Role of nm23H1 in predicting metastases in prostatic carcinoma

Background: Non-metastatic nm23H1 gene is thought to play a critical role in cell proliferation. Studies of nm23H1 have been done in many other malignancies. But none of these studies took up nm23H1 gene as predictor in the metastases of prostatic carcinoma. Aims and Objectives: To study the expression of nm23H1 in prostatic lesion and to correlate nm23H1 expression with presence of metastases, tumour stage, tumour grade and with PSA level serum. Setting and Design: Tertiary hospital based retrospective and prospective study done in a period of one year from thirty patients having prostatic lesion confirmed by biopsy. Material and Methods: Immunohistochemistry for nm23H1 was performed on unstained coated sections of prostatic lesions to study the relation with prostatic lesion and their correlation with age, PSA level, tumour stage, grading. Clinical data was collected from medical records. Statistical Analysis: SPSS Version 15 analysis software was used. The value were presented in number(%) and Mean ± SD. Results: Majority of patients belong to age group 61 to 70yrs.Gleason score >7 were seen in 55% of patients of adenocarcinoma with and without metastasis. The difference in PSA levels between BPH and adenocarcinoma was significant (P < 0.001). IHC expression for nm23H1 gene showed positive findings in all the cases (P = 1). PSA values >20ng/ml showed maximum % mean expression (98.64%) as compared to PSA levels <10 ng/ml (96.91%). Conclusion: IHC expression of nm23H1 is not an effective tool to distinguish among the cases of BPH, adenocarcinoma of prostate with and without metastasis. Hence nm23H1 gene does not behave like an antimetastatic gene in prostatic lesions.

Expression of metastasis associated genes nm23, p53 and S100A4 in conjunctival melanoma and their relationship with invasion and metastasis / 中华实验眼科杂志

Objective To study the significance of metastasis associated genes nm23,p53 and S100A4 in the development of conjunctival melanoma metastasis.Methods Conjunctival melanoma tissue specimens were collected from 42 cases of conjunctival melanoma patients in Henan Eye Hospital from July 2015 to November 2016,meanwhile 30 cases of conjunctival nevus tissue samples served as control group under the informed consent.The expressions of nm23,p53 and S100A4 were detected in conjunctival melanoma group and control group by Western blot and immunohistochemical method.The relationship between the clinical and pathological features of nm23,p53 and S100A4 with conjunctival melanoma patients with lymph nodes metastasis were analyzed.Results Western blot assay showed that the expression level of nm23 in conjunctival melanoma group was lower than that in the control group,with a significant difference between them (P＜0.05);the expression level of p53 and S100A4 in conjunctival melanoma group was significantly higher than those in the control group (both at P＜0.05).Immunohistochemistry showed that nm23 and S100A4 appeared claybank in cytoplasm,while p53 appeared red in cell nucleus.The positive rate of nm23 protein expression in conjunctival melanoma group was significantly lower than that in the control group (14.3％ vs.53.3％,P＜0.05).The positive rate of p53 expression in conjunctival melanoma group was significantly higher than that in the control group (54.8％ vs.6.7％,P＜0.05).The positive rate of S100A4 expression in the conjunctival melanoma group was significantly higher than that in the control group (59.5％ vs.6.7％,P＜0.05).There were no difference in nm23,p53 and S100A4 protein expression positive rate between various gender groups,various age groups and various ulcer groups (all at P＞0.05).There were siginificant differences in nm23,p53 and S100A4 protein expression positive rate between various sclera invasion groups and various distant metastasis groups (all at P＜0.05).Conclusions Expression of nm23,p53 and S100A4 may play an important role in the invasion and metastasis of conjunctival melanoma,which may be the main reference index for the diagnosis and treatment.

The Role of NM23 in Patients with Colorectal Cancer: A Systematic Review and Meta-Analysis / 华中科技大学学报（医学）（英德文版）

This meta-analysis was carried out to evaluate the relationship between NM23 expression and the prognosis of patients with colorectal cancer.We searched PubMed,EMBASE and Web of Science for relevant articles.The pooled odd ratios (ORs) and corresponding 95％CI were calculated to evaluate the prognostic value of NM23 expression in patients with colorectal cancer,and the association between NM23 expression and clinicopathological factors.In total,2289 patients were pooled from 24 available studies.The incorporative OR combined by 16 studies with overall survival showed that high NM23 expression was associated with better overall survival (OR=0.67,95％CI:0.49-0.93,P=0.02,I2=56％,Ph=0.004).And a new estimate without heterogeneity was produced when only combining high-quality studies (OR=0.70,95％CI:0.56-0.86,P=0.0007,I2=46％).In disease free survival (DFS),we also obtained a good prognosis (OR=0.30,95％CI:0.14-0.68,P=0.004).Although we failed to find any significance in N status (P=0.10),elevated NM23 expression was related to well tumor differentiation (OR=0.60,95％CI:0.44-0.820,P=0.001) and Dukes' A&B (OR=0.55,95％CI:0.32-0.95,P=0.03).These results indicated that over-expressed NM23 might be an indicator of good prognosis,well tumor differentiation and Dukes' A&B of patients with colorectal cancer,but no significance was found in N status.

Distribution of Nm23 gene polymorphism in healthy Chinese Hans population in Hubei,China / 中国免疫学杂志

Objective:To develop a method for the detection of 10 single nucleotide polymorphisms(SNPs) of Nm23 gene,and to explore the genotypic and allelic distributions of the 10 SNPs in Chinese Hans population in Wuhan.Methods: Two hundreds healthy subjects ,115 men and 85 women included ,were enrolled as DNA sample donors.The real time TaqMan-MGB genotyping assay was used for the determination of the 10 SNPs selected ,and the results were validated by direct gene sequencing.Results:The method established could accurately and quickly screen the genotypes of the 10 SNPs of Nm23/NDPK gene.Distribution frequencies of the 10 SNPs were similar to these in other researches as well as these of HCB.All the loci follow the Hardy-Weinberg equilibrium.Highly linkage disequilibriums were found between rs 16949649 and rs7207370 , rs16949649 and rs34214448 , rs2159359 and rs2302254 , rs2159359 and rs8075231 ,rs2159359 and rs2041296 ,as well as rs2159359 and rs8071647 ,respectively.Four Tag SNPs:rs34214448 , rs2302254 ,rs11868380 and rs2318785 were initially selected by Heploview software.Conclusion:The method established for SNP gen-otyping can meet the needs for rapid analysis of Nm 23 gene polymorphisms ,and may have great values in investigating the association between gene polymorphisms and diseases as well as adverse drug reactions.

Expression of Mitofusin-2 (mfn2) and nm23 in Different Bladder Tissues / 天津医药

Objective To research the expression of mitofusin-2 (mfn2) and tumor metastasis suppressor genes (nm23)in bladder cancer cells and its correlation with clinical pathological feature. Methods Immunohistochemistry was used to measure the expression of mfn2 and nm23.Sixty-five cases of bladder cancer were sampled,which include fif-ty cases of male and fifteen cases of female. TNM stage:Forty-seven cases were in stage I;Ten cases were in stage II; Five cases were in stageⅢ; Three cases were in stageⅣ. Other fifteen cases were sampled from normal bladder or benign tumor of bladder as control . All cases were collected from department of pathology,affiliated Hospital of hebei union university. Results The positive expression rate of mfn2 in bladder cancer tissues was significantly higher than those in normal blad-der tissues and benign tumor of bladder(χ2=32.528,P<0.05);The positive expression rate of nm23 in bladder cancer tis-sues was significantly lower than those in normal bladder tissues and benign tumor of bladder (χ2=19.719,P<0.05);the high expression level of mfn2 in bladder cancer was associated with tumor differentiation and TNM stage(P<0.05),but not corre-lated with age,sex,lymph node metastasis and clinical grade. The low level of nm23 was associated with TNM stage,clinical grade and LN metastasis. Conclusion The positive expression rate of mfn2 was increased in bladder cancer. It indicated that there was a close relationship between mfn2 and the occurrence and development of bladder cancer;The expression rate of nm23 was decreased in bladder cancer,it may be a predictor for metastasis and prognosis of bladder cancer.

Expression of p53 and nm23-H1 in nasopharyngeal carcinoma and their significance / 肿瘤研究与临床

Objective To sdudy the expression of p53 and nm23-H1 proteins and their clinical significance in nasopharyngeal carcinoma.Methods The expression of p53 and nm23-H1 proteins were detected by immunohistochemistry method in 40 cases with nasopharyngeal carcinoma and 22 cases with chronic inflammation of nasopharyngeal mucosa tissues.Results Positive rates of p53 and nm23-H1 in chronic nasopharyngitis group were 1.0 ％,27.2 ％,and in the NPC group were 92.5 ％,55.0 ％.There were 9 cases with the positive expression of p53 in 22 cases of nasopharyngeal carcinoma tissues with the positive expression of nm23-H1 (40.9 ％).There were 17 cases with the positive expression of p53 in 18 cases with the negative expression of nm23-H1 (94.4 ％).The expression of p53 and nm23-H1 proteins in nasopharyngeal carcinoma were much higher than that in chronic inflammation of nasopharyngeal mucosa tissues.The expression of p53 protein in nasopharyngeal carcinoma with metastatic lymph node was higher than that in nasopharyngeal carcinoma without metastatic lymph node,but nm23-H1 protein lower.The expression of p53 protein was positively correlated with the metastasis,clinnical staging and pathological classification but not correlated with T classification of nasopharyngeal carcinoma.The expression of nm23-H1 protein was negative correlation with the metastasis and clinical staging of nasopharyngeal carcinoma.Conclusion p53 and nm23-H1 play important coordinated regulation roles in the carcinogenesis,development and metastasis of nasopharyngeal carcinoma and will probably become the key biological marks in the judging and evaluating prognosis of nasopharyngeal carcinoma.

The expression and clinical significance of vascular endothelial growth factor-C and nm23-H1 in colorectal carcinoma / 中国医师进修杂志

Objective To discuss the expression and clinical significance of vascular endothelial growth factor (VEGF)-C and nm23-H1 in colorectal carcinoma.Methods Immunohistochemical staining was employed to determine the expression of VEGF-C and nm23-H1 in the carcinoma tissues of 120 cases with colorectal carcinoma and in the adjacent mucosal tissues of 55 cases as control,and analyzed their correlation with cliniopathological features and prognosis.Results The positive expression of VEGF-C in the carcinoma tissues was 71.7％ (86/120),significantly higher than that in the adjacent mucosal tissues [21.8 ％ (12/55)],and there was significant difference (x2 =35.186,P ＜ 0.01).The positive expression of nm23-H1 in the carcinoma tissues was 57.5％ (69/120),significantly lower than that in the adjacent mucosal tissues [90.9％ (50/55)],and there was significant difference (x2 =18.351,P ＜ 0.01).The expression of VEGF-C was significantly correlated with lymph node metastasis (P ＜ 0.05),and the expression of nm23-H 1was significantly correlated with lymph node metastasis and pathological type (P ＜0.01 or ＜0.05).The expression of VEGF-C and nm23-H1 did not show a significant correlation with gender,age,tumor size,tumor site and depth of invasion (P ＞ 0.05).Spearman correlation analysis showed that the expression of VEGF-C was negatively correlated with the expression of nm23-H 1 in colorectal carcinoma (r =-0.472,P ＜0.01).Conclusions The joint detection of VEGF-C and nm23-H1 expression is very promising in prediction of the prognosis of patients with colorectal carcinoma.However,whether it can be used as a marker in prognosis judgment need further investigation.

The expression of CCDC8 gene in breast cancer / 肿瘤研究与临床

Objective To determine the relationship between CCDC8 gene and breast cancer.Methods 40 cancerous breast tissue and 22 benign breast tissue were included.qRT-PCR was performed to investigate the expression level of CCDC8 in breast tissue.The correlation between CCDC8 level and the age of patients,tumor size,clinical staging,and the expression levels of estrogen and progesterone receptors,CerbB2,Ki-67,p53 and nm23 were analyzed.Results The expression level of CCDC8 in benign breast tissue (1685±755) was significantly higher than that in cancerous tissues (502.1 ±223.2).Tissues obtained from patients over age 50 showed an increased level of CCDC8 (789.8±367) in comparison to those from patients age 50 or younger (452.5±170.3).The level of CCDC8 expression was negatively correlated with nm23 level (Correlation Coefficient =-0.400,P =0.039),while no correlation was found between CCDC8 and cancer stages,estrogen and progesterone receptor,CerbB2,Ki-67and p53.Conclusion The negative correlations between CCDC8 and age,tumor size and nm23 indicate that CCDC8 is a potential tumor suppressor,influencing the occurrence and progression in breast cancer.

Research progress on NM23A (expressed in non-metastatic cells) protein / 中国药理学通报

NM23A protein is a kind of multifunctional protein distributed widely in the nature and it exists in almost all the or-ganism and cells. Apart from owning the nucleoside diphosphate kinase activity, NM23A also participates in the physiological process of signal transduction, gene regulation, cell growth and development and so on. NM23A plays important roles in the pa-thology process of the tumor development and metastasis and cen-tral nerve system disease.

Diagnostic value of CD56 and nm23 markers in papillary thyroid carcinoma.

Context: Thyroid cancer is the most common malignant endocrine tumor. Nowadays tissue biopsy and pathological assessment are the best diagnostic modalities for thyroid lesions. Differential diagnosis between adenomas and follicular variant of papillary thyroid carcinoma (PTC) is an important issue in pathology. Aims: This study is designed to show any association between expressions of CD56 and nm23 and types of thyroid lesions (benign vs. malignant). Settings and Design: In this cross-sectional study, 78 paraffin-embedded tissue blocks of thyroid tissue from a tertiary care center were selected, and assessed by using immunohistochemistry for expressions of CD56 and nm23 genes. Materials and Methods: we studied 39 benign and 39 malignant thyroid lesions, CD56 and nm23 expressions were determined by immunohistochemical staining, and the results were used for differentiation of benign and malignant lesions of thyroid. Statistical Analysis: The obtained results were analyzed and evaluated using SPSS (Version 18). Results: CD56 was expressed in 93% of benign specimens and in only 5% of malignant types. The sensitivity and specificity of this test were 94.8% and 92.3, respectively (P = 0.001). All malignant specimens and 95% of benign specimens were positive for nm23. The sensitivity and specificity of nm23 were 100% and 5%, respectively. Conclusion: Considering high sensitivity and specificity of CD56, it is possible to apply immunohistochemistry for definite diagnosis and differentiation of benign lesions from PTC. We conclude that by using this marker, the diagnostic mistakes in pathologic diagnosis of thyroid cancer versus benign lesions like thyroid adenoma will decrease.

Expression of nm23-H1 and heat shock protein 27 and their significance in non-small cell lung carcinoma / 肿瘤研究与临床

Objective To detect the expressions of nm23-H1 and heat shock protein 27 (HSP27) and their clinical significance on development and metastasis in non-small cell lung carcinoma (NSCLC).Methods 75 tumor tissues from patients with NSCLC were included as experimental group and 28 pulmonary benign lesion tissues were as control group.The expressions of nm23-H1 and HSP27 in patients with different clinical and pathological characters were detected by immunohistochemistry.Results nm23-H1 and HSP27 were mainly expressed in cytoplasm,the positive rates of nm23-H1 and HSP27 were significantly higher in the experimental group than that in control group [41.3 ％ (31/75) vs 7.1％ (2/28),x2 =10.946,P =0.001,80.0 ％ (60/75) vs 46.4 ％ (13/28),x2 =11.131,P =0.001].Compared with control group,the positive rate of HSP27 was correlated with the degree of tumor differentiation (x2 =4.191,P =0.041).nm23-H1 was related with HSP27 in lung cancer (r =0.284,P =0.013).Conclusion nm23-H1 and HSP27 are related to the occurrence and development of NSCLC.The joint detection of nm23-H1 and HSP27 should be helpful to the diagnosis and judge the biological behavior of NSCLC.

Significance of VEGF united with nm 23 detection in diagnosis and treatment of non-small cell lung cancer / 肿瘤研究与临床

Objective To detect the expressions of VEGF and nm23 in non-small cell lung cancer (NSCLC) tissues and their relationships,and explore their clinical value in the diagnosis and treatment.Methods lmmunohistochemistry(SP method) was used to detect the expressions of VEGF and nm 23 in NSCLC and peritumor tissues.Results The positive expression rate of VEGF in NSCLC(63.3 ％,38/60)was significantly higher than in the peritumor tissues(16.7 ％,10/60)(x2=27.22,P＜0.01).nm 23 is on the contrary (53.3 ％,32/60)(x2=17.79,P＜0.01).The positive expression of VEGF in NSCLC was positively correlated significantly with the lymph node metastasis and histological classification(P＜0.05).The positive expression of nm 23 in NSCLC was negative correlated significantly with lymph node metastasis,P＜0.01.2-year survival rate of the VEGF-positive patients was significantly lower than that of VEGF-negative patients,and nm 23 is on the contrary(x2=5.55,P＜0.05).No correlation was found between the expressions of VEGF and nm 23 in NSCLC (x2=1.83,P＞0.05) Conclusion The VEGF and nm 23 may be closely associated to carcinogenesis and progression of NSCLC.Detection of VEGF and nm 23 are beneficial to indicate the biologic behavior of NSCLC.It has positive effect on diagnosis and treatment of NSCLC.

Pro-oncogenic potential of NM23-H2 in hepatocellular carcinoma

NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). There is abundant mRNA expression of NM23-H1, NM23-H2, or a read through transcript (NM23-LV) in the primary sites of hepatocellular carcinoma (HCC). Although the NM23-H1 protein is implicated as a metastasis suppressor, the role of NM23-H2 appears to be less understood. Thus, the aim of this study was to examine whether NM23-H2 is associated with hepatocarcinogenesis. The level of NM23-H2 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Its subcellular localization was confined to mainly the cytoplasm and to a lesser extent in the nucleus. Ectopic expression of NM23-H2 in NIH3T3 fibroblasts and HLK3 hepatocytes showed a transformed morphology, enhanced focus formation, and allowed anchorage-independent growth. Finally, NIH3T3 fibroblasts and HLK3 hepatocytes stably expressing NM23-H2 produced tumors in athymic mice and showed c-Myc over-expression. In addition, NF-kappaB and cyclin D1 expression were also increased by NM23-H2. Lentiviral delivery of NM23-H2 shRNA inhibited tumor growth of xenotransplanted tumors produced from HLK3 cells stably expressing NM23-H2. Collectively, these results indicate that NM23-H2 may be pro-oncogenic in hepatocarcinogenesis.

Identification of nm23-H1 as a metastatic suppressor and prognostic factor in nasopharyngeal carcinoma by proteomic analysis / 中南大学学报(医学版)

Objective:To identify proteins associated with nasopharyngeal carcinoma (NPC) metastasis,and provide scientific basis for the prevention and cure of NPC.Methods:A two-dimensional gel electrophoresis and mass spectrometry were performed to screen for differential proteins between highly metastatic 5-8F and non-metastatic 6-10B NPC cell lines.Western blot was used to confirm the differential proteins.We used siRNA to inhibit the expression of differential protein nm23-H1 to determine the association of nm23-H1 with NPC in vitro invasive ability.Immunohistochemistry and statistics were used to evaluate the correlation of nm23-H1 expression with clinicopathological features and clinical outcomes in paraffin-embedded archival tissues including 93 cases of primary NPC and 20 cases of cervical lymphonode metastatic NPC (LMNPC).Results:A total of 15 differential proteins in the 2 cell lines were identified by a proteomic approach,and 3 differential proteins were selectively confirmed.Downregulation of nm23-H1 by siRNA significantly increased the in vitro invasive ability of 6-10B.Significant nm23-H1 downregulation was observed in LMNPC compared with primary NPC.nm23-H1 downregulation in primary NPC was positively correlated with lymphonode and distant metastasis,advanced clinical stage and recurrence.Survival curves showed that patients with nm23-H1 downregulation in primary NPC had a poor prognosis.Multivariate analysis confirmed that nm23-H1 expression level in primary NPC was an independent prognostic indicator.Conclusion:nm23-H1 behaves as a metastasis suppressor in NPC,and nm23-H1 downregulation is a biomarker for poor NPC prognosis.

E-cadherin and NM23HI as metastasis predictors for various degrees of histological malignancy in invasive ductal carcinoma.

Background: This study aims to analyze whether the expressions of E-cadherin and NM23HI can be used as predictors of ductal carcinoma metastasis in various degrees of malignancies. Methods: Paraffin blocks were obtained from 97 patients with invasive breast ductal carcinoma with malignancy grade 1, 2 and 3 who came to several hospitals in Jakarta and Bandung from 2000 to 2006. Histopathological examinations of hematoxylin eosin slides of primary and secondary tumors were done to diagnose the degree of histological malignancy and metastasis status. Further, immunohistochemistry staining of E-cadherin, NM23HI and cytokeratin were done followed by scoring according to the number of positive cells and staining intensity. The associations of E-cadherin and NM23H1 expression with the presence of metastasis and grade of histological malignancy were analyzed. Results: Subjects were 29-75 years old (mean: 48.19 years), with most subjects aged 40–45 years old, with malignancy grade 1, 2 and 3 of 18.56%, 45.36% and 36.1% respectively. There was a significant association between E-cadherin and NM23HI expression in primary tumors. The possibility of invasion and metastasis inhibition by positive E-cadherin and NM23HI was 14 and 11 times respectively compared to those with negative E-cadherin and/ or NM23HI expression. The ROC curve showed that E-cadherin (r= 0.755) and NM23HI (r= 0.827) expressions were strongly associated, sensitive and specific as metastasis markers. However, E-cadherin and NM23HI expression did not show significant association with histological degree of invasive ductal carcinoma. Conclusion: E-cadherin and NM23HI expressions can be used as invasion and metastasis markers, but cannot be used as markers for the degree of histological malignancy of invasive ductal carcinoma.

Clinical application of serum GFAP,NDKA and PARK7 in patients with ischemic stroke / 中华检验医学杂志

Objective To explore the relationship of GFAP, NDKA and PARK7 serum concentrations of patients with IS, and their diagnose and prognosis value in IS. MethodsThe serum concentrations of GFAP, NDKA and PARK7 were detected in 37 IS patients, 28 ICH patients and and 30 healthy persons by ELISA. These indexes of patients were detected in 12 hours, 3 d and 14th day after onset of ischemic stroke. Their neurological injury status were also evaluated by MESSS at corresponding time points, and their activities of daily living were evaluated by BI at 14 d discharge from hospitaL At the same time, the diagnostic efficiency was analysed for IS using the three biomarkers and the combined detection. ResultsIn IS group, the serum concentrations of GFAP in 12 hours, 3rd and 14th day after onset were (5. 49 ±2. 25 )μg,/L, (5. 17 ± 2. 29) μg/L and (5. 96 ± 2.39 ) μg/L, respectively. The serum concentrations of NDKA were 9. 15(6.28 -12.79) μg/L, 9. 13(6.31 - 12.23) μg/L, 9.31(6.40 - 11.83) μg/L respectively,and the serum concentrations of PARK7 were (32. 71 ±6. 34 ) μg/L, (31.23 ±6. 04) μg/L, (32. 79 ±6. 94) μg/L respectively. The serum levels of GFAP, NDKA and PARK were respectively (4. 62 ± 1. 56)μg/L, 4. 24(3. 30 -5. 61 ) μg/L, ( 14. 25 +2. 65) μg/L in healthy control group. The levels in IS groups were remarkably increased compared with the healthy control group except the level of GFAP in the 3rd day (t = 1. 129, P＞0. 05). The levels in other time points were significantly different between patients group and healthy control. t value of GFAP were respectively 2. 642, 1. 870,P＜0. 05; Z value of NDKA were 6. 173, 6.100, 6.278,P ＜0. 01; t value of PARK7 were 14.964, 15.367,16.060, P ＜0. 01. The specificity and sensitivity of the individual detection for diagnosis of IS was 46. 7％ (14/30) and 81.1％( 30/37 ) for GFAP, 90. 0％ ( 27/30 ) and 78.4％ ( 29/37 ) for NDKA, 96. 7％ (29/30) and 97.3％ ( 36/37 )for PARK7. The specificity and sensitivity for combined detection of 3 biomarkers was 96. 7％ (29/30) and 100％ (37/37). The combined detection achieved better specificity and sensitivity. Moreover, the risk of IS with higher level GFAP was 1. 3 times that of the controls ( OR = 1. 300, P = 0. 044 ). The risk of higher NDKA was 1.7 times higher( OR = 1. 668, P = 0. 036 ). The risk of higher PARK7 was 1.8 times higher (OR = 1. 809, P =0. 005 ). The serum levels of GFAP were significantly different between IS and ICH in 12 h(t= 4.097, P=0.000). The serum concentrations of GFAP, NDKA and PARK7 were positively correlated with MESSS score at different time points. In IS, r value were 0. 534, 0. 482, 0. 357 , P ＜ 0. 05at less than 12 h; r value were 0.433, 0.487, 0. 299,P value were 0. 007, 0. 002, 0.073 at 3 d;r value were 0. 394, 0. 200, 0. 084,P value were 0.016, 0. 236, 0.620 at 14 d. And the serum levels of GFAP,NDKA and PARK7 were negatively correlated with BI score at 14th day, r value were -0. 430, -0. 321,-0.076,P value were 0.044,0.050,0.657. Conclusions The concentrations of GFAP, NDKA and PARK7 in serum are closely related with IS. The increased seruro levels of these indexes are risk factors in IS. The detection of these indexes could be helpful for the early diagnosis, timely treatment and prognosis assessment for IS.

Anti-proliferative effect of artesunate on MDA-MB-231 cell and its mechanisms / 中华内分泌外科杂志

Objective To study the effects of artesunate(ART)on estrogen receptor negative breast cancer cell line MDA-MB-231 and its mechanisms.Methods Treated with ART for 3 days,MDA-MB-231 cells proliferation was examined by MTT assay.The morphological and uhrastructural changes of MDA-MB-231 cells were observed under microscope and electronic microscope.Immunocytochemistry was used to detect the expression of Bax,mn23,Bcl-2,and P21 WAFl/CIPl.Results ART treatment led to a dose dependent inhibition of MDA-MB-231 cells.ART could change the morphology and ultrastructure of MDA-MB-231 cens.After treatment with ART(2μmol/L)for 72 hours,immunocytochemical staining showed that the expression of Bax,nm23,and P21WAF1/CIP1 was upregulated in comparison to the control group(P0.05).Conclusions ART shows an anti-proliferative effect on MDA-MB-231 cells.The mechanisms may be related to upregnlation of Bax,nm23 and P21WAF1/CIP1 expression.

Prognostic value of the expression of EGFR and nm23 in nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the prognostic value of the expression of epidermal growth factor receptor (EGFR) and nm23 in patients with nasopharyngeal carcinoma (NPC). Methods From 2003 to 2006, 127 NPC patients who had undergone biopsy before radiotherapy were reviewed retrospectively. All patients received intensity-modulated radiotherapy using 6 MV X-rays combined with platinum-based chemotherapy. Immunohistochemistry SP method was adopted to detect the expression of EGFR and nm23 in NPC biopsy specimens . The relationship between the expression of EGFR and nm23 and survival was analyzed. Results The positive rate of EGFR and nm23 were 80.3% and 47. 2% respectively. The nm23expression was correlated with distant metastasis (χ2=7.03, P = 0. 008 ). The 5-year estimated local control, over-all survival (OS) and disease-free survival (DFS) were 58.3% ,53.5% and 46. 5%. Patients with negative expression of EGFR had a significantly better 5-year OS, DFS (χ2=8.23, P=0.004;χ2=5.25,P=0.022) than those with positive expression. Patients with positive expression of nm23 had a significantly higher 5-year OS (χ2=15.68, P = 0. 000) and DFS (χ2=14. 85, P = 0. 000) than those with negative expression. The clinical stage, EGFR and nm23 expression were independent prognostic factors shown by Cox proportional hazard model (χ2=23.03, 18.33, 39.92, P= 0.000, 0.000, 0.000).Conclusions The EFGR and nm23 expression were correlated with the prognosis in NPC patients.

NM23 protein expression in colorectal carcinoma using TMA (tissue microarray): association with metastases and survival / Expressão da proteína NM23 no carcinoma colorretal preparado em TMA (tissue microarray): associação com metástases e sobrevivência

CONTEXT: NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma. OBJECTIVE: To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma. METHODS: One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001). NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57), vascular invasion (P = 0.85), lymphatic invasion (P = 0.41), perineural infiltration (P = 0.46), staging (P = 0.19), lymph node metastases (P = 0.08), or liver metastases (P = 0.59). Disease-free survival showed significant association (P = 0.01) with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13). CONCLUSIONS: NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma staging, or overall survival. Disease-free survival was higher in patients with increased NM23 expression.

CONTEXTO: O NM23, denominado de gene supressor de metástases, pode estar relacionado com o prognóstico em doentes com carcinoma colorretal. OBJETIVOS: Analisar a expressão do marcador tumoral NM23 relacionando-a com a presença de metástases linfonodais e hepáticas e com a sobrevivência dos doentes operados por carcinoma colorretal. MÉTODO: Cento e trinta doentes operados por carcinoma colorretal foram analisados. Blocos de "tissue microarray" foram obtidos com tecido neoplásico e com mucosa não neoplásica adjacente ao tumor e submetidos ao estudo imunoistoquímico com o anticorpo monoclonal NM23. A imunoexpressão foi avaliada por método semiquantitativo, com contagem do percentual de células coradas. Os resultados encontrados foram relacionados com as características morfológicas e histopatológicas do carcinoma colorretal, presença de metástases linfonodais e hepáticas, estádio e sobrevivência dos doentes. O estudo estatístico foi realizado com os testes de Mann-Whitney, Kruskal-Wallis e exato de Fisher. A análise da sobrevivência foi calculada pelo método de Kaplan-Meier e pelo teste de long-rank. RESULTADOS: A expressão do marcador NM23 foi maior no tecido do carcinoma colorretal do que na mucosa não-neoplásica adjacente (P<0,0001). A expressão da proteína NM23 não apresentou relação com o grau de diferenciação celular (P = 0,57), invasão vascular (P = 0,85), invasão linfática (P = 0,41), infiltração perineural (P = 0,46), estádio (P = 0,19), metástases linfonodais (P = 0,08) ou metástases hepáticas (P = 0,59). A sobrevivência livre de doença mostrou relação significante (P = 0,01) com a intensidade de imunoexpressão da proteína NM23 no tecido do carcinoma colorretal, e a sobrevivência global não mostrou relação com a expressão da proteína NM23 (P = 0,13). CONCLUSÕES: A expressão da proteína NM23 foi mais intensa no tecido neoplásico do carcinoma colorretal do que na mucosa não-neoplásica adjacente. A expressão da proteína NM23 não se relacionou com os aspectos morfológicos, presença de metástases linfonodais ou hepáticas, estádio do carcinoma colorretal ou com a sobrevivência global. A sobrevivência livre de doença foi maior nos doentes com expressão aumentada do gene supressor de metástases NM23.

Expression of CDX-2, PTEN, E-cadherin and NM23 in gastric cancer and its clinical significance / 第二军医大学学报

Objective: To investigate the expression of CDX-2, PTEN, E-cadherin and NM23 in gastric cancer and its clinical significance. Methods: Immunohistochemical S-P method was used to detect expression of CDX-2, PTEN, E-cadherin and NM23 in 77 gastric cancer specimens and 30 normal stomach mucosal tissues, and then the relationship of the expression with clinical pathology parameters was analyzed. Results: The positive rates of CDX-2, PTEN, E-cadherin and NM23 were significantly higher in gastric cancer tissues than those in the normal gastric tissues (P0.05). The l-,3- and 5-year survival rates of CDX-2, PTEN, E-cadherin and NM23 positive patients were higher than those of negative patients(P<0.05, P<0.01). Conclusion: The expression of CDX-2, PTEN, E-cadherin, NM23 in gastric cancer is related to the differentiation, infiltration, lymph node metastasis and TNM stage of gastric cancer, and detecting their expression in gastric cancer may help to judge the prognosis of gastric cancer.