Nucleoside diphosphate kinase (Ndk) is ubiquitous and highly conserved multifunctional key enzyme in nucleotide metabolism. It generates nucleoside triphosphates (NTPs) by transfer of gamma-phosphates from nucleoside triphosphates such as ATP or GTP to nucleoside diphosphate. The formation of an autophosphorylated enzyme intermediate is involved in that mechanism. The phosphate is usually supplied by ATP and Ndk activity in different subcellular compartments. Ndk may regulate the crucial balance between ATP and GTP or other nucleoside triphosphates. Ndk is playing an important role in bacterial pathogenesis and emerging evidences recognize multiple roles of Ndk in host-microbe interaction. Here, I review some examples of the role of Ndk in intra- and extracellular microorganism.
Adenosine Triphosphate ; Guanosine Triphosphate ; Nucleoside-Diphosphate Kinase

OBJECTIVETo discuss the expression and clinical significance of VEGF-C and nm23-H1 in stage II and III colorectal carcinomas.

METHODSSP immunohistochemical staining was employed to determine the expression of vascular endothelial growth factor-C (VEGF-C) and nm23-H1 in the tumor tissues of 110 cases of stage II and III colorectal carcinomas and in the adjacent mucosal tissues of 53 cases as control, and analyze their correlation with cliniopathological features and prognosis.

RESULTSThe positive expression of VEGF-C in the carcinoma tissues was 71.8%, significantly higher than that in the adjacent mucosal tissues (22.6%, P < 0.001). The positive expression of nm23-H1 in the carcinoma tissues was 57.3%, significantly lower than that in the adjacent mucosal tissues (90.6%, P < 0.001). The expression of VEGF-C was significantly correlated with lymph node metastasis (P < 0.05), and the nm23-H1 expression was significantly correlated with lymph node metastasis and pathological type (P < 0.05). The expression of VEGF-C and nm23-H1 did not show a significant correlation with age, gender, primary tumor site, tumor size and depth of invasion (P > 0.05). The VEGF-C expression was negatively related with nm23-H1 expression in colorectal carcinoma (r = -0.361, P < 0.001). The median overall survival (MOS) and median disease free survival (MDFS) of 110 patients with colorectal carcinoma were 55 and 48 months, respectively. The colorectal patients with different VEGF-C and nm23-H1 expression showed significant differences in the 5-year OS rate and 5-year DFS rate (P < 0.001). The patients with negative VEGF-C expression and positive nm23-H1 expression had a better prognosis.

CONCLUSIONSThe joint detection of VEGF-C and nm23-H1 expression is very promising in prediction of the prognosis of patients with stage II and III colorectal carcinoma. However, whether it can be used as a marker in prognosis judgment needs further investigation.

Colorectal Neoplasms ; diagnosis ; metabolism ; Humans ; Lymphatic Metastasis ; diagnosis ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Prognosis ; Vascular Endothelial Growth Factor C ; metabolism

To verify the differential expression of non-metastasis cell 3 (NME3) protein in HL-60 cells when they were induced to differentiate into monocyte and granulocyte like cells, and study its value in diagnosis of acute myeloid leukemia, all-trans retinoic acid (ATRA) and a new steroidal drug NSC67657 were employed to induce acute myeloid leukemia HL-60 cells into monocyte and granulocyte like cells. Then the cell differentiating direction was observed by chemical staining, the degree of differentiation was determined by surface antigen CD11b/CD14 detection, and the apoptosis was excluded by phosphatidylserine valgus analysis, by which cellular differentiating model was constructed. Furthermore, RT-PCR and Western blot were employed to verify the differentially expression of NME3 before and after differentiation of HL-60 cells. At last, samples from bone marrow nucleated cells of 26 patients with myeloid leukemia, which were diagnosed definitely by clinical doctors, and 5 normal people were chosen. Then the expressing trend of NME3 protein in these testing groups was analyzed by means of comparison. The results showed that ATRA (2 µmol/L for 5 d) and NSC67657 (10 µmol/L for 5 d) could induce HL-60 cells to differentiate into monocyte and granulocyte like cells above 90% without cell apoptosis. The expression of NME3 gene and protein were down-regulated by the inducers, which was accorded with the screening results that was got using proteomics technology in the former research. The expression of NME3 protein in bone marrow from acute myeloid leukemia patients was elevated significantly as compared to normal persons. It is concluded that the expression level of NME3 protein is down-regulated after cellular differentiation, according with the changing trend in leukemia patients, which imply that NME3 protein may be a potential biomarker for diagnosis of acute myeloid leukemia.
Adolescent ; Adult ; Aged ; Bone Marrow ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Mesylates ; pharmacology ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Steroids ; pharmacology ; Tretinoin ; pharmacology ; Young Adult

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.
Animals ; Carcinoma, Hepatocellular/*enzymology/genetics/pathology ; Cell Line ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; Humans ; Liver/*enzymology/metabolism/pathology ; Liver Neoplasms/*enzymology/genetics/pathology ; Mice ; Mice, Nude ; NIH 3T3 Cells ; NM23 Nucleoside Diphosphate Kinases/*genetics/metabolism

OBJECTIVETrastuzmab combined therapy has been recommended as standard therapy for HER-2-positive breast cancer. However, more than 70% HER-2-positive cases do not recur and might thus be with overtreatment risk. The aim of this study was to explore the significance of TIMP-1 and nm-23 expression in identifying the good prognosis subtype in HER-2-positive breast cancer.

METHODSOne hundred and sixty-five cases of HER-2-positive breast cancer treated in Tianjin Medical University Cancer Hospital from Jan. 1987 to Dec. 1988 were studied. Expressions of TIMP-1 and nm-23 were detected by immunohistochemistry and the correlation with clinicopathologic characteristics and long-term outcome was analyzed.

RESULTS53.3% (88/165) of TIMP-1 and 72.7% (120/165) of nm-23 expression were detected in the patients. The TIMP-1-negative patients classified as good prognosis group had a 10-year metastasis free survival (MFS) of 58.4% and 10-year overall survival (OS) of 68.8%, compared with the 10-year MFS of 43.2% (P = 0.041) and 10-year OS of 52.0% in the positive group (P = 0.020). The nm-23-positive patients classified as good prognosis group had a 10-year MFS of 54.2% and 10-year OS of 65.7%, compared with the 10-year MFS of 40.0% (P = 0.049) and 44.1% (P = 0.015) in the negative group. The multivariate analysis showed that expressions of TIMP-1 and nm-23, tumor size and lymph node involvement were independent prognostic factors.

CONCLUSIONSIn HER-2-positive breast cancer, TIMP-1 and nm-23 can be used to further distinguish between low-risk and high-risk subgroups, and they are independent factors in prognosis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; surgery ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Receptor, ErbB-2 ; metabolism ; Survival Rate ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism ; Tumor Burden ; Young Adult

OBJECTIVETo study the chemosensitivity of lung adenocarcinoma cell line A549 cells to liposome-encapsulated paclitaxel after treatment by nm23-H1-small interference RNA (nm23-H1-siRNA) in vitro.

METHODSThe A549 cells were divided into two groups: non-transfected group and nm23-H1-siRNA-transfected group. Western blot analysis was used to detect the expression of nm23-H1. MTT and flow cytometry were used to determine the cell mortality rate, apoptosis rate and cell cycle after liposome-encapsulated paclitaxel treatment in both groups.

RESULTSThe expression of nm23-H1 in A549 cells was significantly decreased after transfection with nm23-H1-siRNA. After treatment for 48 hours with liposome-encapsulated paclitaxel, the cell mortality rate was increased with the increasing concentration of liposome-encapsulated paclitaxel in both groups, but increased higher in the nm23-H1-siRNA-transfected group. When the concentration of liposome-encapsulated paclitaxel was above 5 µg/ml, the cell mortality rate was significantly higher than that in the non-transfected group (P < 0.05). The proportion of apoptotic cells also increased in the nm23-H1-siRNA-transfected group, compared with that of the non-transfected group (t = 3.812, P < 0.05), while the proportion of cells at S and G(2)/M phase decreased after transfection with nm23-H1-siRNA (S phase:t = 8.356, P < 0.05; G(2)/M phase:t = 7.256, P < 0.05).

CONCLUSIONSNm23-H1 is related with the chemoresistance to liposome-encapsulated paclitaxel in lung adenocarcinoma cell line A549 cells. Inhibition of the expression of nm23-H1 by nm23-H1-siRNA can improve the in vitro chemosensitivity of A549 cells to liposome-encapsulated paclitaxel.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Humans ; Lung Neoplasms ; metabolism ; pathology ; NM23 Nucleoside Diphosphate Kinases ; genetics ; metabolism ; Paclitaxel ; administration & dosage ; pharmacology ; RNA, Small Interfering ; genetics ; Transfection

OBJECTIVETo explore the correlation of functional genetic variants in Nme1-509 C>T and TGFβ1-1465 T>C genes to the genetic susceptibility of gastric carcinoma in Fujian province, China.

METHODSA case-control study was conducted in a population in Fujian province. The polymorphism of TGFβ1-509 C>T (rs1800469), Nme1-1465 T>C (rs16949649) in 273 gastric carcinoma patients and 277 cancer-free controls, frequency-matched by age and sex, were analysed by using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Adjusted odds ratios (OR) and 95% confidence evaluation intervals (95%CI) measured by multivariate Logistic regression analysis were adopted in studying the correlation of the gene polymorphism with the susceptibility of gastric cancer.

RESULTSAfter the adjustment using Logistic regression or the potential confounding effects of gender and age, as compared with TT+CT genotype gastric carcinoma patients, the homozygous Nme1-1465CC genotype carriers had a significantly higher risk in lymph node metastasis, with the OR of 2.5 (95%CI 0.08-2.10; P=0.029). There was no association obtained between TGFβ1-509 T>C genotype with the tumor size, cell differentiation, tumor invasion and lymph node metastasis in gastric carcinoma. In the intestinal type gastric carcinoma group, when compared with the wild homozygous Nme1 TT* TGFβ1 CC, Nme1 TC* TGFβ1 TC, Nme1 TC* TGFβ1 TT and Nme1 CC* TGFβ1 TC genotype carriers, there was a significantly decrease of risk in gastric carcinogenesis of 0.42 fold (95%CI 0.54-0.94, P=0.022), 0.32 fold (95%CI 0.42-0.97, P=0.013) and 0.26 fold (95%CI 0.42-0.97, P=0.008), respectively.

CONCLUSIONSThere is a significant relationship between polymorphism of Nme1-1465 T>C and the prognosis of carcinoma of stomach. It also demonstrates that coexistence of Nme1-1465 T>C and TGFβ1-509 T>C genes may provide a synergistic effect of increasing the susceptibility of gastric carcinogenesis.

Case-Control Studies ; China ; Confidence Intervals ; Female ; Genetic Predisposition to Disease ; Humans ; Logistic Models ; Lymphatic Metastasis ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Stomach Neoplasms ; genetics ; pathology ; Transforming Growth Factor beta1 ; genetics

OBJECTIVETo evaluate the relationship of expressions of nucleoside diphosphate kinase (nm23) and proliferating cell nuclear antigen (PCNA), as well as apoptosis, with the prognosis of HCC patients by analyzing their pathological and clinical data.

METHODSThe expressions of nm23 and PCNA were analyzed by immunohistochemistry and the apoptotic phenomena were detected by TUNEL technique in the liver samples from 43 HCC tissues, 39 para-neoplastic tissues, and 10 normal tissues. The mean apoptosis index (AI) and proliferative index (PI) in individual sample were calculated.

RESULTSAs shown by the detection, 32.6% of carcinomas had negative nm23 signal in tumor tissues, whereas all para-neoplastic and normal tissues had positive nm23. The AI in nm23 positive HCC was significantly higher than that in nm23 negative one, with statistical difference (P<0.05). Furthermore, the expressions of nm23, and the values of AI and PI were contrastively analyzed with some main pathological and clinical data of HCC. It revealed that HCC with extrahepatic metastasis showed remarkable correlation with the negative nm23 (P=0.013) and higher PI values of HCC (P=0.015). The disease-free survival in HCC patients with negative nm23 expression was significantly poorer than that in patients with positive nm23 expression.

CONCLUSIONSThese data suggest that expressions of nm23 protein in tumor tissues are correlated with occurrences of metastasis and length of survival of the HCC patients, which may be an indicator for their prognosis.

Adult ; Aged ; Apoptosis ; Biomarkers, Tumor ; biosynthesis ; Carcinoma, Hepatocellular ; enzymology ; mortality ; pathology ; Case-Control Studies ; Cell Proliferation ; Disease Progression ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Kaplan-Meier Estimate ; Liver ; enzymology ; pathology ; Liver Neoplasms ; enzymology ; mortality ; pathology ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; biosynthesis ; Neoplasm Metastasis ; Proliferating Cell Nuclear Antigen ; biosynthesis

This experimental study sought to find out the inhibitory effects of Ad-GFP-nm23-H1 on proliferation and metastasis of human colorectal carcinoma cell line Lovo, and, further, to gain an insight into some theoretical and methodical basis for instituting nm23-H1 gene therapy of cancers. MTT assay and Transwell chamber were used to detect the rates of proliferation and invasion as well as the adhesion of Lovo cells in vitro. The results demonstrated that the proliferation inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 84.9% +/- 1.51%, 48.5% +/- 7.23% and 22.5% +/- 5.47%, that the adherence inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 70.3% +/- 2.40%, 60.1% +/- 5.68% and 18.5% +/- 3.61%, and that the invasiveness inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 83.2% +/- 5.71%, 52.2% +/- 6.94% and 28.1% +/- 8.21%. These data suggested that Ad-GFP-nm23-H1 exerted significant inhibitory effects on the proliferation and metastasis of human colorectal carcinoma cell line Lovo in a dose-dependent way.
Adenoviridae ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Genetic Therapy ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; NM23 Nucleoside Diphosphate Kinases ; genetics ; metabolism

OBJECTIVETo explore the differences in the survival, adhesion and diffusion capacity between different carcinomas originating from different immunosurveillance in the same patient.

METHODSThe expressions of survivin, MMP2, TIMP1, CD44, and nm23 proteins were detected immunohistochemically in a patient with acute lymphoblastic leukemia and lymphoma after allogeneic blood stem cell transplantation.

RESULTSSurvivin, MMP2, TIMP1, CD44, and nm23 proteins were positive in acute lymphoblastic leukemia samples obtained before transplantation and negative in the lymphoma tissue occurring after the transplantation.

CONCLUSIONThe expressions of survivin, MMP2, TIMP1, CD44, and nm23 proteins vary between the two carcinomas originating from different immunosurveillance in the same patient.

Adult ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Hyaluronan Receptors ; metabolism ; Inhibitor of Apoptosis Proteins ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; etiology ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Neoplasms, Second Primary ; metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism