Chinese Clinical Oncology

Efficacy and safety of magnesium isoglycyrrhizinate injection to prevent chemotherapy-induced acute liver injury （MAGIC-301）： A multicenter, randomized, controlled clinical study

QIN Shukui，YANG Liuqing，WANG Keming，XIA Liming， ZHOU Jinhua，ZHENG Yitong，LI Yu，YANG Chengxi，CUI Tongjian，WANG Senming，XIAO Mingxing，WANG Hongbing，BAI Li，LIU Hanfeng，AN Yonghui，SONG Qibin， ZHANG Mingzhi，HAN Beiqiu， HUA Dong，CHEN Yuqiang，CHEN Jinfei，DU Nan，CHEN Wensheng，FENG Guosheng，LI Yongqiang，XIONG Jianping，OUYANG Ming，LIU Chaoying， WANG Cailian，ZHANG Hua，ZHONG Meizuo， XIE Shaojian.

Chinese Clinical Oncology. 2017, 22 (2): 97.

Abstract ( 519 )

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Objective Anti-tumor cytotoxic drug is one kind of the most common drugs causing drug-induced liver injury（DILI）. This study aimed to observe and evaluate the efficacy and safety of magnesium isoglycyrrhizinate injection（MgIG）for prevention of chemotherapy-induced acute liver injury in a large-scale population with malignant tumors. Methods It was a prospective， open-label，randomized controlled and nationwide multi-center study（MAGIC-301 Study）. Patients who received the chemotherapy regimen containing one of the following four chemotherapy drugs or more，cisplatin（≥60 mg/m2），oxaliplatin（≥85 mg/m2）， cyclophosphamide（≥600 mg/m2） and gemcitabine（≥2000 mg/m2），were randomized to the MgIG group and the control group. The MgIG group was assigned to receive MgIG injection 200mg/d ivgtt one day before the start of chemotherapy and lasting for at least 5 days. The control group was assigned to receive only chemotherapy regimen without MgIG injection. Referring to National Cancer Institute-Common Terminology Criteria for Adverse Events（NCI-CTC AE） version 4.0，the occurrence of liver injury，including the incidence and severity degree， was strictly observed and compared both before and after chemotherapy. Rescue hepatoprotective treatments were administered if necessary. Results The study was carried out at 28 cancer centers in China between February 28，2013 and December 31，2015. A total of 1200 patients were enrolled into the study. Of these patients，1146（95.5%）patients were included in the full analysis set（FAS）and randomized to the MgIG group（n=766）and the control group（n=380）respectively. The baseline demographics and clinical characteristics，including age，gender，weight，history of liver disease，type of malignancy and chemotherapy regimen etc， were well balanced between the groups（P>0.05）. In the FAS， 62.63% of patients in the control group presented with liver injury after the chemotherapy， while 52.81% in the MgIG group（P=0.0004）. The analyses of NCI grading for the severity of liver injury showed that the incidence of grade 2 or more liver function abnormity was 12.37% in the control group and 10.07% in the MgIG group after the chemotherapy（P=0.0008）. In addition， 32.37% of patients presented with the elevation of liver injury grade for at least one level in the control group，which increased by 11.17% compared with the MgIG group（P<0.0001）. In the MgIG group， the incidence of the liver function abnormity decreased by 7.11%（P=0.0188），22.36% （P=0.0033） and 18.71%（P=0.0380）respectively in the different chemotherapy regimens containing platinum drugs，cyclophosphamide or gemcitabine. The incidence of alanine aminotransferase（ALT）and glutamicoxaloacetic transaminase（AST）abnormity in the MgIG group were significantly lower than those in the control group after chemotherapy. On the second week of chemotherapy（d13-d15），the incidence of ALT and AST abnormity decreased significantly in the MgIG group，which reduced by 50% compared with the control group（ALT：8.63 % vs. 16.58%，P<0.0001；AST：10.72% vs. 20.05%，P<0.0001）. During the study period， the rescue treatments were administered in 1.3% of patients in the MgIG group，while occurring in 9.2% of patients in the control group（P<0.0001）. The incidence of AE was similar between the two groups. Conclusion The study results suggest that the DILI induced by the chemotherapy containing the platinum drug，cyclophosphamide or gemcitabine was characterized by the higher incidence and the more serious hazardness. Thus，more attention should be paid，especially to enhance the surveillance of liver function in the whole course and the management of liver injury in the clinical practice. Prophylaxis with MgIG injection can significantly reduce the incidence and severity of DILI before the chemotherapy initiation and during the concurrent chemotherapy. It is worthy of investigation further and clinical application widely.

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Inhibitory effect of ginkgolide B on human osteosarcoma Saos-2 cells

ZHANG Lei，SUN Chang，LIU Xiaozhou，WU Sujia，LI Chengjun

Chinese Clinical Oncology. 2017, 22 (2): 107.

Abstract ( 367 )

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Objective To explore the effect of ginkgolide B（GB）on the proliferation， apoptosis， migration and invasion of osteosarcoma（OS）cells as well as the potential mechanisms. Methods Human OS Saos-2 cells were incubated with 300，600 and 1200 μmol/L GB for 24， 48 and 72 h. We detected cells viability，apoptosis， migration and invasion with cell counting kit-8（CCK-8）， flow cytometry and Transwell assay，separately. Using the extraction of the mRNA and protein of Saos-2 cells pretreated with GB，we detected the mRNA and protein levels of Bcl-2，Bax，caspase-3，MMP-2 and MMP-9 by using quantitative real-time PCR and Western blotting. The phosphorylation of Erk and Akt and level of cleaved-caspase-3 were detected by Western blotting. Results GB significantly inhibited the proliferation of Saos-2 cells in a time-and dose-dependent manner. GB at 600 and 1200 μmol/L can induce the apoptosis of OS cells. GB exerted a dose-dependent role in the suppression of migration and invasion of OS cells. GB could increase the mRNA and protein levels of Bax，but decreased the mRNA and protein levels of Bcl-2， MMP-2 and MMP-9. The high concentration of GB could inhibit the phosphorylation of Erk and Akt and increase the level of cleaved-caspase-3. Conclusion GB could inhibit the proliferation， migration and invasion of Saos-2 cells and induce apoptosis，which may be related to the inhibition of Erk and Akt phosphorylation.

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Study on the mechanism of sodium valproate combined with G-CSF induced myeloid leukemia cell differentiation

ZHAO Shuqing，LI Junmin，XU Zizhen， YHANG Chenmin

Chinese Clinical Oncology. 2017, 22 (2): 114.

Abstract ( 371 )

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Objective To explore the mechanism of sodium valproate （VPA） combined with granulocyte colony-stimulating factor（G-CSF） in the induction of differentiation of U937 leukemic cell line. Methods The U937 cells at logarithmic growth phase were treated with 0.5 mmol/L VPA or 50 ng/ml G-CSF alone and in combination. Cell differentiation was analyzed by Wright-Giemsa stain cell morphology and flow cytometry. Flow cytometry was performed to detect the expression of G-CSFR in the cells. The protein level of CCAAT/enhancer-binding proteins C/EBPα and G-CSFR were detected by Western blotting. Results VPA induced myeloid differentiation in U937 cells as demonstrated by up-regulation of CD11b from（11.49±3.48）% to （62.48±9.96）% （P<0.05）. When combined with G-CSF， the differentiation was remarkably enhanced to（97.65±0.49）% （P<0.05）. The expressions of G-CSFR（CD114） on U937 cells were also up-regulated from （29.50±6.80）% to （59.88±9.99）% （P<0.05）. VPA can enhance C/EBPα expression in these cells. The expression levels of G-CSFR protein were significantly up-regulated. Conclusion Combinations of VPA with G-CSF had an additive or synergistic effect on induction of myeloid differentiationin U937 cells. This effect may be mainly through the increase of C/EBPα and up-regulation of G-CSFR.

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Effects of miR-147 targeting MDM2 on the proliferation and apoptosis of ovarian cancer cell line Skov3 and its mechanism

LIU Jiarong，WANG Wenyi

Chinese Clinical Oncology. 2017, 22 (2): 118.

Abstract ( 329 )

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Objective To investigate the effect of microRNA-147（miR-147）on the expression of murine double minute 2（MDM2）and its effect on the proliferation and apoptosis of ovarian cancer cell line Skov3. Methods The Skov3 cells were transfected with miR-147 mimics（miR-147 mimics group）or negative control（NC group）by Lipo2000 liposome method. The real-time quantitative PCR（QPCR）method was used to detect the miR-147 level of Skov3 cells at 48 h post-transfection to evaluate the transfect efficiency. MTT method and flow cytometry were used to detect the proliferation and apoptosis of the two groups after transfection, respectively. The levels of MDM2， p53 and caspase-3 were measured by Western blotting. The dual luciferase reporter assay was employed to verify the relationship between miR-147 and target MDM2 and the binding site. Results QPCR results showed that the level of miR-147 in miR-147 mimics group was significantly higher than that in NC group，and the difference was statistically significant（P<0.05）， indicating that miR-147 was successfully over-expressed in Skov3 cells. Compared with NC group， the proliferative rate and MDM2 level of miR-147 mimics group were all decreased， but the apoptotic rate and levels of p53 and caspase-3 were all increased（P<0.05）. Dual luciferase reporter assay showed that miR-147 could significantly inhibit the luciferase activity of cells transfected with wild-type MDM2-3’（untranslated region， UTR） plasmid，and had no effect on the luciferase activity of cells transfected with mutant MDM2-3’UTR plasmid. Conclusion MiR-147 can target the expression of MDM2，and over-expression of miR-147 can inhibit the proliferation and induce apoptosis of Skov3 cells，and it has a certain reference value in the prevention and treatment of ovarian cancer.

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Expression and clinical significance of PD-L1 in head and neck tumors

JIANG Huiyuan，JIANG Bin，LIU Feng，ZHANG Wenying，WANG Meiling

Chinese Clinical Oncology. 2017, 22 (2): 124.

Abstract ( 384 )

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Objective To explore the expression and clinical significance of programmed cell death ligand-1（PD-L1） in head and neck tumors. Methods From January 2015 to June 2016， surgical specimens of 40 cases of head and neck malignant tumors and 20 cases of head and neck cyst tissues were prepared by embedding into paraffin blocks. The expression of PD-L1 protein was detected by immunohistochemistry SP two step method. The relationship between PD-L1 expression and clinical pathological parameters（age， sex and pathological grade and clinical stage） was investigated. Results PD-L1 was not expressed in head and neck cyst tissues， and the positive rate was 65.0%（26/40） in head and neck tumor tissues， significantly higher than that in head and neck cyst tissues（P<0.05）. The expression of PD-L1 was not associated with age， sex and pathological grade（P>0.05）， but was related to clinical stage（P<0.05）. Conclusion The expression of PD-L1 was significantly increased in head and neck malignant tumors，which could provide a reference for the immunotherapy of head and neck malignant tumors.

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Expressions of NIS and TSHR in differentiated thyroid carcinoma and their association with BRAF V600E mutation

RU Xiaoting，LIU Qinjiang，YANG Rong

Chinese Clinical Oncology. 2017, 22 (2): 128.

Abstract ( 332 )

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Objective To investigate the expressions of sodium iodide symporter （NIS） and thyroid stimulating hormone receptor （TSHR） in differentiated thyroid carcinoma （DTC） and their association with BRAF V600E mutation. Methods The immunohistochemistry SP method was used to detect the expressions of NIS and TSHR in 229 cases of DTC， 52 cases of nodular goiter and 31 cases of normal thyroid tissues. The PCR direct sequencing was applied to detect the BRAF V600E mutations. The relationship between the expressions of NIS and TSHR in DTC tissues and the clinicopathological parameters （gender， age， tumor size， lymph node metastasis， TNM stage and recurrence risk stratification） and BRAF V600E mutation were analyzed. Results The positive rate of NIS in DTC was 55.5% （127/229）， lower than 78.9% （41/52） of nodular goiter and 77.4% （24/31） of normal thyroid tissues with statistical significant difference（P<0.05）. NIS expressions were not associated with gender， age， tumor size， lymph node metastasis， TNM staging and recurrence risk stratification. The positive rates of DTC， nodular goiter and normal thyroid tissues were 41.0% （94/229）， 48.1% （25/52） and 45.2% （14/31）， and no significant difference was observed. TSHR expressions were not associated with gender， age， lymph node metastasis， TNM staging and recurrence risk stratification， but related with tumor size （P=0.029）. The positive expression rate of NIS was not related to the mutation of BRAF V600E. However， as for the NIS expression in cell cytoplasm， BRAF V600E mutation type （48.2%） was higher than BRAF V600E wild type （29.5%）. In BRAF V600E mutation type， the expression rate of NIS in cell membrane was 51.8%， lower than 70.5% of BRAF V600E wild type （P<0.05）. The positive rate of TSHR in BRAF V600E mutations type was 47.9%， higher than 28.7% of BRAF V600E wild type， and the difference was statistical significant. TSHR expression in cytoplasm/ormembrane was not associated with BRAF V600E mutations. Conclusion The NIS expression was decreased and the location of NIS expression may be associated with BRAF V600E mutations in DTC， but the location of TSHR expression was not associated with BRAF V600E mutations. The specific mechanisms of the increased TSHR expression in patients with BRAF V600E mutations need further study.

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Expression and clinical significance of Apaf-1 and Ki-67 in breast cancer tissues

LIU Zhuo，LI Xiaofeng，ZHANG Meiyun

Chinese Clinical Oncology. 2017, 22 (2): 133.

Abstract ( 322 )

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Objective To study the expression of apoptotic protease activating facter-1 （Apaf-1） and Ki-67 in breast cancer tissues and normal breast tissues， and to investigate the clinical significance of the two proteins. Methods From January 2014 to December 2015， paraffin blocks of 60 cases of breast cancer tissues and 30 cases of adjacent normal tissues were enrolled in this study. The expressions of Apaf-1 and Ki-67 were detected using immunohistochemical EnVision method. The relationship between the two proteins，as well as the relationship of them with clinicopathological factors（age, tumor size, lymph node metastasis, clinical stage and body mass index） was also analyzed. Results The positive rate of Apaf-1 in breast cancer tissues was 21.7% （13/60）， which was significantly lower than that in adjacent normal tissues （70.0%， 21/30）， and the difference was statistically significant （P<0.05）. The positive rate of Ki-67 in breast cancer tissues was 73.3% （44/60）， which was significantly higher than that in adjacent normal tissue （11/30， 36.7%）， and the difference was statistically significant （P<0.05）. Apaf-1 and Ki-67 were not related with age， body mass index（P>0.05）， but with tumor size， lymph node metastasis and clinical stage （P<0.05）. The expression of the two protein in breast cancer tissues was negatively correlated （r=-0.413，P=0.018）. Conclusion In breast cancer, Apaf-1 expression was decreased but Ki-67 expression was elevated. Apaf-1 and Ki-67 play an important role in the development and invasion of breast cancer，and may be used as a marker to diagnose the breast cancer.

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Relationship between serum miR-143 level and the sensitivity of paclitaxel-based chemotherapy regimen in advanced gastric cancer

LI Jinfeng，CHENG Weili，REN Xusheng，LI Xianghong，LI Dapeng.

Chinese Clinical Oncology. 2017, 22 (2): 137.

Abstract ( 271 )

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Objective To investigate the relationship between serum microRNA-143 （miR-143） level and chemosensitivity to paclitaxel in patients with advanced gastric cancer. Methods A total of 82 patients with advanced gastric cancer treated with paclitaxel-based regimen in our hospital from January 2012 to July 2016 were enrolled. Serum samples were collected before chemotherapy and their miR-143 levels were detected by qPCR method， and then compared with 76 healthy persons in the same period of miR-143. The relationship between different miR-143 levels and clinical pathological characters were analyzed. RECIST1.1 standard was used to evaluate the short-term efficacy and the relationship between different levels of miR-143 and chemosensitivity were evaluated. Median progression free disease （PFS） and survival （OS） were compared between different miR-143 levels according to follow-up data. Results The qPCR detection showed that the miR-143 level of 82 patients with gastric cancer was （0.215±0.021）， lower than those of the healthy subjects （1.099±0.057）， and the difference was statistically significant （P<0.05）. Serum miR-143 level was not related to sex，age， ECOG score， tumor location and pathological type， but with TNM stage and differentiation degree，and the difference was statistically significant （P<0.05）. The serum miR-143 level of 31 patients with chemotherapy sensitive （CR+PR） was （0.341±0.040）， which was higher than that of chemotherapy resistance （SD+PD）in patients （0.138± 0.015），and the difference was statistically significant （P<0.05）. The patients were divided into high expression group （>0.177） and low expression group （≤0.177） according to the medium value. The response rate， median PFS and OS in the high expression group were 48.8%， 8.5 and 12.2 months， significantly better than those in the low expression group （31.7%， 7.3 and 9.4 months）， and the difference was statistically significant （P<0.05）. Conclusion The serum miR-143 level of advanced gastric cancer is lower than normal， and related to the paclitaxel chemotherapy sensitivity and prognosis. High expression of miR-143 had a higher sensitivity and better prognosis，showing a certain value in the diagnosis and prognosis of gastric cancer.

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Expression and clinical significance of long non-coding RNA CCAT-2 in hepatocellular carcinoma tissues

DENG Wenying，ZHANG Chi，LI Ning，XIE Jinling，XU Yingying，LUO Suxia

Chinese Clinical Oncology. 2017, 22 (2): 143.

Abstract ( 273 )

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Objective To explore the expression of long non-coding RNA of colon cancer associated transcript-2（LncRNA CCAT-2） in hepatocellular carcinoma（HCC） tissues as well as its clinical significance. Methods The expression level of CCAT-2 in 60 pairs of HCC tissues which were pathologically confirmed as HCC postoperatively and paired adjacent normal tissues were tested by real-time PCR， and then we investigated the relationship between the expression of CCAT-2 with clinical pathological features such as gender， age， preoperative alpha-fetoprotein（AFP） level， HBsAg， tumor size， number of tumors， tumor stage， portal vein tumor thrombus（PVTT）and differentiation grade. Results The expression of CCAT-2 in HCC tissues elevated significantly with an average fold of 5.26±2.08.The difference was statistically significant（P=0.001）. The level of CCAT-2 expression was not associated with the gender， age， HBsAg and number of tumors（P>0.05）， but significantly related with the AFP level， tumor size， tumor stage，PVTT and differentiation degree（P<0.05）. Conclusion CCAT-2 may play a promoting role in the development， invasion and migration process of HCC.

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Comparison of docetaxel versus cisplatin in concurrent chemoradiotherapy of locally advanced nasopharyngeal carcinoma

AI Ruyu，ZHU Juan，XIE Bo

Chinese Clinical Oncology. 2017, 22 (2): 147.

Abstract ( 294 )

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Objective To compare the efficacy and toxicity between docetaxel （TXT）and cisplatin（DDP） in concurrent chemoradiotherapy of locally advanced nasopharyngeal carcinoma. Methods In this study，72 patients with locally advanced nasopharyngeal carcinoma from March 2015 to June 2016 were enrolled. According to the treatment regimes，27 patients received TXT （75 mg/m2） on day 1 with 21 days as a cycle and 45 patients received DDP 40 mg/m2 on day 1 every 7 days or 80 mg/m2 on day 1 with 21 days as a cycle. Three dimensional conformal radiotherapy with total dose of 70 Gy/35 f was used for radiotherapy. Response to chemoradiotherapy was assessed by RECIST criteria 1.1 at 3 months after treatment and toxicity was evaluated according to Common Terminology Criteria for Adverse Events （CTCAE） v4.0 and RTOG/EORTC acute radiation morbidity scoring criteria. Results Except one patient in DDP group, the remaing patients were evaluated for the short-term efficacy. The complete remission rates of primary focus were 66.7% and 81.8% in TXT and DDP group. The complete remission rates of lymph gland were 81.5% and 95.5% in TXT and DDP group. There was no significant difference in short-term efficacy between TXT group and DDP group（P>0.05）. The incidences of grade 3-4 leucopenia and neutropenia in TXT group were significantly higher than those in DDP group（48.1% vs. 22.2%，P=0.022； 37.0% vs. 15.6%，P=0.048）. The incidence of anemia was significantly higher in TXT group as compared with DDP group （80.0% vs. 53.3%，P=0.039）. The incidence of grade 3-4 mucositis was significantly lower in TXT group as compared with DDP group（29.6% vs. 57.8%，P=0.028）. The occurrence of throat pain in TXT group was later than in DDP group［（11.70±3.930） d vs.（9.38±3.453） d，P=0.011］. The incidence of grade 2-3 nausea or vomiting was statistically significantly lower in TXT group than in DDP group （22.2% vs. 48.9%， P=0.028）. Conclusion There was the similar short-term curative effect for TXT and DDP during concurrent chemotherapy in locally advanced nasopharyngeal carcinoma. TXT had lighter mucositis and gastrointestinal reaction，but the incidence of myelosuppression was higher in TXT. Patients were well tolerated with TXT. TXT can be used to replace cisplatin as one of the chemotherapy drugs for locally advanced nasopharyngeal carcinoma.

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Effect observation of non-small cell lung cancer with osseous metastasis through zoledronic acid combined with radiotherapy

ZENG Shaorong，LING Qinjie，ZENG Weiliang

Chinese Clinical Oncology. 2017, 22 (2): 152.

Abstract ( 274 )

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Objective To explore the short-term curative effect and influencing factors of non-small cell lung cancer（NSCLC）with osseous metastasis through zoledronic acid combined with radiotherapy. Methods In this study，106 NSCLC patients with osseous metastasis in our hospital from May 2013 to May 2015 were randomly divided into the combination group and the control group with 53 cases in each group. The control group received radiotherapy alone，and the combination group were treated with zoledronic acid on the basis of radiotherapy. The pain relief statuses of two groups were compared. The factors influencing the short-term pain relief were analyzed using multivariate Logistic regression analysis. The factors influencing the short-term pain relief of two kinds of treatment methods were analyzed using univariate Logistic regression analysis. Results The effective rate of combination group was 92.5% （49/53）， higher than 69.8%（37/53）of control group（P=0.003）. Multivariate Logistic regression analysis showed that treatment was the independent factor affecting the relief of bone pain in NSCLC with bone metastasis， and the difference was statistically significant （P<0.05）. The univariate Logistic regression analysis showed that patients with CT imaging manifestations of osteolytic lesions in combination group had a better curative effect than in the control group，and the incidence of skeletal-related events was also lower in combination group than the control group（P<0.05）. Conclusion Zoledronic acid in combination with radiotherapy has better clinical curative effect in treatment of NSCLC with osseous metastasis，worth promoting on clinical.

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Morphological characteristics and antibody expression patterns of adenocarcinoma cells in different tissues by liquid based cytology

QI Changhai，LU Yiyan，HOU Fang，LIU Yun

Chinese Clinical Oncology. 2017, 22 (2): 157.

Abstract ( 325 )

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Objective To explore the morphological characteristics and antibody expression patterns of adenocarcinoma cells in different tissues by liquid based cytology. Methods From April 2015 to July 2016， 90 cases of serous cavity effusion diagnosed as adenocarcinoma by histology in our hospital were collected， including 45 ovarian adenocarcinoma samples and 45 lung adenocarcinoma samples. Liquid based cytology was used to observe the morphological features of adenocarcinoma cells from different tissue origin and the expression patterns of carbohydrate antigen 125（CA125）， carbohydrate antigen 199（CA199）and carcinoembryonic antigen（CEA）were also investigated. Results As for ovarian adenocarcinoma，cells were arranged in clusters（tens to hundreds）in a round， oval， and papillary shape. There was often overlap and the edge was smooth with tightly packed cells. Caryoplasm is relatively high but the cytoplasm is relatively small. Small to medium or large nucleoli were visible with sand body in the background. Lung adenocarcinoma cells were arranged into pellets with abundant cytoplasm and strong mucus secretion. The cell mass is very three-dimensional， with large nuclei and obvious nucleoli. The positive expression rates of CA125 and CA199 in lung adenocarcinoma were 33.33%（15/45）and 28.89%（13/45）， lower than 71.11%（32/45）and 51.11%（23/45）of ovarian adenocarcinoma with significant difference（P<0.05）. The positive expression rates of three antigens in Ⅰ-Ⅱ stage of ovarian adenocarcinoma and lung adenocarcinoma samples were significantly lower than those of Ⅲ-Ⅳ stage（P<0.05）. Conclusion There were some differences in the morphological characteristics of adenocarcinoma cells from different tissues， and different expression patterns of CA125， CA199 and CEA had some value in judging the source of adenocarcinoma cells.

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Cause analysis and countermeasures of patient’s expulsion rate in breast cancer drug clinical trials

JIN Yan，ZHANG Qingyuan，LI Liru

Chinese Clinical Oncology. 2017, 22 (2): 161.

Abstract ( 310 )

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Objective To analyze the major causes of breast cancer drug clinical trials’ patients expulsion and find new methods to reduce the expulsion rate. Methods The report collected the messages of patients who participated the breast cancer drug trial in my hospital from June 2012 to January 2015 and analyzed the patient’s expulsion reasons. Results Among the 405 subjects, the expulsion of 85 participants were recorded. The major causes of patient expulsion were patients’ compliance and psychological features. The patients who had less compliance had a higher expulsion rate than those who had better compliance[70.9%（44/62） vs. 11.9%（41/343）] and the difference was significant（P<0.01）. The expulsion rate was more significant in the patients who had obvious psychological features[57.1%（20/35） vs. 17.6%（65/370）] with significant difference（P<0.01）. The distributions of drug types， medication， the courtyard frequency and clinical trial stage between the compliance and fall off patients had no significant difference. Conclusion To reduce the patient expulsion rate of breast cancer drug trials， we can focus on the management of patients and physicians and solve the adverse events in time.

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Effect observation of different concentrations of sufentanil on patient controlled subcutaneous analgesia of postoperative patients receiving esophageal cancer radical surgery

KANG Peipei，CONG Gujun，ZHAO Juncai

Chinese Clinical Oncology. 2017, 22 (2): 167.

Abstract ( 290 )

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Objective To compare effects of different concentrations of sufentanil on patient controlled subcutaneous analgesia（PCSA） after resection of esophageal carcinoma. Methods Ninety patients with esophageal cancer receiving radical surgery were enrolled in this study. Using the random number table， they were divided into 3 groups（Ⅰ-Ⅲ group, n=30） according to the doses of sufentanil (3， 3.5， 4 μg/ml) with PCSA for 2， 24， 48，72 h after the surgery. Postoperative pain degree was evaluated by numerical rating scale（NRS）. The degree of calm on patients receiving opioid analgesic therapy was evaluated by level of sedation（LOS）. The failure rate of patient-controlled analgesia， residual liquid quantity, the total number pressed by the patients with self-control analgesia and the occurrence of adverse reaction(bradycardia， hypotension and itching) were recorded. Results The failure rate of group Ⅰ was 43.3%（13/30）， and that of group Ⅱ and group Ⅲ was about 0. The amount of residual liquid in group Ⅰ was（18.1±0.7） ml， which was less than that in group Ⅱ（33.5±0.2） ml and group Ⅲ（33.2±0.3） ml， and the difference was statistically significant（P<0.05）. The total number of press times in group Ⅰ was 8.1±0.6， which was significantly higher than that in group Ⅱ（1.9±0.5） and group Ⅲ（2.1±0.3）， and the difference was statistically significant（P<0.05）. The scores of NRS in group Ⅰ of 2， 24 and 48 h were higher than those in group Ⅱ and group Ⅲ and the difference was statistically significant（P<0.05）. The score of LOS in group Ⅰ of 2， 24， 48 and 72 h was lower than those in group Ⅱ and group Ⅲ and the difference was statistically significant（P<0.05）. The incidences of itching， hypotension and bradycardia in group Ⅲ were higher than those in group Ⅰ and Ⅱ（P<0.05）. Conclusion The appropriate concentration of sufentanil on postoperative patients of esophageal cancer radical surgery with patient controlled subcutaneous analgesia is 3.5 μg/ml.

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Non-real-time endobronchial ultrasound guided transbronchial lung biopsy for the diagnosis of peripheral lung cancer

XIE Qiang，LIAO Shengxiang，LU Jun，ZHONG Aihong，LIAN Xiuhua.

Chinese Clinical Oncology. 2017, 22 (2): 171.

Abstract ( 259 )

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Objective To evaluate the diagnostic value and safety of non-real-time endobronchial ultrasound （EBUS） guided transbronchial lung biopsy （TBLB） for the diagnosis of peripheral lung cancer. MethodsFrom December 2014 to June 2016，142 patients without obvious pathological changes in ophthalmic examinations by routine bronchoscopy were diagnosed as peripheral lung cancer in Fuzhou Pulmonary Hospital by EBUS， and their clinical data were retrospectively analyzed. In this study，102 cases of peripheral lung cancer patients received non-real-time EBUS guided TBLB，and 42 patients received routine TBLB. The diagnostic positive rate， lesion detection and safety were compared between non-real-time EBUS guided TBLB and conventional TBLB. Moreover，the factors that affect diagnosis positive rate were summarized. Results Among 142 patients receiving EBUS examinations， 71.8%（102/142） of pulmonary lesions were detected by EBUS. The dignostic rate of the EBUS guided TBLB was 69.6% （71/102）， higher than 15.0% （6/40） of conventional TBLB （P<0.05）. The dignostic rate of EBUS guided TBLB on lesions with diameter ≤ 20 mm was 50.0% （11/22），lower than 75.0% （60/80） on lesions with diameter >20 mm （P<0.05）. The dignostic rate of EBUS guided TBLB on probe completely envelop wind the lesions was 84.4% （38/45），higher than 57.9% （33/57） on probe incompletely envelop wind the lesions （P<0.05）. The dignostic rate of EBUS guided TBLB on lesions with the presence of a bronchus sign on HRCT imaging was 82.4% （28/34）， higher than 63.2% （43/68） on lesions without the presence of a bronchus sign on HRCT imaging（P<0.05）. Complications of biopsy occurred in this study included slight haemoptysis and chest pain without pneumothorax. The incidence rates of haemoptysis were 30.3% （43/142） in EBUS guided TBLB and 32.5% （13/40） in conventional TBLB （P>0.05）. The incidence rates of chest pain were 12.7% （18/142） in EBUS guided TBLB and 10.0%（4/40） in conventional TBLB （P>0.05）. Patients with these complications recovered spontaneously without special managements. Conclusion The procedure of non-real-time EBUS guided TBLB was minimally invasive and had higher diagnostic rate with fewer complications. It was a safe and effective method to diagnose peripheral lung cancer，while careful selection of suitable case could further improve the diagnostic accuracy.

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Progression of the roles of apoptosis in breast cancer therapy

ZHAO Xiangxuan，WEN Feng，LU Zaiming

Chinese Clinical Oncology. 2017, 22 (2): 175.

Abstract ( 291 )

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Breast cancer is one of the most common malignant tumors in Chinese women. In last decades，the incidence and mortality of breast cancer showed a gradual upward trend. In addition to conventional treatment including early stage resection and radio/chemo-therapy， endocrine therapy and molecular target therapy have been the standard regime for molecular typing breast cancer. However，these malignancies treatment is usually along with recurrence， metastasis，resistance，high toxicity and side effects. Apoptosis blockage is the hallmark of human cancers including breast cancer. Understanding the deregulation mechanisms of apoptosis signal pathway and inducing breast cancer into apoptosis are the most fundamental approach to cure these diseases. This study has summarized the research advances of key apoptotic signal pathways in breast cancer. We hope to explicit the roles of those apoptotic signal pathways and find out the specific molecular target in breast cancer treatment.

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Basic mechanism and clinical application of anti-PD-L1/PD-1 immune therapies in ovarian cancer

MI Yaqin， JIANG Jingting， WU Changping

Chinese Clinical Oncology. 2017, 22 (2): 180.

Abstract ( 387 )

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Ovarian cancer is the leading cause of mortality from gynecological malignancies， chemotherapies and surgical treatments can do litter to cure this malignancy and novel treatment modalities， including immune therapy，are needed.Tumor immune therapy is currently the focus of substantial attention，especially anti-programmed cell death-1/programmed cell death ligand-1（PD-1/PD-L1） treatment.Inthis review， the importance of local tumor immunitywas discussed， which affects the clinical outcome of ovarian cancer. We subsequently provide an overview of the basicfindings regarding how the PD-L1/PD-1 signal influences local tumor immunity in ovarian cancer. Finally， immunotherapy is in a fledging period compared to other traditional therapies，so we discuss what is needed to apply immune therapy in future clinicalmedicine.

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Effects of EB virus and host immune in the pathogenesis of nasopharyngeal carcinoma and the progress of relative immune therapy

ZHANG Na，HU Chunhong

Chinese Clinical Oncology. 2017, 22 (2): 184.

Abstract ( 292 )

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Nasopharyngeal carcinoma（NPC）is one of the most common head and neck neoplasm in southern China. However， the pathogenesis and etiology of NPC remain unclear. NPC is sensitive to radiotherapy， but the high risk of relapse and metastasis are challenges. Epstein-Barr virus is the most important high risk factor of NPC， which has been the theme to explore the pathogenesis of NPC in nowadays. In order to reveal the immunological effects of EB virus in the pathogenesis of NPC， the relevance of immune response and EB virus related products， as well as the application of immune therapy for NPC will be reviewed in this article.

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标准刊号：	ISSN 1009-0460
	CN 32-1577/R