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@#Objective To analyze the expression and clinical treatment and prognosis assessment significance of FAM83H-AS1 in breast cancer by bioinformatics analysis.Methods The expression of FAM83H-AS1 in various cancer types was analyzed in the Cancer Genome Atlas(TCGA)database by R language.Additionally the expression in breast cancer was examined by Gene Expression Profiling Interactive Analysis(GEPIA)online database.Survival data were downloaded from TCGA to analyze the correlation between FAM83H-AS1 expression levels and prognosis among breast cancer patients.GEPIA and Kaplan-Meier Plotter were used for dual verification.Clinical information was obtained from TCGA for further analysis on the relationship between FAM83H-AS1 and clinical characteristics.And the relationship between FAM83H-AS1 and tumor microenvironment,immunodetection point-related genes and tumor mutation burden(TMB)was analyzed using R language.Gene set enrichment analysis(GSEA)was performed.Results The expression of FAM83H-AS1 was abnormal in many cancers,particularly exhibiting a significant increase in breast cancer.High expression of FAM83H-AS1 is associated with significantly reduced overall survival in breast cancer patients.Furthermore,the expression level of FAM83H-AS1 varies among breast cancer patients with different clinical stages.FAM83H-AS1 exhibits negative correlation with stromal cell score and immune cell score in breast cancer samples,and correlated with immune detection point-related gene.TMB radar map results suggest that the expression of FAM83H-AS1 in breast cancer is positively correlated with tumor mutational burden.GSEA revealed a positive correlation between the expression of FAM83H-AS1 and the function of mismatch repair.Conclusion FAM83H-AS1 is highly expressed in breast cancer,and is related to poor prognosis.Its expression correlates with clinicopathological stage,tumor microenvironment and TMB of breast cancer patients.Furthermore,FAM83H-AS1 exhibits associations with certain immune checkpoint-related genes and mismatch repair genes.These findings provide a important theoretical basis for clinical treatment,prognosis prediction and development of gene-target drugs.
RÉSUMÉ
Objective To prepare a pancreatic cancer-targeted nano-scale ultrasound contrast agent (T-UCA) and to evaluate its in vitro targeting effect. Methods PLGA-PEG-NHS was synthesized with poly(lactic-co-glycolic acid) (PLGA) , N hydroxysuccinimide (NHS) and polyethylene glycol (PEG). The construction of PLGA-PEG-NHS was characterized by1H NMR. Perfluoroctyl bromide (PFOB) loaded PLGA nanoparticle contrast agent was prepared using emulsion evaporation technique with PLGA-PEG-NHS and PFOB , and the products were further conjugated with Hedgehog antibody. The morphology of T-UCA were characterized by transmission electron microscopy , and the size distribution and Zeta potential of T-UCA were characterized by dynamic light scattering method. Furthermore , the drug entrapment efficiency and loading capacity of T-UCA were determined by OC-MS , and the release rate of T-UCA in vitro was examined by dialysis method. Finally , the in vitro targeting performance was quantitatively verified by fluorescence microscopy and flow cytometry with human pancreatic cancer lines SW1990 and CFPAC-1. Results The average diameter and the Zeta potential of T-UCA were 198. 9 nm and -31. 8 mV, respectively. Moreover , the encapsulation efficiency and drug loading of T-UCA was (63. 7 ± 3. 9) % and (14.3 ± 0.9)% , respectively. Nearly 85. 3% liquid perfluorocarbon was released from the T-UCA within 48 h. In vitro cell experiments showed that the targeted contrast agent could bind to SW1990 cells which had high expression of Hedgehog antigen , while not to the CFPAC-1 cells without expression of Hedgehog antigen Conclusion The emulsion evaporation technique can be used to prepare T-UCA with desirable characteristics, and the prepared T-UCA can specifically cancer cells with high expression of Hedgehog, making it a promising pancreatic cancer-targeted nanosacle ultrasound contrast agent.