1.Clinical significance of multiple tumor marker protein chip in monitoring the recurrence,progression and metastasis of lung cancer.
Xueqin YANG ; Dong WANG ; Zengpeng LI ; Ge WANG ; Zhenzhou YANG ; Zhixiang YANG ; Yuqing YANG ; Yaoguang JIANG
Chinese Journal of Lung Cancer 2007;10(4):296-300
BACKGROUNDAccording to the report of the 11th World Conference on Lung Cancer, lung cancer is the leading cause of cancer related death. So there is important clinical significance to monitor the patients with lung cancer through different ways. The aim of this study is to investigate the clinical significance of multiple tumor marker protein chip in monitoring the recurrence, progression and metastasis of lung cancer.
METHODSForty-four patients were selected, who were detected at least 4 times with tumor mar-ker protein chip. Based on efficacy and status, patients were classified as six grades. Correlation of expression level of each tumor marker with grade of efficacy and status was analyzed. And the discriminant functions for recurrence, progression and metastasis of lung cancer were established.
RESULTSGrade of efficacy and status was closely related to CA199, CEA, CA242, AFP and CA125 in adenocarcinoma (AC), to CA125 in squamous cell carcinoma (SqCa), and to CA199 and CA125 in small cell lung cancer (SCLC). Based on the discriminant functions, accuracy rate of efficacy and status judgement was 89.4%, 80.4%, 78.3% and 66.7% for female AC, male AC, SqCa and SCLC respectively.
CONCLUSIONSThere is important clinical significance of multiple tumor marker protein chip in monitoring the recurrence, progression and metastasis of lung cancer (especially adenocarcinoma).
2.Expression of hepatoma-derived growth factor and its clinical implication in stage I non-small cell lung cancer.
Shijie ZHOU ; Shaofa XU ; Haiqing ZHANG ; Zhidong LIU ; Zikun LIANG ; Xiaoyun SONG ; Ying JIANG ; Dan ZHAO
Chinese Journal of Lung Cancer 2007;10(4):291-295
BACKGROUNDHepatoma-derived growth factor (HDGF), a novel growth factor, has a widely expression in many normal cells and tumor cells. It plays an important role in cell proliferation, differentiation and angiogenesis. It is considered as a promising marker for predicting the invasion, matastasis and prognosis of carcinomas in clinical researches. The aim of this study is to evaluate the expression of HDGF and its clinical implication in patients who undergone complete resection for stage I non-small cell lung cancer (NSCLC).
METHODSImmunohistochemical technology was applied to detect the expression of HDGF in 118 lung cancer tissues and 30 normal lung tissues as control.
RESULTSHDGF staining was observed in nuclear as well as in cytoplasm. HDGF positively staining was seen in all patients, and remarkably higher than that in normal lung tissues (52.23±10.35 vs 156.73±70.95, P < 0.01). Expresson of HDGF was closely related to histological classification, but not to other clinicopathological factors, and the expression of HDGF in adenocarcinoma was much stronger than that in squamous cancers (P=0.001). Univariate analysis and multivariate Cox regression analysis showed that the patients with high HDGF expression had a shorter overall survival and HDGF was a significantly independent predictive factor for patients with stage I NSCLC (RR=1.011, P=0.002).
CONCLUSIONSHDGF may be a promising predictive factor for stage I NSCLC, and the assessment of HDGF may provide new insight on carcinogenesis and development of stage I NSCLC .
3.Correlation between OPN and P21 in non-small cell lung cancer.
Xuelin ZHANG ; Song XUE ; Jiahao ZHENG ; Sha LIU
Chinese Journal of Lung Cancer 2007;10(4):288-290
BACKGROUNDAt present, little is known about the correlation between osteopontin (OPN) and P21 in primary non-small cell lung cancer (NSCLC). The aim of this study is to investigate the expression of OPN and P21 and their correlation in NSCLC.
METHODSThe expression of OPN and P21 was detected in 58 NSCLC tissues and 18 pulmonary inflammatory pseudotumor (PIP) as controls by immunohistochemical technique.
RESULTSThe positive rate of OPN and P21 in NSCLC was 58.6% and 70.7% respectively, which was significantly higher than those in PIP (11.1% and 16.7%) (P=0.0008, P < 0.0001). There was a positive correlation between OPN and P21 expression (P < 0.0001). Lymph node metastasis was closely related to OPN expression (P=0.0367), but not to P21 expression (P=0.4898).
CONCLUSIONSThe abnormal expression of OPN and P21 in NSCLC may act in a synergistic way. Immunopositivity of OPN may suggest a potential risk of metastasis in NSCLC.
4.Relationship of clusterin expression with Bax and p53 expression in non-small cell lung cancer.
Linlin NIU ; Jialan ZANG ; Li CAI ; Chunhong LI ; Hongyan CAO
Chinese Journal of Lung Cancer 2007;10(4):284-287
BACKGROUNDIt has been proven that clusterin is a newly apoptosis-related factor and upregulates in many tumors. It plays important roles in carcinogenesis and tumor progression. The antiapoptosis of clusterin seems to be relative to other antiapoptosis factors. The aim of this study is to investigate the expression and significance of clusterin in non-small cell lung cancer (NSCLC) tissue.
METHODSThe expression of clusterin, p53 and Bax in NSCLC were detected by immunohistochemical SP method and Western blot assay.
RESULTSPositive expression rate of clusterin was 79.25% (42/53) in NSCLC tissues which was much higher than that in normal lung tissue (2/16, 12.50%) (Chi-square=23.68, P < 0.05). The expression of clusterin was closely related to pathological differentiation (rs=0.464, P < 0.01), clinical stage (rs =0.320, P < 0.01) and lymph node metastasis (rs=0.255, P < 0.05), but not correlated to the sex (Chi-square=0.007, P > 0.05), age (Chi-square=0.707, P > 0.05) and histological type (Chi-square=0.702, P > 0.05). The expression of clusterin in NSCLC was positively correlated to the expression of p53 (rs=0.589, P < 0.01), but was negatively related to the expression of Bax (rs =-0.346, P < 0.01). The relative expression level of clusterin protein in NSCLC was significantly higher than that in normal lung tissue (0.541±0.010 vs 0.201±0.020) (P < 0.05).
CONCLUSIONSClusterin may play an important role in the biological characteristics of NSCLC by the antiapoptosis pathway.
5.Relationship between metastasis-associated protein 1 expression and metastasis and prognosis in non-small cell lung cancer.
Nan ZHANG ; Qingfu ZHANG ; Enhua WANG ; Xueshan QIU
Chinese Journal of Lung Cancer 2007;10(4):279-283
BACKGROUNDMetastasis is the main cause of the death of lung cancer patients. Much attention has been pain to the research of lung cancer metastasis. Metastasis-associated protein 1 (MTA1) is one member of metastasis associated protein family. Its overexpression is correlated with metastasis of esophageal carcinoma and breast cancer, but the generality of its expression in cancer and the significance for judging biological behaviors of tumor and evaluating prognosis of patients is to be investigated. The aim of the study is to study the relationship between MTA1 expression and clinicopathological factor regarding metastasis and prognosis of human non-small cell lung cancer (NSCLC).
METHODSThe expression of MTA1 was detected in 101 parafin-embedded specimens by immunohistochemistry method, as well as in 35 freshly-taken NSCLC tissues by Western blot.
RESULTSThere were 56 cases (55.4%) of NSCLC with yellow or even brown particles in nucleus of tumor cell among 101 cases, and MTA1 protein showed negative expression in epithelia of bronchi or alveoli in neighboring noncancerous tissue. Western blot analysis showed the level of MTA1 in NSCLC tissues was remarkably higher than that in normal tissues (t=3.953, P=0.000). Expression of MTA1 was remarkably higher in tumor with metastasis than that in tumor without metastasis (t=4.057, P=0.000). Expression of MTA1 significantly correlated with differentiation (Chi-square=10.131, P=0.006), lymphatic metastasis (Chi-square=8.535, P=0.003) and p-TNM stage (Chi-square=17.419, P=0.000). The survival time of pa-tients with negative MTA1 expression was (44.866±12.946) months, which was significantly higher than that of patients with positive MTA1 expression [(23.714±7.498) months] (Chi-square=10.006, P=0.002). In multivariate analysis, only lymphatic metastasis and TNM stage could be considered as independent prognostic factors.
CONCLUSIONSMTA1 might play an important role in the development and metastasis of NSCLC. Patients with MTA1 expression have a greater chance of metastasis and a poorer prognosis. However, MTA1 expression is not an independent prognosis factor.
6.Effects of antisense oligodeoxynucleotides on vascular endothelial growth factor expression in Lewis lung carcinoma cells in vitro.
Ying WANG ; Chunyan LIN ; Chunyan LI
Chinese Journal of Lung Cancer 2007;10(4):275-278
BACKGROUNDVascular endothelial growth factor (VEGF) can specially target the vascular endothelial cells so as to enhance their proliferation and angiogenesis. The aim of this study is to investigate the inhibition effects of VEGF antisense oligodeoxynucleotides (VEGF ASODN) on VEGF expression of Lewis lung carcinoma cells.
METHODSThe phosphorothioate-modified and liposome-encapsulated VEGF ASODN, VEGF SODN were added into the medium of Lewis lung carcinoma cells respectively. VEGF mRNA and protein were detected by RT-PCR and immunohistochemistry. And the proliferation of vascular endothelial cells treated with supernatants was determined.
RESULTSVEGF ASODN could significantly inhibit the expression of VEGF mRNA and protein expression in Lewis lung carcinoma cells, as well as the proliferation of endothelial cells.
CONCLUSIONSIt is hopeful that VEGF ASODN may become a new antiangiogenesis therapy strategy in lung cancer.
7.Effect of Ad-Gax transfection on apoptosis of human lung adenocarcinoma A549 cells and its mechanism.
Shijin XIA ; Xiantao TAI ; Jingcheng DONG ; Guisheng QIAN ; Mingdong HU
Chinese Journal of Lung Cancer 2007;10(4):269-274
BACKGROUNDApoptosis is closely related to development of lung cancer. It is a strategy of lung cancer therapy to induce apoptosis. The aim of this study is to explore the effects of growth arrest-specific homeobox (Gax) transfection on apoptosis and expression of Bcl-2 and Bax proteins of human lung adenocarcinoma A549 cells.
METHODSA549 cells were transfected with Gax gene by a replication-deficient adenovirus expressing the hemagglutinin-tagged Gax cDNA (Ad-Gax). Apoptosis of A549 cells was observed by transmission electronic microscope and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) positive staining. Apoptotic rate of A549 cells was evaluated by flow cytometry. Expressions of Bcl-2 and Bax proteins in A549 cells were detected by immunocytochemistry.
RESULTSBefore Ad-Gax transfection, none or few of TUNEL-positive A549 cells were detected. After Ad-Gax transfection, a marked increase in TUNEL-positive staining occurred, especially at 24 h later. The ratio of apoptosis of A549 cellsin non-transfection group and transfection groups at 12 h, 24 h, 48 h were 0.25%, 12.57%, 17.29%, 15.03%, respectively. Compared with non-transfection group, the apoptotic rates of transfection groups increased significantly (Chi-square value was 7.357, 11.126 and 9.943 respectively, P < 0.01). The average optical density (AOD) of Bcl-2 protein in A549 cells in non-transfection group and transfection groups at 12 h, 24 h, 48 h were 2.02±0.07, 1.79±0.02, 1.25±0.51 and 1.21±0.24 respectively. Compared with non-transfection group, AOD of Bcl-2 protein in A549 cells in transfection groups decreased significantly (t value was 6.651, 7.089 and 7.438 respectively, P < 0.01). On the other hand, Bax protein expression in transfection groups increased, the AODs of Bax were 4.49±0.61, 4.24±0.37 and 3.95±0.43, respectively. Compared with non-transfection group (3.12±0.42), AOD of Bax protein in A549 celle in transfection groups increased significantly (t value was 7.469, 7.287 and 6.473 respectively, P < 0.01). In the Ad-Gax transfection groups the lower Bcl-2/Bax ratio was, the higher the apoptotic rate of A549 cells was (r=-0.49, P < 0.01).
CONCLUSIONSAd-Gax transfection can induce A549 cells apoptosis. Possible mechanism is that Gax can downregulate Bcl-2 protein expression and upregulate Bax protein expression, and A549 cells apoptosis is related to the Bcl-2/Bax ratio.
8.Different proteome of human lung adenocarcinoma cells treated with NS-398 and cisplation.
Yepeng LI ; Chengping HU ; Esheng WU
Chinese Journal of Lung Cancer 2007;10(4):263-268
BACKGROUNDRecent studies have shown that NS-398, a highly selective COX-2 inhibitor, can enhance the inhibition effects of cisplatin on adenocarcinoma cell proliferation, but the mechanism is still unknown. The aim of this study is to explore the mechanism about the synergistic effects of NS-398 and cisplatin to human lung adenocarcinoma cell line.
METHODSDifferentially expressed proteins were separated in human lung adenocarcinoma cells treated with NS-398 and/or cisplatin by immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE), then 19 out of obtained proteins were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and database searching.
RESULTSThere were 22 down-regulated proteins and 2 up-regulated proteins in NS-398+cisplatin combination group compared with control groups. Finally six proteins were identified, in which some were cytokeratins, some were associated with proliferation and apoptosis, and the others were involved in metabolism of tumor cells.
CONCLUSIONSThe down-regulation of HSP90 and triosephosphate isomerase may be related to the synergistic effects of NS-398 and cisplatin on human lung adenocarcinoma cells.
9.Clinical analysis of 8 cases of tracheal adenoid cystic carcinoma.
Yu YANG ; Ming JIANG ; Dan CAO ; Hongfeng GOU
Chinese Journal of Lung Cancer 2007;10(3):237-239
BACKGROUNDTracheal adenoid cystic carcinoma (TACC) is a rare, low malignant and primary tracheal carcinoma, which is easily misdiagnosed and missedly diagnosed. The aim of this study is to increase the knowledge about TACC.
METHODSData including clinical manifestations and treatment were retrospectively analyzed for 8 cases of TACC confirmed by pathology and follow-up was carried out.
RESULTSThe main manifestations were cough, stridor, hemoptysis and progressive inspiratory dyspnea. Fiberoptic bronchoscope and computerized tomography were reliable examinations for final diagnosis. Five cases underwent operative treatment, and three cases underwent interventional treatment by fiberoptic bronchoscope in which 1 case accepted a second operation after recurrence and 2 cases accepted chemotherapy after operation. One case was lost, 1 case treated by interventional treatment died after 11 months and other 6 cases were followed-up from 2 months to 34 months who were alive.
CONCLUSIONSTACC is low malignancy and has good prognosis. The best treatment is operation. The better palliative treatment is interventional treatment by fiberoptic bronchoscope which can relieve symptoms and improve the patient's living quality.
10.The short-term observation of Shenqifuzheng injection combined with NP chemotherapy in treating elder patients with advanced non-small cell lung cancer.
Xiuyun WANG ; Zongqiong HUANG ; Hong LI ; Xuebin CAI
Chinese Journal of Lung Cancer 2007;10(3):234-236
BACKGROUNDAbout 80% lung cancer is non-small cell lung cancer (NSCLC) and 70%-80% are in advanced stage. Chemotherapy is main treatment method. The aim of this study is to compare the therapeutic effects and toxicity of NP regimen combined with Shenqifuzheng injection on elder patients with advanced NSCLC.
METHODSTotally 69 patients enrolled into this study and were randomized into two groups: treatment group (35 patients) and control group (34 patients). Each patient received NVB 25mg/m² intravenously at days 1 and 8 and DDP 30mg intravenously from 1st day to 4th day. Shenqifuzheng injection was used in the treatment group by 250mL per day for 10 days.
RESULTSThere was no significant difference of the response rate between two groups (45.7% vs 41.2%, P > 0.05). The hematological toxicity, nausea and vomiting in the treatment group were lower than those in the control group with significant difference (P < 0.05). The adverse effects were well tolerable.
CONCLUSIONSNP regimen combined with Shenqifuzheng injection on elder patients with advanced NSCLC is effective and safe. Shenqifuzheng injection has definite toxicity relieving effect on treating elder patients with advanced NSCLC.