Ovarian cancer has the highest mortality rate and is the most common of all gynecologic malignancies. Novel treatments for ovarian cancer are urgently required to improve outcomes and the overall survival of patients. The present study investigated whether immunotherapy with natural killer (NK) cells affected the survival of mice with ovarian cancer. Results analysis identified adjunctive NK cells as a potential therapeutic method in ovarian cancer. Patient-derived ovarian cells were isolated, cultured and subsequently injected subcutaneously into immune deficient BALB/c-nude mice. Human NK cells were isolated from peripheral blood mononuclear cells and cultured for expansion in vitro. The present results demonstrated that ovarian cells in BALB/c-nude mice did not induce spontaneous ovarian cancer cell metastasis in the NK-treated group. In addition, NK cells activated immune cells in the immune system, which resulted in inhibition of ovarian tumor growth in vitro and in a murine xenograft model of ovarian cancer. The data also indicated that cytotoxic activity of NK cells prevented migration and invasion of ovarian cancer cells, which contributed to prevention of systemic metastasis and suggested that NK cells could be effective cells for therapy against ovarian cancer. Furthermore, NK cells induced apoptosis and increased the number of cluster of differentiation (CD)4+, CD8+ as well as cytotoxic T lymphocyte responses by intravenous injection in a murine xenograft model of ovarian cancer. These results suggested that NK cells inhibited the systemic metastasis for ovarian cancer cells. In conclusion, the present study suggested that NK cell immunotherapy inhibited systemic metastasis of ovarian cancer cells and improved the survival rate of mice. Sufficient supplementation of NK cells may serve as a promising immunotherapeutic strategy for ovarian cancer.
Sex determining region Y-box protein 5 (SOX5) is a transcriptional factor and serves important roles in various cancer types; however, the pathological role of SOX5 in patients with breast cancer remains unclear. In the present study, the expression and potential role of SOX5 in patients with breast cancer and in breast cancer cells was investigated. The data indicated that SOX5 was highly expressed in breast cancer tissues compared with adjacent healthy tissues, and overexpression of SOX5 was associated with a reduced overall survival rate in patients with breast cancer. Gain and loss of function studies with MTT, colony formation, wound healing and Matrigel invasion assays demonstrated that SOX5 significantly promoted breast cancer cell proliferation and invasion. The chromatin immunoprecipitation (ChIP) assay sequence, quantitative ChIP and luciferase reporter assays were used to identify enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) as a downstream target gene of SOX5. Furthermore, it was determined that ectopic expression of SOX5 increased EZH2 expression at the mRNA and protein level, while the knockdown of SOX5 decreased EZH2 expression. Additionally, the biological effect of SOX5 was investigated, and it was determined to be dependent on the regulation of EZH2 expression. The present results may provide important insights into the biological significance of SOX5 serving as a candidate therapeutic target in breast cancer progression.
Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease characterized by chronic and progressive apoptotic destruction of pancreatic beta cells. During the initial phases of T1DM, cytokines and other inflammatory mediators released by immune cells progressively infiltrate islet cells, induce alterations in gene expression, provoke functional impairment, and ultimately lead to apoptosis. Long noncoding RNAs (lncRNAs) are a new important class of pervasive genes that have a variety of biological functions and play key roles in many diseases. However, whether they have a function in cytokine-induced beta cell apoptosis is still uncertain. In this study, lncRNA microarray technology was used to identify the differently expressed lncRNAs and mRNAs in MIN6 cells exposed to proinflammatory cytokines. Four hundred forty-four upregulated and 279 downregulated lncRNAs were detected with a set filter fold-change ≧2.0. To elucidate the potential functions of these lncRNAs, Gene Ontology (GO) and pathway analyses were used to evaluate the potential functions of differentially expressed lncRNAs. Additionally, a lncRNA-mRNA coexpression network was constructed to predict the interactions between the most strikingly regulated lncRNAs and mRNAs. This study may be utilized as a background or reference resource for future functional studies on lncRNAs related to the diagnosis and development of new therapies for T1DM.
Objective To analyze the newborn screening results, distribution characteristics and incidence rate for inherited metabolic disorders (IMD) by tandem mass spectrometry (MS/MS) in Huai'an. Methods Blood samples were collected from 97410 newborns born in Huai'an from June 2018 to December 2021. Amino acids, acylcarnitines, and succinylacetone in the blood were detected by non-derivatized MS/MS. Gene detection and gas chromatography-mass spectrometry (GC-MS) were carried out to diagnose positive neonates. Data were analyzed using descriptive statistics. Results From 2018 to 2021, the screening rate of inherited metabolic disorders detected using MS/MS in Huai'an increased from 21.15–99.53%.Twenty-five cases of inherited metabolic disease were diagnosed, and the overall incidence rate was 1/3896. Among them, there were 9 cases of disorders of amino acid metabolism(1/10823), 10 cases of disorders of organic acid metabolism(1/9741), and 6 cases of disorders of fatty acid oxidation(1/16235). The top three diseases with the highest incidence were phenylalanine hydroxylase deficiency(1/12176), methylmalonic acidemia(1/24352), and primary carnitine deficiency (1/24352). Among the 25 children clinically diagnosed with IMD, 84.00% (21 cases) underwent gene diagnosis. Biallelic mutations were identified in 21 children, which were inherited from their parents. Conclusion Our study suggests that newborn screening for IMD by tandem mass spectrometry is necessary, which could improve the quality of patient's life and reduce the burden on family and society. More attention should be paid to the early screening, diagnosis and treatment of neonatal genetic metabolic diseases.
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