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Neuroendocrine tumors(NET) is a rare tumor with high heterogeneity.Pancreatic NET is the most common type in China. European Neuroendocrine Tumor Society(ENETS) has launched the ENETS guidelines since 2006 and published the ENETS standard of care in 2009. With the newly targeted therapies and further research on NET, 2017 new edition of the ENETS standard of care has changed a lot in the diagnosis and treatment of NET. This article explains the update of pancreatic NET in the 2017 edition of the ENETS standard of care, and introduces pancreatic NET from pathology, imaging examination, surgery, systemic therapy, etc., and deepens the understanding of the diagnosis and treatment of pancreatic NET.
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Objective To examine the expressions of IKKε protein in the specimens and cells of epithelial ovarian cancer and investigate the effect of IKKε inhibitor on cell proliferation and apoptosis. Methods (1) A total of 118 cases of patients with the median age of 59 who have accepted surgical treatment due to ovarian cancer in the First Affiliated Hospital of Dalian Medical University from January 2006 to April 2013 were selected. Twenty cases of patients with the median age of 55 who have accepted hysterectomy and salpingo-oophorectomy due to uterine leiomyoma during the same period were selected as the control. The expressions of IKKε protein were detected by immunohistochemistry in normal ovarian tissues and epithelial ovarian cancer specimens,and the relationship between the expressions of IKKε and the clinical features of patients was analyzed. IKKε protein was determined by western blot in various ovarian cancer cells, including SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 treated with or without IKKε inhibitor. The cellular proliferation and apoptosis of ovarian cancer cells after 48 hours treatment of IKKε inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results (1) The immunohistochemical results showed that IKKε was highly expressed in epithelial ovarian cancer specimens with the expression rate 66.1% (78/118), compared with normal ovarian tissue with the expression rate 35.0% (7/20), which exhibited statistically significant difference (χ2=6.993, P=0.008). The expression of IKKε protein was correlated with International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade, the level of CA125 in preoperative serum and distribution of the tumor (P0.05). (2) IKKε was widely overexpressed in different levels in SKOV3, OV2008, C13, A2780S, A2780CP, OV4, OV5, OV8, and CAOV3 cells, and the expression of IKKε decreased as the increase of the concentration of IKKε inhibitor (0.1 and 0.5 μmol/L) in OV2008, C13, A2780S, and A2780CP cells after 48 hours treatment. Different concentrations of IKKε inhibitor (0.05, 0.1, 0.5, 1, 5, 10, and 25 μmol/L) significantly inhibited the proliferation of OV2008, C13, A2780S, A2780CP, and SKOV3 cells in a concentration-dependent manner (P<0.05), and the half maximal inhibitory concentration (IC50) was 0.43, 0.86, 0.10, 0.19, and 0.24 μmol/L, respectively. The cell apoptotic rate of OV2008, C13, A2780S, A2780CP, and SKOV3 cells was significantly increased after 48 hours treatment of IKKεinhibitor with the concentration of 0.1 and 0.5 μmol/L (P<0.05). Conclusions The IKKε protein in epithelial ovarian cancer specimens and cells is overexpressed. IKKε inhibitor could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner. Together, the result indicated that IKKε may be a candidate target for the treatment of ovarian cancer in future.
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Objective To investigate the roles of glutamate signaling pathway in the activation of human peripheral blood lymphocytes(PBLs) and pathogenesis of vitiligo.Methods Peripheral blood lymphocytes (PBLs) isolated from 5 patients with generalized vitiligo and 5 healthy controls were cultured in vitro.Flow cytometry was performed to quantify the expression of CD25 and interferon-γ on PBLs derived from healthy controls and treated with MK801 (a non-competitive antagonist of N-methyl-D-aspartic acid receptor,NMDAR) at 100 μmol/L or phosphate buffered saline (PBS) for 48 hours,as well as the level of reactive oxygen species (ROS) in the controlderived PBLs treated with MK801 at 100 μmol/L,NMDA (an agonist of N-methyl-D-aspartic acid receptor) at 0.5 mmol/L or PBS for 48 hours.The protein and mRNA expressions of NMDAR1 and NMDAR2A were measured by flow cytometry and real-time PCR,respectively,in PBLs from the healthy controls and vitiligo patients.Immunohistochemistry was used to observe the expressions of NMDAR1 and NMDAR2A in tissue specimens from depigmented and postinflammatory hyperpigmentation lesions of the patients with vitiligo and from normal skin of the healthy controls.Results Compared with the PBS-treated PBLs from the healthy controls,the MK801-treated PBLs showed a downregulated expression of CD25 (7.28％ ± 0.18％ vs.16.02％ ± 0.42％,P ＜ 0.01),but an upregulated proportion of CD25+IFN-γ+ lymphocytes (1.79％ ± 0.09％ vs.0.78％ ± 0.06％,P ＜ 0.01),and the NMDA-treated PBLs displayed a higher ROS level (101.1 ± 3.50 vs.69.80 ± 2.08,P＜ 0.01 ).The protein expression of NMDAR1 in PBLs was significantly higher in vitiligo patients than in the healthy controls (3.85 ± 2.17 vs.0.97 ±0.55,P ＜ 0.05).Conclusion Glutamate signaling pathway may be involved in the immunopathogenesis of vitiligo via affecting the secretion of interferon-γ by,and ROS level in,activated lymphocytes.
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Objective To investigate the expression and significance of caveolin-1 in breast carcinoma.Methods Using immunohistochemical method the protein expression of caveolin-1 were analyzed in 105 cases of breast carcinoma and 50 cases of non-cancerous breast tissues.The relationship between caveolin-1 expression and CK5/6,EGFR,and E-cadherin expression was investigated.Clinical data of 105 cases of breast carcinoma were retrospectively analyzed.Results Among 105 cases of breast carcinoma,there were 20 cases of basal-like subtype,22 cases of luminal subtype A,23 cases of luminal subtype B,23 cases of HER2 over-expressing subtype,17 cases of normal breast-like subtype.Positive rate of caveolin-1 was significantly lower in breast carcinoma than in non-cancerous breast tissues (24.8％ vs.88.0％,P ＜ 0.05).Positive rate of caveolin-1 (75.0％) was higher in breast carcinoma than in luminal subtype A ( 4.8％ ),luminal subtype B ( 17.4％ ),HER2 over-expressing subtype ( 17.4％ ) or normal breast-like subtype( 11.8％ ),all P ＜0.05.Caveolin-1 expression was associated with expression of CK5/6 and EGFR(P ＜0.01 ).In univariate analysis,positive caveolin-1 was associated with higher lymph node metastasis rate (18/26,69.2％ )than negative (37/79,46.8％ ),P =0.047,and shorter 5-year-disease-free survival (38.46％ vs.74.68％,P =0.0004 ),but in multivariate analysis caveolin-1 was not an independent predictor of 5-year- disease-free survival (P ＞ 0.05).Conclusions Caveolin-1 can be seen as a screening mark of basal-like breast carcinoma,it may promote the invasiveness of breast cancer cells,but it is not an independent prognostic predictor of breast cancer patients.