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A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer.

Tang W, He Y, Zhou S, Ma Y, Liu G - J. Exp. Clin. Cancer Res. (2009)

Bottom Line: Successful clinical management remains a challenge.The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV).Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China. tangwei2060@yahoo.com.cn

ABSTRACT
Bladder cancer is the ninth most common malignancy in the world. Successful clinical management remains a challenge. In order To search for novel targeted and efficacious treatment, we sought to investigate anti-tumor activity of BI-TK suicide gene therapy system in a rat model of bladder tumors. We first constructed and tested an anaerobic Bifidobacterium infantis-mediated thymidine kinase (BI-TK) suicide gene therapy system. To test the in vivo efficacy of this system, we established a rat model of bladder tumors, which was induced by N-methyl-nitrosourea perfusion. Bifidobacterium infantis containing the HSV-TK (i.e., BI-TK) were constructed by transformation of recombinant plasmid pGEX - TK. The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV). Using the rat model of bladder tumors, we found that bladder tumor burdens were significantly lower in the rats treated with BI-TK/GCV group than that treated with normal saline control group (p <0.05). While various degrees of apoptosis of the tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in the BI-TK/GCV treatment group. Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05). Thus, our results demonstrate that the Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system can effectively inhibit rat bladder tumor growth, possibly through increasing caspase 3 expression and inducing apoptosis.

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Histologic evaluation of the MNU-induced rat bladder cancer. MNU-induced bladder tumor samples were retrieved and subjected to paraffin-embedded sectioning and H & E staining. (A) Normal saline group, (B) Bifutobacterium infantis with empty plasmid group, and (C) Bifutobacterium infantis-PGEX-TK group. Representative samples are shown. Magnification, 100×.
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Figure 2: Histologic evaluation of the MNU-induced rat bladder cancer. MNU-induced bladder tumor samples were retrieved and subjected to paraffin-embedded sectioning and H & E staining. (A) Normal saline group, (B) Bifutobacterium infantis with empty plasmid group, and (C) Bifutobacterium infantis-PGEX-TK group. Representative samples are shown. Magnification, 100×.

Mentions: As shown in Figure 2A, in the normal saline group tumors formed wide bases with short stalk structures. Tumor cells were highly heterogeneous, resembling the characteristics of human bladder cancers. Malignant cells were shown to infiltrate focal subtunica mucosa, muscular tunic. In both BI-pGEX-5X-1 and BI-pGEX-TK groups, the tumors grew much more slowly than that of the NS group; and tumor necrosis was more pronounced in these groups (Figures 2B and 2C).


A novel Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system exhibits antitumor activity in a rat model of bladder cancer.

Tang W, He Y, Zhou S, Ma Y, Liu G - J. Exp. Clin. Cancer Res. (2009)

Histologic evaluation of the MNU-induced rat bladder cancer. MNU-induced bladder tumor samples were retrieved and subjected to paraffin-embedded sectioning and H & E staining. (A) Normal saline group, (B) Bifutobacterium infantis with empty plasmid group, and (C) Bifutobacterium infantis-PGEX-TK group. Representative samples are shown. Magnification, 100×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803447&req=5

Figure 2: Histologic evaluation of the MNU-induced rat bladder cancer. MNU-induced bladder tumor samples were retrieved and subjected to paraffin-embedded sectioning and H & E staining. (A) Normal saline group, (B) Bifutobacterium infantis with empty plasmid group, and (C) Bifutobacterium infantis-PGEX-TK group. Representative samples are shown. Magnification, 100×.
Mentions: As shown in Figure 2A, in the normal saline group tumors formed wide bases with short stalk structures. Tumor cells were highly heterogeneous, resembling the characteristics of human bladder cancers. Malignant cells were shown to infiltrate focal subtunica mucosa, muscular tunic. In both BI-pGEX-5X-1 and BI-pGEX-TK groups, the tumors grew much more slowly than that of the NS group; and tumor necrosis was more pronounced in these groups (Figures 2B and 2C).

Bottom Line: Successful clinical management remains a challenge.The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV).Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China. tangwei2060@yahoo.com.cn

ABSTRACT
Bladder cancer is the ninth most common malignancy in the world. Successful clinical management remains a challenge. In order To search for novel targeted and efficacious treatment, we sought to investigate anti-tumor activity of BI-TK suicide gene therapy system in a rat model of bladder tumors. We first constructed and tested an anaerobic Bifidobacterium infantis-mediated thymidine kinase (BI-TK) suicide gene therapy system. To test the in vivo efficacy of this system, we established a rat model of bladder tumors, which was induced by N-methyl-nitrosourea perfusion. Bifidobacterium infantis containing the HSV-TK (i.e., BI-TK) were constructed by transformation of recombinant plasmid pGEX - TK. The engineered BI-TK was injected into tumor-bearing rats via tail vein, followed by intraperitoneal injection of ganciclovir (GCV). Using the rat model of bladder tumors, we found that bladder tumor burdens were significantly lower in the rats treated with BI-TK/GCV group than that treated with normal saline control group (p <0.05). While various degrees of apoptosis of the tumor cells were detected in all groups using in situ TUNEL assay, apoptosis was mostly notable in the BI-TK/GCV treatment group. Immunohistochemical staining further demonstrated that the BI-TK/GCV treatment group had the highest level of caspase3 protein expression than that of the empty plasmid group and normal saline group (p < 0.05). Thus, our results demonstrate that the Bifidobacterium infantis-mediated TK/GCV suicide gene therapy system can effectively inhibit rat bladder tumor growth, possibly through increasing caspase 3 expression and inducing apoptosis.

Show MeSH
Related in: MedlinePlus