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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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SNF was detected by measuring the fluorescent intensity of HEK293 cells using a flow cytomtry. A: The background was 2.45%. The percentages of green fluorescent cells were 99.21%(B), 99.22%(C), 98.65%(D) and 99.39%(E) for group A to D respectively on Day 7 after the treatment. Fluorescence intensity of infected HEK 293 cells was inversely proportional to SNF level. SNF against Ad-EGFP-MDR1 was not detected in all groups.
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Figure 3: SNF was detected by measuring the fluorescent intensity of HEK293 cells using a flow cytomtry. A: The background was 2.45%. The percentages of green fluorescent cells were 99.21%(B), 99.22%(C), 98.65%(D) and 99.39%(E) for group A to D respectively on Day 7 after the treatment. Fluorescence intensity of infected HEK 293 cells was inversely proportional to SNF level. SNF against Ad-EGFP-MDR1 was not detected in all groups.

Mentions: Fluorescence intensity of infected HEK 293 cells, which was measured with a flow cytometry, was inversely proportional to SNF level. The SNF could inhibit the infection efficiency of Ad-EGFP-MDR1 and result in the reduction of the fluorescence intensity. However, almost all samples were infected, the percentages of green fluorescence (infected BMCs) were 99.21%, 99.22%, 98.65% and 99.39% for group A to D respectively on Day 7 posttransplantation. The background was 2.45%. (Figure 3) [see Additional file 4] We inferred that SNF against Ad-EGFP-MDR1 was not detected in all groups.


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)

SNF was detected by measuring the fluorescent intensity of HEK293 cells using a flow cytomtry. A: The background was 2.45%. The percentages of green fluorescent cells were 99.21%(B), 99.22%(C), 98.65%(D) and 99.39%(E) for group A to D respectively on Day 7 after the treatment. Fluorescence intensity of infected HEK 293 cells was inversely proportional to SNF level. SNF against Ad-EGFP-MDR1 was not detected in all groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: SNF was detected by measuring the fluorescent intensity of HEK293 cells using a flow cytomtry. A: The background was 2.45%. The percentages of green fluorescent cells were 99.21%(B), 99.22%(C), 98.65%(D) and 99.39%(E) for group A to D respectively on Day 7 after the treatment. Fluorescence intensity of infected HEK 293 cells was inversely proportional to SNF level. SNF against Ad-EGFP-MDR1 was not detected in all groups.
Mentions: Fluorescence intensity of infected HEK 293 cells, which was measured with a flow cytometry, was inversely proportional to SNF level. The SNF could inhibit the infection efficiency of Ad-EGFP-MDR1 and result in the reduction of the fluorescence intensity. However, almost all samples were infected, the percentages of green fluorescence (infected BMCs) were 99.21%, 99.22%, 98.65% and 99.39% for group A to D respectively on Day 7 posttransplantation. The background was 2.45%. (Figure 3) [see Additional file 4] We inferred that SNF against Ad-EGFP-MDR1 was not detected in all groups.

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