Chinese scholars join hands with Thalidomide

Chinese scholars join hands with Thalidomide

January 9, 2018 Source: Sina medicine Author: Maple footsteps

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At the beginning of the new year, the leading international medical journal Nature Medicine, which has an impact factor of 29.89, was published by Chinese scholars Professor Liu Qiang (Dalian Medical University), Professor Huang Huiqiang (Sun Yat-sen University Cancer Hospital) and Professor Yang Yongliang (Dalian University of Technology) as communication authors. Results of new mechanisms and therapeutic strategies for extranodal NK/T-cell lymphoma (ENK/TL) combined with hemophagocytic syndrome (HPS) ), has received extensive attention in the industry.

At 1 am on January 3, a professor of hematology in the blood tumor WeChat professional group commented: This is a Chinese scholar following acute promyelocytic leukemia-associated retinoic acid (clinical and mechanism), nasal NKT cell lymphoma ( Including the Asahi program), Homoharringtonine (HAA program) and its gene mutation research published in internationally renowned journals, another highly influential Chinese element.

This is a Bto B translational medicine innovation study. The researchers used exon sequencing to find a hot spot mutation ECSIT-V140A present in the evolutionarily conserved signaling intermediate in Toll pathway (ECSIT) by comparing the results of ENKTL tumor tissue and normal tissue sequencing. . The ECSIT-V140A mutation leads to the continuous activation of NF-κB signaling pathway in tumor cells and secretion of various cytokines such as TNF-α and IFN-γ. TNFα and the like further promote the activation of macrophages around the tumor and secrete a large number of cytokines, forming a “cytokine storm”.

In view of the fact that the immunomodulator thalidomide can inhibit the binding of NF-kB to its target gene promoters TNF-α and IFN-γ, preclinical studies have found that thalidomide and dexamethasone can effectively inhibit the over-induced ECSIT V140A mutation. Inflammation. The researchers then found two patients with ECSIT-V140A, treated with thalidomide and dexamethasone, significantly alleviated HPS symptoms, PFS reached 3 years.

ENK/TL is a non-Hodgkin's lymphoma with special clinical manifestations, special cell morphology and immunophenotype. More specifically, the disease is only limited to high incidence in Asia, especially in China, in all lymphoma subtypes. The ratio can reach 6%. In the early stage of ENK/TL, the OS can reach 70%-80% after 5 years of radiotherapy and chemotherapy. Late prognosis is poor, 5-year survival rate is only 7%-31%, and some patients develop extremely rapid disease, easy to concurrent HPS. Once HPS occurs, its average median survival time is only 1-2 months, and almost 100% end in death.

The combination of thalidomide and dexamethasone has significantly extended PFS and OS in the maintenance of multiple myeloma, playing a very important role. It is a classic two-drug combination. In recent years, some scholars have used thalidomide single drug for maintenance treatment or salvage treatment of lymphoma of different pathological types. Peking University Cancer Hospital has reported the use of thalidomide combined with CHOP regimen for first-line treatment of peripheral T-cell lymphoma, and achieved good results. In this study, two cases of ENK/TL combined with HPS, thalidomide and dexamethasone produced synergistic effects, and the initial effect was significant. It is believed that subsequent clinical research will be further developed.

ENK/TL combined with HPS is a hot and difficult point in current clinical treatment. In-depth study of its pathogenesis and explore its control strategy, especially in China, has very important practical significance.

Original title: New Year Kaifanghua: Chinese scholars join hands with Thalidomide

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