

This project belongs to the research category of tumor etiology and diagnosis. It explores the molecular mechanisms and regulation of tumor pathogenesis and treatment, as well as its application value in the clinical diagnosis of tumors. The project uses a transgenic mouse model in which myeloid cells are knocked out of NF-kB/rela and the antibacterial peptide Cathelicidin (hCAP18/LL-37) is completely knocked out. Focusing on the cutting-edge research topics of the role of the tumor microenvironment in tumor development, the project systematically explores the role of myeloid cells and the inflammatory factor Cathelicidin in the tumor microenvironment in the regulation of key factors in tumor cell proliferation signals and signal pathways in cancer development, as well as important inflammatory factors in the tumor microenvironment. Expression regulation mechanism. The diagnostic and prognostic value of Cathelicidin in non-small cell lung cancer (NSCLC) and colorectal cancer was evaluated from the perspective of clinical diagnostic applications. It is proposed that the inflammatory factor Cathelicidin plays an important role in tumor development, discovered a new mechanism by which Cathelicidin promotes tumor growth, and clarified in detail the expression and regulation mechanism of Cathelicidin in the tumor microenvironment. Studies have shown that the Cathelicidi test has good sensitivity and specificity for the diagnosis of NSCLC and colorectal cancer, and has potential clinical application value for the diagnosis and prognosis monitoring of these two tumors. Studies have revealed the important role of the inflammatory factor Cathelicidin in the occurrence and development of tumors and its clinical application value in the diagnosis and prognosis monitoring of NSCLC and colorectal cancer: ① The inflammatory factor Cathelicidin expressed by non-tumor cells in the tumor microenvironment is an important tumor growth factor;②Cathelicidin activates tumor cells PTEN/PI3K/Akt and Wnt/β-catenin signaling pathway promotes tumor growth;③ The expression regulation of Cathelicidin involves the NF-kB signaling pathway;④ In the tumor microenvironment, the glycoprotein Versican V1 secreted by tumor cells regulates the expression of the antibacterial peptide Cathelicidin in a Vitamin D3-dependent manner by activating the Toll-like receptor TLR2 signal of myeloid cells such as macrophages; ③ Serum Cathelicidi detection has good sensitivity and specificity for the diagnosis of NSCLC and colorectal cancer, and has good clinical prognosis monitoring value. The research results of this project were published in 20 SCI articles including PNAS, Oncogene, Theranostics, Oncotarget, etc., with a total impact factor of 100 points. They have been cited more than 200 times in SCI articles and more than 10 Chinese core journals. They have also received 3 general projects from the National Natural Science Foundation of China, 1 Shanghai City Pujiang Talent Plan and a total of 8 other funds. This research results prove the mechanism of the inflammatory factor Cathelicidin in promoting tumor growth and the expression and regulation mechanism of Cathelicidin in the tumor microenvironment, clarify the regulatory network of the interaction between immune cells and tumor cells in the tumor microenvironment, and provide experimental basis for clarifying the role of inflammation in tumor pathogenesis, molecular mechanism and clinical application value. At the same time, serum Cathelicidin testing has important clinical application value in the diagnosis and prognosis monitoring of NSCLC and colorectal cancer.
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