Suicide gene therapy in cancer: Where do we stand now?

Duarte, Sónia; Carle, Georges F.; Faneca, Henrique; Lima, Maria C. Pedroso de; Pierrefite-Carle, Valérie

doi:10.1016/j.canlet.2012.05.023

Cited by 178 publications

(168 citation statements)

References 154 publications

(67 reference statements)

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…With the recent discovery of the stem cell like properties of cancer cells, scientists have faced to a new challenge of finding alternative effective treatment methods (2). In this regard gene therapy has been identified recently as a promising alternative to conventional therapeutic options (3). Cancer gene therapy could be applicable in different forms such as mutation correction, enhancement of the immune response against tumor cells, RNA interference, targeted lysis of tumor cells using selective replicative viruses; antiangiogenic and suicide gene therapies (4 interference (RNAi) introduced into cancer cells via lentiviral infection, to manipulate identified oncogenes is gaining more attention in cancer therapy research (5).…”

Section: Introductionmentioning

confidence: 99%

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Wei

Chen

et al. 2014

Technol Cancer Res Treat

View full text Add to dashboard Cite

Abbreviation: RHBDD1: Rhomboid Domain Containing 1; shRNA: Short Hairpin RNAs; RNAi: RNA Interference.Rhomboid domain containing 1 (RHBDD1) gene, a new member of rhomboid family of proteins is highly responsible for the regulation of apoptosis by cleaving pro-apoptotic Bcl-2 family protein BIK. Therefore, the higher expression levels of RHBDD1 in cancer tissues may have a direct influence on cancer progression by arresting apoptosis. With this background this study was focused to find out the effect of RHBDD1 silencing on the progression of human brain glioblastoma cells, U251 and U87MG. The results indicated that both cell lines show a higher expression level of RHBDD1 and RNA interference (RNA) mediated gene silencing successfully down regulated the RHBDD1 gene expression. As a result of RHBDD1 silencing the proliferation of both cell types was reduced by over 50%, 5 days after silencing. Moreover the colony formation was completely inhibited and there were no cells present following two week RHBDD1 gene silencing. The cell proliferation was inhibited as a result of cell cycle arrest due to RHBDD1 absence. Therefore, these results clearly indicate that, RHBDD1 is essential for the progression of glioblastoma cells and silencing of it is resulting in significant inhibition of cell cycle progression and cell proliferation. Collectively, this study shows that RHBDD1 gene engineering could be used as an effective tool in malignant brain tumor therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Wei

Chen

et al. 2014

Technol Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…To the best of or knowledge , there is no hint that the D 2 R might act as a suicide gene such as the HSV1-Tk (38). However, because the used variant D2R80A is not functional and lentiviral vectors have low genotoxicity (20), the hMSC-D2R80A should have no potential for malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Mesenchymal Stem Cell Tracking with PET Using the Dopamine Type 2 Receptor and ¹⁸F-Fallypride

et al. 2014

View full text Add to dashboard Cite

Human mesenchymal stem cells (hMSCs) represent a promising treatment approach for tissue repair and regeneration. However, little is known about the underlying mechanisms and the fate of the transplanted cells. The objective of the presented work was to determine the feasibility of PET imaging and in vivo monitoring after transplantation of dopamine type 2 receptor-expressing cells. Methods: An hMSC line constitutively expressing a mutant of the dopamine type 2 receptor (D2R80A) was generated by lentiviral gene transfer. D2R80A messenger RNA expression was confirmed by reverse transcriptase-polymerase chain reaction. Localization of the transmembrane protein was analyzed by confocal fluorescence microscopy. The stem cell character of transduced hMSCs was investigated by adipogenic and osteogenic differentiation. Migration capacity was assessed by scratch assays in time-lapse imaging. In vitro specific binding of ligands was tested by fluorescenceactivated cell sorting analysis and by radioligand assay using 18 Ffallypride. Imaging of D2R80A overexpressing hMSC transplanted into athymic rats was performed by PET using 18 F-fallypride. Results: hMSCs showed long-term overexpression of D2R80A. As expected, the fluorescence signal suggested the primary localization of the protein in the membrane of the transduced cells. hMSC and D2R80A retained their stem cell character demonstrated by their osteogenic and adipogenic differentiation capacity and their proliferation and migration behavior. For in vitro hMSCs, at least 90% expressed the D2R80A transgene and hMSC-D2R80A showed specific binding of 18 F-fallypride. In vivo, a specific signal was detected at the transplantation site up to 7 d by PET. Conclusion: The mutant of the dopamine type 2 receptor (D2R80A) is a potent reporter to detect hMSCs by PET in vivo.

show abstract

“…In addition, with population growth and aging, and an unhealthy lifestyle comprising physical inactivity, smoking and 'westernized' diets, the burden of cancer is increasing in developing countries (3)(4)(5)(6). Fortunately, various therapies, including surgical management (7), radiotherapy (8), chemotherapy (9), traditional Chinese medicine therapy (10), biotherapy (11), immunotherapy (12), gene therapy (13), thermotherapy (14), photodynamic therapy (15) and interventional therapy (16), have been successfully used to reduce pain in patients with cancer and prolong life expectancy.…”

Section: Introductionmentioning

confidence: 99%

Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway

2016

View full text Add to dashboard Cite

Abstract. The present study was designed to investigate the antiproliferative activity of isoimperatorin against SGC-7901 cells and to examine the possible mechanisms. The antiproliferative activity of isoimperatorin against SGC-7901 cells was evaluated using an MTT assay, and the mechanisms were investigated using flow cytometry and western blot assays, which were used to determine the apoptotic rate and expression levels of mitochondria-mediated apoptosis-associated proteins, including Survivin, myeloid leukemia cell-1 (Mcl-1), B cell lymphoma-extra large (Bcl-xl), B cell lymphoma 2 (Bcl-2), second mitochondria-derived activator of caspase (Smac), Bcl-2-associated X factor (Bax), cleaved (c)-caspase-3 and c-caspase-9 in SGC-7901 cells. Additionally, a xenograft assay was used to confirm whether isoimperatorin had an inhibitory effect on SGC-7901 cell-induced tumors in vivo. The results of the MTT assay suggested that isoimperatorin significantly inhibited the proliferation of SGC-7901 cells in a dose-and time-dependent manner, and the half maximal inhibitory concentration was 18.75 µg/ml. The results of the flow cytometric analysis indicated that, following treatment with isoimperatorin, the apoptotic rate of SGC-7901 cells was significantly increased, compared with that of cells in the control group. The results of the western blot analysis indicated that, following treatment with isoimperatorin, the expression levels of the pro-apoptotic proteins, Bax, c-caspase-3 and c-caspase-9, were significantly increased and the expression levels of the anti-apoptotic proteins, Survivin and Bcl-2, were significantly reduced, compared with the control group. No alterations in expression were found in the other apoptosis-associated proteins, including Mcl-1, Bcl-xl and Smac. The results of the xenograft assay indicated that isoimperatorin significantly inhibited the growth of SGC-7901 cell-induced tumor in vivo by increasing the expression levels of pro-apoptotic proteins (Bax, c-caspase-3 and c-caspase-9) and reducing the expression levels of anti-apoptotic proteins (Survivin and Bcl-2) without adverse effects on the increasing body weight of nude mice. In conclusion, the present study revealed that isoimperatorin may be able to induce the apoptosis of SGC-7901 cells in vitro and in vivo by regulating the expression levels of mitochondria-mediated apoptosis-associated proteins.

show abstract

Suicide gene therapy in cancer: Where do we stand now?

Cited by 178 publications

References 154 publications

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

In Vivo Mesenchymal Stem Cell Tracking with PET Using the Dopamine Type 2 Receptor and ¹⁸F-Fallypride

Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway

Contact Info

Product

Resources

About

Suicide gene therapy in cancer: Where do we stand now?

Cited by 178 publications

References 154 publications

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

Lentiviral Vector Mediated Delivery of RHBDD1 shRNA down Regulated the Proliferation of Human Glioblastoma Cells

In Vivo Mesenchymal Stem Cell Tracking with PET Using the Dopamine Type 2 Receptor and 18F-Fallypride

Isoimperatorin induces apoptosis of the SGC-7901 human gastric cancer cell line via the mitochondria-mediated pathway

Contact Info

Product

Resources

About

In Vivo Mesenchymal Stem Cell Tracking with PET Using the Dopamine Type 2 Receptor and ¹⁸F-Fallypride