Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene

Shen, Lizong; Wu, Wei; Xu, Dehua; Zheng, Zhiming; Liu, Xinyuan; Ding, Qiang; Hua, Yibing; Yao, Kun

doi:10.3748/wjg.v8.i2.270

Cited by 19 publications

(8 citation statements)

References 22 publications

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“…These antigens are abundant in mucin from cancer cells (3). Malignant transformation also changes the glycosylation of carcinoembryonic antigen (CEA) resulting in higher levels of Lewis X and de novo expression of Lewis Y on tumour-associated CEA (60), but this molecule, although present in a large percentage of cervix carcinoma, is not expressed in HeLa cells (61).…”

Section: H-mrs Can Detect Aberrant Glycosylation In Hela Cellsmentioning

confidence: 99%

¹H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

et al. 2011

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Glycosylation is the most abundant and diverse form of post-translational modification of proteins. Two types of glycans exist in glycoproteins: N-glycans and O-glycans often coexisting in the same protein. O-glycosylation is frequently found on secreted or membrane-bound mucins whose overexpression and structure alterations are associated with many types of cancer. Mucins have several cancer-associated structures, including high levels of Lewis antigens characterized by the presence of terminal fucose. The present study deals with the identification of MR signals from N-acetylgalactosamine and from fucose in HeLa cells by detecting a low-field signal in one-dimensional (1D) spectra assigned to the NH of N-acetylgalactosamine and some cross peaks assigned to fucose in two-dimensional (2D) spectra. The increase of Golgi pH by treatment with ammonium chloride allowed the N-acetylgalactosamine signal assignment to be confirmed. Behaviour of MR peak during cell growth and comparison with studies from literature taken together made it possible to have more insight into the relationship between aberrantly processed mucin and the presence of non-processed N-acetylgalactosamine residues in HeLa cells. Fucose signals, tentatively ascribed to residues bound to galactose and to N-acetylglucosamine, are visible in both intact cell and perchloric acid spectra. Signals assigned to fucose bound to galactose are more evident in ammonium chloride-treated cells where structural changes of mucin-related Lewis antigens are expected as a result of the higher Golgi pH. A common origin for the N-acetylgalactosamine and fucose resonances attributing them to aberrantly processed mucin can be inferred from the present results.

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Section: H-mrs Can Detect Aberrant Glycosylation In Hela Cellsmentioning

confidence: 99%

¹H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

et al. 2011

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“…Gastric cancer is one of the most common malignancies both in China and abroad [1][2][3][4][5][6][7] . Despite the improvements in surgical techniques, radiation and chemotherapeutic regimens, the disease remains a great challenge.…”

Section: Introductionmentioning

confidence: 99%

Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901

Zhang¹,

Wan²,

Yuan³

et al. 2004

WJG

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AIM:To construct and identify the recombinant vectors carrying herpes simplex virus thymidine kinase (HSV-TK) and tumor necrosis factor alpha (TNF-α) or interleukin-2 (IL-2) genes expressed in gastric carcinoma cell line SGC7901. METHODS:The fragments of HSV-TK, internal ribosome entry sites (IRES) and TNF-α or IL-2 genes were inserted in a TK-IRES-TNF-α or TK-IRES-IL-2 order into pEGFP-N 3 and pLXSN to generate the therapeutic vectors pEGFP-TT, pEGFP-TI, pL(TT)SN and pL(TI)SN respectively, which were structurally confirmed by the digestion analysis of restriction endonuclease. The former two plasmids were used for the transient expression of recombinant proteins in the target cells while pL(TT)SN and pL(TI)SN were transfected into SGC7901 cells by lipofectamine for the stable expression of objective genes through G418 selection. The protein products expressed transiently and stably in SGC7901 cells by the constructed vectors were confirmed by fluorescent microscopy and Western blot respectively. RESULTS:The inserted fragments in all constructed plasmids were structurally confirmed to be consistent with that of the published data. In the transient expression, both pEGFP-TT and pEGFP-TI were shown expressed in nearly 50% of the transfected SGC7901 cells. Similarly, the G418 selected vectors PL(TT)SN and PL(TI)SN were confirmed to be successful in the stable expression of the objective proteins in the target cells. CONCLUSION:The constructed recombinant vectors in the present study that can express the suicide gene TK in combination with cytokines genes may serve as the potential tools to perform more effective investigations in future for the gene therapy of gastric carcinoma.Zhang JH, Wan MX, Yuan JY, Pan BR. Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901.

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“…[35][36][37][38][39] In a variety of studies, this CEA promoter fragment has been shown to be able to target therapeutic genes to colorectal cancer cells expressing high levels of CEA. [12][13][14][15][16] Using this CEA promoter fragment, we were able to target hNIS expression to human colon cancer cells resulting in tumor-specific radioiodide accumulation. Functional NIS expression was specific for CEA expressing colon cancer cells as evidenced by lack of iodide uptake activity in control cancer cells without CEA expression.…”

Section: Discussionmentioning

confidence: 99%

Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer

et al. 2004

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We investigated the feasibility of using radioiodine therapy in colon carcinoma cells (HCT 116) following tumor-specific expression of the human sodium iodide symporter (hNIS) using the carcinoembryonic antigen (CEA) promoter. HCT 116 cells were stably transfected with an expression vector, in which hNIS cDNA has been coupled to a CEA promoter fragment. This promoter is responsible for tissue-specific expression of CEA in gastrointestinal tract epithelium, and has been shown to target therapeutic genes to colorectal cancer cells. Functional NIS expression was confirmed by iodide uptake assay, Western blot analysis, immunostaining and in vitro clonogenic assay. The stably transfected HCT 116 cells concentrated 125 I about 10-fold in vitro without evidence of iodide organification. In contrast, transfection of control cancer cells without CEA expression did not result in iodide accumulation. Western blot analysis using a hNISspecific antibody revealed a band of approximately 90 kDa.In addition, immunostaining of stably transfected HCT 116 cells revealed hNIS-specific membrane-associated immunoreactivity. In an in vitro clonogenic assay approximately 95% of stably transfected HCT 116 cells were killed by exposure to 131 I, while only about 5% of NIS-negative control cells were killed. Further, using an adenovirus carrying the NIS gene linked to the CEA promoter, high levels of tumorspecific radioiodide accumulation were induced in HCT 116 cells. In conclusion, a therapeutic effect of 131 I has been demonstrated in colon carcinoma cells following induction of tumor-specific iodide uptake activity by CEA promoterdirected NIS expression in vitro. This study demonstrates the potential of NIS as a therapeutic gene allowing radioiodine therapy of colon cancer following tumor-specific NIS gene transfer. Gene Therapy (2005) 12, 272-280.

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Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene

Cited by 19 publications

References 22 publications

¹H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

¹H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901

Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer

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Specific CEA-producing colorectal carcinoma cell killing with recombinant adenoviral vector containing cytosine deaminase gene

Cited by 19 publications

References 22 publications

1H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

1H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

Construction and identification of recombinant vectors carrying herpes simplex virus thymidine kinase and cytokine genes expressed in gastric carcinoma cell line SGC7901

Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer

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¹H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line

¹H‐MRS can detect aberrant glycosylation in tumour cells: a study of the HeLa cell line