| Background: Malignant tumors are the main diseases that endanger human health.Their global morbidity and mortality have increased year by year.By 2018,global cancer cases have increased to 18.1 million and mortality has increased to 9.6 million,while lung cancer and breast cancer is the leading cause of death in men and women,respectively.Malignant pleural effusion is a common symptom of advanced lung cancer,which is difficult to control and seriously affects the quality of life of patients.The progression of pleural effusion is not only dependent on the primary tumor,but also closely related to immune cells in the pleural effusion.Macrophages exist in a large number of pleural effusions,mainly divided into two phenotypes,M1 and M2.M1 plays an anti-tumor role,while M2 has the function of promoting tumor development and metastasis.M2 type is mainly presence in malignant pleural effusion.Microparticles are small molecular particles with a diameter of about 100-1000 nm,contain various biologically active substances and serve as a carrier for signal transmission between cells.Since the microparticles are subcellular structures formed by the cell membrane protruding outward and wrapping the contents,the microparticles can be targeted and recognized by the cells from which they are derived.The size of the microparticles and their natural biocompatibility make tumor cell-derived microparticles a good carrier for chemotherapeutic drugs,while macrophages can more efficiently take up tumor cell-derived microparticles than normal cells and other immune cells.Therefore,we propose a new method for the treatment of malignant pleural effusion,the chemotherapy drug MTX wrapped into the microparticles to treat malignant pleural effusion,and study the effect of macrophages on the efficacy.Objectives: To demonstrate that macrophages are associated with malignant progression of pleural fluid,and to study the killing effect of TMP-MTX on tumor cells,proving that TMP-MTX can be taken up by macrophages and causing apoptosis;and exploring TMP-MTX combination macrophage scavengers control the production of malignant pleural effusions in mouse models.Methods: The pleural effusion of clinical patients was collected to detect the proportion of macrophages in benign and malignant pleural effusions.In vitro uptake and pro-apoptotic effects of TMP-MTX.Studying the efficacy of TMP-MTX combined with macrophage scavenger(Clodronate)on malignant pleural effusion in C57 immunocompetent mouse MPE model.MPE mouse model groups including: 1.PBS group;2.TMP-MTX group;3.macrophage clearance group;4.macrophage clearance + TMP-MTX group.The anti-tumor effects of pleural tumor,pleural effusion and survival time of each group were observed,and record the body weight and diet of mice,the survival time was calculated from the first day of inoculation of tumor cells,and survival analysis was performed.After the mice were sacrificed,the pleural effusions were collected subphrenic.The pleural effusion volume was compared.The pleural tumors of the mice were counted and the pleural tumor burden was compared.The macrophages in the pleural effusion were separated and the macrophages were flow-detected.proportion.Results: The study of pleural effusion specimens in clinical patients found that the proportion of macrophages in MPE was significantly higher than that in BPE,and mainly based on M2 phenotype.In vitro studies,we confirmed that TMP-MTX has a killing effect on tumor cells,and can be taken up by macrophages and promote apoptosis.Animal studies have shown that mice treated with TMP-MTX after macrophage clearance have reduced pleural tumor burden,reduced pleural effusion,and prolonged survival.Conclusion: Macrophages are associated with malignant progression of tumors.TMP-MTX controls the progression of malignant pleural effusion by killing tumor cells.TMP-MTX can not only kill tumor cells,but also taken up and promote apoptosis by macrophages in the treatment of malignant pleural effusion.After removing macrophages,TMP-MTX can more effectively control the progression of malignant pleural effusion.Background: Non-small cell lung cancer is the most common cancer in the world.The incidence and mortality rate are at the forefront of cancer,causing a huge threat to human health and life.Therefore,early detection of non-small cell lung cancer is essential,and treatment preclinical clinical staging is important for doctors to develop treatment strategies.18F-fluorodeoxyglucose positron emission tomography/computed tomography(18F-FDG PET/CT)is a more accurate and sensitive non-invasive detection method in imaging compared to X-ray,CT,etc.The metabolic activity of the cells is used to detect the uptake rate of the 18F-FDG.The metabolism of the tumor cells is active,and the ability to take 18F-FDG is 2-10 times than normal cells,forming the obvious "light spot" on the image to early found tumors and metastases.Previous studies have shown that inflammation and blood glucose fluctuations have an impact on the detection of non-small cell lung cancer,and smoking is likely to cause airway and lung inflammation.However,there is no research to investigate the smoking status of Chinese people in 18F-FDG PET/CT to determine the impact of staging accuracy of non-small cell lung cancer.Purpose: To explore the influence of smoking on the accuracy of 18F-FDG PET/CT in predicting Chinese NSCLC staging.Patients and Methods: We conducted a retrospective study with 360 NSCLC patients who underwent integrated 18F-FDG PET/CT prior to surgery.The history of cigarette smoking was obtained using verbal census reports that included the amount and duration of smoking.With maximal standard uptake values(SUVmax)= 2.5 as the threshold,the Volume Of Interest(VOI)Of tumor and metastatic lymph nodes was delineated.Differences in several clinical characteristics and four parameters based on 18F-FDG PET/CT,including the SUVmax of the primary tumor(p SUVmax)and lymph nodes(n SUVmax),tumor size,and nodal involvement,between the different subgroups were analyzed.All patients underwent clinical tumor-node-metastasis(TNM)staging after 18F-FDG PET/CT,followed by postoperative pathological staging.The accuracy of preoperative clinical staging in relation to pathologic staging was compared between smokers and nonsmokers.The effects of different pathological types and smoking status on the accuracy of preoperative clinical staging and postoperative pathologic staging were analyzed specifically.Results: A total of 360 patients were divided into two groups: 193 nonsmokers and 167 smokers.Male sex,squamous cell carcinoma,nodal involvement and stage II~III disease were more common among smokers.A high p SUVmax and large tumor size were significantly associated with smoking.Linear regression analysis demonstrated that a longer smoking history was related to a higher p SUVmax(r=0.308,p<0.001)and a larger tumor size(r=0.329,p<0.001).The accuracies for N staging were 88.7% vs 80.9%(p=0.028)for nonsmokers and smokers,respectively.Conclusion: We demonstrated that cigarette smoking is related to a higher p SUVmax and a larger tumor size and is negatively associated with the accuracy of preoperative clinical staging based on 18F-FDG PET/CT compared with postoperative pathological examination in NSCLC patients.No evidence indicates that cigarette smoking combined with pathological type affects the accuracy of preoperative clinical staging and postoperative pathologic staging. |
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