Study on genetic instability of nm23-H1 gene and expression of hMLH1, hMSH2 in sporadic gallbladder carcinoma / 中国病理生理杂志

AIM: To examine the MSI and LOH of locus D17S396 and their influence on the expression of nm23-H1 in gallbladder tumors, and to examine the protein expression of hMLH1/hMSH2, which may provide experimental evidence for the tumor occurrence and metastasis. METHODS: Techniques such as DNA extraction, CR-SSCP, ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision IHC was used to assess the expression of nm23-H1 and hMLH1/hMSH2.RESULTS: ① The frequency of heredity instability of gallbladder carcinoma was 42.55%. The frequency of LOH in liver and lymph node metastasis cases and in stage Nevin IV and V was significantly higher than that without metastasis and stage I, II and III. However, the frequency of MSI showed contrary correlation with some clinicopathologic characteristics. ② The expression of nm23-H1 was 46.81%. The case with lymph node metastasis and Nevin stage IV and V showed significantly lower expression than that without lymph node metastasis and stage I, II and III. ③ The expressions of hMLH1 and hMSH2 were 51.06% and 42.55% respectively. hMLH1 in lymph node and liver metastasis cases and in stage Nevin IV and V were significantly lower than that without metastasis and in stage I, II and III. ④ Positive frequency of hMLH1 in MSI positive group was higher than that in MSI negative group. The positive frequency of nm23-H1 and hMSH2 protein in LOH positive group was lower than that in negative group.CONCLUSION: The heredity instability of nm23-H1 gene may be implicated pathogenesis and progression of gallbladder carcinoma. Both MSI and LOH of nm23-H1 control the development of gallbladder carcinoma independently in different paths. Abnormal expression of hMLH1/hMSH2 may be a molecule marker in early stage of gallbladder carcinoma.

Inhibitory effects of nm23-H1 gene on proliferation and invasion of A549 cell line / 中国病理生理杂志

AIM: To study the inhibitory effects of nm23-H1 gene on proliferation and invasion of human lung adenocarcinoma A549 cell line. METHODS: Recombinant eukaryotic expression vector pcDNA3.1-nm23-H1 containing full length of human nm23-H1 cDNA was constructed and transfected into a human lung adenocarcinoma A549 cell line by lipofectamine. Cell strain that expressed nm23-H1 stably was screened out by G418 and named pcDNA-nm23-A549. Expression of nm23-H1 was identified by RT-PCR and immunohistochemistry. Growth curves were drawn to detect the inhibitory effects on cell proliferation. Cell cycle of pcDNA-nm23-A549 was examined by flow cytometry. Atomic force microscopy was used to observe the filopodia on the surface of the cells. RESULTS: Introduction of nm23-H1 obviously inhibited the proliferation of A549. Expression of nm23-H1 did not induce apotosis in A549 cells but increased the percentage of phase G_1 cells and decreased phase S cells. Meanwhile, phase G_1 to phase S transition was restrained. Filopodia in the cell surface was much fewer and its structure changed in cells transformed. CONCLUSION: nm23-H1 is capable of inhibiting A549 proliferation and decreasing its metastatic ability, probably by interfering with cell cycle and cell surface structure.

Relationship between genetic instability of nm23H1 gene and clinical pathological characteristic in hepatocellular carcinoma / 中国病理生理杂志

AIM:The aim of this study was to examine the microstatellite instability(MSI)and loss of heterozygosity(LOH)of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in hepatocellular carcinoma(HCC),which may provide experimental evidence for the mechanism of nm23H1 gene and tumor metastasis.METHODS:Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues,PCR-SSCP,ordinary silver stain were used to study MSI and LOH of locus D17S396.Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of nm23H1.RESULTS:① The frequency of heredity instability of HCCs was 35.42%.The frequency of LOH in the cases with lymph node or distant organs metastasis or not and with intrahepatic metastasis or embolus of portal vein or not was significantly different(P

Relationship between PCNA,nm23-H1 expression and prognostic factors in supratentorial astrocytoma / 中华放射肿瘤学杂志

Objective To study the expression of proliferating cell nuclear antigen (PCNA), metastasis-related gene nm23-H1 in supratentorial astrocytomas, and analyze the prognostic factors and the relationship between PCNA expression, nm23-H1 expression and clinical, MRI features.Methods From November 1994 to December 1998, 52 pathologically proved astrocytoma patients with complete clinical data were analyzed. The expressions of PCNA and nm23-H1 were detected by streptabitin peroxidase (SP) immunohistochemical method. Clinical and MRI data were collected and analyzed by Cox proportional hazard model .Results There was a significant difference in the expressions of PCNA and nm23-H1 in the lesion and their adjacent tissues (P