test,conventional ultrasound,and ARFI imaing. HE staining was used for pathological observation. Results None of the 32 rats developed liver fibrosis. Based on the pathological results,these rats were divided into M1 [mild-to-moderate simple fatty liver(SS)],M2(severe SS),M3(severe SS with early NASH),and C groups(normal control). Early NASH was seen only in the severe hepatic steatosis groups,and its distribution had a significant difference(P=0.006). The diagnostic accuracy of conventional ultrasound based on histological results was 34.4%(11/32). The ARFI value of M3 group was significantly lower than that of M2 group [(1.16±0.04)m/s vs.(1.22±0.05)m/s;t=2.301,P=0.04),and the low-density lipoprotein of M3 group was significantly higher than M2 group [(1.53±0.07)mmol/L vs.(1.21±0.22)mmol/L;t=3.075,P=0.01),while other clinical indicators had no statistical difference between these two groups. Conclusions The development of early NASH is associated with the severity of hepatic steatosis. ARFI value can provide important information to identify early NASH in patients with severe hepatic steatosis.
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<p><b>OBJECTIVE</b>To analyze the pharmacokinetics of intraperitoneal chemotherapy with mitomycin C (MMC) bound to activated carbon particles.</p><p><b>METHODS</b>A nude mouse model with transplanted human gastric cancer was established. The mice were given MMC by i.v. or intraperitoneal (i.p.) injections, or given i.p. MMC bound to activated carbon particles (MMC-CH). Pharmacokinetic assays were carried out at different time points (0.5, 1, 2, 3, 6, 12 and 24 h) in 7 mice per each time point, to compare the MMC concentrations revealed by the above mentioned methods.</p><p><b>RESULTS</b>The MMC concentration in peritoneal exudate, omentum and lymph nodes of MMC-CH group was significantly higher than that of MMC solution i.p. group and MMC i.v. group (P < 0.001). On the other hand, the MMC level in serum was significantly lower than that in two control groups (P < 0.001). High MMC level was maintained longer than 24 hours in the MMC-CH group. Intraperitoneal chemotherapy with MMC solution resulted in a low MMC concentration in serum, peritoneal exudates and lymph nodes, and only a transient high level of MMC in the omentum. After i.v. administration, a significantly higher level of MMC concentration occurred in the serum, but only a shortly increased concentration of MMC in the omentum, and lower concentration in peritoneal exudate and lymph nodes as compared with those in the other two groups (P < 0.001).</p><p><b>CONCLUSION</b>High concentration of MMC in peritoneal exudate, omentum and lymph nodes maintained longer than 24 hours and a significantly lower MMC serum concentration can be achieved by administration of intraperitoneal administration of MMC bound to activated carbon particles.</p>