Objective： To evaluate transduction efficiency with recombinant adenovirus-mediated p53 （rAd/p53） therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods： The tu...Objective： To evaluate transduction efficiency with recombinant adenovirus-mediated p53 （rAd/p53） therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods： The tumor pieces of human colon cancer SW480 were implanted in the livers of 45 nude mice. These mice were administrated with rAd/p53 by intratumoral injection and intra-artedal delivery. After 24 h, 48 h and 72 h tAd/p53 administration, 5 mice each group were killed with over anesthesia and their livers were removed. P53 expression and apoptosis of tumor and liver were assessed. Results： P53 expression and apoptosis of intratumoral administration group was higher than tail vein group and control group. Apoptosis and p53 expression of livers in three groups had no significant difference. Conclusion： p53 gene transducUon efficiency and anticancer effect of rAd/p53 is much better by intra-tumoral injection than intra-arterial delivery,展开更多
AIM: To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values (0...AIM: To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values (0-800 s/mm<sup>2</sup>) in 25 human gastric cancer-bearing nude mice at baseline (day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups (n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calcium folinate treatment. Together with tumor volumes (TV), the apparent diffusion coefficient (ADC) and IVIM parameters [true water molecular diffusion coefficient (D), perfusion fraction (f) and pseudo-related diffusion coefficient (D<sup>*</sup>)] were measured. The differences in those parameters from baseline to each measurement (ΔTV%, ΔADC%, ΔD%, Δf% and ΔD<sup>*</sup>%) were calculated. After image acquisition, tumor necrosis, microvessel density (MVD) and cellular apoptosis were evaluated by hematoxylin-eosin (HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman’s correlation coefficient analysis were performed.RESULTS: The observed relative volume increase (ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5 (ΔTV<sub>treatment</sub>% = 19.63% ± 3.01% and ΔTV<sub>control</sub>% = 83.60% ± 14.87%, P = 0.008) and day 7 (ΔTV<sub>treatment</sub>% = 29.07% ± 10.01% and ΔTV<sub>control</sub>% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group (ΔADC%<sub>treatment</sub>, median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group (ΔADC%<sub>control</sub>, median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7 (P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group (ΔD%<sub>treatment</sub>, median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group (ΔD%<sub>control</sub>, median -0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5 (P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up (median, -34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016; -50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008; -49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and -46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points (median, -32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008; -44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008; -59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and -47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis (r<sub>s</sub> = 0.720, P < 0.001; r<sub>s</sub> = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D (r<sub>s</sub> = 0.626, P = 0.001; r<sub>s</sub> = 0.542, P = 0.005, respectively). Perfusion-related parameters (f and D<sup>*</sup>) were positively correlated to MVD (r<sub>s</sub> = 0.618, P = 0.001; r<sub>s</sub> = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor (r<sub>s</sub> = -0.550, P = 0.004; r<sub>s</sub> = -0.692, P < 0.001, respectively).CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.展开更多
基金Supported by grants from Guangzhou Health Agency (No. 2008-YB-034)Guangdong Department of Science and Technology (No. 83083)
文摘Objective： To evaluate transduction efficiency with recombinant adenovirus-mediated p53 （rAd/p53） therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods： The tumor pieces of human colon cancer SW480 were implanted in the livers of 45 nude mice. These mice were administrated with rAd/p53 by intratumoral injection and intra-artedal delivery. After 24 h, 48 h and 72 h tAd/p53 administration, 5 mice each group were killed with over anesthesia and their livers were removed. P53 expression and apoptosis of tumor and liver were assessed. Results： P53 expression and apoptosis of intratumoral administration group was higher than tail vein group and control group. Apoptosis and p53 expression of livers in three groups had no significant difference. Conclusion： p53 gene transducUon efficiency and anticancer effect of rAd/p53 is much better by intra-tumoral injection than intra-arterial delivery,
基金Supported by National Research Foundation of South Korea,No.NRF-2013R1A1A2013878 and No.2015R1A2A2A01007827
文摘AIM: To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model.METHODS: IVIM-DWI was performed with 12 b-values (0-800 s/mm<sup>2</sup>) in 25 human gastric cancer-bearing nude mice at baseline (day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups (n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calcium folinate treatment. Together with tumor volumes (TV), the apparent diffusion coefficient (ADC) and IVIM parameters [true water molecular diffusion coefficient (D), perfusion fraction (f) and pseudo-related diffusion coefficient (D<sup>*</sup>)] were measured. The differences in those parameters from baseline to each measurement (ΔTV%, ΔADC%, ΔD%, Δf% and ΔD<sup>*</sup>%) were calculated. After image acquisition, tumor necrosis, microvessel density (MVD) and cellular apoptosis were evaluated by hematoxylin-eosin (HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman’s correlation coefficient analysis were performed.RESULTS: The observed relative volume increase (ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5 (ΔTV<sub>treatment</sub>% = 19.63% ± 3.01% and ΔTV<sub>control</sub>% = 83.60% ± 14.87%, P = 0.008) and day 7 (ΔTV<sub>treatment</sub>% = 29.07% ± 10.01% and ΔTV<sub>control</sub>% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group (ΔADC%<sub>treatment</sub>, median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group (ΔADC%<sub>control</sub>, median, 4.98% ± 3.39%, 6.26% ± 3.08%, 9.24% ± 6.33%) at days 3, 5 and 7 (P = 0.008, P = 0.016, P = 0.008, respectively). Increases in D in the treatment group (ΔD%<sub>treatment</sub>, median 17.12% ± 8.20%, 24.16% ± 16.87%, 38.54% ± 19.36%) were higher than those in the control group (ΔD%<sub>control</sub>, median -0.13% ± 4.23%, 5.89% ± 4.56%, 5.54% ± 4.44%) at days 1, 3, and 5 (P = 0.032, P = 0.008, P = 0.016, respectively). Relative changes in f were significantly lower in the treatment group compared with the control group at days 1, 3, 5 and 7 follow-up (median, -34.13% ± 16.61% vs 1.68% ± 3.40%, P = 0.016; -50.64% ± 6.82% vs 3.01% ± 6.50%, P = 0.008; -49.93% ± 6.05% vs 0.97% ± 4.38%, P = 0.008, and -46.22% ± 7.75% vs 8.14% ± 6.75%, P = 0.008, respectively). D* in the treatment group decreased significantly compared to those in the control group at all time points (median, -32.10% ± 12.22% vs 1.85% ± 5.54%, P = 0.008; -44.14% ± 14.83% vs 2.29% ± 10.38%, P = 0.008; -59.06% ± 19.10% vs 3.86% ± 5.10%, P = 0.008 and -47.20% ± 20.48% vs 7.13% ± 9.88%, P = 0.016, respectively). Furthermore, histopathologic findings showed positive correlations with ADC and D and tumor necrosis (r<sub>s</sub> = 0.720, P < 0.001; r<sub>s</sub> = 0.522, P = 0.007, respectively). The cellular apoptosis of the tumor also showed positive correlations with ADC and D (r<sub>s</sub> = 0.626, P = 0.001; r<sub>s</sub> = 0.542, P = 0.005, respectively). Perfusion-related parameters (f and D<sup>*</sup>) were positively correlated to MVD (r<sub>s</sub> = 0.618, P = 0.001; r<sub>s</sub> = 0.538, P = 0.006, respectively), and negatively correlated to cellular apoptosis of the tumor (r<sub>s</sub> = -0.550, P = 0.004; r<sub>s</sub> = -0.692, P < 0.001, respectively).CONCLUSION: IVIM-DWI is potentially useful for predicting the early efficacy of chemotherapy in a human gastric cancer mouse model.
