Eradication of therapy-resistant human prostate tumors using a cancer terminator virus.
نویسندگان
چکیده
Terminal prostate cancer is refractory to conventional anticancer treatments because of frequent overexpression of antiapoptotic proteins Bcl-2 and/or Bcl-x(L). Adenovirus-mediated delivery of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), a secreted cytokine having cancer-selective apoptosis-inducing properties, profoundly inhibits prostate cancer cell growth. However, forced overexpression of Bcl-2 or Bcl-x(L) renders prostate cancer cells resistant to Ad.mda-7. We constructed a conditionally replication-competent adenovirus in which expression of the adenoviral E1A gene, necessary for replication, is driven by the cancer-specific promoter of progression elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/IL-24 in the E3 region of the adenovirus (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV). This CTV generates large quantities of MDA-7/IL-24 as a function of adenovirus replication uniquely in cancer cells. Infection of Ad.PEG-E1A-mda-7 (CTV) in normal prostate epithelial cells and parental and Bcl-2- or Bcl-x(L)-overexpressing prostate cancer cells confirmed cancer cell-selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 (CTV) into xenografts derived from DU-145-Bcl-x(L) cells in athymic nude mice completely eradicated not only primary tumors but also distant tumors (established in the opposite flank), thereby implementing a cure. These provocative findings advocate potential therapeutic applications of this novel virus for advanced prostate cancer patients with metastatic disease.
منابع مشابه
The Iranian Society of Nuclear Medicine practical guideline on radioligand therapy in metastatic castration-resistant prostate cancer using 177Lu-PSMA
Prostate-specific membrane antigen (PSMA) is a type II transmembrane protein, which is anchored in the cell membrane of prostate epithelial cells. It is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer. Although, 177Lu-PSMA has been recently introduced for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC) with co...
متن کاملKnockdown of HSF1 sensitizes resistant prostate cancer cell line to chemotherapy
The treatment of prostate cancer patients usually starts with androgen ablation and followed by chemotherapy; however, in some cases the tumor develops resistant phenotype. Combination therapy is currently regarded as a cornerstone in cancer therapy to overcome the drug resistance. Herein, we investigated the combinatory effect of Docetaxel and Trastuzumab with a novel nanomedicine, BCc1. Also,...
متن کاملHuman Reoviruses Serotype 3 Effectively Target Huh-7 Cells
Abstract: Background and Aims: Huh-7 is a cell line that was derived from a liver tumor of a Japanese man. Hepatocellular carcinoma (HCC) is considered as a primary liver cancer. Highly resistant tumor to treatment which causes the death of many patients annually. Thus, targeting the cancer cells by using a new method could be effective in...
متن کاملPrevalence of Human Cytomegalovirus Infection in Iranian Prostate Cancer Patients
Background and Aim: Human cytomegalovirus (HCMV) has the potential for oncogenicity and has been associated with many malignancies, including prostate cancer. This study aimed to investigate the genomic prevalence of HCMV in prostate cancer tumors. Materials and Methods: In this case-control study, 31 patients with prostate cancer were enrolled along with 31 patients with benign prostate cance...
متن کاملEvaluation of polymer shielding for adenovirus serotype 6 (Ad6) for systemic virotherapy against human prostate cancers
Oncolytic viruses hold promise as "self-amplifying" cancer therapies wherein a virally killed cell can produce thousands of new viral "drugs" that can kill more cancer cells. Adenoviruses (Ads) are one family of oncolytic viruses. Most human studies have used human Ad serotype 5 (Ad5). Unfortunately, most patients are already immune to Ad5 increasing the likelihood that the agent will be neutra...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 67 11 شماره
صفحات -
تاریخ انتشار 2007