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IL18 in the treatment of pancreatic cancer
Author:Raju Maskey  Date:2017-03-07  Clicks:

A group of scientists including Jiang Jianxin from the Department of Hepatic Surgery of Renmin Hospital conducted a joint research and recently published its findings in the prestigious “Clinical Cancer Research” journal of the American Association for Cancer Research (AACR). The project was funded by The National Natural Science Foundation of China and was the collective effort of Jiang and several other scholars from Johns Hopkins University School of Medicine, University of Minnesota, Tianjin Medical University and Huazhong University of Science and Technology (HUST).

According to the study, Interleukin-18, a human protein previously significant in the treatment of Alzheimer’s, Hashimoto’s thyroiditis and inflammatory disorders, can now possibly be used against cancer cells in combinational immunotherapy with a NF-κB inhibitor.

In this experiment, 8-week-old wild-type C57BL/6J mice, Balb/c nude mice, and IL18−/−C57BL/6J mice were injected with pancreatic cancer cell suspension, and each experimental group of mice were given recombinant mouse IL18 or BAY11-7082 (the NF-κB inhibitor). The tumor size was monitored and later on the spleen cells, and lymph node cells were observed microscopically to confirm the diminution of  immune cells.

The cells were cultured using 3D cultivation and were subcutaneously injected into 6-week-old Balb/c nude mice, and human pancreatic cells were injected into their spleen after two weeks. They suffered splenectomy after just 20 minutes. Their livers were then examined for any signs of metastasis. The experimental groups were compared and analyzed statistically to obtain a series of clinically significant results.

Quantitative analysis of IL18 expression revealed that IL18 is higher in plasma and pancreatic cancer tissues. Flow cytometry was used to examine the cytolytic activities of T cells and NK cells, which was found to have increased significantly. Furthermore, it promotes metastasis of pancreatic cancer cells which are clearly visible in the immunosuppressed specimen. Analysis of mRNA microarray data showed that IL18 promotes the metastasis through the NF-κB pathway.

This conclusion suggested the combined use of  a recombinant IL18 and a NF-κB pathway inhibitor in the treatment of pancreatic cancer. The C57BL/6J mice were orthotopically transplanted with LTPA cells and were divided into four experimental groups. The first was the control group; the second was administered with IL18 only, the third with BAY11-7082 only and the fourth with a combination of both. The fourth group survived for the longest time span. Hence, the antitumor therapeutic effect of a combination of Interleukin-18 and a NF-κB inhibitor (BAY11-7082) was experimentally verified in the mice specimen. The role of Interleukin-18 as a cancer-promotor and cancer-suppressor was thoroughly discussed, and clinical trials have shown that rhIL18 can be administered safely onto human patients.

(Edited by Siyuan Fang, Li Liu, Edmund Wai Man Lai and Hu Sijia)



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