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OBJECTIVE@#To investigate the expression of four-jointed box kinase 1 (FJX1) in gastric cancer (GC), its correlation with survival outcomes of the patients, and its role in GC progression.@*METHODS@#The expression level of FJX1 in GC tissues and normal gastric mucosal tissues and its correlation with the survival outcomes of GC patients were analyzed using TCGA and GEO database GC cohort. Immunohistochemistry was used to detect FJX1 expression level in clinical specimens of GC tissue, and its correlations with the patients' clinicopathological parameters and prognosis were analyzed. Bioinformatic analysis was performed to identify the potential pathways of FJX1 in GC. The effects of FJX1 overexpression or FJX1 silencing on GC cell proliferation and expressions of proliferation-related proteins, PI3K, AKT, p-PI3K, and p-AKT were evaluated using CCK-8 assay and Western blotting. The effect of FJX1 overexpression on GC cell tumorigenicity was evaluated in nude mice.@*RESULTS@#GC tissues showed significantly higher expressions of FJX1 mRNA and protein compared with normal gastric mucosa tissues (P < 0.05). The high expression of FJX1 was associated with poor prognosis of GC patients (P < 0.05) and served as an independent risk factor for poor survival outcomes in GC (P < 0.05). FJX1 was expressed mainly in the cytoplasm of GC cells in positive correlation with Ki67 expression (R=0.34, P < 0.05), and was correlated with CA199 levels, depth of tumor infiltration and lymph node metastasis of GC (P < 0.05). In the cell experiment, FJX1 level was shown to regulate the expressions of Ki67 and PCNA and GC cell proliferation (P < 0.05). Gene set enrichment analysis indicated that the PI3K/AKT pathway potentially mediated the effect of FJX1, which regulated the expressions of PI3K and AKT and their phosphorylated proteins. In nude mice, FJX1 overexpression in GC cells significantly promoted the growth of the transplanted tumors (P < 0.05).@*CONCLUSION@#FJX1 is highly expressed in GC tissues and is correlated with poor prognosis of GC patients. FJX1 overexpression promotes GC cell proliferation through the PI3K/AKT signaling pathway, and may serve as a potential prognostic biomarker and therapeutic target for GC.
Subject(s)
Animals , Mice , Humans , Cell Proliferation , Ki-67 Antigen , Mice, Nude , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Stomach Neoplasms/pathology , Intercellular Signaling Peptides and Proteins/geneticsABSTRACT
Gene engineering has attracted worldwide attention because of its ability of precise location of disease mutations in genome. As a new gene editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system is simple, fast, and accurate to operate at a specific gene site. It overcomes the long-standing problem of conventional operation. At the same time, stem cells are a good foundation for establishing disease model in vitro. Therefore, it has great significance to combine stem cells with the rapidly developing gene manipulation techniques. In this review, we mainly focus on the mechanism of CRISPR/Cas9 technology and its application in stem cell genomic editing, so as to pave the way for promoting rapid application and development of CRISPR/Cas9 technology.
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Objective To evaluate the signal changes of the skull base after salvage surgury via endoscopic transnasal approach for local recurrent nasopharyngeal carcinoma.Methods Twenty patients with nasopharyngeal carcinoma after radiation failure underwent nasophargeryngectomy via an endoscopic transnasal approach were selected from April 2006 to December 2011,including 16 males and 4 females with 31 to 67 years old.Each patient had previously received irradiation and experienced recurrence after 8 to 83 months of completed irradiation.All patients underwent MRI no more than 2 weeks before the salvage surgery and were subjected to repeat MRI scans 2 weeks,3 months,6 months later and semi-annually thereafter,with the follow-up time of 6 to 45 months(median 18 months).A two-sided Chi-square test was used to compare the signal changes and the tendency of changes on all presurgical and postsurgical MR images.Results The MRI signal changes were detected at 92 sites of skull-base between 2 weeks and 3 months after the surgery,which was hypointense on T1 WI with moderate to marked contrast enhancement.In the follow-up period,the signal abnormalities at 36 sites of skull base had resolved or restored to the normal,and 34 sites remained stable,while in 22 sites,the MR signal changes became more obvious.The skull base bones adjacent to the region of the resection were more likely to show signal changes than nonadjacent areas (72 vs.20,x2 =33.128,P ＜0.01).The signal changes were more common on the ipsilateral skull base to the recurrent tumor in contrast to the contralateral skull base (68 vs 24,x2 =21.182,P ＜ 0.01).Conclusions The skull base signal changes after salvage surgury via endoscopic transnasal approach for local recurrent nasopharyngeal carcinoma,and it occurs in specific location.Most of sites tend to resolve or be stable at the follow up.
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Objective To characterize the features of Nasopharyngeal non-Hodgkin's lymphoma (NHL) on MR imaging and find the main points to differentiate it from the other nasopharyngeal tumors.Methods The MR images of 41 patients with pathologically and immunohistochemically proven nasopharyngeal NHLs were reviewed retrospectively. Images were assessed by the size, invasive extent,signal intensity of primary nasopharyngeal tumor, and the distribution of cervical lymphadenopethy. The difference of regional tissues invasion and cervical lymphadenopathy distribution between the patients with B-cell NHLs and the patients with T-cell or NK/T-cell NHLs were analyzed by Pearson's Chi-Square test or Fisher's exact test Results Of the 41 patients, 26 patients had mature B-cell lymphoma, two patients with mature T-cell Iymphoma, and thirteen patients showed Nature killer/T-cell lymphoma in nasopharynx. MRI revealed that NHLs of nasopharynx can be showed as thickening of nasopharyngeal mucosa and (or) lumps in nasopharynx, which were slightly hyper-intensity on T2-weighted images, and intermediate signal intensity (similar to muscle) on T1 -weighted images, with mild or moderated enhancement following contrast medium administration. Twenty four cases had symmetrical disease of all walls of nasopharynx, and 17 cases had unsymmetrical tumor. Of all cases, 5 cases had superficial ulcerations, 9 cases had exceed nasoharynx invasion spreads superficially along the mucosa, 23 cases had invasion of lingual and (or) palatine tonsils,20 cases showed invasion of parapharygeal muscles, 12 cases suffered from skull base bone infiltration,25 cases had retropaharyngeal lymphadenopathy, and 27 cases had cervical lymhadenopathy. Patient with nasopharyngeal Nature killer/T-cell lymphoma had a higher incidence of exceed nasopharynx invasion,parapharyngeal structures invasion, and superficial ulcerations (the cases were 8, 11, 4 in patient with T-cell or N K/T-cell lymphoma, and 4, 10, 1 in patients with B-cell lymphoma, respectively). Patients with nasopharyngeal B-cell lymphoma had a higher incidence of inasion of lingual and (or) palatine tonsils.Conclusions Nasopharyngeal NHL is a homogeneous tumor that tends to diffusely involve all walls of the nasopharynx and spread in an exophytic fashion to fill the airway, rather than infiltrating into the deep tissues. Different pathological types of nasopharyngeal NHLs have some different appearance on MRI between each other. A large tumor in nasopharynx that fills the nasopharynx cavity, with no or minimal invasion into deep structures, but with invasion extend down into the lingual and(or)palatine tonsils, may suggest the diagnosis of nasopharyneal NHL.
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Objective To compare the diagnostic efficacy of bone scintigraphy and MRI on vertebral metastases in patients with nasopharyngeal cancer (NPC). Methods Forty-seven patients of NPC and clinically confirmed metastatic disease in spine underwent bone scintigraphy and MR examination. The number of involved vertebri diagnosed with two methods were calculated and compared retrospectively. Results A total of 187 vertebral metastases were found in 47 patients, among which 153 (81.82%) were detected with bone scintigarphy and 182 (97.33%) were diagnosed with MRI (χ~2＝23.758, P＝0.000). Conclusion Compared with bone scintigraphy, MRI is superior in detecting vertebral metastases from NPC, and can be used as the first choice for the early diagnosis of spinal metastases from NPC.