Development of Prostate-Specific Antigen Promoter-Based Gene Therapy for Androgen-Independent Human Prostate Cancer

Gotoh, Akinobu; Ko, Sungahn; Shirakawa, Toshiro; Cheon, Jun; Kao, Chinghai; Miyamoto, Tadayuki; Gardner, Thomas A.; Ho, Ling Jun; Cleutjens, C.B.J.M.; Trapman, Jan; Graham, Frank L.; Chung, Leland W.K.

doi:10.1016/s0022-5347(01)63094-5

Cited by 109 publications

(48 citation statements)

References 26 publications

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“…These combination therapies involving p53 over expression have consistently demonstrated enhanced tumor suppressing activity, relative to single agents [11,12]. Finally, in androgen-independent prostate cancer cells, significant cytotoxicity has been previously reported with over expression of recombinant wild-type p53 using an adenovirus vector (Ad5CMV-P53) [13,14].…”

Section: Introductionmentioning

confidence: 97%

2-Deoxyglucose combined with wild-type p53 overexpression enhances cytotoxicity in human prostate cancer cells via oxidative stress

Ahmad

Abdalla

Aykin-Burns

et al. 2008

Free Radical Biology and Medicine

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Over expression of the tumor suppressor gene, wild type p53 (wtp53), using adenoviral vectors (Adp53) has been suggested to kill cancer cells by hydroperoxide-mediated oxidative stress [1,2] and nutrient distress induced by the glucose analog, 2-deoxyglucose (2DG), has been suggested to enhance tumor cell killing by agents that induce oxidative stress via disrupting hydroperoxide metabolism [3,4]. In the current study clonogenic cell killing of PC-3 and DU-145 human prostate cancer cells (lacking functional p53) mediated by 4 h exposure to 50 plaque forming units (pfus)/ cell of Adp53 (that caused the enforced over expression of wtp53) was significantly enhanced by treatment with 2DG. Accumulation of glutathione disulfide was found to be significantly greater in both cell lines treated with 2DG+Adp53 and both cell lines treated with 2DG+Adp53 showed a ~2-fold increases in dihydroethidine (DHE) and 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate (CDCFH 2 ) oxidation, indicative of increased steady-state levels of O 2 •-and hydroperoxides, respectively. Finally, over expression of catalase or glutathione peroxidase using adenoviral vectors partially, but significantly, protected DU-145 cells from the toxicity induced by 2DG+Adp53 treatment. These results show that treatment of human prostate cancer cells with the combination of 2DG (a nutrient stress) and over expression of the tumor suppressor gene, wtp53, enhances clonogenic cell killing by a mechanism that involves oxidative stress as well as allowing for the speculation that inhibitors of glucose and hydroperoxide metabolism can be used in combination with Adp53 gene therapy to enhance therapeutic responses.

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Section: Introductionmentioning

confidence: 97%

2-Deoxyglucose combined with wild-type p53 overexpression enhances cytotoxicity in human prostate cancer cells via oxidative stress

Ahmad

Abdalla

Aykin-Burns

et al. 2008

Free Radical Biology and Medicine

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“…Subsequent studies demonstrated that the core enhancer contains at least four non-consensus AREs with variable binding affinity for AR, 16 all of which contribute to the synergistic activation of PSA gene expression. 16 Studies utilizing combinations of native PSA regulatory regions to drive therapeutic genes [17][18][19] in cell culture have demonstrated approximately a 10-fold prostate tissue discriminatory activity and androgen inducibility. The expected therapeutic response of tumor cell ablation was observed in PSA-expressing prostate cancer cells.…”

Section: -1426mentioning

confidence: 99%

“…21,22 Two Ads with either the entire 5.8-kb (−5825 to +12) PSA regulatory region or 1.6-kb (−5322 to −3738) enhancer linked to the proximal PSA promoter (−541 to +12), were able to direct either prostate-specific expression of cytotoxic HSVtk 19 or viral E1A 22 to induce lytic viral replication. The efficacy, tissue specificity and safety of these therapeutic approaches were not fully evaluated in vivo.…”

Section: Bases Include Four Copies Of Are Elements (Underlined and Bomentioning

confidence: 99%

“…Homogenizations of the tissue were performed by a PowerGen 125 (Fisher Scientific) Protein concentrations of tissue homogenized lysates were measured by Coomassie Plus reagent (Pierce) according to the manufacturer's directions. [10][11][12][13][14][15][16][17][18][19][20] l of tissue lysate were measured in luminometer assays.…”

Section: Immobilized Template Pulldown Assaymentioning

confidence: 99%

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Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors

Matherly

Smallwood

et al. 2001

Gene Ther

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“…6 Another solution is to restrict the expression of suicide genes to tumor cells utilizing tumor-or tissue-specific promoters (tsp), as has been reviewed by Nettelbeck et al 7 However, most tsp are only applicable for a certain type of cancer. For example, the tsp human alpha-lactalbumin (hALA) and ovine betalactoglobulin (oBLG) have been utilized for selective gene expression in breast tissue, 8 the prostate-specific enhancing sequence (PSES) promoter for the selective expression in prostate cancer 9,10 and the tyrosinase promoter for the selective expression in melanoma. 11 We report here the suitability of the epithelial glycoprotein-2 (EGP-2) promoter for suicide gene therapy.…”

Section: Introductionmentioning

confidence: 99%

The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and selective gene expression in an adenoviral context

et al. 2005

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Adenoviral vectors are widely used in cancer gene therapy. After systemic administration however, the majority of the virus homes to the liver and the expressed transgene may cause hepatotoxicity. To restrict transgene expression to tumor cells, tumor-or tissuespecific promoters are utilized. The tumor antigen epithelial glycoprotein-2 (EGP-2), also known as Ep-CAM, is expressed in many cancers from different epithelial origins. In this study, the EGP-2 promoter was shown to restrict the expression of luciferase and thymidine kinase in an adenoviral context in different cell lines. In vivo, the EGP-2 promoter mediated efficient expression of luciferase in tumors but showed a 3-log lower activity in liver tissue when compared with the cytomegalovirus (CMV) promoter. Similarly, the EGP-2 promoter mediated specific cell killing after ganciclovir treatment in EGP-2-positive cells. Moreover, in vivo, this treatment regiment did not cause any rise in the liver enzymes aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT), demonstrating absence of liver toxicity. In contrast, CMV-mediated expression of thymidine kinase in combination with ganciclovir treatment resulted in high ASAT and ALAT values. This study demonstrates the value of the EGP-2 promoter to restrict transgene expression to a broad range of tumor types, thereby preventing liver toxicity.

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Development of Prostate-Specific Antigen Promoter-Based Gene Therapy for Androgen-Independent Human Prostate Cancer

Abstract: The 5837 bp long PSA promoter was active in the androgen free environment and could be used to target both androgen-dependent and independent PSA-producing prostate cancer cells in vitro, and prostate tumors in castrated hosts.

Cited by 109 publications

References 26 publications

2-Deoxyglucose combined with wild-type p53 overexpression enhances cytotoxicity in human prostate cancer cells via oxidative stress

2-Deoxyglucose combined with wild-type p53 overexpression enhances cytotoxicity in human prostate cancer cells via oxidative stress

Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors

The carcinoma-specific epithelial glycoprotein-2 promoter controls efficient and selective gene expression in an adenoviral context

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