BACKGROUNDMultidrug resistance (MDR) of lung cancer is a complex procedure involved in multiple genes and multiple pathways. Besides multidrug resistance genes, there is close relationship between expression of apoptosis-related genes and MDR in lung cancer. The aim of this study is to explore the relationship among the expression of apoptosis-related genes (p53, Bcl-2) and clinicopathological characteristics, and their correlation with multidrug resistance genes such as lung resistance protein (LRP), P-glycoprotein (P-gp), glutathione S-transferase π (GST-π), topoisomerase II (Topo II) and multidrug-resistance-associated protein (MRP) in lung cancer.

METHODSThe expression of P53, Bcl-2, LRP, P-gp, GST-π, Topo II and MRP was detected in 68 lung cancer patients (Bcl-2 for 51 patients) with immunohistochemical staining (Envision method).

RESULTSThe positive rate of P53 and Bcl-2 was 75.0% and 33.3% respectively. There was significant difference in P53 expression between non-small cell lung cancer and small cell lung cancer (P=0.001) and among various grades of cell differentiation (P=0.003). There was also significant difference in Bcl-2 expression between squamous cell carcinoma and adenocarcinoma (P=0.002). There was no relationship between the expression of P53 and Bcl-2 (P > 0.05). Spearman analysis showed that there was a positive correlation between the expression of P53 and P-gp (P=0.002), and between P53 and GST-π (P=0.017), and the coexpression rate was 70.6% and 47.1% respectively. There was no correlation between the expression of Bcl-2 and five multidrug resistance factors (P > 0.05).

CONCLUSIONSThe expression of apoptosis-related gene mutant p53 is significantly related to multidrug resistance factors P-gp and GST-π. It is important to detect both apoptosis-related genes and various multidrug resistance genes.

BACKGROUNDSomatostatin receptor (SSTR), as a marker gene in tumors, is being valued gradually. With five subtypes have been identified, many researches are carried out to explore the amino acid sequence of SSTR family members, the molecular biological characteristics, the distribution and expression in the normal tissue and the tumor, and their specific ligands. In this study, the expression and significance of SSTR (SSTR2A, SSTR5) and epidermal growth factor receptor (EGFR) in human non-small cell lung cancer (NSCLC) were investigated, and the relationship among them were evaluated.

METHODSThe expressions of SSTR2A, SSTR5 and EGFR in 62 NSCLC tissues and 7 lung tissues adjacent to the cancer tissues were detected by immunohistochemical method (SP method). All cases were followed up.

RESULTSIn 62 cases of NSCLC, the positive rate of SSTR2A and SSTR5 expression was 48.4% (30/62) and 71.0% (44/62) respectively. The positive rate of SSTR2A and SSTR5 was closely related to TNM stage (P < 0.05), but not to other clinical characteristics of NSCLC (P > 0.05). The positive rate of EGFR expression was 56.5% (35/62), but 0 in 7 lung tissues adjacent to the cancer tissues. The positive rate of EGFR was not related to the age, sex, smoking or not, tumors histological type, tumor size, TNM stage, differentiation classification and the lymph node metastasis (P > 0.05). There was negative relation between the expression of SSTR2A, SSTR5 and EGFR in NSCLC. The 3-year survival rate of patients with SSTR2A and SSTR5 expression was 64.52% and 65.91% respectively, 45.16% and 22.22% for those without expression (P < 0.05); The 3-year survival rate of patients with EGFR expression was 30.77% and 69.44% for those without expression (P < 0.05 ).

CONCLUSIONSThe expression of SSTR and EGFR is significantly upregulated in NSCLC and a negative relation exists between their expressions. Detection of expression of SSTR2A, SSTR5 and EGFR might be helpful to evaluate lymph node metastasis, pathological stages and prognosis of NSCLC.

BACKGROUNDDecorin is a member of the small proteglycans in extracellular matrix of tumor microenvironment, which is known to relate to the initiation, progression and growth of the tumor. The aim of this study is to investigate the effects and mechanism of decorin on the proliferation of A549 lung adenocarcinoma cell line in vitro.

METHODSLung adenocarcinoma cell line A549 was cultured with decorin in a wide range of concentration for different time. Cell activities were studied by MTT. The changes of cell cycle and apoptosis were analyzed by FCM. Decorin mRNA expression was detected by RT-PCR. P21 expression was determined by Western blot. TGF-β concentration in the culture supernatants was determined by ELISA.

RESULTSThe proliferation of A549 cell could be inhibited by decorin in vitro and the inhibition effect was the time- and dose-dependent relationship. Apoptosis of adenocarcinoma cell could be efficiently induced by decorin in a time/dose-dependent manner. Decorin could upregulate the intrinsic decorin mRNA and P21 protein expression, downregulate the TGF-β, and block cell cycle at G1 phase.

CONCLUSIONSDecorin can inhibit adenocarcinoma cell proliferation and induce apoptosis of adenocarcinoma cells in vitro. The proliferation of A549 cell could be inhibited in vitro by decorin through the mechanism of increasing decorin mRNA, decreasing TGF-β, increasing P21 protein expression, inhibiting cell cycle and inducing cell apoptosis.

BACKGROUNDLung cancer cells can upregulate the expression of Fas ligand (FasL) and counterattack tumor-infiltration lymphocyte (TIL) expressing Fas via the FasL/Fas pathway, therefore escape from immunosurveillance and impair local anti-tumor immune capacity. The aim of this study is to investigate the effects of reducing FasL expression on T cell apoptosis in lung cancer cell line H460 via small interfering RNA (siRNA) technology.

METHODSIn vitro chemically synthesized siRNA targeting FasL as well as constructed plasmid vector were transfected into H460 cells, wherein the interfering effect and alterations in T cell apoptosis were observed.

RESULTSSequence-specific interfering effect was detected at RNA and protein levels by RT-PCR and Western blot in the H460 si group, and the reduction of FasL expression was capable of rescuing T cell apoptosis induced by lung cancer cells.

CONCLUSIONSFasL can be utilized as a new target in gene therapy of lung cancer.

BACKGROUNDEndothelin-1 (ET-1) is a potent mitogen involved in tumor cell growth and angiogenesis. The aim of this study is to explore the effect of ET-1 on the proliferation of human lung adenocarcinoma cells SPC-A1.

METHODSCell number was measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide] assay. Cell cycle was detected by flow cytometry.

RESULTSET-1 (1×10⁻¹⁵ -1×10⁻⁸ mol/L) enhanced SPC-A1 cell growth in a dose-dependent manner in vitro, with the greatest effect beginning at 1×10⁻¹¹ mol/L. Effect of ET-1 (1×10⁻¹⁰ mol/L) on the proliferation of SPC-A1 cells was completely blocked by BQ123 (1×10⁻⁷ mol/L), a highly selective endothelin receptor A (ETA) antagonist (P < 0.05), not by BQ788 (1×10⁻⁷ mol/L), a highly selective endothelin receptor B (ETB) antagonist. BQ123 could significantly reduce the basal growth of SPC-A1 cells (P < 0.05), but BQ788 had no such effect. Proliferation induced by ET-1 (1×10⁻¹⁰ mol/L) could also be blocked by the addition of either ethylene diamine tetraacetic acid (EDTA, 0.4mmol/L) or nifedipine (1μmol/L). ET-1 had no significant effect on SPC-A1 cell cycle.

CONCLUSIONSET-1 enhances SPC-A1 cell proliferation by the activation of ETA receptor. Ca(2+) influx from voltage dependent calcium-channel contributes to this process.

BACKGROUNDSarcomatoid carcinoma (SC) is a rare malignant cancer with mixed tumor and sarcomatoid tissues. The aim of this study is to investigate the clinical manifestations and pathological findings of sarcomatoid carcinoma of the lung.

METHODSData including clinical manifestations, pathological findings, treatment were retrospectively analysed from fourteen patients with lung sarcomatoid carcinoma confirmed by pathology and follow-up was carried out.

RESULTSMean age at onset was 62 years old and gender ratios (M/F) in these patients was 6:1. The clinical manifestations of lung sarcomatoid carcinoma were similar to that of other types of lung cancer while there were characteristic findings on the enhancement CT scan. Bronchofiberscopy was not a reliable examination for final diagnosis. Cells with endothelial phenotype could be detected by immunohistochemical method.

CONCLUSIONSThe final diagnosis of this disease depends on histopathological observation, while the diagnosis may be missed among patients without surgical intervention. Immunohistochemical examination is helpful for diagnosis and differential diagnosis. The therapeutic strategy is coincident with that for non-small cell lung cancer.

BACKGROUNDPathology is the "gold standard" of the diagnosis of lung cancer, but at present there are few articles about evaluating the value of cytopathological check. The aim of this study is to evaluate the value of cytopathological check in the diagnosis of primary bronchogenic carcinoma of the lung.

METHODSA total of 552 samples' cytopathological results of 248 patients from January 2003 to May 2005 in this hospital were retrospectively analyzed. The samples included pleural fluids (110 for 68 patients), materials from lung puncture (33 for 31 patients), smears of transcatheter bronchial brushing (152 for 138 patients), bronchoalveolar lavage fluids (30 for 26 patients) and sputa (227 for 118 patients).

RESULTSThe positive results of different specimens were as follow: the pleural fluids was 69.12%, the materials from lung puncture 67.74%, the smears of transcatheter bronchial brushing 65.22%, the bronchoalveolar lavage fluids 23.08% and sputa 21.19% respectively. The positive rates of the pleural fluids, the materials from lung puncture and the smears of transcatheter bronchial brushing were higher than that of the bronchoalveolar lavage fluids and sputa (P < 0.01). There was no significant difference among the positive rates of the pleural fluids, the materials from lung puncture and the smears of transcatheter bronchial brushing, and between the positive rates of the bronchoalveolar lavage fluids and sputa (P > 0.05).

CONCLUSIONSThe cytopathological examination is helpful for the diagnosis of primary bronchogenic carcinoma of the lung, and is one of the important ways to the diagnosis of primary bronchogenic carcinoma of the lung.

BACKGROUNDNow the treatment of non-small cell lung cancer (NSCLC) patients with brain metastasis is not a standard program. The aim of this study is to summarize the factors related to survival of patients with brain metastases from NSCLC.

METHODSA total of 111 NSCLC patients with brain metastases (from September 1995-May 2004) were defined as symptomatic group (37 patients) and asymptomatic group (74 patients) according to central nervous system (CNS) symptoms. The patients in the symptomatic group were given whole brain radiation therapy (WBRT, DT 30-40Gy/20f) first, and then received cisplatin-based chemotherapy. The patients in the asymptomatic group were given cisplatin-based chemotherapy first, and then received WBRT. During the treatment, 49 patients received chemotherapy of BCNU or VM-26 irregularly.

RESULTSThe median survival time was 11 months. The 1-and 2-year survival rate was 40.79% and 13.26% respectively. The survival time was not significantly different between the symptomatic group and asymptomatic group. Median chemotherapy of asymptomatic group was 3 cycles (1-6 cycles) before WBRT. Those patients who received 3 or 4 cycles of chemotherapy before WBRT had better survival (P= 0.0188 , P=0.0035). The treatment of BCNU or VM-26 was a benefit factor for survival (P=0.0219) in asymptomatic group. The hematologic toxicity of grade III or IV was not significantly different between the two groups (P > 0.05). The number of brain metastasis (P=0.000), extracranial metastasis (P=0.022) and WHO performance status (P=0.001) were independent prognostic factors.

CONCLUSIONSThe patients with asymptomatic brain metastases receive 3-4 cycles of chemotherapy before WBRT may be reasonable. During the therapy, the patients with administration of BCNU or VM-26 may have survival benefit.

BACKGROUNDUroacitides is a group of cell differentiation inducers, which is purified from fresh human urine. Preclinical studies of Uroacitides have showed that cancer cells could be induced to differentiate, and the growth of cancer cells could be inhibited by Uroacitides. The aim of this study is to compare the efficacy and toxicity between Uroacitides combined with NP regimen and NP alone in treatment of advanced non-small cell lung cancer (NSCLC).

METHODSForty-two cases of advanced NSCLC were randomized into Uroacitides+NP and NP groups. NP group: NVB 25mg/m² on days 1 and 8, DDP 75mg/m² on day 1. Uroacitides combined with NP group: Uroacitides of 300mL was given through subclavian catheter daily for 7 days prior to the NP chemotherapy, then concurrently with NP regimen for 2 cycles, except the days of administration of chemotherapy.

RESULTSIn the Uroacitides+NP group, the overall response rate was 44.4%, and 20.0% in the NP group (P > 0.05). The median survival time was 9 months in the Uroacitides+NP group and 6 months in the NP group (P=0.0287). The main toxicities were myelosuppression, gastrointestinal reaction and alopecia, and there was no significant difference in incidences of toxicities between the two groups (P > 0.05).

CONCLUSIONSUroacitides combined with NP regimen shows a good curative effect and low toxicity, and may significantly prolong the median survival time for advanced NSCLC.

BACKGROUNDIt is well known that more than 40% patients were initially diagnosed with advanced non-small cell lung cancer (NSCLC) with intrapulmonary or/and distant metastasis. However, up to now, the reports about effects of different metastatic sites on survival were limited. The aim of this study is to investigate the clinicopathologic and survival difference by retrospective analysis among sole intrapulmonary metastasis, sole extrathoracic distant metastasis and simultaneous metastasis of lung and other extrathoracic organs for the patients with advanced NSCLC, and to analyze the prognosis-related factors of NSCLC with intrapulmonary metastasis.

METHODSOf the 425 patients with stage IV NSCLC diagnosed by pathology and through staging evaluation and treated at Beijing Cancer Hospital with long follow-up during Oct. 1995 to Dec. 2003, 81 cases had sole intrapulmonary metastasis, 98 cases had sole extrathoracic distant metastasis and 68 cases presented simultaneous lung metastasis and extrathoracic spread. Kaplan-Meier survival curve was performed to estimate the survival of patients with different metastasis, Log-Rank test was used to compare their survival difference, and univariate analysis was used to find prognostic related factors.

RESULTSMedian survival time (MST) and 1-, 2-, 3-year survival rate (SR) for patients with sole intrapulmonary metastasis were 13 months (95% CI: 11-15), 57%, 21%, 7%, respectively; MST was 22 months (95% CI: 18-26) for patients with N1 and/or N2 and 10 months (95%CI: 7-13) for patients with N3 (P=0.001). Among the patients with ipsilateral, contralateral and bilateral intrapulmonary metastasis, difference of MST and 1-, 2-, 3-year SR had no statistical significance (P > 0.05); Survival of patients with sole intrapulmonary metastasis was not significantly different from that of patients with sole brain or bone metastasis (P > 0.05), but was longer than that of patients with simultaneous lung and extrathoracic spread (P=0.021). One way analysis of variance showed that no significant association were found among age, pathologic subtype, differentiation degree or response of first-line chemotherapy and survival of the patients with sole intrapulmonary metastasis (P > 0.05), but sex and invasive status of lymph node (N1/N2 vs N3) were found to influence the survival of the patients (P= 0.018, P=0.001). Further stratified analysis by age showed that invasion of lymph node was independent prognostic factor (P=0.002); whereas for the patients with simultaneous metastasis of lung and distant organs, metastatic numbers (2 vs ≥3) of organ were independent prognostic factor (P=0.013).

CONCLUSIONSNo statistical difference is found among survival of NSCLC patients with sole intrapulmonary metastasis and with sole brain, bone metastasis. Invasive status of lymph node and metastatic number of organ are important prognostic factors for patients with sole intrapulmonary metastasis and simultaneous metastasis of lung and extrathoracic organs, respectively.