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BACKGROUND@#Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery.@*METHODS@#In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC).@*RESULTS@#A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model.@*CONCLUSIONS@#A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Assuntos
Humanos , Feminino , Neoplasias da Mama/genética , População do Leste Asiático , Recidiva Local de Neoplasia/genética , Mama , Algoritmos , Doença Crônica , Prognóstico , Microambiente TumoralRESUMO
Diabetic nephropathy is a complication of diabete and its incidence is increasing obviously these years. The pathogenic mechanisms of DN are complex, with multiple factors involved such as the glycometabolism disorders , hemodynamic changes, aldose reductase pathway activation, alterations in cytokines, oxidative stress, protein kinase C activation, lipid metabolism disorders and genetic susceptibility etc, which are not completely clear yet. Thus, the research progress of DN pathogenesis is to be reviewed.
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Objective To investigate the changes in cytotoxicity of DC-CIK cells to human multiple myeloma RPMI 8226 cells before and after treatment with oridonin. Methods Normal human peripheral blood mononuclear cells were isolated and induced to obtain DC-CIK cells. Cytotoxicity of DC-CIK cells against RPMI 8226 cells which were treated by oridonin was analyzed by LDH releasing assay. The variation for expression of NKG2D ligands on RPMI 8226 cells were measured by flow cytometry. Results DC-CIK cells were successfully induced from the peripheral blood mononuclear cells. At the same effector to target ratio, oridonin obviously enhanced the cytotocixity of DC-CIK cells against RPMI 8226 cells (P<0.01). Flow cytometry showed the expression of NKG2D ligands ULBP1 of RPMI8226 cells was most significantly increased as the cells were treated by oridonin [(9.19 ± 1.85) vs. (15.47 ± 0.67), P<0.01]. Correlation analysis indicated that cytotocixity was positively correlated with changes in ULBP1. Conclusions Oridonin can improve the cytotoxicity of DC-CIK cells against RPMI 8226 cells, which may be related with the increased expressions of NKG2D ligands on the tumor cell surface.
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ObjectiveTo explore the efficacy and safety of bone marrow mesenchymal stem cells (BMSC)in treatment of aplastic anemia(AA). MethodsTwenty-two patients with aplastic anemia were enrolled with median age of 31 (12-70) years old,including 11 severe aplastic anemia (SAA),and 3 of whom were cyclosporine and anti-thymocyte globulin-resistant. BMSC were isolated from bone marrow of healthy donors and cultured.The third to fifth generation cells were administered intravenously in 1×106/kg to patients once or twice a week.After infusion,complete blood count,bone marrow aspiration,bone marrow biopsy,flow cytometry analysis of lymphocyte subsets of CD3+ CD4+ and CD3+ CD8+ and clinical symptoms were involved in outcome measurement.ResultsAll patients finished 16-time median (5-83 times) infusions of BMSC with 13-month median (2-33 months) treatment course and 23-month median (2-34 months) follow-up.The total response rate was 72.7 ％(16/22), including one patient with essential cure, 9 with remission, 3 with remarkably improvement and 3 with transfusion interval extension.Two of three front-line immunosuppressiveresistant SAA patients achieved remission. Ten of 14 patients recovered from inverted ratio of CD4+/C8+ cells after BMSC treatment. There were no treatment-related side effects observed in the course of treatment.ConclusionBMSC are effective and safe for the treatment of AA in our preliminary study and they deserve further research with larger-scale and long-term clinical trials.