Utilizing Chimeric Proteins for Exploring the Cellular Fate of Endogenous Proteins

Ben‐Yehudah, Ahmi; Aqeilan, Rami I.; Belostotsky, Ruth; Azar, Yehudith; Lorberboum-Galski, Haya

doi:10.1006/bbrc.2001.6163

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…Tumors extracted from treated mice were approximately threefold smaller than tumors from PBS-treated controls (FIGURE 2C). Although these chimeric proteins are delivered from the exterior of the cell, our group showed that they are allocated to the same compartments as their endogenous counterpart proteins [53] and induce apoptosis in a similar way to the normal triggering of apoptosis [46]. This result reinforced our previous results, indicating a direct action of the chimeric protein on tumor cells (FIGURE 1D).…”

Section: Gnrh-dff40supporting

confidence: 86%

Targeted cancer therapy with gonadotropin-releasing hormone chimeric proteins

Ben‐Yehudah¹,

Lorberboum-Galski²

2004

Expert Review of Anticancer Therapy

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Tumor-associated antigens (TAAs) have been identified mainly to determine cancer prognosis. In the past few years, TAAs have been used in the development of treatment modalities such as tumor vaccination. This review describes an additional application of TAAs: as a target for specific antitumor treatment. Since TAAs are overexpressed on the tumor cell surface, they can be targeted to deliver drugs directly to cancer cells. One such delivery system exploits chimeric proteins. Chimeric proteins are a class of targeted molecules designed to recognize and specifically destroy cells that overexpress specific receptors. These molecules, designed and constructed by gene fusion techniques, comprise both cell-targeting and cell-killing moieties. The authors' laboratory has developed a number of chimeric proteins using gonadotropin-releasing hormone (GnRH) as the targeting moiety. These chimeras recognize a GnRH binding site that is expressed on adenocarcinoma cells. GnRH was fused to a large number of killing moieties, including bacterial and human proapoptotic proteins. All GnRH-based chimeric proteins selectively killed adenocarcinoma cells both in vitro and in vivo. Utilizing chimeric proteins for targeted therapy represents a new and exciting therapeutic modality for the treatment of cancer in humans.

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Section: Gnrh-dff40supporting

confidence: 86%

Targeted cancer therapy with gonadotropin-releasing hormone chimeric proteins

Ben‐Yehudah¹,

Lorberboum-Galski²

2004

Expert Review of Anticancer Therapy

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“…IL-2-Bax specifically targets IL-2R-expressing cells and induces cell specific, dose-dependent apoptosis. 5,6 Bax is a proapoptotic member of the Bcl-2 protein family, and has been reported to induce apoptosis in cancer cells after transfection; it can also inhibit growth of many tumor types. Bax can increase the permeability of the mitochondrial outer membrane, leading to the release of apoptosis molecules such as cytochrome C. [7][8][9] p53 has been shown to initiate the mitochondrial apoptosis by modulating the expression of Bcl-2 family members, including Bax.…”

Section: Introductionmentioning

confidence: 99%

683 Recombinant Adenovirus Il-24-Bax Promotes Apoptosis of Hepatocellular Carcinoma Cells in Vitro and in Vivo

Shi¹

2011

Journal of Hepatology

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“…IL-2-Bax specifically targets IL-2R-expressing cells and induces cell specific, dose-dependent apoptosis. 5, 6 …”

Section: Introductionmentioning

confidence: 99%

Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo

Shi

Zhang

et al. 2010

Cancer Gene Ther

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Gene therapy promises to become an alternative choice for the treatment of hepatic cancer. In many cancers, the delivery of chimeric proteins by adenovirus vector has been reported to induce apoptosis. This study was performed to evaluate whether the recombinant adenovirus interleukin (IL)-24-Bax can induce apoptosis in hepatocellular carcinoma cells in vitro and in vivo. Several recombinant adenoviruses were constructed, and the expression of their encoded proteins was measured. The effects of the recombinant adenovirus on hepatocellular carcinoma cells and the normal hepatocyte cell line were investigated through cell viability and apoptosis assays after the cells were treated with Ad.Luc, Ad.IL-24, Ad.Bax or Ad.IL-24-Bax. The mechanism involved was also explored. A tumor-bearing mouse model was used to evaluate the effects of the adenovirus on tumor volume and cell apoptosis in vivo. Ad.IL-24-Bax selectively suppressed growth of hepatocellular carcinoma cells and induced apoptosis, but it had little influence on the normal hepatocytes. The mechanism of this response may include the effect of the 10HRE/VEGF385 promoter and the synergistic effect of IL-24 and Bax. Ad.IL-24-Bax also suppressed tumor growth in nude mice and induced apoptosis. Ad.IL-24-Bax may be a useful tool for gene therapy of hepatic cancer.

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Utilizing Chimeric Proteins for Exploring the Cellular Fate of Endogenous Proteins

Cited by 4 publications

References 32 publications

Targeted cancer therapy with gonadotropin-releasing hormone chimeric proteins

Targeted cancer therapy with gonadotropin-releasing hormone chimeric proteins

683 Recombinant Adenovirus Il-24-Bax Promotes Apoptosis of Hepatocellular Carcinoma Cells in Vitro and in Vivo

Recombinant adenovirus IL-24-Bax promotes apoptosis of hepatocellular carcinoma cells in vitro and in vivo

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