Role of Trypanosoma cruzi nucleoside diphosphate kinase 1 in DNA damage responses

BACKGROUND NME23/NDPKs are well conserved proteins found in all living organisms. In addition to being nucleoside diphosphate kinases (NDPK), they are multifunctional enzymes involved in different processes such as DNA stability, gene regulation and DNA repair among others. TcNDPK1 is the canonical NDPK isoform present in Trypanosoma cruzi, which has nuclease activity and DNA-binding properties in vitro. OBJECTIVES In the present study we explored the role of TcNDPK1 in DNA damage responses. METHODS TcNDPK1 was expressed in mutant bacteria and yeasts and over-expressed in epimastigotes. Mutation frequencies, tolerance to genotoxic agents and activity of DNA repair enzymes were evaluated. FINDINGS Bacteria decreased about 15-folds the spontaneous mutation rate and yeasts were more resistant to hydrogen peroxide and to UV radiation than controls. Parasites overexpressing TcNDPK1 were able to withstand genotoxic stresses caused by hydrogen peroxide, phleomycin and hidroxyurea. They also presented less genomic damage and augmented levels of poly(ADP)ribose and poly(ADP)ribose polymerase, an enzyme involved in DNA repair. MAIN CONCLUSION These results strongly suggest a novel function for TcNDPK1; its involvement in the maintenance of parasite's genome integrity.

Nucleoside Diphosphate Kinase from Microorganisms

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.

Transcription analysis of TIMP-1 and NM23-h1 genes in glioma cell invasion / Análise transcricional dos genes TIMP-1 e NM23-H1 na invasão celular em astrocitoma difuso e glioblastoma multiforme

PURPOSE: To evaluate using transcription analysis the presence and importance of two genes: NM23-H1 and TIMP-1 on control of tumor cell invasion in diffuse astrocytomas (WHO II) and glioblastoma multiforme (WHO IV). METHOD: Northern blot analysis of NM23-H1 and TIMP-1 was performed. Eight diffuse astrocytomas and 19 glioblastomas (WHO IV) were analyzed to determine if TIMP-1 and NM23-H1 were candidates to inhibition of tumor cell invasion quantitated RNA levels. The samples were collected directly from operating room. Total cellular RNA was extracted from frozen tissue samples using guanidinium-isothiocyanate and cesium chloride gradients. Total RNA (10 mg per sample) from tumor tissue were size fractionated through 1 percent agarose-formaldehyde gel and transferred to nylon filters and then hybridized to 32P-labeled DNA probes and placed for autoradiography. Levels of specific RNAs were determined by computer-assisted laser densitometry. Blot filters were sequentially hybridized to nm23 and TIMP-1 probes in addition to GAPDH, as a control. Statistical analyses were carried out according to t-test for equality of means. RESULTS: NM23-H1 were detected in each sample, however it did not correlate with malignancy and invasiveness. On the other side TIMP-1 gene expression showed a clear correlation between low expression and invasiveness. CONCLUSION: The data suggest that TIMP-1 is an inhibitor of high grade gliomas invasion. NM23-H1 was present in the entire gliomas sample, but it did not vary in diffuse astrocytomas and glioblastomas.

OBJETIVO: Comparar através da análise da expressão dos níveis de RNA, a presença e a relevância dos genes NM23-H1 e TIMP-1 no controle da invasão celular tumoral dentro do tecido cerebral normal em: astrocitoma difuso (OMS II) e glioblastoma multiforme (OMS:IV). MÉTODO: Análise em "Northern blot" dos genes NM23-H1 e TIMP-1. Oito astrocitomas fibrilares difusos (OMS II) e 19 glioblastomas multiformes foram analisados para determinar se TIMP-1 e NM23-H1 estavam relacinados à inibição da invasão tumoral nas neoplasias do sistema nervoso central, quantificando os níveis de RNA dos respectivos genes extraídos diretamente dos tumores. 10 mg por amostra de RNA total foram fracionados de gel de formaldeído e transferidos para os filmes de hibridação. Níveis específicos de RNAs foram determinados na espectrofotometria. Valores das razões entre NM23-H1/GAPDH e TIMP-1/GAPDH foram submetidos à análise de variabilidade das médias. RESULTADOS: A análise da expressão do gene TIMP-1 mostrou supressão em tumores gliais malignos. CONCLUSÃO: Os resultados indicam que existe relação direta entre níveis baixos de TIMP-1 e malignidade dos gliomas. O gene NM23-H1 foi detectado em todas as amostras, mas não foi possível relacionar sua subexpressão ou superexpressão com algum fenótipo de invasividade.

nm23-H1 Protein Expression and Gene Mutation in 150 Patients with Non-Hodgkin's Lymphomas

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.

Lymph node micrometastases and expression of metastasis-related gene proteins in patients with colorectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To study lymph node micrometastases (LNMM), expression of nm23-H(1), MMP(9), TIMP(2) proteins, and their relationship and clinical significance in patients with stage Dukes B colorectal cancer.</p><p><b>METHODS</b>Thirty patients with stage Dukes B colorectal cancer were studied. LNMM in these patients was detected by immunohistochemical anti-cytokeratin 20 (CK20) staining. The expression of nm23-H(1), MMP(9) and TIMP(2) proteins in primary tumors was examined by Strept-avidin-biotin complex method. Clinical-pathological data and survival of each patient were recorded and analyzed.</p><p><b>RESULTS</b>(1) The positive dyeing of CK20 was observed in 26.7% for cases and in 7.8% for lymph nodes of 30 patients with stage Dukes B colorectal cancer. (2) Different expression of nm23-H(1) and MMP(9) proteins in the patients between stage Dukes B and stage Dukes CD was observed (P < 0.05). The decreased nm23-H(1) expression, and/or the increased MMP(9) expression in primary stage Dukes B tumors were significantly associated with LNMM (P < 0.05). Sensitivity and specificity for detection of LNMM by using nm23-H(1) or MMP(9) were respectively 62.5% and 81.8% or 75.0% and 69.8%. If by combining nm23-H(1) with MMP(9), specificity for detection of LNMM became 90.9%. The expression of TIMP(2) protein was not related with stage Dukes and LNMM. (3) The percent of tumor recurrence and/or metastasis for the stage Dukes B patients with LNMM was significantly higher than that for the patients without LNMM (P < 0.05), but the survival percent for the patients with LNMM was significantly lower than that for the patients without LNMM. The outcome for the patients with nm23-H(1) (-) LNMM (+) or MMP(9) (+) LNMM (+) was significantly worse than that for patients with nm23-H(1) (+) LNMM (-) or MMP(9) (+) LNMM (-) (P < 0.05).</p><p><b>CONCLUSIONS</b>LNMM is detected by immunohistochemical anti-CK20 staining. The expression of nm23-H(1) and MMP(9) in primary stage Dukes B tumors was significantly associated with LNMM. The outcome in the LNMM patients with nm23-H(1) (-) and/or MMP(9) (+) were worse. Combining examination of CK20 for lymph nodes with expression of nm23-H(1) and MMP(9) for primary tumors is of important clinical significance for staging of Dukes, selection of adjuvant treatment and evaluation of prognosis in patients with colorectal cancer.</p>

Protective Efficacy of Recombinant Proteins Adenylate Kinase, Nucleoside Diphosphate Kinase, and Heat-Shock Protein 70 against Mycobacterium tuberculosis Infection in Mice / 결핵및호흡기질환

BACKGROUND: Priming and boosting vaccination strategy has been widely explored for new vaccine development against tuberculosis. As an effort to identify other vaccine candidates, this study was initiated to evaluate protective efficacy of adenylate kinase (AK), nucleoside diphosphate kinase (NdK), and heat shock protein 70 (Hsp70) of Mycobacterium tuberculosis. METHOD: M. tuberculosis genes encoding AK, NdK, and Hsp70 proteins were amplified by PCR and cloned into E. coli expression vector, pQE30. Recombinant AK, NdK, and Hsp70 was purified through Ni-NTA resin. To evaluate immune responses, we performed enzyme-linked immunosorbent assay (ELISA) for IgG isotype and IFN-gamma after mice were immunized subcutaneously with recombinant proteins delivered in dimethyl dioctadecylammonium bromide (DDA). Immunized- and control groups were challenged by aerosol with M. tuberculosis. The spleens and lungs of mice were removed aseptically and cultured for CFU of M. tuberculosis. RESULT: Vaccination with recombinant proteins AK, NdK, and Hsp70 delivered in DDA elicited significant level of antibody and IFN-gamma responses to corresponding antigens but no protective immunity comparable to that achieved with Mycobacterium bovis BCG. CONCLUSION: Recombinant proteins AK, NdK, and Hsp70 do not effectively control growth of M. tuberculosis in mice when immunized with DDA as an adjuvant.

Expression and significance of PTEN and nm23 in the metastasis of gallbladder cancer / 中南大学学报(医学版)

OBJECTIVE@#To explore the relationship between the expressions of PTEN and the metastasis of the gallbladder cancer.@*METHODS@#The expression of PTEN and nm23 were detected by immunohistochemical staining in 32 cases of gallbladder cancer with metastasis and the staining intensity was scored semi-quantitatively, compared with the cases without metastasis.@*RESULTS@#The intensity score of PTEN and nm23 in gallbladder cancer with metastasis was 8.9947+/-4.5590 and 10.2003+/-3.9031, respectively, which was lower than that in those without metastasis (12.9433+/-4.7618 and 15.8436+/-5.6917 respectively, P < 0.01 ). The expression of PTEN was correlative with that of nm23 ( Pearson = 0.370, P < 0.05).@*CONCLUSION@#The lower expressions of PTEN and nm23 are related to the metastasis of gallbladder cancer.

Expressions of survivin and nm23 and the relationship among the expressions and the axillary lymph node metastasis in breast cancer / 中南大学学报(医学版)

OBJECTIVE@#To investigate the expressions of Survivin protein and nm23 protein and the relationship among the expressions and axillary lymph node metastasis in breast cancer.@*METHODS@#The expression of Survivin and nm23 in 80 cases of breast cancer tissues were detected by immunohistochemistry SP method, and their correlation with axillary lymph node metastasis and 5-year disease free survival (DFS) were analysed.@*RESULTS@#Survivin protein positive expression rate was 68.75% (55/80) in breast cancer tissues, which had positive correlation with the axillary lymph nodes metastasis but negative correlation with 5 years FS (P 0.05).@*CONCLUSION@#The anti-apoptosis effect of Survivin protein and the anti-metastasis effect of nm23 protein may be important in the occurrence and advancement of breast cancer, suggesting that it may be a new indicator of prognostic and judgement in breast cancer.

Feasibility of cationic lipid mediated nm23-h1 plasmid transfecting adnoid cystic carcinoma in vivo / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of plasmid nm23-h1 transfection on high metastatic potential adnoid cystic carcinoma (ACC-M) cell line mediated by cationic lipid.</p><p><b>METHODS</b>ACC-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.</p><p><b>RESULTS</b>nm23-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.</p><p><b>CONCLUSION</b>Cationic 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.</p>

Cancer Metastasis and Metastasis Suppressors / 대한소화기학회지

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.

Screening of molecular markers of lung squamous cell carcinoma by microarrays / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To identify molecular markers of lung squamous cell carcinoma by cDNA microarray technique.</p><p><b>METHODS</b>cDNA expression profiles were examined by microarrays of 6 surgical specimens of stage I lung squamous cell carcinomas. Those genes, either up-regulated or down-regulated in every specimen studied, were identified. The expression levels of nm23 and BRCA2 by the squamous cell carcinoma of the lung were further examined by immunohistochemical techniques.</p><p><b>RESULTS</b>A total of 107 genes were identified, of which 26 were up-regulated and 81 were down-regulated in all six specimens. Immunohistochemical staining showed that, compared with normal lung tissues, the intensity of nm23 expression by the squamous cell carcinoma of lung was significantly increased while that of BRCA-2 was decreased.</p><p><b>CONCLUSION</b>cDNA microarrays can be used to identify gene expression profile of lung cancer, some of which may be used as markers of lung squamous cell carcinoma.</p>

Expression of sialylated carbohydrate antigens and nm23-H1 gene in prognosis of breast cancer / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the significance of expression of sialylated carbohydrate antigens and nm23-H1 gene in metastasis and prognosis of breast cancer.</p><p><b>METHODS</b>Tissue 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.</p><p><b>RESULT</b>Of 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.</p><p><b>CONCLUSION</b>These 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.</p>

In vitro and in vivo study on proliferation of adnoid cystic carcinoma cell lines after nm23-h1. Introduction / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To study the effect of nm23-h1 transfection on proliferation characteristics of adnoid carcinoma cell lines in vitro and in vivo.</p><p><b>METHODS</b>In vitro ACC-M cell lines were incubated after putative anti-metastatic gene nm23-h1 was introduced into the cells with the help of G418 selective incubation base. The ACC-M cells were transplanted into 10 BALB/C nude mices subcutaneously and non-transfected cell lines were taken as control. Immunohisto chemistry and Ki67 antibody were employed to study the proliferation character of cell crawling pieces and paraffin-bedded slice, meanwhile, the solid tumor of both groups were prepared for flow cytometry(FCM).</p><p><b>RESULTS</b>Transfected cells grew slower than non-transfected cells and this trend became more obvious as passages passed on. In vitro the expression of Ki67 of transfected cells was little stronger than non-transfected cells, while the expression of Ki67 in solid slices was almost negative in both groups. Transfected cells presented slower growth than non-transfected cells in the early stage (2 weeks) and 2 weeks later there was no obvious difference in size(P > 0.05). FCM value accorded well with the result.</p><p><b>CONCLUSION</b>Introduction of nm23-h1 into the ACC-M cell lines may have transient inhibitory effects on its proliferation.</p>

Expression of p16 and nm23 genes in salivary gland tumors / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Expression 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.</p><p><b>RESULTS</b>P16 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).</p><p><b>CONCLUSION</b>p16 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.</p>

Transfection of the nm23-H1 gene into BcaCD885 cell line inhibits the potential of invasion, adhesion and mobility / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Lipofect 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.</p><p><b>RESULTS</b>PCMV-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.</p><p><b>CONCLUSION</b>nm23-H1 can inhibit the metastases of BcaCD885 cell lines significantly.</p>

Expression of nm23 genes in acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore nm23 gene mRNA expression and its clinical significance in acute leukemias (AML).</p><p><b>METHODS</b>The 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).</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSION</b>nm23-H1 was overexpressed in AL, especially in AML-M4 and AML-M5. High expression of nm23-H1 may be a poor prognostic factor.</p>

The association of the expression of MTA1, nm23H1 with the invasion, metastasis of ovarian carcinoma / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To understanding the molecular mechanisms in invasion and metastasis of the ovarian carcinoma, we investigate a novel candidate metastasis-associated gene (MTA1) and nm23H1 mRNA expression and mutation in ovarian carcinoma.</p><p><b>METHODS</b>Twenty primary ovarian carcinoma specimens, 20 corresponding lymph nodes and 8 normal ovarian was examined for mRNA expression and mutation of MTA1 and nm23H1 genes by reverse-transcription polymerase chain reaction (RT-PCR) and RT-PCR-SSCP analysis. The level of the expression was determined by the relative optic density (ROD) of the PCR products.</p><p><b>RESULTS</b>The frequency of MAT1 overexpression was 100% (7/7) in primary ovarian carcinoma with metastasis but only 38.5% (5/13) in those without metastasis (P=0.0103). Overexpression of MAT1 was observed in 87.5% (6/7) of lymph nodes with metastasis but only 23% (3/13) of lymph nodes without metastasis (P=0.0118). In contrast with MAT1, low expression of nm23H1 mRNA was seen in 7 of 7 ovarian carcinoma with metastasis but only in 4 of 13 (30%) of those without metastasis (P=0.0043). Low nm23H1 expression was also seen in 7 of 7 lymph nodes with metastasis but only in 5 of 13 (38.5%) nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1 to nm23H1 increased with the development of metastasis. No mutation of MAT1 and nm23H1 genes was found by SSCP analysis.</p><p><b>CONCLUSION</b>The mRNA expression of MTA1 and nm23H1 is positively and negatively correlated with lymph node metastasis, respectively. Expression abnormalities but not mutation of the two genes are frequent events related to lymph node metastasis of ovarian cancer.</p>

The effects of nm23-H1 on metastases ability and chemo-sensitivity in Tca8113 cell lines / 华西口腔医学杂志

<p><b>OBJECTIVE</b>The purpose of this study was to establish a stable, high-efficient and low-toxic way of transfecting nm23-H1 into Tca8113 line cells, and then to find out whether nm23-H1 could affect the invasion and metastases ability of Tca8113 line cells.</p><p><b>METHODS</b>nm23-H1 was transfected into Tca8113 line cells with Lipofect. The different expressions of nm23-H1 between transfected and non-transfected line cells were detected by the method of immunohistochemistry. The difference of the invasion and metastases ability between transfected and non-transfected line cells was detected by transwell-room and wash techniques. The change of chemo-sensitivity was evaluated by MTT.</p><p><b>RESULTS</b>Using pCMV-NEO-BAM system to keep stable expression of nm23-H1, the significant difference of NDPKA expression between transfected and non-transfected Tca8113 line cells was discovered; The metastases ability of transfected Tca8113 line cells decreased significantly; The chemo-sensitivity of transfected Tca8113 line cells to CDDP increased significantly.</p><p><b>CONCLUSION</b>nm23-H1 can inhibit the metastases of Tca8113 line cells and increase the chemo-sensitivity to CDDP significantly.</p>

The regulation of nm23-H1/NDPK-A in different processes of regional lymph node metastases of oral squamous cell carcinomas / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To 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).</p><p><b>METHODS</b>By 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.</p><p><b>RESULTS</b>The 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).</p><p><b>CONCLUSION</b>The 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.</p>

Overexpression of c-erbB-2 and hypoexpression of nm23 relating to poor prognosis of colorectal carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between expression of c-erbB-2, CD44v6 and nm23 gene proteins and the clinicopathological features of colorectal carcinomas.</p><p><b>METHODS</b>Immunohistochemical technique was adopted to detect the protein expression of c-erbB-2, CD44v6 and nm23 genes in 92 cases of colorectal carcinomas. Of the 92 cases, 28 cases were followed up for more than 10 years, in which the prognosis was analyzed.</p><p><b>RESULTS</b>Expression of c-erbB-2 and CD44v6 was correlating with UICC staging (P < 0.05), and c-erbB-2 was associated with prominent peritumoral lymphocytic infiltration (P < 0.05). In the 28 cases with followed-up data, univariant analysis revealed that the survival rate was correlated with histological grading, UICC staging, tumor growth pattern, peritumoral lymphocytic infiltration, and expression of c-erbB-2, CD44v6 and nm23. However, Cox stepwise proportional hazards analysis showed that only UICC staging, c-erbB-2 and nm23 status retained significant independently in prospecting prognosis.</p><p><b>CONCLUSIONS</b>Besides UICC III and IV stage, overexpression of c-erbB-2 and decreased expression of nm23 are considered acceptable as the parameters in predicting of poor prognosis in colorectal carcinoma.</p>