Overexpression of Kin of IRRE-Like Protein 1 (KIRREL) in Gastric Cancer and Its Clinical Prognostic Significance.

BACKGROUND The aim of this study was to examine the expression level of IRRE-like protein 1 (KIRREL) in gastric cancer (GC) and to explore its prognostic significance. MATERIAL AND METHODS Bioinformatics methods were used to predict the differential expression levels of KIRREL mRNA in GC and normal gastric tissues by mining cancer-related databases (TCGA and Oncomine). Immunohistochemistry was done to verify the KIRREL protein expression levels in 71 cases of GC tissues combined with matched normal tissues. The relationship between clinicopathologic parameters and KIRREL differential expression levels in GC was investigated by the chi-square test. Kaplan-Meier univariate and Cox multivariate survival analyses were performed to explore the prognostic significance of KIRREL expression in GC patients. RESULTS TCGA and GEO data analyses showed that KIRREL mRNA expression level was remarkably higher in GC than that in normal gastric tissues (both P<0.05). KIRREL mRNA levels were dramatically increased from stage I to stage IV (P=0.037). Immunohistochemical results showed that the high positive rate of KIRREL staining in GC was 61.97% (44/71). Moreover, GC patients with KIRREL mRNA or protein high levels had significantly shorter overall survival times than those with KIRREL mRNA or low protein levels (All P<0.05). Additionally, Cox multivariate survival analysis revealed that KIRREL differential expression levels (low vs. high) were the only independent parameter predicting the prognosis of GC patients (P=0.000). CONCLUSIONS KIRREL was overexpressed in GC and the overexpression of KIRREL could serve as an independent predictor of poor prognosis in GC patients.

A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new noncoding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10-8) and CNFN (P = 3.77 × 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087-97. ©2018 AACR.

Androgen receptor reverts dexamethasone­induced inhibition of prostate cancer cell proliferation and migration.

The aim of the present study was to determine the role of androgen receptor in the effect of dexamethasone on cell proliferation and migration of multiple prostate cancer cells. The prostate cancer cell lines LNCaP, 22Rv1, C4­2 and PC3 were cultured in vitro. For glucocorticoid­induced experiments, the cells were transferred and cultured in RPMI­1640 medium with 10% charcoal­stripped serum from RPMI­1640 medium with 10% fetal bovine serum for at least 24 h. The effects of dexamethasone on the proliferation and migration of various cell lines were analyzed by MTT and migration assays. Dexamethasone exhibited no effect on LNCaP, C4­2 and 22Rv1 cell lines, but suppressed proliferation of glucocorticoid receptor (GR)+ androgen receptor (AR)­ PC3 cell line. Dexamethasone suppressed PC3 cell migration, and did not affect migration of PC3­AR9 cells. Dexamethasone positively or negatively regulated proliferation of various prostate cancer cells based on AR and GR expression profiles. The data presented in the present study indicates that androgen receptor reverts the dexamethasone­induced inhibition of prostate cancer cell proliferation and migration.

Correlation between the expression of JARID1B/KDM5B in breast cancer tissues and the circulating tumor cells / 基础医学与临床

Objective To investigate the relation between expression of JARID1B/KDM5B in invasive breast cancer tissue and circulating tumor cells of invasive breast patients. Methods The S-P immunohistochemical method was used to observe the expression of JARID1B/KDM5B in lesions.imFISH method was used to detect circulation tumor cells. Results Twenty-seven cases of patients showed CTC positive(the number of CTC was more than or equal to 2) in 35 invasive breast cancer cases,The results of JARID1B/KDM5B expression were as follows:(-) (n=0) and (+) in 1 case,(++) in 3 cases,(+++) in 23 cases,8 cases of negative cases (the number of CTC < 2), JARID1B/KDM5B immune group of results:(-) (n=2),(+) in 2 cases,(++) in 1 case,(+++) in 3 cases, The positive relation was found in expression of JARID1B/KDM5B and circulating tumor cells(P<0.05). Conclu-sions JARID1B/KDM5B positive expression in tumor tissues has a certain significance in predicting the recurrence and metastasis of tumor.

Promoter methylation of DAPK gene may contribute to the pathogenesis of nonsmall cell lung cancer: a meta-analysis.

We performed a meta-analysis of cohort studies to determine whether promoter methylation of the death-associated protein kinase (DAPK) gene contributes to the pathogenesis of nonsmall cell lung cancer (NSCLC). A range of electronic databases were searched: MEDLINE (1966 ∼ 2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980 ∼ 2013), CINAHL (1982 ∼ 2013), Web of Science (1945 ∼ 2013), and the Chinese Biomedical Database (CBM; 1982 ∼ 2013) without any language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated. Our meta-analysis integrated results from 12 clinical cohort studies that met all inclusion criteria with a total of 1,027 NSCLC patients. We observed that the frequency of DAPK gene methylation in cancer tissues were significantly higher than that in the adjacent normal and benign tissues (cancer tissues vs. benign tissues: OR=8.50, 95 % CI=5.88 ∼ 12.28, P<0.001; cancer tissues vs. adjacent tissues: OR=5.95, 95 % CI=4.11 ∼ 8.60, P<0.001; cancer tissues vs. normal tissues: OR=4.75, 95 % CI=3.28 ∼ 6.87, P<0.001; respectively). Subgroup analysis by ethnicity demonstrated that DAPK gene methylation was closely associated with the development and progression of NSCLC among both Asians and Caucasians (all P<0.05). Furthermore, we conducted a subgroup analysis based on sample source and discovered that DAPK gene methylation was implicated in the pathogenesis of NSCLC in both blood and tissue subgroups (all P<0.05). Our results suggest that DAPK promoter methylation may be involved in NSCLC carcinogenesis. Thus, the detection of aberrant DAPK methylation may be helpful in the diagnosis and prognosis of NSCLC.

[Estrogen receptor expression and vitellogenin synthesis induced in hepatocytes of male frogs Rana chensinensis exposed to bisphenol A].

The effects of bisphenol A (BPA) on estrogen receptor (ER) and vitellogenin (VTG) in hepatocytes of male amphibians have attracted significant attention in recent years. Adult male frogs Rana chensinensis were exposed to different concentrations of 10(-7), 10(-6) and 10(-5) mol/L BPA consecutively for 10, 20, and 30 d, respectively. We used 10(-9), 10(-8) mol/L 17ß-esradiol (E(2)) as positive controls. The expressions of ER mRNA in the hepatocytes were detected by in situ hybridization, and ER and VTG protein were detected by immunohistochemistry. The results showed that positive effects of ER mRNA were detected in all BPA and E(2) treatment groups. Compared with the control group, the expression level of ER and VTG protein increased significantly in the hepatocytes of R. chensinensis. Both ER and VTG expression exhibited BPA dose-dependence for the same exposure time. For the same concentration of BPA treatment, VTG synthesis markedly increased with prolonged treatment, whereas the expression of ER did not significantly fluctuate. It is suggested that BPA caused the synthesis of VTG by inducing ER up-regulation in the hepatocytes of male R. chensinensis, but its estrogenic activity was much lower than E(2).

Electrocardiogram Minnesota codings from 30 000 adult cases with Kazakh ethnicity in Xinjiang,China / 中华流行病学杂志

Objective To observe the abnormal Minnesota code (MC) distribution and interrelated characteristic on electrocardiograms (ECGs) of the adult Kazakh population.Methods Resting ECGs and blood press of randomly sampled 30 000 adult Kazakh people in three Northern regions of Xinjiang were continuously examined and analyzed,using Minnesota code recommended by WHO as the classification of ECG.Results The overall rate of abnormal ECG findings was 248.60‰,and the main abnormality in males was 146.83‰,compared to 157.71‰ in females.The prevalence rates of abnormal ST-T changes,the total arrhythmia and atrial fibrillation (AF) were 100.03‰,71.17‰ and 2.83‰ respectively.There were statistically significant differences among the main abnormities from the three regions.Conclusion The ECGs abnormalities of adult Kazakh people were high.There was significant relation found between the main abnormalities and hypertension.The prevalence of AF was different from the domestically reported literature that calls for further study.

Expression changes of metabotropic glutamate receptor 5 in neuropathic pain / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression changes of metabotropic glutamate receptor 5 (mGluR5) in neuropathic pain.</p><p><b>METHODS</b>Eighty-four adult male Sprague Dawley rats weighing 180-220 g were randomly divided into 7 groups (n = 12) : control group; S3, S7, and S14 groups: rats received the sham operation, the mechanical pain threshold was measured, and then the rats were decapitated and the ipsilateral lumbar spinal cord dorsal horn and dorsal root ganglion (DRG) samples were obtained on the 3rd, 7th, 14th postoperative day, respectively; C3, C7, and C14 groups: the chronic sciatic nerve constriction (CCI) model was established, the mechanical pain threshold was measured and the samples were obtained on the 3rd, 7th, 14th postoperative day, respectively. The expression level of mGluR5 mRNA and protein in the spinal cord and DRG were measured using the reverse transcriptase polymerase chain reaction and Western blot.</p><p><b>RESULTS</b>In the CCI group, the mechanical pain threshold in each observation day was significantly lower than in the sham operation group (P < 0.05). In the spinal cord, the expressions of mGluR5 mRNA and protein were significantly elevated in the C3 group than in the S3 and the control group (P < 0.05). On the 7th and the 14th postoperative day, no significant difference was found in the expression of mGluR5 mRNA and protein between CCI groups and the sham operation groups or the control group. No change was detected in DRG mRNA or protein.</p><p><b>CONCLUSION</b>mGluR5 is differentially expressed in spinal cord in response to neuropathic pain, which suggests that mGluR5 may be involved in the mechanism of neuropathic pain.</p>