scholarly journals 590. SuperCD Enables Low Dose 5-FC Application for Effective Suicide Gene Therapy in a Rat Hepatoma Model Both In Vitro and In Vivo

2004 ◽  
Vol 9 ◽  
pp. S223
Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 573 ◽  
Author(s):  
So-Jung Gwak ◽  
Jeoung Soo Lee

Spinal cord tumors (SCT) are uncommon neoplasms characterized by irregular growth of tissue inside the spinal cord that can result in non-mechanical back pain. Current treatments for SCT include surgery, radiation therapy, and chemotherapy, but these conventional therapies have many limitations. Suicide gene therapy using plasmid encoding herpes simplex virus-thymidine kinase (pHSV-TK) and ganciclovir (GCV) has been an alternative approach to overcome the limitations of current therapies. However, there is a need to develop a carrier that can deliver both pHSV-TK and GCV for improving therapeutic efficacy. Our group developed a cationic, amphiphilic copolymer, poly (lactide-co-glycolide) -graft-polyethylenimine (PgP), and demonstrated its efficacy as a drug and gene carrier in both cell culture studies and animal models. In this study, we evaluated PgP as a gene carrier and demonstrate that PgP can efficiently deliver reporter genes, pGFP in rat glioma (C6) cells in vitro, and pβ-gal in a rat T5 SCT model in vivo. We also show that PgP/pHSV-TK with GCV treatment showed significantly higher anticancer activity in C6 cells compared to PgP/pHSV-TK without GCV treatment. Finally, we demonstrate that PgP/pHSV-TK with GCV treatment increases the suicide effect and apoptosis of tumor cells and reduces tumor size in a rat T5 SCT model.


Oncotarget ◽  
2016 ◽  
Vol 7 (44) ◽  
pp. 71710-71717 ◽  
Author(s):  
De-Gui Wang ◽  
Mei-Jun Zhao ◽  
Yong-Qiang Liu ◽  
Xiang-Wen Liu ◽  
Hai-Tao Niu ◽  
...  

2013 ◽  
Vol 13 (5) ◽  
pp. 346-357 ◽  
Author(s):  
Xiao-Ya Dong ◽  
Wen-Qian Wang ◽  
Yu Zhao ◽  
Xu-Dong Li ◽  
Zhi-Gang Fang ◽  
...  

Blood ◽  
1996 ◽  
Vol 88 (6) ◽  
pp. 2192-2200 ◽  
Author(s):  
MS Dilber ◽  
MR Abedi ◽  
B Bjorkstrand ◽  
B Christensson ◽  
G Gahrton ◽  
...  

Suicide gene therapy for plasma cell tumors was attempted in severe combined immunodeficient (SCID) mice injected with human myeloma cell lines. Initially, a ganciclovir-induced bystander effect was observed in vitro using myeloma cells transduced with a herpes simplex thymidine kinase (HSVtk) gene. Transduced cells injected subcutaneously (SC) into SCID mice could be eradicated by the administration of ganciclovir (GCV). Furthermore, an in vivo bystander effect was noticed when mice received mixtures of HSVtk-positive and nontransduced cells. Unexpectedly, a “distant bystander” effect was observed as tumors in regions inoculated with only nontransduced cells were significantly smaller and had increased frequency of apoptotic figures and decreased mitotic frequency in GCV-treated mice transplanted with HSVtk-positive cells at a different region compared with control mice.


Gene Therapy ◽  
2009 ◽  
Vol 17 (1) ◽  
pp. 26-36 ◽  
Author(s):  
M L Gil-Cardeza ◽  
M S Villaverde ◽  
G L Fiszman ◽  
N A Altamirano ◽  
R A Cwirenbaum ◽  
...  

2012 ◽  
Vol 10 (1) ◽  
pp. 3 ◽  
Author(s):  
Yue Chen ◽  
Gang Wang ◽  
Deling Kong ◽  
Zhihong Zhang ◽  
Kuo Yang ◽  
...  

1999 ◽  
Vol 10 (9) ◽  
pp. 1509-1519 ◽  
Author(s):  
Yujo Kawashita ◽  
Akira Ohtsuru ◽  
Yasufumi Kaneda ◽  
Yuji Nagayama ◽  
Yasushi Kawazoe ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4393
Author(s):  
Jessica Pahle ◽  
Dennis Kobelt ◽  
Jutta Aumann ◽  
Diana Behrens ◽  
Ole Daberkow ◽  
...  

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, associated with poor prognosis and restricted therapeutic options. Clostridium perfringens enterotoxin (CPE), is a pore-forming (oncoleaking) toxin, which binds to claudin-3 and -4 (Cldn3/4) causing selective cytotoxicity. Cldn3/4 are highly upregulated in PC and represent an effective target for oncoleaking therapy. We utilized a translation-optimized CPE vector (optCPE) for new suicide approach of PC in vitro and in cell lines (CDX) and patient-derived pancreatic cancer xenografts (PDX) in vivo. The study demonstrates selective toxicity in Cldn3/4 overexpressing PC cells by optCPE gene transfer, mediated by pore formation, activation of apoptotic/necrotic signaling in vitro, induction of necrosis and of bystander tumor cell killing in vivo. The optCPE non-viral intratumoral in vivo jet-injection gene therapy shows targeted antitumoral efficacy in different CDX and PDX PC models, leading to reduced tumor viability and induction of tumor necrosis, which is further enhanced if combined with chemotherapy. This selective oncoleaking suicide gene therapy improves therapeutic efficacy in pancreas carcinoma and will be of value for better local control, particularly of unresectable or therapy refractory PC.


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