1. Experimental Study On Macrophage Membrane-coated Piperine Liposomes To Inhibit Breast Cancer Cell Proliferation, Invasion And Metastasis. 2. A Retrospective Study Of A Predictive Model Combining Clinicopathological Characteristics And Immune Gene Chara

Background:Breast cancer has become the primary cancer to imperil Chinese women,and also the focus of current medical research.Although there are many clinical treatment methods(such as surgery,radiotherapy,chemotherapy,etc),it is still unconquered.So it is imperative to find a new treatment method.With the deepening of the traditional Chinese medicine research,the potential of Chinese medicine for cancer treatment has been explored.Piperine is one of the potential anti-tumor drug,which is the important alkaloid in black pepper,and is proved to inhibit tumor cells growth and metastasis.However,according to the previous pharmacokinetic studies,piperine has a low bioavailability with many side effects.It's urgent to solve the problem about the rational utilization and elevation anti-tumor effect of piperine.The nano-drug delivery system is a widely-used drug modification system.Its application and development greatly improve the effectiveness of anti-tumor drugs.In recent years,the application of nanoparticles in traditional Chinese medicine promotes the development and clinical application of traditional Chinese medicine.Among them,the targeting nano drug delivery s is a hot topic currently.Objective: To explore the inhibition effects of MPL on proliferation,metastasis and invasion of breast cancer cells.Methods:1.Preparation and characterization of MPLFirstly,piperine liposome(PL)was made by using film hydration method,with lectithin and cholesterol.And then macrophage membrane was isolated and purified from the cell line of RAW 264.7.Lastly,the MPL was fabricated by coating isolated macrophage membrane with PL through the direct extrusion.Transmission electron microscope,scanning electron microscope,Fourier transform infrared spectroscopy and ultraviolet spectrophotometer were used to evaluate the morphology,particle size distribution,Zeta potential,encapsulation efficiency and drug loading effciency.2.The inhibition effect of MPL on breast cancer cell in vitroCourmarin-6 was used to label PL and MPL for detecting the capacity of cellular uptake.The cell experiment was divided into Control group,Pipe group,PL group,MPL group and MPL+Mem group.Crystal violet assay,wound-healing assay and transwell assay were used to detect the inhibition effect of MPL on breast cancer cell.3.The inhibition effect of MPL on breast cancer cell in vivoThe BALB/c 4T1-xenograft breast cancer mice were divided into Control group,Docetaxel group,PL group and MPL group.Two weeks after modeling,the Docetaxel group received intraperitoneal injection of docetaxel(50 mg/mL),the PL group received PL(50 mg/mL),and the MPL group received MPL(50 mg/mL),while the contrl group only received same amount of physiological saline,once every 3 days.The body weight and tumor volume were measured every 3 days.Four weeks later,the tumor mass was measured,and pathological changes of lung tissues were observed by HE staining.Results:1.MPL was evenly distributed spherical nanoparticle.The average size was 148.2 nm,and the zeta potential was 19.7±6.39 mV.The encapsulation efficiency is 97.4%,and the drug loading is 16.54%.2.In vitro,the cell uptake capacity of MPL was higher than that of PL.Moreover,compared with pipeline and PL,MPL treatment group showed a lower proliferation rate and a better metastasis inhibition.3.In vivo,MPL was safe with effective ability of inhibition of breast cancer growth and lung metastasis.Conclusion: MPL can effectively inhibit proliferation,invasion and metasis of breast cancer cells.Purpose Accumulating evidence indicated that triple negative breast cancer(TNBC)can stimulate stronger immune responses than other subtypes of breast cancer.We hypothesized that integrating immune-related genomic signatures with clinicopathologic factors may yield a predictive accuracy exceeding that of the currently available system.Methods Ten signatures that reflect specific immunogenic or immune microenvironmental features of TNBC were identified and re-analyzed using bioinformatic methods.Then,clinically annotated TNBC(n=711)with the corresponding expression profiles,which predicted a patient's probability of disease free survival(DFS)and overall survival(OS),were pooled to evaluate their prognostic values and establish a clinicopathologic–genomic nomogram.Three and two immune features were respectively selected out of ten immune features to construct nomogram for DFS and OS prediction based on multivariate backward stepwise Cox regression analyses.Results By integrating the above immune expression signatures with prognostic clinicopathologic features,clinicopathologic–genomic nomograms were cautiously constructed,which showed reasonable prediction accuracies(DFS: HR,1.79;95% CI,1.46-2.18,P < 0.001;AUC,0.71;OS: HR,1.96;95% CI,1.54-2.49;P < 0.001;AUC,0.73).The nomogram showed low-risk subgroup had higher immune checkpoint molecules(PD-L1,PD-1,CTLA-4,LAG-3)expression,and benefited from radiotherapy(HR,0.2,95% CI,0.05-0.89;P=0.034)rather than chemotherapy(HR,1.26,95% CI,0.66-2.43;P=0.485).Conclusions These findings offer evidence that immune-related genomic data provide independent and complementary prognostic information for TNBC,and the nomogram might be a practical predictive tool to identify TNBC patients who would benefit from chemotherapy,radiotherapy and upcoming popularity of immunotherapy.