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Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in mice.

Zhao Z, Liu W, Su Y, Zhu J, Zheng G, Luo Q, Jin X - J. Exp. Clin. Cancer Res. (2010)

Bottom Line: In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor.No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgery and Oncology Laboratory, Pediatric Research Institution, Children's Hospital of ChongQing Medical University, ChongQing, China.

ABSTRACT

Background: The aim of this study is to examine the safety and distribution of Ad-EGFP-MDR1, an adenovirus encoding human multidurg resistance gene (human MDR1), in the mice colon carcinoma model.

Methods: After bone marrow cells (BMCs) were infected with Ad-EGFP-MDR1, they were administered by intra bone marrow-bone marrow transplantation (IBM-BMT). Total adenovirus antibody and serum adenovirus neutralizing factor (SNF) were determined. Biodistribution of Ad-EGFP-MDR1 was detected by in situ hybridization and immunohistochemistry. The peripheral hematocyte white blood cell (WBC), haemoglobin (Hb), red blood cell (RBC) and platelet (Plt) counts were analyzed.

Results: Neither total adenovirus antibody nor SNF increased weeks after BMT. In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor. No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.

Conclusion: The results indicate that IBM-BMT administration of a replication defective adenovirus is a feasible mode of delivery, allowing exogenous transference. The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.

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Adenovirus-specific antibody measured by ELISA. Optical density (OD) of group A and C had no significant difference with that of group B and D. It could be inferred that the levels of adenovirus-specific antibody of group A and C did not increase on Day 3, 7, 14 after transplantation. The error bars represent one standard deviation from the mean values. These results are representative of three independent experiments.
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Figure 2: Adenovirus-specific antibody measured by ELISA. Optical density (OD) of group A and C had no significant difference with that of group B and D. It could be inferred that the levels of adenovirus-specific antibody of group A and C did not increase on Day 3, 7, 14 after transplantation. The error bars represent one standard deviation from the mean values. These results are representative of three independent experiments.

Mentions: The levels of adenovirus-specific antibody were measured by ELISA. Optical density (OD) of group A and C had no significant difference with that of group B and D. (Figure 2) [see Additional file 3] It could be inferred that the levels of adenovirus-specific antibody of group A and C did not increase on Day 3, 7, 14 after transplantation.


Evaluation of biodistribution and safety of adenovirus vector containing MDR1 in mice.

Zhao Z, Liu W, Su Y, Zhu J, Zheng G, Luo Q, Jin X - J. Exp. Clin. Cancer Res. (2010)

Adenovirus-specific antibody measured by ELISA. Optical density (OD) of group A and C had no significant difference with that of group B and D. It could be inferred that the levels of adenovirus-specific antibody of group A and C did not increase on Day 3, 7, 14 after transplantation. The error bars represent one standard deviation from the mean values. These results are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2819043&req=5

Figure 2: Adenovirus-specific antibody measured by ELISA. Optical density (OD) of group A and C had no significant difference with that of group B and D. It could be inferred that the levels of adenovirus-specific antibody of group A and C did not increase on Day 3, 7, 14 after transplantation. The error bars represent one standard deviation from the mean values. These results are representative of three independent experiments.
Mentions: The levels of adenovirus-specific antibody were measured by ELISA. Optical density (OD) of group A and C had no significant difference with that of group B and D. (Figure 2) [see Additional file 3] It could be inferred that the levels of adenovirus-specific antibody of group A and C did not increase on Day 3, 7, 14 after transplantation.

Bottom Line: In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor.No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgery and Oncology Laboratory, Pediatric Research Institution, Children's Hospital of ChongQing Medical University, ChongQing, China.

ABSTRACT

Background: The aim of this study is to examine the safety and distribution of Ad-EGFP-MDR1, an adenovirus encoding human multidurg resistance gene (human MDR1), in the mice colon carcinoma model.

Methods: After bone marrow cells (BMCs) were infected with Ad-EGFP-MDR1, they were administered by intra bone marrow-bone marrow transplantation (IBM-BMT). Total adenovirus antibody and serum adenovirus neutralizing factor (SNF) were determined. Biodistribution of Ad-EGFP-MDR1 was detected by in situ hybridization and immunohistochemistry. The peripheral hematocyte white blood cell (WBC), haemoglobin (Hb), red blood cell (RBC) and platelet (Plt) counts were analyzed.

Results: Neither total adenovirus antibody nor SNF increased weeks after BMT. In situ hybridization and immunohistochemistry demonstrated concordant expression of human MDR1 and P-gp which were found in lung, intestine, kidney and BMCs after BMT, but not detected in liver, spleen, brain and tumor. No significant abnormality of the recovery hematocyte was observed on Day 30 after treatment.

Conclusion: The results indicate that IBM-BMT administration of a replication defective adenovirus is a feasible mode of delivery, allowing exogenous transference. The findings in this study are conducted for the future long-term studies of safety assessment of Ad-EGFP-MDR1.

Show MeSH
Related in: MedlinePlus