Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.

Background and objective Epidermal growth factor receptor (EGFR) and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC).The studies are mainly focused on detection ofEGFR gene for advanced NSCLC,and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown.This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC,and the relationship between the genotype and clinicopathologic features.Methods The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage Ⅰ-Ⅲa NSCLC from Department of Pathology,Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS) real-time PCR kit,and analyzed their correlation with clinical variables.Results The hotspot mutation rates in EGFR and KRAS were 34.5％ and 13.1％ respectively,and there were EGFR-KRAS double mutations in 3 samples.The mutation rate of EGFR was higher in females than that in males (39.5％ vs 29.4％,P=0.076),significantly increased in adenocarcinomas (38.7％) compared to that in the other forms of NSCLC (P＜0.01),but still lower than that reported in some Asian studies of advanced adenocarcinoma (-50％).Meanwhile,the mutation rate of KRAS was remarkably higher in males than that in females (16.6％ vs 9％,P=0.048),increased in adenocarcinomas compared to that in the other forms of NSCLC,but the difference was not significant (P=0.268).Samples harbored EGFR mutation were younger than those harbored KRAS mutation (P=0.031,5),and had significant difference in gender between the two groups (P＜0.01).Conclusion The mutation rate of EGFR in stag Ⅰ-Ⅲa NSCLC patients was lower than that in advanced NSCLC patients.And the percentage of the NSCLC patients with EGFRKRAS double mutations is 0.9％.

Objective To identify the risk factors for positive resection residues after endoscopic submucosal dissection ( ESD ) of early esophageal squamous carcinomas and precancerous lesions. Methods A retrospective analysis was performed in 315 patients with early esophageal squamous cancer and precancerous lesion who underwent ESD. The pathological features of all resection margins in the specimen and the follow?up outcome of the patients with positive resection margin were evaluated. Univariate and multi?variate analysis were used to determine the risk factors for resection margin residues after ESD. Results In 315 lesions,there were 290 lesions with negative resection margins and 25 with positive resection margins.The number of lesions with positive lateral, basal, or both resection margins was 13, 8, and 4, respectively. Multivariate analysis showed that the depth of invasion( submucosal layer invasion, P=0?048) was the only independent risk factor for positive basal resection margin. The proportion of circumferential extension (≥3/4,P=0?014) and the depth of invasion( exceeding muscularis mucosa, P=0?007) were independent risk factors for positive lateral resection margin. Conclusion The diameter of the lesions and the depth of tumor invasion are independent risk factors for esophageal ESD positive resection margins. Accurate evaluation of lesion extension and invasive depth is critical to avoid residual or recurrent tumor after esophageal ESD.

Objective To investigate the ideal dosage of dexmedetomidine( DEX) with 1?0 μg/kg fentanyl for monitored anesthesia care ( MAC) during endoscopic variceal ligation ( EVL) . Methods A total of 60 patients scheduled for elective EVL were randomly divided into 3 groups ( n=20) . After fentanyl was infused intravenously at the dosage of 1?0 μg/kg, the loading dosage of DEX at 1?0 μg/kg ( group D1 ) , 1?5 μg/kg ( group D2 ) , or 2?0μg/kg ( group D3 ) was continuously infused in 10 min, respectively. When the modified OAA/S score reaching≥3 point, EVL was carried out. The change in modified OAA/S score, the operation duration time, recovery time, satisfaction rates of patient and doctor, and complications were recorded. Results There were no significant differences in regarding of general status, operation duration time and satisfaction score of patients between the 3 groups ( P>0?05 ) . Before endoscope insertion, the OAA/S score in group D3(4?4±0?2)was higher than that in D1(3?4±0?5)or D2 groups(3?8±0?3)(P<0?05), and there was no significant difference between the scores of D1 and D2(P>0?05).At the time?point of 5 mins after endoscope insertion, the OAA/S score in group D3(4?5±0?3)was significantly higher than that in D1(3?5±0?6)or D2 groups(3?7±0?4)(P<0?05),there were no significant differences between D1 and D2( P>0?05) . At the end of the procedure,there was no significant difference in OAA/S score between the 3 groups(P>0?05).Compared with group D1(3?1±0?9)min and D2(3?8±0?8)min, the recovery time in group D3(6?6±1?2)min was significantly longer (P<0?05), while there was no significant difference between D1 and D2(P>0?05). The satisfaction score of endoscopist in group D1(8?0±0?8) was significantly lower than that in group D2(9?4±0?6)or D3(9?5±0?5)(P<0?05), there was no significant difference between groups D2 and D3 ( P>0?05 ) . No tachycardia, hypertension or hypoxemia occurred during the procedure. There was no significant difference in rate of hypotension among the three groups ( P>0?05) . The incidences of nausea(30%) and body movement(15%) in group D1 were significantly higher than those in group D2 and D3(P<0?05).There were no differences between D2 and D3(P>0?05). The incidence of bradycardia in group D3(40%) was significantly higher than those in group D1(0) and D2(10%)(P<0?05).There were no differences between those in D1 and D2(P>0?05). Conclusion Combined with 1?0 μg/kg fentanyl, 1?5 μg/kg DEX is more efficient and safer for EVL in the status of MAC.

Objective The aim of this study was to identify the clinical features and prognostic factors of leptomeningeal metastasis ( LM ) in non?small cell lung cancer ( NSCLC ) patients undergoing treatment with epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) . Methods Twenty?five cases of NSCLC with LM, treated in our hospital during January 1, 2003 to October 31, 2013, were enrolled in this study. Medical records were reviewed for clinical features and treatments, and the survival and prognostic factors were analyzed. Results NSCLC?LM were more common in female patients (64.0%), and most were adenocarcinomas (72.0%). Twenty (80.0%) patients underwent anti?cancer treatment, among them 17 patients underwent EGFR?TKIs treatment. The median overall survival ( mOS ) after the diagnosis of LM was 4.9 months for the whole group (25 cases). Patients receiving EGFR?TKIs treatment had a longer median survival than patients not receiving EGFR?TKIs (5.3 months vs. 1.2 months, P=0.022) . Eleven patients who developed LM before the targeted therapy had a prolonged median survival of 8.1 months after EGFR?TKIs treatment. The univariate analysis showed that female gender and EGFR?TKIs treatment were favorable prognostic factors influencing the survival ( P<0.05) , while age, LM at the time of initial diagnosis, LM developed during the EGFR?TKIs treatment, whole?brain radiotherapy ( WBRT), intrathecal chemotherapy, or systemic cytotoxic chemotherapy were not associated with mOS (P>0.05 for all). The multivariate analysis showed that female gender ( P=0. 012 ) and EGFR?TKIs treatment ( P=0.008 ) were significant predictors of a good prognosis. Conclusions EGFR?TKIs treatment may confer benefit for NSCLC?LM patients. Female patients and EGFR?TKIs treatment are favorable prognostic factors for survival.

Objective The aim of this study was to identify the clinical features and prognostic factors of leptomeningeal metastasis ( LM ) in non?small cell lung cancer ( NSCLC ) patients undergoing treatment with epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) . Methods Twenty?five cases of NSCLC with LM, treated in our hospital during January 1, 2003 to October 31, 2013, were enrolled in this study. Medical records were reviewed for clinical features and treatments, and the survival and prognostic factors were analyzed. Results NSCLC?LM were more common in female patients (64.0%), and most were adenocarcinomas (72.0%). Twenty (80.0%) patients underwent anti?cancer treatment, among them 17 patients underwent EGFR?TKIs treatment. The median overall survival ( mOS ) after the diagnosis of LM was 4.9 months for the whole group (25 cases). Patients receiving EGFR?TKIs treatment had a longer median survival than patients not receiving EGFR?TKIs (5.3 months vs. 1.2 months, P=0.022) . Eleven patients who developed LM before the targeted therapy had a prolonged median survival of 8.1 months after EGFR?TKIs treatment. The univariate analysis showed that female gender and EGFR?TKIs treatment were favorable prognostic factors influencing the survival ( P<0.05) , while age, LM at the time of initial diagnosis, LM developed during the EGFR?TKIs treatment, whole?brain radiotherapy ( WBRT), intrathecal chemotherapy, or systemic cytotoxic chemotherapy were not associated with mOS (P>0.05 for all). The multivariate analysis showed that female gender ( P=0. 012 ) and EGFR?TKIs treatment ( P=0.008 ) were significant predictors of a good prognosis. Conclusions EGFR?TKIs treatment may confer benefit for NSCLC?LM patients. Female patients and EGFR?TKIs treatment are favorable prognostic factors for survival.

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard ifrst-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive ifrst-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received ifrst-line chemotherapy and determined prognostic factors. Methods Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001to December 2011hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the inlfuence factors of survival. Results hTe median OS of all extensive-stage small cell lung cancer was14.8 months;1-year, 2-year and 5-year survival rates were 58.9%, 27.2%and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P<0.001), bone metastasis (P<0.001) and chemotherapy (P<0.001). hTe mortality risk of patients who didn’t receive chemotherapy was 4.919 times higher than that who received;the mortality risk of patients without liver, bone metastasis was reduced by approximately 50 percent. hTe ifrst-line chemotherapy was mainly EP (DDP+VP-16) or CE (CBP+VP-16) regimens (accounting for 82.8%) with 4-6 cycles. hTe median OS and PFS in ifrst-line chemotherapy were15.1months and 7.5 months, respectively. hTe result of Cox regression analysis indicated that OS in ifrst-line chemotherapy was remarkably related to smoking history (P=0.041), liver metastasis (P<0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001);PFS was relevant with smoking history (P=0.003), liver metastasis (P=0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001). hToracic radiotherapy was not an independent inlfuence factor of OS and PFS in extensive-stage small cell lung cancer. Con-clusion hTe patients who were younger than 60-year old, with good KPS, absence of liver and bone metastasis had better prognosis. Patients should receive chemotherapy with ifrst-line standard regimen (CE/EP regimen). It was beneifcial to sur-vival if the effect of ifrst-line chemotherapy was SD or PR-CR and the proper chemotherapy cycle number was 4-6 cycles. hTe role of thoracic radiotherapy in extensive-stage small cell lung cancer needed to be investigated further.

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tu-mor and sensitive to chemotherapy and radiotherapy. However, most patients who receive ifrst-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard ifrst-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. hTe aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. Methods 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected.χ2 test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. Results hTe patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. hTe median OS in second-line chemotherapy as 7.0 months and was relevant with smoking his-tory (P=0.004), ECOG PS (P<0.001), liver metastasis (P=0.019) and bone metastasis (P=0.028) independently. hTe median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034), ECOG PS (P=0.011) and bone metastasis (P=0.005). hTe response rate among six regimens was signiifcantly different (P=0.017);hTere was not statistical signiifcance between each group. As to side effects, the incidence of gastrointestinal reaction in group C was higher than any other group. hTe differences of OS and PFS between six regimens in second-line therapy were not statistically differ-ent (P=0.914, P=0.293). Conclusion hTe most signiifcant prognostic factor of extensive-stage small cell lung cancer patients who received second-line chemotherapy was ECOG PS. hTe most optimal second-line chemotherapy regimen with deifnite curatice effect was controversial.

Background and objective At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. hTe aim of this study is to analyze the inlfuencing factors of prognosis for stage IIIa surgical patients. Methods Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological ifnding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically signiifcant. Results 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. hTe median OS and PFS of the whole group were 38.9 and 12.9 months respectively. hTe median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. hTe median PFS of them were 14.9 and 19.8 months respectively. hTere were no signiifcant differences of OS and PFS between two groups. Univariate and multivari-ate analysis indicated that postoperative chemotherapy had a signiifcant inlfuence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a signiifcant inlfuence on PFS (P<0.05). hTe maximum diameter of tumor had a signiifcant inlfuence on PFS only in univariate analysis. Conclusion For stage IIIa NSCLC, postoperative chemotherapy can increase OS and PFS, but postoperative radiotherapy have no beneift on them.