Identification and expression of a tumor-associated antigen in esophageal squamous cell carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To search for novel tumor associated antigens (TAA) in esophageal squamous cell carcinoma (ESCC).</p><p><b>METHODS</b>The proteins extracted from tissues of ESCC were separated by two dimensional polyacrylamide gel electrophoresis and transferred to PVDF membrane. Sera from ESCC patients and healthy individuals were used for primary antibodies for Western blot analysis. The differential spots were excised for trypsin hydrolysis and the tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The identified TAA of ESCC was validated by immunohistochemical staining (IHC).</p><p><b>RESULTS</b>Sera from ESCC patients yielded multiple positive spots, and one 28 800 Da protein that exhibited positive reactivity with 60% (12/20) sera of ESCC patients and only 5% (1/20) sera of healthy controls (P<0.01). The 28 800 Da protein was identified as phosphoglycerate mutase 1 (PGAM1) by MALDI-TOF-MS. Immunohistochemical analysis showed that PGAM1 was located in both cytoplasm and nucleus, and had a higher expression in cancer tissues.</p><p><b>CONCLUSION</b>PGAM1 maybe a candidate of ESCC.</p>

Erlotinib in the treatment of advanced non-small-cell lung cancer (NSCLC) / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement of survival in non-small-cell lung cancer (NSCLC) after the failure of front-line chemotherapy. The aim of this study was to evaluate the antitumor efficacy and toxicity of Erlotinib in the treatment of advanced NSCLC patients.</p><p><b>METHODS</b>A total of 104 patients with advanced NSCLC admitted in our department during December 2006 to November 2008 were enrolled in this study. Eligible patients received oral Erlotinib 150 mg/d until disease progression or intolerable toxicity. Best clinical response was determined using RECIST criteria, the adverse events were evaluated according to the NCI criteria.</p><p><b>RESULTS</b>The total effective rate was 27.9% (29/104) and the clinical benefit was 76.0% (79/104). The median progression-free survival was 5.1 months (95%CI 4.0 - 8.0). The median survival time was 13.1 months (95%CI 10.0 - 15.7). The 1-year survival rate was 61.5%. Significant survival benefit from erlobinib therapy was observed for patients with good personal status (HR 0.56, P = 0.006), adenocarcinoma (HR 0.43, P = 0.004) and skin rash (HR 0.46, P = 0.005). But patients with smoking (HR 2.75, P < 0.001) and liver metastasis (HR 2.91, P = 0.002) add the risk of death. The adverse events were mild (grade < or = 2), most common toxicities were skin rash in 73.1% (76/104) and diarrhea in 41.3% (43/104). Only 6.7% (7/104) patients got adverse events of grade > or = 3.</p><p><b>CONCLUSION</b>Erlotinib is an effective and well-tolerated treatment option for advanced NSCLC and could offer an alternative for patients after the failure of first-line chemotherapy, unsuitable for or not wishing to receive chemotherapy.</p>

Inhibitory effects of a combination of rmhTRAIL and gemcitabine on human non-small cell lung cancer cell line NCI-H460 cells in vitro and in vivo / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the inhibitory effects of recombinant mutant tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) combined with chemotherapeutic agent gemcitabine (GEM) on human lung cancer cell line NCI-H460 cells in vitro and in vivo.</p><p><b>METHODS</b>MTT was used to evaluate the cytotoxic effects of rmhTRAIL and GEM either used alone or in combination treatment on NCI-H460 cells. BAL B/c nude mice were transplanted with NCI-H460 tumor. The tumor-bearing nude mice were randomly divided into 6 groups (n = 6): negative control group (to be injected intraperitoneally with normal saline); rmhTRAIL group; GEM group; rmhTRAIL plus GEM group; GEM plus DDP group; rmhTRAIL plus GEM andDDP group. The tumor size was measured every 3 - 4 days. Twenty one days after the administration of different drugs the mice were killed and the tumors were taken out and weighed.</p><p><b>RESULTS</b>The growth inhibition of NCI-H460 cells was dose-dependent after exposure to rmhTRAIL, GEM alone or together. The combination of rmhTRAIL and GEM showed a synergistic inhibitory effect at different concentrations. The relative tumor volume of rmhTRAIL group, rmhTRAIL plus GEM group, GEM plus DDP group and rmhTRAIL plus GEM and DDP group were 4.75 +/- 3.04, 2.53 +/- 1.25, 4.52 +/- 2.87, and 1.69 +/- 0.97, respectively, all significantly smaller than that of the negative control group (8.82 +/- 5.62, P < 0.05 or P < 0.01). The tumor weight of these four groups were (2.23 +/- 0.29) g, (1.12 +/- 0.77) g, (2.51 +/- 0.87) g, and 0.60 +/- 0.18 g, respectively, all significantly less then that of the negative control group (4.71 g +/- 0.97 g, all P < 0.01). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM group were significantly smaller than those of either rmhTRAIL group or GEM group (P < 0.05 and P < 0.01, respectively). Both the relative tumor volume and tumor weight of rmhTRAIL plus GEM and DDP group were significantly smaller than those of either rmhTRAIL group or GEM plus DDP group (P < 0.05 and P < 0.01, respectively).</p><p><b>CONCLUSION</b>The combination of rmhTRAIL and GEM has a synergistic inhibitory effect on human NSCLC cell line NCI-H460 cells either in vitro and in vivo.</p>

Circulating endothelial cells in the peripheral blood of advanced NSCLC patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the changes and clinical value of circulating endothelial cells (CEC) in the peripheral blood of advanced NSCLC patient.</p><p><b>METHODS</b>Sixty-seven advanced NSCLC patients were randomly divided into either the treatment group with NP plus endostatin or control group with NP alone. Level of CEC and cytokeratin (CK) in the peripheral blood were measured by flow cytometry.</p><p><b>RESULTS</b>The response rate and benefit rate was 44.4%, 80.0% in the treatment group, and 27.3%, 50.0% in the control group, respectively (P = 0.176 and P = 0.012). Time to tumor progression (TTP) was 146.7 days in the treatment group and 91.1 days in the control group (P = 0.061). However, when the cut-off of TTP was defined as > 170 days, there was a significant difference between two groups (cut-off = 170, P = 0.034; cut-off = 180, P = 0.009). The number of CEC decreased by 0.29 +/- 0.47 in the treatment group and by 0.01 +/- 0.43 in the control group (P = 0.033). The correlation between CEC and CK was found to be positive either before (r = 0.381, P = 0.013) or after the treatment (r = 0.450, P = 0.004).</p><p><b>CONCLUSION</b>Chemotherapy combined with endostatin is superior to chemotherapy alone in the treatment of NSCLC. CEC, as a biomarker, may be useful in predicting the efficacy of the combined treatment.</p>

Effect of hypoxic radiosensitizer sodium glycididazole on long-term result of radiotherapy for nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the long-term effect of sodium glycididazole (CMNa) as a hypoxic radiosensitizer on the radiotherapy for nasopharyngeal carcinoma.</p><p><b>METHODS</b>Between May 1999 and May 2002, 211 patients with pathologically confirmed nasopharyngeal carcinoma were randomized into group-A treated by radiotherapy plus CMNa or group-B by radiotherapy alone. The staging was determined according to 92' Fuzhou staging systerm. The type, procession and dosage of radiotherapy were identical in both groups. The early adverse effect grade was assessed based on the CTC2.0 criteria and the late adverse effects were evaluated according to the RTOG/EORTC criteria. The median follow-up time was 52 months. All the data was analyzed by the SPSS 13.0 software. Characteristics and adverse events of these patients were compared between the two groups using t-test and the Wilcoxin rank sum test. Time-to-event curves were estimated using the Kaplan-Meier method. The prognostic parameters were analyzed using univariate analysis and the Cox multivariate regression analysis.</p><p><b>RESULTS</b>The clinical data of the two groups were comparable. The 3-year survival was 88.4% in group-A, while 75.2% in group-B, with a statistically significant difference between two groups (P = 0.010). Univariate analysis showed that the 3-year survival was statistically correlated with N-staging ((N0-1, 86.9%, N2-3 73.8%, P < 0.001), T-staging (T1-2 85.6%, T3-4 79.3%, P = 0.014), TNM staging (P = 0.039), and whether using CMNa or not during rediotherapy (Group-A 88.4%, Group-B 75.2%, P = 0.010). The 5-year recurrence-free survival, 5-year metastasis-free survival and 5-year overall survival were 75.8%, 74.9% and 77.7% in Group-A, while 63.0%, 63.0% and 62.4% in Group-B with a statistically significant difference between two groups (0.013, 0.022 and 0.010, respectively). If stratified in the subgroups, the overall survival of stage III - IV patients was statistically different between group A and B (P = 0.009), however, not of stage I - II patients (P = 0.502). Cox multivariate regression analysis showed that the independent prognostic parameters for survival were N-stage (RR = 3.288) , T-stage (RR = 2.147) and use of CMNa during rediotherapy (RR = 0.407). However, there was no statistically significant difference between two groups in acute or late adverse effects on nervous system or heart, which suggested that use of CMNa during radiotherapy would not aggravate the toxicity caused by radiotherapy.</p><p><b>CONCLUSION</b>Sodium glycididazole is well tolerable effective as a hypoxic radiosensitizer, which can improve the efficacy of radiotherapy and the long-term result of nasopharyngeal carcinom a patients, especially for the stage III - IV patients.</p>