Objective To analyze the distribution of UDP-glucuronosyltransferase1A1（UGT1A1） gene polymorphisms in Chinese Han patients with metastatic colorectal cancer（mCRC）， and to evaluate correlations between UGT1A1 gene polymorphisms and toxicity and efficacy of irinotecan（CPT-11） combined with fluorouracil（5-FU） regimen in patients with mCRC. Methods Chinese Han patients with mCRC in the multicenter phase Ⅱ study were treated with FOLFIRI regimen（CPT-11 180mg／m² iv）and IFL regimen（CPT-11 125mg／m² iv）. UGT1A1*28 and UGT1A1*6 genotypes were determined by direct sequencing. Effect of UGT1A1 gene polymorphisms on toxicity， efficacy and survival of chemotherapy were analyzed. ResultsA total of 192 patients were enrolled， and 189 patients were detected UGT1A1 gene polymorphisms. The rates of wild type， unit point mutation and two points mutation of UGT1A1 were 37.6％， 43.9％ and 18.5％. Treatment options included FOLFIRI or IFL regimens. One hundred and eightythree cases were eligible for toxicity evaluation， incidence of grade 3-4 neutropenia was 266％（51／183）， and grade 3-4 late diarrhea rate was 15.1％（29／183）. Patients with two points mutation had significantly higher incidence of grade 3-4 late diarrhea than patients with wild type（26.5％ vs. 9.0％， P=0.021）. Grade 2-4 late diarrhea rates of UGT1A1*28 wide type， UGT1A1*28 heterozygote and UGT1A1*28 homozygous were 29.6％， 37.5％ and 88.9％，showing significant differences（P＜0.05）. Grade 4 neutropenia rate of UGT1A1*28 homozygous was higher than that of UGT1A1*28 wide type（33.3％ vs. 9.6％）， with no significant difference（P=0.07）. Additionally， poor ECOG status and higher dose intensity of CPT-11 also significantly increased irinotecanrelated toxicity. One hundred and fiftyeight patients were evaluatable for efficacy and response rate was 20.9％. Better response rate was found in patients with two points mutation of UGT1A1 compared with wild type of UGT1A1（33.3％ vs.15.3％）， with no significant difference（P=0.063）. Multiple regression analysis showed treatment duration has a significant impact on treatment outcomes. Less than 6 weeks treatment had significantly increased risk of disease progression（OR=6.106，95％CI： 1.680-22.197， P=0.006）. Prognostic factors were ECOG status， treatment duration and regimens， but not UGT1A1 gene polymorphisms. Conclusion Chinese Han mCRC patients with two points mutation of UGT1A1 were associated with higher incidence of irinotecanrelated toxicity and better response， but treatment duration shortened due to toxicity might impair theefficacy， and it is worth further investigation.

Objective To discuss the platinum related excision repair cross-complementation group 1（ERCC1） mRNA expression in different histological types of lung cancer and its corresponding blood cells， and to explore the clinical significance. Methods Real-time quantitative PCR was used to detect ERCC1 mRNA expression of 105 lung cancer cases（73 adenocarcinoma， 22 squamous cell carcinoma and 10 small cell carcinoma） from paraffin-embedded tissues and control blood samples， and the different expressions of ERCC1 mRNA in different tissue types were analyzed. ResultsERCC1 mRNA expressions were 4.579±1.926 and 8.324±1.280 in 105 paraffinembedded tissues and the corresponding blood samples, showing significant differences（P＜0.05）. In 105 lung cancer specimens，ERCC1 mRNA expressions in lung squamous cell carcinoma， adenocarcinoma and small cell carcinoma from paraffinembedded tumor cells were 4.366±1.822， 4.724±1.434 and 4.366±1.822， with no difference among the three histological types of lung cancer. The expressions in blood cells were 8.146±1.501，8.336±1.928 and 8.664±1.848， without significance among the three types. ERCC1 mRNA expression was significant differences between paraffinembedded tumor cells and corresponding blood cells in all the three tissue types（P＜0.05）. The expressions had no correlation in tumor cells and blood cells（r=0.329， P＞0.05）. Conclusion Histological types of lung cancer cannot guide platinum based chemotherapy， and further individual ERCC1 mRNA detection is needed. Using blood instead of the tumor tissues in individual detection of ERCC1 gene is not advised.

Objective To detect the levels of different phenotypic circulating tumor cells（CTCs） in patients with metastatic breast cancer（MBC） and discuss the predictive significance of CTCs on curative effect. Methods We detected the expression of epithelial（CK18， CK19） and mesenchymal（vimentin，fibronectin） markers in CTCs from 58 MBC patients and 10 healthy people by magnetic activated cell sorting（MACS） technology combined with RT-PCR. Curative effect of chemotherapy in MBC patients with different CTCs subgroups was evaluated using RECIST criteria. ResultsThere was no positive expression of CK18， CK19, vimentin and fibronectin mRNA in blood samples from 10 healthy volunteers. Among 58 MBC samples，62.1％（36／58） was found to express the CKs epithelial markers and 32.8％（19／58） were found to express the mesenchymal markers. In three different breast cancer subgroups， the positive rate of epithelial markers in luminal A and HER-2 positive subgroups higher than that in the triple negative subgroups（P=0.008）. However， the expression of the mesenchymal markers was observed to be reversed（P＜0.001）. Based on the expression of epithelial（CKs） and mesenchymal（EMT） markers in CTCs， the patients could be divided into CKs+／EMT- group, CKs-／EMT- group, CKs+／EMT+ group and CKs-／EMT+ group. The response rates of 4 group were 76.7%, 55.6%, 33.3% and 15.4%, respectively. There was significant difference（P＜0.05）. After two cycles of chemotherapy，the overall response rate（ORR） of EMT+ patients was lower than that of EMT- patients（15.8% vs. 71.8%, P=0.000）. Conclusion Some CTCs undergo EMT and subsequently lose their epithelial markers， such as cytokeratins， and gain the mesenchymal markers， such as vimentin and fibronectin. The presence of mesenchymal CTCs predicted resistance to chemotherapy and they maybe one of the reasons of invalid therapy of triple negative breast cancer.

Objective To study the expression and clinical significance of mesothelin in breast cancer，and investigate the relationship between the expression and clinical pathological characteristics. Methods The expression of mesothelin in 56 breast cancer samples and paired adjacent normal breast tissues was detected by immunohistochemistry. ResultsThe positive expression of mesothelin in 56 breast cancer tissues and adjacent normal breast tissues was 42.9％ （24／56） and 10.7％（6／56） with statistical significance（P＜0.05）. The expression of mesothelin was markedly correlated to the differentiation degree of breast carcinoma， tumor size and expression of ER（P＜0.05），but had no relationship with the age， lymphatic metastasis and expression of HER-2 （P＞0.05）. Conclusion The detection of expression of mesothelin is helpful in the diagnosis of breast cancer， and it might be also regard as an important parameter for determining tumor malignant degree and prediction.

Objective To investigate cancerrelated fatigue （CRF）， anxiety and depression in breast cancer patients and explore the relationship between CRF and the status of anxiety and depression. Methods A convenience sample of 200 breast cancer patients completed a structured questionnaire covering participants’ demographic characteristics， the Chinese version of revised Piper fatigue scale and the hospital anxiety and depression scale. Data analysis was performed by SPSS 17.0 software. ResultsIn 200 patients of breast cancer after operation， 109 patients （54.5％） experienced varying degrees of CRF， and the mean score for general fatigue was 4.38±1.27. The scores of behavior／severity dimension， emotion dimension， feel dimension and cognitive／emotional dimension were 3.73±1.67， 5.06±1.84， 4.39±1.60 and 4.38±1.35. “To what degree is the fatigue you are feeling now interfering with your ability to engage in sexual activity?”， “To what degree would you describe the fatigue which you are experiencing now as being?”， “To what degree are you now feeling weak” and “To what degree are you now feeling unable to remember” got the highest score in those dimensions. In 109 CRF patients， 24 cases （31.2％） companied by anxiety， 45 cases （41.3％） by depression， and 27 cases （24.8％） were associated with both anxiety and depression. CRF in patients with anxiety and depression onset was significantly more than the number of patients with noncancer related fatigue （P＜0.001）. The scores during the four dimensions of fatigue showed significant difference between the patients with the anxiety， depression and the patients without anxiety or depression（P＜0.05）. Conclusion Most breast cancer patients experienced CRF with light to medium degree. Anxiety and depression affect CRF. The cause and the treatment of CRF needs further study.

Objective To investigate the expression of matrix metalloproteinase-2（MMP-2）， vascular endothelial growth factor （VEGF）， CD105 and Ki-67， the correlations among the 4 indicators， the clinical features and prognosis in small cell lung cancer （SCLC）. Methods From 2004 to 2009， 42 cases of SCLC and 8 cases of normal lung tissues were collected. The expression of MMP-2， VEGF， CD105 and Ki-67 were detected by immunohistochemistry SP method. The correlation among expression of MMP-2， VEGF， CD105 and Ki-67， clinical features and prognosis were analyzed. Results The positive rate of MMP-2， VEGF， CD105 and Ki-67 was 50.0％， 66.7％， 81.0％ and 64.3％ in 42 cases of SCLC tissues， higher than 12.5％， 12.5％， 0 and 0 in normal lung tissues（P＜0.05）. The expression of MMP-2，VEGF and CD105 was correlated with tumor size， lymph node metastasis， distant metastasis and clinical stage（P＜0.05）， while Ki-67 was only correlated with lymph node metastasis（P＜0.05）. The expression of MMP-2 and VEGF was correlated with CD105 and Ki67，and there were significant positive correlations between MMP2 and VEGF（r=0.447，P＜0.05）. Single factor survival analysis showed that tumor size， lymph node metastasis， distant metastasis， clinical stage， and MMP-2， VEGF， CD105 and Ki-67 expression was correlated with the overall survival of SCLC. Conclusion MMP-2， VEGF， CD105 and Ki-67 are prognostic predictors in SCLC.The correlation of MMP-2 and VEGF may participate in angiogenesis and proliferation of SCLC.

Objective To evaluate the efficacy and side effects of pemetrexed combined with carboplatin regimen in the treatment for patients with advanced nonsquamous nonsmall cell lung cancer（NSCLC）. Methods Fifty-five advanced nonsquamous NSCLC patients confirmed with pathology or cytology were enrolled in this study. All the patients received pemetrexed（500mg／m² iv d₁） and carboplatin（AUC=5 iv d₁or d₂） with 21 days as a cycle. Each patient received at least 2 cycles. The efficacy and side effects were observed. Results The efficacy of the 55 patients could be evaluated. Four cases got CR， 14 achieved PR， 20 reached SD and 17 were PD. The effective rate was 32.7％ and the disease control rate was 69.1％.The median progression free survival was 5.5 months（95％CI：4.4-6.6 months）. The patients of ECOG score 0-1 compared with ECOG score 2， and first-line treatment compared with secondline treatment had better efficacy（P＜0.05）. The main side effects were myelosuppression， gastrointestinal response， fatigue and peripheral neurotoxicity， and mainly in grade 1-2. Conclusion Administration of pemetrexed combined with carboplatin regimen is beneficial to patients with advanced nonsquamous NSCLC， and the toxic effects are tolerable.

Objective To observe the efficacy and safety of threedimensional conformal radiotherapy （3DCRT） combined with chemotherapy for nonsmall cell lung cancer （NSCLC）， and analyze the factors influencing the prognosis of NSCLC patients. Methods One hundred and seven patients who were treated either by radiotherapy alone （26 patients） or radiotherapy plus chemotherapy （81 patients） from Jan. 2005 to Dec. 2008 were entered into the database for analysis. The radiotherapy dose was delivered at 2Gy／fraction， 5 fractions per week. The median total dose was 60Gy. The efficacy and toxicities were evaluated. Kaplan-Meier and Cox model were applied to analyze the survival of NSCLC. Results The response rate after 3DCRT was 61.7％（66／107） with complete remission 9.3％ （10／107） and partial remission 52.3％ （56／107）. The median followup time was 27 months， and 1-， 3-，5-year overall survival rates were 67％，31％ and 22％. The median survival time（MST） was 20.2 months. The Logrank test showed clinical stage， KPS performance， tumor volume， radiation dose，treatment regimen and response to treatment were correlated with overall survival. By Cox multivariable regression，the independent adverse prognostic factors were clinical stage， treatment type and response to treatment. Grade 2 acute radiation pneumonitis was observed in 3 patients and grade 3 in 2 patients. Late lung injury developed in 1 patient with grade 2， 1 patient with grade 3. Acute radiation esophagitis was observed in 49 patients with grade 1，above grade 2 developed in 9 patients. Acute grade 1，2 hematologic toxicity developed in 32 patients， above grade 2 developed in 5 patients. Conclusion 3DCRT combined with chemotherapy for NSCLC patients is effective and well tolerated. Clinical stage， treatment type and response to treatment may be the factors influencing the prognosis of NSCLC patients.

Objective To explore the value of modifined POSSUM score in predicting complications and surgical mortality of patients received lung cancer radical surgery. MethodsThe clinical data of 86 patients with primary lung cancer performed radical thoracic surgery in the 81st hospital of PLA from October 2007 to October 2011 were analyzed retrospectively. The modifined POSSUM score was used to predict postoperative complications and the number of death cases and compared with the actual values. ResultsThe number of postoperative complications predicted by POSSUM score was 29； a number of practical complications was 32. There was no significant difference between them. The number of postoperative deaths predicted by POSSUM score was eight； in comparison，the actual number of deaths was two. There was significant difference between them（P＜0.05）. ConclusionThe modifined POSSUM score can be used to predict the postoperative complications of lung surgery patients，but the existence of death was over-predicted.

Objective To analyze the features and risk factors of early postoperative on right ventricular dysfunction（RVD） in pneumonectomy for lung cancer. Methods A total of 97 lung cancer patients who received pneumonectomy from March 2007 to September 2010 were included in the study. The patients were assigned into RVD group（Tei＞0.28）and normal group（Tei≤0.28）， and postoperative factors were collected and analyzed between two groups， and the multivariate analysis（Logistic regression） were use to identify the risk factors of RVD. ResultsNo one died during hospitalization. The incidence rate of RVD was 16.5％（16／97）. Univariate analysis revealed that there were significant differences in age， FEV1/FVC, preoperative arrhythmias， preoperative pulmonary function， pulmonary hypertension， right pneumonectomy and volume overload between two groups（P＜0.05）. Three variables were found to be significantly related to the development of RVD by multivariate analysis： age（OR=12.68，P＜0.01）， pulmonary hypertension（OR=8.31，P＜0.05）， volume overload（OR=15.74，P＜0.01）. Conclusion RVD is a serious complication after pneumonectomy. Factors such as age＞70 years，pulmonary hypertension and volume overload are associated with RVD.

Objective To explore the plasma levels of D-dimer in non-small cell lung cancer（NSCLC） patients and its clinical significance. MethodsPlasma D-dimer levels in 215 NSCLC patients，90 patients with benign lung disease and 60 healthy people were measured by enzyme linked immunosorbent assay（ELISA）.The patients were followedup for one year. The rates of relapse and metastasis in operative patients was recorded, and median survival of patients received chemotherapy was measured. Results The plasma D-dimer levels of NSCLC group，benign lung disease group and normal control group were（1.73±0.26）mg／L，（0.26±0.03）mg／L and（0.23±0.01）mg／L，respectively. The levels of NSCLC group were significantly higher than those of benign lung disease group and control group（P＜0.05）.The plasma D-dimer levels of Ⅲ-Ⅳstage NSCLC patients was（2.31±0.34）mg／L, which was higher than （0.87±0.38）mg/L in theⅠ-Ⅱstage patients（P＜0.05）. The positive rates of D-dimer after operation in 105 NSCLC patients was 28.6%（30／105），which was significantly lower than that of preoperative patients（49.5%）. But there was no significant change of D-dimer after chemotherapy. The rates of relapse and metastasis in patients with a positive D-dimer preoperatively（28.8％） was higher than those with a negative D-dimer（5.7％）, the difference was statistically significant（P＜0.05）. The median survival for patients with a positive D-dimer before chemotherapy was 8.7 months, which was shorter than those with a negative D-dimer（12.8 months）, the difference was statistically significant（P＜0.05）. Conclusion The plasma levels of D-dimer is closely related to tumor staging and can also be used to determine effects of surgery and evaluation of prognosis.

Objective To assess the role of systemic treatment after whole-brain radiotherapy（WBRT） in immunohistochemically defined biological subsets of breast cancer patients with brain metastases. MethodsThe clinical data of 101 consecutive breast cancer patients with brain metastases treated in our hospital from Jan. 2002 to Dec. 2010 was analyzed retrospectively. Forty-eight patients were received systemic treatment after WBRT. Patients were divided into 4 immunohistochemically biological subsets based on the levels of estrogen， progesterone， human epidermal growth factor receptor 2 （HER-2） and Ki-67 index， and labeled as luminal A，luminal B，HER-2 positive and triple-negative. Survival was calculated from brain metastases diagnosed. Patients from 4 subtypes were divided into 2 subgroups according to receiving systemic treatment after WBRT or not. Survival analysis was used by Kaplan-Meier method. ResultsThe median survival time of patients received systemic treatment or not after WBRT were 5.1 and 8.5 months， respectively （P＜0.0001）. In the triplenegative subset， median survival of patients received systemic treatment or not were 4.8 and 6.1 months （P=0.051）， in the luminal A subset were 5.3 and 11.0 months （P＜0.0001），in the luminal B subset were 4.8 months and 8.6 months， respectively （P＜0.0001）， in the HER-2 positive subset were 4.8 months and 8.2 months （P＜0.0001）. Conclusion Systemic therapy after WBRT appears to improve survival in patients with the luminal A， luminal B and HER-2 positive breast cancer subtypes.