BACKGROUNDTo study the role of nm23-H1 and CD44v6 gene in non-small cell lung cancer (NSCLC).

METHODSExpressions of nm23-H1 and CD44v6 genes were analyzed in 147 cases of NSCLC by SP immunohistochemistry method.

RESULTSThe overall positive rate of nm23-H1 staining was 62.6% (92/147). Significant differences in the positive rate of nm23-H1 were found between well and poor differentiated groups [68.6% (83/121) [WTBX]vs 34.6% (9/26)], and between adenocarcinoma and squamous cell carcinoma , and between adenocarcinoma and squamous cell carcinoma [78.8% (52/66) [WTBX]vs 50.8% (32/63) ] ( (P < 0.05), but not between stage I+II and stage III+IV [ 65.3% (62/95) [WTBX]vs 57.7% (30/52) ], and between N0 and N1-3 , and between N0 and N1 3 [64.7% (55/85) [WTBX]vs 59.7% (37/62) ]( ( P > 0.05). The positive rate of nm23-H1 of patients who survived for more than 3 years was 71.4% (55/77), which was significantly higher than 52.9% (37/70) of patients who survived for less than 3 years (Chi-square=5.4, P < 0.05). For CD44v6, the overall positive rate was 63.9% (94/147). Significant differences in the positive rate of CD44v6 were found between well and poor differentiated groups [68.6% (83/121) [WTBX]vs 42.3% (11/26)], and between adenocarcinoma and squamous cell carcinoma , and between adenocarcinoma and squamous cell carcinoma [53.0% (35/66) [WTBX]vs 77.8% (49/63) ] ( (P < 0.05), but not between stage I+II and stage III+IV [ 66.3% (63/95) [WTBX]vs 59.6% (31/52) ], and between N0 and N1-3 , and between N0 and N1 3 [63.5% (54/85) [WTBX]vs 64.5% (40/62) ]((P > 0.05). The positive rate of CD44v6 of patients who survived for more than 3 years was much lower than that of patients who survived for less than 3 years (43/74 vs 51/70, P < 0.01 ). The 3-year survival rate in patients with nm23-H1(+)CD4v6(-) was significantly higher than those with nm23-H1(-)CV44v6(+) (22/32 vs 11/34, P < 0.01).

CONCLUSIONSThere are some relationships among expressions of nm23-H1 and CD44v6 in NSCLC and cell differentiation, histological classification and prognosis, and no relation in stage and lymph node metastasis.

BACKGROUNDTo investigate the diagnostic significance of detection of telomerase activity of bronchoalveolar lavage liquid (BALF) in primary lung cancer.

METHODSBALF of 63 patients with lung cancer and 31 patients with non-cancerous pulmonary disease was collected, and telomerase activity was detected with silver-stained TRAP. Brush cytology and BALF cytology were carried out simultaneously.

RESULTSThe positive rate of telomerase was 76.2% (48/63) in lung cancer group, which was higher than 6.5% (2/31) in control group (Chi-square=40.6, P < 0.01). The positive rate was also higher than that of brush cytology (58.7%, 37/63) (Chi-square =3.6, P > 0.05), and higher than that of BALF cytology (14.3%, 9/63) (Chi-square=46.3, P < 0.01). In central type lung cancer group, the positive rate of telomerase was 71.4% (35/49), and higher than that of BALF cytology (12.2%, 6/49) (Chi-square= 35.3 , P < 0.01), but had no significant difference compared to that of brush cytology (61.2%, 30/49) (Chi-square=1.1, P > 0.05). In peripheral-type lung cancer group, the positive rate of telomerase in BALF was 92.9% (13/14), and higher than that of brush cytology (50.0%, 7/14) and that of BALF cytology (21.4%, 3/14).

CONCLUSIONSThe telomerase activity could be detected in the BALF of the primary lung cancer. Hence, detection of telomerase in the BALF of patients may be helpful to diagnose lung cancer.

BACKGROUNDTo study the clinical effects of ¹⁵³Sm-EDTMP plus chemotherapy in the treatment of bone metastasis of lung cancer.

METHODSOne hundred and ten lung cancer patients with one metastasis [male 82 and female 28, aged from 32 to 76 yrs; squamous cell carcinoma 28, adenocarcinoma 27, small cell lung cancer (SCLC) 7, mix type 41, alveolar carcinoma 7] who did not undergo an operation were entered into this study. The patients were divided into 3 groups: ¹⁵³Sm-EDTMP therapy only (37 cases), ¹⁵³Sm-EDTMP plus chemotherapy after 3 days (42 cases), 30 days after chemotherapy plus ¹⁵³Sm-EDTMP (31 cases). The dosages of ¹⁵³Sm-EDTMP ranged from 1 111 to 2 660 MBq. The patients with SCLC were adapted CCNU, MTX and CTX; those with non-small cell lung cancer (NSCLC) were adapted MMC, VCR and DDP. Statistic analysis of the data was performed by Chi-square test.

RESULTSTotal pain relief rate for ¹⁵³Sm-EDTMP only was 89.2% , for ¹⁵³Sm-EDTMP plus chemotherapy was 92.8%, and for chemotherapy plus 153 Sm EDTMP was 90.3% . The foci disappeared in 9 cases with ¹⁵³Sm-EDTMP only, in 12 cases with ¹⁵³Sm-EDTMP plus chemotherapy, and in 9 cases with chemotherapy plus ¹⁵³Sm-EDTMP. The 1 year survival rate was 29.7%(11/37) by 153 Sm only, 40.5%(17/42) by 153 Sm plus chemotherapy, 38.7%(12/31) by chemotherapy plus ¹⁵³Sm-EDTMP.

CONCLUSIONS¹⁵³Sm-EDTMP plus chemotherapy is effective in the treatment of bone metastasis of lung cancer.

BACKGROUNDTo detect dendritic cells (DC)in the peripheral blood and plasma concentration of vascular endothelial growth factor (VEGF) of patients with non-small cell lung cancer (NSCLC) and to evaluate their relationship.

METHODSThe quantitation of DC in the blood was performed in 55 patients with NSCLC, 13 patients with pulmonary benign diseases, and 12 healthy volunteers by a novel flow cytometric assay. The concentration of VEGF in the plasma was measured by ELISA kit.

RESULTSNo significant difference was found in the levels of DC and VEGF between the patients with pulmonary benign diseases and healthy volunteers (P>0.05). In comparison with subjects of healthy volunteers and pulmonary benign diseases, the level of DC was significantly decreased, while that of VEGF was significantly increased in the patients with NSCLC(P < 0.05 to 0.01). The levels of DC and VEGF in the peripheral blood of NSCLC were closely associated with TNM stages and lymph node metastasis. However, no correlation was found among the levels of DC and VEGF and age, gender, cell differentiation and histologic classification. There was a negative correlation between the VEGF concentration and the DC counts.

CONCLUSIONSThe decline of DC count in peripheral blood and the enhancement of plasma VEGF are remarkably related to the malignancy of NSCLC. And VEGF overexpression may be one of mechanisms of DC maturation and differentiation inhibition in patients with NSCLC.

BACKGROUNDTo investigate the roles of E-cadherin and β-catenin genes in metastasis and prognosis of non-small cell lung cancer.

METHODSThe expression of E-cadherin and β-catenin were detected in 112 non-small cell lung cancer tissues and 30 benign pulmonary lesion tissues by immunohistochemical method (LSAB method).

RESULTSThe expression of E-cadherin and β-catenin in lung cancer tissues was significantly lower than that in adjacent non-cancerous lung tissues and benign pulmonary tissues (P < 0.01); The expression of E-cadherin and β-catenin in lung cancer tissues with lymph node and/or distant metastasis was significantly lower than that in those without lymph node and distant metastasis (P < 0.01); The 5-year survival rate in patients with low E-cadherin expression and low β-catenin expression (6.78%) was remarkably lower than that in cases with high expression (6.78% vs 35.85% and 3.78% vs 37.29%) (P < 0.01).

CONCLUSIONSUnderexpressions of E-cadherin and β-catenin are very common in non-small cell lung cancer, and it may play an important role in the progression and metastasis of lung cancer. Detection of expression of E-cadherin and β-catenin in lung cancer might be helpful to predict prognosis.

BACKGROUNDTo explore the expression level of E-cadherin gene and its relationship with lymph node metastasis and prognosis in patients with primary non-small cell lung cancer (NSCLC).

METHODSThe expression of E-cadherin protein was detected in 138 human NSCLC tissues by immunohistochemistry, and 23 normal lung tissues as control.

RESULTSThe positive rate of E-cadherin expression (41.48%) in lung cancer tissues was significantly lower than that in normal lung tissues (73.12%) (P < 0.05). E-cadherin expression rate was closely related to lymph node metastasis (P < 0.05) and TNM stages of lung cancer (P < 0.05), but not to the size of the primary tumor (T), differentiation of cancer cell, histological classification and history of smoking (P > 0.05). The 5-year survival rate of the patients with high expression of E-cadherin ( > 40%) was significantly higher than those with low expression (≤40%) (P < 0.05 ).

CONCLUSIONSDetection of E cadherin expression may be helpful to predict the prognosis of patients with non-small cell lung cancer.

BACKGROUNDTo study the apoptosis-inducing effect of Tanshinone and its molecular mechanism on human lung cancer cells.

METHODSHuman lung cancer cell line (SPC-A-1) was treated in vitro with 0.5 mg/L Tanshinone IIA for five days, and the cells treated with all trans retinoic acid (RA) or DDP as controls. Changes in cell morphology, apoptotic index and apoptosis related gene expression were detected by electron microscope, FCM and DNA-end-labeling.

RESULTSMany apoptotic cells were observed by light and electron microscopes. FCM examination showed that apoptotic index in Tanshinone group was much higher than that of DDP and control groups, but no difference was found statistically compared with RA group. The expression of p53, Fas and Bax genes in Tanshinone group was up-regulated markedly, but Bcl-2 was obviously down-regulated.

CONCLUSIONSTanshinone IIA can induce apoptosis in human lung cancer cell line (SPC-A-1) . Up-regulating expression of p53, Bax, Fas and down-regulating Bcl-2 expression might be its molecular mechanisms.

BACKGROUNDTo elucidate the pattern and mechanism of cisplatin-induced apoptosis and its role in tumor chemotherapy.

METHODSApoptosis induced by cisplatin in human lung adenocarcinoma cell line A549 was detected by cell morphology, agarose gel electrophoresis, DNA-end-labeling and flow cytometry analysis techniques.

RESULTSCisplatin-induced apoptosis of A549 cells persisted and augmented gradually from 12 to 72 hours after treated with 3 mg/L cisplatin. All of A549 cells treated respectively with 1, 3, 5 and 7 mg/L cisplatin showed apoptosis. Apoptotic effects increased in a time-dependent pattern and a concentration-dependent pattern. A549 cells were blocked in G1 phase after treated with cisplatin.

CONCLUSIONSInduction of cell apoptosis may be an important mechanism of anti-tumor efficacy of cisplatin.

BACKGROUNDTo investigate the methylation and deletion of p16 gene and its diagnostic value in non-small cell lung cancer.

METHODSA total of 50 lung cancer tissues and 54 normal lung tissues were examined for p16 gene methylation in exon 1 and deletion in exon 2 by PCR based methylation analysis and duplex PCR respectively.

RESULTSOut of 50 lung cancer tissues, 16 were positive for the p16 gene exon 1 methylation (32.0%), and 14 for the p16 gene exon 2 deletion (28.0%). However, in 54 cases of normal lung tissues, only 2 showed the p16 gene exon 1 methylation(3.7%), and none showed the p16 gene exon 2 deletion. There were significant differences in methylation rate (Fisher's exact= 0.000 ) and deletion rate (Fisher's exact= 0.000) between the two groups.

CONCLUSIONSThe methylation and deletion may be important mechanisms for p16 gene inactivation in non-small cell lung cancer. The detection of p16 gene status may contribute to the diagnosis of lung cancer.

BACKGROUNDTo study the inhibition effects of both extraneous right sense and antisense p53 on malignant phenotype of human lung cancer cell line.

METHODSThe named 801D cell line with p53 deletion and mutation at 248 code was selected as a model in vitro. The recombined plasmid pEGFP-p53(RS) and pEGFP-p53(AS) were constructed. The extraneous gene was detected by PCR. The p53 mutation protein was examined by immunohistochemical stain of p53 antibody. The inhibition effect of extraneous p53 on tumor growth in vitro were determined by clonogenic survival assay. FCM analysis was carried out in cells. The inhibition effect on malignant growth of extraneous p53 in vivo was observed by heteroplastic transplant on nude mouse.

RESULTSThe transfected cell lines, pEGFP-p53(AS)-801D, pEGFP-p53(RS)-801D and pEGFP-801D were established. Presence of extraneous p53 and neo genes in pEGFP-p53(AS)-801D and pEGFP-p53(RS)-801D was proved by PCR and green fluorescence was found out in those cells under the microscope. Mutant protein in pEGFP-p53(AS)-801D was negative by immunohistochemical stain. The malignant growth of these transfected cell lines was inhibited comparing with parents in vivo and in vitro. Inhibition rate of colony formation was 62.0% for pEGFP-p53(AS)-801D and 80.8% for pEGFP-p53(RS)-801D. The tumorigenicity in nude mice was suppressed. Inhibition effects of extraneous right sense p53 on malignant growth of 801D was more distinct. FCM analysis showed that pEGFP-p53(AS)-801D cells were arrested at G1 phase.

CONCLUSIONSThe transfected cell lines with extraneous right sense and antisense p53 appear that malignant growth can be inhibited in vivo and in vitro.