Chinese Clinical Oncology

study of vascular normalization window for tumor induced by bevacizumab and efficacy of bevacizumab plus paclitaxel in lung cancer-bearing mice

ZHANG Jing， ZHANG Wenchao，QIAN Ziqun， GAO Beili， XIANG Yi.

Chinese Clinical Oncology. 2017, 22 (6): 481.

Abstract ( 323 )

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Objective To explore the time window of bevacizumab to normalize the vascular for tumor and analyze the efficacy of bevacizumab plus paclitaxel in lung cancer-bearing mice. Methods Athymic mice bearing A549 xenografts were constructed. The study can be divided into two parts. In first part，24 nude mice were randomly assigned into two groups （n=12 per group）： control group （intraperitoneal injection of saline）and bevacizumab group （intraperitoneal injection of bevacizumab 5 mg／kg）. At four time points after injection （1， 3， 5， 8 d； n=3 at each time point）， the volume of tumor and the weight of nude mice were measured. Meanwhile， the levels of vascular endothelial growth factor （VEGF） and microvessel density （MVD） in tumor tissues were detected by Western blotting and immunofluorescence methods， respectively. In second part， 30 nude mice were randomly divided into four groups： control group （n=5）， bevacizumab monotherapy group （n=5）， paclitaxel monotherapy group （n=5） and paclitaxel plus bevacizumab group （n=15）. On the day of administration or the third and fifth day after administration of bevacizumab， paclitaxel plus bevacizumab group received intraperitoneal injection of paclitaxel with five mice at each time point. The paclitaxel and bevacizumab were administered at doses of 3 mg／kg and 5 mg／kg， respectively. The volumes of tumor were measured at 6 time points including 3， 7， 10， 14， 17， 20 days after administration. The nude mice were killed and the weight of tumor was measured 21 days later. The VEGF and MVD of the tumor were detected by Western blotting and immunohistochemistry. Results In the first part of our study， the tumor growth was suppressed gradually after the treatment of bevacizumab as compared with control group. Tumor volume， VEGF level and MVD reached a nadir at 3 days after bevacizumab administration. In the second part， compared with the control group， bevacizumab in combination with paclitaxel at different time points could suppress the tumor growth with a much significant inhibition effect on day 3 after bevacizumab administration. The average tumor volume， tumor weight， VEGF level and MVD were less in combined administration on day 3 than other combined groups. Conclusion The possible timing of the normalization window was typically 1-3 days after the administration of bevacizumab. The normalization window may provide an opportunity to enhance the effect of paclitaxel with the aid of bevacizumab.

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Expression and role of Kv1.3 potassium channel in human osteosarcoma

CHEN Zhida， DAI Lilin， ZENG Wenrong， XIONG Yuanfei， WU Jin.

Chinese Clinical Oncology. 2017, 22 (6): 487.

Abstract ( 310 )

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Objective To explore the effects of silencing Kv1.3 potassium channel by short hairpin RNA （shRNA） on the proliferation and apoptosis of osteosarcoma cells. Methods The expression of Kv1.3 potassium channel in osteosarcoma MG-63 cells was detected by real time quantitative polymerase chain reaction， Western blotting and immunohistochemistry. Next， we measured the proliferation， growth and cell apoptosis of MG-63 cells using CCK-8，xenograft model in vivo and flow cytometry. Finally，Western blotting was performed to detect the expression of cell apoptosis related genes including poly ADP-ribose polymerase（PARP） and caspase-3 in MG-63 cells. Results Kv1.3 potassium channel was overexpressed in osteosarcoma cells and tissues. Knockdown of Kv1.3 by shRNA significantly suppressed osteosarcoma cell proliferation and inhibited the growth of MG-63 in vivo and in vitro. Additionally，cell early apoptosis was also induced. Silencing Kv1.3 gene enhanced the leavel of cleaved caspase-3 and cleaved PARP. Conclusion Kv1.3 potassium channel is involved in proliferation and apoptosis process of human osteosarcoma and may represent a potential target for osteosarcoma diagnosis and treatment.

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Impact of Livin antisense oligonucleotide on the activity of osteosarcoma MG-63 cells

LI Chengjun，LIU Xiaozhou，SHI Xin，SUN Chang，ZHANG Lei，WU Sujia.

Chinese Clinical Oncology. 2017, 22 (6): 493.

Abstract ( 269 )

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Objective To investigate the expression of Livin in osteosarcoma MG-63 cells and the effect of Livin anti-sense oligonucleotide（ASODN） on its activity and function. Methods The ASODN targeting Livin were designed and constructed. According to the results of transfection efficiency evaluation， the liposome／oligonucleotide complexes were prepared by adding oligonucleotide and then transferred into MG-63 cells. The immunohistochemical staining and Western blotting were used to detect the expression of Livin at 24th h after transfection in MG-63 cells.The proliferation at 72nd h and apoptosis at 24th h after transfection were measured by CellTiter-Glo and Flow cytometry，respectively. Results The Livin was mainly expressed in the cytoplasm of MG-63 cells. We chose ASODN with the highest transfection efficiency to transfer MG-63 cells. The expression of Livin protein decreased significantly after the transfection， and Livin ASODN at different concentrations inhibit the proliferation and migration of MG-63 cells with significant difference. The apoptotic rate of Lip-ASODN group was higher than those of blank control group and negative control group in a dose-dependent manner （P＜0.05）. Conclusion The ASODN targeting Livin can inhibit the proliferative capacity and promote the apoptosis of osteosarcoma MG-63 cells.

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Expression of C17orf76-AS1 in epithelial ovarian cancer and effect on the biological function of SKOV3

FAN Weimin，XU Pengfei，FU Ziyi，CHEN Yun.

Chinese Clinical Oncology. 2017, 22 (6): 500.

Abstract ( 318 )

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Objective To investigate the expression of C17orf76-AS1 between normal ovarian epithelial cell and epithelial ovarian cancer cells and the effect of C17orf76-AS1 overexpression on the biological function of SKOV3 cells. Methods The quantitative real-time PCR（QPCR）was used to detect the expression of C17orf76-AS1 in normal ovarian cell （IOSE80） and ovarian cancer cells （A2780，SKOV3，OVCAR3，HO-8910 and HO-8910PM）. Construction of C17orf76-AS1 overexpression plasmid based on pcDNA3.1 plasmid and transient transfection of ovarian cancer cell SKOV3 with Lipo2000 were carried out. QPCR was used to detect the overexpression efficiency of C17orf76-AS1 in SKOV3 cells. CCK-8 was used to detect the proliferation of SKOV3.Transwell and wound healing assay were used to detect the migration of SKOV3. Results Compared with IOSE80， C17orf76-AS1 showed low expression in A2780，SKOV3，OVCAR3，HO-8910 and HO-8910PM about 0.36，0.30，0.46，0.32 and 0.31 folds（P＜0.05）. The proliferation of SKOV3 cells significant decreased about 1.5 folds after C17orf76-AS1 overexpression with CCK-8 assay. The Transwell assay demonstrated C17orf76-AS1 overexpression significant decreased the migration of SKOV3 by about 1.3 times， and the wound healing assay confirmed that the healing ability of SKOV3 was significantly lower than that of the control group after the overexpression of C17orf76-AS1（P＜0.05）. Conclusion LncRNA C17orf76-AS1 was downregulated in ovarian cancer cells. The overexpression of C17orf76-AS1 significant decreased the proliferation and migration of ovarian cancer cell.

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Effects of miRNA-199b-3p on the targeted regulation of SOX6 and proliferation and apoptosis of colon cancer cell line SW620

LING Binxun， ASIMUGULI Abdukerim， CAI Yun.

Chinese Clinical Oncology. 2017, 22 (6): 505.

Abstract ( 316 )

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Objective To investigate the effects of microRNA-199b-3p （miR-199b-3p） on the expression of SOX6 and its effect on proliferation and apoptosis of colon cancer cell line SW620. Methods The miR-199b-3p inhibitor and negative control （NC） were transfected into SW620 cells by Lipofectamine liposome method and then divided into inhibitor group and NC group. The SW620 cells without transfection were used as control （non-transfection group）. Real-time quantitative PCR （QPCR） was used to detect the expression of miR-199b-3p in three groups as to evaluate the transfection efficiency. MTT and Annexin Ⅴ-FITC／PI flow cytometry were used to detect the proliferative activity and apoptotic rate after transfection， respectively. The mRNA and protein levels of apoptosis related genes （Bax and caspase-3） and SOX6 were detected by QPCR and Western blotting. The luciferase reporter gene plasmids containing wild type and mutant SOX6-3’UTR were constructed. The effect of miR-199b-3p on the regulation of SOX6 was verified by double luciferase reporter assay. Results The QPCR results at 48 h after transfection showed that the level of miR-199b-3p in the inhibitor group was 0.526±0.034， lower than 1.009±0.064 of non-transfection group and 0.960±0.057 of NC group， and the difference was statistically significant （P＜0.05）. Compared with other two groups， the proliferative activity of the inhibitor group was decreased at 24，48 and 72 h after transfection （P＜0.05）. The apoptotic rate of the inhibitor group was （37.533±1.459）％， higher than （6.101±0.663）％ of non-transfection group and （8.753±1.061）％ of NC group， and the difference was statistically significant （P＜0.05）. The mRNA and protein levels of SOX6， Bax and caspase-3 in inhibitor group were higher than those in non-transfection group and the NC group， and the difference was statistically significant （P＜0.05）. Dual luciferase reporter gene assay showed that miR-199b-3p could significantly inhibit the luciferase activity of wild-type SOX6-3’UTR， but had no effect on the luciferase activity of mutant plasmid transfected cells. Conclusion MiR-199b-3p can regulate the expression of SOX6， and inhibiting the expression of miR-199b-3p can inhibit the proliferation of SW620 cells and induce apoptosis， which provide a potential molecular therapeutic target for the treatment of colon cancer.

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Expression and clinical significance of E-cadherin in invasive ductal carcinoma

YANG Liang，WU Tao，ZHU Liping，WANG Hongli，WANG Bing， ZHAO Qian， WANG Xiyan.

Chinese Clinical Oncology. 2017, 22 (6): 511.

Abstract ( 379 )

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Objective To investigate the expression of E-cadherin（E-cad） in invasive ductal carcinoma and its relationship with clinicopathological features， lymph node metastasis and prognosis. Methods Immunohistochemical SP method was used to detect the expression of E-cad in 30 cases of breast fibroadenoma and 450 cases of breast invasive ductal carcinoma. The relationship between its expression and clinical pathological features was analyzed. The survival curve was drawn by Kaplan-Meier method. Results The positive expression rate of E-cad in non-metastatic breast cancer tissues was 49.04％（77／157）， which was significantly higher than that of E-cad in metastatic breast cancer（P＜0.05）. The expression of E-cad was correlated with age， lymph node metastasis， tumor size， ER expression， molecular type and histological grade （P＜0.05）， but not with tumor stage， the expression of HER-2 and Ki-67. The 5-year survival rate of patients with E-cad positive expression in breast cancer lymph node metastasis group and triple-negative breast cancer group was better than those with E-cad negative expression（P＜0.05）. Conclusion The expression of E-cad is closely related to the lymph node metastasis of breast cancer， and it may also be a prognostic indicator of breast cancer with lymph node metastasis or triple-negative breast cancer.

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Study of plasma microRNA-7 levels in advanced gastric cancer and its clinical significance

ZHANG Lanfang， KUAI Jun， ZHU Yanli

Chinese Clinical Oncology. 2017, 22 (6): 516.

Abstract ( 263 )

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Objective To investigate the level of microRNA-7 （miR-7） and its clinical significance in advanced gastric cancer. Methods The plasma samples of 75 patients with advanced gastric cancer and 73 healthy subjects were collected from June 2013 to June 2016 in this hospital. The miR-7 level was detected by quantitative real-time PCR （QPCR） technique. The relationship between plasma miR-7 levels and clinicopathological features was analyzed in patients with gastric cancer. According to the follow-up data，the relationship between plasma miR-7 level and prognosis was analyzed in patients with gastric cancer. Results The QPCR detection showed that miR-7 level was （0.351±0.258） in 75 cases of gastric cancer patients， less than （1.088±0.464） of 73 healthy subjects and the difference was statistically significant （P＜0.05）. The plasma miR-7 levels were independent of sex， age， ECOG score， tumor site and pathological type in patients with gastric cancer， but were related to the degree of differentiation. Among them， the miR-7 level of the low differentiation group was （0.254±0.155）， lower than （0.514±0.313） of the high／middle differentiation group， and the difference was statistically significant （P＜0.05）. The median progression free survival （PFS） and overall survival （OS） of 75 patients were 6.6 and 10.5 months. The median PFS of miR-7 high expression group （＞0.351） was 7.1 months， better than 5.8 months of the low expression group （≤0.351）（P＜0.05）. There was no significant difference between the two groups in OS （10.3 months vs. 10.6 months， P＞0.05）. Conclusion The plasma miR-7 level decreased in advanced gastric cancer， and patients with low miR-7 level were poorly differentiated. The PFS of a high miR-7 level is better，and the index has a good value in the prediction of prognosis on gastric cancer.

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Expression and significance of KLF9，SP1 and HPV16／18 in serous or mucinous ovarian cystadenocarcinoma

ZHU Lixia，LIU Qin，XU Song，LI Hai，YANG Ning，CHEN Fang.

Chinese Clinical Oncology. 2017, 22 (6): 521.

Abstract ( 266 )

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Objective To investigate the expressions of KLF9， SP1 and HPV16／18 protein in ovarian serous or mucinous cystadenocarcinoma and their clinicopathological significance， and further investigate the effect of KLF9， SP1 and HPV16／18 on the occurrence and development of ovarian serous or mucinous cystadenocarcinoma. Methods Sixty cases of ovarian serous or mucinous mucinous cystadenocarcinoma and 20 cases of ovarian serous or mucinous cystadenoma were collected in this study. KLF9， SP1 and HPV16／18 were detected by immunohistochemical SP method and in situ hybridization. We also analyzed the relationship of their expression and clinicopathological features as well as the correlation among them. Results The positive rates of SP1， KLF9 and HPV16／18 were 71.7％（43／60），63.3％（38／60）and 30.0％（18／60） in ovarian serous or mucinous cystadenocarcinoma，higher than 15％（3／20）， 10％（2／20）and 0（0／20）in ovarian serous or mucinous cystadenoma （P＜0.05）. Spearman correlation showed that there was significantly positive correlation between KLF9 and SP1（r=0.443，P=0.000）， and also positive correlation between HPV16／18 and SP1（r=0.331，P=0.010）. The expression of KLF9 was not correlated with any clinicopathological features （P＞0.05）. The expression rate of SP1 was significantly correlated with clinical stage （P＜0.05）. The expression of HPV16／18 was correlated with pathological grade （P＜0.05）. Conclusion KLF9， SP1 and HPV16／18 were highly expressed and may affect the biological behavior of ovarian serous or mucinous cystadenocarcinoma. They may play an important role in the occurrence and development of ovarian serous or mucinous cystadenocarcinoma.

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Value of 18F-FDG PET-CT imaging in predicting epidermal growth factor receptor mutations in unresectable lung adeocarcinoma

TANG Bo，DING Chongyang，LI Tiannv.

Chinese Clinical Oncology. 2017, 22 (6): 526.

Abstract ( 263 )

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Objective To investigate the value of fluorodeoxyglucose F18 positron emission tomography-computed tomography （18F-FDG PET-CT） in predicting the presence of epidermal growth factor receptor （EGFR） mutations in unresectable lung adeocarcinoma. Methods From April 2012 to May 2016， 151 patients with stage ⅢB or Ⅳ lung adeocarcinoma who underwent 18F-FDG PET-CT and EGFR mutation analysis were enrolled in this study. Receiver-operating characteristic （ROC） curve was used to test the cut-off of maximum standard uptake value（SUVmax）. Logistic regression model was employed to analyze the independent predictive factors for EGFR mutatuin. Results ROC curve showed that the cut-off of SUVmax was 10.28. Among 151 lung adeocarcinoma patients，68（45.0％） were identified with EGFR mutation. Univariate analysis showed that gender，smoking status，CEA and SUVmaxwere all associated with EGFR mutation （P＜0.05）. And no significant differences were found regarding partical CT characteristics of lesions including cavitation，air bronchogram， attenuation，lobulation and pleural-indentation （P＞0.05）. Logistic multivariate analysis showed that smoking status and SUVmax were the independent factors for predicting EGFR mutation （P＜0.05）. Conclusion SUVmax of 18F-FDG PET／CT is an independent factor for predicting EGFR mutation in patients with unresectable lung adeocarcinoma， and it has certainly reference value for predicting EGFR mutation.

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Detection of tumor coagulation indexes in patients with gastric cancer and their clinical significance

WANG Chao，PENG Wanren，WANG Xuewei，XIAO Xin，LIU Ke.

Chinese Clinical Oncology. 2017, 22 (6): 531.

Abstract ( 285 )

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Objective To investigate the association between coagulation detection and tumor invasion， nodal status， staging in patients with gastric cancer. Methods From Jan 2014 to Nov 2014，a total of 120 patients with gastric cancer as the experimental group and 60 healthy volunteers as control were enrolled to receive coagulation index detection. The test items included prothrombin time （PT）， activated partial clotting enzyme live time （APTT）， thrombin time （TT）， fibrinogen （Fib）， D-dimer （DD） and platelet （PLT）.We compared the difference of the blood coagulation indexes of both groups and analyzed the correlation between these blood coagulation indexes and the depth of tumor invasion， lymph node metastasis， and clinical staging. Results Compared with control group， Fib， DD and PLT were significantly higher in gastric cancer group with statistical significant （P＜0.05）， while APTT， TT and PT were not significantly different between both group （P＞0.05）. In gastric cancer patients， T2-T4 staging compared to T1 staging， N1-N3 staging compared to N0 staging， and Ⅳ staging compared to Ⅰ-Ⅲ staging， Fib， D-D， PLT were significantly elevated with statistical difference （P＜0.05）. Conclusion Compared with the healthy volunteers， blood coagulation function of patients with gastric cancer significantly deteriorated. The blood coagulation function is closely related to the depth of tumor invasion， clinical staging and lymph node metastasis.

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Clinical observation of GEMOX and FOLFOX regimens as first-line chemotherapy for advanced duodenal cancer

PAN Jun， QIN Shukui， YANG Ningrong， HUANG Wei， WANG Lin

Chinese Clinical Oncology. 2017, 22 (6): 535.

Abstract ( 336 )

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Objective To evaluate the efficacy and safety of GEMOX and FOLFOX regimens as first-line chemotherapy for advanced duodenal cancer. Methods From June 2008 to Jan 2016， 30 advanced duodenal cancer patients were analyzed. Only 20 patients received chemotherapy， including 9 patients of GEMOX regimen and 11 patients of FOLFOX regimen as first-line chemotherapy. The efficacy and safety were evaluated by RECIST 1.1 and NCI-CTC 4.0 criteria. Overall survival （OS） and progression-free survival （PFS） were analyzed by Kaplan-Meier method. Results Among patients receiving chemotherapy， CR and PR were not observed. For GEMOX regiem， 6 cases of SD and 3 cases of PD were observed with disease control rate （DCR） of 66.7％. For FOLFOX regiem， 4 cases of SD and 7 cases of PD were observed with DCR of 36.4％. No difference in DCR was observed between different regimes （P＞0.05）. The median OS of GEMOX and FOLFOX regimes were 27.9 months and 15.2 months（P=0.179）. The median PFS of GEMOX regime was 8 months，superior to 4.4 months of FOLFOX regime （P=0.038）. The major treatment-related side effects included leucopenia， neutropenia， nausea， vomiting， fatigue， erythra and etc， mainly in grade1-2. The median OS of patients receiving chemotherapy was 26.9 months，superior to 4.4 months of patients receiving non-chemotherapy （P＜0.001）. Conclusion Chemotherapy was effective in advanced duodenal cancer. Both GEMOX and FOLFOX regimes were effective and well-tolerated in the first-line chemotherapy. GEMOX had a longer PFS in first-line chemotherapy.

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Disease spectrum analysis of 4635 in-patients with malignant tumors in Kashgar

NUERAILI Kade，ZHOU Yi，ATIKAN Kawuli， MUHETAER Wubulikasimu， ABUDUXUKUER Mijiti.

Chinese Clinical Oncology. 2017, 22 (6): 540.

Abstract ( 274 )

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Objective To investigate the characteristics of disease order and constitutes of in-patients with malignant tumors in the Second People’s Hospital of Kashgar during 2010 to 2016， and to provide reference for the prevention and control of cancer in this region. Methods The basic data of patients with malignant tumors in the Second People’s Hospital of Kashgar from 2010 to 2016 was collected， and Microsoft Excel was used to analyze the disease order and constitutes of disease in patients with malignant cancers. Results A total of 4635 patients were registered， including 861（18.58％） of Han nationality， 3718 （80.22％） of Uygur nationality， and 56 （1.20％） from other nationalities. The top 10 kinds of malignant tumors accounted for about 73.25％ of all malignant tumors. The top 10 kinds of malignant tumors for Han nationality were lung cancer， gastric cancer， colorectal cancer， breast cancer， liver and intrahepatic bile duct cancer， esophageal cancer， prostate cancer， cervical cancer， bladder cancer and ovarian cancer. Meanwhile， the order for Uygur nationality was gastric cancer， esophageal cancer， cervical cancer， breast cancer， colorectal cancer， lung cancer， liver and intrahepatic bile duct cancer， other malignant neoplasms of skin， prostate cancer and ovarian cancer. Conclusion A different characteristics of disease order and constitutes of malignant tumor existed between Uygur and Han nationalities in Kashgar. Further study on the characteristics of malignant tumor disease in this area is helpful to the prevention and treatment of malignant tumor.

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Feasibility study of volume modulated arc therapy for total body irradiation

WANG Kai， CUI Maoyan， LUO Di， ZHOU Hongping， YIN Yongmei.

Chinese Clinical Oncology. 2017, 22 (6): 544.

Abstract ( 261 )

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Objective To investigate the feasibility and dosimetry characteristics of a volumetric arc therapy （VMAT） technique for total body irradiation （TBI）. Methods VMAT technique was performed for fifteen patients receiving TBI therapy as a preconditioning regimen of hemapoietic stem cell transplantation at BenQ Medical Center， between August，2012 and January， 2015. Eclipse 10.0 Treatment Planning system was employed to perform treatment plan. The VMAT plan consisted of three centers： the head and neck， the chest and the pelvis（each with a 360° arcs）. The prescription dose was 12 Gy／6 f. The homogeneity of planning target volume （PTV） and organs at risk （OAR） were measured by dose volume histograms （DVH） curve. Monitor units （MU）， the bean time and total treatment time were prescribed to ensure the efficiency of the VMAT planning. Finally， the 2D ionization chamber array Matrix X was used to verify the VMAT treatment. Results In all patients， there were average MUs of （2308±210.7）MU， and dose rate of 400 cGy／min. The total treatment delivery time was approximately 30 min. Using this technique， the average median dose for PTV was （12.58±0.45）Gy， with a range of（11.27±0.13）Gy to（5.35±0.65）Gy. Simultaneously， a considerable OAR dose reduction of 14.9％～61.9％ was observed by using this planning. Conclusion VMAT technique could obtain dose conformality of PTV， reduce the dose of OAR， and improve the treatment delivery efficiency. And it is expected to facilitate the clinical transition of TBI for the patients with hematologic malignancies.

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Efficacy of apatinib combined with temozolomide in the treatment of advanced melanoma patients after conventional treatment failure

CUI Chuanliang， SHENG Xinan， LIAN Bin， SI Lu， CHI Zhihong， TANG Bixia， WANG Xuan， YAN Xieqiao， BAI Xue， GUO Jun.

Chinese Clinical Oncology. 2017, 22 (6): 548.

Abstract ( 386 )

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Objective To investigate the safety and preliminary efficacy of apatinib combined with temozolomide in the treatment of advanced melanoma patients. Methods Nine patients with advanced melanoma after conventional treatment failures wereenrolled from December 2016 to May 2017.The patients were enrolled to three dose escalating groups（3 cases in each group）， with traditional 3+3 method， temozolomide100mg，apatinib 250 mg；temozolide 200 mg， apatinib 250 mg； temozolomide 200 mg，apatinib 500 mg， repeated every 28 days. Tumor response was evaluated by RECIST 1.1 criteria， and adverse events were graded according to NCI-CTCAE 4.0. The primary end point was safety （dose-limiting toxicity and maximum tolerated dose）， and the secondary endpoint was objective response. Results Dose escalation had been finished in nine patients without dose limiting toxicity （3 cases in each group）. Common adverse events included hypertension （33.3％）， hand foot syndrome （33.3％）， proteinuria（22.2％），white blood cell decrease （22.2％）， nausea（22.2％）， fatigue （11.1％）， etc. All adverse events were grade 1-2，maximum tolerated dose was not reached.Until May 2017， 7 patients could be evaluated， 1 got partial response（PR）， 4 got stable disease（SD） and 2 got progression disease（PD）， the objective response rate was 14.3％. Conclusion Apatinib combined with temozolomide is well tolerated withoutdose-limiting toxicity， and has shown its efficacy in advanced melanoma patients.

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Advantages of modified double-ring areola incision in the application of multicenter breast fibroadenoma operation

ZHANG Mingliang， JIN Gongshen， QIAN Jun

Chinese Clinical Oncology. 2017, 22 (6): 553.

Abstract ( 238 )

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Objective To investigate the advantages of clinical application between modified double ring areola incision and ordinary areola incision in multi-center breast fibroadenoma operation. Methods The data of forty patients diagnosed as multi-center breast fibroadenoma from January 2016 to December 2016 were reviewed. Among them， 20 were in modified double ring areola incision group and 20 in ordinary areola incision group. The advantages and disadvantages of the two approaches were compared. Results There was no significant difference in age， tumor distribution，operation time and extubation time between the two groups（P＞0.05）. Compared with ordinary areola incision group， double ring incision group showed the advantages of greater number and size of tumors， and less amount of blood loss（P＜0.05）. In addition，the two approaches both showed cosmetic results with clinic satisfactory rate over 90％. Conclusion Compared with theordinary areola incision，the modified double ring areola incision shows advantages in the treatment of tumor distributed in different quadrants， especially larger tumors. For glands need immediate remodeling in the operation， double ring approach is more feasible.

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Research progress of trastuzumab emtansine in breast cancer

YUAN Yang， ZHANG Shaohua， JIANG Zefei

Chinese Clinical Oncology. 2017, 22 (6): 557.

Abstract ( 525 )

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Trastuzumab emtansine （T-DM1） is an antibody-drug conjugate. Through a stable linker， the HER-2 targeting antitumor properties of trastuzumab is conjugated with the cytotoxic activity of the microtubule-inhibitory agent DM1 （derivative of maytansine）. Efficacy has now been demonstrated in randomized trials as first-line， second-line， and later than the second-line treatment of advanced breast cancer. The NCCN panel recommends T-DM1 as a preferred option for treatment of patients with HER2-positive metastatic breast cancer who have previously received a trastuzumab-based regimen. Ongoing studies are also evaluating the use of T-DM1 in neoadjuvant， and adjuvant settings and in combination with other agents. In this article， we review the mechanism of action of T-DM1， efficacy and safety data in critical clinical studies， predictors of response or resistance to T-DM1 and the strategies to overcome resistance， may offer practical reference for clinicians.

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Reasearch progress of immune checkpoint inhibitors in the treatment of lung cancer

TANG Shuxian， CHEN Jun

Chinese Clinical Oncology. 2017, 22 (6): 562.

Abstract ( 258 )

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Morbidity and mortality of the lung cancer increased very highly. Although recently chemotherapy， radiotherapy and molecular targeted therapy made great progress， five-year survival rate was not improved. Immune checkpoint inhibitors as the new direction for the treatment of tumors， have attracted attention due to the fact that they have the characteristics of efficiently and low toxicity. Current research on immune checkpoint inhibitors， such as CTLA-4， PD-1／PDL-1， Tim-3 and so on， have already been launched. In this review， we mainly summarized the progress in the immune checkpoint inhibitors in recent years.

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Progression on the mechanism of PRL-3 in tumors

SONG Xiujun， LIU Jianhong，LV Jin，JIANG Qisheng.

Chinese Clinical Oncology. 2017, 22 (6): 566.

Abstract ( 290 )

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Phosphatase of regenerating liver-3 （PRL-3） is a metastasis-associated phosphatase which was highly expressed in various types of cancers， such as acute myeloid leukemia， colorectal cancer， breast carcinoma， non-small cell lung cancer and so on. It can promote cell proliferation， migration and invasion. In recent years， with the development of research methods，the research on mechanism of PRL-3 in tumor is increasing. These studies found that the pathways of tumorigenesis and metastatic was not all the same in deferent tumors. So it has the wide prospect of the clinical application in targeted therapy. This review is about the mechanism of action of PRL-3 in tumors.

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Clinical value of the time-intensity parameters of CEUS in hepatocellular carcinoma

LIANG Xitian， WU Bolin， SHANG Haitao， TIAN Yuhang， CHENG Wen.

Chinese Clinical Oncology. 2017, 22 (6): 570.

Abstract ( 268 )

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As a new functional imaging technology， contrast-enhanced ultrasound （CEUS） can clearly show the characteristic of blood flow perfusion of the lesions. And we can get the time-intensity curve in the region of interest， which can reflect the level of enhancement varying with time by quantitative analysis software. It can reveal the microvessel density of lesions objectively. Therefore， the quantitative analysis of CEUS can play an important role in the diagnosis of tumor and the evaluation of treatment effect. The paper introduced the mechanism of quantitative analysis of CEUS and its primary parameters， and summarized the role of some parameters in distinguishing benign and malignant liver diseases， assessing the prognosis of hepatocellular carcinoma， as well as evaluating therapeutic effect.

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标准刊号：	ISSN 1009-0460
	CN 32-1577/R