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 investigate the feasibility of plasmid nm23-h1 transfection on high metastatic potential adnoid cystic carcinoma (ACC-M) cell line mediated by cationic lipid.

METHODSACC-M cell were implanted in the maxillofacial region in each of 40 BALB/c nude mice. After the tumor growth to 1 cm in diameter, 0.1 ml Lipofctamine-nm23-hl plasmid complex were injected intratumorally in 10 mice, 3 days after the first injection, 10 mices injected for twice, 10 mice as plamid-blank control, another 10 mice were injected 0.2 ml complex, 2, 3, 7days after the injection, the mice were killed and the specimen for HE and immunohistological chemistry study.

RESULTSnm23-h1 expression initiated in the tumor cells 3 days after the complex injection, 7 days later, the expression level increased accompanying with extracellular matrix increase, twice injection and multiple channel injection would gain better nm23-h1 expression than once injection and single-channel injection respectively.

CONCLUSIONCationic lipid mediated nm23-h1 plamid transfecting adnoid cystic carcinoma can gain small range positive expression, but the results give little prospect for further clinical treatment in such a manner.

Animals ; Carcinoma, Adenoid Cystic ; Humans ; Lipids ; Mice ; Mice, Nude ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; Plasmids ; Transfection

Cancer metastasis, a complex and sequential network of cellular events involved in the migration and establishment of malignant cells from original site to distant foci, is an important and significant contributor to morbidity and mortality of cancer patients. Despite the clinical importance of cancer metastasis, its molecular and biochemical mechanism remains unclear. The identification of tumor suppressor gene confirmed that metastasis might involve the functional loss of genes that maintain the cellular differentiation optimally. Metastasis suppressor is defined by the ability to reduce the metastatic property of cancer cells without affecting its tumorigenesis. Since NM23 was first identified in 1988 as a metastasis suppressor, several metastasis suppressor genes have been identified and characterized. In this article, we review the complex and multi-step process of cancer metastasis and describe the recent progress of metastasis suppressors in the studies of identified. Consequently, we hope to introduce the new therapeutic target for the metastasis suppressors in cancer patients.
English Abstract ; *Genes, Tumor Suppressor ; Humans ; Neoplasm Metastasis/genetics/*physiopathology ; Nucleoside-Diphosphate Kinase/genetics/metabolism

OBJECTIVETo study the expression of p16 and nm23 genes in salivary gland tumors and the relation of P16 and nm23 proteins with fumorigenesis of salivary gland tumors.

METHODSExpression of P16 and nm23 proteins was examined by SABC immunohistochemical method in 39 cases of paraffin blocks of normal salivary gland tissues and salivary gland tumors.

RESULTSP16 and nm23 protein positive staining were mainly found in the cytoplasm and cytoblast of all salivary gland tissues. Positive rate of P16 protein expression was 76.9% (10/13) and 40.9% (9/22) in benign and malignant salivary gland tumors, respectively. There was significant difference between P16 protein expression of benign and malignant tumors by chi 2 test (P < 0.05). mm23 protein positive staining was found in 84.6% (11/13) and 45.5% (10/22) of benign and malignant tumors respectively. The expression of nm23 protein in benign and malignant tumors was significantly different (P < 0.05). There was no correlation of the expression of P16 and nm23 in salivary gland tumors was found (P > 0.05).

CONCLUSIONp16 and nm23 genes may play an important role in different sides in salivary gland tumorigenesis and the reduce of the expression of p16 and nm23 genes may contribute to the generation of malignant salivary gland tumors.

Adenoma, Pleomorphic ; genetics ; metabolism ; Carcinoma, Mucoepidermoid ; genetics ; metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; biosynthesis ; genetics ; Humans ; Immunohistochemistry ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; Protein Biosynthesis ; Proteins ; genetics ; Salivary Gland Neoplasms ; genetics ; metabolism ; Salivary Glands ; metabolism

OBJECTIVETo transfect nm23-H1 into the BcaCD885 cell lines in order to get safe high-efficiency and low-toxicity, and to find out whether nm23-H1 could affect the invasion and metastases ability of BcaCD885 cell lines.

METHODSLipofect was used to transfect nm23-H1 into BcaCD885 cell lines; immunohistochemistry was used to detect the difference expression of nm23-H1 between transfected and non-transfected cell lines; then transwell-room and wash way were used to detect the difference of invasion and metastases ability between transfected and non-transfected cell lines.

RESULTSPCMV-NEO-BAM system gave the stability expression of nm23-H1; there was significant different NDPKA expression between transfected and non-transfected BcaCD885 cell lines; the invasion and metastases ability of transfected BcaCD885 cell lines decreased obviously.

CONCLUSIONnm23-H1 can inhibit the metastases of BcaCD885 cell lines significantly.

Cell Adhesion ; physiology ; Cell Movement ; physiology ; Genetic Vectors ; genetics ; Humans ; Monomeric GTP-Binding Proteins ; genetics ; metabolism ; Mouth Neoplasms ; genetics ; pathology ; physiopathology ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; Transcription Factors ; genetics ; metabolism ; Transfection ; Tumor Cells, Cultured

OBJECTIVETo explore nm23 gene mRNA expression and its clinical significance in acute leukemias (AML).

METHODSThe levels of nm23-H1 and nm23-H2 transcripts in 22 patients with acute myeloid leukemia (AML), 9 AML in complete remission (AML-CR), 12 acute lymphoblastic leukemia (ALL) and 4 chronic myeloid leukemia in chronic phase (CML-CP) were assayed by reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSThe expression of nm23-H1 in AL especially in AML-M4 and AML-M5 was significantly higher than that in normal blood cells. An analysis of correlation between nm23 expression and clinicopathological parameters showed that increased nm23-H1 mRNA levels were associated with some poor-prognostic factors such as extramedullary infiltration, high white blood cell count (WBC), high lactate dehydrogenase (LDH) activity and high CD(7) expression, while inversely correlated with t(8; 21) and t(15; 17) which had a good-prognostic effect. The expression of nm23-H1 in AML patients in CR was significantly decreased compared with those untreated.

CONCLUSIONnm23-H1 was overexpressed in AL, especially in AML-M4 and AML-M5. High expression of nm23-H1 may be a poor prognostic factor.

Adult ; Female ; Gene Expression ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo assess the significance of expression of sialylated carbohydrate antigens and nm23-H1 gene in metastasis and prognosis of breast cancer.

METHODSTissue specimens from 102 cases of primary breast cancer were stained with antibodies against sialyl Lewis A (SleA) and salyl Lewis X (SleX), and nm23-H1 proteins by immunohistochemical methods.

RESULTOf the 102 cases, the positive cases of SleA and SleX were 24.5% (25/102) and 59.89% (61/102),respectively; the reduced expression of nm23-H1 was showed in 37.3% (38/102) of the cases. The positive expression of SleX and the reduced expression of nm23-H1 gene were significantly associated with lymph node involvement. Among the 100 patients who underwent curative surgery, the disease-free survival rate was significantly correlated with nm23-H1 and SleX expression, respectively,but not with SleA expression. In multivariate analysis using Cox regression model, combination assay of nm23 H1 and SleX expression emerged as independent prognostic factors.

CONCLUSIONThese results suggest that nm23-H1 gene and SleX may be involved in the metastatic process in human breast cancer, and immunohistochemical detection of SleX and nm23-H1 may be used as a biologic marker of prognosis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; chemistry ; genetics ; mortality ; Female ; Gangliosides ; analysis ; Humans ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; genetics ; Oligosaccharides ; analysis ; Prognosis ; Survival Rate

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; genetics ; mortality ; Female ; Genes, Tumor Suppressor ; Humans ; Lung Neoplasms ; diagnostic imaging ; genetics ; mortality ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; genetics ; Prognosis ; Tomography, X-Ray Computed

OBJECTIVETo investigate the relationship between expression of cell adhesion molecular CD44, epithelial cadherin (E-cad) and metastatic suppressor gene nm23-H1 as well as the clinicopathologic features including cell differentiation, invasion and metastasis of thyroid follicular-derived carcinoma.

METHODSForty two (42) thyroid follicular carcinomas (FTC) and 54 papillary carcinomas (PTC) were collected for studying the expression of CD44, E-cad and nm23-H1 using immunohistochemical staining.

RESULTSNeoplastic epithelium and infiltrating lymphocyte expressed CD44 in an intense plasma membrane pattern. CD44 expression rates in poorly differentiated FTC (80%) and PTC cases with metastasis (78%) were significantly higher than those of well-differentiated FTC cases (64%) and PTC without metastasis cases (59%) respectively. Thyroid carcinoma tissue was positive for E-cad and nm23-H1 in a cytoplasm pattern. Well-differentiated FTC presented a higher E-cad and nm23-H1 expression rate than poorly-differentiated FTC, but both had a lower expression rate than that of PTC (70% and 76%, P < 0.01). The expression rate and intensity of E-cad and nm23-H1 were lower and less in metastatic PTC than those in primary PTC. Expression rate of CD44 (72%) in thyroid follicular-derived carcinoma was higher than those of E-cad (54%, P < 0.01) and nm23-H1 (61%, P < 0.05). E-cad expression was adversely correlated with that of nm23-H1 (chi(2) = 15.75, P < 0.011, r = 0.522 2). There was a reverse relationship between expression of CD44 and E-cad or nm23 (P > 0.05).

CONCLUSIONSCell differentiation degree in FTC and metastasis in PTC have positive correlation with the expression of E-cad and nm23, but have a reverse correlation with the expression of CD44. There was a relationship between expression of CD44, E-cad, nm23 and the characteristics of the degree of differentiation, metastatic potential and the prognosis of thyroid follicular-derived carcinoma.

Adult ; Aged ; Cadherins ; analysis ; Carcinoma, Papillary, Follicular ; chemistry ; pathology ; Female ; Humans ; Hyaluronan Receptors ; analysis ; Immunohistochemistry ; Male ; Middle Aged ; Monomeric GTP-Binding Proteins ; analysis ; NM23 Nucleoside Diphosphate Kinases ; Neoplasm Invasiveness ; Nucleoside-Diphosphate Kinase ; Thyroid Neoplasms ; chemistry ; pathology ; Transcription Factors ; analysis

OBJECTIVETo study the regulation and effect of the expression of nm23-H1 gene in different processes of regional lymph node metastases of oral squamous cell carcinomas(OSCC).

METHODSBy immunohistochemical analysis in 200 paraffin-embedded tissues of OSCC and Western Blot in 9 fresh tissues of OSCC using a monoclonal antibody, the expression of nm23-H1/NDPK-A were detected in dividing groups accompanied with the clinical and pathological data of cervical lymph node metastases and modes of invasion.

RESULTSThe rates of negative expression of nm23-H1/NDPK-A had significant differences between metastatic cases(34/81) and non-metastatic cases(15/119). The nm23-H1/NDPK-A negative group showed higher frequency of lymph node metasteses (P < 0.01). In the different metastatic processes, There were significantly differential expressions of nm23-H1/NDPK-A among stage N0, N1 and N2(P < 0.01), distinct involved quantities of lymph nodes (P < 0.01), dissimilar metastatic involved levels(P < 0.05), definite modes of invasion(P < 0.01) and different cell differentiations(P < 0.01). There were much higher negative expressions in those cases of N1 stage(23/38), only one lymph node to be involved(23/39), metastasized to submandibular nodes or/and superior deep cervical nodes(17/28 and 12/29, respectively), IV c types of invasion(33/54) and poor differentiations(9/19).

CONCLUSIONThe results indicated that nm23-H1/NDPK-A played an more important role in switching the initial metastases formation than in influencing the later metastases spread because the negative expressions of nm23-H1/NDPK-A in solid tumors of OSCC would induce the formation of high metastatic cellular subpopulations. It was also confirmed that nm23-H1 gene might be a metastatic suppressor and may be useful in predicting the initial lymph node metastases in OSCC.

Carcinoma, Squamous Cell ; genetics ; pathology ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Lymphatic Metastasis ; Mouth Neoplasms ; genetics ; pathology ; NM23 Nucleoside Diphosphate Kinases ; Nucleoside-Diphosphate Kinase ; Protein Biosynthesis ; Proteins ; genetics