In vivo Recombinant Adenovirus-mediated p53 Gene Therapy in a Syngeneic Rat Model for Colorectal Cancer

Baek, Jeong‐Heum; Agarwal, Munna L.; Tubbs, Raymond R.; Vladisavljevic, Alex; Tomita, Hiroshi; Bukowski, Ronald M.; Milsom, Jeffrey W.; Kim, Jin Man; Kwak, Jin-Young

doi:10.3346/jkms.2004.19.6.834

Cited by 11 publications

(10 citation statements)

References 21 publications

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“…62 In colon cancer, adenovirus mediated p53 gene transfer could induce apoptosis and inhibit growth and angiogenesis. 63 In addition, overexpression of Sufu, PTEN or Gli3R has shown anti-tumor effects on colon cancer cells. 35,42,64 So they may be developed to be effective therapeutic molecules for colon cancer.…”

Section: Implications For Colon Cancer Therapymentioning

confidence: 99%

Crosstalk between Wnt/β-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy

Song

Li²,

Liu

et al. 2015

Cancer Biology & Therapy

111

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Section: Implications For Colon Cancer Therapymentioning

confidence: 99%

Crosstalk between Wnt/β-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy

Song

Li²,

Liu

et al. 2015

Cancer Biology & Therapy

111

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“…Since the p53 gene exhibits a strong suppressing effect on human malignant tumor growth, it is one of the most promising targets for gene targeted therapy (19)(20)(21). Previous studies have demonstrated that p53 gene therapy has an anticancer effect on various solid tumors in vivo and in vitro (12,(22)(23)(24).…”

Section: Discussionmentioning

confidence: 99%

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The present study was conducted to identify the anti-tumor effects of rAd/p53, which is a recombinant human serotype 5 adenovirus, in cutaneous squamous cell carcinoma (cSCC). Mouse models of human cSCC were constructed by injecting human cutaneous squamous cell carcinoma cells into both flanks of nude mice. Subsequently, the 75 nude mice with cSCC xenograft tumors were randomly divided into recombinant human serotype 5 adenovirus (rAd)/p53, rAd/p53 + 5-fluorouracil (5-Fu) and 5-Fu groups. One side of the tumors was administered the therapeutic agents as the therapeutic group, whereas the remaining side was treated with medical saline as the control. At 24, 48, 72, 120 and 168 h post-intratumoral injection, alterations in tumor volume, tumor necrosis and the expression of several tumor-associated genes, including Smad4, Brca1 and matrix metalloproteinase (MMP-2), were analyzed. Compared with its control group, the rAd/P53 group exhibited a significantly increased tumor necrosis ratio. In addition, Smad4 and Brca1 expression levels increased significantly at various time points (P<0.05), and MMP-2 expression decreased significantly (P<0.05). In the rAd/p53 + 5-Fu group, the tumor necrosis ratio, and Smad4 and Brca1 expression levels also significantly increased at various time points (P<0.05). MMP-2 gene transcription gradually decreased, high expression of Smad4 was prolonged, and high expression of Brca1 was observed in the early period following treatment compared with the rAd/P53 group. In addition, p53 expression exhibited a positive correlation with the tumor necrosis ratio and Smad4 expression, and showed a negative correlation with MMP-2 gene transcription (P<0.05). These findings indicate that rAd/p53 has a potent anti-tumor effect in cSCC via the promotion of tumor necrosis and regulating the expression of various tumor-associated genes.

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“…The wt-p53 gene has been a popular candidate for gene replacement therapy since it suppresses tumor growth in various types of solid tumors (11)(12)(13)(14)(15). Mutation in the p53 gene may cause various types of cancers.…”

Section: Introductionmentioning

confidence: 99%

“…The protein activity is regulated by phosphorylation and is readily degraded (8,9). In contrast, the p53 protein loses its function quite readily due to its gene mutation, especially on its 393 amino acid residue (10).The wt-p53 gene has been a popular candidate for gene replacement therapy since it suppresses tumor growth in various types of solid tumors (11)(12)(13)(14)(15). Mutation in the p53 gene may cause various types of cancers.…”

mentioning

confidence: 99%

Anticancer activity of oncolytic adenoviruses carrying p53 is augmented by 11R in gallbladder cancer cell lines in vitro and in vivo

Wang

Yan

et al. 2013

Oncology Reports

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Abstract. Gallbladder cancer (GBC) is a rare disease associated with an extremely poor patient prognosis, and occasionally, aberrant expression of p53 is present. Considering that p53 is one of the most widely studied tumor-suppressor genes, we used a cell-penetrating peptide, 11R, to enhance the transferring efficiency of the oncolytic adenovirus carrying the p53 gene by constructing SG7605-11R-p53, a gene-viral therapy system which has higher specificity, enhanced safety, and efficacy. After infection with SG7605-11R-p53 at a multiplicity of infection (MOI) of 1 PFU/cell in vitro, the survival rate of EH-GB1 cells was lower than 50%, and that of EH-GB2 cells was lower than 40%, while the survival rate was higher than 90% for BJ human fibroblast cells, demonstrating that SG7605-11R-p53 has potent specific cytotoxicity against GBC cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB2 xenografts when the total dose of SG7605-11R-p53 was 1x10 9 PFU, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was 66.75±6.702%. Compared with existing gene therapy with longstanding shortcomings, our new system offers an additional option for patients with advanced GBC and other cancers who may not be suitable for chemotherapy, radiotherapy or who are not indicated for surgical treatment. IntroductionGallbladder cancer (GBC) is a rare but highly lethal disease, known to humans since 1777 (1,2). It is now recognized as one of the most common biliary tract malignancies (3). Up to 75% of such patients suffer from this unresectable disease at the time of surgical evaluation (4).Currently available treatments such as chemotherapy and radiotherapy have little effect on advanced GBC, and the 5-year survival rate is only ~5% in such cases (5). Therefore, development of new treatment modalities, such as gene therapy, merits high priority. Yet, few studies are available concerning GBCs.Gene therapy has been widely accepted as an important strategy for treating malignancies (6). Yet, the clinical application of tumor gene therapy still has some limitations, such as low gene transferring efficiency, poor transgene expression, and limited target specificity to tumors (7). Among the possible candidate genes is the gene that codes for the p53 protein, whose product is mainly enriched around the nucleoli of normal cells and can specifically bind with DNA. The protein activity is regulated by phosphorylation and is readily degraded (8,9). In contrast, the p53 protein loses its function quite readily due to its gene mutation, especially on its 393 amino acid residue (10).The wt-p53 gene has been a popular candidate for gene replacement therapy since it suppresses tumor growth in various types of solid tumors (11)(12)(13)(14)(15). Mutation in the p53 gene may cause various types of cancers. Researchers have also proven that the growth of tumors with p53 gene mutation may be inhibited even in the late stages, and the function of p53 may still be recovered by clinical therapy. As a resu...

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In vivo Recombinant Adenovirus-mediated p53 Gene Therapy in a Syngeneic Rat Model for Colorectal Cancer

Cited by 11 publications

References 21 publications

Crosstalk between Wnt/β-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy

Crosstalk between Wnt/β-catenin and Hedgehog/Gli signaling pathways in colon cancer and implications for therapy

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice

Anticancer activity of oncolytic adenoviruses carrying p53 is augmented by 11R in gallbladder cancer cell lines in vitro and in vivo

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