scholarly journals Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA MEG3 Enhances Gene Therapy in Castration-Resistant Prostate Cancer

2020 ◽  
Vol Volume 15 ◽  
pp. 10305-10320
Author(s):  
Zongguang Tai ◽  
Jinyuan Ma ◽  
Jianing Ding ◽  
Huijun Pan ◽  
Rongrong Chai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Laura Kasman ◽  
Georgiana Onicescu ◽  
Christina Voelkel-Johnson
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Chemotherapeutic Agents ◽  
Viral Gene ◽  
Castration Resistant Prostate Cancer ◽  
Cmv Promoter ◽  
Castration Resistant ◽  
Adenoviral Delivery

Adenoviral gene therapy using the death receptor ligand TRAIL as the therapeutic transgene can be safely administered via intraprostatic injection but has not been evaluated for efficacy in patients. Here we investigated the efficacy of adenoviral TRAIL gene therapy in a model of castration resistant prostate cancer and found that intratumoral injections can significantly delay tumor growth but cannot eliminate established lesions. We hypothesized that an underlying cause is inefficient adenoviral delivery. Using the LNCaP progression model of prostate cancer we show that surface CAR expression decreases with increasing tumorigenicity and that castration resistant C4-2b cells were more difficult to transduce with adenovirus than castration sensitive LNCaP cells. Many genes, including CAR, are epigenetically silenced during transformation but a new class of chemotherapeutic agents, known as histone deacetylase inhibitors (HDACi), can reverse this process. We demonstrate that HDACi restore CAR expression and infectivity in C4-2b cells and enhance caspase activation in response to infection with a TRAIL adenovirus. We also show that in cells with high surface CAR expression, HDACi further enhance transgene expression from the CMV promoter. Thus HDACi have multiple beneficial effects, which may enhance not only viral but also non-viral gene therapy of castration resistant prostate cancer.

scholarly journals Aptamer-Functionalized Dendrimer Delivery lncRNA MEG3 Enhances Castration-Resistant Prostate Cancer Gene Therapy

2020 ◽  
Author(s):  
Zongguang Tai ◽  
Jinyuan Ma ◽  
Jianing Ding ◽  
Huijun Pan ◽  
Rongrong Chai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Cell Adhesion Molecule ◽  
Treatment Method ◽  
Inhibitory Effect ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Traditional Treatment ◽  
Castration Resistant ◽  
New Treatment

Abstract Androgen castration therapy is an effective treatment method for prostate cancer patients who cannot be completely cured by surgery. However, drug resistance often leads to treatment failure and poor prognosis. For castration-resistant prostate cancer (CRPC), some new treatment methods have been gradually put into clinical validation or use. Considering the side effects of traditional treatment, gene therapy has been applied in recent studies to combat prostate cancer (PCa). A 19-nt RNA aptamer, termed as EpDT3, is endocytosed when bound to epithelial cell adhesion molecule EpCAM-overexpressing cells, including various types of prostate cancer cells. Therefore, poly (amidoamine) dendrimer (PAMAM) conjugated with EpDT3 on the surface was developed for gene delivery targeting the CRPC. Moreover, the PAMAM-PEG-EpDT3 vehicles were accumulated in CRPC cells. The CRPC-inhibitory effect of PAMAM modified with EpDT3 was significantly higher than that of the unmodified construct when loading the plasmid that encodes long noncoding (lnc) RNA MEG3 (pMEG3). In summary, the above results suggested that PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) have great potential for enhancing CRPC gene therapy.

New combination therapies for castration-resistant prostate cancer

2019 ◽  
Author(s):  
Mitchell G Lawrence ◽  
Laura H Porter ◽  
Daisuke Obinata ◽  
Shahneen Sandhu ◽  
Luke A Selth ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
New Combination ◽  
Combination Therapies ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant
Sign in / Sign up

Export Citation Format

Share Document