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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.
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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.
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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.
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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.
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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.
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Objective To investigate the effects of transcatheter arterial chemoembolization(TACE) on the expression of nm23, tissue inhibitor of metalloproteinase-2 (TIMP-2) and extrahepatic metastasis in hepatocellular carcinoma (HCC). Methods The specimens were collected from resectable HCC in 72 patients. Patients were divided into two groups. In one group, TACE was performed before tumor resection (Group A, n=36). In another group, the tumors were resected directly without preoperative TACE (Group B, n=36). The expression and distribution of nm23, TIMP-2 in the tumor tissue and liver parenchyma in the two groups were compared. All patients were followed up for 24 months,and the incidence of extrahepatic metastasis was compared between the two groups. Chi-square test was applied to compare the expression levels of nm23-H1 and TIMP-2. Results The number of cases of strong, moderate and no expression of nm23 were 24, 6 and 6 cases in group A respectively, and were 9, 6 and 21 cases in group B. Statistical differences were found between the two groups(X~2=15.52, P<0.01). The number of cases of strong, moderate and no expression of TIMP-2 were 21,3 and 12 cases in group A respectively, and were 9, 9 and 18 cases in group B. Statistical differences were demonstrated between them (X~2=9.00, P<0.05). There were 13 cases in group A and 15 cases in group B being diagnosed to have extrahepatic metastasis within 24- month period of follow up, but there was no significant difference between the two groups(X~2= 0.23, P>0.05). Conclusions TACE could enhance the expression of nm23-H1 and TIMP-2 in tumor tissues. Therefore, the potential of metastasis of tumor cells might be prohibited by TACE.
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Objective Through studying the apoptosis induced by stichopus japonicus acid mucopoly saccharide in the hepatocellular carcinoma cell line HepG2 in vitro, analysing the expression of Bcl-2 and nm-23in HepG2, to provide the theory foundation and its feasibility on whether it can be used for the chemotherapy of hepetocellular carcinoma. Methods The cells of HepG2 were cultured in vitro and treated with SJAMP at different doses(0.25,0. 5,1.0,2.0,4.0 g/L). MTT was used to observe the inhibitory effects of SJAMP on cell growth, Western blotting was used to detect apoptosis, and the apoptosis related change of expression of protein Bcl-2 and nm23-H1. Results (1) MTT identified that SJAMP produced an obvious time-and-dose-dependent inhibitory effect on the HlepG2 cells. (2) Western blot showed that SJAMP could induce the apoptosis of HepG2 cells through changing the expression of the protein of Bcl-2 and nn23-H1 (P<0.05). Conclusion (1)SJAMP produced obvious inhibitory effects on HepG2 cells and induce HepG2 apoptosis. (2)SJAMP can enduce the anti-tumor function in the method of changing the expression of protein Bcl-2 and nm23-H1.
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Objective To Study the expression and clinical meaning of nm23-H1,c-Met and survivin protein in gastric carcinoma tissue.Methods Expression of nm23-H1,c-Met and survivin protein in 50 paraffin block samples of gastric carcinoma were detected by S-P immunohistochemistry technology.The relationship of expression to tumor differentiation degree,infiltration depth,lymph node metastasis,TNM stage,tumor metastasis and reeidivation were analyzed.Results The positive expression rates of nm23-H1,c-Met and survivin protein were 46%,72% and 80%,low nm23-H1 protein expression and high c-Met protein expression correlated tightly with TNM stage and lymph node metastasis of gastric carcinoma,high survivin protein expression correlated tightly with differentiation degree,TNM stage and lymph node metastasis of gastric carcinoma,there was a inverse correlation between nm23-H1 protein expression and survivin,but a direct correlation between c-Met and survivin.Conclusions Low nm23-H1 protein expression and high c-Met and survivin expression has important guidance significance of making a early diagnosis and judging prognosis.Selective gene therapy guided by these may be helpful.
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Objective To study the relationship of expression of metastasis suppressor gene nin23-H1 protein in gastric carcinoma tissue and tumor infiltration and metastasis.Methods The expression of metastasis suppressor gene nm23-H1 protein in 50 gastric carcinoma tissues was detected by SP immunohistocbemistry tech-nology.Results Correlations were presented among expression of nm23-H1 protein, infiltrate grade of gastric carcinoma, lymph node metastasis and TNM stage.Conclusions Expression of nm23-H1 may suppress infiltra-tion and metastasis of gastric carcinoma, Low expression of nm23-H1 protein may be of great reference value in judgement of tumor progression, metastasis and reeidivation.
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OBJECTIVE: Cancer metastasis is a complex process involving a sequential series of multi-step genetic events, which produces an imbalance between stimulatory and inhibitory genes for metastasis. Presently, we examined the expression of metastatic tumor antigen 1 (MTA1) and nonmetastatic protein 23 homologue H1 (nm23-H1) proteins in metastasized epithelial ovarian cancer cells. METHODS: Fifty-one primary epithelial ovarian tumors and corresponding lymph nodes (LNs) were examined immunohistochemically for expression of MTA1 and nm23-H1. Expression of these proteins was statistically evaluated. RESULTS: The frequency of MTA1 expression was 30.3% (10/33) in stage III/IV LNs but was absent (0/18) in stage I/II LNs (p=0.01). MTA1 expression was observed in 50% (6/12) of metastasizing LNs but in only 10.3% (4/39) of non-metastasizing LNs (p=0.01). In contrast with MTA1, nm23-H1 expression was evident in 16 of 18 (88.9%) stage I/II ovarian cancer tissue samples but only in 20 of 33 (60.6%) stage III/IV tissues (p=0.05), and nm23-H1 production was also observed in 75.6% (34/45) of ovarian cancer tissue with residual tumors under 2 cm in diameter, but in 2/6 (33.3%) of cancer tissue with residual tumors exceeding 2 cm in diameter (p=0.03). CONCLUSION: The degree of expression and imbalance of MTA1 and nm23H1 are correlated with ovarian cancer LN metastasis.
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Lymph Nodes , Lymphatic Metastasis , Neoplasm Metastasis , Neoplasm, Residual , Neoplasms, Glandular and Epithelial , Ovarian Neoplasms , ProteinsABSTRACT
Objective:To construct prokaryotic expression vector of mutant nm23-H1(S120G,S120G-P96S, S44A), and then express and purify the proteins. Methods: Mutant nm23-H1 fragments were amplified by PCR. The prokaryotic expression vectors of pET28a-nm23-H1 were constructed by gene recombination technique and verified by restriction enzyme analysis and sequencing. The positive clones were transformed into E. coli BL21(DE3) and soluble analysis of the expression was conducted in these systems. The proteins were purified by nickel column chromatography and identified by Western blot. Results: The sequences and open read frames of all the pET28a-nm23-H1 were completely correct. After transforming, these plasmids could express the target proteins. The protein production was very high. Among these mutant proteins, S44A was soluble expression and S120G was partly soluble. However, S120G-P96S was mostly in the inclusion bodies. The molecular weight of these mutant proteins was 20 kD detected by Western blot, which was as the same as the objective protein. Conclusion: We have succeeded in constructing the prokaryotic expression vectors of pET28a-nm23-H1(S120G, S120G-P96S, S44A), and the S120G and S44A proteins can be used in following studies. However, S120G-P96S protein which expressed in this system may not be suitable for the following studies.
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The metastasis-suppressing role of the nm23 gene in the metastatic spread of malignant tumor is still debated. We examined the nm23-H1 protein expression and gene mutation in non-Hodgkin's lymphomas to compare with the clinicopathologic parameters. The expression of nm23-H1 protein was immunohistochemically examined in 150 cases of non-Hodgkin's lymphomas; 85 diffuse large B cell lymphomas (DL-BCL), 18 marginal zone B cell lymphomas (MZL), 3 mantle cell lymphomas, 25 peripheral T cell lymphomas, not otherwise specified (TCLNOS), and 19 NK/T cell lymphomas (NK/T). Eighty-one cases (58 DLBCL, 6 MZL, 4 TCLNOS, and 13 NK/T) were studied for nm23-H1 gene mutation in exon 1 to 5. The high expression of nm23-H1 protein was associated with the high IPI score (p=0.019) and the low survival rate of the patients (p=0.0039). The gene mutation of nm23-H1 was detected in 10.3% of DLBCL and 30.7% of NK/T; but none in MZL and TCLNOS. The mutation was found in exon 1 in 5 cases, exon 2 in two cases, exon 4 in one case and both exon 1 and 2 in two cases. Our results suggest that the expression of nm23-H1 protein can be used as a poor prognostic marker in non-Hodgkin's lymphomas, and the mutational change of gene may operate in the lymphomagenesis.
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Middle Aged , Male , Humans , Female , Tissue Array Analysis , Survival Analysis , Prognosis , Polymorphism, Single-Stranded Conformational , Nucleoside-Diphosphate Kinase/genetics , Mutation/genetics , Lymphoma, T-Cell/genetics , Lymphoma, Non-Hodgkin/genetics , Lymphoma, Mantle-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, B-Cell/genetics , Immunohistochemistry , DNA Mutational Analysis , Base SequenceABSTRACT
Objective To investigate the ex pr ession of nm23-H1 protein and proliferating cell nuclear antigen (PCNA) in huma n glioma cells. Methods Expression of nm23-H1 and PCNA in 53 br ain gliomas were detected by immunohistochemistry. Results The immunohistochemistry staini ng of nm23-H1 protein in low-grade astrocytomas (grades Ⅰ and Ⅱ) was significantly higher than that in high-grade astrocytomas (grades Ⅲ and Ⅳ). The immunohistochemistry staining of PCNA in high-grade astrocytomas was s ignificantly higher than that in low-grade astrocytomas. Conclusion The lower expression of nm23-H1 protein and the higher expression of PCNA are correlated with the pathological grade of glioma cells. The expression of nm23-H1 may be used as a hopeful marker for predicting the metastastic potential of gliomas.
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Objective To explore the relationship between the loss of the heterozygosity of nm23-H_1 and the lymph node metastasis in no-small-cell lung cancer (NSCLC). Methods The loss of the heterozygosity of nm23-H_1 gene of cancer tissue and peri-cancerous tissue was detected in 39 patients with NSCLC by Southern blotting. Results The heterozygosity gene of nm23-H_1 is 7.6 kb and 2.3 kb. The LOH rate of the patients with lymph node metastasis (48%, 12/25) was higher than those without lymph node involvement (8%, 1/11) (P
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0.05).Conclusion The increase in the amount of nm23H1 protein expression can play an important role in restraining metastasis of squamous cell lung carcinoma.The heredity instability(MSI and LOH) of nm23H1 gene may not be implicated in expression of the gene and pathogenesis and progression of squamous cell lung carcinoma.
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Purpose:To study the relation between regional lymph node metastasis and nm23 H 1 protein expression and DNA ploidy of esophageal squamous cell carcinoma patients. Methods:Flow cytometry was used to analyze nm23 H 1 protein and DNA ploidy in surgical specimens from the patients with esophageal carcinoma. The object tissues included: the primary tumor tissue, the pericancerous mucosa, the incisional margin and the regional lymph node. Results:There were obvious differences between nm23 H 1 protein expression in lymph node metastasis positive and negative groups, primary tumor tissue and pericancerous mucosa, cancer tissue and the incisal margin( P 0.05).The differences of DI were distinct between cancer tissue and the pericancerous mucosa, cancer tissue and the incisal margin, cancer tissue and the lymph node( P 0.05).In corresponding tissues of lymph node metastasis positive and negative groups, nm23 H 1 protein expression was different( P 0.05). As to DI, it was different only among pathological grades( P 0.05). Conclusions:nm23 H 1 protein higher expression can produce certain inhibitory effect on metastasis of esophageal carcinoma. Combining DNA ploidy detection can help to understand the biological behavious and deduce the prognosis of esophageal carcinoma.
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Objective: To study the expression of CD15 mRNA,CD44v6 mRNA and nm23H1 mRNA in colon carcinoma and its relationship with clinical pathological parameters and prognosis of colon carcinoma. Methods: In situ hybridization was used to detect the expression of CD15 mRNA, CD44v6 mRNA and nm23H1 mRNA in 90 cases of colon carcinoma, and 53 cases were followed up for more than 5 years. Results: In 90 cases of colon carcinoma, the expression of CD15 mRNA,CD44v6 mRNA and nm23H1 mRNA were 84.4%,68.9%,66.7%, respectively. The high level expression of CD15 mRNA, CD44v6 mRNA and the low level expression of nm23H1 mRNA were positively corelated with the Dukes staging,serosa infiltration,lymph node and liver metastasis of colon carcinoma.The expression of CD15 mRNA in colon carcinoma was positively associated with that of CD44v6 mRNA and negatively with that of nm23H1 mRNA. Conclusion: CD15 mRNA,CD44v6 mRNA and nm23H1 mRNA play an up-regulation and a down-regulation role, respectively, and have a synergistic action in metastasis of colon carcinoma. CD15 mRNA can be used as a new biological index to predict the invasive potential of colon carcinoma and objectively evaluate the prognosis of patients.
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Objective:To clone human nm23-H1 c DNA gene and to recombine it into adenovirus vector.Methods:Nm23 -H1cDNA fragment was amplified from human liver by reverse transcription-polym erase chain reaction(RT-PCR) and cloned into pMD18-T plasmid. The gene was exa mined by sequencing. Then pAd-Shuttle-CMV vector containing nm23-H1 was const ructed. Results:The results showed that the gene fragment cloned in pMD18-T was coincident with the sequence of nm23-H1.A pAd-Shuttle -CMV v ector containing nm23-H1 gene with correct order was con firmed by Kpnl digestion. Conclusion:nm23-H1 may be cloned into recombined adenovirus vector pAd-Shuttle-CMV.
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Purpose:To study the expression of CD 44 V 5 and Nm23 H 1 gene products and their significance in esophageal cancer patients.Methods:The expression of CD 44 V 5 and Nm23 H 1 in 85 cases of formalin fixed, paraffin embedded specimens of esophageal cancer were measured by immunohistochemistry S P method. Fifty cases were followed up for 3 years after operation.Results:①The positive expression rate of CD 44 V 5 and Nm23 H 1 was 61.2% 、57 6%, respectively in esophageal cancer.②Overexpression of CD 44 V 5 gene products were closely related with the invasive extent , histopathologic classification , TNM stage ,lymph node metastasis(LNM) and prognosis of Ec( P
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砄bjective:To investigate the variation of nm23 H1 gene structure and its expression in oral squamous cell carcinoma (OSCC) and to study the relationship between nm23 H1 expression and OSCC metastasis to neck lymph nodes.Methods: nm23 H1 gene in the samples of 30 cases of OSCC,7 of normal oral mucous tissue,human OSCC cell line TSCCa and human oral metastatic cancer cell line GNM was extracted and amplified by PCR. PCR products were investegated with SSCP analysis; nm23 m RNA level in the samples was studied by in situ hybridization.The relationship between mRNA expression and metastasis to neck lymph nodes was analyzed statistically.Results: All samples showed no change in nm23 H1 gene structure except deletion in one case of OSCC;7 out of 9 cases with metastasis to neck lymph nodes showed no hybridization signal of nm23 H1 mRNA,however,only 5 were found no nm23 H1 mRNA in 21 cases without metastasis,positive rate of nm23 H1 expression in GNM cells was lower than that in TSCCa (41.2% versus 63.1%);The expression of nm23 H1 gene showed significant negative relationship with neck lymph nodes metastasis ( P