Nm23 Expression Research Articles

Expression and Clinical Significance of EGFR, NM23 and BCL-2 in Hypopharynx Carcinoma

Expression and Clinical Significance of EGFR, NM23 and BCL-2 in Hypopharynx Carcinoma

NM23 as a prognostic biomarker in ovarian serous carcinoma

The nm23 gene is a reported metastasis suppressor gene. Recent studies have shown that its expression has tissue specificity. The role of nm23 in human ovarian cancer is still controversial. This study examines the prognostic significance of nm23 expression in patients with serous ovarian carcinoma. Following comparative proteomics in 13 fresh frozen ovarian serous cancer tissues with other histological types of ovarian cancers, validation was performed using immunohistochemistry on clinically well-designed 73 ovarian serous carcinoma microarray samples that were retrieved from ovarian cancer patients from 1990 to 2003. Statistical analysis of the results was performed using χ2 test, Cox proportional regression, the Kaplan–Meier method and log-rank test. We found that the expression of nm23 inversely correlated with peritoneal seeding (P=0.009). However, strong nm23 expression was associated with mortality in patients with ovarian carcinoma in univariate analysis (P=0.04). Poor prognostic factors of disease-free survival included tumor residue more than 2 cm (P=0.02), bilaterality (P=0.01) and peritoneal seeding (P<0.01), whereas poor prognostic factors affecting overall survival included peritoneal seeding (P=0.05). In Kaplan–Meier analysis, strong nm23 immunoreactivity correlates with poor overall survival (P=0.04) but not with poor disease-free survival. In conclusion, overexpression of nm23 is independently associated with decreased overall survival in patients with ovarian carcinoma and also significantly correlates with mortality. Nm23 may have a biological function that leads to poor clinical outcomes in ovarian carcinoma.

The expression of the chosen proteins in ovaries of BRCA1 gene mutation carriers after prophylactic adnexectomy

22191 Among women with BRCA1 mutation the risk of developing breast cancer is 50 - 80%, ovarian cancer 40% and about 10% for Fallopian tube and peritoneal cancer. One of the possibilities to reduce the risk of developing cancer in BRCA1 positive patients is prophylactic adnexectomy. It decreases the risk of ovarian cancer to 5% and breast cancer to 30 - 40%. The aim of our study was to investigate the expression of the TP53, BRCA1, NM23 and KAI1 in the ovaries of the 14 operated women that might be involved in development of breast and ovarian cancer in BRCA1 positive patients. As a control we have studied 11 patients operated at our department which were BRCA1 negative. The determination of TP53, BRCA1, NM23 and KAI1 was performed using immunohistochemistry method. We have observed the differences in the expression of BRCA1, NM23 and KAI1 between study group and control group. The expression of these proteins in the study group were respectively: 78,6%, 71,4%, 92,8% and in control and in the control group: 45%, 36,4% and 63,6%. The expression level of the analysed proteins differs between right and left ovary in BRCA1 carriers. In cases of BRCA1, NM23 and KAI1 the expression was higher in right ovary in case of TP53 the expression was higher in left ovary. No significant financial relationships to disclose.

Biophytum sensitivum (L.) DC Inhibits Tumor Cell Invasion and Metastasis Through a Mechanism Involving Regulation of MMPs, Prolyl Hydroxylase, Lysyl Oxidase, nm23, ERK-1, ERK-2, STAT-1, and Proinflammatory Cytokine Gene Expression in Metastatic Lung Tissue

Biophytum sensitivum is a traditional oriental herbal medicine that is known for its immunostimulatory and antitumor effects. Tumor metastasis is the most important cause of cancer death. Although B sensitivum was shown to inhibit metastasis, the mechanism underlying this action is not well understood. In the present report, the authors had studied the effect of B sensitivum on the invasion and motility of B16F-10 melanoma cells and investigate the regulatory effect on the expression of matrix metalloproteases (MMPs), prolyl hydoxylase, lysyl oxidase, nm23, extracellular signal-regulated kinase (ERK)-1, ERK-2, signal transducer and activator of transcription (STAT)-1, and proinflammatory cytokines in metastatic tumor-bearing lungs. B sensitivum inhibited the invasion and motility of B16F-10 cells in a dose-dependent manner. B sensitivum inhibited the expression of MMP-2 and MMP-9, whereas it activated STAT-1 expression in metastatic tumor-bearing lungs. Similarly, inhibition of prolyl hydroxylase, lysyl oxidase, ERK-1, ERK-2, and vascular endothelial growth factor (VEGF) expression but activation of nm23 by B sensitivum was observed in metastatic tumor-bearing lungs. B sensitivum treatment also downregulated the expression of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and granulocyte monocyte-colony stimulating factor in metastatic tumor-bearing lungs. In B16F-10 cells, B sensitivum also inhibited the production of proinflammatory cytokines. Overall, the results indicate that B sensitivum exhibits antimetastatic effects through the inhibition of invasion and motility. The results also suggest that MMPs, prolyl hydroxylase, lysyl oxidase, nm23, ERKs, VEGF, STAT, and proinflammatory cytokines are critical regulators of the B sensitivum-mediated antimetastatic effect.

Establishment and biological characteristics of a multi-drug resistant cell line A549/Gem.

Multi-drug resistance is one of the most important reason why the survival time of non-small cell lung cancer patients is so short. The aim of this study is to establish multi-drug resistant cell line A549/Gem and discuss its biological characters so as to elaborate the possible mechanisms of gemcitabine resistance. Human gemcitabine-resistant non-small cell lung cancer cell line A549/Gem was established by repeated clinical serous peak concentration then low but gradually increasing concentration of gemcitabine from its parental cell human lung adenocarcinoma cell line A549 which is sensitive to gemcitabine. During the course of inducement, monitored its morphology, checked its resistance index and resistant pedigree by MTT method, gathered its growth curve and calculated its doubling time, examined its DNA contents and cell cycles by flow cytometry; at the same time, measured its expression of P53, EGFR, c-erb-B-2, PTEN, PCNA, c-myc, VEGF, MDR-1, Bcl-2, nm23, MMP-9, TIMP-1, CD44v6 Proteins, and RRM1 mRNA. The resistance index of A549/Gem' to gemcitabine was 163.228, and the cell line also exhibited cross-resistance to vinorelbine, taxotere, fluorouraci, etoposide and cisplatin, but kept sensitivity to paclitaxol and oxaliplatin. The doubling time of it was shorter and figures in G0-G1 phase were increased than A549. Compared with A549, A549/Gem' achieved EGFR and c-myc protein expression, nm23 protein expression enhanced, p53, Cerb-B-2 and bcl-2 protein expression reduced, PTEN, PCNA and MDR-1 protein expression vanished, but that of MMP-9, VEGF, CD44v6 and TIMP-1 protein changed trivially. Meanwhile, the expression of RRM1 mRNA was augmented markedly. The resistance index of A549/Gem to gemcitabine was 129.783, and the cell line also held cross-resistance to vinorelbine, taxotere, etoposide, cisplatin and sensitivity to paclitaxol. But the resistance to fluorouracil and sensitivity to oxaliplatin vanished. And the expression of RRM1 mRNA decreased visibly. The doubling time of A549/Gem was longer and figures in G0-G1 phase were decreased than A549/Gem'. It's expressions of P53, EGFR, PCNA and MDR-1 protein was same to that of A549/Gem'. A549/Gem achieved TIMP-1 and PTEN protein expression, Cerb-B-2, MMP-9, cmyc and bcl-2 protein expression enhanced, nm23 protein expression vanished, but the expression of VEGF and CD44v6 protein changed trivially. Furthermore, Compared with its parental cell, A549/Gem was mixed with giant cells of different sizes that were larger and more irregular. The multi-drug resistant non-small cell lung cancer cell line A549/Gem has multi-drug resistance and great change of biological character compared with its parental cell. And the change can participate in the formation of multidrug resistance.

Expression of nm23 and KAI1 and their clinical significance in primary gall bladder carcinoma

Expression of nm23 and KAI1 and their clinical significance in primary gall bladder carcinoma

Gene expression and MR diffusion-weighted imaging after chemoembolization in rabbit liver VX-2 tumor model

To investigate the dynamic characteristics and the correlation between PCNA, Bax, nm23, E-cadherin expression and apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) after chemoembolization in rabbit liver VX-2 tumor model. Forty New Zealand rabbit liver VX-2 tumor models were included in the study. DWI was carried out periodically after chemoembolization. All VX-2 tumor samples in each group were examined by histopathology and Strept Avidin-Biotin Complex (SABC) immunohistochemical staining. The PCNA expression index in VX-2 tumors was higher than in the normal parenchyma around the tumor (P < 0.001). Nm23, Bax or E-caderin expression index in VX-2 tumors were lower than in the normal parenchyma around the tumor (all P < 0.001). PCNA and nm23 expression in the VX-2 tumor periphery first increased and then decreased (P < 0.001 and P = 0.03, respectively), while the expression of Bax and E-cadherin before and after chemoembolization was insignificant. When b-value was 100 s/mm(2), there was a linear correlation between PCNA expression and ADC in the area of VX-2 tumor periphery (P < 0.001), and PCNA expression in VX-2 tumor periphery influenced the ADC. The potential of VX-2 tumor infiltrating and metastasizing decreases, while its ability to proliferate increases for a short time after chemoembolization. To some degree, the ADC value indirectly reflects the proliferation of VX-2 tumor cells.

Expression of nm23 in the spectrum of pre-invasive, invasive and metastatic breast lesions

BackgroundNm23 protein is a metastasis suppressor protein, expressed in all tissues. Reduced Nm23 expression is related to a high incidence of lymph node and distant metastasis and poor prognosis in patients with cancers. The present study was done to analyze the expression of Nm23 using immunohistochemistry in non-neoplastic and neoplastic breast lesions.MethodsSections from 93 samples were studied and classified into non-proliferative breast lesion (13), fibrodenoma (7), proliferative breast lesion (13), carcinoma in situ (20), invasive carcinoma (23) and metastatic deposits in lymph nodes (17).ResultsNm23 expression in these groups showed a progressive down regulation with increasing neoplastic transformation. On comparing the various groups, nm23 expression was significantly different between the various subgroups with greatest expression in non-proliferative lesions and least in metastatic deposits (p < 0.050).ConclusionIt is concluded that the modulation of nm23 in a spectrum of breast lesions can be indicative of metastatic phenotype and help to predict the aggressiveness of disease.

Amentoflavone Inhibits Experimental Tumor Metastasis Through a Regulatory Mechanism Involving MMP-2, MMP-9, Prolyl Hydroxylase, Lysyl Oxidase, VEGF, ERK-1, ERK-2, STAT-1, nm23 and Cytokines in Lung Tissues of C57BL/6 Mice

Amentoflavone has been shown to inhibit tumor metastasis in vivo, but its mechanism of action remains unclear. Here, C57BL/6 mice were injected once with B16F-10 melanoma cells via tail vein followed by amentoflavone treatment (50mg/kg BW) for 10 consecutive days. Twenty-one days after tumor injection, animals were euthanized, and tumor metastasis was found to confine in the lungs. As compared with the tumor controls, amentoflavone treatment significantly lowered the number of lung nodules (p<0.001). Amentoflavone treatment markedly decreased the mRNA expression of MMP-2, MMP-9, prolyl hydroxylase, lysyl oxidase, VEGF, ERK-1, ERK-2, TNF-α, IL-1β, IL-6, and GM-CSF in lung tissues. However, amentoflavone treatment increased the mRNA expression of STAT-1 and nm23 in lung tissues. Also in vitro studies indicate that amentoflavone treatment inhibits tumor cell invasion and migration. These results show that amentoflavone treatment reduces experimental tumor metastasis and suggest that such an action is associated with attenuation of tumor invasion, proliferation and angiogenesis.

Prognostic impact of KI67, p53, human epithelial growth factor receptor 2, topoisomerase IIα, epidermal growth factor receptor, and nm23 expression of ovarian carcinomas and disseminated tumor cells in the bone marrow

Examination of tumor biological factors for prognostic and predictive indicators is not part of routine testing in ovarian cancer. As in other tumors, the detection of hematogenous tumor spread could help to estimate the risk of metastatic disease. We examined the expression of p53, KI67, topoisomerase IIalpha (Top IIa), epidermal growth factor receptor (EGFR), human epithelial growth factor receptor 2 (HER2) and nm23 in tumor tissues from 90 patients with ovarian cancer. All underwent bone marrow (BM) aspiration and screening for disseminated tumor cells in the bone marrow (DTC-BM) at primary diagnosis. BM aspiration, cytospin preparation, and immunocytochemical staining with the anticytokeratin antibody (A45-B/B3) were done following a standardized protocol. The expression of p53, KI67, Top IIa, EGFR, HER2, and nm23 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells or immunoreactive score (IRS). The prognostic impact of the individual factors together with standard histologic parameters was calculated by univariate and multivariate analyses. Expression rates for HER2 (2+/3+: 34.5%), KI67 (median 30%), p53 (median IRS 5), and Top IIa (median IRS 4) were relatively high, whereas nm23 (median IRS 2) and EGFR (IRS 0: 61%) showed weak staining. In 21/90 patients (23.3%), DTC-BM (>/=1/2 x 10(6) cells) could be detected. The presence of DTC-BM was inversely related to nodal status (P = .015) but not to the other factors examined. Tumor stage (P = .02), lymph node involvement (P = .003), grade (P = .046), postoperative tumor residue (P < .001), peritoneal seeding (P = .02), and KI67 (P = .046) significantly correlated with overall survival (OS) after a median observation time of 28 months (2-105). The finding of ascites was borderline significant (P = .050). The presence of DTC-BM (P = .04) and KI67 positivity (P = .02) predicted reduced distant disease-free survival. By multivariate analysis, postoperative tumor residue remained an independent factor for OS (P = .02, relative risk = 4.6). As a primarily locoregional disease, tumor stage and postoperative tumor residue are the main determinants of prognosis in patients with ovarian cancer. However, even in advanced stages, examination of tumor biological factors could help to stratify subgroups of patients and establish targeted therapies.

Dermatopathological indicators of poor melanoma prognosis are significantly inversely correlated with the expression of NM23 protein in primary cutaneous melanoma

Some dermatopathological parameters are recognized as dominant indicators of high metastatic potential in melanoma, especially Breslow thickness, ulceration, Clark's level of invasion and mitotic rate. Because NM23 protein is the product of a melanoma metastasis suppressor gene, the aim of this study was to compare such dermatopathological indicators of melanoma prognosis with NM23 protein expression in primary cutaneous melanoma. The immunohistochemical NM23 expression was semiquantitatively assessed in 30 primary cutaneous melanomas. Ten dermatopathological parameters were evaluated and compared with NM23 expression. A significant inverse correlation was found for NM23 expression in comparison with Breslow thickness (p < 0.01), ulceration (p < 0.05), Clark's level (p < 0.01), mitotic rate (p < 0.05), and vertical growth phase (p < 0.05). By contrast, no significant correlation was found for NM23 expression in comparison with cell morphology, presence of adjacent nevus, pigmentation, tumor-infiltrating lymphocytes, and regression was impossible to evaluate. The expression of NM23 protein in primary cutaneous melanoma is significantly inversely correlated with dermatopathological parameters currently recognized as powerful indicators of melanoma prognosis. NM23 may be therefore considered in the dermatopathological evaluation of primary cutaneous melanoma.

Relationship between expression of nm23 protein and clinical morphological factors and content of plasminogen activation system components in tumors of patients with gastric cancer

Immunohistochemical studies revealed a relationship between the expression of nm23 protein in gastric cancer cells and some parameters characterizing plasminogen activation system and clinical morphological factors. Expression of nm23 in the cytoplasm was detected almost 3-fold more often than in the nuclei; cytoplasmic expression more strictly correlated with patient's age, tumor location, and its histological structure than nuclear expression.

Reduced protein expression of metastasis‐related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer

Metastasis remains an incurable common complication in patients with gastric cancer. A variety of theories have been proposed to explain the inefficiency of the metastatic process. To compare protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) between primary tumours and metastatic tumours may be useful in illustrating these theories. Metastasis-related tissue microarrays (including normal tissues, primary tumours, nodal metastases and liver metastases) were constructed. The protein expression of nm23, KISS1, KAI1 and p53 in lymph node and liver metastases from advanced gastric cancer specimens was mainly examined by immunohistochemical staining in relation to primary tumours. Immunohistochemical staining showed reduced protein expression of nm23, KISS1 and KAI1 in lymph node and liver metastases compared with primary tumours. Results for p53 were to the contrary. Our investigations revealed a tendency of reduced protein expression of metastasis suppressor genes nm23, KISS1 and KAI1 in gastric cancer with the progress of metastasis. This means that the progression theory is an important determinant of metastatic efficiency.

Effects of body-resistance strengthening and tumor-suppressing granules on immune adhesion function of red blood cells and expression of metastasis protein CD44 in tumor cells of patients with esophageal carcinoma

To investigate the effects of Fuzheng Yiliu granules (body-resistance strengthening and tumor-suppressing granules) in patients with esophageal carcinoma. We compared the immune adherent properties of red blood cells (RBCs), the expression of metastasis protein CD44, and the metastasis inhibition factor nm23, in esophageal carcinoma tumor cells of patients before and after radiotherapy in the presence and absence of orally administered Fuzheng Yiliu granules. Sixty-three hospitalized patients with esophageal carcinoma were treated with standard radiotherapy and randomly divided into treatment group (n = 30) treated with both radiotherapy and Fuzheng Yiliu granules and control group (n = 33) given radiotherapy only. Blood samples and tumor tissue were obtained before and after 21 d of treatment. The rosette rates for complement receptor type 3b (C3bRR) and immune complex receptor (ICRR) on RBCs were measured by erythrocyte immunological methods. Expression of CD44 and nm23 in tumor tissue sections was determined by immunohistochemical staining with monoclonal antibodies CD44v6 ad nm23H-1, respectively. The positivity of RBC-C3bRR before and after 21 d of treatment increased from 7.78% +/- 1.59% to 10.03% +/- 2.01% in the double treatment group, while it changed only slightly from 7.18% +/- 1.29% to 7.46% +/- 1.12% in the radiotherapy group. The positive rate for RBC-ICRR decreased from 37.68% +/- 2.51% to 22.55% +/- 1.65% after the double treatment, and from 37.28% +/- 2.41% to 24.69% +/- 1.91% in radiotherapy group at the same time points. The difference in erythrocyte immune adherent function between the two groups was significant (P < 0.01, t-test). The CD44(+)-cases were reduced from 21 (70.00%) to 12 (40.00%) after treatment with Fuzheng Yiliu granules, whereas the CD44(+)-cases (69.70%) in the radiotherapy group remained unchanged. The difference between the treatment (40.00%) and control (69.70%) groups was significant (P < 0.05). Although the nm23(+)-cases were increased from 4 (13.33%) to 6 (20.00%) in the double treatment group and from 6 (18.18%) to 7 (21.21%) in the radiotherapy group, the difference was not significant (P > 0.05). Fuzheng Yiliu granules enhance the immune adhesion function of RBCs and reduce the number of CD44(+)-cells in esophageal carcinoma patients, suggesting a potential role of these Chinese herbals in suppression of invasion and metastasis of malignant cells. However, this anti-metastatic effect has yet to be validated in vivo.

0224: Prognostic Value of Nm23 Expression and its Correlation with Expression of Mmp-9 in Serous Ovarian Carcinoma

0224: Prognostic Value of Nm23 Expression and its Correlation with Expression of Mmp-9 in Serous Ovarian Carcinoma

Nm23 expression in node-positive and node-negative endometrial cancer

Objective To examine the relationships between the expression of protein Nm23 and surgical stage, histologic grade, histopathologic findings, and survival in women with endometrial carcinoma. Methods 19 patients with lymph node involvement were matched with 24 patients without lymph node involvement and the best paraffin-embedded blocks were selected for Nm23 immunohistochemical staining. The slides were evaluated semiquantitatively according to their degree of cytoplasmic staining. Statistical analysis was performed to determine whether there was a relationship between Nm23 expression and surgical stage, histologic grade, depth of myometrial invasion, lymph node metastasis, and/or lymphovascular space involvement. Survival analysis was also performed. Results Slides from 15 patients (79%) with lymph node involvement and 22 patients (88%) without lymph node involvement were found to be positive for Nm23 ( P = 0.01). No significant relations were observed between Nm23 expression and surgical stage, histologic grade, depth of myometrial invasion, or lymphovascular space involvement. Nm23 expression was found to be significantly related to lower rates of lymph node metastasis and longer survival ( P = 0.02). Conclusion Elevated Nm23 expression is related to lower rates of lymph node metastasis and longer survival.

Proteomics-Based Strategy to Identify Biomarkers and Pharmacological Targets in Leukemias with t(4;11) Translocations

Translocations and other aberrations involving the MLL (mixed lineage leukemia) gene result in aggressive forms of leukemias. Heterogeneity in partner genes, in chromosomal breakpoints, in MLL itself, and in the different partner genes results in heterogeneous fusion transcripts that can be alternatively spliced, which complicates deciphering a unifying mechanism of leukemogenesis. However, recent microarray studies completed with clinical leukemia specimens have uncovered several distinct mRNA signatures within MLL leukemia that differ from other types of leukemia. A global proteomics strategy using MV4-11 and RS4:11 cells in culture was employed to investigate possible protein signatures common to different MLL leukemias and to identify disease biomarkers and protein targets for pharmacological intervention. Initial proteomics screening experiments with two-dimensional differential in-gel electrophoresis revealed heat shock protein 90 alpha (HSP90alpha) as a potential target for pharmacological inhibition and nucleoside diphosphate kinase (nm23) as a biomarker for measuring treatment efficacy. Using a modified stable isotope labeling of amino acids in cell culture (SILAC) approach, coupled with two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS), changes in abundance for over 500 proteins were measured. In addition, decreased expression of the novel biomarker nm23 was observed during HSP90 inhibition with 17-allylamino-17-demethoxygeldanamycin (17-AAG) in the MV4-11 cell line. The present study validates the use of a global proteomics strategy to uncover novel biomarkers and pharmacological targets for leukemias with MLL translocations. Additionally, several proteins were found to be expressed in concordance with microarray studies of mRNA expression in specimens from patients showing the value in comparing mRNA transcript and proteomic profiles. This work represents one of the most comprehensive proteomics screens of MLL leukemias that have been conducted to date.

Translational approaches using metastasis suppressor genes

Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. In order to develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene identified was nm23, also known as NDP kinase. Nm23 represents the most widely validated metastasis suppressor gene, based on transfection and knock-out mouse strategies. The biochemical mechanism of metastasis suppression via Nm23 is unknown and likely complex. Two potential mechanisms include binding proteins and a histidine kinase activity. Elevation of Nm23 expression in micrometastatic tumor cells may constitute a translational strategy for the limitation of metastatic colonization in high risk cancer patients. To date, medroxyprogesterone acetate (MPA) has been identified as a candidate compound for clinical testing.

Anti-tumor mechanism of norcantharidin for the implanted tumors of human gallbladder carcinoma in nude mice in vivo

To explore the anti-tumor mechanism of norcantharidin (NCTD) for the implanted tumors of human gallbladder carcinoma in nude mice in vivo. Animal model of implanted tumors of human gallbladder carcinoma in nude mice was established. Mice were randomly divided into control, 5-FU, NCTD and NCTD + 5-FU groups and were taken different treatment. The expressions of PCNA, Ki-67, cyclin D1, p27, Bcl-2, Bax, Survivin, nm23/nm23-H1, MMP2 and TIMP2 proteins or genes in each tissue section of every group were determined by immunohistochemistry and RT-PCR. (1) On proliferation-related gene proteins, the expression of PCNA, Ki-67, cyclin D1 was significantly decreased, with significantly increased expression of p27 protein, in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of PCNA mRNA, cyclin D1 mRNA was decreased, with significantly increased expression of p27 mRNA in NCTD group. (2) On apoptosis-related gene proteins, the expression of Bcl-2 was significantly decreased in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of Bcl-2 mRNA, Survivin mRNA was significantly decreased, with significantly increased expression of Bax mRNA in NCTD group. (3) There was significant difference on invasion around tumor and lung metastasis in NCTD group when compared with control group (P < 0.01). On metastasis-related gene proteins, the expression of nm23 and TIMP2 was significantly increased, with significantly decreased expression of MMP2 in paraffin sections of NCTD group when compared with control group (P < 0.05); The expression of nm23-H1 mRNA, TIMP2 mRNA was significantly increased, with significantly decreased expression of MMP2 mRNA in NCTD group. The anti-tumor mechanism of NCTD for human gallbladder carcinoma in nude mice might correlated with inhibition of cell proliferation, blockage of cell cycle, induction of cell apoptosis, reducing of cell motility and invasive capability, alteration of the expression of proliferation-, apoptosis- and metastasis-related gene proteins such as PCNA, Ki-67, cyclin D1, p27, Bcl-2, Bax, Survivin, nm23, MMP2 and TIMP2.

Pathologic and Biological Assessment of Lung Tumors Showing Ground-Glass Opacity

We evaluated the pathologic and biological aspects of lung tumors 3.0 cm or less in diameter with the appearance of ground-glass opacity (GGO). Of 988 patients with non-small cell lung cancer who underwent operations at our institute between January 1994 and December 2004, 87 resected lung tumor specimens that showed GGO appearance on helical computed tomography were obtained from 81 patients. Forty-four lesions were pure GGO with no solid component in the tumor and 43 lesions were mixed GGO consisting of areas of attenuation with a solid component. Together with histological features, MIB1 and nm23 expression within tumors were examined immunohistochemically. The mean tumor size in the pure GGO group was significantly smaller than that in the mixed GGO group. The composition of pathologic subtypes and biological characteristics were clearly different between the two groups. Although atypical adenomatous hyperplasia and localized bronchioloalveolar cell carcinoma of Noguchi's A and B were the predominant pathologic subtypes and nm23 negativity was rare in the pure GGO group, a high score for expression of MIB1 was often found in pure GGO tumors even though the tumors were less than 10 mm in diameter. If the tumor is 2 cm or less in diameter, the ability of invasion and metastasis seems to be low in pure GGO tumors. However, the proliferation ability of these tumors suggests the necessity of a careful follow-up schedule if the tumor is greater than 5 mm in diameter. For mixed GGO tumors, surgical resection instead of observation is justified.