Chinese Clinical Oncology

The study on YM155-sensitized lexatumumab-induced apoptosis in hepatocellular carcinoma cells

ZHAO Xiangxuan， WEN Feng， REN Ying， SUN Wei， LIANG Hongyuan， ZHAO Gang， LU Zaiming.

Chinese Clinical Oncology. 2016, 21 (5): 385.

Abstract ( 597 )

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Objective To investigate the roles of small molecule compound YM155 in lexatumumab-induced apoptosis in hepatocellular carcinoma（HCC） LH86 cells and the possible mechanism. Methods HCC LH86 cells were cultured in vitro. Control group（DSMO）， YM155-treated group（1 μmol／L）， lexatumumab-treated group（1 μg／ml） and YM155 plus lexatumumab-treated group（1 μmol／L YM155+1 μg／ml lexatumumab） were set up. Cells untreated or treated with various conditions were observed under microscope to show necleus fragmentation and calculate cell apoptotic rate. Western blotting was performed to detect apoptotic marker molecule caspase-3 cleavage activation and Bax conformational activation. Results YM155（1 μmol／L） and lexatumumab（1 μg／ml）did not induce nucleus fragmentation in LH86 cells. Interestingly， 1 μmol／L YM155 significantly sensitized lexatumumab-induced apoptosis in HL86 cells. The apoptotic rate of YM155 plus lexatumumab-treated group was 60％，higher than the other 3 groups（P＜0.05）. The combination treatment effectively increased cleaved caspase-3 protein levels. Mechanism analysis revealed that YM155 and lexatumumab could promote Bax activation through its conformational change. Conclusion YM155 is able to sensitize monoclonal antibody lexatumumab-induced apoptosis in HCC cells，which may be mediated by Bax conformational activation.

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Chemokine CX3CL1／CX3CR1 biological axis promote ovarian cancer cell apotosis induced by platinum drug

LIU Hongmei，LI Mengdi， MAO Yannan， HUANG Yongzhi， LIU Yingzhao， LI Li， WANG Qi.

Chinese Clinical Oncology. 2016, 21 (5): 390.

Abstract ( 571 )

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Objective To study the relationship between the chemokine CX3CL1／CX3CR1 and platinum drug resistance， as well as prognosis in ovarian cancer patients. To dynamically detect the resistance nude mice model of CX3CL1 and its receptor CX3CR1 in the course of platinum resistance. To analyze the expression of CX3CL1， CX3CR1 and the correlation of Fas signaling pathway. Methods The cancer gene atlas（TCGA） database of patients with ovarian cancer genomewide expression was employed to analyze the relationship of CX3CL1／CX3CR1 in platinum sensitivity or resistant patients with clinical features. Ovarian cancer SKOV3 sensitive cells（SKOV3-GFP） with green fluorescent marker and cisplatin resistant cells（SKOV3-GFP／DDPⅢ） were subcutaneously injected in nude mice. After xenograft was constracted， cisplatin was intraperitoneally injected. Real time fluorescence quantitativePCR（qRT-PCR） was used to detect the expression of CX3CL1， CX3CR1 and genes on Fas signal pathway after 0， 2， 5， 8 times of cisplatin injection.Results CX3CL1 expression was negatively correlated with FIGO and platinum resistance（r=-0.112，P=0.030；r=-0.106，P=0.044）， CX3CR1 expression was negatively correlated with progression-free survival time（r=-0.130，P=0.029） and positively correlated with 1-year relapse rate（r=0.119，P=0.045）. The average expression of CX3CL1 in platinum sensitive group was 3.96±0.039， higher than 3.64±0.55 of platinum resistant group（P=0.000）. After the intervention of cisplatin， xenograft grew gradually. The weight of xenograft in SKOV3-GFP／DDPⅢ group was higher than SKOV3GFP group， and xenograft in the both two groups shrank at the fifth time of infection. After cisplatin stimulation， the expression of CX3CL1／CX3CR1 in SKOV3GFP group increased significantly（P=0.001， P=0.002）， but it remained low in SKOV3-GFP／DDPⅢ group. The expression of Fas and FADD of Fas signal pathway in SKOV3-GFP／DDPⅢ group was also significantly lower than them in SKOV3-GFP group（P＜0.001）. However， PARP1 gene significantly rose in SKOV3-GFP／DDPⅢ group than that in SKOV3-GFP group（P＜0.001）. The expression of CX3CL1 and CX3CR1 was positively correlated with Fas and FADD， while it was negatively correlated with PARP1 of Fas signaling pathways. Conclusion The down-regulation of CX3CL1 and CX3CR1 is associated with platinum resistance. They may play a role in maintain the sensitivity of tumor cells to platinum. The low expression of CX3CL1 and CX3CR1 may suppress Fas signal pathway through some mechanism， resulting in transduction disorder， inhibiting cell apoptosis and inducing platinum resistance of ovarian cancer. The lower expression of drugresistant cells may be a mechanism inhibiting Fas signaling pathways， which make its conduction misbalance， finally inhibiting cell apoptosis， inducing the resistance of ovarian cancer. It may be a platinum promote ovarian cancer therapy targeting molecules.

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Experimental study on antiangiogenic effect of crocin on breast cancer

CHEN Shuangshuang，ZHAO Shuang，GU Yuan，JIANG Enze，ZHU Jianjun，YU Zhenghong.

Chinese Clinical Oncology. 2016, 21 (5): 397.

Abstract ( 604 )

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Objective To observe the antiangiogenic effect of crocin on breast cancer and explore its possible mechanism. Methods In order to screen of appropriate drug concentrations, MTT assay was performed to test the inhibitory effect of crocin on breast cancer cell MDA-MB-231 and human umbilical vein endothelial cells（HUVECs）. The effect of crocin on MDA-MB-231 cell apoptosis and cell cycle was detected by flow cytometry. Transwell and Tubular formation test were used to detect the inhibitory of crocin on HUVECs migration and forming tubular. Nude mouse model of breast MDA-MB-231 cell was constracted, and the mice were given crocin（5 mg/ml） for 7 times. Immunohistochemistry was applied to detect CD34 and Ki-67 expression after MDA-MB-231 subcutaneous xeno-transplanted tumors treated with crocin. Results MTT method showed that crocin had a significant inhibitory effect on the proliferation of MDA-MB-231 cells（P＜0.05） and the IC50 of 48 h was 5.0 mg／ml. Crocin had a mild inhibitory effect on HUVECs without a dose-dependent manner at 24 h. But the effect was quite opposite at 48 h and 72 h， and the IC50 of 48 h was 5.97 mg／ml. Crocin induced the apoptosis and cell cycle arrest in G2／M phase of MDA-MB-231 cells in a dose-dependent manner（P＜0.05）. Transwell and Tubule formation test showed that crocin could inhibit HUVECs migration（P＜0.05） and tube formation（P＜0.05） in a dose-dependent manner. The subcutaneous transplantation tumor growth in 5 mg／ml crocin group was slower than that in blank control group. And the expression of CD34 and Ki-67 in blank group and 5 mg／ml crocin group were 26.00±2.65 and 14.67±4.16（P＜0.05）， 502.67±88.48 and 262.67±75.08（P＜0.05）. Conclusion Crocin has certain effect of anti-angiogenesis， which may be related to the inhibition of tumor cell proliferation， reduce the micro vascular density in vivo and can inhibit vascular endothelial cell proliferation， migration， as well as tubule formation in vitro. The exact molecular mechanism remains to study further.

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The effect of bifidobacterium infantis on chemotherapy-induced intestinal mucositis in cancer rats

WANG Haonan，FU Hong，DONG Yan，GAO Yajie.

Chinese Clinical Oncology. 2016, 21 (5): 404.

Abstract ( 525 )

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Objective To investigate the influence and curative effect of bifidobacterium infantis（B.infantis） on intestinal mucositis of cancer rats induced by chemotherapy. Methods A model of cancer rats by subcutaneous injection of dimethyl hydrazine with rectal mucosa of cancer cells was created， and experimental rats were randomly divided into three groups： control group（saline）， chemotherapy group（5-FU+oxaliplatin）， bifidobacterium infantis group（5-FU+oxaliplatin+B.infantis）. The changes of diarrhea， body weight， villus height， crypt depth and levels of the proinflammatory factors IL-1β， IL-6 and TNF-α were recorded. Results In 41 mice, 12 mice consctracted tumor successfully, including 3 mice in control group, 5 mice in chemotherapy group and 4 mice in bifidobacterium infantis group. In the model of cancer rats， after 72 hours treatment，B.infantis administration prevented the loss in body weight（P＜0.05）. B.infantis reduced the occurrence of diarrhea（1.43±0.53 vs. 2.43±0.79，P＜0.05）. Compared to the chemotherapy treated rats， B.infantis could attenuate the injuries of the morphology of intestine.B.infantis-treated rats in a villus height［（379.37±53.80）μm vs.（335.33±89.54）μm，P＜0.05］ and a crypt depth［（219.22±38.05）μm vs.（331.24±69.24）μm，P＜0.05］. Intestinal IL-1β， IL-6 and TNF-α levels， which increased significantly in all rats receiving chemotherapy， were lowered by B.infantis administration except TNF-α level. However， there were no significant differences in plasma IL-1β， IL-6 and TNF-α levels. Conclusion The Bifidobacterium infantis effectively reduce intestinal injury due to chemotherapy-induced intestinal mucositis in cancer rats.

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Effects of tetrandrine on radiosensitvity of lung adenocarcinoma cell line and it’s mechanism

DING Wei， YANG Aizhen， XV Haijun， CHEN Longhua.

Chinese Clinical Oncology. 2016, 21 (5): 409.

Abstract ( 507 )

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Objective To investigate the effects of tetrandrine（Tet） on radiosensitivity of human lung adenocarcinoma SPC-A1 cells and its mechanism. Methods MTT assay was used to evaluate the cytotoxicity of Tet on SPC-A1. MTT assay were used to evaluate the inhibition ratio of irradiation group（X-ray 4 Gy）， Tet （1 μmol／L）+irradiation （X-ray 4 Gy） group and Tet group （1 μmol／L）. Cell viability after radiation was calculated by clonogenic assay. According to cell survival curve， the parameters including D0， Dq，SF2 were calculated. Flow cytometry was used to detect the cell cycle distribution of irradiation group and Tet+irradiation group. Results The IC50 of Tet on SPC-A1 cells at 24， 48 and 72 h were 10.77， 5.78 and 3.89 μmol／L， respectively. The values of D0，Dq，and SF2 of Tet+irradiation group were（1.551±0.045）Gy, （0.522±0.023）Gy and 0.503±0.008, which were lower than those of irradiation group， and SER was 1.48. Flow cytometry showed that exposure of SPC-A1 cells to 4 Gy of Xrays caused G2／M arrests （P＜0.05）. The arrests were abrogated by treated with Tet（P＜0.05）. Conclusion Tet can efficiently enhance the radiosensitivity of SPC-A1 cell. The mechanism maybe abrogating the radiation-induced G2 phase arrest. It fixes the damage of DNA，and causes reproductive cell death.

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The correlation and expressions of Fn14， p-JAK2 and p-STAT3 in esophageal squamous cell carcinoma

LIU Kai， LI Xiaofei， ZHANG Zhipei， SUN Ying.

Chinese Clinical Oncology. 2016, 21 (5): 413.

Abstract ( 545 )

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Objective To investigate the role of Fn14 with JAK2／STAT3 pathway in esophageal squamous cell carcinoma（ESCC）， and the expression of JAK2／STAT3 molecules were detected and the correlation of Fn14 with JAK／STAT was discussed. Methods Fn14，p-JAK2 and p-STAT3 expressions in tumor tissues were assessed using immunohistochemical（IHC） methods in 118 patients with resected ESCC， and the correlation of Fn14 expression with JAK2／STAT3 expression was analyzed. Results The expression of Fn14 was mainly located on cell membrane and the expression of p-JAK2， p-STAT3 were mainly located in cytoplasm and cell nucleus. The positive expression rates of Fn14， p-JAK2 and p-STAT3 protein in ESCC were 51.7％（61／118）， 50.9％（60／118） and 57.6％（68／118）， which were higher than 4.2％（5／118） of corresponding adjacent non-cancerous tissue with statistical difference（P＜0.05）. There were significant differences for Fn14， p-JAK2， p-STAT3 expressions in pathological grades and TNM stages groups（P＜0.05）， while there were no significant differences for Fn14， p-JAK2， p-STAT3 in sex and age （P＞0.05）. The correlation of Fn14 with p-JAK2， p-STAT3 were obvious in pathological grades and TNM stages in ESCC（P＜0.05）. Conclusion The Fn14， p-JAK2， p-STAT3 proteins were highly expressed in ESCC， which suggest that Fn14， p-JAK2， p-STAT3 would be likely to be associated with the development of ESCC.

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Expression of Foxp3 in ovarian cancer and its clinical significance

XIE Quanqin， CHEN Lujun， WU Changping， DENG Guohua， XU Bin， JIANG Jingting.

Chinese Clinical Oncology. 2016, 21 (5): 418.

Abstract ( 514 )

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Objective To investigate the expression of Forkhed box protein 3（Foxp3） in ovarian cancer and its relationship with prognosis. Methods Expression of Foxp3 was assessed by immunohistochemistry in tissue microarrays containing tumor tissues from 45 ovarian patients and 7 normal ovarian tissues. The rank sum test was utilized to compare the differences between different pathological types. Chi-square test was utilized to analyze recationship between Foxp3 expression and clinicopathological features. Kaplan-Meier method was utilized to analyze the correlation between Foxp3 expression and prognosis. The multi-factor Cox proportional hazards model was used to estimate the intensity of association between different clinicopathological features and mortal outcomes. Results The Foxp3 expression was located in nucleus of tumor cells. The expression of Foxp3 was related to FIGO stage（P＜0.05）， but age， pathological type， differentiation， tumor size and lymph node metastasis（P＞0.05）. Kaplan-Meier method revealed that patients with lower Foxp3 expression had prolonged survival time than that with higher Foxp3 expression（61.83 months vs. 25.03 months， P=0.03）. The Cox regression model multifactor analyze showed that without postoperative chemotherapy（HR=6.603， 95％CI： 1.147-32.057， P=0.03）， higher FIGO stage（HR=3.861， 95％CI： 1.427-10.417， P＜0.01） were independent prognostic factors of ovarian cancer. Conclusion Expression of Foxp3 was related to FIGO stage， and can predict survival of ovarian cancer.

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Efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small cell lung cancer previously treated with EGFR-TKIs

QU Binbin， CHEN Xia， WANG Lisheng， HUANG Xiao, LI Xvtong.

Chinese Clinical Oncology. 2016, 21 (5): 422.

Abstract ( 551 )

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Objective To explore the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small cell lung cancer（NSCLC） previously treated with epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs）. Methods In this retrospective study， 67 cases of NSCLC patients failed to EGFR-TKIs were enrolled. According to the treatment regimen， the patients were assigned to receive docetaxel（75 mg／m2 d1， n=31） or pemetrexed（500 mg／m2 d1， n=36） with 21 days for a cycle. The efficacy was evaluated according to response evaluation criteria in solid tumors（RECIST 1.1）. The toxicity was evaluated by international standard adverse reaction NCI CTC 3.0 version. The longterm survival was followed up and the Cox hazard regression model to analyze the influencing factors for the prognosis. Results All patients can be evaluated for the short-term efficacy. The response rates of pemetrexed group and docetaxel group were 19.4％ and 12.9％， and disease control rates were 58.3％ and 41.9％ without significant difference（P＞0.05）. In pemetrexed group， the incidence of grade 3-4 white blood cell reduction， thrombocytopenia， skin rash and elevated aminotransferase were all lower than that of docetaxel group（P＜0.05）. The median progression free survival（PFS） was 6.4 months in the pemetrexed group， higher than 4.7 months in docetaxel group with significant differences（P＜0.05）. No significant difference was observed in the median overall survival between both groups（P＞0.05）. Factors affecting the PFS included age， clinical stage， pathological type， PS score and save program. Conclusion Similar efficacy was observed between pemetrexed and docetaxel in NSCLC patients failed to EGFR-TKIs. However， the median PFS was relatively high， and the side effects were slight and could be tolerated in pemetrexed regiem. In view of the factors influencing the prognosis， it could be recommended to use in the treatment of the patients.

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Clinical application of peripheral blood circulating tumor cells with therapeutic effect of chemotherapy in ovarian cancer

LIANG Xiuting， DING Xiaoping， MA Li， ZHANG Junqin， LIU Dan.

Chinese Clinical Oncology. 2016, 21 (5): 427.

Abstract ( 537 )

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Objective To investigate the relationship between the change of circulating tumor cells （CTC） in peripheral blood and the chemotherapy effect of ovarian cancer. Methods A total of 28 ovarian cancer patients treated with chemotherapy in our department from February 2013 to April 2015 were enrolled in this study. Venous blood samples of 4 ml were collected from them before and after chemotherapy. The CTC in peripheral blood were purified by negative selection using immunomagnetic， and detected by immune fluorescence in situ hybridization （imFISH）. The CTC number over 2 in 3.2 ml was defiend as positive. The RECIST 1.0 criteria was used to assess the efficiency of chemotherapy， the relationship between the change of CTC before and after chemotherapy to the therapeutic effect of chemotherapy was studied. Results The positive rate of CTC before chemotherapy was 60.71%（17/28）， which was related with tumor stage （P=0.017） and CA125 levels （P=0.049）， while it of CTC detected after chemotherapy was 25％（7／28）. According to the status of CTC before and after chemotherapy，the patients were divided into 4 groups，that is，positive to positive，positive to negative， negative to positive and negative to negative groups.Their efficiencies was 80％（4／5），83.33％（10／12），0（0／2）and 88.89％（8／9） respectively, with significant difference（P=0.045）. Conclusion The changes of CTC before and after chemotherapy has a certain relationship with the efficiency to chemotherapy. CTC can be regarded as a predictor for evaluating chemotherapy.

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The value of radiotherapy in patients with T1-2N1M0 triple-negative breast cancer after modified radical mastecomy

SUN Liyun， SHEN Zan.

Chinese Clinical Oncology. 2016, 21 (5): 431.

Abstract ( 553 )

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Objective To analyze the prognosis of patients with T1-2N1M0 triple-negative breast cancer（TNBC） after modified radical mastectomy with or without postoperative radiotherapy. Methods One hundred and twenty-nine patients diagnosed with T1-2N1M0 TNBC after modified radical mastectomy from Jan. 2004 to Sep. 2010 were retrospectively reviewed. Of whom 61 cases received postoperative radiotherapy and 68 cases did not. The 5-year overall survival（OS）， locoregional recurrencefree survival（LRFS）and diseasefree surviva（DFS） rates of the two groups were observed. The risk factors for LRFS were analyzed in combination with clinical and patholgical features. Results With a median follow-up of 67 months， 27 patients developed locoregional recurrence. The patients treated with radiotherapy had significantly higher LRFS rates（88.5％ vs. 70.6％， P=0.017） as well as slightly higher DFS rates（78.7％ vs. 63.2％，P=0.068）.The 5-year OS rates were 88.5％ and 82.4％（P=0.068）， respectively. The univariate analysis indicated that age， T stage， the number of positive lymph nodes and postoperative radiotherapy were significant influencing factors for LRFS（P＜0.05）. The multivariate analysis showed that no radiotherapy（HR=3.432，P=0.010）and 3 positive lymph nodes（HR=2.915，P=0.020）were independent prognostic factors for LRFS. Conclusion T1-2N1M0 TNBC after modified radical mastectomy patients may benefit from radiotherapy， which significantly improves locoregional recurrence-free survival. The local control rates of patients with 3 positive axillary nodes was worse， so increasing regional lymph node irradiation should be feasible.

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Influence of biological characteristics of breast cancer in mammography on surgical margin status of breast-conserving surgery

ZHAO Kaihua， LI Peiying， GONG Lei， XU Jing， TAN Zhengshuai， LIU Songling， WANG Binggao， YAN Zheng.

Chinese Clinical Oncology. 2016, 21 (5): 437.

Abstract ( 506 )

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Objective To explore the influence of biological characteristics of breast cancer in mammography on surgical margin status of breast-conserving surgery. Methods One hundred and twenty patients diagnosed with stage Ⅰ or Ⅱ primary breast cancer received breast-conserving surgery were enrolled in this study. According to the mammography images， the breast cancer patients were divided into five groups， including masses type group， mass associated with calcification type group， calcification type group， asymmetries type group and architectural distortion type group. Total excision of breast lumps and surrounding tissue were performed about 1 cm. Intraoperative rapid pathological was employed to determine the initical state of cutting edge， which was confirmed by paraffin pathology. The relationship between biological characteristics of breast cancer in mammography and surgical margin status was analyzed. Results Pathologic features including age， tumor size， grade， nodal metastases， estrogen receptor status， progesterone receptor status and HER-2 expression were not associated with margin status of breast cancer patients. The positive rate of patients with tumor thrombus in vascular was 26.3％（5／19）， higher than 6.9％（7／101） of patients without tumor thrombus in vascular with statistical significance （P＜0.05）. No statistically significant difference was observed on the initial surgical margin status among five groups according to mammography classification. As for isolated malignant carcinoma， surgical margin status was not correlated with imaging characteristics of the tumor. However， mixed malignant carcinoma was significantly correlated with the margin status （P=0.005）. Conclusion For breast-conserving surgery， we may need to consider characteristics of the tumor mammography classification and estimate pathological type in order to reduce the probability of positive margin.

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Application of percutaneous coaxial core needle biopsy via director assisted CT guidance in retroperitoneal lymphomas

FENG Weijian，WU Xiangrong， YANG Linfeng，YAO Jie，FANG Hua， WEI Yaping.

Chinese Clinical Oncology. 2016, 21 (5): 442.

Abstract ( 508 )

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Objective To study the application value and safety of percutaneous coaxial-core needle biopsy via director assisted CT guidance in retroperitoneal lymphomas. Methods From June 2013 to May 2015， a total of 18 patients with retroperitoneal masses couldn’t undertaking surgercal biopsy were enrolled in this study. The 18 patients received percutaneous coaxial-core needle biopsy via director assisted CT guidance. At least five biopsy samples from different position were taken for pathology and immunohistochemistry examination. A dosage of 10-30 mg of cisplatin was injected into the lesion by trocar needle. Results Of the 18 patients underwent percutaneous coaxial-core needle biopsy via director assisted CT guidance. The success rate of puncture and biopsy was 100％. Operation time was 20-40 min （average 30 minutes）， and 5-9 sequence with 45-90 pictures of scan were used. No complications such as hemorrhage and pneumothorax occurred. Ten cases of retroperitoneal lymphomas were diagnosed， among whom there were 6 cases of diffuse large B lymphoma， 2 cases of follicular lymphoma and 2 cases of lymphoid cell lymphoma. According to Ann Arbor stage，there were 2 of stage Ⅱ， 6 of stage Ⅲ， and 2 of stage Ⅳ. The combination of chemotherapy and radiation was performed on lymphoma patients. Conclusion Percutaneous coaxial core needle biopsy via director assisted CT guidance with minimal invasiveness and fewer complications is a safe and effective minimally invasive technology， worthy of clinical application in the diagnosis of retroperitoneal lymphoproliferative disease.

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Comparative analysis of simultaneous integrated boost intensity-modulated radiotherapy treatment plans in the cervical and upper thoracic esophageal carcinoma

TAN Cheng， YANG Yanguang， HANG Daming， NI Feng， CAI Jing.

Chinese Clinical Oncology. 2016, 21 (5): 447.

Abstract ( 509 )

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Objective To compare the dosimetric parameters of 4 simultaneous integrated boost intensity-modulated radiotherapy （SIB-IMRT） treatment plans with different beams. Methods Four SIB-IMRT treatment plans with different beams of 3， 5， 7 and 9 were designed for twenty-four eligible patients with cervical and upper thoracic esophageal carcinoma. PTV-G and PTV-C were defined as the GTV and CTV plus 10 mm in all directions， which were delivered simultaneously to 60.2 Gy and 56 Gy in 28 fractions， respectively. Compared and evulated the dosimetric parameters of planning target volums and organs at risk（OARs） through the DVH diagram. Results The values of conformity index （CI） and heterogeneity index （HI） of four SIB-IMRT treatment plans with different beams of 3， 5， 7 and 9 were 0.33，0.55，0.77，0.80 and 1.09，1.07，1.07，1.05 in PTV-G，with significant difference（P＜0.05）. The values of CI and HI of SIB-IMRT treatment plans with four different beams were 0.69， 0.71，0.72，0.79 and 1.22，1.13，1.075，1.073 in PTV-C，with significant difference （P＜0.05）. The values of maximal dose of spinal cord were 4511.27，4288.31， 4224.60 and 4201.43 cGy in 3，5，7，9beams SIB-IMRT plans （P＜0.05）. With increased beam numbers， the V5 increased and the V20 decreased. The 9-beams plan had significantly increased V5 and nonsignificantly decreased V20 compared to the 7-beams plan. The V5 and V20 were 44.56％ and 19.28％ in 9-beams plan and 32.36％ and 19.65％ in 7-beams plan. Conclusion 7-beams SIB-IMRT plan was the preferred technique in cervical and upper thoracic esophageal carcinoma with uniform target dose and high degree conformity， which could provide the best protection to the lung and other vital organs.

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Strategies and advances in immunotherapy of non-small cell lung cancer

LU Chang， WANG Aman， LI Ying， Ning Zhen， LIU Jiwei.

Chinese Clinical Oncology. 2016, 21 (5): 452.

Abstract ( 581 )

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Non-small cell lung cancer（NSCLC） is a highly prevalent and aggressive disease. In recent years， the long time survival rate of patients with advanced NSCLC remains low despite of advances in surgery， irradiation， chemotherapy and targeted therapy. The aim of immunotherapy is to specifically enhance the immune response directed to the tumor. Many trials have addressed the role of novel immunotherapeutic agents， such as checkpoint inhibitors and antigenspecific tumour vaccines， which has made breakthrough progress in NSCLC. Immunotherapy will be a fundamentally new concept for the treatment of NSCLC.

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Progression of bone-modifying agents for the treatment of bone metastases in breast cancer

WANG Ruliang， JIANG Zefei.

Chinese Clinical Oncology. 2016, 21 (5): 458.

Abstract ( 547 )

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The bone-modifying agents （BMAs）， including the bisphosphonates （BPs） and the monoclonal antibody denosumab which was approved by FDA in 2010， have a long established role in the management of osteoporosis， hypercalcemia of malignancy and bone metastases from malignant tumors. In recent years， the use of the agents such as the medication time， the usage and side effects has certain progress and controversy. In this review we summarize the development of bone-modifying agents for the treatment of bone metastases in breast cancer.

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Progression of molecular-targeted drugs for hepatocellular carcinoma

LI You， HUA Haiqing.

Chinese Clinical Oncology. 2016, 21 (5): 462.

Abstract ( 489 )

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Primary liver carcinoma is one of the most common malignancies in China， which is marked by its insidious onset and rapid progression. Most of the cases are unresectable when detected， making the prognosis extremely poor. As the one and only molecular-targeted drug which can bring about survival benefit for advanced hepatocellular carcinoma， sorafenib has aroused a mass research fervor of molecular-targeted drugs since 2007， the year it appeared on the market. Regrettably， no new drugs are available for clinical use. This review focuses on central questions regarding molecular-targeted drugs in clinical study for hepatocellular carcinoma.

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Progession of the experimental and clinical research of 5-aminolevulinic acidbased photodynamic and sonodynamic therapy of tumor

XU Tongying， ZHU Wenting， XIE Rui， WEI Xiaoli， LI Yanjing， BAI Yuxian.

Chinese Clinical Oncology. 2016, 21 (5): 469.

Abstract ( 589 )

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5-aminolevulinic acid（5-ALA） is a strong photosensitizer， and it is widely used in photodynamic and sonodynamic therapy. 5-ALA is a precursor of PpⅨ which is generally accumulated higher in tumor cells than normal cells. Irradiation and ultrasound irradiation excitate PpⅨ in tumor cells and produce reactive oxygen species（ROS）， and damage DNA， mitochondria membrane and the other cell membrane then causes the apoptosis， necrosis. This article reviews the experimental and clinical research progression of 5-ALA in photodynamic and sonodynamic therapy of tumor recent years.

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标准刊号：	ISSN 1009-0460
	CN 32-1577/R