Chinese Clinical Oncology

Influence of autophagy on radiosensitivity of lung adenocarcinoma cells

GU Xin，CHEN Dongqin，PAN Banzhou，WANG Rui，HUANG Jiayuan，HUANG Guichun，CHEN Longbang.

Chinese Clinical Oncology. 2015, 20 (4): 289.

Abstract ( 972 )

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Objective To explore the influence of autophagy on radiosensitivity of drug resistant lung adenocarcinoma cells. Methods Transmission electron microscopy and fluorescence microscope were applied to assess autophagy activity of parent lung adenocarcinoma cells（SPC-A1） and drug resistant lung adenocarcinoma cells（SPC-A1／DTX）. After the pretreatment of autophagy inhibitor 3-methyladenine（3-MA） with SPC-A1／DTX， Western blotting analysis was used to detect autophagy related protein expression of LC3， p62 and Beclin-1 with or without 6 Gy-radiation. Apoptosis and cell cycle distribution were analyzed by flow cytometry. Cell viability and proliferation were examined by MTT and colony formation assay, respectively. Results The chemoresistant SPC-A1／DTX cells with higher autophagy activity were also radioresistant compared with the parental SPC-A1 cells（P＜0.05）. SPC-A1／DTX cells showed an increase in autophagosome and punctate localization of green fluorescent protein-LC3（characteristic of autophagy） compared to SPC-A1 cells. Irradiation elevated autophagy levels of both cells. Autophagy inhibitor 3-MA combination with irradiation suppressed the expression of autophagy markers, including LC3， p62 and Beclin-1（P＜0.05）. Irradiation-induced G2／M phase delay was increased and S phase arrest was decreased by combination of 3-MA with irradiation（P＜0.05）. The apoptotic rate was elevated when pretreatment with 3-MA before radiation. Conclusion Our results demonstrated that irradiation-induced autophagy provided a cytoprotective mechanism against radiotherapy in SPC-A1／DTX cells. Autophagy contributed to radioresistance of docetaxel-resistant human lung adenocarcinoma cells， and blocking autophagy would be a potential strategy for reversing chemoradiotherapy cross resistance of lung adenocarcinoma patients.

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Experimental study of combination therapy with ginsenoside Rg3, sorafenib and oxaliplatin versus monotherapy on anti-angiogenic effect in hepatocelluar carcinoma

SUN Rong， GAO Shu， HUA Haiqing， YANG Aizhen， QIN Shukui.

Chinese Clinical Oncology. 2015, 20 (4): 296.

Abstract ( 997 )

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Objective To observe the effect of ginsenoside Rg3，sorafenib，oxaliplatin alone or with different combination in neovascularization of tumor in nude mice with human hepatocellular carcinoma， and investigate the possible mechanisms. Methods Sixty nude mice with high metastatic human hepatocellular carcinoma transplanted in situ（LCI-D20）were randomly divided into ginsenoside Rg3 group（Group A），oxaliplatin group（Group B），sorafenib group（Group C），ginsenoside Rg3+ sorafenib group（Group D），ginsenoside Rg3+oxaliplatin group（Group E），oxaliplatin+sorafenib group（Group F），ginsenoside Rg3+ oxaliplatin+sorafenib group（Group G）and formal saline group（Group H）. The drug was administered eleven days later after the inoculation of tumor. The dosage of the medicine was as follows：ginsenoside Rg3（5mg／kg， qd， 14 days， intraperitoneal injection） and oxaliplatin（5mg／kg， q2d， 14 days， intraperitoneal injection） and sorafenib（30mg／kg， qd， 14 days， gastric lavage）. All mice were sacrificed at 14 days after administration，and tumor tissues were resected. Immunohistochemical method and Western blotting were used to detect the expression rate and relative quantity of vascular endothelial growth factor（VEGF）， hypoxia-inducible factor（HIF）-1α， VEGF receptor（VEGFR）-2 and micro-vessel density（MVD） in the tumor. Results The treatment groups presented different degrees of MVD lower than that of Group H（P＜0.01）. Positive expression rates of VEGF in all treatment groups were decreased significantly compared with the Group H（P＜0.05）. Compared with Group H， positive expression rates of HIF-1α had a overall downward trend（P＞0.05）.The positive expression rates of VEGFR-2 in Group A， D and E were decreased significantly than that in Group H（P＜0.05）. Relative quantity of VEGF， HIF-1α and VEGFR-2 in Group A， B， C，D and E were decreased significantly than those in Group H（P＜0.05）. Conclusion Ginsenoside Rg3 has an anti-angiogenic effect. Its anti-angiogenic effect might be related to the down-regulated expression of VEGF， HIF-1α and VEGFR-2. Ginsenoside Rg3 in combination with oxaliplatin or sorafenib can enhance the anti-angiogenic effect， but the expression of VEGF， HIF-1α and VEGFR-2 protein didn’t decreased significantly in the combination of three drugs. It shows that the antitumor effect of three drugs may still relate other mechanisms, which needed further study.

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Effect of IR-780 photothermal therapy on breast cancer in xenograft mice

ZHOU Qunfang， DUAN Wanlu， LI Guofeng， YAN Fei， LIU Ruihong， LI Yekuo.

Chinese Clinical Oncology. 2015, 20 (4): 303.

Abstract ( 1002 )

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Objective To explore the effect of IR-780 combined with laser on breast cancer xenograft in mice. Methods 4T1 breast cancer cells were inoculated in the right subcutaneous abdomen of BALB／c mice to establish tumor models. Experimental mice were randomly divided into four groups（five mice for each group）： Control group（mice injected with 0.1 ml saline）， Laser group（mice irradiated with laser of 2.2 W／cm2 for 4 min）， IR-780 group（mice injected with 80 μg IR-780） and IR-780+Laser group（mice injected with 80 μg IR-780 following irradiation with laser of 2.2 W／cm2 for 4 min）. The tumor volume was measured and recorded. The ultrasonic echo of tumor tissue in each group was evaluated with Vevo 2100 high frequency system at 0， 12 and 6 h after treatment， respectively. The apoptotic index of tumor tissue in each group was detected with TUNEL at 60 h after treatment. Results Compared with other three groups， the tumor volume of IR-780+Laser group was significantly decreased at 60 h after treatment（P＜0.05）. There were lower gray scale values of ultrasonic echo in IR-780+Laser group at 12 and 60 h versus 0 h after treatment（P＜0.05）. The gray scale values of ultrasonic echo in IR-780+Laser group were also lower than other three groups（P＜0.05）. There were higher apoptotic index of IR-780+Laser group versus other three groups（P＜0.05）. No significant difference was observed on the tumor volume， gray scale value of ultrasonic echo and apoptotic index among Control group， Laser group and IR-780 group（P＞0.05）. Conclusion The obvious suppressive effect was observed in photothermal therapy with IR-780 on breast cancer tumor， evidenced by change of ultrasonic echo of tumor tissue in high frequency and increased apoptosis.

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Effect of melittin on the proliferation， apoptosis and PI3K／Akt signal pathway in non-small cell lung cancer

LI Aiming， ZHAO Huimin， JIE Junqing.

Chinese Clinical Oncology. 2015, 20 (4): 307.

Abstract ( 946 )

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Objective To investigate the effect of melittin on proliferation， apoptosis and PI3K／Akt signal pathway in non-small cell lung cancer（NSCLC）. Methods The NSCLC cell lines A549， SPC-A1 and human lung epithelial cell line 16HBE were treated with different doses of melittin（0， 10， 20， 50， 100 μmol／L）. The Methyl thiazolyl tetrazolium（MTT） was used to determine the changes of proliferation inhibition rate at 24， 48， 72 and 96 h after the treatment of melittin. Meanwhile， the Annexin-FITC／PI double staining method and PI single staining method were used to measure the apoptotic rates and cell cycle via flow cytometry. Western blotting was used to detect the protein levels of Akt，PTEN and caspase-9 at 48 h after treatment with different concentrations of melittin. Results Melittin elevated the proliferation inhibition rates in a dose-and time-dependent manner on A549 and SPC-A1 cells（P＜0.05） without cytotoxic effect on 16HBE（P＞0.05）. In addition to similar proportion of G2／M phase and late apoptotic rate at 24 h of 10 μmol／L， there were increased early and late apoptosis rates， cell percentage of G0／G1 phase and protein levels of PTEN and caspase-9 but decreased cell percentage of S and G2／M phases and Akt level in 10-100 μmol／L melittin versus 0 μmol／L melittin with statistical significant differences（P＜0.05）. Significant difference was observed on the above indices during the concentration of 10-100 μmol／L（P＜0.05）. Conclusion Melittin have toxic effects on the NSCLC cells， but have no effect on normal cells. It can induce the apoptosis and cell cycle arrest of A549 cell with the effects of inhibiting the PI3K／Akt signaling pathway.

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Effect of simvastatin on the proliferation of human breast cancer cell MCF-7 and related mechanisms

SHEN Yuanyuan， DU Yingying， YUAN Yuan， PAN Yueyin.

Chinese Clinical Oncology. 2015, 20 (4): 312.

Abstract ( 937 )

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Objective To observe the effect of simvastatin（SVA） on the proliferation of MCF-7 cells and elucidate its possible molecular mechanisms. Methods MCF-7 cells were cultured in vitro. The inhibitory effects of different concenrations of SVA（0， 3.25， 6.25， 12.5， 25， 50， 100 μmol／L） on MCF-7 cells were measured by a tetrazolium-based colorimetric assay at 24， 48 and 72 h after treatment. The morphological changes of apoptosis induced by SVA（0， 2， 4， 8 μmol／L） were observed by fluorescence staning under the fluorescence microscope. Cell cycles after treatment with SVA（0， 4 μmol／L） were detected by flow cytometry. In addition， expression of intracellular Bcl-2 and Bax proteins were analyzed at 72 h after treatment with SVA（0， 2， 4， 8 μmol／L） by Western blotting. Results SVA inhibited proliferation of MCF-7 cells significantly in a dose- and time-dependent manner. Flow cytometry showed that the cell cycle was arrested at the G0／G1 phase after the treatment with SVA. Typical apoptotic morphologic changes were observed by fluorescence microscope，such as nuclear condensation and chromatin condensation. Analysis on expressions of intracellular Bcl-2 and Bax protein by Western blotting showed that， with the drug concentration increasing， the expressions of anti-apoptotic protein Bcl-2 were gradually suppressed but the expressions of apoptotic protein Bax were gradually increased. Conclusion SVA has the capabilities of inhibiting proliferation of MCF-7 cells in a dose- and time-dependent manner. Its cytotoxic effects seem to be of inducing cell cycle arrest and down-regulation of Bcl-2 and up-regulation of Bax.

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Expression of regenerating gene Ⅳ in endometrial carcinoma tissues and its clinical significance

WANG Shuxiang， CHEN Xiuwei， LI Xueting， ZHAN Yu， SHANG Pan，GAO Ya.

Chinese Clinical Oncology. 2015, 20 (4): 317.

Abstract ( 846 )

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Objective To investigate the expression of regenerating gene Ⅳ（RegⅣ） in human endometrial carcinoma，atypical hyperplasia of endometrium and normal endometrium tissues， and analyze its correlation with clinicopathlogical characteristics and prognosis in endometrial carcinoma. Methods Immunohistochemistry method was used to detect the expression of RegⅣ in 138 cases of endometrial carcinoma，25 cases of atypical hyperplasia of endometrium and 31cases of normal endometrium. Then the relationship between the expression of RegⅣ and clinicopathlogical characteristies of endometrial carcinoma was analyzed. The overall survival of patients was estimated using the Kaplan-Meier method. The factors affecting the prognosis of endometrial carcinoma was analyzed by Cox multivariate survival analysis. ResultsThe positive expression rates of RegⅣ in normal endometrium，atypical hyperplasia of endometrium and endometrial carcinoma tissues were 9.7％（3／31）， 32.0％（8／25） and 60.1％（83／138）， respectively. The differences among the three groups was statistically significant（P＜0.05）. The expression of RegⅣ was correlated with the age of endometrial carcinoma patient， surgical pathologic stage，grade of histological, invasive depth and lymph node metastasis（P＜0.05）， but no significant difference among the pathological types（P＞0.05）. Cox multivariate survival analysis showed that gene expression of RegⅣ was the independent predictor from disease free survival of patients with endometrial cancer. Conclusion RegⅣ may contribute to the development of endometrial carcinoma， and guide the evaluation for prognosis.

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Predictive value of TUBB3 and MAPT expression in patients with non-small cell lung cancer receiving chemotherapy with taxanes

DAI Hongyu， LI Suyi， MA Guodong， WAN Mingyue， YU Cunjun， CHEN Wenping.

Chinese Clinical Oncology. 2015, 20 (4): 322.

Abstract ( 845 )

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Objective To explore the expressions of class Ⅲ β-tubulin（TUBB3） and microtubule associated protein-tau（MAPT） in tumor tissue of patients with non-small cell lung cancer（NSCLC）， and to evaluate the value of TUBB3 and MAPT in predicting the chemosensitivity of taxanes. Methods The tumor tissue specimens from 55 patients with chemo-naive and unoperable metastatic or recurrent NSCLC were collected. All patients received platinum-taxanes chemotherapy as the first-line therapy. According to the efficacy assessed after two cycles， 55 patients were divided into 3 groups. Patients with complete remission or partial remission were classed as sensitive group， and patients with stable disease were less sensitive group， and patients with progressive disease were resistance group. Reverse transcription polymerase chain reaction was used to measure the mRNA levels of TUBB3 and MAPT， and the correlation between mRNA expression of TUBB3 and MAPT were analyzed. The immunohistochemistry was used to detect the protein expression levels of TUBB3 and MAPT. Results Expression of TUBB3 and MAPT mRNA in 55 cases of NSCLC tissues were obesrved in varying degrees. TUBB3 and MAPT protein were located in cytoplasm. In sensitive group， less sensitive group and resistance group， the levels of TUBB3 mRNA were 0.12±0.13， 0.17±0.24 and 0.51±0.19 and the levels of MAPT mRNA were 0.09±0.05， 0.14±0.09 and 0.46±0.21， respectively. The positive expression rates of TUBB3 and MAPT were 22.22％（4／18） and 16.67％（3／18） in sensitive group， 20.00％（5／20） and 25.00％（4／20） in less sensitive group， and 70.59％（12／17） and 52.94％（9／17） in resistance group. The mRNA levels and positive expression rates of both TUBB3 and MAPT were higher in resistance group versus other two groups（P＜0.05）. No significant difference were observed on the above indices between sensitive group and less sensitive group（P＞0.05）. There was a positive correlation between the mRNA expression of TUBB3 and MAPT（r=0.219， P=0.047）. Conclusion The expression of TUBB3 and MAPT might predict the chemosensitivity of taxanes in patients with NSCLC. Patients with high expression of TUBB3 and MAPT might show resistance to taxanes. Combined detection of TUBB3 and MAPT might be more valuable in predicting chemosensitivity to taxanes.

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Efficacy and safety of dose-dense EC followed by P regimen in neoadjuvant chemotherapy for breast cancer：a retrospective comparison with the TEC regimen

HU Sainan，YU Qiao，HU Yiqing，YUAN Yuan，GAO Jing，ZHANG Lili.

Chinese Clinical Oncology. 2015, 20 (4): 327.

Abstract ( 934 )

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Objective To compare the efficacy and safety of dose-dense EC followed by P regimen versus TEC regimen in neoadjuvant chemotherapy for breast cancer. Methods In a retrospective comparison， the clinical data of 64 breast cancer patients with stage Ⅱa-Ⅲc in our hospital from February 2011 to August 2012 were analyzed. According to the chemotherapy regimen，31 cases received dose-dense EC followed by P regimen for 3-8 cycles before surgery（dose-dense group）， and 33 cases received TEC regimen for 2-6 cycles before surgery（TEC group）. Dose-dense regimen was as follows： epirubicin（90 mg／m2， d1） plus cyclophosphamide（600 mg／m2， d1） every two weeks for four cycles followed by paclitaxel（175 mg／m2， d1） every two weeks for four cycles. TEC regimen was as follows： docetaxel（75 mg／m2， d1）， epirubicin（70 mg／m2， d1） and cyclophosphamide（600 mg／m2， d1） every 21 days. Response to chemotherapy was assessed by RECIST criteria 1.1 and histopathological reaction after surgery. The toxicity was evaluated according to Common Terminology Criteria Adverse Events（CTCAE） 4.0. Results All patients were evaluable for efficacy and toxicity. The assessments of 64 patients were available. The pathologic complete response rates were 16.1％ and 12.1％， and the response rates were 80.6％ and 66.7％ in dose-dense group and TEC group， respectively. No difference was observed on the pathologic complete response rate and response rate between both groups. The 1-， 2-year disease free survival rates were 93.5％ and 86.7％ in dose-dense group and 93.9％ and 81.8％ in TEC group， and the 1-， 2-year overall survival rates were 100.0％ and 90.3％ in dose-dense group and 100％ and 85.8％ in TEC group without significant difference（P＞0.05）. There were higher incidences of grade 1-2 neurotoxicity（80.6％ vs. 36.4％） and muscle arthrosis ache（67.7％ vs. 30.3％） but a lower incidence of grade 3-4 neutropenia（6.4％ vs. 33.3％） in dose-dense group versus TEC group（P＜0.05）. Conclusion The efficacy of dose-dense and TEC neoadjuvant chemotherapy regimens are similar. The dose-dense regimen is well tolerated and more secure， which showed a non-significant trend toward better disease free survival and overall survival when compared with the TEC regimen. It is a preferred regimen in neoadjuvant chemotherapy.

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Analysis of prognosis-related factors for breast cancer with positive estrogen receptors

CHEN Hui， MO Lin， XU Xiaofan， GU Jun.

Chinese Clinical Oncology. 2015, 20 (4): 333.

Abstract ( 906 )

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Objective To investigate the related factors for prognosis of estrogen receptor（ER）-positive breast cancer. Methods The clinical and pathological data of 229 patients with ER-positive breast cancer from Jan 2006 to Nov 2009 were collected. The onset of age， menstrual status， tumor size， tumor grade， lymph node ratio（LNR）， expression patterns of PR and Her-2， neoadjuvant chemotherapy and radiotherapy were analyzed by Kaplan-Meier survival plots and multivariable Cox hazard regression analysis to identify prognostic factors for survival. Results In this retrospective analysis，15.70％ of 223 patients who had completed the follow-up suffered from local recurrence or metastasis. The Cox regression revealed that the tumor size， LNR， expression patterns of PR and Her-2 affected the recurrence-free survival after the endocrine therapy of breast cancer. Conclusion Large size of tumor， high LNR， over-expression of Her-2 and loss of PR are risk factors for recurrence／metastasis of ER-positive breast cancer.

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Correlation between TTF-1 expression and EGFR expression and EGFR mutations of 19 and 21 exons in lung adenocarcinoma

YAO Juan， WANG Jianjun， WANG Haiyan， YU Bo， SHI Qunli， ZHANG Rusong， WANG Xuan， ZHOU Xiaojun， WANG Jiandong.

Chinese Clinical Oncology. 2015, 20 (4): 338.

Abstract ( 907 )

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Objective To investigate the relationship between expressions of thyroid transcription factor 1（TTF-1） and epidermal growth factor receptor（EGFR）， and EGFR mutations of 19 and 21 exons in lung adenocarcinomas. Methods For 153 cases of lung adenocarcinomas obtained by surgical resection and puncture biopsy，immunohistochemistry was used to detect the expression of TTF-1 and EGFR， and amplification refractory mutation system was used to detect mutations of EGFR 19 and 2l exons. Furthermore， the relationship between expressions of TTF-1 and EGFR， and EGFR mutations of 19 and 21 exons were also investigated. Results Sixty-eight cases of EGFR gene mutations were found， including 32 cases in 19 exons and 36 cases in 21 exons. Among 153 cases of lung adenocarcinomas， 50.0％（24／48）， 62.5％（25／40） and 83.1（54／65） of EGFR expression（+++） and 25.0％（12／48）， 37.5（15／40）， 63.08％（41／65） of EGFR mutations were found in 48， 40 and 65 cases of TTF-1 expression（0-+）、（++） and（+++）， respectively. Besides， 16.7％（3／18）， 34.4％（11／32） and 52.4％（54／103） of EGFR mutations were found in 18， 32， 103 cases of EGFR expression of（0-+），（++），（+++）. It was observed that the ratios of EGFR expression（+++） and EGFR mutations also increased with the increased expression of TTF-1. It was also found that the EGFR mutations increased correspondingly with the increased EGFR expression. The correlations of TTF-1 expression and EGFR expression， TTF-1 expression and EGFR mutations， EGFR expression and EGFR mutations were statistically significant with the corresponding r of 0.940， 0.916， and 1.000， respectively. Conclusion Expressions of TTF-1 and EGFR and EGFR mutations of 19 and 21 exons are relevant to each other in lung adenocarcinomas. Detection of TTF-1 expression can be used to preselect the EGFR mutations for target therapy. Clinical doctors can predict EGFR mutations to guide the timely and effective clinical diagnosis and treatment by combined evaluating the expression of TTF-1 and EGFR when it is urgent for chemotherapy or target therapy but hard to undertake the detection of EGFR gene mutation in some areas.

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Comparison of contrast-enhanced ultrasound and contrast-enhanced magnetic resonance imaging in extrahepatic bile duct carcinoma

ZHANG Bo， SI Qin， QIAN Xiaoli， HUANG Shengxi， YANG Lu， LIU Yuanyuan.

Chinese Clinical Oncology. 2015, 20 (4): 343.

Abstract ( 943 )

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Objective To investigate the imaging features of extrahepatic bile duct carcinoma with the real-time contrast-enhanced ultrasonography（CEUS） and contrast-enhanced MRI（CEMRI）. Methods A retrospective analysis was made on the imaging features in 56 patients with extrahepatic bile duct carcinoma in our hospital from January 2009 to December 2013， who were confirmed by pathology and examined by CEUS and CEMRI. Results As for CEUS， most of extrahepatic bile duct carcinoma lesions were hyper-enhanced（37／56，66.0％） in arterial phase， and hypo-enhanced in portal（50／56，89.3％） and late phase（56／56，100％）；when at peaking， 34 lesions（34／56） showed diffuse heterogeneous enhancement， and 22（22／56） showed homogeneous enhancement. As for CEMRI， most of extrahepatic bile duct carcinoma lesions were hyper-enhanced（37／56，66.0％） in arterial phase， iso-enhanced（29／56，51.7％） in portal phase and iso-enhanced（17／56，30.3％）or hyper-enhanced（33／56，58.9％）in late phase； when at peaking， 39 lesions（39／56） showed diffuse heterogeneous enhancement， and 17（17／56） showed homogeneous enhancement. The difference of lesion enhancment in arterial phase between CEUS and CEMRI was not sianificant（P＞0.05）. But there was a significant difference between CEUS and CEMRI on lesion enhancement in portal and late phase（P＜0.05）; there was no significant difference between CEUS and CEMRI on the number of the lesions showing diffuse homogeneous or heterogeneous enhancement（P＞0.05）. Conclusion Compared with CEMRI， CEUS can observe real-time micro perfusion of extrahepatic bile duct carcinoma.For the patients who were highly suspected of extrahepatic bile duct carcinoma， CEUS combined with CEMRI can provide an important imaging evidence for the diagnosis of extrahepatic bile duct carcinoma.

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Clinical observation of gamma knife for orbital apex cavernous hemangioma

YANG Yuanyou， CHENG Haimin， MU Xiaofeng， NING Jian， XIAO Lihua.

Chinese Clinical Oncology. 2015, 20 (4): 347.

Abstract ( 884 )

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Objective To analyze the efficacy and side effects of gamma knife for orbit apex cavernous hemangioma. Methods From Mar. 2005 to Jun. 2013 in our hospital, 16 cases of orbital apex cavernous hemangioma were treated with gamma knife to perform fractionated stereotactic radiotherapy. A total dose was prescribed to the targets in 6-20 fractions of 2.3-5 Gy each. Visual acuity， visual field， the degree of exophthalmos and orbital MRI should be tested before treatment and at about each 6 months post-treatment. The median followed-up time was 21months（12-111 months） and ended in July 2014. Results All the tumors shrank in different degrees，including 5 cases of CR， 7 cases of PR and 4 cases of SD. The tumor response rate was 75.0％， and tumor control rate was 100.0％. The preservation rate of vision acuity was 81.3 ％（10 cases increased， 1 case kept stable and 2 cases decreased mildly）. Three cases with a visual acuity of hand movements or light perception disappeared. The improvement rate of vision field and exophthalmos were 81.3％ and 100.0％, respectively. All the symptoms including ambiopa， orbital ache and dizziness were disappeared. During the treatment, 3 cases showed mild acute reaction. The differences of the local efficacy and visual acuity change in all the dose groups were not significant（P＞0.05）. Before and after treatment， visual acuity（0.310±0.324 vs. 0.625±0.477）and exophthalmos（15.500±2.066 mm vs. 14.875±1.708 mm） improved and there were statistical significance（P=0.001，P=0.007），respectively. Conclusion Gamma knife-stereotactic radiotherapy treatment for orbital apex cavernous hemangioma is safe and effective with the effect of improving visual function and exophthalmos.

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Clinicopathologic study of 6 patients with myeloid sarcoma

JIANG Qingming， LU Ping， ZHOU Wenwen，YE Xuezheng， LI Jin.

Chinese Clinical Oncology. 2015, 20 (4): 351.

Abstract ( 942 )

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Objective To investigate the clinicopathologic features，immunophenotyping， differential diagnoses， treatment and prognosis of myeloid sarcoma（MS）. Methods The clinical and pathologic data of 6 cases of MS were reviewed. HE stain，immunohistochemistry stain by EnVision method and bone marrow slides examination were carried out. The followed up information was available in all patients. Results There were 3 males and 3 females. The age ranged from 23 to 66 years. The sites of involvement included small intestine， palate， palm of the hand， colon， lung and cervix.The tumor cells were widespread infiltration，diffused distribution with no adhesion each other； tumor cells were middle size， little cytoplasm and large nucleolus. Nucleolus were round and orbicular-ovate. Chromatin was exquisite and uniform distribution; nucleolus was clear with different sizes in 2 cases. Some eosinophilic granulocytes were visible. Immunohistochemical study showed that cases were positive for MPO， CD43， CD117， CD68-KP1， CD13， CD15 and lysozyme. According to histopathology feature and immunohistochemical result， the 6 patients were granulocytic sarcoma. During the follow-up， 3 cases with AML died at 5， 6， 11months after diagnosis. Other three patients survived. Conclusion MS is a scarce malignant tumor that is myeloid cells morphology and immunophenotype characters. The diagnosis should be based on tissue morphology and immunohistochemistry observation.

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Research progress of proteinuria associated with vascular endothelial growth factor inhibito

MA Xingqun， CHENG Yuan， CHEN Yingxia.

Chinese Clinical Oncology. 2015, 20 (4): 357.

Abstract ( 884 )

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Vascular endothelial growth factor signalling pathway is indispensable for the normal development and maintenance of glomerular filtration barrier. Proteinuria is shared toxic effect among all the vascular endothelial growth factor inhibitors， which may result in podocyte cell injury， glomerular endothelial cell injury， even renal thrombotic microangiopathy. The mechanisms of proteinuria secondary to vascular endothelial growth factor inhibitors were not well interpreted， and now no specific recommendation for antiproteinuric agent can be available. We review the mechanisms， incidence and managements for proteinuria associated with vascular endothelial growth factor inhibitors.

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Application of sentinel lymph node mapping in gynecological tumors

FANG Yichen， WU Qiang.

Chinese Clinical Oncology. 2015, 20 (4): 363.

Abstract ( 883 )

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Numerous studies have been involved in sentinel lymph node mapping in gynecological tumors， such as vulvar cancer， cervical cancer and endometrial cancer. The sentinel lymph node technique can accurate clinical staging of patients in early stage，screen out patients without lymph node metastasis， thus avoid unnecessary extensive surgery， ensuring efficacy while reducing the incidence of complications， and improving the patients’ life quality. In this review， we will focus on recent developments abroad of sentinel lymph node mapping in gynecological malignant tumors.

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Research progress of the application of chimeric antigen receptor-engineered T lymphocytes for solid cancer

ZHU Tong， WANG Jiejun， ZHOU Wenli.

Chinese Clinical Oncology. 2015, 20 (4): 367.

Abstract ( 940 )

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In recent years， the researches on chimeric antigen receptor（CAR） engineered T lymphocytes in curing cancer have made great progresses. CAR has several technical advantages， such as endowing great targeting ability to CAR-engineered T cells， breaking the state of immune tolerance and so on， which make great progress in curing Hematology. Because of existed off-target effects of solid tumor and the poor penetration of immune cells into the tumor tissue， this application is still in phase I clinical trial. This paper will make a review of the application of CAR enjineered T lymphocyte to some solid tumor experiments.

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Research progress of metabolic symbiosis in cancer

YANG Qiong， XIA Liangping.

Chinese Clinical Oncology. 2015, 20 (4): 371.

Abstract ( 863 )

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In the 1920s， German biochemist Warburg found that tumor cells used glycolysis for energy generation to maintain survival even under aerobic conditions， a phenomenon known as the Warburg effect. However， a growing number of studies have found that not all kinds of tumor showed the Warburg effect， or not all of tumor cells used the Warburg effect for energy generation. There is the diversity of metabolism in tumor cells. Some cells used glycolysis for energy production， but other cells used oxidative phosphorylation for energy production. Two types of cells can mutually coordinate and coexist with each other through lactic acid shuttle system， which is named metabolic symbiosis. This review will discuss the material basis of metabolic symbiosis and symbiosis phenomenon among cells in tumor. This review will also discuss the effect by metabolic symbiosis on characteristics of tumor cells and the clinical significance of metabolic symbiosis. A fully understanding of metabolic symbiosis in tumor cells is helpful for designing new and effective anti-cancer treatment strategies.

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CTLA-4 T cells immune targeted therapy based and status of transformation research in non-small cell lung cancer

YU Zongyang， MO Xiangyang， OUYANG Xuenong.

Chinese Clinical Oncology. 2015, 20 (4): 376.

Abstract ( 871 )

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Cytotoxic T lymphocyte associated（CTLA-4） is a kind of leukocyte differentiation antigens， it participates in the negative regulation of immune response. As the treatment of non-small cell lung cancer （NSCLC） model by the driver gene targeted therapy to immune targeted therapy，CDLA-4 has become a new research hotspot. This article combing CDLA-4 research of NSCLC in recent years and reviews the connecting with the related basic and clinical research progress.

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标准刊号：	ISSN 1009-0460
	CN 32-1577/R