Erratum: A modified hTERT promoter-directed oncolytic adenovirus replication with concurrent inhibition of TGFb signaling for breast cancer therapy

Hu, Zhigang; Robbins, Joan; Pister, Amanda; Zafar, Maria; Zhang, Z. W.; Gupta, Jeena; Lee, K. J.; Newman, Kam; Yun, Chae Ok; Guise, Theresa A.; Seth, Prem

doi:10.1038/cgt.2010.61

Cited by 4 publications

(8 citation statements)

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“…Adenoviral vectors used in these studies were as follows: Ad(E1-).sTbRFc, an E1adenovirus expressing sTGFbRIIFc; Ad.GFPluc, an adenovirus expressing the GFP-luc gene; Ad .sTbRFc, an oncolytic adenovirus expressing the sTGFbRIIFc gene; and TAd.sTbRFc, an oncolytic adenovirus expressing the sTGFbRIIFC gene except that the TERT promoter drives viral replication. Oncolytic adenoviruses were constructed with a dl01/07 mutant of Ad5, containing two deletion mutations in the E1A region (Howe et al, 2000) as previously described (Seth et al, 2006;Hu et al, 2010a). Adenoviral vectors were grown in HEK293 cells and purified by double CsCl 2 gradient centrifugation as described (Katayose et al, 1995).…”

Section: Adenoviral Vectorsmentioning

confidence: 99%

“…Considering these, and other studies that suggest oncolytic adenoviruses as a potential new class of antitumor agents (Bischoff et al, 1996;de Vrij et al, 2010;Toth et al, 2010), our laboratory is interested in developing recombinant oncolytic adenoviruses that will kill tumor cells and simultaneously target the TGF-b pathways. We have created Ad.sTbRFc, an oncolytic adenovirus expressing sTGFbRIIFc, a protein that can directly target TGF-b and inhibit TGF-b signaling (Seth et al, 2006;Hu et al, 2010a). Because human telomerase reverse transcriptase (TERT) promoter is generally expressed at higher levels in prostate cancer (Shay and Bacchetti, 1997), we have also developed an oncolytic adenovirus, TAd.sTbRFc (Hu et al, 2010a), which is similar to Ad.sTbRFc except that the human TERT promoter drives adenoviral replication.…”

Section: Introductionmentioning

confidence: 99%

“…We have created Ad.sTbRFc, an oncolytic adenovirus expressing sTGFbRIIFc, a protein that can directly target TGF-b and inhibit TGF-b signaling (Seth et al, 2006;Hu et al, 2010a). Because human telomerase reverse transcriptase (TERT) promoter is generally expressed at higher levels in prostate cancer (Shay and Bacchetti, 1997), we have also developed an oncolytic adenovirus, TAd.sTbRFc (Hu et al, 2010a), which is similar to Ad.sTbRFc except that the human TERT promoter drives adenoviral replication.…”

Section: Introductionmentioning

confidence: 99%

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Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Gupta

Zhang

et al. 2012

Human Gene Therapy

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We have examined whether Ad.sTβRFc and TAd.sTβRFc, two oncolytic viruses expressing soluble transforming growth factor-β receptor II fused with human Fc (sTGFβRIIFc), can be developed to treat bone metastasis of prostate cancer. Incubation of PC-3 and DU-145 prostate tumor cells with Ad.sTβRFc and TAd.sTβRFc produced sTGFβRIIFc and viral replication; sTGFβRIIFc caused inhibition of TGF-β-mediated SMAD2 and SMAD3 phosphorylation. Ad(E1-).sTβRFc, an E1(-) adenovirus, produced sTGFβRIIFc but failed to replicate in tumor cells. To examine the antitumor response of adenoviral vectors, PC-3-luc cells were injected into the left heart ventricle of nude mice. On day 9, mice were subjected to whole-body bioluminescence imaging (BLI). Mice bearing hind-limb tumors were administered viral vectors via the tail vein on days 10, 13, and 17 (2.5×10(10) viral particles per injection per mouse, each injection in a 0.1-ml volume), and subjected to BLI and X-ray radiography weekly until day 53. Ad.sTβRFc, TAd.sTβRFc, and Ad(E1-).sTβRFc caused significant inhibition of tumor growth; however, Ad.sTβRFc was the most effective among all the vectors. Only Ad.sTβRFc and TAd.sTβRFc inhibited tumor-induced hypercalcemia. Histomorphometric and synchrotron micro-computed tomographic analysis of isolated bones indicated that Ad.sTβRFc induced significant reduction in tumor burden, osteoclast number, and trabecular and cortical bone destruction. These studies suggest that Ad.sTβRFc and TAd.sTβRFc can be developed as potential new therapies for prostate cancer bone metastasis.

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Section: Adenoviral Vectorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Gupta

Zhang

et al. 2012

Human Gene Therapy

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“…Ad.luc2 is identical to Ad.sTbRFc except that the luc2 gene is cloned in the E3 region. Ad(E1 À ).sTbRFc (Hu et al, 2010) is a nonreplicating virus expressing the CMV promoter driving sTGFbRIIFc in the E3 region. All adenoviral vectors were amplified in HEK293 cells and purified as described earlier (Katayose et al, 1995).…”

Section: Methodsmentioning

confidence: 99%

“…Thus, there is an urgent need to develop novel therapies for the treatment of bone metastases of breast cancer. Our laboratory has been interested in developing recombinant adenoviruses for the treatment of breast cancer (Katayose et al, 1995;Seth, 1999;Seth et al, 2006;Wang et al, 2006;Hu et al, 2010). Although oncolytic adenoviruses have been developed in many laboratories, their application in targeting bone metastasis has not been described (McCormick, 2005;Crompton and Kirn, 2007).…”

Section: Introductionmentioning

confidence: 99%

Systemic Delivery of an Oncolytic Adenovirus Expressing Soluble Transforming Growth Factor-β Receptor II–Fc Fusion Protein Can Inhibit Breast Cancer Bone Metastasis in a Mouse Model

Zhang

Guise

et al. 2010

Human Gene Therapy

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We have investigated whether systemic delivery of an oncolytic adenovirus, Ad.sTβRFc, expressing the soluble form of transforming growth factor-β receptor II fused with human immunoglobulin Fc fragment (sTGFβRIIFc), could inhibit breast cancer bone metastasis in a mouse model. MDA-MB-231 (human breast cancer) cells were inoculated into the left heart ventricles of nude mice. Once the skeletal tumors were visible by X-rays, mice were intravenously injected with either buffer, Ad.sTβRFc, Ad(E1⁻).sTβRFc (a replication-deficient adenovirus expressing sTGFβRIIFc), or Ad.luc2 (a replicating adenovirus expressing firefly luciferase gene). On days 2 and 7 after viral injections, viral replication and sTGFβRIIFc expression were detected in the skeletal tumors in Ad.sTβRFc-treated group; only viral replication in Ad.luc2 group, and sTGFβRIIFc expression in the Ad(E1⁻).sTβRFc group, were detected. To examine the therapeutic effects, buffer or various viral vectors were administered on days 4 and 7 after intracardiac injection of MDA-MB-231 cells. On day 28, X-ray radiography showed a highly significant reduction in lesion size by Ad.sTβRFc, a significant reduction by Ad.luc2, and some reduction by Ad(E1⁻).sTβRFc. Goldner's trichrome and hematoxylin-eosin staining of the bone sections revealed a significant reduction of tumor burden in the Ad.sTβRFc group, but not in the Ad(E1⁻).sTβRFc or Ad.luc2 group. There were significant reductions in free calcium levels by Ad.sTβRFc, Ad(E1⁻).sTβRFc, and Ad.luc2; however, only in the Ad.sTβRFc group were calcium levels reduced to the normal values. These results suggest that concomitant viral replication and sTGFβRIIFc production are important to inhibit bone metastasis and osteolysis, and that Ad.sTβRFc could be developed for targeting breast cancer bone metastases.

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Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy

Chan

et al. 2023

Exploration of Targeted Anti-Tumor Therapy

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Transforming growth factor-β (TGF-β) signaling is an important pathway for promoting the pathogenesis of inflammatory diseases, including cancer. The roles of TGF-β signaling are heterogeneous and versatile in cancer development and progression, both anticancer and protumoral actions are reported. Interestingly, increasing evidence suggests that TGF-β enhances disease progression and drug resistance via immune-modulatory actions in the tumor microenvironment (TME) of solid tumors. A better understanding of its regulatory mechanisms in the TME at the molecular level can facilitate the development of precision medicine to block the protumoral actions of TGF-β in the TME. Here, the latest information about the regulatory mechanisms and translational research of TGF-β signaling in the TME for therapeutic development had been summarized.

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Erratum: A modified hTERT promoter-directed oncolytic adenovirus replication with concurrent inhibition of TGFb signaling for breast cancer therapy

Cited by 4 publications

References 0 publications

Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Systemic Delivery of Oncolytic Adenoviruses Targeting Transforming Growth Factor-β Inhibits Established Bone Metastasis in a Prostate Cancer Mouse Model

Systemic Delivery of an Oncolytic Adenovirus Expressing Soluble Transforming Growth Factor-β Receptor II–Fc Fusion Protein Can Inhibit Breast Cancer Bone Metastasis in a Mouse Model

Transforming growth factor-β signaling: from tumor microenvironment to anticancer therapy

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