In non-small cell lung cancer( NSCLC),a major characteristic is the abnormal methylation of some certain genes. The hypomethylation of proto-oncogene has the potential to promote carcinogenesis and the formation of neoplasm may also be induced by the hypermethylation of tumor suppressor genes. Meanwhile, the balance between histone acetylation and deacetylation is closely connected to the tumorigenesis. While the histone acetyltransferases can directly acetylate genes related to proliferation,causing cell growth and transfor-mation,histone deacetylase will also alter the level of acetylation of certain proteins,and eventually affect NSCLC. Hence,these abnormal epigenetic modifications play a fundamental role in the formation and develop-ment of NSCLC.

Nucleotide excision repair (NER) pathway is one of the principal ways of the repair of DNA damage.The single nucleotide polymorphisms (SNP) of its key genes such as xeroderma pigmentosum group A (XPA) gene,excision repair cross complementingl (ERCC1) gene and xeroderma pigmentosum group D (XPD) gene may be associated with differences in the DNA repair capacity and may influence an individual's risk of lung cancer,because the variant genotype in those polymorphisms might destroy or alter repair function.

Objective To elucidate the molecular mechanisms of sorafenib inhibitting human pe-ripheral blood T cells. Methods CFSE(5, 6-carboxyfluorescein diacetate succinimidyl ester) proliferation assay and MTS [3-(4, 5-diethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-( 4-sulfophenyl) -2H-etrazoli-um, inner salt] assay were used to examine the proliferation and the viability of T cells; Annexin V-FITC and PI staining was used to detect apoptosis; Flow cytometry was used to detect the expression of CD25, CD69; Western blot was used to detect the expression of cell cycle proteins; ELISA was used to detect the level of IL-2; Picryl chloride-induced delayed-type hypersensitivity model to be used to for the evaluation of in vivo immunocompetency. Results Sorafenib inhibited proliferation of human peripheral blood T cells in-duced by phytohemagglutinin(PHA) in a dose-dependent manner without inducing their apeptosis. Sorafenib caused human blood T cells arrest in the G_0/G_1 phase of the ceLl cycle. Sorafenib decreased CD25 and CD69 expressions and IL-2 production in human T cells. Sorafenib inhibited picryl chloride-induced delayed-type hypersensitivity in mice. Conclusion Sorafenib could inhibit proliferation and activation of peripheral blood T cells. These finding indicated that long term administration of sorafenib might lead to immunosuppressive effects.

Targeted therapy combined with chemotherapy has achieved great success in palliative treatment for metastatic colorectal cancer.Recent studies gave more emphasis on new fields,such as maintenance treatment,adjuvant treatment and the prognostic & predictive biomarker.These advances have been gradually changing the treatment strategies for colorectal cancer.The latest advances on the targeted therapy for colorectal cancer from the 2010 Annual Meeting of American Society of Clinical Oncology are reviewed below.

Purpose:To evaluate the efficacy and toxicity of the combination of paclitacxel and carboplatin on advanced non-small-cell lung cancer (NSCLC). Methods:Forty-eight patients with locally advanced (stageⅢb) or metastatic (stage Ⅳ) NSCLC were enrolled into the study. The patients received paclitacxel 55-60 mg/m 2 on day 1,8,15, carboplatin at an AUC of 5 on day 1. administreted in a 28-day cycle. Results:An objective response was obtained in 37.5% of patients (2 complete and 16 partial responses),Significant difference existed between the naive patients and pretreated patients (46.4% Vs 25.0%,P

Background and purpose:At present, the relationship between tumor length and prognosis of esophageal carcinoma patients has been a controversial topic, and there have been few studies describing the effect of tumor length on clinicopathology and prognosis of node-negative esophageal carcinoma patients. The purpose of this study was to investigate the effect of the tumor length on clinicopathology and prognosis of node-negative esophageal carcinoma patients.Methods:The clinicopathological characteristics and survival time of 686 node-negative esophageal carcinoma patients, conifrmed by surgical pathology specimens in the First Afifliated Hospital of Nanjing Medical University from Jan. 2008 to Dec. 2010, were retrospectively analyzed. The optimal cut-off value was determined by decision tree model. Univariate and multivariate methods were used to analyze the prognostic factors of node-negative esophageal carcinoma patients.Results:In decision tree analysis, esophageal tumor length was correlated with an increasing hazard ratio for death with a cut-off value at 3 cm. No signiifcant differences were found in gender, onset age, lesion site and pathological type between 2 groups which were patients with tumor length≤3 cm and tumor length >3 cm (P>0.05). The only 1 difference between 2 groups was T stage (P<0.001), and tumor length had a positive correlation with T stage (r=0.373). The 1-, 3- and 5-year survival rates of patients with tumor length≤3 cm and tumor length >3 cm were 95.7%, 84.4%, 76.1% and 88.3%, 57.8%, 46.5% respectively, and the difference was statistically signiifcant (P<0.001). Tumor length was signiifcantly associated with overall survival in univariate and multivariate analyses.Conclusion:Tumor length has close relationship with T stage in node-negative esophageal carcinoma patients. Tumor length≤3 cm could be considered as T1-2 and >3 cm as T3. Tumor length is an important prognostic factor for esophageal carcinoma patients without lymphatic metastasis.

Carcinoma, Non-Small-Cell Lung ; pathology ; therapy ; Humans ; Immunotherapy ; Lung Neoplasms ; pathology ; therapy ; Neoplasm Staging ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Vascular Endothelial Growth Factor A ; antagonists & inhibitors

BACKGROUNDp53 gene is the most commonly mutated gene in lung cancer. p53 mutation results in insensitivity of cells when exposed to chemotherapy. It has been reported that adenovirus-mediated wild-type p53 gene transfection into lung cancer cells can enhance the cytotoxic effect of anti-cancer drugs. The aim of this study is to evaluate the effects of domestic recombinant adenovirus-p53 (Ad-p53, Gendicine) on growth and chemosensitivity of human lung adenocarcinoma cell lines.

METHODSHuman lung adenocarcinoma cell lines GLC-82 (including mutant p53) and A549 (including wild-type p53) were treated with Ad-p53, cisplatin (DDP) or Ad-p53+DDP respectively. p53 expression was detected by Western blot. The cell growth inhibition was assessed by MTT, and cell cycle and apoptosis were detected by flow cytometry.

RESULTSHigh-level p53 expression was detected in Ad-p53 infected GLC-82 and A549 cells by Western blot. There was a dose-dependent and time-dependent inhibition of cell proliferation by Ad-p53. After combined treatment with Ad-p53 (100MOI) and DDP (0.5mg/L) for 72h, the growth inhibition rate of A549 cells was 43.13%±0.72%, which was significantly higher than that in Ad-p53 group ( 23.44%±0.54%, P < 0.001) and DDP group (14.17%±1.39%, P < 0.001); and the growth inhibition rate of GLC-82 cells was 63.73%±0.92%, which was significantly higher than that in Ad-p53 group ( 41.51%±0.59%, P < 0.001) and DDP group (56.11%±1.12%, P < 0.001). Combined administration of Ad-p53 and DDP remarkably arrested A549 and GLC-82 cells in G0-G1, and cells in S phase significantly decreased. Meanwhile the apoptotic rate of A549 cells was 28.99%±1.07% in Ad-p53+DDP group, which was significantly higher than that in Ad-p53 group (15.35%±1.31%, P < 0.001) and DDP group (1.74%±0.77%, P < 0.001). The apoptotic rate of GLC-82 cells was 62.98%±2.43% in Ad-p53+DDP group, which was significantly higher than that in Ad-p53 group (20.88%±0.71%, P < 0.001) and DDP group (6.91%±1.52%, P < 0.001).

CONCLUSIONSAd-p53 (Gendicine) can inhibit the growth of human lung adenocarcinoma cell lines irrespective of the status of endogenous p53 gene. Its combination with DDP may significantly enhance the chemosensitivity of human lung adenocarcinoma cells to DDP.

Objective To investigate the surgical methods and the differences of postoperative complications in esophageal canccr patients aged 60 years and over undergoing different operation models.Methods A total of 542 elderly esophageal cancer patients who underwent thoracic surgery at our hospital between January 2010 and December 2016 were enrolled.Patients were divided into 4 groups:left thoracic incision operation group (n =202),lvor-Lewis two incisions operation group (right chest posterolateral and upper abdomen median) (n=251),three incision operation group (left neckright chest-abdominal midian (n =29),and McKneown under-endoscope minimally invasive operation group (n=60).Clinical data,including the postoperative days,numbers of lymph nodes dissection,pulmonary infection,serous membrane fluid,arrhythmia,chylous fistula,gastric emptying dysfunction and anastomotic leakage,were retrospectively compared between the four groups.Results There was no significant difference in the postoperative days,serous membrane fluid,arrhythmia,chylous fistula,gastric emptying dysfunction and anastomotic leakage (P ＞ 0.05).The number of lymph nodes dissection in Sweet group,Ivor-Lewis group,Mckeown operation group and minimally invasive Mckneown group were (12.9±7.4)、(19.3±8.6)、(14.3±6.9)and(15.4±7.3)respectively.The number of lymph nodes dissection was more in the Ivor-Lewis group than in the other three groups (F =23.915,P =0.000).Sweet group,Ivor-Lewis group,Mckeown group and minimally invasive Mckneown group were 31.7％、40.2％、24.1％ and 50.0％ respectively.The incidence of pulmonary infection was higher in the minimally invasive surgery group than in the other three groups (x2 =9.941,P =0.019).Conclusions Ivor-Lewis surgery is more effective in lymph nodes dissection and has a lower incidence of complications in elderly esophageal cancer patients.The minimally invasive surgery group has a higher incidence of pulmonary infection than in the other surgical groups,which may be related with the immaturity of endoscopic technique.

BACKGROUNDWe evaluated the impact of the number of metastatic lymph nodes and the metastatic lymph nodes ratio (the ratio between metastatic lymph nodes and total dissected lymph nodes, MLNR) in patients with gastric adenocarcinoma following curative gastrectomy and also analyzed the relationship between the number of removed lymph nodes and prognosis in node-negative gastric cancer.

METHODSFrom January 2005 to December 2010, 1 390 patients who were diagnosed with gastric adenocarcinoma and underwent curative gastrectomy were included. In particular, lymph node metastasis was not present in 515 patients. The number of metastatic lymph nodes and the metastatic lymph nodes ratio were selected for univariate and multivariate analyses to evaluate their influences on the disease outcome. The survival curve was presented according to the number of removed lymph nodes in node-negative gastric cancer using Kaplan-Meier plots.

RESULTSThe overall 5-year survival rate was 54% in this group. Univariate analysis revealed that age category, macroscopic appearance, histological grade, tumor size, depth of primary tumor invasion, number of metastatic lymph nodes, metastatic lymph nodes ratio, tumor, nodes, metastasis-classification (TNM) stage and status of lymphovascular, and vessel invasion have significant impact on survival. The number of metastatic lymph nodes and the metastatic lymph nodes ratio both have significant impact on survival (P < 0.001). However, in multivariate analyses, only the metastatic lymph nodes ratio was identified to be an independent prognostic factor (P < 0.001). The number of removed lymph nodes in node-negative was a strong prognostic factor of survival, the more lymph nodes dissected, the better the survival.

CONCLUSIONSThe metastatic lymph nodes ratio has more significant prognostic value for survival in patients with gastric cancer following curative gastrectomy than the number of metastatic lymph nodes. The number of removed lymph nodes might be an important prognostic factor for gastric cancer without lymph node metastasis.

Adenocarcinoma ; mortality ; surgery ; Aged ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Stomach Neoplasms ; mortality ; surgery