Colorectal cancer is an aggressive malignancy with a high mortality rate; however, effective therapies are currently lacking. Cancer-targeting gene-virotherapy (CTGVT) has been proposed to be a promising strategy for cancer therapy. The purpose of this study was to investigate the antitumor activity of the oncolytic adenovirus harboring Lipocalin-2 (ZD55-Lipocalin-2, an example of CTGVT) in colorectal cancer. ZD55-Lipocalin-2 was generated by deleting E1B55-KD and inserting the Lipocalin-2 gene. Its cytopathic effects and cell growth inhibition were detected in vitro, and antitumor effects were examined in a nude mouse model of human colorectal cancer xenografts. Results showed that ZD55-Lipocalin-2 significantly inhibited the colorectal cancer growth by selective cytolysis, inducing apoptosis and decreasing the microvessel density in tumors. The anticancer potential of ZD55-Lipocalin-2 showed stronger than that of the isolated Lipocalin-2 gene therapy or isolated ZD55 oncolytic adenovirus therapy. ZD55-Lipocalin-2 may serve as a potential anticancer agent for colorectal cancer treatment.

01 Nov 2012·CancerQ1 · MEDICINE

Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin‐2 gene

Q1 · MEDICINE

Article

Author: Wen-yan Zheng ; Da-yong Jin ; Dan-song Wang ; Bin Xu ; Xin-yu Qin ; Xin-yuan Liu

AbstractBACKGROUND:The 5‐year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer‐targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)‐harboring lipocalin‐2, is capable of treating pancreatic cancer.METHODS:Tissue microarrays were constructed to detect the expression of lipocalin‐2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin‐2 was investigated in an analysis of correlations between lipocalin‐2 expression and matched clinical characteristics. A lipocalin‐2–expressing OV, ZD55‐lipocalin‐2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo.RESULTS:Lipocalin‐2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55‐lipocalin‐2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase‐dependent apoptosis.CONCLUSIONS:Higher lipocalin‐2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55‐lipocalin‐2, which specifically expressed higher levels of lipocalin‐2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations. Cancer 2012. © 2012 American Cancer Society.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Preclinical	CN	Shanghai No. 10 People's Hospital	-

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